Acute liver failure as the sole manifestation of relapsing non-Hodgkin's lymphoma.

Acute liver failure due to hepatic involvement by haematological malignancies is very rare, and usually has a rapidly fatal prognosis. We describe the case of a man who was treated for diffuse large B-cell lymphoma, and achieved a complete remission after eight courses of chemotherapy. He then presented with acute liver failure. Transjugular liver biopsy revealed massive infiltration by lymphomatous cells, with extensive necrosis. A CT scan did not show any evidence of extrahepatic lymphoma. The patient recovered from the liver failure following combined immuno-chemotherapy. Recurrence of the disease should be included in the differential diagnosis of patients with haematological malignancies and acute liver failure, even without evidence of extrahepatic involvement.

Peritoneovenous shunting restores atrial natriuretic factor responsiveness in refractory hepatic ascites.

BACKGROUND: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive, antinatriuretic forces such as the renin aldosterone angiotensin system and the sympathetic nervous system, and vasodilatory, natriuretic agents such as atrial natriuretic factor (ANF). Patients with diuretic resistant refractory ascites may require peritoneovenous shunting (PVS) to control ascites. METHODS: To study the factors responsible for the improvement in sodium homeostasis post-PVS, we compared the response to ANF infusion before and 1 month after PVS in 6 patients with massive ascites. RESULTS: Before PVS, sodium excretion at baseline and in response to ANF infusion was blunted but became more normal post-PVS. ANF infusion post-PVS induced a significant increase in the glomerular filtration rate and filtration fraction and also in distal delivery of sodium. ANF's distal effect of increasing the fractional excretion of distally delivered sodium was present pre-PVS and was not significantly increased post-PVS. Changes in sodium handling were accompanied by a significant decrease in antinatriuretic forces (baseline aldosterone, 2079 +/- 507 vs. 647 +/- 17 nmol/L; P < 0.04) post-PVS. CONCLUSIONS: The improvement in sodium homeostasis and response to ANF infusion post-PVS appears to be associated with the decrease in antinatriuretic forces with the loss of massive refractory ascites. Thus, PVS restores the balance toward ANF responsiveness.

Angiotensin II modulates atrial natriuretic factor-induced natriuresis in cirrhosis with ascites.

Resistance to the natriuretic action of atrial natriuretic factor (ANF) in cirrhosis with ascites has been correlated with rising levels of antinatriuretic factors, such as renin, angiotensin II (AII), and aldosterone, as well as increased sympathetic nerve activity. To determine whether AII can serve as a mediator rather than only as a marker of the antinatriuresis, a nonpressor dose of AII (5 ng/kg/min) was given during an ANF infusion in eight patients with cirrhosis and ascites who responded to ANF infusion with a natriuresis. Patients were maintained in metabolic balance and measurements of para-aminohippuric acid, inulin, and lithium clearance were taken before and during infusion of ANF with or without AII. Atrial natriuretic factor infusion was associated with a natriuretic response accompanied by an increase in glomerular filtration rate, filtration fraction, and lithium clearance compared with baseline. The addition of AII was associated with a return of the glomerular filtration rate to baseline, with no change in filtration fraction. This was reversible on withdrawal of AII infusion. Natriuresis induced by ANF occurred despite baseline elevations of the renin angiotensin aldosterone system and was associated with an increase in distal delivery of sodium and a decrease in fractional reabsorption of distally delivered sodium as estimated by lithium clearance parameters. Angiotensin II infusion exerted effects on both proximal and distal nephron sites to abrogate ANF-induced natriuresis. These results suggest that AII may serve as a mediator as well as a marker of resistance to the natriuretic effect of ANF in patients with cirrhosis and ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of age and duration of disease on the clinical manifestations of brucellosis. A study of 73 consecutive patients in Israel.

