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P Rogers

Publications and source records attributed to P Rogers.

At least 73 records · Page 4Linked to original sources
PubMed1996

GABA transamination regulates neuronal glutamate content in the retina.

We have used quantitative immunocytochemistry to examine the content of GABA and glutamate in rabbit retinae where the enzyme GABA transaminase has been selectively inhibited. Inhibition of GABA breakdown led not only to the expected rise in GABA levels in neurones and glial cells but also to a reduction in neuronal pools of glutamate, particularly in neuronal elements in the inner plexiform layer. We suggest that a significant proportion of the glutamate pool in nerve terminals is derived from GABA via the GABA shunt. This observation is of practical significance since GABA transaminase inhibitors are used in the treatment of epilepsy; accordingly GABA-transaminase inhibitors may modify uncontrolled excitatory episodes in the brain both by raising levels of GABA, and reducing levels of the excitatory transmitter, glutamate.

Animals↗
PubMed1996

Acute hemodynamic responses to inhaled nitric oxide in patients with limited scleroderma and isolated pulmonary hypertension.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator that reduces pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension. Their responses to inhaled NO predict their responses to other vasodilators, such as prostacyclin, and provide an estimate of the "fixed" component of their increased PVR. Some patients with limited cutaneous systemic sclerosis develop isolated pulmonary hypertension with a similar clinical course. Therefore, we have measured the acute hemodynamic response to inhaled NO in such patients. METHODS AND RESULTS: Seven patients were studied during inhalation of increasing concentrations of NO (0 to 80 ppm). Complete hemodynamic data were collected on five patients. They demonstrated a selective, dose-dependent, and rapidly reversible fall in PVR (34%) and mean pulmonary artery pressure (17%). There was a nonsignificant increase in cardiac index but no change in mean arterial pressure or systemic vascular resistance. The mean right atrial pressure fell (27%), but there was no change in pulmonary artery occlusion pressure. Of the seven patients, five responded to inhaled NO ( < or = 40 ppm) with a decrease in total pulmonary resistance of at least 20%. CONCLUSIONS: Inhaled NO is an effective and selective pulmonary vasodilator in a significant number of patients with pulmonary hypertension associated with limited cutaneous systemic sclerosis. It may be useful in determining the potentially reversible contribution to the increased PVR and should be considered for patients with acute pulmonary vascular crisis.

Administration, Inhalation↗
PubMed1996

Antitumour evaluation of dolastatins 10 and 15 and their measurement in plasma by radioimmunoassay.

Dolastatins 10 and 15 are small peptides isolated from the marine sea hare Dolabella auricularia that have been shown to interact with tubulin. Their growth-inhibitory properties were compared using panels of human ovarian and colon-carcinoma cell lines. Both agents were very potent inhibitors of cell growth, with dolastatin 10 being an average of 9.1-fold more potent than dolastatin 15 [mean 50% inhibitory concentrations (IC50 values) 2.3 x 10(-10) and 2.1 x 10(-9) M, respectively; P < 0.05] and more potent than paclitaxel or vinblastine. While neither dolastatin exhibited marked cross-resistance in cisplatin- or etoposide-resistant cell lines, contrasting effects were observed using an acquired doxorubicin-resistant (CH1doxR, 100-fold resistant, P-glycoprotein overexpressing) cell line. Resistance was significantly higher to dolastatin 15 (12.7-fold) than to dolastatin 10 (only 3.2-fold; P < 0.05) and was reversible in both cases by verapamil. In vivo, using a s.c. advanced-stage human ovarian carcinoma xenograft and equitoxic doses, greater activity was observed with dolastatin 10 (6.1-day growth delay) versus 0.4 days for dolastatin 15. A radioimmunoassay for dolastatin 10 (limit of detection in mouse plasma 5 ng/ml) was developed. The rabbit antiserum aslo cross-reacted by 65% with dolastatin 15. Comparative mouse pharmacokinetics following i.v. administration of 1 mg/kg showed that both compounds are rapidly eliminated, but with a shorter second-phase half-life (t1/2 beta) being observed for dolastatin 15 (being detectable for only up to 4 h post-administration), the t1/2 beta being 3 times longer for dolastatin 10. In addition, areas under the plasma concentration-time curve (AUC values) were 1.6-fold higher for dolastatin 10 (333 versus 208 ng ml-1 h). Plasma binding of dolastatin 10 exceeded 90%. The highly sensitive RIA will be useful for pharmacokinetic studies in conjunction with the planned phase I clinical trials of these novel, extremely potent, tubulin-binding agents, of which dolastatin 10 appears to possess the more promising preclinical features.

