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1.
Eur Spine J ; 22 Suppl 6: S933-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24043339

ABSTRACT

PURPOSE: The clinical outcome of polytrauma patients underwent spine fixation was analyzed and correlated both to surgical time (early versus delayed) and to fixation type (open versus percutaneous). METHODS: Twenty-four polytrauma patients were retrospectively evaluated. Patients were evaluated according to age, accident dynamic, mechanical ventilation need, blood transfusion need, SAPS II score, type of vertebral injury, time of fixation (within or after 72 h) and type of fixation. RESULTS: Nine patients underwent percutaneous pedicle screw fixation and 12 open fusion. An early fixation allows better clinical outcome considering ICU stay (13.7 versus 21.71 days), H-LOS (25.8 versus 69.5 days), mechanical ventilation need (7 versus 16.2), blood transfusion need (250 versus 592 cc). CONCLUSIONS: In polytrauma patients an early spine fixation improves clinical outcome. Patients underwent percutaneous screw fixation showed a better outcome compared to open surgery group obtained despite worst clinical conditions.


Subject(s)
Multiple Trauma/surgery , Pedicle Screws , Spinal Fusion/instrumentation , Spinal Fusion/methods , Spinal Injuries/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
2.
Gastroenterology ; 117(4): 806-13, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10500062

ABSTRACT

BACKGROUND & AIMS: The role of the interleukin (IL)-1 receptor antagonist (IL-1ra) in predisposing an individual to inflammatory bowel disease (IBD) is controversial. This study aimed to determine the association between intron 2 IL-1ra polymorphism and IBD by performing a multiethnic case-control study and to assess its functional significance. METHODS: A total of 236 patients with ulcerative colitis (UC), 196 patients with Crohn's disease (CD), and 338 ethnically matched control patients treated at LAC-USC and Cedars-Sinai Medical Centers and the University of Milan Medical Center were genotyped for a variable length polymorphism in intron 2 of the IL-1ra gene (IL-1RN). Total IL-1ra protein production rates in peripheral blood mononuclear cells (PBMCs) were correlated with carriage of allele 2 of the IL-1RN gene (IL-1RN*2). RESULTS: In the LAC-USC group, UC patients (n = 60) had an increased frequency of at least 1 copy of IL-1RN*2 compared with controls (n = 129) (70% vs. 33%; P < 0.01; odds ratio [OR], 4.7). The frequency of IL-1RN*2 carriage in the Cedars-Sinai group was 59% in UC, 45% in CD, and 42% in controls (P < 0.01; OR, 2.0). A significant difference was observed only in the Jewish subgroup (P = 0.003; OR, 5.0). The association was not detected in UC or CD patients treated at the University of Milan. The ORs of 4.7 and 5.0 appear to be the highest reported in any UC population for any genetic markers. Further, carriage of IL-1RN*2 was associated with decreased production of total IL-1ra protein in cultured PBMCs from both UC patients and controls. CONCLUSIONS: These results provide further evidence that IL-1ra is important in the predisposition to UC, there may be genetic or pathogenetic heterogeneity between different ethnic groups, and UC and CD are genetically distinct diseases.


Subject(s)
Alleles , Black People/genetics , Colitis, Ulcerative/genetics , Sialoglycoproteins/genetics , White People/genetics , Adolescent , Adult , Aged , Case-Control Studies , Cells, Cultured , Colitis, Ulcerative/metabolism , Crohn Disease/genetics , Female , Heterozygote , Humans , Interleukin 1 Receptor Antagonist Protein , Jews/genetics , Male , Middle Aged , Monocytes/metabolism , Polymorphism, Genetic/genetics , Reference Values , Sialoglycoproteins/biosynthesis , Sialoglycoproteins/blood
3.
Eur J Gastroenterol Hepatol ; 11(9): 1061-5, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10503849

