the benzodiazepine bonanza

1
964 of us, more accustomed to performing in a system with firearm and high-velocity highway hazards, found his capabilities frequently exceeded by the hidden steps, low ceilings, and slanted floors characterising some charm- ing London shops. While the injuries thus incurred were minor, they point to a remediable source of more severe injuries among those with even greater performance decrements. The clumsy, frail, and intoxicated, like the poor, will be with us always. Would it not be in the best tradition of preventive medicine to provide them safe passage ? School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205. U.S.A. PARK ELLIOTT DIETZ SUSAN P. BAKER. THE BENZODIAZEPINE BONANZA SIR,-Dr Tyrer is certainly right to draw attention to the multiplicity of benzodiazepines (Sept. 21, p. 709). Not only are there too many, but one suspects that they are too often prescribed in ways which cause harm to the patient. In the past three months I have seen 3 patients who were all receiving over 50 mg. of diazepam daily and had been doing so for several months. They were all young women of unstable personalities who had shown no improvement in their behaviour while on diazepam: if anything, suicide attempts had increased. If not physically dependent they were emotionally dependent on the drug to the extent that they would apply great pressure to obtain further supplies, including threatening suicide. I have not read of any evidence that diazepam is more effective in doses over .- 30 mg. daily, and my own impression is that it is of much greater benefit when given for short courses lasting a maximum of 2-3 weeks. Perhaps more useful than this is to allow a patient to keep a small supply of diazepam to take at times of anxiety, but not as a regular prescription, and under these circum- stances patients usually reduce their intake to perhaps three tablets a week, and by avoiding tolerance, gain the maxi- mum benefit. Department of Psychiatry, St. George’s Hospital Medical School, Blackshaw Road, London SW17. JOHN M. KELLETT. SERUM-MURAMIDASE IN LEUK&AElig;MIC RETICULOENDOTHELIOSIS SiR,&mdash;The cell line of origin of the abnormal mono- nuclear cells of leukxmic reticuloendotheliosis (hairy-cell leukxmia) has been argued. I read with interest the scanning-electron-microscope study by Dr Schnitzer and Dr Hammack (Sept. 14, p. 649) of cells from patients with this disorder. They interpret their findings as supporting the view that the cells are lymphocytes, and they refer to the opposing evidence for a lymphocytic versus mono- nuclear-phagocytic cell line of origin. Muramidase is a low-molecular-weight enzyme contained in various mammalian tissue. Of the hxmatopoietic cells, only monocytes and granulocytes contain the enzyme. The serum levels of muramidase are usually raised in prolifera- tive diseases of monocytes or granulocytes, and normal or decreased in those of lymphocytes. 1 Previous reports included determinations of that enzyme in the serum of only a few persons with leukaemic reticuloendotheliosis.2,3 We have now performed the spectrophotometric assay on 1. Hansen, N. E. Ser. h&oelig;mat. 1974, 7, 70. 2. Catovsky, D., Pettit, J. E., Galton, D. A. G., Spiers, A. S. D., Harrison, C. V. Br. J. H&oelig;mat. 1974, 26, 9. 3. Burns, C. P., Maca, R. D., Hoak, J. C. Cancer Res. 1973, 33, 1615. Serum-muramidase of patients with leukaemic reticuloendo- theliosis (L.R.E.) and normal subjects (N). the serum of 13 such patients. The values are decreased (p < 0-001) compared with normal subjects (see accompany- ing figure). These observations add further evidence that the disease should be included in the broad category of lymphoproliferative diseases, or at least that the abnormal cells are hybrids with many characteristics of lymphocytes. Department of Medicine, University Hospitals, Iowa City, Iowa 52242, U.S.A. C. PATRICK BURNS. TWINNING AND NEURAL-TUBE DEFECTS SIR,-We have examined relationships between twinning and neural-tube closure defects in a series of 1560 cases of anencephaly, encephalocele, and meningomyelocele (A.S.B.) born in New South Wales, Australia, during the nine years 1965-73. We noted during 1950-73 a declining trend in rates for anencephaly and twins. Elwood has described similar trends in Canadian and U.S. data. In N.S.W. the A.S.B. incidence was 2 per 1000 births; average twinning-rates were 10-74 cases per 1000 births. The observed rate of recurrence after a first child with meningomyelocele is 5-5%. 35 twin pairs were identified among index cases with A.S.B.; 24 were like-sexed (7 male, 17 female). Zygosity was assigned from recorded evidence of chorion status thus: 18 dizygotic (D.z.), 14 monozygotic (M.z.), 3 not recorded. These findings confirm previous observations. There were 4 instances of concordance, all among like-sexed twins, thus : 1970 M.z. Male Both meningomyelocele (both died) 1966 mt.z. Female Both encephalocele (one survivor) 1970 M.z. Female One anencephaly, other meningomyelo- cele (both died) 1968 D.z. Female One anencephaly, other meningomyelo- cele (both died) In addition we have records from outside the survey period: 1963 M.z. Female Both meningomyelocele (both survived) 1961 anencephaly, 2 normal (all died) triplets It appears that concordance is associated with mono- zygosity, by contrast to the preponderance of D.z. pairs containing only one affected twin. However, relative frequencies of each twin class (M.z. 21-4%, D.z. 5-5%) are 1. Elwood, P. Lancet, 1974, i, 31. 2. Yen, S., MacMahon, B. ibid. 1968, ii, 623.

