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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 55 records · Page 3Linked to original sources

Measurement of the branching ratio and asymmetry of the decay Xi degrees -->Sigma degrees gamma.

We have studied the rare weak radiative hyperon decay Xi degrees -->Sigma degrees gamma in the KTeV experiment at Fermilab. We have identified 4045 signal events over a background of 804 events. The dominant Xi degrees -->Lambdapi degrees decay, which was used for normalization, is the only important background source. An analysis of the acceptance of both modes yields a branching ratio of B(Xi degrees -->Sigma degrees gamma)/B(Xi degrees -->Lambdapi degrees ) = (3.34+/-0.05+/-0.09)x10(-3). By analyzing the final state decay distributions, we have also determined that the Sigma degrees emission asymmetry parameter for this decay is alpha(XiSigma) = -0.63+/-0.09.

Journal Article↗

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

PURPOSE: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds. PATIENTS AND METHODS: Patients who had progressed after one platinum-based regimen were randomized to either topotecan (1.5 mg/m(2)/d) x 5 every 21 days (n = 112) or paclitaxel (175 mg/m(2) over 3 hours) every 21 days (n = 114). A total of 110 patients received cross-over therapy with the alternative drug (61 topotecan, 49 paclitaxel) as third-line therapy. RESULTS: Response rates to third-line cross-over therapy were 13.1% (8 of 61 topotecan) and 10.2% (5 of 49 paclitaxel; P =.638). Seven patients who responded to third-line topotecan and four patients who responded to paclitaxel had failed to respond to their second-line treatment. Median time to progression (from the start of third-line therapy) was 9 weeks in both groups, and median survival was 40 and 48 weeks for patients who were receiving topotecan or paclitaxel, respectively. The principal toxicity was myelosuppression; grade 4 neutropenia was more frequent with topotecan (81.4% of patients) than with paclitaxel (22.9% of patients). CONCLUSION: Topotecan and paclitaxel have similar activity as second-line therapies with regard to response rates and progression-free and overall survival. We demonstrated that the two drugs have a degree of non-cross-resistance. Thus, there is a good rationale for incorporating these drugs into future first-line regimens.

Adult↗

Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae.

Combination therapy that includes artemisinin derivatives cures most falciparum malaria infections. Lowering transmission by reducing gametocyte infectivity would be an additional benefit. To examine the effect of such therapy on transmission, Gambian children with Plasmodium falciparum malaria were treated with standard regimens of chloroquine or pyrimethamine-sulfadoxine alone or in combination with 1 or 3 doses of artesunate. The infectivity to mosquitoes of gametocytes in peripheral blood was determined 4 or 7 days after treatment. Infection of mosquitoes was observed in all treatment groups and was positively associated with gametocyte density. The probability of transmission was lowest in those who received pyrimethamine-sulfadoxine and 3 doses of artesunate, and it was 8-fold higher in the group that received pyrimethamine-sulfadoxine alone. Artesunate reduced posttreatment infectivity dramatically but did not abolish it completely. The study raises questions about any policy to use pyrimethamine-sulfadoxine alone as the first-line treatment for malaria.

Adolescent↗

Study of the K(0)(L) --> pi(+)pi(-)gamma Direct Emission Vertex.

We have performed studies of the K(0)(L)-->pi(+)pi(-)gamma direct emission ( DE) and inner Bremsstrahlung ( IB) vertices, based on data collected by KTeV during the 1996 Fermilab fixed target run. We find a(1)/a(2) = -0.737+/-0.034 GeV2 for the DE form-factor parameter in the rho-propagator parametrization, and report on fits of the form factor to linear and quadratic functions as well. We concurrently measure gamma(K(0)(L)-->pi(+)pi(-)gamma,E(*)(gamma)>20 MeV)/gamma(K(0)(L)-->pi(+)pi(-)) = (20.8+/-0.3)x10(-3), and a K(0)(L)-->pi(+)pi(-)gamma DE/(DE+IB) branching ratio of 0.683+/-0.011.

