A preliminary evaluation of plasma b-type natriuretic peptide as a screening test for left ventricular diastolic dysfunction in non-cardiac intensive care.

Left ventricular filling and thus diastolic function are frequently monitored and managed in critical care. However, scant data exist regarding possible screening tests for diastolic dysfunction in the intensive care unit (ICU). The present study aimed to evaluate plasma b-type natriuretic peptide (BNP) as a marker of diastolic dysfunction in a single-centre cohort of 'non-cardiac' ICU patients. The ICU is non-cardiac in that it provides mixed medical/surgical services with the exception of cardiology, cardiac surgery and solid organ transplantation. Clinical data were recorded over the first 24 hours of ICU stay for 32 consecutive patients. Transthoracic echocardiogram and blood collection for BNP assay were then performed. Diastolic dysfunction was demonstrated in 34% (n=11). Mean ± standard deviation BNP values were higher with diastolic dysfunction (238 ± 195 vs 72 ± 78 pg/ml; P=0.003). A BNP threshold of >43 pg/ml yielded a sensitivity of 80% and a specificity of 59%; area under the receiver operating characteristic curve was 0.82. BNP correlated independently with E/e' (R=0.425; P=0.015) (E/e': peak early transmitral velocity [E]/early diastolic mitral annular velocity [e']) but not left ventricular ejection fraction (P=0.8), illness severity (Acute Physiological and Chronic Health Evaluation II; P=0.3) or fluid balance (P=0.4). Diastolic dysfunction was common in this cohort of non-cardiac ICU patients and was independently associated with a significantly higher BNP. The potential application as a screening test for diastolic dysfunction is likely to require a threshold lower than previously proposed for heart failure.

Role of plaque in the clearance of salivary sucrose and its influence on salivary ph.

BACKGROUND: The prevalence of dental caries in children, in India, is higher than many of the industrialized countries. The sugar most commonly associated with dental caries is sucrose, as the microorganisms in the dental plaque have the ability to convert this dietary constituent into various organic acids. AIMS AND OBJECTIVES: This study was conducted to study the effect of the presence of plaque on the salivary clearance of sucrose and to study the effect of the presence of plaque on salivary pH, following sucrose clearance. MATERIALS AND METHODS: Salivary sucrose determination was done by using the anthrone technique. A Digital MHOS pH meter estimated the salivary pH. RESULTS: Presence of plaque increased the salivary sucrose clearance time and decreased the salivary pH at various time intervals. CONCLUSIONS: The microbial etiology of dental caries is the dynamic relationship among the dental plaque microbiota, dietary carbohydrates, saliva and pH lowering, and the cariogenic potential of the dental plaque. Caries occur preferentially in the dentition sites characterized by high exposure to carbohydrate and diminished salivary effect.

Comparative study of alkaline phosphatase and prostate specific antigen in prostate cancer.

The study comprised between healthy and benign controls and proven 62 cases of prostate cancer at different clinical stages. The mean value of increasing level of PSA in group III was found to be highly significant when compared with group I. Whereas, the mean value of elevated levels of ALP in stage III and IV from group III was found to be highly significant when compared with group I. Though the mean value of ALP was increased in stage I and II from group III when compared with group I, it was not found highly significant. Hence the elevated levels of ALP were significantly correlated with advanced stages of prostate cancer. Whereas, increased levels of PSA contribute to the diagnosis of potentially increased volume of the prostate cancer.

Large ex vivo expansion of human umbilical cord blood CD4+ and CD8+ T cells.

The use of human umbilical cord (UC) blood as a source of transplantable hematopoietic stem cells and progenitor cells may present some advantages over the use of BM. For example, it has been suggested that the degree of HLA matching may be less stringent, and the risk of GvHD may be lower. We have been studying the ex vivo expansion of UC blood T lymphocytes with a view to their use in the adoptive immunotherapy of cancer, autoimmunity, and infectious disease. We have developed a new method involving the use of a conditioned medium (XLCM) that consistently results in levels of UC blood T cell expansion not hitherto possible. Primary cultures of unfractionated low-density MNC (LDMNC) derived from UC blood treated with 5% XLCM routinely show expansions greater than 10,000-fold within 4 weeks. By contrast, similar FBS-free cultures treated with IL-2 expand less than 10-fold and not after 1 week, and cultures treated with IL-2 and concanavalin A (ConA) expand to a maximum of only 300-500-fold over 2 weeks and fail to continue to proliferate thereafter. The MAb, OKT3, which, when combined with IL-2 and FBS, is known to stimulate proliferation of adult peripheral blood lymphocytes, permitted only a 17-fold expansion of UC blood lymphocytes under the same conditions. Thus, XLCM, which can also stimulate adult peripheral blood lymphocyte expansion to levels exceeding 100,000-fold in 3-4 weeks, is uniquely able to stimulate proliferation of UC blood lymphocytes to high levels. From initiation of the UC blood or adult peripheral blood LDMNC/XLCM cultures up to approximately 2 weeks, the cultures are dominated by CD4+ T lymphocytes. By 4 weeks, >80% of the cultured cells bear the CD8+ phenotype, whereas UC blood T lymphocytes cultured in the presence of IL-2 are predominantly CD8+. Thus, XLCM not only allows high levels of expansion of UC blood T lymphocytes not heretofore possible but also permits the selective expansion of different T lymphocyte subsets from a single source.

