Saturday
BACTERIAL OVERGROWTH SYNDROME WITHOUT "BLIND LOOP": A CAUSE FOR MALNUTRITION IN THE ELDERLY
S. H. ROBERTS
OLIVER JAMES E. H.
JARVIS
Departments of Medicine and Geriatrics, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
Summary
Probable bacterial contamination of the small bowel without an anatomical sump
occurred in 5 elderly patients (age 68-94). They presented with severe general deterioration in health rather than with obvious features of malabsorption. This syndrome has not been clearly described before. Bacterial deconjugation of bile salts was identified by the 14C-glycocholic-acid breath test. Investigations for other causes of malabsorption, including small-bowel biopsy and pancreatic scan, revealed no abnormality. After prolonged ill-health despite an adequate diet in hospital, all 5 subjects made a striking recovery after treatment with antibiotics. This condition may be quite common, particularly in malnourished elderly people.
10
December 1977
1967. Her symptoms were successively attributed to irritable bowel syndrome, diverticular disease, and finally malabsorption of unknown setiology (see accompanying table). For 2 years she received vitamin-B12 and pancreatic supplements with no improvement in the diarrhoea and persistent measured weight-loss. In October, 1976, an abnormal 14C-glycocholate breath test was consistent with bacterial contamination of the small intestine. Treatment with tetracycline and then clindamycin led to improvement in diarrhoea and weight-gain. She returned home fit and well. Case 2 A staunchly independent 85-year-old man began to lose weight soon after he fractured his humerus in 1975. In hospital constipation was a problem, and a raised mean corpuscular volume (M.c.v.) was noted, but he apparently made an uneventful recovery. At the beginning of 1977 an attack of severe diarrhoea woke him early and continued throughout the day. In May neighbours found him collapsed in a faecal pool. On
admission he was clear-headed but embarrassed, weak, and cachectic. Investigations included a 14C-glycocholate breath test which was grossly abnormal and suggested a "blind loop" syndrome. Treatment with clindamycin led to a dramatic improvement in wellbeing, complete resolution of diarrhoea, and weight-gain. He returned home with full social-services support.
Introduction INTESTINAL malabsorption due to bacterial contamination of the small bowel is a cause of malnutrition in persons of all ages. In the elderly, duodenal and jejunal diverticula and previous gastric surgery are common causes of such a "blind loop" syndrome.1,2 In old people malabsorption tends to present with generalised illhealth and debility, rather than with diarrhoea and the typical features of steatorrhcea more often seen in younger patients.3 We now describe 5 elderly patients (aged 68-92 yr) who presented with a general decline in health rather than with specific symptoms of malabsorption and who had bacterial contamination of the small bowel without any anatomical blind loop.
Case-reports Case 1 A
of 68 living in poor social circumstances had comof intermittent diarrhoea and severe weight-loss since
woman
plained
Case 3 A loss.
72-year-old woman was admitted During the preceding 4 months
with extreme weighther mobility had declined, she had fallen, and a pressure-sore had developed. For 20 years she had received parenteral B12 for pernicious anaemia. Investigations for diarrhoea had been carried out 10 years previously, but diarrhoea was no longer a complaint. Indeed, one year before admission she had had large-bowel obstruction, but no abnormality had been found at laparotomy. During investigation of her malnutrition a 14 C-glycocholate breath test was abnormal, consistent with bacterial overgrowth in the small intestine. Treatment with clindamycin led to clinical improvement. She gained weight, became mobile, and returned home. Case 4
This frail 93-year-old woman began to deteriorate 3 months before admission. She became confused and fell. She had clearly lost weight and was malnourished. A macrocytic
8050
1194 INVESTIGATIONS IN
5
PATIENTS WITH MALABSORPTION
*Consistent with malabsorption ofB12 not due to absence of intrinsic factor. tall specimens showed considerable infiltration of the lamina propria with lymphocytes and plasma cells, but normal villi.