We describe our experience with 73 patients diagnosed with brucellosis during the years 1979-91 at two Jerusalem hospitals: Hadassah Mount Scopus (37 patients from 1979-1984) and Shaare Zedek (36 patients from 1979-1991). The patients included 32 children less than 14 years old and 41 adults; 70 of the patients were non-Jews. In all cases the pathogen was Brucella melitensis. The high proportion of children and the equal sex distribution was quite different from the age and sex distribution of brucellosis in Western countries where it is more common in adult males, and similar to that reported from other near-Eastern countries where household dairy products, and not occupational exposure, are the most common source of infection. The short duration of disease (< 2 weeks) prior to diagnosis in 70% of the patients is attributed to the ready availability of appropriate medical care, and a very high index of suspicion for brucellosis in the Jerusalem non-Jewish population. Abdominal symptoms were more common in adults, whereas enlarged lymph nodes and liver, skin rash and pharyngitis were more frequently observed in children. Some of these differences may be attributed to the very short duration of disease in most children at the time of presentation. Combination therapy with tetracycline-streptomycin or tetracycline-rifampin yielded superior results as compared with single-drug treatment in terms of early defervescence and relapse rates. The present experience underlines the importance of endemic brucellosis which still represents a significant public health problem in children and adults in Mediterranean countries.

Is duodenal ulcer a seasonal disease? A retrospective endoscopic study of 3105 patients.

The monthly pattern of distribution of endoscopically diagnosed duodenal ulcer disease was evaluated for the years 1975-1989. A retrospective review of 3105 endoscopies performed for peptic disease was recorded and analyzed. Among them, 2020 endoscopies revealed duodenal bulb deformity, and 1035 revealed the presence of acute duodenal ulcer. Chi-square analysis of the data for goodness of fit revealed statistical differences for certain months. Slightly more patients with chronic deformity presented in June and November, whereas more patients with acute duodenal ulcer presented in July, November, and December (p < 0.001). The ratio of acute to chronic disease was nearly constant throughout the year. The Edwards chi 2 test for seasonal trends did not reveal any seasonality (p > 0.75). The differences observed in June-July and November-December, as compared with the rest of the year, were so small that they should not be relied upon for the clinical management of peptic disease.

Refractory ascites: modulation of atrial natriuretic factor unresponsiveness by mannitol.

We have previously shown that unresponsiveness to atrial natriuretic factor is a marker of the severity of ascites. The tubular mechanisms are unknown, but it seems that increased reabsorption of sodium proximal to the main site of action of atrial natriuretic factor (i.e., the inner medullary collecting duct) plays an important role. We attempted to decrease the proximal reabsorption of sodium with mannitol in patients unresponsive to atrial natriuretic factor. The results of mannitol in such a group of patients has previously been conflicting. We studied 10 patients with massive, resistant ascites who were off diuretics and on a 20-mmol/day sodium diet for 7 days. Atrial natriuretic factor unresponsiveness was confirmed by failure of a 2-hr atrial natriuretic factor infusion to induce a natriuresis. The next day all patients received an infusion of 40 gm of mannitol and subsequently a combined infusion of mannitol and atrial natriuretic factor. Proximal reabsorption of sodium and water were evaluated by lithium clearance, and glomerular filtration rate and renal blood flow were evaluated by inulin clearance and p-aminohippurate clearances, respectively. Six patients responded to mannitol alone with an increased diuresis (from 39 +/- 7 to 148 +/- 35 ml/hr) and natriuresis (from 0.27 +/- 0.05 mmol/hr to 1.65 +/- 0.53 mmol/hr; p less than 0.05) (responders), whereas four did not (nonresponders). The combination of atrial natriuretic factor and mannitol induced a further significant increase in sodium excretion (3.28 +/- 0.68 mmol/hr) but not in urine excretion, compared with mannitol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle sympathetic nerve activity and renal responsiveness to atrial natriuretic factor during the development of hepatic ascites.

