Effect of immunosuppressant blood levels on serum concentration of interleukin-17 and -23 in stable liver transplant recipients.

INTRODUCTION: T(H)17 cells have been recently described to be involved in inflammatory and immune-mediated diseases, but there is no evidence of their role in human liver transplantation. Interleukin (IL)-23 is considered an inducer cytokine, whereas IL-17 is the main cytokine released by T(H)17 cells. The aim of our study was to measure the serum levels of IL-17 and IL-23 in stable liver transplant recipients and examine the influence of immunosuppressant concentrations. MATERIALS AND METHODS: Serum levels of IL-23 and IL-17 were determined in 38 healthy subjects and 35 stable hepatic transplant recipients who were free of rejection episodes for at least 8 years. The results were analyzed according to the simultaneous blood levels of cyclosporine (n = 20) or tacrolimus (n = 15). RESULTS: No significant differences were observed in the serum levels of IL-17 and IL-23 between healthy subjects and transplanted patients. In addition, patients with low blood levels of tacrolimus (<6 ng/mL), but not cyclosporine, showed significantly lower serum levels of the 2 cytokines. CONCLUSION: These preliminary results suggested a lack of activation of the T(H)17 pathway, which was more pronounced among the patient subgroup treated with tacrolimus.

[Gene expression in obese patients with non-alcoholic steatohepatitis]. / Expresión génica en pacientes obesos con enfermedad hepática por depósito de grasa.

UNLABELLED: Although the molecular basis for the pathophysiology of non-alcoholic steatohepatitis (NASH) is poorly understood, we evaluate the hepatic gene expression of cytokines, chemokines, cell receptors, growth factors, intracellular transducers and extracellular communication proteins in liver tissue of obese patients (with and without NASH), and we determine the specific intrahepatic gene expression profiles associated with histological severe NASH.Thirty-eight obese patients with BMI > 35 were analyzed, who underwent bariatric surgery. Biopsy specimen samples were snap-frozen in liquid nitrogen. Hepatic gene expression was determined in liver biopsy specimens from 3 groups: a) obese patients without NASH (n = 12); b) patients with NASH without fibrosis (n = 13); and c) patients with NASH and fibrosis (n = 13). Genes were considered to be expressed differentially in NASH only if there was a greater than 2-fold difference in abundance of mRNA when compared with each of the control group. These results were confirmed by real-time PCR. Fourteen genes were differentially expressed (10 overexpressed and 4 underexpressed) in patients with NASH. Genes that were significantly overexpressed included prohibitin, TNF, TNF RI (p55), MCSF, R2-TRAIL, b1-CTGF, FGF, VEGF, and BIGH3OBR. Insulin growth factor-1, insulin growth factor-2, interleukin-2 and tyrosine-receptor were underexpressed in NASH patients. IN CONCLUSION: 1. The obese patients with NASH without fibrosis show an overexpression of proinflammatory and proapoptotic genes. Also, the NASH patients with fibrosis show an overexpression of fibrogenic genes, including the leptin receptor Ob-Rb.2. The up-regulated gene expression of prohibitin suggests mitochondrial dysfunction in NASH patients.

Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis.

BACKGROUND: Intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. OBJECTIVES: The aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. MATERIAL AND METHODS: We included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. RESULTS: The prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The small-intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/- 5.7 cm) than in control animals (p < 0.001). CONCLUSIONS: These results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the pathogenesis of IBO.

Different time course of circulating adhesion molecules and hyaluran during hepatic allograft rejection.

BACKGROUND: Inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, the endothelium is the main target of this process. This study investigated, whether soluble (s) forms of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are elevated during cellular rejection and whether hyaluran is a useful marker of endothelial function in liver transplantation. METHODS: Serum levels of sICAM-1, sVCAM-1, and hyaluran were determined in 24 controls and 27 hepatic transplant recipients. These patients were divided in two groups: group I, 14 patients without rejection; and group II, 13 patients with rejection. Samples were collected on day 1 and 7 after transplantation, on the day of liver biopsy, and after treatment of the rejection. RESULTS: We found a significant increase in sICAM-1 levels in the postoperative period in the rejection group compared with the non rejection group. It persisted significantly elevated until the diagnosis of rejection was made. In contrast, sVCAM-1 was only significantly elevated in the rejection group when diagnosis of rejection was evident. Hyaluran levels were also significantly elevated in the rejection group at diagnosis of rejection. We noticed a significant decline in sICAM-1, sVCAM-1, and hyaluran levels after successful treatment of rejection. In addition, we observed in the non-rejection group a stable lower levels of hyaluran during the entire postoperative period. CONCLUSIONS: The release of circulating adhesion molecules is a prominent feature coinciding with the first episode of hepatic rejection. Differential patterns of sICAM-1 and sVCAM-1 exist during rejection. In addition, hyaluran levels may be a sensitive marker of liver endothelial cell function in the postoperative period of liver transplantation.

Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis?

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity characterized by the presence of steatosis and lobular and/or portal inflammation with or without fibrosis. Patients with non-alcoholic fatty liver and fibrosis on liver biopsy have increased liver-related deaths. METHODS: 181 wedge liver biopsies, taken at the time of bariatric surgery from patients with a mean body mass index (BMI) of 47, were studied. In all cases, the liver biopsy was performed without knowledge of the patient's clinical and biochemical data, which were then examined with univariate and multivariate analysis. RESULTS: Diagnosis of NASH was established in 105 patients (91%); 74 patients (70%) showed mild steatosis, 20 (19%) had moderate inflammation and fibrosis, and 11 (10%) had steatosis with severe fibrosis. None of the liver biopsies showed cirrhosis. Age was the only independent predictor of moderate and severe fibrosis (p = 0.001). CONCLUSIONS: Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.

Natural killer cell activity in alcoholic cirrhosis: influence of nutrition.

Forty-five patients with alcoholic cirrhosis, 20 chronic alcoholics with normal liver function tests and 36 healthy subjects were investigated. A combined index of nine anthropometric and biochemical parameters (triceps skinfold, arm muscle circumference, mid-arm muscle area, body fat percentage, creatinine-height index, serum albumin, plasma transferrin, prealbumin and retinol-binding protein levels) was used to evaluate nutritional status, allowing a distinction to be made between those patients with adequate nutrition (group I: 40 per cent of cirrhotics and 55 per cent of alcoholics), those with slight malnutrition (group II: 37.7 per cent of cirrhotics and 45 per cent of alcoholics) and those with severe malnutrition (group III: 22.2 per cent of cirrhotics and none alcoholic). Natural Killer (NK) cell activity of peripheral blood lymphocytes was determined using a 51Cr releasing cytotoxicity assay against K562 target cells. This was significantly lower in the cirrhotics than in the controls and chronic alcoholics (P less than 0.001 and P less than 0.01 respectively), but there was no difference between the latter two groups. Natural Killer activity was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with adequate nutrition, suggesting that malnutrition may play a role in the onset of the immunological disorder. No relationship could be established between nutritional status, NK activity and the clinical activity of the disease using Orrego's index on the liver function tests.

Interleukin-1 in alcoholic cirrhosis of the liver: the influence of nutrition.

Interleukin-1 (IL-1) is a cytokine produced by the macrophage-monocyte system that has important effects on immunological responses and inflammatory reactions. Several clinical studies have shown that severe protein energy malnutrition adversely effects cell-mediated immune responses and the functional state of macrophages. The objective of this study was to analyse IL-1 production by adherent cells stimulated in vitro with lipopolysaccharide B (LPS) from patients with alcoholic cirrhosis of the liver and its possible relationship with nutritional states. Forty-five patients with alcoholic cirrhosis and 28 healthy donors were investigated. A combined index of nine anthropometric and biochemical parameters was used to evaluate nutritional status of cirrhotic patients, allowing a distinction to be made between those patients with acceptable nutrition (group I: 40%), those with slight malnutrition (group II: 37.7%), and those with severe malnutrition (group III: 22.3%). IL-1 activity was significantly lower in the cirrhosis patients than in the controls (P less than 0.001). This activity also was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with acceptable nutrition (P less than 0.05); the combined index and the sole anthropometric index gave the same results, suggesting that malnutrition may play a role in the immunoregulatory disturbances in the pathogenesis of alcoholic liver disease.

Interleukin-2 and natural killer activity in acute type B hepatitis.

