Increased risk of pneumococcal infections in cardiac transplant recipients

We observed 5 episodes of pneumococcal infection among 129 cardiac transplant patients between March 1985 and December 1987, giving an estimated incidence of 36 cases per 1000 patient-years. Infections occurred a mean of 58 days after transplantation and included bacteremia with empyema, bacteremia alone, and pneumonia. All patients recovered from their infections. There was no correlation between infection and age, sex, immunosuppression, or rejection episodes. We also measured antibody levels to 12 pneumococcal antigens in 6 unvaccinated, uninfected patients before and after cardiac transplantation, to see if baseline antibody levels decreased. Protective levels of antibody were defined as greater than or equal to 300 ng of anticapsular antibody nitrogen per milliliter serum. Before transplantation patients had protective antibody levels to a mean of 8.7 +/- 1.2 pneumococcal serotypes; after transplantation, the number of presumably protective antibody levels decreased to 6.5 +/- 1.4 (P = 0.021). One of these patients subsequently developed pneumococcal pneumonia. Cardiac transplant patients are at increased risk of pneumococcal infections. Vaccinating transplant candidates prior to transplantation may provide protection after transplantation.     

Counseling strategies for dietary management: expanded possibilities for effecting behavior change

Successful nutrition counseling culminates when a client develops a sound working knowledge and practice of good health behaviors, compatible with his/her capabilities and environment. Attainment of that goal requires the cooperation and active participation of both the nutrition counselor and the client. Counseling methodologies abound. The incorporation of strategies and techniques from different approaches into the treatment protocol, using a multidisciplinary approach, may enhance the effectiveness of nutrition counseling in facilitating dietary behavior change. A schematic model of nutrition counseling is presented, and varying counseling theories are introduced that could be incorporated into the model.     

Influence of preformed α-helix and α-helix induction on the activity of cationic antimicrobial peptides

One prominent class of cationic antibacterial peptides comprises the α-helical class, which is unstructured in free solution but folds into an amphipathic α-helix upon insertion into the membranes of target cells. To investigate the importance of α-helicity and its induction on interaction with membranes, a series of peptides was constructed based on a hybrid of moth cecropin (amino acids 1-8) and bee melittin (amino acids 1-18) peptides. The new peptides were predicted to have a high tendency to form α-helices or to have preformed α-helices by virtue of construction of a lactam bridge between glutamate and lysine side-chains at positions i and i+ 4 at various locations along the primary sequence. In two examples where the use of lactam bridge constraints induced and stabilized α-helical structure in benign (aqueous buffer) and/or hydrophobic medium, there was a decrease in antibacterial activity relative to the linear counterparts. Thus the preformation of α-helix in solution was not necessarily beneficial to antimicrobial activity. In the one case where the lactam bridge did result in increased antibacterial activity (lower minimal inhibitory concentration values) it did not increase α-helical content in benign or hydrophobic medium. Broadly speaking, good activity of the peptides against Pseudomonas aeruginosa correlated best (r²= 0.88) with a helican parameter which was calculated as the induction of α-helix in α membrane-mimicking environment divided by the α-helix formation under benign conditions. Interestingly, the activity of the lactam bridge peptide constructs correlated in part with alterations in bacterial outer or cytoplasmic membrane permeability.     

Antimicrobial susceptibility changes in Enterococcus faecalis following various penicillin exposure regimens.

