A Phase III study of radiation therapy (RT) and O6-benzylguanine + BCNU versus RT and BCNU alone and methylation status in newly diagnosed glioblastoma and gliosarcoma: Southwest Oncology Group (SWOG) study S0001.

AIMS: To determine the efficacy of methylguanine methyltransferase (MGMT) depletion + BCNU [1,3-bis(2-chloroethyl)-1- nitrosourea: carmustine] therapy and the impact of methylation status in adults with glioblastoma multiforme (GBM) and gliosarcoma. METHODS: Methylation analysis was performed on GBM patients with adequate tissue samples. Patients with newly diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial. At registration, patients were randomized to Arm 1, which consisted of therapy with O(6)-benzylguanine (O(6)-BG) + BCNU 40 mg/m(2) (reduced dose) + radiation therapy (RT) (O6BG + BCNU arm), or Arm 2, which consisted of therapy with BCNU 200 mg/m(2) + RT (BCNU arm). RESULTS: A total of 183 patients with newly diagnosed GBM or gliosarcoma from 42 U.S. institutions were enrolled in this study. Of these, 90 eligible patients received O(6)-BG + BCNU + RT and 89 received BCNU + RT. The trial was halted at the first interim analysis in accordance with the guidelines for stopping the study due to futility (<40 % improvement among patients on the O6BG + BCNU arm). Following adjustment for stratification factors, there was no significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups (one sided p = 0.94 and p = 0.88, respectively). Median OS was 11 [95 % confidence interval (CI) 8-13] months for patients in the O6BG + BCNU arm and 10 (95 % CI 8-12) months for those in the BCNU arm. PFS was 4 months for patients in each arm. Adverse events were reported in both arms, with significantly more grade 4 and 5 events in the experimental arm. CONCLUSIONS: The addition of O(6)-BG to the standard regimen of radiation and BCNU for the treatment patients with newly diagnosed GBM and gliosarcoma did not provide added benefit and in fact caused additional toxicity.

Unmasking of neonatal renovascular hypertension by milrinone used for cardiac dysfunction.

A neonate initially presented with heart failure, with severe cardiac dysfunction confirmed by echocardiography, at 3 days of age. Blood pressure at presentation was in the high normal range. It was not until there was a rapid improvement of left-ventricular function on intravenous milrinone that the infant was noted to be hypertensive on day of life 7. It is noteworthy that milrinone, a drug with vasodilator and inotropic properties, paradoxically unmasked hypertension by rapidly improving left-ventricular function. Subsequent work-up showed the etiology of hypertension to be left renal artery stenosis. We present this case to alert clinicians to the rarer causes of left-ventricular dysfunction and to point out that its etiology, i.e., hypertension, may not be apparent until there is improvement in the systolic function of the left ventricle.

Baylisascaris Procyonis Neural Larva Migrans in an Infant in New York City.

Neural larva migrans (NLM) with eosinophilic meningoencephalitis secondary to raccoon roundworm (Baylisascaris procyonis) infection has been reported in rural and suburban areas of North America and Europe with extant raccoon populations. Most cases have occurred in infants less than two years of age exposed to areas of raccoon fecal contamination. Here, we present a case of Baylisascaris-induced NLM from the densely populated borough of Brooklyn in New York City and alert urban pediatricians to consider this cause of clinical neurologic disease even in areas not typically thought to be associated with endemic risk factors. Infected raccoons also occur in urban settings, and urban children may be exposed to environmental areas or materials contaminated with their feces and the parasite's eggs.

Giant cell arteritis and mortality.

BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis of elderly individuals associated with significant morbidity, including blindness, stroke, and myocardial infarction. Previous studies have investigated whether GCA is associated with increased mortality, with conflicting results. The objective of this study is to determine whether GCA, is associated with increased mortality. METHODS: Forty-four cases with GCA were identified from the University of Utah Health Sciences Center, the major tertiary care center for the Intermountain West. The Utah Population Database, a unique biomedical information resource, selected cases and age- and gender-matched controls. Cases were defined as patients with a temporal artery biopsy-proven diagnosis of GCA (international classification of diseases [ICD]-9 code 446.5) between 1991 and 2005. Exclusion criteria included a negative biopsy, alternative diagnoses, or insufficient clinical data. For each of the 44 cases, 100 controls were identified; thus, 4,400 controls were included in the data analysis. Median survival time and 5-year cumulative survival were measured for cases and controls. RESULTS: The median survival time for the 44 GCA cases was 1,357 days (3.71 years) after diagnosis compared with 3,044 days (8.34 years) for the 4,400 controls (p = 0.04). Five-year cumulative survival was 67% for the control group versus 35% for the cases (p < .001). Survival rates for cases and controls converged at approximately 11.12 years. CONCLUSIONS: Patients with GCA were more likely than age- and gender-matched controls to die within the first 5 years following diagnosis.

Persistent pulmonary infection with an azole-resistant Coccidioides species.

We report a case of a life-threatening, recurrent, and azole-resistant pulmonary coccidioidomycosis in a patient receiving long-term fluconazole therapy for a history of coccidioidal meningitis. Since this diagnosis, the patient has received weekly amphotericin B for more than four years and remains in remission with a stable serum Coccidioides complement fixation antibody titer.

Survival outcomes in glioblastoma multiforme, including the impact of adjuvant chemotherapy.

Glioblastoma is an uncommon cancer, but one that is disproportionately represented in mortality rates. Recent developments in adjuvant chemotherapy have regenerated enthusiasm for the treatment of this tumor. Ongoing translational and clinical research has led to a greater understanding of the biologic and molecular behavior and heterogeneity of this tumor. Recent shifts in treatment standards, as well as further selective individualizing of therapies based on molecular information, promise progress for this difficult-to-treat neoplasm.

Adenotonsillectomy as a treatment option for poststreptococcal uveitis.

OBJECTIVES: To report recurrent uveitis as a manifestation of poststreptococcal syndrome and discuss a role of adenotonsillectomy as a treatment option. STUDY DESIGN: Case study. METHODS: A case report of a 6-year-old, otherwise healthy girl with group A streptococcal uveitis managed successfully with adenotonsillectomy. RESULTS: In the year after surgery there were only two episodes of uveitis, contrasted with a preoperative 3-year history of 8 to 10 annual episodes despite corticosteroid therapy. Moreover, as a result of the postoperative improvement the child was able to avoid impending methotrexate therapy. CONCLUSIONS: Although the role of tonsillectomy in managing poststreptococcal uveitis is unknown, our results suggest a positive impact independent of the baseline tonsillitis frequency. Otolaryngologists should be aware of these uncommon sequelae of streptococcal infection and the potential role of tonsillectomy in treatment.