PubMed Health⌕ Search

Biomedical subjects

D M Black

Publications and source records attributed to D M Black.

At least 19 recordsLinked to original sources
PubMed1999

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Adult↗
PubMed1999

Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines.

We identified CAVEOLIN-1 as a candidate for a tumour suppressor gene mapping to human chromosome 7q31.1. A number of studies suggest that caveolin could function as a tumour suppressor. Expression of caveolin, and in turn the number of caveolae within a cell, are inversely correlated with the transforming ability of numerous oncoproteins, including H-ras, v-abl, and bcr-abl, and caveolin is a major transformation-dependent substrate of v-src. Heterologous expression of caveolin has been shown to abrogate anchorage-independent growth and induce apoptosis in transformed fibroblasts and also to suppress anchorage-independent growth in human mammary carcinoma cells. We have analysed the status and expression of the human CAVEOLIN-1 gene in primary tumours and tumour-derived cell lines. We found no evidence for mutation of CAVEOLIN-1 in human cancers. Additionally, we found that while the first two exons of CAVEOLIN-1 are associated with a CpG island, this is not methylated in either primary tumours or in tumour-derived cell lines in which Caveolin-1 expression is low or undetectable. The level of expression of Caveolin-1 does not correlate with loss of heterozygosity at the CAVEOLIN-1 locus in these same cell lines. Contrary to other published studies, we have shown that CAVEOLIN-1 is not expressed in normal breast ductal epithelial cells in vivo. CAVEOLIN-1 is however highly expressed in breast myoepithelial cells and its expression is retained in tumours derived from breast myoepithelium. Together our data refute a role for CAVEOLIN-1 as a breast tumour suppressor gene in vivo.

Breast Neoplasms↗
PubMed1999

The perioperative complication rate of orthopedic surgery in sickle cell disease: report of the National Sickle Cell Surgery Study Group.

Orthopedic disease affects the majority of sickle cell anemia patients of which aseptic necrosis of the hip is the most common, occurring in up to 50% of patients. We conducted a multicentered study to determine the perioperative complications among sickle cell patients assigned to different transfusion regimens prior to orthopedic procedures: 118 patients underwent 138 surgeries. The overall serious complication rate was 67%. The most common of these were excessive intraoperative blood loss, defined as in excess of 10% of blood volume. The next most common complication was sickle cell-related events (acute chest syndrome or vaso-occlusive crisis), which occurred in 17% of cases. While preoperative transfusion group assignment did not predict overall complication rates, higher risk procedures were associated with significantly higher rates of overall complications. Transfusion complications were experienced by 12% of the patients. Two patients died following surgery. Both deaths were associated with an acute pulmonary event. The 52 patients undergoing hip replacements experienced the highest rate of complications with excessive intraoperative blood loss occurring in the majority of patients. Sickle cell-related events occurred in 19% of patients, and surgical complications occurred after 15% of hip replacements and included postoperative hemorrhage, dislocated prosthesis, wound abscess, and rupture of the femoral prosthesis. There were twenty-two hip coring procedures. Acute chest syndrome occurred in 14% of the patients. Overall, decompression coring was a safer, shorter operation. A randomized prospective trial to determine the perioperative and long-term efficacy of core decompression for avascular necrosis of the hip in sickle cell disease is needed. In conclusion, this study demonstrates a high rate of perioperative complications despite compliance with sickle cell perioperative care guidelines. Pulmonary complications and transfusion reactions were common. This study supports the results previously published by the National Preoperative Transfusion in Sickle Cell Disease Group. These results stated that a conservative preoperative transfusion regimen to bring hemoglobin concentration to between 9 and 11 g/dl was as effective as an aggressive transfusion regimen in which the hemoglobin S level was lowered to 30%.

Adolescent↗
PubMed1999

The BRCA2 transactivation domain does not interact with JNK.

The N-terminal region of BRCA2 has the capacity to activate transcription when fused to a heterologous DNA binding domain and includes a segment with amino acid similarity to the JNK-docking site in the cellular JUN protein. However, unlike JUN, we have determined that this region of BRCA2 neither interacts with nor serves as a substrate for JNK, or any other kinase that can be detected in extracts from either fibroblasts or epithelial cells. While this clearly does not rule out a transcriptional role for BRCA2, our findings indicate that BRCA2 is not regulated by the JNK pathway in a manner analogous to JUN. Genes Chromosomes Cancer 25:407-409, 1999.

