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Biomedical subjects

J Warren

Publications and source records attributed to J Warren.

At least 19 recordsLinked to original sources
PubMed2006

Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice.

Membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease) is an inflammatory renal disease characterized by electron-dense deposits and complement C3 on the glomerular basement membrane. There is no effective therapy. We investigated the role of C5 activation in a model of MPGN that develops spontaneously in complement factor H-deficient mice (Cfh(-/-)). At 12 months there was a significant reduction in mortality, glomerular cellularity, neutrophil numbers, and serum creatinine levels in Cfh(-/-) mice deficient in C5. Excessive glomerular neutrophil numbers, frequently seen in patients with MPGN during disease flares, were also observed in Cfh(-/-) mice after the administration of an antiglomerular basement membrane antibody. This exaggerated injurious phenotype was absent in Cfh(-/-) mice deficient in C5 but not in Cfh(-/-) mice deficient in C6, indicating a key role for C5 activation in the induction of renal lesions. Importantly, the renal injury was completely reversed in Cfh(-/-) mice pretreated with an anti-murine C5 antibody. These results demonstrate an important role for C5 in both spontaneous MPGN and experimentally induced nephritis in factor H-deficient mice and provide preliminary evidence that C5 inhibition therapy might be useful in human MPGN type II.

Animals↗
PubMed2006

Report of a National Conference on Donation after cardiac death.

A national conference on organ donation after cardiac death (DCD) was convened to expand the practice of DCD in the continuum of quality end-of-life care. This national conference affirmed the ethical propriety of DCD as not violating the dead donor rule. Further, by new developments not previously reported, the conference resolved controversy regarding the period of circulatory cessation that determines death and allows administration of pre-recovery pharmacologic agents, it established conditions of DCD eligibility, it presented current data regarding the successful transplantation of organs from DCD, it proposed a new framework of data reporting regarding ischemic events, it made specific recommendations to agencies and organizations to remove barriers to DCD, it brought guidance regarding organ allocation and the process of informed consent and it set an action plan to address media issues. When a consensual decision is made to withdraw life support by the attending physician and patient or by the attending physician and a family member or surrogate (particularly in an intensive care unit), a routine opportunity for DCD should be available to honor the deceased donor's wishes in every donor service area (DSA) of the United States.

Adolescent↗
PubMed2005

Complications following full-thickness small intestinal biopsy in 66 dogs: a retrospective study.

OBJECTIVES: To retrospectively report the complications seen after full-thickness multiple small intestinal biopsies were performed in 66 dogs. METHODS: Animals that died as a result of enteric wound breakdown were compared with the surviving population to identify fatal risk factors. RESULTS: Seventeen dogs had hypoalbuminaemia and eight had albumin levels below 20 g/I at surgery. Twelve dogs had concurrent disease, of which seven had skin disease. Seven dogs suffered minor complications which resolved with treatment. Eight dogs (12 per cent) died or were euthanased between three and nine days postoperatively (mean [sd] 4.5 [2.1]) due to enteric wound breakdown. Seven of these dogs developed septic peritonitis and one died of haemorrhage. No statistically significant differences were identified in any of the parameters examined for the development of fatal enteric wound dehiscence. CLINICAL SIGNIFICANCE: Full-thickness intestinal biopsy is not a benign procedure. However, this study concludes that there are no consistent predictors for patients at increased risk of enteric wound breakdown.

Animals↗
PubMed2004

The effects of oxidative stress on telomerase activity and other stress-related proteins in lens epithelial cells.

Telomerase is a ribonucleoprotein complex responsible for maintaining the ends of chromosomes and for repair of DNA strand breaks. While telomerase activity is generally found in cells that have unlimited proliferative potential such as neoplastic cells, germline cells and some stem cells, lens epithelial cells (though not highly proliferative) have telomerase activity. Our previous studies indicated that lens epithelial cells express high levels of telomerase despite their low proliferative potential, thus we hypothesized that telomerase expression protects lens epithelial cells from oxidative stress. We also determined levels of the stress proteins gadd45 and p16 and the stress and proliferation-related protein, proliferating cell nuclear antigen (PCNA). In acute studies, lenses were exposed to TBHP for 0-120 min. In recovery studies, lenses were exposed to TBHP for 1 hr, then allowed to recover for up to 18 hr. In acute studies, telomerase activity was increased, p16 initially decreased then normalized, PCNA levels did not change significantly even in the overnight recovery groups, and gadd45 was decreased in some TBHP exposed groups. In recovery studies, telomerase activity was increased in all groups, gadd45 decreased then became elevated, and p16 levels were decreased at later recovery times. PCNA levels remained constant during the studies, indicating that there was no change in proliferation. These studies showed that elevated telomerase activity did not correlate with increased proliferation in lens epithelial cells; instead, increased telomerase activity was associated with increased levels of the stress-related protein gadd45 only in the later recovery times. These findings support the hypothesis that telomerase plays a protective rather than a proliferative role in lens epithelial cells.

Animals↗
PubMed2004

A preliminary investigation of the effectiveness of a sleep apnea education program.

OBJECTIVES: This study aimed to evaluate a standardised sleep apnea patient education program and develop a study design that may be used to evaluate other such education programs. METHOD: Thirty-four adults diagnosed with obstructive sleep apnea hypopnea syndrome (OSAHS) underwent a standard sleep apnea education program and completed measures of knowledge of and beliefs about sleep apnea before, after, and 3 months following education. Two outcome measures were used: the Apnea Knowledge Test (AKT) and the Apnea Beliefs Scale (ABS). RESULTS: AKT results showed significant knowledge gains posteducation, which were maintained at follow-up. Patients also reported more positive beliefs about their ability to change their behaviour and comply with continuous positive airway pressure (CPAP) treatment recommendations after education. DISCUSSION: Findings from this preliminary investigation suggest that the education program used in this study may improve patients' knowledge of CPAP and promote functional beliefs about OSAHS treatment. This program clearly warrants further research, and ultimately such programs may prove important in improving CPAP compliance.

