Preventing mother-to-child transmission in Guayaquil, Ecuador: HIV knowledge and risk perception.

An important step in preventing mother-to-child transmission is testing pregnant women for HIV. Health literacy measures, such as HIV knowledge and risk perception, may determine which women are tested in prenatal clinics where routine opt-out testing is not available. A survey was conducted in Guayaquil, Ecuador in 2006 (n=485), where approximately 0.7% of HIV tests in prenatal clinics were positive. Pregnant women over the age of 18 were invited to complete the survey in the waiting rooms at four city hospitals. There were 67.2% of women reported being tested previously for HIV. The most notable finding was that women who perceived a risk were 1.74 times more likely to request testing (p=0.021), but a woman's risk perception was not related to established risk factors. In addition, a physician's recommendation would result in the testing of nearly all women (94.3%). This data suggest that interventions in prenatal care clinics should incorporate educational strategies to increase accurate perception of personal risk. These efforts must occur in conjunction with increasing the access to HIV tests to achieve the goal of universal prenatal testing.

Validation of the 13c-urea breath test for the initial diagnosis of helicobacter pylori infection and to confirm eradication after treatment.

OBJECTIVES: the breath test with 13C-urea (UBT) is a method widely used in Spain, but its diagnostic accuracy has not been evaluated in a clinical trial until now. Our objective was to validate the UBT (TAU-KIT) both as an initial diagnostic method for the detection of H. pylori infection and as a method to confirm eradication. METHODS: a multi-centre study in 7 Spanish hospitals was performed. A group of dyspeptic patients who had not previously received eradication treatment was included, and a second group of patients with gastric ulcer or upper gastrointestinal bleeding due to peptic ulcer was also included (eradication of H. pylori was confirmed 6 to 8 weeks after treatment completion with omeprazole, clarithromycin and amoxycillin). In both groups an endoscopy was performed with biopsies for histology and rapid urease test. Patients were considered infected if both tests yielded positive results, and not infected when both tests were negative. The UBT 13C-urea (TAU-KIT, Isomed S.L., Madrid, Spain) was performed with citric acid and 100 mg of 13C-urea. The pathologist and persons responsible for endoscopy, urease test and UBT were all unaware of the results from the other diagnostic methods. RESULTS: in the pre-treatment group (36 patients) the prevalence of H. pylori was 72%, the area under the ROC curve for the diagnosis of infection with the UBT was 0.99, and the best cut-off point was 5 units, with the following results: sensitivity= 96% (95% CI = 81-99%), specificity= 100% (69-100%), positive predictive value (PPV) = 100% (87-100%), negative predictive value (NPV) = 92% (59-100%), likelihood ratio (LR) + = infinity, and LR- = 0.04. In the post-treatment group (85 patients) the prevalence of H. pylori was 16%, the area under the ROC curve was 0.99, and the best cut point was 4.6, with the following results: sensitivity= 100% (77-100%), specificity = 97% (90-99%), PPV = 88% (62-98%), NPV = 100% (95-100%), LR+ = 35, and LR- = 0. CONCLUSION: UBT provides excellent accuracy both for the initial diagnosis of H. pylori infection and to confirm eradication after treatment.

Validación de la prueba del aliento con 13C-urea para el diagnóstico inicial de la infección por Helicobacter pylori y la confirmación de su erradicación tras el tratamiento / Validation of 13 C-urea breath test for the initial diagnosis of Helicobacter pylori infection and for the confirmation of its eradication after treatment

