RESUMEN
The association between the restriction length polymorphisms of the Vitamin D receptor (VDR) gene and the bone mineral density (BMD) or the rate of bone loss is still under debate. In a longitudinal study of untreated postmenopausal elderly women, we evaluated the relationship between the VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and the rate of bone loss over a 3-year period. We also examined the effect of adjustments for dietary and lifestyle factors on these associations. Before adjustments, the rate of femoral neck bone loss was - 3.76 +/- 1.58% in women with BB genotype and 0.45 +/- 0.65% in women with bb genotype, which was not significantly different. Upon adjustment for dietary and lifestyle factors, statistically significant (P = 0.03) bone loss was observed at femoral neck in women with BB genotype (- 3.66 +/- 2.44%) compared to that of bb genotype (2.39 +/- 1.32%). Similar results were observed with TaqI genotypes. The rates of bone loss at other skeletal sites were not different between VDR genotypes defined by BsmI and TaqI. VDR gene polymorphisms defined by ApaI and FokI were not related to the rate of bone loss.
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Resorción Ósea/prevención & control , Dieta , Estilo de Vida , Polimorfismo Genético , Receptores de Calcitriol/genética , Anciano , Densidad Ósea , Femenino , HumanosRESUMEN
BACKGROUND: The role of caffeine as a risk factor for bone loss is controversial. OBJECTIVE: Our goals were 1) to compare in both a cross-sectional study and a 3-y longitudinal study the bone mineral density (BMD) of postmenopausal women consuming high or low amounts of caffeine and 2) to study the interaction between caffeine intake, vitamin D receptor (VDR) polymorphism, and BMD in the longitudinal study. DESIGN: The results are derived from cross-sectional measurements of BMD in 489 elderly women (aged 65-77 y) and from longitudinal measurements made in 96 of these women who were treated with a placebo for 3 y. Changes in BMD were adjusted for confounding factors and were compared between groups with either low (< or =300 mg/d) or high (>300 mg/d) caffeine intakes and between the VDR genotype subgroups of the low- and high-caffeine groups. RESULTS: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (-1.90 +/- 0.97% compared with 1.19 +/- 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (-8.14 +/- 2.62%) than did women with the TT genotype (-0.34 +/- 1.42%) when their caffeine intake was >300 mg/d. CONCLUSIONS: Intakes of caffeine in amounts >300 mg/d ( approximately 514 g, or 18 oz, brewed coffee) accelerate bone loss at the spine in elderly postmenopausal women. Furthermore, women with the tt genetic variant of VDR appear to be at a greater risk for this deleterious effect of caffeine on bone.
Asunto(s)
Densidad Ósea/efectos de los fármacos , Densidad Ósea/genética , Cafeína/efectos adversos , Calcio/metabolismo , Osteoporosis Posmenopáusica/inducido químicamente , Receptores de Calcitriol/genética , Absorciometría de Fotón , Anciano , Cafeína/administración & dosificación , Estudios de Casos y Controles , Estudios Transversales , Registros de Dieta , Femenino , Genotipo , Humanos , Estudios Longitudinales , Osteoporosis Posmenopáusica/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Posmenopausia , Columna Vertebral , Vitamina DRESUMEN
OBJECTIVE: To evaluate the diagnostic and prognostic significance of ST-segment deviation detected by ambulatory Holter monitoring in unselected chest pain patients referred for coronary angiography. METHODS: Two hundred seventy-seven patients (71% were men) who underwent coronary angiography for evaluation of chest pain were studied with 24-h ambulatory Holter monitoring within 72 h of angiography. A lumen diameter reduction of > or = 50% was considered coronary artery disease. The ST-segment deviation was defined as > or = 1-mm deviation from the baseline lasting > or = 1 min separated by a minimum of 1 min. The patients were followed up for 65 +/- 21 months (mean +/- SD) for occurrences of death, myocardial infarction, hospitalization for unstable angina, and need for revascularization. RESULTS: Of the 277 patients, 223 (80%) had coronary artery disease. The prevalence of coronary artery disease was not significantly different in patients with (43 of 48 patients; 90%) and without (180 of 229 patients; 79%) Holter-detected ST-segment deviation. The diagnostic accuracy of Holter-detected ST-segment deviation in predicting the presence of coronary artery disease was poor (33%), with a sensitivity of 19% and a specificity of 91%. The presence of Holter-detected ST-segment deviation was not predictive of future cardiac events or death. CONCLUSION: The ST-segment changes detected on ambulatory Holter monitoring are of limited value in identifying coronary artery disease and predicting the future adverse cardiac events or death in unselected patients with chest pain.
