- Email: [email protected]
ANALYSIS OF PSYCHIATRIC DIAGNOSIS
153 shrunken liver. Light microscopy suggested the picture of fulminant atrophy. More details on the reported observations will be given elsewhere. The purpose of this letter is to draw attention to a simple technique, which has not hitherto been applied in " viral " hepatic coma, and the value of which seems comparable with that of more expensive and extensive, and not completely harmless, methods. Medical Clinic and Polyclinic and Department of Intensive Care, Academic Hospital of the State University,
Ghent, Belgium.
L. DEMEULENAERE F. BARBIER P. VERMEIRE.
CEREBRAL METABOLISM AFTER PORTACAVAL SHUNT wish to on the article by Dr. Read and comment SIR,-We his colleagues,! which underlines the frequency of neuropsychiatric abnormalities and electroencephalographic changes in patients with cirrhosis after portacaval anastomosis. Persistently high levels of ammonia in arterial blood is one of the most accepted pathogenetic factors; on this point Dr. Read and his colleagues report the value of prophylactic treatment with neomycin and a low-protein diet in preventing the development of neuropsychiatric abnormalities after portacaval anastomosis. We also support this view, and have noted the presence of cerebral metabolic disturbances early after shunt operation even in mentally alert and oriented patients. We have studied cerebral hxmodynamics and metabolism in 13 patients who had undergone portacaval anastomosis 1-10 months before. These patients at no time had signs of hepatic encephalopathy. Significantly high values of cerebral blood-flow were observed; this resultant increase in no way correlated with arterial PC02 and with hsmatocrit variations. In most cases, moreover, the cerebral metabolic rate of oxygen was slightly higher than normal, with an even greater increase in cerebral metabolic rate of glucose; as a consequence the glucose/oxygen cerebral quotient was significantly increased
(table I). Similar haemodynamic and metabolic results were found in 20 cirrhotic patients within 24 hours of the onset of hepatic coma or of an acute episode of encephalopathy. On the contrary, in patients with chronic coma or chronic encephalopathy there was a striking decrease in both cerebral blood-flow 1.
Read, A. E., McCarthy, C. F., Ajdukiewicz, Lancet, 1968, ii, 999.
A.
and cerebral metabolism (table n). It is worth while to underline the different behaviour of these indices in cirrhotic patients, mentally alert but previously submitted to portacavalshunt ; in these patients, in fact, high values of cerebral bloodflow and cerebral metabolic rate of glucose were found even 1 or 2 years after surgery. These results support the hypothesis that some modifications of brain metabolism occur within a short period after operation, and persist, even though no neuropsychiatric disturbances are clinically evident. We support the view that presumptive mechanism of this cerebral metabolic disorder is a partial glycolysis blockade by animation of oc-ketoglutarate to form glutamic acid and glutamine. In favour of this hypothesis, we have found increased cerebral metabolic uptake of ammonia in these clinical conditions in which there are often higher levels of ammonia in the arterial blood.2 Regarding the increase in cerebral blood-flow, an acceptable hypothesis is that it is the result of modified brain metabolic requirements. Cerebral blood-flow and cerebral metabolic rates of oxygen and glucose were determined by the methods of Kety and Schmidt.3 E. POLLI Istituto di Patologia, G. BIANCHI PORRO Medica e Metodologia Clinica, A. T. MAIOLO. University of Milan, Italy.
ANALYSIS OF PSYCHIATRIC DIAGNOSIS SIR,-Your leader on analysis of psychiatric diagnosis (Jan. " 4, p. 35), remarks that this present-day pastime is still somewhere in the 1760s ". If only it were: unfortunately it is too much in the 1880s. Your comparison is unfair-to the 18th century. The case-registers of this hospital-the erstwhile York Lunatic Asylum-reveal in the 1770s three groupings. These were " flighty ", " flighty and wild ", and "melancholy". Unfortunately, matters did not rest there. Encouraged by the success of this simple and easily understood classification (with no observer variation), the clinical practice of this hospital moved on to include other matters. For example, " furious "; and, as an indication of the first appearance of the problems of old age," loss of memory ". Worse was to come-as witness the arrival of the horrid and incomprehensible paraphrenias (systematica and confabulatoria, to name but a couple). 2.
B., Brown, G. J. A. 3.
