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Medicină Militară

Revista de

Fondată în 1897 • Anul CXVII • Nr. 1-2/2014

• An unusual cause for cerebellar syndrome

• Nonalcoholic fatty liver disease – an etiological approach

• Clostridium difficile - emergent hospital flora

• News and Perspectives on Treatment of Normal Pressure Internal Hydrocephalus

• New decontaminants based on quaternary ammonium salts

• Past and future

• Stress management for optimization of Organizational activity

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r.ro

Revista de Medicină Militară nr. 1-2 / 2014ISSN 1222-5126

Nr. 1-2/2014 Revista de Medicină Militară

3

CONTENTSCarmen Adella Sîrbu, Octavian-Mihai Sîrbu, Anca-Maria Sandu, Cristina Petronela Sandu, Marian Ștefănescu

• An unusual cause for cerebellar syndrome 6

Florentina Ioniță Radu, Mariana Jinga, Petruț Nuță, Raluca Costache, Sandica Bucurica, Bogdan Macadon, Vasile Balaban, Mihăiță Pătrășescu

• Nonalcoholic fatty liver disease – an etiological approach 10

Gabriela Victoria Dumitrescu, Viorel Ordeanu, Simona Bicheru, Lucia Ionescu, Diana Popescu, Marius Necşulescu

• Clostridium difficile - emergent hospital flora 16

Cristian Năstase, Marian Mitrică, Cristian Popescu

• News and Perspectives on Treatment of Normal Pressure Internal Hydrocephalus 24

Diana M. Popescu, Viorel Ordeanu, Lucia E. Ionescu, Gabriela V. Dumitrescu, Simona N. Bicheru, Marius Necşulescu

• New decontaminants based on quaternary ammonium salts 32

Necșulescu Andrei

• Past and future 38

Iuliana Guiţă – Alexandru

• Stress management for optimization of Organizational activity 40

RMM • Fondată în 1897 • Anul CXVII

• Nr. 1-2/2014Editată de Direcția Medicală a Ministerului Apărării Naționale și Asociația Medicilor și Farmaciștilor Militari din România

Revista de Medicină Militară

Revista de Medicină Militară Nr. 1-2/2014

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EDITORIAL BOARD

Editor-in-chief: �� Dragoş CUZINOAssociate editors: �� Silviu STANCIU �� Mariana JINGASecretary of the Editorial Board: �� Dan DOBREAssistant secretary of the Editorial Board: ��Cristina ENCIU��Claudia ȚIGLEA

Junior-editors: Ion BULACU, Simona COSTIN, Alina CONDOR, Valentin GHEORGHIȚĂ, Radu HERTZOG, Alexandru KERESZTES, Adrian POPENŢIU, Aurel TRANĂ, Vlad ZAHIU, Bogdan ZAMFIR Technical editor: �� Andrei PopescuPublic relations ��Oana Ciobanu

SCIENTIFIC COMMITTEEProf. Silviu ALBU, Prof. Adrian BARBILIAN, Prof. Ioan CODOREAN, Aurora COTEA, Constantin GROZAVU, Răsvan-Nicolae HRISTEA, Ştefan ION, Prof. Dan MISCHIANU, Aurelian-Corneliu MORARU, Prof. Dorin MERCUŢ, Adrian NISTOR, Prof. Gerald ROUL, Viorel TRIFU, Bogdan TEUŞDEA, Prof. Ion ȚINTOIU, Daniel VASILE

THE ASSOCIATION OF MILITARY DOCTORS AND PHARMACISTS IN ROMANIAHONOURABLE MEMBERS: �� Major General (ret) PETRU CHERTIC, MD�� Major General (ret) MIHAI AUGUSTIN, MD, PHD�� BriGadier General (ret) VIOREL BÂTCĂ, MD

DIRECTORATE BOARD – EXECUTIVE BUREAU PRESIDENT: �� Major General prof� IOAN SÎRBU, MD, PHD, Chief of MediCal direCtorateVICE-PRESIDENTS: ��Col� leCt� DRAGOş CUZINO, MD, PHD – Military MediCal institute�� Col� CRISTIAN IORDACHE – preventive MediCine Center�� COL. LECT. OVIDIU NICODIN - eMerGenCy universitary Central Military hospital, BuCharest

SECRETARY GENERAL: ��MAJ. DAN DOBRE, MD – MediCal direCtorateTREASURER: ��PAULA BĂDĂRĂU – Military MediCal institute

ADVISORY BOARDMEMBERS: ��COL. DOINA BĂLTARU, MD – EMERGENCY MILITARY HOSPITAL CLUJ��Col� GEORGIAN TUDOSE, MD – eMerGenCy Military hospital Braşov��COL. IULIAN PETRESCU, MD – MediCal direCtorate �� Col� IOAN BARB, MD – eMerGenCy Military hospital siBiu��Col� EUGEN PREDA, MD – eMerGenCy CliniCal Military hospital Craiova��Col� DANIELA POPA, MD – air forCe��Col� VIOREL TRIFU, MD – eMerGenCy universitary Central Military hospital, BuCharest

Board of Censors �� Col� IULIAN PETRESCU ��leGal advisor IRINA POP

EDITORIAL OFFICE:

no� 3-5 Medico-Military institute street, sector 1, BuCharest, romania, r – 010919, tel�/fax:+4021/312�53�86

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MILITARY MEDICAL JOURNALThe journal is published by Medical Directorate, Ministry of National Defence – Romania and The Association

of Military Doctors and Pharmacists in Romania


5Editorial

This goal can be achieved through the implementation of a modern management both of the Medical Directorate and of the subordinate units, which basically involves a reform of these institutions, keeping them out of the incertitude of annual budgetary provision, looking for contractual stability with National Defence, Internal Affaires,

National Security and Justice Authority Health Insurance Company (C.A.S.A.O.P.S.N.A.J) and placing them on the right path for institutional performance.

The reform of the military medical institution is an act of courage that has to be accomplished with great determination.

The first step would be submitting to the Supreme Council of National Defence (CSAT) the concept of the modernization of the military medical system including elements of innovative vision on the military medical phenomenon. One of these issues is the need for modernisation of medical equipment and hospital infrastructure in order to allow the treatment in national military hospitals of soldiers injured in combat theaters and of civilians after natural disasters or industrial accidents with multiple victims.

Another goal is to create a fully equipped base for physical and neuropsychological recovery of military personnel executing missions in operation theaters and of their family members, allowing a fast and complete social and family reintegration.

A particular attention should be paid to hero combatants, wounded in combat theaters; they will take benefit from the best specialists in health care in the new social-medical edifice which will be available since 2015.

In 2015 also, the construction of the new Emergency Universitary Central Military Hospital will begin in Bucharest in Garrison 867, part of the Ministry of National Defense estate patrimony, under Government Decision no 1594/04.12.2008.

This investment is the natural consequence of the need to be aligned with the realities of modern medicine promoted by North Atlantic Alliance through ROL 4 level hospital units, covering all medical and surgical specialties required for complete rehabilitation and recovery of military personnel wounded in the operation theaters or in the current training activities, on national territory.

In the same time with updating of the clinical basis, we should concentrate our attention on improving the continuous training of our healthcare staff regarding the achievement of new treatment techniques and solutions. Continuous professional training is an asset that our physicians are providing to the military personnel in distress.

From the experience of some colleagues, who have chosen to leave the system, the main reasons for discontent were: the working environment and the lack of modern investigation means; to the surprise of many, the financial reason was the last one.

Promoting team spirit and preserving the values in the system has been a permanent concern of the Medical Directorate Management.

All these contribute to achieving outstanding results in our activity, leading to increasing satisfaction for patients and doctors.

Major General IOAN SÎRBU

Reconsidering the importance of Military Medicine at the level of National Ministry of Defence and into society

Major General IOAN SÎRBU

Chief of Medical Directorate, Ministry of National Defence, Romania

Professor, Head of Oral Implantology Department of the Faculty of Dental Medicine, Bucharest, Romania


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An unusual cause for cerebellar syndrome

– case report –

Carmen Adella Sîrbu¹, Octavian-Mihai Sîrbu², Anca-Maria Sandu², Cristina Petronela Sandu³, Marian Ștefănescu³

¹Universitary Emergency Central Military Hospital Bucharest, Department of Neurology;²University of Medicine and Pharmacy ,,Carol Davila’’ Bucharest

³Universitary Emergency Central Military Hospital Bucharest, department of Radiology and Imaging

A male from rural area, S.M., aged 77 years, was admitted in our department for discontinuous headache. His medical history was

irrelevant. He has been experiencing intermittent right parietal-occipital headaches during the last 3 months. Neurologic exam revealed a slight right limb ataxia. Initial laboratory findings revealed a white blood cell

count of 6500/mm3 with 75% polymorphonuclear leukocytes, 15% lymphocytes and 8% monocytes. His serum glucose was 90 mg/dL.

Non Gadolinium CT scan shows rounded, inhomogenous spontaneous hyperdense area (40-45 UH) between 5-12 mm diameter, localized

frontal, temporal, occipital and cerebellar bilaterally (fig.1). The question was whether the lesions were metastasis or parasitic infection?


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Fig. 1

Fig. 2


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Discussions:Neurocysticercosis is a parasitic brain infection,

caused by larval cysts of the tapeworm Taenia solium by accidental ingestion of eggs. It is the most common parasitic disease of the nervous system and it is the main cause of acquired epilepsy mainly in developing countries. Once in the human intestine, Taenia eggs evolve to oncospheres that cross the intestinal wall and lodge in the brain where cysticerci develop.

Time from infestation until first symptoms is between days and many years (30).This extremely long incubation is due to hipnobiosis. They may be located in subarachnoid space, ventricular system, or spinal cord too, causing a clinical heterogeneity.

Onset of most symptoms is usually insidious to chronic, with seizures (most common presenta-tion), headache, dizziness, stroke, neuropsychiatric dysfunctions. Almost every neurological sign or symptom may be present but physical findings oc-cur in less than 20% of the cases.

There is a pleomorphism of the immune re-sponse against Taenia solium. In some cases, cysticerci are destroyed by immunological attack, while in others, parasites may live unchanged for years. CT scan shows a rounded, homogeneous hy-perdense area with no enhancement with contrast medium. This phase corresponds to the inactive pa-renchymal form of ‘the disease.

CT findings are depending on the stage of evolution: • vesicular stage (viable larva): hypodense, non-

enhancing lesions• colloidal stage (larval degeneration): hy-

podense/isodense lesions with peripheral en-hancement and edema

• nodular-granular stage: nodular-enhancing lesions

• cysticercotic encephalitis: diffuse edema, collapsed ventricles, and multiple enhancing parenchymal lesions

• active parenchymal stage: the scolex within a cyst may appear as a hyperdense dot

• calcified stage: when the parasite dies, nodular parenchymal calcifications are seen.Our patient has multiple lesions in different

phases of evolution (active and calcified).

MRI is the ,,gold standard’’ method for neuro-cysticercosis diagnosis, especially for evaluation of intraventricular and cisternal/subarachnoidal cysts. The ventricular ependymal lining reacts to the cysts and an inflammatory reaction or ependymitis oc-curs, as a high-intensity signal in the ependymal layer. Hyperintense T2 scolex as an eccentric nod-ule is visible in vesicular stage (fig. 2). On MRI, the capsule shows higher signal than the adjacent brain with thick-ring enhancement on T1-weighted im-ages, while on T2-weighted images a low-ring signal surrounded by high signal lesion is seen. When the parasite dies, a resorption process occurs and calci-fied nodule lodges permanently in the CNS.

Accurate diagnosis is possible after interpreta-tion of clinical data together with findings of neu-roimaging studies and results of immunologic tests, in a proper epidemiologic scenario. Several immu-noglobulin (Ig) classes are produced as specific an-tibodies against the parasite. The most frequent is immunoglobulin G (IgG), which can be detected in serum, CSF, and saliva and suggests that infec-tion is long lasting. The immune response against T solium cysticerci appears to have components of both T helper type 1 cells (Th1) and T helper type 2 cells (Th2), although the underlying mechanisms are not fully understood yet. The immune response is unpredictable and may vary from a complete tol-erance to an intense immune response. The natural history of cysticerci in the CNS is to be clarified.

C erebral Mri showed un-enhanced, well defined, multiple lesions between 3 -17 mm, with iso-hyper-

intensity t1, t2, and flair, spread out periventriculary, subcortically, in frontal, temporal, parietal lobes and subtentorially, right and left cere-bellum (fig�2)� after serological tests from blood and Csf the diagnostic of neurocysticercosis was certified (an enzyme-linked immunosorb-ent assay of the Csf was positive for immunoglobulin G cysticercosis antibody, with 1�32 optical density units (od) (positive result > 0�50 od); his serum igG cysticercosis an-tibody was positive with 5�12 od)�


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CSF analysis for neurocysticercosis is indicat-ed in every patient presenting with new-onset sei-zures or neurologic deficit in whom neuroimaging shows cerebral lesion but does not offer a defini-tive diagnosis. CSF is contraindicated in cases of large cysts causing severe edema and displacement of brain structures, as well as in lesions causing obstructive hydrocephalus. A large proportion of infection is asymptomatic and discovered inciden-tally at necropsy.

Guidelines issued in April 2013 by the Ameri-can Academy of Neurology recommend use of 400 mg albendazole twice daily for adults plus either dexamethasone or prednisolone to decrease the number of active lesions on brain imaging studies. The duration of the treatment remains unknown.

