The effect of intravenous pamidronate on bone mineral density, bone histomorphometry, and parameters of bone turnover in adults with type IA osteogenesis imperfecta.

The type IA osteogenesis imperfecta (OI) phenotype is characterized by multiple fractures, blue sclerae, and minimal skeletal deformity without dentinogenesis imperfecta. The object of this study was to determine the effect of treatment with intravenous pamidronate (30 mg) every 3 months on bone density and bone histomorphometry in adults with type IA OI. After an initial iliac crest bone biopsy eight subjects, 5 women and 3 men, entered a treatment program lasting 21-30 months. Five subjects, all women, completed the study which included a posttreatment iliac crest bone biopsy. Pamidronate treatment led to significant increases in bone mineral density (BMD), measured by DXA, in the lumbar spine at 12 months (P = 0.05) and in the femur neck (P = 0.02) at 24 months. Significant increases in BMD were also seen in femoral trochanter at 12 months (P = 0.05) and at 24 months (P = 0.02), and in Ward's triangle at 12 months (P = 0.02) and 24 months (P = 0.05). Mean osteocalcin levels decreased 32%, C-terminal procollagen peptide and bone alkaline phosphatase declined 12% and 47% at 15 and 21 months, respectively. Deoxypyridinoline crosslink excretion decreased 31%. Posttreatment bone biopsy revealed a significant 6.3% increase in mean bone trabecular volume (P = 0.01). Mean cortical thickness increased from 848 mm to 1384 mm (P = 0.01) and cortical porosity decreased 13.2% (P = 0.01). Bone formation rate increased significantly in all 5 patients from 6.6 to 15.3 mm2/yr (P = 0.01). Mineral apposition rate was unchanged. These results indicate that intravenous pamidronate, 30 mg every 3 months, may have significant effects on bone density and histomorphometry in adults with type IA OI. Responses at higher doses remain to be evaluated.

Evaluating gene x psychological risk factor effects in the pathogenesis of anxiety: a new model approach.

The present study evaluated the singular and interactive effects of a functional polymorphism (variation) in the serotonin transporter (5-HTT) gene and a psychological trait (anxiety sensitivity [AS], i.e., fear of arousal symptoms) in predicting subjective and physiological responses to a 35% carbon dioxide (CO2) challenge in a community sample (N = 72). Genotypes were divided into 2 groups in accord with prior research. Findings were partially supportive of the hypothesized risk model. These indicated that the Group L genotype (homozygous for the 1 allele), compared with the Group S genotype (homozygous for the s allele plus heterozygous individuals), predicted greater fearful response to the biological challenge. There was also an AS x Genotype interaction predicting heart rate variability (HRV) in response to the CO2, suggesting that high AS plus Group L status predicts decreased HRV.

Prognostic value of mental stress testing in coronary artery disease.

This study assesses the prognostic value of mental stress-induced ischemic left ventricular wall motion abnormalities and hemodynamic responses in patients with stable coronary artery disease (CAD). Seventy-nine patients (76 men and 3 women) with prior positive exercise test results were exposed to mental arithmetic and a simulated public speech stress in 2 prior studies. Ischemic wall motion abnormalities were monitored using echocardiography or radionuclide ventriculography (RNV). During mental stress testing, new or worsened ischemic wall motion abnormalities to mental stress and exercise were ascertained, as were peak changes in blood pressure and heart rate to mental stress. The occurrence of subsequent cardiac events (including cardiac death, nonfatal myocardial infarction, or revascularization procedures) was ascertained. New cardiac events were observed in 28 of 79 patients (35%) after a median follow-up duration of 3.5 years (range 2.7 to 7.3). Survival analysis indicated that 20 of 45 patients with mental stress ischemia (44%) experienced new cardiac events more frequently than those without mental stress ischemia (8 of 34; 23%; p = 0.048). Type of cardiac event did not differ between mental stress-positive and stress-negative patients. After controlling for baseline blood pressure and study group status (echocardiography vs RNV), there was a significantly higher relative risk of subsequent events for patients with high versus low peak stress-induced diastolic blood pressure responses (RR = 2.4, confidence interval 1.1 to 5.2; p = 0.03). These results demonstrate that ischemic and hemodynamic measures obtained from mental stress testing may be useful in assessing prognosis in CAD patients with prior positive exercise test results.

Mental stress as a trigger of myocardial ischemia and infarction.

Recent research on the effects of behavioral activities on myocardial ischemia in coronary artery disease patients has provided a pathophysiologic model for understanding the mechanisms by which mental stress can trigger clinical cardiovascular events. This article reviews epidemiologic research implicating psychosocial stress as an acute trigger of myocardial infarction in patients with pre-existing coronary artery disease, and evidence for the pathophysiologic effects of acute mental stress in individuals with pre-existing coronary artery disease. Via its actions on the central and autonomic nervous systems, stress can produce a cascade of physiologic responses in vulnerable individuals that may lead to myocardial ischemia, ventricular fibrillation, plaque rupture, or coronary thrombosis. Also reviewed are field and laboratory studies that suggest important causal links between mental stress and myocardial ischemia, and evidence suggesting clinical significance for vulnerability to mental stress-induced ischemia.