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Biomedical subjects

T B Reynolds

Publications and source records attributed to T B Reynolds.

At least 19 recordsLinked to original sources

Hyperthyroidism and hepatic dysfunction. A case series analysis.

Liver dysfunction in hyperthyroid patients has not been well characterized. We analyzed the clinical records of 43 patients with hyperthyroidism to define the spectrum of clinical and liver test abnormalities. The patients were divided into three categories: (a) 18 patients with uncomplicated hyperthyroidism (HT) (b) 19 with hyperthyroidism and congestive heart failure (HT/CHF), and (c) 6 with hyperthyroidism and concomitant unrelated liver disease (HT/ULD). Hepatomegaly and/or spenomegaly were noted in 15 of 19 (79%) patients with HT/CHF as compared to 6 of 18 (33%) patients with HT and 3 of 6 (50%) patients with HT/ULD. Four patients with HT/CHF had ascites. Serum aminotransferase levels greater than 250 IU/L were noted in only 1 of 37 (3%) patients without unrelated liver disease. Patients with HT/ULD or HT/CHF had markedly low prothrombin time. Serum bilirubin levels as high as 323 microM were noted in patients with HT. No characteristic liver histology due to hyperthyroidism was noted. Severe liver test abnormalities, including deep jaundice and prolonged prothrombin time, can occur in patients with hyperthyroidism alone or with HT/CHF. This makes the diagnosis of concomitant, unrelated liver disease difficult until the hyperthyroidism has been controlled.

Adult

Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models.

Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed.

Adult

Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis.

Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.

Acute Disease

Failure of rifampin to relieve pruritus in chronic liver disease.

We investigated the effect of rifampin on pruritus in 12 patients with chronic liver disease: non-A, non-B hepatitis (n = 3), alcoholic cirrhosis (n = 4), primary biliary cirrhosis (n = 4), and primary sclerosing cholangitis (n = 1). The study was a crossover, randomized, double-blind trial where placebo and drug were given daily in identical capsules (300 mg) for 2 weeks each, with a 1 week washout before and after each cycle. Mean duration of pruritus was 1.6 years (range of 4 months-5 years). Blood tests were done weekly and patients used a visual analogue scale (VAS) from 0 to 100 to mark their level of itchiness daily. Only transaminases were significantly lower while the patients were on rifampin. VAS scores were minimally affected by either rifampin or placebo. At the end of the trial, four patients said they were less itchy on rifampin and three preferred placebo. Of these seven patients, small falls in VAS scores occurred in two patients on rifampin and two on placebo; there was no change in the remaining three. There was little change in serum bile salt levels during the trial. No patient became jaundiced and deepening of jaundice did not occur in the four patients with initially elevated bilirubin. We conclude that a daily 300 mg dose of rifampin was not effective in relieving pruritus in a variety of chronic liver diseases.

Adult

Renaissance of paracentesis in the treatment of ascites.

The dangers of large-volume paracentesis have been overemphasized in the past. Recent data fail to show hypovolemia or any other complications ascribable to 5-L paracentesis when it is accompanied by IV infusion of 40 gm of albumin. Other data question the need for albumin infusion. Large-volume paracentesis is now a therapeutic option for relief of symptomatic, tense ascites, and, in company with sodium restriction, for chronic management of ascites refractory to diuretics.

Ascites

Polymorphonuclear cell count response and duration of antibiotic therapy in spontaneous bacterial peritonitis.

The purposes of this study were (a) to measure serially ascitic fluid polymorphonuclear cell response in treated spontaneous bacterial peritonitis and (b) to determine whether an ascitic fluid polymorphonuclear cell count of less than 250 per mm3 on serial paracenteses was a satisfactory endpoint for antibiotic therapy. Thirty of 33 patients showed an exponential fall in ascitic fluid polymorphonuclear cell count after 48 hr of antibiotic therapy; the magnitude of decrease correlated with survival (p less than 0.01). Among the patients whose antibiotic therapy was discontinued when the ascitic fluid polymorphonuclear cell count reached 250 per mm3 or less, the duration of therapy was considerably shorter than for the patients who received "conventional" therapy (p less than 0.01). Recurrence of spontaneous bacterial peritonitis was similar in the two groups. Mortality correlated with the severity of underlying liver disease but not with duration of antibiotic therapy.

Anti-Bacterial Agents

Comparative acute effects of diflunisal and indomethacin on renal function in patients with cirrhosis and ascites.

Nonsteroidal anti-inflammatory drugs such as indomethacin induce a rapid reduction in renal perfusion and blunt the effects of diuretics in patients with cirrhosis and ascites. Nonacetylated salicylates reportedly cause less reduction in renal prostaglandins than do aspirin and other nonsteroidal anti-inflammatory drugs. To determine whether nonacetylated salicylates affect renal function, we compared diflunisal with indomethacin in nine patients with cirrhosis and ascites. One 50-mg dose of indomethacin reduced inulin clearance (91 +/- 11 to 76 +/- 11 ml/min) and blunted furosemide-stimulated natriuresis (58 +/- 12 to 36 +/- 9 mEq/h) and diuresis (1103 +/- 148 to 809 +/- 170 ml/h, all p less than 0.05). Three doses of diflunisal had no effect on inulin clearance (94 +/- 16 ml/min), natriuresis (60 +/- 12 ml/h), or diuresis (1041 +/- 112). Indomethacin caused greater reduction in urinary prostaglandin E2 (50% vs. 10%) and in serum thromboxane (94% vs. 80%) than diflunisal (p less than 0.05). Thus, nonacetylated salicylates avoid renal impairment and may be the preferred nonsteroidal anti-inflammatory drug in patients with cirrhosis and ascites.

