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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 289 records · Page 16Linked to original sources
PubMed2000

Antioxidant properties of colchicine in acute carbon tetrachloride induced rat liver injury and its role in the resolution of established cirrhosis.

Antioxidant and antifibrotic properties of colchicine were investigated in the carbon tetrachloride (CCl(4)) rat model. (1) The protective effect of colchicine pretreatment on CCl(4) induced oxidant stress was examined in rats subsequently receiving a single lethal dose of CCl(4). Urinary 8-isoprostane, kidney and liver malondialdehyde and kidney glutathione levels increased following CCl(4) treatment, but only the rise in kidney malondialdehyde was significantly inhibited by colchicine pretreatment. Serum total antioxidant levels were significantly higher in the colchicine pretreatment group. (2) The long term effects of colchicine treatment on CCl(4) induced liver damage were investigated using liver histology and biochemical markers (hydroxyproline and type III procollagen peptide). Co-administration of colchicine with sub-lethal doses of CCl(4) over 10 weeks did not prevent progression to cirrhosis. However, rats made cirrhotic with repeated CCl(4) challenge and subsequently treated with colchicine for 12 months, all showed histological regression of cirrhosis. (3) The antioxidant effect of colchicine in vitro was evident only at very high concentrations compared to other plasma antioxidants. In summary, colchicine has only weak antioxidant properties, but does afford some protection against oxidative stress; more importantly, long term treatment with this drug may be of value in producing regression of established cirrhosis.

Animals↗
PubMed2000

Measurements of the mass, total width, and two-photon partial width of the eta(c) meson.

Using 13.4 fb(-1) of data collected with the CLEO detector at the Cornell Electron Storage Ring, we have observed 300 events for the two-photon production of ground-state pseudoscalar charmonium in the decay eta(c)-->K(0)(S)K-/+pi(+/-). We have measured the eta(c) mass to be [2980.4+/-2.3 (stat)+/-0.6 (syst)] MeV and its full width as [27.0+/-5.8 (stat)+/-1.4 (syst)] MeV. We have determined the two-photon partial width of the eta(c) meson to be [7.6+/-0.8 (stat)+/-0.4 (syst)+/-2.3 (br)] keV, with the last uncertainty associated with the decay branching fraction.

Journal Article↗
PubMed2000

Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study.

BACKGROUND: An association between HIV-1 and malaria is expected in theory, but has not been convincingly shown in practice. We studied the effects of HIV-1 infection and advancing immunosuppression on falciparum parasitaemia and clinical malaria. METHODS: HIV-1-positive and HIV-1-negative adults selected from a population-based cohort in rural Uganda were invited to attend a clinic every 3 months (routine visits) and whenever they were sick (interim visits). At each visit, information was collected on recent fever, body temperature, and malaria parasites. Participants were assigned a clinical stage at each routine visit and had regular CD4-cell measurements. FINDINGS: 484 participants made 7220 routine clinic visits between 1990 and 1998. Parasitaemia was more common at visits by HIV-1-positive individuals (328 of 2788 [11.8%] vs 231 of 3688 [6.3%], p<0.0001). At HIV-1-positive visits, lower CD4-cell counts were associated with higher parasite densities, compared with HIV-1-negative visits (p=0.0076). Clinical malaria was significantly more common at HIV-1-positive visits (55 of 2788 [2.0%] vs 26 of 3688 [0.7%], p=0.0003) and the odds of having clinical malaria increased with falling CD4-cell count (p=0.0002) and advancing clinical stage (p=0.0024). Participants made 3377 interim visits. The risk of clinical malaria was significantly higher at visits by HIV-1-positive individuals than HIV-1-negative individuals (4.0% vs 1.9%, p=0.009). The risk of clinical malaria tended to increase with falling CD4-cell counts (p=0.052). INTERPRETATION: HIV-1 infection is associated with an increased frequency of clinical malaria and parasitaemia. This association tends to become more pronounced with advancing immunosuppression, and could have important public-health implications for sub-Saharan Africa.

Adolescent↗
PubMed2000

Predictors of bone mass in healthy older men in the community.