Attitude to Health↗
PubMed2003

Sexual dimorphism in fat patterning in a sample of 5 to 7-year-old children in Oxford.

It is now well recognised that, in addition to total body fat, fat distribution is a major risk factor for cardiovascular disease and insulin resistance/diabetes in both adults and children. Traditionally, sexual dimorphism in fat patterning has been regarded as occurring at puberty. The aim of this study was to investigate gender differences in fat patterning in a group of children in Oxford. Anthropometric data was collected for 95 girls and 93 boys aged 5-7 years. Body mass index, percentage body fat and fat patterning indices were calculated using skinfold thickness measurements. While girls at this age had significantly larger percentage body fat and skinfolds, the fat patterning indices showed no differences between genders and no indication of greater truncal adiposity. The boys had a larger mean waist-hip ratio (0.96+/-0.04) compared with the girls (0.93+/-0.04) (P<0.001). The larger ratio in boys was the outcome of the smaller hip circumference in the boys reflecting less gluteal adiposity. This suggests that even at this young age there is clear evidence of sexual dimorphism in fat patterning, with girls showing greater subcutaneous adiposity mainly contributed by gluteal fat. The present study confirms the findings of American and European workers that sexual dimorphism of fat patterning in children is present at 5-7 years of age. Second, that these differences in fat patterning can be detected using simple anthropometric measurements such as hip circumference and skinfold thicknesses. The significance and importance of hip circumference measurements in predicting health outcome is an area that merits further investigation.

Adipose Tissue↗
PubMed2003

A pilot clinical trial of oral pentosan polysulfate and oral hydroxyzine in patients with interstitial cystitis.

PURPOSE: This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial. MATERIALS AND METHODS: A 2 x 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months. RESULTS: A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports. CONCLUSIONS: The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.

Adult↗
PubMed2002

Growth pulsations in symmetric dendritic crystallization in thin polymer blend films.

The crystallization of polymeric and metallic materials normally occurs under conditions far from equilibrium, leading to patterns that grow as propagating waves into the surrounding unstable fluid medium. The Mullins-Sekerka instability causes these wave fronts to break up into dendritic arms, and we anticipate that the normal modes of the dendrite tips have a significant influence on pattern growth. To check this possibility, we focus on the dendritic growth of polyethylene oxide in a thin-film geometry. This crystalline polymer is mixed with an amorphous polymer (polymethyl-methacrylate) to "tune" the morphology and clay was added to nucleate the crystallization. The tips of the main dendrite trunks pulsate during growth and the sidebranches, which grow orthogonally to the trunk, pulsate out of phase so that the tip dynamics is governed by a limit cycle. The pulsation period P increases sharply with decreasing film thickness L and then vanishes below a critical value L(c) approximately 80 nm. A change of dendrite morphology accompanies this transition.

Journal Article↗
PubMed2001

The landing of the NEAR-Shoemaker spacecraft on asteroid 433 Eros.

The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution.

Journal Article↗
PubMed2001

Causes of obesity.

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Appetite Regulation↗
PubMed2001

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

Journal Article↗
PubMed2001

Euthanasia.

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Aged↗
PubMed2001

Urinary tract infection in adults: research priorities and strategies.

Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.

Adult↗
PubMed2001

Spermatogenesis in Bclw-deficient mice.

Bclw is a death-protecting member of the Bcl2 family of apoptosis-regulating proteins. Mice that are mutant for Bclw display progressive and nearly complete testicular degeneration. We performed a morphometric evaluation of testicular histopathology in Bclw-deficient male mice between 9 days postnatal (p9) through 1 yr of age. Germ cell loss began by p22, with only few germ cells remaining beyond 7 mo of age. A complete block to elongated spermatid development at step 13 occurred during the first wave of spermatogenesis, whereas other types of germ cells were lost sporadically. Depletion of Sertoli cells commenced between p20 and p23 and continued until 1 yr of age, when few, if any, Sertoli cells remained. Mitochondria appeared to be swollen and the cytoplasm dense by electron microscopy, but degenerating Bclw-deficient Sertoli cells failed to display classical features of apoptosis, such as chromatin condensation and nuclear fragmentation. Macrophages entered seminiferous tubules and formed foreign-body giant cells that engulfed and phagocytosed the degenerated Sertoli cells. Leydig cell hyperplasia was evident between 3 and 5 mo of age. However, beginning at 7 mo of age, Leydig cells underwent apoptosis, with dead cells being phagocytosed by macrophages. The aforementioned cell losses culminated in a testis-containing vasculature, intertubular phagocytic cells, and peritubular cell "ghosts." An RNA in situ hybridization study indicates that Bclw is expressed in Sertoli cells in the adult mouse testis. Consequently, the diploid germ cell death may be an indirect effect of defective Sertoli cell function. Western analysis was used to confirm that Bclw is not expressed in spermatids; thus, loss of this cell type most likely results from defective Sertoli cell function. Because Bclw does not appear to be expressed in Leydig cells, loss of Leydig cells in Bclw-deficient mice may result from depletion of Sertoli cells. Bclw-deficient mice serve as a unique model to study homeostasis of cell populations in the testis.

Alleles↗