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Page 1: THE BENZODIAZEPINE BONANZA

964

of us, more accustomed to performing in a system withfirearm and high-velocity highway hazards, found his

capabilities frequently exceeded by the hidden steps,low ceilings, and slanted floors characterising some charm-ing London shops. While the injuries thus incurred wereminor, they point to a remediable source of more severeinjuries among those with even greater performancedecrements. The clumsy, frail, and intoxicated, like thepoor, will be with us always. Would it not be in the besttradition of preventive medicine to provide them safe

passage ?School of Hygiene and Public

Health,Johns Hopkins University,Baltimore, Maryland 21205.

U.S.A.

PARK ELLIOTT DIETZSUSAN P. BAKER.

THE BENZODIAZEPINE BONANZA

SIR,-Dr Tyrer is certainly right to draw attention to themultiplicity of benzodiazepines (Sept. 21, p. 709). Not

only are there too many, but one suspects that they are toooften prescribed in ways which cause harm to the patient.

In the past three months I have seen 3 patients who wereall receiving over 50 mg. of diazepam daily and had beendoing so for several months. They were all young womenof unstable personalities who had shown no improvementin their behaviour while on diazepam: if anything, suicideattempts had increased. If not physically dependent theywere emotionally dependent on the drug to the extent thatthey would apply great pressure to obtain further supplies,including threatening suicide. I have not read of anyevidence that diazepam is more effective in doses over

.- 30 mg. daily, and my own impression is that it is of muchgreater benefit when given for short courses lasting a

maximum of 2-3 weeks.

Perhaps more useful than this is to allow a patient tokeep a small supply of diazepam to take at times of anxiety,but not as a regular prescription, and under these circum-stances patients usually reduce their intake to perhaps threetablets a week, and by avoiding tolerance, gain the maxi-mum benefit.

Department of Psychiatry,St. George’s Hospital Medical School,

Blackshaw Road,London SW17. JOHN M. KELLETT.

SERUM-MURAMIDASE IN LEUK&AElig;MICRETICULOENDOTHELIOSIS

SiR,&mdash;The cell line of origin of the abnormal mono-nuclear cells of leukxmic reticuloendotheliosis (hairy-cellleukxmia) has been argued. I read with interest the

scanning-electron-microscope study by Dr Schnitzer andDr Hammack (Sept. 14, p. 649) of cells from patients withthis disorder. They interpret their findings as supportingthe view that the cells are lymphocytes, and they refer tothe opposing evidence for a lymphocytic versus mono-nuclear-phagocytic cell line of origin.Muramidase is a low-molecular-weight enzyme contained

in various mammalian tissue. Of the hxmatopoietic cells,only monocytes and granulocytes contain the enzyme. Theserum levels of muramidase are usually raised in prolifera-tive diseases of monocytes or granulocytes, and normal ordecreased in those of lymphocytes. 1 Previous reportsincluded determinations of that enzyme in the serum of

only a few persons with leukaemic reticuloendotheliosis.2,3We have now performed the spectrophotometric assay on

1. Hansen, N. E. Ser. h&oelig;mat. 1974, 7, 70.2. Catovsky, D., Pettit, J. E., Galton, D. A. G., Spiers, A. S. D.,

Harrison, C. V. Br. J. H&oelig;mat. 1974, 26, 9.3. Burns, C. P., Maca, R. D., Hoak, J. C. Cancer Res. 1973, 33, 1615.

Serum-muramidase of patients with leukaemic reticuloendo-theliosis (L.R.E.) and normal subjects (N).

the serum of 13 such patients. The values are decreased

(p < 0-001) compared with normal subjects (see accompany-ing figure). These observations add further evidence thatthe disease should be included in the broad category of

lymphoproliferative diseases, or at least that the abnormalcells are hybrids with many characteristics of lymphocytes.Department of Medicine,University Hospitals,

Iowa City, Iowa 52242,U.S.A. C. PATRICK BURNS.

TWINNING AND NEURAL-TUBE DEFECTS

SIR,-We have examined relationships between twinningand neural-tube closure defects in a series of 1560 casesof anencephaly, encephalocele, and meningomyelocele(A.S.B.) born in New South Wales, Australia, during thenine years 1965-73. We noted during 1950-73 a decliningtrend in rates for anencephaly and twins. Elwood hasdescribed similar trends in Canadian and U.S. data.

In N.S.W. the A.S.B. incidence was 2 per 1000 births;average twinning-rates were 10-74 cases per 1000 births.The observed rate of recurrence after a first child with

meningomyelocele is 5-5%.35 twin pairs were identified among index cases with

A.S.B.; 24 were like-sexed (7 male, 17 female). Zygositywas assigned from recorded evidence of chorion status

thus: 18 dizygotic (D.z.), 14 monozygotic (M.z.), 3 notrecorded.These findings confirm previous observations. There

were 4 instances of concordance, all among like-sexedtwins, thus :1970 M.z. Male Both meningomyelocele (both died)1966 mt.z. Female Both encephalocele (one survivor)1970 M.z. Female One anencephaly, other meningomyelo-

cele (both died)1968 D.z. Female One anencephaly, other meningomyelo-

cele (both died)In addition we have records from outside the survey

period:1963 M.z. Female Both meningomyelocele (both survived)1961 anencephaly, 2 normal (all died)triplets

It appears that concordance is associated with mono-zygosity, by contrast to the preponderance of D.z. pairscontaining only one affected twin. However, relativefrequencies of each twin class (M.z. 21-4%, D.z. 5-5%) are

1. Elwood, P. Lancet, 1974, i, 31.2. Yen, S., MacMahon, B. ibid. 1968, ii, 623.