Suitability of bupropion SR for nicotine-dependent smokers: problems in a practice setting

BACKGROUND: Bupropion SR (Zyban) has been shown in randomized controlled trials to be an efficacious pharmacological aid for smoking cessation; however, recent reports have raised serious concerns about the breadth of its applicability without complications or contraindications. METHODS: We examined this issue in a well-documented medical population, i.e. veterans volunteering to participate in a smoking cessation treatment research program involving the use of bupropion SR. RESULTS: Overall, 22% of the 78 subjects who met the study criteria were appropriate for and completed the course of medication. CONCLUSIONS: Thus, bupropion SR in nicotine-dependent veterans may not be broadly applicable when conservative prescribing guidelines are carefully followed.     

Rebound eosinophilia after treatment of hypereosinophilic syndrome and eosinophilic gastroenteritis with monoclonal anti-IL-5 antibody SCH55700

BACKGROUND: Hypereosinophilic syndrome and eosinophilic gastroenteritis with peripheral eosinophilia are characterized by sustained eosinophilia and eosinophil-mediated tissue damage. Although treatment with the humanized monoclonal anti-IL-5 antibody SCH55700 resulted in improvement of eosinophilia and clinical symptoms in 6 of 8 of patients with hypereosinophilic syndrome or eosinophilic gastroenteritis with peripheral eosinophilia for as long as 12 weeks, eosinophil counts subsequently rose above baseline levels, accompanied by an exacerbation of symptoms. OBJECTIVE: To identify the mechanism underlying this rebound eosinophilia. METHODS: Purified eosinophils from patients or normal donors were cultured with IL-5, patient serum, and/or anticytokine antibodies, and eosinophil survival was assessed by flow cytometry. Serum and intracellular cytokine levels were measured by multiplex sandwich ELISA and flow cytometry, respectively. RESULTS: Before treatment with SCH55700, in vitro eosinophil survival in media and in response to recombinant IL-5 was similar in patients and normal donors. At 1 month posttreatment, the eosinophil survival curves were unchanged in 4 of 5 patients in media and in all 5 patients in response to recombinant IL-5. Normal eosinophil survival was prolonged in cultures containing posttreatment but not pretreatment sera (pretreatment vs posttreatment, 10.74% vs 73.02% live cells; P = .01). This posttreatment serum effect on eosinophil survival was reversed by the addition of the monoclonal anti-IL-5 antibody TRFK5. Although increased levels of serum IL-5 were observed at 1 month compared with 2 to 3 days posttreatment in 5 of 6 patients ( P = .04), intracellular cytokine analysis did not reveal increased production of IL-5 by peripheral blood mononuclear cells. CONCLUSIONS: The rebound eosinophilia after SCH55700 treatment is a result of a serum factor that enhances eosinophil survival. Reversal of this effect by the addition of antibody to IL-5 suggests that this factor may be IL-5 itself.     

Null mutation of calpain 3 (p94) in mice causes abnormal sarcomere formation in vivo and in vitro

The giant protein titin serves a primary role as a scaffold for sarcomere assembly; however, proteins that mediate this remodeling have not been identified. One potential mediator of this process is the protease calpain 3 (C3), the protein mutated in limb girdle muscular dystrophy type 2A. To test the hypothesis that C3 mediates remodeling during myofibrillogenesis, C3 knockout (C3KO) mice were generated. The C3KO mice were atrophic containing small foci of muscular necrosis. Myogenic cells fused normally in vitro, but lacked well-organized sarcomeres, as visualized by electron microscopy (EM). Titin distribution was normal in longitudinal sections from the C3KO mice; however, EM of muscle fibers showed misaligned A-bands. In vitro studies revealed that C3 can bind and cleave titin and that some mutations that are pathogenic in human muscular dystrophy result in reduced affinity of C3 for titin. These studies suggest a role for C3 in myofibrillogenesis and sarcomere remodeling.     

Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting

Objective:  Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus marked by characteristic biochemical derangements. Diagnosis and management involve frequent evaluation of these biochemical parameters. Reliable bedside equivalents for these laboratory studies may help reduce the time to treatment and reduce costs.
Methods:  We evaluated the precision and bias of a bedside serum ketone meter in the acute care setting. Serum ketone results using the Precision Xtra™ glucometer/ketone meter (Abbott Laboratories, MediSense Products Inc., Bedford, MA, USA) correlated strongly with the Children's Medical Center of Dallas' laboratory values within the meter's value range.
Results:  Meter ketone values steadily decreased during the treatment of DKA as pH and CO₂ levels increased and acidosis resolved.
Conclusion:  Therefore, the meter may be useful in monitoring therapy for DKA. This meter may also prove useful in identifying patients at risk for DKA in physicians' offices or at home.     