Polli, E., Bianchi Porro, G., Della Porta, P., Maiolo, A. T. 68th Congress of the Society of Italian Internal Medicine (edited by L. Pozzi); p. 463. Rome, 1967. Kety, S. S., Schmidt, C. F. J. clin. Invest. 1948, 27, 476.
TABLE I-CEREBRAL HMMODYNAMICS AND METABOLISM IN 12 NORMAL SUBJECTS, 20 MENTALLY ALERT PATIENTS WITH HEPATIC values ± S.D.) CIRRHOSIS, AND 13 PATIENTS WITH HEPATIC CIRRHOSIS AFTER PORTACAVAL SHUNT
(mean
* r<0·001. t0-05>p>0-025. t0-02>p>0-01. c.s.F.=cerebral blood-flow (ml./lOO g. tissue/min.); C.v.x.=cerebral vascular resistances (mm. Hg/ml./100 of oxygen (ml./100 g./min.) ; C.M.R.G. = cerebral metabolic rate of glucose (mg.J100 g./min.) ; c.G./O Q. =cerebral
g./min.); c.m.R.0 =cerebral metabolic glucose/oxygen quotient.
TABLE II-CEREBRAL HaeMODYNAMICS AND METABOLISM IN 13 PATIENTS ON, AND 28 PATIENTS AFTER, FIRST DAY OF HEPATIC 7 PATIENTS WITH ACUTE AND 9 WITH CHRONIC ENCEPHALOPATHY (mean values S.D.)
Abbreviations as in table *P<0.001. p
i.
rate
COMA,
154
Finally, we have reached, as you observe, the complexities and misunderstandings of the International Classification. I must further defend my predecessors of the 18th century by pointing out that they did not use the presumptuous term diagnosis ". In what was doubtless a prescient and graceful anticipatory compliment to the work of Wing et al. on presentstate examination ", to which you refer, they contented themselves with the simple heading " state of mind ". (They did "
"
the term, to which you also refer, " mental status schedule ". At the time this hospital was founded the American Revolution then in progress had not made its full contribution to our nomenclature.) Unaware of the difficulties inherent in the terms " diagnosis ", " rehabilitation ", or " community care ", they concentrated their efforts on what they were pleased to call the " reception and relief " of the mentally ill. not use
Bootham Park, York.
ARTHUR BOWEN.
SIGNIFICANCE OF ADRENERGIC INNERVATION OF THE BLADDER OUTLET DURING
EJACULATION SIR,—Part of the urogenital tract receives its postganglionic sympathetic nerve-supply from short adrenergic neurons arising in ganglia near or within the effector organs 1-4 (fig. 1). These neurons differ from the ordinary long adrenergic nerves 1. 2. 3. 4.
Hamberger, B., Norberg, K.-A. Acta physiol. scand. 1965, 65, 235. Owman, Ch., Sjöstrand, N. O. Z. Zellforsch. mikrosk. Anat. 1965, 66, 300. Owman, Ch., Owman, T., Sjöberg, N.-O. Acta physiol. scand. 1968 (in the press). Baumgarten, H. G., Falck, B., Holstein, A.-F., Owman, Ch., Owman, T. Z. Zellforsch. mikrosk. Anat. 1968, 90, 81.
originating in prevertebral and paravertebral sympathetic ganglia in the rate of transmitter release.5-’ The very dense adrenergic innervation of the vas deferens, the seminal vesicle, and probably also the prostate, is thought to have an important role in the emission of semen during ejaculation.24 However, the functional significance of the rich sympathetic nerve-supply, notably by short adrenergic neurons, to the trigonum area of the bladder1 and the smooth muscles of the urethra9 is not clear. Our observations on a patient with retrograde ejaculation may contribute to the understanding of these adrenergic mechanisms. Retrograde ejaculation in man is most probably due to failure of the internal urethral sphincter apparatus to close the outlet of the bladder during the sexual act, thus permitting semen to be shot backwards into the urinary bladder. This rare condition is seen most often after prostatic surgery or in diabetic neuropathy. We have found retrograde ejaculation in a man who has never undergone prostatic surgery and who has a normal glucoseload test. Clinical investigation showed aplasia of the right kidney, absence of the right testicle, a small prostate, and an abnormally configurated proximal urethra (fig. 2). Since the motor function of the bladder was normal, and since the internal sphincter is not morphologically separate from the detrusor muscle, it seems most probable that the dysfunction is due to a defect of sympathetic innervation rather than absence of muscular elements in the sphincter apparatus. In view of the abnormal route of transport of the semen in this patient, it can be assumed that the malformation of the urethra involves absence of the intramural adrenergic ganglia in the smooth muscle of the internal sphincter-i.e., in the bladder trigonum, the proximal urethra, and probably also in the prostate. The short adrenergic neurons arising outside the genital organs and supplying the vas deferens and seminal vesicle are presumably intact. Thus, the sympathetic innervation of the bladder trigonum and the proximal urethra seems to control the closing mechanism of the bladder outlet during ejaculation, normally directing the semen through the distal urethra. This investigation was supported by a Ford Foundation grant, no.
