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TREATMENT OF HEPATIC ENCEPHALOPATHY BY ALTERATION OF INTESTINAL FLORA WITH LACTOBACILLUS ACIDOPHILUS
764
(menstrual cycle), while other mammals bleed around the time of ovulation (oestrus cycle),u Since steroid hormones are inactivated mainly in the liver, there must be a possibility that hepatic dysfunction entails disturbances of the endocrine balance and, secondarily, changes of carbohydrate, protein, and electrolyte metabolism. The significance of a portocaval shunt in this connection is increased by the fact that after biliary excretion the steroid hormones re-circulate in the entero-hepatic circulation. Thus, a portocaval collateral circulation might-in part primarily and in part because of interference with endocrine feedback processes-be the underlying reason for the abnormally wide range of many biological parameters which constitute one of the most constant findings in schizophrenia.12 Department of Medicine, De Gamles By, J. KRØLL. Copenhagen, Denmark. DIABETES INSIPIDUS AND OBSESSIONAL NEUROSIS
SIR,-Dr. Barton (Jan. 16) described the histories of patients with obsessional neurosis associated with a syndrome of compulsive water-drinking, but did not elaborate on the well-documented metabolic characteristics of patients with psychogenic polydipsia.
My colleagues and I 13 severe personality disorder
have described a young man with who consumed and passed, without apparent concern, up to 40 litres of fluid daily. He was admitted for evaluation of a possible brain tumour manifesting as diabetes insipidus. Important in this patient’s history was the fact that he had no preference for iced fluids." Most persons with true diabetes insipidus desire cold liquids.
In summary, patients presenting with marked polydipsia and polyuria who (1) have a psychoneurotic disorder (2) have no preference for iced fluids, and (3)
respond by antidiuresis and/or water deprivation
to are
hypertonic saline, nicotine, likely to have the syndrome
of diabetes insipidus and obsessional neurosis. Department of Medicine, Lahey Clinic Foundation, Boston, Massachusetts, U.S.A.
LEONARD E. REAVES,
III.
TREATMENT OF HEPATIC ENCEPHALOPATHY BY ALTERATION OF INTESTINAL FLORA WITH LACTOBACILLUS ACIDOPHILUS
SIR,-We were interested to read the report of Mr. Macbeth and his colleagues (Feb. 20) because three patients with this condition have been treated here with
’Enpac’ (Lloyd-Hamol, Ltd.), of Lactobaccillus acidophilus.
a
commercial
preparation
an effect on the bowel flora, factor in the treatment of hepatic important encephalopathy. J. C. B. FENTON E. J. KNIGHT St. Bartholomew’s Hospital, F. W. O’GRADY. E.C.1. London,
diet, perhaps partly through is
an
READING, WRITING, AND WRITHING SIR,—With reference to last week’s annotation
on
Sir
Theodore Fox’s Heath Clark lectures: Amen! Central Public Health Laboratory, London, N.W.9.
J. C. KELSEY.
USE OF MONOAMINE-OXIDASE INHIBITORS
SIR,-Professor Burn’s suggestion (March 13) that L-3, 4-dihydroxyphenyl alanine (L-dopa) should be given to depressed patients in combination with monoamine-oxidase (M.A.O.) inhibitors must be accepted by clinicians only with considerable caution.
orally
Normally the amine derivatives of dopa (dopamine and noradrenaline) are rapidly inactivated after oral loading with the aminoacid, and there are no significant rises of bloodpressure. Under the influence of M.A.O. inhibitors, however, this inactivation happens only slowly, and pressor effects may be noted after 50 mg. doses of dopa.! I have studied the effect on urinary amine excretion of oral dopa in normal subjects receiving an M.A.o. inhibitor (pargyline, 50 mg. daily). The pressor response under these circumstances is unpredictable, but in the fasting state may be considerable. One subject who showed no pressor phase after 400 mg. dopa reacted severely to a dose of 600 mg. (as shown in the accompanying figure). The blood-pressure rose from 120/80 mm. Hg to 204/104 at 55 minutes from the time of dopa ingestion, and prevention of further rise was achieved only by the intravenous administration of phentolamine (’ Rogitine ’) in a total dosage of 30 mg. At the time of maximal effect there were symptoms of throbbing in the head and neck, pounding in the chest, and apprehension, and the electrocardiogram showed an atrial arrhythmia together with marked T-wave elevation. Blood-pressure levels of up to 240/150, with similar symptoms, have been reported by Klerman et al.2 Clear evidence that dopa, with or without M.A.o. inhibitors, has a beneficial effect in depressive states is still lacking. Even if this were available the combination has sufficient potential danger to be avoided in routine therapeutics, and should be used only where 1.
