687
-
We have trained fifty-six patients in this technique during the past 10 months. The average training period was 10 dialysis days. Most patients exchange 2 litres of dialysate four times a day 7 days a week while nine of them whose serum-creatinine is less than 10 mg/dl exchanging three times a day. The mean (±s.D.) laboratory values at the time of this report are: serum creatinine 12-1+3-33 mg/dl, blood-ureanitrogen 39+19 mg/dl, calcium 9-1±0-9mg/dl, phosphorus 4-8±1-5 mg/dl, albumin 3-3±0’S g/dl, total protein 6-4±0-6
g/dl, haemoglobin 9-0+1-99 g/dl. episodes of peritonitis occurred among twenty-two pa(1 episode every 7 patient-months), which is a significant improvement over the rate reported by Popovich and his colleagues.7 With further improvements C.A.P.D. could become the treatment of choice for most patients requiring chronic dialysis. 35 tients
Toronto Western
Hospital,
Toronto, Ontario, Canada M5T 2S8
D. G. OREOPOULOS
SOMATOSTATIN DECREASES URINARY CALCIUM EXCRETION SIR,-Somatostatin is widely distributed in the bodyl and may help to regulate the secretion of growth hormone, insulin, glucagon, and several gastrointestinal hormones.’The localisation of somatostatin in some parafollicular cells of the thyroid gland’ stimulated studies designed to elucidate the possible importance of somatostatin in the control of the secretion of calcitonin, thyroid hormones,’ and parathyroid hormone (P.T.H.). As to calcitonin and P.T.H., most studies gave negative reults.3 Our findings indicate that somatostatin may aid the regulation of the calcium balance in the body. 24-HOUR
URINARY EXCRETION OF CALCIUM
A.M.P.
(mol/mmol
(mmol) AND CYCLIC
CREATININE) (MEAN±S.E.M.)
Our observation that cyclic A.M.P. levels altered may indicate that parathyroid hormone does not mediate the effect of the peptide on urinary calcium excretion. P. E. LINS Department of Endocrinology, S. EFENDIC Karolinska Hospital, S-104 01 Stockholm, Sweden. H. LÖW
handling of calcium. were not
COMBINATION THERAPY OF DENDRITIC KERATITIS WITH TRIFLUOROTHYMIDINE AND INTERFERON
SIR,-Topical human leucocyte interferon accelerates healing and shortens herpes simplex virus shedding when given after debridement in dendritic keratitis.l-4 Interferon alone does not seem to be sufficiently effective in the local therapy of this disease; it needs a strong therapeutic partners and until recently debridement has been that partner. We wondered whether trifluorothymidine, which is the best available synthetic antiherpetic for topical ocular therapy, could substitute for debridement in such a combination. Three randomly selected groups of patients with virologically confirmed dendritic keratitis were given 5 drops of 1-0% trifluorothymidine per day. In addition, group 1 (n=15) was treated with 2 drops of. coded albumin, group 2 (n=11) with coded human leucocyte interferon 106 units/ml, and group 3 (n=l1) with interferon 30x 106 units/ml. No significant difference was found between groups 1 and 2, whereas fluorescein-negative epithelial healing was significantly quicker in group 3 (P005; y=2-32, d.f.=1). If the difference is still non-signifi1 Sundmacher, R , Neumann-Haefelin, D , Cantell, K. Lancet, 1976, i, 1406. 2. Sundmacher, R , Neumann-Haefelin, D., Cantell, K. Graefes Arch. klin. exp. Ophthal 1976, 201, 39. 3. Jones, B R., Coster, D. J., Falcon, M. G., Cantell, K. Lancet, 1976, ii, 128. 4. Coster, D. J., Jones, B. R., Falcon, M. G. Trans ophthalm. Soc. U.K., 1977,
97, 314. 5 Sundmacher, R., Cantell, K., Haug, P , Neumann-Haefelin, D. Arch. klin. exp. Ophthal. 1978, 207, 77
Graefes
688 in late September, this will mean that there is more than 1 chance in 20 that the outcome could have been due to chance alone. Thus, by blind application of statistics, one could not be sure that the Red Sox were the better team. But, as every true fan will tell you, "The Sox are just murderin’ them Yankees."
cant
WARD CASSCELLS STEPHANIE TAYLOR
Harvard Medical School, Boston, MA 02115, U.S.A.