ABSTRACT

The pathogenesis of ascites, a severe and the most frequent complication during cirrhosis, is still not completely understood, but present evidence indicates that portal hypertension principally triggers renal sodium and water retention. Ascites is associated with profound disturbances of splanchnic and systemic haemodynamics, which in turn may influence renal function. Within the kidney the balance between vasoconstricting and vasodilating factors is critical for the maintenance of renal function. As the disease progresses, vasoconstricting factors (mainly angiotensin II, catecholamines, thromboxane, leucotrienes and endothelins) prevail, probably due to the exhaustion of the vasodilating renal autacoid system (mainly prostaglandins). In this setting, vasoconstriction of the intrarenal vascular system induces marked and often irreversible sodium and water retention, leading to refractory ascites, a progressive rise in plasma creatinine levels and reduction of renal clearances (hepatorenal syndrome, HRS). This persistent renal hypoxia may also favour the occurrence of tubular damage due to several causes. A careful therapeutic approach is first based on sequential diuretic treatment (and the addition of adequate plasma expansion with human albumin for patients with diuretic resistant ascites), which may lead to control of ascites for years. However, when HRS occurs, all the proposed treatments (such as paracentesis, administration of renal vasodilators, systemic vasoconstrictors, calcium channel antagonists, TIPS, surgical portosystemic shunts) have been shown to moderately or temporarily improve renal function only, leaving liver transplantation as the only choice of treatment for patients.


Subject(s)
Angiotensin II/antagonists & inhibitors , Ascites/therapy , Diuretics/therapeutic use , Hepatorenal Syndrome/therapy , Ascites/etiology , Hemodynamics , Hepatorenal Syndrome/etiology , Humans , Liver Cirrhosis/complications , Liver Transplantation
4.
J Hepatol ; 30(4): 639-45, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10207805

ABSTRACT

BACKGROUND/AIMS: Diuretic treatment of ascites could result in intravascular volume depletion, electrolyte imbalance and renal impairment. We investigated whether intravascular volume expansion with albumin exert beneficial effects in cirrhosis with ascites. METHODS: In protocol 1, 126 cirrhotic inpatients in whom ascites was not relieved following bed rest and a low-sodium diet, were randomly assigned to receive diuretics (group A) or diuretics plus albumin, 12.5 g/day (group B). In protocol 2, group A patients continued to receive diuretics and group B diuretics plus albumin (25 g/week) as outpatients and were followed up for 3 years. End points were: disappearance of ascites, duration of hospital stay (protocol 1), recurrence of ascites, hospital readmission and survival (protocol 2). RESULTS: The cumulative rate of response to diuretic treatment of ascites was higher (p < 0.05) and hospital stay was shorter (20 +/- 1 versus 24 +/- 2 days, p < 0.05) in group B than in group A patients. After discharge, group B patients had a lower cumulative probability of developing ascites (19%, 56%, 69% versus 30%, 79% and 82% at 12, 24 and 36 months, p < 0.02) and a lower probability of readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively, p < 0.02). Survival was similar in the two groups. CONCLUSIONS: Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2.


Subject(s)
Ascites/therapy , Diuretics/therapeutic use , Furosemide/therapeutic use , Liver Cirrhosis/complications , Serum Albumin/therapeutic use , Adult , Aged , Ascites/etiology , Bed Rest , Bilirubin/blood , Blood Pressure , Blood Urea Nitrogen , Canrenoic Acid/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Electrolytes/blood , Female , Hepatitis, Viral, Human/complications , Humans , Liver Cirrhosis/physiopathology , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis, Alcoholic/physiopathology , Male , Middle Aged , Probability , Recurrence , Serum Albumin/metabolism
5.
Ann Ital Med Int ; 14(4): 264-84, 1999.
Article in English | MEDLINE | ID: mdl-10638019

