1
504 erytheinato-papular rash, mainly over trunk and face, in his 2 cases. The 125 cases of lymphocytic meningo-encephalitis reported by Lyle (1956b) were similar to our cases, in particular in C.S.F. findings. 48 of his patients, however, had acute and severe myalagia ; and though only 24 had much neck stiffness, 68 had neurological abnormalities not encountered in our series. Some of Lyle’s cases also had hepatitis or abnormal liver-function tests. The disease as seen by us did not usually conform to McAlpine’s (1947) criteria of encephalitis (nystagmus, photophobia, and neck stiffness after fever and headache), as did the cases described by Lyle. Our series bears most resemblance to 24 cases described by Karzon et al. (1956) in the U.S.A., which was called " seasonal aseptic meningitis." The causal agent isolated from Karzon’s patients was Echo virus strain 6. Onset in July, household aggregation, and age-incidence were all similar to those observed here. The preponderance of males and the short duration of the epidemic described by Karzon might be accounted for by the localised outbreak in a closed community. There is little similarity between the condition described here and the outbreak at the Royal Free Hospital in 1955. Summary and Conclusions 100 patients suffering from an aseptic meningitis were admitted to the Leicester Isolation Hospital between July 4 and Nov. 23, 1956. The main clinical features of the disease were acute onset, headache, pyrexia, vomiting, neck and back rigidity, and occasionally a rubelliform rash and photophobia. A predominantly lymphocytic pleocytosis was found in the c.s.F. of most patients. Adenopathy was not a feature of the disease. All patients recovered without specific treatment, and with no serious sequelae. A cytopathogenic virus related to Echo virus type 9 was isolated from feces, C.S.F., and throat swabs in several cases. It is concluded that this essentially benign disease is probably not identical with Lyle’s lymphocytic meningo-encephalitis, but shows clinical similarity with cases described by Karzon and by Dodd. ADDENDUM Since the present survey was concluded, more cases of M.v.o., some of increased severity, have been admitted to this hospital. Monthly incidence is on the decline. I wish to thank Dr. J. C. H. Mackenzie, consultant and physician-superintendent, for permission to publish this paper and for his helpful criticism ; Dr. N. S. Mair and Dr. H. J. Mair for help and advice on virology : and Dr. J. P. Anderson and Dr. J. R. Barton for the use of some of their case-notes. BIBLIOGRAPHY Boissard, G. P. B., Stokes, L. J., Macrae, A. D., MacCallum, F. O. (1957) Lancet, i, 500. Dodd, W. (1956) Cited in Ibid, 1956, ii, 947. Eastwood, N. B. (1956) Practitioner, 177, 39. Hesling, G. (1956) Lancet, ii, 993. Karzon, O. T., Barron, A. L., Winkelstein, W. jun., Cohen, S. (1956) J. Amer. med. Ass. 162, 1298. Kelly, F. E. B. (1956) Practitioner, 177, 39. Lancet (1956) ii, 838. Lyle, W. H. (1956a) Ibid, p. 1042. — (1956b) Ibid, p. 1158. McAlpine, O. (1947) Proc. R. Soc. Med. 40, 929. Pickles, W. N. (1956) Lancet, ii, 1046. "... Would any one of us, taken with a grievous illness far from home, care to be nursed by a keen diagnostician, an amateur microscopist or an earnest student of pathology ? What we want is a nurse who loves nursing, and the sicker we are the more we long for someone who can combine wife, sister and mother rather than an efficient technician, however well intentioned. Knowledge of sick people is gained by being with sick people and though this knowledge once acquired can be greatly enhanced by book learning, that learning itself can not be a substitute for the bedside experience. The fine arts of nursing are only unimposing to those who have never themselves been gravely ill."-Dr. JOHN ZERNY and Dr. HUMPHRY OSMOND, Canad. 7red. Ass. J. 1956, 752, 75. METABOLIC EFFECTS OF CARBUTAMIDE IN SELECTED DIABETICS P. A. BASTENIE M.D. Brussels PROFESSOR OF CLINICAL MEDICINE R. DE MEUTTER M.D. Brussels ASSISTANT V. CONARD M.D. Brussels SENIOR ASSISTANT J. R. M. FRANCKSON M.D. Brussels ASSISTANT T. C. DEMANET M.D. Brussels ASSISTANT From the University Department of Medicine, St. Pierre Hospital, Brussels THE mechanism whereby certain sulphonamides exert a hypoglycsemic and (in certain diabetics) an anti. diabetic effect remains a matter of debate. The following explanations have been suggested: inhibition or destruction of glucagon-secreting a cells (Franke and Fuchs 1955, Mellinghoff 1955, You Holt et al. 1955, Ferner and Runge 1956) ; insulin sparing action (Kinsell et al. 1956, Mohnicke 1956); inhibition of insulinase (Mirsky 1956, Mirsky et al. 1956); increased production of insulin (Gepts et al. 1955, 1956, Loubatieres 1955, Ashworth and Haist 1956); depression of gluconeogenesis by a direct effect on the pituitary gland and the adrenal cortex ; and increased permeability of the cells to glucose, possibly due to release of an inhibitor of hexokinase (Best 1956). Although none of these hypotheses has been proved, in-vitro experiments have shown that hypoglycsemic drugs reduce the activity of certain enzyme systems in the liver (Clarke et al. 1956, Hawkins et al. 1956, Mohnicke and Knitsch 1956). Many diabetics have already been treated with oral sulphonamide, but the results show that sulphonamideis is no substitute for insulin and is only effective in "those subjects who possess a source of appreciable amounts of endogenous insulin " (Wrenshall and Best 1956). Only a few clinical studies concerned with metabolic investigations have been published. We report here such studies made on diabetics treated with carbutamide B.Z.55 ’). Material 18 patients were kept in hospital for a few weeks on a Fig. 1-.Intravenous glucose-tolerance curve in healthy people : a, mean of observed values ; b, semilogarithmic line derived from a. 1500-calorie diet (carbohydrates 180 g., fats 50 g., and proteins 80 g.), Afterwards they were under ambula- tory control with a slightly more liberal diet. Gross over- weight was reduced before the start of treatment. During the treatment the patients maintained their weight. After 1-3 months’ treat, ment the patients were readmitted for control metabolic studies. 16 of these pati- ents, aged 42-82, had diabetes of the middle-age onset type ; they had or

