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Biomedical subjects

K Fawaz

Publications and source records attributed to K Fawaz.

11 recordsLinked to original sources
PubMed2001

Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial.

OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations (p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr (p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5-8 at 6 months and 1 yr (p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials.

Adenoma↗
PubMed2001

Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate status among individuals ingesting physiologic quantities of folate.

Folate status is inversely related to the risk of colorectal cancer. Whether conventional blood measurements of folate status accurately reflect folate concentrations in the colorectal mucosa has been a controversial topic. This is an important issue because accurate measures of folate status in the colorectal mucosa are important for ascertaining the risk of colorectal cancer in epidemiological studies and for determining the effects of folate supplementation in clinical trials. We examined whether conventional blood measurements of folate and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflect folate concentrations in human colonic mucosa obtained by endoscopic biopsy. Study subjects (n = 20) were participants in a randomized trial that investigated the effect of folate supplementation (5 mg daily for 1 year) on provisional molecular markers of colon cancer. Blood samples and biopsies of normal rectosigmoid mucosa were obtained at baseline, at 6 months, and at 1 year. Serum, RBC, and colonic mucosal folate and serum homocysteine concentrations were determined. Colonic mucosal folate concentrations correlated directly with serum folate concentrators at each time point (r = 0.572-0.845; P < 0.015) and with RBC folate concentrations at 6 months and 1 year (r = 0.747-0.771; P < 0.001). Colonic mucosal folate concentrations correlated inversely with serum homocysteine concentrations at each time point (r = -0.622-0.666; P < 0.008). Systemic measures of folate status did not correlate with colonic mucosal folate concentrations among individuals receiving supplemental folate. Our observations indicate that colonic mucosal concentrations of folate may be predicted accurately by blood measurements of folate status only among individuals not ingesting supraphysiological quantities of folate.

Adenoma↗
PubMed1998

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps.

BACKGROUND: Estimates of habitual dietary folate intake are known to be imprecisely correlated with systemic measures of folate status. Furthermore, measurements of blood folate concentrations may not accurately reflect the concentration of folate in tissues of interest. This issue is important for assessing folate status in the colorectal mucosa because low dietary intake or blood concentrations of folate are associated with an increased risk of colorectal neoplasia. OBJECTIVE: We examined whether conventional measures of folate in blood and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflected folate concentrations in human colonic mucosa obtained by endoscopic biopsy. DESIGN: In 30 persons with colorectal polyps, blood samples were taken and biopsies of normal rectosigmoid mucosa performed at the time of colonoscopic polypectomy. Serum, red blood cell, and colonic mucosal folate and serum homocysteine concentrations were measured. RESULTS: Serum and red blood cell folate and serum homocysteine concentrations accurately reflected colonic mucosal folate concentrations; among these, serum homocysteine correlated best with mucosal concentrations. Folate concentrations in the normal rectosigmoid mucosa were significantly lower in persons with adenomatous polyps than in those with hyperplastic polyps (P=0.04). Conventional measures of systemic folate status were not significantly lower in those with adenomas, although serum homocysteine was mildly elevated (P=0.04). CONCLUSIONS: Our data underscore the ability of systemic measures of folate status, particularly serum homocysteine, to reflect folate concentrations in the colonic mucosa. Nevertheless, future studies that examine the ability of folate to modulate colorectal carcinogenesis may benefit from direct measurement of folate in the colon.

Adenoma↗
PubMed1993

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Acyclovir↗
PubMed1991

Practice patterns and costs of hospitalization for upper gastrointestinal hemorrhage.

We conducted an observational study at three hospitals in Boston to examine the patterns of practice and the costs involved in the medical management of noncirrhotic, upper gastrointestinal bleeding. A total of 111 patients were identified and studied: 42 from hospital 1, 38 from hospital 2, and 31 from hospital 3. There were no significant differences in the management of the patients, except for the more frequent use of upper gastrointestinal radiography at hospital 3 and the more frequent use of cimetidine at hospital 2. Only a small percentage (3-7%) of patients required surgery, and overall mortality (0-8%) was low. The average cost of hospitalization, determined by using the New England Medical Center cost model, was calculated for direct costs ($3,180). The majority of costs incurred were for hospital bed or intensive care unit stay (63%) and transfusion of blood products (14%), with costs for physicians' services (9%), endoscopy (2%), and upper gastrointestinal radiography (1%) accounting for only a small percentage. This study demonstrates remarkable similarity in practice patterns and resource utilization at three different hospitals and provides data on the actual costs involved in hospitalization for noncirrhotic, upper gastrointestinal hemorrhage.

Acute Disease↗
PubMed1990

Recurrent acute pancreatitis as a manifestation of Wegener's granulomatosis.

We report a case of recurrent acute pancreatitis in a 57-year-old man with reactivation of Wegener's granulomatosis. An association between acute pancreatitis and Wegener's granulomatosis has not been reported previously. Six episodes of abdominal pain and hyperamylasemia occurred and were complicated by development of a pancreatic pseudocyst. New cavitary lung lesions typical of Wegener's granulomatosis led to treatment with increased glucocorticoid dosage, resulting in rapid resolution of the pancreatitis and pulmonary lesions. Acute pancreatitis may be a clinical manifestation of the histologic pancreatic vasculitis observed in Wegener's granulomatosis. Reactivation of Wegener's granulomatosis should be considered when a patient with the disorder develops otherwise unexplained acute pancreatitis.

Acute Disease↗
PubMed1983

Increased oxidation of a chemical carcinogen, benzo(a)pyrene, by colon tissue biopsy specimens from patients with ulcerative colitis.

Colonic biopsy specimens from patients with ulcerative colitis and normal subjects were studied for the ability to metabolize an environmental carcinogen, benzo(a)pyrene. Approximately 73% of 30 colonic biopsy specimens from 7 ulcerative colitis patients could metabolize benzo(a)pyrene to oxidized products, with an average production of 11.6 nmol/mg biopsy protein. In contrast, 39% of 23 biopsy specimens from 5 normal persons showed metabolic activity, with an average of 2.79 nmol benzo(a)pyrene metabolites/mg biopsy protein. Thus, benzo(a)pyrene oxidation activity in colonic tissue from colitis patients was, on the average, fourfold greater than that in normal subjects. This elevated metabolic activity appeared to be unrelated to the state of inflammation in the biopsy section. There was a tendency toward increased metabolic activity in the distal colon. Although there is no evidence that benzo(a)pyrene itself is "the colon carcinogen," this chemical belongs to a broad class of environmental carcinogens, the polycyclic aromatic hydrocarbons. Our findings suggest that the colonic mucosa of patients with ulcerative colitis has a greater ability than that of normal subjects to oxidize such chemicals possibly to electrophiles with higher mutagenic potential.

Adult↗
PubMed1977

Multifocal malignant hemangioendothelioma presenting as acute hepatitis. A clinicopathologic study.

A patient with malignant hemangioendothelioma of the liver is described. The patient's clinical presentation and course were that of fulminant hepatic necrosis. Complications included upper gastrointestinal hemorrhage, hepatic encephalopathy, abnormal coagulation parameters and the hepatorenal syndrome. The duration of the illness from the onsetof symptoms to its fatal outcome was five weeks.

Acute Disease↗