Lectins as antimicrobial agents.

The resistance of micro-organisms to antimicrobial agents has been a challenge to treat animal and human infections, and for environmental control. Lectins are natural proteins and some are potent antimicrobials through binding to carbohydrates on microbial surfaces. Oligomerization state of lectins can influence their biological activity and maximum binding capacity; the association among lectin polypeptide chains can alter the carbohydrate-lectin binding dissociation rate constants. Antimicrobial mechanisms of lectins include the pore formation ability, followed by changes in the cell permeability and latter, indicates interactions with the bacterial cell wall components. In addition, the antifungal activity of lectins is associated with the chitin-binding property, resulting in the disintegration of the cell wall or the arrest of de novo synthesis from the cell wall during fungal development or division. Quorum sensing is a cell-to-cell communication process that allows interspecies and interkingdom signalling which coordinate virulence genes; antiquorum-sensing therapies are described for animal and plant lectins. This review article, among other approaches, evaluates lectins as antimicrobials.

Serum gastrin and gastrin-immunoreactive cells in the antral mucosa of patients with alcoholic liver disease.

BACKGROUND/AIMS: Hypergastrinaemia has been reported in liver cirrhosis; meanwhile, it is unclear whether it is associated with an increase in gastrin cell function. The serum gastrin concentration and the number of gastrin cells in antral biopsies were studied in patients with alcoholic liver disease. METHODS: Immunocytochemical and quantification techniques were used to localize and determine the number of gastrin cells. RESULTS: Slight non-significantly higher serum gastrin values were observed in the alcoholic liver disease patients compared with controls, but the individual variation within the groups was considerable. The frequency of gastrin cells did not differ between groups. However, the size of the gastrin cell nuclei was larger in patients with liver disease than in controls, indicating increased cellular activity. CONCLUSIONS: Alcoholic liver disease, with a disturbed liver function, influences the gastrin cells. The observed alterations may reflect the effect of alcohol and/or malnutrition, or may be secondary to the influence of liver disease on other regulatory peptides.

Non-alcoholic fatty liver: another feature of the metabolic syndrome?

BACKGROUND AND AIMS: Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been associated with obesity, non insulin-dependent diabetes mellitus and hyperlipidemia. The present study was designed in order to evaluate whether patients with steatosis/NASH presented common features with the metabolic syndrome. METHODS: In 30 patients with nonalcoholic fatty liver the prevalence of hypertension and diabetes; the glucose/insulin profile, lipid profile, and serum leptin were evaluated and correlated with body composition and energy expenditure, assessed by bioimpedance spectroscopy and indirect calorimetry, respectively. Results were compared with a group of eight controls. RESULTS: Obesity was present in 80% of patients, hypertension in 50% and non insulin dependent diabetes in 33%. Glucose metabolism was altered in 69%, with elevated insulin in 14 patients. Serum leptin, higher in women, was increased in patients: 33.9 +/- 38.9 vs 9.6 +/- 6.9 ng/ml, P< 0.05. There was a correlation between insulin and leptin, both of which correlated with body mass index, fat mass and percentage of body fat. Dyslipidaemia was found in 80% of patients: 45% presented low high density lipoproteins cholesterol, 58% high low density lipoproteins and 38% elevated very low density lipoproteins. CONCLUSIONS: There is a strong association between nonalcoholic fatty liver and features of the metabolic syndrome, suggesting a simultaneous insulin resistance and decreased sensitivity to leptin.

The changing epidemiological pattern of hepatitis A in Lisbon, Portugal.

OBJECTIVE: To evaluate the prevalence of anti-hepatitis A virus (HAV) in an urban population, in order to assess the changing epidemiological pattern of hepatitis A. SUBJECTS: We studied 325 health care workers from Santa Maria Hospital and 201 students of the Medical School of Lisbon. RESULTS: The prevalence of anti-HAV was lower in the younger age groups: 29% in the first 3 years of Faculty compared to 46% in the last 3 years, P < 0.001. The overall prevalence for students was 35%, whereas in health care workers of less than 30 years it was 65%, P < 0.001. These findings show a declining prevalence of anti-HAV, particularly in younger age groups, when compared with the results obtained in 1983, which showed a prevalence of 85%. CONCLUSION: The epidemiological pattern of hepatitis A in Lisbon, Portugal, is changing in some urban groups, with prevalences approaching those of more developed countries.

Long-term gallbladder stone recurrence and risk factors after successful lithotripsy.