Patients with vasculitis, arachnoiditis, or encepha-litis need a course of steroids or immunosuppres-sants before the use of anticysticercal drugs.

Surgery is the recommended procedure for:

• hydrocephalus due to an intraventricular cyst: placement of a ventricular shunt, followed by surgical extirpation of the cyst and subsequent medical treatment

• multiple cysts in the subarachnoid space (ie, the racemose form)

• obstruction due to arachnoiditis: placement of a ventricular shunt followed by administration of steroids and subsequent medical therapy.

Bibliography1. Brooks M. AAN Issues Guideline

on Parenchymal Neurocysticerco-sis. Medscape Medical News. April 9, 2013. Available at http://www.medscape.com/viewarticle/782211 accessed jul 15, 2014.

2. Baird RA, Wiebe S, Zunt JR, Hal-perin JJ, Gronseth G, Roos KL. Evi-dence-based guideline: Treatment of parenchymal neurocysticercosis: Report of the Guideline Develop-

ment Subcommittee of the Ameri-can Academy of Neurology. Neuro-logy. Apr 9 2013;80(15):1424-1429. [Medline].

3. Del Brutto OH. Neurocysticercosis. Handb Clin Neurol. 2014;121:1445-59. doi: 10.1016/B978-0-7020-4088-7.00097-3.

4. http://www.cdc.gov/parasites/cysti-cercosis/ acessed on 14.07.2014

5. http://emedicine.medscape.com/

article/1168656-overview acessed on 20. 07. 2014

6. Gagandeep Singh, Arthur Clinton White. Determining better treatments for neurocysticercosis The Lancet Infectious Diseases, Volume 14, Is-sue 8, Pages 658 - 659, August 2014 doi:10.1016/S1473-3099(14)70829-1

7. http://www.who.int/neglected_di-seases/diseases/cysticercosis/en/ acessed on 17 .07. 2014


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Nonalcoholic fatty liver disease – an etiological

approachCol. Florentina Ioniță Radu MD, Col. Mariana Jinga MD, LTC Petruț Nuță MD, LTC Raluca Costache MD, Maj. Sandica Bucurica MD, Maj. Bogdan Macadon MD, Vasile Balaban MD, Maj. Mihăiță Pătrășescu MD

Gastroenterology Clinic of Emergency Universitary Central Military Hospital, Bucharest, Romania

AbstractNonalcoholic fatty liver disease (NAFLD) is defined as the presence of fat in the liver (hepatic steatosis) either on ima-ging or on liver histology only after the exclusion of secon-dary causes of fat accumulation in the liver (e.g. high alcohol drinking, drugs and other medical ailments). Considering the fact that there are many causes of hepatic steatosis, the term NAFLD is reserved for the liver disease that is predominantly

associated with obesity and metabolic syndrome. The pre-sence of inflammation and cell injury defines steatohepatitis (NASH) which has the potential to evolve into cirrhosis and hepatocarcinoma, being, therefore, the stage of NAFLD most amenable to treatment. Among the treatments available, the most important are: weight loss, vitamin E and, last but not least, probiotics.

Excessive alcohol consumption must be excluded (>21 drinks per week in men and >14 drinks per week in women over a 2-year period before the baseline liver

biopsy). Insulin resistance (figure 1) is, therefore,

central to the development of NAFLD, as it is central to metabolic syndrome (MS). The Adult Treatment Panel III defines MS as the presence of three or more of the following features:1. a waist circumference greater than 102 cm in

men or greater than 88 cm in women,2. a triglyceride level greater than or equal to 150

mg/dL, 3. a high-density lipoprotein cholesterol level less

than 40 mg/dL in men and less than 50 mg/dL in women,

4. a systolic blood pressure greater than or equal to 130 mm Hg or a diastolic pressure greater than or equal to 85 mm Hg, and

5. a fasting plasma glucose level greater than or equal to 110 mg/dL.1Patients with features of MS are at high risk for

NAFLD.

The gold standard for the diagnosis of NAFLD is hepatic biopsy which further characterizes the ailment deriving two stages of histological evolution: nonalcoholic fatty liver (NAFL) (this may be the plain hepatic steatosis) and nonalcoholic steatohepatitis (NASH). NAFL is defined as hepatic steatosis with no evidence of hepatocellular injury in the form of hepatocyte ballooning. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. Although NAFL may be proportionally more common than NASH, only patients with NASH have the potential to progress to cirrhosis. The presence of the characteristic ballooning injury is considered to be the key to the diagnosis. Ballooning injury results in enlarged vacuolated cells, classically containing Mallory- Denk bodies, which are eosinophilic cytoplasmic inclusions near the nucleus. The most important injury may be identified in zone 3 (around the central venule of the hepatic lobule) and this pattern of distribution is also characteristic of NAFLD. The cardinal histologic feature of NAFLD is the presence of an excessive accumulation of triacylglycerols


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(TAG) and in hepatocytes. The presence of obesity and insulin resistance lead to an increased hepatic-free fatty acid (FFA) flux creating an environment appropriate for the development of NAFLD/NASH. The resultant net increase in hepatic FFA is hepatotoxic unless it is converted to nontoxic intracellular triglyceride (TG). When the synthesis of TG is impaired, the level of FFA in the liver is increased with subsequent augmentation of hepatic fatty acid oxidation resulting in the overproduction of reactive oxygen species (ROS) also known as free radicals causing hepatocellular injury.

Based on this biochemical knowledge, a two-hit hypothesis for the pathogenesis of NASH has been proposed. The first hit involves the accumulation of excess triglyceride and particularly FFA in hepatocytes. The second hit is the generation of toxic reactive oxygen species with the production of hepatic injury and inflammation as a consequence of FFA oxidation which ultimately leads to the initiation and progression of fibrosis1.

Hence, steatosis is mandatory for the diagnosis of NAFLD but alcohol consumption and chronic hepatitis C should be taken into account as two of the most important alternative causes amenable to different treatments.

STEATOSIS

• insulin resistance• obesity• type 2 diabetes mellitus• dyslipidemia• hypertension• sedentary lifestyle• Corticosteroids• estrogens• amiodarone• antiretroviral medications• obesity surgery (e�g�, jejunoileal

bypass)• rapid weight loss• Carbohydrate excess (e�g�, diet and

total parenteral nutrition)• Chronic hepatitis C virus, mainly

genotype 3• hypothyroidism• polycystic ovarian syndrome

Table 1: Conditions Associated With the Risk of Hepatic Steatosis

INSULIN RESISTANCE

INFLAMATION

CELL INJURY STEATOSIS

FIBROSIS

Figure 1: Insulin resistance- central to metabolic syndrome


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The diagnosis of NAFLD requires the following: (1) hepatic steatosis according to imaging or histology, (2) no significant alcohol consumption, (3) no competing etiologies for hepatic steatosis (table 1), and (4) no coexisting causes for chronic liver disease.

NAFLD is the most common cause of abnormal liver chemistry, so other causes, like those in table 1, should be ruled out. The majority of patients with NAFLD are asymptomatic. The most frequently encountered symptoms are: vague right upper quadrant dull ache or discomfort. Hepatomegaly is

the most common physical finding. Other clinical symptoms and physical findings are, also, nonspecific: general malaise, abdominal discomfort, nausea.

Celiac disease always should be ruled out in suspected individuals considering the fact that this disease is often underdiagnosed and seldom to be taken into account as a differential diagnosis of hipertransaminasemia.

Once NAFLD is diagnosed, the next step is to determine the severity as it is necessary to establish the prognosis. Clinical examinations and laboratory and

Figure 2 : Algorithm for liver biopsy in NAFLD


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imaging studies in combination lack the sensitivity and specificity for distinguishing NAFL from NASH and for determining the presence and stage of fibrosis, which is the most important determinant for the severity and progression of disease.

Circulating levels of cytokeratin 18 fragments have been investigated extensively as novel biomarkers for the presence of steatohepatitis in patients with NAFLD, but this testing is not routinely recommended. Other noninvasive tests are emerging; however, these are not yet ready for prime time.1,2, 3

Liver biopsy still remains the most reliable ap-proach for identifying the presence of steatohepati-tis and fibrosis in patients with NAFLD.

The recommendations for liver biopsy are as follows (figure 2):

1. Patients at increased risk for steatohepatitis and advanced fibrosis according to the presence of features of MS and possibly the NAFLD fibrosis score.

2. Patients with suspected NAFLD for whom competing etiologies of hepatic steatosis and coexisting chronic liver diseases cannot be excluded without liver biopsy.

There is a general consensus that patients with NAFL have a very slow progression (if any). On the other hand, patients with NASH can exhibit histological progression and can develop fibrosis (37%-41%) and cirrhosis (Approximately 5%)3. Importantly, hepatic cancer can occur in NASH in the absence of cirrhosis. This is why every effort should be made to identify patients with NASH as they are the ones to progress to more severe forms of disease. The presence of NASH can be associated with higher liver-specific mortality in comparison with the general population. Cardiovascular ailments associated with NASH (as metabolic syndrome) contribute significantly to mortality and morbidity. Patients with NAFLD are also at increased risk for hepatocellular carcinoma, but this risk is likely limited to those with advanced fibrosis and cirrhosis (1%-42%)2. Furthermore, a comparison of the natural history of NASH cirrhosis with hepatitis C cirrhosis reveals that patients with NASH cirrhosis have a significantly lower risk of hepatocellular carcinoma.2

NAFLD is typically characterized by a hepatocellular pattern of liver-related enzymes with mild elevations (1-2 times the upper limit of normal) in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Up to 50% of NAFLD patients have normal liver biochemistry. Therefore, several biomarkers may aid in the diagnosis. The diagnosis of NASH without a liver biopsy remains the most significant clinical challenge in the evaluation of a patient with hepatic steatosis. Several biomarkers may distinguish between simple steatosis and NASH. Some of the inflammatory markers include serum C-reactive protein, interleukin-6, ferritin, hyaluronic acid (HA), tumor necrosis factor a, leptin, adiponectin, and resistin. Apoptosis plays a key role in the pathogenesis of NASH. Among the markers of apoptosis, plasma cytokeratin 18 (CK-18) is emerging as one of the promising biomarkers for the noninvasive detection of NASH. Since oxidative stress also plays an important role in the pathogenesis of NASH, several biomarkers of oxidative stress have been investigated. Among these, oxidized low-density lipoprotein, thiobarbituric acidreacting substances, superoxide dismutase, and glutathione peroxidase dismutase have been examined. The NASH test combined 13 variables [age, sex, height, weight, and serum levels of triglycerides (TGs), cholesterol, a2-macroglobulin, apolipoprotein A1, haptoglobin, gammaglutamyl transpeptidase (GGT), ALT, AST, and total bilirubin] to achieve positive predictive value, and negative predictive value of 66%, and 81%, respectively.2, 3, 4

Two of the most promising tests for diagnosing advanced fibrosis in NAFLD are the European Liver Fibrosis (ELF) score and the NAFLD fibrosis score. The ELF score includes HA, tissue inhibitor of metalloproteinase 1 (TIMP1), aminoterminal peptide of procollagen 3, and age. The NAFLD fibrosis score is helpful in the clinical setting because it uses routinely available variables in the clinical setting, including age, BMI, hyperglycemia, platelet count, serum albumin, and AST/ALT ratio. We use routinely available models or markers that increase the pretest likelihood of finding more advanced liver disease on liver biopsy. These tests can aid in clinical decision making for patients with NAFLD. Some of these markers are a high AST/ALT ratio, a high AST/platelet ratio, low albumin levels, and low platelet levels.2, 3


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Treatment landmarksAmong patients suffering from NAFLD (more

than 50% of them being asymptomatic) treatment is mandatory only in NASH patients because only those have the potential to evolve into more severe diseases (cirrhosis, hepatocarcinoma)5.

Because NASH is linked to excess body weight and resulting insulin resistance, diet and lifestyle measures are the recommended first-line therapy. Optimal treatment begins with weight loss and physical exercise. A tangible target for patients with NAFLD is a weight loss of 5% to 10% of total body weight over a 6- to 12-month period 6. Those measures may improve insulin sensitivity, increase adiponectin expression, lipid profiles, and liver biochemistry. The improvement in liver enzyme does not always correlate with improvement in hepatic histology, unfortunately. As it is already demonstrated, weight loss by dietary changes may be beneficial even without physical exercise; although physical exercise may lead to further improvement in insulin sensitivity. The initiation of increased physical activity must be the first step to the treatment of NAFLD; vigorous exercise and resistance training are more helpful than aerobic exercises. The intensity may be more important than the duration or total volume of exercise.7,8, 9

Current guidelines do not recommend the use of hepaticopharmacological therapy in patients with steatosis alone. Instead, patients with NASH and significant liver disease (bridging fibrosis) are good candidates for this type of therapy. According to the clinical practice guidelines of the American Association for the Study of Liver Diseases, the first choice of therapy is vitamin E (preferably 800 IU/ day). A 2-year treatment in the PIVENS trial (800 IU/day) reversed steatohepatitis and improved all histological features of NASH (except fibrosis) in comparison with a placebo. This beneficial effect of vitamin E was not associated with an improvement in insulin sensitivity. Recent studies and meta-analyses showed increased mortality, a risk of hemorrhagic stroke, and a risk of prostate in long term vitamin E treatments.10, 11

Animal studies have shown that omega-3 polyunsaturated fatty acids promote insulin sensitivity, reduce intrahepatic triglyceride content, and ameliorate steatohepatitis.10, 11

The drugs to increase insulin sensitivity (glita-zone, metformin) may be indicated as a treatment

alternative in NASH 16. Ursodesoxicholic acid and pentoxifilin, which may benefit marginally.6

Probiotics and NAFLDThe newest topic in treatment of NAFLD is

that of the involvement of gut microbiota in the pathogenesis of liver steatosis and inflammation.

