Storage of sperm and embryos. Counselling will be needed when embryos are donated as well as when they are stored.
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Counseling↗
Biomedical subjects
J Robinson
Publications and source records attributed to J Robinson.
Cosmic string formation and the power spectrum of field configurations.
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Journal Article↗
Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.
In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process.
Administration, Oral↗
Combining specialist and primary health care teams for HIV positive patients: retrospective and prospective studies.
OBJECTIVE: To develop and evaluate a model of health care for HIV positive patients involving specialist, hospital based teams and primary health care teams. DESIGN: One year retrospective and a 2 1/2 year prospective study. SETTING: Two hospitals in West London and 88 general practitioners in 72 general hospitals. SUBJECTS: 209 adults with HIV infection. INTERVENTION: General practitioners enrolled in the project were faxed structured outpatient clinic summaries. When hospital inpatients were discharged, a brief discharge summary was faxed. General practitioners had access to consultant physicians skilled in HIV medicine through a 24 hour mobile telephone service. An HIV/AIDS management and treatment guide containing relevant local information was produced. Quarterly discussion forums for general practitioners were held, and a regular newsletter was produced. MAIN OUTCOME MEASURES: Hospital attendance and general practitioner consultations; perceived benefits and problems of patients and general practitioners. RESULTS: The average length of a hospital inpatient stay was halved for those patients who had participated in the project for two years, and the average number of visits to the outpatient clinic per month fell for patients with AIDS. There was a substantial increase in the number of visits to general practitioners by patients with AIDS and symptomatic HIV infection. Patients and general practitioners both felt that the standard of health care provided had improved. CONCLUSIONS: This model of health care efficiently and effectively utilised existing teams of hospital and primary health care professionals to provide care for HIV positive patients. Simple, prompt, and regular communication systems which provided information relevant to the needs of general practitioners were central to its success.
Adult↗
Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults.
BACKGROUND: Passive smoking has been linked to an increased risk of dying from atherosclerotic heart disease. Since endothelial dysfunction is an early feature of atherogenesis and occurs in young adults who actively smoke cigarettes, we hypothesized that passive smoking might also be associated with endothelial damage in healthy young-adult nonsmokers. METHODS: We studied 78 healthy subjects (39 men and 39 women) 15 to 30 years of age (mean +/- SD, 22 +/- 4): 26 control subjects who had never smoked or had regular exposure to environmental tobacco smoke, 26 who had never smoked but had been exposed to environmental tobacco smoke for at least one hour daily for three or more years, and 26 active smokers. Using ultrasonography, we measured the brachial-artery diameter under base-line conditions, during reactive hyperemia (with flow increase causing endothelium-dependent dilatation), and after sublingual administration of nitroglycerin (an endothelium-independent dilator). RESULTS: Flow-mediated dilatation was observed in all control subjects (8.2 +/- 3.1 percent; range, 2.1 to 16.7) but was significantly impaired in the passive smokers (3.1 +/- 2.7 percent; range, 0 to 9; P < 0.001 for the comparison with the controls) and in the active smokers (4.4 +/- 3.1 percent; range, 0 to 10; P < 0.001 for the comparison with the controls; P = 0.48 for the comparison with the passive smokers). In the passive smokers, there was an inverse relation between the intensity of exposure to tobacco smoke and flow-mediated dilatation (r = -0.67, P < 0.001). In contrast, dilatation induced by nitroglycerin was similar in all groups. CONCLUSIONS: Passive smoking is associated with dose-related impairment of endothelium-dependent dilatation in healthy young adults, suggesting early arterial damage.
Adolescent↗
Causality and the power spectrum.
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Journal Article↗
Quantal components of spontaneous excitatory junction potentials at visualised varicosities.
