Myocardial ischaemia and ventricular arrhythmias precipitated by physiological concentrations of adrenaline in patients with coronary heart disease.

The clinical and haemodynamic effects of adrenaline infusion (30 ng kg-1 min-1) producing plasma adrenaline concentrations in the range seen during acute myocardial infarction and of placebo were investigated in a crossover design in 14 patients with stable coronary heart disease. Adrenaline infusion resulted in electrocardiographic evidence of myocardial ischaemia (greater than or equal to 1 mm (0.1 mV) horizontal or downsloping ST segment depression) in 10 patients and angina in four, although the mean (SEM) increase in heart rate was modest (14 (2) beats/min) and mean coronary vascular resistance fell from 1.56 (0.21) to 1.16 (0.14) mm Hg min ml-1 (p less than 0.005). New or increasingly frequent or complex ventricular arrhythmias occurred in five patients. Placebo infusion had no effect on the variables measured. Supine bicycle exercise during infusion of the saline placebo was associated with a similar degree of ST segment depression (0.9 (0.2) mm) as adrenaline infusion at rest (0.9 (0.1) mm) but exercise performed during adrenaline infusion (10 patients) resulted in more pronounced ST segment depression (1.9 (0.3) mm) (p less than 0.005) than either intervention alone. Angina occurred in three of 11 patients during control exercise and in six of 10 during the combination of adrenaline infusion and exercise. Such potentially adverse consequences of low dose adrenaline infusion in patients with stable coronary heart disease are consistent with the suggestion that adrenal activation is detrimental during acute myocardial infarction, being both arrhythmogenic and proischaemic.     

Human papillomavirus type 16 alters human epithelial cell differentiation in vitro.

Human papillomavirus (HPV) types 16, 18, 31, and 33 have been implicated as etiologic agents of cervical and penile cancer. Using a cell culture system for keratinocytes which allows stratification and production of differentiation-specific keratins, we have examined the effects of one of these viruses, HPV-16, on the differentiation capabilities of human epithelial cells. A plasmid containing the HPV-16 genome and a neomycin-selectable marker was transfected into primary human epidermal cells and SCC-13 cells, an immortalized squamous cell carcinoma cell line. Cloned neomycin-resistant cell lines were isolated and examined by cell culture on raised collagen rafts. Cell lines containing HPV-16 DNA retained the ability to stratify and express differentiation-specific keratins in the raft system but otherwise failed to differentiate normally. The histological abnormalities induced by HPV-16 closely resembled those seen in genital intraepithelial neoplasia in vivo. Hence, our results support the role of HPV-16 as an etiologic agent in the development of genital neoplasias and suggest a specific system for the study of HPV-16-induced epithelial cancers.     

A King type II curve pattern treated with selective thoracic fusion: case report with 44-year follow-up.

The optimal surgical treatment of the King-Moe type II thoracic curve pattern is controversial. The issue of postoperative "decompensation" has arisen in conjunction with the use of third-generation instrumentation systems. This report presents the 44-year clinical and radiographic follow-up of a patient with a type II scoliosis treated with uninstrumented selective thoracic fusion using the criteria of King and Moe. The caudal extent of the fusion was defined by proper identification of the neutral and stable vertebra. At final follow-up, the patient remained well balanced and essentially pain free. Her level of function was "above average" for her age, as per SF-36 evaluation.     

Effect of the alpha-adrenergic blocker, doxazosin, on endothelial function and insulin action

Essential hypertension is associated with impairment of both endothelial function and insulin action, and this has provided rationale for the use of antihypertensive agents that are at least neutral, if not beneficial, in these areas. This study examines the effect of the alpha-adrenergic blocker, doxazosin, on endothelial function and insulin action. Sixteen patients with essential hypertension were recruited with 13 (3 men/10 women; median age, 55 years; range, 38 to 65 years) completing the study. A double-blind, placebo-controlled crossover study design was used. After a 6-week placebo run-in, there were two 12-week treatment periods of either placebo or doxazosin, separated by a 6-week wash out period. Subjects were studied at the end of each treatment period with endothelial function assessed by forearm plethysmography and insulin action by the hyperinsulinemic clamp technique. Blood pressure was significantly lowered by doxazosin (doxazosin 144 +/-3/86 +/- 2 mm Hg; placebo 159 +/- 3/96 +/- 1 mm Hg, P <.005 for both systolic and diastolic pressure; mean +/- SEM). Baseline forearm blood flow (FBF) was unchanged (doxazosin 4.9 +/- 0.9; placebo 4.0 +/- 0.7 mL x 100 mL(-1) x min(-1), P >.05), however, FBF responses (area under dose response curve, percentage change in infused:control arm ratio) to acetylcholine (endothelium-dependent vasodilation) were improved by doxazosin (doxazosin 58.6 +/- 11.7 standard units [SU]; placebo 22.1 +/- 7.0 SU, P =.03) with responses to sodium nitroprusside (endothelium-independent vasodilation) unchanged (doxazosin 40.3 +/- 5.5 SU; placebo 46.3 +/- 8.1 SU, P >.05). Exogenous glucose infusion rates to maintain euglycemia during hyperinsulinemia were not significantly different (doxazosin 30.4 +/- 0.9; placebo 32.3 +/- 1.0 micromol x kg(-1) min(-1), P >.05). Suppression of postabsorptive endogenous glucose production by insulin was also unchanged by treatment (doxazosin 65.6% +/- 7.5% suppression; placebo 68.3% +/- 11.2% suppression, P >.05). Doxazosin has a neutral effect on both peripheral and hepatic insulin action, but improves endothelium-dependent vasodilation. These results indicate that doxazosin can be used safely in patients with insulin resistance, while its positive effect on endothelial function may lessen the subsequent incidence of atherosclerosis.