Gitelman syndrome: pathophysiological and clinical aspects.

Giltelman syndrome (GS) is a recessive salt-losing tubulopathy of children or young adults caused by a mutation of genes encoding the human sodium chloride cotransporters and magnesium channels in the thiazide-sensitive segments of the distal convoluted tubule. The plasma biochemical picture is characterized by hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hypereninemic hyperaldosteronism. However, patients with GS present some clinical and biochemical alterations resembling that observed in thiazide diuretics abuse. On the pathophysiological point of view, GS represents a useful and interesting human model to better understand the clinical consequences of plasma hydro-electrolytes and acid-base derangements, associated with multiple hormonal alterations. The impact of this complex disorder involves cardiovascular, muscle-skeletal and some other physiological functions, adversely affecting the patient's quality of life. This review tries to summarize and better explain the linkage between the electrolytes, neurohormonal derangements and clinical picture. Moreover, the differential diagnosis between other similar electrolyte-induced clinical disorders and GS is also discussed.

Vertebral osteopenia due to bone marrow hyperplasia during interferon-alpha and ribavirin therapy for chronic hepatitis C.

We report the magnetic resonance imaging of a severe, but fully reversible, vertebral osteopenia, due to bone marrow hyperplasia, occurring in a patient with chronic hepatitis C treated with the interferon-alpha/ribavirin combination.

Hepatitis C, cryoglobulinemia, and cutaneous vasculitis associated with unusual and serious manifestations.

Hepatitis C viral infection is currently the leading cause of chronic hepatitis and cirrhosis. It also is a major predisposing factor for the development of hepatocellular carcinoma. It is estimated that approximately 1-2% of patients with hepatitis C infection have nonhepatic manifestations that are protean in nature. In this report, we describe six unusual cases of nonhepatic manifestations: abdominal vasculitis in two, peripheral neuropathy in two, and one patient each with central nervous system vasculitis and necrotizing cutaneous vasculitis. All patients had cutaneous vasculitis and cryoglobulinemia. None of our patients had cirrhosis, yet three of the six patients died. Because of the severe manifestations, aggressive therapy was instituted with interferon, immunosuppressive medications, i.v. immunoglobulin, and plasmapheresis. Our report underscores the importance of recognizing nonhepatic manifestations in patients with hepatitis C infection that may be associated with high morbidity and mortality.

Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome.

From 1983 through 1997, our center diagnosed 130 cases of benign neoplasms: 27 with focal nodular hyperplasia (FNH), 25 with hepatic adenoma, 71 with cavernous hemangioma, and seven with mixed tumors of different diagnoses. Most often these lesions were seen in females [female-to-male ratio (f/m): 5.5/1]. Hepatic adenomas and mixed tumors were seen exclusively in females and FNH predominantly in females (f/m: 26/1). Hemangiomas, however, were not uncommon in men (f/m: 52/19) relative to the other tumors (P < 0.001). Furthermore patients with hemangioma were older (mean age: 49 years) whereas patients with hepatic adenoma, FNH, and mixed tumors were often younger (mean age: 33, 35, and 44 years respectively; P < 0.004). Oral contraceptive steroid use was related by 21 of 25 patients (84%) with hepatic adenoma, 22 of 26 (85%) females with FNH, five of seven (71%) females with mixed tumors, and 10 of 52 (19%) patients with hemangioma. Ninety-five of the 130 patients (73%) had one or more symptoms. There was no statistically significant correlation between symptoms and the size of the lesion, the final diagnosis, and whether there were solitary or multiple masses. Three of 25 (12%) with hepatic adenoma presented with rupture, and one of 27 (4%) with FNH had such a consequence. None of the hemangiomas presented with rupture or progressed to such a state. One patient with hepatic adenoma (4%) had a focus of malignancy. Surgical removal of benign tumors was performed in 82 of 130 patients (63%), and there was one operative mortality (1.2%) in a patient who had a caudate lobe FNH. The types of surgical procedures included segmentectomy (62%), lobectomy (34%), and trisegmentectomy (4%). In two of 84 patients who had undergone laparotomy resection was not technically possible. Resection is recommended in all cases of hepatic adenoma because of fear of rupture or associated focus of malignancy. FNH was not observed to undergo a malignant transformation and will rarely rupture. Surgery is only recommended for symptomatic hemangioma, and size of the lesion is not a criterion for excision.