Natural killer (NK) cell activity against K562 cell line, and interleukin-2 (IL-2) activity in supernatants from lectin-activated PBMC cultures from 17 patients with acute hepatitis B in the early phase of illness were studied. These patients showed enhanced NK cytotoxicity and higher levels of IL2 activity as compared with control subjects. There was a positive correlation between cytotoxicity values and levels of IL2 activity. Furthermore, in the recovery phase of illness there was a tendency towards normalization in both parameters. When patients were divided in accordance with markers of HBV replication, HBV-DNA positive patients showed increased NK cell activity and IL2 levels as compared with the control group, whereas in HBV-DNA-negative patients no differences were found. However, no differences were found between patients with HBeAg and patients with anti-HBe. These results suggest that natural cytotoxicity is increased early in the course of acute hepatitis B, while NK cell activity returns to normal later, during convalescence. Enhanced NK cell activity appears to be secondary, at least in part, to increased production of IL2. Natural cytotoxicity may be one mechanism that controls the HBV infection before other cytotoxic mechanisms become fully operative.

[Hepatita B and C virus infections in patients with hepatocellular carcinoma]. / Infección por los virus de la hepatitis B y C en pacientes con carcinoma hepatocelular.

BACKGROUND: The prevalence of HBV and HCV infections in patients with hepatocellular carcinoma may be related to variations in the geographic area of study. For this reason, we have analized the relative prevalence of HBV and HCV infections in 94 patients with hepatocellular carcinoma from Cantabria (North of Spain). PATIENTS AND METHODS: We have studied 94 patients with hepatocellular carcinoma from January 1988 to December 1993. Commercially available radioimmunoassay or ELISA were used for detection of HBsAg, anti-HBs and anti-HBc. The HBV DNA was analized by PCR. The HCV infection was assayed by ELISA-2 and RT-PCR. RESULTS: The HBV infection was detected in 27 patients: 19 patients were HBsAg positive and 8 patients HBsAg negative, anti-HBc positive, DNA HBV positive by PCR. The HCV infection was found in 57 patients. Forty patients were infected with both viruses. Of the remain twenty-four, forty were alcoholics. We found in 61 patients more than one etiological factor. Hepatoma was the first manifestation of liver disease in 24 cases and these were more frequently in HCV than in those with HBV infection. Moreover, the first group were older and have lower alcohol intake. CONCLUSIONS: 1) In Cantabria, Spain, the majority of cases of hepatocellular carcinoma are related to HBV, HCV and alcohol. 2) Analysis of DNA HBV and RNA HCV by PCR allows the diagnosis of cryptic infections by both viruses, especially in the cases of HBV and HCV coinfection. 3) Hepatoma is the first manifestation of liver disease in a high percentage of cases.

[The prevalence of the Cys282Tyr mutation in the hemochromatosis gene in Cantabria in patients diagnosed with hereditary hemochromatosis]. / Prevalencia de la mutación Cys282Tyr del gen de la hemocromatosis en Cantabria y en los pacientes diagnosticados de hemocromatosis hereditaria.

BACKGROUND: The aim of our study was to evaluate the prevalence of Cys282Tyr mutation in patients with genetic haemochromatosis (GH) in Cantabria. PATIENTS AND METHODS: The HFE Cys282Tyr mutation was determined in a cohort of 60 patients with GH and 213 controls. RESULTS: The frequency of the Cys282Tyr mutation in control individuals was 4.4%. Sixty-seven percent of patients with GH were homozygous for the Cys282Tyr mutation. Twenty-seven percent of patients were normal at Cys282Tyr loci. CONCLUSIONS: The prevalence of the Cys282Tyr mutation in patients with GH in Cantabria, Spain, seems to be lower than in North America and in North Europe patients.

[Cell-mediated and humoral immunity in ulcerative colitis. Acute phase reactants (author's transl)]. / Inmunidad celular y humoral en colitis ulcerosa. Reactantes de fase aguda.

Many findings suggest that the alterations in immune response observed in intestinal inflammatory diseases may play a part in their pathogenesis. This observation led us to study 22 patients with chronic ulcerative colitis, of whom seven were in the acute stage and the other 15 were asymptomatic. The T and B lymphocyte populations were determined as well as the serum levels of immunoglobulins and acid alpha-1-glycoprotein as acute phase reactants. The results were compared with those obtained from a control group of 10 normal individuals. No statistically significant differences were observed in the percentages and absolute values of T and B lymphocytes as compared with the controls. nor in relation to the activity of the lesions. Neither were there any observable variations in the serum concentrations of immunoglobulins. On the other hand, analysis of the acid alpha-1-glycoprotein showed highly significant values as related to the degree of activity of the inflammatory lesion (p less than 0.005). Our results confirmed the value of determining serum acid alpha-1-glycoprotein levels as an index of inflammatory activity. The immunitary parameters under study did not vary in the different stages of the disease.

