Hepatitis B vaccination in haemodialysis patients: an underestimated problem. Factors influencing immune responses in ten years of observation in an Italian haemodialysis centre and literature review.

OBJECTIVES: Despite universal infection control precautions, the risk of hepatitis B virus (HBV) infection in patients on chronic haemodialysis (HD) remains high. For this reason anti-HBV vaccination is recommended in these subjects. In hemodialyzed patients vaccinal response is often suboptimal and it's not clear what factors may influence it. STUDY DESIGN: The aim of our study is to assess the influence of some clinical and laboratory factors on seroconversion rate after anti HBV vaccination in a cohort of patients on maintenance HD. METHODS: We analysed 60 patients on regular HD, 40 men and 20 women (age 64±12 years, range 40-88 years), immunized with Engerix B ® vaccine, followed for an average time of 62 month (12-120 months). For each patient the following data were collected: age, serum albumin (sAlb), Blood urea nitrogen before HD session (BUN), age at vaccination, dialysis vintage, presence of systemic disease, type of vascular access, dialysis modality. Correlation between these factors and anti Hbs titer was estimated with multiple regression analysis. RESULTS: Anti-Hbs seroconversion rate ( Anti Hbs > 10 IU/l) was 77%. Better rate of seroconversion (86%) was observed in patients with arteriovenous fistula (AVF) and serum albumin > 3,5 g/dL (93%), while higher rate of not responders (50%) in patients with systemic diseases. The only parameter correlated to anti Hbs titer was sAlb (p =0,0012). sAlb was correlated to age in all patients (p=0,01) and age was correlated to higher anti Hbs titer in the responder group (p=0,018). DISCUSSION: In our experience an early vaccination, when patients on chronic HD are younger and in better nutritional conditions, improves anti-HBV response.

Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

The syndrome of inappropriate ADH secretion (SIADH), also recently referred to as the "syndrome of inappropriate antidiuresis", is an often underdiagnosed cause of hypotonic hyponatremia, resulting for instance from ectopic release of ADH in lung cancer or as a side-effect of various drugs. In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, whereas external Na+ balance is usually well regulated. Despite increased total body water, only minor changes of urine output and modest edema are usually seen. Renal function and acid-base balance are often preserved, while neurological impairment may range from subclinical to life-threatening. Hypouricemia is a distinguishing feature. The major causes and clinical variants of SIADH are reviewed, with particular emphasis on iatrogenic complications and hospital-acquired hyponatremia. Effective treatment of SIADH with water restriction, aquaretics, or hypertonic saline + loop diuretics, as opposed to worsening of hyponatremia during parenteral isotonic fluid administration, underscores the importance of an early accurate diagnosis and careful follow-up of these patients.

Helicobacter pylori diagnosis in patients with liver cirrhosis.

BACKGROUND: In cirrhotics, Helicobacter pylori infection is the major cause of peptic lesions, which are an important cause of upper intestinal haemorrhage in these patients. However, some diagnostic methods are not accurate for H. pylori detection in cirrhotics. AIMS: The study assessed the accuracy of different diagnostic methods for H. pylori detection in cirrhotics with and without gastroduodenal lesions. METHODS: The study population comprised of 53 cirrhotics. All patients underwent upper endoscopy: three biopsies were taken in the antrum and three in the gastric body. Four biopsies were used for Giemsa staining, while two were used for a rapid urease test. A blood sample was obtained for serology using Western blotting, and a [13C]urea breath test was performed in all patients. Histological assessment was regarded as the gold standard for diagnosis of H. pylori infection. RESULTS: H. pylori infection was detected at histological assessment in 28 (52.8%) patients. The [13C]urea breath test, rapid urease test, and serology were positive in 27 (51%) patients, 23 (43.4%) patients, and 34 (64.1%) patients, respectively. Sensitivity and specificity were 92.9 and 96% for the [13C]urea breath test, 78.6 and 96% for the rapid urease test, and 78.6 and 52% for serology. CONCLUSIONS: The [13C]urea breath test is very accurate in cirrhotics, whilst both serology and the rapid urease test give disappointing results.

[Mechanisms of repair after renal injury]. / Meccanismi di riparazione del danno renale.