68-383.
Department of Obstetrics and Gynæcology General Hospital, Malmö. Institute of Anatomy and Histology, University of Lund. Department of Diagnostic Radiology, General Hospital, Malmö, Sweden.
GERHARD GENNSER. CHRISTER OWMAN TORBEN OWMAN. LENNART WEHLIN.
5. Von Euler, U. S., Lishajko, F. Life Sci. 1966, 5, 687. 6. Owman, Ch., Sjoberg, N.-O. ibid. 1967, 6, 2549. 7. Sjöstrand, N. O., Swedin, G. Acta physiol. scand. 1968, 8. Owman, Ch. Unpublished.
72,
370.
Fig. 1-Sympathetic innervations of the lower urogenital tract, as studied by fluorescence microscopy of the adrenergic transmitter and by denervation. Neurons 1-3 supply the bladder trigonum. The rest of the bladder wall has only a poor adrenergic innervation.
(1) Adrenergic nerves arising in inferior mesenganglion (presacral plexus) to run down the hypogastric nerves (cat 1). (2) Short adrenergic neurons originating in intramural ganglia (cat,! macaque 8). (3) Adrenergic nerves from paravertebral sympathetic ganglia S1-S3 to run in the pelvic nerve (cat 1). (4) Intramural ganglia giving rise to
teric
adrenergic neurons in the urethra (female 3). (5) Short adrenergic neurons in the prostatic smooth muscle (macaque,2man 4). (6) Short adrenergic neurons arising in ganglia near accessory male genital organs and supplying vas deferens with very dense adrenergic nerve plexus (macaque,22 man 4). short cat
Fig. 2-Urethrocystograms, retrograde injection of the contrast medium. A. Frontal projection. B. Oblique projection. Abnormal course and configuration the prostatic part of the urethra indicated by arrows.
of
Ghent, Belgium.
L. DEMEULENAERE F. BARBIER P. VERMEIRE.
CEREBRAL METABOLISM AFTER PORTACAVAL SHUNT wish to on the article by Dr. Read and comment SIR,-We his colleagues,! which underlines the frequency of neuropsychiatric abnormalities and electroencephalographic changes in patients with cirrhosis after portacaval anastomosis. Persistently high levels of ammonia in arterial blood is one of the most accepted pathogenetic factors; on this point Dr. Read and his colleagues report the value of prophylactic treatment with neomycin and a low-protein diet in preventing the development of neuropsychiatric abnormalities after portacaval anastomosis. We also support this view, and have noted the presence of cerebral metabolic disturbances early after shunt operation even in mentally alert and oriented patients. We have studied cerebral hxmodynamics and metabolism in 13 patients who had undergone portacaval anastomosis 1-10 months before. These patients at no time had signs of hepatic encephalopathy. Significantly high values of cerebral blood-flow were observed; this resultant increase in no way correlated with arterial PC02 and with hsmatocrit variations. In most cases, moreover, the cerebral metabolic rate of oxygen was slightly higher than normal, with an even greater increase in cerebral metabolic rate of glucose; as a consequence the glucose/oxygen cerebral quotient was significantly increased
(table I). Similar haemodynamic and metabolic results were found in 20 cirrhotic patients within 24 hours of the onset of hepatic coma or of an acute episode of encephalopathy. On the contrary, in patients with chronic coma or chronic encephalopathy there was a striking decrease in both cerebral blood-flow 1.
Read, A. E., McCarthy, C. F., Ajdukiewicz, Lancet, 1968, ii, 999.