[Analysis of the DNA of the hepatitis B virus (HBV) in the serum and mononuclear cells of the peripheral blood in subjects with chronic infection by the HBV]. / Análisis del ADN del virus de la hepatitis B (VHB) en suero y células mononucleares de sangre periférica en sujetos con infección crónica por el VHB.

BACKGROUND: Viral replication is one of the determining factors of the natural history of infection by the hepatitis B virus (HBV). The clinical significance of the viremia and the DNA-HBV findings in mononuclear cells was therefore analyzed. METHODS: The epidemiologic history, liver function tests and the Knodell index were analyzed in 117 patients with chronic hepatitis B (CHB) and 33 healthy HBV carriers. The DNA-HBV was studied in serum and mononuclear cells by dot-blot and polymerase chain reaction (PCR). RESULTS: The DNA-HBV was detected by dot-blot in 62/117 subjects with and in CHB 3/33 healthy carriers. Viremis was determined by PCR in 107/117 patients with CHB and in 22/23 healthy carriers. Both aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) and the Knodell index were greater in the patients with positive DNA-HBV dot-blot. No significant differences were observed in the liver function tests and Knodell index with regard to the viremia detectable exclusively by PCR. In the mononuclear cells of peripheral blood, DNA-HBV was observed in 62% by dot-blot and in 95% by PCR. The presence of DNA-HBV by dot-blot in these cells was associated to greater disease activity. CONCLUSIONS: The activity of chronic hepatitis B was correlated with the presence of high viremic levels with no direct relation being observed between low grade viremia and disease aggressivity. The finding of DNA-HBV by dot-blot in mononuclear cells was associated with a greater activity of chronic hepatitis B, with these results being in agreement with the serologic data reported.

[Acute hepatitis C. A clinical and epidemiological study]. / Hepatitis aguda C. Estudio clínico y epidemiológico.

BACKGROUND: The discovery of the hepatitis C virus (HCV) and the possibility of determining anti-HCV serum antibodies has permitted greater etiological, clinical and epidemiological knowledge of non A non B hepatitis (NANB). METHODS: The clinical and epidemiological characteristics of 47 patients with acute hepatitis C were studied. Diagnosis was based on compatible clinical and analytical picture as well as positivity of the anti-HCV antibodies. RESULTS: Thirty-eight percent of the patients were intravenous drug abusers (IVDA). Thirty-four percent had transfusion antecedents and the remaining were sporadic forms of which 3 cases corresponded to health care workers. The study of other viral markers demonstrated that only in the IVDA collective did infections by hepatitis B and delta (HBV and HDV) and by the human immunodeficiency virus (HIV) coexist. Anti-HCV antibodies were detected between 15 days and 8 months (mean 38 +/- 74 days) of clinic initiation; with no differences being found regarding the form of contagion. The incubation period of transfused patients was 50 +/- 15 days. In 2 cases the disease followed a biphasic course, in 4 patients a cholestatic profile was observed, and in 12 the hepatitis was anicteric. In 28% of the cases controlled over 6 months the disease autolimited itself and 72% developed active chronic hepatitis. CONCLUSIONS: Most cases of acute hepatitis C are of intravenous origin with a prolonged period of anti-HCV positivization. No differences exist in the clinical picture of the disease regarding the form of contagion and the great tendency to chronicity of hepatitis C is confirmed, regardless of the mechanisms of acquiring the disease.

[Recurrence of hepatitis caused by hepatitis c virus in patients receiving a liver transplant]. / Recidiva de la hepatitis por el virus de la hepatitis C en los pacientes receptores de trasplante hepático.

BACKGROUND: Liver disease due to hepatitis C virus (HCV) is an increasingly frequent indication for liver transplantation. We performed a clinical and virological study of 20 HCV-infected liver transplant recipients to correlate virological markers with histological recurrence of disease. PATIENTS AND METHODS: In ninety-four patients who were given transplants for end-stage cirrhosis, IgG and IgM antibodies to HCV and IgM to HCV tested by ELISA; all samples were further examined in a four-antigen recombinant immunoblot assay (2-RIBA). HCV viremia was measured by the conventional nested PCR, HCV genotype was determined by PCR amplification using type-specific primers. We have analyzed de novo infection by HCV, HCV recurrence and the influence of genotype in these recurrence. RESULTS: Nineteen of 20 antibody-positive patients (95%) had HCV RNA before transplantation. All 19 patients who were viremic before transplantation had persistent infection after LT. HCV genotype 1b was the predominant type before and after LT (75%). Ten of the 20 (50%) patients developed histological findings of chronic hepatitis (CH) in liver allografts. HCV recurrent liver disease after LT was not related with HCV genotype. Of 4 deaths after transplant in hepatitis C group, only one was related to recurrent disease. We have not found de novo hepatitis C. CONCLUSIONS: Our results indicate the general persistence of hepatitis C virus infection and the excellent short-term prognosis after liver transplantation. Chronic hepatitis by HCV in liver transplant was not related with HCV genotype.