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504

erytheinato-papular rash, mainly over trunk and face,in his 2 cases.The 125 cases of lymphocytic meningo-encephalitis

reported by Lyle (1956b) were similar to our cases, inparticular in C.S.F. findings. 48 of his patients, however,had acute and severe myalagia ; and though only 24had much neck stiffness, 68 had neurological abnormalitiesnot encountered in our series. Some of Lyle’s cases alsohad hepatitis or abnormal liver-function tests. The diseaseas seen by us did not usually conform to McAlpine’s(1947) criteria of encephalitis (nystagmus, photophobia,and neck stiffness after fever and headache), as did thecases described by Lyle.

Our series bears most resemblance to 24 cases described

by Karzon et al. (1956) in the U.S.A., which was called" seasonal aseptic meningitis." The causal agent isolatedfrom Karzon’s patients was Echo virus strain 6. Onsetin July, household aggregation, and age-incidence wereall similar to those observed here. The preponderanceof males and the short duration of the epidemic describedby Karzon might be accounted for by the localisedoutbreak in a closed community.There is little similarity between the condition described

here and the outbreak at the Royal Free Hospital in 1955.

Summary and Conclusions100 patients suffering from an aseptic meningitis were

admitted to the Leicester Isolation Hospital betweenJuly 4 and Nov. 23, 1956. The main clinical featuresof the disease were acute onset, headache, pyrexia,vomiting, neck and back rigidity, and occasionally arubelliform rash and photophobia. A predominantlylymphocytic pleocytosis was found in the c.s.F. of mostpatients. Adenopathy was not a feature of the disease.All patients recovered without specific treatment, andwith no serious sequelae. A cytopathogenic virus relatedto Echo virus type 9 was isolated from feces, C.S.F.,and throat swabs in several cases. It is concluded thatthis essentially benign disease is probably not identicalwith Lyle’s lymphocytic meningo-encephalitis, but showsclinical similarity with cases described by Karzon andby Dodd.

ADDENDUM

Since the present survey was concluded, more cases ofM.v.o., some of increased severity, have been admitted tothis hospital. Monthly incidence is on the decline.

I wish to thank Dr. J. C. H. Mackenzie, consultant andphysician-superintendent, for permission to publish this

paper and for his helpful criticism ; Dr. N. S. Mair and Dr.H. J. Mair for help and advice on virology : and Dr. J. P.Anderson and Dr. J. R. Barton for the use of some of theircase-notes.