Diflunisal

Phenytoin toxicity and hepatic encephalopathy: simulation or stimulation?

Two cases of phenytoin toxicity in patients with chronic liver disease who were taking 300 mg phenytoin daily are described. Each patient developed encephalopathy, characterized by confusion, disturbed conscious state, asterixis, and nystagmus, which was resistant to treatment with protein restriction, lactulose, and neomycin, but responsive to withdrawal of phenytoin. We suggest that the phenytoin did not precipitate hepatic encephalopathy, but caused an encephalopathy that mimicked it. We recommend that phenytoin be used cautiously in patients with liver disease, and that the drug's unbound serum level be measured if encephalopathy occurs.

Diagnostic Errors

Rapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema.

Serial measurements of plasma volume and ascites volume were made during treatment with large doses of oral diuretics in 14 patients with stable chronic liver disease. Eight patients had pitting edema in addition to ascites. Reproducibility of ascites and plasma volume measurements was verified in 10 control subjects not receiving diuretics. Six patients without edema undergoing rapid diuresis lost a mean of 1.2 +/- 0.2 L of ascites and an equivalent amount of weight (1.3 +/- 0.4 kg) per day. All had a rise in blood urea nitrogen or creatinine, or both, and a fall in creatinine clearance. Eight patients with edema undergoing rapid diuresis lost more weight (1.8 +/- 0.5 kg/day, p = 0.06) but less ascites (0.7 +/- 0.35 L/day, p less than 0.05) than those without edema, and none developed renal insufficiency. After edema disappeared, ascites mobilization increased (1.4 +/- 0.7 L/day) and renal dysfunction occurred. Plasma volume fell an average of 24% +/- 9% in patients without edema but did not change in patients with edema (-0.4% +/- 3%). When edema disappeared, plasma volume fell significantly (28% +/- 8%, p less than 0.001). Electrolyte changes including hyponatremia, hyperkalemia, and hypochloremia were seen only in the group without edema. Patients with ascites and no edema are able to mobilize more than 1 L/day during rapid diuresis, but at the expense of plasma volume contraction and renal insufficiency. Patients with peripheral edema appear to be protected from these effects because of the preferential mobilization of edema and may safely undergo diuresis at a rapid rate (greater than 2 kg/day) until edema disappears.

Amiloride

Results of a randomized trial of end-to-side portacaval shunt and distal splenorenal shunt in alcoholic liver disease and variceal bleeding.

Since 1976, we have compared the end-to-side portacaval shunt (PCS) with the distal splenorenal shunt (DSRS) in patients with alcoholic liver disease and recurrent variceal bleeding. Fifty-four patients were randomly assigned to receive either shunt procedure. There were 27 patients in each group and both groups were highly comparable in clinical and laboratory characteristics. Median follow-up was 31 mo in each group. Postoperative complications and operative mortality (7% after PCS, 12% after DSRS) were comparable. Spontaneous portasystemic encephalopathy developed in 32% of the patients at risk after PCS and in 39% after DSRS. Rebleeding from varices occurred in 4% of the patients after PCS and in 27% after DSRS. Cumulative survival was not significantly different between groups (5-yr survival: 31% after PCS, 43% after DSRS). We have failed to demonstrate superiority of DSRS in our patients with alcoholic liver disease with respect to postoperative encephalopathy or survival, and have experienced an unusually high rate of variceal rebleeding after DSRS.

Adult

Spontaneous liver cell adenoma in children.

The clinical and pathologic features observed in five children with spontaneous liver cell adenoma are described. All tumors showed benign biologic behavior. Two patients had untreated tumors that were followed for 5 years and 26 years, respectively, and showed no evidence of malignant transformation; the latter tumor unprecedentedly showed signs of spontaneous regression over time. Unusual physical findings associated with the liver cell adenomas included generalized osteoporosis, urticaria, and koilonychia. Microscopically, the liver cell adenomas were composed of cords, rarely sheets, of neoplastic hepatocytes with negligible pleomorphism and rare to absent mitoses; bile ducts, portal tracts, and central veins were absent. A fibrous capsule was present in all cases. Previously undescribed histologic features of this tumor type included focal extramedullary hematopoiesis and multinucleate giant cell formation in association with tumor necrosis. Benign neoplasms of the type described in this and previous studies probably should be managed conservatively.

Carcinoma, Hepatocellular

Ruptured amebic liver abscess.

Fifteen cases of extrahepatic rupture of amebic liver abscess have been reviewed. Five patients had thoracic rupture and ten had intra-abdominal rupture. Celiotomies were performed in five patients, with a preoperative diagnosis of acute appendicitis with perforation in four patients and generalized peritonitis of unknown origin in one patient. All 15 patients were treated with amebicides, including three patients with documented free intraperitoneal perforation who were not treated surgically. Twelve patients recovered uneventfully. Two patients with thoracic rupture developed secondary bacterial complications and in one case of free intraperitoneal rupture, a mistaken diagnosis of ruptured pyogenic abscess was made. Amebicidal therapy was delayed for four days. The patient died of multisystem organ failure. Amebicidal therapy is effective in the treatment of both unruptured and extrahepatic rupture of amebic liver abscess. Surgery should be required only for secondary bacterial complications.

Adult