Infectious disease physicians rate microbiology services and practices

Recent years have seen increasing emphasis on cost containment and quality improvement in clinical laboratory activities. Modifying those activities to enhance clinical relevance is one strategy that should be satisfying to both laboratory scientists and administrators. This guest commentary describes one approach to quality improvement--the use of user surveys to identify areas for improvement. As an initial attempt to define such areas in clinical diagnostic microbiology, infectious disease specialists, targeted for their particular interest and expertise in microbiology laboratory results, were polled and their responses were analyzed. Some of these data have been presented previously (E. J. Baron, D. P. Francis, and K. M. Peddecord, abstr. C-170, p. 520, in Abstracts of the 94th General Meeting of the American Society for Microbiology, 1994; K. M. Peddecord, E. J. Baron, D. P. Francis, and A. S. Benenson, abstr. C-172, p. 520, in Abstracts of the 94th General Meeting of the American Society for Microbiology, 1994; K. M. Peddecord, E. J. Baron, D. P. Francis, and J. A. Drew, Am. J. Clin. Pathol. 105:58-64, 1996). The discussion includes our recommendations for the use of these survey responses, and their limitations, as stimuli to initiate reexamination of certain microbiology laboratory practices in the interest of developing more cost-effective and clinically relevant protocols.     

Anhedonia and premorbid competence in young, nonpsychotic psychiatric inpatients

Earlier studies have demonstrated a significant relation between scores on the Physical Anhedonia Scale--but not on the Perceptual Aberration Scale--and premorbid social adjustment in schizophrenics (Chapman, Chapman, & Raulin, 1976, 1978; Schuck, Leventhal, Rothstein, & Irizarry, 1984). A similar relation between scores on these 2 scales and interpersonal competence in college students has also been noted (Beckfield, 1985; Haberman, Chapman, Numbers, & McFall, 1979; Numbers & Chapman, 1982). The present study extends this work by examining the relation of premorbid adjustment to scores on these 2 scales among young, nonpsychotic psychiatric inpatients. Consistent with the earlier findings, anhedonic Ss had poorer premorbid social competence when compared with nonanhedonic Ss, whereas no relation was found between scores on perceptual aberration and premorbid social competence.     

Normal reproductive neuroendocrinology in the female

The reproductive axis in women comprises a number of components that must function in a highly orchestrated manner for reproductive potential to be optimal. The neuroendocrine components of this axis, including the hypothalamus and the pituitary gland, are central to this system. Within the hypothalamus, the specialized neuronal system responsible for synthesizing and secreting gonadotropin-releasing hormone (GnRH) is itself modulated by a number of peptide and biogenic amine neurotransmitters that mediate feedback signals of ovarian origin. The luteinizing hormone and follicle-stimulating hormone secreting anterior pituitary gonadotropes perceive and transduce neural input in the form of GnRH, but are themselves also modulated by the ambient gonadal hormone concentrations. The authors review the physiologic relevance of the pulsatile nature of the GnRH signal, and some proposed mechanisms through which these signals are stimulated and modulated and subsequently perceived and transduced by gonadotropes.     

Serum fatty acids and the risk of fatal cancer. MRFIT Research Group. Multiple Risk Factor Intervention Trial

To examine the relation between serum fatty acids and cancer, the authors conducted a nested case-control study of 108 middle-aged men who died of cancer and 215 men without cancer, who were enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) between 1973 and 1976. Control subjects were matched to case subjects on age, smoking status, treatment assignment, date of randomization, and clinical center. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and analyzed their association with cancer. In stepwise logistic regression analyses that controlled for the MRFIT selection criteria variables and for alcohol consumption, no fatty acid was significantly associated with overall risk of cancer death (all p > 0.05). Serum levels of phospholipid dihomogammalinolenic acid (20:3), an essential fatty acid, were inversely associated with the risk of dying from lung cancer; a standard deviation increase was associated with a 32% decrease in risk (p = 0.05). Dietary cholesterol intake was associated with the risk of nonlung, non-digestive tract cancers; a standard deviation increase (331 mg/day) was associated with a 75% increase in risk (p = 0.02). The authors found no evidence to suggest that increased dietary intake or serum levels of polyunsaturated fatty acids were associated with an increased risk of fatal cancer among middle-aged men at high risk for coronary heart disease. The clinical significance of the inverse association between dihomogammalinolenic acid and lung cancer death is uncertain and requires confirmation.     

