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Biomedical subjects

J T Wright

Publications and source records attributed to J T Wright.

At least 19 recordsLinked to original sources

Lack of effect of topical iodostearic acid on cervical intraepithelial neoplasia II-III.

Stearic and iodostearic acid inhibit growth of a cervical carcinoma cell line in vitro. This study was performed to determine if iodostearic acid would induce regression of cervical intraepithelial neoplasia (CIN). Women with histologically-proven CIN II or III were randomised into two groups. Those in the first group were given pessaries composed of iodostearic acid in polyethylene glycol (PEG) base. Women in the second group were given pessaries containing only the PEG base. One pessary was inserted into the vagina nightly for 30 nights, and each woman then had the CIN lesion removed by CO2 laser cone excision. There was no difference in the histology of the cone biopsies between the groups, demonstrating that this regime of iodostearic acid has no useful role in the treatment of CIN II-III.

Adult

Impact of an electronic medication compliance aid on long-term blood pressure control.

A two-phase study was conducted to assess the effect of an electronic medication compliance aid on hypertension control and pharmaceutical compliance in ambulatory patients. In Phase I (12 weeks), 36 patients were randomly assigned to a medication vial equipped with a cap containing a digital timepiece that displays the last time the cap was removed. The control group included 34 patients randomly assigned to a standard medication vial. Subjects using the timepiece cap showed an average compliance rate of 95.1%, an average decrease in systolic pressure of 7.6 mm Hg (P = .006), and an average decrease in diastolic pressure of 8.8 mm Hg (P less than .001). Controls had an average compliance rate of 78% and decreases of 2.8 mm Hg and 0.2 mm Hg in systolic and diastolic pressures, respectively. Phase II (12 weeks) combined use of the timepiece cap with other compliance aids: a pocket-size card for recording blood pressure and a blood pressure cuff for self-monitoring. Patients using the timepiece cap and the card had an average compliance rate of 98.7% with mean decreases of 11 mm Hg in systolic pressure (P less than .01) and 7.64 Hg mm in diastolic pressure (P = .0001). The combined use of the cap, the card, and the blood pressure cuff resulted in an average 100.2% compliance rate with mean decreases of 15 mm Hg (P = .0006) and 6.60 mm Hg (P = .0006) in systolic and diastolic pressures, respectively. Results of the two-phase study showed statistically significant increases in medication compliance associated with statistically and clinically significant reductions in blood pressure for all patients using the timepiece cap.

Aged

Flow cytometric analysis of porcine preadipocytes.

In this report, conditions have been established for utilizing monoclonal antibodies and fluorescence activated flow cytometry in studying antigen expression by primary porcine stromal-vascular cells cultured under various conditions. Single cells were isolated from cultures maintained in DME/F12 medium containing 10% fetal bovine serum, 2% pig serum, and containing 2% pig serum and 10 nM dexamethasone supplemented with growth hormone (GH), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta). Flow cytometric analyses revealed that the proportion of cells expressing detectable levels of the AD-1 cells surface antigen was greater in cultures supplemented with 2% pig serum and 10 nM dexamethasone than in other media. In cultures, GH, TNF-alpha and TGF-beta each inhibited lipid deposition, whereas TNF-alpha and TGF-beta, but not GH, inhibited AD-1 antigen expression. Inhibition of lipid deposition as well as antigen expression by TNF-alpha and TGF-beta was reversible, but inhibition of cluster formation by GH was not reversed upon removal from cultures. In summary, differential effects of factors on surface antigen expression by preadipocytes are detectable by flow cytometry. Flow cytometric analysis using monoclonal antibodies produced against key developmentally regulated cell surface antigens is potentially a powerful analytical approach to the study of adipocyte development.

Adipose Tissue

Practical pharmacokinetics of ventricular antiarrhythmic therapy.

An increasing number of antiarrhythmic agents have become available for the treatment of ventricular tachyarrhythmias. Appropriate application of pharmacokinetic principles is essential to determine dosage amount and frequency, particularly because of the life-threatening consequences of inadequate therapy. Therefore absorption, distribution, metabolism, and elimination of antiarrhythmic agents must be considered in their use. Although some may be given intramuscularly, antiarrhythmic drugs are usually administered either intravenously for rapid onset of action or orally during long-term therapy. Distribution of antiarrhythmic drugs may be influenced by physicochemical properties of the drug (i.e., protein binding) or by tissue blood flow. Drug interactions and half-life are also important considerations. Finally, the major routes of elimination of antiarrhythmics are hepatic metabolism and renal and biliary excretion. The pharmacokinetic profiles of drugs used for the treatment of ventricular tachyarrhythmia, all of which are types I and III antiarrhythmic agents, are discussed.

