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Biomedical subjects

A Foster

Publications and source records attributed to A Foster.

At least 73 records · Page 4Linked to original sources
PubMed1991

Peptide leukotriene involvement in pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig.

Male Dunkin Hartley guinea pigs, actively sensitized to ovalbumin (OA) and pretreated with mepyramine (1 mg/kg i.p.), were challenged with OA as an aerosol. Histological analysis of the lung for eosinophils (EOs) showed significant accumulations in the submucosa of the airways (8 h: 1.477.3 +/- 43 EOs/mm2 airway, n = 3, p less than 0.01), after antigen challenge compared to saline control (478.6 +/- 104 EOs/mm2 airway, n = 4). Pretreatment with both mepyramine and cimetidine (10 mg/kg i.p.) did not affect this response. Aerosolization of OA to unsensitized guinea pigs resulted in no significant accumulation of EOs (360.2 +/- 49 EOs/mm2 airway, n = 4) when compared with the saline-challenged sensitized control group. Pretreatment with the leukotriene (LT)D4 receptor antagonist MK-571 (1 mg/kg p.o.) significantly inhibited the OA-induced EO migration (95 +/- 5% inhibition, n = 5, p less than 0.01) compared to vehicle in the presence of mepyramine and cimetidine, while indomethacin (3 mg/kg p.o., n = 4) had no effect. Aerosolization of synthetic LTC4 (0.3-30 micrograms/ml) resulted in a dose-dependent migration of EOs into the submucosal layer over 8 h, reaching significance at the 10-micrograms/ml dose, with comparable results obtained with LTD4. Pretreatment of animals with MK-571 (1 mg/kg p.o.) before LTC4 and LTD4 aerosol results in inhibition of the response in both cases, suggesting that this effect may be mediated through the LTD4 receptor. We conclude that peptide LTs produce eosinophilia in the airways of the guinea pig.

Animals↗
PubMed1991

Are cohort mortality rates autocorrelated?

In this paper the author examines the proposition that heterogeneity in individual frailty leads to autocorrelation in cohort mortality rates. A simple model is used to construct analytic expressions for the covariance of cohort mortality rates at different ages under a number of alternative assumptions about the stochastic process generating shocks in mortality. The model then is used to construct a procedure that uses correlations in cohort mortality rates to estimate the extent of heterogeneity in a population without relying on strong assumptions about the distribution of frailty or the shape of the underlying hazard. The procedure then is used to show that cohort mortality data from France are consistent with a generalized random-effects model in which frailty is gamma-distributed.

Age Factors↗
PubMed1991

Vitamin A deficiency and corneal ulceration in south-east Nepal: implications for preventing blindness in children.

A retrospective review of the outpatient records of 4601 children aged 0-10 years who had been seen between January 1986 and December 1988 at Lahan Eye Hospital, south-east Nepal, revealed that 15.4% had evidence of active or past xerophthalmia. Of 293 children with corneal xerosis or corneal ulcer, 49% had been examined in the 4-month period May-August. The peak age for active noncorneal xerophthalmia was 5 years and for active corneal xerophthalmia, 3 years. Previous population-based studies in Nepal have documented the presence of noncorneal xerophthalmia (Bitot's spots) in children. The present study confirms that vitamin A deficiency is a major cause of blindness and loss of vision among children in the eastern plains of Nepal.

Blindness↗
PubMed1990

Clinical and pathological features of chronic glaucoma in north-east Ghana.

Of 34 consecutive patients with chronic glaucoma seen in north-east Ghana, 22 (65%) were male and seven (21%) were aged under 40 years. Only 17% of eyes had a visual acuity better than 6/18 at presentation. Sixteen of 23 patients who underwent gonioscopy had PAS of which 13 had positive skin snips for onchocerciasis, compared with two out of seven patients with positive skin snips who had open angle glaucoma (p = 0.003). Of 22 trabecular meshworks examined by light microscopy ten (45%) showed marked melanin pigmentation which was more common in younger patients but did not correlate with onchocerciasis infection.

Adolescent↗
PubMed1990

Chronic glaucoma in northern Ghana--a retrospective study of 397 patients.

A retrospective study of 397 patients with chronic glaucoma in North-East Ghana seen in 1986/87 showed 71% of the patients to be male and 26% to be aged under 40 years. Fifty two per cent of eyes were already blind (V/A less than 3/60) at presentation. Blindness was associated with younger age at presentation, and greater distance of residence from the hospital. Only 19% of patients undergoing treatment were attending for follow-up at six months. Of those patients treated medically who returned for follow-up at six months only 17% had an intraocular pressure less than 22 mmHg. While of the patients treated surgically 84% of those seen at six months had an IOP below 22 mmHg.

Adolescent↗
PubMed1989

An unusual uveitis in Tanzanian children.

In 1982-7, 254 children with panuveitis were seen at Mvumi Hospital, Tanzania, representing 56% of all cases of uveitis seen. Half were aged under 2. No consistent abnormality accounted for the uveitis and it resolved spontaneously over 6-12 weeks. A trial of prednisolone was performed in 30 children: 18 showed improvement by four weeks compared with 20 of 35 controls given only topical steroids and mydriatics.

Child↗
PubMed1989

Metabolism and excretion of exogenous [3H]-LTC4 in primates.