OBJECTIVE: The risk of recurrence has limited the acceptability of conservative therapies of gallbladder stones. The aim of the present study was to determine the rate of stone recurrence and its risk factors, after successful shock-wave lithotripsy. DESIGN: Prospective ultrasound follow-up at yearly intervals or whenever biliary pain was reported. METHODS: One hundred and fifty-eight consecutive patients (single stone, n = 130; two or three stones, n = 28) were followed up to 70 months (median, 33 months) after stone disappearance and discontinuation of ursodeoxycholic acid. RESULTS: Forty-three patients developed recurrent stones. By actuarial analysis, the recurrence rates (as a percent) at 1, 2, 3, 4 and 5 years were, respectively: 6+/-2, 14+/-3, 27+/-4, 35+/-5, and 44+/-6 (observed +/- SE). Cox's regression analysis identified high body mass indexes to be a risk factor (P = 0.02) for newly formed stones. Having had a single primary stone did not seem to be protective. Fourteen of the 43 patients (33%) had early symptoms of recurrence. Thirty-eight patients (89%) chose to undergo oral dissolution again, which was complemented by lithotripsy in eight patients (19%). CONCLUSION: The 5-year gallbladder stone recurrence after lithotripsy and ursodeoxycholic acid is not substantially smaller than that reported by post-bile acid studies. Obesity is a risk factor for recurrent stones as it is for primary stones. Most patients with secondary stones choose to have conservative therapy again. Gallbladder stone recurrence still is one of the major drawbacks of these treatments and cost-effective strategies are needed to prevent it.

Streptococcus bovis spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.

Spontaneous bacterial peritonitis (SBP) is a frequent cause of decompensated alcoholic cirrhosis. The authors describe the first two cases caused by infection with Streptococcus bovis. They suggest that this microorganism may be present in the intestinal flora of these patients more frequently than assumed. Furthermore, the course of SBP due to S. bovis may be particularly severe.

An aggressive protocol of ESWL and dissolution therapy of gallbladder stones.

OBJECTIVES: to assess the overall efficacy and which factors are independent predictors of success of ESWL and oral dissolution therapy of gallbladder stones using an aggressive protocol (high energy shock waves -median 22 Kv- and allowance to up to 6 sessions with an electro-hydraulic lithotripter). PATIENTS AND METHODS: inclusion criteria were 1) biliary pain; 2) 1 to 3 radiolucent stones or with slight calcification; 3) total stone volume under 15 cm3, equivalent to a single stone 3 cm diameter and 4) opacified cholecystography. Data was collected prospectively for 139 consecutive patients undergoing this treatment and the stone-free curves up to 12 months were analyzed as a function of age, sex, body-mass index, total stone volume, number of stones and the presence of slight calcification. RESULTS: patients underwent a mean of 2.6 sessions (range: 1-6) and 2834 shock waves (range: 589-8175). The global stone-free rate at 12 months was 54% (95% confidence interval: 45-64%). Factors that significantly -and adversely- influenced outcome were total stone volume (P < 0.001), number of stones (P = 0.005) and slight calcification (P = 0.038), using Cox's regression. Beyond significance, these three factors showed a marked effect on the stone-free curves. CONCLUSIONS: our data suggest that, even with this aggressive protocol, these factors are clearly detrimental. Thus, the results of our study agree with the current trend to restrict this combination therapy to patients with single, non-calcified stones with a small volume, or up to 2 cm diameter as is usually quoted.

Autoimmune cholangitis: case report.

We report on 2 patients who showed mixed signs of primary biliary cirrhosis and autoimmune hepatitis. Both patients were female, in their fifties (54 and 58), their laboratory tests indicated cholestasis, and a liver biopsy revealed liver cirrhosis with significant lesions of the bile ducts. Both were treated with prednisolone with their liver tests showing a rapid normalization of their aminotransferases. These patients can be considered as presenting with what is known as the overlap syndrome or autoimmune cholangitis, which has the clinical, biochemical, immunological, and histopathological characteristics of primary biliary cirrhosis and autoimmune hepatitis type I.

