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Biomedical subjects

L Campbell

Publications and source records attributed to L Campbell.

At least 55 records · Page 3Linked to original sources
PubMed1999

Caveolin and its cellular and subcellular immunolocalisation in lung alveolar epithelium: implications for alveolar epithelial type I cell function.

Caveolae are flask-shaped invaginations of the plasmalemma which pinch off to form discrete vesicles within the cell cytoplasm. Biochemically, caveolae may be distinguished by the presence of a protein, caveolin, that is the principal component of filaments constituting their striated cytoplasmic coat. Squamous alveolar epithelial type I (ATI) cells, comprising approximately 95% of the surface area of lung alveolar epithelium, possess numerous plasmalemmal invaginations and cytoplasmic vesicles ultrastructurally indicative of caveolae. However, an ultrastructural appearance does not universally imply the biochemical presence of caveolin. This immunocytochemical study has utilised a novel application of confocal laser scanning and electron microscopy unequivocally to localise caveolin-1 to ATI cells. Further, cytoplasmic vesicles and flask-shaped membrane invaginations in the ATI cell were morphologically identified whose membranes were decorated with anti-caveolin-1 immunogold label. Coexistent with this, however, in both ATI and capillary endothelial cells could be seen membrane invaginations morphologically characteristic of caveolae, but which lacked associated caveolin immunogold label. This could reflect a true biochemical heterogeneity in populations of morphologically similar plasmalemmal invaginations or an antigen threshold requirement for labelling. The cuboidal alveolar epithelial type II cell (ATII) also displayed specific label for caveolin-1 but with no ultrastructural evidence for the formation of caveolae. The biochemical association of caveolin with ATI cell vesicles has broad implications for the assignment and further study of ATI cell function.

Animals↗
PubMed1999

Physical mapping of a tandem duplication on the long arm of chromosome 7 associated with a multidrug resistant phenotype.

Both the expression of the multidrug transporter, P-glycoprotein (Pgp), and abnormalities of the long arm of chromosome 7 have been shown to be adverse prognostic indicators in acute leukemias. In this study, a clonal duplication, dup(7)(q11.1q31.1), inherited with the classical multidrug resistant phenotype in a drug-resistant derivative of a human T-cell leukemia cell line was characterized. The position of the duplication was of interest as the gene which encodes Pgp, MDR1, is located on the long arm of chromosome 7 at position 7q21.1. Fluorescence in situ hybridization (FISH) analysis with a chromosome 7-specific painting probe confirmed the composition of the abnormal chromosome. A YAC clone hybridizing to the MDR1 locus confirmed that this gene was located within the duplicated region of the derivative chromosome. With a panel of well-characterized YAC clones, the duplicated segment was found to be a direct tandem duplication, somewhat larger than estimated by conventional cytogenetics. The proximal and distal breakpoints of the abnormality were located and a YAC clone spanning the distal breakpoint was identified. This clone is of particular interest, as it harbors the markers D7S523 and D7S471, close to which a putative tumor suppressor gene is thought to lie. Further examination of the breakpoint region may therefore illuminate the mechanism of Pgp upregulation as well as providing information about a tumor suppressor gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus?

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.

Acarbose↗
PubMed1999

Reduction of potential contamination of breast implants by the use of 'nipple shields'.

Forty-three breast implant operations in 25 patients were studied prospectively to determine the effectiveness of covering the nipple-areolar complex with an adhesive film dressing in preventing perioperative expression of bacteria from nipple ducts contaminating the operative field. One swab from the nipple after skin preparation and none of the swabs taken from the outer surface of the film dressing postoperatively yielded any bacterial growth. Fourteen breasts (33%) in 11 patients (44%) yielded bacterial growth from swabs under the film postoperatively. Six of 9 breasts (67%) in 5 patients who had capsulectomies had bacteria isolated from under the film postoperatively. Ten of 14 (71%) control breasts (no shields) in 6 of 7 patients (86%) had positive postoperative swabs. This study confirms the potential risk of bacterial contamination arising from nipple duct flora during intra-operative breast manipulation, and the effectiveness of a perioperative adhesive film placed over the nipple-areolar complex in preventing subclinical bacterial contamination of implanted breast prostheses.