[Influence of the nutritional status on the characteristics of the ascitic fluid in alcoholic hepatic cirrhosis]. / Influencia del estado nutricional sobre las características del líquido ascítico en cirrosis hepática alcohólica.

A common characteristic of the patients with alcoholic liver cirrhosis is malnutrition, which in turn favors a large number of complications. The development of spontaneous bacterial peritonitis is partly related to the low concentrations of total proteins an C3 in the ascitic liquid. The objective of the present study has been to analyze the influence of the nutritional state on the characteristics of the ascitic liquid, before and after three weeks of an enteral nutritional support supplement, in a group of patients with alcoholic liver cirrhosis. On the whole, 38 patients were studied, who received a standard diet of 45 grams of protein and 2308 calories per day, additionally giving 27 of them an enteral diet of 1680 calories, composed of 294 grams of carbohydrates, 36.9 grams of fat, and 43.5 grams of protein in the form of branched chain amino acids. The group of patients supplemented in their diet presented a positive nitrogen balance which was significantly superior to the unsupplemented (p < 0.001). The nutritional state showed a significant improvement after three weeks with an additional enteral diet (p < 0.025). This improvement was translated into an also significant increase in the concentrations of total proteins and C3 of the ascitic liquid in the same group of patients (p < 0.001 for both parameters). These data appear to show that the nutritional support in patients with alcoholic cirrhosis may be a good strategy in the fight against some complications.

[Prospective study of the prognostic value of C reactive protein, alpha 1-antitrypsin and alpha 1-acid glycoprotein in acute pancreatitis]. / Estudio prospectivo del valor pronóstico de la proteína C reactiva, alpha 1-antitripsina y alpha 1-glicoproteína ácida en la pancreatitis aguda.

Early recognition of severity of acute pancreatitis is very uncertain. For this reason it is necessary to have objective criteria to predict with accuracy the course of the disease. The aim of this study was to examine the value of the determination of the acute phase reactants: C reactive protein (CRP), alpha 1-antitrypsin (alpha-AT) and alpha 1-glycoprotein acid (alpha-GA) as prognostic indicators of acute pancreatitis on admission and on the third day. We have studied 40 patients with acute pancreatitis and serum concentrations of CRP, alpha-AT and alpha-GP were related to the Ranson Index. On admission the median levels of CRP: 74 mg/L, alpha-AT: 208 mg% and alpha-GA: 303 mg% were significantly higher (p less than 0.001) in patients with Ranson Index greater than or equal to 3 than in those with Ranson Index less than or equal to 2 (CRP: 166 mg/L, alpha-AT: 303 mg% and alpha-GA: 121 mg%). The values which differentiated patients with better and worse prognosis were: CRP 100 mg/L (sensitivity 100% and specificity 86%); alpha--AT 275 mg% (sensitivity 71% and specificity 85%); and alpha-GA 90 mg% (sensitivity 87.5% and specificity 57.9%). CRP, and to a lesser degree the alpha-AT and alpha-GA, were related to the duration of the ileus, and to the severe complications of the acute pancreatitis.

[Development of spontaneous bacterial peritonitis in an experimental model in cirrhotic rats. Relationship with intestinal bacterial translocation]. / Desarrollo de peritonitis bacteriana espontánea en un modelo experimental de rata cirrótica. Relación con la traslocación bacteriana intestinal.

Spontaneous bacterial peritonitis (SBP) is one of the most important complication in cirrhotic patients with ascites, but is pathogenesis is not well known. It is thought that the impaired host defences and the passage of enteric bacteria into the mesenteric lymph nodes, named bacterial translocation, may be two important mechanisms in the pathogenesis of SBP. We have studied this phenomenon in an experimental model with oral CC14 induced cirrhotic rats. SBP occurred in 36% of ascitic rats, all cases being produced by enteric Gram (-) bacteria. Bacterial translocation was observed in 100% of rats with SBP but in 53% of rats without SBP (p < 0.05). In all cases the same organism was isolated in ascitic fluid and in mesenteric lymph nodes. These results suggest that bacterial translocation could play an important role in the pathogenesis of SBP.

