Measurements of HCV neutralizing antibodies and of HCV-specific CD4+ and CD8+ cells using hepatitis C virus pseudo-particles (HCVpp)

BackgroundFor the medical management, it would be of great relevance to get a diagnostic marker predicting the outcome of infection.ObjectivesFor this purpose, the envelope antigens of the individual HCV strain in a patient was tested for their capacity to induce neutralizing antibodies and cytotoxic T lymphocytes.Study designA system for the measurement of neutralizing antibodies as well as for the stimulation of a HCV-specific T-cell response using pseudo-typed HCV particles (HCVpp) was established. A report on results of a pilot study conducted with blood specimens of 19 chronically infected patients is also presented.ResultsNeutralization of HCVpp could be measured in nearly all HCV sero-positive patient samples. Nevertheless, in more than half of the patient samples (11/19), no HCV-specific CD4+ response was detectable. In addition, HCV-specific CD8+ response was measurable in most of the patients when HCVpp were used for T-cell stimulation. Although the same antigens (HCVpp) were used, there was no relevant correlation between neutralization titers and T-cell response.ConclusionOur study shows that HCVpp are appropriate antigens for specific stimulation of lymphocytes as well as for the investigation of antibody neutralization activity.     

The use of the kidney biopsy to predict allograft loss in a pediatric transplant population

Forty-seven biopsy specimens of renal allografts from pediatric transplant recipients were evaluated by light microscopy using a 117 item survey of histopathologic changes. The presence and distribution of immunofluorescent staining were also evaluated. Histopathologic findings associated with irreversible allograft rejection were determined using statistical methods and then correlated with one another. The effect on allograft survival when several of these features were present on the same specimen was assessed. Glomerular, arteriolar and small artery changes were associated with irreversible rejection. When several of these histologic findings occurred on the same biopsy specimen the allograft was always lost. Interstitial and tubular changes generally not predictive of rejection and immunofluorescent staining was not associated with graft loss.     

Hypertension guidelines and their limitations--the impact of physicians' compliance as evaluated by guideline awareness.

OBJECTIVE : The initial step of an optimal therapeutic strategy for patients with arterial hypertension is the recognition and acceptance of new recommendations by the physicians themselves. This guideline awareness of the physicians has never been evaluated in detail. DESIGN : The awareness of content of current recommendations in hypertension diagnosis, treatment and treatment control was therefore assessed in primary care physicians using a questionnaire. The guidelines of the German Hypertension Society were used as the reference standard. PARTICIPANTS : A total of 24 899 German physicians, including all internists, all cardiologists and 22% of general practitioners were contacted in a nationwide survey. MAIN OUTCOME MEASURES : The number of answers in agreement with the guideline was used as a measure of guideline awareness. Adequate awareness of content of guideline recommendations was defined as the correct answer to five out of eight questions; the correct answers had to include the appropriate definition of hypertension. RESULTS : The analysis was based on 11 547 returned questionnaires (47.1%). An adequate guideline awareness was found in 23.7% of the total study population, especially in 37.1% of cardiologists, in 25.6% of internists and in 18.8% of general practitioners. While the guideline awareness was significantly influenced by the duration of private practice, regional and municipal factors had only minor influence on the results. CONCLUSION : The impact of hypertension guidelines on actual medical knowledge is modest. Thus, the information strategies about current treatment guidelines must be improved and tailored to the needs of physicians in clinical practice to ultimately improve patient care.     

Antagonism of sexual behavior in female rats by ventromedial hypothalamic implants of antiestrogen

The present experiments sought to identify brain regions in which implants of an antiestrogen would antagonize the ability of a systemic estradiol treatment to activate sexual behavior in female rats. In experiment 1, ovariectomized female rats were implanted subcutaneously with 5-mm Silastic capsules containing a 5% concentration of estradiol and injected with 500 micrograms progesterone 2 days later, 4-5 h before testing for sexual behavior. Bilateral intracranial implants of 1% crystalline concentrations of the high-affinity antiestrogens monohydroxytamoxifen (TAM) or keoxifene placed into the ventromedial nucleus of the hypothalamus (VM) 24 h prior to estradiol treatment significantly reduced lordosis responsivity compared with control females receiving empty cannulae. Implants of 1% TAM into the medial preoptic area or medial amygdala 24 h prior to estradiol that no significant effect on lordosis. Similarly, implants of 1% TAM into the VM 12 h after estradiol had no effect on lordosis. In experiment 2, lordosis was activated by subcutaneous implants of Silastic capsules containing 1% estradiol plus 500 micrograms progesterone. In this experiment, implants of 1% TAM into the VM 24 h prior to estradiol significantly reduced lordosis only if both cannulae tips were in, or adjacent to, the VM. Females receiving intracranial 1% TAM, but whose cannulae (even unilaterally) were outside the VM, had levels of lordosis equivalent to those of control females. Increasing the concentration of intracranial TAM to 10% virtually eliminated lordosis in females with bilateral implants in the VM, whereas females receiving intracranial 10% TAM in the region of, but outside, the VM showed no evidence of a lordosis deficit.(ABSTRACT TRUNCATED AT 250 WORDS)     

The 70-kDa heat shock cognate protein (Hsc73) gene is enhanced by ovarian hormones in the ventromedial hypothalamus

