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.     

Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.     

Digital palpation of intraocular pressure

BACKGROUND AND OBJECTIVE: Previous studies investigating the accuracy of digital palpation through the eyelids to estimate intraocular pressure (IOP) have shown disappointing results. In this study, the accuracy of digital assessment of IOP by palpation of the bare cornea is investigated. MATERIALS AND METHODS: The IOP of a cadaveric eye model was varied from 5 to 40 mm Hg in increments of 5 mm Hg. Two examiners, one experienced and one inexperienced, digitally palpated the corneas and estimated IOP. The results were compared before and after a 1-hour training session. RESULTS: Prior to the training session, the experienced examiner guessed correctly 46% of the time and was correct within 5 mm Hg 100% of the time. The inexperienced examiner guessed correctly 21% of the time and was within 5 mm Hg 62% of the time. After the training session, the experienced examiner's score did not significantly (38% correct, 88% within 5 mm Hg, P = .05. CONCLUSIONS: Digital assessment of IOP by palpation of bare cornea is accurate when performed by experienced individuals. A minimal amount of training using the eye model may improve one's accuracy.     

Relation between coronary artery disease, aortic stiffness, and left ventricular structure in a population sample

With the use of the degenerated nucleotides that contain the conserved sequence of G protein-coupled receptor, we have identified a 648-bp clone (HDGRC02) from human genomic DNA with significant sequence homology to human neurotransmitter receptors. HDGRC02 was then used as a probe for the screening of full length gene. From human Lambda DASH II genomic library, a 1.6 Kb clone encoded a full length gene was isolated and named putative neurotransmitter receptor (PNR). PNR has a single open reading frame which predicts a 38.3 KD protein of 338 amino acids with seven transmembrane domain topography. The amino acid sequence of PNR exhibits considerable homology to the rat 5-HR1D receptor with 35% amino acid identity and 56% amino acid similarity. PNR also shows significant sequence homology to the 5-HT1D receptor from Japanese puffer fish fugu, to the 5-HT4L receptor from mouse, to the alpha-2 adrenergic receptor and to the D2 dopamine receptor. Northern blot analysis indicates that PNR is expressed in skeletal muscle and selected areas of the brain. A chromosome mapping study located the PNR gene with human chromosome band of 6q23. The findings in the present study demonstrate that PNR is a putative neurotransmitter receptor.     

Factors affecting the efficiency of collection of CD34-positive peripheral blood cells by a blood cell separator

BACKGROUND: The yield of CD34-positive cells obtained from an apheresis procedure is determined, in part, by the efficiency of collection. Optimization of the efficiency of CD34-positive peripheral blood cell collection requires identification of predictive factors. STUDY DESIGN AND METHODS: Demographic, stem cell collection, mobilization, and disease-related measures from autologous and allogeneic donors undergoing 252 progenitor cell apheresis procedures were retrospectively reviewed. Statistical relationships between CD34 collection efficiency and the various measures were determined by correlation and multiple linear regression analysis. RESULTS: CD34 collection efficiency inversely correlated with the peripheral white cell count, hematocrit, and serum albumin concentration (R2 = 0.29). White cell count was the single best predictor of CD34 efficiency (R2 = 0.19). Donor groups with cytopenias (patients vs. normal donors; increased cycles of prior chemotherapy; bone marrow involvement; chemotherapy plus growth factor mobilization) had higher collection efficiencies. Only 29 percent of the variability in the data could be attributed to white cell count, hematocrit, and albumin concentration. The majority of the remaining variability was due to unexplained differences between donors. CONCLUSION: CD34 collection efficiencies show considerable variation. Higher peripheral white cell counts, hematocrits, and/or albumin concentrations result in decreased CD34 collection efficiency, but most of the variability in the data is not accounted for by these three factors.     

Do we know what inappropriate laboratory utilization is? A systematic review of laboratory clinical audits

OBJECTIVE: Laboratory utilization has steadily increased, and some studies suggest inappropriate utilization. Therefore, we wished to assess studies that measure inappropriate laboratory use in light of methodological criteria. DESIGN: Systematic review of published studies. DATA SOURCES: MEDLINE, HEALTHSTAR, and EMBASE databases were searched from 1966 to September 1997 using a broad and inclusive strategy with no language restriction. In addition, the references of all retrieved studies and 3 textbooks on diagnostic testing were hand-searched. STUDY SELECTION: All studies that provided and applied criteria for inappropriate laboratory use. DATA EXTRACTION: Studies were categorized based on whether the criteria were implicit (objective criteria for inappropriate utilization not provided or very broad) or explicit. Guidelines for evaluation were applied to each study by a single reviewer. DATA SYNTHESIS: Forty-four eligible studies were identified. Eleven studies used implicit criteria for inappropriate laboratory utilization and contained small numbers of patients or physicians. Most did not adequately assess the reliability of the implicit criteria. Thirty-three studies used explicit criteria based on the appropriateness of test choice, frequency, and timing, as well as the probability of a positive result. There were large variations in the estimates of inappropriate laboratory use (4.5%-95%). Evidence supporting the explicit criteria was frequently weak by the standards suggested for therapeutic maneuvers, but was nonetheless compelling based on principles of physiology, pharmacology, and probability. CONCLUSIONS: Many studies identify inappropriate laboratory use based on implicit or explicit criteria that do not meet methodological standards suggested for audits of therapeutic maneuvers. Researchers should develop alternative evidentiary standards for measuring inappropriateness of laboratory test use.     

Spatial and temporal expression of angiogenic molecules during tumor growth and progression

The growth and metastasis of cancer directly correlates with tumor angiogenesis. A better understanding of the expression of regulatory factors controlling angiogenesis is important in exploiting this process therapeutically. Our present study demonstrates that small tumors (3-4 mm in diameter) express more basic fibroblast growth factor (bFGF) and interleukin 8 (IL-8) than large tumors (> 10 mm in diameter), whereas more vascular endothelial growth factor (VEGF) is expressed in large tumors. Immunostaining showed a heterogeneous distribution of angiogenic factors within the tumor; expression of bFGF and IL-8 was highest on the periphery of a large tumor, where cell division is maximum. VEGF expression was higher in the center of the tumor. In vitro studies demonstrated that sparse cultures of tumor cells expressed higher levels of bFGF and IL-8 than confluent cultures. In contrast, the expression of bFGF and IL-8 was not diminished in tumor cells growing on confluent monolayers of normal cells. VEGF expression was upregulated by cell density irrespective of contact with tumor cells or normal cells. These results demonstrate that the expression of different angiogenic factors in tumor cells can be regulated by their proximity to other tumor cells or host cells.