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Biomedical subjects

L S Friedman

Publications and source records attributed to L S Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Complications of chronic liver disease.

The patient with advanced cirrhosis presents unique challenges to the critical care physician, in great measure because of the protean functions attributable to the liver and the multiplicity of derangements that may occur. Portal hypertension, once it develops, is the source of potentially devastating complications that include life-threatening hemorrhage, infection, renal failure, and coma. Parenchymal disease can result in coagulopathy as well as altered handling of both endogenous (hormones, metabolites) and exogenous (drugs) substances. Cirrhosis also can be complicated by the development of HCC, which may worsen portal hypertension, deplete parenchymal reserves, and result in catastrophic complications. The prospect of cure by liver transplantation in selected cases serves to underscore the importance of prompt and vigilant management of patients with decompensated cirrhosis in the critical care setting.

Ascites↗
PubMed1995

Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.

Thirty-seven families with four or more cases of breast cancer or breast and ovarian cancer were analyzed for mutations in BRCA1. Twelve different germ-line mutations, four novel and eight previously observed, were detected in 16 families. Five families of Ashkenazi Jewish descent carried the 185delAG mutation and shared the same haplotype at eight polymorphic markers spanning approximately 850 kb at BRCA1. Expressivity of 185delAG in these families varied, from early-onset breast cancer without ovarian cancer. Mutation 4184delTCAA occurred independently in two families. In one family, penetrance was complete, with females developing early-onset breast cancer or ovarian cancer and the male carrier developing prostatic cancer, whereas, in the other family, penetrance was incomplete and only breast cancer occurred, diagnosed at ages 38-81 years. Two novel nonsense mutations led to the loss of mutant BRCA1 transcript in families with 10 and 6 cases of early-onset breast cancer and ovarian cancer. A 665-nt segment of the BRCA1 3'-UTR and 1.3 kb of genomic sequence including the putative promoter region were invariant by single-strand conformation analysis in 13 families without coding-sequence mutations. Overall in our series, BRCA1 mutations have been detected in 26 families: 16 with positive BRCA1 lod scores, 7 with negative lod scores (reflecting multiple sporadic breast cancers), and 3 not tested for linkage. Three other families have positive lod scores for linkage to BRCA2, but 13 families without detected BRCA1 mutations have negative lod scores for both BRCA1 and BRCA2.

Alleles↗
PubMed1994

The search for BRCA1.

BRCA1, a gene predisposing to breast and ovarian cancer, was mapped to chromosome 17q21 by linkage analysis. Loss of heterozygosity in breast and ovarian tumors from BRCA1-linked patients always involved loss of wild-type alleles from chromosome 17q21, suggesting that BRCA1 acts as a tumor suppressor gene. Meiotic recombination in linked families constrained the BRCA1 region to an estimated physical size of 650 kilobases. Twenty-two candidate genes were isolated by screening complementary DNA libraries with yeast artificial chromosomes and cosmids from the critical region. Of these, 8 were known human genes, 7 were homologues of genes identified in other species, and 7 encoded novel transcripts. Each gene were sequenced and analyzed for variation, revealing 44 variants, including two missense mutations in two genes which segregated with breast cancer and were not found in controls. However, no frame-shift, nonsense, or regulatory mutations were found.

Base Sequence↗
PubMed1994

Limonene in expired lung air of patients with liver disease.

As part of an effort to examine the relationship between chemosensory disturbance and oral chemistry, we analyzed expired lung air samples from a series of 24 patients with liver disease and 24 healthy controls using gas chromatography-mass spectrometry. Compared to samples from controls, lung air from patients with liver disease contained unusually high levels of limonene, a monoterpene that is a major component of the essential oil of citrus fruits (0.1 vs 7.0 micrograms/20 liters for controls and patients). Only half the patients showed high levels of limonene. Patients with noncholestatic liver disease were significantly more likely to have elevated lung air limonene levels than those with cholestatic liver disease (0.2 vs 13.8 micrograms/20 liters). Responses to food frequency and dietary behavior questionnaires indicated a pattern of diet selection and food preferences that were consistent with a dietary origin for the limonene in these patients.

