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Biomedical subjects

J Fryer

Publications and source records attributed to J Fryer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.

PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.

Antimetabolites, Antineoplastic↗
PubMed1998

Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.

PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.

Colorectal Neoplasms↗
PubMed1997

Budesonide, a locally acting steroid, prevents graft rejection in a rat model of intestinal transplantation.

BACKGROUND: The requirement for potent systemic immunosuppression to prevent intestinal graft rejection has resulted in high rates of infection and post-transplant lymphoproliferative disease. Budesonide (BUD) is a locally acting steroid that is almost completely metabolized during its first pass through the intestinal wall and liver. The present study examined whether BUD could prevent small bowel allograft rejection without causing the adverse systemic effects associated with prednisolone. METHODS: Orthotopic Brown Norway to Lewis rat small bowel allotransplants were randomly assigned to treatment with low-dose BUD (0.1 mg/kg/day, p.o.) and high-dose BUD (1.0 mg/kg/day, p.o.) with and without cyclosporine (CsA; 2 mg/kg/day s.c.). The following parameters were assessed: allograft survival, recipient plasma adrenocorticotrophic hormone (ACTH) levels, recipient adrenal, splenic and thymic weights, recipient CsA levels, and graft histopathology. RESULTS: Low- and high-dose BUD alone did not prolong graft survival compared with the untreated group (9.1+/-0.4 days vs. 11+/-0.8 days vs. 9.7+/-0.4 days, respectively). However, when low-dose BUD and high-dose BUD were given in combination with CsA, the mean graft survival times were prolonged to 27.6+/-5.3 and 36.6+/-8.0 days, respectively (P<0.01). ACTH levels, adrenal weights, and thymic weights were not significantly different in the treatment and control groups receiving intestinal transplants. CONCLUSIONS: BUD enhances the immunosuppressive effects of CsA and prolongs small bowel allograft survival in rats without inhibiting normal ACTH release. These data suggest that BUD may be a useful immunosuppressive agent for clinical intestinal transplantation.

Adrenocorticotropic Hormone↗
PubMed1997

Gender differences and other determinants of the rise in plasma homocysteine after L-methionine loading.

The methionine load test is widely used to identify subjects with mild homocysteinemia. We studied factors influencing the rise in plasma homocysteine (tHcy) levels following oral methionine loading, after taking into account determinants of the basal level. The study population comprised 522 persons (mean age 53, range 17 to 95; 63% male; 60% with coronary disease). tHcy was measured fasting and 4 h after administration of L-methionine (dose 4 g/m2). The percentage rise in tHcy was greater in females, at younger ages, and with lower serum creatinine. Basal tHcy was lower in those with high levels of serum folate, red cell folate and serum B12; they also showed a greater percentage rise with loading. After adjustment for age, creatinine and serum vitamins the percent rise was greater in females (mean 230%, S.D. 92) than in males (mean 172%, S.D. 71, P < 0.0001). About 1/4 of this effect was explained by the methionine dose, but important independent gender effects remained. When the results of the loading test were compared with an overall reference range, females were systematically labelled as 'high' but comparison with age and gender-specific reference ranges normalised the sex distribution. Our data show that a single L-methionine loading protocol for both sexes is not appropriate. Gender-specific reference ranges should be used to define post-load homocysteinemia and previous studies which have identified a high proportion of females with this trait probably reflect the need for gender specific reference ranges.

Adolescent↗
PubMed1997

Fasting and post-methionine homocyst(e)ine levels in a healthy Australian population.

BACKGROUND: Plasma homocyst(e)ine (H[e]) is frequently measured in patients with occlusive vascular disease, but levels vary between populations and between laboratories. AIMS: We sought to derive reference values for an Australian population over a wide age range. METHODS: We measured plasma H(e) in the fasting state and after methionine loading in 116 volunteers selected at random from the Hunter districts of the New South Wales electoral roll and in 49 apparently healthy, active subjects recruited from the region's lawn bowling clubs. Reference ranges were derived for both sexes, in three age strata. We collaborated with two international laboratories in standardising our results. RESULTS: Mean fasting H(e) levels were approximately 2.7 mumol/L higher in men than women, at all ages (95% CI for the difference, 1.2 to 4.1 mumol/L). Levels increased with age (approximately 1.0 mumol/L/decade, 95% CI 0.5 to 1.5) and were correlated with serum creatine (r = 0.48), serum folate (r = -0.30), red cell folate (r = -0.25) and serum B12 (r = -0.31) (all p < 0.001). These results are similar to those reported in other populations. CONCLUSIONS: We have defined reference ranges for a typical Australian population, following careful laboratory standardisation. H(e) levels must be interpreted with regard to age, sex, renal function and vitamin B12 and folate status.