Anti-Arrhythmia Agents

The Cleveland Veterans Affairs Medical Center firm system.

Hospital-based "firms" provide a means for combatting the fragmentation experienced by both patients and caregivers in the modern teaching hospital environment. A "firm" is an academic group practice that includes attending physicians, physician trainees, nurses, other staff, and patients. Each person's relationship with a firm lasts throughout his or her association with a particular institution. This article describes the firm system that was recently implemented on the Medical Service of the Cleveland VAMC. This system incorporates both inpatient and outpatient general medical services and provides for unbiased assignment of patients, physicians, and nurses.

Adult

Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol.

The N-demethylation of erythromycin and 6 beta-hydroxylation of cortisol are both functions of the glucocorticoid-inducible CYP3A in human liver microsomes. To determine whether 6 beta-hydroxylation and erythromycin N-demethylation are catalyzed by similar or distinct CYP3A isoforms, erythromycin N-demethylase activity, as reflected by the recently described 14[C]-erythromycin breath test, was compared with urinary 6 beta-hydroxycortisol/cortisol ratios, a measure of cortisol 6 beta-hydroxylase activity, in nine patients. Erythromycin N-demethylation varied fourfold and 6 beta-hydroxycortisol/cortisol ratios varied sevenfold among the subjects; no correlation was found between these activities (r2 = 0.065). New noninvasive tests of CYP3A strongly suggest cortisol 6 beta-hydroxylation and erythromycin N-demethylation are performed by distinct CYP3A isoforms.

Aged

Effect of conventional dental restorative treatment on bacteria in saliva.

Dental caries results from the dissolution of mineralized dental tissues by the metabolic by-products of oral bacteria colonizing the surface of teeth. The principal modality for dealing with this infectious process is through restorative treatment which removes the pathologic tissue and replaces it with a variety of inert materials. The purpose of this study was to evaluate the effect of traditional restorative treatment on select oral bacterial populations. Fifty-two females demonstrating high levels of mutans streptococci (greater than or equal to 2.5 x 10(4) colony forming units (cfu) per ml saliva) with no more than four missing posterior teeth were recruited for this study. Salivary levels of mutans streptococci, lactobacilli, total streptococci, and total cultivable bacteria were evaluated before, during, and after restorative treatment. Initial DMFS scores were established by two standardized examiners using bitewing radiographs and clinical examination, which was conducted under optimal conditions. All restorative treatment was completed by faculty members of the University of Alabama School of Dentistry using treatment plans developed by the DMFS examiners. The participants received a mean of 16.4 restored surfaces, which resulted in significant reductions of all the bacterial populations tested. All microbial populations monitored were predicted to return to their baseline levels within 151 days after restorative treatment in 50% of the participants. This study shows that conventional restorative treatment results in a significant reduction of bacterial populations including those associated with the dental caries process, i.e., mutans streptococci and lactobacilli.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Enamel ultrastructure in pigmented hypomaturation amelogenesis imperfecta.

Hypomaturation amelogenesis imperfecta (AI) is a hereditary condition of enamel that is presumed to result from defects during the maturation stage of enamel development. This study characterized the enamel ultrastructure and enamel crystallite morphology, as well as the distribution of organic material in enamel affected with pigmented hypomaturation AI. Enamel exhibiting autosomal recessive pigmented hypomaturation AI was sectioned or fractured and examined using light microscopy, scanning electron microscopy and transmission electron microscopy. Enamel samples were treated with 30% NaOCl or 8 M urea to remove organic components and determine the effect of deproteinization on crystallite morphology. These were compared with untreated normal enamel samples. The enamel crystallites in hypomaturation AI exhibited considerable variability in size and morphology. Examination of deproteinized tissue indicated that the AI crystallites had a thick coating, presumably of organic or partially mineralized material, which was not visible in normal enamel. The results of this investigation provide further evidence that hypomaturation AI is associated with the retention of organic material that is most probably enamel protein. Enamel protein retention is likely to be involved in the inhibition of normal crystallite growth resulting in the morphological crystallite abnormalities associated with this disorder.

