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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 253 records · Page 14Linked to original sources
PubMed2000

Type IV phosphodiesterase inhibitor is effective in prevention and treatment of experimental crescentic glomerulonephritis.

BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-alpha synthesis. METHODS: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. RESULTS: In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-alpha in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-alpha by 63% on day 7. TNF-alpha was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. CONCLUSIONS: Rolipram is effective both in prevention and treatment of experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-alpha.

Animals↗
PubMed2000

Leukotriene receptor antagonists and synthesis inhibitors reverse survival in eosinophils of asthmatic individuals.

Eosinophilia is a feature of airway inflammation associated with asthma. Leukotriene antagonists provide therapeutic benefit in asthma, but their potential antiinflammatory actions have not been fully explored. We have examined the role of eosinophil-derived cysteinyl leukotrienes in the maintenance of eosinophil survival, and the involvement of leukotrienes in the paracrine stimulation of eosinophil survival by mast cells and lymphocytes. We obtained eosinophils and autologous lymphocytes from peripheral blood of asthmatic subjects. Leukotriene (LT)-B(4), LTC(4) and LTD(4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and fibronectin promoted eosinophil survival. LTD(4) (10(-)(6) M) was as effective as GM-CSF (5 ng/ml) and fibronectin (400 ng/ml) in promoting survival. Lymphocytes and conditioned medium from a human mast cell line (HMC-1) induced eosinophil survival. Blockade of cysteinyl leukotriene receptors with SKF 104353 (pobilukast, 3 nM), and inhibition of 5-lipoxygenase (5-LO) with BW A4C (1 microM) and of 5-LO activating protein with MK 886 (1 microM), all increased basal rates of eosinophil apoptosis and reversed GM-CSF-induced eosinophil survival. Fifty percent reversal of GM-CSF- induced survival was achieved with SKF 104353 at 0.3 nM. The potency of SKF 104353 was two orders of magnitude greater than that of the LTB(4) receptor antagonist SB 201146. Mast cell- and lymphocyte-induced eosinophil survival were completely reversed by SB 201146, SKF 104353, BW A4C, and MK 886. These findings provide evidence for the involvement of an autocrine cysteinyl leukotriene pathway that supports eosinophil survival in response to a range of survival stimuli. They also suggest that LTB(4) could act as a paracrine stimulus of eosinophil survival.

Acrylates↗
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

Polymorphisms in the IL-1A gene are correlated with levels of interleukin-1alpha protein in gingival crevicular fluid of teeth with severe periodontal disease.

Interleukin-1 (IL-1) is a potent stimulator of bone resorption and is strongly implicated in the destruction due to bystander damage seen in periodontal disease. Recent studies suggest that polymorphisms of the (IL-1) gene complex may be significant risk factors for a number of chronic inflammatory diseases. The severity of periodontal disease has been positively associated with carriage of allele 2 at position -889 of the IL-1A gene in conjunction with allele 2 of the IL-1B gene at position +3953. In this study, we tested the hypothesis that allele 2 of the IL-1A gene at position -889 might act to elevate levels of IL-1alpha protein in patients with periodontal disease. Since levels of IL-1alpha protein are low in healthy individuals, we used a group of patients with severe periodontal disease to investigate if levels of IL-1alpha protein in gingival crevicular fluid can be correlated to patient genotype. IL-1alpha levels were measured by enzyme immunoassay in 46 patients with severe periodontal disease. These patients were genotyped by PCR and allele-specific restriction digests. The carriage rate for allele 2 in the diseased population was 68%. Overall, the carriage of allele 2 was associated with almost a four-fold increase in IL-1alpha protein levels. Differences were most pronounced in non-smokers, while heavy smokers showed reduced levels of IL-1alpha protein regardless of genotype. These results suggest a mechanism whereby this genetic polymorphism acts to modulate IL-1alpha protein production and may influence the pathogenesis of periodontal disease by affecting the extent of IL-1-associated bystander damage.

Adult↗
PubMed2000

Primary care groups and trusts: stages in a process of organizational evolution.