A.
and cerebral metabolism (table n). It is worth while to underline the different behaviour of these indices in cirrhotic patients, mentally alert but previously submitted to portacavalshunt ; in these patients, in fact, high values of cerebral bloodflow and cerebral metabolic rate of glucose were found even 1 or 2 years after surgery. These results support the hypothesis that some modifications of brain metabolism occur within a short period after operation, and persist, even though no neuropsychiatric disturbances are clinically evident. We support the view that presumptive mechanism of this cerebral metabolic disorder is a partial glycolysis blockade by animation of oc-ketoglutarate to form glutamic acid and glutamine. In favour of this hypothesis, we have found increased cerebral metabolic uptake of ammonia in these clinical conditions in which there are often higher levels of ammonia in the arterial blood.2 Regarding the increase in cerebral blood-flow, an acceptable hypothesis is that it is the result of modified brain metabolic requirements. Cerebral blood-flow and cerebral metabolic rates of oxygen and glucose were determined by the methods of Kety and Schmidt.3 E. POLLI Istituto di Patologia, G. BIANCHI PORRO Medica e Metodologia Clinica, A. T. MAIOLO. University of Milan, Italy.
ANALYSIS OF PSYCHIATRIC DIAGNOSIS SIR,-Your leader on analysis of psychiatric diagnosis (Jan. " 4, p. 35), remarks that this present-day pastime is still somewhere in the 1760s ". If only it were: unfortunately it is too much in the 1880s. Your comparison is unfair-to the 18th century. The case-registers of this hospital-the erstwhile York Lunatic Asylum-reveal in the 1770s three groupings. These were " flighty ", " flighty and wild ", and "melancholy". Unfortunately, matters did not rest there. Encouraged by the success of this simple and easily understood classification (with no observer variation), the clinical practice of this hospital moved on to include other matters. For example, " furious "; and, as an indication of the first appearance of the problems of old age," loss of memory ". Worse was to come-as witness the arrival of the horrid and incomprehensible paraphrenias (systematica and confabulatoria, to name but a couple). 2.
B., Brown, G. J. A. 3.
Polli, E., Bianchi Porro, G., Della Porta, P., Maiolo, A. T. 68th Congress of the Society of Italian Internal Medicine (edited by L. Pozzi); p. 463. Rome, 1967. Kety, S. S., Schmidt, C. F. J. clin. Invest. 1948, 27, 476.
TABLE I-CEREBRAL HMMODYNAMICS AND METABOLISM IN 12 NORMAL SUBJECTS, 20 MENTALLY ALERT PATIENTS WITH HEPATIC values ± S.D.) CIRRHOSIS, AND 13 PATIENTS WITH HEPATIC CIRRHOSIS AFTER PORTACAVAL SHUNT
(mean
* r<0·001. t0-05>p>0-025. t0-02>p>0-01. c.s.F.=cerebral blood-flow (ml./lOO g. tissue/min.); C.v.x.=cerebral vascular resistances (mm. Hg/ml./100 of oxygen (ml./100 g./min.) ; C.M.R.G. = cerebral metabolic rate of glucose (mg.J100 g./min.) ; c.G./O Q. =cerebral
g./min.); c.m.R.0 =cerebral metabolic glucose/oxygen quotient.
TABLE II-CEREBRAL HaeMODYNAMICS AND METABOLISM IN 13 PATIENTS ON, AND 28 PATIENTS AFTER, FIRST DAY OF HEPATIC 7 PATIENTS WITH ACUTE AND 9 WITH CHRONIC ENCEPHALOPATHY (mean values S.D.)
Abbreviations as in table *P<0.001. p
i.
rate
COMA,
154
Finally, we have reached, as you observe, the complexities and misunderstandings of the International Classification. I must further defend my predecessors of the 18th century by pointing out that they did not use the presumptuous term diagnosis ". In what was doubtless a prescient and graceful anticipatory compliment to the work of Wing et al. on presentstate examination ", to which you refer, they contented themselves with the simple heading " state of mind ". (They did "
"
the term, to which you also refer, " mental status schedule ". At the time this hospital was founded the American Revolution then in progress had not made its full contribution to our nomenclature.) Unaware of the difficulties inherent in the terms " diagnosis ", " rehabilitation ", or " community care ", they concentrated their efforts on what they were pleased to call the " reception and relief " of the mentally ill. not use
Bootham Park, York.
ARTHUR BOWEN.
SIGNIFICANCE OF ADRENERGIC INNERVATION OF THE BLADDER OUTLET DURING
EJACULATION SIR,—Part of the urogenital tract receives its postganglionic sympathetic nerve-supply from short adrenergic neurons arising in ganglia near or within the effector organs 1-4 (fig. 1). These neurons differ from the ordinary long adrenergic nerves 1. 2. 3. 4.