Objetivos: el test del aliento con l3C-urea (TAU) es un método ampliamente utilizado en España, pero su validez diagnóstica no ha sido evaluada hasta hoy en un ensayo clínico. Nuestro objetivo fue validar el TAU-KIT® tanto para el diagnóstico inicial de H. pylori como para la confirmación de su erradicación. Métodos: estudio multicéntrico realizado en 7 hospitales españoles. Se incluyó un grupo de pacientes dispépticos en los que no se había administrado tratamiento erradicador previo y otro grupo con úlcera gástrica o hemorragia digestiva por úlcera gastroduodenal en el que se confirmaba la erradicación de H. pylori 6 a 8 semanas después de finalizar el tratamiento con omeprazol, claritromicina y amoxicilina. En ambos grupos se realizó gastroscopia con biopsias para histología y test rápido de la ureasa. Se consideró infectado a un paciente cuando ambas pruebas eran positivas, y no infectado cuando ambas eran negativas. Se realizó el TAU (TAU-KIT®, Isomed S.L., Madrid) con ácido cítrico y 100 mg de 13C-urea. El endoscopista, el patólogo y la persona responsable de la lectura del test de la ureasa y del TAU desconocían el estado de infección por los demás métodos diagnósticos. Resultados: en el grupo pretratamiento (36 pacientes) la prevalencia de H. pylori fue del 72 por ciento, el área bajo la curva ROC para el diagnóstico de la infección con el TAU fue de 0,99 y el mejor punto de corte se situó en 5 unidades , con los siguientes resultados: sensibilidad (S)=96 por ciento (IC 95 por ciento=81-99), especificidad (E)=100 por ciento (69-100), valor predictivo positivo (VPP)=100 por ciento (87100), valor predictivo negativo (VPN)=92 por ciento (59-100), cociente de probabilidades (CP) += y CP-=0,04. En el grupo postratamiento (85 pacientes) la prevalencia de H. pylori fue del 16 por ciento, el área bajo la curva ROC de 0,99 y el punto de corte óptimo de 4,6, con los siguientes resultados: S=100 por ciento (77-100), E=97 por ciento (90-99), VPP=88 por ciento (62-98), VPN=100 por ciento (95-100), CP+=35 y CP-=0.Conclusión: el TAU posee una excelente exactitud tanto para el diagnóstico inicial de la infección por H. pylori como para la confirmación de su erradicación después del tratamiento (AU)

PGE1 protection against apoptosis induced by D-galactosamine is not related to the modulation of intracellular free radical production in primary culture of rat hepatocytes.

D-galactosamine (D-GalN) toxicity is a useful experimental model of liver failure in human. It has been previously observed that PGE1 treatment reduced necrosis and apoptosis induced by D-GalN in rats. Primary cultured rat hepatocytes were used to evaluate if intracellular oxidative stress was involved during the induction of apoptosis and necrosis by D-GalN (0-40mM). Also, the present study investigated if PGE1 (1 microM) was equally potent reducing both types of cell death. The presence of hypodiploid cells, DNA fragmentation and caspase-3 activation were used as a marker of hepatocyte apoptosis. Necrosis was measured by lactate dehydrogenase (LDH) release. Oxidative stress was evaluated by the intracellular production of hydrogen peroxide (H2O2), the disturbances on the mitochondrial transmembrane potential (MTP), thiobarbituric-reacting substances (TBARS) release and the GSH/GSSG ratio. Data showed that intermediate range of D-GalN concentrations (2.5-10mM) induced apoptosis in association with a moderate oxidative stress. High D-GalN concentration (40 mM) induced a reduction of all parameters associated with apoptosis and enhanced all those related to necrosis and intracellular oxidative stress, including a reduction of GSH/GSSG ratio and MTP in comparison with D-GalN (2.5-10 mM)-treated cells. Although PGE1 reduced apoptosis induced by D-GalN, it was not able to reduce the oxidative stress and cell necrosis induced by the hepatotoxin in spite to its ability to abolish the GSH depletion.

Pre-emptive oral ganciclovir can reduce the risk of cytomegalovirus disease in liver transplant recipients.