Plasma concentrations of alpha-melanocyte-stimulating hormone are elevated in patients on chronic haemodialysis.

BACKGROUND: Clinical and/or laboratory signs of systemic inflammation occur frequently in patients undergoing long-term haemodialysis. It is likely, therefore, that a compensatory release of endogenous anti-inflammatory molecules occurs to limit host reactions. The aim of the present research was to determine if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating products of activated monocytes, nitric oxide (NO) and neopterin. METHODS: Thirty-five chronic haemodialysis patients, 20 patients with chronic renal failure not yet on dialysis, and 35 normal controls were included in the study. In the haemodialysis group, blood samples were obtained before and at the end of a dialysis session. Plasma alpha-MSH was measured using a double antibody radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked immunosorbent assays. Plasma nitrites were determined by a colorimetric method, and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate) method. RESULTS: Mean plasma alpha-MSH was higher in haemodialysis patients than in control subjects, with the peptide concentrations being particularly elevated in dialysed patients with detectable endotoxin. High alpha-MSH concentrations were observed in the pre-dialysis samples, with no substantial change at the end of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and NO were generally elevated in chronic haemodialysis patients and there was a negative correlation between circulating alpha-MSH and IL-6. In patients with renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of normal subjects. CONCLUSIONS: alpha-MSH is increased in the circulation of chronic haemodialysis patients and particularly so in case of detectable endotoxaemia. Reduction of renal clearance is unlikely to contribute to the observed rise of the peptide because alpha-MSH concentration is not increased in patients with chronic renal failure who are not yet on dialysis. It is likely that dialysis-associated endotoxaemia, directly and/or through cytokine release, enhances the production of the anti-inflammatory mediator alpha-MSH that limits host reactions.

Amebiasis.

More than 80% of cases of amebic liver abscess can be managed with a 14-day course of intravenous or oral metronidazole. In cases of suspected amebic liver abscess, treatment should be started before diagnostic confirmation. If no clinical improvement is evident by 72 to 96 hours, treatment should be changed to dehydroemetine and chloroquine. Invasive treatment is necessary only in patients in whom medical treatment fails within 5 days or in whom signs of clinically severe disease are present. A 10-day course with a luminal agent such as paromomycin to eliminate intestinal cysts, which are resistant to imidazoles, should always follow treatment of the liver abscess. Percutaneous catheter drainage is indicated in patients with impending rupture, with a lesion 6 cm or more in diameter, with an abscess located in the left lobe or high in the dome of the right lobe, or in whom medical treatment fails. Although sympathetic pleural effusion is not an indication for drainage, direct pulmonary involvement or spread to pleural or lung tissues requires drainage. Intraperitoneal rupture and peritonitis necessitate open surgical drainage. Only a small minority of amebic liver abscesses are secondarily infected by other organisms. Because relapses are possible, feces should be checked for cysts monthly for several months after therapy.

Hepatitis C virus infection and acute or chronic glomerulonephritis: an epidemiological and clinical appraisal.