ansemia responded poorly to haematinics and eventually she required blood-transfusion. For 3 months she continued to lose weight in hospital. Further investigations included a 14C-glycocholate breath test which was consistent with a "blind loop" syndrome and antibiotics were prescribed. From that moment there was a general improvement in wellbeing, she began to put on weight, and she is now on her feet and ready for resi-
dential care. 5 Case
woman,
This 82 years old, lived alone and was admitted as emergency with gradual deterioration in mental function, incontinence of urine, and a history of a recent fall. She was malnourished and had clearly lost weight. Investigations showed a macrocytic anoemia and a grossly abnormal 14C-glycocholate breath test which was consistent with a "blind loop" syndrome. Treatment with hxmatinics and metronidazole led to a dramatic clinical improvement, she regained weight, and she returned to independence at home. an
Discussion
Malabsorption due to bacterial contamination of the small bowel in patients with no demonstrable anatomical sump (blind loop, diverticula, or stricture) has not previously been described. We believe that these 5 cases establish the existence of such a syndrome in the elderly, but the cause is at present unknown. It is interesting to note that Ryder3 described 4 out of 9 cases of steatorrhoea in the elderly as examples of "idiopathic steatorrhoea". The factors which contributed to overgrowth of bacteria in the small bowel of these patients may be the absence (or low level) of free gastric acid (3 in the present series and 3 of Ryder’s patients) together with very slow small-intestinal transit (case 2). However, abnorma-
lities of transit, particularly intestinal pseudo-obstruction (case 3), may themselves be secondary to bacterial
overgrowth.4
.
It is notable that all 5 patients had spent a considerable time under medical supervision, deteriorating in health before the very eyes of their doctors. In 2 patients (cases 1 and 2), although malabsorption was noted, the possibility of bacterial overgrowth had not been considered because of the absence of a recognised "blind loop". In the remaining 3 patients malabsorption was
occult. There was no obvious steatorrhoea, and diarrhoea in one patient was intermittent. Macrocytic anxmia, biochemical evidence of osteomalacia, and weight-loss were prominent factors. Such consequences of nutritional deficiency are not uncommon in old people and are often attributed to the failure of solitary old people to obtain an adequate diet. For this reason cases of malabsorption presenting at geriatric clinics may well be missed. Patients over the age of 65 are less commonly seen in gastroenterology clinics,2 and the recognition of this syndrome by specialist gastroenterologists may also have been delayed. The D.H.S.S. Nutrition Survey of the Elderly5 detected only 27 cases of malnutrition in a sample of 841, a prevalence of 3.2%. It should be noted that about half of these had malnutrition secondary to disease rather than to poor diet, and of the remainder 8 were severely malnourished despite an adequate diet. A similar prevalence among the elderly (over the age of 65) in our own catchment area would imply 1500 malnourished elderly people of whom therefore 400 might have an underlying cause for the malnutrition. The 5 patients we report here were all discovered within 8 months. It seems possible, therefore, that the syndrome is quite common in the very elderly and should be looked for more often.
1195 Until the development of the 14C-glycocholate breath test,6.7 the detection of bacterial deconjugation of bile salts was uncomfortable for patients and demanded highly sophisticated bacteriological techniques. The measurement of urinary indicans has been an unreliable estimate of bacterial deconjugation.9 Other investigations of malabsorption or indices of malnutrition are non-specific. The 14C-glycocholate breath test is simple and causes no discomfort to the patient-an important consideration in infirm elderly subjects. Furthermore there are few false positive results. Although small intestinal bacterial culture and counts were not made in these patients, the abnormal 14C-glycocholate tests, exclusion of other lesions (normal jejunal villous pattern and pancreatic scan,10 and absence of anatomical sump on smallbowel radiology), and the remarkable improvement in health of all 5 patients after broad-spectrum antibacterial treatment with no other change in therapy makes the diagnosis very probable. It is suggested that the 14C-glycocholic acid breath test should be used more often in elderly people who are undernourished without obvious cause or who fail to gain weight on an adequate diet. We gratefully acknowledge the help and cooperation of colleagues and nursing staff in medical and geriatric wards. We also thank Dr T. Bird, consultant heematologist, for much help and advice.