SPERM BASIC PROTEINS IN CERVICAL
CARCINOGENESIS a study of the effects of chronic cannabis use on ultrastructure and histochemistry we found that arginine-rich protamines were greatly decreased in the nuclei of the users’ spermatozoa compared with controls.1 Material for the study was obtained from a population of chronic hashish users, who came largely from refugee families from Asia
SIR,-In
sperm
a working-class, low-income section of Athens. Controls were non-users, but tobacco smokers, and were matched to the users for age, refugee origin, upbringing, and low socioeconomic status. Dr Reid and his colleagues (July 8, p. 60) correlate low .socioeconomic status with a high ratio of arginine-rich protamines/somatic histones in the sperm of a large group of healthy males. They view their findings as a biochemical index linking cervical cancer with an accepted xtiological factor, low socioeconomic status. At first glance, it would seem that chronic hashish use by our subjects reversed the repercussions of low socioeconomic status on the basic protein ratio of their sperm nuclei. However, because tranquillisers reversibly increase, at least in peripheral blood-cells, certain histone basic protein fractions,2 I would suggest to the Australian and British groups of researchers that they screen their subjects for therapeutic and/or recreational use of psychotropic drugs as a factor to be correlated with their findings on sperm basic protein ratios. Such additional data would greatly contribute to the search for setiological factors in cervical cancer in particular, and oncogenesis in general. They would also help to define the limits of the much debated oncogenic potential of psycho-
Minor, residing in
tropic drugs. Department of Psychiatry, Neurobiology Research Laboratory, University of Athens, Eginition Hospital, Athens 603, Greece *Present address: Marine 02543, U S.A
MARIETTA R. ISSIDORIDES* Biological Laboratory, Woods Hole, Massachusetts
VITILIGO AND STEROIDS is often associated with autoimmune disease Hashimoto’s thyroiditis,3 and patients with vitiligo also 4 an increased incidence of organ-specific autoantibodies. found to react Despite this, autoantibodies are rarely against melanocytes in the skin, and then only in patients with polyendocrinopathy and skin lesion. We have seen a patient in whom prolonged treatment with corticosteroids produced complete remission of extensive vitiligo. The patient, a previously fit 73-year-old man, had had vitiligo for 20 years. His face was piebald and embarrassed him so much that he had used face make-up daily for more than 15 years. In 1976 he had a prolonged pyrexial illness with
SiK,—Vitiligo
such have
as
Stefanis, C. N., Issidorides, M. R. in Marihuana: Chemistry, Biochemistry, and Cellular Effects (edited G. G. Nahas); p. 533. New York, 1976. 2. Issidorides, M. R., Zioudrous, C., Lykouras, E., Stefanis, C. N. Progr. Neuro-Psychopharmac. 1978, 2, 79. 3. Doniach, D , Roitt, I. M in Clinical Aspects of Immunology (edited by P. G. H. Gell and R. R. A. Coombs). Oxford, 1968. 4. Brostoff, J , Bor, S., Feiwel M. Lancet, 1969, ii, 177 5. Hertz. K. C., Gazze, L. A., Kirkpatrick, C. H., Katz, S. I. New Engl. J. Med. 1977, 297, 639.
aches and pains for which no infectious cause could be found. His erythrocyte-sedimentation rate at that time was more than 100 mm in the first hour. Polymyalgia rheumatica was diagnosed, and he responded dramatically to prednisone, the initial dose being 30 mg daily. He was then maintained, free of symptoms, on 15 mg daily for a year (a lower dose leading to a recurrence of symptoms). He now takes Prednisone 4 mg daily. His vitiligo disappeared completely by the end of the first year of treatment and has not returned. It would seem that this patient’s vitiligo could have had an autoimmune basis as the recovery was so complete after his steroid treatment. There are other clinical situations, such as in pernicious ansemia, where steroid treatment can reverse the autoimmune process, leading to a fall in intrinsic-factor antibody and a return of the Schilling test to normal. This response lasts only as long as the steroids are given. Here, the balance of cell destruction due to the autoimmune process is tipped towards regeneration by the treatment. This seems to have happened in the patient we describe.
