The ribonucleotide reductase inhibitor (E)-2''-fluoromethylene-2''-deoxycytidine (MDL 101,731): a potential topical therapy for herpes simplex virus infection

Recent advances in diagnosis, treatment, and tumor biology of the lymphoid blastic malignancies have challenged historical concepts and created a need for revised classification of these diseases. The authors review this material and present a classification relevant to current therapeutic protocols and available biological data. Further advances in understanding of these diseases can be anticipated, with possible further evolution of classification. The exact clinical role of sensitive studies to monitor residual disease during and after treatment remains to be established. These diseases may present difficult differential diagnostic problems. The importance of accurate diagnosis cannot be overemphasized, as highly successful but divergent treatments have evolved for these various hematopoietic diseases. Diagnostic problems are usually resolved with systematic analysis including careful morphology, cytochemistry, immunologic analysis, and addition of EM and other studies in selected circumstances.     

Effects of clorazepate, diazepam, and oxazepam on a laboratory measurement of aggression in men

The liver S9 head space vial equilibration technique is an in vitro alternative that holds promises for a satisfactory in vivo extrapolation of liver metabolism of volatile organic chemicals. The aim of this study was to investigate the suitability of this methodology for the extrapolation of in vitro metabolic data from rodent to man by allometry with the two highly metabolized organic solvents toluene and n-hexane as model substances. The calculated hepatic clearance of toluene in man from rodent liver S9 in this study was equal to the reported total body clearance of toluene in man, suggesting insignificant extrahepatic clearance of toluene in humans. The calculated hepatic clearance of n-hexane was less than the reported values of total body clearance of n-hexane in man, indicating an about 80% extrahepatic clearance of n-hexane in humans. Both results are in line with our present knowledge of the metabolism of the two organic solvents in man. Allometric scaling from rodent liver S9 head space incubations to in vivo metabolism of toluene and n-hexane in man thus seems promising and could be a method of choice for scaling of organic solvent metabolism in general.     

Environmental information systems in malaria risk mapping and epidemic forecasting

Every year between one and two million African children under five die of malaria. If one adds to this the contribution of malaria to all-cause infant mortality then clearly the burden of the disease is catastrophic--a disaster quietly happening each and every year. New tools are needed urgently to support those currently available for control of the disease. An effective vaccine remains elusive. This article outlines the potential contribution to malaria control services of satellite information, which is being used by resource managers in other sectors. In particular, it highlights the lessons which can be learned from early warning systems in other areas, especially those designed to respond to famine. An appendix provides a brief introduction to satellite data and their interpretation.     

Effects of time compression and time compression plus reverberation on the intelligibility of Northwestern University Auditory Test No. 6

The Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0 audio compact disc developed in 1992 includes several sets of degraded speech materials, two of which, time compression and reverberation, are described in this paper. The digital techniques used to compress the NU No. 6 materials (female speaker) on an 80386-based computer are described, along with a series of experiments on subjects with normal hearing that document the effects of the time compression on recognition performance. Experiment I examined at 70 dB SPL the effect on word recognition of 45, 55, 65, 70, and 75 percent compressions. Experiment II developed psychometric functions for the 45, 65, and 75 percent time-compression conditions. Experiment III defined the effects that time-compression degradation (45% and 65%) plus reverberation degradation (0.3 sec) had on the recognition performance on the NU No. 6 materials. Based on the experiments, four conditions (45% compression, 65% compression, 45% compression plus 0.3-sec reverberation, and 65% compression plus 0.3-sec reverberation) were selected and recorded on the compact disc. In the compact disc trials, normative data on the four conditions were developed from 120 listeners with normal hearing.     

Geometric and mechanical properties of the coracoacromial ligament and their relationship to rotator cuff disease

One of the most common causes of pain and disability in the upper limb is inflammation of the rotator cuff tendons. When no significant bony abnormality exists in the surrounding structures, the coracoacromial ligament has been implicated as a possible cause of impingement on the cuff tendons. Geometric and mechanical properties of 20 coracoacromial ligaments, 10 from shoulders with rotator cuff tears and 10 from normal shoulders, were accurately determined. In comparing rotator cuff tear and normal specimens, statistically significant changes in geometric properties were measured in the lateral band, but not in the medial band, of the ligament. The lateral band, which is the region most likely to impinge on the rotator cuff, was shorter and had a larger cross-sectional area in specimens with rotator cuff tears. Although there were no statistical differences in structural properties of the ligament between normal and rotator cuff tear groups, significant changes were evident in material properties. Previously reported histologic differences in the ligament in shoulders with rotator cuff tears are supported by the decreased material properties measured in the current study. Whether the differences in the coracoacromial ligament cause impingement or are due to impingement is still unknown at this time.     

Interbacterial binding among strains of pathogenic and commensal oral bacterial species

OBJECTIVE: Family resources and coping skills are important to adaptation to pediatric chronic illness. Psychological and educational interventions have been found to enhance the coping skills of children with juvenile rheumatic disease (JRD) and their families. We examined the efficacy of a 3-day family retreat as a multidisciplinary, comprehensive treatment. METHODS: Children with JRD and their caregivers completed questionnaires assessing the children's behavioral and emotional functioning, pain, strain on caregivers' work and leisure activities, and caregivers' psychological distress before and 6 months after the family retreat. Principal caregivers were both parents for 16 children, mothers only for 10 children, and an aunt for 1 child. RESULTS: Improvements were found in children's emotional functioning, strain on caregivers' work, and strain on caregivers' leisure activities. Reductions in reported pain were not consistently revealed. CONCLUSIONS: Family retreats are an efficacious, multidisciplinary approach to helping families of children with JRD cope with the disease and its manifestations. Importantly, retreats offer a comprehensive intervention package that might not be available to families on an individual basis.     

Initial processing of human proenkephalin in bovine chromaffin cells

The opioid peptide precursor preproenkephalin (PPE) contains seven enkephalin sequences and is synthesized by epinephrine-producing adrenal chromaffin cells and various peripheral and central neurons. After removal of its signal peptide, PPE undergoes processing at dibasic amino acid sites to yield its final opioid products-Met-enkephalin, Leu-enkephalin, and various larger, enkephalin-containing peptides. Processing of PPE was examined in bovine chromaffin cells using a plasmid containing the human PPE (hPPE) cDNA under the control of the cytomegalovirus immediate early enhancer/promoter. Following transfection of this hPPE-containing plasmid into bovine chromaffin cells, several proenkephalin-immunoreactive bands were observed on western blots with monoclonal antibodies that recognize human, but not bovine, proenkephalin sequences. The pattern of hPPE-derived peptides observed was similar to that of bovine PPE processing products. A series of recombinant plasmids containing mutations in the hPPE sequence at putative processing sites was then constructed. Conversion of Lys-Lys and Lys-Arg sequences to Lys-Gln and of Arg-Arg to Arg-Gln altered initial hPPE processing at only three of the putative processing sites. When hPPE cDNA containing mutations at all of these initially processed sites was expressed, one or more alternative processing sites were revealed. These data suggest the importance of structural features in addition to the dibasic sequences that limit the processing of proenkephalin.