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Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 343 records · Page 19Linked to original sources
PubMed1996

Genetic analysis of the human cytochrome P450 CYP2C9 locus.

Cytochrome P450 CYP2C9 metabolizes a wide variety of clinically important drugs, including phenytoin, tolbutamide, warfarin and a large number of non-steroidal anti-inflammatory drugs. Previous studies have shown that even relatively conservative changes in the amino acid composition of this enzyme can affect both its activity and substrate specificity. To date six different human CYP2C9 cDNA sequences, as well as the highly homologous CYP2C10 sequence have been reported suggesting that the CYP2C9 gene is polymorphic. Only nine single base substitutions in the coding region of CYP2C9 account for the differences seen between the CYP2C9 proteins. In this report we have developed polymerase chain reaction (PCR)-based assays to distinguish all seven sequences, and have determined their allele frequencies in the Caucasian population. Of the seven sequences studied in one hundred individuals only three appeared to be CYP2C9 alleles. These alleles termed CYP2C9*1, CYP2C9*2 and CYP2C9*3 had allele frequencies of 0.79, 0.125 and 0.085 respectively. The CYP2C10 gene could not be found in any of the samples studied. The assays developed here will allow the prediction of CYP2C9 phenotype, thus identifying those individuals who may exhibit different drug pharmacokinetics for CYP2C9 substrates.

Alleles↗
PubMed1996

Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.

Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.

Amino Acid Sequence↗
PubMed1996

The effect of syntocinon on blood loss during first trimester suction curettage.

We have studied 64 pregnant women (9 weeks gestation and greater undergoing elective vaginal termination of pregnancy). They were allocated randomly to one of two groups to receive either 1 ml (10 units) of syntocinon or 1 ml of saline (placebo) after cervical dilatation. Anaesthesia was standardised and surgery was performed by a single blinded gynaecologist, who assessed the size of the uterus and graded uterine contractility. All patients received a Cervagem vaginal suppository 70-270 min before surgery. The volume of blood loss was calculated colorimetrically and found to be less than 100 ml in all patients. The median blood loss in the syntocinon group (n = 30) was 17.6 ml, (range 6.1-72.7) and was significantly less than that in the placebo group (n = 34), median blood loss 24.5 ml, (range 6.7-94.3) (p = 0.02). Six patients in the saline group had unsatisfactory uterine contraction compared with none in the syntocinon group (p = 0.025).

Abortion, Induced↗
PubMed1996

Two dentigerous cysts in the mandible of one patient. Case report.

This paper reports a case of two separate dentigerous cysts in the mandible of one patient. An unusual feature was the relationship of one of the cysts to an unerupted lateral incisor. The prudence of accounting for any missing teeth in patients and the value of panoramic radiographic screening is illustrated.

Adult↗
PubMed1996

Quantitative radioimmunohistochemical measurements of p185(erbB-2) in frozen tissue sections.

The relationship between expression of the c-erbB-2 proto-oncogene and the biology of breast cancer has been investigated widely, most studies using immunohistochemistry in formalin-fixed, paraffin-embedded tissues. This technique is at best semiquantitative and there is a high degree of interstudy variability because of its subjective nature and poor methodological standardization. The relationship between the levels of expression and biology can be examined thoroughly only with an accurately quantitative technique. We have developed a radioimmunohistochemical assay to measure p185(erbB-2) in tissue biopsy specimens. The method involves incubating frozen sections with 125I-labeled monoclonal antibody, microautoradiograpy, and grain counting with image analysis. Sections of cell pellets with known c-erbB-2 levels are processed with each batch of samples as internal calibration standards. We have quantified c-erbB-2 expression in 60 breast carcinomas and compared the results with conventional immunohistochemistry. Radioimmunohistochemistry measured receptor levels throughout the range of expression in breast carcinomas, whereas conventional immunohistochemistry detected the protein only in the highest expressing tumors. The quantitative, objective data produced by radioimmunohistochemistry allow a more thorough evaluation of the relationship between c-erbB-2 expression and tumor biology. This technique may have applications in other fields where quantitative data is required and relevant monoclonal antibodies are available.

