When deep venous thrombosis fails to respond to therapy

BACKGROUND: Deep venous thrombosis in primary care is usually treated with rest, analgesics, intravenous or low-molecular-weight heparin, and coumadin. In some cases, however, a less familiar course of diagnosis and management is required. METHODS: We describe the case of a 53-year-old truck driver who had an acute deep venous thrombosis of his right lower extremity, which failed to respond to routine therapy with heparin and warfarin. A literature search was undertaken to research the differential diagnosis and management of deep venous thrombosis and to review specifically the role of venal caval filters and inherited thrombotic disorders and occult cancer in this context. RESULTS AND CONCLUSION: The ultimate diagnosis in our patient appeared to be signet ring cell cancer of the colon that had metastasized to the right thigh. This case is an example of the inherent limitations of even an aggressive diagnostic and therapeutic approach to the entity of refractory deep venous thrombosis.     

The toxicity of metal mixtures to the estuarine mysid Neomysis integer (Crustacea: Mysidacea) under changing salinity

Water quality criteria are mainly based on data obtained in toxicity tests with single toxicants. Several authors have demonstrated that this approach may be inadequate as the joint action of the chemicals is not taken into account. In this study, the combined effects of six metals on the European estuarine mysid Neomysis integer (Leach, 1814) were examined. Acute 96-h toxicity tests were performed with mercury, copper, cadmium, nickel, zinc and lead, and this as single compounds and as a mixture of all six. The concentrations of the individual metals of the equitoxic mixtures were calculated using the concentration-addition model. The 96-h LC50's for the single metals, at a salinity of 5 per thousand, ranged from 6.9 to 1140 microg/l, with the following toxicity ranking: Hg>Cd>Cu>Zn>Ni>Pb. Increasing the salinity from 5 to 25 per thousand resulted in lower toxicity and lower concentrations of the free ion (as derived from speciation calculations) for all metals. This salinity effect was strongest for cadmium and lead and could be attributed to complexation with chloride ions. The toxicity of nickel, copper and zinc was affected to a smaller extent by salinity. The 96-h LC50 for mercury was the same for both salinities. In order to evaluate the influence of changing salinity conditions on the acute toxicity of metal mixtures, tests were performed at different salinities (5, 10, 15 and 25 per thousand ). The 96-h LC50 value (1.49 T.U.) of the metal mixture, at a salinity of 5 per thousand, was clearly lower than the expected value (6 T.U.) based on the non-additive hypothesis, thus confirming the additive effect of these metals in the marine/estuarine environment. Changing salinity had a profound effect on the toxicity of the mixture. The toxicity clearly decreased with increasing salinity until 15 per thousand. Higher salinities (25 per thousand ) had no further influence on the 96-h LC50 of the mixture which is situated at a value between 4.4 and 4.6. Finally, the relative sensitivity to the selected metals was compared with the relative sensitivity of the commonly used mysid Americamysis (=Mysidopsis) bahia.     

Validation of the telephone and in-person interview versions of the 7-day PAR

PURPOSE: To validate the 7-d Physical Activity Recall (PAR) telephone interview version and its activity intensity categories. METHODS: Seventy-four adults (47 women, 27 men), ranging in age (18-67) and activity levels, were interviewed by phone and in-person using the same PAR protocol. Each participant wore a TriTrac-R3D accelerometer for 10 d. Validity was assessed by comparing the phone and in-person PAR interviews with the TriTrac-R3D data. RESULTS: Sixty-nine adults (44 women, 25 men) were used for all statistical analyses. Intraclass correlations between the two PAR interviews for total minutes per week of activity were r = 0.96, and r = 0.94 for moderate, r = 0.97 for hard, and r = 0.97 for very hard intensity activities. Pearson product moment correlations between the phone PAR and TriTrac-R3D for total minutes per week of physical activity were r = 0.43, and r = 0.31 for moderate, r = 0.39 for hard, and r = 0.78 for very hard intensity activities. Pearson correlations between the in-person PAR and TriTrac-R3D for total minutes per week of physical activity were r = 0.41, and r = 0.33 for moderate, r = 0.43 for hard, and r = 0.74 for very hard intensity activities. Participants overestimated the amount of physical activity in both interviews as compared with the TriTrac-R3D. CONCLUSION: The phone and in-person versions of the PAR are equivalent measures for self-reported physical activity. Regardless of age, body mass index, or physical activity level both interview methods had similar estimates for total minutes per week of moderate, hard, and very hard activity. Correlations between each interview method and the TriTrac-R3D were lower for moderate and hard activities as compared with very hard activities.     

Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG?

Epileptiform EEG discharges are not confined to people with epilepsy, and their frequency is only weakly related to severity. A fundamental principle of EEG practice is, therefore, to avoid overinterpretation of epileptiform activity. Epileptiform discharges not accompanied by obvious clinical events are generally regarded as subclinical or interictal. However, in many patients sensitive methods of observation, notably continuous psychological testing, show brief episodes of impaired cognitive function during such discharges. This phenomenon of transitory cognitive impairment (TCI) is found in about 50% of patients who show discharges during testing. TCI is not simple inattention. The effects are material and site specific: lateralised discharges are associated with deficits of functions mediated by the hemisphere in which the discharges occur. Conversely, specific tasks can activate or suppress focal discharges over the brain regions that mediate the cognitive activity in question. TCI clearly contributes to the cognitive problems of some people with epilepsy and may cause deficits that pass unrecognised. TCI is demonstrable in many cases of benign partial epilepsy of childhood, a disorder once thought to have no adverse psychological effects. TCI can contribute to abnormalities of psychological test profiles and interferes with daily tasks, such as reading and driving. In children it may be associated with behavioural disorders. An important practical issue is whether TCI materially impairs psychosocial function and, if so, whether drug treatment is desirable or effective. Uncontrolled reports and two preliminary randomised controlled trials of antiepileptic treatment of TCI have suggested that suppression of discharges is associated with significant improvement in psychosocial function.     

Use of radiotherapy in the primary treatment of cancer in South Australia

Previous studies point to a lower use of radiotherapy by Australian cancer patients in lower socioeconomic areas and in country regions that are some distance from urban treatment centres. These were cross-sectional studies with the potential for error from changes in place of residence. We used a cohort design to avoid such error. South Australian patients diagnosed in 1990-1994 were followed until the date of censoring of 31 December 1999 using data from the State Cancer Registry. The percentage found to have had megavoltage therapy in the first 12 months following diagnosis varied by leading primary incidence site from 44% for the prostate to 40% for female breast, 38% for lung, 17% for rectum, 3% for colon and 2% for skin (melanoma). Multivariate analysis indicated that determinants of not receiving megavoltage therapy in the first 12 months were older age, female sex, residence in a country region and country of birth. Melanoma data revealed earlier stages for women than men. If this difference by sex applies to other cancers, it might explain the lower exposure of women to radiotherapy. Fewer older patients received radiotherapy, consistent with trends observed in hospital-based cancer-registry data. The influence on this finding of differences in stage and comorbidity requires additional study. While earlier findings of a lower exposure of country residents to radiotherapy were confirmed, the difference was comparatively small in this study. Variations in exposure by socioeconomic status of residential area were not observed.     

Squamous cell carcinoma and transitional cell carcinoma arising in bladder augmentations

Tumours arising in bowel-augmented bladders are rare. Usually these tumours are adenocarcinomas that occur along the anastomotic line. We present two unusual tumours, squamous cell carcinoma and transitional cell carcinoma, that occurred in bladder augmentations. We also emphasize the need for regular cystoscopic surveillance.     

Genome-wide screening for complete genetic loss in prostate cancer by comparative hybridization onto cDNA microarrays

We demonstrate that comparative genomic hybridization (CGH) onto cDNA microarrays may be used to carry out genome-wide screens for regions of genetic loss, including homozygous (complete) deletions that may represent the possible location of tumour suppressor genes in human cancer. Screening of the prostate cancer cell lines LNCaP, PC3 and DU145 allowed the mapping of specific regions where genome copy number appeared altered and led to the identification of two novel regions of complete loss at 17q21.31 (500 kb spanning STAT3) and at 10q23.1 (50-350 kb spanning SFTPA2) in the PC3 cell line.     

EDD,the human orthologue of the hyperplastic discs tumour suppressor gene,is amplified and overexpressed in cancer

EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene 'hyperplastic discs' and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT-PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression.