Cross-reactivity in HIV-infected patients switched from trimethoprim-sulfamethoxazole to dapsone

STUDY OBJECTIVE: To evaluate the cross-reactivity of dapsone after a documented hypersensitivity reaction to trimethoprim-sulfamethoxazole (TMP-SMX) during prophylaxis for Pneumocystis carinii pneumonia. DESIGN: Retrospective, chart review, cohort study. SETTING: Two university-affiliated teaching hospitals. PATIENTS: Sixty patients infected with the human immunodeficiency virus. MEASUREMENTS AND MAIN RESULTS: Thirteen patients (21.7%) had cross-reactivity to dapsone after the reaction to TMP-SMX. No significant risk factors for this response were identified. Most reactions were of mild or moderate severity and rated as possibly or probably caused by one of the agents. Of the 13 patients, 4 (30.8%) continued therapy. CONCLUSIONS: Although cross-reactivity can occur, dapsone may be considered in patients with mild hypersensitivity reactions to TMP-SMX.     

Wavelength-tunable asymmetric cladding ridge-waveguide distributedBragg reflector lasers with very narrow linewidth

Narrow-linewidth ridge-waveguide distributed Bragg reflector (DBR) lasers with asymmetric cladding are demonstrated. This design requires only a single epitaxial growth of an asymmetric cladding laser structure while the grating and the ridge waveguide are fabricated after the growth. These lasers have a threshold current as low as 9 mA, a slope efficiency of 0.3 W/A, and a T₀ of 100 K. Wavelength tuning of 8 nm is achieved by current injection heating of the DBR section. A spectral-linewidth minimum of 36 kHz is achieved at an output power of 20 mW and is limited by linewidth rebroadening due to current injection in both the gain section and DBR section     

Cystic prostatic disease associated with adrenocortical lesions in the ferret (Mustela putorius furo)

CONTEXT: In British Columbia, human immunodeficiency virus (HIV)-infected persons eligible for antiretroviral therapy may receive it free but the extent to which HIV-infected injection drug users access it is unknown. OBJECTIVE: To identify patient and physician characteristics associated with antiretroviral therapy utilization in HIV-infected injection drug users. DESIGN: Prospective cohort study with record linkage between survey data and data from a provincial HIV/AIDS (acquired immunodeficiency syndrome) drug treatment program. SETTING: British Columbia, where antiretroviral therapies are offered free to all persons with HIV infection with CD4 cell counts less than 0.50 x 10(9)/L (500/microL) and/or HIV-1 RNA levels higher than 5000 copies/mL. SUBJECTS: A total of 177 HIV-infected injection drug users eligible for antiretroviral therapy, recruited through the prospective cohort study since May 1996. MAIN OUTCOME MEASURES: Patient use of antiretroviral drugs through the provincial drug treatment program and physician experience treating HIV infection. RESULTS: After a median of 11 months after first eligibility, only 71 (40%) of 177 patients had received any antiretroviral drugs, primarily double combinations (47/71 [66%]). Both patient and physician characteristics were associated with use of antiretroviral drugs. After adjusting for CD4 cell count and HIV-1 RNA level at eligibility, odds of not receiving antiretrovirals were increased more than 2-fold for females (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.08-5.93) and 3-fold for those not currently enrolled in drug or alcohol treatment programs (OR, 3.49; 95% CI, 1.45-8.40). Younger drug users were less likely to receive therapy (OR, 0.47/10-y increase; 95% CI, 0.28-0.80). Those with physicians having the least experience treating persons with HIV infection were more than 5 times less likely to receive therapy (OR, 5.55; 95% CI, 2.49-12.37). CONCLUSIONS: Despite free antiretroviral therapy, many HIV-infected injection drug users are not receiving it. Public health efforts should target younger and female drug users, and physicians with less experience treating HIV infection.     

Detection of irradiated food by immunoassay – development and optimization of an ELISA for dihydrothymidine in irradiated prawns

This paper describes the development and use of a competitive enzyme‐linked immunosorbent assay (ELISA) to detect prawns which have been irradiated. The ELISA utilizes a monoclonal antibody against a modified DNA base, dihydrothymidine. A comparison of extraction procedures demonstrated that DNA purification was not required and that crude prawn homogenate could be used in the ELISA. The ELISA was applied successfully to two prawn species, North Atlantic prawn (Pandalus borealis) and Tiger prawn (Penaeus monodon). The ELISA has a working range of 0.5–2 kGy with CVs typically below 10%. Storage of irradiated prawns for up to 12 months at ?20 °C had no effect on ELISA performance. As most food contains DNA the assay has potential to be applied in a wide range of foodstuffs.     