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Angina de Pecho/diagnóstico , Electrocardiografía Ambulatoria , Adulto , Anciano , Anciano de 80 o más Años , Angina de Pecho/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Radiografía , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Benefits of aspirin and beta-blocker use in patients with coronary artery disease and angiotensin-converting enzyme (ACE) inhibitors in those with left ventricular systolic dysfunction are well documented in all age groups. OBJECTIVE: To investigate whether aspirin, beta-blockers, and ACE inhibitors are equally used in geriatric (> or =65 years) versus younger (<65 years) patients with coronary artery disease. SETTING: University-affiliated major academic hospital. METHODS: Records of 402 patients with coronary artery disease were analyzed for use of aspirin, beta-blockers, and ACE inhibitors. One hundred thirty patients with contraindications to use of these agents were excluded. RESULTS: Of 272 study patients, 85% were using aspirin and 71% beta-blockers. Among the patients with left ventricular systolic dysfunction, 79% were using ACE inhibitors. One hundred forty-seven patients were of geriatric age, whereas 125 were of younger age. No significant difference in the use of aspirin (82% versus 89%, P = 0.10), beta-blockers (71% versus 70%, P = 0.85), or ACE inhibitors (86% versus 69%, P = 0.13) was found between geriatric and younger patients. This lack of difference in use of cardiac medications between geriatric and younger patients persisted on gender-based subgroup analysis. On decade-of-age-based analysis, aspirin use was not equally distributed among all the decades of age (P < 0.005), but beta-blocker use was. CONCLUSION: Results of this study demonstrate equal use of aspirin, beta-blockers, and ACE inhibitors in geriatric versus younger patients with coronary artery disease. Aspirin use was not equally distributed among all the decades of age.
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Antagonistas Adrenérgicos beta/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aspirina/uso terapéutico , Enfermedad Coronaria/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Aspirina/efectos adversos , Enfermedad Coronaria/epidemiología , Estudios Transversales , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Published reports on the effect of alcohol consumption on bone mineral density (BMD) are inconsistent. OBJECTIVE: The objective of this study was to examine the relation between alcohol intake and BMD, calcitropic hormones, calcium absorption, and other biochemical indexes of bone and mineral metabolism in elderly women. DESIGN: The results presented are derived from baseline observations of 489 elderly women (aged 65-77 y) recruited for an osteoporosis study. The nondrinking group comprised 297 women and the drinking group comprised 148 women. Furthermore, the effect of different alcohol intakes (28.6 to 57.2 to 142.9 g/wk) was studied. RESULTS: Women who consumed alcohol had significantly higher spine (10%), total body (4.5%), and midradius (6%) BMD than did nondrinkers. An alcohol intake >28.6 g/wk was associated with higher BMD; maximum effect was seen with an intake of >28.6 to
Asunto(s)
Consumo de Bebidas Alcohólicas , Huesos/metabolismo , Absorciometría de Fotón , Absorción , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Densidad Ósea , Remodelación Ósea , Calcifediol/sangre , Calcitriol/sangre , Calcio/metabolismo , Colágeno/orina , Colágeno Tipo I , Etanol/efectos adversos , Femenino , Humanos , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Péptidos/orina , Radio (Anatomía) , Columna VertebralRESUMEN