A cohort of 65 liver transplant recipients was prospectively monitored with qualitative polymerase chain reaction (PCR) in plasma. The first 25 patients did not receive prophylaxis. From a consecutive group of 40 recipients, 11 high-risk patients donor CMV-seropositive/receptor CMV-seronegative (D+/R-), persistent CMV replication) received pre-emptive oral ganciclovir (1000 mg three times daily), when a marker of risk was identified, until day 90. The overall incidence of cytomegalovirus (CMV) disease at six months was 20% (five of 25 patients) in the non-prophylaxis group and 2.5% (one of 40 patients) in the group treated with pre-emptive oral ganciclovir (relative risk, 0.11; 95% confidence interval; 0.01-0.96; P = 0.04). The PCR sensitivity for detecting CMV disease was 80%, the specificity was 90%, and the positive and negative predictive values were 66% and 95%, respectively. Adverse events, graft rejection and survival were similar between groups. We conclude that pre-emptive oral ganciclovir in high-risk patients can reduce the risk of CMV disease.

Improved cardiac function in patients with obstructive jaundice after internal biliary drainage: hemodynamic and hormonal assessment.

OBJECTIVE: To investigate myocardial function in patients with obstructive jaundice before and after internal biliary drainage. SUMMARY BACKGROUND DATA: Increased plasma levels of atrial natriuretic peptide (ANP) have been found in patients with biliary obstruction. METHODS: Thirteen patients with newly diagnosed obstructive jaundice and no previous heart, lung, or renal disease were studied using a Swan-Ganz catheter. Hemodynamic measurements were taken before and 4 days after internal biliary drainage. Levels of ANP and brain natriuretic peptide (BNP) were obtained and liver function tests were also determined. RESULTS: Plasma levels of ANP and BNP were increased twofold to fourfold in the basal state and declined after biliary drainage. Independent variables predicting left ventricular systolic work were total bilirubin concentrations, duration of jaundice, and BNP. In addition, bilirubin concentrations correlated with pulmonary vascular resistance, mean arterial pulmonary pressure, and right ventricular systolic work. Internal biliary drainage resulted in an improvement in left ventricular systolic work. A correlation was found between decreasing ANP concentrations and increasing cardiac output. CONCLUSIONS: Increased plasma levels of natriuretic peptides in patients with obstructive jaundice may reflect a subclinical myocardial dysfunction correlating with the degree of jaundice. After internal biliary drainage, there is a measurable improvement of cardiac function.

Factors predicting nutritional derangements in patients with obstructive jaundice: multivariate analysis.

Patients with obstructive jaundice (OJ) that requires surgery often have malnutrition associated with increased perioperative morbidity. This study investigated the factors influencing nutritional derangements in these patients. A series of 46 OJ patients were investigated prospectively (28 malignant tumors, 18 benign obstructions). A nutritional risk index of < 83.5 was used to define protein-calorie malnutrition. Liver function, cholecystokinin (CCK), tumor necrosis factor-alpha (TNFalpha), and endotoxin levels were determined. A multivariate analysis was performed, and an obstructive jaundice malnutrition index (OJMI) was obtained. Altogether, 22 (48%) OJ patients had malnutrition (33% with benign obstructions, 57% with malignant disease). Malnourished patients had higher serum bilirubin levels (258 +/- 120 vs. 154 +/- 62 mmol/L; p = 0.005), longer duration of jaundice (16 +/- 9 vs. 9 +/- 5 days; p = 0.03), and higher plasma levels of CCK (4.0 +/- 1.3 vs. 1.7 +/- 1.0 pmol/L; p = 0.005), alanine aminotransferase (ALT) (226 +/- 209 vs. 187 +/- 161 UI/L; p = 0.01), endotoxin (15 +/- 10 vs. 6.5 +/- 7.0 EU/L; p = 0.007), and TNFalpha (69 +/- 82 vs. 23 +/- 15 pg/ml; p = 0.008) than those without malnutrition. However, only serum bilirubin, CCK, ALT, and patient age were predictors for malnutrition by multivariate analysis. Malnutrition might be expected (95% confidence interval) in patients older than 68 years with increased bilirubin (> 290 mmol/L) and ALT (> 210 UI/L) levels that corresponded with an OJMI > 55. It was concluded that nutritional alterations in patients with obstructive jaundice were determined by the intensity of the biliary obstruction correlated with increased plasma CCK levels as well as with liver dysfunction and patient age.

Anorexia and the effect of internal biliary drainage on food intake in patients with obstructive jaundice.

BACKGROUND: Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage. STUDY DESIGN: Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage. RESULTS: Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.

Cytokines and acute-phase response markers derangements in patients with obstructive jaundice.

BACKGROUND/AIMS: Prolonged acute-phase response and increase of cytokines have been associated with higher mortality and surgical complications. This study investigated the status of cytokines and acute-phase response markers in patients with obstructive jaundice. METHODOLOGY: Forty-one patients were investigated. Endotoxin, tumor necrosis factor-alpha, interleukin-6, nitric oxide, C-reactive protein, liver enzymes, albumin and percentage of weight loss were determined at admission. RESULTS: Endotoxin, interleukin-6 and C-reactive protein were significantly elevated in both benign and malignant obstructive jaundice. Increased plasma levels of tumor necrosis factor-alpha were only detected in malignant tumors (68 vs. 24 pg/mL; P < 0.001). Patients with positive acute-phase response (C-reactive protein > mean + 2 SD of controls) had greater weight loss (P = 0.02), endotoxin (P = 0.03) and interleukin-6 plasma levels (P = 0.05) than those with no inflammatory response. Prolonged biliary obstruction (> 10 days) was associated with higher weight loss (P = 0.04), tumor necrosis factor-alpha (P = 0.003) and interleukin-6 (P = 0.05) plasma levels. CONCLUSIONS: A prolonged high-grade biliary tract obstruction prompted an increase in endotoxin levels, associated with a positive acute-phase response and cytokine elevation.

Evolution tunes the excitability of individual neurons.

The relationship between the genome and the evolution of the nervous system may differ between an animal like C. elegans with 302 neurons, and mammals with tens of billions of neurons. Here we report that a class of nonconserved potassium channels highly expanded in C. elegans may play a special role in the evolution of its nervous system. The C. elegans genome contains an extended gene family of potassium channels whose members fall into two evolutionary divergent classes. One class constitutes an ancient conserved "set" of K+ channels with orthologues in both humans and Drosophila and a second larger class made up of rapidly evolving genes unique to C. elegans. Chief among this second class are novel potassium channels having four transmembrane domains per subunit that function as regulated leak conductances to modulate cell electrical excitability. This inventory of novel potassium channels is far larger in C. elegans than in humans or Drosophila. We found that, unlike conserved channel genes, the majority of these genes are expressed in very few cells. We also identified DNA enhancer elements associated with these genes that direct gene expression to individual neurons. We conclude that C. elegans may maintain an exceptionally large inventory of these channels (as well as ligand-gated channels) as an adaptive mechanism to "fine tune" individual neurons, making the most of its limited circuitry.

TNF-alpha dependent production of inducible nitric oxide is involved in PGE(1) protection against acute liver injury.

BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) and nitric oxide modulate damage in several experimental models of liver injury. We have previously shown that protection against D-galactosamine (D-GalN) induced liver injury by prostaglandin E(1) (PGE(1)) was accompanied by an increase in TNF-alpha and nitrite/nitrate in serum. AIMS: The aim of the present study was to evaluate the role of TNF-alpha and nitric oxide during protection by PGE(1) of liver damage induced by D-GalN. METHODS: Liver injury was induced in male Wistar rats by intraperitoneal injection of 1 g/kg of D-GalN. PGE(1) was administered 30 minutes before D-GalN. Inducible nitric oxide synthase (iNOS) was inhibited by methylisothiourea (MT), and TNF-alpha concentration in serum was lowered by administration of anti-TNF-alpha antibodies. Liver injury was evaluated by alanine aminotransferase activity in serum, and histological examination and DNA fragmentation in liver. TNF-alpha and nitrite/nitrate concentrations were determined in serum. Expression of TNF-alpha and iNOS was also assessed in liver sections. RESULTS: PGE(1) decreased liver injury and increased TNF-alpha and nitrite/nitrate concentrations in serum of rats treated with D-GalN. PGE(1) protection was related to enhanced expression of TNF-alpha and iNOS in hepatocytes. Administration of anti-TNF-alpha antibodies or MT blocked the protection by PGE(1) of liver injury induced by D-GalN. CONCLUSIONS: This study suggests that prior administration of PGE(1) to D-GalN treated animals enhanced expression of TNF-alpha and iNOS in hepatocytes, and that this was causally related to protection by PGE(1) against D-GalN induced liver injury.