The electrical signs of spontaneous transmitter release were recorded with an extracellular electrode from single visualized sympathetic varicosities on the mouse vas deferens. Ultrastructural examination of these varicosities with the electron microscope showed that they formed close-contacts with smooth muscle cells. Amplitude-frequency histograms of the spontaneous excitatory junction potentials (SEJPs) were constructed in order to determine the statistical nature of spontaneous transmitter release from a varicosity. SEJP histograms often possessed several peaks. Statistical tests showed that these were separate modes in the histograms indicating that the SEJPs were composed of subunits. The SEJP histograms were described by a mixture of distributions in which the components were identified as quanta and there was a Poisson release of quanta. The second mode in the SEJP histograms was sometimes twice that of the first mode but generally greater, suggesting a potentiation of the effects of one quantum released nearly simultaneously with another quantum. The components in the SEJP histograms were well fitted by either a Gaussian or a gamma distribution indicating that the quantum of transmitter could be described as a Gaussian or gamma variate.
Animals↗
Fluorescence spectral properties of troponin C mutant F22W with one-, two-, and three-photon excitation.
We report the first measurements of protein fluorescence with three-photon excitation, using a mutant of troponin C (TnC) that contains a single tryptophan residue F22W. From the emission intensity dependence on laser power we determine that TnC F22W displays one-, two-, and three-photon excitation at 285, 570, and 855 nm, respectively. The emission spectra and intensity decays are identical for one-, two-, or three-photon excitation. The steady-state and time 0 anisotropies are distinct for each mode of excitation, but the correlation times were the same, suggesting that three-photon excitation of proteins can be accomplished without significant effects of the locally intense illumination. The excitation anisotropy spectrum from 830 to 900 nm displays only negative values, suggesting dominant excitation via the 1Lb state of tryptophan from 830 to 900 nm.
Animals↗
An ex vivo method for studying inflammation in cynomolgus monkeys: analysis of interleukin-1 receptor antagonist.
Nonhuman primates have been used as models for testing the role of interleukin-1 (IL-1) in inflammatory diseases, including endotoxemia. The objective of this investigation was to develop a reproducible and rapid method for in vivo evaluation of IL-1 antagonists using cynomolgus monkeys. IL-1 alone can induce many of the symptoms of endotoxemia in monkeys including fever, loss of appetite, and lethargy, however, test animals are slow to recover and may become desensitized to IL-1. We have developed an ex vivo method using whole blood for analysis of IL-1 antagonists administered in vivo to the monkeys and report here results for the naturally occurring IL-1 receptor antagonist, IL-1ra. In this procedure, animals are given an i.v. infusion of IL-1ra, and blood samples are taken preinfusion and during the infusion. The samples are incubated with or without IL-1 beta and the subsequent ex vivo induction of IL-6 determined. This allows analysis of the effects of in vivo pharmacodynamics on the efficacy of antagonists without exposing the test animals to IL-1. In this ex vivo protocol, each animal serves as its own control, eliminating from the assessment the large animal to animal variation observed with in vivo responses. By testing various doses, we estimate that 50% inhibition of IL-1 induced IL-6 can be achieved with an infusion of IL-1ra at 5 micrograms/kg/15 min. This method allows simple and efficient analysis of inhibitors and antagonists of IL-1 and, potentially, other effectors.
Animals↗
Hormone replacement therapy is associated with improved arterial physiology in healthy post-menopausal women.
OBJECTIVE: Oestrogen replacement therapy is associated with a marked reduction in coronary event rates in post-menopausal women. As older age is associated with progressive arterial endothelial damage, a key event in atherosclerosis, we assessed whether hormone replacement therapy (HRT) with oestrogen alone, or oestrogen and progesterone combined, is associated with improved endothelial function in healthy women after the menopause. DESIGN: Using high resolution external vascular ultrasound, brachial artery diameter was measured at rest and in response to reactive hyperaemia, with increased flow causing endothelium-dependent dilatation (flow-mediated dilatation). PATIENTS: We investigated 135 healthy women; 40 were pre-menopausal (mean +/- SD age/26 +/- 6 years, group 1), 40 were post-menopausal and had never taken HRT (aged 58 +/- 3 years; group 2) and 55 were age-matched post-menopausal women who had taken HRT for > or = 2 years, from within 2 years of the menopause (aged 57 +/- 4 years; group 3). In group 3, 40 women were on combined oestrogen and progesterone and 15 on oestrogen-only HRT. RESULTS: In group 2, flow-mediated dilatation was significantly reduced compared with group 1 (4.4 +/- 3.4 vs 9.6 +/- 3.6%, P < 0.001), consistent with a decline in arterial endothelial function after the menopause. In group 3, however, flow-mediated dilatation was significantly better than group 2 (6.2 +/- 3.3 vs 4.4 +/- 3.4%, P = 0.01), suggesting a protective effect of HRT. Flow-mediated dilatation was similar in women taking oestrogen alone and in those on combined HRT (5.5 +/- 2.8 vs 6.5 +/- 3.4%, P = 0.40). CONCLUSIONS: Long-term HRT is associated with improved arterial endothelial function in healthy post-menopausal women. This benefit was observed in both the combined hormone replacement and unopposed oestrogen therapy groups. This may explain some of the apparent cardioprotective effect of HRT after the menopause.
