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D Black

Publications and source records attributed to D Black.

At least 55 records · Page 3Linked to original sources
PubMed1999

Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group.

OBJECTIVE: To investigate whether the incidence of vertebral fractures is related to the magnitude of change in bone mineral density (BMD) during alendronate treatment. METHODS: Women in this study were age 55-81 years (n = 2,984). While participating in the Fracture Intervention Trial, they received 5 mg/day of alendronate for 2 years followed by 10 mg/day for the remaining 12-30 months of the study. Their BMD was measured at baseline and at 12 and 24 months, and spine radiographs were obtained at baseline and again at 36 or 48 months to identify new vertebral fractures. RESULTS: After 12 months of alendronate treatment, 35% of participants had increases of > or =3% in total hip BMD, and 21% had either decreased total hip BMD or no change. Women who had larger increases in total hip BMD during the first 12 months had a lower incidence of new vertebral fractures during the entire followup period. Only 3.2% of women with increases of > or =3% in total hip BMD experienced new vertebral fractures, whereas twice as many women (6.3%) whose BMD declined or stayed the same experienced new fractures (adjusted odds ratio 0.45, 95% confidence interval 0.27-0.72). Similar patterns were observed for spine BMD at 12 months, and for both sites using change in BMD at 24 months. CONCLUSION: Women with increases of > or =3% in BMD during the first 1 or 2 years of alendronate treatment had the lowest incidence of new vertebral fractures. These findings suggest that, among women taking antiresorptive agents, greater increases in BMD are associated with lower risk of new vertebral fractures.

Aged↗
PubMed1999

Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor.

BACKGROUND: An abundance of eukaryotic initiation factor 4E (eIF4E), a rate-limiting initiation component in protein synthesis of mRNAs with long 5'-UTRs, has been shown to upregulate a number of oncogene products. Elevation of eIF4E protein has been detected both in infiltrating ductal carcinoma of the breast (IDCA) and in head and neck squamous cell carcinoma (HNSCC) specimens. We hypothesized that malignant progression in solid tumor is associated with progressive eIF4E gene amplification and protein overexpression in cells sampled from the tumor-free resection margin, transition zone (area adjacent to cancer), and tumor core (center of tumor). MATERIALS AND METHODS: Thirty-eight resected specimens were evaluated: 10 IDCA, 13 HNSCC, and 15 benign specimens from similar sites of noncancer patients. IDCA and HNSCC specimens were divided into three different zones: (1) tumor core, (2) transition zone, and (3) tumor-free zone. Quantitative PCR for the eIF4E gene and Western blots for the eIF4E protein were performed on each of these zones and on the normal controls of benign tissue. Immunohistochemical staining was performed to localize the eIF4E protein overexpression in situ. RESULTS: The eIF4E gene was amplified in the tumor core of both IDCA (3.8 +/- 1.4, P < 0.05, Student's t test) and HNSCC (4.3 +/- 1.4, P < 0.05) specimens. Similarly, the eIF4E protein was overexpressed in the cells from these same sites (17.4 +/- 7.3- and 14.0 +/- 9.7-fold elevation, respectively, P < 0.0001). In the transition zone of IDCA and HNSCC, the degrees of eIF4E gene amplification (4.2 +/- 1.0 and 3.7 +/- 1.2, respectively) and overexpression (4.0 +/- 1.0 and 4.4 +/- 4.6, respectively) were intermediate. In contrast, the eIF4E gene copy number and protein level were near baseline in the tumor-free zone. CONCLUSIONS: Progressive eIF4E gene amplification and protein overexpression were present in cells sampled from the microscopically tumor-free margin to tumor core in surgical specimens of both HNSCC and IDCA. In this study, eIF4E gene amplification and protein overexpression appear to be associated with malignant progression in these two solid tumors.

Blotting, Western↗
PubMed1999

Selecting screening criteria for clinical trials: an example from the Systolic Hypertension in the Elderly Program.

In clinical trials that study people with a continuous measure defined categorically, even repeated measurements within a visit and over successive visits do not prevent error-free classification. We describe the design of a screening procedure for the Systolic Hypertension in the Elderly Program (SHEP), a randomized clinical trial designed to test whether regular administration of antihypertensive medication reduces the risk of stroke in elderly persons with isolated systolic hypertension. Data from a pilot study performed before the inauguration of SHEP allowed empirical study of a variety of possible screening rules for SHEP. A desirable screening rule would require only two screening visits, would lead to a randomized cohort with high mean systolic blood pressure, and would not impede recruitment. We emphasize two classes of rules, "serial" and "conditional." A serial rule uses only the values observed at a given screen to determine eligibility to proceed to the next screen. A conditional rule uses the value observed at a given screen along with values already observed to determine eligibility to proceed. For the SHEP study, we chose a conditional rule for screening because of its efficiency in identifying eligible participants. Our approach to selection of screening rules should be applicable to other clinical trials in which the measurement that defines the primary entry criterion has considerable measurement error.

