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Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 127 records · Page 7Linked to original sources
PubMed1992

Deposition of aerosolized pentamidine and failure of pneumocystis prophylaxis.

OBJECTIVE: To determine if outcome of Pneumocystis carinii prophylaxis is related to total lung dose of aerosolized pentamidine. SETTING: AIDS treatment centers at a VA and University Hospital. PATIENTS: Fifty-eight HIV-infected patients receiving P carinii prophylaxis with aerosolized pentamidine using a nebulizer (CIS-US AeroTech II) were followed up over a 90-week period. Treatment consisted of 60 to 90 mg every two weeks. MEASUREMENTS: In all patients, deposition of pentamidine aerosol was measured using a radioaerosol filter technique. Factors thought to be important in deposition, nebulizer output and breathing pattern were also measured. Six months later, repeated deposition studies were performed in 20 patients. Pentamidine dose to the lung was related to occurrence of P carinii pneumonia and correlated with nebulizer function and breathing parameters. Outcome was assessed in terms of pentamidine deposition and patient characteristics, including demographic, immunologic, physiologic, and medical variables. RESULTS: Ten patients (17.2 percent) had development of P carinii pneumonia. However, pentamidine deposited in the failures (8.18 +/- 4.74 mg) was no different than deposition in protected patients (6.39 +/- 3.07 mg, p = NS). Most of the variability in deposition was accounted for by variability in nebulizer output (r = 0.919, p less than 0.001). Deposition did not significantly correlate with any of the measured breathing parameters. Serial deposition measurements were not significantly different by paired analysis. The incidence of P carinii pneumonia did not correlate with any measured patient characteristic. CONCLUSIONS: Failure of aerosolized pentamidine prophylaxis is not related to total lung dose of pentamidine. Other factors such as inadequate microscopic deposition between alveoli, pentamidine clearance, or drug resistance may be important. In HIV-infected patients, interpatient variability in aerosol deposition can be reduced by reducing variability in nebulizer output rather than control of breathing pattern.

Aerosols↗
PubMed1991

Evaluation of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer.

A series of experiments were conducted to evaluate the effects of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer. In the first experiment, oral administration of Win 49,596 at doses of 30, 100, or 300 mg/kg/day for 28 days inhibited (P less than 0.05) the growth of the androgen-sensitive PAP variant of the Dunning R-3327 prostatic carcinoma in intact male rats relative to intact controls. The degree of inhibition at 100 and 300 mg/kg/day Win 49,596 was similar (P greater than 0.10) to that observed in castrate controls as well as in intact rats administered the nonsteroidal androgen receptor antagonist flutamide orally at 15 mg/kg/day. Castration as well as treatment with either Win 49,596 or flutamide also decreased (P less than 0.05) the weight of the prostate in tumor-bearing animals. Additional studies were conducted to determine the effect of Win 49,596 on the growth of the androgen-dependent PC-82 human prostatic carcinoma xenografted into athymic nude male mice. Oral administration of Win 49,596 at 30, 100, or 300 mg/kg/day for 35 days inhibited (P less than 0.05) tumor growth relative to intact controls. The degree of tumor inhibition was similar to that observed in intact male mice administered the nonsteroidal androgen receptor antagonist flutamide orally at 30 mg/kg/day but was less than that observed following castration. Ventral prostate weights were also reduced (P less than 0.05) in castrate mice as well as in intact mice administered either Win 49,596 or flutamide. In the last experiment, at equivalent total daily dosages of either 150 or 300 mg/kg/day Win 49,596, twice a day (BID) dosing was more effective than once a day (SID) dosing in inhibiting tumor growth. The inhibitory effects of Win 49,596 at 150 mg/kg BID on tumor growth were similar to those observed following castration. Although Win 49,596 treatment reduced (P less than 0.05) ventral prostate weights relative to intact controls, there was no difference (P greater than 0.10) between SID vs. BID dosing. Based on the results of these studies and subject to further testing, Win 49,596 may have utility in the treatment of hormonally dependent metastatic prostate cancer in humans.

Administration, Oral↗
PubMed1991

Dietary calcium and blood pressure: modifying factors in specific populations.

Epidemiologic findings continue to add to the body of evidence supporting a relationship between calcium intake and blood pressure. These findings also indicate that there is a threshold of the potential protective effect of adequate calcium intake, below which the risk of hypertension increases at a greater rate. The set point of this threshold, estimated at 700-800 mg/d, may be modified by a variety of factors including dietary patterns and components, lifestyle, and genetics. This may explain, at least in part, the heterogeneous response observed in dietary-intervention studies. In animal models of hypertension it was shown that greater amounts of calcium must be given to cause a blood pressure change comparable with that in normal animals, suggesting that in high-risk human populations in which calcium metabolism may be disordered, calcium intake may have to be increased to amounts greater than 700-800 mg/d to demonstrate the blood-pressure-lowering effect. Calcium intake at or above the currently recommended daily allowance of 800 mg could be of potential benefit to certain racial groups, individuals ingesting excessive alcohol, and pregnant women, all of whom generally consume low amounts of calcium and who are at higher risk of developing hypertension.

Animals↗
PubMed1991

IgE antibodies to Pityrosporum ovale in atopic dermatitis.

An enzyme-linked immunosorbent assay (ELISA) was developed to assess serum IgE antibodies directed against Pityrosporum ovale in patients with atopic dermatitis (AD), atopic patients with allergic respiratory disease (ARD: rhinitis or asthma) but without eczema, and in healthy controls. IgE binding to P. ovale extract was demonstrated in 49% (35/72) of AD patients. In contrast, anti-P. ovale IgE was found in only one of 27 atopic controls without eczema; all healthy control sera (n = 17) were negative. Of 37 AD patients tested intracutaneously with P. ovale, 31 showed immediate-type reactivity, and 20 of these 31 patients had anti-P. ovale IgE detectable by ELISA, while sera from the six non-responders were all negative. Levels of anti-P. ovale IgE were highest in AD patients aged 20-30 years. No correlation was found with the severity of AD, but there was a non-significant tendency (P = 0.06) to higher levels in AD patients with concomittant respiratory allergy. Anti-P. ovale IgE was significantly correlated with total serum IgE, with specific IgE against various aeroallergens as measured by RAST, and with levels of anti-Candida albicans IgE, measured with a similar ELISA. Thus, production of IgE antibodies against P. ovale occurs very frequently in AD, and rarely in patients with atopic disease without skin involvement.

Adolescent↗
PubMed1991

Clinical evaluation of a double-blind dust-mite avoidance trial with mite-allergic rhinitic patients.

Inheritance and allergen exposure are key factors in the development and the course of atopic allergy, expressed as conjunctivitis, rhinitis, asthma or dermatitis. This study concerns the clinical significance of mite and mite-allergen avoidance measures based on intensive cleaning with acaricide (solidified benzylbenzoate) added (10 dwellings), and without biocidal activity (10 other homes) as a control in a double-blind trial with matched pairs. Twenty subjects with persisting rhinitic complaints were selected. They lived in 20 different dwellings and were all sensitized to pyroglyphid mites; 12 of them were also sensitized to stored product mites (Acari). Daily symptoms and medication score, guanine and dust exposure, total and mite-specific IgE in serum, eosinophilia in the blood and in the nasal smear, intracutaneous tests with house dust mite and storage mite extracts were compared in both pairs and groups. Acarological data, physiochemical aspects and exposure assessment are discussed in detail elsewhere. Symptom scores dropped significantly, as did the total IgE and exposure to dust and mite products in the acaricidal cleaner treatment group. After 1 year, the daily symptoms median was 47% (P = 0.025), total IgE was 38% (P = 0.0049), and exposure to dust and mite products (guanine exposure) was 53% (P = 0.0449) better or lower than in the controls. Intensive cleaning, without acaricidal treatment performed twice a year, resulted in clinical improvement in four out of 10 subjects, of whom none became free of complaints. In the Acarosan treatment group (cleaning + benzylbenzoate) eight out of 10 subjects improved, in three cases subjective symptoms disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Self-perceived needs of primary caregivers of home-hospice clients.

The purpose of this study was to assess the self-perceived needs of primary caregivers of terminally ill home-hospice clients. A home interview was conducted using an instrument based on the Neuman Systems Model. Data were analyzed in relation to intrapersonal stressors (within the individual), interpersonal stressors (between the individual and others), and extrapersonal stressors (between the individual and the environment). Five community nursing diagnoses (Porter, 1987) were identified: (a) Population at risk for health problems, (b) population at risk for role constriction/role fatigue, (c) population at risk for insufficient support, (d) population at potential risk for lack of information, and (e) population at potential risk for lack of service coordination. Early attention to limiting the impact of stressors on the caregiver can improve the caregiver's ability to care for the hospice client.

Adult↗
PubMed1991

Experimental ocular onchocerciasis in cynomolgus monkeys. IV. Chorioretinitis elicited by Onchocerca volvulus microfilariae.

Onchocerciasis is a major cause of blindness worldwide, and much of the blindness is caused by onchocercal chorioretinitis. In an experimental animal model for ocular onchocerciasis, intravitreal injections of 10,000 live Onchocerca volvulus microfilariae isolated from infected humans into the eyes of cynomolgus monkeys (Macaca fascicularis) resulted in patchy, progressive loss of retinal pigment with pigment clumping. Areas of pigment loss were less extensive in animals that had been sensitized with microfilariae. Intravitreal injections of dead O. volvulus microfilariae resulted in mild vitritis with relatively less clinical change noted in the retina and choroid. Histopathologic examination revealed thinning and loss of outer retinal layers with pigment migration into the retina, and inflammation was more pronounced in eyes that received live microfilariae. Clinical changes appeared in eyes receiving live microfilariae before the development of significant antibody or cell-mediated immune responses. O. volvulus microfilariae appear to be more suitable than O. lienalis microfilariae in producing lesions which resemble human onchocerciasis in the primate model.

Animals↗
PubMed1990

Contribution of red blood cells to the saturable mechanism of heparin clearance.

The pattern of clearance of intravenously administered heparin suggests the participation of a saturable mechanism which has been ascribed to heparin binding to the endothelium. Another potential site of heparin binding which may contribute to the saturable mechanism is the red blood cells. We have examined this possibility using unfractionated heparin together with a chemically-modified low affinity heparin labelled with tritium as tracer. Unfractionated heparin and the radioactive tracer were added to pooled plasma at a fixed concentration. The heparinized plasma was mixed with red cells to reconstitute whole blood. After centrifugation, the radioactivity, APTT, anti-Xa and anti-IIa activities were measured in the resultant plasmas. No evidence of significant binding to red cells could be detected even when the hematocrits of the reconstituted whole blood were increased. These results are at variance with those of a previously published report. We conclude that red cell binding does not contribute to the saturable mechanism of heparin clearance.

Antithrombin III↗
PubMed1990

Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study.

OBJECTIVE: To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy. DESIGN: Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist. SETTING: Outpatient diabetic clinics of three teaching hospitals and three district general hospitals. PATIENTS: 2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle. MAIN OUTCOME MEASURES: Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported. RESULTS: Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral. Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons. Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed. Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01). Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001). CONCLUSIONS: Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy.

Adolescent↗
PubMed1990

Prenatal diagnosis of Morquio disease type A using a simple fluorometric enzyme assay.

A new fluorogenic substrate, 4 methylumbelliferyl beta-D-6-sulphogalactoside, was used for the assay of galactose-6-sulphate sulphatase activity in chorionic villi, cultured villus cells, and amniocytes. The fluorometric assay is much more convenient than the conventional assay using radiolabelled, sulphated oligosaccharides. Both types of substrate were used in the prenatal diagnosis of three pregnancies at risk for Morquio type A disease using amniocytes. These enzyme tests, as well as electrophoresis of glycosaminoglycans in the amniotic fluid, indicated affected fetuses in two pregnancies and a non-affected fetus in one.

Amniotic Fluid↗
PubMed1990

Temporal expression of HIV-1 envelope proteins in baculovirus-infected insect cells: implications for glycosylation and CD4 binding.

Three different human immunodeficiency virus type I (HIV-1) envelope derived recombinant proteins and the full length human CD4 polypeptide were expressed in Spodoptera frugiperda (Sf9) cells. DNA constructs encoding CD4, gp120, gp160, and gp160 delta (full length gp160 minus the transmembrane and cytoplasmic region of gp41) were cloned into the baculovirus expression vector pVL941 or a derivative and used to generate recombinant viruses in a cotransfection with DNA from Autographa californica nuclear polyhedrosis virus (AcMNPV). Western blotting of cell extracts of the recombinant HIV-1 proteins showed that for each construct two major bands specifically reacted with anti-HIV-1 envelope antiserum. These bands corresponded to glycosylated and nonglycosylated versions of the HIV proteins as determined by 3H-mannose labeling and tunicamycin treatment of infected cells. A time course of HIV envelope expression revealed that at early times post-infection (24 hours) the proteins were fully glycosylated and soluble in nonionic detergents. However, at later times postinfection (48 hours), expression levels of recombinant protein reached a maximum but most of the increase was due to a rise in the level of the nonglycosylated species, which was largely insoluble in nonionic detergents. Thus, it appears that Sf9 cells cannot process large amounts of glycosylated recombinant proteins efficiently. As a measure of biological activity, the CD4 binding ability of both glycosylated and nonglycosylated recombinant HIV envelope proteins was tested in a coimmunoprecipitation assay. The results showed that CD4 and the glycosylated versions of recombinant gp120 or gp160 delta specifically associated with one another in this analysis. Nonglycosylated gp120 or gp160 delta proteins from tunicamycin-treated cultures did immunoprecipitate with anti-HIV-1 antiserum but did not interact with CD4. We conclude that production of native HIV envelope proteins, as measured by addition of carbohydrate side chains and ability to bind CD4, peaks early after infection in baculovirus-infected insect cells.

Animals↗
PubMed1990

Autosomal dominant transmission of autoantibodies to thyroglobulin and thyroid peroxidase.

The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, -DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man.

Adolescent↗
PubMed1990

Comparison of narrow-band UV-B phototherapy and PUVA photochemotherapy in the treatment of psoriasis.

The therapeutic effectiveness of a new fluorescent lamp, Philips TL-01, which emits a narrow peak around 311-312 nm, was compared with the currently used PUVA photochemotherapy consisting of oral 8-MOP followed 2 h later by UV-A from fluorescent lamps Philips TL-09. Comparisons of therapeutic efficacy were performed in 10 patients with widespread, symmetrically distributed psoriasis lesions. They received treatment with PUVA on one half of the body and with TL-01 light on the other half; both treatments were given twice a week. It is concluded that on the average phototherapy with narrow-band UV-B is an effective as PUVA; it is certainly more convenient and probably less carcinogenic.

Adult↗
PubMed1989

Survey of colourings and preservatives in drugs.

OBJECTIVE: To assess the prevalence of colourings and preservatives in drug formulations in the United Kingdom. DESIGN: Postal survey. PARTICIPANTS: All pharmaceutical manufacturers in the United Kingdom were requested to supply data on drug formulations with particular regard to the content of colourings and preservatives. MAIN OUTCOME MEASURE: Prevalence in proprietary drugs of colourings or preservatives, or both, that have been implicated in adverse reactions. Computation of a list of formulations of bronchodilators, antihistamines, and antibiotics that are free of such additives. RESULTS: A total of 118 out of 120 pharmaceutical companies supplied the data requested. In all, 2204 drug formulations were analysed and found to contain 419 different additives, of which 52 were colourings and preservatives that have been implicated in adverse reactions; 930 formulations contained such an additive. Tartrazine was the fourth most commonly occurring colouring, being present in 124 drug formulations. CONCLUSION: Many drugs contain additives that help to identify them and prolong their shelf life but are implicated in adverse reactions in some people. Some form of labelling of drug additives would enable these people to avoid drugs containing such additives.

Chemistry, Pharmaceutical↗