Intestinal microbiota plays an important role in health and disease. The gut-liver axis involves an interaction between bacterial components like lipopolysaccharide and hepatic receptors (Toll-like receptors). Our gut has approximately 100 trillion (1014) microbes, which make up approximately 1 to 2 kilograms of our weight. Gut microbiota perform diverse immunologic, digestive, and metabolic functions.11

Changes in microbiota may be involved in various disease pathogenesis (nonalcoholic fatty liver disease (NAFLD), hepatic encephalopathy, alcohol-related liver disease, and hepatocellular carcinoma). Gut microbiota may cause NAFLD by luminal ethanol production by metabolization of carbohydrates, causing an increased intestinal permeability (“leaky gut”) just like in alcohol associated steatohepatitis (ASH).12, 13

In 2009 Miele was the first author to provide evidence of increased intestinal permeability in patients suffering from NAFLD and this fact was associated with increased prevalence of small bowel bacterial overgrowth (SIBO) in those patients14. The increased permeability appears to play an important role in the pathogenesis of NAFLD. Loguercio demonstrated in 2005 that probiotics may improve NAFLD histology and biochemistry15. In October 2013 Yan-Yan Ma et al published a meta-analysis in World Journal of Gastroenterology to conclude that the treatment with probiotics and prebiotics may definitely benefit patients with NASH 11. Probiotics can inhibit the proliferation of harmful bacteria, reduce SIBO, restore gastrointestinal barrier function and modulate the immune system, all of which contribute to the improvement of NAFLD. This meta-analysis showed that probiotics significantly reduced ALT, AST, T-chol, TNF-α and insulin resistance, which are all related to the process and consequences of NAFLD. Regular consumption of probiotics reduced, also, cholesterol levels which is part of metabolic disturbances in NAFLD patients. 11


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A high fat diet that induces obesity, insulin resistance and hepatic steatosis also leads to hepatic NKT cell depletion. The hepatic NKT cell is the key mediator of HF diet-induced metabolic abnormalities. Moreover, recently, Cani and colleagues reported that a high-fat diet increases plasma lipopolysaccharide (LPS) level, which also contributes to the pathogenesis of insulin resistance and increased liver triglyceride content. It is possible that this bacterial endotoxinemia caused by high fat diet reduces intrahepatic NKT cells and leads to worsened or amplified insulin resistance. The ability of probiotics to restore hepatic NKT cells and improve HF diet-induced insulin resistance and fatty liver are novel findings and intriguing.12, 13

These data suggest that strategies designed to down regulate inflammatory mediators with

probiotics have promising potential in patients with NAFLD.

ConclusionsNAFLD/NASH is a prevalent health problem

in general population in close proximity with the same increased rate of obesity, diabetus mellitus and metabolic syndrome to which it is pathogenically related. Proper management of insulin resistance by diet, weight loss and physical exercise may provide the patients with strong tools to fight the disease. The increasing evidence of the role of gut microbiota in disease pathogenesis and the role of probiotics in decreasing hepatic steatosis and inflammation points firmly towards new and handy solutions in the nearest future.

Bibliography1. Sanyal AJ, Banas C., Sargeant C.,

Luketic VA et al; .Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology 2006;43:682-689.

2. Adams LA, Lymp JF, St Sauver J, Sanderson SO et al; The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129:113-121.

3. Bashar M. and David H. ; Van Thiel

Current Concepts and Management Approaches in Nonalcoholic Fatty Liver Disease ScientificWorldJournal. 2013; 2013: 481893. Published online 2013 March 20

4. Rafiq N., Bai C., Fang Y., Srishord M., McCullough A., Gramlich T. et al; Longterm follow-up of patients with non-alcoholic fatty liver. Clin Gastroentrol Hepatol 2009;7:234-238.

5. Ong JP, Pitts A, Younossi ZM.; Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease. J Hepatol 2008;49:608-612.

6. Zein CO, Yerian LM, Gogate P., Lopez R, Kirwan JP, Feldstein AE et al; Pentoxifylline improves

nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology 2011;54:1610-1619

7. Huang MA, Greenson JK, Chao C., Anderson L., et al; One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol 2005;100:1072-1081.

8. Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA.et al; Orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial. Hepatology 2009;49:80-86.

9. Levy JR, Clore JN, Stevens W.; Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats. Hepatology 2004;39:608-616.

10. Williams CD, Stengel J, Asike MI, Torres DM, et al; Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population using ultrasound and liver biopsy: a prospective study. Gastroenterology 2011;140:124-131.

11. Yan-Yan Ma, Lin Li, Chao Hui Yu, Zhe Chen et al; Effects of probiotics on nonalcoholic fatty liver disease: A

meta-analysis World J Gastroenterol. 2013 October 28; 19(40): 6911–6918. Published online 2013 October 28.

12. Cani P., Amar J, Iglesias M., Poggi M., et al. Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes. 2007;56:1761–1772.

13. Vishal Sh., Shashank G. , Sourabh A. et al ; Probiotics and Liver Disease Perm J 2013 Fall;17(4):62-67

14. Miele L, Valenza V, La Torre G, Montalto M et al; Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009 Jun;49(6):1877-87.

15. Loguercio C., Alessandro F., Tuccillo C., Terracciano F. et al; Beneficial Effects of a Probiotic VSL#3 on Parameters of Liver Dysfunction in Chronic Liver Diseases; J Clin Gastroenterol 2005;39:540–543

16. Boettcher E., Csako G., Pucino F., Wesley R., and Loomba R.; Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis; Aliment Pharmacol Ther. 2012 January ; 35(1): 66–75.


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IntroductionClostridium difficile (C. difficile) is a Gram-

positive sporogenous bacillus strictly anaerobic, which in the last decade has became the most important anaerobic bacterium in nosocomial human pathology. Cl.dificile is the etiological agent of more than 20% of diarrhea postantibiotics, over 95% of pseudo-membranous colitis and the first cause of nosocomial infectious diarrhea in adults.

Although this bacterium usually colonizes the intestine of vertebrates (the normal microbiota), the toxinogenic strains (tcdA and tcdB) are patho-genic in the digestive tract. Given the excessive use of antibiotics and the increased spores resistance, it is possible an environment contamination, with strains which may already be resistant to antibiot-ics. The main causes of this infection are decreased resistance to antibiotic-induced colonization, con-

tamination with a pathogenic strain of Cl.difficile, secretion of A and/or B toxins and deficient im-mune response.

Microbiological diagnosis is made by sev eral methods and techniques for bacteria or toxins iden-tification. Cytotoxicity test reveals the cytopathic effect of fecal filtrate with pg sensitivity. Immuno-enzymatic assay enables a rapid diagnosis, first generation with ELISA, the second generation by immuno-enzymatic or immuno-chromatography cassette. Molecular biology techniques based on quantitative real-time PCR detect tcdA and tcdB genes in stool, responsible for toxigenesis with very good sensitivity and specificity. Through cultiva-tion and microscopy Cl. difficile can be revealed in the stool or on contaminated surfaces; spores are resistant in the environment and are found in no-socomial flora. A characteristic enzyme, glutamate

Clostridium difficile - emergent hospital flora

Gabriela Victoria Dumitrescu, Viorel Ordeanu, Simona Bicheru, Lucia Ionescu, Diana Popescu, Marius Necşulescu

Military Medical Research Center (CCSMM), Bucharest

DUMITRESCU Victoria Gabriela,

Mobile: +40722.227.415

E-mail: gabriella.dumitrescu@,vahoo.com

AbstractClostridium difficile (C� difficile) is a Gram-positive sporoge-nous bacillus strictly anaerobic, which in the last decade has became the most important anaerobic bacterium in nosoco-mial human pathology. Cl.dificile is the etiological agent of more than 20% of diarrhea postantibiotics, over 95% of pse-udo-membranous colitis and the first cause of nosocomial infectious diarrhea in adults.

Although this bacterium usually colonizes the intestine of vertebrates (the normal microbiota), the toxinogenic strains (tcdA and tcdB) are pathogenic in the digestive tract. Given the excessive use of antibiotics and the increased spores re-sistance, it is possible an environment contamination, with

strains which may already be resistant to antibiotics. The main causes of this infection are decreased resistance to antibiotic-induced colonization, contamination with a patho-genic strain of Cl�difficile, secretion of A and/or B toxins and deficient immune response.

Due to the increasing worldwide incidence of infections with C. difficile on one hand and to the discovery of new ways of trans-mitting the infection according with some studies regarding the genetic diversity of bacterium strains on the other hand, a new approach is necessary for C. difficile related topics.

Keywords: antibiotics, Clostridium difficile, epidemiology, no-socomial infection, toxins.


17

dehydrogenase (GDH) can be revealed in stool by immuno-enzymatic assay correlated with the out-come of cultivation, or latex agglutination test with antiGDH antibody.

Due to the increasing worldwide incidence of infections with C. difficile on one hand and to the discovery of new ways of transmitting the infection according with some studies regarding the genetic diversity of bacterium strains on the other hand, a new approach is necessary for C. difficile related topics.

ClinicalClostridium difficile (C. difficile) is a Gram-

positive, spore forming bacteria, spread by the fecal-oral route. It is non-invasive, produces toxins A and B, which cause disease, ranging from asymptomatic carriage, to mild diarrhea, to colitis, or pseudomembranous colitis. Clostridium difficile infection (CDI) is defined as the acute onset of diarrhea with toxigenic C. difficile or its toxin and no other cause for diarrhea.

Since 2000 the rate of CDI has been increasing,

especially in the elderly with a recent hospitalization or residing in long-term care facility (LTCF). Carriage of C. difficile occurs in 5– 15% of healthy adults, up to 57 % in residents in LTCF and can reach 84.4 % in newborns and healthy infants.

In simple diarrhea cases, the classic symptoms may not occur and the endoscopic examination shows normal or ulcerated mucous; in 25% of cases ending the antibiotic therapy was followed by clini-cal recovery in 2-3 days. Further on antibiotheraphy is a prolonging factor of diarrhea relapse.

Pseudomembranous colitis represent up to 9% of CDI and starts with abundant watery diarrhea, over 7 stools a day, with heterogenic no bleeding aspect. They are accompanied by fever in 75% of cases and abdominal pains in 70% cases. The symptoms are non-specific, leukocytolysis up to ex 80.000 PMN/I¼l, extracellular dehydrating caused by exudative enteropathy. Digestive endoscopy confirms the diagnosis, allowing canker yellowish sores visualization, named pseudomembrane, on mucous colon membrane. In the first stage they are isolated, afterwards they come together. In CDI forms with severe onset and no obvious etiology

Fig.1. Pathogenesis of Clostridium difficile - Associated Disease (http://bioweb.uwlax.edu/bio203/s2009/kumm_jakl/pathology.htm)


18

of diarrhea an endoscopy is recommended, but this test is difficult to perform on aged and fragile patients. Complications such as septic shock and toxic megacolon may occur, septic shock and toxic megacolon occur and provoke the colon perforation (colectomy required) and even death.

The ratio of severe forms differs (7-18%), depending on the studies we consider. Consecutive mortality with C. difficile varies 0,6-3% and when complications occur is 35-50%. Some studies show

increased mortality in North America, a double no. of cases in EU, heading to 24/milion, C. difficile being involved in death cases three times more frequent than Staphilococcus aureus MRSA.

In 20% of cases, relapses appear in the first two months after the initial episode. In over 50% of cases they are connected with the persistence of pathogen strain (spores) inside digestive tract; a new stain could appear and provoke reinfection especially during hospital admission. Multiple

Three sample algorithms:

A)

B)

C)

GDH assay

GD-Toxin A/B combination lateral flow assay

NAAT as stand alone test (To date PCR is most sensitive and specific)

positive

toxin a/B assay or Cytotoxin neutralization

positive = positive for toxigenic C. difficile

negative naat assay or toxigenic Culture

both tests positive = positive for toxigenic C. difficile

both tests negative = negative for toxigenic C. difficile

one test + and one test –

naat ortoxigenic Culture




negative = negative for toxigenic C. difficile




Fig.2. Diagnostic algorithm of Clostridium difficile (Surawicz et al., 2013)


19

strains have been identified during one episode of infection. Approximately 3% of adults are asymp-tomatic carriers and often with toxin-free strains and sometimes specific toxins may be identified in some asymptomatic patients stool. The asympto-matic transmission of toxinogen strains in neonates is 5-70%, but there is no explanation what so ever.

Although nosocomial infections are the most frequent, some of them could be communal. There are recorded 17,5% postantibiotics diarrhea in EU, from which 66% have one day manifestation. After two weeks antibiotherapy, the frequency becomes 3,8%, from which 70% are toxic. In North America were identified a lot of cases but no strain high pathogen 027 had been isolated in communal infectious. Differential diagnosis will be made with other infectious diarrhea: bacterial, viral, fungus and parasitic or non-infectious causes; for example, the outcome of some ”cool” drugs is in reality

laxative ones (supplements for straitening the immunity, sugar free sweets, food with magnesium and decaf products) with no connection with CDI etiology. [Duker Freuman T., 2014]

Microbiological diagnosticCDI diagnostic is based on revealing the

toxins in stool or isolating a toxinogenic strain of Cl.difficile, this being the only pathogenic strain.