Cigarette smoking has been implicated as a risk factor for osteoporosis. In the present study, the relationship between smoking and bone mineral density, calcitropic hormones, calcium absorption, and biochemical indices related to bone and mineral metabolism was examined at baseline, in subjects recruited for an osteoporotic study. The subjects included 489 elderly women, aged 65-77 years. After exclusions (thiazide users), 54 women constituted the smoking group and 390 women were classified as nonsmokers. The effect of frequency of smoking was also examined in this population (33 light smokers [<1 pack/day] and 21 heavy smokers [>1 pack/day]). Adjusted mean total body bone mineral density was 4% lower (0.968 +/- 0.019 vs. 1.009 +/- 0.004) and the total hip density was 6% lower (0.778 +/- 0.024 vs. 0.826 +/- 0.006) in heavy smokers compared with nonsmokers. At the other sites measured (spine, midradius, femoral neck, trochanter, and Ward's triangle), a similar nonsignificant trend was observed. The adjusted mean calcium absorption corrected for weight was lower (13%) both in light and heavy smokers compared with nonsmokers, and serum 25-hydroxyvitamin D was significantly lower (16%) in heavy smokers than nonsmokers. Serum parathryroid hormone (PTH) was higher in heavy smokers, but was not significantly different from that of nonsmokers. A significant increase in bone remodeling markers, serum osteocalcin (4.35 +/- 0.271 vs. 3.79 +/- 0. 066) and urine N-telopeptide/creatinine (NTx/Cr) ratio (74.5 +/- 5. 75 vs. 49.8 +/- 1.4) was seen in heavy smokers compared with nonsmokers. These results suggest that smoking lowers bone mineral density, and is a result of decreased calcium absorption associated with secondary hyperparathyroidism and increased bone resorption.
Asunto(s)
Huesos/metabolismo , Osteoporosis Posmenopáusica/etiología , Fumar/efectos adversos , Fumar/metabolismo , Absorción , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Densidad Ósea , Calcio/metabolismo , Estudios de Casos y Controles , Colágeno/orina , Colágeno Tipo I , Creatinina/orina , Femenino , Humanos , Osteocalcina/sangre , Osteoporosis Posmenopáusica/metabolismo , Péptidos/orina , Factores de Riesgo , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
OBJECTIVES: To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD. DESIGN: A retrospective chart analysis over 24 months. SETTING: A university Veterans Affairs medical center. PATIENTS: Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD. METHODS: Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV(1) percent predicted using American Thoracic Society guidelines (stage I, FEV(1) > or = 50%; stage II, FEV(1) 35 to 49%; stage III, FEV(1) < 35%). Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem. Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks. RESULTS: One-hundred seven patients with COPD (mean age +/- SD, 66.9 +/- 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14. 7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV(1) < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0. 0001), frequency of exacerbation (3.8 +/- 2.0 vs 1.6 +/- 0.91; p < 0. 001), history of previous pneumonia (64.3% vs 35.1 p < 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009) and use of maintenance steroids (32.1% vs 15.2% p = 0.052). Using stepwise logistic regression analysis to identify the top independent variables, the use of home oxygen (p = 0.0002) and frequency of exacerbation (p < 0.0001) correctly classified failures in 83.3% of the patients. Surprisingly, age, the choice of an antibiotic, and the presence of any one or more comorbidity did not affect the treatment outcome. CONCLUSION: The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.
Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Enfermedad Aguda , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Anciano , Atención Ambulatoria , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Comorbilidad , Eritromicina/efectos adversos , Eritromicina/uso terapéutico , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Humanos , Enfermedades Pulmonares Obstructivas/diagnóstico , Enfermedades Pulmonares Obstructivas/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug discontinuance. The fixed-dose combination of amlodipine/benazepril achieves its goal of effective BP lowering with a minimum of significant side effects.