Hepatic stellate cell activation occurs in nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Hepatic stellate cell activation has a major role in the pathogenesis of hepatic fibrosis, considered to constitute part of the healing response to a necroinflammatory stimulus. However, steatosis per se, has also been shown to induce this activation. This study evaluates if hepatic stellate cell activation is present, and how it correlates with steatosis, in nonalcoholic steatohepatitis, whose hallmark is steatosis. METHODOLOGY: Steatosis, hepatocyte damage, inflammation and fibrosis were graded from 0 to 3+, in liver biopsies from 15 well documented nonalcoholic steatohepatitis and 5 normal controls. Activated hepatic stellate cell activation were identified immunohistochemically using a monoclonal antibody raised against cytoplasmic alpha-smooth muscle actin, and semiquantitatively graded using a scoring method. RESULTS: Nonalcoholic steatohepatitis patients showed significantly greater numbers of alpha-smooth muscle actin-reactive hepatic stellate cell than controls: hepatic stellate cell index of 3.6 +/- 1.9 versus 1.5 +/- 0.5, P < 0.05. The distribution of alpha-smooth muscle actin-reactive hepatic stellate cell was higher in the perivenular areas, than in the intermediate zone and portal area, with no significant association between steatosis and alpha-smooth muscle actin-expressing hepatic stellate cell. However, a significant association was found between portal and lobular inflammation and hepatic stellate cell index, r = 0.72, P = 0.0005 and r = 0.75, P = 0.0002, respectively. CONCLUSIONS: This study demonstrates that hepatic stellate cell activation occurs in nonalcoholic steatohepatitis, clearly correlating with portal and lobular inflammation, but not with steatosis, suggesting that the mechanisms implicated in fibrosis in nonalcoholic steatohepatitis are probably related with inflammation.

Centrocytic lymphoma presenting as a subphrenic abscess and a solitary liver nodule.

Non Hodgkin's lymphoma revealed by hepatic manifestations is extremely rare. We describe here a 82-year old male patient who presented with a right subphrenic abscess and a solitary liver tumour that was shown to be a centrocytic lymphoma. Furthermore, asymptomatic cryptogenic liver cirrhosis was diagnosed. This previously unreported form of clinical presentation of a non Hodgkin's lymphoma as well as the association with liver cirrhosis are discussed in the context of the recent literature.

Diphenylhydantoin-induced hepatitis: a case report.

This case report is of a 25-year old man with severe diphenylhydantoin-induced hepatitis, fever, rash and generalized lymphadenopathy. Hepatic histology and lymphocyte transformation tests strongly supported the diagnosis. He made an uneventful recovery with supportive therapy.

[Non-A, non-B hepatitis: hepatitis C]. / Hepatite não-A, não-B: hepatite C.

Non-A, non-B hepatitis (NANB), whether following the transfusion of blood products or occurring sporadically without percutaneous exposure, is complicated in approximately 50% of cases by the development of chronic hepatitis. Emerging as a consistent observation is the insidious progression of such cases of chronic NANB hepatitis to cirrhosis. Among patients with chronic NANB hepatitis followed for up to 10 years, cirrhosis is demonstrable in 20%. In May, 1988, the identification of the agent of NANB hepatitis was described by Houghton and colleagues of the Chiron Corporation. Hepatitis C, a 10,000 nucleotide single-stranded RNA virus with properties similar to those of flavivirus, was identified by developing a cDNA library from the genetic material in a chimpanzee inoculum of high infectivity and locating a clone which elaborated a virus-specific protein. Serologic evidence for HCV infection can be detected in 60-90% of cases of transfusion-associated hepatitis and 50% of cases of sporadic NANB hepatitis. Antibody to HCV (anti-HCV) can be detected in 30% of chronic hepatitis B, in 10-46% of alcoholic cirrhosis, in 40-70% of cases of hepatocellular carcinoma HBsAg negative and in 0-83% of patients with auto-immune chronic active hepatitis. Assays for HCV antigen will require technology more sensitive such than current immunoassays, such as the polymerase chain reaction. The introduction into blood banks of a screening test for anti-HCV is expected to reduce the risk of transfusion-associated NANB hepatitis and is highly recommended.

[Prognostic factors and survival model for decompensated hepatic cirrhosis]. / Factores de prognóstico e modelo de sobrevida para a cirrose hepática descompensada.

A group of 207 consecutive patients admitted for decompensated liver cirrhosis of different etiologies (alcoholic, HBsAg-associated and cryptogenic), was studied in order to assess the independent long-term (up to 5 years) prognostic value of 13 clinical, biochemical and etiological factors. These were analyzed by the Cox Regression Model using a step-wise backward procedure. The final model included bilirubin (p = 0.003), HBsAg (p = 0.006), encephalopathy (p = 0.010) and a factor comprising urea and albumin (p less than 0.001). The model was validated by a split-sample testing technique and may be used to predict survival in decompensated cirrhosis. A comparison with Child-Pugh's score in terms of survival prediction was carried out and was favorable to our model. We conclude that this model can be useful for predicting short and long-term survival in the three most common types of liver cirrhosis and that the additional overhead to calculate it seems justified in view of the large availability of microcomputers where simple programs can be run to perform this task and draw the predicted survival curves.