Animals↗
PubMed1996

Endometrial lymphomyeloid cells in abnormal uterine bleeding due to levonorgestrel (Norplant).

Endometrial lymphomyeloid cell subsets were evaluated in samples from normal women and from women with abnormal uterine bleeding due to subcutaneous levonorgestrel implants (Norplant) or an intrauterine device (IUD). The frequency of CD3(+), CD68(+), CD43(+) and endometrial granulated lymphoid cells was evaluated by immunohistochemical or phloxine-tartrazine staining of formalin-fixed paraffin-embedded samples. In normal women, cyclic variation in lymphomyeloid subsets was seen. In women using Norplant for contraception, the frequency of CD3(+), CD68(+) and CD43(+) cells was dramatically decreased, compatible with endometrial atrophy. When Norplant users with abnormal bleeding were compared to women without bleeding, however, the number of CD68(+) cells was significantly increased and the number of CD3(+) and CD43(+) cells was preserved, contrary to the hypothesis that this group would show a greater degree of atrophy and hence, tissue fragility. A similar pattern was seen in a preliminary study of women with bleeding associated with use of copper-only IUD contraception, and in samples taken from late secretory and menstrual biopsies from normal cycling women. Whether these changes in endometrial lymphomyeloid cells represent a result of bleeding arising from a common mechanism or rather cause the uterine bleeding is discussed.

Adult↗
PubMed1996

Inhaled nitric oxide in cardiac failure: vascular versus ventricular effects.

Inhaled nitric oxide (INO) is a powerful and selective pulmonary vasodilator in pulmonary hypertension, including that related to cardiac disease. Recently, NO was shown to have a direct negative inotropic action on the myocardium, but whether INO can impair left ventricular (LV) function is not known. We administered INO during right heart catheterisation in 10 subjects with LV failure and secondary pulmonary hypertension. INO was delivered for 10 min at concentrations of 10, 20, and 40 ppm in spontaneous respiration. Average age was 49.9 years (range 19-59 years), and mean LV ejection fraction EF (LVEF) was 19.9% (range 15-27%). INO produced an average decrease in pulmonary vascular resistance (PVR) of 40% as compared with baseline (p < 0.0001) with no significant change in systemic vascular resistance (SVR). There was no significant difference in the haemodynamic response to the three doses of INO. The large decrease in PVR was due mainly to an increase in pulmonary capillary wedge pressure (PCWP). Cardiac index (CI) rose in 7 patients and was unchanged in 2. One patient had a marked increase in PAWP and a marked decrease in CI during administration of INO, which rapidly reversed after discontinuation of INO. This study demonstrates that the administration of INO to patients with impaired cardiac reserve may result in marked increase in ventricular preload with little benefit to pulmonary pressures. In view of the known in vitro effects of NO and the marked haemodynamic changes demonstrated in response to INO in this study, caution should be exercised when using INO in this population.

Administration, Inhalation↗
PubMed1995

Ceruloplasmin gene expression in the rat uterus.

In this paper we identify the uterine epithelial cells as the site of ceruloplasmin gene expression in the uterus. We show that during the estrous cycle ceruloplasmin RNA levels change substantially reaching a maximum at estrous. In the absence of endocrine control by the ovaries, ceruloplasmin RNA is still present suggesting that this gene is constitutively expressed by the uterine epithelial cells. However, the changes in RNA level immediately after ovariectomy and during pregnancy suggest that it is also the subject of a complex regulatory system.

Acute-Phase Reaction↗
PubMed1995

Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality.

Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflorescein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C-reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leukocytes from patients who died was significantly higher (P < 0.001) than paired controls, and greater (P < 0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte-derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.

Acute-Phase Reaction↗
PubMed1995

Elevated conversion of alpha-2-macroglobulin to the complexed form in gingival crevicular fluid from adult periodontitis patients.