2.
Schildkraut, J. J., Klerman, G. L., Friend, D. G., Greenblatt, M. Ann. N. Y. Acad. Sci. 1963, 107, 1005. Klerman, G. L., Schildkraut, J. J., Hasenbush, L. L., Greenblatt, M., Friend, D G. J. psychiat. Res. 1963, 1, 289.
Interest in this organism arose from an observation that a patient with hepatic encephalopathy was much improved when on a diet containing milk and cheese protein. It seemed that this might be due, in part, to the resulting change in ftcal flora, and trials of enpac were therefore made. In the first case, a patient being treated with neomycin and protein restriction developed diarrhoea associated with grossly abnormal faecal flora. The neomycin was discontinued and treatment begun with enpac, 6 g. four times daily, but the diarrhoea continued for a further 48 hours in which time there was an episode of encephalopathy. As the diarrhoea diminished, the patient’s mental state improved; and on this treatment she continued to make sufficiently good progress to be discharged week later. Two further patients have since been treated with short courses of enpac: in one this treatment appeared to cause a fall m the plasma ammonia, but in the second there was no obvious
a
benefit.
We are 11. 12 13. 14
at
present
preparing
a
report
showing that
Turner, C. D. General Endocrinology. Philadelphia, Reiss, M. Psychoendocrinology. New York, 1958. Reaves, L. E. J. Neurosurg. (in the press). Thomas, W. C., Jr. J. clin. Endocrin. 1957, 17, 565.
1948
Blood-pressure changes after single oral dose subject receiving pargyline (50 mg. daily).
of L-dopa in
a
normal
Phentolamine (’ Rogitine ’) was given intravenously in three separate doses of 5, 10, and 15 mg. at the times shown.
(menstrual cycle), while other mammals bleed around the time of ovulation (oestrus cycle),u Since steroid hormones are inactivated mainly in the liver, there must be a possibility that hepatic dysfunction entails disturbances of the endocrine balance and, secondarily, changes of carbohydrate, protein, and electrolyte metabolism. The significance of a portocaval shunt in this connection is increased by the fact that after biliary excretion the steroid hormones re-circulate in the entero-hepatic circulation. Thus, a portocaval collateral circulation might-in part primarily and in part because of interference with endocrine feedback processes-be the underlying reason for the abnormally wide range of many biological parameters which constitute one of the most constant findings in schizophrenia.12 Department of Medicine, De Gamles By, J. KRØLL. Copenhagen, Denmark. DIABETES INSIPIDUS AND OBSESSIONAL NEUROSIS
SIR,-Dr. Barton (Jan. 16) described the histories of patients with obsessional neurosis associated with a syndrome of compulsive water-drinking, but did not elaborate on the well-documented metabolic characteristics of patients with psychogenic polydipsia.
My colleagues and I 13 severe personality disorder
have described a young man with who consumed and passed, without apparent concern, up to 40 litres of fluid daily. He was admitted for evaluation of a possible brain tumour manifesting as diabetes insipidus. Important in this patient’s history was the fact that he had no preference for iced fluids." Most persons with true diabetes insipidus desire cold liquids.
In summary, patients presenting with marked polydipsia and polyuria who (1) have a psychoneurotic disorder (2) have no preference for iced fluids, and (3)
respond by antidiuresis and/or water deprivation
to are
hypertonic saline, nicotine, likely to have the syndrome
of diabetes insipidus and obsessional neurosis. Department of Medicine, Lahey Clinic Foundation, Boston, Massachusetts, U.S.A.
LEONARD E. REAVES,
III.
