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Biomedical subjects

J T Wright

Publications and source records attributed to J T Wright.

At least 127 records · Page 7Linked to original sources

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↗

Oral soft tissues in hereditary epidermolysis bullosa.

Epidermolysis bullosa (EB) is associated with diverse oral manifestations, which can potentially involve both hard and soft tissues, depending on the specific EB subtype. This study determined the frequency and extent of oral soft tissue involvement in the inherited forms of EB. Examination of 216 affected persons revealed significant differences in the oral soft tissue involvement among the various types of EB. The frequency of oral involvement was greater in the dominant dystrophic (81.1%) and simplex (generalized, 58.6%; localized, 34.7%) types than previously reported. The marked frequency of oral blistering was similar in both major subtypes of junctional (Herlitz, 83.3%; non-Herlitz, 91.6%) and recessive dystrophic EB (generalized, 100%; localized, 92.3%). Obliteration of the oral vestibule, ankyloglossia, and microstomia were consistent findings in generalized recessive dystrophic EB. Oral milia were present in all major EB categories, most prevalently in the dystrophic forms, but were not seen in all the distinct EB subtypes. These findings indicate that although there are no pathognomonic intraoral soft tissue manifestations in the various forms of inherited EB, there are predictable patterns of involvement associated with specific subtypes of this disease. Understanding the oral involvement associated with EB may aid clinicians in the development of more advanced therapeutic approaches that are compatible with and directed at the unique characteristics of each EB subtype.

Blister↗

Characterization of the enamel ultrastructure and mineral content in hypoplastic amelogenesis imperfecta.

Amelogenesis imperfecta (AI) comprises a diverse group of hereditary enamel disorders that are characterized by hypoplastic and in some cases hypomineralized defects. The specific biochemical abnormalities remain unknown for all AI types, making histologic and chemical analyses of affected dentitions essential for resolving the etiology of AI. The purpose of this investigation was to characterize the ultrastructure and mineral content of smooth hypoplastic AI enamel. The AI enamel showed no evidence of surface pitting and was uniformly reduced in thickness by approximately 60% compared with control enamel. Imbibition studies indicated that the AI enamel was generally porous. The first 30 microns of AI enamel adjacent to the dentinoenamel junction was translucent with poorly formed prisms. Abnormal prism structure was seen throughout the AI enamel. Amorphous, presumably organic material that may have been retained enamel protein was also seen. Although the crystallite widths were similar in both AI and normal enamel, the AI teeth showed areas where the crystallite order and continuity appeared disrupted. The mean mineral content was similar for all variables measured except sodium, which was significantly lower in the AI teeth. The calcium concentration was very low in the AI enamel directly adjacent to the dentinoenamel junction and showed a steeper concentration gradient moving from the dentin to the surface compared with control teeth. It may be concluded that the ameloblasts in smooth hypoplastic AI produce a tissue of reduced thickness, which is excessively porous and displays alterations in its ultrastructural organization.

Ameloblasts↗

Maternal death associated with ovum donation twin pregnancy.

A case of maternal death due to sub-arachnoid haemorrhage in an ovum donation twin pregnancy complicated by hypertension is described. Attention is drawn to a forecasted increase in maternal morbidity and mortality in in-vitro fertilization (IVF) pregnancies, which occur in older women and are often multiple.

Adult↗

The effect of phenylpropanolamine on 24-hour blood pressure in normotensive subjects administered indomethacin.

We evaluated the effect of phenylpropanolamine hydrochloride (PPA) in 14 young, healthy, normotensive women who concurrently received indomethacin. Subjects received sustained-release (SR) indomethacin 75 mg bid and were randomly assigned to receive double-blind SR PPA 75 mg/d or placebo for four days. After a six-day washout period, subjects were crossed over to the opposite four-day double-blind treatment. Following an additional six-day washout period, subjects received indomethacin placebo and PPA placebo during a final, single-blind four-day period. Twenty-four-hour blood pressure (BP) monitoring every 30 minutes and a 24-hour urine collection for prostaglandin E2 (PGE2) were performed on the fourth day of each treatment period. Compliance with the medication regimen was confirmed by drug concentrations, pill counts, and urinary PGE2 concentrations. Compared with the indomethacin and placebo treatment periods, the combination of indomethacin and PPA had no significant effect on mean systolic or diastolic BP during the 24-hour study period or during any four-hour interval. We conclude that the combination of SR PPA 75 mg/d and SR indomethacin 150 mg/d for four days has no adverse effect on BP in normotensive women.

Adult↗

Hypertension in African Americans: evaluation and treatment issues.

