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Biomedical subjects

A Phillips

Publications and source records attributed to A Phillips.

At least 127 records · Page 7Linked to original sources

A survey of yeast ureases and characterisation of partially purified Rhodosporidium paludigenum urease.

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.

Basidiomycota↗

Antiphospholipid antibodies and adrenal hemorrhage.

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.

Adrenal Gland Diseases↗

Development of an enzyme-linked immunosorbent assay for the detection and measurement of the trypanocidal drug isometamidium chloride in cattle.

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.

Animals↗

Pre-treatment prognostic factors in stage III non-small cell lung cancer patients receiving combined modality treatment.

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.

Adenocarcinoma↗

Fatal necrotizing mediastinitis secondary to acute suppurative parotitis.

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.

Acute Disease↗

Personnel identities.

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Administrative Personnel↗

Migration and geographic variations in blood pressure in Britain.

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.

Adult↗

Separation of Psychodopygus carrerai carrerai and P. yucumensis (Diptera: Psychodidae) by gas chromatography of cuticular hydrocarbons.

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.

Animals↗

Pharmacologic and pharmacokinetic characteristics of norgestimate and its metabolites.

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.

Animals↗

Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins.

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.

Animals↗

Relative binding affinity of norgestimate and other progestins for human sex hormone-binding globulin.

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.

Binding, Competitive↗

Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy.

Attempting to improve local disease control in bulky (greater than 8 cm) primary or recurrent pelvic tumors, 29 patients with squamous cell carcinoma of the cervix (stage II, 4; III, 10; IV, 6; recurrent, 9) were treated with concomitant chemotherapy and split-course hyperfractionated radiation therapy between April 1983 and August 1988. Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been shown to be radiation enhancers; furthermore, CDDP, radiation therapy, and continuous-infusion 5-FU have elicited high local response rates in head and neck squamous cell carcinoma. A pilot study of cyclical week on/week off CDDP, continuous-infusion 5-FU, and hyperfractionated radiation therapy was developed. Radiation was administered at 116 cGy twice daily, Days 1-5, every other week for a median dose of 4600 cGy to a pelvic field, with paraaortic extension if indicated. Concomitant chemotherapy included CDDP 60 mg/m2 IV Day 1 and 5-FU 600 mg/m2 IV continuous infusion for 96 hr following CDDP infusion. Patients received a median of four cycles of combined treatment, and intracavitary or interstitial brachytherapy followed in 21 patients. Local pelvic response was achieved in 29 of 29 (100%): complete response (CR) in 19 of 29 (66%), partial response (PR) in 10 of 29 (34%). Among CR patients 10 of 19 (53%) were without evidence of disease at a mean follow-up of 29 (range 12-76) months. Five-year actuarial disease-free survival among complete responders was 65%. Of the 10 CR patients 2 failed in the pelvis, for a local control rate of 17/19 (89%). Chemotherapy-related and acute radiation morbidity was minimal but 2 patients required surgical correction of radiation injury. Aggressive combination of split-course hyperfractionated radiation therapy with radiation enhancers resulted in promising local control of bulky pelvic tumor, with an acceptable complication rate, in this otherwise very poor prognostic group of patients.

Adult↗

Intraspecific variation in the cuticular hydrocarbons of the sandfly Phlebotomus perfiliewi from Italy.

The cuticular hydrocarbons of Phlebotomus perfiliewi Parrot from representative localities on both sides of Italy show contrasts which support the view of Ward et al., (1981) that there are distinguishable populations of this sandfly on the Adriatic and Tyrrhenian coasts. It is suggested that the Appennine mountains form a barrier between the Adriatic and Tyrrhenian populations. A third distinct hydrocarbon type of P. perfiliewi was detected in Calabria, southern Italy, where contact between the Adriatic and Tyrrhenian types of flies is most likely to occur. P. perfiliewi from a trans-Appennine pass were also of the Calabrian hydrocarbon type. These hydrocarbon contrasts between allopatric populations of P. perfiliewi may result from clinical variation across the Appennines, associated with different host preferences, or they may represent apomictic populations with differential mate recognition systems.

Animals↗