generalised
36 Eton Avenue, London NW3
Department
of
HARRY BROSTOFF
Immunology,
Middlesex Hospital Medical School, London W1
JONATHAN BROSTOFF
NALOXONE AS AN ANTAGONIST IN SEVERE ALCOHOL INTOXICATION 4
SIR,-Naloxone hydrochloride is
pure opiate antagonist in doses below 50 mg/kg.’ In humans the respiratory depression caused by opiates may be reversed by naloxone in doses of 5-10 In animals the depressant effects of barbiturates,23 benzodiazepines,4ethanol,5 and some inhalation anaesthetics6have also been reversed by naloxone, but the doses used were much higher (1-5 mg/kg) than those necessary to reverse opiate-induced respiratory depression in humans, suggesting that different mechanisms might be involved. The depleting effects of both morphine and ethanol on cerebral calcium levels, and their reversal by naloxone (1 mg/kg) in rats, have led to the suggestion that these two compounds share a common mechanism of action in the central nervous system.23 There are two case-reports of the reversal by small doses of naloxone (less than 25 g/kg) of coma in humans induced by diazepam alone4and by a combination of ethanol, barbiturate, and diazepam.5 We have recently observed reversal of coma with 0.8 mg naloxone in a patient, who was apparently intoxicated by ethanol only. A 43-year-old man had been out drinking with a friend and, when he returned home, his wife hit him on the head. When he fell asleep he could not be wakened soon after. On admission he was unconscious and he did not react to noxious stimuli. Blood-pressure was 180/80 mm Hg, pulse-rate was 124/min, breathing was slow with periods of apnoea. His breathing was assistedond intravenous saline was started. He had a superficial bruise in the right frontal region but neurological examination revealed no focal cerebral disease or increased intracranial pressure. Blood-sugar was 11-4 mmol/1 and plasma-bicarbonate was 21-3 mmol/l. He remained unconscious for 1-Lh. Because intoxication was a probable reason for the coma 0-4 mg naloxone was given intravenously. He began reacting to stimuli within a few minutes and when a a
ugkg.
1.
6. Ardeman, S., Chanarin, I. ibid. 1965, 273, 1352. 1. Blumberg, H , Dayton, H. B. in Agonist and Antagonist Actions of Narcotic Analgesic Drugs (edited by H. W Kosterlitz, H O. J. Collier, J. E. Villareal), p. 110, New York, 1973. 2 Ross, D.H , Medina, M. A, Cardenas, H.L. Science, 1974, 186, 63. 3. Ross, D H. Ann N.Y Acad. Sct. 1976, 273, 280. 4. Bell, E. F J. Pediat. 1975, 87, 803. 5. Moss, L.M.J. Am. Coll. Emergency Phys. 1973, 1, 46.
-
We have trained fifty-six patients in this technique during the past 10 months. The average training period was 10 dialysis days. Most patients exchange 2 litres of dialysate four times a day 7 days a week while nine of them whose serum-creatinine is less than 10 mg/dl exchanging three times a day. The mean (±s.D.) laboratory values at the time of this report are: serum creatinine 12-1+3-33 mg/dl, blood-ureanitrogen 39+19 mg/dl, calcium 9-1±0-9mg/dl, phosphorus 4-8±1-5 mg/dl, albumin 3-3±0’S g/dl, total protein 6-4±0-6
g/dl, haemoglobin 9-0+1-99 g/dl. episodes of peritonitis occurred among twenty-two pa(1 episode every 7 patient-months), which is a significant improvement over the rate reported by Popovich and his colleagues.7 With further improvements C.A.P.D. could become the treatment of choice for most patients requiring chronic dialysis. 35 tients
Toronto Western
Hospital,
Toronto, Ontario, Canada M5T 2S8
D. G. OREOPOULOS
SOMATOSTATIN DECREASES URINARY CALCIUM EXCRETION SIR,-Somatostatin is widely distributed in the bodyl and may help to regulate the secretion of growth hormone, insulin, glucagon, and several gastrointestinal hormones.’The localisation of somatostatin in some parafollicular cells of the thyroid gland’ stimulated studies designed to elucidate the possible importance of somatostatin in the control of the secretion of calcitonin, thyroid hormones,’ and parathyroid hormone (P.T.H.). As to calcitonin and P.T.H., most studies gave negative reults.3 Our findings indicate that somatostatin may aid the regulation of the calcium balance in the body. 24-HOUR
URINARY EXCRETION OF CALCIUM
A.M.P.
(mol/mmol
(mmol) AND CYCLIC
CREATININE) (MEAN±S.E.M.)
