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Biomedical subjects

D Black

Publications and source records attributed to D Black.

At least 37 records · Page 2Linked to original sources
PubMed2000

Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group.

CONTEXT: The principle of "regression to the mean" predicts that patients with unusual responses to treatment might represent outliers who are likely to have more typical responses if treatment is continued without change. OBJECTIVE: To test whether women who lose bone mineral density (BMD) during the first year of treatment for osteoporosis continue to lose BMD if the same treatment is continued beyond 1 year. DESIGN AND SETTING: Two randomized, double-blind, placebo-controlled trials in 11 US clinical research centers for the Fracture Intervention Trial and 180 centers in the United States and other countries for the Multiple Outcomes of Raloxifene Evaluation Trial. PARTICIPANTS AND INTERVENTIONS: Postmenopausal women with low BMD assigned to treatment with 5 mg/d of alendronate sodium in the Fracture intervention Trial who completed 2 years of BMD monitoring and adhered to study medication (n = 2634), and postmenopausal women with osteoporosis assigned to treatment with 60 or 120 mg/d of raloxifene hydrochloride in the Multiple Outcomes of Raloxifene Evaluation trial who similarly completed 2 years of monitoring while adhering to study medication (n = 3954). MAIN OUTCOME MEASURES: Baseline, 12-, and 24-month hip and spine BMD. RESULTS: Women with the greatest loss of BMD during the first year of treatment were the most likely to gain BMD during continued treatment. Specifically, among women taking alendronate whose hip BMD decreased by more than 4% during the first year, 83% (95% confidence interval [CI], 82%-84%)had increases in hip BMD during the second year, with an overall mean increase of 4.7%. In contrast, those who seemed to gain at least 8% during the first year lost an average of 1% (95% CI, 0.1%-1.9%) during the next year. Similar results were observed among women taking raloxifene for 2 years. CONCLUSIONS: Our data suggest that most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year. These results illustrate the principle of regression to the mean and suggest that effective treatments for osteoporosis should not be changed because of loss of BMD during the first year of use.

Absorptiometry, Photon↗
PubMed2000

Upper gastrointestinal tract safety profile of alendronate: the fracture intervention trial.

OBJECTIVES: To determine whether alendronate sodium treatment is associated with upper gastrointestinal (GI) tract adverse experiences (AEs)-particularly those of the stomach, duodenum, or esophagus-in the Fracture Intervention Trial, and to assess the relationship between alendronate use and upper GI tract events among women at increased risk for these outcomes. DESIGN: Randomized, double-blind, placebo-controlled trial with a mean follow-up of 3.8 years. Women were initially randomized to receive alendronate sodium, 5 mg/d, or placebo. After 2 years, the alendronate sodium dose was increased to 10 mg/d. PARTICIPANTS: A total of 6459 women aged 54 to 81 years recruited from 11 US clinical centers. All participants had low hip bone mineral density. Women with major upper GI tract disease (recent ulcers, upper GI tract bleeding, or use of daily medication for dyspepsia) were excluded. Regular nonsteroidal anti-inflammatory drug users were not excluded. MEASUREMENTS: Self-reported upper GI tract AEs were ascertained by interview every 3 months. Serious upper GI tract AEs were confirmed and classified by review of hospital records and endoscopy reports, if available. Upper GI tract AEs were further analyzed in 2 specified groups-gastroduodenal and esophageal-to examine events that might be related to upper GI tract mucosal irritation. Gastric and duodenal perforations, ulcers, and bleeding events were combined for analysis of these clinically important outcomes. RESULTS: The overall incidence of upper GI tract events was similar in the alendronate and placebo groups (47.5% vs. 46.2%; relative risk [RR], 1.02; 95% confidence interval [CI], 0.95-1.10). The incidence of gastroduodenal perforations, ulcers, and bleeding events was 1.6% in the alendronate group and 1.9% in the placebo group (RR, 0.86; 95% CI, 0.59-1.24). The incidence of nonspecific upper GI tract conditions, such as abdominal pain, dyspepsia, nausea, and vomiting, was also similar in the 2 groups. Esophageal events occurred in 10.0% and 9.4% of patients in the alendronate and placebo groups, respectively (RR, 1.06; 95% CI, 0.91-1.24). Esophagitis not reported as reflux was more common in the alendronate group (0.7%) than in the placebo group (0.4%), but not significantly so (RR, 1.71; 95% CI, 0.90-3.39). Alendronate use was not associated with a significant increase in upper GI tract events among women at increased risk for these events (those aged > or =75 years with previous upper GI tract disease or using nonsteroidal anti-inflammatory drugs). CONCLUSION: In these older women, upper GI tract complaints, particularly dyspepsia and abdominal pain, were common, but alendronate treatment was not associated with an increased incidence of upper GI tract events, even in high-risk subgroups.

