Female-to-male transmission of HIV.
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Biomedical subjects
Publications and source records attributed to A Phillips.
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The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices.
Norgestimate is a novel progestin with highly selective progestational activity and minimal androgenicity. In rabbits, norgestimate binds to uterine progestin receptors, stimulates the endometrium, and inhibits ovulation. Norgestimate acts directly on target organs, stimulating rabbit endometrium when injected into the uterine cavity and inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone release in dispersed rat pituitary cells in culture. Norgestimate has no estrogenic activity, and like other progestins, it suppresses the action of estrogen. Unlike some other progestins, it is relatively free of androgenic activity. Norgestimate and its 17-deacetylated metabolite demonstrate very poor affinity for androgen receptors compared with levonorgestrel and gestodene and do not exhibit androgenic activity when measured as the stimulation of prostatic growth in immature rats. Norgestimate's lack of affinity for human sex hormone-binding globulin is further evidence of its minimal androgenicity.
Enterococcus faecalis and Enterococcus faecium isolates that are resistant to vancomycin have recently been identified in North America and Europe. Of 155 clinical isolates of enterococci (113 E. faecium and 42 E. faecalis), we found that 98 were resistant, 52 were moderately susceptible, and 5 had intermediate susceptibilities to vancomycin by using broth microdilution susceptibility testing according to the National Committee for Clinical Laboratory Standards (NCCLS) (Approved Standard M7-A2). Using NCCLS disk diffusion methodology (Approved Standard M2-A4), we evaluated the NCCLS supplemental M100-S3 revisions for zone diameter interpretive standards and incubation conditions and found 5.8% minor errors. A total of 234 isolates, which included an additional 79 E. faecium isolates that were moderately susceptible to vancomycin, were used to evaluate the Vitek GPS-TA card (bioMerieux, Inc., Hazelwood, Mo.) and the Pos MIC type 6 panel (MicroScan; Baxter Health Care Corp., West Sacramento, Calif.) for the detection of vancomycin resistance. The Vitek card was 100% specific and 72% sensitive, whereas the MicroScan panel with the Walk/Away system was 98% specific, with a sensitivity of 93% which increased to 99% when readings were performed manually. An agar screen plate method was evaluated with vancomycin concentrations of 6, 8, 10, or 12 micrograms/ml; plates were inoculated so as to obtain a final concentration of 10(5) CFU per spot. This method was found to be 100% sensitive and specific at all concentrations.
A randomized trial was conducted in five general practices in and around Aylesbury, Buckinghamshire to assess the motivational effect of cholesterol measurement on compliance with advice to reduce dietary fat intake and to stop smoking. The advice was given by practice nurses during health checks for cardiovascular risk factors. A total of 578 patients were recruited to the study and randomized into two groups. Both groups were given the same advice and were followed up after a median of three months, but the intervention group was also given immediate feedback on their cholesterol concentration. Follow up was completed for 88.2% of subjects, and those who were not followed up were assumed not to have changed their behaviour. The mean fall in total cholesterol at follow up was 0.11 mmol l-1 (95% confidence interval 0.03 to 0.18) in the intervention group who were told their cholesterol result and 0.02 mmol l-1 (95% CI -0.06 to 0.10) in the control group who were not. The proportion of smokers who were not smoking at follow up was 10.7% and 10.1% in the two groups, respectively. Patients in the intervention group with an initial total cholesterol level of 6.50 mmol l-1 or greater showed a mean fall of 6.2% in cholesterol level whereas those with an initial cholesterol level of less than 5.20 mmol l-1 experienced a mean increase of 3.6%, but as differences of this magnitude were also seen in the control group they probably reflect regression to the mean rather than an effect of knowledge of cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the inter-relationship of leucopenia and PMN elastase release we undertook a prospective crossover study of 6 patients dialysed with new and reused cuprophane, cellulose acetate and polysulfone membranes. Serial blood samples were analysed for PMN count, and elastase-alpha 1-proteinase inhibitor complex (E alpha 1PI) concentrations. After 15 min dialysis with new membranes median PMN counts fell by 72.2%, 25.3% and 22.1% with cuprophane, cellulose and polysulfone, respectively. With reuse the decreases were reduced to 6.4%, 8% and 13.6%. All membranes produced a gradual increase of E alpha 1PI. Median E alpha 1PI accumulation rates (ng ml-1 min-1) with new membranes were 175, 169 and 187 for cuprophane, cellulose acetate and polysulfone, respectively. With reuse of cuphrophane and cellulose acetate these rates fell to 99 and 109 (p less than 0.05 and p less than 0.05, respectively), however, with polysulfone it remained unchanged at 180 ng ml-1 min-1. This study highlights differences between two aspects of the neutrophil response to haemodialysis, and demonstrates that extrapolation from individual parameters to conclusions concerning biocompatibility may be inappropriate.