Diagnostic testing for C. difficile has rapidly evolved in the past decade. Previously, toxin A + B EIAs were the most widely used diagnostic tests because of ease of use and objective interpretation. However, EIA tests have substantially reduced sen-sitivities compared with reference standards. More-over, toxin A immunoassays (without toxin B) lack detecting the small number of pathogenic strains that only produce toxin B. Two major advances in the laboratory diagnosis are the use of GDH detec-

Fig.3. Analysis of anaerobic bacterial isolates in the microbiology laboratory of CCSMM


20

tion in stools as a means of screening for CDI and the development of Nucleic acid amplification tests (NAATs) such as PCR to detect toxigenic strains of C. difficile. Glutamate dehydrogenase (GDH) screening tests for C.difficile can be used in two- or three-step algorithms with subsequent toxin A + B EIA testing, but the sensitivity of such strategies is lower than NAATs [Surawicz et al., 2013].( fig 2)

Testing the toxigenic C. difficile should be limited to patients with > 3 nonformed stool specimens per 24 hr period, unless ileus (obstruction) is suspected. Repeat testing following a positive test (test of cure) is not recommended since patients may carry toxigenic C. difficile for months after clinical cure. Repeated testing following a positive test is appropriate if the patient improves with therapy and relapses after the completion of a treatment regimen (clinical relapse). Testing a second specimen from a negative patient is more likely to be a false positive [American Society for Microbiology, 2010].

The optical microscopy swab is pathognomonic, revealing long gram-positive bacilli with a bulge at terminal ends, with long terminal and isolated spores, visible with Gray coloration. While the presence of C. difficile can be suspected, we cannot differentiate the pathogencal strains from the non-pathogencal ones, therefore the examination should be supplemented with toxigenical and molecular biology tests. In the last years, a very pathogenical and virulent strain, C. difficile 027, has been identified, that causes severe epidemic episodes. (Fig 3)

The epidemic strain currently described in North America and EU, has the following features: PCR ribotype 027 in accordance with Anaerobe Reference Laboratory surveillance data [ECDC, 2006], pulsotype NAP 1 on pulsed-field electrophoresis, enzymatic restriction-profile BI, toxinotype III by Rupnik toxinotyping method, positive for binary toxin actinia-specific ADP-ribozyltransferase, deletion of 18 bp in tcdC gene controlling the expression of toxins A and B, hyperproduction of toxins A and B (Ax16 and Bx23) in comparison with strains of other genotypes, resistant to macrolides (erythromycin) and la flororquinolones (moxifloxacin, gatifloxacin and levofloxacin). Only specialised laboratories

are able to perform the techniques for identifying these features and a two weeks period is required for confirmation [INVS, 2006].

In practice, CDI diagnostic is based on toxin B detection in stool or revealing the toxigen strain. A- and B+ strains cannot be detected by current imunoenzymatic assays which detect only A stain. The strain isolation through culture is a necessary stage for epidemic clone 027 characterisation; PCR profile identification provides the certainty diagnosis. This clone presence is clinically suspected if a severe form of the disease is diagnosed, epidemiologically suspected if several cases occur, or microbiologically suspected if the isolated strain is resistant to new fluoroquinolones (moxifloxacin CMI > 4 mg/l) or to erythromycin (CMI > 256 mg/l). These characteristics are not specific to clone 027, but justify the stool culture in anaerobiosis in order to isolate the responsible stain and to send it to a specialised reference laboratory for further examination.

The genes encoding TcdA and TcdB, tcdA and tcdB, respectively, have been sequenced and are found in single open reading frames located within a 19.6-kb pathogenicity locus (8, 38). As expected, both open reading frames are large, with tcdA found within an 8,133-nucleotide region and tcdB is 7,098 nucleotides in length. (fig.4)

Both tcdA and tcdB are low-G C (28%) genes, which are comparable to the G C content (29%) of the C. difficile genome, and the toxins exhibit a high degree of overall similarity (66%). Given the proximal locations of tcdA and tcdB and the high sequence and functional homology between the two proteins, it has been proposed that the two genes may have arisen as the result of a gene duplication event. Further-more, the similarity in the biochemical activity of TcdA and TcdB, wherein both toxins use a highly conserved N-terminal domain to modify identical substrates, supports the notion of gene duplication. The major regions of homology between TcdA and TcdB fall within the enzymatic and receptor-binding domains of the two toxins. The N-terminal domains of TcdA and TcdB show 74% homology, and this homology pro-vides a basis for the similar substrate specificity of these two toxins.

The C terminus of TcdA and TcdB show a num-ber of short, homologous regions termed combined


21

repetitive oligopeptides (CROPs). TcdA encodes five groups of CROPs, which range in size from 21 to 50 residues and can be repeated throughout the C terminus of the protein. TcdB also encodes five groups of CROPs, four of which show homology to the CROPs of TcdA. Yet the CROPs found in TcdB are more divergent and less frequent than those found in TcdA. CROPs appear to play a putative role in initial target cell interaction and receptor binding, but the mechanism explaining the neces-sity for these repeats in cell binding remains unclear [Daniel E. Voth, 2005].

EpidemiologyC. difficile transmission is made by fecal-

oral route, by hands and contaminated objects or environment. The fast transmission in healthcare environments is a result of several factors: strain dissemination in CDI patients, half of samples from patients rooms being positive; high resistance of spores on inert supports for several months; too many patients crowded in common healthcare settings; numerous healthcare maneuvers creating a high possibility of contamination by the medical personnel hands; inadequate usage of antibiotics

19.6 kb

TcdEputative

holin function

TcdBcytotoxin

TcdDpositive

regulator

NH2 COOH

CROPS

Enzymatic Domain

Substrate Specificity

Putative Translocation Domain

W102 & DXD

Glucosyltransferase activity

Receptor-binding Domain

TcdCregulator

TcdAenterotoxin

tedD tedE tedCtedB tedA

Fig. 4. Genetic arrangement of the C. difficile pathogenicity locus and proposed protein domain structures of TcdA and TcdB. Both TcdA and TcdB are encoded on the 19.6-kb pathogenicity locus. In addition to the two toxin genes tcdA and tcdB, three additional regulatory open reading frames are located on this island. tcdD is a proposed positive regulator, tcdE is a putative holin protein, and tcdC is a proposed negative regulator of toxin gene expression. Through deletion mutagenesis, research combined from multiple research groups has revealed a three-domain structure of the large clostridial toxins. The glycosyltransferase activity is located at the N terminus of the protein, and the C terminus is involved in receptor binding. Located in the middle domain of the protein is a putative transmembrane segment that is thought to be involved in membrane translocation. [Daniel E. Voth, 2005]


22

which diminishes the resistance to colonization and facilitates C. difficile development.

The main individual risk factors are the ad-vanced age and antibiotherapy. There are several studies which correlate the consumption of some classes of antibiotics with CDI incidence: clindami-cyn, 3-rd generation cephalosporins, macrolides, and amoxicillin with clavulanic acid, 1-st genera-tion cephalosporins and fluoroquinolones. It seams that the role of fluoroquinolones in C. difficile 027 strains emergence and spreading is connected to the resistance level towards them [INVS, 2006].

All factors stimulating the digestive ecosystem alteration, like laxatives, antacids, antisecretors, transit retarders, baritosis transit, gastrointestinal surgery, etc. may facilitate this infection [Duker Freuman, 2014].

In March 2014, an epidemic episode with 31 cases of postantibiotic C. difficile infection was recorded in Ploiesti Emergency Hospital (Romania) and the patients were isolated and treated. Most of them were aged people from Neurology, Nephrology and Intensive Care Unit [Libertatea newspaper, 2014].

In May 2014 the Ministry of Health of Roma-nia gave the alert for C.difficile in Vaslui and Bucha-rest hospitals. The beginning of the year is worry-ing, in only 4 months, in Bucharest health facilities were registered 462 infected patients [Pro TV, 22 Mai 2014].

In accordance with Annual epidemiological report: Reporting on 2011 surveillance data and 2012 epidemic intelligence data, 2013, uttered by European Centre for Disease Prevention and Con-trol (ECDC), 48% cases of HAI (Healthcare-Asso-ciated Infections) associated with gastro-intestinal infections were connected with C.difficile, and from all HAI (15.000 cases) in 3 only 5,4% of cases the Clostridium difficile has been isolated. Taking into consideration that in Romania over 92.3% of patients were the beneficiary of an antimicrobial prophylaxis during more than a day surgeries, the HAI risk associated with C. difficile is very high [ECDC, 2013]

TreatmentThere is worldwide observed natural resistance

and/or acquired to the medicines of the quinolone group.

A mild CDI can usually be controlled by withdrawing treatment with the antibiotics caus-ing the infection (25% of patients could recover in 2-3 days). More severe cases can be treated using an oral specific treatment with metronidazole (1gr/day) or vancomycin (1-2gr/day) for 10 days. The metronizadole is a better choice, being a less expen-sive treatment with no risk of selecting glycopep-tides resisting germs like golden enterococcus and staphylococcus.

Failure to respond to metronidazole therapy within 5 – 7 days should prompt consideration of a change in therapy to vancomycin at standard dosing. For mild-to-moderate CDI in patients who are in-tolerant /allergic to metronidazole and for pregnant / breastfeeding women, vancomycin should be used at standard dosing. In patients in whom oral antibi-otics cannot reach a segment of the colon, such as with Hartman’s pouch, ileostomy, or colon diversion, vancomycin therapy delivered via enema should be added to treatments (500 mg in 100 – 500 ml of nor-mal saline every 6 h) until the patient improves.

However, relapse is common and requires fur-ther treatment with repeated series of metronida-zole or vancomycin, in high doses first and smaller doses associated with probiotics (i.e. Saccharomy-ces boulardii) after improvement. Severe cases may need intensive care for maintaining the vital func-tions and even surgical treatment for colectomy (in case of toxic megacolon or colon perforation). CT scanning is an important technique for perfo-ration diagnosis in comparison with colonoscopy technique which presents a perforation risk due to gas inflation. The antibiotic treatment for healthy individuals colonised with C.difficile is not recom-mended, being inefficient for eradicating for good this bacteria in digestive tract.

[Ordeanu, 2010; Ordeanu 2012]

Considering the antibiotherapy limitations, there has been designed the fecal bacteriother-aphy, known as “stool transplant”/fecal microbiota transplant (FMT) of bacterial flora acquired from the feces of a healthy donor to reverse the bacte-rial imbalance responsible for the recurring nature of the infection, with good results [ASGE, 2013]. This “synthetic stool” is a super-biotic obtained us-ing several cultures of saprophyte intestinal culture [Allen-Vercoe, 2013]. Studies show that patients with recurrent CDI (RCDI) have abnormally pro-


23

portioned colon microbiota, and that reintroduc-tion of normal bacteria via donor feces corrects this imbalance, restoring phylogenetic richness and colonization resistance.

There is no international consensus for defining and surveillance CDI, but we have to consider local (regional and national) epidemiology conditions and possibilities. ECDC created a working group for early detection and monitoring the CDI. They have suggested recorded signals criteria for severe and grouping cases of CDI.

C. difficile infectious can usually be prevented by practicing good hygiene in healthcare envi-ronments, such as: individual bed space, washing hands regularly (mechanical action of washing af-ter gloves removal), using gloves, protection mask, glasses and gown in bed space area and in contact with patients, using medical supplies for one usage only, cleaning surfaces using bleach wipes of sodi-

um hypochlorite containing 0,5 % active chlorine, and patient removal limitation. [CCLIN, 2013]

CommentDue to the increasing worldwide incidence of

infections with C. difficile on one hand, and to the discovery of new ways of transmitting the infection according with some studies regarding the genetic di-versity of C. difficile strains on the other hand, (http://www.pharmacypracticenews.com) a new approach is necessary for C. difficile related topics

It is important to adopted NAAT testing alone or a 2 or 3 step algorithm for CDI diagnosis.

If the C. difficile is confirmed and classified as a severe form or in an epidemic context it should be reported to Public Health Territorial Authorities and to The Anaerobe Reference Laboratory from INCD-MI Cantacuzino, for a clear diagnosis and adequate measures.

ConclusionDue to the increasing worldwide incidence of infections with C. difficile on one hand and to the

discovery of new ways of transmitting the infection according with some studies regarding the genetic diversity of bacterium strains on the other hand, a new approach is necessary for C. difficile related topics.