Adult↗
PubMed1997

Knee pain and knee osteoarthritis severity in self-reported task specific disability: the Johnston County Osteoarthritis Project.

OBJECTIVE: To evaluate the contributions of radiographic knee osteoarthritis (OA) and knee pain severity to self-reported disability performing upper and lower extremity tasks in a rural, population based sample. METHODS: Data from 1192 African-American and Caucasian participants in the Johnston County Osteoarthritis Project were analyzed with multiple logistic regression to examine the roles of Kellgren-Lawrence radiographic knee OA grade and knee pain severity in self-reported difficulty performing 20 activities of the Health Assessment Questionnaire. Potential confounders included age, sex, race, marital status, education, and body mass index. RESULTS: Forty-three percent reported difficulty performing at least one task. Mild knee pain was independently associated with difficulty performing 16 upper and lower extremity tasks, and moderate/severe knee pain with all 20 tasks, with little change after adjustment (p < 0.0001). In contrast, mild radiographic knee OA was associated with difficulty in only 4 mobility and transfer tasks: climbing 5 steps, taking a tub bath, getting in/out of a car, and performing chores. Moderate/severe radiographic knee OA was associated with difficulty in 17 of 20 tasks (in 10 of 17, p < 0.0001), except lifting a cup, opening car doors, and turning faucets. However, no associations between radiographic knee OA and difficulty were statistically significant after adjustment for knee pain and the above factors. CONCLUSION: Knee pain severity was the strongest risk factor for self-reported difficulty performing tasks of upper and lower extremity function. Future studies of disability should include data on knee pain severity.

Activities of Daily Living↗
PubMed1996

Influence of macrophage depletion on bacterial translocation and rejection in small bowel transplantation.

Rejection and sepsis can be intimately related following small bowel transplantation when rejection compromises normal intestinal barrier mechanisms and bacterial translocation results. Macrophages play a role in controlling the egress of intestinal luminal bacteria--and they have also been implicated in allograft rejection. In this study, the role of macrophages in rejection and bacterial translocation was evaluated by depleting macrophages in donors and/or recipients of rat small bowel allografts with injection of liposome-encapsulated dichloromethylene diphosphonate (CL2MDP). In preliminary studies, we demonstrated that a single intraperitoneal injection of liposome-encapsulated CL2MDP (350 mg/kg) depleted ED2-positive macrophages by > 90% in the liver mesenteric lymph nodes and proximal and distal small bowel, and by approximately 50% in the spleen. ED1-positive macrophages were depleted by > 90% in the liver and by approximately 50% at the other sites. ED3-positive macrophages were completely depleted. Dendritic cells were > 90% depleted in the spleen and mesenteric lymph nodes, but were not depleted in the small bowel. Macrophage depletion in the donor resulted in increased translocation of bacteria to the peritoneal cavity (P = 0.03) if recipient macrophages were present. With histopathologic analysis, a significantly milder rejection with less arteritis was seen in the allografts of the recipient macrophage-depleted group compared with nondepleted controls (P = 0.045). This suggests that recipient macrophages play an important role in rejection. With macrophage depletion in both the donor and the recipient, graft survival was prolonged significantly (13.2 +/- 1.9 days) compared with non-macrophage-depleted controls (9.2 +/- 1.3 days) (P = 0.003). These studies suggest that strategies targeting recipient macrophages may be useful in controlling small bowel allograft rejection without increasing bacterial translocation.

Animals↗
PubMed1996

An analysis of late deaths after liver transplantation.

