Bilateral cerebellopontine angle tumors in neurofibromatosis type 2

In a series of over 500 cases of cerebellopontine angle tumors, 19 patients had bilateral neurinomas. Four of these tumors arose from the facial rather than the acoustic nerve. A conservative policy regarding surgery had been adopted in an effort to prevent hearing loss for as long as possible. Nevertheless, all patients operated on in this series are now totally deaf. The results of managing these patients surgically and conservatively are discussed.     

Method of single-lung transplantation in the absence of a left atrial cuff.

A method used clinically for anastomosing the pulmonary veins to the left atrium, in the absence of a left atrial cuff, during single-lung transplantation by reconstructing the atrium with pericardium is described. Postoperative ventilation/perfusion scans show normal pulmonary blood flow.     

Optimization of the quinoline and substituted benzyl moieties of a series of phenyltetrazole leukotriene D4 receptor antagonists.

This report describes the development of a series of highly potent quinoline-based leukotriene D4 (LTD4) receptor antagonists containing an N-benzyl-substituted phenyltetrazole moiety. They were designed to provide both the correct positioning of the acidic function and secondary lipophilic domain required for strong receptor binding. Members of this series possess high activity in blocking LTD4-induced contractions of isolated guinea pig ileum. Compound 32, LY287192 (2-[[5-[3-[2-(7-chloroquinolin-2- yl)ethenyl]phenyl]-2H-tetrazol-2-yl]methyl]-5-fluorobenzoic acid sodium salt), blocked contraction with a pKB value of 9.1 +/- 0.3. Qualitative structure-activity studies have demonstrated specific requirements for the best activity. In particular, ortho substitution of the benzyl group with an acidic function was crucial for maximum potency. In cases similar to 32, where the benzyl group possesses an ortho carboxylate, the N-2-substituted tetrazole isomer showed 100-fold greater activity relative to the corresponding N-1 isomer. This pattern was reversed when the acid was substituted at the para position. The quinoline unit may be replaced by other nitrogen-containing heterocycles.     

Synergistic Deposition of C4d by Complement-Activating and Non-activating Antibodies in Cardiac Transplants

The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection.     

Predictors of incident depression after hip fracture surgery.

OBJECTIVE: Depression after hip fracture surgery is prevalent and associated with increased mortality rates and impaired functional recovery. The incidence of new-onset depressive symptoms in patients initially not depressed after hip fracture surgery and their relationship with functional recovery is unknown. METHODS: A cohort of 139 nondepressed elderly patients (>60 years) hospitalized for hip fracture surgery were followed up for six months. Clinically significant depressive symptoms were defined as a score of 7 or more on the 15-item Geriatric Depression Scale. RESULTS: The authors found a cumulative incidence rate of 20.5% adjusted for dropouts. Multiple Cox-regression analyses yielded the presence of subthreshold symptoms of depression, anxiety, pain, and cognitive impairment at baseline, the premorbid level of mobility, and a history of (treated) depression as risk factors for incident depression (p <0.05). A forward, conditional procedure identified postoperative pain (hazard ratio [HR] = 1.32, 95% confidence interval [CI]: 1.14-1.53, Wald chi(2) = 13.57, df = 1, p <0.001) and baseline anxiety (HR = 1.25, 95% CI: 1.08-1.44, Wald chi(2) = 8.86, df = 1, p = 0.003) as the strongest independent risk factors. Incident depression was associated with a less favorable outcome at 3 months follow-up. CONCLUSION: This exploratory study identified two treatable baseline characteristics that predicted incident depression in nondepressed patients after hip-fracture surgery.     

A pilot study of medical student 'abuse'. Student perceptions of mistreatment and misconduct in medical school

A pilot survey of one third-year medical school class was carried out to explore student perceptions of mistreatment and professional misconduct in medical school training. Students were asked to rate the frequency and cite sources of mistreatment and misconduct among classmates, faculty, residents, and interns. They were also asked to assess the effects of such episodes on their physical health, emotional well-being, social and family life, and attitudes toward becoming a physician. The results indicate that students perceive mistreatment (particularly verbal abuse and unfair tactics) to be pervasive and professional misconduct all too common. As many as three fourths of the students report having become more cynical about academic life and the medical profession as a result of these episodes. Two thirds feel they are worse off than their peers in other professions. More than a third have considered dropping out of medical school and one fourth report they would have chosen a different profession had they known in advance about the extent of mistreatment they would experience. Rather than dismiss these problems as isolated events, we need to examine this issue more closely.