Bibliography1. Allen-Vercoe E. “Syntetic stool can

cure clostridium difficile infection” University of Guelph, Science Daily, 2013

2. Coignard B., Barbut F. “Conduite a tenir: diagnostic, investigation, surveillance, et principes de prevention et de maitrise des infections a Clostridium difficile” INVS, RAISIN, France, 2006

3. Duker Freuman T. “Surprise! It’s a laxative” blog www.tamaraduker.com, 2014

4. Hemker Oliva, Hourigan Suchitra “Fecal Microbiota Transplantation” www.news-medical. net/health , 2014

5. Ordeanu V. et all. “Elements of pharmaceutical microbiology” 2nd edition, Universitary Publishing House “Carol Davila” Bucharest, 2010

6. Ordeanu V. “ Antibiotheraphy individualisation” UMF conference, 2012

7. Ordeanu V. et all. “Clostridium difficile a threat emerging in zooantroponotic pathology”, Book of abstracts, Scientific Conferences, 2nd Edition 2014, Timisoara, pg. 112-113”

8. Stoica O. “31 cases of postantibiotic C. difficile infection recorded in Ploiesti” Libertatea newspaper, 7 March 2014

9. Surawicz Christina M., Brandt Lawrence J., Binion David G., Ananthakrishnan Ashwin N., Curry Scott R., Gilligan Peter H., McFarland Lynne V., Mellow Mark, and Zuckerbraun Brian S. “Guidelines for Diagnosis, Treatment, and Prevention of Clostridium diffi cile Infections”, The American Journal of GASTROENTEROLOGY, Guidelines for CDI, 2013

10. Voth Daniel E. and Ballard Jimmy D. “Clostridium difficile Toxins: Mechanism of Action and Role in Disease”, Clin. Microbiol. Rev. 2005, 18(2):247.

11. http://www.pharmacypracticenews.com/ViewArticle.aspx?d=Clinical&did=50&i=Januar y+2014&i id=1029&a id=24792

12. *** American Society for Microbiology “A Practical Guidance Document for the Laboratory Detection of Toxigenic Clostridium difficile”, September 21, 2010

13. *** CDC “Clostridium difficile - information for healthcare providers”, Atlanta, USA, 2005

14. *** CCLIN “Conduite a tenir devant un ou plusieurs cas de diarhee a Clostridium difficile” France, 2013

15. *** ECDC “027 Clostridium difficile - An emerging epidemic in European Health Care”, Stockholm, Sweden, 2006

16. *** ECDC ’’Annual epidemiological report: Reporting on 2011 surveillance data and 2012 epidemic intelligence data”, 2013

17. *** Pro TV, 22 May 2014


24

News and Perspectives on Treatment of Normal

Pressure Internal Hydrocephalus

Introduction

We would like to present the experi-ence of our clinic over the last five years regarding the treatment of normal pressure internal hydro-

cephalus (28 patients operated between January 2009 and December 2013), to report our results and compare them with the statistics and results from the international literature. Normal pressure inter-nal hydrocephalus (NPIH) represents an increase of CSF volume, with different etiology, that causes an enlargement of the ventricular system as a conse-quence of the hydrodynamic CSF circulation disor-ders. The cause of this disease cannot be identified in 60% of cases. It was described in 1965 with the Hakim & Adams triad: gait disorders and impaired balance, cognitive disorders (progressive dementia), sphincter disorders (8). The imagistic explorations (CT scan) indicate the size of hydrocephalus; ICP < 15 mmHg and the pressure gradient between the

ventricles and subarachnoid space is very low. For treatment there are extrathecal shunts (particularly ventriculoperitoneal shunt) and intrathecal shunts (particularly endoscopic ventriculocisternostomy). Both methods have been practiced successfully in our clinic.

The ideal treatment method for hydrocephalus still does not exist. None of the surgical techniques is perfect and no shunting device gave total satisfac-tion (4, 7).

Hydrocephalus represents the enlargement of one or more parts of the CSF containing anatomic structures. The CSF total volume is about 150 ml in adult; the ventricular system contains 25-30 ml, the spinal subarachnoid space contains 30 ml and the rest of CSF is contained by the cranial subarachnoid space and basal cisterns (1). The total production of CSF is about 600 – 700 ml/24 hours, approximately 0,35 ml/min. The CSF participates in maintaining the endocranial volume constant by adjusting the production/absorption ratio depending on the cere-

Cristian Năstase MD, PhD; Marian Mitrică MD, PhD; Cristian Popescu MD; Department of Neurosurgery, “Dr. Carol Davila” Emergency Universitary Central Military Hospital,

Bucharest, Romania

AbstractMany patients, usually over 60 years old, presenting prese-nile dementia associated with marked gait disorders, impai-red balance, urinary incontinence, have been shown to have enlarged ventricles associated with relatively small cortical atrophy. Intracranial pressure monitoring indicates normal values, or subject to only minor peaks, usually at night. Beca-use some of these patients improve markedly after ventricular

shunting procedures it has been suggested that their neuro-logical dysfunction may be caused by a pressure effect on the brain from the increased internal surface of the ventricles. Many of these patients do benefit from surgery, and a lot of them have a history of subarachnoid haemorrhage, traumatic brain injury or meningitis which might have impaired the CSF absorption.


25

bral parenchyma volume and the intracranial blood volume variations according to the Monro-Kellie relationship. Changing the volume of one of the three intracranial components (brain tissue, blood, CSF) is followed by a compensatory reaction from the other two components in order to maintain in-side an inextensible space the endocranial volume constant (9).

Based on its underlying mechanisms, hydro-cephalus can be classified into obstructive and com-municating. The obstructive hydrocephalus is de-fined by any condition that restricts the CSF flow to and from the ventricular system. Any CSF flow interruption outside the ventricular system defines the communicating hydrocephalus (5).

The NPIH etiology is not fully known. There are many possible congenital or acquired causes, but the most important are the subarachnoid hemor-rhages (20%), meningitis (1%), parasite infections, traumatic brain injuries, neurosurgical procedures with open ventricular system, intoxications, Alzhei-mer disease (15%).

Hydrocephalus of the adult patients is a com-municating, chronic and normal pressure hydro-cephalus (3).

DiagnosticThe CT scan and the MRI revolutionized the

diagnosis and the postoperative follow-up of the hydrocephalus. The CT scan is the first stage of di-agnosis. It highlights an obstructive cause, evaluates the ventricular enlargement, appreciates the cerebral parenchyma condition (periventricular hypodensity) and the subarachnoid spaces condition (basal cis-terns, sylvian fissures, interhaemispheric fissure, cor-tical sulci) Bifrontal index measuring (the distance between frontal horns / intracranial distance ratio, on the same CT slice) > 50% is suggestive for a possible decompensation of hydrocephalus. The Evans index > 30% has the same meaning (the frontal horns size / the maximum biparietal diameter ratio). It suggests an active hydrocephalus. The MRI completes the CT scan by describing the obstructive lesions accurately and obtaining dynamic information over the CSF flow (the absence of CSF flow through Sylvius aque-duct). The preventing treatment is important because of the existing risk of postoperative hydrocephalus af-ter any neurosurgical procedure. Cisternograms with radioactive markers (99Tc-DTPA) remain contro-versial and rarely used. The radionuclide is injected into the subarachnoid space by a lumbar puncture

Fig.1. The ventricular enlargement shown on CT scan


26

and serial images are taken by planar scintigraphy 3, 6 and 24 hours after the injection. In case of NPIH intraventricular radioactivity can be obtained even 48 hours after the injection. Serial lumbar punctures with repeated evacuation of 15 – 30 ml CSF associ-ated with clinical improvement can predict a favora-ble response to shunting procedures. Patients with initial measured CSF pressure >15 mmHg responded favorably after ventriculoperitoneal shunting (6, 8, 9).

TreatmentThe treatment of hydrocephalus depends on

the moment of diagnosis, etiology, age and clini-cal condition of the patient (particularly the acute form) and the complementary investigations results. The treatment with acetazolamide, a carbonic anhy-drase inhibitor has favorable effects predominantly by inhibiting the chorioid plexus secretion and less by the diuretic effect. The acetazolamide dose is 25 mg/kg/day with simultaneously administration of furosemide 1 mg/kg/day.

The treatment of obstructive hydrocephalus is removing the obstacle (excision of tumors). The sur-gical treatment seeks not returning to normal size of ventricles but regaining most of the lost neurological functions. The diuretic and corticosteroid therapies

complete the CSF evacuation by lumbar punctions. The CSF lumbar drainage will be performed only after the confirmation of communicating chronic hydrocephalus by imagistic methods.

There are several types of extrathecal deriva-tions of CSF: controlled external ventricular drain-age, ventriculoperitoneal drainage, ventriculoatrial drainage, ventriculopleural drainage. The currently used valves are predetermined opening pressure valves (low, medium and high pressure), modular opening valves and programmable valves with vari-able resistances, self-regulating valves etc.

The intrathecal derivation (particularly the endoscopic ventricular cysternostomy) represents an alternative treatment method. Both extra- and intrathecal derivations have been successfully per-formed in our clinic.

The intrathecal CSF derivations consist of en-doscopic ventriculostomy through the 3rd ventricle floor aiming to restore the communication between intraventricular and subarachnoid liquidian com-partments.

Material and MethodsWe retrospectively studied 28 patients admit-

ted to our clinic between January 2009 and De-

Fig.2. Lateral ventricles puncture


27

cember 2013. The patients were all neurological and imagistic diagnosed with normal pressure in-ternal hydrocephalus. Only in 18 cases, a cause for impaired CSF absorption and ventricular enlarge-ment could be detected. 8 patients had a history of traumatic brain injury, 4 patients had a history of subarachnoid hemorrhage (First and second grade on Hunt and Hess scale) with normal “4 vessels” cerebral angiogram, 2 patients were diag-nosed with Alzheimer disease prior to admission and 4 patients had a history of ischemic stroke. 3 of the patients with NPIH after subarachnoid hemorrhage underwent endoscopic procedures with intrathecal derivations (ventriculocisternos-tomy). On the other 15 patients were performed ventriculoperitoneal shunts using various valves (most of them were low pressure valves). The most frequently used were the Delta (Medtronic), Spitz - Holter, Heyer - Schulte, Pudenz, Cordis - Hakim valves. In 10 cases, a cause for NPIH was not re-vealed and these patients were diagnosed with idiopathic NPIH. They have also been performed ventriculoperitoneal shunts with low pressure valves. Clinical improvement was significant in

most patients, but only partial in the patients diag-nosed with Alzheimer disease.

According to statistics from literature, urinary incontinence is the main symptom that resolves after shunting procedures. Gait disorders and impaired balance are subsequently remitted and dementia is the last that improves (3, 4, 8). Black and collabo-rators established few criteria that can predict the favorable clinical course after shunting procedures:

- clinical: the presence of symptomatic triad; approximately 77% of the patients presenting gait disorders as primary symptom improve their lo-comotor function after shunting; the patients with dementia without gait disorders rarely improve after drainage;

- patients with CSF pressure >18 mmHg on lumbar puncture or continuous monitoring im-prove their neurological status after ventriculoperi-toneal drainage;

- patients with CT or MRI showing large ventricles with minimal cortical atrophy have fa-vorable evolution after shunting procedures.

The response to drainage is especially good as the symptoms started recently (1, 5).

Illustrative Cases

Case 1. 66 year old male patient complaining of gait disorders, impaired balance, cognitive impair-ment (occasionally) and sphincter disturbances (imperious need to urinate) which started about a year ago, slowly progressive despite of conserva-

tive treatment. We decided to install ventriculperi-toneal drainage with self-regulating valve. Postop-erative evolution was favorable, symptoms thereby improving considerably about 3 months after the procedure.

Fig.3. The ventricular catheter placed inside the right lateral ventricle and the self-regulating valve placed in the right parietal region, under the scalp.


28

Case 2. 59 year old male patient complaining of headache, nocturnal insomnia, depressive syndrome, cognitive impairment, gait disorders and locomotor’s instability.

Case 3. 68 year old female patient hospitalized for memory disorders, sphincter disturbances (imperious need to urinate), gait disorders, vertigo, occasional headaches and depressive syndrome. The CT scan reveals enlarged ventricular system. It was decided to install VP drainage with Delta low pressure valve. The symp-toms improved partially after one month with significant improvement 6 months after the procedure.

Fig.4. The ventricular catheter placed inside the frontal horn of the right lateral ventricle, near septum pellucid; VP drainage with Delta (Medtronic) low pressure valve.

Fig.5. The ventricular catheter placed inside right lateral ventricle (functional drainage).


29

Case 4. 64 year old male patient facing important balance disorders, persistent vertigo, extremely difficult gait, urinary incontinence (and incipient stercoral), onset of Alzheimer disease (after neurological and psy-chiatric examinations). It was inserted a Delta low pressure valve. The symptoms improved partially after 3-4 months; the gait has become easier, sphincter disturbances have improved and the cognitive impairment still exist, but more tolerable.

Case 5. 72 year old female patient hospitalized for walking difficulties, balance disorders, persistent ver-tigo and vomiting, dehydration. A central venous catheter was inserted into the right subclavian vein and VP drainage with a Delta low-pressure valve was inserted on the left side; intraoperative CSF pressure was 15 mmHg.

Case 6. 66 year old male patient with memory disorders, impaired balance and gait disorders, cognitive impairment, urinary incontinence (occasionally), started over a year ago, with progressive evolution. Intra-operative measured ICP was 18 mmHg. Ventriculoperitoneal drainage with Holter low pressure valve was installed. The symptoms improved after one month with the complete remission of gait disorders, impaired balance and sphincter disturbances.

Fig.6. Preoperative MRI (T2 sequence) and postoperative CT scan; right ventricular catheter; prominent convexity sulci; incipient cortical atrophy.


30

Fig.7. Preoperative and postoperative CT images; the catheter has been placed inside the left lateral ventricle because a central venous catheter was inserted into the right subclavian vein (functional drainage).