The broad spectrum protease inhibitor, alpha 2-macgrolobulin (alpha 2M), is one of the host's principal regulators of both endogenous and exogenous proteases and is likely to have an important role in the regulation of proteolytic activity at inflammatory sites. We have determined the amount of complexed (com alpha 2M) and total alpha 2M (tot alpha 2M) in gingival crevicular fluid (GCF) harvested from shallow and deep sites in adult periodontitis (AP) patients (n = 21). An ELISA technique was developed to measure both forms of alpha 2M in the same sample utilizing a monoclonal antibody (MAb) specific for the complexed form. In addition, protease activity towards human serum albumin (Prot1), transferrin (Prot2) and N alpha-benzoyl-L-arginine 7-amido-4-methylcoumarin-hydrochloride (BAAMc; Prot3) were determined in a second GCF sample from the same site. Plasma alpha 2M concentrations were only positively correlated (p = 0.0163) with GCF tot alpha 2M from highly inflamed sites. We observed a significant positive correlation between tot alpha 2M and proteolytic activity in GCF from deep sites but not from shallow sites (Prot1: p = 0.002; Prot2: p = 0.005). A similar correlation between tot alpha 2M and proteolytic activity was found at highly inflamed sites (Prot1: p = 0.014; Prot2: p = 0.002). A very high proportion of the tot alpha 2M in GCF was in the complexed form at both shallow (71.14% +/- 29.13) and deep sites (68.17% +/- 28.5) Com alpha 2M was positively correlated with proteolytic activity only in deep sites (Prot1: p = 0.015; Prot2: p = 0.031). Our results suggest that the concentration of tot alpha 2M in the gingival crevice is positively associated with the amount of proteolytic activity at the site and that protease activities in GCF may only partly explain the high percentage conversion alpha 2M to the complexed form. The high level of alpha 2M inactivation in GCF from AP patients reported here may have significance not only in view of its role as a broad spectrum protease inhibitor but also through the differential effects of native vs complexed alpha 2M on the regulation of immune responses.

Adult↗
PubMed1995

Male rape: the impact of a legal definition on the clinical area.

Recently the awareness of the issues surrounding male rape has received increased attention by both mental health workers and the general public following the introduction of the Sexual Offences Act 1994, and the recent case at the Old Bailey where a historical breakthrough was made in June 1995 following the first conviction for male rape under the new law. However, most of this attention has not resulted in many clinical breakthroughs in helping male rape survivors overcome the post-assault impact. Little is known about the prevalence, types of assault, consequences facing survivors and therapeutic options. Some evidence is being reported that male rape survivors develop Post Traumatic Stress Disorder following the assault. It has long been recognized that this is the case with female rape survivors, but to date there have been no significant UK prevalence studies which have examined this relationship. This paper discusses some of the issues surrounding male rape by focusing on the possible effects of the recent legal change on the clinical area.

Criminal Law↗
PubMed1994

Analysis of Tn916-induced mutants of Clostridium acetobutylicum altered in solventogenesis and sporulation.

The conjugative transposon Tn916 was used for mutagenesis of Clostridium acetobutylicum ATCC 824. Tetracycline-resistant mutants were screened for loss of granulose synthesis and five classes of granulose mutants, that contained single transposon insertions, were identified on the basis of altered solvent production. Class 1 mutants did not make acetone or butanol, lacked activity of enzymes induced during solventogenesis, and did not sporulate, indicating that they are regulatory mutants. The class 2 mutant strains also did not produce acetone but did form small amounts of butanol and ethanol, while the class 3 mutants produced low amounts of all solvents. Class 4 and 5 mutants produced essentially the same or higher amounts of solvents than the parent strain. Transposon insertions in the class 1 mutants were used as markers for in vitro synthesis of flanking chromosomal DNA using Tn916-specific primers. The DNA fragments were labeled to produce specific probes. Transposon insertion sites in the chromosomes of 13 different class 1 regulatory mutants were compared by hybridization of the specific probes to Southern blots of restriction endonuclease-digested parental chromosomal DNA. Insertions in two mutants appeared to be in the same region of the chromosome. These results predict that multiple regulatory elements are required to induce solvent production and sporulation.

Acetone↗
PubMed1994

Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection.