Cytosolic phospholipase A2 (cPLA2) distribution in murine brain and functional studies indicate that cPLA2 does not participate in muscarinic receptor-mediated signaling in neurons

Children (aged 4 and 7 years) and young adults produced a six-syllable utterance 15 times. The displacement of the lower lip was recorded with an Optotrak system and analyzed in a number of ways. First, using a procedure recently developed in our laboratory, displacement records from the 15 repetitions were amplitude- and time-normalized, and the spatiotemporal index (the STI) was computed. The STI reflects the degree to which repeated performance of a task produces movement trajectories that converge on a single pattern. Children produced less stable movement trajectories, as reflected in higher values on the STI. In a second analysis, standard measurements of amplitude and peak velocity were made for two opening and two closing lip movements. These measures suggested that, relative to the size of their oral structures, children have large movement ranges in speech. Also, children tend to move with a lower peak velocity. This large-amplitude, low-velocity movement style may reflect different underlying control processes. Finally, another analysis focused on open-close movement sequences associated with two words of the utterance. A pattern-recognition algorithm applied to the normalized waveforms from the open-close sequences revealed that children and adults produced equally distinctive movement trajectories for the two syllables. Taken together, these preliminary results suggest that nonlinear and nonuniform changes occur in components of the speech motor system during development.     

Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan

Overproduction of interleukin-10 (IL-10) may play an important role in the development of systemic lupus erythematosus (SLE) or lupus nephritis. There is also a polymorphic dinucleotide repeat in the human IL-10 promoter region (IL-10PR). Our aim was to study whether or not the IL-10PR alleles contributed to the susceptibility to SLE or lupus nephritis. One hundred SLE patients and 103 healthy controls were studied for IL-10PR by PCR and electrophoretic analysis. The distribution of IL-10PR alleles, genotypes and the sum of both alleles (SBA) from different groups or subgroups were analyzed. SLE patients showed no difference in the distribution of IL-10PR alleles, genotypes and SBA, as compared to healthy controls. Lupus nephritis patients (N = 49) also showed no difference in IL-10PR alleles, genotypes and SBA, as compared to SLE patients without nephritis (N = 51). Of 49 lupus nephritis patients, ten developed end-stage renal disease (ESRD) and four of them were found to suffer from rapid progressive renal failure (RPRF). Patients with RPRF presented much smaller SBA than other ESRD patients (p = 0.005). Lupus nephritis patients carrying small SBA (< 18) suffered from a higher prevalence of RPRF than lupus nephritis patients without small SBA (50% V.S. 0%, p < 0.001, relative risk 82). Our data provide the first evidence of a strong association between IL-10PR and severe progression of lupus nephritis in human patients. In the future, a prospective genetic analysis of IL-10PR for patients with lupus nephritis is recommended. It might be helpful for physicians to identify the lupus nephritis subgroup with a high risk of developing RPRF early, because this might lead to a better therapy and prognosis for these patients.     

The heterocyclic substituted pyridine derivative (+/-)-2-(-3-pyridinyl)-1-azabicyclo[2.2.2]octane (RJR-2429): a selective ligand at nicotinic acetylcholine receptors

