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GENERALISED VACCINIA IN HUMAN FŒTUS
1422
Although the blood-urea concentration per 100 ml. ranged between 38 and 270 mg. in case 1, between 35 and 55 mg. in case 2, and between 40 and 155 mg. in case 3, this raised level seems unlikely to have been the cause of the abdominal distension. Mesenteric thrombosis also seems unlikely, since the patients were on anticoagulant therapy with prothrombin levels optimally controlled. At no time was there any evidence of haemorrhage. It should also be noted that at necropsy in cases 1 and 3 no abnormality was found in the gastrointestinal tract. Since no other causes can be found to explain the occurrence of paralytic ileus in these patients, and since the condition improved in cases 2 and 3 on withdrawal of phenindione, it is assumed that the ileus was due to the toxic effect of phenindione. Burns and Desmond2 suggest that sensitivity to phenindione may be due to the presence of a potentially toxic modified benzene ring in the compound. I should like to thank Dr. J. Simpson and Dr. C. B. Willey of West Cumberland Hospital for allowing me to study cases under their care, Dr. R. Dallachy and Dr. A. C. Ogilve for necropsy reports, and Mrs. M. Tackson for literarv helo.
Department of Cardiology, Royal Victoria Infirmary, Newcastle upon Tyne.
I. SUDHAKARAN MENON.
VACCINATOR’S THUMB SIR,-Small plastic tubes have recently replaced glass tubes as containers for amounts of glycerinated vaccine lymph sufficient for single vaccinations. They are convenient to transport, store, and use. The end of a container may be snipped open and the lymph then expelled by squeezing the plastic between thumb and index finger. During the squeezing process the operator’s thumb may come into contact with lymph. The pressure applied when squeezing may result in inoculation, and no abrasion is necessary. vaccinator’s thumb " is painful, and may be accompanied by lymphangitis and axillary adenitis. In the early stage, the lesion is easily mistaken for a septic pulp infection or A
"
paronychia. The simple precaution of wearing a glove when vaccinating with lymph presented in plastic tubes is advocated. Alternatively the end of a tube may be pierced with a needle-greater control in expelling the vaccine is then possible, and selfinflicted dilital vaccination unlikelv. Good Hope General Hospital, Sutton
Coldfield,
Warwickshire.
D. D. GIBBS.
GENERALISED VACCINIA IN HUMAN FŒTUS SIR,-Dr. Green and his colleagues (June 11) record further cases of this interesting example of infection persistently pathogenic in the presence of antibody (maternal at least, though recent studies of rubella suggest that antibody can be formed in prenatal life). The characteristic circinate vaccinia lesions illustrated in their case 1 are on a larger scale reminiscent of the slowly growing circular plaques of cell destruction found in tissue-culture monolayers infected with viruses such as vaccinia and herpes simplex and incubated in the presence of sufficient antiserum to prevent spread of infection except by direct cell-to-cell extension. Normal recovery from such infections presumably requires additional and non-immunological defence reactions-e.g., interferon production. Inter-4 feron production and response by embryonic cells is poor. 3 Chronic vaccinia of the foetus may thus exemplify infection prevented from becoming fully generalised by (maternal) antibody, but not eradicated by the immature or absent interferon response. Similar mechanisms may partly explain some other persistent foetal infections-e.g., with rubella. University Department of Infectious Diseases, NORMAN R. GRIST. Ruchill Hospital, Glasgow N.W. 2. Burns, C., Desmond, F. B. N. Z. J. Med. 1958, 3. Isaacs, A., Baron, S. Lancet, 1960, ii, 946. 4. Sawicki, L. Nature, Lond. 1961, 192, 1258.
57, 283.
INFECTION IN AN EYE HOSPITAL
SIR,-I share Dr. Crompton’s anxieties (June 11) and remain an admirer of his continuing efforts to alert all sectors of medical endeavour to the dangers of ill-prepared ophthalmic solutions. Nevertheless I cannot agree with him that" informed medical supervision of the methods used in the dispensary " would necessarily provide the safeguards he seeks. In my experience medical and surgical opinion is not always well informed about the complexities and practicalities of ophthalmic formulation and packaging. I have already indicated the action being taken in pharmaceutical circles to provide scientific appraisal of many aspects of ophthalmic medication. Only with maximum knowledge of such factors as the effectiveness of preservatives and medicaments at varying pH values, the stability of components during sterilisation and storage, and the efficiency of containers, can the best procedures for any preparation be determined. I strongly support Dr. Crompton’s view that it is possible to produce sterile solutions for intraocular use in single-dose containers, and that these should not include a preservative. The 1966 Supplement to the British Pharmaceutical Codex also
emphasises this point. Judging by the number of inquiries received by this school of pharmacy most pharmacists, particularly those engaged in hospital practice, are anxious to provide the best ophthalmic products attainable. In a few hospitals perhaps outmoded and even dangerous practices survive. Vigorous action should be taken to eradicate them. I believe the most rapid progress will be achieved if, firstly, the procedures recommended by the British Pharmaceutical Codex are followed for all ophthalmic products whether or not they are the subject of an official monograph and, secondly, clinicians will accept expert pharmaceutical advice regarding both the mode of drug presentation and the preparative processes to be employed. Bristol
School of Pharmacy, College of Science and Technology, Bristol 7.