BIBLIOGRAPHY

Boissard, G. P. B., Stokes, L. J., Macrae, A. D., MacCallum, F. O.(1957) Lancet, i, 500.

Dodd, W. (1956) Cited in Ibid, 1956, ii, 947.Eastwood, N. B. (1956) Practitioner, 177, 39.Hesling, G. (1956) Lancet, ii, 993.Karzon, O. T., Barron, A. L., Winkelstein, W. jun., Cohen, S.

(1956) J. Amer. med. Ass. 162, 1298.Kelly, F. E. B. (1956) Practitioner, 177, 39.Lancet (1956) ii, 838.Lyle, W. H. (1956a) Ibid, p. 1042.

— (1956b) Ibid, p. 1158.McAlpine, O. (1947) Proc. R. Soc. Med. 40, 929.Pickles, W. N. (1956) Lancet, ii, 1046.

"... Would any one of us, taken with a grievous illness farfrom home, care to be nursed by a keen diagnostician, anamateur microscopist or an earnest student of pathology ?What we want is a nurse who loves nursing, and the sicker weare the more we long for someone who can combine wife, sisterand mother rather than an efficient technician, however wellintentioned. Knowledge of sick people is gained by being withsick people and though this knowledge once acquired can begreatly enhanced by book learning, that learning itself cannot be a substitute for the bedside experience. The fine artsof nursing are only unimposing to those who have neverthemselves been gravely ill."-Dr. JOHN ZERNY and Dr.HUMPHRY OSMOND, Canad. 7red. Ass. J. 1956, 752, 75.

METABOLIC EFFECTS OF CARBUTAMIDE

IN SELECTED DIABETICS

P. A. BASTENIEM.D. Brussels

PROFESSOR OF CLINICAL MEDICINE

R. DE MEUTTERM.D. Brussels

ASSISTANT

V. CONARDM.D. Brussels

SENIOR ASSISTANT

J. R. M. FRANCKSONM.D. Brussels

ASSISTANT

T. C. DEMANETM.D. Brussels

ASSISTANT

From the University Department of Medicine, St. Pierre Hospital,Brussels

THE mechanism whereby certain sulphonamides exerta hypoglycsemic and (in certain diabetics) an anti.diabetic effect remains a matter of debate.The following explanations have been suggested:

inhibition or destruction of glucagon-secreting a cells(Franke and Fuchs 1955, Mellinghoff 1955, YouHolt et al. 1955, Ferner and Runge 1956) ; insulinsparing action (Kinsell et al. 1956, Mohnicke 1956);inhibition of insulinase (Mirsky 1956, Mirsky et al. 1956);increased production of insulin (Gepts et al. 1955,1956, Loubatieres 1955, Ashworth and Haist 1956);depression of gluconeogenesis by a direct effect on thepituitary gland and the adrenal cortex ; and increasedpermeability of the cells to glucose, possibly due torelease of an inhibitor of hexokinase (Best 1956).

Although none of these hypotheses has been proved,in-vitro experiments have shown that hypoglycsemicdrugs reduce the activity of certain enzyme systems inthe liver (Clarke et al. 1956, Hawkins et al. 1956,Mohnicke and Knitsch 1956).Many diabetics have already been treated with oral

sulphonamide, but the results show that sulphonamideis isno substitute for insulin and is only effective in "thosesubjects who possess a source of appreciable amounts ofendogenous insulin

" (Wrenshall and Best 1956).Only a few clinical studies concerned with metabolic

investigations have been published. We report heresuch studies made on diabetics treated with carbutamideB.Z.55 ’).

Material

18 patients were kept in hospital for a few weeks on a

Fig. 1-.Intravenous glucose-tolerancecurve in healthy people : a, mean ofobserved values ; b, semilogarithmicline derived from a.

1500-calorie diet

(carbohydrates180 g., fats 50 g.,and proteins 80 g.),Afterwards theywere under ambula-tory control with aslightly more liberaldiet. Gross over-weight was reducedbefore the start oftreatment. Duringthe treatment the

patients maintainedtheir weight. After1-3 months’ treat,ment the patientswere readmitted forcontrol metabolicstudies.

16 of these pati-ents, aged 42-82,had diabetes of themiddle-age onset

type ; they had or