In this paper, the origins and early experiences of the new national network of primary care groups (PCGs) in the NHS are explored, emphasizing that they represent the latest stage in an evolutionary process in the development of primary care organizations. Using Greiner's five stages of organizational growth, an analysis is made of the development of PCGs and the future primary care trusts (PCTs). The author asserts that, having grown through creativity in the pre-1997 NHS, primary care organizations in the 'New NHS' are experiencing growth through direction, with a much greater degree of central control and management being brought to bear on PCGs. The likely future shape of PCGs and PCTs is then described, drawing on the analysis of PCGs within Greiner's framework for organizational growth. The paper concludes by setting out guidelines for managers and clinicians charged with the responsibility of developing PCGs and PCTs, based on the premise that these new organizational forms are not an end in themselves, but a stage in the organizational development of primary care in the NHS.

Cooperative Behavior↗
PubMed2000

Childhood sexual abuse and dating experiences of undergraduate women.

Child sexual abuse is a prevalent social problem with a variety of negative consequences for adult survivors. Whereas most studies have focused on intrapersonal effects including depressive symptomatology and post-traumatic stress disorder, recent work has begun to call attention to interpersonal results as well. The current study examined the relationship between the experience of childhood sexual abuse and being a victim of psychological aggression, physical violence, or sexual coercion in a dating relationship in the past year. Participants were 219 female college undergraduates. Child sexual abuse was significantly related to having experienced both physical and psychological dating aggression even after controlling for the presence of conflict in the family of origin. Child sexual abuse was not significantly related to sexual coercion or reports of silencing oneself in relationships.

Adolescent↗
PubMed2000

Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans.

We describe a radioimmunoassay (RIA) for total leptin and a gel filtration procedure for the separation of free and bound leptin in human serum. The RIA, based on a locally prepared antibody, has a minimum detection limit of 0.9 ng/mL, a working range (CV < 10%) of 2.5-50 ng/mL, inter-assay precision of 10.2, 7.2 and 8.9%CV at 7.9, 15.4 and 30.0 ng/mL, respectively, 94% recovery of exogenous leptin (range 81.1-120.6%), exhibited parallelism and demonstrated no significant cross-reactivity or interferences. A difference plot of results from this method and those from a commercially available kit (Linco Research) demonstrated satisfactory agreement up to concentrations of 50 ng/mL total leptin, with no significant bias. A gender-dependent correlation was obtained between body mass index (BMI) and total leptin (r = 0.91, P<0.001, n = 75 for men; r = 0.79, P<0.001, n = 72 for women), with women having higher leptin concentrations than men for any given BMI. Gel filtration studies (inter-assay precision: 4.7%CV, n = 18) demonstrated that a variable fraction (between 10% and 40%) of total leptin in serum was bound with high affinity (Keq = 1.0-1.45 x 10(9) L/mol) to a non-albumin, non-lipid macromolecule. Binding affinities were found to be similar irrespective of gender or fat mass. A significant positive correlation between free or bound leptin concentrations and BMI was obtained for both men and women (r = 0.87-0.94); free and bound leptin concentrations were also significantly higher in women (P<0.01) than in men for any given BMI, and higher in obese (P<0.01) than in lean individuals. We conclude that leptin 'resistance' associated with obesity cannot be accounted for by reduced free leptin concentrations in serum and that the methods described are suitable for the investigation of total, free and bound leptin for both clinical and research purposes.

Body Mass Index↗
PubMed2000

Personal control and the ecology of community living settings: beyond living-unit size and type.

Personal control exercised by 74 adults from community living settings in Minnesota was evaluated. Comparisons between living-unit sizes or types controlled statistically for pre-existing differences in adaptive and challenging behavior. Individuals living semi-independently exercised more personal control than did residents of HCBS Waiver-funded settings, who had more personal control than persons from community ICFs/MR. Within the 1- to 5-person size range, size-related differences were detected in personal control. Using hierarchical regression, we found that personal characteristics, self-determination competencies, and environmental variables all made significant, unique contributions to predicting personal control. Path analysis also revealed that this range of variables was related to personal control. These findings strongly support an ecological approach to self-determination.

Adult↗
PubMed2000

Pathology of fatal West Nile virus infections in native and exotic birds during the 1999 outbreak in New York City, New York.

