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.     

The vagaries of self-reports of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice.

BACKGROUND: The assessment of levels of physical activity relies upon suitable measurement tools. OBJECTIVE: We aimed to investigate whether a practice nurse, using a motivational interview technique, could encourage older patients to increase their physical activity. METHODS: Health and well-being were monitored at baseline and 8 weeks following intervention. Physical activity levels were ascertained using both a self-report measure and ambulatory heart-rate monitoring. RESULTS: Whilst patients reported higher levels of physical activity at follow-up, this finding was not confirmed by the heart-rate data. CONCLUSION: The study concludes that patients tend to overestimate the amount of physical activity undertaken and that ambulatory heart-rate monitoring may be more useful for verifying actual behaviour.     

'Culture-negative' prosthetic valve endocarditis. Hazards of postoperative steroid therapy for unexplained fever

Two patients had prolonged unexplained fever along with multiple negative blood cultures after cardiac valve replacement surgery. Following the administration of corticosteroids for presumed postpericardiotomy syndrome, both patients improved symptomatically and defervesced, only to have positive blood cultures for Staphylococcus epidermidis shortly thereafter. The theoretical and practical risks of the empiric use of anti-inflammatory agents for unexplained post-operative fever are reviewed. "Culture-negative" prosthetic valvular infection due to prior antibiotic prophylaxis or therapy must be strongly considered in the evaluation of such unexplained fever.     

Chronic toxicity of dietary disodium arsenate heptahydrate to juvenile rainbow trout (Oncorhynchus mykiss)

Juvenile rainbow trout were fed semi-purified diets containing graded levels of disodium arsenate heptahydrate (DSA) for 12–24 weeks under standard laboratory conditions to define the maximum acceptable toxicant concentration (MATC) and to correlate signs of toxicity with diet and tissue arsenic concentrations. The MATC for DSA was between 13 and 33 g As/g diet or 0.281–0.525 mg As/kg body weight/day. The most sensitive and reliable indicator of chronic dietary DSA toxicity in rainbow trout was chronic inflammation of the gallbladder wall. Chronic inflammatory changes in the sub-epithelial tissues of the gallbladder wall were evident in 71% of rainbow trout exposed to 33 g As/g diet for 24 weeks, and 100% of rainbow trout exposed to 65 g As/g diet for 24 weeks or 49 g As/g diet for 12 weeks. No fish exposed to 13 g As/g diet or less for up to 24 weeks showed any demonstrable gallbladder lesions or any other ill effect of arsenic exposure. Other signs of chronic dietary DSA toxicity to rainbow trout included decreased growth rate, mild to moderate anemia, and, at higher levels of exposure, active feed refusal leading to decreased feed consumption. Mild nephrocalcinosis was noted in one experiment where kidney arsenic residues exceeded 14 g As/g tissue dry weight.Supported by the Natural Sciences and Engineering Research Council of Canada and the Ontario Ministry of Agriculture and FoodPortions of this material were presented at the 29th Annual Meeting of the Canadian Federation of Biological Societies, June 16–20, 1986, Guelph, Ontario, and the 14th Annual Aquatic Toxicity Workshop, November 2–4, 1987, Toronto, Ontario, Canada     

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.     

Targeted liposomal c-myc antisense oligodeoxynucleotides induce apoptosis and inhibit tumor growth and metastases in human melanoma models.

PURPOSE: Melanoma is a highly malignant and increasingly common tumor. Because the cure rate of metastatic melanoma by conventional treatment is very low, new therapeutic approaches are needed. We previously reported that coated cationic liposomes (CCL) targeted with a monoclonal antibody against the disialoganglioside (GD(2)) and containing c-myb antisense oligodeoxynucleotides (asODNs) resulted in a selective inhibition of the proliferation of GD(2)-positive neuroblastoma cells in vitro. EXPERIMENTAL DESIGN: Here, we tested the in vivo antitumor effects of this novel antisense liposomal formulation by targeting the c-myc oncogene on melanoma, a neuroectodermal tumor sharing with neuroblastoma the expression of GD(2). RESULTS: Our methods produced GD(2)-targeted liposomes that stably entrapped 90% of added c-myc asODNs. These liposomes showed a selective binding for GD(2)-positive melanoma cells in vitro. Melanoma cell proliferation was inhibited to a greater extent by GD(2)-targeted liposomes containing c-myc asODNs (aGD(2)-CCL-myc-as) than by nontargeted liposomes or free asODNs. The pharmacokinetic results obtained after i.v. injection of [(3)H]-myc-asODNs, free or encapsulated in nontargeted CCLs or GD(2)-targeted CCLs, showed that free c-myc-asODNs were rapidly cleared, with less than 10% of the injected dose remaining in blood at 30 min after injection. c-myc-asODNs encapsulated within either CCL or aGD(2)-CCL demonstrated a more favorable profile in blood, with about 20% of the injected dose of each preparation remaining in vivo at 24 h after injection. In an in vivo melanoma experimental metastatic model, aGD(2)-CCL-myc-as, at a total dose of only 10 mg of asODN per kilogram, significantly inhibited the development of microscopic metastases in the lung compared with animals treated with myc-asODNs, free or entrapped in nontargeted liposomes, or aGD(2)-CCL encapsulating scrambled asODNs (P < 0.01). Moreover, mice bearing established s.c. human melanoma xenografts treated with aGD(2)-CCL-myc-as exhibited significantly reduced tumor growth and increased survival (P < 0.01 versus control mice). The mechanism for the antitumor effects appears to be down-regulation of the expression of the c-myc protein and interruption of c-myc-mediated signaling: induction of p53 and inhibition of Bcl-2 proteins, leading to extensive tumor cell apoptosis. CONCLUSION: These results suggest that inhibition of c-myc proto-oncogene by GD(2)-targeted antisense therapy could provide an effective approach for the treatment of melanoma in an adjuvant setting.