D. A. NORTON.
ANTICONVULSANT MEGALOBLASTIC ANÆMIA
SIR,-The letter from Dr. Matthews and Dr. Reynolds
(Jan. 22) prompts
me to
record
a
similar
case.
The patient, a woman aged 35 years, developed epilepsy at the age of 6, and was treated with phenobarbitone and phenytoin sodium (’ Epanutin ’) from then up till October, 1964. She developed megaloblastic anaemia in October, 1959, while she was pregnant, and was treated with folic acid and bloodtransfusion at this hospital. In October, 1964, she became grossly anxmic, and was admitted to the Royal Northern Infirmary, Inverness, where phenytoin sodium was considered the most likely cause of her megaloblastic anaemia, and was therefore changed to primidone (’ Mysoline ’). In April, 1965, she was readmitted to Raigmore Hospital because of backache, and was found to have osteomalacia as a result of malabsorption syndrome. In July, 1965, she was admitted to the Royal Infirmary, Edinburgh, for further investigation, and our diagnosis of malabsorption was confirmed by jejunal biopsy, which showed grossly abnormal mucosa of small-intestinal pattern, and complete villous atrophy. Relevant Investigations October,1959.-Oct. 13: Hb 31 % ; red blood-cells 1,540,000, and white blood-cells 3450, per c.mm.; bone-marrow megaloblastic. Oct. 26: Hb 70%; red blood-cells 3,500,000, and white blood-cells 9050, per c.mm. October, 1964.-Hb 3-3 (repeat 12’3) g. per 100 ml.; packedcell volume 19% (repeat 390;,); mean corpuscular hxmoglobin concentration (M.C.H.c.) 330;, (repeat 31%); reticulocytes 1-8%; blood-film suggestive of macrocytic megaloblastic anxmia; serum-iron 232, and serum iron-binding capacity (I.B.c.) 326, g. per 100 ml.; blood-urea 31 mg. per 100 ml.; faecal occult blood test negative. Free acid was found in the stomach. On 1. Norton, D. A.
Lancet, 1965, ii, 1237.
Although the blood-urea concentration per 100 ml. ranged between 38 and 270 mg. in case 1, between 35 and 55 mg. in case 2, and between 40 and 155 mg. in case 3, this raised level seems unlikely to have been the cause of the abdominal distension. Mesenteric thrombosis also seems unlikely, since the patients were on anticoagulant therapy with prothrombin levels optimally controlled. At no time was there any evidence of haemorrhage. It should also be noted that at necropsy in cases 1 and 3 no abnormality was found in the gastrointestinal tract. Since no other causes can be found to explain the occurrence of paralytic ileus in these patients, and since the condition improved in cases 2 and 3 on withdrawal of phenindione, it is assumed that the ileus was due to the toxic effect of phenindione. Burns and Desmond2 suggest that sensitivity to phenindione may be due to the presence of a potentially toxic modified benzene ring in the compound. I should like to thank Dr. J. Simpson and Dr. C. B. Willey of West Cumberland Hospital for allowing me to study cases under their care, Dr. R. Dallachy and Dr. A. C. Ogilve for necropsy reports, and Mrs. M. Tackson for literarv helo.
Department of Cardiology, Royal Victoria Infirmary, Newcastle upon Tyne.
I. SUDHAKARAN MENON.
VACCINATOR’S THUMB SIR,-Small plastic tubes have recently replaced glass tubes as containers for amounts of glycerinated vaccine lymph sufficient for single vaccinations. They are convenient to transport, store, and use. The end of a container may be snipped open and the lymph then expelled by squeezing the plastic between thumb and index finger. During the squeezing process the operator’s thumb may come into contact with lymph. The pressure applied when squeezing may result in inoculation, and no abrasion is necessary. vaccinator’s thumb " is painful, and may be accompanied by lymphangitis and axillary adenitis. In the early stage, the lesion is easily mistaken for a septic pulp infection or A
"
paronychia. The simple precaution of wearing a glove when vaccinating with lymph presented in plastic tubes is advocated. Alternatively the end of a tube may be pierced with a needle-greater control in expelling the vaccine is then possible, and selfinflicted dilital vaccination unlikelv. Good Hope General Hospital, Sutton
Coldfield,
Warwickshire.