Aged↗
PubMed2000

c-Jun does not mediate hepatocyte apoptosis following NFkappaB inhibition and partial hepatectomy.

Inhibition of the transcription factor nuclear factor kappa B (NFkappaB) induces marked hepatocyte apoptosis and liver dysfunction after partial hepatectomy (PH) in rats. Hepatocyte apoptosis may be due to direct inhibition of NFkappaB-induced hepatocyte survival genes or due to indirect increased signaling through the stress-activated protein kinase pathway (SAPK), resulting in increased c-Jun. c-Jun, an AP-1 transcription factor, induces apoptosis in fibroblasts. Our aim was to determine if hepatocyte apoptosis following inhibition of NFkappaB and partial hepatectomy in rats is due to increased c-Jun. Adult male Sprague-Dawley rats (200 g) were injected intraportally with 6 x 10(9) PFU adenoviral vector containing luciferase (Ad5Luc) or superrepressor IkappaB (Ad5IkappaB) transgene that inhibits NFkappaB translocation into the nucleus. Two-thirds PH was performed 24 h after vector administration, and the remnant liver was harvested 30 min or 24 h after PH. Northern and Western blots were performed to examine the presence of IkappaB and c-Jun. A GST c-Jun kinase assay was used to examine Jun-N-terminal kinase (JNK) activity. AP-1 DNA binding activity was assessed by electrophoretic mobility shift assay. TUNEL assay was performed to assess apoptosis. All rats receiving adenoviral vectors expressed the luciferase or superrepressor IkappaB transgenes. c-Jun mRNA, protein levels, and DNA binding activity were not increased in rats treated with Ad5IkappaB at 30 min after PH compared to rats injected with Ad5Luc. Jun kinase activity increased following partial hepatectomy, but activity was similar in Ad5Luc- and Ad5IkappaB-treated animals. AP-1 DNA binding activity was not altered substantially in rats treated with Ad5IkappaB. The percentage of apoptotic hepatocytes was similar between Ad5Luc- and Ad5IkappaB-injected animals at 0 h, but livers from Ad5IkappaB-treated rats had increased apoptosis at 24 h compared to Ad5Luc rats (24% vs. 4%) after PH. Hepatocyte apoptosis after NFkappaB inhibition and PH is not mediated by increased JNK activity or c-Jun.

Adenoviridae↗
PubMed2000

Risk of mortality following clinical fractures.

To examine the risk of mortality following all clinical fractures, we followed 6459 women age 55-81 years participating in the Fracture Intervention Trial for an average of 3.8 years. All fractures and deaths were confirmed by medical record or death certificate. Clinical fractures were fractures that came to medical attention. Fracture status was used as a time-dependent covariate in proportional hazards models. The 907 women who experienced a fracture were older, had lower bone mineral density and were more likely to report a positive fracture history. A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture. The age-adjusted relative risk (95% confidence intervals) of dying following a clinical fracture was 2.15 (1.36, 3.42). This primarily reflected the higher mortality following a hip fracture, 6.68 (3.08, 14.52); and clinical vertebral fracture, 8.64 (4.45, 16.74). Results were similar after adjusting for treatment assignment, health status and specific common comorbidities. There was no increase in mortality following a forearm or other fracture (non-hip, non-wrist, nonvertebral fracture). In conclusion, clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women.

Aged↗
PubMed2000

Lipid and apolipoprotein levels and distribution in patients with hypertriglyceridemia: effect of triglyceride reductions with atorvastatin.