Asunto(s)
Hipertensión/tratamiento farmacológico , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Amlodipino/uso terapéutico , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Benzazepinas/administración & dosificación , Benzazepinas/efectos adversos , Benzazepinas/uso terapéutico , Combinación de Medicamentos , Humanos , Lisinopril/efectos adversos , Lisinopril/uso terapéutico , Resultado del Tratamiento , Verapamilo/efectos adversos , Verapamilo/uso terapéuticoRESUMEN
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have become the drugs of choice for the treatment of patients with hypercholesterolemia. However, one of the major concerns with these drugs is cost. In an attempt to develop a cost-effective treatment strategy for patients referred to our lipid clinic, we conducted a meta-analysis to estimate the lipid-lowering efficacy of the various HMG-CoA reductase inhibitors alone or in combination with niacin or cholestyramine. Based on cholesterol-lowering efficacy estimates derived from a literature-based meta-analysis, we performed a population-based treat-to-target analysis. Fifty-six trials with 101 monotherapy cohorts and 20 trials with 31 combination-therapy cohorts (573 patients) were included in the meta-analysis. Based on reduction in low-density lipoprotein cholesterol (LDL-C), the most effective monotherapy was atorvastatin and the least effective monotherapy was fluvastatin. Combination therapy was more effective in reducing LDL-C than monotherapy with the respective HMG-CoA reductase inhibitor. However, on the basis of dollars spent per percentage of LDL-C reduction, combination therapy was frequently less cost-effective than monotherapy. In addition, combination therapy was associated with a higher rate of noncompliance and a greater risk of drug-drug interactions. As a result, we based our treat-to-target analysis on the use of monotherapy as first-line treatment, with combination therapy reserved for patients failing to achieve the target LDL-C levels of the US National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) with monotherapy. In the population-based treat-to-target analysis, atorvastatin was the most cost-effective drug for high-risk patients (those with coronary heart disease [CHD]), whereas fluvastatin was the most cost-effective agent for low-risk patients (<2 risk factors for CHD) and moderate-risk patients (> or =2 risk factors for CHD). If 1 drug is chosen to treat all patients (i.e., in cases of formulary restriction), atorvastatin would be the most cost-effective agent. In adapting the findings on cholesterol-lowering efficacy from this analysis to our lipid clinic, we concluded that the most cost-effective treatment approach is to individualize the selection of an HMG-CoA reductase inhibitor based on both coronary risk and the LDL-C reduction required to achieve NCEP ATP-II goals. Based on our results, 2 agents--atorvastatin and fluvastatin--should be available on the formulary.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/economía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/economía , Colesterol/sangre , Análisis Costo-Beneficio , Quimioterapia/economía , Femenino , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
STUDY OBJECTIVE: To evaluate 24-hour blood pressure control and frequency of adverse effects in patients with mild to moderate hypertension switched from nifedipine gastrointestinal therapeutic system (Nif-GITS) to nifedipine coat core (Nif-CC). DESIGN: Open-label, prospective, switch study SETTING: University-affiliated outpatient cardiology clinic. SUBJECTS: Twenty patients with mild to moderate essential hypertension, who were taking Nif-GITS 30, 60, or 90 mg/day for 8 weeks or longer. INTERVENTIONS: Patients stabilized with Nif-GITS 30, 60, or 90 mg were monitored over 24 hours with an ambulatory blood pressure monitor and were then switched to an equivalent dosage of Nif-CC. After 8 weeks+/-1 week taking Nif-CC, they were again monitored with a 24-hour blood pressure monitor. The 24-hour blood pressure load (percentage of values > 135/85 mm Hg for 24 hrs), daytime blood pressure load (percentage of values > 140/90 mm Hg from 7:00 A.M.-10:00 P.M.), nighttime blood pressure load (percentage of values > 120/80 mm Hg from 10:00 P.M.