Logistics and design issues in the use of biological samples in observational epidemiology

Standard epidemiological study designs are well suited to answering questions involving the collection of biological samples. However, different designs are better suited--both for design and logistic reasons--to different questions. The strengths and weaknesses of each design are discussed in relation to markers of exposure, susceptibility and early outcome, and to markers used to classify cancers into biologically defined subsets.     

High populations of non-native structures in the denatured state are compatible with the formation of the native folded state

The structures of the denatured states of the spectrin SH3 domain and a mutant designed to have a non-native helical tendency at the N terminus have been analyzed under mild acidic denaturing conditions by nuclear magnetic resonance methods with improved resolution. The wild-type denatured state has little residual structure. However, the denatured state of the mutant has an approximately 50% populated helical structure from residues 2 to 14, a region that forms part of the beta-sheet structure in the folded state. Comparison with a peptide corresponding to the same sequence shows that the helix is stabilized in the whole domain, likely by non-local interactions with other parts of the protein as suggested by changes in a region far from the mutated sequence. These results demonstrate that high populations of non-native secondary structure elements in the denatured state are compatible with the formation of the native folded structure.     

Effect of resistance exercise training on cortical and cancellous bone in mature male rats

The thermal inactivation kinetics of Salmonella enteritidis PT4 between 49 and 60 degrees C were investigated. Using procedures designed to eliminate methodological artifacts, we found that the death kinetics deviated from the accepted model of first-order inactivation. When we used high-density stationary-phase populations and sensitive enumeration, the survivor curves at 60 degrees C were reproducibly biphasic. The decimal reduction time at 60 degrees C (D60 degrees C) of the tail subpopulation was more than four times that of the majority population. This difference decreased with decreasing temperature; i.e., the survivor curves became more linear, but the proportion of tail cells remained a constant proportion of the initial population, about 1 in 10(4) to 10(5). Z plots (log D versus temperature) for the two populations showed that the D values coincided at 51 degrees C, indicating that the survivor curves should be linear at this temperature, and this was confirmed experimentally. Investigations into the nature of the tails ruled out genotypic differences between the populations and protection due to leakage from early heat casualties. Heating of cells at 59 degrees C in the presence of 5 or 100 micrograms of chloramphenicol per ml resulted in reductions in the levels of tailing. These reductions were greatest at the higher chloramphenicol concentration. Our results indicate that de novo protein synthesis of heat shock proteins is responsible for the observed tailing. Chemostat-cultured cells heated at 60 degrees C also produced biphasic survivor curves in all but one instance. Cells with higher growth rates were more heat sensitive, but tailing was comparable with batch cultures. Starved cells (no dilution input) displayed linear inactivation kinetics, suggesting that during starvation a rapid heat shock response cannot be initiated.     

Endemic subcutaneous Dirofilaria repens filariasis in Southern France

BACKGROUND: Human dirofilariosis is endemic in southern France. The causal agent is Dirofilaria repens transmitted to man by mosquitos. The human organism is an accidental host while the dog is the reservoir. Approximately 60 cases have been reported in France, mainly in southern continental areas and Corsica. Most cases involve subcutaneous and occular manifestations. CASE REPORT: A 47-year old woman living in the Var department in southern france consulted for a subcutaneous nodule with the aspect of an epidermoid cyst. At incision, the nodule was found to contain a helminth found at parasite examination to be Dirofilaria repens. DISCUSSION: The prevalence of endemic subcutaneous dirofilariosis is probably underestimated as the clinical expression is non-specific and spontaneous cure is common. The diagnosis of epidermoid cyst is frequently suggested. History taking does not reveal travel to intertropical areas. The helminth is discovered when the nodule is opened, also providing successful cure.     

Clinical utility of clozapine in 16 patients with neurological disease

Patients who develop psychosis or agitated behavior secondary to neurological disorders present a therapeutic dilemma. The authors review clinical efficacy and side effect profiles of clozapine in a cohort of 16 patients with various neurobehavioral disorders. One-third showed a marked decrease in symptoms while on clozapine. However, one-quarter developed an acute confusional state; of these, all had diffuse slowing on their baseline EEG prior to starting the drug.     

A study of caloric restriction and cardiovascular aging in cynomolgus monkeys (Macaca fascicularis): a potential model for aging research

Caloric restriction has been demonstrated to retard aging processes and extend maximal life span in rodents, and is currently being evaluated in several nonhuman primate trials. We initiated a study in 32 adult cynomolgus monkeys to evaluate the effect of caloric restriction on parameters contributing to atherosclerosis extent. Following pretrial determinations, at which time a baseline measure of ad libitum (ad lib) dietary intake was assessed, animals were randomized to an ad lib fed group (control) or a caloric restriction group (30% reduction from baseline intake). The animals are being evaluated for glycated proteins, insulin, glucose, insulin sensitivity measures, and specific measures of body fat composition by CT scans (e.g., intra-abdominal fat) over specified intervals. The results from the first year of observation demonstrate a significant diet effect on body weight, and specifically intra-abdominal fat. Further, insulin sensitivity has been significantly increased after 1 year of caloric restriction compared to the ad lib fed group. These studies indicate that caloric restriction has a marked effect on a pathologic fat depot, and this change is associated significantly with an improvement in peripheral tissue insulin sensitivity.