Amelogenesis Imperfecta

Destructive periodontal disease in healthy children.

This study determined the prevalence of destructive periodontal disease affecting the deciduous dentition among otherwise healthy subjects, who were diagnosed with juvenile periodontitis (JP) in their permanent dentitions. There were 4,757 subjects in this retrospective, cross-sectional study. Diagnosis of JP was based on age (< or = 15 years), negative medical history, and radiographic evidence of arc-shaped alveolar bone loss. The study population was one-third white and two-thirds black and the male/female ratio was 1:1, reflecting the general patient population. The prevalence among whites was 0.3%, with a female/male ratio 4:1; whereas among blacks the prevalence was 1.5%, with a female/male ratio approximately 1:1. Among the black JP subjects with radiographs of the mixed dentition, 85.7% presented evidence of bone loss, and of those with radiographs of the deciduous dentition, 71.4% had discernible alveolar bone loss. This study suggests that JP is much more prevalent in blacks and that it does indeed occur in the prepubertal years affecting the deciduous as well as the permanent dentitions in otherwise healthy children. These data imply the importance of including a periodontal evaluation in the examination of children, using the periodontal probe and radiographs sufficient to adequately view the alveolar bone.

Adolescent

Characteristics of smokeless tobacco use among high school football players as related to type of smokeless tobacco and period of use.

The present study was conducted to assess differences in the behavioral and demographic characteristics of snuff (dip) users as compared to users of chewing tobacco. High School football players (1116) were surveyed concerning their use and perceptions of smokeless tobacco. Adolescent athletes who tried smokeless tobacco were more likely to be white, to use cigarettes, alcohol, and cigars and to have family users than those who never tried. Initial use was highest before the age of fourteen years and was influenced by friends, curiosity and family. Dippers tended to initiate use because of friends, while chewers started because of family users. Users of both dip and chew started primarily because of curiosity. Users of both were more likely to consume greater amounts to alcohol and cigarettes and to smoke cigars and pipes. It appears that the longer smokeless tobacco is consumed, the more likely both dip and chew will be used. Users of smokeless tobacco for more than two years tended to consume more of the product each week, used it for more hours/day, initiated use at an earlier age, and used it more often at school and work than those using it for less than two years. Use of cigars/pipes, consumption of alcohol, and quantity of cigarette consumption increased significantly with longer duration of smokeless tobacco use. Intervention and prevention programs would be helped by understanding differences between users of various smokeless tobacco products and differences related to the duration of use. In addition, further analyses of smokeless tobacco users should study chewers, dippers, and users of both separately.

Adolescent

Expression of transforming growth factor-beta (TGF-beta 1) and insulin-like growth factor II (IGF-II) messenger RNA in the developing subcutaneous tissue (SQ) of the fetal pig.

Studies (in situ hybridization) were performed on the developing subcutaneous tissue (SQ) of the pig fetus to determine sites of synthesis of TGF-beta 1 and IGF-II. Tissues from 50, 70, 90, 110-day-old pig fetuses and 7-day-old postnatal pigs were Bouin's fixed, paraffin embedded and hybridized with biotin labelled cDNA probes. The expression of TGF-beta 1 messenger RNA was detectable primarily in the dermis, hair follicle fat lobule, outer and inner SQ areas at all ages. Cells adjacent to adipocyte clusters and some small adipocytes were positive for TGF-beta 1. There was no positive hybridization of TGF-beta 1 probes in the developing muscle below the SQ. The expression of IGF-II was evident in the developing muscle below the SQ at 50 d and 70 d, and could be detected in the outer and inner SQ at 70 d. Much lower levels of IGF-II expression were observed in 90 and 110 d fetuses, but an increase in IGF-II expression was evident in the muscle of 7d postnatal pigs. Our results suggest that paracrine and autocrine regulatory systems may be operative for developing adipocytes (TGF-beta 1) and muscle (IGF-II), with specific areas and times of TGF-beta 1 and IGF-II expression being evident in developing pig SQ tissue.

Animals

Comparison of gemfibrozil and lovastatin in patients with high low-density lipoprotein and low high-density lipoprotein cholesterol levels.

