Search PubMed⌕ Search

Biomedical subjects

J T Wright

Publications and source records attributed to J T Wright.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Adrenergic beta-Antagonists↗
PubMed2001

Novel COL1A1 mutation (G559C) [correction of G599C] associated with mild osteogenesis imperfecta and dentinogenesis imperfecta.

A genotype-phenotype analysis of a three-generation family segregating for an autosomal-dominant osteogenesis imperfecta (OI) variant is reported here. The family was ascertained through the presentation of a proband concerned about discoloration of her teeth, found to be dentinogenesis imperfecta (DGI). Examination of 36 family members identified 15 individuals with DGI. Linkage studies were performed for genetic markers from candidate intervals known to contain genes responsible for DGI on chromosomes 4q, 7q, and 17q. Conclusive evidence for linkage of DGI was obtained to genetic markers on chromosome 17q21-q22 (DLX-3, Z(max) = 5.34, theta = 0.00). All DGI-affected family members shared a common haplotype, which was not present in individuals without DGI. Haplotype analysis sublocalized the gene to a 5-cM genetic interval that contained the collagen 1 alpha 1 (COL1A1) gene. More than 150 different COL1A1 gene mutations have been associated with various forms of OI, and five of these have been associated with DGI and type IV OI. After excluding these five mutations, mutational analysis was performed on the remaining exons including intron--exon boundaries, which resulted in identification of a Gly559Cys mutation in exon 32, present in all DGI-affected family members. Clinical features segregating with this G559C mutation included hyperextensible joints, joint pain and an increased propensity for bone fractures with moderate trauma. This is the first report of joint pain associated with a COL1A1 mutation and DGI. The mild skeletal features and reduced penetrance of the non-dental findings illustrate the importance of genetic evaluations for families with a history of DGI.

Amino Acid Substitution↗
PubMed2001

Laparoscopic treatment of complete obliteration of the cul-de-sac associated with endometriosis: long-term follow-up of en bloc resection.

OBJECTIVE: To evaluate symptom relief following a laparoscopic technique designed for treatment of complete obliteration of the cul-de-sac associated with endometriosis, with fertility preserved. DESIGN: Preoperative and postoperative questionnaire study of a cohort of patients with complete obliteration of the cul-de-sac undergoing a standardized laparoscopic surgical treatment. SETTING: American tertiary referral center for the surgical treatment of endometriosis. PATIENTS: Eighty-four consecutive patients undergoing laparoscopic treatment of endometriosis with complete cul-de-sac obliteration with 67 replying to a postoperative questionnaire. INTERVENTIONS: Laparoscopic excision of all endometriosis including treatment of complete obliteration of the cul-de-sac by en bloc resection and bowel resection as needed. MAIN OUTCOME MEASURES: Symptom relief as measured on a 5-point ranked ordinal scale administered before and after surgery, as well as perioperative complications, postoperative fertility, and prognostic value of preoperative findings on pelvic examination. RESULTS: Symptom reduction was obtained for all symptoms related to cul-de-sac disease, particularly for patients with severe or debilitating symptoms preoperatively. There was no significant complication, and the postoperative fertility rate was 43%. Seventy-three percent of patients with obliteration of the cul-de-sac had histologically proved rectal endometriosis. Nodularity and tenderness on examination were predictive of symptom improvement. CONCLUSIONS: Aggressive laparoscopic excision of endometriosis carried out in a specialist center offers good symptom relief, especially for those with severe or debilitating symptoms. To ensure complete removal of all disease, intestinal surgery is required in most patients with complete obliteration of the cul-de-sac.

Adult↗
PubMed2001

Operational aspects of terminating the doxazosin arm of The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, practice-based trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The double-blind, active-controlled component of ALLHAT was designed to determine whether the rate of the primary outcome-a composite of fatal coronary heart disease and nonfatal myocardial infarction-differs between diuretic (chlorthalidone) treatment and each of three other classes of antihypertensive drugs: a calcium antagonist (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin) in high-risk hypertensive persons ages 55 years and older. In addition, 10,377 ALLHAT participants with mild to moderate hypercholesterolemia were also enrolled in a randomized, open-label trial designed to determine whether lowering serum LDL cholesterol with an HMG CoA reductase inhibitor (pravastatin) will reduce all-cause mortality as compared to a control group receiving "usual care." In January 2000, an independent data review committee recommended discontinuing the doxazosin treatment arm. The NHLBI director promptly accepted the recommendation. This article discusses the steps involved in the orderly closeout of one arm of ALLHAT and the dissemination of trial results. These steps included provisional preparations; the actual decision process; establishing a timetable; forming a transition committee; preparing materials and instructions; informing 65 trial officers and coordinators, 628 active clinics and satellite locations, 313 institutional review boards, over 42,000 patients, and the general public; reporting detailed trial results; and monitoring the closeout process. Control Clin Trials 2001;22:29-41