Cell-free extracts of a selection of yeasts were analysed for urease activity. Species in the genera Filobasidiella, Rhodotorula and Rhodosporidium had the highest specific activities. Immune inactivation experiments showed widely different degrees of cross-reactivity between antiserum to jack bean urease and yeast ureases, with Rhodosporidium paludigenum (71%) the most and Schizosaccharomyces pombe (3%) the least affected. Only R. paludigenum urease was detected with anti-jack bean urease antiserum on Western blots. The urease of Rhodosporidium paludigenum was partially purified by column chromatography. The native enzyme was found to have a subunit size of 72 +/- 7 kDa probably in an octamer arrangement of 560 +/- 8 kDa, having a specific activity of 62.5 mumol urea hydrolysed min-1 (mg protein)-1. The enzyme was stable in the pH range 5-11 with optimum activity at pH 7.8. Vmax and Km values were determined as 65.2 +/- 3.8 mumol min-1 (mg protein)-1 and 3.81 +/- 0.47 mM, respectively.
We recently encountered two cases of massive bilateral adrenal hemorrhage in patients with antiphospholipid antibodies. A search of the records of this institution covering the past 15 years revealed two additional patients with massive adrenal hemorrhage associated with evidence of antiphospholipid antibodies. Three of these four patients were receiving anticoagulant drug therapy. The presence of the antiphospholipid antibodies may increase the risk of massive adrenal hemorrhage, particularly in patients who receive anticoagulant drugs.
An enzyme-linked immunosorbent assay (ELISA) was developed to measure accurately levels of the trypanocidal drug isometamidium in the serum of treated cattle. The assay requires only 5 microliters of test serum, is sensitive to a level of 0.5 pg ml-1 and is highly specific. Cross reactivity does not occur with the two other widely used trypanocidal drugs diminazene aceturate and homidium bromide. Serum drug levels are detectable for up to six months in cattle after a single dose of 1 mg kg-1 intramuscularly, the maximum period under field conditions for which effective prophylaxis can be maintained against tsetse challenge. Application of the assay will aid the rationalisation of treatment campaigns and assist in assessing the occurrence of drug-resistant trypanosome populations.
Approximately one-third of non-small cell lung cancer (NSCLC) patients present with locally advanced disease. Increasing numbers of clinical trials are being conducted in this group of patients and recently a new international staging system has been introduced, resulting in the sub-division of Stage III into IIIa (potentially operable disease) and IIIb (inoperable disease). Kaplan-Meier survival analyses and Cox regression analyses were used to analyze data from 129 Stage III NSCLC patients who had been treated on two consecutive Phase II trials testing combined modality treatment. The pretreatment characteristics of these patients were: median age--59 years, males/females--87/42, caucasian/non-caucasian--111/18, squamous cell or adenocarcinoma/large cell carcinoma--57/72, previous weight loss less than or equal to 5%/greater than 5%-76/46, previous history of cardiorespiratory disease--no/yes--91/36, performance status (PS) 0-1/2-3--102/27, Stage III, 2 groups--IIIa/IIIb--83/46, Stage III, 3 groups--IIIa T3 N0/IIIa N2/IIIb--41/41/47, surgical eligibility--eligible/ineligible--83/46. Kaplan-Meier statistics revealed significantly longer survival for PS 0-1 versus 2-3 (p = .001), for eligible versus ineligible for surgery (p = .003), for Stage-IIIa versus IIIb (p = .004), and for Stage-IIIa T3N0 versus IIIa N2 versus IIIb (p = .004). The best model developed from Cox regression analyses included stage (IIIa T3 N0 vs IIIa N2 vs IIIb), PS, and sex. These observations appear to have implications for clinical research in Stage III NSCLC.
A unique case of fatal necrotizing mediastinitis secondary to acute suppurative parotitis is reported. The infection was the result of synergistic necrotizing cellulitis caused by mixed aerobic and anaerobic bacteria. To the best of the authors' knowledge, this is the first reported case of necrotizing mediastinitis resulting from a descending acute suppurative parotitis. Acute parotitis should be included in the broad spectrum of infections resulting from synergism between aerobic and anaerobic bacteria in which anaerobes indigenous to the oral cavity predominate.