PURPOSE: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive antinatriuretic forces such as the sympathetic nervous system and vasodilatory natriuretic agents such as atrial natriuretic factor (ANF). With the development of refractory ascites, cirrhotic patients become unresponsive to the natriuretic effect of ANF. Animal data suggest that the sympathetic nervous system plays a key role in mediating the refractoriness to ANF. We therefore studied the relationship between sympathetic nerve activity (SNA) and the natriuretic response to ANF in normal subjects and cirrhotic patients. We also attempted to localize the intrarenal site of refractoriness to ANF by lithium clearance. PATIENTS AND METHODS: Twenty-six patients with biopsy-proven cirrhosis and seven age- and sex-matched normal volunteers were studied after a week of 20 mmol/day sodium intake and no diuretics. Muscle SNA was recorded from the peroneal nerve (microneurography) and correlated with responsiveness to a 2-hour ANF infusion. Lithium clearance was used as a marker of sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action. Plasma norepinephrine, renin, and aldosterone levels were also determined. Patients were categorized into three groups: nine patients free of ascites (by ultrasonography), five ascitic patients who responded to a 2-hour ANF infusion (i.e., had a natriuretic response to ANF above 0.83 mmol/hour), and 12 ascitic patients who did not respond. RESULTS: Muscle SNA was greatly increased in the ascitic nonresponder patients compared with the normal subjects (64 +/- 4 versus 27 +/- 7 bursts/minute, p less than 0.001), moderately increased in ascitic responders (47 +/- 6 bursts/minute, p less than 0.05), but not significantly increased in nonascitic patients with cirrhosis (34 +/- 5 bursts/minute). SNA was positively correlated with plasma norepinephrine levels (r = 0.69; p less than 0.005) and inversely correlated with peak sodium excretion during the ANF infusion (r = -0.63; p less than 0.001). Plasma renin activity and aldosterone were markedly elevated in ascitic nonresponders, and normal in ascitic responders and nonascitic patients. Lithium clearance was reduced in ascitic patients compared with nonascitic patients, did not change after the ANF infusion, and correlated inversely with SNA (r = -0.61; p less than 0.01). CONCLUSION: These results support the concept that the sympathetic nervous system is a factor in renal sodium handling in cirrhosis, especially in the initiation of sodium retention and the development of refractory ascites. Refractoriness to ANF might be explained, at least in part, by increased neurally mediated sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action.

Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics.

Cholelithiasis is more prevalent in diabetics than in nondiabetics. Gallbladder dysmotility is supposed to be one of the causative factors. Reduced alpha-adrenergic tone has been demonstrated in the enterocytes of diabetic rats, and its correction by clonidine might explain the beneficial effect that the drug has on diabetic diarrhea. We therefore surmised that diabetic cholecystoparesis could also be due to alpha-adrenergic alterations. To test this hypothesis, we studied gallbladder contractions by real time ultrasonography, and small bowel transit time by lactulose hydrogen breath test, in 13 insulin-requiring diabetics before and after administration of the alpha-adrenergic stimulant clonidine (0.3 mg orally). That plasma levels were sufficient was evidenced indirectly by a fall in blood pressure. Clonidine significantly improved the rate of emptying (0.0193 +/- 0.00057/min vs. 0.0318 +/- 0.0027/min; p less than 0.005), but not the fasting and residual gallbladder volumes. Small bowel transit time was significantly prolonged after clonidine (169 +/- 17 min vs. 208 +/- 17; p less than 0.05). These results suggest that 1) reduced alpha-adrenergic tone corrected by clonidine may be present in the diabetic gallbladder, and 2) clonidine's antidiarrheal effect might be explained, at least in part, by a prolongation of the small bowel transit time.

Aldosterone, atrial natriuretic factor and sodium intake as determinants of the natriuretic response to head-out water immersion in healthy subjects.

1. The effect of sodium intake on the natriuresis and hormonal changes induced by head-out water immersion was studied in seven normal subjects during head-out water immersion and on a control day while successively on 20 mmol of sodium/day and 100 mmol of sodium/day diets. The effects of head-out water immersion were compared with those seen on the control day for both diets. 2. The natriuresis on the 100 mmol of sodium/day diet was significantly greater than on the 20 mmol of sodium/day diet (natriuretic peak: 10.3 +/- 2.2 versus 3.9 +/- 1 mmol of sodium/h; P less than 0.01). The total sodium excretion during the 3 h of head-out water immersion was 26.2 +/- 2.0 mmol on the 100 mmol of sodium/day diet and 9.9 +/- 0.9 mmol on the 20 mmol of sodium/day diet (P less than 0.01). In contrast, the increase in the plasma atrial natriuretic factor level was similar on both diets (peak plasma atrial natriuretic factor level 23.1 +/- 1.9 versus 26.2 +/- 1 pg/ml; not significant). As expected, the baseline serum aldosterone level was higher on the 20 mmol of sodium/day diet and, despite a significant suppression, remained significantly higher at the end of the third hour of head-out water immersion (peak serum aldosterone level: 495 +/- 130 versus 197 +/- 26 pmol/l, P less than 0.06). Furthermore, there was an inverse relationship between the serum aldosterone level and the urinary sodium excretion at the time of peak natriuresis (r = -0.59, P less than 0.01). 3. We conclude that the effect of sodium intake on the natriuresis induced by head-out water immersion is more dependent upon anti-natriuretic agents, such as aldosterone, than on natriuretic factors, such as atrial natriuretic factor.

Successful treatment of pancreatic pseudocyst with a somatostatin analogue and catheter drainage.

We report a patient with bile duct stone-induced pancreatitis who subsequently developed a large pseudocyst that became infected after endoscopic retrograde cholangiopancreatography (ERCP) was done for extraction of the stones. Percutaneous external drainage allowed control of the infection, but failed to seal the pseudocyst. We then treated the patient with a long-acting somatostatin analogue which shrunk the cyst within a week. Patients with pancreatic pseudocyst resistant to drainage should be offered a course of somatostatin before surgery is contemplated.

Increased sympathetic outflow in cirrhosis and ascites: direct evidence from intraneural recordings.

OBJECTIVE: To determine if central sympathetic outflow is increased in patients with cirrhosis and ascites. PATIENTS: Eleven patients with cirrhosis and ascites, 8 patients with cirrhosis but without ascites, and 7 age-matched and 8 young healthy volunteers. METHODS: With subjects supine, direct microneurographic recordings of efferent post-ganglionic muscle sympathetic nerve activity were obtained from the peroneal nerve, and sympathetic burst frequency was compared with subjects' blood pressure, heart rate, sodium excretion, catecholamines, and plasma renin activity. All patients with cirrhosis were studied at least 5 days after withdrawal from all medications and after 7 days of a 20 mmol/d sodium, 1-L fluid-restricted diet. Age-matched volunteers were studied after 7 days of 20 mmol/d sodium intake and young healthy volunteers after 7 days of 150 mmol/d sodium intake. RESULTS: Sympathetic nerve activity in ascitic patients (65 +/- 15 bursts/min; mean +/- SD) was markedly increased, whether compared with patients with cirrhosis but without ascites (34 +/- 16 bursts/min; P less than 0.001), age-matched healthy volunteers on similar sodium intake (27 +/- 22 bursts/min; P less than 0.001), or young healthy subjects (21 +/- 10 bursts/min; P less than 0.001). The frequency of muscle sympathetic nerve discharge was directly related to plasma norepinephrine and epinephrine concentrations, plasma renin activity, and heart rate, all of which were increased in those patients with cirrhosis and ascites, and inversely related to 24-hour urinary sodium excretion, the fractional excretion of sodium, and subjects' pulse pressures. Sympathetic nerve activity fell from 78 to 6 bursts/min in one patient after liver transplantation. CONCLUSIONS: This study provides the first direct evidence that elevated plasma norepinephrine concentrations in patients with cirrhosis and ascites are due to increased central sympathetic outflow. Sympathetic nerve activity is not increased in patients with cirrhosis but without ascites. Because there were direct positive correlations of sympathetic nerve activity with plasma norepinephrine concentrations, plasma epinephrine concentrations, plasma renin activity, and heart rate, the increase in central sympathetic outflow in patients with cirrhosis and ascites appears generalized and not restricted to muscle nerves. The anti-natriuretic effects of parallel increases in renal and muscle sympathetic nerve activity could account for the inverse correlation between muscle sympathetic nerve activity and sodium excretion.

[Incompetence of the sphincter of Oddi in duodenal ulcer disease].

The association of post-bulbar duodenal scarring and incompetence of the sphincter of Oddi is rare. Radiographic and endoscopic procedures should exclude concomitant neoplastic disease invading the duodenum, and duodenal Crohn's disease. The pancreatico-biliary system should be visualized before attributing ampullar reflux to duodenal ulcer disease. The treatment is that of the primary disease.

[Pneumatosis cystoides intestinalis of the splenic flexure].

We describe a case of pneumatosis cystoides intestinalis with unusual localization and radiologic features. Barium enema showed multiple, rounded, submucosal masses, which were polypoid and airless and were localized to a 20 cm segment of the splenic flexure. There was no extraluminal gas on X-ray. Puncture of these formations via colonoscopic biopsy did not result in deflation of air. Surgical resection was performed and the classical features of pneumatosis cystoides intestinalis were found. Isolated splenic flexure involvement in conjunction with atherosclerotic cardiovascular disease may suggest that pneumatosis cystoides intestinalis is a reparative process after ischemic injury.

The response of atrial natriuretic factor and sodium excretion to dietary sodium challenges in patients with chronic liver disease.