[The intrahepatic expression of the hepatitis B virus in chronic delta hepatitis]. / A expressão intra-hepática do vírus da hepatite B na hepatite crónica delta.

In order to evaluate the interference of hepatitis delta virus (HDV) in hepatitis B viral particle (HBsAg, HBcAg) expression in the liver of chronic HDV patients, 39 and 81 liver biopsies of HBsAg carriers seropositive for anti-HDV and anti-HDV negative controls, respectively, were studied. HBcAg was positive in 16.7% of the HBeAg-positive patients with HDAg in the liver and in 91,4% of controls. In contrast, in HBeAg- and anti-HDV negative patients the intrahepatic expression of HBcAg was detected in 32.6%. In anti-HDV negative patients the HBcAg liver expression correlated significantly with the HBeAg in serum (p < 0.00001). The distribution of HBcAg was exclusively cytoplasmatic in 30% of HDV-infected patients but mixed nuclear and cytoplasmic in 38.3% of the controls. The nuclear expression of HBcAg was decreased in chronic HDV infection. HBsAg was positive in 70.3% of patients who were anti-HDV positive and in 82.3% of controls. The membranous expression of HBsAg was detected less frequently in HDV-infected patients (p < 0.05) than in controls, while associated with HBeAg in serum of HBV carriers without HDV superinfection (p < 0.00001). The prevalence and the HBsAg cytoplasmic expression was not different for the chronic HDV infection or controls. Our results show: 1) decreased intrahepatic expression of HBcAg and membranous HBsAg in HBV carriers superinfected with HDV, suggesting decreased HBV replication in the liver of these patients. 2) the changing of HBcAg and HBsAg expression in the liver of HDV-infected patients, suggest not so much a decrease but rather a modulation in HBV replication.

[Chronic hepatitis: the etiological spectrum. The implications for treatment]. / Hepatite crónica: o espectro etiológico. Implicações para o tratamento.

The prevalence of chronic hepatitis and its different aetiologies was studied in all patients above 10 years of age seen in the specialised outpatient clinic of our hospital over a 3 year period. Defining chronic hepatitis as a persistent elevation of the transaminases, 988 patients (62% of all the patients observed) were classified as follows: viral aetiology in 82%, metabolic in 2%, biliary in 2%, alcoholic in 11%, autoimmune in 1.5% and idiopathic in 2%. Among the viral group, hepatitis B virus infection was predominant (65%), followed by hepatitis C virus (26%) and delta hepatitis (8%). While the hepatitis C and delta patients presented high transaminases, in the HBsAg carriers this occurred in 94% and 20% of the HBeAg and anti-HBe-positive patients, respectively. Thirty per cent of the patients with chronic hepatitis B, 35% of those with chronic hepatitis C and 18% with delta hepatitis were selected for alpha interferon therapy. This demonstrated that in a significant proportion of patients with chronic viral hepatitis, therapy with interferon is not indicated. Corroborating other studies, with even stronger data, our study shows that viral aetiology is the most frequent type of chronic hepatitis.

[Extracorporeal shockwave lithotripsy in the treatment of gallbladder lithiasis. The first 109 patients]. / A litotrícia extra-corporal por ondas de choque no tratamento da litíase vesicular. Os primeiros 109 doentes.

The AA report their 15-month experience with extracorporeal shock-wave lithotripsy (ESWL) in the treatment of gallbladder stones (GS). The selection criteria included symptomatic patients, with 1 to 3 radiolucent stones in a functioning gallbladder. All patients were put on adjuvant therapy with 10 mg/Kg weight/day of ursodeoxycholic acid (ursodiol). ESWL sessions were performed in an ambulatory setting, using high-energy shock-waves (mean: 23 Kv) until fragments < or = 4mm were obtained, if possible. By the end of December 1992, 109 patients had completed the ESWL protocol, undergoing a total of 265 sessions (mean: 2.4 sessions per patient, variation 1-5). The stone-free (SF) rates and respective 95% confidence intervals were 31% (22%-43%) at 6 months and 59% (38%-76%) at 1 year of follow-up. For the subset of patients with a single stone < or = 2 cm (n = 59), were 47% (33%-63%) at 6 months and 77% (40%-95%) at 1 year. The most significant complication was acute biliary pancreatitis, of which we report 4 cases (4%). They were always mild and non-complicated. There was no mortality. The AA conclude that ESWL is a safe and effective treatment for selected patients with GS.

[Therapy of chronic non-A, non-B hepatitis with recombinant interferon alfa and factors that influence the response to the treatment]. / Terapêutica da hepatite crónica não-A, não-B com interferão alfa recombinado e factores que influenciam a resposta ao tratamento.

