Simple physical treatment as an effective tool to improve the functional properties or rapeseed (Brassica campestris var. toria) and sesame seed (Sesamum indicum) meals

Dry and 24 h imbibed rapeseeds and sesame seeds were defatted with hexane and the resulting freeze-dried powder was analysed for the functional properties of the meals. Water absorption capacity (WAC) of imbibed rapeseed meal and fat absorption capacity (FAC) of both the imbeded meals were higher than those for dry meals. Protein solubility of rapeseed meals was improved by imbibition and both the imbibed meals exhibited maximum protein solubility at pH 12. Rapeseed meal possessed better foaming properties and viscosity than sesame seed meal. Imbibition considerably enhanced the foaming properties of rapeseed meal while the emulsification properties and viscosity did not change appreciably. Emulsification properties of sesame meal were higher than rapeseed meal.     

Intensive short courses in biostatistics for fellows and physicians

At both of our universities we teach (with colleagues) introductory courses in statistics for fellows and physicians. We do not expect that those taking these courses will be able to do their own statistical work, but rather the intention is for them to 'learn the language' and to facilitate future collaboration. Basic principles of study design are introduced in the courses, as well as some of the most common statistical procedures. We will discuss the factors (what works and what does not) that may contribute to a successful course, a comparison to other courses, and our self-evaluation strategy. Finally, we will cover the financial arrangements that we have made when teaching these courses.     

Investigation of geo-spatial hotspots for the occurrence of tuberculosis in Almora district, India, using GIS and spatial scan statistic

Background  

The World Health Organization has declared tuberculosis a global emergency in 1993. It has been estimated that one third of the world population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. The emergence of TB/HIV co-infection poses an additional challenge for the control of tuberculosis throughout the world. The World Health Organization is supporting many developing countries to eradicate tuberculosis. It is an agony that one fifth of the tuberculosis patients worldwide are in India. The eradication of tuberculosis is the greatest public health challenge for this developing country. The aim of the present population based study on Mycobacterium tuberculosis is to test a large set of tuberculosis cases for the presence of statistically significant geographical clusters. A spatial scan statistic is used to identify purely spatial and space-time clusters of tuberculosis.     

Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.

PURPOSE: To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were treated continuously with erlotinib at doses of 100, 125, and 150 mg/d orally along with fixed i.v. doses of paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg x min/mL, both on day 1 every 3 weeks. RESULTS: Twenty evaluable patients were treated with 136 courses of erlotinib, paclitaxel, and carboplatin. Myelosuppression, skin rash, and diarrhea were the principal toxicities. Dose limiting diarrhea occurred in 1 of 6 patients at the 100 mg erlotinib dose level, whereas 0 of 9 evaluable patients at the 125 mg erlotinib dose level experienced dose limiting toxicity and 3 of 5 evaluable patients at 150 mg erlotinib experienced dose limiting skin rash and neutropenic sepsis. There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib. No consistent downstream effects on EGFR inhibition were found in skin. Durable objective responses were observed in non-small-cell lung and head and neck cancers. CONCLUSIONS: A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg.min/mL is recommended for disease-directed studies. This phase I trial was followed by a randomized phase III study in non-small-cell lung cancer using a similar regimen.     

Recurrent malaria--an enigma?

Management of recurrent malaria has to be individualised. A careful history, details of the drugs received, family history, laboratory evaluation will definitely help us in arriving at a reasonable diagnosis. For the future, genotyping, PCR testing and gamma interfiron levels may help us in identifying causes for recurrences.     

Comparison of methotrexate resistance conferred by a mutated dihydrofolate reductase (DHFR) cDNA in two different retroviral vectors

We previously reported the protection of hematopoietic cells from methotrexate (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)-mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of SFG-based dicistronic vectors will lead to improvement in gene transfer over the DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and hematopoietic progenitor cells infected with these retroviral constructs containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose values of MTX conferred by the SFG vector were 8-fold higher than those obtained with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than that seen for the DC/SV6 vector according to Northern blot and real-time polymerase chain reaction analysis, respectively. However, DHFR protein expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the SFG vector, respectively, indicating that the mRNA from the SFG vector is translated less efficiently than the mRNA generated from the DC/SV6 vector. Furthermore, the degree of MTX protection conferred by each vector in both mouse and human hematopoietic cells was the same. These results indicate that the in vitro transduction efficiency and transgene expression of human DHFR in hematopoietic progenitor cells is equally conferred by both vectors.     