Our observation that cyclic A.M.P. levels altered may indicate that parathyroid hormone does not mediate the effect of the peptide on urinary calcium excretion. P. E. LINS Department of Endocrinology, S. EFENDIC Karolinska Hospital, S-104 01 Stockholm, Sweden. H. LÖW
handling of calcium. were not
COMBINATION THERAPY OF DENDRITIC KERATITIS WITH TRIFLUOROTHYMIDINE AND INTERFERON
SIR,-Topical human leucocyte interferon accelerates healing and shortens herpes simplex virus shedding when given after debridement in dendritic keratitis.l-4 Interferon alone does not seem to be sufficiently effective in the local therapy of this disease; it needs a strong therapeutic partners and until recently debridement has been that partner. We wondered whether trifluorothymidine, which is the best available synthetic antiherpetic for topical ocular therapy, could substitute for debridement in such a combination. Three randomly selected groups of patients with virologically confirmed dendritic keratitis were given 5 drops of 1-0% trifluorothymidine per day. In addition, group 1 (n=15) was treated with 2 drops of. coded albumin, group 2 (n=11) with coded human leucocyte interferon 106 units/ml, and group 3 (n=l1) with interferon 30x 106 units/ml. No significant difference was found between groups 1 and 2, whereas fluorescein-negative epithelial healing was significantly quicker in group 3 (P005; y=2-32, d.f.=1). If the difference is still non-signifi1 Sundmacher, R , Neumann-Haefelin, D , Cantell, K. Lancet, 1976, i, 1406. 2. Sundmacher, R , Neumann-Haefelin, D., Cantell, K. Graefes Arch. klin. exp. Ophthal 1976, 201, 39. 3. Jones, B R., Coster, D. J., Falcon, M. G., Cantell, K. Lancet, 1976, ii, 128. 4. Coster, D. J., Jones, B. R., Falcon, M. G. Trans ophthalm. Soc. U.K., 1977,
97, 314. 5 Sundmacher, R., Cantell, K., Haug, P , Neumann-Haefelin, D. Arch. klin. exp. Ophthal. 1978, 207, 77
Graefes
688 in late September, this will mean that there is more than 1 chance in 20 that the outcome could have been due to chance alone. Thus, by blind application of statistics, one could not be sure that the Red Sox were the better team. But, as every true fan will tell you, "The Sox are just murderin’ them Yankees."
cant
WARD CASSCELLS STEPHANIE TAYLOR
Harvard Medical School, Boston, MA 02115, U.S.A.
SPERM BASIC PROTEINS IN CERVICAL
CARCINOGENESIS a study of the effects of chronic cannabis use on ultrastructure and histochemistry we found that arginine-rich protamines were greatly decreased in the nuclei of the users’ spermatozoa compared with controls.1 Material for the study was obtained from a population of chronic hashish users, who came largely from refugee families from Asia
SIR,-In
sperm
a working-class, low-income section of Athens. Controls were non-users, but tobacco smokers, and were matched to the users for age, refugee origin, upbringing, and low socioeconomic status. Dr Reid and his colleagues (July 8, p. 60) correlate low .socioeconomic status with a high ratio of arginine-rich protamines/somatic histones in the sperm of a large group of healthy males. They view their findings as a biochemical index linking cervical cancer with an accepted xtiological factor, low socioeconomic status. At first glance, it would seem that chronic hashish use by our subjects reversed the repercussions of low socioeconomic status on the basic protein ratio of their sperm nuclei. However, because tranquillisers reversibly increase, at least in peripheral blood-cells, certain histone basic protein fractions,2 I would suggest to the Australian and British groups of researchers that they screen their subjects for therapeutic and/or recreational use of psychotropic drugs as a factor to be correlated with their findings on sperm basic protein ratios. Such additional data would greatly contribute to the search for setiological factors in cervical cancer in particular, and oncogenesis in general. They would also help to define the limits of the much debated oncogenic potential of psycho-
Minor, residing in
tropic drugs. Department of Psychiatry, Neurobiology Research Laboratory, University of Athens, Eginition Hospital, Athens 603, Greece *Present address: Marine 02543, U S.A
MARIETTA R. ISSIDORIDES* Biological Laboratory, Woods Hole, Massachusetts
VITILIGO AND STEROIDS is often associated with autoimmune disease Hashimoto’s thyroiditis,3 and patients with vitiligo also 4 an increased incidence of organ-specific autoantibodies. found to react Despite this, autoantibodies are rarely against melanocytes in the skin, and then only in patients with polyendocrinopathy and skin lesion. We have seen a patient in whom prolonged treatment with corticosteroids produced complete remission of extensive vitiligo. The patient, a previously fit 73-year-old man, had had vitiligo for 20 years. His face was piebald and embarrassed him so much that he had used face make-up daily for more than 15 years. In 1976 he had a prolonged pyrexial illness with
SiK,—Vitiligo
such have
as
Stefanis, C. N., Issidorides, M. R. in Marihuana: Chemistry, Biochemistry, and Cellular Effects (edited G. G. Nahas); p. 533. New York, 1976. 2. Issidorides, M. R., Zioudrous, C., Lykouras, E., Stefanis, C. N. Progr. Neuro-Psychopharmac. 1978, 2, 79. 3. Doniach, D , Roitt, I. M in Clinical Aspects of Immunology (edited by P. G. H. Gell and R. R. A. Coombs). Oxford, 1968. 4. Brostoff, J , Bor, S., Feiwel M. Lancet, 1969, ii, 177 5. Hertz. K. C., Gazze, L. A., Kirkpatrick, C. H., Katz, S. I. New Engl. J. Med. 1977, 297, 639.