Adolescent↗
Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children.
Phase I trials were conducted in human immunodeficiency virus type 1 (HIV-1)-infected children to examine the pharmacokinetics, safety, and antiretroviral activity of nevirapine, a nonnucleoside HIV-1 reverse transcriptase inhibitor. Nevirapine was rapidly absorbed, but the time to peak plasma concentrations increased with higher doses. Clearance was more rapid in chronic dosing studies than predicted by single-dose studies and was more rapid in younger children than in adolescent children. Rash, which occurred in 1 of the 21 study participants, was the single toxicity regarded as nevirapine-related. At doses > or = 240 mg/m2/day, 5 of 10 children experienced durable suppression of plasma p24 antigen to < 50% of baseline values through 8 weeks of nevirapine monotherapy. Viruses resistant to nevirapine were isolated from all children during therapy, but their isolation did not always predict loss of antiviral activity. The evaluation of nevirapine in combination therapy trials is underway in children.
Acquired Immunodeficiency Syndrome↗
The protective action of polyvinylpyrrolidone-Percoll during the cryopreservation of mouse 2-cell embryos and its effect on subsequent developmental potential post-thaw in vitro and in vivo.
The effects of cryopreservation, in media containing (FS3+) or omitting (FS3) polyvinylpyrrolidone (PVP) in the form of Percoll (PVP-Percoll), on the survival of 2-cell mouse embryos was studied. Survival and zona pellucida disruption post-thaw, growth (assessed by in-vitro culture until the blastocyst stage) and development in vivo (assessed by implantation and living fetus rates and the birth of live progeny) were all investigated. Initial post-thaw survival showed no statistically significant difference (P > 0.05) between FS3+ (91.1 +/- 9.8%) and FS3 (84.5 +/- 6.6%). However, there was a statistically significant (P < 0.05) reduction in the incidence of zona damage when the freezing solution contained PVP-Percoll compared to the control (3.6 +/- 1.0 and 8.7 +/- 0.6% respectively) and a statistically significant (P < 0.05) greater number of embryos developing in vitro to the blastocyst stage (84.8 +/- 7.1 and 72.3 +/- 6.1% respectively). The rates of implantation were not significantly different: 72.2 +/- 7.0% for FS3+ and 51.2 +/- 30.7% for the non-frozen control group. The percentage of live fetuses was also similar between the experimental and control groups: 27.4 +/- 10.6 and 24.3 +/- 11.3% respectively. We conclude that the presence of polymers can protect embryos against cryoinjury and that PVP in the form of PVP-Percoll provides a non-toxic alternative to PVP in its native form, during the cryopreservation of mouse 2-cell embryos.
Animals↗
The antibacterial effect of porous hydroxyapatite granules.
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Blood↗
Explant culture, immunofluorescence and electron-microscopic study of flexor retinaculum in carpal tunnel syndrome.
Although flexor-retinaculum (FR) release provides dramatic relief from carpal tunnel syndrome (CTS), the role of this ligament in CTS is not well understood. We have adopted a unique approach to study the cellular pathogenesis of CTS by establishing a method for the culture of cells of FR from subjects with and without CTS. The cultured cells were characterized by light, immunofluorescence, electron microscopy, Western blot analysis, and growth studies. Two main differences between the CTS and control cells included a faster growth rate and an altered fine morphology that reveals the contractile nature of the CTS cells. It is possible that the presence of these contractile cells in FR is responsible for increasing the contractility of the FR, leading to a decrease in the volume of the carpal tunnel, thus exerting pressure on the median nerve and triggering CTS.
