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Biomedical subjects

T L Fong

Publications and source records attributed to T L Fong.

18 recordsLinked to original sources

A pilot study of ribavirin therapy for chronic hepatitis C.

Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used.

Adult

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

Absence of hepatitis C viral RNA from saliva and semen of patients with chronic hepatitis C.

Body fluids from 14 patients with chronic hepatitis C were analyzed for the presence of hepatitis C viral RNA using the polymerase chain reaction. Nucleic acids were extracted from serum, saliva, and semen in guanidinium thiocyanate, subjected to reverse transcription, and then amplified by a double polymerase chain reaction technique using "nested" primers from the highly conserved 5' non-coding region of the hepatitis C virus genome. Hepatitis C viral RNA was found in the serum of all patients in titers ranging between 10(-1) and 10(-3). The hepatitis C viral genome was not detected in any saliva or semen sample. These findings suggest that body fluids of patients with chronic hepatitis C are rarely, if ever, contaminated with the hepatitis C virus. This may help to explain the infrequent transmission of this disease by sexual or close physical contact.

Adult

The significance of antibody to hepatitis C virus in patients with chronic hepatitis B.

We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection.

Adult

Helicobacter pylori infection in pernicious anemia: a prospective controlled study.

Although some authors believe that Helicobacter pylori is the etiologic agent in chronic nonspecific gastritis, it has also been suggested that the bacterium colonizes inflamed mucosa as a secondary event. This study documents the prevalence of H. pylori in 28 patients with pernicious anemia and compares the findings with those of a group of 28 age-, race-, and sex-matched asymptomatic control subjects. All subjects underwent endoscopy with biopsy of the gastric antrum and corpus. A sample of serum was obtained before endoscopy for determination of antibodies (immunoglobulin A and immunoglobulin G) to H. pylori. The prevalence of H. pylori (by biopsy) in patients with pernicious anemia was significantly less than that in controls (11% vs. 71%, P less than 0.0001). All patients with pernicious anemia had abnormalities of corpus histology (inflammation and/or atrophy). In addition, 50% of patients with pernicious anemia had a lymphocytic infiltration of the antrum. All controls with H. pylori had gastritis, 50% having active chronic gastritis. Atrophic changes of the corpus were more commonly found in patients with pernicious anemia (75% vs. 7%, P less than 0.0001). Serology and biopsy results correlated poorly in the patients with pernicious anemia: all 5 patients with positive serology results had negative biopsy results, whereas all 3 patients with positive cultures on biopsy had negative serological studies. In conclusion, patients with pernicious anemia are protected from infection with H. pylori, and H. pylori does not passively colonize mucosa inflamed by an unrelated process.

Anemia, Pernicious

Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C.

The hepatitis C virus is a positive stranded hepatotropic RNA virus. We describe a method of detecting positive and negative strands of hepatitis C viral RNA using the polymerase chain reaction. We tested serum and liver tissue from nine patients with chronic hepatitis C. The positive RNA strand of HCV was detected in the sera and livers of all nine, the negative strand was detected in the livers of eight (89%), and in the sera of five (55%). Titers of both strands of HCV RNA were determined by serial endpoint dilutions. The amount of the negative strand in the serum and liver was usually 10-100 times less than the positive strand. Predigestion of serum with ribonucleases did not alter the detection of the negative strand. This suggests that the negative strand found in the serum may be protected from digestion by being associated with virions.

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

Spontaneous reactivation in chronic hepatitis B: patterns and natural history.

We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.

Adult

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

Pancreatic nesidioblastosis in adults.

Nesidioblastosis, a condition characterized by diffuse islet cell hyperplasia arising from the ductal epithelium, is often associated with hyperinsulinemic hypoglycemia. This is a childhood disease and is rarely found in adults. Only 10 histologically proven cases have been recorded, including 3 new cases described in this article. Most clinical and biochemical features are identical to those of an insulinoma, except the proinsulin-like component of circulating immunoreactive insulin, which is usually within the normal range in nesidioblastosis. Limited observations show that some patients may be managed medically with diazoxide. Patients who remain hypoglycemic despite medical therapy require pancreatectomy, although greater than 90% resection frequently results in insulin dependency and permanent diabetes.

Adult

Markers of viral replication in patients with chronic hepatitis B virus infection.