Requests for reprints should be addressed to 0. J. Donaldson,
R. M. in Gastrointestinal Disorders
(edited by
Introduction BLEEDING is a common complication in patients with renal failure,1-3 but the factors which impair hsemostasis have not been established. The dialysable metabolites which accumulate in uraemic plasma have been thought to play a part in the defective platelet function observed by many authors.4-6 However, attention has recently been drawn to the possibility that non-dialysable factors, such as factor vm, the von Willebrand factor, and red cells might be involved in the haemorrhagic diathesis of patients with renal failure.7-9 We were therefore interested in the recent discovery that human vascular tissues produce prostacyclin, a potent inhibitor of platelet aggregation.l0.11 It has been suggested that prostacyclin may impair the interaction between platelets and the vessel wall.lo-’1 This vascular factor may therefore be of importance in normal or abnormal haemostasis. We report here increased prostacyclin-like activity in venous tissues from three patients with renal failure and very
prolonged bleeding-times. Patients
REFERENCES 1.
from the three uræmic patients. These findings may be relevant to the pathogenesis of bleeding in renal failure.
M. H.
Sleisenger
and J. S. Fordtran); p. 927. Toronto, 1973. 2. Price, H. L., Gazzard, B. G., Dawson, A. M. Br. med. J. 1977, i, 1582 3. Ryder, J. B. Geront. clin. 1963, 5, 30. 4. Barry, R. E., Chow, A. W., Billesdon, J. Gut, 1977, 18, 356. 5. Exton-Smith, A. N. Department of Health and Social Security Reports on Health and Social Security Subjects, no. 3. H.M. Stationery Office, Lon-
don,1972. 6. Fromm, H., Hofmann, A. F. Lancet, 1971, ii, 621. 7. James, O. F. W., Agnew, J. E., Bouchier, I. A. D. Br. med. J. 1973, iii, 191. 8. Losowsky, M. S., Walker, B. E., Kelleher, J. in Malabsorption in Clinical
Practice; p. 29. Edinburgh, 1974. Hamilton, J. D., Dyer, N. H., Dawson, A. M., O’Grady, F. W., Vince, A., Fenton, J. C. B., Mollin, D. L. Q.Jl Med. 1970, 39, 265. 10. Youngs, G. R., Agnew, J. E., Levin, G. E., Bouchier, I. A. D. ibid. 1973, 42, 597. 9.
PROSTACYCLIN-LIKE ACTIVITY AND BLEEDING IN RENAL FAILURE
Three patients with renal failure, normal platelet-counts, and very prolonged bleeding-times8 were studied before admission to a dialysis unit. Two of them had developed acute ischaemic renal failure after operations, and the third had chronic renal failure due to membranous glomerulonephritis. There was no history of abnormal bleeding in the patients or their families. Case l.-A 60-year-old woman had an emergency gastrectomy for a perforated ulcer and a second operation 4 days later for intestinal obstruction. Severe surgical shock was followed by acute renal failure. On the 4th postoperative day, haemodialysis was started. Case 2.-A 53-year-old man was referred to our department of nephrology from another hospital 20 days after an accident in which he had suffered multiple injuries and severe shock. During that period he had shown signs of progressive renal failure; his condition prompted us to start dialysis soon after admission. Case 3.-A 47-year-old man had had chronic membranous glomerulonephritis for many years.
Methods
G. REMUZZI G. MECCA G.
DE
A. E. CAVENAGHI M. B. DONATI GAETANO
Nephrology and Dialysis Division, Ospedali Riuniti, Bergamo, Italy, and Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature. The specimens from all three uræmic patients showed more prostacyclin-like activity than those from the controls. After repeated washings, when this activity could hardly be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissue
Summary
Selected laboratory data for each patient at the time vascular tissue was removed are given in the accompanying table. After informed consent had been obtained from all the subjects, specimens (10-50 mg wet weight and approximately 1 mm in diameter) were removed under local anxsthesia from a superficial vein of the forearm from the three patients and from three control subjects matched for age and sex. The platetet-counts and bleeding-times of the three controls were within the normal ranged Vascular specimens were cut into rings" of about 10 mg wet weight. The mean weights of 6 paired rings from the three patients and their controls were 11-6±2-9 mg and 12-8+4-2 mg respectively. The rings were incubated in 200 1 "tris" buffer (0-05 mol/l, pH 7.5) at 22°C. 100 fl-l samples of the supernatant fluid from the incubation mixtures were then incubated for 1 min in 250 all platelet-rich plasma (300 000 platelets/fl-l). Platelet aggregation was initiated with 1 mol/1 adenosine-5’-diphosphate disodium salt (Sigma, Milan). Prostacyclin-like activity was evaluated by the method described by Moncada et al." in an Elvi 840 aggreg-
BACTERIAL OVERGROWTH SYNDROME WITHOUT "BLIND LOOP": A CAUSE FOR MALNUTRITION IN THE ELDERLY
S. H. ROBERTS
OLIVER JAMES E. H.