BACKGROUND: The efficacy of gemfibrozil and lovastatin in the treatment of patients who have an elevated low-density lipoprotein cholesterol (LDL-C) level and a low high-density lipoprotein cholesterol (HDL-C) level was compared. METHODS: After at least 6 weeks of a cholestgerol-lowering diet, 17 patients who had a mean baseline LDL-C level above 4.14 mmol/L (160 mg/dL) and an HDL-C level below 1.03 mmol/L (40 mg/dL) received gemfibrozil 600 mg twice daily and lovastatin 20 mg twice daily each for 6 weeks according to a randomized, crossover, double-blind research design. RESULTS: Lovastatin and gemfibrozil reduced LDL-C levels 34% and 9% and raised HDL-C levels 15% and 18%, respectively. CONCLUSIONS: Lovastatin is more effective in lowering LDL-C levels and is as effective as gemfibrozil in increasing HDL-C levels in these patients.

Cholesterol, Dietary

The effect of low-dose phenytoin on high-density lipoprotein cholesterol.

We examined whether low doses of phenytoin, which should be associated with few dose-related side effects, may increase the levels of high-density lipoprotein (HDL) cholesterol. Of 35 healthy adult men who consented to participate, 31 completed the study. They took no medications and consumed no alcohol during the study. We used a three-arm, parallel, prospective, randomized, double-blind research design. Subjects took a single-blind placebo capsule once daily at bedtime for 2 weeks and then were randomly assigned to receive identical-appearing capsules containing 30 mg or 100 mg of phenytoin or placebo, once daily at bedtime for 4 weeks. The HDL cholesterol and HDL subfractions were determined from 12-hour fasting blood samples obtained at the beginning and end of the single-blind period and at the end of the third and fourth weeks of the double-blind period. Mean differences between baseline and posttreatment HDL cholesterol levels with placebo, 30 mg phenytoin, and 100 mg phenytoin were 0.010 mmol/L (0.4 mg/dl), 0.005 mmol/L (0.2 mg/dl), and 0.096 mmol/L (3.7 mg/dl), respectively (p = 0.2947); baseline and posttreatment HDL2 and HDL3 levels were not different among the groups. Total cholesterol levels were significantly higher in subjects taking phenytoin 100 mg than in those taking phenytoin 30 mg or placebo. The results suggest that phenytoin in dosages of up to 100 mg daily for 4 weeks has no substantial effect on HDL cholesterol or HDL subfractions.

Adolescent

Once-daily pravastatin in patients with primary hypercholesterolemia: a dose-response study.

This multicenter, double-blind, placebo-controlled study was conducted to evaluate dose-response effects and safety of once-daily administration of pravastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Pravastatin 5, 10, 20, 40 mg or placebo was administered at bedtime to 150 patients with primary hypercholesterolemia inadequately controlled on a low-fat, low-cholesterol (AHA Phase I) diet. After 8 weeks of treatment, pravastatin produced dose-dependent reductions in low-density lipoprotein (LDL) cholesterol of 19.2 to 34.1% (p less than or equal to .001 vs. baseline and placebo) and reductions in total cholesterol of 14.3 to 25.1% (p less than or equal to .01 to p less than or equal to .001 vs. placebo and p less than or equal to .001 vs. baseline). The relationship between the loge dose of pravastatin and decrease in LDL cholesterol was linear (p less than 0.002). High-density-lipoprotein cholesterol increased up to 11.7% and triglycerides decreased by as much as 23.9%. Pravastatin was well tolerated; no patient withdrew from the study as a consequence of treatment-related adverse events. Despite its relatively short serum half-life of approximately 2 h, once-daily administration of pravastatin provides a safe and effective means of reducing elevated LDL and total cholesterol.

Acyl Coenzyme A

Cytoplasmic proteins of porcine adipocytes: identification with monoclonal antibodies.

In the present study, monoclonal antibodies were produced using porcine adipocyte extracts as the immunogen. Two of the monoclonal antibodies, designated CB6 and IB4, exhibited reactivity toward only cells containing lipid in stromal-vascular cell cultures. The antigens recognized by the CB6 and IB4 monoclonal antibodies were 50 kD and 55 kD proteins, respectively. In vivo, IB4 immunoreactivity was detected only in lipid-containing cells, whereas immunofluorescence using CB6 was also detectable around muscle fiber bundles underlying the subcutaneous mesenchyme. In fetal subcutaneous mesenchyme, CB6 and IB4 immunoreactivities toward lipid-containing cells increased with developmental age, but each was not detectable in cells containing the smallest lipid droplets. In stromal-vascular cultures containing adipocytes, 48 hour treatment with the anti-lipogenic agent, growth hormone, only slightly altered CB6 immunoreactivity, whereas IB4 immunoreactivity was reduced by more than sixfold. The exact identity of the CB6 and IB4 antigens was not determined, but each may be useful as markers for studying regulation of adipocyte metabolism.