D. D. GIBBS.
GENERALISED VACCINIA IN HUMAN FŒTUS SIR,-Dr. Green and his colleagues (June 11) record further cases of this interesting example of infection persistently pathogenic in the presence of antibody (maternal at least, though recent studies of rubella suggest that antibody can be formed in prenatal life). The characteristic circinate vaccinia lesions illustrated in their case 1 are on a larger scale reminiscent of the slowly growing circular plaques of cell destruction found in tissue-culture monolayers infected with viruses such as vaccinia and herpes simplex and incubated in the presence of sufficient antiserum to prevent spread of infection except by direct cell-to-cell extension. Normal recovery from such infections presumably requires additional and non-immunological defence reactions-e.g., interferon production. Inter-4 feron production and response by embryonic cells is poor. 3 Chronic vaccinia of the foetus may thus exemplify infection prevented from becoming fully generalised by (maternal) antibody, but not eradicated by the immature or absent interferon response. Similar mechanisms may partly explain some other persistent foetal infections-e.g., with rubella. University Department of Infectious Diseases, NORMAN R. GRIST. Ruchill Hospital, Glasgow N.W. 2. Burns, C., Desmond, F. B. N. Z. J. Med. 1958, 3. Isaacs, A., Baron, S. Lancet, 1960, ii, 946. 4. Sawicki, L. Nature, Lond. 1961, 192, 1258.
57, 283.
INFECTION IN AN EYE HOSPITAL
SIR,-I share Dr. Crompton’s anxieties (June 11) and remain an admirer of his continuing efforts to alert all sectors of medical endeavour to the dangers of ill-prepared ophthalmic solutions. Nevertheless I cannot agree with him that" informed medical supervision of the methods used in the dispensary " would necessarily provide the safeguards he seeks. In my experience medical and surgical opinion is not always well informed about the complexities and practicalities of ophthalmic formulation and packaging. I have already indicated the action being taken in pharmaceutical circles to provide scientific appraisal of many aspects of ophthalmic medication. Only with maximum knowledge of such factors as the effectiveness of preservatives and medicaments at varying pH values, the stability of components during sterilisation and storage, and the efficiency of containers, can the best procedures for any preparation be determined. I strongly support Dr. Crompton’s view that it is possible to produce sterile solutions for intraocular use in single-dose containers, and that these should not include a preservative. The 1966 Supplement to the British Pharmaceutical Codex also
emphasises this point. Judging by the number of inquiries received by this school of pharmacy most pharmacists, particularly those engaged in hospital practice, are anxious to provide the best ophthalmic products attainable. In a few hospitals perhaps outmoded and even dangerous practices survive. Vigorous action should be taken to eradicate them. I believe the most rapid progress will be achieved if, firstly, the procedures recommended by the British Pharmaceutical Codex are followed for all ophthalmic products whether or not they are the subject of an official monograph and, secondly, clinicians will accept expert pharmaceutical advice regarding both the mode of drug presentation and the preparative processes to be employed. Bristol
School of Pharmacy, College of Science and Technology, Bristol 7.
D. A. NORTON.
ANTICONVULSANT MEGALOBLASTIC ANÆMIA
SIR,-The letter from Dr. Matthews and Dr. Reynolds
(Jan. 22) prompts
me to
record
a
similar
case.
The patient, a woman aged 35 years, developed epilepsy at the age of 6, and was treated with phenobarbitone and phenytoin sodium (’ Epanutin ’) from then up till October, 1964. She developed megaloblastic anaemia in October, 1959, while she was pregnant, and was treated with folic acid and bloodtransfusion at this hospital. In October, 1964, she became grossly anxmic, and was admitted to the Royal Northern Infirmary, Inverness, where phenytoin sodium was considered the most likely cause of her megaloblastic anaemia, and was therefore changed to primidone (’ Mysoline ’). In April, 1965, she was readmitted to Raigmore Hospital because of backache, and was found to have osteomalacia as a result of malabsorption syndrome. In July, 1965, she was admitted to the Royal Infirmary, Edinburgh, for further investigation, and our diagnosis of malabsorption was confirmed by jejunal biopsy, which showed grossly abnormal mucosa of small-intestinal pattern, and complete villous atrophy. Relevant Investigations October,1959.-Oct. 13: Hb 31 % ; red blood-cells 1,540,000, and white blood-cells 3450, per c.mm.; bone-marrow megaloblastic. Oct. 26: Hb 70%; red blood-cells 3,500,000, and white blood-cells 9050, per c.mm. October, 1964.-Hb 3-3 (repeat 12’3) g. per 100 ml.; packedcell volume 19% (repeat 390;,); mean corpuscular hxmoglobin concentration (M.C.H.c.) 330;, (repeat 31%); reticulocytes 1-8%; blood-film suggestive of macrocytic megaloblastic anxmia; serum-iron 232, and serum iron-binding capacity (I.B.c.) 326, g. per 100 ml.; blood-urea 31 mg. per 100 ml.; faecal occult blood test negative. Free acid was found in the stomach. On 1. Norton, D. A.
Lancet, 1965, ii, 1237.