ORGANIC DISEASE IN GASTROINTESTINAL PATIENTS

1329

enkephalin preabsorbed with 1 mg/ml of the corresponding antigen (Sigma). Fluorescence microscopy

was done on a Leitz ’Dialux 20 EB’ microscope with

epi-illumination. No enkephalin-positive immunoreactivity was observed and the immunocytochemical controls were negative. Substance-P-positive immunoreactivity was noted in a few nerve terminals, typically possessing an irregular, glomerular-like structure (figure). No solitary nerve fibres with substance-P-like immunoreactivity were found in the present material. The substance-P-positive fibres could be followed through in serial sections and they were all inside the glomerular structures. Large concentrations of substance P have been found in the dorsal horn of the spinal cord and it is much depleted from this site after dorsal root sectioning.Substance P is present in those fibres of the dorsal spinal horns which transmit nociceptive stimuli.9no On the

other hand, substance P excites those neurons of the dorsal horn which respond to painful stimuli of the skin. 11Substance P may be an excitatory agent in spinal pathways mediating pain, acting perhaps at the first afferent synapse. 12 Our findings are compatible with this suggestion, but not with the earlier proposal on the nociceptive character of the free nerve terminals. We suggest a sensory, perhaps nociceptive, character of the glomerular complex nerve endings. It seems reasonable to suggest that substance P is involved in the primary pain transmission of low back pain

syndrome. PÄIVI LIESI MATS GRÖNBLAD OLLI KORKALA ERKKI KARAHARJU MATTI RUSANEN

Department of Orthopaedics and Traumatology, University Central Hospital, 00260 Helsinki

26, Finland; Department of Virology, of Helsinki University and

Identification of substance P in nerve terminal in posterior longitudinal ligament. Upper: immunocytochemical pattern. Lower: same area under phase-contrast microscopy. Corresponding sites (an area with the maximal immunoreactivity) are marked with arrowheads (x 240).

layers of the annuli fibrosi. A full low back pain syndrome can be evoked by injection of hypertonic saline into the annulus fibrosusi or by a distraction of the posterior longitudinal ligament and the posterior layers of the annulus fibrosus.2 One suggestion is that low back pain is often the result of increased intradiscal irritating nearby sensory nociceptive nerve The characteristics of these terminals in the posterior terminals. pressure, longitudinal ligament and annulus fibrosus are not fully known. Histological appearances suggest that some might act as pain receptors, some as mechanoreceptors. The possible sensory outermost

transmitter is unknown. Substance P may be involved in pain pathways.Thus, detection of immunoreactivity for substance P in the nerve terminals of the sinovertebral nerve would strongly suggest involvement of this neuropeptide in the pain transmission of the low back pain

syndrome. Small (1 pl) samples of the posterior longitudinal ligament were taken from five patients during operations for sciatica of the fifth lumbar or first sacral nerve roots and fixed immediately in paraformaldehyde in phosphate buffered saline for 24 h, rinsed in phosphate buffered saline overnight, and cut in 6 11m thick cryostat sections. The sections were processed for immunocytochemical detection5 of substance P and leucine and methionine Antibodies (kindly donated by Dr J. M. Polak, Hammersmith Hospital, London) were used in dilutions of 1:500 and the sections were incubated with the primary antisera overnight at 4°G. After a rinse in phosphate buffered saline the sections were incubated with sheep anti-rabbit immunoglobulins coupled to fluorescein isothiocyanate (Wellcome) diluted 1:20. These antibodies are specific. Immunocytochemical controls included omission of one of the two antibodies and incubation with anti-substance P or anti-leu/met-

enkephalin.6

C, Ingelmark B-E, Miller M.The anatomical basis for low back pain. Acta Orthop Scand 1963; 33: 1-17. 2. Smyth MJ, Wright VJ. Sciatica and the intervertebral disc: an experimental study Clin Orthoped Res 1977; 129: 9-21 3. Armstrong JR. Lumbar disc herniations. Edinburgh: E & S Livingstone, 1958. 4. Turek SL. Orthopedics: Principles and their application. Philadelphia: JB Lippincott, 1. Hirsch

1977.

5.

Jessell

TM. Pain Lancet

1982; ii: 1084-87.

ORGANIC DISEASE IN GASTROINTESTINAL PATIENTS

SIR,-Dr Harvey and colleagues’ survey (March 19, p 632) of the prevalence of organic and functional disorders in 2000 patients attending two hospitals in Bristol provides information on gastrointestinal outpatients in England which is otherwise unavailable. A similar prospective survey was done in Kingston, Jamaica,1on all patients aged twelve or more presenting to the one gastrointestinal physician at the University Hospital of the West Indies. In two years, 807 patients were seen-333 (41%) inpatients and 474 (59%) outpatients. Sometimes more than one diagnosis was made. (Of the 1139 diagnoses 866 were primarily gastroenterological, 211 were significantly associated with other disease or the patient had disease which involved primarily a non-gastrointestinal system, and 62 had no proven disease). While multiple diagnoses were avoided, this principle could not be strictly adhered to either in purely gastroenterological diagnoses (eg, gastric and duodenal ulcers in the same patient) or in gastroenterological and non-gastroenterological diagnoses (eg, intrahepatic cholestasis in sickle cell haemoglobinopathies). Tabler compares the organic diseases seen in Bristol and Kingston. To count multiple diagnoses will exaggerate organic diagnosis since organic diseases are frequently multiple; conversely to use a single major diagnosis will emphasise functional disorders since a gastroenterologist will usually be satisfied with a single label for this type of problem. To try to eliminate bias introduced by multiple ,

6. Liesi

P, Dahl D, Vaheri A. Laminin is produced by early culture. J Cell Biol 1983; 96: 920-24.