BRCA2 Protein↗
PubMed1999

Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial.

BACKGROUND: The positive association between body weight and bone mineral density (BMD) is well documented; in contrast, the effect of changes in body weight on BMD is not well understood, particularly, in normal-weight populations. OBJECTIVE: We examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y. DESIGN: All women were participating in a clinical trial known as The Women's Healthy Lifestyle Project and were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial. RESULTS: The intervention group (n = 115) experienced a mean (+/-SD) weight loss of 3.2 +/- 4.7 kg over the 18 mo compared with a weight gain of 0.42 +/- 3.6 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group (0.81 +/- 1.3%) than in the control group (0.42 +/- 1.1%); a similar, although nonsignificant pattern was observed for the loss in spine BMD: 0.70 +/- 1.4% and 0.37 +/- 1.5% (P = 0.093) in the intervention and control groups, respectively. Large increases in physical activity attenuated spine BMD loss, but had no significant effect on BMD loss at the hip. CONCLUSIONS: The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss.

Adult↗
PubMed1999

Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group.

Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age >/=65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20-25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20-25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.

Aged↗
PubMed1999

Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. Study of Osteoporotic Fractures Research Group.

Although vertebral deformities are known to predict future vertebral deformities, little is known about their ability to predict other osteoporotic fractures. We examined the association between prevalent vertebral deformities and incident osteoporotic fractures in the Study of Osteoporotic Fractures, a prospective study of 9704 women aged 65 years and older. Prevalent vertebral deformities were determined morphometrically from spinal radiographs at baseline and incident deformities from repeat spinal radiographs after a mean of 3.7 years. Appendicular fractures were collected by postcard every 4 months for a mean of 8.3 years. During follow-up, 389 women with new vertebral deformities, 464 with hip fractures, and 574 with wrist fractures were identified. Prevalent vertebral deformities were associated with a 5-fold increased risk (relative risk 5.4, 95% confidence interval [CI] 4.4, 6.6) of sustaining a further vertebral deformity; the risk increased dramatically with both the number and severity of the prevalent deformities. Similarly, the risks of hip and any nonvertebral fractures were increased with baseline prevalent deformity, with relative risks of 2.8 (95% CI 2.3, 3.4) and 1.9 (95% CI 1.7, 2.1), respectively. Risk increased with number and severity of deformities. These associations remained significant after adjustment for age and calcaneal bone mineral density (BMD). Although there was a small increased risk of wrist fracture, this was not significant after adjusting for age and BMD. In conclusion, the presence of prevalent morphometrically defined vertebral deformities predicts future vertebral and nonvertebral fractures, including hip but not wrist fractures. Spinal radiographs identifying prevalent vertebral deformities may be a useful additional measurement to classify further a woman's risk of future fracture.

Aged↗
PubMed1999

Biochemical markers of bone turnover and prediction of hip bone loss in older women: the study of osteoporotic fractures.

To examine the ability of commercially available biochemical markers of bone formation and resorption to predict hip bone loss, we prospectively obtained serum and timed 2-h urine specimens from 295 women age 67 years or older who were not receiving estrogen replacement therapy. Serum was assayed for two markers of bone formation: osteocalcin (OC) and bone-specific alkaline phosphatase (BALP). Urine specimens were assayed for four markers of bone resorption: N-telopeptides (NTX), free pyridinolines (Pyr), free deoxypyridinoline (Dpyr), and C-telopeptides (CTX). Measurements of hip bone mineral density were made at the time the samples were collected and then repeated an average of 3.8 years later. Higher levels of all four resorption markers were, on average, significantly associated with faster rates of bone loss at the total hip, but not at the femoral neck. Women with OC levels above the median had a significantly faster rate of bone loss than women with levels below the median, but there was no significant association between levels of BALP and hip bone loss. The sensitivity and specificity of higher marker levels for predicting rapid hip bone loss was limited, and there was considerable overlap in bone loss rates between women with high and low marker levels. We conclude that higher levels of urine NTX, CTX, Pyr, Dpyr, and serum OC are associated with faster bone loss at the hip in this population of elderly women not receiving estrogen replacement therapy, but these biochemical markers have limited value for predicting rapid hip bone loss in individuals.

