Egg handling and storage

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.     

Design and implementation of clinical trials of antimicrobial drugs and devices used in periodontal disease treatment

The design and implementation of clinical trials (CTs) carried out to evaluate antimicrobial and anti-infective drugs and devices are one of the most difficult challenges in contemporary periodontal research and product development. The overwhelming amount of evidence which has established a microbial etiology for periodontitis is the basis for developing and testing antimicrobial treatments. Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a protocol which explicitly integrates the requirements of the patient, the clinician, the sponsor, and regulatory authorities. Surrogate variables for effectiveness must be clinically relevant, scientifically sound, and statistically valid. Currently, clinical attachment level measurements and alveolar bone assessments are accepted as proof of effectiveness. Indication and claim support of the antimicrobial product guide the design and implementation of the CT. Adverse microbiologic consequences, such as lack of antimicrobial susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug interference, must be monitored. Successful CTs balance a large group of variables used to screen, randomize, and assign subjects to experimental and control groups to ensure that prognostic and risk factors are properly accounted for.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Functional topography of cat primary auditory cortex: response latencies

Minimum onset latency (Lmin) of single- and multiple-unit responses were mapped in the primary auditory cortex (AI) of barbiturate-anesthetized cats. Contralateral Lmin for multiple units was non-homogeneously distributed along the dorso-ventral/isofrequency axis of the AI. Responses with shorter latencies were more often located in the central, more sharply tuned region while longer latencies were more frequently encountered in the dorsal and ventral portions of the AI. For single units, a large scatter of Lmin values was found throughout the extent of the AI including cortical depth. The relationship between Lmin and previously reported spectral, intensity and temporal parameters was analyzed and revealed statistically significant correlations between minimum onset latency and the following response properties in some but not all studied animals: sharpness of tuning of a frequency response area 10 dB above threshold, broadband transient response, strongest response level, monotonicity of rate/level functions, dynamic range, and preferred frequency modulation sweep direction. This analysis suggests that Lmin is determined by several independent factors and that the prediction of Lmin based on relationships with other spectral and temporal response properties is inherently weak. The spatial distribution and the functional relationship between these response parameters may provide an important aspect of the time-based cortical representation of specific features in the animal's natural environment.