ABSTRACT

Ascites is the most frequent major complication of liver cirrhosis. Even if a significant decrease in renal clearances may be observed in the first stages of chronic active hepatitis, true renal impairment, often with the typical signs of hepatorenal syndrome, only occurs in patients with ascites, especially when tense and refractory. Experimental and clinical data suggest the presence of primary sodium and water retention, perhaps as a consequence of an increase in intrahepatic hydrostatic pressure. The abnormal sodium retention leads to plasma volume expansion, followed by decreased peripheral vascular resistances and increased cardiac output. This second stage concords with the peripheral arterial vasodilation theory, characterized by an increase in total blood volume, but with a decrease in effective arterial blood volume. This discrepancy leads to the activation of sympathetic nervous and renin-angiotensin-aldosterone systems. This activation, while protective against splanchnic and systemic vasodilation, provoked by the increased availability of nitric oxide and other vasodilating substances, induces renal vasoconstriction. This phenomenon can be considered as the basis of the progressive renal failure that leads to hepatorenal syndrome, favored by progressive exhaustion of the renal autacoid vasodilating substances. The first therapeutic approach to ascites is sequential and based on diuretic administration. Subsequently, paracentesis with albumin infusion is carried out, as well as transjugular intrahepatic portosystemic shunting, surgical portosystemic shunting, and liver transplantation: these procedures are essential for the treatment of hepatorenal syndrome.


Subject(s)
Ascites/etiology , Hepatorenal Syndrome/etiology , Liver Cirrhosis/complications , Ascites/genetics , Ascites/physiopathology , Ascites/therapy , Causality , Diagnosis, Differential , Hemodynamics , Hepatorenal Syndrome/genetics , Hepatorenal Syndrome/physiopathology , Hepatorenal Syndrome/therapy , Humans , Liver Cirrhosis/physiopathology , Natriuretic Agents/physiology , Renal Insufficiency/diagnosis , Sodium/metabolism , Vasopressins/physiology , Water/metabolism
6.
Clin Ter ; 149(2): 127-30, 1998.
Article in Italian | MEDLINE | ID: mdl-9780477

ABSTRACT

PURPOSE: To evaluate the therapeutic effects of drinking mineral water, its influence on gastrointestinal drug consumption as well as on working days missed in patients with dyspeptic syndrome or chronic constipation due to irritable bowel syndrome. MATERIALS AND METHODS: A questionnaire was sent to 1500 physicians and 965 forms were available concerning patients who had mineral water treatment at Montecatini. RESULTS: Mineral water therapy determined a striking short- and medium-term improvement on clinical symptoms. Furthermore, this treatment reduced gastrointestinal drug consumption per year, as well as the number of working days missed. CONCLUSIONS: This epidemiological study confirms the utility of drinking mineral water in the treatment of some gastrointestinal syndromes either in the short and in the medium run.


Subject(s)
Balneology/methods , Gastrointestinal Diseases/therapy , Mineral Waters/therapeutic use , Chronic Disease , Colonic Diseases, Functional/therapy , Constipation/therapy , Gastrointestinal Diseases/classification , Health Resorts , Humans , Italy
7.
Am J Gastroenterol ; 92(5): 852-7, 1997 May.
Article in English | MEDLINE | ID: mdl-9149200

ABSTRACT

OBJECTIVES: Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites. METHODS: Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit. RESULTS: The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion. CONCLUSIONS: Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.


Subject(s)
Ascites/physiopathology , Atrial Natriuretic Factor/pharmacology , Hemodynamics/drug effects , Hypertension, Portal/physiopathology , Kidney/drug effects , Liver Cirrhosis/physiopathology , Aldosterone/blood , Analysis of Variance , Ascites/blood , Ascites/complications , Atrial Natriuretic Factor/administration & dosage , Atrial Natriuretic Factor/blood , Creatinine/urine , Cyclic GMP/blood , Female , Hematocrit , Humans , Hypertension, Portal/blood , Hypertension, Portal/complications , Infusions, Intravenous , Kidney/physiopathology , Kidney Function Tests , Liver Cirrhosis/blood , Liver Cirrhosis/complications , Middle Aged , Natriuresis , Norepinephrine/blood , Renin/blood
8.
Ann Ital Med Int ; 12(2): 84-91, 1997.
Article in Italian | MEDLINE | ID: mdl-9333317