Recovery from kidney injury through repair mechanisms often linked to inflammation is conditioned by nature and severity of the insult. In the assessment of kidney repair, functional recovery should be kept distinct from structural repair: compensatory hypertrophy/function of intact nephrons often masks the inability of the kidney to heal or replace damaged structures. The mechanisms of repair reflect three degrees of injury, differently handled by the kidney. First, repair of DNA damage is accomplished through proofreading DNA polymerases, along with other controls for sequence misalignment / nucleotide replacement. If DNA cannot be repaired, cells carrying mutation(s) are disposed of through apoptosis, which is also critical to clearing damaged kidney cells and infiltrating leukocytes in acute and chronic ischemic, immunological, or chemical damage. A second mechanism of repair is linked to proliferation of surviving cells. At least 5 types of reparative proliferation are known to occur, some of which implicate stem cell immigration from distant reservoirs, followed by in situ differentiation. A third mode of repair could be referred to as structural repair, indeed limited in the human kidney by the absence of postnatal nephrogenesis. Recovery from acute tubular necrosis involves remodelling of the proximal tubule, with a strict requirement for integrity of the basement membrane. Contrary to the current dogma that only acute injury can be repaired, whereas chronic damage leads to irreversible loss of nephrons, evidence is emerging that some degree of renal remodelling occurs even in chronic renal disease, despite the occurrence of stabilized structural changes.

[Syndrome of inappropriate ADH secretion: a late complication of hemopoietic stem cell allograft]. / Sindrome da inappropriata secrezione di ormone antidiuretico: una complicanza tardiva del trapianto di cellule staminali emopoietiche.

An 11-year old boy with acute lymphoid leukemia underwent umbilical cord stem cell infusion. This was followed at day 15 by the onset of asymptomatic hypotonic isovolemic hyponatremia. The disorder could be attributed to a syndrome of inappropriate ADH secretion (SIADH), most probably related to the massive i.v. induction treatment with cyclophosphamide. The major causes and clinical variants of SIADH are reviewed, with particular emphasis on the complications of chemotherapy in hematological diseases. Worsening of hyponatremia during routine parenteral feeding, as opposed to normalization of plasma Na+ by infusion of hypertonic saline, emphasize the importance of early accurate diagnosis and careful follow-up of these iatrogenic sequelae of stem cell allograft.

[The long-term results of low-calorie diet therapy in the obese]. / Risultati a lungo termine della terapia dietetica ipocalorica negli obesi.

PURPOSE: To evaluate long-term results of hypocaloric dietetic treatment in patients with essential obesity. PATIENTS AND METHODS: The study was carried out in 1,479 woman and 320 men. Body weight was evaluated at 3 months and at 1, 2 and 3 years. RESULTS: The best results in short term reduction of weight excess were found in obesity due to sedentariness or arisen after operation or emotional stress. It has been also observed that the percentage of subjects loosing weight decreased after the first year of treatment, while the percentage of subjects gaining body weight. CONCLUSIONS: Long term hypocaloric dietetic treatment in subjects with low or moderate essential obesity should primarily be aimed preventing further gain in body weight.

[Thyroid tumors in obesity]. / Tumori della tiroide nell'obesità.

BACKGROUND: The presence of nodules in the thyroid gland is the most frequent cause of endocrinopathy. The prevalence of thyroid nodules in the United States is estimated to be between 3-10%, whereas the prevalence of thyroid nodules in European adult population is estimated to be between 4-10%. At our Clinic of Obesity, the presence of nodules in the thyroid gland of obese patients is often found, incidentally, for this reason, we decide to investigate the prevalence of this pathology in obese patients and to quatify the number of times in which the presence of nodules had not been previously diagnosed. METHODS: 3248 obese patients were examined during in the last six years (1991-1996); of these patients 747 were affected by obesity and thyropathy; of these 747 we took into consideration only those with a cold single nodule and correlated the presence of the nodule with BMI, sex and age. RESULTS AND CONCLUSIONS: The prevalence of a cold single nodule in the obese patients was 31%, of which 83% has not been previously diagnosed. Of cold nodules 8% was represented by carcinoma. The carcinoma appeared more often in females than in males (3:1). The incidence of cold nodules was more frequent in adults and in mild-medium obesity.

[Latent thyroid diseases in obesity]. / Tireopatie latenti nell'obesità.

We have investigated 2672 obese subjects (2324 females and 348 males); of these, the following two groups were considered: obese subjects with or without thyroid disease. Subjects were stratified according to age, sex, and BMI. The prevalence of thyroid disease was correlated to age, sex and BMI increased body weight. Our data showed that 22% of patients affected by essential obesity and not resident in area of iodine deficiency is affected by thyroid diseases which are not diagnosed (18%). In the obese subjects, presence of goiter is more frequent than in the normal weight subjects and affects mainly adult males. Chronic thyroiditis is typical of females (9:1 female:male ratio) with no difference between normo and overweight subjects. Prevalence of single nodule in the obese is similar to the normal weight subjects, it is more frequent in adults and in subjects with medium size obesity. However, occurrence of carcinoma (8%) in single nodules appears higher in the overweight (5-6%) as compared to the normal weight subjects.

Most Helicobacter pylori-infected patients have specific antibodies, and some also have H. pylori antigens and genomic material in bile: is it a risk factor for gallstone formation?