Journal Article↗

Search for the decay KL --> pi(0)e+e-.

We report on a search for the decay KL-->pi(0)e+e- carried out by the KTeV/E799 experiment at Fermilab. This decay is expected to have a significant CP violating contribution and the measurement of its branching ratio could support the Cabibbo-Kobayashi-Maskawa mechanism for CP violation or could point to new physics. Two events were observed in the 1997 data with an expected background of 1.06+/-0.41 events, and we set an upper limit B(KL-->pi(0)e+e-)<5.1 x 10(-10) at the 90% confidence level.

Journal Article↗

A longitudinal study of motor ability and kinaesthetic acuity in young children at risk of developmental coordination disorder.

Several studies have linked poor kinaesthetic ability with poor motor coordination in school-aged children. However, few studies have investigated kinaesthesis in younger children. The aim of this study was to determine if preschool aged children who have been identified as at risk of developing developmental coordination disorder (DCD) have poorer kinaesthetic ability than matched controls. Kinaesthetic ability and performance IQ were examined in a group of children aged between 4 and 5 years. Following individual assessment of 291 children, 31 were identified as at risk of DCD at this age. One year later, 30 of these children were retested, and 23 were still found to be at risk. These children were matched on verbal IQ, age and sex with control children and their performance compared on the kinaesthetic acuity test (KAT) [D.J. Livesey and N.A. Parkes, Aust. J. Psychol., 47 (1995) 160] and three subtests of the WPPSI-R performance IQ (D. Wechsler, Manual for the Wechsler preschool and primary scale of intelligence--revised, Psychological Corporation, New York, 1989). Both the KAT and the performance subtest scores were found to be significantly poorer in the children at risk of DCD. Follow-up testing one year later showed that both groups improved their kinaesthetic acuity score although the control children remained significantly better than the children with poor motor coordination.

Awareness↗

Effect of tauroursodeoxycholate and S-adenosyl-L-methionine on 17beta-estradiol glucuronide-induced cholestasis.

BACKGROUND/AIMS: S-adenosyl-L-methionine (SAMe) and tauroursodeoxycholate (TUDC) exert an additive ameliorating effect on taurolithocholate (TLC)-induced cholestasis. The aims were to investigate the protective effect of SAMe on 17beta-estradiol-glucuronide (17betaEG) cholestasis and to find out whether SAMe and TUDC may exert an additive, ameliorating effect. METHODS: Hepatocyte couplet function was assessed by canalicular vacuolar accumulation (cVA) of cholyllysylfluorescein (CLF). Cells were co-treated with 17betaEG and SAMe, TUDC, or both (protection study), or treated with 17betaEG and then with SAMe, TUDC or both (reversion study) before CLF uptake. Couplets were also co-treated with SAMe and dehydroepiandrosterone (DHEA), a competitive substrate for the sulfotransferase involved in 17betaEG detoxification. The effects of 17betaEG, SAMe and TUDC were also examined on intracellular distribution of F-actin. RESULTS: Both SAMe and TUDC significantly protected against, and reversed, 17betaEG-induced cholestasis, but their effects were not additive. DHEA abolished the protective effect of SAMe. 17BetaEG did not affect the uptake of CLF into hepatocytes at the concentrations used, and also, it did not affect the intracellular distribution of F-actin. CONCLUSIONS: 17BetaEG does not affect the uptake of CLF into hepatocytes. SAMe and TUDC protect and reverse 17betaEG-induced cholestasis, but without an additive effect. Protection by SAMe may involve facilitating the sulfation of 17betaEG.

Actins↗

Recovery of muscles of old rats after hindlimb immobilisation by external fixation is impaired compared with those of young rats.