To assess the efficacy of therapy with alfa Interferon in chronic hepatitis C (NANB), 18 patients were enrolled in an open trial. Eleven were males and 7 females with a mean age of 43 years. Interferon alfa 2b was used in titrated doses for 9 months and the treatment was started with 5 m.U./Ti. During therapy, the patients were evaluated clinically and biochemically. A liver biopsy was done within 3 months after the completion of treatment. The serum alanine aminotransferase (ALT) level 1 became completely normal in 11 patients (61%) at 3 months of therapy and a partial response was seen in 3 (16%). At the 6 months the ALT sustained normal in 10 patients (55%) and a partial response was seen in 5 (27.7%). Four out of 7 patients (57%) who completed the therapy had complete response and 2 (28.5%) a partial response. From 5 patients who completed the follow-up, 3 (60%) had a relapse of ALT levels. A low level of ALT at the beginning of treatment had a predictive value of response to the therapy (P less than 0.05). The side effects of interferon therapy were usually mild. Fever, myalgias and headaches were seen in 72% of patients in the first two weeks of therapy. No haematological alterations were seen. We conclude that a 9 month course of interferon therapy is effective in controlling disease activity in many patients with chronic NANB hepatitis. However, the high relapse rate suggest that future studies should establish the optimal dose and duration of treatment to induce a complete resolution of the disease.

[Vaccine against hepatitis B. Eight years of experience]. / Vacinação contra a hepatite B. Oito anos de experiência.

Hepatitis B virus infection is one of the world's major health problems and health care workers are especially at risk, leading to the need for a high priority vaccination program. Such a program was begun in 1989 in S. Maria Hospital and included all hospital personnel and students of the Faculty of Medicine. The screening included 2360 health care workers and 1153 students. Fifty-five percent of hospital health care workers and 41% of the students participated in the vaccination program. The overall prevalence of hepatitis B markers was 16.8%, for hospital personnel, the chronic carrier being 0.95%, and for the students, 5.5% and 0.3% respectively. The highest prevalence was observed in the Biochemical Laboratory--64% (7/11), Surgery--42% (13/31), Pneumology--39% (9/23), Emergency Department--29% (7/24), Hematology Laboratory--29% (7/24) and Orthopedics--29% (10/35). The prevalence was also higher in students in the last three years of Medical School compared to those in the first three years, 12.2% vs 7.2%, p = NS. Local pain has been the most frequent complaint in 8.6% of vaccinees. The control with the quantification of anti-HBs in the 7th month has shown a serological efficacy of about 95%. A non-response was observed in male workers, 13% compared to 5% for females, p < 0.05. Older employees also showed higher non-response: the average age of workers with anti-HBs of 0 U/L was 52.3 years, and those with anti-HBs of more than 100 U/L was 38.4 years, p < 0.02. Hepatitis B vaccine is a safe and effective preventative measure that has been widely used for years. Our study shows the need for a more aggressive approach to the vaccination of health care workers because a significant percentage of them in our country are not protected.

[Collagenous colitis: clinical and histologic improvement after sulfasalazine and topical betamethasone]. / Colite colagenosa: melhoria clínica e histológica após sulfasalazina e betametasona tópica.

We here by report a case of a 42 year-old white woman with an eight-year history of watery diarrhea where the rectal biopsies performed in endoscopically normal mucosa led to the diagnosis of collagenous colitis, characterized histologically by a thickening of the colonic subepithelial basement membrane. A brief review of the current etiopathogenic concepts of this entity is done and the importance of performing rectal biopsies in patients with unexplained diarrhea and normal appearing colon mucosa is stressed. A clinical improvement following therapy with Sulfasalazine and Beta-methasone enemas was found in this patient. We discuss the current views on the therapy and the difficulties of assessing responses to drugs in this condition.

[Autoimmune cholangiopathy]. / Colangiopatia auto-imune.

We report two patients with mixed characteristics of primary biliary cirrhosis and autoimmune hepatitis. They are two female patients in their fifties (54 and 58 years-old) one of them with autoimmune phenomenon, rheumatoid arthritis and Sjögren syndrome. Both of them showed laboratory values of cholestasis and the liver biopsy revealed liver cirrhosis with significant lesions of the bile ducts. They were treated with prednisolone with a rapid improvement and normalisation of their blood tests. They belong to a group called as overlap syndrome or autoimmune cholangitis with mixed characteristics, clinical, biochemical, immunological, and histopathologic overlapping between primary biliary cirrhosis and autoimmune hepatitis type I.