Health care in the new Russia: a western perspective

OBJECTIVE: To evaluate the growth and insulin secretion from microencapsulated beta TC6-F7 cells in vitro and to assess the in vivo function of microencapsulated cells transplanted in rats with steptozotocin (STZ)-induced diabetes. METHOD: Alginate-poly-L-lysine encapsulated beta TC6-F7 cells were exposed to glucose, isobutylmethylxanthine (IBMX) and glucagon-like peptide I (7-36 amide) in a static in vitro challenge. In vivo, 2.5-3.5 x 10(7) encapsulated cells were implanted into diabetic rats. Graft function was evaluated by monitoring blood glucose concentrations and by an intraperitoneal glucose tolerance test. RESULTS: The cell density (number of cells per capsule) of cultured microencapsulated beta TC6-F7 cells increased almost 35-fold over a 55 day observation period to reach a plateau of approximately 3500 cells/capsule. While insulin secretion per capsule remained unchanged over the first 21 days of culture, a 7-fold increase was observed during the last 14 days of the 55 day observation period. Intraperitoneal transplantation of 3.5 x 10(7) encapsulated cells into diabetic rats resulted, within 24 hours, in reversal of hyperglycemia for up to 60 days. Post-transplantation blood glucose concentrations varied between 2 and 4 mM. Glucose clearance rates evaluated by an intraperitoneal glucose tolerance test at 30 days post-transplantation resulted in a markedly flat glucose clearance curve with blood glucose never rising above 4 mM. The glucose challenge of microencapsulated cells recovered 30 days post-transplantation resulted in a 2-fold increase in insulin response at glucose concentrations greater than 5.5 mM as compared to glucose-free media. In addition, immunostaining of recovered grafted tissue for insulin, reveals a strong presence of the peptide within the cell population. CONCLUSIONS: These data demonstrate the potential use of an immunoisolated beta-cell line for the treatment of diabetes.     

Internalin B promotes the replication of Listeria monocytogenes in mouse hepatocytes

The uptake of Listeria monocytogenes by a variety of cell types in vitro is facilitated by the protein products of the inlAB (internalin) operon expressed by the organism. In the case of mouse hepatocytes, the extent to which inlAB expression influenced the uptake of Listeria in vitro was markedly dependent upon the ratio of bacteria to cells. At a ratio of 100:1, greater than 40-fold fewer transposon-induced inl4B mutant listeriae entered hepatocytes compared to the isogenic wild-type control; the difference was only fourfold, however, in cultures inoculated at a 1:1 ratio. Similarly, the uptake of in-frame inlB or inlAB deletion mutants differed only fourfold from the uptake of wild-type or inlA mutant Listeria at a 1:1 multiplicity of infection. Mutations affecting inlB or inlAB, on the other hand, resulted in a marked decrease in the capacity of Listeria to proliferate within mouse hepatocytes in vivo and in vitro. Electron micrographs of Listeria-infected hepatocytes demonstrated the impaired capacity of inlB mutants to escape from endocytic vacuoles and to enter the cytoplasm where proliferation occurs. These findings indicate that the protein product of inlB exerts a significant effect on the intracellular replication of Listeria.     

Accuracy of asthma treatment in schoolchildren in NSW, Australia

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.     

Perception of discrimination and ethnocultural variables in a diverse group of adolescents

Despite current interest in the multi-dimensionality of culture and ethnicity there are few studies that have explored the role of discrimination with ethnocultural variables. In this study social identity theory was used as a framework to test the relation between discrimination and components of ethnic identity, and attitudes towards out-groups. A school-based survey in a large south-west metropolitan area in 1994 was undertaken with students (n=3071) of African-American, European-American, Mexican-American, and Vietnamese-American descent using multiple measures of ethnicity. Hierarchical multiple regression results indicated that two components of ethnic identity played different roles in the relation between discrimination and attitudes towards others. Consistent with social identity theory, results indicated that perception of more discrimination was predicted by high ethnic exploration, and having more negative attitudes towards out-groups. However, ethnic affirmation, which is a positive sense of belonging to one's ethnic group, was only indirectly related to discrimination through attitudes toward others. In fact, contrary to social identity theory, a stronger sense of belonging to one's group was associated with more positive attitudes toward out-groups. Results have important implications for race relations.     