Bile may contain a 130-kDa protein endowed with aminopeptidase activity and the ability to promote cholesterol crystallisation. As >90% of H. pylori strains have a similar peptidase activity, and half the isolates express a 110- to 140-kDa antigen, the CagA protein, we investigated a possible association between H. pylori infection and gallstones, and the presence in bile samples of factors related to H. pylori that could increase cholesterol crystallization. The prevalence of H. pylori infection was 82.1% in 112 patients with gallstones and 80.3% in 112 controls (NS). Fifteen bile samples out of 23 specimens from infected patients (65.2%) contained anti-CagA antibodies. A approximately 60-kDa antigen only reacting with an anti-CagA antibody was found in five bile samples (21.7%) from 23 infected patients. One bile sample (4.1%) contained ureA and cagA genes of H. pylori. The homology of CagA with the N-terminal sequence of aminopeptidase N was very low. We concluded that the presence of specific antibody to H. pylori in most bile samples tested and of an H. pylori putative antigen in a discrete number of cases may represent factors that increase the risk of gallstone formation.

[Drugs inhibiting the hepatic fibrogenesis]. / Farmaci che inibiscono la fibrogenesi epatica.

The treatment of chronic liver disease represents still now an open problem in medicine. The first objective of therapy has to be the causal agent removal; however, there are many cases (viral infections, autoimmunity, genetic disease) in which it is not possible to reach this issue; in these situations the secondary objective of the therapy is to inhibit the hepatic fibrogenesis, in attempt of easing or blocking the transformation of chronic liver disease in cirrhosis. The aim of this work is to review the various compounds which showed an antifibrotic activity, using a simple classification model, allowing a fast setting of different compounds. These last, on the basis of their main action, can be divided into two main groups: drugs with direct action, which interfere with collagen metabolism (for instance interferons, glucocorticoids, prolyl 4-hydroxylase inhibitors, cyclosporin A, colchicine, D-penicillamine, phosphatidylcholine and so on) and drugs with indirect action, that decrease the inflammatory stimuli, capable of stirring up the fibrogenetic hepatic process (S-adenosylmethionine, malotilate, ursodeoxycholic acid, ribavirin and so on). There are drugs that have both mechanisms of action, without the prevalence of one or other mechanism (prostaglandins).

[Serum markers of liver fibrogenesis and fibrosis]. / Marker sierici di fibrogenesi e fibrosi epatica.

Serum levels of some extracellular matrix components increased in different liver diseases are studied. Hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PNIIIP) have been the most extensively studied serum components. In particular, serum levels of PNIIIP seem to be mainly correlated with histological activity in chronic hepatitis. Considering the close pathophysiological relationship between histological activity and fibrogenesis, it is possible to consider PNIIIP as a marker of fibrogenesis. Thus, serum PNIIIP could be a useful tool for monitoring the therapeutic response in patients with chronic hepatitis in treatment with antifibrogenetic and antifibrotic agents. Like PNIIIP, serum HA concentrations increase in patients with liver fibrosis. There is evidence that serum levels of HA are more strongly correlated with histological grades of liver fibrosis than serum PNIIIP. This suggests that serum HA may be preferable for discriminating patients with cirrhosis from those without cirrhosis. There are other extracellular matrix components and a combination of several serum markers could increase their diagnostic value, but further studies are needed to confirm this.

[The physiopathological mechanism of hepatic fibrosis]. / La fibrosi epatica ed il suo meccanismo fisiopatologico.

Liver fibrosis is the end result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. The extracellular matrix of the liver is complex. It comprises multiple components of three major types of macromolecules: proteins, glycoproteins and proteoglycans. The normal liver contains limited amounts of extracellular matrix composed of elastin, fibronectin, collagen, proteoglycans and other macromolecules. These molecules have specific structure-function properties. In the liver they provide a structural framework and modulate tissue repair. The fibrogenesis is a reaction to liver injury, it leads to marked impairment of hepatic sinusoidal blood flow and ultimately to cirrhosis associated with portal hypertension and hepatocyte dysfunction. The process of fibrosis is the result from complex interactions between extracellular matrix macromolecules, hepatic cells, cytokines and growth factors, that activate the stellate cells of the liver to induce the synthesis of extracellular matrix components that deposit into the local extracellular matrix and to produce the inhibitor of metalloproteinase. The end result of these activities is an imbalance in the synthesis/degradation homeostasis of the liver, that is, liver fibrosis.

[Comparison of results of short- and long-term therapy of obesity]. / Confronto dei risultati a breve e a lungo termine nel trattamento dell'obesità.

A study concerning long term results of dietetic treatment of obesity has been conducted on 1479 obese women, aged 16 to 76 years, who attended the ambulatory during the period 1992-1995. Best results in short term reduction of weight excess were found in obesity due to sedentariness or arisen after operations or emotional stress. Also, it has been noticed that percentage of subjects who went on to loose weight decreased after first year of treatment instead, percentage of subjects who grew fat increased. So, authors believe that long term therapy main object in obese people isn't loss of weight but to avoid further weight increases.