Miguel A. Cumsille

Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population

Objective: To describe the baseline characteristics of the participants in the Three-City (3C) Study, a study aiming to evaluate the risk of dementia and cognitive impairment attributable to vascular factors. Methods: Between 1999 and 2001, 9,693 persons aged 65 years and over, noninstitutionalized, were recruited from the electoral rolls of three French cities, i.e. Bordeaux, Dijon and Montpellier. Health-related data were collected during face-to-face interviews using standardized questionnaires. The baseline examination included cognitive testing and diagnosis of dementia, and assessment of vascular risk factors, including blood pressure measurements, ultrasound examination of the carotid arteries, and measurement of biological parameters (glycemia, total, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinemia); 3,442 magnetic resonance imaging (MRI) examinations were performed in subjects aged 65–79. Measurements of ultrasound, blood, and MRI parameters were centralized. Two follow-up examinations (at 2 and 4 years) were planned. Results: After exclusion of the participants who had subsequently refused the medical interview, the 3C Study sample consisted of 3,649 men (39.3%) and 5,645 women, mean age 74.4 years, with a relatively high level of education and income. Forty-two percent of the participants reported to be followed up for hypertension, about one third for hypercholesterolemia, and 8% for diabetes; 65% had elevated blood pressure measures (systolic blood pressure ≧140 or diastolic blood pressure ≧90). The proportion of Mini-Mental State Examination scores below 24 was 7% and dementia was diagnosed in 2.2% of the participants. Conclusion: Distribution of baseline characteristics of the 3C Study participants suggests that this study will provide a unique opportunity to estimate the risk of dementia attributable to vascular factors.

Early Hospital Discharge Followed by Outpatient Management Versus Continued Hospitalization of Children With Cancer, Fever, and Neutropenia at Low Risk for Invasive Bacterial Infection

PURPOSE To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection (IBI). PATIENTS AND METHODS Children presenting with febrile neutropenia at six hospitals in Santiago, Chile, were categorized as high or low risk for IBI. Low-risk children were randomly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution. Outcome and cost were determined for each episode and compared between both groups using predefined definitions and questionnaires. RESULTS A total of 161 (41%) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk, of which 149 were randomly assigned to ambulatory (n = 78) or hospital-based (n = 71) treatment. In both groups, mean age (ambulatory management, 55 months; hospital-based management, 66 months), sex, and type of cancer were similar. Outcome was favorable in 74 (95%) of 78 ambulatory-treated children and 67 (94%) of 71 hospital-treated children (P = NS). Mean cost of an episode was US 638 dollars (95% CI, 572 dollars to 703 dollars) and US 903 dollars (95% CI, 781 dollars to 1,025 dollars) for the ambulatory and hospital-based groups, respectively (P =.003). CONCLUSION For children with febrile neutropenia at low risk for IBI, ambulatory management is safe and significantly cost saving compared with standard hospitalized therapy.

Predictive factors of stenosis after stapled colorectal anastomosis: prospective analysis of 179 consecutive patients.

The incidence, risk factors, and clinical relevance of stenosis of stapled colorectal anastomosis (CRA) were studied prospectively. Anastomotic stricture was defined as the inability of traversing the anastomosis with the rigid proctoscope. The population studied consisted of 179 patients (94 males) with an average age of 59.3 years (range: 20 to 91 years). The main indication for surgery was colorectal cancer in 59% of the cases, followed by diverticular disease in 23%. The first endoscopic control was performed before 4 months in 25% of the patients, between 5 and 10 months in 50%, and during the following 10 months in 25%. Stenosis was verified with the rigid instrument in 21.1% of the cases and with the flexible colonoscope in 4.4%. The barium enema performed in 12 cases confirmed a punctiform stenosis in 5 patients, 4 of whom had been asymptomatic. An endoscopic dilatation was performed on 5 of the 8 symptomatic patients, with one relapse that required an additional dilatation. In the univariate analysis only the lesser 4-month interval was statistically significant (p = 0.033; odds ratio (OR) = 2.3; confidence interval (CI) 95% = 1.06 to 4.97). Male patients (p = 0.057; OR = 2.08; IC 95% = 0.97–4.44) show a tendency to CRA stricture that does not reach statistically significant levels. In the multivariate analysis, only sex (p = 0.04; OR = 4.11; IC 95% = 1.03 to 5.41) and the time interval (p = 0.012; OR = 2.87; IC 95% = 1.25 to 6.57) appear as independent variables in stenosis risk of a stapled CRA. The incidence of this complication depends on the criteria used for defining it. It is clinically relevant in no more than 5% of the patients. Five out of eight patients in category II were treated successfully with an endoscopic dilatation, while the other three improved spontaneously. Early stenosis, although frequent, is generally asymptomatic and disappears spontaneously. Considering the lack of correlation between the degree of stricture and its symptomatology, it is convenient to combine both the anatomic and the clinical criteria in the selection of candidates for an eventual therapeutic procedure.