The present report describes in vitro studies demonstrating that the heterocyclic substituted pyridine compound (+/-)-2-(3-pyridinyl)-1-azabicyclo[2.2.2]octane (RJR-2429) is extremely potent in activating human muscle nicotine ACh receptor (nAChR) (EC50 = 59 +/- 17 nM; Emax = 110 +/- 09% vs. nicotine). RJR-2429 is markedly less potent in activating nAChRs in the clonal cell line PC12, with EC50 = 1100 +/- 230 nM and Emax = 85 +/- 20% when compared with nicotine. The activation of a putative alpha 3 beta 4-containing nAChR in PC12 by RJR-2429 reveals a potency intermediate between nicotine and epibatidine (EC50 of 20,000 nM for nicotine and 30 nM for epibatidine). Dose-response curves for agonist-induced ileum contraction indicate that RJR-2429 is equipotent with nicotine, having an EC30 of approximately 2 microM. RJR-2429 binds with high affinity to alpha 4 beta 2 receptor subtype (Ki = 1.0 +/- 0.3 nM), and chronic exposure results in significant up-regulation of the high-affinity [3H]nicotine binding sites. In addition, RJR-2429 does not activate nAChRs present in rat thalamic preparations but is a potent inhibitor of this receptor subtype. It antagonizes nicotine-stimulated ion flux in thalamic synaptosomes with an IC50 of 154 +/- 37 nM. It also is a potent partial agonist at nAChRs mediating dopamine release from rat synaptosomal preparations (EC50 = 2 +/- 1 nM; Emax = 40%; epibatidine and nicotine have EC50 values of 0.4 and 100 nM, respectively). A model for the structure-activity profile of RJR-2429, nicotine and epibatidine was derived by molecular forcefield and quantum mechanics calculations and may provide important clues for the development of ligands selective for nAChR subtypes as probes in the life sciences or as potential therapeutic tools.     

Lung-specific expression of adenovirus E3-14.7K in transgenic mice attenuates adenoviral vector-mediated lung inflammation and enhances transgene expression

Herein, we report that the adenovirus E3-14.7K protein inhibits the inflammatory response to adenovirus in transgenic mice in which the E3-14.7K gene was selectively expressed in the respiratory epithelium, using the human surfactant protein C (SP-C) promoter. E3-14.7K mRNA and protein were detected specifically in the lungs of SPC/E3-14.7K transgenic mice. Responses of the transgenic mice to Av1Luc1, an E1-E3-deleted Ad vector encoding the luciferase reporter gene, were examined, including vector transgene expression and lung inflammation. In wild-type mice, luciferase activity declined rapidly and was lost 14 days following Av1Luc1 administration. The loss of luciferase activity was associated with pulmonary infiltration by macrophages and lymphocytes. In heterozygous SPC/E3-14.7K mice, luciferase activity was increased by 7 days compared with control littermates, and pulmonary infiltration by macrophages was decreased. In homozygous (+/+) SPC/E3-14.7K mice, luciferase activity was increased 7, 14, and 21 days following administration compared with wild-type mice, and lung inflammation was markedly reduced. After Av1Luc1 administration, PCNA staining of bronchiolar and alveolar respiratory epithelial cells was decreased in SPC/E3-14.7K transgenic mice, indicating decreased epithelial cell proliferation, a finding consistent with the observed reduction in inflammation. CD4 and CD8 lymphocyte populations were only mildly altered, while humoral responses to adenoviral vectors were unchanged in the SPC/E3-14.7K mice. The E3-14.7K protein expressed selectively in respiratory epithelial cells suppresses Ad-induced pulmonary epithelial cell cytotoxicity and lung inflammation in vivo and prolongs reporter gene expression.     

Einfluß der Laminatkomponenten von CFK-Werkstoffen auf das statische und das dynamische Verhalten

Influence of Different Laminate Components on the Static and Dynamic Properties of CERP The static and the dynamic properties of a conventional and a modified, toughened matrix system reinforced with two high strength carbon fibres of a different strain to failure was investigated. Three different laminates were chosen, an unidirectional laminate [0₈], a cross ply laminate [0₂, 90₂, 0₂, 90₂]_s, and a nearly quasi-isotropic laminate [0₂, ±45, 90 ]_s. It is shown, that the damage development under static as well as dynamic loading is delayed when using a toughened matrix system. This delay in damage development results in improved mechanical properties. However, when using a toughened matrix system together with fibres of a high strain to failure, the improvement of the static properties does not lead in the same extent to an improvement of the dynamic properties.