Factor V Leiden and G20210A prothrombin mutation and the risk of subclavian vein thrombosis in patients with breast cancer and a central venous catheter.

BACKGROUND: To analyze the influence of the prothrombotic gene mutation factor V G1691A (factor V Leiden) and prothrombin G20210A on the risk of a first episode of catheter-related deep venous thrombosis (DVT) in a group of patients with breast cancer treated with chemotherapy. PATIENTS AND METHODS: Between January 1999 and February 2001, the occurrence of a first symptomatic DVT was investigated in a cohort of 300 consecutive patients with locally advanced or metastatic breast cancer treated at a single institution with fluorouracil-based chemotherapy, administered continuously through a totally implanted access port. A nested case-control study included 25 women (cases) with catheter-related DVT and 50 controls without DVT matched with cases for age, identical chemotherapy, stage of disease and prognostic features. The G1691A factor V and G20210A prothrombin mutation genotypes were analyzed. RESULTS: Five cases [20%; 95% confidence interval (CI) 9% to 39%)] and two controls (4%; 95% CI 1% to 14%) were heterozygous carriers of G1691A factor V (P = 0.04). The age-adjusted odds ratio for catheter-related DVT was 6.1 (95% CI 1.1-34.3). Only one patient (case) had the G20210A prothrombin gene mutation. Time from start of chemotherapy infusion to DVT was not significantly different between patients with (median 31 days) and without (median 43 days) G1691A factor V mutation (P = 0.6). CONCLUSIONS: Factor V Leiden carriers with locally advanced or metastatic breast cancer have an increased risk of developing catheter-related DVT during chemotherapy.     

Trends in childhood cancer incidence and mortality in Catalonia, Spain, 1975-1998.

Childhood cancer mortality has sharply declined in most economically developed countries over the last years, whereas no substantial changes in the incidence have been observed. In Catalonia (Spain), childhood cancer mortality showed a considerable decline until 1992, but incidence trends have not been analysed in this population. To assess both recent incidence and mortality trends in this population, we analysed childhood (0-14 years) cancer data from the population-based Tarragona Cancer Registry and from the Mortality Registry of Catalonia (Spain) from 1980 to 1998. All cancer mortality decreased by -2.6% annually in boys (95% confidence interval, 95% CI -3.7, -1.6) and -3.7% in girls (95% CI -4.9, -2.5). Mortality due to leukaemia decreased annually -3.0% in boys (95% CI -4.7, -1.4) and -4.4% in girls (95% CI -6.3, -2.4). Mortality for brain tumours showed a reduction of -3.2% in boys (95% CI -5.5, -0.9) and of -4.4% in girls (95% CI -6.3, -2.4). No significant trend in incidence rates, either in boys or in girls, was observed (annual per cent of change for all cancers -0.5%, 95% CI -3.5, 2.7, in boys and 1.7%, 95% CI -1.9, 5.5, in girls). These results suggest an improvement in both childhood cancer diagnosis and treatment, which may explain current higher childhood cancer survival rates.     

Diagnosis and treatment of hepatic artery thrombosis after liver transplantation

The aim of this study was to examine the clinical presentation and time of hepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT), stressing the role of imaging modalities. Therapeutic options are described, such as retransplantation (Re-OLT), hepatic resections and revascularization procedures, focusing on complications and outcome in a consecutive series of 687 OLT. Over the period from 1986 to 1999, 687 OLT were carried out in 601 patients, 592 of whom were adults and 95 pediatric subjects. Of these operations 601 were primary OLT and 86 Re-OLT (71 I Re-OLT, 14 II Re-OLT and 1 III Re-OLT). In this retrospective study, we reviewed rejection episodes, time of HAT (early or late), possible cause of HAT, day of suspected diagnosis of HAT and day of confirmation of diagnosis. Clinical presentation, management, complications, outcome, survival rates and the need for Re-OLT were also recorded. The incidence of HAT was 2.47% (17/687). Early HAT (n = 9, < 30 days) was diagnosed 15.6 days after OLT (range: 3-25 days), whereas late HAT (n = 8, > 30 days) occurred 295.1 days after OLT (range: 38-1830 days). In two asymptomatic patients (2/17: 11.7%), HAT was discovered incidentally. Most of the patients (11/17: 64.7%) presented with increased liver function test values and fever. Relapsing bacteremia occurred in 7/17 cases (41.1%), whereas a biliary stricture and biliary leak were diagnosed in 3/17 (17.6%) and in 1/17 patients (5.8%), respectively. Fulminant hepatic failure was the clinical presentation in 2/17 cases (11.7%). In one case the clinical presentation was acute and chronic rejection (1/17: 5.8%). Intrahepatic abscesses were diagnosed in one case (1/17: 5.8%), as well as an intrahepatic haemorrhage (1/17: 5.8%). Doppler ultrasound (DUS) correctly revealed HAT in 9 of the 17 patients (52.9% sensitivity). In 8 of the 9 patients (88.8%) in whom HAT was diagnosed by DUS, angiography was also performed to confirm the diagnosis. Overall, angiography detected HAT in 14/17 patients (82.3% sensitivity). HAT management consisted of immediate Re-OLT in 6 patients 6.8 days (range: 3-12 days) after diagnosis. Delayed Re-OLT was performed in 6 patients 529.1 days (range: 68-1920 days) after diagnosis. The overall retransplantation rate was 70.5% (12/17). Two patients died despite undergoing intraarterial urokinase treatment. Three grafts were salvaged, but suffered biliary stricture due to ischemic cholangitis and underwent hepatico-jejunostomy. A II Re-OLT was carried out in 4 of 12 patients (33.3%). The overall mortality rate was 41.1% (7/17). One-year and 3-year overall survival rates were 58.8% (10/17) and 47.0% (8/17), respectively. Both 5- and 10-year overall survival rates were 11.7% (2/17). Although the results of OLT have improved dramatically over the past few years, HAT is still associated with substantial morbidity, a high incidence of graft failure and high mortality rates. The use of DUS to screen for HAT has permitted earlier diagnosis, but early angiographic evaluation of the hepatic arteries is still needed for accurate diagnosis of HAT and remains the gold standard. Retransplantation is the definitive solution for HAT in the majority of cases, though it is essentially the patient's clinical condition that dictates the form of management.     

Synthesis and Antimuscarinic Activity of Derivatives of 2-Substituted-1,3-Dioxolanes

Geometric cis, trans isomers, derivatives of 2-substituted-1,3-dioxanes were designed and studied as antimuscarinic agents. The synthesized compounds were evaluated as perchlorides and methiodides by functional tests with rabbit vas deferens (putative M₁), guinea-pig heart (M₂) and guinea-pig ileum (M₃). The effect of the replacement of a trimethylammonium group with a dimethysulfonium in the two rings was also evaluated. Pharmacological results indicate that the 1,3-dioxane nucleus shows the highest stereoselective values on the studied receptors.     

Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.