The influence of polymorphisms of VKORC1 and CYP2C9 on major gastrointestinal bleeding risk in anticoagulated patients

The VKORC1 c.-1639G>A and CYP2C9 c.430C>T and c.1075A>C polymorphisms have been associated with increased sensitivity to oral anticoagulants. However, their role in gastrointestinal bleeding is unknown. We studied the risk of gastrointestinal bleeding associated with these polymorphisms, and how this risk was influenced by the anticoagulant dose and the use of common drugs. Eighty-nine patients with gastrointestinal bleeding during acenocoumarol therapy and 177 patients free of bleeding during acenocoumarol therapy were studied. None of the three polymorphisms constituted a serious gastrointestinal bleeding risk factor. However, patients bearing at least one of these polymorphisms were at high risk, when they simultaneously met one of the following conditions: a weekly dose of acenocoumarol higher than 15 mg [adjusted Odds Ratio (OR) (95% confidence interval (CI) = 4.19 (1.59-11.04)]; amiodarone use [adjusted OR (95% CI) = 9.97 (1.75-56.89)]; or aspirin use [adjusted OR (95% CI) = 8.97 (1.66-48.34)]. The consumption of statins was associated with a lower risk of gastrointestinal bleeding [adjusted OR = 0.50 (0.26-0.99)]. The risk of gastrointestinal bleeding during acenocoumarol therapy in carriers of any of the studied polymorphisms is severely increased with exposure to weekly doses of acenocoumarol higher than 15 mg or the use of amiodarone or aspirin.     

Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

Cost of care of arterial hypertension and its impact on the budget assigned to health in Mexico

OBJECTIVE: To assess the medical care costs of hypertension and their impact on the health care expenditures and on Mexico's Gross National Product (GNP). MATERIAL AND METHODS: An ecological study was conducted from June to November 1999, at Instituto Mexicano del Seguro Social (Mexican Institute of Social Security, IMSS), in Monterrey, Nuevo Leon, Mexico. A random sample of medical charts of patients with hypertension was selected, to extract data on utilization of health services and unitary costs per care episode. The cost per care episode and per hypertensive patient was calculated by adjusting the unitary cost as a function of standard and extreme utilization of IMSS health services. The resulting figure was then projected to the total population of hypertensive patients and compared to the annual health care expenditures of Mexico. RESULTS: The annual cost per patient with hypertension was $1,067 in the standard scenario and $3,913 in the extreme scenario. The annual expenditures from hypertension corresponded to 13.95% of the budget allocated to health care and to 0.71%, of Mexico's GNP. These figures changed to 51.17% and 2.61% in the extreme scenario, respectively. CONCLUSIONS: The costs of hypertension medical care account for a good portion of healthcare resources. This problem should be analyzed by multidisciplinary health teams in search of more efficient medical care alternatives.     

Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses

We studied the association between CD34 cell dose and transplant outcomes in 359 bone marrow (BM) and 511 peripheral blood stem cell (PBSC) transplant recipients from human leucocyte antigen (HLA)-identical siblings, reported to the International Bone Marrow Transplant Registry (IBMTR). Transplants for leukaemia were performed between 1995 and 1998. Patients were divided into those receiving below or above the median CD34+ dose, for BM (3 x 106/kg) and PBSC (6 x 106/kg) grafts respectively. Cox proportional hazards regression was used to adjust for baseline patient-, disease- and transplant-related characteristics. Analysis of the BM recipients showed that high CD34 cell dose was associated with lower transplant-related mortality [relative risk (RR) = 0.60, P = 0.033] and treatment failure (inverse of leukaemia-free survival, RR = 0.69, P = 0.032). Among PBSC recipients, high CD34 dose was associated with faster recovery of neutrophils to > 0.5 x 109/l (RR = 1.38, P < 0.001) and platelets to > 20 x 109/l (RR = 1.34, P = 0.003), lower risk of relapse (RR = 0.62, P = 0.029) and treatment failure (RR = 0.74, P = 0.03). We conclude that higher CD34 cell doses decrease treatment failure in recipients of HLA-identical sibling BM and PBSC transplants.     

Revisiting serum thyroglobulin in the follow-up of patients with differentiated thyroid carcinoma

This study analyzed serum thyroglobulin (Tg) during hypothyroidism in 207 patients with differentiated thyroid carcinoma treated with total thyroidectomy and radioiodine ablation and undetectable anti-Tg antibodies. Disease staging was defined by clinical examination, stimulated Tg, pre- and post-ablative radioiodine scanning, and other imaging methods (X-Ray, US, CT and MIBI-scan). The average interval from initial therapy was 2.3 years. 153 patients (74%) had no evident disease, 34 (16.4%) presented neck/mediastinal disease, and 20 (9.6%) had distant metastases (Mt). The best cut-off for Tg was 1 ng/ml, showing 100% sensitivity for distant Mt and 88.2% for local recurrence or lymph node Mt, and 88.8% specificity for any Mt and 74.8% for distant Mt. In patients with Tg <1 ng/ml, 2.8% showed cervical lymph nodes Mt. Cervical or mediastinal disease were 26% of cases with Tg between 1 and 5 ng/ml. Tg from 5 to 10 ng/ml was associated to distant Mt in 14.2% of the cases and others showed lymph nodes Mt. In patients with Tg >10 ng/ml, 51.3% presented distant Mt. We suggest the need for neck US even in cases with Tg <1 ng/ml. In addition, patients with Tg levels <5 ng/ml should be investigated by neck US and mediastinal CT only, and empirical therapy should be limited to patients with a minimum Tg level >5 ng/ml.     

A single injection of pregabalin induces short- and long-term beneficial effects on fear memory and anxiety-like behavior in rats with experimental type-1 diabetes mellitus

Metabolic Brain Disease - Anxiety Disorders and Posttraumatic Stress Disorders (PTSD) associated with type-1 diabetes mellitus (T1DM) are increasingly common comorbidities and the treatment is...