OBJECTIVES: To determine the predictors of bone mass (in lumbar spine and femoral neck) in healthy older men living in the community. DESIGN: Cross-sectional study. Bone mineral density (BMD) was measured and known predictors of bone mass and bone turnover were assessed. SUBJECTS AND SETTING: 113 independent, healthy men (70 years and over), not taking glucocorticoid therapy and without medical conditions known to affect bone mass and bone turnover, were recruited from recreational and sports clubs in southern Sydney in April/May 1997. MAIN OUTCOME MEASURES: BMD (measured by dual-energy x-ray absorptiometry); known predictors of bone mass (height; weight; body mass index; calcium level; serum 25-hydroxyvitamin D and free testosterone levels); and markers of bone turnover (serum bone Gla protein and procollagen-1 concentrations, and urinary deoxypyridinoline excretion rates). RESULTS: The mean age of the men was 76.6 years (range, 70-92 years). Mean (SE) BMD of the lumbar spine was 1.143 (0.019) g/cm2 and that of the femoral neck was 0.897 (0.013) g/cm2. BMD values indicating osteoporosis were found in the lumbar spine in 13 men (11.5%) and in the femoral neck in 35 men (31%). The best predictor of lumbar spine BMD was weight (R = 0.37; P = 0.001), and weight- and age-predicted femoral-neck BMD (R = 0.49; P < 0.001). The study group was analysed in two groups with BMD higher or lower than median bone mass corrected for age. Men with lower femoral-neck BMD for age had significantly lower weight, lower lean mass and higher bone Gla protein concentrations. In addition, men with lower lumbar spine BMD for age also had significantly lower fat mass. CONCLUSIONS: These data indicate that measures of body composition, such as weight and lean mass, are the main predictors of bone mass in healthy, community-dwelling older men.

Absorptiometry, Photon↗
PubMed2000

Neuromedin U is a potent agonist at the orphan G protein-coupled receptor FM3.

Neuromedins are a family of peptides best known for their contractile activity on smooth muscle preparations. The biological mechanism of action of neuromedin U remains unknown, despite the fact that the peptide was first isolated in 1985. Here we show that neuromedin U potently activates the orphan G protein-coupled receptor FM3, with subnanomolar potency, when FM3 is transiently expressed in human HEK-293 cells. Neuromedins B, C, K, and N are all inactive at this receptor. Quantitative reverse transcriptase-polymerase chain reaction analysis of neuromedin U expression in a range of human tissues showed that the peptide is highly expressed in the intestine, pituitary, and bone marrow, with lower levels of expression seen in stomach, adipose tissue, lymphocytes, spleen, and the cortex. Similar analysis of FM3 expression showed that the receptor is widely expressed in human tissue with highest levels seen in adipose tissue, intestine, spleen, and lymphocytes, suggesting that neuromedin U may have a wide range of presently undetermined physiological effects. The discovery that neuromedin U is an endogenous agonist for FM3 will significantly aid the study of the full physiological role of this peptide.

Calcium↗
PubMed2000

Exclusion limits on the WIMP-nucleon cross section from the cryogenic dark matter search.

The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment.

Journal Article↗
PubMed2000

Residential radon exposure and adult acute leukaemia.

Exposure to radioactive radon gas in homes, from natural sources, is an important public-health issue for many countries. We found no association between household exposure to radon and leukaemia in adults in the UK.

Acute Disease↗
PubMed2000

Mosaic rearrangement of chromosome 18: characterization by FISH mapping and DNA studies shows trisomy 18p and monosomy 18p both of paternal origin.

Structural abnormalities of chromosome 18p mainly consist of isochromosomes of the short arm, which result in tetrasomy 18p. Trisomy 18p is much rarer, and less well characterized. We report on a 12-year-old girl with minor facial anomalies, delayed development, abnormal hands, atopic dermatitis, and hearing loss. She was mosaic for two abnormal cell lines in peripheral blood. In 90% of cells, a dicentric chromosome with duplication of the whole short arm of chromosome 18 resulted in trisomy 18p; 10% of cells had monosomy 18p, arising from a t(14;18)(p11;q11). FISH mapping, with multiple region specific and locus specific probes from the short and long arm of chromosome 18, showed that the structure of the dicentric chromosome 18 was 18pter-->18q23::18q11-->18pter. DNA polymorphisms for chromosome 18 showed that the abnormalities of chromosome 18 were paternal in origin. Combining all results, we could link the trisomy 18p and monosomy 18p to a common origin via a complex series of events in an early mitosis.