ConclusionsThe ventricular enlargement and the pressure

on the frontal lobes are probably responsible for the occurrence of cognitive disorders and dementia. The pressure on the regulator centers of the sphinc-ter functions located in the paracentral lobule may be responsible for the urinary incontinence. The ventricular dilatation may compress the internal capsule and secondary the pyramidal tract, respon-sible for the gait disorders, impaired balance and py-ramidal syndrome (4, 5, and 9).

To determine the surgical indication and to an-ticipate the subsequent postoperative evolution, sev-eral clinical and imaging criteria must be established:• the obstructive causes for hydrocephalus must be exclud-

ed; it must be a communicating form;• a periventricular hypodensity on CT scan or hyperinten-

sity on T2 sequence (MRI) might be transependimar CSF resorption and might anticipate a favorable evolution after the shunt procedure;

• the rounding and symmetrical ballooning of the frontal horns;

• dilated focal of convexity sulci may be revealed by imag-ing studies and they are atypical CSF reservoirs which subsequently decrease after drainage and they should not be confused with cortical atrophy; typical cortical atrophy (ex vacuo hydrocephalus) occurs frequently with Alzhei-mer disease, and there is a limited response to ventricu-loperitoneal drainage (11).

Maintaining good results depends on periodic medical checks, immediate recognition and treat-ment of complications (insufficient drainage should be suspected first). There is no ideal method for the treatment of hydrocephalus. None of the surgical techniques is perfect and no device gave total satisfac-tion. The accelerated development of technology and the practical experience in CSF intra- and extrathecal drainage allow overcoming the current difficulties. The world population undergoes a pronounced aging process, the number of people aged over 60, increas-ing to 400 million over the last 40 years. The ratio of the eldely population has been modified, representing over 50% in developed countries, with the European zone being the aged (10).


31

Fig.8. Important hydrocephalus with cortical sulcus persistent; catheter placed inside the left lateral ventricle (coronal section).

Bibliography1. Black P., Kaye A. - Operative Ne-

urosurgery. Churchill Livingstone. 2000, pp. 1235-1247.

2. Connelly S., Mc Khann G., Huang J., Chondhry T. – Fundamentals of Operative Techniques in Neurosur-gery. Thieme 2001, pp. 345 - 355

3. Constantinovici A., Ciurea A.V. – Practical Guide of Neurosurgery, Medical Publishing House 1998, pp. 353-414

4. Jennett B., Lindsay K. – Neurosur-gery; Fifth Edition; Springer-Verlag 1996 ; pp.283-289;

5. Greenberg M. – Handbook of Ne-urosurgery, fifth edition, Thieme 2001, pp. 191-195;

6. Gorgan R. M. – Handbook of Sur-gery ( Prof. Irinel Popescu), II, Ro-manian Academy Publishing Hou-se, 2007, pp. 114 – 120;

7. Kempe G. L. - Operative Neuro-surgery, Springer – Verlag 1968, pp. 203-214;

8. Karaguiosov L. - Operative Neu-rosurgery, Medicina I Fizkultura, Sofia 1982, pp. 159-166;

9. Wilkins R.H. – Principles of Neuro-

surgery, McGraw Hill inc.1985.pp. 2341 – 2356.

10. Yasargil M.G. – Microsurgery vol. II, Clinical Considerations Surgery of Intracranial Aneurysms and Re-sults. New York. Georg Thieme Ver-lag 1984, pp. 232-295

11. Youmans J.R. - Neurological Sur-gery, Fourth Edition, W. B. Saunders Company, 2000.


32

New decontaminants based on quaternary

ammonium saltsDiana M. Popescu, Viorel Ordeanu, Lucia E. Ionescu, Gabriela V. Dumitrescu,

Simona N. Bicheru, Marius NecşulescuMilitary Medical Research Center (CCSMM), Bucharest

POPESCU DianaMobile: + 40726.747.338

E-mail: [email protected]

AbstractDecontamination after terrorist attacks or industrial accidents with biological and/or chemical agents („bio-chem“) must be fast and efficient, in order to reduce the number of victims and to eliminate the consequent damages. The decontamination of living biological agents (bacteria, viruses) or nonliving ones (to-xins, regulators) and toxic chemicals could be accomplished by reactions of hydrolysis in various experimental conditions, in particular in alkaline medium, reactions with amines or ammo-nia, alcohols, phenols etc. and by their transformation into less toxic degradation products.

“Bio-chem” intentional or unintentional contamination is a

real risk, towards which an effective management must be available to prevent and control it. Decontamination is an essential measure to protect the personnel and the environ-ment. Synthesis and testing of new „bio-chem“ decontami-nants, based on quaternary ammonium salts, complete the arsenal of protection against chemical and biological agents. The most effective selected substances could be produced and used for decontamination in accordance with legal pro-cedures.

Keywords: „bio-chem“ contamination, decontaminants, disin-fectant, quaternary ammonium salts, chemical synthesis.

Decontamination. After terrorist attacks, bi-ological and/or chemical attacks or industrial haz-ards with bio-chem agents, the decontamination must be prompt and efficient, in order to reduce the number of victims and to eliminate the conse-quent damages. The decontamination of the living biological agents (bacteria, viruses, fungus, and parasites) or of the nonliving agents (toxins, regu-lators) and of the toxic chemicals could be accom-plished by hydrolytic reactions in various experi-mental conditions (especially in alkaline medium), reactions with amines or ammonia, with alcohols and phenols etc. or by their transformation in less toxic degradation products.

The biological contamination refers to bac-teria and viruses generating diseases as anthrax, plague, smallpox, botulism etc. From the chemical structure point of view, the range of the products used in microbial decontamination is wide but

very few fulfill the conditions of a good decontam-inant. In this paper there are taken into account the quaternary ammonia salts obtained by treating the tertiary amines with alkyl halogen, particularly alkyl chlorides or benzyl chlorides. These com-pounds are the most important agents having a biocide action.

Synthesis and conditioning decontaminant by Mechanical Engineering and Research Institute, Bucharest (ICTCM) in different forms with the chemical structure of quaternary ammonium salt soluble in water was carried out in accordance with national and European Union legislation related to ecology and environmental protection.

Spectrum of activity and penetrating ability of decontaminating substance is enhanced by a sur-factant that is designed to reduce surface tension thus facilitating contact between the microbian cell and decontaminant compound.

Decontaminant qualities of each product are


33

determined by the choice of the active substance and should take account of its antimicrobial quali-ties, the purpose, and the conditions that will be used in.

Decontamination efficiency is determined by the contact time of each decontaminant prod-uct, decontaminating solution concentration, the amount of solution used per unit area and, not the last, by the decontaminant agent application mode.

Screening test. Screening of potential decon-taminating substances was performed in the Labo-ratory of Microbiology-Epidemiology, in diagnosis laboratory for biological agents, ranked by P2+ biosafety level for the pathogen microorganisms. Bacterial sensitivity assays were performed (the antibiotic disc diffusion method on several lots), according to the following parameters: cultiva-tion on solid culture medium Mueller-Hinton, 72 hours aerobic incubation at 37°C, with daily read-

ing. The following bacterial species were tested: Staphylococcus aureas, Bacillus anthracis, Escheri-chia coli, Pseudomonas aeruginosa, Vibrio cholerae. Results were quantified by measuring with 0.1mm of accuracy (caliper and magnifier), comparatively, on many tests, to calculate the average of each sub-stance on each species.

Product code DC-3 and code DC-7 was car-ried out on quaternary ammonium salts and N- alkylpyridinium basis. Their testing revealed that the best microbiological activity was recorded in the product code DC-7. The possible synergistic effect with oxidizing compounds was tested in or-der to achieve possible decontaminating mixtures.

The bactericidal effect of the substance was tracked for a set of standard bacterial (gram-positive and gram-negative, anaerobic bacterial and spores) and other pathogenic microorganisms; bacterial sensitivity results were read after 24 and 48 hours of

Figure 1. Microbiological testing of decontaminating substances, in vitro, in CCSMM

microbiology laboratory


34

incubation and then, after storage at room tempera-ture 48 hours, to watch the effect in time.

The antimicrobial effect was quantified by cal-culating the average diameter of bacterial inhibi-tion zone and bactericidal concentration (g/liter), calculated as the quantity of substance (20 mg) divided by the volume in which the antimicrobial diffusion was effective. (figure 1, 2)

Toxicological testing. Toxicological screen-ing for acute toxicity aimed to confirm that these substances are not highly toxic and are not dan-gerous to operators. To demonstrate, 0.5 ml of each substance was injected in mice (approx. 20g weight, young adult), tracking morbidity and mor-tality for three days. The test results have enabled experiment achievements under conditions of a specially arranged experimental minipolygon.

Experiencing decontaminating products. Representative microbial strains were used for the main groups of pathogenic bacteria: gram-posi-tive cocci: Staphylococcus aureus, Streptococcus

pneumoniae, Enterococcus fecalis; gram-positive bacilli: Bacillus anthracis (vaccine strain), Bacil-lus cereus, Bacillus subtilis; gram-negative bacilli: Escherichia coli, Proteus vulgaris, Klebsiella pneu-moniae, Pseudomonas aeruginosa; vibrio: Vibrio cholerae.

The experimental contamination and decon-tamination have been carried out on an out of service military vehicle, representing the “target” (figure 3, 4) marked with numbered areas of ap-proximately 0.1 square meters on which have been implemented operating procedures for CBRN (chemical, biological, radiological and nuclear) contamination control.

Areas were chosen as follows: vertical painted metal sheet, for aqueous solution decontaminants; glass window for aqueous solution decontami-nants; rubber tires for aqueous solution decontam-inants and horizontal painted metal sheet for sup-plied powder decontaminants as a positive control.

Microbial contamination was done by spray-ing the allocated surface, separately, with every mi-

Figure 2. Microbiological testing of decontaminating substances in various materials, CCSMM minipolygon biological testing


35

crobial strain and with a mixture of them also. A microbial suspension culture in a liquid medium was used, with approximately 1 million live bacte-ria per ml. Also, it was sprayed 1 ml of suspension per square decimeter, enough to create a uniform contaminant film. For liquid decontaminating substances, the aqueous solution (conc.10%) was sprayed to cover the contaminated area until the excess liquid begun to tear, about, 10ml/sqdm on smooth surfaces (glass, metal sheets) and about 20ml/sqdm on rough surfaces (peeling metal sheet, tires).

Microbiological samples were collected by means of hygienic-sanitary pad, as follows:

0. before contamination (to establish a base-line level of natural contamination);

1. immediately after contamination (to check the level of contamination experiment);

2. after decontamination for each decon-taminant upon each biological agent within 10 min

(as required for military using decontaminant);3. at every 45 min (as for general household

disinfectant).

In addition, at the end of the experiment, samples were collected from different parts of the operator’s protective equipment and from the envi-ronment to detect any residual contamination. All samples were immediately transported under bi-osafety conditions and tested in the microbiology P2+ laboratory. Decontamination achieved results after 45 min are shown in Table 1.

CommentsThe antimicrobial effect remains and is more

obvious after 45 min, suggesting that these prod-ucts can be proposed as potential disinfectants for medical or hygienic-sanitary use, according with Drug Law.

Figure 3. Decontaminating microbiological testing substances on target vehicles in CCSMM minipolygon biological testing


36

The decontamination with powder is less ef-fective in all cases, compared with the laboratory control sample, because of weak contact between micro-organism and decontaminant, so a residual contamination remains on surfaces.

In all cases, the final stage of decontamination should be washing with water because the sub-stances used can be corrosive upon certain materi-als or irritating for personnel. After the final wash-ing action, a microbiological analyze was made to determine residual contamination of surfaces, waste water or protection equipment, but a signifi-cant contamination was not recorded, so it can be concluded that there is no risk to the environment.

ConclusionsA number of potential decontaminating sub-

stances were synthesized and tested, eight of which were selected and recommended as decontaminat-ing agents because these can be characterized by

high chemical stability. These products are soluble in water and various organic solvents. These bioc-idal products have bactericidal and fungicidal ca-pabilities, with a large spectrum of usability. The substances are characterized by low toxicity on animals.

Theoretical and experimental scientific re-search has been made to design and implement polyvalent “bio-chem” decontaminants for de-struction of biological and toxic chemical agents, hazardous to health. Technologies have been de-veloped for obtaining polyvalent decontaminants, selected by efficiency assays, in laboratory. The ex-perimental polyvalent model for chemical and bi-ological decontamination with decontaminants of quaternary ammonium salts types was developed.

Among the tested products, the best antimi-crobial activity is achieved by products based on mixture of oxidizing compounds and quaternary ammonium salts, which also have a synergic effect when used, expanding the action spectrum.

Figure 4. Microbiological testing of decontaminating substances on combat vehicle with Biological Mobile Intervention Team of CCSMM in CBRN training area from Campulung,


37

Bibliography1. 1. ORDEANU V., LUTA N.,

VOICU V., TARALUNGA GH., MIRCIOIU CTIN., NEAMTU

2. CTIN., ANDRIES A., IRIMIA ADRIANA, Alkyl-Phosphates as New Substances for

3. Disinfection and Decontamination “Bio-Chem”, Chemistry Mag. Bu-charest, 59, no. 6, 2008.

4. 2. LUTA N., ORDEANU V., TA-RALUNGA GH., CHIRALEU E., POPESCU M., NEAMTU C.,

5. HANGANU M., Polyvalent decon-taminants for the terrorist attacks combat BIO-CHEM,

6. International Forum “The priorities of chemistry for a durable develop-ment”, 20-21 Oct. 2005,

7. ICECHIM Bucharest, Romania.8. 3. ORDEANU V., LUTA N.,

VOICU V., TARALUNGA GH., MIRCIOIU C., ANDRIES A.,

9. NEAMTU CTIN., IRIMIA ADRIA-

NA, New substances for disinfecti-on and decontamination

10. “bio-chem”, The XIII National Con-gress of Pharmacy, 28-30 Sept. 2006, Cluj-Napoca,

11. Romania.12. 4. STEPAN E., NEAMTU C.,

ENASCUTA C., ORDEANU V., NECSULESCU M., ANDRIES

13. A., IRIMIA ADRIANA, N,N,N’,N’-tetraacetyletylenedyamine (TAED) as an activator for

14. persodiums, in modern compositi-ons of detergents and disinfectants, Chemistry Mag.