The evaluation and treatment of hypertension in the African-American patient with an elevated blood pressure presents a diagnostic challenge. We are less able to rely on young age and resistance to treatment as indications for more extensive evaluation of secondary causes of hypertension; thus, greater reliance on history, physical examination, and clinical judgment is required if we are to identify potentially treatable causes. The treatment of hypertension in the African-American patient also presents a therapeutic challenge. Thiazide diuretics remain the drugs of first choice for treating hypertension in the African-American hypertensive. The calcium channel blockers (CCBs) are attractive alternatives to thiazides in patients uncontrolled by or intolerant of thiazides or who have specific indications for these agents (eg, angina, severe diastolic dysfunction). Beta-blockers should not be denied to African-American hypertensives if indications for their use exist. Although beta-blockers may be less effective as monotherapy, 50% of African-American hypertensives can be so controlled. Resistance to beta-blockers may be eliminated by administering them with a diuretic. The angiotensin converting enzyme inhibitors (ACEIs), like CCBs, are well tolerated, but also lack long-term primary prevention data. As is the case with beta-blockers, ACEIs are less effective in African-American hypertensives when used as monotherapy. ACEIs have particular value in therapy for African-American hypertensives with concomitant congestive heart failure and may protect against progression of diabetic nephropathy. Finally, all hypertensives, especially African-American hypertensives, should have access to treatment prior to the development of end organ damage. The cost of early intervention is minimal compared with the economic consequences of neglect.

Adrenal Gland Neoplasms↗

Renin profile, race, and antihypertensive efficacy with atenolol and labetalol.

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.

Atenolol↗

Inherited blistering diseases of the skin.

Inherited epidermolysis bullosa (EB) comprises some 23 different phenotypic disorders which have as common features the presence of mechanically fragile skin and the tendency to develop blisters, erosions, and in some cases, scarring of the skin. While some forms of this disease are relatively mild, other rarer variants may prove to be life-threatening. In the past 15 years, a wealth of new information has elucidated new clinical and laboratory characteristics of specific EB subsets. In this brief review, the most important aspects of inherited EB are summarized to update the practicing pediatrician about the ever-increasing complexities being discovered about this disease.

Basement Membrane↗

Comprehensive dental care and general anesthetic management of hereditary epidermolysis bullosa. A review of fourteen cases.

Dental management of persons with epidermolysis bullosa remains challenging because of the severe hard and soft tissue manifestations of these diseases. This study reviews the dental treatment of 14 cases requiring 24 general anesthetics. Twenty-three of the cases were managed with oral tracheal intubation to accomplish full-mouth dental rehabilitation. Dental therapy consisted of preventive, restorative, and surgical procedures, with extractions and stainless steel crowns being the most common treatment modalities. There were no serious postoperative complications, and no airway problems were experienced. Although extensive intraoral mucosal blistering did occur in several cases, postoperative healing progressed normally. Soft tissue trauma may be lessened through the use of small suction tips, flat tissue retractors, and extensive lubrication of all tissues requiring manipulation. This study provides further evidence that even the most severely affected patients with epidermolysis bullosa can receive comprehensive dental treatment directed at maintaining a functional dentition.

Anesthesia, Dental↗

Fatty acid control of growth of human cervical and endometrial cancer cells.

Stearic acid and iodo-stearic and inhibited cell growth in a cervical cancer cell line (HOG-1) in a dose-related manner, with a half maximal effect at 50 microM stearic acid. Addition of oleic acid abrogated the effect of stearic acid. EGF-stimulated DNA synthesis and growth of HOG-1 cells was inhibited in the presence of stearic acid without any apparent effect on EGF receptor number or affinity.

Cell Division↗

Regulation of insulin-like growth factor-I ribonucleic acid expression, polypeptide secretion, and binding protein activity by growth hormone in porcine preadipocyte cultures.

Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide postulated to mediate the effect of GH on adipose tissue development. To determine if the effect of GH could be mediated by the local production of IGF-I, we have characterized IGF-I RNA expression, polypeptide secretion, and binding protein activity in primary preadipocyte cultures derived from porcine adipose tissues. GH acutely regulated the abundance of multiple IGF-I RNA transcripts and resulted in a 2-fold increase in secreted immunoreactive IGF-I (iIGF-I) polypeptide in medium conditioned for 48 h by preadipocyte cultures relative to those not receiving GH. Immunocytochemical data indicated that IGF-I is synthesized by presumptive and mature adipocytes. The effect of GH on iIGF-I secretion was observed in cultures derived from both fetal and postnatal animals, while secreted IGF-binding protein activity was increased due to GH only in cultures from fetal animals. The increase in local IGF-I production in response to GH was associated with a decrease in adipocyte development, suggesting that local IGF-I may contribute to suppression of differentiated phenotype.

Adipose Tissue↗