Prognostic significance of systolic blood pressure changes during dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain and known or suspected coronary artery disease

To investigate the prognostic value of dobutamine stress-induced changes in systolic blood pressure (BP) 418 patients (mean age 60 years, 238 men) with chest pain and known or suspected coronary artery disease, who underwent a dobutamine-atropine stress technetium-99m sestamibi myocardial perfusion scintigraphic study, were followed up for 25 +/- 15 months. Blood pressure was measured by automatic sphygmomanometry every 3 minutes. A marked decrease and increase in systolic BP from rest to peak were defined as changes of > or = 20 mm Hg, and > or = 30 mm Hg, respectively. Worst outcome events were cardiac death (n = 30), nonfatal myocardial infarction (n = 17), and hospitalization for congestive heart failure (n = 8). A decrease in systolic BP (prevalence 16%) was associated with older age and higher baseline systolic BP. Fixed and reversible sestamibi perfusion defects and follow-up results were similar to patients without a systolic BP decrease. In contrast, an increase in systolic BP (prevalence 24%) was associated with younger age, lower baseline systolic BP, and with absence of a history of prior congestive heart failure or treatment with angiotensin-converting enzyme inhibitors. Furthermore, these patients had fewer fixed perfusion defects and tended to have fewer annual event rates (3.5% vs 7.5%, p < 0.10). In a multivariate model, an increase in systolic BP was not an independent predictor for subsequent events. In conclusion, a dobutamine-induced decrease in systolic BP is not associated with fixed or reversible sestamibi defects or adverse prognosis. An increase in systolic BP, however, is associated with less fixed sestamibi defects and a tendency toward less annual event rates.     

Hepatic expression of ErbB3 is repressed by insulin in a pathway sensitive to PI-3 kinase inhibitors

ErbB3 is an epidermal growth factor receptor-related type I tyrosine kinase receptor capable, in conjunction with ErbB2 or epidermal growth factor receptor, of transmitting proliferative and differentiative signals in a variety of cell types. We previously showed that ErbB3 messenger RNA and protein increase in cultured hepatocytes during the first 12 h in culture, as does the binding of heregulin beta1, a ligand for ErbB3. Insulin inhibits the increase in heregulin beta1 binding, as well as the increase in ErbB3 messenger RNA and protein. Two models of insulin deficiency in vivo (diabetes and fasting) demonstrated elevated levels of hepatic ErbB3 protein, strengthening the relevance of our observations in vitro. Using chemical activators or antagonists, we sought to identify the signaling pathways that link insulin to ErbB3 expression. The PI-3 kinase inhibitors, wortmannin and LY294002, completely blocked the inhibition of ErbB3 protein expression by insulin, suggesting a role for PI-3 kinase in the regulation of this growth factor receptor. Rapamycin, an inhibitor of p70 S6 kinase, an enzyme downstream of PI-3 kinase, failed to block the effect of insulin on ErbB3 expression. These results suggest a complex regulatory paradign for ErbB3 that includes PI-3 kinase and may be linked, via insulin, to the metabolic status of the animal.     

Electrospray ionisation mass spectrometry facilitates detection of fibrinogen (Bbeta 14 Arg --> Cys) mutation in a family with thrombosis

We report the first direct detection of a fibrinogen mutation by electrospray ionisation mass spectrometry. The propositus, from a family with a history of thrombosis, came to attention after a pulmonary embolism subsequent to a spontaneous abortion. Prolonged thrombin (41 s) and reptilase times (26 s) together with an impairment of fibrinopeptide B release suggested a mutation at the thrombin cleavage site of the Bbeta chain. Direct mass analysis of purified fibrin chains from a thrombin induced clot showed that 50% of the Bbeta chains remained uncleaved. The measured mass of the mono sialo isoform of this uncleaved chain was 54150 Da, compared to a value of 54198 Da for normal Bbeta chains. This decrease of 48 Da in the intact protein is indicative of either a Bbeta 14 Arg to Cys, or Arg to Leu substitution. Heterozygosity for the Bbeta 14 Arg --> Cys mutation was verified by PCR amplification and DNA sequence analysis.     

MR of the brain in Sj?gren-Larsson syndrome

Cerebral MR was performed in three patients with Sj?gren-Larsson syndrome. In each case, a 1.5-T system was used, and the patient was under general anesthesia. The MR findings included confluent hyperintense white matter lesions in the periventricular and deep white matter of the centrum semiovale, with sparing of the subcortical U fibers. The topography of the white matter abnormalities correlated well with the clinical signs and symptoms.     

Correlation of occlusal factors and condyle position asymmetry with signs and symptoms of temporomandibular disorders in young adults

The role of the occlusion in the etiology and prevalence of temporomandibular disorders (TMD) has not been conclusively demonstrated. Occlusal factors and condyle position asymmetry as deduced from computed tomography (CT) axial scans were correlated with signs and symptoms of TMD in 49 young adults (mean age 24 years, range 15-33 years) with complete or almost complete dentition. A statistically significant correlation was noted between these signs and symptoms and occlusal variables describing asymmetry (the amount and lateral deviation of the slide from the retruded contact position (RCP) to the intercuspal position (IP), deviation of protrusion and asymmetry in bilateral cuspid occlusion). It seems that occlusal discrepancy can be a predisposing factor to TMD, especially when it is asymmetrically expressed.     

Postmortem distribution of nicotine and cotinine from a case involving the simultaneous administration of multiple nicotine transdermal systems

A 31-year-old female was found dead with 18 nicotine transdermal system patches taped to her upper body and a plastic bag taped over her nose and mouth (the cause of death was ruled asphyxiation). Nicotine concentrations in biological fluids and tissues were analyzed using a liquid-liquid extraction followed by injection onto and HP-5890 gas chromatograph (GC) equipped with a nitrogen-phosphorus detector. Cotinine was separated from the biological matrices using solid-phase extraction followed by analysis on an HP-5890 GC with flame ionization detection. A variety of specimens were analyzed, including blood, urine, vitreous, brain, liver, and gastric contents. Heart and femoral blood concentrations (1.4 and 0.46 micrograms/mL, respectively) were 175 and 57 times, respectively, the mean C(max) value reported following the proper administration of a single 7-mg/day patch.