Cumulative pregnancy rates and selective drop-out of patients in in- vitro fertilization treatment

The validity of the cumulative pregnancy rate (CPR) calculated by life- table approach, obtained in a transport in-vitro fertilization (IVF) programme, was tested by the determination of possible influence of selective drop-out of patients with a poor treatment prognosis. A cohort of 1211 patients who had a first IVF cycle was followed, and the CPR after three IVF cycles was assessed. First cycles of patients who discontinued treatment after failed IVF, and of those who did not achieve a pregnancy but proceeded to a subsequent cycle, were compared for fertilization rate and for occurrence of prognosticators of poor treatment outcome: oocyte yield < or =2, and replacement of <2 embryos. The CPR after three cycles was 54.9%. No differences were found in the first and second cycles of patients who continued treatment and those who dropped out. Selective drop-out of patients with a poor treatment prognosis was not found. Therefore, although calculations of CPR using life-table analysis generally overestimate the real probability of pregnancy after successive IVF cycles, the calculated CPR after three IVF cycles gives a reliable indication of the chance of occurrence of a pregnancy for the population studied.      

2,4-Disubstituted thiazoles II. A novel class of antitumor agents, synthesis and biological evaluation

A series of 2,4-disubstituted thiazole derivatives bearing N-n-butyl or N-cyclohexylthioureido synthon at position 2 and N-substituted thiosemicarbazone moiety at position 4 have been synthesized and tested for antitumor activity using the National Cancer Institute's in-vitro-disease-oriented antitumor screen. All of the tested compounds showed antineoplastic activity at concentrations less than 100 μM. Compounds 7, 9, 15 and 17 in particular showed activity with GI₅₀ (mean-graph midpoint) of 17.8, 8.5, 9.5 and 7.4 μM, respectively. The detailed syntheses, spectroscopic and biological data are discussed.     

PGD13 Does the Duration of Pulmonary Rehabilitation Affect the Magnitude of Patient Response?

OBJECTIVE: To determine if there is a dosage effect associated with the length of pulmonary rehabilitation (PR).
METHODS: We used a battery of outcome measures to quantify the amount of change that was achieved from baseline to discharge in 286 patients completing a PR program in 1 of 12 institutions participating in PROAS. The programs were of varying durations. Paired t-tests indicated overall that while the pulmonary rehabilitation programs did not yield improvements in physiologic (FEV1, FVC, % predicted FEV1) outcomes, the patients did achieve significant improvements in symptomatic (Borg score), functional (6-minute walk), general healthrelated quality of life [SF-36 Health Survey (SF-36)], and disease-specific HRQL [Chronic Respiratory Disease Questionnaire (CRQ) variables.
RESULTS: Based on a series of stepwise multiple regressions using the amount of change in each outcome variable as the dependent variable and adjusting for the corresponding baseline value and 11 clinical and sociodemographic characteristics, the number of hours of education (HREDU, 13.5 hr ± 6.7), activities of daily living (HRADL, 2.2 hr ± 6.6), and psychosocial support (6.5 hr ± 5.6) both individually and collectively (42.4 hr ± 11.8) generally did not contribute to explaining the magnitude of change achieved by the patients. However, the number of hours of supervised exercise (HREX, 25.4 hr ± 9.2) did contribute to explaining increases in 5 of the 8 SF-36 domains: physical function (p = 0.027), physical role (p = 0.0002), health perceptions (p = 0.0167), vitality (p = 0.034), and social function (p = 0.0035).
CONCLUSION: These data suggest that outcomes specifically related to pulmonary diseases are not affected by a longer duration for this type of intervention, but that broader, population-based assessments may need an additional period of intervention, or elapsed time, to detect improvement.     

Clinical islet isolation outcomes with a highly purified neutral protease for pancreas dissociation

Background: Pancreas dissociation is a critical initial component of the islet isolation procedure and introduces high variability based on factors including the enzyme type, specificity and potency. Product refinement and alterations to the application strategies have improved isolation outcomes over time; however, islet utilization from donor organs remains low. In this study we evaluate a low endotoxin-high activity grade neutral protease in clinical islet isolation.

Materials and Methods: The use of a non-collagenolytic enzyme, either thermolysin or high active neutral protease, was randomized in clinical islet isolations to evaluate efficacy. Additionally a retrospective comparison to neutral protease NB was conducted.

Results:The thermolysin group had lower trapped islet population and increased purity and post-culture islet mass in comparison to high active grade neutral protease. Comparison of neutral protease NB GMP grade to high active neutral protease displayed no measurable difference in islet mass or viability and transplantation outcomes at 1 mo post-transplant were favorable for both groups.

Conclusions: High activity neutral protease can generate clinical grade islets and may prove beneficial to islet function and viability based on a reduced endotoxin load but dosing of neutral protease requires ongoing optimization.