Hamberger, B., Norberg, K.-A. Acta physiol. scand. 1965, 65, 235. Owman, Ch., Sjöstrand, N. O. Z. Zellforsch. mikrosk. Anat. 1965, 66, 300. Owman, Ch., Owman, T., Sjöberg, N.-O. Acta physiol. scand. 1968 (in the press). Baumgarten, H. G., Falck, B., Holstein, A.-F., Owman, Ch., Owman, T. Z. Zellforsch. mikrosk. Anat. 1968, 90, 81.
originating in prevertebral and paravertebral sympathetic ganglia in the rate of transmitter release.5-’ The very dense adrenergic innervation of the vas deferens, the seminal vesicle, and probably also the prostate, is thought to have an important role in the emission of semen during ejaculation.24 However, the functional significance of the rich sympathetic nerve-supply, notably by short adrenergic neurons, to the trigonum area of the bladder1 and the smooth muscles of the urethra9 is not clear. Our observations on a patient with retrograde ejaculation may contribute to the understanding of these adrenergic mechanisms. Retrograde ejaculation in man is most probably due to failure of the internal urethral sphincter apparatus to close the outlet of the bladder during the sexual act, thus permitting semen to be shot backwards into the urinary bladder. This rare condition is seen most often after prostatic surgery or in diabetic neuropathy. We have found retrograde ejaculation in a man who has never undergone prostatic surgery and who has a normal glucoseload test. Clinical investigation showed aplasia of the right kidney, absence of the right testicle, a small prostate, and an abnormally configurated proximal urethra (fig. 2). Since the motor function of the bladder was normal, and since the internal sphincter is not morphologically separate from the detrusor muscle, it seems most probable that the dysfunction is due to a defect of sympathetic innervation rather than absence of muscular elements in the sphincter apparatus. In view of the abnormal route of transport of the semen in this patient, it can be assumed that the malformation of the urethra involves absence of the intramural adrenergic ganglia in the smooth muscle of the internal sphincter-i.e., in the bladder trigonum, the proximal urethra, and probably also in the prostate. The short adrenergic neurons arising outside the genital organs and supplying the vas deferens and seminal vesicle are presumably intact. Thus, the sympathetic innervation of the bladder trigonum and the proximal urethra seems to control the closing mechanism of the bladder outlet during ejaculation, normally directing the semen through the distal urethra. This investigation was supported by a Ford Foundation grant, no.
68-383.
Department of Obstetrics and Gynæcology General Hospital, Malmö. Institute of Anatomy and Histology, University of Lund. Department of Diagnostic Radiology, General Hospital, Malmö, Sweden.
GERHARD GENNSER. CHRISTER OWMAN TORBEN OWMAN. LENNART WEHLIN.
5. Von Euler, U. S., Lishajko, F. Life Sci. 1966, 5, 687. 6. Owman, Ch., Sjoberg, N.-O. ibid. 1967, 6, 2549. 7. Sjöstrand, N. O., Swedin, G. Acta physiol. scand. 1968, 8. Owman, Ch. Unpublished.
72,
370.
Fig. 1-Sympathetic innervations of the lower urogenital tract, as studied by fluorescence microscopy of the adrenergic transmitter and by denervation. Neurons 1-3 supply the bladder trigonum. The rest of the bladder wall has only a poor adrenergic innervation.
(1) Adrenergic nerves arising in inferior mesenganglion (presacral plexus) to run down the hypogastric nerves (cat 1). (2) Short adrenergic neurons originating in intramural ganglia (cat,! macaque 8). (3) Adrenergic nerves from paravertebral sympathetic ganglia S1-S3 to run in the pelvic nerve (cat 1). (4) Intramural ganglia giving rise to
teric
adrenergic neurons in the urethra (female 3). (5) Short adrenergic neurons in the prostatic smooth muscle (macaque,2man 4). (6) Short adrenergic neurons arising in ganglia near accessory male genital organs and supplying vas deferens with very dense adrenergic nerve plexus (macaque,22 man 4). short cat
Fig. 2-Urethrocystograms, retrograde injection of the contrast medium. A. Frontal projection. B. Oblique projection. Abnormal course and configuration the prostatic part of the urethra indicated by arrows.
of