A placebo-controlled crossover study of ketanserin in elderly hypertensive patients

Summary The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (> 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p<0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p<0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p=0.002; analysis of variance on log transformed data) compared with the placebo phase.     

Tumour profile ofN-[2-(dimethylamino)ethyl]acridine-4-carboxamide after intraperitoneal administration in the mouse

N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC) is an experimental antitumour agent that is being considered for phase I trials. After i.p. administration of 150 mg/kg [³H]-AC to tumour-bearing mice, AC was absorbed rapidly into the plasma and tissues such as the heart, liver, kidney and brain but more slowly into the s.c. tumour. The maximal AC concentration (86±36 mol/kg) in the tumour occurred at 35–60 min and was 3-fold the maximal plasma concentration, which occurred at 15 min. Although higher maximal concentrations were observed in other tissues, these concentrations fell rapidly in parallel with plasma concentrations. In contrast, AC concentrations in the tumour remained elevated, thet1/2 value (16.3 h) and mean residence time (MRT, 9.5 h) being prolonged in comparison with those in the plasma and other tissues (t1/2 range, 1.0–2.9 h; MRT, 1.2–1.4 h). AC concentrations were not detectable by our high-performance liquid chromatographic (HPLC) method (limit of detection, 0.02 mol/l) in the plasma or other tissues at 24 or 48 h after administration but were measurable in the tumour (1.6±0.8 and 0.6±0.3 mol/kg, respectively). Radioactivity concentrations in the plasma, tissues and tumour were very variable but were greater than the corresponding levels of unchanged parent AC. By 24 h, radioactivity concentrations in the plasma, tissues and tumour had fallen to similar levels with prolonged elimination profiles. Thus, the exposure of the s.c. implanted tumour to a threshold AC concentration for a prolonged time (>24 h) may partly explain the greater efficacy of AC against this tumour, whereas the shorter period of exposure of blood and other tissues may explain its low haematological toxicity.     

Laparoscopic Splenectomy

Splenectomy is a powerful tool for treatment of hematologic disease, with 70% to 90% of patients achieving long-term improvement. In recent years laparoscopic splenectomy has gained acceptance as a viable alternative to open splenectomy. This review summarizes the indications for laparoscopic splenectomy, the operative techniques, and the most recent results. Laparoscopic splenectomy is evolving and may become the standard operative method for the treatment of the problem spleen.     

Generalization of the extended transmission disequilibrium test to two unlinked disease loci

The extended transmission disequilibrium test (ETDT) of Sham and Curtis [1995] is a powerful test of the null hypothesis of no linkage between a multi-allelic marker locus and a disease susceptibility locus of unknown location in the presence of association between alleles at the two loci. We propose a generalization of the ETDT to test simultaneously for linkage of markers to two unlinked disease loci. Analysis of the simulated data for Problem 2 would suggest improvements in power to detect linkage to pairs of disease loci over single locus tests. This is as a result of the two locus model taking account of epistasis between the disease loci.     

Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of the Breast Cancer Family Registry.

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04-2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.     

Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation.

Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.     

Publication rates of abstracts presented at annual scientific meetings: How does the Royal Australian and New Zealand College of Radiologists compare?

The abstract to publication ratio (APR) is a measure of the quality of scientific meetings. The aim of the present study was to determine the publication rate of abstracts presented at annual Royal Australian and New Zealand College of Radiologists (RANZCR) conferences, and to identify the publishing journals. All free paper research abstracts (oral or poster) presented by RANZCR radiologists, radiation oncologists and trainees at the four consecutive meetings between 1996 and 1999 were identified retrospectively from conference programmes. The PubMed database ( http:www.ncbi.nlm.nih.govPubMed ) was searched to determine whether or not the abstract had been published as a full paper. Of the 480 free paper research abstracts, 168 (35%) had been published as full articles. The overall abstract to publication ratio for radiology was 29% and for radiation oncology was 41%. Papers were published in a variety of journals but Australasian Radiology accounted for 27%. The mean time between presentation and publication was 16.5 months (median 17 months). These overall abstract to publication ratios are lower than those reported for overseas‐based meetings in each respective area. Guidelines to scientific committees could increase the APR by more rigorous selection of abstracts. Future research should look at barriers to the publication of research findings, and identify ways to assist the publication process.