Cytotoxic T lymphocyte therapy for Epstein-Barr virus+ Hodgkin's disease

Epstein Barr virus (EBV)+ Hodgkin's disease (HD) expresses clearly identified tumor antigens derived from the virus and could, in principle, be a target for adoptive immunotherapy with viral antigen-specific T cells. However, like most tumor-associated antigens in immunocompetent hosts, these potential targets are only weakly immunogenic, consisting primarily of the latent membrane protein (LMP)1 and LMP2 antigens. Moreover, Hodgkin tumors possess a range of tumor evasion strategies. Therefore, the likely value of immunotherapy with EBV-specific cytotoxic effector cells has been questioned. We have now used a combination of gene marking, tetramer, and functional analyses to track the fate and assess the activity of EBV cytotoxic T lymphocyte (CTL) lines administered to 14 patients treated for relapsed EBV+ HD. Gene marking studies showed that infused effector cells could further expand by several logs in vivo, contribute to the memory pool (persisting up to 12 mo), and traffic to tumor sites. Tetramer and functional analyses showed that T cells reactive with the tumor-associated antigen LMP2 were present in the infused lines, expanded in peripheral blood after infusion, and also entered tumor. Viral load decreased, demonstrating the biologic activity of the infused CTLs. Clinically, EBV CTLs were well tolerated, could control type B symptoms (fever, night sweats, and weight loss), and had antitumor activity. After CTL infusion, five patients were in complete remission at up to 40 mo, two of whom had clearly measurable tumor at the time of treatment. One additional patient had a partial response, and five had stable disease. The performance and fate of these human tumor antigen-specific T cells in vivo suggests that they might be of value for the treatment of EBV+ Hodgkin lymphoma.     

The Health Insurance Portability and Accountability Act Privacy Rule: a practical guide for researchers

BACKGROUND: The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, intended to address potential threats to patient privacy posed by the computerization and standardization of medical records, provides a new floor level of federal protection for health information in all 50 states. In most cases, compliance with the Privacy Rule was required as of April 2003. Yet considerable confusion and concern remain about the Privacy Rule and the specific changes it requires in the way healthcare providers, health plans, and others use, maintain, and disclose health information. Researchers worry that the Privacy Rule could hinder their access to health information needed to conduct their research. OBJECTIVES: In this article, we explain how the final version of the Privacy Rule governs disclosure of health information, assess implications of the Privacy Rule for research, and offer practical suggestions for researchers who require access to health information. CONCLUSION: The Privacy Rule is fundamentally changing the way that healthcare providers, health plans, and others use, maintain, and disclose health information and the steps that researchers must take to obtain health data. The Privacy Rule requires researchers who seek access to identifiable health information to obtain written authorization from subjects, or, alternatively, to demonstrate that their research protocols meet certain Privacy Rule requirements that permit access without written authorization. To ensure continued access to data, researchers will need to work more closely than before with healthcare providers, health plans, and other institutions that generate and maintain health information.     

Are there race/ethnicity differences in outpatient congestive heart failure management, hospital use, and mortality among an insured population?

OBJECTIVE: The objective of this study was to assess the quality of outpatient care received by patients with congestive heart failure (CHF) and whether differences in care and outcomes exist by race/ethnicity. BACKGROUND: Appropriate outpatient CHF management can improve patient well-being and reduce the need for costly inpatient care. Yet, little is known regarding outpatient CHF management or whether differences in this care exist by race/ethnicity. METHODS: Using automated data sources, we identified a cohort of insured patients seen in an outpatient setting for CHF between September 1992 and August 1993. Medical record abstraction was used to confirm diagnosis of CHF. Patients (N = 566) were followed until September 1998. Race/ethnicity differences in outpatient management and medical care utilization were assessed using generalized estimating equations. Differences in mortality and hospitalization for CHF, controlling for patient characteristics and outpatient management, were assessed using Cox and Andersen-Gill models, respectively. RESULTS: With the exception of beta blocker use and primary care visit frequency, few differences by race/ethnicity in patient characteristics and CHF management were found. However, older black patients had more hospital use both at baseline and during follow up. These differences persisted after adjusting for patient characteristics and clinical management. No race/ethnicity differences were found in mortality. CONCLUSIONS: In an insured population, older black patients with CHF have substantially more hospital use than older white patients. This increased use was not explained by differences in CHF outpatient management. Further research is needed to understand why race/ethnicity differences in hospital use are observed among older patients with CHF.     

Trichofolliculoma with incidental focal acantholytic dyskeratosis

Incidental focal acantholytic dyskeratosis has been described in a variety of cutaneous lesions, including benign and malignant epithelial lesions, fibrohistiocytic lesions, inflammatory lesions, and melanocytic lesions. It has also been observed in follicular lesions such as comedones and ruptured follicles. We report the case of a 47-year-old man with a firm, flesh-colored 2-mm pruritic papule in the sun-exposed area above the left eyebrow. An excisional biopsy was performed, the tissue was processed, and the hematoxylin and eosin slides were evaluated. Microscopic examination showed a dilated cystic cavity filled with keratinous debris and scattered fragments of hair. Smaller secondary follicular structures branched from the primary cyst's walls into the adjacent dermis. Hyperkeratosis, acantholysis, dyskeratosis, and suprabasilar clefts were also focally present. Correlation of the lesion's clinical morphology and microscopic features established a diagnosis of trichofolliculoma with incidental focal acantholytic dyskeratosis. Hence, trichofolliculoma can be added to the list of follicular lesions in which focal acantholytic dyskeratosis may be observed as an incidental microscopic change.