Breast Neoplasms↗
PubMed1996

Effects of training in monitoring accuracy on processing speed in mental retardation.

Monitoring accuracy during choice RT allows subjects to maintain fast, safe RT bands and avoid overly fast, unsafe RT bands. 5 retarded adults received trial-by-trial feedback on accuracy over a number of sessions to train monitoring of accuracy and to improve RT performance. Training was introduced according to a multiple-baseline-across-subjects (with reversal) design. Training had no significant effect on subsequent RT performance, suggesting that inefficient monitoring of accuracy may be a structural characteristic of mental retardation.

Adult↗
PubMed1996

Strongyloides stercoralis: maintenance of exceedingly chronic infections.

Two hypotheses were tested to identify the mechanism(s) by which chronic Strongyloides stercoralis infections are maintained in experimental dogs as a model to explain delayed onset recrudescence in humans. Investigations tested the hypotheses that chronic infections result from 1) periodic reactivation of third-stage larvae from a reservoir of dormant parasites outside the gastrointestinal tract or 2) the periodic rejuvenation of postreproductive female worms remaining from a previous infection, lodged in the mucosal crypts. Populations of parenteral larvae survived in mature experimentally infected female dogs for 66 days; individual worms survived for 88 days, but there was no evidence that these larvae re-established patent, adult worm infections. Late in these infections, female worms were present in greater than predicted numbers with no evidence that autoinfection had occurred, suggesting that some postreproductive worms were long-lived. In separate trials, long-lived spent females were once again capable of producing viable larvae when the host was treated with corticosteroids.

Animals↗
PubMed1996

In vitro sensitivity of macropodid herpesvirus 2 to selected anti-herpetic compounds.

We tested the in vitro sensitivity of Macropodid Herpesvirus 2 to eight commonly used anti-herpetic compounds using plaque reduction tests, March and April, 1995. The virus was most susceptible to inhibition by (E)-5-(2'-bromovinyl)-2'-deoxyuridine and adenine 9-beta-D-arabino-furanoside. Both compounds have been used for anti-herpetic therapy in humans and may prove useful in the treatment of macropodoids in captivity.

Acyclovir↗
PubMed1996

A basic risk management manual: a step in the "write" direction.

Written policies are central to successful risk management. The task of developing a risk management manual may seem overwhelming at first. To approach this task, agencies might start first with the most important aspects of risk management.

Inservice Training↗
PubMed1996

Formulary: what it is and how it works.

Estimates for healthcare expenditures in 1993 exceeded $900 billion, approaching 15% of GNP. Of this, approximately 7.5% ($62 billion) was spent on drugs. More recently, costs show that the US spends over $3,000 per person per year on healthcare. Although no one disputes that the cost of healthcare is rising, generally the rate at which it rises is not as rapid in a managed care environment compared to a fee-for-service one. Because of this, the boundaries of managed care and pharmacy benefits management (PBM) continue to expand. Outpatient drug benefits, for instance, are being carved out of the medical benefit offered by several types of insurance programs. This is mainly a result of point-of-sale claims processing and enhanced information system data base reporting making the drug portion easier to identify and separate from other medical claims. Self-funded employers are now actively seeking PBM companies to contract with for this type of service. The services being offered by PBM companies include: Pharmacy networks in which plan members fill prescriptions at a discounted or contracted rates. Disease state management. Drug utilization review. Financial reporting. Formulary management. The main component of formulary management is the development and distribution of a drug formulary. This article discusses what a drug formulary is and how it works.

Cost-Benefit Analysis↗
PubMed1996

Dopamine transporters decrease with age.

