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Objective Currently used reference values for immunologic markers in children are largely derived from cross-sectional data from historic, small sample size studies in predominantly white children. There is a lack of reliable age-related standards for immunologic markers, such as CD4+ cell counts, in particular in black children whose values according to recent reports may differ from those in white children. Standards are essential for diagnosing and monitoring childhood diseases such as pediatric human immunodeficiency virus (HIV) infection. Design Prospective cohort study with data on 1781 uninfected children born to HIV-infected mothers in the European Collaborative Study. Methods Age-related standards (centiles) for immunologic markers (CD4+ and CD8+ cell counts and total lymphocyte counts) up to 5 years in black and up to 10 years in white children were constructed using Generalized Additive Models for Location, Scale and Shape method, which allows for variability and skewness of the data. The optimal model was chosen according to the Akaike Information Criterion. Results Patterns and values of total lymphocyte, CD4+ and CD8+ cell counts varied with age, especially in the first 3 years of life, but less so thereafter. Values of all 3 immunologic markers were substantially and significantly lower in black than in white children of the same age. Conclusions We present age-related standards separately for black and white children to aid clinicians in the monitoring of childhood diseases. These standards may also contribute to the decision on an accurate cutoff for CD4+ cell counts for initiating treatment of HIV-infected children.

Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: • To understand the pathogenesis of hepatic encephalopathy  To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy  To describe the new classification of hepatic encephalopathy and its clinical implications  To recognize the clinical manifestations and stages of the disease  To understand the main diagnostic tests used to detect the hepatic encephalopathy  To describe the main therapeutic treatments of hepatic encephalopathy.

According to epidemiological studies, gallstonedisease is a very common disease in Mexican-Americansand Mexicans. However, the major risk factors forcholelithiasis in Mexicans have not been identified. We designed a case-control study in a group ofMexican subjects with and without gallstone diseaseconfirmed by ultrasound. These subjects wereprospectively studied over a three-year period. Clinical and epidemiological data were collected bymeans of a questionnaire. A total of 1500 subjects wereincluded in this study: 1000 with and 500 withoutgallstone disease. The major risk factor in both men and women was body mass index [odds ratio (OR)1.64 and 1.96, respectively; P < 0.008 and 0.001]. Inaddition, parity was an important factor in women (OR2.17, P < 0.001), whereas age was associated withgallstone disease in men (OR 1.43, P < 0.001). Wefound that body mass index, parity, and age were theprincipal risk factors for gallstone disease in thisgroup of Mexican subjects. These results are similar tothose found in Mexican-Americanpopulations.

The most widely used treatment of portal-systemic encephalopathy (PSE) is the administration of oral, non-absorbable disaccharides. Theoretically, the inhibition of intestinal disaccharidases should induce malabsorption of disaccharides and increase delivery of undigested carbohydrates to the colon, thus stimulating the effects of lactulose and other non-absorbable disaccharides (that is, lactitol and lactose). AO-128 is an N-substituted derivative of valeolamine, an aminocyclitol that selectively inhibits intestinal disaccharidases. This study was performed to investigate whether AO-128 could be used as adjuvant therapy for the treatment of mild PSE in cirrhotic patients.A double-blind, randomized, controlled trial was performed in 35 cirrhotic patients with PSE. Patients were given a 2-week treatment consisting of AO-128 (2 mg three times daily) or an identical placebo. The following features of PSE syndrome were assessed in a semiquantitative fashion before and after I and 2 weeks of therapy: mental state, asterixis, number connection test (NCT), venous blood ammonia concentration, electroencephalogram (EEG), and overall PSE index (PSEI). More patients receiving AO-128 than patients receiving placebo showed40% improvement in the PSEI (83% versus 35%; P0.05). The mean stool pH decreased from 5.8+/-0.3 to 5.5+/-0.3 (P0.004) after AO-128 treatment, whereas no changes were observed in the placebo group. The EEG and nitrogen balance did not show significant changes in any of the two groups. A significant improvement was seen in the NCT performance after AO-128 (from grade 2.0+/-1.04 to grade 1.25+/-0.87; P0.05). Seven patients treated with AO-128 developed diarrhea, as compared with none in the placebo group (P0.05).These results suggest that AO-128 may be useful in the treatment of PSE, although further studies are required to establish the benefit of AO-128 and determine adequate individual doses.

BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)

In the early 1970s, we began to perform selective shunts on a regular basis for the treatment of portal hypertension. In a 15-year period, 177 patients (155 with liver cirrhosis) were treated with 3 kinds of selective shunts: the Warrent shunt (128 patients) the end-to-end splenorenal shunt (29 patients), and the splenocaval shunt (20 patients). One hundred sixty-seven of the procedures were elective. Operative mortality was 14%, and survival for the Child's class A group was 75% at 1 year, 69% at 5 years, and 65% at 15 years. Incapacitating encephalopathy was observed in 7% of the patients, rebleeding in 6%, and shunt thrombosis in 6%. Postoperative portal vein alterations included reduced venous diameter (13%) and thrombosis (21%). Experience with the Warren shunt in schistosomiasis, a disease in which normal liver function is the rule in Latin American countries, is discussed. We believe that, when feasible, the selective shunts are the treatment of choice for portal hypertension in Latin American countries.

A double-blind crossover trial was performed to test the therapeutic usefulness and safety of lactitol, a beta-galactoside sorbitol, against lactose in 18 patients with chronic portal-systemic encephalopathy (PSE). The study included four periods: two for washout and two for lactitol and lactose administration. During washout periods, which lasted two weeks each, patients were stabilized with neomycin plus milk of magnesia. Lactitol and lactose were administered during four weeks each. Ten patients were randomly assigned to receive lactose (group A) and eight patients to receive lactitol (group B) first. PSE parameters, ie, mental state, number connection test performance, asterixis and blood ammonia levels were assessed fortnightly. Electroencephalographic tracings and stool pHs were evaluated at the end of each study period. After the first administration of lactose and lactitol, no statistically significant differences in PSE parameters were found. At the same stage, a significant stool acidification (P less than 0.05) was detected. It is concluded that lactitol seems to be safe and efficacious in treating patients with chronic PSE.

Selective portasystemic shunts were performed in 55 consecutive patients; 27 underwent end-to-end selective renosplenic shunt, 18 distal splenorenal shunt and 10 splenocaval shunt. Thirty-one patients were in Child's class A, 18 were in class B and 6 in class C. Hospital mortality for the whole group was 16 percent and occurred less frequently in class A than in class B and C patients. Five year predicted survival for the whole group was 59 percent. At the same period of follow-up, class A patients had a higher survival rate than those in class B and C (83 percent versus 36 percent; p < 0.01). No striking difference in 5 year survival was evident in alcoholics and nonalcoholics (52 percent versus 61 percent). After surgery, long-term portasystemic encephalopathy and bleeding were noted in 2 of 36 survivors. For class A patients, selective portal shunts offer an adequate and relative safe method for decreasing mortality due to variceal bleeding.

A randomized double-blind clinical comparison of bromocriptine, a new dopamine agonist, and placebo was performed on 7 cirrhotic patients with chronic portal systemic encephalopathy (PSE). Before given either medication, patients were stabilized with a standard treatment (neomycin and cathartics). Serial semiquantitative assessments were done, including mental state, asterixis, number connection test, electroencephalogram, and ammonia blood levels. Three patients developed signs of precoma while ingesting both placebo and bromocriptine. Two patients experienced precoma only with placebo, and another patient only while taking bromocriptine. One patient remained awake throughout the study. All patients responded initially to neomycin and cathartics. Bromocriptine proved not to be significantly superior to placebo and was always inferior to standard treatment. During treatment with bromocriptine, 3 patients experienced constipation. This may be partially responsible for the ineffectiveness in the treatment of PSE.

Portal vein thrombosis has been considered idiopathic in 50% of cases reported in adults. Protein C deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein C was present. Both cases were very similar, with a history of recurrent episodes of systemic thromboembolic disease, mesenteric venous thrombosis that required intestinal resection and upper gastrointestinal bleeding from gastroesophageal varices. Portal hypertension as well as portal vein thrombosis were demonstrated. The hematologic work-up revealed a deficiency of protein C. Both patients were subjected to the Sugiura procedure, and anticoagulation was instituted thereafter. At the time of surgery, a liver biopsy was performed, which was reported as “normal.” Two years and 3 months, respectively, after surgery both patients are in good condition. We conclude that protein C deficiency should be investigated in all cases of portal vein thrombosis, especially in those with a history of thromboembolic disease elsewhere.