ABSTRACT

The liver plays a major role in the regulation of glucose metabolism: plasma glucose concentration is the result of peripheral glucose utilization and liver production. Several hormones, including insulin, glucagon, growth hormone, cortisol, and catecholamines contribute to the regulation of glucose metabolism by the liver. In this review, we examine hepatic glucose metabolism, in particular the actions of insulin and contrainsular hormones on glucose hepatic uptake and production in patients with diabetes or chronic liver disease. The most frequent patterns of hepatic involvement that take place during diabetes, i.e. nuclear glycogenesis, steatosis, portal fibrosis, and diabetic steatonecrosis, are discussed. Also considered are anomalies of glucose homeostasis observed in chronic liver disease, including glucose intolerance, diabetes, and hypoglycemias. There is a strong correlation between diabetes mellitus and the liver: diabetic patients have typical histological lesions, while several glucose metabolism alterations are commonly found in subjects with chronic liver disease. The pathogenesis of impaired glucose metabolism during chronic liver disease has not yet been fully understood: further clinical and experimental studies should clarify this issue.


Subject(s)
Diabetes Mellitus/metabolism , Glucose/metabolism , Liver Diseases/metabolism , Liver/physiology , Chronic Disease , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Fatty Liver/metabolism , Homeostasis , Humans , Hypoglycemia/metabolism , Liver/metabolism , Liver Cirrhosis/metabolism
9.
Am J Gastroenterol ; 92(1): 66-72, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8995940

ABSTRACT

OBJECTIVE: Chronic infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) is now recognized as a major cause of liver cirrhosis. This study was aimed at evaluating the natural history of the disease in a large series of Italian patients with HBV- and HCV-related cirrhosis without portal hypertension at entry. METHODS: The clinical records of 405 patients (233 males, mean age 54 +/- 9 yr) with histologically proven cirrhosis (321 with HCV-related and 84 with HBV-related cirrhosis) and no clinical evidence of portal hypertension at entry were retrospectively examined to evaluate the occurrence of complications and the cumulative mortality rate during follow-up. RESULTS: Patients had a mean follow-up of 8 +/- 3 yr. The cumulative survival rate was 99.1% at 5 yr, 76.8% at 10 yr, and 49.4% at 15 yr. The age-adjusted death rate was 3.14 and 2.84 times higher than in the general Italian population in men and women, respectively. Only the bilirubin level was an independent indicator of survival. Esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy, and hepatocellular carcinoma significantly reduced the survival rate (major complications), whereas thrombocytopenia, diabetes, and cholelithiasis did not affect survival (minor complications). The incidence of hepatocellular carcinoma was similar in patients with either HBV- or HCV-related disease and was quite frequent, especially in males. CONCLUSIONS: This study demonstrates that the course of virus-induced liver cirrhosis is not influenced by the etiology of the disease and that the occurrence of complications significantly shortens life expectancy. The longer survival rate observed in this study is probably due to the fact that cirrhosis was here recognized by liver biopsy in the absence of clinical evidence of portal hypertension.


Subject(s)
Hepatitis B/complications , Hepatitis C/complications , Liver Cirrhosis/etiology , Bilirubin/blood , Carcinoma, Hepatocellular/complications , Chronic Disease , Esophageal and Gastric Varices/complications , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/complications , Hepatic Encephalopathy/complications , Humans , Jaundice/complications , Liver Cirrhosis/mortality , Liver Neoplasms/complications , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
10.
Ann Ital Med Int ; 11 Suppl 2: 23S-29S, 1996 Oct.
Article in Italian | MEDLINE | ID: mdl-9004817