The right hindlimbs of 24-month-old female Wistar rats were immobilised for 4weeks using external fixation of the knee joint. In a further group, after the external fixation was removed, the rats were allowed to remobilise for an additional 4weeks. Hindlimb immobilisation for 4weeks caused a 32-42% reduction in wet weights of the hindlimb muscles of the rats as compared to those of the contralateral non-immobilised legs. After 4weeks of remobilisation the hindlimb muscles had not returned to the "control" weights. Biochemical changes in the gastrocnemius muscle resulting from the external fixation showed greatly elevated acid phosphatase activities (33.2%) and markedly reduced creatine phosphokinase activities (17.2%), which did not recover to preimmobilisation values after 4weeks of remobilisation. Light and transmission electron microscopy showed that remobilisation for 4weeks (after external fixation) resulted in only partial morphological restoration of the damage to the muscles in these aged rats. A comparison of similar hindlimb external fixation and remobilisation in young (6months old) rats showed that remobilisation caused a substantial recovery in biochemical parameters in both age groups, with the muscles of the young group (but not the old group) often reaching almost complete recovery accompanied by morphological restoration. We conclude that the net gain in the recovery period of biochemical and morphological parameters is significantly greater in the young rats compared to the old rats indicating that muscle metabolism and capacity for recovery from disuse atrophy is impaired with ageing.

Aging↗

Age-related changes in upper airway muscles morphological and oxidative properties.

Obstructive sleep apnea (OSA) is a common disorder of the middle aged and elderly. It results from the decrease in upper airway muscle (UAM) tone that occurs during sleep. It is unclear whether age-related changes in UAM could constitute a contributory mechanism to the increased prevalence of OSA with increasing age, and previous papers evaluating the effects of aging on UAM in rats reported conflicting results. In the present study, we compared, in four age groups of Wistar rats (6-24 months), fiber-type distribution, mean cross-sectional fiber area and succinate dehydrogenase optical density of dilating and non-dilating UAM, and the diaphragm. Succinate dehydrogenase optical density, a marker of oxidative capacity, decreased significantly after the age of 6 months in all muscles (except for the sternohyoid), particularly in the genioglossus, the main tongue protrudor. In this muscle, we also found a significant decrease in type IIa and an increase in IIb fibers after the age of 18 months. Age-related changes in fiber-type distribution in other muscles were mostly insignificant. Dilating UAM could not be distinguished from their non-dilating neighboring muscles by their histochemical properties or aging-related changes. The aging-related changes observed in the present study may decrease UAM endurance, particularly that of the main tongue protrudor, the genioglossus.

Aging↗

Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci.

We have carried out a genome screen for atopic dermatitis (AD) and have identified linkage to AD on chromosomes 1q21, 17q25 and 20p. These regions correspond closely with known psoriasis loci, as does a previously identified AD locus on chromosome 3q21. The results indicate that AD is influenced by genes with general effects on dermal inflammation and immunity.

Child↗

Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria.

As part of a study to assess the infectivity of gametocytes after treatment with four antimalarial regimens, the efficacy of each treatment was also determined. From September to December 1998, 598 children with uncomplicated malaria were treated; 135 received chloroquine (CQ) alone, 276 received pyrimethamine/sulfadoxine (Fansidar, PSD) alone, 113 received PSD with a single dose of artesunate (PSD + 1ART) and 74 received PSD combined with three doses of artesunate (PSD + 3ART). On day 28 19/63 (30.2%; 95% C.I. 19.2% to 43.1%) of children treated with CQ alone, 5/134 (3.7%; 95% C.I. 1.2% to 8.5%) treated with PSD alone, 1/71 (1.4%, 95% C.I. 0.0% to 7.9%) treated with PSD + 1ART and 0/45 (0.0%; 95% C.I. 0.0% to 7.9%) treated with PSD + 3ART were parasitaemic. The proportion of children with gametocytes on day 7 after treatment with CQ alone was 16/89 (18.0%; 95% C.I. 10.6% to 27.6%), 98/174 (56.3%; 95% C.I. 48.6% to 63.8%) after treatment with PSD alone, 8/70 (11.4%; 95% C.I. 5.1% to 21.3%) after treatment with PSD + 1ART and 4/46 (8.7%; 95% C.I., 2.4% to 20.8%) after treatment with PSD + 3ART. CQ thus has a lower efficacy than PSD or either of the PSD and artesunate combinations. Use of PSD alone as an alternative first line treatment results in a very high post-treatment gametocyte prevalence that is likely to enhance transmission. There would be greater and more sustainable benefits from using PSD and artesunate combinations.