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OBJECTIVE: To evaluate the relative contributions of factors acting at different stages in life to regional differences in adult blood pressure. DESIGN: Prospective cohort study (British regional heart study). SETTING: One general practice in each of 24 towns in Britain. SUBJECTS: 7735 Men aged 40-59 years when screened in 1978-80 whose geographic zone of birth and zone of examination were classified as south of England, midlands and Wales, north of England, and Scotland. Non-migrants (n = 3144) were born in the town where they were examined; internal migrants (n = 4147) were born in Great Britain but not in the town where they were examined; and international migrants (n = 422) were born outside Great Britain. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures and height. RESULTS: Regardless of where they were born, men living in the south of England had lower mean blood pressures than men living in Scotland (142.5/80.1 v 148.1/85.2 mm Hg). The effects of the place of birth and place of examination on adult blood pressure were examined in a multiple regression model. For internal migrants the modelled increase in mean systolic blood pressure across adjacent zones of examination was 2.1 mm Hg (95% confidence interval 1.3 to 2.9); for adjacent zones of birth the corresponding increase was 0.1 mm Hg (-0.7 to 0.7). The place of examination seemed to be a far more important determinant of mean adult blood pressure than the place of birth. Height is an accepted marker of genetic and early life influences. Regional differences in height were therefore analysed to test whether the multiple regression model could correctly distinguish between the influence of place of birth and place of examination. As expected, men born in Scotland were shorter on average than men born in the south of England irrespective of where they lived in Britain (172.6 cm v 175.1 cm for internal migrants). CONCLUSION: Regional variations in blood pressure were strongly influenced by where the men had lived for most of their adult lives rather than by where they were born and brought up. Among middle aged men, factors acting in adult life seemed to be more important determinants of regional differences in blood pressure than those acting early in life such as genetic inheritance, intrauterine environment, and childhood experience.
Specimens of two species of sandfly, Psychodopygus carrerai carrerai and P. yucumensis, vectors of Leishmania braziliensis braziliensis in the subandean lowlands of Bolivia, were subjected to cuticular hydrocarbon analysis to ascertain if the technique could separate the females. A high degree of separation (87%) was obtained based on significant differences in the cuticular hydrocarbon composition of these two species. Statistical treatment of the data shows that these species, initially identified by the colour of the mesonotum, can also be distinguished by their hydrocarbons.
Biotransformation, pharmacologic, and pharmacokinetic studies of norgestimate and its metabolites indicate that 17-deacetyl norgestimate, along with the parent drug, contributes to the biologic response. The postulated metabolic pathway, which is based on the identification of urinary products had indicated that three metabolites of norgestimate, 17-deacetyl norgestimate, 3-keto norgestimate, and levonorgestrel, might participate in the response. The pharmacologic evaluation of these metabolites demonstrates that only 17-deacetyl norgestimate has a pharmacologic profile consistent with that of norgestimate, and significant concentrations of this metabolite have been measured in the serum of women after the administration of norgestimate. These studies indicate that 17-deacetyl norgestimate contributes to the pharmacologic response to norgestimate.
The progestational and androgenic in vitro receptor binding affinity and the in vivo activity of norgestimate was compared with that of its metabolites and other progestins. The relative binding affinities (RBAs) of norgestimate and its 17-deacetylated metabolite for rabbit uterine progestin receptors were similar to that of progesterone (P); those of 3-keto norgestimate and levonorgestrel were about five times that of P; those of gestodene and 3-keto desogestrel were about nine times that of P. The RBAs of norgestimate, P, and 3-keto norgestimate for rat prostatic androgen receptors were from 0.003 to 0.025 times that of dihydrotestosterone (DHT); those of 3-keto desogestrel, gestodene, and levonorgestrel were from 0.118 to 0.220 times that of DHT. The order of receptor level selectivity represented by the ratio of androgen:progestin IC50 values (with a greater ratio value reflecting a better selectivity) was norgestimate greater than P = 3-keto norgestimate greater than 17-deacetylated norgestimate greater than 3-keto desogestrel greater than gestodene greater than levonorgestrel. In vivo studies demonstrated similar profiles for norgestimate and its 17-deacetylated metabolite. These latter two steroids were equally potent as progestins in stimulating rabbit endometrium, and compared with the other progestins, both steroids exhibited minimal androgenicity as measured by the stimulation of rat prostate growth. In conclusion, these studies, as well as previous preclinical and clinical studies, provide evidence of the selectivity of norgestimate based on minimal androgenicity, indicating an improvement over other progestins used in oral contraceptives.
The relative binding affinity of norgestimate for human sex hormone-binding globulin was compared with that of its metabolites and other progestins by measuring their abilities to displace [3H]testosterone from this carrier protein in vitro. Norgestimate and its 17-deacetylated and 3-keto metabolites did not significantly displace [3H]testosterone from sex hormone-binding globulin at concentrations up to 10,000 nM, whereas gestodene, levonorgestrel, and 3-keto desogestrel displaced [3H]testosterone from sex hormone-binding globulin with IC50 concentrations of 23.1, 53.4, and 91.0 nM, respectively. Since it is believed that a progestin may exert androgenic effects by displacing testosterone from sex hormone-binding globulin, thereby increasing circulating levels of free, active testosterone, these data are consistent with the results of preclinical and clinical studies demonstrating the selective progestational activity of norgestimate.