Late deaths (after more than 1 year) after liver transplantation were analyzed in a series of 464 consecutive patients who received liver grafts between 1982 and 1993. Recipients who survived the first posttransplant year (n = 365) had actuarial 5- and 10-year survival rates of 92% and 84%, respectively. Thirty-five patients died between 1.1 and 7.6 years after transplantation (mean, 3.2 +/- 1.9 years). The most common causes of death were related to immunosuppression (40%), namely, chronic rejection, opportunistic infection, and lymphoma. The second most common causes of death were related to the primary disease for which liver transplantation was performed (34.3%), mainly recurrence of hepatobiliary malignancy and hepatitis B. Eight patients (22.9%) died of unrelated and unpredicted causes, most commonly of cardiovascular disease. Although the survival of liver recipients who live beyond the first posttransplant year is excellent, control of rejection and the consequences of chronic immunosuppression are continual threats. Modification of immunosuppression may help in decreasing the mortality of long-term survivors. In addition, better selection of recipients and effective adjuvant therapies (antiviral and antineoplastic) are needed in patients in whom the primary liver disease is notorious for recurrence.

Adolescent↗
PubMed1996

Quadruple immunosuppression in a pig model of small bowel transplantation.

Rejection remains a major obstacle to successful small bowel transplantation in humans, irrespective of the immunosuppressants. Previous large animal studies have not used quadruple immunosuppression (with high-dose intravenous cyclosporine A [CSA]) for induction, followed by triple immunosuppression for maintenance therapy. Nor have immunosuppressive doses been comparable to clinical solid organ transplants. We studied, in 78 nonrelated outbred pigs, the effect of quadruple immunosuppression (including horse anti-pig thymocyte globulin [ATG] and high-dose intravenous CSA) on the incidence and severity of rejection in the early, critical posttransplant period. Group A (n = 19) pigs were nonimmunosuppressed. Group B (n = 20) received quadruple immunosuppression: pig ATG (10 mg/kg/day x 10 days), intravenous CSA (3.0 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); prednisolone and azathioprine were each reduced by 50% on posttransplant Days 8 and 15. Trough CSA levels were > or = 400 ng/ml for the first 7 days posttransplant, > 200 ng/ml thereafter. Recipient pigs underwent resection of large and small bowel; orthotopic transplants (proximal duodenojejunostomy, distal ileostomy) were done with systemic vein drainage. We developed a scoring system (no, mild, moderate, severe rejection) to grade the extent of both interstitial and vascular rejection: biopsies were obtained daily from the ileostomy. Rejection-free graft survival at posttransplant Days 7, 10, and 14 was 32, 26, and 16% in the nonimmunosuppressed group versus 95, 90, and 85% in the immunosuppressed group (P < 0.0001). Rejection grades were significantly better over the whole observation period in immunosuppressed pigs: interstitial rejection was not present in up to 67% of all daily biopsy specimens. Rejection was present in all specimens of nonimmunosuppressed pigs. Vascular rejection was uncommon (incidence < 10%) in both groups. Isolated vascular rejection without interstitial rejection was not found. Graft-versus-host reaction was noted in both groups in the skin only; liver and native bowel were not involved. We conclude that quadruple immunosuppression with pig ATG and high-dose intravenous CSA for induction effectively prevents moderate and severe rejection in this model. Since clinical transplant complications (rejection, lymphomas) have persisted under FK 506 treatment, our immunosuppressive regimen should be considered an alternative for bowel transplantation in humans to prevent early rejection.

Animals↗
PubMed1996

Pemphigoid gestationis occurring in a patient with HELLP syndrome.

A case of pemphigoid gestationis occurring in a 40 year old female who developed HELLP syndrome during her fourth pregnancy is reported. Seven days after emergency Caesarean section for pre-eclampsia, she developed a pruritic blistering eruption which clinically resembled pemphigoid gestationis. The diagnosis was supported by skin histology and immunofluorescence. She responded rapidly to oral corticosteroids, with no evidence of recurrence after 12 weeks of follow up. In the current case report, the previously unreported simultaneous occurrence of two uncommon conditions is described.

Administration, Oral↗
PubMed1995

The outcomes and costs of care for acute low back pain among patients seen by primary care practitioners, chiropractors, and orthopedic surgeons. The North Carolina Back Pain Project.