Bacteria↗
PubMed1999

Special practice.

Explore the source record for details and available documents.

Ambulatory Surgical Procedures↗
PubMed1999

Outpatient self-management of warfarin therapy: a pilot study.

Self-testing and adjusting of warfarin dosages by patients is an evolving strategy for management of oral anticoagulation. We performed this open, prospective, 3-month pilot study to assess the feasibility of conducting a large, randomized trial comparing self-managed with physician-managed anticoagulation. Ten competent patients with planned anticoagulation for at least 3 months were provided education on warfarin therapy and trained to use an individualized warfarin nomogram. International normalized ratios (INRs) were determined weekly for 12 weeks and reported with warfarin dosages to the investigator for the first 8 weeks only. Eight patients elected to use a home monitor (ProTime) to measure INRs. Patients maintained 76.5% (range 50-91.7%) of INRs within the target range. In 119 dosage adjustment decisions, there were only 3 errors (2.5%). No bleeding or thrombotic complications occurred. To confirm concordance, initial and final INRs were measured concurrently by the ProTime monitor and laboratory. The mean absolute difference for 16 paired INR determinations was 0.33 (range 0.02-0.9). All patients expressed satisfaction and a desire to continue with self-management. This pilot study provides support for conducting a prospective, large-scale, randomized trial.

Administration, Oral↗
PubMed1999

Occupational physical demands and hip osteoarthritis.

The authors investigated the influence of physical strain at work on radiological signs of hip osteoarthritis. The study included 295 men and 298 women aged over 45 from an urban area who were classified in four groups according to physical demands of their occupation. The evaluation included clinical and radiological signs of hip osteoarthritis. The association between hip osteoarthritis and occupation was analysed using logistic regression. Though not significantly, radiological signs of hip osteoarthritis were common in subjects who worked in a standing position (odds 1.45 for men, 1.50 for women). Clinical signs of osteoarthritis in women were significantly associated with performance in a standing position (odds 3.00), whereas in men the association was more significant for jobs with high physical strain (odds 2.19). There was a sustained trend toward an increase in health risk with years of work in all job categories. Occupation did not appear to influence the development of radiological hiposteoarthritis, but the authors did establish association between clinical signs of hip osteoarthritis and work.

Adult↗
PubMed1998

Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical activity.

Hip osteoarthritis is a major cause of pain and disability. The authors explored individual risk factors for hip osteoarthritis in a population-based case-control study. The study was performed in two English health districts (Portsmouth and North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period were compared with an equal number of controls selected from the general population and individually matched for age, sex, and family practitioner. Information about suspected risk factors was obtained by a questionnaire administered at interview and a short physical examination. Obesity (odds ratio (OR) = 1.7, 95% confidence interval (CI) 1.3-2.4; highest vs. lowest third of body mass index), previous hip injury (OR = 4.3, 95% CI 2.2-8.4), and the presence of Heberden's nodes (OR = 1.6, 95% CI 1.2-2.2) were independent risk factors for hip osteoarthritis among men and women. Hip injury was more closely related to unilateral as compared with bilateral disease. There were a negative association between cigarette smoking and osteoarthritis among men and a weak positive association with prolonged regular sporting activity. Obesity and hip injury are important independent risk factors for hip osteoarthritis, which might be amenable to primary prevention. Hip osteoarthritis may also arise as part of the polyarticular involvement found in generalized osteoarthritis.

Aged↗
PubMed1998

Osteoarthritis of the hip and occupational lifting.

To test the hypothesis that occupational lifting is a cause of hip osteoarthritis, the authors examined associations with lifting and other occupational activities in a case-control study. The study was performed in two English health districts (Portsmouth and North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period were compared with an equal number of controls selected from the general population and individually matched for age, sex, and general practice. Information about suspected risk factors was obtained by a questionnaire administered at interview and a short physical examination. Analysis was by conditional logistic regression. After adjustment for potential confounders, the risk in men increased progressively with the duration and heaviness of occupational lifting. Relative to those with low exposure, men who had regularly lifted weights in excess of 50 kg for 10 years or longer had an odds ratio of 3.2 (95% confidence interval 1.6-6.5). No comparable association was found in women. Of the other occupational activities examined, only frequent climbing of stairs showed a pattern suggestive of a causal relation. These findings are consistent with the results of other studies, and there is now a strong case for regarding hip osteoarthritis as an occupational disease in men whose work has involved prolonged and frequent heavy lifting.