ABSTRACT

The role of hepatitis B virus (HBV) and hepatitis C virus (HCV) as a major cause of chronic liver disease is now accepted worldwide. This study was aimed at evaluating the natural history of the disease in patients with virus-induced chronic active hepatitis or cirrhosis, and the influence played by age, sex and etiology, liver function tests and by the occurrence of different complications. We retrospectively examined the clinical records of 506 inpatients: 194 were affected by chronic active hepatitis (125 males, 69 females, mean age 45 +/- 11 years, 146 HCV- and 48 HBV-related), and 312 by cirrhosis without clinical evidence of portal hypertension (178 males, 134 females, mean age 53 +/- 9 years, 249 HCV- and 63 HBV-related). The occurrence of cirrhosis in the chronic active hepatitis group was then calculated, together with the occurrence of complications and the cumulative mortality rate of established cirrhosis. During follow-up 93 patients with chronic hepatitis developed cirrhosis. The cumulative probability of developing cirrhosis in this group was 6.64% at 5 years, 56.1% at 10 years and 86.8% at 15 years. These patients were therefore included in the cirrhosis group for the final analysis, so that a total of 405 cirrhotic patients were evaluated: these patients had a cumulative survival rate of 99.1% at 5, 76.8% at 10 and 49.4% at 15 years. Comparing the age-adjusted death rate of our patients with the general Italian population, we observed that in patients with liver cirrhosis it was 3.14 and 2.84 times higher in men and women, respectively. Bilirubin was an independent indicator of survival. Several complications, such as esophageal varices, ascites, jaundice, hemorrhage, hepatic encephalopathy and hepatocellular carcinoma significantly reduced the survival rate and were indicated as major complications, while thrombocytopenia, cholelithiasis and diabetes did not affect survival and thus were called minor complications. Incidence of hepatocellular carcinoma was very high especially in males, without correlation with etiology. In conclusion, the progression of virus-induced chronic active hepatitis to cirrhosis is not influenced by sex and etiology. Similarly, the different etiology does not modify the natural history of cirrhosis while the occurrence of one or more major complications significantly shortens survival. The longer survival rate observed in patients with cirrhosis included in this study is probably due to the selective inclusion of patients with early disease and no evidence of portal hypertension.


Subject(s)
Hepatitis, Viral, Human/complications , Liver Cirrhosis/complications , Liver Cirrhosis/virology , Adult , Ascites/etiology , Carcinoma, Hepatocellular/etiology , Esophageal and Gastric Varices/etiology , Female , Gastrointestinal Hemorrhage/etiology , Hepatic Encephalopathy/etiology , Humans , Jaundice/etiology , Liver Cirrhosis/mortality , Liver Cirrhosis/physiopathology , Liver Neoplasms/etiology , Male , Middle Aged , Retrospective Studies , Survival Analysis
11.
Hepatology ; 22(6): 1745-50, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7489983

ABSTRACT

Patients with cirrhosis and ascites have high plasma levels of atrial (ANP) and brain (BNP) natriuretic peptides, two cardiac hormones released by the atria and ventricles, respectively. We evaluated renal hemodynamics, sodium excretion, and intrarenal sodium handling (lithium clearance method) in seven cirrhotic patients with ascites and avid sodium retention before, during, and after the infusion of synthetic human BNP, at the dose of 4 pmol/kg.min for 1 hour, which has been shown to increase renal plasma flow, glomerular filtration rate (GFR), and sodium excretion in healthy subjects without affecting systemic hemodynamics. Plasma BNP levels were 7.31 +/- 0.85 pmol/L in baseline conditions, and increased to 33.60 +/- 2.96 pmol/L at the end of the infusion (P < .01 vs. baseline). Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) also significantly increased during the infusion, indicating stimulation of natriuretic peptide receptors by BNP. BNP administration did not modify renal plasma flow, GFR, sodium excretion or tubular sodium reabsorption to any appreciable extent. Arterial pressure heart rate, plasma norepinephrine, and plasma renin activity (PRA) where also unchanged, whereas plasma aldosterone concentration showed a significant, 35% reduction at the end of the postinfusion period, ruling out the possibility that BNP-induced vasodilation might be responsible for failure of the peptide to induce a natriuretic response. Overactivity of antinatriuretic factors is probably the main determinant of the blunted natriuretic effect of BNP in these patients.