Animals↗

The long-term reproductive health consequences of female genital cutting in rural Gambia: a community-based survey.

This paper examines the association between traditional practices of female genital cutting (FGC) and adult women's reproductive morbidity in rural Gambia. In 1999, we conducted a cross-sectional community survey of 1348 women aged 15-54 years, to estimate the prevalence of reproductive morbidity on the basis of women's reports, a gynaecological examination and laboratory analysis of specimens. Descriptive statistics and logistic regression were used to compare the prevalence of each morbidity between cut and uncut women adjusting for possible confounders. A total of 1157 women consented to gynaecological examination and 58% had signs of genital cutting. There was a high level of agreement between reported circumcision status and that found on examination (97% agreement). The majority of operations consisted of clitoridectomy and excision of the labia minora (WHO classification type II) and were performed between the ages of 4 and 7 years. The practice of genital cutting was highly associated with ethnic group for two of the three main ethnic groups, making the effects of ethnic group and cutting difficult to distinguish. Women who had undergone FGC had a significantly higher prevalence of bacterial vaginosis (BV) [adjusted odds ratio (OR)=1.66; 95% confidence interval (CI) 1.25-2.18] and a substantially higher prevalence of herpes simplex virus 2 (HSV2) [adjusted OR=4.71; 95% CI 3.46-6.42]. The higher prevalence of HSV2 suggests that cut women may be at increased risk of HIV infection. Commonly cited negative consequences of FGC such as damage to the perineum or anus, vulval tumours (such as Bartholin's cysts and excessive keloid formation), painful sex, infertility, prolapse and other reproductive tract infections (RTIs) were not significantly more common in cut women. The relationship between FGC and long-term reproductive morbidity remains unclear, especially in settings where type II cutting predominates. Efforts to eradicate the practice should incorporate a human rights approach rather than rely solely on the damaging health consequences.

Adolescent↗

New options for outpatient chemotherapy--the role of oral fluoropyrimidines.

For several decades fluoropyrimidines, especially 5-fluorouracil (5-FU), have played a role in standard chemotherapy regimens for a range of solid tumours, including breast and colorectal cancers. In recent years, schedule modification and biomodulation have achieved improved efficacy and tolerability. However, the complications arising from infused intravenous administration are well-recognized and there is an unmet medical need for oral agents with improved efficacy and tolerability, offering more convenient outpatient therapy. Several oral fluoropyrimidines are in development, including capecitabine, UFT (uracil plus tegafur), S-1 and eniluracil. As yet, only UFT/leucovorin and capecitabine have been evaluated in randomized phase III clinical trials in metastatic colorectal cancer. Both have demonstrated safety benefits and equivalent survival compared with the Mayo Clinic regimen, and capecitabine has demonstrated a significantly superior response rate. Time to disease progression was equivalent to the Mayo Clinic regimen with capecitabine, but inferior with UFT/leucovorin. Capecitabine is also effective in patients with taxoid-pretreated metastatic breast cancer, a population which previously had no established treatment options. Both capecitabine and UFT/leucovorin are being evaluated in combination with irinotecan and oxaliplatin in colorectal cancer, and vinorelbine and docetaxel/paclitaxel in breast cancer. In the future, these more convenient, oral fluoropyrimidines may replace intravenous 5-FU in the treatment of breast and colorectal cancer.

Administration, Oral↗

Breast cancer in two sisters with Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder causing progressive ataxia and dysarthria. We report two sisters who had breast cancer aged 39 years and 42 years and who both developed a late onset form of FRDA with onset of neurological symptoms in their thirties. We discuss whether there may be an association between the late onset form of FRDA and malignancy.

Adult↗

Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: a study in vivo and in isolated hepatocyte couplets.