JARVIS
Departments of Medicine and Geriatrics, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
Summary
Probable bacterial contamination of the small bowel without an anatomical sump
occurred in 5 elderly patients (age 68-94). They presented with severe general deterioration in health rather than with obvious features of malabsorption. This syndrome has not been clearly described before. Bacterial deconjugation of bile salts was identified by the 14C-glycocholic-acid breath test. Investigations for other causes of malabsorption, including small-bowel biopsy and pancreatic scan, revealed no abnormality. After prolonged ill-health despite an adequate diet in hospital, all 5 subjects made a striking recovery after treatment with antibiotics. This condition may be quite common, particularly in malnourished elderly people.
10
December 1977
1967. Her symptoms were successively attributed to irritable bowel syndrome, diverticular disease, and finally malabsorption of unknown setiology (see accompanying table). For 2 years she received vitamin-B12 and pancreatic supplements with no improvement in the diarrhoea and persistent measured weight-loss. In October, 1976, an abnormal 14C-glycocholate breath test was consistent with bacterial contamination of the small intestine. Treatment with tetracycline and then clindamycin led to improvement in diarrhoea and weight-gain. She returned home fit and well. Case 2 A staunchly independent 85-year-old man began to lose weight soon after he fractured his humerus in 1975. In hospital constipation was a problem, and a raised mean corpuscular volume (M.c.v.) was noted, but he apparently made an uneventful recovery. At the beginning of 1977 an attack of severe diarrhoea woke him early and continued throughout the day. In May neighbours found him collapsed in a faecal pool. On
admission he was clear-headed but embarrassed, weak, and cachectic. Investigations included a 14C-glycocholate breath test which was grossly abnormal and suggested a "blind loop" syndrome. Treatment with clindamycin led to a dramatic improvement in wellbeing, complete resolution of diarrhoea, and weight-gain. He returned home with full social-services support.
Introduction INTESTINAL malabsorption due to bacterial contamination of the small bowel is a cause of malnutrition in persons of all ages. In the elderly, duodenal and jejunal diverticula and previous gastric surgery are common causes of such a "blind loop" syndrome.1,2 In old people malabsorption tends to present with generalised illhealth and debility, rather than with diarrhoea and the typical features of steatorrhcea more often seen in younger patients.3 We now describe 5 elderly patients (aged 68-92 yr) who presented with a general decline in health rather than with specific symptoms of malabsorption and who had bacterial contamination of the small bowel without any anatomical blind loop.
Case-reports Case 1 A
of 68 living in poor social circumstances had comof intermittent diarrhoea and severe weight-loss since
woman
plained
Case 3 A loss.
72-year-old woman was admitted During the preceding 4 months
with extreme weighther mobility had declined, she had fallen, and a pressure-sore had developed. For 20 years she had received parenteral B12 for pernicious anaemia. Investigations for diarrhoea had been carried out 10 years previously, but diarrhoea was no longer a complaint. Indeed, one year before admission she had had large-bowel obstruction, but no abnormality had been found at laparotomy. During investigation of her malnutrition a 14 C-glycocholate breath test was abnormal, consistent with bacterial overgrowth in the small intestine. Treatment with clindamycin led to clinical improvement. She gained weight, became mobile, and returned home. Case 4
This frail 93-year-old woman began to deteriorate 3 months before admission. She became confused and fell. She had clearly lost weight and was malnourished. A macrocytic
8050
1194 INVESTIGATIONS IN
5
PATIENTS WITH MALABSORPTION
*Consistent with malabsorption ofB12 not due to absence of intrinsic factor. tall specimens showed considerable infiltration of the lamina propria with lymphocytes and plasma cells, but normal villi.