BACKGROUND: The relationship between hepatitis C virus (HCV) infection and acute or chronic glomerulonephritis (GN) is not well understood. METHODS: Two hundred and eighty-four patients with biopsy-proven GN and other renal diseases were studied in a multicentre survey performed during the period 1992-1995. Several clinical parameters were collected for each patient at the time of renal biopsy. We made a multivariate analysis by logistic regression model to evaluate the independent association of clinical and histological patient characteristics with HCV infection, as detected by anti-HCV antibody testing. In addition, three patients with HCV-related liver disease, membranous nephropathy, and proteinuria in the nephrotic range received therapy with interferon-alpha in standard doses. RESULTS: The prevalence of anti-HCV positivity was 13% (38/284). The frequency of anti-HCV positivity ranged between 0 and 100% in the different types of renal diseases, the difference was statistically significant (P = 0.0001). The anti-HCV rate was significantly higher in patients with cryoglobulinaemic membranoproliferative and mesangioproliferative GN than among the other individuals (14/14 (100%) vs 24/270 (9%), P = 0.0002). Our multivariate analysis by logistic regression model showed that age (P = 0.0017) and type of renal diseases (P = 0.0007) were independently and significantly associated with anti-HCV antibody. At the completion of treatment with interferon-alpha, 67% (2/3) of patients with membranous nephropathy had lowering of hepatic enzyme levels into the normal range whereas 100% (3/3) of these did not show significant reduction of proteinuria. CONCLUSIONS: We observed strong association between HCV infection and cryoglobulinaemic GN. Age and type of renal disease were important independent predictors of anti-HCV positivity in our cohort of patients. Three anti-HCV-positive patients with membranous nephropathy did not show significant remission of nephrotic proteinuria after treatment with interferon-alpha. Our data do not appear to support an association between HCV and non-cryoglobulinaemic GN. Further epidemiological surveys, experimental studies and clinical trials are warranted to fully elucidate the role of HCV in non-cryoglobulinaemic GN.

Current practices regarding visitation policies in critical care units.

BACKGROUND: Previous research has emphasized the importance of visitation in critical care units and its beneficial effects on patients and their families. However, nurses' attitudes and beliefs about visitation did not correlate with those of patients and their families, nor did actual visitation practices correlate with written policy. OBJECTIVE: To investigate nurses' perceptions about open vs restricted visiting hours and the effects on the patient, the patient's family, and the nurse. METHODS: Quantitative and qualitative data were collected from 201 nurses who completed a survey instrument about nurses' perceptions of visitation at five metropolitan hospitals in a midwestern city. RESULTS: Seventy percent of official policies for visitation were restrictive. In practice, 78% of nurses were nonrestrictive in their visitation practices. Variables that affected practices regarding visiting hours were the patient's need for rest, the nurse's workload, and the beneficial effects of visitation on patients. Requests from patients and their families were ranked least important. Significant differences in practices were found regarding restriction of visiting by immediate family members and of the number of visitors. Restricted hours were perceived to decrease noise (83%) and promote patients' rest (85%). Open visitation practices were perceived to beneficially affect the patient (67%) and the patient's family (88%) and to decrease anxiety (64%). Perceptions of ideal visiting hours included restrictions on the number of visitors (75%), hours (57%), visits by children (55%), and duration of visits (54%), but no restriction on visitation by immediate family members (60%). Qualitative data revealed recurrent themes in visitation practices, policies and exceptions, control of visitation by patients, and nurses' wishes. CONCLUSION: Data indicate that most nurses do not restrict visitation, regardless of whether restrictive policies are in place. Most nurses base their visitation decisions on the needs of the patient and the nurse. Needs of the family were ranked as less important in decision making about family visitation.

Lack of renal effects of fish oil administration in patients with advanced cirrhosis and impaired glomerular filtration.