Randomized trials stopped early for benefit: a systematic review

Context  Randomized clinical trials (RCTs) that stop earlier than planned because of apparent benefit often receive great attention and affect clinical practice. Their prevalence, the magnitude and plausibility of their treatment effects, and the extent to which they report information about how investigators decided to stop early are, however, unknown. Objective  To evaluate the epidemiology and reporting quality of RCTs involving interventions stopped early for benefit. Data Sources  Systematic review up to November 2004 of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify RCTs stopped early for benefit. Study Selection  Randomized clinical trials of any intervention reported as having stopped early because of results favoring the intervention. There were no exclusion criteria. Data Extraction  Twelve reviewers working independently and in duplicate abstracted data on content area and type of intervention tested, reporting of funding, type of end point driving study termination, treatment effect, length of follow-up, estimated sample size and total sample studied, role of a data and safety monitoring board in stopping the study, number of interim analyses planned and conducted, and existence and type of monitoring methods, statistical boundaries, and adjustment procedures for interim analyses and early stopping. Data Synthesis  Of 143 RCTs stopped early for benefit, the majority (92) were published in 5 high-impact medical journals. Typically, these were industry-funded drug trials in cardiology, cancer, and human immunodeficiency virus/AIDS. The proportion of all RCTs published in high-impact journals that were stopped early for benefit increased from 0.5% in 1990-1994 to 1.2% in 2000-2004 (P<.001 for trend). On average, RCTs recruited 63% (SD, 25%) of the planned sample and stopped after a median of 13 (interquartile range [IQR], 3-25) months of follow-up, 1 interim analysis, and when a median of 66 (IQR, 23-195) patients had experienced the end point driving study termination (event). The median risk ratio among truncated RCTs was 0.53 (IQR, 0.28-0.66). One hundred thirty-five (94%) of the 143 RCTs did not report at least 1 of the following: the planned sample size (n = 28), the interim analysis after which the trial was stopped (n = 45), whether a stopping rule informed the decision (n = 48), or an adjusted analysis accounting for interim monitoring and truncation (n = 129). Trials with fewer events yielded greater treatment effects (odds ratio, 28; 95% confidence interval, 11-73). Conclusions  RCTs stopped early for benefit are becoming more common, often fail to adequately report relevant information about the decision to stop early, and show implausibly large treatment effects, particularly when the number of events is small. These findings suggest clinicians should view the results of such trials with skepticism.      

Laboratory and field evaluation of a new personal sampling system for assessing the protection provided by the N95 filtering facepiece respirators against particles

OBJECTIVES: We have recently developed a new personal sampling system for the real-time measurement of the protection provided by respirators against airborne dust and micro-organisms. The objective of this study was to evaluate the performance characteristics of the new sampling system in both laboratory and field conditions. METHODS: The measurements were conducted using the N95 filtering facepiece respirators and the newly developed personal sampling system put on a manikin (laboratory study) or donned by a human subject (laboratory and field studies). Two inhalation flow rates (0 and 40 l min(-1)) in conjunction with the sampling flow rate (10 l min(-1)) were tested in the manikin-based experiments to investigate the effects of the leak location (nose, cheek and chin) and the depth of the sampling probe (0, 5, 10 and 15 mm) within the respirator. The effect of human activity on the protection factor was evaluated using a variety of head movements and breathing patterns when a human subject wore the respirator in a room-size laboratory test chamber. The field study was conducted during corn harvesting with a respirator worn by a human subject on a combine. RESULTS: There was no significant difference in the protection factors for different leak locations, or for sampling probe depths, when the inhalation rate was 0 l min(-1). For the inhalation rate of 40 l min(-1), the protection factors for nose leaks were higher than those for chin and cheek leaks. Furthermore, the protection factor was the lowest and showed the least variation when the sampling probe depth was equal to 0 mm (imbedded on the respirator surface). Human subject testing showed that the grimace maneuver decreased the protection factor and changed the original respirator fit. The protection factor during breath holding was lower than that found during inhalation and exhalation. Field results showed greater variation than laboratory results. CONCLUSIONS: The newly designed personal sampling system efficiently detected the changes in protection factors in real time. The sampling flow was least affected by the inhalation flow when the sampling probe was imbedded on the respirator surface. Leak location, breathing patterns and exercises did affect the measurement of the protection factors obtained using an N95 filtering facepiece respirator. This can be attributed to the differences in the in-mask airflow dynamics contributed by the leak, filter material, sampling probe and inhalation. In future studies, it would be beneficial if the laboratory data could be integrated with the field database.     

Dietary vitamin E does not inhibit the promotion of liver carcinogenesis by polychlorinated biphenyls in rats

In this study, the effect of dietary vitamin E on the hepatic tumor-promoting activity of PCB-77 and PCB-153 in female Sprague-Dawley rats (175-200 g) was investigated. One week after diethylnitrosamine injection, rats were fed purified diets containing 10, 50, or 250 mg/kg vitamin E in the form of alpha-tocopheryl acetate. Starting 1 wk later, we injected rats i.p. with vehicle (corn oil) or PCB-77 or PCB-153 (300 mumol/kg) every 14 d for 4 injections. All rats were killed 10 d after the last PCB injection. The number and volume of placental glutathione S-transferase (PGST)-positive foci were increased by PCB-77 but not by PCB-153. Vitamin E did not affect the induction of PGST-positive foci. PCB-77, but not PCB-153, increased hepatic NF-kappaB activity. In conclusion, dietary vitamin E supplementation does not protect against the induction of altered hepatic focal lesions by PCBs.