UNLABELLED: Postmortem studies have documented degeneration of dopamine cells with age, but the changes that occur in healthy aging individuals is less clear. The purpose of this study was to evaluate the extent to which age-induced changes in dopamine transporters occur in subjects with no evidence of motor impairment. METHODS: We evaluated 23 right-handed healthy volunteers (age range 20-74 yr) using PET and [11C]d-threo-methylphenidate. The ratio of the distribution volume for [11C]d-threo-methylphenidate in striatum to that in cerebellum was used as model parameter for dopamine transporter availability (Bmax/Kd + 1). RESULTS: Dopamine transporter availability was significantly lower in subjects > 40 yr of age than in those < 40 yr. Estimates of dopamine transporter availability showed a significant negative correlation with age both for the putamen (r = -0.72, p < 0.0001) and the caudate (r = -0.74, p < 0.0001). Dopamine transporter availability was higher in the left than in the right putamen but did not differ between the left and right caudate. CONCLUSION: This study documents a 6.6% decrease per decade of life in striatal dopamine transporters of healthy volunteers.

Adult↗
PubMed1996

New treatments for breast cancer.

The development of new treatments for breast cancer has been fueled by the plateau in median survival which has been observed using standard drugs. Chemotherapy scheduling and dose-intensity are areas of intense research. As the same time, new drug development has been remarkably productive. Novel agents have been evaluated that induce high response rates. Clinical superiority may ultimately emerge as new spindle poisons, topoisomerase inhibitors, and antifolates are compared with standard therapy. New inhibitors have also been developed for hormone sensitive breast cancer. Immunologic therapy has reached phase III trials. Novel liposomal delivery systems allow maximum bioavailability with minimal toxicity. Finally, palliation of bone pain is now possible with site-specific agents such as pamidronate and 89Strontium. As the arsenal of treatments continues to expand, these new agents are primed to enter clinical practice. If current progress continues, the next decade promises exciting hope for the treatment of breast cancer.

Antineoplastic Agents↗
PubMed1996

Determination of the radius of curvature of the anterior lens surface from the Purkinje images.

A new method for calculating the radius of curvature of the anterior surface of the crystalline lens from the measured heights of the Purkinje image PI and PIII is given. Equations are developed for determination of the radius of curvature of the equivalent mirror for three configurations commonly used in phakometry. The method can be applied to targets at any distance from the corneal vertex, for both a stationary target mounted independently of the camera, and for a mobile source attached to the camera where the distance of the target to the corneal vertex will change as the camera is refocused from image PI to PIII. The situation where only one recording is made of images PI and PIII, where the camera is focused on image PI, and the height of the defocused image of PIII is measured is also considered. The errors in calculating the anterior lens radius with the equivalent mirror method if no allowance is made for an object at a finite distance is examined. The new method described is an alternative to collimating targets to overcome the errors in phakometry that occur with targets at finite distances.

Lens, Crystalline↗
PubMed1996

Biomechanics of the thoracolumbar vertebral column of dogs during lateral bending.

OBJECTIVE: To study biomechanical characteristics of the normal and surgically altered canine thoracolumbar vertebral column to determine the effects of surgery and trauma on lateral stability. ANIMALS: The T13-L1 vertebral motion units of 48 mixed-breed dogs were dissected free of surrounding musculature and prepared for biomechanical testing by cross-pinning the vertebral bodies and mounting in polymethylmethacrylate. PROCEDURE: Normal and surgically altered spinal specimens were subjected to lateral bending. The mean slope of the bending moment versus angular displacement curve and the load to failure were compared between treatment groups and significance was determined by the method of least squares (P < 0.05). Specimens were surgically altered by facetectomy, lateral fenestration, diskectomy, and combinations of these procedures. Each specimen was subjected to lateral bending to failure at a rate of 2.5 cm/min in a swing arm bending jig designed to simulate 4-point bending and subject the specimen to pure bending. RESULTS: Only specimens undergoing diskectomy had a significant decrease in slope and load at failure. Unilateral and bilateral facetectomies and fenestration induced a nonsignificant decrease in stiffness, compared with control specimens. CONCLUSIONS: Fenestrations and facetectomies do not appear to increase the risk of injury to the canine thora-columbar spinal cord during lateral bending. CLINICAL RELEVANCE: Fenestrations and facetectomies, as used in routine laminectomies, may be performed without concern for significant destabilization of the spine in lateral bending; however, it is possible that thoracolumbar spinal fractures involving only the vertebral body may significantly destabilize the spine in all modes of bending.

Animals↗