7. Wharton J, Polak JM, Bloom

rat

astrocytes in primary

SR, Will JA, Brown MR, Pearse AGE. Substance P-like immunoreactive nerves in mammalian lung. Invest Cell Pathol 1979; 2: 3. 8. Takahashi T, Otsuka M. Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section. Brain Res 1975; 87: 1-11. 9. Hökfelt T, Johansson O, Ljungdahl Å, Lundberg JM, Schultzberg M. Peptidergic neurones. Nature 1980; 284: 515-21. 10. Hökfelt T, Kellerth JO, Nilsson G, Pernow B. Substance P:localization in the central nervous system and in some primary sensory neurons. Science 1975; 190: 889-90. 11. Henry JL. Substance P and pain: an updating. Trends Neurosci 1980; 3: 95-97. 12. Henry JL. Relation of substance P to pain transmission: neurophysiological evidence. In: Porter R, O’Connor M, eds. Substance P. (Ciba Found Symp 91). London: Pitman, 1982: 2. Terry SI. Tropical gastroenterology in Jamaica. Trop Doctor 1980; 10: 147-51.

1330 TABLE I-ORGANIC DISEASES SEEN IN REFERRED PATIENTS BRISTOL

(%) IN

(B) AND KINGSTON, JAMAICA (K)

TABLE Il-"NON-ORGANIC" DISORDERS

(%) IN BRISTOL (B) AND KINGSTON, JAMAICA (K)

diagnoses in the Jamaican series and make the two series more directly comparable, the denominator used in table 1 (1139) is the total number of diagnoses, gastrointestinal and other. Most of the differences between the two centres reflect real geographical variations in organic disease-for example, in Jamaica, the lower incidence of oesophagitis and inflammatory bowel disease, the absence of coeliac disease, and the increased frequency of cirrhosis of the liver, alcoholism, and infective diarrhoea. The ratio of colon to stomach cancer was 2:1 in Bristol and 1:5 in

Kingston. What is surprising is the rarity in Bristol of gastritis, duodenitis, and diverticular disease. However, if diverticular disease was counted by Harvey et al as organic only if there was evidence of complications, that may account for the apparent marked difference between the two surveys (table n) and this methodological device will tend to boost the number of patients purported to have functional disease. In the same way, was gastritis and duodenitis, which in Jamaica was counted as organic, counted as endoscopy negative dyspepsia in Bristol and therefore non-organic? Are the differences in prevalence of non-organic disease at the two centres true differences or are they simply a reflection of the foibles and biases of the individual diagnosticians? While it is impossible to answer the question by simply comparing the two surveys, it is difficult to ignore the very large proportion of patients from Jamaica who have real disease, as shown by structural changes in tissues macroscopically or microscopically. I have to record my personal prejudice in diagnosing disease where I see a structural abnormality, and I find it difficult to dismiss demonstrable changes as insignificant and to classify the patient’s symptoms as functional. By underplaying the organic nature of some disorders and by introducing novel categories of functional gastrointestinal diseases the Bristol workers have made it much more difficult to relate their findings to those of previous surveys. If 40% of outpatients referred to specialist gastrointestinal units in the UK really have no organic disease and if gastrointestinal inpatients have solely haematemesis and melaena, is the UK the ideal place for doctors from developing countries to train in gastroenterology? It may be much better for local medical graduates to be trained locally (or at least in countries with a comparable pattern) to achieve the necessary blend of clinical acumen, understanding, and experience of local problems. Department of Medicine, University of the West Indies, Mona, Kingston 7, Jamaica

S. I. TERRY

TRUNCAL VAGOTOMY IN HYPOTHALAMIC OBESITY

SIR,-Injury to the ventromedialhypothalamus (VMH) produces hypothalamic obesity, a syndrome characterised by hyperinsulinaemia, hyperphagia, and rapid weight gain. In experimental VMH injury subdiaphragmatic vagotomy led to weight loss. 1.2 These findings and follow-up data of vagotomy in patients with exogenous obesity3,4 prompted us to try truncal vagotomy in a woman with hypothalamic obesity. This patient first presented at age 12-55 years with lethargy, anorexia, weight loss, and deteriorating school performance. In both height and weight she was below the third percentile for age. Secondary sexual characteristics were absent. She appeared clinically euthyroid. Serum thyroxine was 3-6g/dl with a depressed thyroid stimulating hormone (0 -3 ng/ml). Bone age was delayed 3 years. A cerebral angiogram revealed a suprasellar lesion, found to be a craniopharyngioma. Resection was incomplete and radiotherapy was administered. Postoperatively, she had transient personality changes and pituitary insufficiency. She was discharged on thyroxine and hydrocortisone. Over the ensuing years, she gained a lot of weight (fig 1). On thyroxine she remained euthyroid. Hydrocortisone doses were increased at times of stress. Oestrogen therapy (at age 15) resulted in slight breast development. Polyuria, polydypsia, persistence of dilute urine during water restriction and restoration of concentrating ability with exogenous vasopressin suggested partial diabetes insipidus. Compliance with vasopressin therapy and an 800 kcal diet was poor. Her weight stabilised around 82 kg until she had a right hemispheric cerebrovascular accident. Oestrogen therapy was stopped. At age 19, she was admitted to hospital depressed and suicidal. She was obese (106 kg, height 157 cm), lacked secondary sexual characteristics, and had a moderate left-sided hemiparesis. A 24 h dietary recall indicated an intake of 3800 kcal. The patient was transferred to the Clinical Studies Center where she underwent a 72 h fast (water only). Urinary ketones remained negative. Serum insulin levels were high (58-104 jL
1. Inoue S, 2. 3. 4.

Fig 1-Body weight from age (1Ib=0’454 kg.)

12 to age 21.