Aged↗
PubMed1998

A phase I and pharmacokinetic trial of terephthalamidine (NSC 57155) as a 120-hour continuous infusion.

In this phase I study, terephthalamidine was administered as a 120-hour continuous infusion repeated every 21 days. Thirteen patients received 27 courses of terephthalamidine at four dose levels ( 14, 28, 46, and 70 mg/m2/day). Dose-limiting toxicity consisted of profound and intractable anorexia, weight loss and prostration in all patients. Toxicity was delayed and accompanied by hyponatremia and hypokalemia. No hematologic or other toxicity was documented. One patient with adenocarcinoma of the lung had a 40% decrease in mediastinal lymph nodes and resolution of a pleural effusion lasting 2 months. Pharmacokinetic analysis by HPLC was performed in all patients during their first course. The harmonic mean terminal half-life for terephthalamidine was 23 hours with a plasma clearance of 1.7 1/hr/m2. Both plasma concentrations achieved during infusion (r2 = 0.9) and area under the curve (AUC) (r2 = 0.8) were proportional to increase in dose (p < 0.002). Renal excretion accounted for 64% of the total cumulative dose, with an average renal clearance of 1.16 1/hr/m2. Due to the unacceptable toxicity seen at all doses with this schedule, no further studies are recommended unless the mechanism of toxicity is better understood and can be prevented.

Adult↗
PubMed1998

A phase II study of gemcitabine in platinum pre-treated patients with advanced epithelial ovarian cancer.

BACKGROUND: Most patients with advanced ovarian cancer will relapse following platinum-based combination chemotherapy and be considered for second-line treatment. Gemcitabine, a nucleoside analogue, is active against a range of solid tumors. This phase II study investigated the activity of single-agent gemcitabine in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients with FIGO stage III (34%) or IV (64%) ovarian cancer who were previously treated with platinum-containing regimens were enrolled. Patients received 1200 mg/m2 gemcitabine on days 1, 8 and 15 of a 28-day cycle. RESULTS: Patients completed an average of 3.6 cycles. Two complete and three partial responses were seen in 36 evaluable patients, for an overall response rate of 13.9% (95% CI: 4.7%-29.5%). The median survival time was 6.7 months. Toxicities were generally mild. The most common were grade 3-4 neutropenia and grade 3 leukopenia reported in 23.7% and 10.5% of patients, respectively. One patient had grade 4 pulmonary toxicity. CONCLUSION: Single-agent gemcitabine is active and well tolerated in patients with recurrent ovarian cancer.

Adult↗
PubMed1998

Maternal mosaicism for a second mutational event in a type I spinal muscular atrophy family.

Spinal muscular atrophy (SMA) is a common fatal motor-neuron disorder characterized by degeneration of the anterior horn cells of the spinal cord, which results in proximal muscle weakness. Three forms of the disease, exhibiting differing phenotypic severity, map to chromosome 5q13 in a region of unusually high genomic variability. The SMA-determining gene (SMN) is deleted or rearranged in patients with SMA of all levels of severity. A high de novo mutation rate has been estimated for SMA, based on the deletion of multicopy microsatellite markers. We present a type I SMA family in which a mutant SMA chromosome has undergone a second mutation event. Both the occurrence of three affected siblings harboring this same mutation in one generation of this family and the obligate-carrier status of their mother indicate the existence of maternal germ-line mosaicism for cells carrying the second mutation. The existence of secondary mutational events and of germ-line mosaicism has implications for the counseling of SMA families undergoing prenatal genetic analysis.

Alleles↗
PubMed1998

Acetabular dysplasia and hip osteoarthritis in Britain and Japan.