-7:00 A.M.), diurnal blood pressure variation, average 24-hour blood pressure, daytime blood pressure, nighttime blood pressure, mean blood pressure for the first 4 hours, and last 8 hours of the dosing interval were measured. Adverse effects such as headache, dizziness, and edema were also reported. MEASUREMENTS AND MAIN RESULTS: No differences in average 24 hour-blood pressure readings were observed but significant differences in blood pressure control during the first 4 and last 8 hours of the dosing interval were seen. Systolic and diastolic blood pressures were higher after approximately 16 hours in patients switched from Nif-GITS to Nif-CC. Although Nif-CC caused a greater initial response, it was less effective than Nif-GITS after 16 hours. This could explain the lack of differences in average 24-hour blood pressure values between formulations. Of the 20 patients, 20% experienced increased headaches, 20% showed signs of increased peripheral edema, and 10% reported occasional dizziness after switching agents. Three patients discontinued Nif-CC, two as ordered by their primary care physician and one on his own due to headache. CONCLUSION: This study suggests that patients switched from Nif-GITS to Nif-CC could experience increased blood pressure during the night or toward the end of the dosing interval. They could also experience adverse effects such as headache, edema, and dizziness, which could result in more physician visits and put patients with other disease states such as coronary heart disease at increased risk.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Bloqueadores de los Canales de Calcio/administración & dosificación , Hipertensión/tratamiento farmacológico , Nifedipino/administración & dosificación , Adulto , Anciano , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Formas de Dosificación , Femenino , Humanos , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Nifedipino/efectos adversos , Nifedipino/farmacocinética , Estudios ProspectivosRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy and safety of atropine in preventing vasovagal reactions (VVRs) during removal of femoral arterial sheaths after diagnostic left heart catheterization. DESIGN: Prospective, double-blind, randomized, placebo-controlled study. SETTING: University-affiliated, 450-bed teaching hospital. PATIENTS: One hundred sixty-five patients undergoing left heart catheterization. INTERVENTIONS: Eighty-eight patients were assigned to receive atropine 0.5 mg intravenously and 77 received placebo 5 minutes before sheath removal. MEASUREMENTS AND MAIN RESULTS: The frequency of VVRs was significantly reduced in the atropine group compared with the placebo group, 2.3% and 10.4%, respectively (overall relative risk in the atropine group 0.22, 95% CI 0.12-0.41, p=0.03). Significant decreases in systolic (35.2 +/- 5.8 mm Hg, p<0.001) and diastolic blood pressures (12.6 +/- 12.6 mm Hg, p=0.002) occurred in the 10 patients with VVRs compared with those without VVR. No cardiac arrhythmias occurred after atropine administration. Dry mouth was the only side effect reported with atropine (8/88, 9%). CONCLUSION: Atropine significantly reduced the frequency of VVRs associated with removal of femoral arterial sheaths after diagnostic left heart catheterization. The drug should be studied in a larger series of patients to assess its ability to decrease the morbidity and costs associated with VVR.
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Atropina/uso terapéutico , Cateterismo Cardíaco/efectos adversos , Arteria Femoral/cirugía , Antagonistas Muscarínicos/uso terapéutico , Enfermedades Vasculares/prevención & control , Atropina/efectos adversos , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Electrocardiografía/efectos de los fármacos , Femenino , Arteria Femoral/inervación , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Estudios Prospectivos , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiología , Enfermedades Vasculares/fisiopatologíaRESUMEN
OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A university hospital and a teaching Veteran Affairs Medical Center. METHODS: Retrospective analysis of 52 patients who had undergone both CT scan of the chest and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan was classified as abnormal or normal. Utilizing Bayesian analysis, the probability of cancer using "standard criteria" available in the literature, based on patient's age, history of previous malignancy, smoking history, size and edge of nodule, and presence or absence of calcification were calculated and compared to the probability of cancer based on an abnormal or normal FDG-PET scan. Histologic study of the nodules was the gold standard. RESULTS: The likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as a single test alone was more accurate than the standard criteria and standard criteria plus PET scan in correctly classifying nodules as malignant or benign. CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in solitary pulmonary nodules than the standard criteria using Bayesian analysis. FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary nodules.