Levels of HBV-DNA and HBsAg after acute liver allograft rejection treatment by corticoids and OKT3.

The aim of this work was to analyze whether the treatment of acute rejection of orthotopic liver transplants (OLT), either with corticoids or OKT3, has any effect on the levels of hepatitis B virus (HBV)-DNA and HBsAg in individuals which were originally affected by cirrhosis or fulminant hepatic failure as a result of B virus. We have found that HBV-DNA is present in macrophages, B cells and both CD4+ and CD8+ T cells after OLT in all cases studied. Interestingly, the levels of HBV-DNA and HBsAg in the serum analyzed were increased extremely rapidly in the patients treated with OKT3 in an acute rejection episode. However, the serum levels of HBV-DNA and HBsAg found were lower when the patients were treated with steroids, and were not found in non-treated patients. As the serum levels of HBV-DNA increase, the process of liver reinfection could be accelerated; therefore, these results may help to understand how OKT3 and corticoids immunosuppressive therapy may accelerate the reinfection of OLT by HBV. In conclusion, our results suggest that special care must be taken in the use of OKT3 in the treatment of acute liver rejection episodes in chronic or fulminant HBV transplanted patients.

TNF-alpha but not IL-1alpha is correlated with PGE1-dependent protection against acute D-galactosamine-induced liver injury.

BACKGROUND: Prostaglandin E1 (PGE1) treatment of humans and rodents during acute hepatic failure ameliorates different parameters of hepatic dysfunction. PURPOSE: To investigate whether prevention of acute liver injury induced by D-galactosamine (D-GalN) with preadministration of PGE1 is correlated with a change in the concentration of two proinflammatory cytokines, as tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1alpha, and/or nitrite+nitrate (NOx), as nitric oxide-related end products in serum. RESULTS: D-GalN significantly increased alanine aminotransferase (ALT) and TNF-alpha concentration in serum 5 and 10 mins, respectively, after treatment compared with the control group (P< or =0.05). D-GalN did not change the IL-1alpha concentration at any time during the study. Preadministration of PGE1 to D-GalN-treated rats significantly reduced the ALT content and increased significantly the TNF-alpha concentration in serum 1, 2.5, 5 and 10 mins after D-GalN treatment compared with the D-GalN group (P< or =0.05). Nitric oxide was not involved in either the toxic effect due to D-GalN or the protection observed with PGE1 against D-GalN toxicity. CONCLUSIONS: Acute liver injury induced by D-GalN is correlated with an increased TNF-alpha release. Preadministration of PGE1 to D-GalN-treated rats exerted a priming effect on inflammatory cells to release enhanced levels of TNF-alpha but not IL-1alpha. These findings indicate that stimulation of TNF-alpha release may be involved in the acute D-GalN-induced liver injury and also in PGE1 protection from hepatotoxicity in clinical and experimental studies.

Randomized trial of weekly sulfadoxine/pyrimethamine vs. daily low-dose trimethoprim-sulfamethoxazole for the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.