Estrogen (E) and progesterone (P) orchestrate many cellular responses involved in female reproductive physiology, including reproductive behaviors. E- and P-binding neurons important for lordosis behavior have been located within the ventromedial hypothalamus (VMH), and several hormone-responsive genes have been observed there as well. In attempts to identify additional E- and P-responsive genes in the VMH that may contribute to sexual behaviors, we used the differential display mRNA screening technique. One of the genes identified encodes the 73-kDa heat shock cognate protein (Hsc73). Quantitative in situ hybridization analysis of brains from naturally cycling female rats revealed a significant increase in Hsc73 mRNA in the VMH and arcuate nucleus of animals during proestrus compared with those at diestrus-1. To confirm that these increases were steroid hormone dependent, we compared vehicle-treated ovariectomized females with ovariectomized females treated with estradiol benzoate and P. Northern analysis and in situ hybridizations showed that the Hsc73 gene is enhanced by E and P in the pituitary and subregions of the VMH. Incidentally, by examining the primary amino acid sequence of rat, human, and chicken progesterone receptors, we noticed that putative Hsc73 binding sites are conserved across species with similar sites existing in the androgen and glucocorticoid receptors. Together these findings suggest a possible mechanism through which E could influence the activities of progesterone, androgen, and glucocorticoid receptors, by enhancing the expression of Hsc73 in cells where these proteins colocalize.     

Once again, the routine preoperative thorax photo

A prospective study of the influence of radiological findings upon operation policy was carried out in 810 patients over 40 years of age who underwent elective non cardiopulmonary surgery. Only in 5 patients did it appear that a preoperative X-ray yielded any relevant extra information, and only in 3 cases was the operation planning influenced. If no preoperative chest X-rays has been taken, all except one of the significant abnormalities would have been discovered anyway. By differentiating between patients graded ASA 1 and those classed ASA 2 or higher, it would be possible to reduce the number of preoperative chest X-rays by 41% without any loss of precision. Preoperative chest X-rays in patients over 40 years of age scheduled for non-cardiopulmonary surgery can be restricted to those whose history requires further radiological analysis.     

Effects of total and partial spinal transections on the pudendal nerve-evoked response in rat lumbar axial muscle

The pudendal nerve-evoked activity in lumbar axial muscle nerves 24–48 h following transections was studied in order to examine the supraspinal control of the pudendal nerve-evoked response (PNER). After total transections of the spinal cord in the thoracic region the overall activity in the muscle nerves was much reduced; the evoked responses consisted only of a single peak in activity 19.8 ms (± 1.4 ms) following the last shock of a 3-shock pudendal nerve stimulus demonstrating that some of the earliest responses previously described for the PNER are segmental in origin. To help identify supraspinal inputs to the PNER a series of partial transections were made to cut selectively different fiber columns within the cord. Four different surgical procedures were performed: transections of the entire dorsal half of the cord; ablations of all of the medial columns; combined lesions of the dorsal half and medial columns, sparing the tracts within the ventrolateral columns and bilateral transections of the lateral columns. Following all partial transections except those of the lateral columns, the PNER was similar to that seen in intact animals. After lateral column transections however, the responses were like those seen in the totally transected animals. The combined results suggest that supraspinal influences upon the PNER are conveyed primarily via the ventrolateral columns of the spinal cord. Bilateral convergence of afferent information was evident in the totally transected animals, indicating that such convergence can occur at segmental levels. The lesions which substantially altered the PNER closely paralleled those which eliminated lordotic responsiveness in behaving female rats.     

Consequences for hospitals resulting from demographic, social and morbidity changes: a European perspective.

The last 40 years has been a time of rapid demographic, social and economic change in most countries of the world. In Europe, the ageing of the population, a decrease in household size, and the reduced importance of parasitic and infectious diseases along with an increase in chronic and degenerative diseases are some of the most notable results of industrialization, urbanization and medical progress. These developments lead to changing demands not only for the services of hospitals but upon the health care system at large. Most recently, and in addition, these changes have had to be faced under resource constraints resulting from decreased economic growth. This article focuses on the similarities and differences within and across the health care systems of European countries, and on their efforts to respond to the changes which have taken place and are likely to continue in the near future. In so doing, it relates the various demographic, social and economic changes taking place in these countries to the structural changes noticeable in the hospital sector. The results obtained by statistical analyses of empirical evidence lead us to conclude that demographic and social variables may better explain the differences in hospital use within a given country over longer stretches of time than across countries at a given point in time. In the latter case, economic variables--differences in gross domestic product (GDP) per capita--serve as major explanations of the cross-country differences found. Changes in demographic, social and morbidity factors are also mirrored in the relative importance of hospital departments, at a given point in time and also in changes over time. Major changes have taken place within the health care systems. Hospitals are losing ground to other forms of health care: for instance, to institutions providing pre-hospital and post-hospital treatment. The need for more caring patterns of service, rather than for more curing, accounts for yet another overall trend. Hospitals have started to respond to this need by offering more 'semi-stationary' and part-time health care facilities. These developments go hand in hand with the establishment of closer relations between hospitals and other facilities within the health care system, and with improved non-stationary health care services.