aches and pains for which no infectious cause could be found. His erythrocyte-sedimentation rate at that time was more than 100 mm in the first hour. Polymyalgia rheumatica was diagnosed, and he responded dramatically to prednisone, the initial dose being 30 mg daily. He was then maintained, free of symptoms, on 15 mg daily for a year (a lower dose leading to a recurrence of symptoms). He now takes Prednisone 4 mg daily. His vitiligo disappeared completely by the end of the first year of treatment and has not returned. It would seem that this patient’s vitiligo could have had an autoimmune basis as the recovery was so complete after his steroid treatment. There are other clinical situations, such as in pernicious ansemia, where steroid treatment can reverse the autoimmune process, leading to a fall in intrinsic-factor antibody and a return of the Schilling test to normal. This response lasts only as long as the steroids are given. Here, the balance of cell destruction due to the autoimmune process is tipped towards regeneration by the treatment. This seems to have happened in the patient we describe.
generalised
36 Eton Avenue, London NW3
Department
of
HARRY BROSTOFF
Immunology,
Middlesex Hospital Medical School, London W1
JONATHAN BROSTOFF
NALOXONE AS AN ANTAGONIST IN SEVERE ALCOHOL INTOXICATION 4
SIR,-Naloxone hydrochloride is
pure opiate antagonist in doses below 50 mg/kg.’ In humans the respiratory depression caused by opiates may be reversed by naloxone in doses of 5-10 In animals the depressant effects of barbiturates,23 benzodiazepines,4ethanol,5 and some inhalation anaesthetics6have also been reversed by naloxone, but the doses used were much higher (1-5 mg/kg) than those necessary to reverse opiate-induced respiratory depression in humans, suggesting that different mechanisms might be involved. The depleting effects of both morphine and ethanol on cerebral calcium levels, and their reversal by naloxone (1 mg/kg) in rats, have led to the suggestion that these two compounds share a common mechanism of action in the central nervous system.23 There are two case-reports of the reversal by small doses of naloxone (less than 25 g/kg) of coma in humans induced by diazepam alone4and by a combination of ethanol, barbiturate, and diazepam.5 We have recently observed reversal of coma with 0.8 mg naloxone in a patient, who was apparently intoxicated by ethanol only. A 43-year-old man had been out drinking with a friend and, when he returned home, his wife hit him on the head. When he fell asleep he could not be wakened soon after. On admission he was unconscious and he did not react to noxious stimuli. Blood-pressure was 180/80 mm Hg, pulse-rate was 124/min, breathing was slow with periods of apnoea. His breathing was assistedond intravenous saline was started. He had a superficial bruise in the right frontal region but neurological examination revealed no focal cerebral disease or increased intracranial pressure. Blood-sugar was 11-4 mmol/1 and plasma-bicarbonate was 21-3 mmol/l. He remained unconscious for 1-Lh. Because intoxication was a probable reason for the coma 0-4 mg naloxone was given intravenously. He began reacting to stimuli within a few minutes and when a a
ugkg.
1.
6. Ardeman, S., Chanarin, I. ibid. 1965, 273, 1352. 1. Blumberg, H , Dayton, H. B. in Agonist and Antagonist Actions of Narcotic Analgesic Drugs (edited by H. W Kosterlitz, H O. J. Collier, J. E. Villareal), p. 110, New York, 1973. 2 Ross, D.H , Medina, M. A, Cardenas, H.L. Science, 1974, 186, 63. 3. Ross, D H. Ann N.Y Acad. Sct. 1976, 273, 280. 4. Bell, E. F J. Pediat. 1975, 87, 803. 5. Moss, L.M.J. Am. Coll. Emergency Phys. 1973, 1, 46.
