Respiration during acute hypoxia: angiotensin- and vasopressin-receptor blocks.

In normoxic conscious dogs, increased angiotensin II (ANG II), or activation (disinhibition) of the renin-angiotensin system by vasopressin (AVP) V1-receptor block, increases ventilation and decreases arterial PCO2. Both hormones can be increased during hypoxia and might modulate ventilatory drive. Six conscious dogs were studied before and during hypocapnic, isocapnic, and hypercapnic hypoxia. To study potential hormonal effects during hypocapnic hypoxia, experiment 1 included three protocols in which 12.8% O2 was breathed for 60 min: protocol 1, control studies without block; protocol 2, AVP V1 receptors were blocked at the onset of hypoxia; and protocol 3, ANG II receptors were blocked 20 min before hypoxia. To study potential effects of acid-base changes during acute hypoxia, experiment 2 included two protocols (with and without AVP V1-receptor block). A 40-min period of hypocapnic hypoxia was followed by two successive 20-min periods with hypoxia maintained but inspired CO2 progressively increased. Neither hormonal block affected respiration during the hypoxic conditions. Unlike normoxia in conscious dogs, during acute hypoxia, respiratory control by ANG II is not modulated by AVP and acid-base effects on receptors do not account for this difference.

Outcome of previous tricuspid valve operation and arrhythmias in adult patients with congenital heart disease.

BACKGROUND: Tricuspid valve operation or replacement has been associated with high perioperative mortality and poor long-term results. The prevalence of atrial arrhythmias before and after operation in these patients is undefined. METHODS: We retrospectively examined the outcome and frequency of atrial arrhythmias in 85 adult patients (46% men) with congenital heart defects who underwent tricuspid valve operation between 1961 and 1995. RESULTS: The majority had either Ebstein's anomaly (22%), congenitally corrected transposition (19%), tetralogy of Fallot (15%), atrial (13%), or ventricular (11%) septal defects. Forty-two (49%) patients had sustained arrhythmias within 1 year before operation. After tricuspid valve operation, 21 patients (50%) had recurrence of atrial arrhythmias, and 7 in preoperative sinus rhythm developed late rhythm disturbances. Multivariate analysis identified age at operation and preoperative arrhythmias as independent predictors of late arrhythmias. Perioperative mortality was 5%, and there were seven late deaths. Survival was 91% at 5 years, and 83% at 10 years. CONCLUSIONS: Surgical intervention does not prevent recurrence of atrial arrhythmias. Tricuspid valve operation in patients with congenital heart disease can be performed with a low risk of perioperative mortality and good long-term outcome.

Biotechnology stock prices before public announcements: evidence of insider trading?

BACKGROUND: Unique financial challenges faced by biotechnology companies developing therapeutics have contributed to the creation of a highly sensitive market, where stock prices are capable of great fluctuation. The potential for significant financial reward and the nature of the scientific review process make this industry susceptible to illegal share trading on nonpublic information. We examined stock prices of biotechnology products before and after announcement of Phase III clinical trial and Food and Drug Administration (FDA) Advisory Panel results for indirect evidence of insider trading. METHODS: Biotechnology stock prices were recorded for 98 products undergoing Phase III clinical trials and 49 products undergoing FDA Advisory Panel review between 1990 and 1998. Prices were recorded for 120 consecutive trading days before and after public announcement of these two events. We compared the average change in stock price of successful products ('winners') with unsuccessful products ('losers') before the public announcement of results for both critical events. RESULTS: The difference between average stock price change from 120 to 3 days before public announcement of results of Phase III clinical trial winners (+27%) and losers (-4%) was highly significant (P = 0.0007). A similar but non-significant difference was observed between the average stock price of winning (+27%) and losing products (+13%) before FDA Advisory Panel review announcements (P = 0.25). CONCLUSIONS: Our results provide indirect evidence that insider trading may be common in the biotechnology industry. Clinical investigators may wish to consider this issue before participating in any equity position in the biotechnology industry, especially if they are going to perform research for those companies.

Fatal cardiomyopathy after revision total hip replacement for fracture of a ceramic liner.

Symptomatic cobalt toxicity from a failed total hip replacement is a rare but devastating complication. It has been reported following revision of fractured ceramic components, as well as in patients with failed metal-on-metal articulations. Potential clinical findings include fatigue, weakness, hypothyroidism, cardiomyopathy, polycythaemia, visual and hearing impairment, cognitive dysfunction, and neuropathy. We report a case of an otherwise healthy 46-year-old patient, who developed progressively worsening symptoms of cobalt toxicity beginning approximately six months following synovectomy and revision of a fractured ceramic-on-ceramic total hip replacement to a metal-on-polyethylene bearing. The whole blood cobalt levels peaked at 6521 µg/l. The patient died from cobalt-induced cardiomyopathy. Implant retrieval analysis confirmed a loss of 28.3 g mass of the cobalt-chromium femoral head as a result of severe abrasive wear by ceramic particles embedded in the revision polyethylene liner. Autopsy findings were consistent with heavy metal-induced cardiomyopathy.We recommend using new ceramics at revision to minimise the risk of wear-related cobalt toxicity following breakage of ceramic components.

Randomized Trial of Primary PCI with or without RoutineManual Thrombectomy

During primary percutaneous coronary intervention (PCI), manual thrombectomymay reduce distal embolization and thus improve microvascular perfusion. Smalltrials have suggested that thrombectomy improves surrogate and clinical outcomes,but a larger trial has reported conflicting results.MethodsWe randomly assigned 10,732 patients with ST-segment elevation myocardial infarction(STEMI) undergoing primary PCI to a strategy of routine upfront manualthrombectomy versus PCI alone. The primary outcome was a composite of deathfrom cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, orNew York Heart Association (NYHA) class IV heart failure within 180 days. The keysafety outcome was stroke within 30 days.ResultsThe primary outcome occurred in 347 of 5033 patients (6.9%) in the thrombectomygroup versus 351 of 5030 patients (7.0%) in the PCI-alone group (hazard ratio in thethrombectomy group, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.86). Therates of cardiovascular death (3.1% with thrombectomy vs. 3.5% with PCI alone;hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.34) and the primary outcome plusstent thrombosis or target-vessel revascularization (9.9% vs. 9.8%; hazard ratio,1.00; 95% CI, 0.89 to 1.14; P = 0.95) were also similar. Stroke within 30 days occurredin 33 patients (0.7%) in the thrombectomy group versus 16 patients (0.3%)in the PCI-alone group (hazard ratio, 2.06; 95% CI, 1.13 to 3.75; P = 0.02).ConclusionsIn patients with STEMI who were undergoing primary PCI, routine manual thrombectomy,as compared with PCI alone, did not reduce the risk of cardiovasculardeath, recurrent myocardial infarction, cardiogenic shock, or NYHA class IV heartfailure within 180 days but was associated with an increased rate of stroke within30 days. (Funded by Medtronic and the Canadian Institutes of Health Research;TOTAL ClinicalTrials.gov number, NCT01149044.