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Biomedical subjects

J Reynolds

Publications and source records attributed to J Reynolds.

At least 19 recordsLinked to original sources
PubMed2000

Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes.

BACKGROUND: Troglitazone promotes adipocyte differentiation in vitro and increases insulin sensitivity in vivo. Therefore, troglitazone may have therapeutic benefit in lipoatrophic diabetes. OBJECTIVE: To determine whether troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat mass in lipoatrophic patients. DESIGN: Open-labeled prospective study. SETTING: United States and Canada. PATIENTS: 20 patients with various syndromes associated with lipoatrophy or lipodystrophy. INTERVENTION: 6 months of therapy with troglitazone, 200 to 600 mg/d. MEASUREMENTS: Levels of hemoglobin A1c triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of body fat; liver volume; and regional fat mass. RESULTS: In the 13 patients with diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI, 0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels decreased by 325 micromol/L (CI, 135 to 515 micromol/L; P = 0.035). The respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001), suggesting that troglitazone promoted oxidation of fat. Body fat increased by a mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044). Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but not in visceral fat. In one patient, the serum alanine aminotransferase level increased eightfold during the 10th months of troglitazone treatment but normalized 3 months after discontinuation of treatment Liver biopsy revealed an eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of hepatotoxicity. CONCLUSION: Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment course.

Adipose Tissue↗
PubMed2000

The internal phosphodiesterase RegA is essential for the suppression of lateral pseudopods during Dictyostelium chemotaxis.

Dictyostelium strains in which the gene encoding the cytoplasmic cAMP phosphodiesterase RegA is inactivated form small aggregates. This defect was corrected by introducing copies of the wild-type regA gene, indicating that the defect was solely the consequence of the loss of the phosphodiesterase. Using a computer-assisted motion analysis system, regA(-) mutant cells were found to show little sense of direction during aggregation. When labeled wild-type cells were followed in a field of aggregating regA(-) cells, they also failed to move in an orderly direction, indicating that signaling was impaired in mutant cell cultures. However, when labeled regA(-) cells were followed in a field of aggregating wild-type cells, they again failed to move in an orderly manner, primarily in the deduced fronts of waves, indicating that the chemotactic response was also impaired. Since wild-type cells must assess both the increasing spatial gradient and the increasing temporal gradient of cAMP in the front of a natural wave, the behavior of regA(-) cells was motion analyzed first in simulated temporal waves in the absence of spatial gradients and then was analyzed in spatial gradients in the absence of temporal waves. Our results demonstrate that RegA is involved neither in assessing the direction of a spatial gradient of cAMP nor in distinguishing between increasing and decreasing temporal gradients of cAMP. However, RegA is essential for specifically suppressing lateral pseudopod formation during the response to an increasing temporal gradient of cAMP, a necessary component of natural chemotaxis. We discuss the possibility that RegA functions in a network that regulates myosin phosphorylation by controlling internal cAMP levels, and, in support of that hypothesis, we demonstrate that myosin II does not localize in a normal manner to the cortex of regA(-) cells in an increasing temporal gradient of cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2000

CD28-B7 blockade prevents the development of experimental autoimmune glomerulonephritis.

Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture's disease, can be induced in Wistar Kyoto (WKY) rats by a single injection of rat glomerular basement membrane (GBM) in adjuvant. EAG is characterized by circulating and deposited anti-GBM antibodies, accompanied by focal necrotizing glomerulonephritis with crescent formation. The role of T cells in the pathogenesis of EAG remains unclear. T-cell costimulation is provided by ligation of CD28 with either B7.1 (CD80) or B7.2 (CD86) on antigen-presenting cells, and can be inhibited by a soluble form of CTLA4 (CTLA4-Ig) that binds to both B7.1 and B7.2. We examined the effect of CD28-B7 blockade on the development of EAG using native CTLA4-Ig or mutant CTLA4-Ig (Y100F-Ig), which selectively blocks B7.1. Native CTLA4-Ig treatment ameliorated EAG by several measures, including the levels of circulating anti-GBM antibodies, albuminuria, the deposition of IgG and fibrin in the glomeruli, the severity of glomerular abnormalities, and the numbers of infiltrating T cells and macrophages. Y100F-Ig resulted in a similar reduction in the severity of nephritis, but produced no overall reduction in circulating anti-GBM antibodies, although there was a reduction in IgG2a antibodies. We concluded that CD28-B7 blockade reduced autoantibody production and cellular infiltration of glomeruli, and prevented target organ injury. Our results suggest a key role for B7. 1 in costimulation of Th1-like autoimmune responses in the rat, and show that glomerular injury in EAG is largely dependent on cell-mediated mechanisms.