The selective expansion of functional T cell subsets.

Adoptive cellular immunotherapy is considered a potential treatment for a wide range of diseases, including cancer, infectious diseases, and autoimmune disorders. We have developed a method using a conditioned medium, XLCM, that selectively expands several different T cell subsets with a view to their use in cell therapy. Primary FBS-free suspension cultures of human peripheral blood low-density mononuclear cells treated with XLCM reproducibly expand over 100,000-fold within a period of 4 weeks. CD4+ T cells and CD8+ T cells expand sequentially in the unfractionated cultures, and relatively pure populations of CD4+ and CD8+ T cells may be expanded from populations first enriched in the respective T cell subset. CD4+ T cells cultured in XLCM produce cytokines consistent with the expansion of Th1, Th2, and Th0 subsets, whereas CD8+ T cells cultured in XLCM are cytolytically competent. An interesting feature of T cells cultured in XLCM is the persistence of 5%-10% CD4+CD8+ double-positive T cells in spite of substantial single-positive T cell expansion, suggesting that these cells also proliferate in XLCM. In addition to subsets of TCRalphabeta+ T cells, TCRgammadelta+ T cells are also significantly expanded by XLCM. These results demonstrate that XLCM efficiently expands several functional T cell subsets and provides a means of obtaining selected populations suitable for use in cellular immunotherapy.

Differences in bovine lymphocyte antigen associations between immune responsiveness and risk of disease following intramammary infection with Staphylococcus aureus.

This study evaluated the relationships between immune response, disease resistance, and bovine leukocyte antigens, BoLA, in Holstein cows following intramammary challenge with Staphylococcus aureus. This investigation was to determine whether immune responsiveness differed between these cows and whether differences were related to expression of class I BoLA antigens, which might explain the increased resistance or susceptibility to S. aureus mastitis. Antibody responses to S. aureus in milk and serum, total IgG1 in milk, and blastogenic responses with and without concanavalin A were evaluated. The CA42 allele, previously associated with increased risk of infection, was relatively uninformative for the immune response parameters examined. Other alleles, such as W3, were associated with higher milk antibody responses to S. aureus and higher milk IgG1 postchallenge. Alleles W7, W4, and W26 were associated with lower milk IgG1 and lower antibody titers in serum postchallenge. The association reported between allele CA42 and increased risk of S. aureus mastitis did not relate to lower antibody or blastogenic responses by these cows; however, indicators of innate resistance were not examined. In addition, the different associations detected between milk and serum emphasize the importance of considering mucosal immunity and unique immunological compartments when searching for relevant genetic markers of disease resistance.

[3H]bumetanide binding to avian erythrocyte membranes. Correlation with activation and deactivation of Na/K/2Cl cotransport.

The relationship between Na/K/2Cl cotransport activation in duck erythrocytes and binding of the diuretic [3H]bumetanide to isolated membranes from stimulated cells has been assessed. Cotransport was activated by either cAMP-dependent (norepinephrine) or -independent (fluoride, hypertonicity) pathways. Membranes isolated from unstimulated cells possessed no specific bumetanide binding. In the presence of norepinephrine, cotransport and saturable binding rose in parallel, reaching a maximum after 5-7 min. In membranes from maximally stimulated cells the K1/2 and Bmax for bumetanide binding were 100 nM and 1.7 pmol/mg protein, respectively. The diuretic binding properties of these membranes were characteristic of interactions of ligands with the Na/K/2Cl cotransporter: specific binding required the presence of all three cotransported ions (Na, K, and Cl), and the rank order of potency for diuretic competition with bumetanide for binding sites was benzmetanide greater than bumetanide greater than furosemide. The appearance of specific bumetanide binding was also seen in membranes from erythrocytes activated by non-cAMP-dependent stimuli, with an excellent temporal correlation between cotransport activation and diuretic binding. On removal of all stimuli both cotransport and bumetanide binding declined in parallel. Duck erythrocytes treated with norepinephrine in a solution containing 15 mM K+ swell to a new stable cell volume after 60 min, during which time cotransport becomes inoperative. Bumetanide binding to both whole cells and isolated membranes paralleled the decline in cotransport activity. It is concluded that bumetanide binding to isolated membranes faithfully reflects the state of activation of the Na/K/2Cl cotransporter in intact cells under a variety of conditions.

Suicide in rural community.

51 suicides in a rural community of Northern Karnataka were studied for incidence, age and sex distribution, methods adopted for suicides, and causes of suicides. Suicides in rural area did not show any difference from urban suicide pattern.