Experimental endolymphatic hydrops and its relief by interrupting the lateral semicircular duct in guinea pigs.

It has been demonstrated that endolymphatic hydrops can be produced in guinea pigs by obliteration of the endolymphatic sac and this phenomenon was reproduced in our own laboratory. Interruption of the lateral semicircular duct of animals with labyrinthine hydrops produced a diminution of the hydrops in 4 out of 8 cases, and these did not show any collapse in the cochlear duct. It was considered that the hydrops was diminished by drainage of the surplus endolymph into the perilymphatic space, and that the cochlear duct was kept secure from collapse because of its distance from the operated lateral semicircular duct and of the utriculo-endolymphatic valve. Persistence of hydrops in the other four cases was thought to be due to closure of the operated lateral semicircular duct or to labyrinthitis. Although this series is not comprehensive enough, it seems to indicate that interruption of the lateral semicircular duct has a possibility of diminishing labyrinthine hydrops, as in cases of Ménière's disease, without hearing disturbance, provided that complications do not develop. Further investigation with many more animals, for a longer period of time after the operation, is required to gain more precisely detailed information.     

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure.     

The truncated glucocorticoid receptor in the P1798 mouse lymphosarcoma is associated with resistance to glucocorticoid lysis but not to other glucocorticoid-induced functions.

Glucocorticoid receptors in lines of the P1798 mouse lymphosarcoma either sensitive or resistant to glucocorticoid-induced lysis have been characterized and their functional significance determined. The glucocorticoid receptor from the cortisol-sensitive tumor is an Mr approximately 98,000 protein with a Stokes radius of 7.4 nm in the oligomeric, non-DNA-binding state and 5.6 nm in the transformed, DNA-binding state. This receptor binds glucocorticoid and reacts with the BUGR-2 monoclonal antibody. In contrast, two abnormal receptor species were identified in the cortisol-resistant tumor. One is an Mr approximately 98,000 non-steroid-binding but immunologically reactive protein. The other is an Mr approximately 45,000 species which contains both steroid- and DNA-binding sites but exhibits little or no reactivity with BUGR-2, suggesting that its NH2 terminus is truncated in a region within or adjacent to the BUGR epitope. This species had Stokes radii of 5.8 and 3.5 nm in nontransformed and transformed states, respectively. In both tumor lines, glucocorticoids stimulated the activities of glutamine synthetase and 5'-nucleotidase and the synthesis of glucocortin. However, glucocorticoid-induced tumor regression occurred only in the cortisol-sensitive tumor. Additionally, the glucocorticoid inducibility of a specific protein in the sensitive, but not in the resistant, tumor was demonstrated, as well as the presence of a protein specific to the resistant line. Taken together, these results suggest that the truncated glucocorticoid receptor in the P1798 lymphosarcoma is functional, although possibly in a more restricted gene-specific manner, and that the lysis defect, while possibly resulting from a truncated receptor, may also result from the inability of glucocorticoids to induce a critical protein in the pathway of programmed cell death and/or from the presence of a protein which inhibits the lytic response.     

Applying evidence-based medicine to traditional chinese medicine: debate and strategy

Drawing on recent paper published literature in both English and Chinese, this explores reactions to the evaluation of Chinese medicine using randomized controlled trials (RCTs) and the standards of evidence-based medicine (EBM). The literature review revealed a few sources which contend that Chinese medicine should not be evaluated on the basis of RCTs, but a far greater number which advocate for applying RCT and EBM standards to Chinese medicine. This paper describes the position of the detractors and points out ways in which their arguments contain oversimplified representations of Chinese medicine, biomedicine, EBM, and RCTs. In describing the position of the proponents, the analysis outlines some of the numerous innovative techniques they are developing for dealing with issues of control and standardization in efficacy research. Overall, the analysis indicates that important refinements are being generated in Chinese medicine research and clinical trial design in response to the challenges posed by the forced encounter of these two paradigms.     