ansemia responded poorly to haematinics and eventually she required blood-transfusion. For 3 months she continued to lose weight in hospital. Further investigations included a 14C-glycocholate breath test which was consistent with a "blind loop" syndrome and antibiotics were prescribed. From that moment there was a general improvement in wellbeing, she began to put on weight, and she is now on her feet and ready for resi-
dential care. 5 Case
woman,
This 82 years old, lived alone and was admitted as emergency with gradual deterioration in mental function, incontinence of urine, and a history of a recent fall. She was malnourished and had clearly lost weight. Investigations showed a macrocytic anoemia and a grossly abnormal 14C-glycocholate breath test which was consistent with a "blind loop" syndrome. Treatment with hxmatinics and metronidazole led to a dramatic clinical improvement, she regained weight, and she returned to independence at home. an
Discussion
Malabsorption due to bacterial contamination of the small bowel in patients with no demonstrable anatomical sump (blind loop, diverticula, or stricture) has not previously been described. We believe that these 5 cases establish the existence of such a syndrome in the elderly, but the cause is at present unknown. It is interesting to note that Ryder3 described 4 out of 9 cases of steatorrhoea in the elderly as examples of "idiopathic steatorrhoea". The factors which contributed to overgrowth of bacteria in the small bowel of these patients may be the absence (or low level) of free gastric acid (3 in the present series and 3 of Ryder’s patients) together with very slow small-intestinal transit (case 2). However, abnorma-
lities of transit, particularly intestinal pseudo-obstruction (case 3), may themselves be secondary to bacterial
overgrowth.4
.
It is notable that all 5 patients had spent a considerable time under medical supervision, deteriorating in health before the very eyes of their doctors. In 2 patients (cases 1 and 2), although malabsorption was noted, the possibility of bacterial overgrowth had not been considered because of the absence of a recognised "blind loop". In the remaining 3 patients malabsorption was
occult. There was no obvious steatorrhoea, and diarrhoea in one patient was intermittent. Macrocytic anxmia, biochemical evidence of osteomalacia, and weight-loss were prominent factors. Such consequences of nutritional deficiency are not uncommon in old people and are often attributed to the failure of solitary old people to obtain an adequate diet. For this reason cases of malabsorption presenting at geriatric clinics may well be missed. Patients over the age of 65 are less commonly seen in gastroenterology clinics,2 and the recognition of this syndrome by specialist gastroenterologists may also have been delayed. The D.H.S.S. Nutrition Survey of the Elderly5 detected only 27 cases of malnutrition in a sample of 841, a prevalence of 3.2%. It should be noted that about half of these had malnutrition secondary to disease rather than to poor diet, and of the remainder 8 were severely malnourished despite an adequate diet. A similar prevalence among the elderly (over the age of 65) in our own catchment area would imply 1500 malnourished elderly people of whom therefore 400 might have an underlying cause for the malnutrition. The 5 patients we report here were all discovered within 8 months. It seems possible, therefore, that the syndrome is quite common in the very elderly and should be looked for more often.
1195 Until the development of the 14C-glycocholate breath test,6.7 the detection of bacterial deconjugation of bile salts was uncomfortable for patients and demanded highly sophisticated bacteriological techniques. The measurement of urinary indicans has been an unreliable estimate of bacterial deconjugation.9 Other investigations of malabsorption or indices of malnutrition are non-specific. The 14C-glycocholate breath test is simple and causes no discomfort to the patient-an important consideration in infirm elderly subjects. Furthermore there are few false positive results. Although small intestinal bacterial culture and counts were not made in these patients, the abnormal 14C-glycocholate tests, exclusion of other lesions (normal jejunal villous pattern and pancreatic scan,10 and absence of anatomical sump on smallbowel radiology), and the remarkable improvement in health of all 5 patients after broad-spectrum antibacterial treatment with no other change in therapy makes the diagnosis very probable. It is suggested that the 14C-glycocholic acid breath test should be used more often in elderly people who are undernourished without obvious cause or who fail to gain weight on an adequate diet. We gratefully acknowledge the help and cooperation of colleagues and nursing staff in medical and geriatric wards. We also thank Dr T. Bird, consultant heematologist, for much help and advice.
Requests for reprints should be addressed to 0. J. Donaldson,
R. M. in Gastrointestinal Disorders
(edited by
Introduction BLEEDING is a common complication in patients with renal failure,1-3 but the factors which impair hsemostasis have not been established. The dialysable metabolites which accumulate in uraemic plasma have been thought to play a part in the defective platelet function observed by many authors.4-6 However, attention has recently been drawn to the possibility that non-dialysable factors, such as factor vm, the von Willebrand factor, and red cells might be involved in the haemorrhagic diathesis of patients with renal failure.7-9 We were therefore interested in the recent discovery that human vascular tissues produce prostacyclin, a potent inhibitor of platelet aggregation.l0.11 It has been suggested that prostacyclin may impair the interaction between platelets and the vessel wall.lo-’1 This vascular factor may therefore be of importance in normal or abnormal haemostasis. We report here increased prostacyclin-like activity in venous tissues from three patients with renal failure and very
prolonged bleeding-times. Patients
REFERENCES 1.
from the three uræmic patients. These findings may be relevant to the pathogenesis of bleeding in renal failure.