Adverse Drug Reaction Reporting Systems↗
PubMed2001

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): clinical center recruitment experience.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized clinical outcome trial of antihypertensive and lipid-lowering therapy in a diverse population (including substantial numbers of women and minorities) of 42,419 high-risk hypertensives aged > or = 55 years with a planned mean follow-up of 6 years. In this paper, we describe our experience in the identification, recruitment, and selection of clinical centers for this large simple trial capable of meeting the recruitment goals outlined for ALLHAT, and we highlight factors associated with clinical center performance. Over 135,000 recruitment brochures were mailed to physicians. Requests for information and application packets were received from 9351 (6.8%) interested investigators. A total of 1053 completed applications were received and 909 sites (86%) were eventually approved to join the trial. Of the approved sites, 278 either later declined participation or were never activated, and 8 were closed within a year for lack of enrollment. The final 623 randomizing centers exceeded the trial's recruitment goal to enroll at least 40,000 participants into the trial, although the recruitment period was extended 1.5 years longer than planned. Fewer than a quarter of the sites (22.6%) were recruited from academic medical centers or Department of Veterans Affairs Medical Centers. More than half of the sites (54.7%) were private solo or group practices, which contributed 53% of randomized participants. Community health centers comprised about 8% of the ALLHAT sites and 2.9% were part of health maintenance organizations. More than 22% of the principal investigators reported that they had no previous clinical research experience. In summary, ALLHAT was successful in recruiting a diverse group of clinical centers to achieve its patient recruitment goals.

Antihypertensive Agents↗
PubMed2001

Race and the decision to refer for coronary revascularization: the effect of physician awareness of patient ethnicity.

OBJECTIVES: We sought to assess whether there were differences, relative to racial ethnicity, in coronary revascularization recommendations made by a panel that had no knowledge of the patients' ethnicity. BACKGROUND: Coronary revascularization is employed less frequently in African American than in white patients. It is unclear whether this utilization pattern is driven by clinical differences between the two populations or by nonclinical factors. METHODS: Data were reviewed from 938 (26.5% African American, 73.5% white) consecutive cardiac catheterizations done between 1993 and 1995. Revascularization recommendations were made by cardiologists and cardiothoracic surgeons provided with the patients' clinical and angiographic data, but without knowledge of their ethnicity. Revascularization recommendations were compared between African American and white patients and correlated with clinical characteristics. RESULTS: No difference was noted in the percentage of African American and white patients recommended for revascularization, without reference to whether the recommendation was for percutaneous transluminal coronary angioplasty (PTCA) or for coronary artery bypass graft surgery (CABG) 40 vs. 46%, p = NS). African Americans were recommended more frequently for PTCA (22 vs. 18%, p = NS), whereas CABG was recommended for more white patients (28 vs. 18%, p = 0.002). Significantly fewer African Americans had disease in the left main or left anterior descending coronary artery or in multiple arteries. After adjusting for age, co-morbidity, left ventricular dysfunction and the extent of coronary disease, African Americans were more likely to have a recommendation for PTCA (odds ratio [OR] 1.42, 95% confidence interval [CI] 0.96 to 2.11, p = 0.08) and less likely to have a recommendation for CABG (OR 0.59, 95% CI 0.37 to 0.94, p = 0.02). CONCLUSIONS: This study suggests that when only clinical factors are considered, the rates of recommendations for revascularization will be similar for white and African American patients; but the type of revascularization procedure may differ by ethnicity and may depend, in part, on clinical factors.

Black or African American↗
PubMed2001

Relationship between 24-H blood pressure and sleep disordered breathing in a normotensive community sample.