The treatment of renal failure in cirrhotic patients with ascites remains unsatisfactory. Recent studies have shown that the dietary supplementation with fish oil improves the renal function of normal subjects, as well as that of patients with renal failure of different etiologies. We have investigated the renal effects of a daily supplementation for 1 month of 12 g fish oil (27% C20:5 n-3 eicosapentanoic acid [EPA], and 23% C22:6 n-3 docosahexanoic acid [DHA]) in a prospective study of cirrhotic patients with ascites, nine with normal renal function (group 1) and eight with renal failure (glomerular filtration rate [GFR] < 60 mL/min, group 2). Compliance with the dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentration of EPA (from 1.5 +/- 0.7% to 3.7 +/- 0.8%, P = .024, in group 1; and from 0.53 +/- 0.3% to 2.9 +/- 0.8%, P = .03, in group 2) and of DHA (from 2.1 +/- 0.4% to 3.4 +/- 0.3%, P = .008, in group 1; and from 1.45 +/- 0.5% to 3.8 +/- 0.4%, P = .05, in group 2). At the end of the study, in patients from group 1, the glomerular filtration rate increased by 19% (from 94 +/- 8 to 113 +/- 13 mL/min, P = .039), and the urine flow increased by 39% (from 0.85 +/- 0.14 to 1.12 +/- 0.2 mL/min, P = .039), while no changes occurred in the renal function of patients from group 2. No changes were observed in the urinary excretion of prostaglandin (PG) E2 or of 6-keto prostaglandin-1-alpha (6-K-PGF1-alpha) nor in plasma renin activity (PRA) or the plasma concentration of aldosterone (PA) or antidiuretic hormone (ADH) in both groups. As far as undesirable effects of fish oils were considered, the mean arterial pressure (MAP) decreased in both groups (group 1: from 88.6 +/- 2 to 85.3 +/- 2 mm Hg, P = .015; group 2: from 88.2 +/- 3 to 82.8 +/- 3 mm Hg, P = .05), and bleeding time displayed a significant increase when patients were considered collectively (from 744 +/- 89 to 872 +/- 106 seconds, P = .0068). In conclusion, the administration of fish oil for 1 month was unable to improve renal function in cirrhotic patients with ascites and renal failure. The occurrence of undesirable effects, such as the reduction of arterial pressure and the prolongation of bleeding time, argues against the use of fish oils in these patients.

Hepatitis G virus infection in hemodialysis patients.

The increased risk of hemodialysis patients for infections sustained by hepatitis viruses is likely to extend to a newly discovered parenterally transmitted virus, HGBV-C/HGV, able to cause acute and chronic hepatitis. The aim of this study was to assess the prevalence and clinical relevance of this infection in Italian hemodialysis patients. Nineteen of 100 patients (19%) on maintenance hemodialysis were viremic for HGBV-C/HGV, and all of them were infected with a HGV-like genotype. Eight of these patients were coinfected by hepatitis B or hepatitis C viruses. A clinical picture of chronic hepatitis was not appreciable in patients with isolated HGV infection and the presence of HGV did not appear to modify the clinical course of hepatitis B and hepatitis C infections.

Renal effects of dietary supplementation with fish oil in cyclosporine-treated liver transplant recipients.

Nephrotoxicity is the main untoward effect of cyclosporine (CsA) treatment. Experimental and clinical data suggest that dietary supplementation with fish oil may lessen cyclosporine nephrotoxicity, possibly by lowering renal thromboxane (Tx) production. We have studied the renal effects of a daily supplementation for 2 months of 12 g fish oil (18% C20:5 n-3 eicosapentaenoic acid [EPA] and 12% C22:6 n-3 docosahexanoic acid [DHA]) in a placebo-controlled (12 g corn oil), prospective, randomized, double-blind study of stable CsA-treated liver transplant recipients. Thirteen patients ingested corn oil capsules and 13 fish oil. Compliance with dietary regimen was confirmed by fatty acid chromatography that showed increased plasma concentrations of EPA (from 0.4 +/- 0.02% to 4.6 +/- 0.5%, P < .0001) and DHA (from 1.8 +/- 0.2% to 3.9 +/- 0.1%, P < .0001) in the fish oil group and increased plasma concentration of linoleic acid (C18:2 n-6) in the corn oil group (from 25 +/- 2% to 28.4 +/- 2%, P < .001). At the end of the 2 months of the study, in the fish oil group the effective renal plasma flow increased by 22% (P = .012), the glomerular filtration rate increased by 33% (P = .057), the renal blood flow increased by 17% (P = .024), and the calculated total renal vascular resistances decreased by 20% (P = .034). In contrast, none of these parameters changed in the corn oil group. The renal functional reserve determined during L-arginine infusion, plasma renin activity (PRA), and plasma aldosterone (PA) remained unchanged during the study in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of five maintenance therapies for reflux esophagitis.