OBJECTIVE: Geographic differences in the prevalence of hip osteoarthritis (OA) have been ascribed to differences in the frequency of acetabular dysplasia among different ethnic groups. However, there are few data on the shape of the acetabulum in various populations around the world. We examined this issue in samples of pelvic radiographs from Britain and Japan. METHODS: Measurements were made on the pelvic radiographs of 1303 men and 195 women, aged 60-75 yr, who attended for i.v. urography in two British centres. These were compared with 99 men and 99 women aged 60-79 yr who were included in a population-based study in a rural community in Japan, and who agreed to undergo standardized pelvic radiography. Acetabular dysplasia was assessed by morphometric measurement of the centre-edge (CE) angle and acetabular depth. RESULTS: The mean CE angle among men was 36 degrees (95% CI 35-37 degrees ) in Britain and 31 degrees (95% CI 29-32 degrees ) in Japan; that in women was 37 degrees (95%, CI 36-38 degrees ) in Britain and 31 degrees (95% CI 29 33 degrees ) in Japan. The mean values of acetabular depth were also significantly (P < 0.001) lower in Japan than in Britain. However, the prevalence of hip OA was lower in Japan (0% in men, 2% in women) than in Britain ( 11% in men, 4.8 / in women). In a random effects model, there were negative relationships between measures of acetabular dysplasia and minimum joint space among individuals. CONCLUSIONS: We conclude that there are marked differences in pelvic morphometry between Britain and Japan. The acetabular dimensions of Japanese subjects are considerably shallower than those of their British counterparts of similar age and sex. Nevertheless, hip OA is more frequent in Britain than in Japan. Further studies are required on the risk factors for hip OA in Oriental populations, in order that the aetiology of this disorder can be better understood.

Acetabulum↗
PubMed1997

Genomic organization and chromosomal localization of a member of the MAP kinase phosphatase gene family to human chromosome 11p15.5 and a pseudogene to 10q11.2.

Mitogen-activated protein kinase phosphatases (MKPs) play a central role in a variety of signaling pathways. We recently described a novel murine MKP, M3/6, which is uniquely specific for c-Jun N-terminal kinase/stress-activated protein kinase and p38 kinase. Here we report the localization of the human orthologue of this gene, HB5, to within 150 kb of H19 on human chromosome 11p15.5. The gene consists of six exons. Two of the introns in HB5 are not found in other genes of this family, suggesting an evolutionary split between MKPs displaying specificity toward different MAP kinases. An intronless pseudogene is present on chromosome 10q11.2. Although 11p15.5 is an imprinted region, HB5 is almost entirely unmethylated on both alleles in lymphocytes. Chromosome 11p15 has been implicated in the development of a number of tumor types, including lung, a tissue known to express this gene. Loss of heterozygosity was found in one of eight informative lung tumors studied.

Alleles↗
PubMed1997

Validity of a questionnaire for assessing occupational activities.

The objective of this article is to assess the validity of data on occupational activities obtained by a questionnaire. 152 employees from 16 jobs were interviewed independently about activities in their work, using a structured questionnaire. For 11 of the jobs, two further workers were observed during a typical shift, and their activities recorded. The agreement of reporting between subjects doing the same job and with observation was assessed. There was good agreement between subjects and with observation for most of the activities examined when the activities were classified dichotomously. However, frequency of heavy lifting was reported inconsistently. Questionnaires are able to distinguish major differences in physical activity that occur between jobs in the general population, but do not allow more detailed quantification of activities.

Adult↗
PubMed1997

Mortality in employees of a Scottish paper mill.

To assess possible health risks associated with the manufacture of paper, we carried out a retrospective analysis of mortality among 4,242 men and women employed at a Scottish paper mill between 1955 and 1992. During follow-up to 1994, 959 subjects had died giving an SMR of 0.85 (95% CI 0.80-0.90) in comparison with the national population. Mortality from all cancer (SMR 0.77, 95% CI 0.68-0.88) and particularly from lung cancer (SMR 0.64, 95% CI 0.50-0.81) was lower than expected. An excess of lymphatic and hematopoietic cancer (11 deaths, SMR 2.17) was observed in the making department. These findings do not support an occupational hazard of lung cancer as suggested by several earlier studies. The excess of lymphatic and hematopoietic cancer in the making department was unexpected, and may be a chance occurrence.

Cause of Death↗