15. (Bucharest) 59, No. 5, 2008, p.558.16. 5. STOICA L., IRIMIA ADRIA-

NA, OPROIU G.C., ORDEANU V., Kinetic modeling of As(V)

17. Separation by dissolved air flotati-on, Chemistry Mag. (Bucharest) 59, No. 4, 2008, p.379.

18. 6. CRACIUNOIU S., BARBU-

LESCU EMILIA, RADUCANU CARMEN, ORDEANU V.,

19. NECSULESCU M., Decontami-nants BIO-CHEM based on oxidi-zing compounds and quaternary

20. ammonium salts, Innovative Tech-nology Mag., No. 3, 2008.

21. 7. VOICU V., LUTA N., OR-DEANU V., ANDRIES A., Research for the development of

22. decontaminating products to com-bat the effects of terrorist, chemical and biological attacks,

23. Defense NBC Mag., No. 17, 2009, p. 31.

24. 8. JUNGERMAN E., Cationic Surfactants, Marcel Dekker Inc. New York 1970

25. 9. JACKSON J.B., Deconta-minating solution, Brevet SUA no.3.079.346, 1963

26. 10. *** Antiseptics and disinfec-tants, AFNOR, ed. 2, AFNOR 1989

Table 1. Contamination level after decontamination by 10% aqueous solution

No. Decontaminant Biologicalagent Surface Time

(min�)Growth(tube)

Growth(pane) Remarks

1 dC 17 iCtCM Mixture Glass 45 - ++hem� contaminated2 dC 17 iCtCM B�cereus Glass 45 - - uncontaminated

3 dC 17 iCtCM Mixture verticalmetal sheet 45 +dep� - contaminated

4 dC 17 iCtCM B�cereus verticalmetal sheet 45 +/- - uncontaminated

5 dC 18 iCtCM Mixture Glass 45 - - uncontaminated6 dC 18 iCtCM B�cereus Glass 45 +/- - uncontaminated

7 dC 18 iCtCM Mixture verticalmetal sheet 45 +dep� - contaminated

8 dC 18 iCtCM B�cereus verticalmetal sheet 45 +dep� - contaminated

9 dC 19 iCtCM Mixture Glass 45 - - uncontaminated10 dC 19 iCtCM B�cereus Glass 45 +/- - uncontaminated

11 dC 19 iCtCM Mixture verticalmetal sheet 45 +dep - contaminated

12 dC 19 iCtCM B�cereus verticalmetal sheet 45 +veil,

dep� + contaminated

- or +/-: no microbial growth; dep. : bacterial deposit at medium bottom; veil : bacterial population at medium top; hem. : hemolytic colonies.


38

The 18th edition of the Balkan Military Medical Committee Congress was the start point. I can say that it remains, so far, the most important scientific event I have par-

ticipated. I also had the opportunity to visit Istanbul, a city like a story that I truly recommend everyone to visit. Novelty began for me at the military airport Ba-neasa when, in a cold morning, I had the chance to see a C17 Spartan military transport aircraft for the first time. I was curious because that type of military aircraft had to take me to destination offering me a unique experience. First flight was quiet and we were

greeted in Istanbul by friendly hosts and a beautiful weather. Coach riding to the hotel in the bustling me-tropolis gave me a chance to admire the panorama for the first time especially because there was quite a dis-tance between the airport and our hotel, the complex where we were accommodated being in Asia. When I reached the destination I had the honor to admire one of the most beautiful hotels in Istanbul, a true pride of the Turkish army and also a proof of their elite role in society. Beyond the luxury and good taste I noticed again the perfect planning of every detail, starting with accommodation. The Congress began. In the first

Past and futureSecond Lieutenant Necșulescu Andrei, Medical student

I was thinking a lot about choosing this title which at first glance doesn’t seem not to be related to the main topic of this article. However, I think these two opposites have the ability to describe in the most subtle form my journey in Istanbul, the city on two continents. The streets covered with history invites you to discover them step by step and the congress showed me a picture of my future when I will have the opportunity to

present important projects in front of a selected audience.


39

evening I started meeting my colleagues from other countries during an elegant and discreet reception. That was the first time I changed impressions with my fellow military students from the other participating countries. We linked friendships that I’m sure will be long-lasting and we set up a future collaboration for the upcoming congresses, everything in a festive and friendly atmosphere. Beyond the congress I ventured for the first time into crowded Istanbul with my col-league Robert Popescu.

In the second day of the congress I went for the first time at the Military Museum from Istanbul where I attended the opening ceremony. After visiting the museum, my colleague and I were invited in the hall where the presentations were kept. In front of a huge picture of Mustafa Kemal Ataturk I attended military medical exposures from Serbia, Greece, Turkey, Bul-garia and Romania. I started to get ready for my first speech in front of an audience composed mostly of doctors.

Day three was the high-light of the congress for me. Al-though I knew Robert Popescu was going to present the pro-ject with doctors and univer-sity students, I was told that my poster will be exhibited in the museum lobby where I should provide clarifications for the numerous ques-tions that might be asked. I admit that things for me were much more effortless but I was kept up-to-date with the events of the congress thank to my colleague who was getting ready to present his project. I appre-ciated the presentations of my colleagues from other countries and together we agreed to collaborate in the future and gather together at these conferences with bigger projects that will integrate more teamwork. I left there convinced that at the next congress I will come with an oral presentation. I gathered the mini-mum necessary experience to deal with future con-gress work and I hope I managed to fit in that great atmosphere provided by the hosts. The presentation of my colleague was praised; his experience at previ-ous congresses he attended made a difference. I left there thinking that I fulfilled the task of coping with challenges and building the idea that I can come up with a lot more and improve myself.

Day four was great. It was time to visit the im-pressive Dolmabahce, a true monument and one of the most spectacular buildings in Istanbul. That day it

was warm, summer was definitely approaching. Many people were gathered in front of the palace, a sign of the importance of that particular place. Huge halls, sophisticated architecture, historical significance and opulence made me think about what many years ago was considered absolute luxury. I recommend visiting the palace along with other major sights of Istanbul. The evening was one of the most important moments of the congress due to the cruise on the Bosphorus. The boat that was waiting for us was state-of-the-art, impressive and equipped with a luxury dining room. As already expected, we were welcomed aboard with friendship. It was the last moment when I changed impressions about congress with my colleagues from other countries. There were five delegations in the debut of the party but at the end we were a single group with many things in common. That was the moment when we had the chance to know us bet-

ter than we did before. Seen from the Bosphorus, Istanbul was like a fairytale. I think one of the most spectacular city’s overall images can be seen at night. Picture of opulence was reflected in every detail when I saw the most famous clubs from the city during the cruise.

I went back to the hotel thinking that an experience like that was unique and I rarely had the opportunity to see so much luxury gathered in a single place. Last day brought me back at the military museum which hosted the closing ceremony. Beyond the speeches from heads of delegations I was very happy to see that the prize for the best project was awarded to Roma-nia. It was a pride for the whole delegation and we re-turned to the hotel very happy. Those were already the last hours in Turkey. We started preparing to go back home so we had lunch and then we started packing the luggage. At the airport our plane was waiting for us. After a turbulent flight we arrived back in Roma-nia on a cold and rainy weather, a lot different than the sun and the heat from Turkey.

The experience was unforgettable. I recommend everyone to take part in this kind of event even if they have to deal with oral presentations. I think that what matters the most is participation and the numerous things that you can learn. Since little, brick by brick, experience accumulates and allows overcoming new limits. I hope I gave a good read and I want to thank you for the time you have given me.

Beyond the speeches from heads of delegations I was very happy to see

that the prize for the best project was awarded to Romania. It was a pride

for the whole delegation and we returned to the hotel very happy.


40

Stress management for optimization of

Organizational activity

Stress: definition, types and causes of its occurrence

We meet every day people who are overworked, overwhelmed or underpaid. We wonder what to do to cope with the stress in our life. Often we forget to put on paper all the endless tasks we have to do during the day, and paradoxically we receive other new tasks to fulfill.

According to Peter Drucker, we have to make a clear distinction regarding those who are accom-plishing an intellectual work today, the situation being more complicated for them than for produc-tion line workers of the past, who knew what they have to do. Instead, those involved in intellectual work should not only execute the plan, but also to conceive it. This puts an important pressure on the human brain so in case you see a doctor, one of the question is: “How stressed are you?” Certainly, stress at work can affect anyone at any level. It is pro-duced in no matter what domain and in organiza-tions of any size. Stress affects the health and safety of individuals and also welfare of organizations and national economies.

Stress was introduced by Hans Hugo Bruno Selye, professor of histology, who sets up the foun-dation of International Institute of Stress with Alvin Tofler in 1977. He believes that stress is related to ad-aptation syndrome as a reaction of individual against environmental aggressions. Hans Selye defines stress as “the set of reactions of the body to the external action of the causative agents (physical, chemical, biological and psychological) consisting in morpho-functional changes, most often endocrine”.

According to the Romanian Language Explan-atory Dictionary (1998), stress is “the name given to any environmental factor (or set of factors) causing an abnormal reaction to human body; adverse effect on the human body produced by an environmental factor.”

According to Terry Looker, Olga Gregson (2009, p.31.), “Stress is seen as a reaction of the organism against changes occured in our environ-ment.” All mentioned authors consider that “stress can be defined as the condition that we feel when we perceive a discrepancy between perceived demands and ability to cope with them.”

Psychologist, Maj. Iuliana GUIŢĂ – ALEXANDRUMilitary Emergency Hospital “Dr. Ion Jianu “, Pitești, Romania

Researcher in the Research Center for the Promotion of Excellence in Training - University of Pitești

AbstractStress is a constant presence in our lives, whether we analyze it in professional, social or family terms. This daily reality cre-ates a state of tension, strain and discomfort, causing signifi-cant changes in physical and mental health. Stress at work can affect anyone, at any level, in any sector and in organizations of any size. Stress affects health and safety of individuals and

also organizations’ welfare and national economies. There is a definite correlation between the level of stress at work and the changes in organization’s productivity.

Keywords: stress management, organizational optimization, occupational stress, organizational culture, psychological contract.


41

Lazarus and Folkman (1984) define stress as “a cognitive and behavioral effort (with obvious emotional expression) to reduce, control or tolerate external or internal demands that exceed personal resources.”

Ioan Bratu Iamandescu (2002) believes that mental stress is a syndrome consisting of exac-erbation, beyond the level of simple homeostatic adjustments, certain psychic reactions and their somatic connections (affecting almost all body components), in connection with external and internal excitement exerted by triggering factors (stressor factors) acting intense, surprisingly, sud-den and / or persistent and having a symbolic na-ture , “threating”, or, othertime, extremely favora-ble to the subject (perceived or anticipated by the subject) . In other cases, stressor factors could be psychical excitants with major affective resonance (positive - eustress or negative - distress) or over-loading factors of cognitive (attention, thinking, etc.) and volitional process, mentioning that men-tal stress is mainly based on a major emotional in-volvement.”

The definition given by Golu M. (1981) should also be taken into consideration: “state of tension, tightness, discomfort, caused by afective agents with negative significance (or positive, in case of eustress), frustration or repression of some motiva-tions (needs, desires, aspirations - including under-loading), the difficulty or impossibility of solving problems”.

However, Paul Popescu Neveanu, in the “Dic-tionary of Psychology “ (1978 ), defines stress in terms of two meanings: “a) situation, stimulus which puts the body into a state of tension ; b ) the special tension state, itself, of the body as an activation of all its resources to cope with physical or psychical aggression ( strong emotion )”.

“Stress is an individual reaction and the result of interaction between environmental demands on one hand and the resources, capabilities and oppor-tunities of the individual on the other hand.”

It is certain that stress is characterized by intense hormonal changes, massive secretion of adrenaline. There are also morbid changes (hypertension, gastric ulcer etc). Psychical stress is caused by prolonged emotions primarily mainly due to frustration, conflict and anxiety. There is

stress of overload and also stress of underload. A moderate stress boosts and stimulates the body vitality. The harmful feature of stress occurs when the damage is too large, exceeding the individual adaptive capacity.”

Doctor Ioan Bratu Iamandescu, in his book “Psychical stress and internal diseases” (1993), be-lieves that stress can be positive (eustress) or nega-tive (distress ).

Eustress (“positive stress“) has beneficial ef-fects on the human body, occurring when the stress agents have positive significance for the in-dividual. These triggers positive emotions (intense joy, ecstasy, triumph, laugh out loud), and posi-tively affect the body’s organs and apparatus. Eu-stress appears in the course of positive emotional states or coupled with moderate exercise (eg sex or jogging). Eustress is essentially acute. Frequent repetition of eustress contributes to increase an-tiinfection and antitumor immunity, becoming a longevity premise.