Despite intensive investigation, the pathogenesis of sodium retention in patients with chronic liver disease is not fully known. We have studied 19 chronic liver disease patients, 13 without (group 1) and six with (group 2) histories of clinical sodium retention (ascites or edema) by varying dietary sodium intake. The patients were placed on a 20 mmol/day constant diet for 1 wk, followed by a constant 100 mmol/day sodium diet for 1 wk under strict metabolic conditions. After 5 days of equilibration on each diet, blood and urine samples were collected for plasma atrial natriuretic factor levels and urinary sodium excretion. Group 1 patients (n = 6) achieved near sodium balance in 5 days on both a 20-mmol (urinary sodium output = 17 +/- 3 mmol/day) and a 100-mmol sodium diet (urinary sodium output = 80 +/- 5 mmol/day). Atrial natriuretic factor levels in these patients tended to be elevated, but the increase was not significantly greater than that in normal control subjects (10 +/- 4 pg/ml to 19 +/- 4 pg/ml) on the same diets. In contrast, group 2 patients (n = 5) were in significant positive sodium balance on both the 20 mmol/day sodium diet (mean urinary sodium output = 9.5 +/- 3.3 mol/day) and the 100 mmol/day sodium diet (urinary sodium output = 37 +/- 13 mmol/day). This occurred despite significantly elevated baseline atrial natriuretic factor levels and a significant increase in plasma atrial natriuretic factor levels after sodium challenge (62 +/- 9 pg/ml, p less than 0.05) on a 100 mmol/day sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Campylobacter pylori in Israel: prospective study of prevalence and epidemiology.

Antral biopsy samples were taken from 147 patients undergoing gastroscopy. Campylobacter pylori was cultivated from 100 of these patients. C. pylori was isolated from 76% of the specimens showing any degree of histologic gastritis, but from only 11% of specimens with completely normal histology. A questionnaire was completed on all patients and included demographic, epidemiologic and clinical information. Sephardic origin, smoking, and a bad taste in the mouth were more prevalent in the campylobacter-positive group. Previous use of antibiotics was negatively associated with the presence of C. pylori. Histologically confirmed gastritis was highly associated with the presence of C. pylori, especially in the moderate or severe grades in which 84% of biopsy specimens were positive. C. pylori was also cultivated from 50% of patients with mild gastritis, in 88% of patients with duodenal ulcer and in 71% of patients with gastric ulcer. The presence of C. pylori in 11% of normal specimens and the absence of C. pylori in 24% of specimens with gastritis further raises the question of the exact role played by C. pylori in the etiology of gastritis.

Abnormal liver enzymes and ketonuria in hyperemesis gravidarum. A retrospective review of 80 patients.

We reviewed retrospectively a cohort of 80 patients with hyperemesis gravidarum hospitalized between 1976 and 1986 for the presence of abnormal liver enzymes and ketonuria. Thirteen (16%) had abnormal liver enzymes, generally less than four times the upper limit of normal. In this group, hyperemesis gravidarum began at the 14th week of pregnancy as compared to the 6th week in the normal enzyme group (p less than 0.01). Both groups were similar with regard to age, number of children and pregnancies, and duration of vomiting. Ketonuria was significantly more severe (p less than 0.01) in the abnormal enzyme group, implying a more severe state of starvation and dehydration. The correlation coefficient between the degree of ketonuria and level of liver enzymes was low for alkaline phosphatase (r = 0.18), GPT (r = 0.15), and GOT (r = 0.28). The concept that dehydration and starvation are important factors for the induction of liver cell injury is supported by our data. Lack of correlation between the degree of ketonuria and liver enzyme levels is suggestive of other mechanisms (hormonal, genetic) that may interact to produce transaminasemia.

Ornithine decarboxylase: an unreliable marker for the identification of population groups at risk for colonic neoplasia.

Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. Polyamines have been studied as potential markers of neoplastic diseases, including colonic cancer. Previous studies have pointed out the possible value of this enzyme as a biochemical marker of colonic neoplasia, we studied 100 patients undergoing diagnostic total colonoscopy. There were 40 normal controls and 20 patients in each of the following groups: 1) family members of patients diagnosed as having colonic tumors, 2) patients with adenomas, and 3) patients with colonic adenocarcinoma. Six forceps biopsies were obtained from the normal-appearing sigmoid mucosa for the analysis of ODC. No difference was found among the four groups studied. We therefore conclude that ODC is unreliable for clinical use as a biochemical marker for the identification of population groups at risk for colonic neoplasia.