The combination of ursodeoxycholic acid and methotrexate for primary biliary cirrhosis is not better than ursodeoxycholic acid alone

BACKGROUND/AIMS Many therapies have been tried in primary biliary cirrhosis. It has been suggested that a combination of ursodeoxycholic acid and methotrexate may offer advantages. Because the benefit and safety of this combination is uncertain, we conducted this prospective, randomized, double-blind, controlled trial. METHODS Twenty-five patients with well-defined primary biliary cirrhosis were randomly assigned to receive either ursodeoxycholic acid (500 mg/day) plus methotrexate (10 mg/week) or ursodeoxycholic acid plus placebo for a period of 48 weeks. Clinical, biochemical and histologic evolution were assessed. RESULTS In both groups the clinical response was similar and heterogeneous. In patients of ursodeoxycholic acid alone group, biochemical and histologic changes were comparable to those of patients of ursodeoxycholic acid plus methotrexate at 48 weeks. The addition of methotrexate was not associated with substantial adverse affects. CONCLUSIONS The use of methotrexate in combination with ursodeoxycholic acid was not followed by an additive benefit over ursodeoxycholic acid alone, nor was substantial toxicity added. Unless larger and longer controlled trials with clinical, biochemical and histologic controls show it to be a safe and effective therapy for primary biliary cirrhosis, ursodeoxycholic acid+methotrexate should not be used as a proven and accepted treatment.

Enalapril and prednisone in children with nephrotic-range proteinuria

Abstract The effect of enalapril and low prednisone doses on the urinary protein electrophoretic pattern was studied in 13 pediatric patients with glomerular diseases and steroid-resistant nephrotic syndrome. Enalapril was administred at doses of 0.2–0.6 mg/kg per day for 24–84 months, and prednisone was introduced 2 months later in 11 patients at doses of 30 mg/m2 on alternate days. The urine protein electrophoretic pattern showed a reduction of 80% and 70% in the total protein and albumin, respectively, after enalapril. Total urinary protein decreased from 5.46 to 1.1 g/m2 per day (P<0.001). A marked change from a pattern of non-selective urinary protein loss to an albumin-selective proteinuria was observed. Mean total plasma proteins increased from 4.7 to 5.43 g/dl (P<0.001). Four patients became free of proteinuria 24 months after enalapril was started, but only 2 remained free of proteinuria at 48 months of follow-up. The other 11 patients had persistent albuminuria of between 0.5 and 2.6 g/m2 per day with a selective urinary electrophoretic pattern. No additional decrease was observed after steroids were introduced. A clinical improvement in edema was observed in all children. Three patients developed transient acute renal failure, during the course of an infectious disease; 2 developed peritonitis and 1 pneumopathy. In these patients withdrawal of enalapril was necessary until a complete recovery of renal function was observed. Four patients were hypertensive on admission, achieving normal blood pressure 1 month after enalapril was started. No episodes of systemic arterial hypotension were seen. Creatinine clearance and serum potassium showed no statistically significant change.