Abatacept↗
PubMed2000

Clathrin plays a novel role in the regulation of cell polarity, pseudopod formation, uropod stability and motility in Dictyostelium.

Although the traditional role of clathrin has been in vesicle trafficking and the internalization of receptors, a novel role in cytokinesis was recently revealed in an analysis of a clathrin-minus Dictyostelium mutant (chc(-)). chc(-) cells grown in suspension were demonstrated to be defective in assembling myosin II into a normal contractile ring. To test whether this defect reflected a more general one of cytoskeletal dysfunction, chc(-) cells were analyzed for cell polarity, pseudopod formation, uropod stability, cell locomotion, chemotaxis, cytoskeletal organization and vesicle movement. chc(-) cells crawled, chemotaxed, localized F-actin in pseudopods, organized their microtubule cytoskeleton in a relatively normal fashion and exhibited normal vesicle dynamics. Although chc(-) cells extended pseudopods from the anterior half of the cell with the same frequency as normal chc(+) cells, they extended pseudopods at twice the normal frequency from the posterior half of the cell. The uropods of chc(-) cells also exhibited spatial instability. These defects resulted in an increase in roundness, a reduction in polarity, a reduction in velocity, a dramatic increase in turning, a high frequency of 180 degrees direction reversals and a decrease in the efficiency of chemotaxis. All defects were reversed in a rescued strain. These results are the first to suggest a novel role for clathrin in cell polarity, pseudopod formation, uropod stability and locomotion. It is hypothesized that clathrin functions to suppress pseudopod formation and to stabilize the uropod in the posterior half of a crawling cell, two behavioral characteristics that are essential for the maintenance of cellular polarity, efficient locomotion and efficient chemotaxis.

Actins↗
PubMed1999

Anterior discectomy and fusion for the management of neck pain.

STUDY DESIGN: Data were collected prospectively on 38 patients who underwent anterior cervical discectomy and fusion for neck pain with no symptoms or signs of radiculopathy or myelopathy. OBJECTIVES: To determine the changes in pain and function after anterior cervical discectomy and fusion for nonradicular neck pain. SUMMARY OF BACKGROUND DATA: There is considerable controversy regarding the role of anterior cervical discectomy and fusion for neck pain in the absence of radiculopathy or myelopathy. Although no studies have addressed this specific and common problem, it is known that anterior cervical discectomy and fusion for radiculopathy or myelopathy may also provide relief of neck pain for many patients. METHODS: Thirty-eight patients who underwent anterior cervical discectomy and fusion for neck pain were evaluated. Before and after surgery, the authors measured pain with a numerical rating scale, function with the Oswestry Disability Questionnaire, and final patient satisfaction. Final evaluation was done by a disinterested third party. RESULTS: All 38 patients were available for follow-up study. Mean age was 42.4 years, and mean duration of follow-up study was 53 months. All patients had painful disc(s) proven by discography. No patients had nerve root compression. Anterior cervical discectomy and fusion was performed at one level in 21 patients, two levels in 16 patients, and three levels in one patient. The mean score on the numerical rating scale for neck pain before surgery was 8.3 (range, 3-10) versus 4.1 (range, 0-10) after surgery. This difference is significant (P < 0.001). The mean score on the Oswestry Disability Questionnaire was 57.5 (range, 0-89) before surgery versus 38.9 (range, 0-80) after surgery. This difference is significant (P < 0.001). There were 30 (79%) patients who were satisfied with their outcome, and 8 (21%) who were not satisfied. There was no statistical difference in change of pain or function between patients with worker's compensation and those with other insurance or between men and women. Twenty patients were not working because of neck pain before surgery, and 15 were not working at the time of follow-up examination. CONCLUSION: A significant decrease in pain, a significant increase in function, and a high degree of patient satisfaction were found with anterior cervical discectomy and fusion for neck pain. Improvements were not affected by worker's compensation status or gender.

Adult↗
PubMed1999

Increased carriage of resistant non-pneumococcal alpha-hemolytic streptococci after antibiotic therapy.