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Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor , Pulmón/diagnóstico por imagen , Radiofármacos , Nódulo Pulmonar Solitario/diagnóstico por imagen , Nódulo Pulmonar Solitario/epidemiología , Tomografía Computarizada de Emisión , Teorema de Bayes , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18 , Humanos , Funciones de Verosimilitud , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/epidemiología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada de Emisión/estadística & datos numéricosRESUMEN
Calcium absorption declines with age. Because 1,25-dihydroxyvitamin D (1,25(OH)2D) is the major hormone controlling calcium absorption, changes in vitamin D metabolism may account for the malabsorption of aging. Serum levels of 1,25(OH)2D have been reported to either decrease or remain unchanged with age. To assess the effect of aging on renal production of 1,25(OH)2D, we evaluated the response of renal 25OHD 1 alpha hydroxylase to human parathyroid hormone (hPTH(1-34) stimulation in 119 women ages 25-83 years. In this population, baseline serum 25OHD and 1,25(OH)2D values did not significantly change with age, but serum iPTH (r = 0.44; p < 0.001) and serum creatinine (r = 0.31; p < 0.01) increased with age. However, the stimulatory activity of hPTH(1-34) on the renal production of 1,25(OH)2D declined with age (r3 = -0.36; p < 0.001) and was most apparent after age 75, being 50% less than that of younger women. Besides age, the production of 1,25(OH)2D was found to be dependent on baseline serum iPTH (r = -0.31; p < 0.0001). Administration of hPTH(1-34) led to suppression of endogenous PTH, and suppressibility of endogenous PTH declined with age (r = 0.53; p < 0.0001). The increase in serum PTH and decreased suppressibility of PTH with age could be due to mild secondary hyperparathyroidism. The increase in PTH with age is probably responsible for maintaining normal serum 1,25(OH)2D levels in elderly subjects; however, decreased metabolism of 1,25(OH)2D in the elderly could also maintain normal serum 1,25(OH)2D levels.
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Proteínas Sanguíneas/metabolismo , Calcitriol/sangre , Hormona Paratiroidea/metabolismo , Teriparatido/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Envejecimiento/orina , Análisis de Varianza , Proteínas Sanguíneas/análisis , Calcitriol/orina , Creatinina/sangre , Creatinina/orina , Femenino , Humanos , Bombas de Infusión , Infusiones Intravenosas , Persona de Mediana Edad , Análisis de Regresión , Teriparatido/administración & dosificaciónRESUMEN
In addition to efficacy and safety, the cost of therapy has become an increasingly important factor to consider when selecting drugs to treat patients with mild-to-moderate hypertension. However, acquisition prices alone do not determine the total cost of therapy. To better assess total costs, we conducted a systematic, retrospective, cost-minimization analysis of drugs used to treat 673 patients with newly diagnosed, mild-to-moderate (> 95 to < 110 mmHg) diastolic hypertension between the years 1985 and 1992. Patients included in the study had started antihypertensive monotherapy, and a minimum of one dose titration was required before adding another antihypertensive agent to the regimen. A patient had to have a diastolic blood pressure of < or = 90 mmHg while undergoing therapy to be included in the analysis. Drug classes included diuretics, beta-adrenergic blockers, centrally acting alpha 2-agonists, alpha 1-adrenergic blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Costs, adjusted to 1992 price levels, were analyzed for 32 individual agents for each of the following five cost variables: initial drug acquisition, supplemental drug acquisition, laboratory monitoring, clinic visits, and treatment of side effects. Mean total costs per patient for all five variables by drug class were $895 for beta-blockers, $1043 for diuretics, $1165 for centrally acting alpha 2-agonists, $1243 for ACE inhibitors, $1288 for alpha 1-blockers, and $1425 for calcium channel blockers. However, costs within each class varied considerably. Acquisition cost was often a poor predictor of the total cost of treatment. Therefore, acquisition cost must be considered in conjunction with a number of outcome variables to assess the true cost of antihypertensive therapy.
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Antihipertensivos/economía , Hipertensión/economía , Agonistas alfa-Adrenérgicos/economía , Agonistas alfa-Adrenérgicos/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/economía , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/economía , Bloqueadores de los Canales de Calcio/uso terapéutico , Análisis Costo-Beneficio , Costos y Análisis de Costo , Diuréticos/economía , Diuréticos/uso terapéutico , Estudios de Evaluación como Asunto , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Simpaticolíticos/economía , Simpaticolíticos/uso terapéuticoRESUMEN
Diethyldithiocarbamate (DTC) was used to treat the murine, retrovirus-induced, immunodeficiency disease (MAIDS). Once-weekly treatment was not effective and 800 mg/kg was toxic. When 200, 400 and 600 mg/kg were given i.p., 5 days per week, starting either on the day of virus inoculation or 14 days later, a dose-response and time-response relationship was noted. Higher doses and a 2-week delayed onset of treatment were generally more effective in reducing the development of lymphadenopathy, hypergammaglobulinemia and in prolonging survival than treatment started on the day of virus inoculation. When treatment was delayed until 10 weeks after virus inoculation existing lymphadenopathy was abrogated (treated node area 0 mm2 compared to control 175 mm2, P < 0.0001) and survival was improved (treated 100% compared to control 12.5%, P < 0.0001). However, when therapy was stopped animals died at the same rate as the untreated controls. These data indicate that DTC is active in MAIDS in a dose-responsive and time-dependent manner.