Serum samples from 56 patients with biopsy-proven chronic B viral hepatitis without superimposed delta hepatitis were analyzed for the various markers of viral replication, including serum hepatitis B e Ag (HBeAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA), and hepatitis B core antigen (HBcAg) in the liver tissues. Twenty-seven patients had persistent viral hepatitis (PH) and 29 patients had chronic active hepatitis (CAH) with or without cirrhosis. HBV-DNA was identified in the sera of 81% of patients with PH and 60% of patients with CAH. Significantly higher levels of HBV-DNA were found in patients with PH than in those with CAH. Both HBeAg in serum and HBcAg in liver correlated positively with serum HBV-DNA. Nine patients had serum HBV-DNA in the absence of HBeAg (four had anti-HBe), and seven of these nine patients had stainable HBcAg in the liver (two did not have staining). None of these patients had hepatic HBcAg in the absence of serum HBV-DNA. When these patients were stratified according to their epidemiologic background, serum HBV-DNA was present in a significantly higher number of male homosexuals than in any other groups. This was unrelated to their status of human immunodeficiency viral serology.

Chronic Disease

Concanavalin A affinity of alpha-fetoprotein. Its use in differentiating tumors.

Using affinity chromatography on concanavalin A Sepharose, the authors studied the molecular heterogeneity of the serum alpha-fetoprotein of 53 patients with hepatocellular carcinoma, 16 patients with metastatic tumors to the liver, and 16 patients with germ cell tumors. Mean concanavalin binding of alpha-fetoprotein in the sera of patients with hepatocellular carcinoma was 79%, whereas the mean binding in metastatic tumors was 52% and that of germ cell tumors was 45%. This striking molecular variation of the alpha-fetoprotein produced by these different tumors is helpful in the clinical distinction of these tumors.

Carcinoma, Hepatocellular

Status of hepatitis B virus DNA in alcoholic liver disease: a study of a large urban population in the United States.

Two reports have shown hepatitis B virus DNA in serum and liver tissue in alcoholic liver disease with negative serum HBsAg, suggesting a pathogenetic role for hepatitis B virus. We studied hepatitis B virus DNA in serum and liver from three groups of alcoholic patients; (Group 1) 50 patients without liver disease, (Group 2) 108 patients with alcoholic liver disease and (Group 3) five patients with alcoholic liver disease and hepatocellular carcinoma. Serum was tested for HBsAg, anti-hepatitis B core and anti-hepatitis B surface by radioimmunoassay and hepatitis B virus DNA by direct spot hybridization. Liver tissue from Groups 2 and 3 (113 patients) was examined by Southern blot analysis using 32P-labeled hepatitis B virus DNA clone from pBR322. Controls were 21 patients with chronic hepatitis B virus (14 patients with chronic active hepatitis, seven patients with cirrhosis and hepatocellular carcinoma). Serum and tissue were analyzed for hepatitis B virus DNA. Hepatitis B virus DNA was not detected in either serum or liver tissue in any of the 163 patients (Groups 1 to 3). In contrast, among the controls, hepatitis B virus DNA was present in the serum of 15 of the 21. Tissue DNA in those with chronic active hepatitis revealed 10/14 with free hepatitis B virus DNA, two with integrated sequences and two with no viral sequences. All seven patients with hepatocellular carcinoma had integrated viral DNA sequences in the tumor tissues. From these results, it appears that hepatitis B virus does not play a role in the pathogenesis of alcoholic liver disease.

Adult

Oral anomalies in the neonate, by race and gender, in an urban setting.

A broad range of developmental anomalies and morphologic variants may occur in the oral cavity of the newborn. Because many of these are transient (e.g.: palatal and alveolar cysts, lymphangioma), self-correcting with age, conventional assessments of older children can yield significantly altered trait incidences. A total of 500 normal full-term newborns (blacks and whites) were assessed by standardized criteria for 11 oral conditions, in addition to collating data on maternal conditions (age, gravidity, tobacco and alcohol use). Leukoedema and median alveolar notches were significantly more common in blacks, whereas palatal cysts were 2.5 times as likely to occur in whites. Ankyloglossia, three times as common in males, was the one trait to exhibit a significant predilection by gender. Low maternal age (less than 20 years) significantly enhanced the risk of alveolar lymphangioma in these data.

Female