Air↗
PubMed1994

Inflammatory bowel disease in older patients.

The onset of UC and CD may occur later in life. Although making the diagnosis of IBD in the elderly can be challenging, the clinical course, natural history, and response to treatment are similar for older and younger patients. In fact, both UC and CD tend to be less extensive in older patients, a feature that may contribute to the overall favorable prognosis for elderly patients with IBD. Overall mortality rates for both UC and CD appear to be similar to that of the general population except for those few patients that present with severe initial disease. Typical features of IBD in the elderly are summarized in Table 3. The differential diagnosis of IBD in the elderly includes infectious causes of enterocolitis, ischemic colitis, and diverticular disease as well as several other mimics of IBD. Awareness of the possibility of late-onset disease and the unique manifestations of disease in the elderly contributes to accurate diagnosis and timely treatment.

Aged↗
PubMed1994

Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q.

Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis. We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus, BRCA1, on chromosome 17q. We found strong evidence against linkage to BRCA1 (lod score-16.63) and the best estimate of the proportion of linked families was 0% (95% CI 0-18%). Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early-onset breast cancer in women and which confers a higher risk of male breast cancer. Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene.

Breast Neoplasms↗
PubMed1994

Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families.

We provide genetic evidence supporting the identity of the candidate gene for BRCA1 through the characterization of germline mutations in 63 breast cancer patients and 10 ovarian cancer patients in ten families with cancer linked to chromosome 17q21. Nine different mutations were detected by screening BRCA1 DNA and RNA by single-strand conformation polymorphism analysis and direct sequencing. Seven mutations lead to protein truncations at sites throughout the gene. One missense mutation (which occurred independently in two families) leads to loss of a cysteine in the zinc binding domain. An intronic single basepair substitution destroys an acceptor site and activates a cryptic splice site, leading to a 59 basepair insertion and chain termination. The four families with both breast and ovarian cancer had chain termination mutations in the N-terminal half of the protein.

BRCA1 Protein↗
PubMed1994

Liver abscesses due to Staphylococcus aureus in a patient with AIDS who underwent small bowel biopsy: case report and review.

A 36-year-old man with overgrowth of Staphylococcus aureus in the small bowel underwent a biopsy of the small bowel and presented 5 weeks later with multiple liver abscesses. To our knowledge, small bowel biopsy has never been associated with liver abscesses. We discuss the literature on liver abscesses in patients with AIDS and the risks of bacteremia following upper endoscopy and small bowel biopsy and propose that the etiology of the liver abscesses in our patient was seeding of the portal vein following biopsy of a small bowel that had significant bacterial overgrowth.

AIDS-Related Opportunistic Infections↗
PubMed1994

Hepatitis C in sickle cell anemia.

We evaluated the contribution of hepatitis C virus infection to liver disease in patients with sickle cell anemia. Antibody to hepatitis C virus (anti-HCV) by commercial enzyme immunoassay and a second confirmatory assay were assayed in 121 consecutive patients with sickle cell anemia. Anti-HCV was detected in 25 of 121 patients (20.7%). Of patients transfused > 10 units of blood products, 30.3% were anti-HCV seropositive, whereas 8.6% of those patients who transfused < 10 units were seropositive. In 11 of the 121 patients, serum alanine aminotransferase levels were repeatedly elevated. Nine of these 11 patients were anti-HCV seropositive, one was positive for hepatitis B surface antigen, and one was negative for all viral markers. In contrast, of 110 patients with normal serum alanine aminotransferase levels, only 14% were anti-HCV seropositive. In patients with sickle cell anemia, exposure to hepatitis C is common, related to the number of previous transfusions, and the most likely cause of persistently elevated aminotransferase levels.

Adolescent↗
PubMed1994

Relationship between liver biochemical tests and dietary intake in patients with liver disease.

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.

Alkaline Phosphatase↗
PubMed1994

Formulary management of antiulcer drugs: clinical considerations.