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Ditiocarba/administración & dosificación , Síndrome de Inmunodeficiencia Adquirida del Murino/tratamiento farmacológico , Animales , Relación Dosis-Respuesta a Droga , Femenino , Hipergammaglobulinemia/prevención & control , Inmunoglobulina M/sangre , Ganglios Linfáticos/patología , Ratones , Ratones Endogámicos C57BL , Síndrome de Inmunodeficiencia Adquirida del Murino/inmunología , Síndrome de Inmunodeficiencia Adquirida del Murino/patología , Factores de TiempoRESUMEN
Limited data are available on mitral valve replacement in the elderly patient. Therefore we report our 10-year experience including predictors of perioperative mortality and subsequent long-term cardiac mortality in elderly patients with mitral valve replacement compared to younger patients. Of the 126 consecutive patients with mitral valve replacement, 26 were older (77 +/- 4, group 1) and 100 were younger (62 +/- 9, group 2) than 70 years. Bioprostheses were used more frequently in patients in group 1 (65% vs 7%, p less than 0.0001). Of the 21 clinical, ECG, hemodynamic, and angiographic variables studied, patients in group 1 had higher pulmonary artery systolic pressure (57 +/- 15 vs 48 +/- 19, p less than 0.05), fascicular block on ECGs (70% vs 33%, p less than 0.005), and greater pump time on cardiopulmonary bypass (160 +/- 75 vs 120 +/- 50 minutes, p less than 0.025). A trend toward a higher perioperative mortality rate was also seen in group 1 (27% vs 12%, p = 0.058). Predictors of perioperative mortality by multivariate analysis were the presence of aortic calcification and prolonged pump time on cardiopulmonary bypass in group 1 and coronary artery disease, female sex, elevated mean pulmonary artery pressure, and postoperative complete atrioventricular block in group 2. During a mean 4-year follow-up period, cardiac mortality and total mortality rates were 42% and 54%, respectively, for group 1 compared to 24% and 35%, respectively, for group 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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Bioprótesis , Prótesis Valvulares Cardíacas/mortalidad , Insuficiencia de la Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/cirugía , Anciano , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Intraoperatorias/epidemiología , Tablas de Vida , Masculino , Válvula Mitral , Insuficiencia de la Válvula Mitral/mortalidad , Estenosis de la Válvula Mitral/mortalidad , Análisis Multivariante , Complicaciones Posoperatorias/epidemiología , Factores de RiesgoRESUMEN
The effects of therapy with the immunomodulator diethyldithiocarbamate (DTC) on the manifestation and natural history of LP-BM5 murine retrovirus infection in adult C57 Black 6 mice was investigated. DTC itself, had limited effects on the spleen weight, serum IgM, or mitogen responses of the non-virus-infected control mice when evaluated over a 9-week period. The virus inoculum administered was such that there was approximately a twofold increase in serum IgM and a halving of phytohemagglutinin (PHA) and lipopolysaccharide (LPS) responses in about two weeks and death of all animals by about 26 weeks postinfection. Doses of DTC of 20 and 200 mg/kg weekly or 5 days per week (intraperitoneally) in mice with LP-BM5 infection did not alter the manifestations or course of the disease. Doses of 400 or 600 mg/kg given 5 days per week, starting either 2 weeks before or the day of virus inoculation significantly reduced hypergammaglobulinemia, spleen weight, lymphadenopathy, and also prolonged survival. A dose of 400 mg/kg started 2 weeks after virus inoculation resulted in partial prevention of hypergammaglobulinemia, splenomegaly, and lymphadenopathy as well as 100% survival compared with 12.5% in non-drug-treated controls at 23 weeks after virus inoculation. The 9 surviving animals in the treated group were then allocated to continue treatment or stop treatment. In the animals without further treatment, lymphadenopathy and mortality occurred starting within 6 weeks after cessation of therapy while the animals with continued treatment remained in good condition for 40 weeks. There was only a very limited and transient effect of DTC therapy on the decline of the proliferative responses to phytohemagglutinin or lipopolysaccharide in any of the treated groups in the above described experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Ditiocarba/uso terapéutico , Animales , Modelos Animales de Enfermedad , Ditiocarba/administración & dosificación , Relación Dosis-Respuesta a Droga , Ratones , Ratones Endogámicos C57BLRESUMEN
The value of chromosomal analysis is well established in human hematologic neoplasms. In contrast, the relation between chromosomal abnormalities and clinical outcome in solid tumors in humans has received little study. We undertook this study to determine whether chromosomal abnormalities could provide information on the survival of patients with malignant melanoma. Chromosome-banding analysis was performed on tumor-biopsy samples from 62 patients with metastatic melanoma, and recurring cytogenetic abnormalities were correlated with survival. Patients with structural abnormalities of chromosome 7 or 11 had significantly shorter survival than patients without these abnormalities. We conclude that cytogenetic analysis may provide useful prognostic information about patients with metastatic melanoma.
