Estimation with Tc-99m tetrofosmin SPECT of salvaged myocardial mass after emergent reperfusion therapy in acute myocardial infarction.

The original publication is available at www.springerlink.com authorOBJECTIVES: The purpose of this study was to validate a new quantitative index of salvaged myocardial mass calculated from Tc-99m tetrofosmin SPECT for evaluating the therapeutic effect of emergent reperfusion therapy in acute myocardial infarction (AMI). METHODS: Tc-99m tetrofosmin SPECT was performed before and after emergent percutaneous transluminal coronary angioplasty (PTCA) in eight patients with AMI. In the pre-PTCA study, Tc-99m tetrofosmin was injected before emergent PTCA. Two weeks after the PTCA, post-PTCA study was performed. As a quantitative index of salvaged myocardial mass, salvaged myocardial volume (SMV) was defined as the difference of myocardial functional volume between the SPECT studies before and after the PTCA. To investigate the clinical significance of SMV, SMV was compared with the grade of therapeutic efficacy determined visually from pre- and post-PTCA SPECT images and clinical parameters, namely peak creatine phosphokinase level (pCK) and the time from the onset of the AMI to reperfusion (RPT). RESULTS: SMV showed a significant correlation with the visual grade of therapeutic efficacy (r = 0.737, p 6 hr) were 30.0 +/- 14.0 and -6.2 +/- 25.5 ml, showing a greater mean SMV value in the early-reperfusion group (p < 0.07). CONCLUSION: SMV could be used as a quantitative index of salvaged myocardial mass for evaluating the therapeutic effect of emergent reperfusion therapy

DNA topoisomerase II interacts with Lim15/Dmc1 in meiosis

Lim15/Dmc1 is a meiosis specific RecA-like protein. Here we propose its participation in meiotic chromosome pairing-related events along with DNA topoisomerase II. Analysis of protein–protein interactions using in vitro binding assays provided evidence that Coprinus cinereus DNA topoisomerase II (CcTopII) specifically interacts with C.cinereus Lim15/Dmc1 (CcLim15). Co-immunoprecipitation experiments also indicated that the CcLim15 protein interacts with CcTopII in vivo. Furthermore, a significant proportion of CcLim15 and CcTopII could be shown to co-localize on chromosomes from the leptotene to the zygotene stage. Interestingly, CcLim15 can potently activate the relaxation/catenation activity of CcTopII in vitro, and CcTopII suppresses CcLim15-dependent strand transfer activity. On the other hand, while enhancement of CcLim15's DNA-dependent ATPase activity by CcTopII was found in vitro, the same enzyme activity of CcTopII was inhibited by adding CcLim15. The interaction of CcLim15 and CcTopII may facilitate pairing of homologous chromosomes

Cytogenetic alterations in ovarian clear cell carcinoma detected by comparative genomic hybridisation

Ovarian clear cell carcinoma (OCCC) accounts for a small but significant proportion of all ovarian cancers and is a distinct clinical and pathological entity. It tends to be associated with poorer response rates to chemotherapy and with a worse prognosis. Little is known about possible underlying genetic changes. DNA extracted from paraffin-embedded samples of 18 pure OCCC cases was analysed for genetic imbalances using comparative genomic hybridisation (CGH). All of the 18 cases showed genomic alterations. The mean number of alterations detected by CGH was 6 (range 1–15) indicating a moderate level of genetic instability. Chromosome deletions were more common than amplifications. The most prominent change involved chromosome 9 deletions in 10 cases (55%). This correlates with changes seen in other epithelial ovarian cancers. This deletion was confirmed using microsatellite markers to assess loss of heterozygosity (LOH) at four separate loci on chromosome 9. The most distinct region of loss detected was around the IFNA marker at 9p21 with 41% (11 out of 27cases) LOH. Other frequent deletions involved 1p (five out of 18; 28%); 11q (four out of 18; 22%) and 16 (five out of 18; 28%). Amplification was most common at chromosome 3 (six out of 18; 33%); 13q (four out of 18; 22%) and 15 (three out of 18; 17%). No high-level amplifications were identified. These features may serve as useful prognostic indicators in the management of OCCC

DNA topoisomerase I and II expression in drug resistantgerm cell tumours

A small number of testicular germ cell tumours are refractory to current chemotherapy regimens. DNA topoisomerase I is the target for several new drugs and a potential candidate treatment for chemorefractory germ cell tumours. DNA topoisomerase IIα is the target for etoposide, which is currently used regularly in germ cell tumour treatment. The expression of DNA topoisomerase I and IIα were therefore assessed immunohistochemically in a range of testicular tumours, especially those with persistent malignant elements on retroperitoneal lymph node dissection. Pre-chemotherapy orchidectomy specimens were matched with post-chemotherapy retroperitoneal lymph node dissections to examine changes in expression. There was considerable variation in the expression of topoisomerase I in different tumour types. Both yolk sac tumours and teratoma, mature showed universal expression of topoisomerase I, while 38% of seminomas and 30% of embryonal carcinomas were positive. Strong topoisomerase IIα expression was found in embryonal carcinoma. There was a negative correlation between topoisomerase I and IIα expression (P=0.004) and downregulation of topoisomerase IIα after chemotherapy (P=0.02). Topoisomerase I expression appears to increase in those cases with residual teratoma, mature, but is largely unchanged in those cases remaining as embryonal carcinoma. These results suggest that topoisomerase I inhibitors may be useful in chemorefractory germ cell tumours, especially yolk sac tumours and where there are unresectable residual teratoma, mature deposits

Radiotherapy in the treatment of Graves ophthalmopathy—to do it or not?

To the objective of this study is to evaluate the role and toxicity of radiotherapy in the treatment of Graves ophthalmopathy. In the years 2000–2003, 121 patients with malignant exophthalmos were treated with radiotherapy of the retrobulbar area to the total dose of 20 Gy in ten fractions with a 6 MeV photon beam. The treatment was performed by the team of the Clinic of Oncology of the Jagiellonian University Medical College in Cracow. The radiotherapy was preceded by intravenous steroid therapy: methylprednisolone acetate administered at the dose of 2 g/week for four consecutive weeks. The highest efficacy, expressed as improvement of all ocular symptoms, was observed for the combined treatment. Female and non-diabetic patients responded positively to the combined treatment. Radiotherapy combined with steroid therapy in the treatment of Graves ophthalmopathy seems to be an effective treatment for strictly defined indications. In the treatment of Graves–Basedow disease, radiotherapy is a well-tolerated treatment modality. Diabetes is a factor that worsens prognosis in Graves ophthalmopathy and female sex is a favourable factor for this condition

The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation