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Biomedical subjects

G Young

Publications and source records attributed to G Young.

At least 91 records · Page 5Linked to original sources
PubMed1998

Immunolocalization of steroidogenic enzymes (P450scc, P450c17, P450arom, and 3beta-HSD) in immature and mature testes of rainbow trout (Oncorhynchus mykiss).

We examined the localization of steroidogenic cells in rainbow trout (Oncorhynchus mykiss) testis during spermatogenesis by using polyclonal antibodies generated against rainbow trout cholesterol side-chain cleavage enzyme cytochrome P450 (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17alpha-hydroxylase/C17,21 lyase (P450c17), and aromatase cytochrome P450 (P450arom) as markers of steroid production. Since we had previously produced specific antibodies against 3beta-HSD and P450arom, antibodies against oligopeptides corresponding to C-terminal sequences of P450scc and P450c17, predicted from rainbow trout P450scc and P450c17 cDNAs, were produced in this study. These two antibodies recognized 54-kDa (P450scc) and 59-kDa (P450c17) bands specifically in several steroidogenic organs, i.e., testis, ovary, and interrenal tissue (head kidney) in Western blots. Immunohistochemically, immunoreactive P450scc, P450c17, and 3beta-HSD, but not P450arom, were found only in interstitial Leydig cells of immature and mature testes. Immunoreactive P450arom was not detected in either testis. This study suggests that Sertoli cells and germ cells of rainbow trout testis do not contain P450scc, P450c17, P450arom, or 3beta-HSD.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Thrombopoietin levels in HIV-associated thrombocytopenia in children.

OBJECTIVES: To determine the mechanism of human immunodeficiency virus (HIV)-associated thrombocytopenia by using thrombopoietin (TPO) levels. STUDY DESIGN: TPO levels were measured in 14 HIV+ children with thrombocytopenia (TCP+), 28 HIV+ children without thrombocytopenia (TCP-), and 15 matched control subjects. RESULTS: For the patients with moderate symptoms, TPO levels were similar for the TCP+ and TCP- groups (251 pg/mL vs 263 pg/mL; P =.98) and similar to those of control subjects. For the patients with severe symptoms, TPO levels were significantly higher for the TCP+ group versus the TCP- group (1172 pg/mL vs 222 pg/mL; P =.03). Patients with severe symptoms and thrombocytopenia had significantly higher TPO levels than those with moderate symptoms and thrombocytopenia (P <.005), were more likely to require growth factors, and did not respond to treatment with intravenous immunoglobulin. CONCLUSIONS: TPO levels can distinguish 2 groups of patients with HIV-associated thrombocytopenia. Patients with severe disease had elevated TPO levels, did not respond to treatment with intravenous immunoglobulin, and were more likely to be growth factor-dependent, suggesting marrow failure.

Child↗
PubMed1998

The effect of rigid lens design on fluorescein fit.

This paper describes an evaluation of rigid lens design undertaken using a computer spreadsheet-based model of fluorescein fit. The study systematically varied rigid lens parameters and corneal topography while monitoring the following key aspects of lens fit. percentage area of apparent corneal alignment, average tear layer thickness and edge clearance. The effect of changes in corneal curvature, corneal asphericity, astigmatism, back optic zone radius, back optic zone diameter and peripheral radii were evaluated. The findings enable a clearer understanding of the relationship between corneal topography, rigid lens parameters and rigid lens fit.

Journal Article↗
PubMed1998

Radiological assessment in psoriatic arthritis.

Our objective was to compare the reliability and responsiveness of the original Steinbrocker's (OS), our modified Steinbrocker's (MS) and Larsen's (L) radiological scoring methods for detecting radiological change in psoriatic arthritis over time. Two sets of radiographs of the hands and feet at least 2 yr apart were selected from 68 patients. Films were randomly presented and scored independently by a rheumatologist (DDG) and a radiologist (DS), in a blinded fashion using all methods. The index of reliability was the intraclass coefficient (ICC) and the responsiveness was assessed using plots and regression analyses. All three radiological scoring methods have excellent interobserver and good intra-observer reliability. L and MS are equally responsive and superior to OS in detecting change in joint damage over time. Thus, the L or MS radiological scoring methods can be used to monitor disease progression in psoriatic arthritis.

Adult↗
PubMed1998

The impact of molecular diagnosis on familial colorectal cancer.

We have shown the impact of molecular diagnostics related to mutation detection in an extensive family with a strong history of colorectal cancer. The nature and presentation of the cancers suggested that hereditary nonpolyposis colorectal cancer was the most likely cause. The strategies employed have enabled the detection and characterisation of the causative mutation in the proband and predictive testing in the remaining relatives where requested. Using the chemical cleavage of mismatches technique and direct sequencing, the MSH2 and MLH1 genes of the proband were investigated. A single base substitution, C-->T at nucleotide 350, codon 117, of the MLH1 gene was identified. Across the family pedigree at specific points, 22 other relatives have been tested for the mutation by direct DNA sequencing from genomic DNA. Of the total of 23 patients tested to date, 11 have the mutation. In conjunction with appropriate genetic counselling, this service has clarified the genetic status of many individuals within this family. Predictive information provided prior to the development of symptoms enables individuals to make informed choices regarding disease management and the future, removing the anxiety associated with the unknown.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The use of sulfasalazine in psoriatic arthritis: a clinic experience.

OBJECTIVE: To assess the tolerability of sulfasalazine in a clinic setting and determine its longterm effectiveness with respect to articular disease and prevention of radiographic progression in patients with psoriatic arthritis (PsA). METHODS: Patients who were given sulfasalazine during their attendance at the University of Toronto Psoriatic Arthritis Clinic were enrolled in the study. For patients that were able to tolerate sulfasalazine for at least 3 months a matched control was identified who did not receive sulfasalazine. The primary outcome measures were the tolerability of sulfasalazine, clinical response of the actively inflamed joints at 6 and 12 months, and the change in radiographic score at 24 months. RESULTS: Thirty-six patients received sulfasalazine. Fourteen of 16 patients discontinued sulfasalazine due to one or more side effects occurring within 3 months of treatment initiation. For the remaining 20 patients, a 50% reduction in actively inflamed joint count was noted in 7/20 patients at 6 months and 11/15 patients at 12 months, compared to 7/19 patients in the control group at 6 months and 10/20 patients at 12 months. The mean change in the radiographic score at 24 months between the 2 groups was not statistically significant. CONCLUSION: Sulfasalazine was not well tolerated in patients with PsA in our clinic. For those able to tolerate sulfasalazine, there was no evidence of a treatment effect with respect to articular involvement. In addition, sulfasalazine does not appear to halt radiographic progression in PsA.

Adolescent↗
PubMed1997

Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis.

STUDY OBJECTIVE: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population. DESIGN: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy. MEASUREMENTS AND RESULTS: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. CONCLUSION: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.

Adolescent↗
PubMed1997

Canine chondrocytes seeded in type I and type II collagen implants investigated in vitro.

Synthetic and natural absorbable polymers have been used as vehicles for implantation of cells into cartilage defects to promote regeneration of the articular joint surface. Implants should provide a pore structure that allows cell adhesion and growth, and not provoke inflammation or toxicity when implanted in vivo. The scaffold should be absorbable and the degradation should match the rate of tissue regeneration. To facilitate cartilage repair the chemical structure and pore architecture of the matrix should allow the seeded cells to maintain the chondrocytic phenotype, characterized by synthesis of cartilage-specific proteins. We investigated the behavior of canine chondrocytes in two spongelike matrices in vitro: a collagen-glycosaminoglycan (GAG) copolymer produced from bovine hide consisting of type I collagen and a porous scaffold made of type II collagen by extraction of porcine cartilage. Canine chondrocytes were seeded on both types of matrices and cultured for 3 h, 7 days, and 14 days. The histology of chondrocyte-seeded implants showed a significantly higher percentage of cells with spherical morphology, consistent with chondrocytic morphology, in the type II sponge at each time point. Pericellular matrix stained for proteoglycans and for type II collagen after 14 days. Biochemical analysis of the cell seeded sponges for GAG and DNA content showed increases with time. At day 14 there was a significantly higher amount of DNA and GAG in the type II matrix. This is the first study that directly compares the behavior of chondrocytes in type I and type II collagen matrices. The type II matrix may be of value as a vehicle for chondrocyte implantation on the basis of the higher percentage of chondrocytes retaining spherical morphology and greater biosynthetic activity that was reflected in the greater increase of GAG content.

Animals↗
PubMed1997

A simple two-step method for the conversion of [3H]cortisol to [3H]-11-ketotestosterone.

Despite the existence of several protocols, problems appear to persist in the small scale chemical synthesis of radiolabeled 11-ketotestosterone from cortisol. We investigated the possibilities of using the mild oxidant pyridinium dichromate for the oxidative cleavage of the dihydroxyacetone side chain of cortisol and 17 beta-hydroxysteroid dehydrogenase for the subsequent reduction of the resulting 17-keto group. Our protocol has resulted in consistently high yields of both the intermediate, adrenosterone (70-80%), and the product, 11-ketotestosterone (up to 60%). This, taken together with the convenience and relatively low cost of our method, recommends the protocol for its use for the synthesis of [3H]-11-ketotestosterone for endocrine studies.

Androstenes↗
PubMed1997

Matrix collagen type and pore size influence behaviour of seeded canine chondrocytes.

This study directly compared the behaviour of chondrocytes in porous matrices comprising different collagen types and different pore diameters. There was a dramatic difference in the morphology of the cells in the type I and type II collagen matrices. The cells in the type II collagen matrix retained their chondrocytic morphology and synthesized glycosaminoglycans, while in the type I matrix the chondrocytes displayed a fibroblastic morphology with less biosynthetic activity than those in the type II. Small pore diameter affected morphology initially in the type I matrices and showed a higher increase of DNA content, but with time the cells lost the chondrocytic morphology. Our results demonstrate the marked influence of collagen type and pore characteristics on the phenotypic expression of seeded chondrocytes.

Analysis of Variance↗
PubMed1997

Comparative performance of disposable soft contact lenses.

A short-term clinical study was undertaken to compare and evaluate the fit and clinical behaviour of eight disposable hydrogel contact lenses. Thirty subjects were enrolled in a 1-day, randomised, double-masked study. The lenses compared were Vistakon Acuvue (8.80), Vistakon Surevue (8.80), Aspect Frequency-55, Bausch & Lomb Medalist (SeeQuence 2), Ciba Focus (8.90), Lunelle Rythmic, Pilkington Barnes Hind Precision-Wand Wesley Jessen Freshlook. Three of the eight designs, Acuvue (86.7%), Precision-UV (86.7%) and Frequency-55 (90%), achieved relatively high levels of fitting success. The Rythmic lenses achieved the lowest success rate (70%) showing significantly greater downward decentration than the other designs. Although all the lenses were designed to fit a wide variety of eyes, they exhibited widely varying fitting characteristics. Some were more successful than others. The study shows that it is necessary for practitioners to utilise a range of lens designs in order to fit satisfactorily the typical contact lens population.

Journal Article↗
PubMed1997

Improvement in specificity of [14C]d-xylose breath test for bacterial overgrowth.

The aim of the study was to determine whether the specificity of the [14C]d-xylose breath test could be improved, by excluding false-positive tests due to premature colonic metabolism of the [14C]d-xylose caused by rapid colonic transit. Forty-seven patients with suspected small bowel bacterial overgrowth were investigated by (1) aspiration and culture of duodenal fluid and (2) a [14C]d-xylose breath test. Those with either a positive duodenal culture or breath test had a repeat [14C]d-xylose breath test given with one of three transit markers (barium, Gastrografin or 99mTc-labeled tin colloid) to determine if the site of metabolism was in the small bowel or colon. Fourteen patients had positive duodenal cultures, four of whom had a negative [14C]d-xylose breath test, 15 patients had a positive [14C]d-xylose breath test, three of which were due to colonic metabolism of the xylose. Where transit markers were used, 14C was detectable in the breath and serum before barium had entered the small bowel, thus the barium did not comigrate with the xylose. Gastrografin accelerated small bowel transit, leading to malabsorption of the xylose in the small intestine and subsequent colonic metabolism of the xylose. 99mTc-labeled tin colloid had no obvious disadvantages and appeared to be the marker of choice. The use of a transit marker increased the specificity of the [14C]d-xylose breath test from 85% to 94%. The specificity of the [14C]d-xylose breath test for the detection of small bowel bacterial overgrowth is improved to greater than 90% by the use of an appropriate transit marker.

Bacteria↗
PubMed1997

Overdiagnosis of TIA and minor stroke: experience at a regional neurovascular clinic.

We compared the referral diagnoses of TIAs and minor strokes made by non-specialists with those of two consultant neurologists, in 565 consecutive cerebrovascular clinic patients, of whom 508 (90%) were referred with a diagnosis of any TIA or stroke. In 373 (73%), the neurologists felt the diagnosis of a cerebrovascular event to be correct. Agreement with the vascular syndrome (CVA vs. TIA) was significantly higher for patients with a referral diagnosis of stroke (136/176) (77%) than it was for patients with a referral diagnosis of TIA (200/332) (60%) (difference in proportions 17%, 95% CI 9-25). In 37 patients (7%) the neurologists confirmed the diagnosis of cerebrovascular disease but not the specific TIA/stroke diagnosis. Vascular surgeons were more likely to be correct in their referral diagnosis of carotid territory cerebrovascular disease (88% correct) than all other sources combined (63% correct) (difference in proportions 25%, 95% CI 11-39), but there was no significant variation in diagnostic accuracy between other individual groups. In 135/508 patients (27%) referred as any TIA or stroke, the diagnosis of cerebrovascular disease was undone. Alternative diagnoses included migraine (3%), epilepsy (1%), hyperventilation (1%), multiple sclerosis (1%) and a case of idiopathic Parkinson's disease, but many symptoms (8%) were unclassifiable. A strict comparison of diagnostic accuracy would have required assessment of patients not referred for specialist opinion, to estimate false-negative as well as false-positive diagnoses. However, in this patient group (which reflects current local practice) TIAs and strokes seem overdiagnosed.

Adult↗
PubMed1997

Discriminating between barley genotypes using microsatellite markers.

Eleven microsatellite loci were used to survey 24 barley genotypes representing 23 cultivars and a breeding line in official trials. Three separate combinations of four microsatellites had overall probabilities of identity of less than 1 in 1000 and could distinguish between all 24 barley genotypes. It is shown that the microsatellites could distinguish genotypes with the same pedigree and also that patterns of discrimination were different from those obtained from botanical descriptors. The stability of microsatellites across different generations was demonstrated by a retrospective analysis of the pedigree of Golden Promise. One of the parents of Maythorpe, the immediate ancestor of Golden Promise, was shown to be Irish Goldthorpe rather than Goldthorpe, thereby resolving conflicting published pedigrees.

DNA, Plant↗
PubMed1997

Transferring managed care principles to VA.

The Under Secretary for Health asked the Health Services Research and Development (HSR&D) service to identify the managed care principles that would enable The Department of Veterans Affairs (VA) to most improve its efficiency and effectiveness while retaining its unique mission. In response to this request, HSR&D's Management Decision & Research Center (MDRC) prepared this article. This article represents the initial work done by the MDRC to determine the extent to which readily available published evidence on implementing managed care principles meets the Under Secretary's information needs and to outline potential areas for further work. It provides an overview and synthesis of existing literature. The document was prepared by the MDRC Technology Assessment Program, which took responsibility because of its expertise in systematic reviews and syntheses of the literature, with contributions from the MDRC's programs in information dissemination and management research.

Community Health Planning↗
PubMed1997

Six month clinical evaluation of a biomimetic hydrogel contact lens.

PURPOSE: We performed a six-month, comparative, contralateral/bilateral study to assess the clinical performance of the Proclear contact lens, which is manufactured from a novel, biomimetic, 59% water content, hydrogel material (Omafilcon A). Omafilcon A is a hydrogel polymer and is based on a new biomimetic approach to the design of biomaterials for biomedical applications. The polymer incorporates a synthetic analogue of the phosphorylcholine (PC) headgroup, an important component found in all human cells. METHODS: Forty-two subjects were fit with the Proclear lens for 6 months of daily wear; 20 subjects wore a Proclear lens in one eye and a Permaflex lens in the fellow as a control, while 22 subjects wore Proclear lenses in both eyes. A one-step hydrogen peroxide system was used for disinfection and no protein remover was used. RESULTS: No subject was required to withdraw due to unacceptable physiological findings with the Proclear lens. At the 3-month visit, corneal staining was present in 33% of the Proclear eyes compared to 72% of the Permaflex-wearing eyes. At one month, the Proclear lens was graded significantly more comfortable than the Permaflex lens (P < 0.01), and all 11 of the subjects who expressed a preference did so in favor of the Proclear lens. Overall, the fitting characteristics and visual performance of the Proclear lens did not appear to vary during the study. Spectrofluorimetric analysis of worn lenses confirm that Proclear showed minimal protein and lipid spoliation, which was found to be independent of wear time and subject variations. In contrast, despite the use of a surfactant cleaner, Permaflex lenses showed measurable and significant levels of lipid spoilation. Despite significant differences in average mean thicknesses and the level of bulk water in the lenses, in vivo dehydration of the Proclear lens was significantly lower than that of the Permaflex lens. CONCLUSIONS: The results of this study have confirmed the viability of biomimetic PC-hydrogels in contact lens applications. In vivo and in vitro analyses tended to confirm that Omafilcon A has a number of superior material attributes, as compared to conventional hydrogels when used in contact lens applications.

Adolescent↗