Posterior pelvic exenteration for primary rectal cancer

Background  Indications for and the prognosis of posterior pelvic exenteration (PPE) in rectal cancer patients are not clearly defined. The aim of this study was to analyse the indications, complications and long‐term results of PPE in patients with primary rectal cancer.

Alcohol and Hemorrhagic Stroke in Santiago, Chile

Background and Purpose: Hemorrhagic stroke (HS) is a major cause of disability and death worldwide. There is a dearth of information on HS from geographically defined populations in Latin America. In this study we assessed the importance of alcohol consumption as a risk factor for HS in Chile. Methods: Case-control study in Santiago, Chile, of 140 consecutive patients with CT-confirmed HS, matched by sex and age with 140 hospital controls. Alcohol consumption was measured in grams (ethanol) per week, using a questionnaire administered to the patients or caregivers or both. We defined four categories of alcohol consumption: nondrinkers (0.0 g/week), light (0.1–115 g/week), moderate (116–402.5 g/week) and heavy drinkers (>402.5 g/week). Other variables measured included diabetes mellitus (DM), cigarette smoking, arterial hypertension, liver disease and chronic use of nonsteroidal anti-inflammatory drugs (NSAID). Statistical analysis was performed with STATA 6.0® software. Results: A total of 280 subjects with a mean age of 65.5 years were studied over a 3-year period, 122 men (43.5%) and 158 women (56.5%). Alcohol intake was 394.1 g/week among cases and 174.5 g/week in controls (p = 0.01). The following odds ratios (OR) with 95% confidence intervals (CI) were found: hypertension 4.89 (2.86–10.3) and chronic use of NSAID 3.44 (2.15–12.9). Using conditional logistic regression analysis high alcohol intake was found to have a statistically significant OR of 4.47 (CI 1.14–17.2). Conclusions: In Chile, a high alcohol intake (>402.5 g/week) increased more than 4 times the risk of HS and remained a significant risk factor for HS after controlling for hypertension, cigarette smoking, liver disease, blood cholesterol levels, and chronic use of NSAID. The risk was higher in younger patients (<65 years of age).

Identificación de asociaciones clínico-patológicas e hipermetilación de genes supresores de tumores en cáncer gástrico difuso a través de análisis de Hierarchical clustering

Eighty three patients with diffuse gastric cancer with information about survival andinfection with Epstein Barr virus, were studied. DNA was extracted from pathological slides and themethylation status of genes p14, p15, p16, APC, p73, FHIT, E-caderin, SEMA3B, BRCA-1, MINT-2 yMGMT, was studied using sodium bisulphite modification and polymerase chain reaction. Resultswere grouped according to the methylation index or Hierarchical clustering (TIGR MultiExperimentViewer).

PORCENTAJE DE COMPROMISO DE LESION CERVICAL DE ALTO GRADO Y PERSISTENCIA DE ENFERMEDAD RESIDUAL POSTCONO

El objetivo de este trabajo fue evaluar la relacion entre el porcentaje de cuello comprometido por neoplasia intraepitelial de alto grado en pacientes conizadas por asa leep y la persistencia de lesion residual en la pieza de histerectomia. Se presentan 78 casos de pacientes conizadas por asa leep y que posteriormente fueron sometidas a histerectomia entre junio de 1994 y diciembre del 2000 por enfermedad residual u otra patologia ginecologica concomitante. Una vez obtenida la pieza de conizacion esta fue analizada en anatomia patologica evaluando el porcentaje de muestras comprometidas por nie de alto grado y se comparo con la persistencia de enfermedad en la pieza de histerectomia. Encontramos un valor significativamente estadistico entre el porcentaje de muestras comprometidas y la persistencia de enfermedad.

Evaluación de la Globulina transportadora de Hormonas Esteroidales (SHBG) durante el embarazo como factor predictor de pre-eclampsia y restricción del crecimiento intrauterino.

BACKGROUND Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). AIM To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. PATIENTS AND METHODS Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. RESULTS Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). CONCLUSIONS Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.Background: Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). Aim: To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Patients and Methods: Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselectedpregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Results: Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Conclusions: Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.