West Nile fever caused fatal disease in humans, horses, and birds in the northeastern United States during 1999. We studied birds from two wildlife facilities in New York City, New York, that died or were euthanatized and were suspected to have West Nile virus infections. Using standard histologic and ultrastructural methods, virus isolation, immunohistochemistry, in situ hybridization and reverse-transcriptase polymerase chain reaction, we identified West Nile virus as the cause of clinical disease, severe pathologic changes, and death in 27 birds representing eight orders and 14 species. Virus was detected in 23/26 brains (88%), 24/ 25 hearts (96%), 15/18 spleens (83%), 14/20 livers (70%), 20/20 kidneys (100%), 10/13 adrenals (77%), 13/ 14 intestines (93%), 10/12 pancreata (83%), 5/12 lungs (42%), and 4/8 ovaries (50%) by one or more methods. Cellular targets included neurons and glial cells in the brain, spinal cord, and peripheral ganglia; myocardial fibers; macrophages and blood monocytes; renal tubular epithelium; adrenal cortical cells; pancreatic acinar cells and islet cells; intestinal crypt epithelium; oocytes; and fibroblasts and smooth muscle cells. Purkinje cells were especially targeted, except in crows and magpies. Gross hemorrhage of the brain, splenomegaly, meningoencephalitis, and myocarditis were the most prominent lesions. Immunohistochemistry was an efficient and reliable method for identifying infected cases, but the polyclonal antibody cross-reacted with St. Louis encephalitis virus and other flaviviruses. In contrast, the in situ hybridization probe pWNV-E (WN-USAMRIID99) reacted only with West Nile virus. These methods should aid diagnosticians faced with the emergence of West Nile virus in the United States.

Animals↗
PubMed2000

Displaced scaphoid fractures treated with open reduction and internal fixation with a cannulated screw.

BACKGROUND: This study was performed to determine if the accuracy of screw placement was improved with use of the Herbert-Whipple cannulated screw compared with use of the AO/ASIF cannulated screw and also to evaluate the functional results in patients with an acute displaced fracture of the waist of the scaphoid treated with open reduction and internal fixation with a cannulated screw. METHODS: We retrospectively reviewed the results for thirty-five patients in whom an acute displaced fracture of the waist of the scaphoid had been treated with internal fixation with use of a cannulated screw. The patients were divided into two groups; Group 1 consisted of nineteen patients managed with a 3.5-millimeter cannulated AO/ASIF screw from 1990 through 1997, and Group 2 consisted of sixteen patients managed with a Herbert-Whipple screw from 1993 through 1997. RESULTS: There were no clinical or radiographic differences between the two groups. The average time to union (and standard deviation), confirmed with tomography, was 4.2 +/- 1.2 months for Group 1 and 4.0 +/- 1.2 months for Group 2. Both screws significantly improved the alignment of the scaphoid and decreased carpal collapse (p < 0.01). Importantly, the use of either cannulated screw improved the height-to-length ratio and the lateral intrascaphoid angle, which were correlated with an increase in the range of motion of the wrist (r = 0.584 and 0.625). In addition, both screws allowed for accurate placement in the central portion of the proximal pole. Regardless of the type of screw used, the time to union increased with increasing age of the patient (r = 0.665) and with increasing initial displacement of the fracture (r = 0.541). Within both groups, the time to union was longer for the patients who smoked (p < 0.01). CONCLUSIONS: Within both groups, cannulated screw fixation maintained the corrected fracture alignment and promoted healing and return of function. Our study shows cannulated screws to be a safe and effective method of treatment.

Adult↗
PubMed2000

Creatine use among a select population of high school athletes.

OBJECTIVE: To determine the prevalence, frequency, and patterns of creatine use among a local population of high school athletes. SUBJECTS AND METHODS: Male and female high school athletes completed an anonymous questionnaire on creatine use during the August 1999 preparticipation examinations at a single institutional sports medicine center. RESULTS: A total of 328 students (182 males and 146 females) aged 14 to 18 years (mean +/- SD 15.2 +/- 1.3 years) completed the survey (100% response rate), although not all athletes answered each question. Twenty-seven athletes (8.2% of total group), 1 of whom was female, reported creatine use. Of these 27 athletes, 14 (52%) were taking creatine at the time of the survey. The frequency of creatine use among past and current users was equally distributed among rarely (30%), weekly (35%), and daily (35%). Creatine users were older than nonusers (mean 16.5 +/- 1.2 vs 15.0 +/- 1.3 years; P < .001). Of creatine users, 21 (78%) were male football players. Nineteen of 24 respondents (79%) believed creatine improved their performance. Overall, 78% of users either did not know how much creatine they were taking (12/22 respondents) or were taking greater than the recommended doses (5/22 respondents). Minor gastrointestinal side effects or muscle cramps were reported by 5 (20%) of 25 respondents. Creatine users were more likely than nonusers to know other creatine users (81% vs 22%; P < .001) and to use other supplements (67% vs 9%; P < .001). Creatine users obtained creatine information primarily from friends (74%) and purchased creatine predominantly from health food stores (86%). CONCLUSIONS: High school male and female athletes as young as 14 years use creatine. Of high school athletes participating in our study, 8.2% reported creatine use. Relatively minor side effects, diarrhea, cramps, and loss of appetite, were reported. Creatine users seem to believe that creatine improves their performance, but they may lack sufficient information to make informed decisions regarding creatine use. Further larger scale study is warranted.