The effect of silymarin (SIL) on 17alpha-ethynylestradiol (EE)-induced cholestasis was evaluated in rats. EE (5 mg/kg, subcutaneously, daily, for 5 days) decreased both the bile-salt-dependent and the bile-salt-independent fractions of the bile flow. The decrease in the former was associated to a reduction in the bile salt pool size (-58%), and this effect was completely prevented by SIL. This compound also counteracted the inhibitory effect induced by EE on HCO(3)(-) but not glutathione output, 2 major determinants of the bile-salt-independent bile flow. EE decreased the secretory rate maximum (SRM) of tauroursodeoxycholate, (-71%) and bromosulfophthalein (BSP; -60%), as well as the expression of the BSP canalicular carrier, mrp2; SIL failed to increase mrp2 expression, and had only a marginal beneficial effect on both tauroursodeoxycholate and BSP SRM values. However, the two-compartment model-based kinetic constant for BSP canalicular transfer was significantly improved by SIL (+262%). SIL decreased rather than increased CYP3A4, the cytochrome P450 isoenzyme involved in the oxidative metabolism of EE, and had no inhibitory effect on the UDP-glucuronosyltrasferase isoforms involved in the formation of its 17beta-glucuronidated, more cholestatic metabolite. Pretreatment of isolated rat hepatocyte couplets with silibinin, the major, active component of SIL, counteracted the estradiol 17beta-glucuronide-induced decrease in the percentage of couplets secreting apically the fluorescent bile acid analogue, cholyl-lysyl-fluorescein. These results show that SIL protects against EE-induced cholestasis by normalizing mainly the decrease in the bile salt pool size and HCO(3)(-) output, and probably by counteracting the cholestatic effect of its cholestatic, glucuronidated metabolite.

ATP Binding Cassette Transporter, Subfamily B↗

Docetaxel-carboplatin as first line chemotherapy for epithelial ovarian cancer.

A prospective, non-randomized, multicentre, open, dose-finding study of a carboplatin-docetaxel (C-D) combination as first-line chemotherapy in FIGO stage Ic-IV epithelial ovarian cancer. C-D was given 3-weekly for 6 planned cycles, with a 3-day prophylactic dexamethasone regimen (8 mg b.i.d.). 139 eligible patients (Pts) (median age 56 years, range 28-85) were given a total of 750 cycles of chemotherapy in 5 cohorts: Co1, 32 pts, 169 cycles (C at AUC 5 + D 60 mg/m(2)); Co2, 22 pts, 122 cycles (5 + 75), Co3, 29 pts, 156 cycles (6 + 75), Co4, 27 pts, 146 cycles (7 + 75), Co5, 30 pts, 157 cycles (6 + 85). 110 patients (79%) completed 6 cycles; 17 (12%) stopped due to toxicity. 104 patients (75%) had CTC grade IV neutropenia, and 5 patients (4%) had this associated with fever. There were 2 probable treatment-related deaths. Only 8 patients (6%) experienced grade II-III neurotoxicity (all sensory; no motor > grade I). The maximum tolerated dose was reached in cohorts 4 and 5, and the dose limiting toxicities were myelosuppression and diarrhoea. The overall response rate for the study was 66% (49/74); CA125 response was 75% (70/93). Median progression-free survival was 16.6 months (95% CI 13.3-19.1). Recommended doses are carboplatin AUC 5 (via(51)Cr EDTA) or AUC 6 (if calculated) plus docetaxel 75 mg/m(2). A randomized trial comparing this regimen with carboplatin-paclitaxel has just completed recruitment.

Adenocarcinoma↗

Safety in the histochemistry laboratory.

Histochemistry and histopathology laboratories are extremely dangerous workplaces owing to the abundance of chemical hazards that constitute major safety and health concerns. A brief review is presented of some of the hazards to which laboratory personnel are exposed. These include fixatives, solvents, embedding media, dyes and stains, and histochemical substrates. Laboratory staff should be fully informed of the dangers and potential long-term health hazards and take the necessary precautionary measures. Despite the abundance of chemical hazards in the histochemistry laboratory, the overall number of work accidents and injuries remains low.

Female↗