Aged↗
PubMed1999

Vascular surgical society of great britain and ireland: superficial femoral angioplasty

BACKGROUND: Superficial femoral angioplasty (percutaneous transluminal angioplasty, PTA) is a widely performed therapeutic modality used throughout the UK in the treatment of intermittent claudication. However, there is still concern over its efficacy in the management of atherosclerotic occlusive disease. Long-term outcome was examined in patients undergoing PTA for short (less than 10 cm) occlusions or stenoses. METHODS: Data were collected prospectively for 413 patients undergoing femoral angioplasty and entered into a database for long-term outcome analysis. Patients were seen at 3, 6 and 12 months and at yearly intervals. Doppler ultrasonography and clinical assessment were performed in all patients and duplex imaging was carried out in those in whom there was doubt about patency. Finally, surviving patients were simply questioned as to whether they felt the original PTA to have been worthwhile. RESULTS: Mean follow-up time was 7 (range 2-11) years. Excluding an initial technical failure rate of 8 per cent, cumulative primary patency at 1, 2, 3, 4 and 5 years was 64, 55, 36, 21 and 14 per cent respectively. Moreover, clinical assessment revealed improvement of the presenting complaint in only 40, 29, 17, 9 and 7 per cent respectively. CONCLUSION: Superficial femoral PTA does not appear to be effective in the management of intermittent claudication in most patients.

Journal Article↗
PubMed1999

Vascular surgical society of great britain and ireland: influence of contralateral stenosis on long-term mortality rate following carotid surgery

BACKGROUND: Recent evidence suggests that high-grade contralateral stenosis has an adverse effect on perioperative morbidity in carotid endarterectomy (CEA). The relationship between contralateral high-grade stenosis and long-term survival after CEA was examined. METHODS: Three hundred and twenty-seven patients undergoing 333 CEA operations were entered prospectively into a database and long-term follow-up was instituted. Cardiac and stroke risk factors were identified before operation and correlated with long-term survival and cause of death. RESULTS: Mean age at operation was 68 (range 42-86) years. Median follow-up was 2 (range 1-8) years. There were 45 deaths (seven perioperative), 17 myocardial, 16 from stroke (four perioperative), five from neoplasia, three respiratory and four others. The cumulative 5-year survival rate was 75 per cent. Patients with high-grade contralateral stenosis (greater than 80 per cent) had a significantly reduced life expectancy after CEA (P < 0. 05). CONCLUSION: Severe contralateral carotid disease is not only an adverse perioperative risk factor but also has negative implications for survival of the patient in the longer term. Following CEA, patients in general have a lower life expectancy than a normal age-matched population.

Journal Article↗
PubMed1999

Lamotrigine attenuates cortical glutamate release during global cerebral ischemia in pigs on cardiopulmonary bypass.

BACKGROUND: The dose-response effects of pretreatment with lamotrigine (a phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine cerebral ischemia model during cardiopulmonary bypass were studied. METHODS: Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, followed by 40 min of reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen metabolism was calculated using cerebral blood flow (radioactive microspheres) and arterial-venous oxygen content gradients. Concentrations of microdialysate glutamate and aspartate were quantified; electroencephalographic signals were recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for metabolic profile. RESULTS: Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in cerebral metabolism, electroencephalographic scores, cortical metabolites, brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and blood. CONCLUSIONS: Lamotrigine 50 mg/kg significantly attenuated excitatory neurotransmitter release during normothermic cerebral ischemia during cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine caused arterial and venous dilation, which limits its clinical usefulness.

Analgesics↗
PubMed1998

Are menopausal symptoms associated with bone mineral density and changes in bone mineral density in premenopausal women?

BACKGROUND: The relationship between menopausal symptoms and bone mineral density (BMD) was examined in 290 premenopausal women, ages 44-50 years, participating in a randomized clinical trial of a dietary and exercise intervention: The Women's Healthy Lifestyle Project. METHODS: Information on hot flashes (presence, absence), menstrual cycles (irregular, regular) and menstrual flow per period (variable, same) over the past 6 months was collected at entry. Participants reporting at least one menopausal symptom were classified as symptomatic and compared to those having no symptoms. Bone mineral density (BMD) at the lumbar spine (L1-L4), total hip and whole-body were made at baseline and at 30 months using a dual-energy X-ray absorptiometer (Hologic QDR 2000 densitometer). RESULTS: Baseline BMD at the spine, hip and whole-body were significantly reduced in women reporting menopausal symptoms compared to asymptomatic women, after adjustment for age, weight and intervention status (all p < 0.05). Women with irregular menstrual cycles had greater annualized rates of bone loss at the spine and hip than asymptomatic women (spine, -0.77 (1.6)% per year vs. -0.19 (1.0)% per year, p = 0.0043; hip, -0.37 (1.1)% per year vs. -0.04 (1.0)% per year, p = 0.061), after adjustments for age, percent change in weight, intervention status, and baseline BMD. Similar findings were not found for whole-body BMD. CONCLUSIONS: These results suggest that menopausal symptoms are useful for the effective identification of premenopausal women at higher risk of low BMD and perhaps, of osteoporosis.

Absorptiometry, Photon↗
PubMed1998

The dying child.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1998

Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction.

The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study is to determine whether early, rapid, and profound cholesterol lowering therapy with atorvastatin can reduce early recurrent ischemic events in patients with unstable angina or non-Q-wave acute myocardial infarction. Within 1 to 4 days of hospitalization for one of these conditions, 2,100 patients will be randomly assigned to receive atorvastatin, 80 mg/day, or placebo in a double-blind design. Both groups receive dietary counseling. Over a 16-week follow-up period, the primary outcome measure is the time to occurrence of an ischemic event, defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia requiring emergency rehospitalization. Secondary outcome measures are the time to occurrence and incidence of each of the primary outcome components, as well as nonfatal stroke, worsening angina, congestive heart failure requiring hospitalization, and need for coronary revascularization not anticipated before randomization. The sample size of 1,050 patients in each group is expected to provide 95% power to detect a 30% reduction in the primary outcome measure with a 5% level of significance. The results of the MIRACL study will determine the utility of profound cholesterol lowering as an early intervention in acute coronary syndromes.

Angina, Unstable↗