We conducted a prospective, randomized clinical trial among liver transplant patients to assess the efficacy and safety of weekly sulfadoxine/pyrimethamine compared with daily trimethoprim-sulfamethoxazole in the prevention of Pneumocystis carinii pneumonia. The studied drugs were given during 6 months after transplantation. One hundred twenty patients were included. None of the 60 patients receiving weekly sulfadoxine/pyrimethamine developed Pneumocystis carinii pneumonia, whereas two cases (3%) developed among the 60 patients who received trimethoprim-sulfamethoxazole. For both patients, the studied medication had been discontinued several weeks earlier because of adverse effects. No differences were observed in the incidence of adverse effects. We conclude that weekly sulfadoxine/pyrimethamine is as effective and safe as is daily trimethoprim-sulfamethoxazole in the prophylaxis of Pneumocystis carinii pneumonia after liver transplantation.

Nutritional assessment of patients with benign and malignant obstructions of the biliary tract.

OBJECTIVES: the aim of this study was to assess the severity and type of nutritional deficiencies observed in patients with benign and malignant obstructive jaundice (OJ). METHOD: in this prospective cross-sectional study 51 patients with OJ (21 with benign and with 30 malignant obstruction) were investigated. Nutritional status was assessed by anthropometric parameters (ideal body weight, midarm muscle area and skinfold thickness), visceral proteins, creatinine height index and total lymphocyte count. Observed values in patients with OJ were normalized to the percentage value of the lower limit of normal (obtained from 17 healthy subjects matched for age and sex) and averaged to obtain a total score for protein-energy malnutrition. RESULTS: forty-two (82%) patients with OJ had protein-calorie malnutrition (PCM). Malnutrition was mild in 55%, moderate in 35% and severe in 10%. Severity of PCM was associated with intensity (p < 0.05) and duration of jaundice (p < 0.01). Kwashiorkor (74%) was the dominant type of malnutrition. PCM was common in benign (71%) as well as in malignant obstruction (90%), but the total score (92 +/- 20 vs 80 +/- 19; p < 0.05) and the proportion of mild PCM in patients with benign obstruction (80% vs 41%, p < 0.01) was significantly higher than in patients with malignant tumors. CONCLUSIONS: a high percentage of patients with OJ had PCM. The degree of nutritional alteration was associated with the intensity of jaundice. Malnutrition was equally prevalent among patients with benign obstructions and patients with malignant causes of biliary obstruction, although it was more severe in the latter. Acute malnutrition (kwashiorkor) was the dominant type of malnutrition in both groups of patients.

Changes in the pattern of visceral protein concentrations after internal biliary drainage in patients with obstructive jaundice.

OBJECTIVE: To evaluate the influence of internal drainage on status of nutritional markers in patients with obstructive jaundice. DESSING: Prospective longitudinal study. SETTING: University hospital, Spain. SUBJECTS: 39 patients with obstructive jaundice (18 benign and 21 malignant obstructions). INTERVENTIONS: Nutritional state was assessed before and 10 days after endoscopic drainage. MAIN OUTCOME MEASURES: One anthropometric (body weight <95% of ideal) and two biochemical (albumin <35 g/L and prealbumin < 170 mg/L) as an indication of protein calorie malnutrition. Retinol binding protein and transferrin concentrations, total lymphocyte count, and nutritional prognostic index (NPI) were also measured. RESULTS: Thirty patients (77%) had protein calorie malnutrition. After internal drainage, 6 patients with benign obstruction and 11 with malignant tumours remained malnourished. No anthropometric variables or concentrations of proteins with long half-lives were affected by drainage. However, prealbumin (p < 0.01) and transferrin (p < 0.01) concentrations, and total lymphocyte count (p < 0.001) increased significantly in both groups. NPI also improved significantly after drainage from 43 (9) compared with 37 (5) in benign obstructions (p < 0.05) and 58.7 (14) compared with 52 (12) in malignant (p < 0.05), although in the latter group the mean nutritional risk index remained high. CONCLUSIONS: Concentrations of some of the visceral proteins studied (prealbumin and transferrin) improved 10 days after internal biliary drainage for both benign and malignant obstruction. However, many patients with malignant tumours remained malnourished with a high nutritional risk index.