Adolescent↗
PubMed2000

Proprioception.

Although definitions of proprioception may vary, its importance in preventing and rehabilitating athletic injuries remains constant. Proprioception plays a significant role in the afferent-efferent neuromuscular control arc. This control arc is disrupted with joint and soft tissue injury. Restoring proprioception after injury allows the body to maintain stability and orientation during static and dynamic activities. By focusing on aspects of neuromuscular function, such as dynamic joint stability, practitioners can design and study interventions to maximize sport and daily life neuromuscular function. Further research is necessary to elucidate how proprioceptive deficits can be remedied or compensated to improve function and prevent reinjury.

Athletic Injuries↗
PubMed2000

National evaluation of general practitioner commissioning pilots: lessons for primary care groups.

BACKGROUND: The national evaluation of general practitioner (GP) commissioning pilots was commissioned by the Department of Health in 1997 as part of its Policy Research Programme. It was conducted by the Health Services Management Centre at the University of Birmingham. AIM: To monitor the development of the 40 national pilot sites, identify the factors that inhibited or facilitated progress, and consider the implications for the implementation and development of primary care groups (PCGs). METHOD: Semi-structured face-to-face interviews with GPs, health authority (HA) managers, and pilot managers from each of the 40 pilot sites (141 interviews in total) and focus group discussions with nurses, social services officers, and community health council officers in the 40 sites. RESULTS: Stakeholders reported the key achievements of the pilots during their first six months as being improved collaboration between GPs, the establishment of organisational arrangements, and work towards managing the group prescribing budget. Obstacles for the groups included changes to government policy regarding primary care, the workload involved for clinical staff, the pilots' relationship with the local HA, and problems with information management and technology (IM&T). A more detailed analysis of the pilots' management arrangements, prescribing work, IM&T support, and stakeholder involvement points to a set of lessons for emerging PCGs. CONCLUSIONS: In their early stages of development, PCGs are likely to focus on issues of structure and process. Prescribing will be an area receiving particular attention, prefiguring some of the challenges of clinical governance in primary care. IM&T will prove to be more problematic than first assumed. The involvement of a wider range of stakeholders will be addressed by primary care groups, particularly in relation to GPs and nurses.

England↗
PubMed2000

A genetic epidemiological study of hereditary prostate cancer (HPC) in Finland: frequent HPCX linkage in families with late-onset disease.

Several predisposition loci for hereditary prostate cancer (HPC) have been suggested, including HPC1 at 1q24-q25 (OMIM #601518) and HPCX at Xq27-q28 (OMIM #300147). Genetically homogeneous populations, such as that of Finland, and distinct subsets of families may help to minimize the genetic heterogeneity that complicates the genetic dissection of complex traits. Here, the role of the HPC1, and HPCX loci in a series of Finnish prostate cancer families was studied, especially in subgroups of families defined by age, number of affected cases, and the mode of disease transmission. DNA samples were collected from 57 Finnish HPC families with at least two living prostate cancer patients. Linkage analysis was carried out with 39 microsatellite markers for the HPC1 region and 22 markers for the HPCX region. The maximum two-point LOD score for the HPCX was 2.05 (marker DXS1205, at theta = 0.14), whereas HPC1 LOD scores were all negative. In HOMOG3R analyses, significant evidence of heterogeneity was observed. Subgroup analyses performed to explore the nature of this heterogeneity indicated that families with no male-to-male (NMM) transmission and a late age of diagnosis (>65 years) accounted for most of the HPCX-linked cases. The maximum HPCX LOD score in this subgroup was 3.12 (theta = 0.001). Nonparametric sibling pair analyses gave a peak LOD score of 3.04 (P < 0.000093) for the NMM transmission subgroup. No subgroup showed any positivity for HPC1. This study suggests that the HPCX-linked prostate cancer families represent a distinct subgroup characterized by NMM transmission of disease and late age of diagnosis.

Age of Onset↗