Abnormalities, Multiple↗
PubMed2000

17p- syndrome arising from a novel dicentric translocation in a patient with acute myeloid leukemia.

The cytogenetic contribution to the poor prognosis when myelodysplastic syndrome (MDS) progresses to acute myeloid leukemia (AML) is not well understood. We present a 66-year-old male who had thrombocytopenia with dysplastic features in peripheral blood neutrophils (hypogranular, hyposegmented neutrophils) comprising the Pelger-Huet anomaly, increased blasts in the marrow, and markers consistent with AML. Diagnostic marrow cytogenetics showed a complex karyotype including del(5q), a novel unbalanced dicentric translocation, t(17;20), resulting in both del(20q) and del(17p). Fluorescence in situ hybridization (with probe TP53) showed deletion of 17p13 on the dicentric chromosome, completing the criteria for the 17p- syndrome. Fluorescence in situ hybridization with probes for two tumor suppressor genes on chromosome 5q also showed deletion (CSF1R [at 5(q33.2-q33.4) and EGR-1 [5(q31-q32)]). Remission was difficult to achieve and cytogenetic relapse occurred 6 months postdiagnosis, and clinical relapse approximately one month later. Our case provides a novel mechanism for the 17p- syndrome, and highlights the difficulty of attributing prognostic significance to a particular cytogenetic abnormality in AML.

Aged↗
PubMed2000

Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer.

The collection of small aliquots of bone marrow (BM), followed by ex vivo expansion for autologous transplantation may be less morbid, and more cost-effective, than typical BM or blood stem cell harvesting. Passive elimination of contaminating tumor cells during expansion could reduce reinoculation risks. Nineteen breast cancer patients underwent autotransplants exclusively using ex vivo expanded small aliquot BM cells (900-1200 x 10(6)). BM was expanded in media containing recombinant flt3 ligand, erythropoietin, and PIXY321, using stromal-based perfusion bioreactors for 12 days, and infused after high-dose chemotherapy. Correlations between cell dose and engraftment times were determined, and immunocytochemical tumor cell assays were performed before and after expansion. The median volume of BM expanded was 36.7 mL (range 15.8-87.0). Engraftment of neutrophils greater than 500/microL and platelets greater than 20,000/microL were 16 (13-24) and 24 (19-45) days, respectively; 1 patient had delayed platelet engraftment, even after infusion of back-up BM. Hematopoiesis is maintained at 24 months, despite posttransplant radiotherapy in 18 of the 19 patients. Transplanted CD34(+)/Lin(-) (lineage negative) cell dose correlated with neutrophil and platelet engraftment, with patients receiving greater than 2.0 x 10(5) CD34(+)/Lin(-) cells per kilogram, engrafting by day 28. Tumor cells were observed in 1 of the 19 patients before expansion, and in none of the 19 patients after expansion. It is feasible to perform autotransplants solely with BM cells grown ex vivo in perfusion bioreactors from a small aliquot. Engraftment times are similar to those of a typical 1000 to 1500 mL BM autotransplant. If verified, this procedure could reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which small stem cell doses are available, eg, cord blood transplants. (Blood. 2000;95:2169-2174)

Adult↗
PubMed2000

Spatial separation of parental genomes in preimplantation mouse embryos.

We have used two different experimental approaches to demonstrate topological separation of parental genomes in preimplantation mouse embryos: mouse eggs fertilized with 5-bromodeoxyuridine (BrdU)-labeled sperm followed by detection of BrdU in early diploid embryos, and differential heterochromatin staining in mouse interspecific hybrid embryos. Separation of chromatin according to parental origin was preserved up to the four-cell embryo stage and then gradually disappeared. In F1 hybrid animals, genome separation was also observed in a proportion of somatic cells. Separate nuclear compartments during preimplantation development, when extreme chromatin remodelling occurs, and possibly in some differentiated cell types, may be associated with epigenetic reprogramming.