BACKGROUND: Patients with back pain receive quite different care from different types of health care practitioners. We performed a prospective observational study to determine whether the outcomes of and charges for care differ among primary care practitioners, chiropractors, and orthopedic surgeons. METHODS: Two hundred eight practitioners in North Carolina were randomly selected from six strata: urban primary care physicians (n = 39), rural primary care physicians (n = 48), urban chiropractors (n = 32), rural chiropractors (n = 32), orthopedic surgeons (n = 29), and primary care providers at a group-model health maintenance organization (HMO) (n = 28). The practitioners enrolled consecutive patients with acute low back pain. The patients were contacted by telephone periodically for up to 24 weeks to assess functional status, work status, use of health care services, and satisfaction with the care received. RESULTS: The status at six months was ascertained for 1555 of the 1633 patients enrolled in the study (95 percent). The times to functional recovery, return to work, and complete recovery from low back pain were similar among patients seen by all six groups of practitioners, but there were marked differences in the use of health care services. The mean total estimated outpatient charges were highest for the patients seen by orthopedic surgeons and chiropractors and were lowest for the patients seen by HMO and primary care providers. Satisfaction was greatest among the patients who went to the chiropractors. CONCLUSIONS: Among patients with acute low back pain, the outcomes are similar whether they receive care from primary care practitioners, chiropractors, or orthopedic surgeons. Primary care practitioners provide the least expensive care for acute low back pain.

Acute Disease↗
PubMed1995

Care-seeking among individuals with chronic low back pain.

STUDY DESIGN: This was a stratified, random telephone survey of adults in North Carolina. OBJECTIVE: To determine the prevalence of chronic low back pain and the extent to which treatment is sought for this condition. SUMMARY OF BACKGROUND DATA: Chronic low back pain is a major problem. Previous studies often have combined acute and chronic back pain. METHODS: Telephone interviews regarding back pain were conducted with 4437 North Carolina adults during 1992. RESULTS: Chronic back pain affects 3.9% of the North Carolina population. Thirty-four percent considered themselves permanently disabled and 52% assessed their overall health as fair or poor. The median number of bed-disability days per year was three. Seventy-three percent saw a health care provider. Of those who sought care, 91% saw a medical doctor, 29% saw a physical therapist, and 25% saw a chiropractor. Use of technology was extensive: 37% received a computed tomography scan, 25% received a magnetic resonance imaging scan, and 10.4% underwent surgery. CONCLUSIONS: Chronic back pain is common, and the level of care-seeking and costs of care among those afflicted are extremely high.

Adult↗
PubMed1995

Subcutaneous fat necrosis following traumatic pancreatitis.

A 25 year old female who developed subcutaneous fat necrosis and polyarthritis secondary to post-traumatic pancreatitis is reported. This is a well documented but uncommon phenomenom, affecting less than 1% of patients with pancreatic disease.

Abdominal Injuries↗
PubMed1995

Immunolocalization of proton pumps (H+-ATPase) in pavement cells of rainbow trout gill

The expression of the V-type proton ATPase (H+-ATPase) was examined in the gill of the freshwater rainbow trout (Oncorhynchus mykiss) using immunocytochemistry in concert with laser scanning confocal or electron microscopy. A synthetic peptide consisting of the carboxy-terminal region of the 31 kDa subunit of the bovine renal H+-ATPase was used to generate an antiserum in rabbits, and its suitability for use in trout gill was confirmed by western blotting. Gill epithelial cells demonstrated specific immunoreactivity, the intensity of which was increased markedly after 18 h of exposure to hypercapnia (1 % CO2 in air). The increased intensity of H+-ATPase immunoreactivity was associated with elevated branchial net acid excretion. In the hypercapnic fish, the specific immunoreactivity was associated with both the apical membrane and cytoplasm. Electron microscopy revealed that specific immunoreactivity was localized to the pavement cells and was particularly associated with the apical membrane and subapical cytoplasmic vesicles. The increased H+-ATPase immunoreactivity in the epithelial cells of hypercapnic fish and the increased intensity of the immunoreactive bands in western blots from hypercapnic fish demonstrate an 'up-regulation' of this protein in response to respiratory acidosis. The results are discussed with reference to current models of acid&shy;base and ion regulation in the gill of freshwater fish.

Journal Article↗