Aged↗
PubMed1999

The radiologist and the patient: breaking bad news.

Radiologists may be asked to disclose results directly to patients. Studies of radiologist-patient communication show that radiologists have a direct responsibility to their patients, that many patients wish to learn the results of imaging tests from the radiologist at the time of the examination, and that many referring physicians support the principle of radiologists disclosing results when patients ask for them. In some areas, such as breast imaging and interventional radiology, disclosure by radiologists is very common. The authors, who work in a perinatology unit in which obstetrical ultrasonography is performed, have developed a template to help them with the often-emotional interactions associated with pregnancy failure. They recommend that radiologists inform the patient clearly of the examination results, choosing everyday words such as "miscarriage" and "pregnancy." They also recommend that physicians show compassion, acknowledge patients' grief and inform the referring physician as soon as possible. These steps should be part of a policy of direct, honest communication with patients.

Female↗
PubMed1998

Prostate cancer: new therapies in the pipeline?

Cancer of the prostate gland is the highest unavoidable cause of cancer mortality in men. The recent identification and characterisation of genes specifically expressed in prostate cancer helps us to understand its molecular basis and should offer new therapeutic avenues to combat this disease.

Antigens, Neoplasm↗
PubMed1998

The association of radiographically detected vertebral fractures with back pain and function: a prospective study.

BACKGROUND: Vertebral fractures are a hallmark of postmenopausal osteoporosis and an important end point in trials of osteoporosis treatment, but the clinical significance of these fractures remains uncertain. OBJECTIVE: To determine the association of new vertebral fractures with back pain and back-related functional limitation in older women. DESIGN: Prospective observational study. SETTING: Multicenter Study of Osteoporotic Fractures. PARTICIPANTS: 7223 white women aged 65 years and older. MEASUREMENTS: Lateral spine radiographs were obtained at baseline and at a follow-up examination an average of 3.7 years later. Prevalent and incident radiographic vertebral fractures were assessed by quantitative morphometry. Frequency and severity of back pain, disability in doing six activities involving the back, and days of bed rest and days of limited activity due to back pain were assessed annually by questionnaire during follow-up. RESULTS: Among women without a vertebral fracture at baseline, those with at least one incident vertebral fracture were more likely to have increased back pain (odds ratio [OR], 2.4 [95% CI, 1.7 to 3.3]) and back disability (OR, 2.6 [CI, 1.9 to 3.7]) and at least 1 day of bed rest due to back pain (OR, 6.7 [CI, 4.4 to 10.2]) and 7 days of limited activity due to back pain per year (OR, 3.8 [CI, 2.7 to 5.0]). Among women with a fracture at baseline, those with an incident vertebral fracture also had a greater risk for increased back pain (OR, 2.0 [CI, 1.4 to 2.8]) and back disability (OR, 2.2 [CI, 1.5 to 3.1]) and at least 1 day of bed rest (OR, 7.9 [CI, 4.9 to 12.9]) and 7 days of limited activity per year (OR, 3.5 [CI, 2.4 to 5.0]). Women with incident fracture had about 10 additional limited-activity days and 1 to 2 days of bed rest per year. New vertebral fractures that did not come to medical attention were associated with increased back pain and functional limitation. CONCLUSION: New vertebral fractures, even those not recognized clinically, are associated with substantial increases in back pain and functional limitation due to back pain in older white women. Prevention of new vertebral fractures should reduce the burden of back pain and functional limitation in women with vertebral osteoporosis.

Activities of Daily Living↗
PubMed1998

An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG-CoA reductase inhibitor.

