In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers.

Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 microCi injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer.     

Retroperitoneoscopic right-sided donor nephrectomy with pre- and postcaval renal arteries

A 56-year-old male donor was evaluated for a kidney donation. Computed tomography angiography revealed 2 right renal arteries, 1 coursing in front and 1 behind the inferior vena cava. The renal scan showed a lower glomerular filtration rate on the right side. We present a technique of retroperitoneoscopic right-sided donor nephrectomy.     

Survivors of childhood cancer: long-term edocrine and metabolic problems dwarf the growth distrubance

The long-term effects of radiotherapy and chemotherapy are becoming increasingly reconginzed as the cure rates of certain childhood malignancies improve. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer who received cranial irradiation have been shown to have lower than predicted height, an increased prevalence of obesity and redutions in strength, exercise tolerance, bone mineral density, quality of life and academic achievement. Growth hormone deficiency (GHD) is the most frequent endocrine deficiency observed following cranial irradiation. Adults with GHD resulting from primary hypothalamic-pituitary disease during childhood have been shown to exhibit a clinical picture similar to that described in long-term survivors of childhood cancer: increased fat mass and reduced lean mass, strength, exercise tolerance, bone mineral density and quality of life. This review considers the possible contributin of GHD to the adverse sequelae observed in long-term survivors of childhood malignancy and includes our preliminary experience in treating 14 adults with GHD resulting from the treatment of childhood malignancies.     

Studies on the bioactivity and elementology of marine algae from the coast of Karachi, Pakistan

Some species of marine benthic algae belonging to the Chlorophyta, Phaeophyta and Rhodophyta collected from different coastal areas of Karachi (Pakistan) were investigated for their antibacterial, antifungal, phytotoxic and insecticidal activities. Brown seaweeds showed greater antibacterial activity than the green and red ones. Botryocladia leptopoda (J. Ag.) Kylin exhibited the greatest antifungal activity and Codium shameelii Nizam. the least. The highest phytotoxic activity (95%) was displayed by Enteromorpha intestinalis (L.) Nees at 100 microg/mL concentration, while Osmundea pinnatifida (Huds.) Stack. showed the low insecticidal activity as compared to the other investigated species. Many elements e.g. Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Na, Pb, Zn were determined quantitatively. Among them Ca, Cr and Pb were found to occur in largest amount in green seaweeds, Co, Cu, Fe and Zn in greatest quantity in brown seaweeds, while Cd, K, Mg and Na in highest proportion in the investigated red seaweeds.     

Trials which randomize practices II: sample size

BACKGROUND: When practices are randomized in a trial and observations are made on the patients to assess the relative effectiveness of the different interventions, sample size calculations need to estimate the number of practices required, not just the total number of patients. OBJECTIVE: Our aims were to introduce the methodology for appropriate sample size calculation and discuss the implications for power. METHOD: A worked example from general practice is used. DISCUSSION: Designs which randomize practices are less powerful than designs which randomize patients to intervention groups, particularly where a large number of patients is recruited from each practice. Studies which randomize few practices should be avoided if possible, as the loss of power is considerable and simple randomization may not ensure comparability of intervention groups.      

Facets of career satisfaction for women physicians in the United States: a systematic review

Women make up a growing proportion of the physician workforce, and their career satisfaction may affect their health. The authors hypothesized that many facets adversely affecting career satisfaction in women physicians were extrinsic, therefore, preventable or modifiable. The authors conducted a systematic review of the literature in English published through February 2010 to examine facets of career satisfaction of U.S. women physicians. The authors used the women physician AND job satisfaction OR career satisfaction Medical Subject Headings (MeSH) terms, and reviewed bibliographies of key articles to ensure inclusion of relevant studies. The authors used the "Strengthening the Reporting of Observation Studies in Epidemiology" quality tool. Of an initial 1,000 studies, only 30 met the inclusion criteria. Facets reported most frequently to influence career satisfaction for women physicians were income/prestige, practice characteristics, and personal/family characteristics. Overall, career satisfaction for women and men physicians was 73.4% (range = 56.4% to 90%) and 73.2% (range = 59% to 90%), respectively. When compared with men, women physicians were more concerned with perceived lack of time for relationships with patients, colleagues, and family; less satisfied with mentoring relationships and support from all sources; and less satisfied with career-advancement opportunities, recognition, and salary. Career satisfaction can affect health, as well as health and safety of patients. Many factors adversely affecting career satisfaction for women physicians are extrinsic and, therefore, modifiable.     

Anti-HIV-1 and cytotoxicity studies of piperidyl-thienyl chalcones and their 2-pyrazoline derivatives

A series of 12 new pyrazoline derivatives was prepared from piperidyl chalcones, which in turn were synthesized by condensing 4-piperidin-1-ylbenzaldehyde with diverse acetylthiophenes. The target compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemental analysis. All the compounds were screened for cytotoxic and anti-HIV-1 activities. Compounds 1c, 1g, 1j, 2a, 2c, 2e, 2g, and 2k demonstrated potential anti-HIV activity but were cytotoxic except for 2e and 2k, which displayed no cytotoxicity in primary human cells. Bioassay results show that the type and positions of the substituents seem to be critical for their cytotoxic and anti-HIV-1 activities.