Citations

Laparoscopic adrenalectomy is one of the most clinically important advances in the past 2 decades for the treatment of adrenal disorders. When compared to open adrenalectomy, laparoscopic adrenalectomy is equally safe, effective, and curative; it is more successful in shortening hospitalization and convalescence and has less long-term morbidity. The laparoscopic approach to the adrenal is the procedure of choice for the surgical management of cortisol-producing adenomas and for patients with corticotropin (ACTH) dependent Cushing's syndrome for whom surgery failed to remove the source of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with the technique of laparoscopic adrenalectomy.

SUMMARYStaphylococcus lugdunensishas gained recognition as an atypically virulent pathogen with a unique microbiological and clinical profile.S. lugdunensisis coagulase negative due to the lack of production of secreted coagulase, but a membrane-bound form of the enzyme present in some isolates can result in misidentification of the organism asStaphylococcus aureusin the clinical microbiology laboratory.S. lugdunensisis a skin commensal and an infrequent pathogen compared toS. aureusandS. epidermidis, but clinically, infections caused by this organism resemble those caused byS. aureusrather than those caused by other coagulase-negative staphylococci.S. lugdunensiscan cause acute and highly destructive cases of native valve endocarditis that often require surgical treatment in addition to antimicrobial therapy. Other types ofS. lugdunensisinfections include abscess and wound infection, urinary tract infection, and infection of intravascular catheters and other implanted medical devices.S. lugdunensisis generally susceptible to antimicrobial agents and shares CLSI antimicrobial susceptibility breakpoints withS. aureus. Virulence factors contributing to this organism's heightened pathogenicity remain largely unknown. Those characterized to date suggest that the organism has the ability to bind to and interact with host cells and to form biofilms on host tissues or prosthetic surfaces.

Purpose We conducted a pediatric phase I trial of the vascular endothelial growth factor (VEGF)–neutralizing antibody bevacizumab (BV). Primary aims included estimating the maximum-tolerated dose (MTD) and determining the dose-limiting toxicities (DLTs), pharmacokinetics, and biologic effects of BV in children with cancer. Patients and Methods BV (5, 10, 15 mg/kg) was administered intravenously every 2 weeks in 28-day courses to children with refractory solid tumors. Results Twenty-one patients enrolled, 20 (median age, 13 years) were eligible, and 18 completed one course and were fully assessable for toxicity. A total of 67 courses were administered (median, three courses per patient; range, one to 16 courses). Treatment was well tolerated with no DLTs observed. Non-DLTs included infusional reaction, rash, mucositis, proteinuria, and lymphopenia. Increases in systolic and diastolic blood pressure not meeting Common Terminology Criteria for Adverse Events (CTCAEv3) pediatric-specific criteria for hypertension were observed. There was no hemorrhage or thrombosis. Growth perturbation was not detected in a limited sample over the first course. The serum exposure to BV as measured by area under the concentration-time curve (AUC) seemed to increase in proportion to dose. The median clearance of BV was 4.1 mL/d/kg (range, 3.1 to 15.5 mL/d/kg), and the median half-life was 11.8 days (range, 4.4 to 14.6 days). No objective responses were observed. Exploratory analyses on circulating endothelial mobilization and viability are consistent with the available adult data. Conclusion BV is well tolerated in children. Phase II pediatric studies of BV in combination with chemotherapy in dosing schedules similar to adults are planned.

AbstractHypertrophic cardiomyopathy (HCM) has a variable clinical presentation and penetrance. Many patients will have a benign course, but others will become symptomatic and develop left ventricular outflow tract obstruction. Echocardiograph remains the standard for diagnosis and assessment of obstruction, but gains are being made in the our understanding of the genetic basis of this condition. Pharmacologic therapy remains the first‐line therapy in the majority of patients, but alcohol septal ablation and surgical septal myectomy may be considered in many patients. Patients should assess both the benefits and risks of each procedure based on the best available current evidence. This paper summarizes important recent developments in HCM diagnosis and therapy.

Alterations in cerebrovascular regulation related to vascular oxidative stress have been implicated in the mechanisms of Alzheimer's disease (AD), but their role in the amyloid deposition and cognitive impairment associated with AD remains unclear. We used mice overexpressing the Swedish mutation of the amyloid precursor protein (Tg2576) as a model of AD to examine the role of reactive oxygen species produced by NADPH oxidase in the cerebrovascular alterations, amyloid deposition, and behavioral deficits observed in these mice. We found that 12- to 15-month-old Tg2576 mice lacking the catalytic subunit Nox2 of NADPH oxidase do not develop oxidative stress, cerebrovascular dysfunction, or behavioral deficits. These improvements occurred without reductions in brain amyloid-β peptide (Aβ) levels or amyloid plaques. The findings unveil a previously unrecognized role of Nox2-derived radicals in the behavioral deficits of Tg2576 mice and provide a link between the neurovascular dysfunction and cognitive decline associated with amyloid pathology.