OBJECTIVE: The authors determined the effect of glutamine-supplementation of TPN on postoperative peripheral blood T-cell response and proinflammatory cytokine production in patients undergoing colorectal resection. SUMMARY BACKGROUND DATA: Several vital tissues, including the immune system, are very dependent on glutamine; however, this amino acid, which may be essential in conditions of stress, only now is becoming formulated suitably for incorporation into TPN. The effects of such supplementation on the immune function of stressed surgical patients is unknown. METHODS: Patients (n = 20) were randomized to receive conventional TPN (0.2 g nitrogen/kg/d) or an isonitrogenous/isocaloric regimen with 0.18 g of glutamine/kg/d from days 1 to 6 postoperatively. T-cell DNA synthesis and interleukin (IL)-2 production and peripheral blood mononuclear cell IL-6 and tumor necrosis factor (TNF) production were measured in vitro preoperatively and on days 1 and 6 postoperatively. RESULTS: T-cell DNA synthesis after 5 days of TPN was increased compared with preoperative values in the glutamine-supplemented group (median preoperative tritiated thymidine uptake: 78.3 x 10(3) cpm, day 6: 95.0 x 10(3) cpm, p < 0.05). There was no such increase in the control TPN group (preoperative: 89.0 x 10(3) cpm, day 6: 69.4 x 10(3) cpm, p > 0.05). Glutamine supplementation did not influence IL-2 production or the production of TNF or IL-6. CONCLUSIONS: Glutamine supplementation may be a method of enhancing T-cell function in the surgical patient receiving TPN.

Adolescent↗
PubMed1994

Severe Pneumocystis carinii pneumonia produces a hyperdynamic profile similar to bacterial pneumonia with sepsis.

OBJECTIVES: To investigate the effects of Pneumocystis carinii on the cardiovascular system. To compare the hemodynamic data from patients with P. carinii pneumonia with those data from patients with bacterial pneumonia with sepsis. DESIGN: Retrospective, descriptive study of prospectively gathered hemodynamic and clinical data. SETTING: Tertiary referral hospital, medical intensive care unit. PATIENTS: Forty-one consecutive patients with severe P. carinii pneumonia and 31 patients with bacterial pneumonia who had invasive hemodynamic monitoring for management of hypotension and/or hypoxemia. MEASUREMENTS AND MAIN RESULTS: On initial presentation, both groups had a hyperdynamic hemodynamic profile that included tachycardia, an increased cardiac index, and a low systemic vascular resistance index. The mean heart rate of the P. carinii pneumonia patients (113 +/- 3 beats/min) was significantly lower than that of the patients with bacterial pneumonia (126 +/- 4 beats/min). The cardiac index, systemic vascular resistance index, pulmonary vascular resistance index, and pulmonary artery pressures did not differ significantly between the two groups. The patients with bacterial pneumonia had a significantly lower mean left ventricular stroke volume index and stroke work index than the patients with P. carinii pneumonia. CONCLUSION: P. carinii can produce a hyperdynamic hemodynamic profile similar to that seen in patients with bacterial pneumonia with sepsis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Doctors under the knife.

With Bill Clinton's new reforms only a month away, the health-care system is on the operating table--and the doctors are under the knife. Americans have a love-hate relationship with physicians: they like the care that doctors provide but hold them to blame for the nation's health-care mess. NEWSWEEK looks at how the culture of medicine may change, assesses doctors' fears--and examines the brave new world of HMOs.

American Medical Association↗
PubMed1993

Audit of nutritional support provided to surgical patients by a nutrition team.

An audit was carried out over a 24 month period to assess the practice, safety and efficacy of nutritional support provided to surgical patients by a designated team. 135 patients received nutritional support: 51% were fed parenterally, 32% enterally and 17% via combined nutritional support. The duration of feeding ranged from 1-177 days with 23% being supported for < 7 days. The line infection rate for patients receiving intravenous nutrition was 6.5%. Nutritional outcome was assessed using weight, anthropometry and bioelectrical impedance analysis. Pre-and post-feeding results were available for 67% of patients. These patients were classified as either oedematous (n = 21), normally nourished (n = 23) or nutritionally depleted (n = 46). Overall, the oedematous patients lost water, the protein status of the normally nourished group deteriorated slightly and the nutritional status of the nutritionally depleted patients was maintained. Audit is a valuable means of defining the efficacy of a nutrition support service and has identified areas which require review.

Journal Article↗