Atorvastatin is a new hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor that has been demonstrated to be efficacious in reducing both triglyceride (TG) and cholesterol (CHOL) levels in humans. Twenty-seven (N = 27) patients with primary hypertriglyceridemia (TG > 350 mg/dL) were studied before and after 4 weeks on atorvastatin treatment at a dosage of either 20 (n = 16) or 80 (n = 11) mg/d. The present report examines changes in the plasma levels of several apolipoproteins, including apolipoprotein C-II (apoC-II), apoC-III, and apoE, after atorvastatin. Dose-dependent reductions in both CHOL (20.3% v 43.1%) and TG (26.5% v 45.8%) for the low and high dose, respectively, have been reported in these individuals. In addition to the reductions in apoB commonly associated with the use of HMG-CoA reductase inhibitors, significant reductions in apoE (37% and 49%), apoC-II (28% and 42%), and apoC-III (18% and 30%) were observed with this agent at the 20- and 80-mg/d dosage, respectively. Using fast protein liquid chromatography (FPLC) to fractionate whole plasma according to particle size, the effect of atorvastatin on lipid and apolipoprotein distribution in 20 lipoprotein fractions was also determined. Our results indicate that after 4 weeks on atorvastatin, (1) there was a 2-fold increase in the CHOL content as assessed by the CHOL/apoB ratio for 13 subfractions from very-low-density lipoprotein (VLDL) to small low-density lipoprotein (LDL); (2) there was a statistically significant reduction in the percentage of plasma apoB associated with VLDL-sized particles (30.5% v 26.8%); (3) there was a preferential reduction in plasma apoE from non-apoB-containing lipoproteins with treatment; (4) the losses of apoC-II and apoC-III, on the other hand, were comparable for all lipoprotein fractions; and (5) the fraction of plasma TG associated with HDL was increased after treatment. These changes in lipids and apolipoproteins did not depend on the dose of atorvastatin. There was, on the other hand, a dose-dependent reduction in cholesteryl ester transfer protein (CETP) activity, defined as the percentage of 3H-cholesteryl oleate transferred from high-density lipoprotein (HDL) to LDL. CETP activity was reduced by 10.3% and 26.4% with the low and high dose of atorvastatin. Together, these composition data would be consistent with a net reduction in the number of TG-rich lipoproteins that may be explained by (1) a reduction in VLDL synthesis, (2) a preferential removal of VLDL without conversion to LDL, and (3) a preferential accelerated removal of a subpopulation of LDL.

Anticholesteremic Agents↗
PubMed2000

Characterisation of gravity-induced facial skin oedema using biophysical measurement techniques.

BACKGROUND/AIMS: In humans, the microgravity environment can be expected to induce swelling of facial tissues and shrinking of the tissues in the lower limbs, together with a loss in body weight. To evaluate fluid shifts in skin, the head-down bed-rest model was used. The aim of the present study was to evaluate the appearance of facial oedema in subjects undergoing anti-orthostatic bed-rest at an angle of -10 degrees. METHODS: The forehead of each of four subjects was measured before and after 1, 10 and 24 h in this head-down tilt position. At these time points, interstitial fluid migration and facial oedema were assessed using a high resolution B-scan ultrasound and a device for measuring the skin's mechanical properties. RESULTS: The results obtained showed a progressive increase in dermal thickness and initial stress, and a reduction in stiffness and elasticity of the skin during the study period. CONCLUSIONS: This preliminary study has demonstrated the feasibility of the method in measuring fluid displacement and retention in the skin. Furthermore, it highlights the influence of fluids on the mechanical behaviour of the skin. These techniques could be used for studying the redistribution of liquid masses during periods spent in space.

Aerospace Medicine↗
PubMed2000

Effect of atorvastatin on blood lipid levels in the first 2 weeks of treatment: a randomized, placebo-controlled study.

BACKGROUND: The rate and degree of LDL cholesterol reduction, in the first 2 weeks of therapy, may relate to the early benefit of hydroxymethyl glutaryl coenzyme A reductase inhibitor therapy. In patients with similar baseline LDL cholesterol levels as in the Cholesterol and Recurrent Events (CARE) trial, we report the results of a 2-week placebo-controlled, double-blind investigation of 10 mg/day atorvastatin. METHODS AND RESULTS: The 22 participants were non-Hispanic whites younger than age 72 (average age 47 years) who were modestly overweight and had normal blood pressure. There were no significant baseline lipid and lipoprotein differences. By day 5, there were significant (P <.01) reductions in total cholesterol and LDL levels. The total cholesterol level fell by 25% (226 mg/dL to 169 mg/dL) and LDL cholesterol fell 35% by day 14 (P <.001). Triglyceride levels declined by 24% (from 137 mg/dL to 104 mg/dL) by day 14, but this was not statistically significant. There was no significant difference in HDL cholesterol. The total/HDL level dropped from 4.54 (day 0) to 3.32 (day 14), and the LDL/HDL level dropped from 2.92 to 1.88; both results were highly significant (P <. 001). CONCLUSION: The rapid lipid reduction observed with atorvastatin may benefit the vascular endothelium.