Four novel omega- and beta-oxidation (from the omega end) products of peptide leukotrienes, 20-hydroxy and 20-carboxy-LTE4, 18-carboxy-19, 20-dinor-LTE4 and 16-carboxy-17,18,19,20-tetranor-14,15-dihydro-LTE4 were prepared by total synthesis and used as standards for identification of biliary and urinary metabolites in the cynomolgus monkey. After intravenous administration 14, 15-[3H] leukotriene C4 (10 microCi kg-1) was partially metabolized in and rapidly cleared from the vascular circulation. This resulted, within 24 hours, in significant urinary excretion (14.8 +/- 2.1%, n = 4), consisting largely of material more polar than LTE4 (61% of urinary excretion) as shown by reverse phase HPLC. The polar fraction demonstrated two predominant metabolites which coeluted in several HPLC solvent systems with synthetic 16-carboxytetranordihydro-LTE4 (major component) and 18-carboxydinor-LTE4 (minor component). Characterization of the major polar metabolite as 16-carboxytetranordihydro-LTE4 was substantiated by conversion to its N-acetylated derivative. The absence of the 14, 15 double bond was confirmed by product analysis of oxidative ozonolysis. In a single animal, the bile duct was cannulated, with significant biliary excretion of radioactivity demonstrated over 4 hours (58.6% recovery). The predominant polar biliary metabolites were also identified as the 18-carboxydinor and 16-carboxytetranordihydro derivatives of LTE4 mentioned above. These data suggest that beta-oxidation products generated from the omega-carboxyl end of the 20-carboxy-LTE4 are important products of [3H] LTC4 metabolism in the monkey. Quantitation of these urinary metabolites may be an important index of in vivo leukotriene production.

Animals↗
PubMed1989

Metabolism of leukotriene C4 in the anesthetized guinea pig.

The distribution and metabolism of [3H] leukotriene (LT)C4 has been studied in the anesthetized guinea pig. The intravenous administration of [3H] LTC4 (1 muCi/kg) to seven guinea pigs showed a rapid vascular clearance of radioactivity with significant metabolism evident at the 15 sec and 1 min time points with material chromatographing like LTC4 (45.6 +/- 7.5%, 35.0 +/- 4.4%). LTD4 (18.4 +/- 5.1%, 33.2 +/- 4.4%) as well as polar material (25.5 +/- 6.0%, 29.7 +/- 4.7%) respectively. The biliary recovery of radioactivity was found to be 74.5 +/- 5.5% n = 4, over 120 min in the guinea pig with less than 1% of radioactivity present in the urine. Examination of the metabolic profile of the biliary radioactivity showed total conversion of LTC4 to LTD4 which was the major metabolite at early time points, and LTD4 as well as LTE4 at later time points. Significant radioactivity which increased with time was also present at the solvent front of the chromatogram indicating the presence of polar biliary metabolites. These results show that the major route of elimination of peptide leukotrienes is through the bile duct in the anesthetized guinea pig and that LTD4 is the major eliminated metabolite in this model.

Anesthesia↗
PubMed1989

Cutaneous anthrax leading to corneal scarring from cicatricial ectropion.

Eleven patients with cutaneous anthrax of the eyelids are presented. The complications were cicatricial ectropion (eight patients), resulting in corneal scarring (three patients). The ectropion was corrected by full thickness postauricular skin grafts, with good results. The predilection of this infection for the eyelids of young children and a seasonal variation suggest that a vector may be involved in transmission.

Adult↗
PubMed1989

National survey of blindness and low vision in The Gambia: results.

A population based survey of blindness and eye disease has been conducted throughout the whole country of The Gambia, and 8174 people were examined. The prevalence of blindness (best acuity less than 3/60) was 0.7% and low vision (6/24-3/60) 1.4%. The causes of blindness were cataract (55%), non-trachomatous corneal opacity/phthisis (20%), and trachoma (17%). An estimated 5500 people in The Gambia require cataract surgery, 4600 eyelid surgery for entropion, and 4600 people spectacles to correct a refractive error which causes a visual acuity of less than 6/18. More than half the current burden of blindness in The Gambia is potentially remediable through the provision of cataract surgery and aphakic spectacles.

Adolescent↗
PubMed1989

L-663,536 (MK-886) (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2 - dimethylpropanoic acid), a novel, orally active leukotriene biosynthesis inhibitor.

L-663,536 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2, 2-dimethylpropanoic acid) is a potent inhibitor of leukotriene (LT) biosynthesis in intact human polymorphonuclear leukocytes (PMN) (IC50, 2.5 nM). Similarly, L-663,536 inhibited A23187-induced LTB4 formation by rat peripheral blood and elicited PMN. At concentrations where inhibition of leukotriene biosynthesis occurred in human whole blood (1.1 microM), no effect was seen on cyclooxygenase or 12-lipoxygenase, an effect also observed in washed human platelets. The compound had no effect on rat or porcine 5-lipoxygenase indicating that L-663,536 is not a direct 5-lipoxygenase inhibitor. When administered in vivo L-663,536 was a potent inhibitor of antigen-induced dyspnea in inbred rats pretreated with methysergide (ED50, 0.036 mg/kg p.o.) and of Ascaris-induced bronchoconstriction in squirrel monkeys (1 mg/kg p.o.). The compound inhibited leukotriene biosynthesis in vivo in a rat pleurisy model (ED50, 0.2 mg/kg p.o.), an inflamed rat paw model (ED50, 0.8 mg/kg), a model of leukotriene excretion in rat bile following antigen provocation, and a model in the guinea-pig ear where leukotriene synthesis was induced by topical challenge with ionophore A23187 (ED50, 2.5 mg/kg p.o. and 0.6 micrograms topically). The results indicate that L-663,536 is a potent inhibitor of leukotriene biosynthesis both in vitro and in vivo indicating that the compound is suitable for studying the role of leukotrienes in a variety of pathological situations.

Animals↗