OBJECTIVE: We compared colonization and resistance rates of non-pneumococcal alpha-hemolytic streptococci (AHS) and Streptococcus pneumoniae in children receiving antibiotic therapy for acute otitis media. STUDY DESIGN: Between December 1997 and September 1998, children 6 months to 6 years of age, diagnosed with acute otitis media were randomly assigned to receive amoxicillin/clavulanate (Augmentin) 45 mg/kg/d in 2 divided doses for 10 days or azithromycin (Zithromax), 10 mg/kg, once on the first day, followed by 5 mg/kg daily for 4 days. Nasopharyngeal swabs for culture were obtained before and at 2 weeks and 2 months after the start of therapy. Streptococci were identified by species, and antibiotic susceptibility was determined by the epsilometric test. RESULTS: One hundred six children completed the 2-week follow-up and 2-month follow-up, respectively. The nasopharyngeal carriage rate of non-pneumococcal AHS increased from 14% before treatment to 32% at the 2-week follow-up (P =.02) and was similar in both treatment groups. In contrast, the carriage of S pneumoniae decreased from 51% before therapy to 27% at the 2-week follow-up (P =.002). The carriage of penicillin-resistant AHS strains (minimum inhibitory concentration > 1 microg/mL) increased from 9% before treatment to 26% at 2 weeks and 36% at 2 months. CONCLUSIONS: Amoxicillin/clavulanate and azithromycin therapy resulted in increased isolation of nasopharyngeal non-pneumococcal AHS, many of which were multidrug-resistant, in contrast to a decrease in pneumococcal carriage. This suggests that the competitive balance between these 2 groups of organisms was disturbed as a result of differential antibiotic susceptibility. The importance of drug-resistant AHS as a reservoir for resistance genes for S pneumoniae warrants further investigation.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1998

Randomised controlled trial of effects of early discharge after surgery for breast cancer.

OBJECTIVE: To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. DESIGN: Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). SETTING: Regional breast unit. SUBJECTS: 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). MAIN OUTCOME MEASURES: Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. RESULTS: Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P = 0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P = 0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98) P = 0.035), but rates of psychological illness generally did not differ between groups. CONCLUSIONS: Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.

Adult↗
PubMed1998

Dissolution of multicomponent microbubbles in the bloodstream: 2. Experiment.

The effect of the nature of the filling gas on the persistence of microbubbles in the bloodstream was studied. All the microbubbles were covered with the same shells. Various perfluorocarbons and perfluoropolyethers alone and as mixtures with nitrogen were used as the filling gases. The persistence time of microbubbles in the bloodstream tau increased with the molecular weight of the filling gas, from approximately 2 min for perfluorethane, to > 40 min for perfluorodiglyme, C6F14O3, and then decreased again to 8 min for C6F14O5. An acceptable ultrasound scattering efficacy was exhibited by the filling gases with intermediate molecular weights that possessed both a high saturated vapor pressure and a comparatively low water solubility (Ostwald coefficient). On the basis of the experimental data, it is concluded that the microbubble persistence tau is controlled primarily by the dissolution of microbubbles and not by the removal of the microbubbles by the reticular endothelial system. Although the qualitative experimental trends are in good agreement with the theoretical model developed previously, there are some quantitative differences. Possible reasons for these differences are discussed.

Air↗
PubMed1998

Take Five, a nutrition education intervention to increase fruit and vegetable intakes: impact on consumer choice and nutrient intakes.

This study reports results from a randomized controlled intervention trial, focusing on: (1) the identification of successful consumer strategies for increasing fruit and vegetable intakes to the recommended levels of more than five (80 g) portions per day and (2) impact on overall diet and nutrient intakes. Adult men and women (n 170) fulfilling the main recruitment criterion of eating less than five fruit and vegetable portions per day but contemplating increasing intakes were recruited. Complete valid dietary data was provided by 101 intervention (fifty-nine estimated fruit and vegetable intakes, and forty-two simultaneous weighted total dietary and estimated fruit and vegetable intakes) and twenty-four control subjects (weighed total dietary intakes). Intervention advice included the specific association of high fruit and vegetable intake with reduced risk of disease, practicalities, and portion definition with a target intake of greater than five 80 g fruit and vegetable portions per day for 8 weeks. There were significant effects (P < 0.001) on weighed intakes of fruit and vegetables in the intervention group, rising from 324 (SE 25) to 557 (SE 31) g/d and reflected by validated portion measures at 8 weeks intervention. Successful strategies chosen by 'achievers' of the target intake (65% of subjects) were conventional (fruit as a snack, vegetables with main meals etc.) and favoured fruit. There were significant increases in percentage energy from carbohydrate (from sugars not starch), vitamin C, carotenes and NSP and there was a significant decrease in percentage energy from fat for subjects who had high fat intakes (> 35% energy) at baseline. Follow-up self-reported measures at 6 and 12 months indicated mean intakes of 4.5 and 4.6 defined portions/d respectively, suggesting some sustainable effect. In conclusion, the intervention led to significant increases in fruit and vegetable intakes largely via conventional eating habits, with some desirable effects on macro- and micronutrient intakes.