TREATMENT OF HEPATIC ENCEPHALOPATHY BY ALTERATION OF INTESTINAL FLORA WITH LACTOBACILLUS ACIDOPHILUS
SIR,-We were interested to read the report of Mr. Macbeth and his colleagues (Feb. 20) because three patients with this condition have been treated here with
’Enpac’ (Lloyd-Hamol, Ltd.), of Lactobaccillus acidophilus.
a
commercial
preparation
an effect on the bowel flora, factor in the treatment of hepatic important encephalopathy. J. C. B. FENTON E. J. KNIGHT St. Bartholomew’s Hospital, F. W. O’GRADY. E.C.1. London,
diet, perhaps partly through is
an
READING, WRITING, AND WRITHING SIR,—With reference to last week’s annotation
on
Sir
Theodore Fox’s Heath Clark lectures: Amen! Central Public Health Laboratory, London, N.W.9.
J. C. KELSEY.
USE OF MONOAMINE-OXIDASE INHIBITORS
SIR,-Professor Burn’s suggestion (March 13) that L-3, 4-dihydroxyphenyl alanine (L-dopa) should be given to depressed patients in combination with monoamine-oxidase (M.A.O.) inhibitors must be accepted by clinicians only with considerable caution.
orally
Normally the amine derivatives of dopa (dopamine and noradrenaline) are rapidly inactivated after oral loading with the aminoacid, and there are no significant rises of bloodpressure. Under the influence of M.A.O. inhibitors, however, this inactivation happens only slowly, and pressor effects may be noted after 50 mg. doses of dopa.! I have studied the effect on urinary amine excretion of oral dopa in normal subjects receiving an M.A.o. inhibitor (pargyline, 50 mg. daily). The pressor response under these circumstances is unpredictable, but in the fasting state may be considerable. One subject who showed no pressor phase after 400 mg. dopa reacted severely to a dose of 600 mg. (as shown in the accompanying figure). The blood-pressure rose from 120/80 mm. Hg to 204/104 at 55 minutes from the time of dopa ingestion, and prevention of further rise was achieved only by the intravenous administration of phentolamine (’ Rogitine ’) in a total dosage of 30 mg. At the time of maximal effect there were symptoms of throbbing in the head and neck, pounding in the chest, and apprehension, and the electrocardiogram showed an atrial arrhythmia together with marked T-wave elevation. Blood-pressure levels of up to 240/150, with similar symptoms, have been reported by Klerman et al.2 Clear evidence that dopa, with or without M.A.o. inhibitors, has a beneficial effect in depressive states is still lacking. Even if this were available the combination has sufficient potential danger to be avoided in routine therapeutics, and should be used only where 1.
2.
Schildkraut, J. J., Klerman, G. L., Friend, D. G., Greenblatt, M. Ann. N. Y. Acad. Sci. 1963, 107, 1005. Klerman, G. L., Schildkraut, J. J., Hasenbush, L. L., Greenblatt, M., Friend, D G. J. psychiat. Res. 1963, 1, 289.
Interest in this organism arose from an observation that a patient with hepatic encephalopathy was much improved when on a diet containing milk and cheese protein. It seemed that this might be due, in part, to the resulting change in ftcal flora, and trials of enpac were therefore made. In the first case, a patient being treated with neomycin and protein restriction developed diarrhoea associated with grossly abnormal faecal flora. The neomycin was discontinued and treatment begun with enpac, 6 g. four times daily, but the diarrhoea continued for a further 48 hours in which time there was an episode of encephalopathy. As the diarrhoea diminished, the patient’s mental state improved; and on this treatment she continued to make sufficiently good progress to be discharged week later. Two further patients have since been treated with short courses of enpac: in one this treatment appeared to cause a fall m the plasma ammonia, but in the second there was no obvious
a
benefit.
We are 11. 12 13. 14
at
present
preparing
a
report
showing that
Turner, C. D. General Endocrinology. Philadelphia, Reiss, M. Psychoendocrinology. New York, 1958. Reaves, L. E. J. Neurosurg. (in the press). Thomas, W. C., Jr. J. clin. Endocrin. 1957, 17, 565.
1948
Blood-pressure changes after single oral dose subject receiving pargyline (50 mg. daily).
of L-dopa in
a
normal
Phentolamine (’ Rogitine ’) was given intravenously in three separate doses of 5, 10, and 15 mg. at the times shown.