Subject(s)
Liver Cirrhosis/physiopathology , Natriuresis/drug effects , Nerve Tissue Proteins/pharmacology , Sodium/metabolism , Adult , Aged , Atrial Natriuretic Factor/blood , Blood Pressure , Diuresis/drug effects , Female , Glomerular Filtration Rate/drug effects , Humans , Kinetics , Male , Middle Aged , Natriuretic Peptide, Brain , Nerve Tissue Proteins/administration & dosage , Nerve Tissue Proteins/blood , Renal Plasma Flow/drug effects , Sodium/blood
12.
Gastroenterology ; 109(3): 812-8, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7657109

ABSTRACT

BACKGROUND & AIMS: Proinflammatory cytokines such as interleukin (IL) 1, IL-8, and tumor necrosis factor (TNF) have been implicated as primary mediators of intestinal inflammation. The aim of the present study was to determine the effects of a novel cytokine antagonist (CGP 47969A) in a rabbit model of acute colitis. METHODS: Colitis was induced using the formalin-immune complex technique. Animals were pretreated intrarectally with CGP 47969A (30, 10, or 3 mg/kg), hydrocortisone (0.8 mg/kg), or vehicle (4 mL saline) 2 hours before the induction of colitis and twice daily thereafter until death 48 hours after the induction of colitis. The severity of inflammation of colonic tissue was assessed using histological analysis and myeloperoxidase activity assay, and IL-1 alpha, IL-8, TNF-alpha, and IL-1 receptor antagonist levels were determined. RESULTS: Compared with vehicle, CGP 47969A (10 mg/kg) significantly reduced the acute inflammatory index by 58%, edema by 67%, necrosis by 99%, and myeloperoxidase activity by 49% (all P < 0.02) with efficacy similar to that of steroids. These effects were associated with a significant inhibition of colonic IL-1 alpha and IL-8 by 56% and 90%, respectively (p < 0.01). CONCLUSIONS: Administration of CGP 47969A reduces inflammation and tissue damage in rabbit immune complex colitis through mechanisms involving the inhibition of mucosal proinflammatory cytokines.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colitis/drug therapy , Cytokines/antagonists & inhibitors , Immune Complex Diseases/drug therapy , Piperazines/therapeutic use , Animals , Colitis/immunology , Colitis/metabolism , Colon/enzymology , Colon/metabolism , Colon/pathology , Cytokines/biosynthesis , Hydrocortisone/therapeutic use , Immune Complex Diseases/immunology , Immune Complex Diseases/metabolism , Interleukin-1/antagonists & inhibitors , Interleukin-1/biosynthesis , Interleukin-8/antagonists & inhibitors , Interleukin-8/biosynthesis , Male , Peroxidase/metabolism , Rabbits
13.
Am J Hypertens ; 8(8): 799-807, 1995 Aug.
Article in English | MEDLINE | ID: mdl-7576396

ABSTRACT

We assessed the cardiovascular and renal effects of human brain natriuretic peptide (BNP) infused at a dose inducing an increase in plasma BNP to pathophysiologic levels, in eight hypertensive patients in a randomized, placebo-controlled, cross-over study. Left ventricular performance, cardiac output (echocardiography), heart rate, arterial pressure, glomerular filtration rate (GFR; creatinine clearance), sodium excretion, intrarenal sodium handling (lithium clearance method), and urine flow rate were measured in the infusion and postinfusion periods (1 h each), together with plasma BNP and the urinary excretion rate of cGMP. Plasma BNP levels increased from 2.90 +/- 0.74 to 36.43 +/- 5.51 pmol/L (P < .01) at the end of the infusion and were still elevated at the end of the postinfusion period (7.03 +/- 1.41 pmol/L, P < .05). The urinary excretion of cGMP was also significantly higher during BNP infusion. Left ventricular performance, cardiac output, arterial pressure, and peripheral vascular resistance were not affected by BNP. Peptide infusion induced a significant increase in GFR (placebo, 115 +/- 24; BNP, 147 +/- 19 mL/min), sodium excretion (placebo, 129 +/- 40; BNP, 243 +/- 60 mumol/min), and urine flow rate. All these effects were observed also in the postinfusion period. The natriuretic effect of BNP was attributable to both an increase in filtered sodium load and a reduction of distal sodium reabsorption. These results suggest that BNP may contribute to maintain renal function and sodium excretion in patients with essential hypertension.