Sleep disordered breathing (SDB) and hypertension are commonly associated. In this study, we assessed how longitudinal measures of SDB predict a 24-h ambulatory blood pressure monitoring (ABPM) profile. Participants (n = 82) were recruited from a community-based urban (26% African American) sample and included family members of patients with laboratory diagnosed SDB (cases) and family members of neighborhood control subjects evaluated at baseline and at 5 years. Nearly all participants were normotensive and were not receiving therapy for SDB. During both examinations, the respiratory distress index (RDI) was assessed with overnight in-home polysomnography. Seated blood pressure (BP) was assessed at a baseline examination (t,) and after a 5-year follow-up period (t5), when 24-h ABPM also was performed. The change in RDI (t5-t1) over 5 years was significantly associated with 24-h mean systolic blood pressure (SBP) (P = .04), 24-h maximum diastolic blood pressure (DBP) (P = .03), sleep mean SBP (P = .05), sleep mean DBP (P < .05), and sleep maximum SBP (P = .02). Regression analysis revealed that average 24-h mean arterial pressure (MAP) and mean 24-h DBP were each best predicted by change in RDI, explaining 5% of the variance in these 24-h BP readings, and by current smoking status. After accounting for these variables, BP was not predicted by any of the other potential confounders (all P > .10). Mean RDI (averaged between t5 and t1) was associated with mean MAP, mean SBP, and maximal SBP measured during sleep. This study documents for the first time the association between changes in sleep apnea activity and BP and in a community-based normotensive sample. Further long-term evaluation of the effects of these findings and the long-term consequences of hypertension are needed.

Adult↗
PubMed2000

Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth.

Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-beta1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-beta1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).

Animals↗
PubMed2000

Management of patients with hypertension and diabetes mellitus: advances in the evidence for intensive treatment.

Diabetes mellitus is common in patients with hypertension, and greatly increases the risk of cardiovascular disease, including myocardial infarction, stroke, and peripheral vascular disease. "The pharmacologic therapy of patients with hypertension and diabetes has been surrounded by controversy because of concerns about the metabolic effects of several antihypertensive agents, as well as concerns about the safety of calcium antagonists. The objective of this review is to re-evaluate the management of diabetic patients with hypertension in light of the latest clinical trials. We also review the importance of intensive blood pressure control in these patients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

The chemical composition of tooth enamel in junctional epidermolysis bullosa.

The junctionalis form of epidermolysis bullosa (EBJ) is associated with a number of clinical problems involving tooth enamel, including increased susceptibility to caries. The aim here was to carry out a chemical characterization of the enamel of teeth from EBJ patients compared with that of unaffected controls. The results showed that while protein concentration, amino acid composition and carbonate content were similar in both groups, EBJ enamel contained a significantly reduced mineral per volume content, resulting in enamel hypoplasia. In addition, Western blotting revealed the presence of serum albumin (a known inhibitor of enamel crystal growth) in EBJ enamel. This was not detected in control enamel or in enamel of teeth from patients with the dystrophic form of the disease. It is concluded that EBJ enamel is developmentally compromised and that the enamel defects are commensurate with the reported genetic lesions.

Amelogenesis↗
PubMed2000

Mutational analysis of X-linked amelogenesis imperfecta in multiple families.

Seven mutations in the amelogenin gene are associated with X-linked amelogenesis imperfecta. These mutations can produce reductions in the amount of enamel and the degree of mineralization. Two families have been identified from western North Carolina exhibiting features of amelogenesis imperfecta, characterized by brown enamel in affected males and interposed vertical bands of normal appearing and brown enamel in presumably heterozygous females. Mutational analysis reveals a C-A mutation in exon 6 at codon 41 of the X-chromosomal amelogenin gene, resulting in a pro-thr change in all individuals having the amelogenesis imperfecta phenotype. This mutation was previously reported in a family with X-linked hypomaturation amelogenesis imperfecta. There is no known relationship between any of the three families but the presence of similar phenotypes and common mutations suggests they may be distantly related. For individuals from all three families, the haplotype for six highly polymorphic loci flanking the amelogenin gene was determined. A common haplotype was demonstrated among two of the three families, suggesting that the mutation may have been inherited from a common ancestor. The finding that the third family had a distinct haplotype may indicate that the C-A mutation at codon 41 represents a mutational hotspot that occurs with greater frequency than other known amelogenin gene mutations. The phenotype resulting from this mutation was highly consistent in affected male members of the same family and between families.

Amelogenesis Imperfecta↗
PubMed2000

Normal formation and development defects of the human dentition.