Peptic ulcer disease (PUD) is thought to result from an imbalance between aggressive (excessive) {especially gastric acid and pepsin} and protective (diminished) factors (gastric mucus and bicarbonate, prostaglandins and others) in the stomach. Recent attention has focused on the role of Helicobacter pylori as a cause of chronic active gastritis and a pathogenic factor in PUD. Antiulcer medications with proven efficacy in the treatment of acute PUD include histamine 2 (H 2)-receptor antagonists, H +/K +-ATPase (proton pump) inhibitors, antacids, sucralfate and prostaglandin analogues. The advent of proton pump inhibitors in particular has resulted in effective therapy for ulcers that previously would have been considered refractory. H 2-receptor antagonists and sucralfate are also useful for maintenance therapy of PUD. Recent interest has focused on strategies aimed at eradicating H. pylori and the ensuing change in the natural history of PUD, specifically a marked decrease in ulcer recurrence. In contrast, with standard treatment regimens there is a high rate of ulcer relapse (50 to 90%) after acute ulcer healing. Eradication of H. pylori has until now required a triple drug regimen of bismuth and 2 antibiotics, and is too cumbersome for routine use. It is likely, however, that treatment aimed at eradicating H. pylori will be routine in the near future and will represent a cost-effective alternative to standard long term maintenance therapy.

Anti-Ulcer Agents↗
PubMed1994

Less frequent causes of lower gastrointestinal bleeding.

In the United States, four diseases account for the vast majority of cases of lower intestinal bleeding: arteriovenous malformation, diverticulosis, neoplasms, and internal hemorrhoids. In this article the authors discuss less frequent causes of gastrointestinal bleeding. "Common" less frequent causes of gastrointestinal bleeding include solitary rectal ulcer syndrome, colonic varices, mesenteric vascular insufficiency, small bowel diverticula, Meckel's diverticulum, aortoenteric fistula, vasculitis, small intestinal ulceration, endometriosis, radiation-induced injury, and intussusception. Less frequent causes of gastrointestinal bleeding that have been recently described include portal colopathy, diversion colitis, and gastrointestinal bleeding in runners.

Colon↗
PubMed1993

Chemosensory function, food preferences and appetite in human liver disease.

We evaluated chemosensory function, food preferences, and appetite in 88 patients with liver disease including those with hepatitis, cirrhosis, primary biliary cirrhosis, and sclerosing cholangitis. Reported chemosensory disturbances were common in the patients with liver disease: over 40% reported recent taste changes, and 27% reported recent changes in smell, compared to only 6% of healthy, age- and gender-matched controls with no history of marked chemosensory malfunction. Compared to controls, a greater proportion of liver patients reported food cravings (47 vs. 17%) and food aversions (33 vs. 16%). Foods with a predominantly bitter taste were specifically less preferred in patients with liver disease compared to healthy controls. Patients were also more likely to report poor to fair appetite than controls (37 vs. 5%). Groups of patients with different types of liver pathology showed varying patterns of food preferences, suggesting that dietary recommendations to liver patients might be tailored to the altered preferences associated with a particular type of hepatic dysfunction.

Adult↗
PubMed1993

Immunogenicity of two recombinant hepatitis B vaccines in older individuals.

PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived preparations given in 10-micrograms or 20-micrograms doses. The optimum dose remains controversial. We sought to assess the relative immunogenicity of two hepatitis B vaccines, given in different doses, in older individuals. PATIENTS AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total of 460 healthy subjects between 39 and 70 years of age were screened and immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to continue vaccination. Immunogenicity was measured by determination of antibody to hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates, and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects receiving the 20-micrograms dose of vaccine were slightly, but not significantly, greater than for subjects receiving the 10-micrograms dose, at each time point. However, at 3 months, males receiving the higher dose had significantly higher seroprotection rates than males receiving the lower dose: 63% versus 37% (p < 0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20 micrograms were significantly greater than that for the group receiving Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001). CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B virus vaccine appeared to result in more rapid development of seroprotective anti-HBs titers in older men and in higher titers of anti-HBs at the completion of vaccination when compared to the 10-micrograms dose. The latter data suggest that the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs titers.

Adult↗