Penicillin-"virgin" strains of Enterococcus faecalis collected from a population of individuals with no previous antibiotic exposure were subjected in vitro to penicillin delivered as repeated pulses, stepwise increasing concentrations, or sustained levels of a single concentration. Changes in resistance to penicillin were assessed by determination of MICs, and time-kill studies were performed to evaluate changes in tolerance to the bactericidal effects of penicillin. Isogenic clones, derived from various exposure regimens, which exhibited changes in either resistance or tolerance were further examined for changes in penicillin-binding proteins. Exposure to repeated pulses of penicillin resulted in the development of tolerance to penicillin without changes in the level of resistance. Clones derived from a regimen of stepwise increases in the penicillin concentration acquired both increased penicillin resistance and tolerance. Clones selected after prolonged continuous exposure to a fixed concentration of penicillin displayed minimally increased resistance to penicillin, but they retained the lytic, nontolerant response to the bactericidal effect of penicillin. Clones which acquired tolerance to the bactericidal effect of penicillin without changes in penicillin resistance exhibited a penicillin-binding protein pattern identical to that of the parental strain. Increased labeling of several penicillin-binding proteins accompanied the development of increased penicillin resistance in both penicillin-tolerant and nontolerant strains. Exposure of E. faecalis to penicillin in repeated pulses of brief duration, for prolonged periods at a constant concentration, or in stepwise graded concentrations can result in the selection of clones with increased resistance to the inhibitory or bactericidal effects of penicillin, or both. These observations may be relevant to the selection of dosing regimes for penicillin in the treatment of enterococcal infections, when bactericidal synergism cannot be achieved with penicillin-aminoglycoside combinations.     

Improved radial maze performance induced by the benzodiazepine antagonist ZK 93 426 in lesioned and alcohol-treated rats

Effects of the benzodiazepine receptor antagonist ZK 93 426 were examined in two groups of rats with long lasting radial maze impairments caused by either ibotenic acid lesions to cholinergic forebrain projections or 28 weeks of alcohol treatment. Animals were trained on the 8-arm radial maze prior to ibotenic acid treatment or following chronic alcohol treatment. Spatial and associative working and reference memory were investigated in parallel. Lesioned rats showed high error rates in all aspects of memory, but particularly in spatial working memory, whilst error rates in alcohol-treated rats were low and uniform. ZK 93 426 improved performance in both experiments. In lesioned rats working memory errors were selectively decreased, in line with evidence that ZK 93 426 enhances attention. However in alcohol-treated rats both reference and working memory errors were reduced to control level, suggesting that these animals primarily showed a mild attentional deficit. Alcohol treatment and lesions were both found to reduce cortical choline acetyltransferase activity, but in view of the non-specificity of alcohol or ibotenic acid to cholinergic neurons and the wide distribution of the GABA-BZ receptor complex, interactions of ZK 93 426 with other systems cannot be ruled out.     

Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha

The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85alpha-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85alpha-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85alpha in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals.     

Antigenicity and protective effects of type 3 pneumococcal polysaccharide in rats.

Total hemolytic complement and C3 levels were found to drop to 6.25% and 50% of preinfection levels, respectively, during trypanosome infections. Chemotherapeutic elimination of the trypanosomes with Berenil led to recovery of preinfection levels within 7 days and 11 days when cattle infected with Trypanosome congolense and Trypanosoma vivax, respectively, were treated 37 days after onset of infection. Recovery was slower in T. vivax-infected cattle treated on day 50. Berenil treatment had no effect on complement levels in control animals. The possible causes and implications of these low complement levels in bovine trypanosomiasis are discussed.     

Semantic dementia with category specificity:acomparative case-series study

Patients with semantic dementia, the temporal variant of frontotemporal dementia, are relevant to both the neuroanatomical and neuropsychological debates in the category-specific literature. These patients present with a selective and progressive semantic deficit consequent on circumscribed atrophy of the inferolateral polar temporal lobes bilaterally, including the inferotemporal gyrus. In this study, a patient KH with a significant advantage for artefacts over living things was compared to five other semantic dementia patients with commensurate levels of semantic impairment. KH demonstrated a consistent category difference in favour of artefacts across all the expressive and receptive semantic tests. This difference was reliable even when familiarity, frequency, and other potential confounding factors were controlled. While KH demonstrated an association between poor knowledge of sensory attributes and a consistently greater impairment on living things than artefacts, the other patients did not. As observed in a number of previous studies, all five of the patients, contrasted to KH, exhibited an advantage for functional/associative over sensory attributes but without demonstrating the category-specific deficit that the sensory-functional theory (and the locus of their atrophy) might predict. The results of this and other studies are discussed in relation to four accounts of category specificity: the sensory-functional theory, domain-specific knowledge systems, intercorrelated features, and individual differences.