Adult↗
Evaluating services for women with serious and ongoing mental health problems: developing an appropriate research method.
Despite an increase in the literature on women with less disabling or transitory mental health problems, there is little relating to women with serious and ongoing difficulties. In considering the means by which the needs of this population might be studied, tension arises over methodology. Research comparing the clinical, functional and service use characteristics of women and men might demonstrate their different mental health problems but would neither elucidate women's particular needs nor examine the social reasons for this difference. A feminist methodology would, however, offer a means of exploring the experiences of women, a framework for understanding sex differences, and generate findings that would be beneficial to women. The present study gives an insight into ways in which the exploration of sex differences can be combined with a study of women for women without compromising the relevance and impact of the findings.
Female↗
Eating pathology among women with alcoholism and/or anxiety disorders.
Two hundred one non-treatment seeking women with alcoholism, anxiety disorders, alcoholism and anxiety disorders, or neither alcoholism nor anxiety disorders were interviewed to assess core psychopathology associated with eating disorders using the Eating Disorders Examination and DSM-IIIR psychiatric diagnoses using the Schedule of Affective Disorders and Schizophrenia-Lifetime version. Alcoholic women had significantly higher mean scores on each of the Eating Disorders Examination subscales of Restraint, Overeating, Eating Concern, Shape Concern, and Weight Concern compared with nonalcoholic women. Women with anxiety disorders had significantly elevated scores on subscales of Overeating, Eating Concern, and Weight Concern compared with women without anxiety disorders. Women with both alcoholism and anxiety disorders had higher rates of bulimia nervosa and/or eating disorder NOS compared with women with either disorder alone. Implications of these findings are discussed in the context of the co-morbid association between alcoholism, eating disorders, and anxiety disorders.
Adolescent↗
Resistance of human immunodeficiency virus type 1 to neutralization by natural antisera occurs through single amino acid substitutions that cause changes in antibody binding at multiple sites.
The ability of human immunodeficiency virus type 1 (HIV-1) to replicate in the presence of strong immune responses to the virus may be due to its high mutation rate, which provides envelope gene variability for selection of neutralization-resistant variants. Understanding neutralization escape mechanisms is therefore important for the design of HIV-1 vaccines and our understanding of the disease process. In this report, we analyze mutations at amino acid positions 281 and 582 in the HIV-1 envelope, where substitutions confer resistance to broadly reactive neutralizing antisera from seropositive individuals. Neither of these mutations lies within an antibody-binding site, and therefore the mechanism of immune escape in both cases is by alteration of the shape of the envelope proteins. The conformation of the CD4-binding site is shown to be critical with regard to presentation of other discontinuous epitopes. From our analysis of the neutralization of these variants, we conclude that escape from polyclonal sera occurs through alterations at several different epitopes, generally resulting from single amino acid substitutions which influence envelope conformation. Experiments on a double mutant showed that the combination of both mutations is not additive, suggesting that these variants utilized alternate pathways to elicit similar alterations of the HIV-1 envelope structure.
Animals↗
Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses.
Previous observations that the gp120 envelope glycoprotein contents of some primary, clade B human immunodeficiency virus type 1 (HIV-1) isolates were higher than those of laboratory-passaged HIV-1 isolates suggested the hypothesis that increased envelope glycoprotein spike density or stability contributes to the relative neutralization resistance of the primary viruses. To test this, the structural, replicative, and neutralization properties of a panel of recombinant viruses with HIV-1 envelope glycoproteins from divergent clades were examined in an env complementation assay. In this system, although the spike density and stability of envelope glycoproteins from primary HIV-1 isolates were not greater than those from a laboratory-adapted isolate, relative resistance to neutralizing antibodies and soluble CD4 was observed for the viruses with primary envelope glycoproteins. Thus, neither high envelope glycoprotein spike density nor stability is necessary for the relative neutralization resistance of primary HIV-1 viruses.
Antigens, CD↗