Adolescent↗
PubMed1998

Take Five, a nutrition education intervention to increase fruit and vegetable intakes: impact on attitudes towards dietary change.

To assess the response of low consumers of fruit and vegetables to a nutrition education intervention programme, data were collected from 104 adults on attitudinal variables related to 'eating more fruit, vegetables and vegetable dishes'. Questionnaires (based on the theory of planned behaviour) assessing perceived barriers to increasing fruit and vegetable consumption were administered before an action-orientated intervention programme and at the end of the intervention period (8 weeks). Questionnaire scores for belief-evaluations in the intervention groups pre- and post-study indicated that support of family and friends, food costs, time constraints and shopping practicalities (in order to increase intake of fruit, vegetable and vegetable dishes) were barriers to greater consumption of these foodstuffs. Perceived situational barriers to increasing intakes of fruits and vegetables were: limited availability of vegetables, salads and fruit at work canteens, take-aways, friends' houses and at work generally. Following the intervention the number of visits to the shops was perceived as a greater barrier for increasing intakes of fruit and vegetables. Perceived practical opportunities for increasing intakes high-lighted drinking fruit juice, taking fruit as a dessert, having fruit as a between-meal snack and eating two portions of vegetables with a meal. About two-thirds of intervention subjects achieved the recommended fruit and vegetable target, but it is concluded that practical issues and situational barriers need to be addressed for the success of future public health campaigns.

Adolescent↗
PubMed1998

Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group.

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.

Female↗
PubMed1998

Experimental autoimmune glomerulonephritis (EAG) induced by homologous and heterologous glomerular basement membrane in two substrains of Wistar-Kyoto rat.

BACKGROUND: Goodpasture's, or antiglomerular basement membrane (GBM), disease presents with rapidly progressive glomerulonephritis, and is caused by auto-immunity to the NC1 domain of the alpha 3 chain of type IV collagen. In order to investigate mechanisms involved in the induction and regulation of glomerulonephritis, experimental models of Goodpasture's disease have been developed in the rat which share many characteristics with the human disease. Induction of experimental autoimmune glomerulonephritis (EAG) involves immunization of susceptible strains with either heterologous or homologous GBM in FCA. However, pathological changes have tended to be mild and/or variable, except in certain protocols using Wistar-Kyoto (WKY) rats. METHODS: We studied the susceptibility of inbred WKY rats from two different suppliers to the development of EAG. These substrains of rat had different MHC haplotypes (WKY/CR, RT1-1; WKY/Olac, RT1-k), so we proposed that they might show differences in their immune response to GBM antigens. Both substrains were immunized with sheep GBM, pH 7, or rat GBM buffered to pH 3, pH 5 or pH 7. RESULTS: All immunized rats developed circulating anti-GBM antibodies detectable at 14 days and rising until 28 days, at which time there was linear deposition of IgG on the GBM. WKY/CR rats developed severe focal segmental proliferative and necrotizing glomerulonephritis, with heavy albuminuria, following immunization with rat GBM, pH 7, but only moderate disease following sheep GBM. WKY/Olac rats showed a more variable response, with moderate disease following both rat and sheep GBM. Immunization of either substrain with rat GBM, pH 5, produced a response similar to that with rat GBM, pH 7, but disease was mild following rat GBM, pH 3. CONCLUSION: EAG in the WKY rat varies in severity according to the substrain of animal and preparation of GBM used for immunization. The model with the most severe and consistent changes was that induced in the WKY/CR rat by rat GBM at pH 7. This model of EAG will be of value for investigating mechanisms of autoimmunity and inflammation in glomerulonephritis, and for attempting novel forms of immunotherapy prior to trials in man.

Albuminuria↗
PubMed1998

Organizing health care for people with seizures and epilepsy.

The day-to-day responsibilities of managing seizures and epilepsy fall most heavily on patients and their families. Unfortunately, health care services in the United States are not organized to identify, diagnose, and treat people with seizures effectively nor are they delivered in such a way that patients and their families can engage in a positive, collaborative relationship with health care providers. This article describes a model of chronic illness care as applied to seizures and epilepsy, that is, how care should be structured to help people with seizures live as well as possible.

Chronic Disease↗