Distress (“negative mental stress“) is widely recognized as pathological. It usually produces pain and inadaptation as a result of contact with a stress-or agent.

Situations generating mental stress: • theexistenceofunusualcircumstancesfor

the individual, which find him unprepared to deal with them

• thesignificanceofanevent• engagingtheindividualintoanexaggerated

action or relation • peculiaritiesofthesocialcontext• lackofinternalconditions• subjectivewayofperceivingenvironmental

demands • underload/overload• existingconflictualsituationsinthefamily,

profession or intellectually related• lackoftime• isolation• theemergenceofaphysicalormental

obstacle in the way of a goal that leads to frustration

• disturbingcircumstancesarisingfromphysical agents (noise, vibration, temperature fluctuations).


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Stress and health at workplace. Manifestations of stress at workplace.

Stress at work can affect anyone, at any level. It is produced in every sector and in organizations of any size. Stress affects the health and safety of individuals and also welfare of organizations and national economies.

Workplace stress occurs when job demands exceed the available resources of human beings. Stress is not only the result of major adverse events, but also is the result of stress and daily pressures. The latter, by their frequency, have an important role in the professional environment and affect more individuals than major adverse events, which are rare.

Andreescu Anghel, Liţă Ştefan (2006), states that “sometimes, professional stress is considered as a positive, beneficial factor on performance. This refers to eustress which means activation, mobi-lization of individual resources. It is important to distinguish between eustress and distress, one as a state of stress with beneficial effects, the other with adverse health effects.”

Today’s world, more dynamic in work field perspective, brings in the foreground workers, per-sonnel reductions and services externalization, in-creased flexibility in terms of position and compe-tencies, the growth in number of determined time job contracts, growing uncertainty of jobs and in-tensity of work (overload and higher pressure ), and unstable balance of life and work. That is why stress can bring disease and pain to individuals, both at work and at home.

Stress can compromise safety at work too, thus contributing to other health issues related to work, such as musculoskeletal disorders.

Stress greatly affects the image of an organi-zation. Reducing stress associated with work and psychosocial risks is not only a moral imperative but also a legal one. It is also an important prob-lem of economic efficiency. The good news is that stress associated with work can be approached in the same logical and systematic way as other health and safety issues. There is an abundance of prac-tical examples to cope this problem in the area of Eurpean Union countries. Using the appropriate method, workers may be stress protected.

Considering the example of a person who feels great pressure meaning job demands (worktime, li-

ability) larger than individual capabilities and cor-roborated by conflicts with colleagues/leaders, fre-quent changes or threats on job security - such as the possible personnel downsizing; all these could be perceived as a stressful situation by someone or challanging by another. What makes the difference in perception depends on job nature, the psycho-logical profile of individuals, as well as physical health or health, in general.

Manifestations of stress at workplace can lead to: depression, anxiety, feelings of being over-whelmed and unable to cope with them, a decrease in professional performance, an increase in the number of days for sickness treatment, absen-teeism, insomnia, cognitive difficulties (reduced ability to concentrate or make decisions), fatigue, headache, palpitations, gastrointestinal problems, increased aggressivity, etc..

All these lead to the following consequences:

• adecreaseinproductivity• anincreasedriskofhavinganaccidentat

work • damageinpersonalrelationships• anincreasedriskofhealthproblems

(cardiovascular disease, digestive problems, cervical pain, etc.)

Strategies to eliminate and prevent stress at work

Recent studies of the so-called “healthy organ-izations” suggest that policies for employee health lead to benefits for organizations. A healthy organi-zation is defined as an organization with a low rate of illness or disability in working personnel. That means an increased competitivity. Researches have identified that a minimum stress at work leads to a higher level of productivity as definition for a healthy organization.

These relate to: • Recognizingemployee’sperformance• Opportunitiesforcareerdevelopment• Organizationalculturethatvaluesemployee• Managerialactionsinconcordancewiththe

values of the organization.


43

Strategies to reduce stress at work include:

a) psychological assistance for employees is an occupational health service; that is provided by organization in order to reduce or eliminate the de-creasing performance at workplace;

b) training services for employees: perfor-mance management, time management, stress man-agement, career management , etc. ;

c) educational workshops: parenting , work-life balance, time management, stress management, emotional control, anger management, decision making and problem solving, alertness, communi-cation in couple, smoking quitance, weight control , etc. ;

d) online educational resources: newsletter, ac-cess to educational information for the employee and his family ( web resources , brochures );

e) career management services;f) services for managers and professionals in

human resources departments are:- management of critical incidents ;- assistance for enhancing skills in control of

inadequate behaviors of employees;- assistance and training in management of

employees capabilities;- development and implementation of employ-

ee assistance programs in the company.

Stress prevention at workplace There is no standardized approach or a manual

for developing stress prevention programs. Design programs and solutions will be influenced by many factors: the size and complexity of the organiza-tion, available resources, and in particular the type of problems the organization faces. For example, in some companies the main problem is overloading employees and others, an inflexible program or lack of communication with the public. In other words, it is not possible to find a universal prescription for stress prevention in the workplace, but it is possible to provide some guide lines for the prevention of stress in organizations.

In all cases, the process of stress prevention programs involves three distinct approaches: prob-lem identification, intervention and evaluation. Or-ganizations must be prepared properly to lead this process successfully.

A minimum level in preparing a stress preven-tion program should include the following:

• workplacestressawareness(causes,costs,control);

• ensuringaqualitymanagementandsupportfor the program;

• employeeinvolvementinallphasesoftheprogram;

• establishingthetechnicalcapabilityofprogram management (specific training for members or consultants involvement).

Assembling employees or employers and man-agers in the same committee or “solving problem group” can be a very useful approach for developing a stress prevention program.

Researches show that these participatory ef-forts were successfully achieved on ergonomic is-sues in the workplace, partialy due to the capitali-zation of direct knowledge of employees about the problems encountered in their workplace.

The “psychological contract” as a mean of pre-venting and combating stress is today a frecvent approach. In the literature the term “psychological contract” is commonly used in the sense of mutual-ly shared set of expectations between the employee and the organization.

The author Denise Rousseau defines the psy-chological contract as “individual beliefs shaped by an organization, in terms of exchange between the individual and the organization”. Psychological con-tract can be accepted as a mental model that em-ployees use to inframe and interpret organizational phenomena. Its terms shall constitute a reference system to which employees report their work and the attitude of employers towards employees is also very important.

Characteristics of the psychological contract:

• represents,essentially,asubjectiveperception that differs from one individual to another;

• psychologicalcontractisdynamic,thatmeans it is changing over time, during the relationship between employer and employee;

• referstothemutualobligationsbased


44

on investment in promises made by both parties, with the hope of a positive outcome for each party;

• iscloselylinkedtothecontextoflaborrelationship, the psychological contract can not be created by individual or organization only.

The main functions of the psychological contract:

• reducesincertitude,becausenotallpossible

aspects of the employment relationship may be covered by a formal written contract between the two parts: employer and employee;

• dictatesemployeebehaviors-likeasystem,the employee weighs their commitment to the organization and the organization’s obligations to themselves and change their behavior in relatation with critical company outcomes;

• thethirdfunctionofpsychologicalcontract,gives to employee a sense of influence on what happens to him, in the organization.

Bibliography1. Labor Safety and Health Agency –

https://osha.europa.eu/ro/topics/stress index_ html

2. Anderson, N.; Schalk, R., The psychological contract in retrospect and prospect. Journal of Organiza-tional Behavior, vol. 19, 1998, p. 640

3. Aradavoaice Gheorghe, (2010), Stres, eustres, distres, Antet Publi-shing House, Bucharest

4. Băban, A. (1998), Stress and per-sonality, Dacia Publishing House, Cluj-Napoca

5. Charly, C. (2003), How to face stress, Polirom Publishing House, Iași

6. Cocoară, Mihai (2005), Stress-de-finition, manifestation, prevention, Category: Medicine for all. ISBN: 973-87431-2-5

7. Derevenco, P., Anghel, I., Baban, A. (1992), Stress in health and illness –

from theory to practice, Dacia Pu-blishing House, Cluj-Napoca

8. Floru, R. (1974), Mental stress, En-ciclopedic Publishing House, Bu-charest

9. Gherman L., Pănoiu, L., Răcășan M (2010), Human resource and career management, “Independenţa Eco-nomic” Publishing House, Pitești

10. Holdevici, I. (1995), Autosuggesti-on and relaxation, Ceres Publishing House, Bucharest

11. Holdevici, I. (1995), Suggestion and suggestive psychotherapy, Victor Publishing House, Bucharest

12. Horney, K. (1998), Our inner con-flicts, IRI Publishing House, Bucha-rest

13. Iamandescu, I.B. (1993), Psychical stress and internal diseases, All Pu-blishing House, Bucharest

14. Iamandescu, I.B. (1995), Manual of Medical Psychology, InfoMedica Publishing House, Bucharest

15. Iamandescu, I.B. (2002), Mental stress, InfoMedica Publishing Hou-se, Bucharest

16. Ionescu, G. (1980), Normal and pathological mental life, Academic Publishing House, Bucharest

17. Lacombe F. (2005), Solving commu-nication difficulties, Polirom Publi-shing House, Iasi,

18. Lăzărescu, M. (1994), Clinical psychopathology, Helicon Publi-shing House., Timisoara

19. Rousseau, D. M.( 1996), Psychologi-cal Contracts in Organizations: Un-derstanding Written and Unwritten Agreements. Newbury Park, CA: Sage

To conclude, stress is a “disease” of our time, affecting people no matter of their lifestyle. Stress is found everywhere, more obvious and more frequent in advanced countries. To find the way to manage stressful situations is up to each of us.

45

În perioada 8 – 11 octombrie 2014, la Cercul Militar Naţional, se vor desfăşura

lucrările celei de a 4-a ediţii a Zilelor Spitalului Universitar de Urgenţă

Militar Central „Dr. Carol Davila”.Manifestare știinţifică recunoscută deja din ediţiile anterioare, Zilele SUUMC și-au

câștigat un binemeritat loc în peisajul profesional al medicinii militare din ţara noastră, fiind în momentul de faţă indiscutabil conferinţa cea mai amplă din punct de vedere al programului știinţific și al participării colegilor noștri.

Dacă anul trecut lucrările Zilelor SUUMC s-au derulat împreună cu Prima Conferință Națională de Medicină Militară, ediţia actuală aduce un nou element de noutate, anume asocierea cu a 33-a Săptămână a Uniunii Medicale Balcanice. Astfel, experienţa și performanţele colegilor noștri medici militari vor fi expuse unui public amplu, iar îngemănarea cu experienţa medicilor civili din cele mai prestigioase spitale universitare din ţara noastră, precum și a celor din celelalte ţări balcanice va permite dezvoltarea de relaţii profesionale noi, în beneficiul medicilor și pacienţilor în egală măsură.

Tema generală a conferinţei va fi: Interdisciplinaritate şi actualităţi în medicina balcanică.

Abstractele vor fi publicate în Archives of the Balkan Medical Union, publicaţie indexată și citată în Scopus. Detalii suplimentare pot fi obţinute pe www.zilelesuumc.ro

Fiind siguri de valoarea profesională și știinţifică a muncii tuturor colegilor noștri militari, vă invităm să participaţi la această manifestare știinţifică, convinși fiind că este un excepţional prilej de informare, educare continuă și schimb de opinii de înaltă ţinută.

Col. Dr. Florentina Ioniță RaduComandant, Spitalul Universitar de Urgenţă Militar Central Dr. Carol Davila



46

Dear colleagues and friends,It’s our pleasure to invite you, to attend

the 20th Balkan Military Medical Committee Congress,

which will be held in June, 2015, in Greece, most probably in Athens.

We kindly invites authors to submit abstracts for presentations (oral and poster), within any of the Military Medicine themes.

Submission can be made via the following email addresses: [email protected], [email protected].

All accepted abstracts will be included within the Congress Proceedings.

Looking forward to hearing from you,

LTC Bogdan Marinescu, MD, PhD.MAJ Ciprian Constantin, MD.

Cu ocazia Zilei Medicinei Militare sărbătorită pe 21 august în fiecare an,

Comitetul Editorial al Revistei de Medicină Militară le urează „La Mulți Ani”! cititorilor,

colaboratorilor, membrilor Asociației Medicilor și Farmaciștilor Militari și tuturor

celor care iubesc, cunosc și înțeleg importanța medicinei militare românești.

Anul acesta se împlinesc 152 de ani de când Domnitorul Alexandru Ioan Cuza a

semnat la 21 august actul de înființare a corpului de ofițeri sanitari. Prin înaltul Decret

Domnesc a luat ființă la data de 21 august 1862 Corpul Ofițerilor Sanitari din Armata și

Direcția Generală a Serviciului Sanitar Român, atestându-se astfel medicina militară ca

element specializat pentru asigurarea sănătății efectivelor militare.

Noi îi urăm organizației noastre viață lungă și plină de realizări cât mai diverse într-o

lume tot mai complexă și plină de provocări în care este tot mai necesară asistența

medicală specializată.

Comitetul Editorial al Revistei de Medicină Militară

Revista de Medicină Militară nr. 1-2 / 2014ISSN 1222-5126

medicină - spitalul universitar de urgenţă militar central · mri is the ,,gold standard’’...

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