M. H.
Sleisenger
and J. S. Fordtran); p. 927. Toronto, 1973. 2. Price, H. L., Gazzard, B. G., Dawson, A. M. Br. med. J. 1977, i, 1582 3. Ryder, J. B. Geront. clin. 1963, 5, 30. 4. Barry, R. E., Chow, A. W., Billesdon, J. Gut, 1977, 18, 356. 5. Exton-Smith, A. N. Department of Health and Social Security Reports on Health and Social Security Subjects, no. 3. H.M. Stationery Office, Lon-
don,1972. 6. Fromm, H., Hofmann, A. F. Lancet, 1971, ii, 621. 7. James, O. F. W., Agnew, J. E., Bouchier, I. A. D. Br. med. J. 1973, iii, 191. 8. Losowsky, M. S., Walker, B. E., Kelleher, J. in Malabsorption in Clinical
Practice; p. 29. Edinburgh, 1974. Hamilton, J. D., Dyer, N. H., Dawson, A. M., O’Grady, F. W., Vince, A., Fenton, J. C. B., Mollin, D. L. Q.Jl Med. 1970, 39, 265. 10. Youngs, G. R., Agnew, J. E., Levin, G. E., Bouchier, I. A. D. ibid. 1973, 42, 597. 9.
PROSTACYCLIN-LIKE ACTIVITY AND BLEEDING IN RENAL FAILURE
Three patients with renal failure, normal platelet-counts, and very prolonged bleeding-times8 were studied before admission to a dialysis unit. Two of them had developed acute ischaemic renal failure after operations, and the third had chronic renal failure due to membranous glomerulonephritis. There was no history of abnormal bleeding in the patients or their families. Case l.-A 60-year-old woman had an emergency gastrectomy for a perforated ulcer and a second operation 4 days later for intestinal obstruction. Severe surgical shock was followed by acute renal failure. On the 4th postoperative day, haemodialysis was started. Case 2.-A 53-year-old man was referred to our department of nephrology from another hospital 20 days after an accident in which he had suffered multiple injuries and severe shock. During that period he had shown signs of progressive renal failure; his condition prompted us to start dialysis soon after admission. Case 3.-A 47-year-old man had had chronic membranous glomerulonephritis for many years.
Methods
G. REMUZZI G. MECCA G.
DE
A. E. CAVENAGHI M. B. DONATI GAETANO
Nephrology and Dialysis Division, Ospedali Riuniti, Bergamo, Italy, and Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy
Specimens of venous tissue from three normal subjects and three patients with renal failure and very prolonged bleeding-times showed prostacyclin-like activity (inhibition of platelet aggregation) during incubation at room temperature. The specimens from all three uræmic patients showed more prostacyclin-like activity than those from the controls. After repeated washings, when this activity could hardly be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissue
Summary
Selected laboratory data for each patient at the time vascular tissue was removed are given in the accompanying table. After informed consent had been obtained from all the subjects, specimens (10-50 mg wet weight and approximately 1 mm in diameter) were removed under local anxsthesia from a superficial vein of the forearm from the three patients and from three control subjects matched for age and sex. The platetet-counts and bleeding-times of the three controls were within the normal ranged Vascular specimens were cut into rings" of about 10 mg wet weight. The mean weights of 6 paired rings from the three patients and their controls were 11-6±2-9 mg and 12-8+4-2 mg respectively. The rings were incubated in 200 1 "tris" buffer (0-05 mol/l, pH 7.5) at 22°C. 100 fl-l samples of the supernatant fluid from the incubation mixtures were then incubated for 1 min in 250 all platelet-rich plasma (300 000 platelets/fl-l). Platelet aggregation was initiated with 1 mol/1 adenosine-5’-diphosphate disodium salt (Sigma, Milan). Prostacyclin-like activity was evaluated by the method described by Moncada et al." in an Elvi 840 aggreg-
