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BACKGROUNDA 13‐year retrospective study was undertaken to determine the incidence of posttonsillectomy hemorrhage, to evaluate potential risk factors, and to assess the efficacy and safety of ambulatory tonsillectomy.METHODSFrom January 1985 to December 1997, 4662 patients underwent tonsillectomy at our institution. Ninety patients with posttonsillectomy bleeding were identified. For each patient with posttonsillectomy bleeding, 2 nonbleeding control subjects were selected and matched by age and sex to evaluate potential risk factors.RESULTSAge was the only factor found to be statistically significant among the bleeding patients and the control group. The highest incidence (3.61%) of posttonsillectomy hemorrhage occurred in patients 21 to 30 years of age. In our experience, secondary hemorrhage was more common than primary hemorrhage, presenting most frequently on postoperative days 5 to 7.CONCLUSIONSThe incidence of posttonsillectomy bleeding in this review was 1.93%, and about half (47%) of the patients with posttonsillectomy hemorrhage returned to the operating room for hemorrhage control. The highest incidence (3.61%) of posttonsillectomy hemorrhage occurred in patients 21 to 30 years of age. Patients with posttonsillectomy hemorrhage, regardless of management, had a 12% incidence of subsequent hemorrhage. We found no difference in the incidence of posttonsillectomy bleeding between outpatient and inpatient procedures.

OBJECTIVE:Recent studies have identified the capacity of transforming growth factor‐α (TGF‐α) to stimulate mammalian labyrinthine hair cell regeneration after acute ototoxic damage. Augmenting hair cell regeneration with such growth factors may have a role in potentiation of recovery of cochlear function after hair cell injury. Transtympanic application of aqueous solutions to the round window membrane (RWM) has proved successful as a drug delivery route. The purpose of this study was to test the permeability of the mammalian RWM to TGF‐α in an inexpensive and reliable in vitro model.METHODS:Guinea pig RWM niches were harvested and transferred to a 2‐chamber apparatus, and TGF‐α was applied to the middle‐ear side of the chamber. ELISAs of TGF‐α were measured at intervals during a 96‐hour period.RESULTS:Aliquots taken during a 96‐hour interval demonstrated passage of TGF‐α in concentrations sufficient to stimulate hair cell regrowth.CONCLUSIONS:The apparatus allows study of RWM permeability to other substances and provides a basic model for study of RWM physiology. TGF‐α is able to pass through a mammalian RWM.

Atherogenesis is enhanced in arterial segments exposed to disturbed blood flow, indicating the active participation of the hemodynamic environment in lesion formation. Turbulent shear stress selectively regulates responsive genes in the endothelium and increases the damage induced by free radicals. The purpose of the present study was to evaluate the effects of intervention with antioxidants and l -arginine on endothelial NO synthase (eNOS) and oxidation-sensitive gene perturbation induced by disturbed flow in vitro and in vivo . Both human endothelial cells exposed to shear stress and high atherosclerosis-prone areas of hypercholesterolemic low-density lipoprotein receptor knockout (LDLR −/− ) mice showed increased activities of redox-transcription factors (ELK-1, p -Jun, and p -CREB) and decreased expression of eNOS. Intervention with antioxidants and l -arginine reduced the activation of redox-transcription factors and increased eNOS expression in cells and in vivo . These results demonstrate that atherogenic effects induced by turbulent shear stress can be prevented by cotreatment with antioxidants and l -arginine. The therapeutic possibility to modulate shear stress-response genes may have important implications for the prevention of atherosclerosis and its clinical manifestations.

The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 Å, and squirrel monkey FKBP51, to 2.8 Å, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex.

A paradoxical increase in mortality attributable to diabetes has occurred, particularly during the last decade, despite the overall decrease in mortality attributable to coronary artery disease in patients without diabetes. Insulin resistance with or without frank type 2 diabetes has emerged as a major determinant of accelerated coronary artery disease and its sequelae. The advent of insulin sensitizers enables clinicians to target treatment of insulin resistance, as well as hyperglycemia and dyslipidemia. The prevalence of diabetes in the United States is enormous and is increasing rapidly. Patients with diabetes respond less favorably to percutaneous coronary interventions and surgery compared with nondiabetic patients. These considerations led to the initiation of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. It is designed to determine whether treatment targeted to attenuate insulin resistance can arrest or retard progression of coronary artery disease compared with treatment targeted to the same level of glycemic control with an insulin-providing approach. It is designed also to determine whether early revascularization reduces mortality and morbidity in patients with type 2 diabetes whose cardiac symptoms are mild and stable. Despite challenges in study design and enrollment, intensive follow-up, and the long duration of follow-up planned, the questions being addressed are compelling and seem to merit the effort.

The WD-repeat proteins Rae1 and Bub3 show extensive sequence homology, indicative of functional similarity. However, previous studies have suggested that Rae1 is involved in the mRNA export pathway and Bub3 in the mitotic checkpoint. To determine the in vivo roles of Rae1 and Bub3 in mammals, we generated knockout mice that have these genes deleted individually or in combination. Here we show that haplo-insufficiency of either Rae1 or Bub3 results in a similar phenotype involving mitotic checkpoint defects and chromosome missegregation. We also show that overexpression of Rae1 can correct for Rae1 haplo-insufficiency and, surprisingly, Bub3 haplo-insufficiency. Rae1-null and Bub3-null mice are embryonic lethal, although cells from these mice did not have a detectable defect in nuclear export of mRNA. Unlike null mice, compound haplo-insufficient Rae1/Bub3 mice are viable. However, cells from these mice exhibit much greater rates of premature sister chromatid separation and chromosome missegregation than single haplo-insufficient cells. Finally, we show that mice with mitotic checkpoint defects are more susceptible to dimethylbenzanthrene-induced tumorigenesis than wild-type mice. Thus, our data demonstrate a novel function for Rae1 and characterize Rae1 and Bub3 as related proteins with essential, overlapping, and cooperating roles in the mitotic checkpoint.