Oral health and systemic health are intimately related, and a thorough evaluation of the oral health of children is critical in providing appropriate health care. By understanding the normal sequence and patterns of tooth development, clinicians can readily identify children who deviate from normal dental development and provide appropriate interventions or make appropriate referrals. Developmental defects of the human dentition are not uncommon and can severely adversely affect the physical and psychological health of children. Despite the severity of some developmental defects of the dentition, the ability to diagnose and manage these conditions, in most cases, allows children the benefit of optimal oral health.

Child↗
PubMed2000

Abdominal fat pad mass reduction by in ovo administration of anti-adipocyte monoclonal antibodies in chickens.

The effect of in ovo administration of antiadipocyte monoclonal antibodies (MAb) on growth and adipose tissue development in chickens was investigated. In Trial 1, 60 fertilized eggs from layer-type chickens were injected into allantoic circulation with different amounts of MAb against chicken adipocyte plasma membranes (0, 0.05, 0.1, 0.2, and 0.4 mg) on Day 15 of embryogenesis. In Trial 2, 180 fertilized broiler eggs were injected into allantoic circulation with 0.2 mg MAb on Day 15 of embryogenesis. In Trial 1, high doses (0.2 and 0.4 mg) of MAb in in ovo injection reduced (P < or = 0.05) abdominal fat pad weight without affecting total body weight at 42 d of age. Only the highest dose (0.4 mg) significantly reduced hatch rate. In Trial 2, adipose tissue (pectoral, femoral, and abdominal), major organ (heart, liver, and spleen), and total body weights at 14 d of age were not affected by in ovo injection. Hatch success rate of eggs was not significantly different among treatments. However, by 6 wk of age, in ovo injection of MAb significantly reduced (P < or = 0.05) abdominal fat pad weight by more than 28%. This relative fat pad mass reduction occurred without affecting femoral or pectoral fat tissues. Total body weight and feed intake were not affected among treatments. Our experiments demonstrated for the first time that in ovo administration of anti-adipocyte MAb on Day 15 of embryogenesis reduced the chicken abdominal fat pad mass by 42 d of age without affecting growth or body weight.

Abdomen↗
PubMed2000

Inhibition of chicken adipocyte differentiation by in vitro exposure to monoclonal antibodies against embryonic chicken adipocyte plasma membranes.

Specific monoclonal antibodies (MAb) against adipocyte precursor antigens were developed. These MAb identified adipocyte precursors and reduced their prominence in primary stromal-vascular (SV) cultures by complement-mediated cytotoxicity or by inhibition of differentiation. Binding of antibodies to chicken adipocyte precursors was confirmed by immunofluorescence visual examination following secondary exposure to fluorescein isothiocyanate-conjugated goat antimouse IgG. Cross-reaction of MAb with muscle, kidney, liver, fibroblasts, and other cell types not containing lipid droplets was not observed in primary cultures. Adipocyte precursors were obtained from 18-d chick embryo adipose tissue by collagenase digestion to investigate complement-mediated cytotoxicity of preadipocytes. Cultures were maintained in Medium 199 with 5% fetal bovine serum (FBS) for 4 d. Subsequently, Medium 199 supplemented with 10% chicken serum initiated adipocyte differentiation. At Day 5 postinoculation, individual or combinations of MAb were administered to preadipocyte cultures; rabbit complement was added 30 min later. After 1 d of incubation, four of the six individual MAb with complement significantly (P < 0.05) reduced the number of fat cell clusters that developed by 40 to 60%. These MAb in the presence of complement also significantly (P < 0.05) reduced mean cell width and apparent cell area or cell cluster area of lipid-containing cells. Neither MAb nor complement alone reduced fat cell cluster number, cell size, or cluster size. Treatment with pools of two and four MAb decreased the total amount of MAb protein required to reduce fat cell cluster number. Four antibodies, alone or in combination, reduced fat cell cluster development in a complement-dependent manner.

Adipocytes↗
PubMed2000

The diagnosis and management of infiltrating nodular recto-vaginal endometriosis.

This paper reviews the history of infiltrating recto-vaginal endometriosis, its clinical and histological diagnosis, together with discussion of treatment options available. Important new work demonstrates significant serious symptomatology which patients suffer, and the relief that can be obtained by radical surgical excision. However this treatment is only available in certain specialist centres. The appropriate methods of management are yet to be subject to a proper randomized control trial, and results of treatment can only be assessed by meticulous recording of patient signs and symptomatology pre- and post-operation associated with histological confirmation of the disease.

Endometriosis↗