[Natural killer (NK) cells and interleukin 2 (IL-2) in Crohn disease]. / Células natural killer (NK) e interleucina 2 (IL-2) en la enfermedad de Crohn.

An analysis was made of spontaneous Natural Killer (NK) activity, the proportion of NK cells and Interleukin 2 (IL-2) production in response to a phytohemagglutinin (PHA) using isolated mononuclear peripheral blood cells from 27 patients with Crohn's disease (CD) and 27 healthy controls. The results obtained showed a decrease in NK activity in comparison with the control group (p less than 0.05), occurring mainly in patients in whom the disease was in an active phase (p less than 0.005), with no apparent relationship to the proportion of NK cells. IL-2 production was, however, similar to that of the healthy controls. A positive correlation between spontaneous NK activity and IL-2 production was evident. The origin of these findings is controversial, suggesting that other factors with a negative modulating effect may inhibit NK function.

Relationship between the presenting symptoms and age at diagnosis in alcoholic and nonalcoholic chronic pancreatitis: analysis of 164 patients.

OBJECTIVE: To study the different forms of presentation, patient age, delay in diagnosis and incidence of calculi in alcoholic and nonalcoholic chronic pancreatitis. METHODS: We have studied 130 men and 34 women diagnosed as having chronic pancreatitis on the basis of clinical criteria and morphological and/or functional tests. RESULTS: Alcohol was the most common cause of chronic pancreatitis in men (89.1%) existing a significant difference with respect to women (p < 0.05). The mean age of the patients with alcoholic chronic pancreatitis was 45.6 +/- 11.3 years and that of patients presenting nonalcoholic chronic pancreatitis was 54.5 +/- 11.5 years (p < 0.01), the latter showing a bimodal distribution. The ages of the patients in whom the presenting symptom was abdominal pain and acute inflammatory episodes were 43.9 +/- 12.8 and 45.3 +/- 13.5 years, respectively, significantly lower (p < 0.05) than the age of patients in whom presentation was signaled by the onset of diabetes or diarrhea (53.1 +/- 11.2 and 61.2 +/- 12.9 years, respectively). Statistically significant differences existed in the delay in diagnosis when comparing the patients before and after 1985 (12.3 +/- 14.5 years, range 0 to 50 years, versus 0.42 +/- 0.9 years, range 0 to 5 years; p = 0.005). At diagnosis, 14.3% of the patients whose presenting symptom was acute pancreatitis had pancreatic calculi, versus 42.2% of those who reported abdominal pain as the first indication. CONCLUSIONS: Alcoholic chronic pancreatitis predominates in men. Nonalcoholic chronic pancreatitis presents two peaks of prevalence. A substantial number of patients may remain pain-free up to diagnosis. Calculi are not uncommon during the initial period of chronic pancreatitis when pain is the presenting symptom, either in the form of isolated episodes of abdominal pain or attacks of acute pancreatitis.

Cleaning and disinfection of gastrointestinal endoscopes. Comparative analysis of two disinfectants.

UNLABELLED: Gastrointestinal endoscopy can lead to infectious complications, and endoscopes must be disinfected to prevent them. AIM: to evaluate three methods of disinfection: 1) usual cleaning technique and immersion in glutaraldehyde phenolate (GP); 2) meticulous cleaning and immersion in GP, and 3) meticulous cleaning and immersion in hydrogen peroxide. METHOD: thirty endoscopes (15 gastroscopes and 15 colonoscopes) were disinfected with each method. Samples were taken following endoscopic exploration, after cleaning and after disinfection, and were cultured. The number of positive culture (cfu/ml > 1) was counted. RESULTS: the rate of contamination of endoscopes did not decrease significantly after cleaning with method 1 (66 vs 60%), but did decrease with method 2 (38 vs 16%) and method 3 (53 vs 17%). The contamination rate after cleaning was significantly lower with methods 2 and 3 (p < 0.005). This rate was also lower after disinfection (p < 0.025). Method 3 achieved 0% contamination following disinfection. CONCLUSIONS: the greatest decrease in contamination rate was achieved with conscientious cleaning followed by disinfection. Both disinfectants yielded similar results, although hydrogen peroxide produced a higher level of disinfection.