Adult↗
PubMed2000

POM + EBM = CPD?

Explore the source record for details and available documents.

Clinical Competence↗
PubMed2000

Albumin revisited.

Explore the source record for details and available documents.

Evidence-Based Medicine↗
PubMed2000

Vertebral fracture prevalence among women screened for the Fracture Intervention Trial and a simple clinical tool to screen for undiagnosed vertebral fractures. Fracture Intervention Trial Research Group.

OBJECTIVE: To evaluate the ability of self-reported risk factors to identify postmenopausal women likely to have extant vertebral fractures because approximately two thirds of women with radiographic evidence of vertebral fracture are unaware of the fracture. PATIENTS AND METHODS: Questionnaire and spinal radiographic data were collected from postmenopausal women with a femoral neck bone mineral density T score of -1.6 or lower during screening for the Fracture Intervention Trial. Logistic regression was used to identify risk factors for extant vertebral fractures and to derive a final multivariable model. RESULTS: Almost two thirds of 25,816 women 55 years and older met the bone density criterion, and 21% of those had an extant vertebral fracture. The final model consisted of 5 self-reported items: history of vertebral fracture, history of nonvertebral fracture, age, height loss, and diagnosis of osteoporosis. These were combined to yield a Prevalent Vertebral Fracture Index (PVFI). The prevalence of women with vertebral fracture varied from 3.8% to 62.3% over the range PVFI of 0 to greater than 5. Among the 13,051 women screened with spinal radiographs, a PVFI of 4 or greater identified 65.5% of women with vertebral fractures (sensitivity), with a specificity of 68.6%. Excluding 881 women who reported prior vertebral fractures reduced the sensitivity to 53.6 % and increased the specificity to 70.7% but did not alter the fracture prevalence at PVFI values less than 6. CONCLUSION: In this population, 5 simple questions identified women who were likely to have undiagnosed vertebral fractures. Further research is needed to determine the validity of this index in other populations, including women without low bone mineral density.

Age Distribution↗
PubMed2000

Demographics of the gay and lesbian population in the United States: evidence from available systematic data sources.

This work provides an overview of standard social science data sources that now allow some systematic study of the gay and lesbian population in the United States. For each data source, we consider how sexual orientation can be defined, and we note the potential sample sizes. We give special attention to the important problem of measurement error, especially the extent to which individuals recorded as gay and lesbian are indeed recorded correctly. Our concern is that because gays and lesbians constitute a relatively small fraction of the population, modest measurement problems could lead to serious errors in inference. In examining gays and lesbians in multiple data sets we also achieve a second objective: We provide a set of statistics about this population that is relevant to several current policy debates.

Adolescent↗
PubMed1999

The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.

CONTEXT: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting. OBJECTIVE: To determine whether women taking raloxifene have a lower risk of invasive breast cancer. DESIGN AND SETTING: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe. PARTICIPANTS: A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded. INTERVENTION: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets. MAIN OUTCOME MEASURES: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review. RESULTS: Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7). CONCLUSION: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.

Aged↗
PubMed1999

Competitive PCR to detect eIF4E gene amplification in head and neck cancer.

BACKGROUND: The protein eukaryotic initiation factor 4E (elF4E) binds to messenger ribonucleic acid (mRNA) as the initial step in protein synthesis. Overexpression of elF4E results in upregulation of specific proteins essential to cell growth and division. Overexpression of elF4E has been found in head and neck squamous cell carcinoma (HNSCC) and breast carcinoma. This study's purpose is to determine whether elF4E overexpression is present and associated with elF4E gene amplification in HNSCC. METHODS: Competitive polymerase chain reaction (PCR) was performed on eight HNSCC and seven intraoral benign lesions to determine the copy number of elF4E relative to a reference gene, gastrin. Western blots were performed to quantify elF4E protein expression. RESULTS: All eight HNSCC specimens demonstrated significant (p < .005) overexpression of elF4E protein (14.1+/-10.4) and elF4E gene amplification (4.5+/-1.2). Benign tissue did not exhibit elF4E protein overexpression or gene amplification. CONCLUSIONS: Overexpression and associated gene amplification of elF4E were present in HNSCC but not in benign tissue. Gene amplification of elF4E may be an important mechanism for elF4E overexpression.

Blotting, Western↗