Adipose Tissue

Vascular and cellular development in fetal adipose tissue: lectin binding studies and immunocytochemistry for laminin and type IV collagen.

A cytochemical study of vascular and cellular development in fetal adipose tissue was conducted utilizing 10 plant lectins (fluorescein isothiocyanate (FITC)-labeled), antibodies against laminin, types II and IV collagen, and a probe for actin. Throughout fetal development (50-110 days) blood vessels were stained by galactose binding lectins and stained for actin, type IV collagen, and laminin. Adipocyte reactivity for laminin was strong throughout development, whereas adipocyte staining for type IV collagen and several lectins increased from weak to moderate between 70 and 110 days of fetal life. In general, staining intensity for lectins was greater for blood vessels than for adipocytes at every age, and staining for lectins and type IV collagen was detected much earlier on blood vessels than on adipocytes. However, the ontogeny and intensity of laminin staining were similar for developing adipocytes and vasculature. Adipocyte staining by several lectins was dependent on location within the tissue, whereas blood vessel lectin staining was not location-dependent. Neuraminidase pretreatment abolished the variation in cellular lectin staining due to location (within the tissue) but did not alter age-related changes in cellular staining. This study indicates that the differentiation of the extracellular matrix of blood vessels and adipocytes is clearly distinct in regard to glycoconjugate composition and temporal pattern of glycoconjugate and type IV collagen deposition.

Actins

Oral leukoplakia and adolescent smokeless tobacco use.

The recent increase in smokeless tobacco (ST) use has prompted investigators to assess the health effects of ST use. This study attempted to evaluate the prevalence of oral leukoplakia among adolescent users and to determine factors associated with its presence. During their annual physical examination, 1116 teenaged football players (567 black, 546 white) answered a 34-question survey and received an oral screening examination. Results indicated that 0.5% of nonusers, 1.5% of previous users, and 13% of current users had clinically evident oral leukoplakia. Factors statistically associated with higher leukoplakia rates included history of ST use, regular ST use, years of ST use, and the weekly quantity consumed. Factors not associated included use of alcohol, use of cigarettes, type of ST used, and hours of ST use. One brand of snuff was found to be associated with a relative risk of leukoplakia higher than that of another brand of snuff. Overall, in ST users oral leukoplakia was six times more likely to develop than in nonusers. Earlier ages of ST use may lead to greater periods of use (in years) and to possible increases in deleterious long-term health effects in current adolescents.

Adolescent

Salivary function of persons with hereditary epidermolysis bullosa.

Oral alterations of the hard and/or soft tissues are commonly associated with the different types of epidermolysis bullosa (EB). The relationship of oral soft and hard tissue changes to the disease mechanisms in different EB types remains to be elucidated. The purpose of this investigation was to evaluate selected aspects of salivary function in a healthy control population and in persons affected with different types of EB. Sixty-one patients with EB, representing all the major types of EB, and 36 unaffected persons were examined to measure their stimulated salivary flow rates and salivary levels of IgA, albumin, and total protein. Our results show that none of the types of EB demonstrated a decreased salivary flow rate. However, patients with recessive dystrophic EB had significantly elevated salivary IgA, albumin, and total protein levels. The increased IgA level seen in this form of EB appears most likely to be related to the high prevalence of oral blistering rather than the result of altered mucosal immune function. Despite severe cutaneous and extracutaneous involvement associated with inherited EB, we found no evidence to support the hypothesis of abnormal salivary function or mucosal immunity in this disease. Taken together, these findings suggest that the rampant dental caries seen in the severe forms of EB are likely attributable to nonsalivary factors such as enamel involvement, soft tissue alterations, and/or diet. Alternatively, there may be mucosal immunity or salivary enzyme alterations that influence oral disease in these patients, but these were not evaluated in this investigation.

Adolescent