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Aberraciones Cromosómicas , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 7 , Melanoma/genética , Bandeo Cromosómico , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 6 , Femenino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
One hundred seven patients with echocardiographically documented mitral anular calcium (MAC) and 107 age- and sex-matched control subjects without MAC were studied and followed for a mean of 4.4 +/- 2.4 (standard deviation) years. Fourteen (7%) patients were lost to follow-up. Compared with the control group, patients with MAC had higher frequency of precordial murmurs (p less than 0.0001), cardiomegaly (p less than 0.0001), left atrial enlargement (p less than 0.0001), and rhythm and conduction disturbances (p less than 0.0001). During the follow-up, patients with MAC had higher incidence of valve replacement (p less than 0.0025), permanent pacemaker implantation (p less than 0.0025), congestive heart failure (p less than 0.0001), thromboembolic cerebrovascular event (p less than 0.01), sudden death (p less than 0.001) and total cardiac death (p less than 0.0001). However, the frequencies of myocardial infarction, coronary artery bypass surgery and angioplasty, endocarditis or noncardiac death were not significantly different between patients with MAC and the control subjects. Thus, patients with MAC have higher frequencies of precordial murmurs, cardiomegaly, left atrial and ventricular enlargement, rhythm and conduction disturbances. They more frequently undergo valve replacement and permanent pacemaker implantation, develop congestive heart failure and die of cardiac causes than age- and sex-matched control subjects.
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Calcinosis/complicaciones , Cardiomiopatías/complicaciones , Ecocardiografía , Adulto , Calcinosis/fisiopatología , Calcinosis/terapia , Cardiomiopatías/fisiopatología , Cardiomiopatías/terapia , Electrocardiografía , Femenino , Estudios de Seguimiento , Cardiopatías/etiología , Cardiopatías/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Válvula MitralRESUMEN
Seventy-six consecutive patients, mean age 66 +/- 9 years (+/- standard deviation), with isolated aortic valve replacement for calcific valvular aortic stenosis (AS) were studied. Mitral anular calcium (MAC) was detected by echocardiography in 45 patients (59%). Patients with MAC were older (p less than 0.01), had greater peak systolic aortic valve gradients (p less than 0.025), lower cardiac indexes (p less than 0.025) and smaller valve areas (p less than 0.05) than patients without MAC. Thirty-three percent of patients (15 of 45) with MAC required permanent pacemaker implantation after aortic valve replacement, compared with only 10% of patients (3 of 31) without MAC (p less than 0.025). During the follow-up of 7 years (mean 3.8 +/- 1.6), 27% of patients (12 of 45) with MAC died from cardiac causes, compared to only 7% (2 of 31) without MAC (p less than 0.025). Thus, patients with AS and MAC are older, have more severe AS, more frequently undergo permanent pacemaker implantation after aortic valve replacement and more frequently die of cardiac causes than patients with AS and no MAC during follow-up.