Animals↗
PubMed2000

Interventions for chronic suppurative otitis media.

BACKGROUND: Chronic suppurative otitis media (CSOM) is a serious bacterial infection of the middle ear that can follow untreated acute otitis media. OBJECTIVES: To assess the effects of different treatments for CSOM. SEARCH STRATEGY: We searched Medline from 1966 to 1996 and a bibliographic collection of the Hearing Impairment Research Group in Liverpool, UK. We handsearched two otolaryngology journals and contacted members of an international hearing network. SELECTION CRITERIA: Randomized trials of any method of management for patients with eardrum perforation and persistent otorrhea. DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed eligibility and trial quality. One reviewer extracted data. We contacted investigators for clarifications. MAIN RESULTS: Twenty-four trials involving 1660 people were included. Clinical definitions and severity of CSOM varied, methodological quality was generally low and follow-up was short. Treatment with antibiotics or antiseptics accompanied by aural toilet was more effective in resolving otorrhea than no treatment (two trials, odds ratio 0.37, 95% confidence interval 0.24 to 0. 57) or aural toilet alone (six trials, odds ratio 0.31, 95% confidence interval 0.23 to 0.43). Topical treatment with antibiotics or antiseptics was more effective than systemic antibiotics (six trials, odds ratio 0.46, 95% confidence interval 0.30 to 0.69). Combining topical and systemic antibiotics was not more effective than topical antibiotics. Topical quinolones were more effective than non-quinolones (five trials, odds ratio 0.26, 95% confidence interval 0.16 to 0.41). No difference in the effectiveness of topical antibiotics and topical antiseptics was found (three studies, odds ratio 1.34, 95% confidence interval 0.64 to 2.81). Some topical antibiotic combinations may be more effective than others in resolving otorrhea. Rates of adverse drug events were low and equal between groups. REVIEWER'S CONCLUSIONS: Treatment of CSOM with aural toilet and topical antibiotics, particularly quinolones, is effective in resolving otorrhea and eradicating bacteria from the middle ear. Longterm outcomes such as preventing recurrences, closure of tympanic perforation and hearing improvement need to be further evaluated.

Chronic Disease↗
PubMed2000

Bone marrow transplantation in multiple sclerosis.

There is strong circumstantial evidence that multiple sclerosis (MS) is an autoimmune disease. Nonspecific immunosuppressive therapy has not been successful in altering the natural course of the illness. Bone marrow transplantation has heretofore been a radical therapy used in patients with life-threatening malignancies but has potential as a treatment for human autoimmunity. In MS there have been no controlled studies. We report here four patients with MS undergoing bone marrow transplantation with 6-48 months of follow-up. In three this was carried out for co-existing malignancy and in one as an experimental treatment for MS using the patient's unaffected identical twin as a donor. The limited outcome that can be evaluated in these patients supports further experimentation into this treatment modality in MS patients with poor prognostic indications.

Adult↗
PubMed2000

Iatrogenic thoracic migration of the stomach complicating laparoscopic nissen fundoplication.

BACKGROUND: Intrathoracic gastric herniation after laparoscopic Nissen fundoplication is an uncommon but potentially life-threatening complication that may present in the early or late postoperative period. METHODS: A retrospective analysis was performed on all patients undergoing antireflux surgery from December 1991 to June 1999. RESULTS: Nine cases of gastric herniation occurred after 511 operations (0.17%). Patients presented with the condition 4 days to 29 months after surgery. Eight of these nine patients (89%) had reported vomiting in the immediate postoperative period. Seven patients (78%) reported persistent odynophagia. A factor common to all patients was that posterior crural repair had not been performed. CONCLUSIONS: Measures should be undertaken to prevent postoperative vomiting after laparoscopic Nissen fundoplication. Posterior crural repair is essential after surgery in all cases.

Adult↗