Molecular characterization of N-methyl-D-aspartate receptors expressed in mammalian cells yields evidence for the coexistence of three subunit types within a discrete receptor molecule

The N-methyl-D-aspartate R1 (NMDA R1), NMDA R2A, and NMDA R2C subunits were expressed transiently in double or triple combinations in human embryonic kidney (HEK) 293 cells. The biochemical and pharmacological properties of the cloned receptors were compared with those of adult mouse forebrain and cerebellum. Under conditions established for maximal expression, cotransfection of the NMDA R1 and R2C subunits yielded a protein detected immunologically with a molecular size of 780,000-850,000 daltons. No cell death was observed in the transfected cells, and the KD for [3H]MK801 binding to the NMDA R1/R2C receptor was 346 +/- 158 nM. This was in contrast to a value of KD = 22 +/- 9 nM found for native cerebellar receptors. Co-transfection with NMDA R1/R2A/R2C subunits with a DNA ratio, 1:3:3, resulted in the expression of a protein with a size similar to the NMDA R1/R2C combination, but the affinity of [3H]MK801 was now 22 +/- 5 nM, and the percentage cell death post-transfection was 89 +/- 17%. Immunoprecipitation assays of detergent-solubilized transfected cells with NMDA R1 subunit-specific antibodies co-precipitated the NMDA R2A and NMDA R2C subunits in 1/2A and 1/2C transfections, respectively. Similarly, immunoprecipitations with either NMDA R1 or NMDA R2C subunit-specific antibodies co-precipitated the NMDA R2A subunit in the R1/2A/2C triple transfections. These results show that the three NMDA receptor subunit types can co-assemble following their co-expression in mammalian cells with a pharmacological profile that is similar to that found for adult cerebellar NMDA receptors.     

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.     

Arteriovenous malformation of the base of tongue: case report and literature review

Arteriovenous malformations of the head and neck pose a challenging therapeutic and reconstructive problem. In this report we describe a rare case of an arteriovenous malformation of the base of tongue. The patient, a young adult female, was treated with embolization followed by surgical resection using a lateral pharyngotomy approach. Reconstruction of the extensive base of tongue defect was accomplished using a radial forearm free flap. Currently, the patient is decannulated, articulates clearly, tolerates a normal diet, and is without recurrence. Our treatment approach is discussed in detail and compared with alternative techniques.     

Teaching hospital costs: implications for academic missions in a competitive market

CONTEXT: As the managed care environment demands lower prices and a greater focus on primary care, the high cost of teaching hospitals may adversely affect their ability to carry out academic missions. OBJECTIVE: To develop a national estimate of total inpatient hospital costs related to graduate medical education (GME). DESIGN: Using Medicare cost report data for fiscal year 1993, we developed a series of regression models to analyze the relationship between inpatient hospital costs per case and explanatory variables, such as case mix, wage levels, local market characteristics, and teaching intensity (the ratio of interns and residents to beds). SETTING AND PARTICIPANTS: A total of 4764 nonfederal, general acute care hospitals, including 1014 teaching hospitals. MAJOR OUTCOME MEASURES: Actual direct GME hospital costs and estimated indirect GME-related hospital costs based on the statistical relationship between teaching intensity and inpatient costs per case. RESULTS: In 1993, academic medical center (AMC) costs per case were 82.9% higher than those for urban nonteaching hospitals (actual cost per case, $9901 vs $5412, respectively). Non-AMC teaching hospital costs per case were 22.5% higher than those for nonteaching hospitals (actual cost per differences in case, $6630 vs $5412, respectively). After adjustment for case mix, wage levels, and direct GME costs, AMCs were 44% more expensive and other teaching hospitals were 14% more costly than nonteaching hospitals. The majority of this difference is explained by teaching intensity. Total estimated US direct and indirect GME-related costs were between $18.1 billion and $22.8 billion in 1997. These estimates include some indirect costs, not directly educational in nature, related to clinical research activities and specialized service capacity. CONCLUSIONS: The cost of teaching hospitals relative to their nonteaching counterparts justifies concern about the potential financial impact of competitive markets on academic missions. The 1997 GME-related cost estimates provide a starting point as public funding mechanisms for academic missions are debated. The efficiency of residency programs, their consistency with national health workforce needs, financial benefits provided to teaching hospitals, and ability of AMCs to maintain higher payment rates are also important considerations in determining future levels of public financial support.     

Molecular mechanics parameterization of thionucleoside disulfides for modeling cross-linked duplex DNA

We describe a solution to a molecular mechanics parameterization problem involving disulfide bonds between thionucleosides. Key torsional and bending parameters developed from ab initio calculations were incorporated into the AMBER* force-field in order to accurately represent the disulfide linkage in DNA cross-linked via this bond.