BACKGROUND: Patients with reflux esophagitis have a high rate of relapse within one year after therapy is discontinued. METHODS: We enrolled 175 adults with endoscopy-confirmed reflux esophagitis in a prospective study comparing five maintenance therapies. All the patients were initially treated with omeprazole (40 mg orally once a day) for four to eight weeks, and healing was confirmed by endoscopy. Participants were then stratified according to their initial grade of esophagitis and randomly assigned to 12 months of treatment with one of the following: cisapride (10 mg three times a day), ranitidine (150 mg three times a day), omeprazole (20 mg per day), ranitidine plus cisapride (10 mg three times a day), or omeprazole plus cisapride. Endoscopy was repeated after 6 and 12 months of treatment; the endoscopists were blinded to the treatment assignments. Remission was defined as the absence of esophageal lesions on scheduled or unscheduled follow-up endoscopy. RESULTS: In an intention-to-treat analysis, the numbers of patients in continued remission at 12 months were 19 of 35 (54 percent) in the cisapride group, 17 of 35 (49 percent) in the ranitidine group, 28 of 35 (80 percent) in the omeprazole group, 23 of 35 (66 percent) in the ranitidine-plus-cisapride group, and 31 of 35 (89 percent) in the omeprazole-plus-cisapride group. Omeprazole was significantly more effective than cisapride (P = 0.02) or ranitidine (P = 0.003), and combination therapy with omeprazole plus cisapride was significantly more effective than cisapride alone (P = 0.003), ranitidine alone (P < 0.001), or ranitidine plus cisapride (P = 0.03). Ranitidine plus cisapride was significantly better than ranitidine alone (P = 0.05). CONCLUSIONS: For maintenance treatment of reflux esophagitis, omeprazole alone or in combination with cisapride is more effective than ranitidine alone or cisapride alone, and the combination of omeprazole and cisapride is more effective than ranitidine plus cisapride.

High prevalence of a rare hepatitis C virus in patients treated in the same hemodialysis unit: evidence for nosocomial transmission of HCV.

Hepatitis C virus (HCV) is a major cause of hepatitis among patients treated with maintenance hemodialysis. Blood transfusion appears to be the primary risk factor, but nosocomial transmission of HCV in the dialytic environment has been hypothesized. We addressed this issue by analyzing the individual variation of genomic sequences of HCV in 28 patients on chronic hemodialysis (HD) from the same department and 25 environmentally unrelated patients with HCV-related liver disease. Genome variations of HCV were studied by single strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products obtained from the 5'-untranslated region of the viral genome and by sequence analysis. Six different SSCP patterns were identified in HD patients versus 16 in control patients. Among HD patients the three more frequent SSCP patterns accounted for 85% of observations, while in the control group each pattern was found in 4 to 12% of patients. The ability of SSCP to discriminate sequence variation was proven by sequence analysis which confirmed identity/diversity of sequences selected by SSCP. Moreover, sequence analysis permitted a recognition of the most frequent genome observed in HD patients as a type 4 HCV, which is considered to be rare in the Italian population. The relative homogeneity of HCV variants in HD patients treated in the same HD and the high prevalence in this unit of a rare viral variant support the possibility of a nosocomial transmission of HCV in the dialytic environment.

Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects.

BACKGROUND: Phosphate-induced hyperparathyroidism still represents an intriguing problem in dialysis patients. Postprandial hyperphosphataemia is considered to be the main stimulus to parathyroid hyperfunction, and therefore many efforts have focused on the use of phosphate binders to prevent phosphate absorption. METHODS: We investigated whether the pH-mediated gastric ionization of calcium phosphate dietary salts is necessary for its intestinal absorption. In eight normal subjects we measured 24-h urinary calcium phosphate excretion and the postprandial blood calcium phosphate profile after a meal containing 1 g of calcium and 2 g of phosphate salts in a crossover placebo-omeprazole study. On two occasions the subjects received either placebo or omeprazole 60 mg/day 2 days before and during the day test. RESULTS: Serum gastrin levels were measured as an indicator of achlorhydria and were 13.7 +/- 1 pg/ml after placebo and 30.4 +/- 4.7 after omeprazole (P < 0.003). Postprandial plasma phosphate profiles were not significantly different between the two studies (+36 +/- 8% after placebo and +24 +/- 8% after omeprazole, NS), while plasma calcium increased by +6.1 +/- 1% after placebo and decreased by -4.2 +/- 0.7% after omeprazole (P < 0.01). The 24-h urinary phosphate excretion was 1068 +/- 85 mg after placebo and 773 +/- 55 after omeprazole (P < 0.002), while the 24-h urinary calcium excretion was 360 +/- 21 after placebo and 238 +/- 15 after omeprazole (P < 0.0001). A negative relationship was observed between absolute changes in plasma gastrin and those in urinary calcium (P < 0.009) and phosphate (P < 0.05). CONCLUSIONS: The inhibition of gastric acid secretion by omeprazole significantly reduces both urinary phosphate and calcium excretion after an oral load. The behaviour of the postprandial calcium-phosphate plasma profile suggests that gastric acid inhibition is more effective in reducing calcium rather than phosphate dietary salts absorption in normal subjects.

Single-tube reverse transcription and heminested polymerase chain reaction of hepatitis C virus RNA to detect viremia in serologically negative hemodialysis patients.

Detection of hepatitis C virus genome is the only method currently available for detecting viremia in infected individuals. We describe a substantial simplification of current methods for viral RNA reverse transcription and polymerase chain reaction amplification, which allows cDNA synthesis and nested amplification in a single tube; this is achieved through compartmentalization of the reagents for the two reactions with a wax barrier. This procedure retains a high sensitivity: analysis of serum samples from hemodialysis patients, a high-risk group for hepatitis C virus infection, confirmed the presence of the virus in 88% of antibody-positive patients and detected viremia in patients without serological or biochemical evidence of hepatitis C virus infection.

A pharmacodynamic study of two omeprazole regimens suitable for long-term treatment of duodenal ulcer.

BACKGROUND: The experience with long-term treatment of peptic ulcer with omeprazole is still scant, but the possibility cannot be excluded that its better pharmacodynamic effect on gastric acidity also has a positive result in the relapse rate. Moreover, this drug acts via a mechanism other than receptorial binding, and therefore its efficacy should not dissipate with time. This study was carried out to assess the pharmacodynamic properties and the possible changes with time of two dose regimens of omeprazole that could be suitable for long-term treatment in duodenal ulcer. METHODS: Twenty patients with endoscopically proven duodenal ulcer were studied by means of 24-h gastric pH-metry both in basal conditions and on the 5th day of acute treatment with 40 mg omeprazole in the morning. All the ulcers healed after 4 weeks, and thereafter 10 patients were randomized to receive orally 20 mg omeprazole daily at 0800 h in single-blind fashion (group A) and 10 to receive 20 mg omeprazole every other day (group B) for up to 6 months. At the end of the 1st, 3rd, and 6th month of these maintenance treatments 24-h gastric pH-metry was repeated to assess the antisecretory effect of each regimen over time. In group-B patients the test was performed on 2 consecutive days (without and with medication) at each time interval. The fasting gastrin values were also determined. The patients underwent esophagogastroduodenoscopy every 2 months. RESULTS: Three patients in group B were lost to follow-up for various reasons, and only seven remained eligible for final analysis. The two long-term regimens of omeprazole were able to increase significantly pH values (p < 0.02-0.001) and the times spent at and above pH 3.0 (p < 0.001) over 24 h compared with basal conditions. In group A the 24-h pH value obtained in the 6th month was higher (p < 0.02) than that in the 3rd month of maintenance treatment. In group B the pharmacologic effect tended to decrease on the day without medication compared with the day with medication, but the difference between them was significantly (p < 0.05) only at the 6-month interval. There was no significant difference between the gastrin levels of the two groups in the long-term treatment. No ulcer relapse was detected at any long-term endoscopic control in the two groups of patients. CONCLUSIONS: The two omeprazole regimens we tested are effective in reducing gastric acidity, and their pharmacodynamic action does not decrease with time. They are therefore suitable for maintenance treatment in acid-related disorders.