Temporal integration at 6 kHz as a function of masker bandwidth

Thresholds were measured for a 6-kHz sinusoidal signal presented within a 500-ms masker. The masker was either a bandpass Gaussian noise of varying bandwidth, or a sinusoid of the same frequency as the signal. The spectrum level of the noise masker was kept constant at 20 dB SPL, and the level of the sinusoidal masker was 40 dB SPL. Thresholds for signal durations between 2 and 300 ms were measured for masker bandwidths ranging from 60 to 12,000 Hz. The masker was spectrally centered around 6 kHz. For masker bandwidths less than 600 Hz, the slope of the temporal integration function decreased with decreasing masker bandwidth. The results are not consistent with current models of temporal integration or temporal resolution. It is suggested that the results at narrow bandwidths can be understood in terms of changes in the power spectrum of the stimulus envelope or modulation spectrum. According to this view, the onset and offset ramps of the signal introduce detectable high-frequency components into the modulation spectrum, which provide a salient cue in narrowband maskers. For broadband maskers, these high-frequency components are masked by the inherent rapid fluctuations in the masker envelope. Additionally, for signal durations between 7 and 80 ms, signal thresholds decreased by up to 5 dB as the masker bandwidth increased from 1200 to 12,000 Hz. The mechanisms underlying this effect are not yet fully understood.     

Treatment algorithm use to optimize management of symptomatic patients with a history of mania

BACKGROUND: While monotherapy has significant limitations in bipolar disorder, few published data addressing alternatives exist. Treatment algorithms have been proposed, but none have undergone empirical evaluation. This study provides a systematic prospective, open evaluation of the effectiveness and tolerability of a treatment algorithm for patients with histories of mania. METHOD: Twenty-eight symptomatic outpatients from a public mental health facility who were diagnosed as having either bipolar I or schizoaffective illness, bipolar type, entered the study. Minimum blood levels of lithium and divalproex sodium were defined. Medications were pushed to predetermined levels (as tolerated) before proceeding to the next algorithm step. Clinical symptoms were assessed monthly using the Brief Psychiatric Rating Scale (BPRS, 27 item) and Clinical Global Impressions scale. RESULTS: Pretreatment and posttreatment clinical symptoms were compared. Over 50% of patients attained 30% improvement from baseline BPRS after 4 months. Thirty-six percent of patients (N = 10) became mood stable, 46% (N = 13) remained mood unstable, and 18% (N = 5) dropped out before completing the algorithm. Although patients who finished the algorithm were taking more medication, either dosage and/or drugs, somatic complaints did not increase. CONCLUSION: The potential benefit of a defined treatment algorithm was demonstrated for these complex and persistently ill patients. Despite long treatment histories, patients improved with more frequent visits and addition of medication(s). A randomized controlled trial comparing a similar treatment algorithm with treatment-as-usual is warranted.     

Potent and selective bicyclic lactam inhibitors of thrombin: Part 2: P1 modifications

The synthesis and antithrombotic activity of a series of nonpeptide bicyclic thrombin inhibitors is described. We have explored the SAR with modifications to the P1 site. The introduction of arginine mimetics at the P1 site led to potent and selective thrombin inhibitors.     

Clinical outcome of patients infected with hepatitis C virus infection on survival after primary liver transplantation under tacrolimus

In 1994, as a result of both programme evaluations which identified students' fears and apprehensions about their practical ability, and a review of the literature on skill acquisition, experiential skills teaching was resumed within the faculty. Having invested considerable finance into the reconstruction of a skills centre to teach skills, it is now imperative that its use be formally evaluated. Part of the evaluative process includes a review of the empirical literature on the acquisition of psychomotor skills in nursing. This paper summarizes this review.