ABO blood group in Kuwaitis: detailed allele frequency distribution and identification of novel alleles

BACKGROUND: The ABO blood group is clinically the most important blood group system and can now be genotyped easily by DNA-based methods without family studies. STUDY DESIGN AND METHODS: Samples (n = 166) from a Kuwaiti population were phenotyped by standard serologic techniques for the ABO blood group and genotyped for the ABO locus by an established multiplex polymerase chain reaction protocol followed by single-strand conformation polymorphism (SSCP) analysis. Nonstandard SSCP patterns were investigated by DNA sequencing of exons 6 and 7 and, if necessary intron 6. RESULTS: Standard SSCP patterns identified six classical alleles in this population: A101 (0.1115), A102 (0.0181), A201 (0.0301), B101 (0.1627), O101 (0.3103), and O201 (0.2500). One A, 1 B, and 8 O variant alleles were identified (total frequency, 0.1175). All variant alleles were each present in one or two chromosomes (< or =0.0060) in our samples except O109 (0.0813). Three of these 10 variant alleles were novel alleles defined by newly identified single-nucleotide polymorphisms in exon 7 (527G>A, 687C>T, and 1116G>A). One new base substitution result in amino acid change. CONCLUSIONS: This is the first study reporting the detailed distribution of ABO alleles and genotypes in Kuwaitis. Sixteen alleles were identified, including 3 novel alleles.     

Managing oral anticoagulation therapy: improving clinical outcomes. A review

Many physicians are reluctant to prescribe oral anticoagulation therapy (OAT) because of the fear of haemorrhagic complications. Changes in patient health, lifestyle or diet and other drugs can alter the effectiveness of oral anticoagulants. These potential interferences, added to the fact that each individual has a different reaction to these drugs, requires that therapy is monitored regularly. This article aims to review those strategies which help to achieve optimal anticoagulation control and improve the outcomes of OAT. Relevant articles were identified through a search of MEDLINE and included publications reporting on intensity of anticoagulation, the initiation of therapy and the role of pharmacogenetics, the transition from primary to secondary care, management by specialized clinics using decision support software and home‐testing. Implementation of these strategies would increase the use of oral anticoagulants by physicians and offers the potential to improve patient safety and reduce adverse events.     

Quality of life among implantable cardioverter-defibrillator recipients in the primary prevention therapeutic era

BACKGROUND: Although patients receiving implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death are the fastest growing segment of the ICD recipient population, the quality-of-life (QOL) effects of the ICD among primary prevention patients are not well understood. The purpose of this study was to measure and compare the health-related QOL among primary and secondary prevention ICD recipients, and to determine predictive factors for high or low QOL in each group. METHODS: Forty-five primary prevention and 75 secondary prevention ICD recipients receiving routine care in electrophysiology clinics within the University of Pennsylvania Health System were assessed using several well-validated general and ICD-specific QOL instruments. RESULTS: Between primary and secondary prevention patients, there were no significant differences in EuroQol 5D (medians: 0.84 vs 0.84, P = 0.71), Health Utilities Index (medians: 0.88 vs 0.85, P = 0.95), Short Form-12 aggregate physical summary (means: 45 vs 46, P = 0.64), and Short Form-12 aggregate mental summary (means: 46 vs 47, P = 0.93) scores. Both primary and secondary prevention patients viewed their devices favorably according to the Florida Patient Acceptance Survey scale, with no significant differences between group means (80 vs 83, P = 0.71). However, substantial fractions of both primary and secondary prevention recipients had particular concerns about lifting (40%), sexual activity (19%), and driving (14%). CONCLUSIONS: QOL does not significantly differ between primary prevention and secondary prevention ICD recipients. Device recipients had comparable QOL to published, nationwide QOL estimates among non-ICD patients of similar age. The ICD was highly acceptable to most primary and secondary prevention patients.