Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with > or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p<0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p<0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.     

Differentiation of Mycoplasma hyopneumoniae, M flocculare, and M hyorhinis on the basis of amplification of a 16S rRNA gene sequence

Cell damage is caused by energy depletion or by direct membrane damage, or a combination when a direct membrane damage affects energy depleted cells. In this report it was investigated whether the extent of direct membrane damage induced by lysophosphatidyl choline (LPC) or phospholipase C (PhC) on quiescent fibroblasts depended on the metabolic state of the cells. When glycolysis was inhibited cell damage was always extensively increased, whereas cell damage was also increased to a minor degree when exposed to PhC during sole inhibition of oxidative phosphorylation. Acceleration of glycolysis in cells with a low rate of glycolysis resulted in a dramatic improvement of the membrane susceptibility within a few minutes. Thus, susceptibility of the cell membrane to direct membrane damage depends on the metabolic state. The results also emphasize previous findings that glycolysis has a special role in maintaining membrane function and integrity.     

Pharmacokinetics of cyclophosphamide and its metabolites in bone marrow transplantation patients

Classical swine fever virus infection of pigs causes a severe leukopenia and immunosuppression. In the present study, the kinetics of virus infection, and identification of target cells for the virus in peripheral blood were analysed. Virus infection was often not detectable before 5-7 days p.i. A minority of animals yielded detectable infected cells at 3 days p.i., but < 5% PBMC. It was not until 10 days p.i. that this figure increased-to 35-70% PBMC depending on the animal. Detailed analysis of Ficoll-Hypaque-purified PBMC identified the major population to be SWC3+SWC8+CD14+MHCII- granulocytic cells. Microscopic observations determined that these low density granulocytic cells in the PBMC from CSFV infected animals were indeed immature cells. Both the low density granulocytic cells and monocytes were major targets for CSFV infection in the peripheral blood. This is the first demonstration that low density granulocytic cells dominate the blood leukocyte population during CSF, and that such cells are targets for virus infection. The present work also demonstrates that the leukocyte population changes, such as B lymphocyte depletion and the relative dominance of myeloid cells in the blood during CSF, occur before virus infection of the affected cells. Thus, the pathological mechanism therein is not a direct consequence of virus infection.     

Peripheral nerve insult induces NMDA receptor-mediated, delayed degeneration in spinal neurons

Injury of a peripheral nerve gives rise to adaptive functional and structural alterations in spinal neurons. We report that the rearrangement of the spinal circuitry in response to sciatic nerve transection in adult rats involves a delayed mode of degeneration of lumbar spinal cord neurons. Nuclear fragmentation was detected by the TUNEL technique 7 days after sciatic neurectomy but not after 3 or 14 days. Dying cells were preferentially located in the ipsilateral superficial dorsal horn and expressed the neuronal cytoskeletal marker SMI-31. Degeneration was prevented by continuous systemic treatment with the NMDA receptor-antagonist MK-801. These data are supportive that apoptosis is induced in spinal neurons in a transsynaptic manner by an early signal from injured afferent fibres via activation of spinal NMDA receptors.     

PET instrumentation: what are the limits?

This report has emphasized the attributes of positron emission tomography (PET) through a discussion of the historical development with attention to limitations or factors that are of importance in using and further developing this technology. As is the case for all nuclear detector developments, the factors that require consideration are spatial resolution, uniformity of resolution, sensitivity, distortions (attenuation), background noise (scatter and randoms), image volume, data acquisition capabilities (count-rate saturation), and limitations based on allowable radiation doses to the subject. Forty years ago, the fact that dual gamma-cameras could not handle the count-rates from the short half-life radionuclides that had clinical applications at that time (ie, 15O, 11C, 13N) precluded their acceptance in nuclear medicine. With the advent of 18F applications particularly with FDG in oncology, this limitations was no longer a barrier. Twenty years ago and until recently, the promise of time-of-flight PET has been stifled by the fact that the appropriately fast scintillator BaF2 had too low an efficiency (low density) to be useful in improving the signal to noise of a time-of-flight tomograph over contemporary systems. With the development of dense scintillators with high light output and high speed such as LSO30 the time-of-flight potentials are now once again worth pursuing. Twenty years ago systems that theoretically would have improved sensitivity by minimal or no septa with spherical geometric arrangements of detectors were ignored because it appeared that scatter backgrounds would lead to a signal to noise less than 1. But in the last 5 years, cylindrical systems without speta have shown that noise effective sensitivity improvements of a factor of 4 can be realized. With time-of-flight additional improvements in sensitivity will be realized. Horizons for detector development include discovery of new scintillators, new methods of registering scintillation light, deployment of larger field of view systems and methods of compensating for scatter, randoms, attenuation, and irregular sampling associated with new geometries which can encircle most of the body. The expected limit for PET is 2 mm isotropic resolution for the head and appendages including joints and breasts. Clinical realization of this resolution for the thorax and abdomen requires compensation for motion and even in this area strategies are underdevelopment which rely on the improvement in sensitivity being realized by 3D systems.     

Evaluation of an enforcement program to reduce tobacco sales to minors

OBJECTIVES: This study evaluated an active enforcement program to increase retailers' compliance with the law prohibiting tobacco sales to minors. METHODS: Tobacco sales to minors were monitored in 319 outlets in 6 pairs of communities in Erie County, New York. One community in each pair was randomly assigned to an enforcement intervention. RESULTS: Retailers' compliance with the law increased from 35% in 1994 to 73% in 1995. However, the change in compliance rates was roughly the same for stores in the enforcement and nonenforcement communities. CONCLUSIONS: Active compliance checking of retail outlets as a strategy to reduce illegal tobacco sales to minors may only be necessary insofar as it contributes to an increase in retailers' perception that the threat of enforcement is real.     

Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons

Recent scientific studies have demonstrated the efficacy of various forms of immunotherapy for the treatment of allergic diseases. Traditional subcutaneous immunotherapy, sublingual, oral, and intranasal immunotherapy have been shown to significantly reduce symptoms and favorably modulate the immune response. Outcome studies that use patient response data from standardized surveys represent the next challenge to all practicing allergists.     

Analysis of neuronal nitric oxide synthase isoform expression and identification of human nNOS-mu

Basonuclin was first described as a human keratinocyte zinc finger protein present in the nuclei of proliferative basal keratinocytes in the epidermis. It disappears from keratinocytes that have lost their proliferative ability and have entered terminal differentiation. We now report that basonuclin is present also in the germ cells of the mouse testis and ovary. Immunocytochemical staining detected basonuclin in the nuclei of spermatogonia and spermatocytes at various developmental stages. During spermiogenesis, it relocated from the nucleus to the midpiece of the flagellum of the spermatozoa. In the ovary, basonuclin was found mainly in the nuclei of developing oocytes. The dual presence of basonuclin in differentiated spermatozoa and oocytes suggests that it may play a role in their differentiation and the early development of an embryo.