Quadruple immunotherapy of Bacillus Calmette-Guérin,interferon, interleukin-2, and granulocyte-macrophage colony-stimulating factor as salvage therapy for non–muscle-invasive bladder cancer

Background

Bacillus Calmette-Guérin (BCG) is the most effective initial intravesical therapy for high-grade non–muscle invasive bladder cancer, but many patients still fail. Combination intravesical BCG and interferon (IFN) will salvage some patients but results remain suboptimal.

Revascularization of the Posterior Circulation

The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.     

Analysis of Factors Associated with Outcome in Patients Undergoing Isolated Hepatic Perfusion for Unresectable Liver Metastases from Colorectal Center

Aim  To define the indications for hyperthermic isolated hepatic perfusion (IHP) in patients with unresectable liver metastases (LM) from colorectal cancer (CRC) with particular focus on IHP’s utility as a second-line option for patients whose tumors have progressed following combination systemic chemotherapy treatment. Methods  From June 1994 through July 2005, 120 patients with unresectable CRC LM underwent IHP with melphalan (n = 69), tumor necrosis factor (TNF) (n = 10) or both (n = 41). Hepatic arterial infusion (HAI) with floxuridine started 6–8 weeks post IHP in 46 (38%). Patients were followed for toxicity, radiographic response, and overall survival (OS). Wilcoxon rank-sum and Fisher’s exact tests were used to compare parameters by response category; survival and hepatic progression-free survival were calculated by the Kaplan–Meier method. Results  Of 79 males and 41 females, 96 (80%) received prior chemotherapy. There were five (4%) operative/treatment mortalities. There were 69 responses in 114 evaluable patients (61%). Total melphalan dose and combination melphalan/TNF were each associated with response; age, preoperative carcinoembryonic antigen (CEA), prior chemotherapy for established LM, tumor burden, and post-IHP HAI therapy were not. Median overall survival was 17.4 months and 2-year survival was 34%. Factors found to be independently related to survival were preoperative CEA <30 ng/mL and use of post-IHP HAI (P < 0.015). Conclusions  IHP results in marked tumor regression and prolonged survival in patients with CRC LM. Continued development of IHP in this clinical setting is warranted.     

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.     

Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones

In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte- macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum.     

Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations

PURPOSE: To investigate in vivo the retinal microstructure in X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations as a prelude to treatment initiatives for this common form of RP. METHODS: Patients with RPGR-XLRP (n = 12; age range, 10-56 years) were studied by optical coherence tomography (OCT) in a wide region of central retina. Overall retinal thickness and outer nuclear layer (ONL) and inner retinal parameters across horizontal and vertical meridians were analyzed and compared. RESULTS: Retinal architecture of all patients with RPGR mutations was abnormal. At the fovea in younger patients, the ONL could be normal; but, at increasing eccentricities, there was a loss of photoreceptor laminar structure, even at the youngest ages studied. At later ages and advanced disease stages, the ONL was thin and reduced in extent. Inner retinal thickness, in contrast, was normal or hyperthick. Inner retinal thickening was detectable at all ages studied and was strongly associated with ONL loss. CONCLUSIONS: Inner retinal laminar abnormalities in RPGR-XLRP are likely to reflect a neuronal-glial retinal remodeling response to photoreceptor loss and are detectable relatively early in the disease course. These results should be factored into emerging therapeutic strategies for this form of RP.     

The role of percutaneous nephrostomy in the management of obstructing candidiasis of the urinary tract in infants

We report on 5 neonates with obstructive urinary tract candidiasis in whom percutaneous nephrostomy had a major role in management. The advantages of percutaneous nephrostomy in this setting include prompt drainage of the obstructed renal pelvis or ureter, direct access to obtain specimens from the renal pelvis to confirm the diagnosis, direct irrigation of the fungus balls with amphotericin B and an access route for fragmentation of fungus balls by guide wire manipulation. In 3 cases percutaneous placement of the nephrostomy tube was successful in obtaining and maintaining access to the renal pelvis, while in 2 surgical intervention was required because of problems maintaining placement of the percutaneous catheters. Percutaneous nephrostomy with antegrade amphotericin B irrigation, coupled with systemic antifungal therapy, is the mainstay of treatment. The usefulness of ultrasonography in the early diagnosis of renal candidiasis also is emphasized.     

Permanent skin pigmentation for decorative and reconstructive purposes

Permanent pigmentation can be useful in dermatology to both highlight natural body structures and reconstruct defects. It is popular to add color to aging lips or provide enhancement of the eyes through permanent eyeliner. Permanent pigmentation is also finding its way into breast reconstruction to restore the appearance of an areola or to add beard stubble to a scarred face. This method of professional tattooing is becoming a part of the dermatologic armamentarium.     

Culture isolation of Acanthamoeba species and leptomyxid amebas from patients with amebic meningoencephalitis, including two patients with AIDS.

Acanthamoeba species and leptomyxid organisms are free-living amebas that cause meningoencephalitis, primarily in immunocompromised patients. We report the isolation and culture of Acanthamoeba species and leptomyxid amebas from four patients with fatal amebic meningoencephalitis. Acanthamoeba species were cultured from brain abscess specimens from three immunocompromised patients (including two patients with AIDS). In the case of the fourth patient, who had no identifiable immunodeficiency, leptomyxid amebas were cultured from a specimen from a subcutaneous nodule and were identified in amebic granulomas in brain tissue by the indirect immunofluorescence test. Persons with advanced infection due to the human immunodeficiency virus may be at increased risk for amebic meningoencephalitis, but the diagnosis should be considered in the differential diagnosis of any immunocompromised patient with cerebral abscesses.     

Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.