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) have been used for a decade to lower low-density lipoprotein (LDL) cholesterol levels and to improve cardiovascular disease and clinical outcomes. OBJECTIVE: To evaluate the safety profile of atorvastatin (Lipitor). METHODS: Data were pooled for 21 completed (2502 patients) and 23 ongoing (1769 patients) clinical trials of atorvastatin conducted in US and international community- and university-based research centers. In these trials, patients with lipid disorders received atorvastatin at dosages of 10 to 80 mg/d. The majority of patients had moderate to severe hypercholesterolemia and were treated from 4 weeks to more than 24 months. MAIN OUTCOME MEASURES: Transaminase and creatine phosphokinase levels and adverse events were recorded. RESULTS: Atorvastatin was well tolerated; fewer than 2% of the atorvastatin-treated patients withdrew due to drug-attributable adverse events. The overall adverse event profile for atorvastatin was similar to that observed with other statins. The most common adverse events with atorvastatin as well as with other statins tested were constipation, flatulence, dyspepsia, and abdominal pain. Approximately 5% of atorvastatin-treated patients had serious adverse events; only 2 of these events were possibly associated with treatment. Thirty patients (0.7%) had confirmed transaminase elevations greater than 3 times the upper limit of the normal range. Most elevations occurred within 16 weeks of beginning treatment. No patients had a conclusive characterization of drug-induced myopathy. CONCLUSIONS: The safety profile of atorvastatin was consistent with that of all statins tested and was similar to that seen in all compounds of this class.

Acyl Coenzyme A↗
PubMed1998

Cloning and characterization of human and mouse telomerase RNA gene promoter sequences.

Variation in telomerase activity is correlated with cellular senescence and tumour progression. However, although the enzymatic activity of telomerase has been well studied, very little is known about how expression of telomerase genes is regulated in mammalian cells. We have therefore cloned the promoter regions of the human (hTR), and mouse, (terc), telomerase RNA genes in order to identify the regulatory elements controlling telomerase RNA gene transcription. 1.76 kb encompassing the hTR gene promoter region was sequenced, as was 4 kb encompassing the terc promoter. No significant sequence similarity could be detected in comparisons between human and mouse 5'-regions, flanking the transcribed sequences. However, both the human and mouse telomerase RNA genes are within CpG islands and may therefore be under the regulation of DNA methylation. Transient expression of hTR-reporter gene constructs in HeLa and GM847 cells identified the elements responsible for promoter activity are contained in a 231 bp region upstream of the transcriptional start site. Transient expression of terc-reporter gene constructs in Swiss3T3 and A9 cells identified the elements responsible for promoter activity are contained in a 73 bp region upstream of the transcriptional start site. These studies have implications for novel transcription targeted cancer therapies.

Animals↗
PubMed1998

Comparison of the Heart and Estrogen/Progestin Replacement Study (HERS) cohort with women with coronary disease from the National Health and Nutrition Examination Survey III (NHANES III)

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) is the first large clinical trial designed to test the efficacy of postmenopausal estrogen/progestin therapy for secondary prevention of coronary heart disease (CHD). To examine the representativeness of the HERS cohort to the general population of postmenopausal women with CHD, we compared the baseline cardiovascular risk factor data from HERS with similar data from women presumed to have CHD from the National Health and Nutrition Examination Survey (NHANES) III. METHODS: Age, race, and cardiovascular disease risk factors were compared in the 2763 postmenopausal women younger than 80 years old, with a uterus, and with documented CHD in HERS versus 145 similarly aged women with clinical or electrocardiographic evidence of CHD from phase I of NHANES III. RESULTS: There were fewer current smokers in HERS (13%) than in the NHANES cohort (21.7%, p = 0.05). Similarly, a history of hypertension was less prevalent in HERS (58.6%) than in the NHANES cohort (69.3%, p = 0.03). Women with fasting triglyceride levels >3.39 mmol/L or fasting glucose levels >16.6 mmol/L were excluded from HERS, resulting in fewer diabetics (22.9% vs 29.5%, p = 0.26) and lower serum triglyceride levels (1.88 mmol/L vs 2.25 mmol/L, p = 0.19) in HERS versus the NHANES cohort. Systolic and diastolic blood pressure, body mass index, physical activity, and total LDL and HDL cholesterol were not significantly different between the two groups. CONCLUSIONS: The HERS cohort had fewer CHD risk factors than women with myocardial infarction or angina in NHANES III, although comparison is hindered by differences in selection criteria. The many women with diabetes and hypertriglyceridemia in the NHANES cohort emphasizes the importance of testing strategies for secondary prevention of CHD in this high-risk subgroup.

Aged↗