Subject(s)
Hemodynamics/physiology , Hypertension/physiopathology , Kidney/physiology , Nerve Tissue Proteins/physiology , Adult , Creatinine/metabolism , Cross-Over Studies , Female , Heart Ventricles/physiopathology , Hormones/metabolism , Humans , Hypertension/metabolism , Infusions, Intravenous , Male , Middle Aged , Natriuretic Peptide, Brain , Nerve Tissue Proteins/administration & dosage , Single-Blind Method , Sodium/metabolism
14.
Aliment Pharmacol Ther ; 9(2): 127-35, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7605852

ABSTRACT

BACKGROUND: H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major causes of gastroduodenal injury in man. We assessed the effect of daily NSAID ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production. METHODS: Fifty-two healthy volunteers with normal baseline endoscopy were randomly assigned to receive identical-appearing naproxen 500 mg b.d., etodolac 400 mg b.d., or placebo b.d. for 4 weeks. The number and size of all erosions and ulcers were recorded by endoscopy at weeks 1 and 4. Biopsies taken at baseline, week 1 and week 4 were assessed for H. pylori, histology and gastric prostaglandin E2 production. RESULTS: No significant changes occurred with treatment in any histological feature in the three study groups or in H. pylori positive or negative subsets. Antral inflammation scores (scale, 0-6) for the NSAID group were: week 0--1.2 +/- 0.3; week 1--1.1 +/- 0.3; week 4--1.3 +/- 0.3; findings of 'chemical gastritis' were not seen. No significant difference in gross gastroduodenal injury (number or total surface area of ulcers or erosions) was seen between H. pylori positive and negative subjects in the three groups at week 1 or 4. Baseline prostaglandin E2 production was significantly higher in H. pylori positive subjects (2398 +/- 400 vs. 1064 +/- 255 pg/mg protein) and decreased significantly with 1 week of naproxen in H. pylori positive and negative subjects. CONCLUSIONS: NSAID ingestion does not cause diffuse histological injury. Any diffuse histological injury in the gastric mucosa is related to the presence of H. pylori, and this H. pylori-associated gastritis is not altered by NSAID ingestion. Furthermore, the development of gross gastroduodenal damage with 4 weeks of NSAID use is not influenced by underlying H. pylori infection.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Gastrointestinal Diseases/etiology , Helicobacter Infections/complications , Prostaglandins/metabolism , Adolescent , Adult , Aged , Double-Blind Method , Etodolac/pharmacology , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/microbiology , Helicobacter pylori , Humans , Inflammation/drug therapy , Middle Aged , Naproxen/pharmacology , Stomach Ulcer/drug therapy
15.
J Immunol ; 154(5): 2434-40, 1995 Mar 01.
Article in English | MEDLINE | ID: mdl-7868909

ABSTRACT

The etiology and pathogenesis of inflammatory bowel disease (IBD) are unknown. Increasing evidence supports the theory that chronic IBD is the result of dysfunctional immunoregulation manifested by an inappropriate production of mucosal cytokines. The aim of the present study was to test the hypothesis that a specific mucosal imbalance of IL-1 and IL-1 receptor antagonist (IL-1ra) production plays an important role in the perpetuation and chronicity of intestinal inflammation. Total IL-1, IL-1ra, and the IL-1ra/IL-1 ratio were measured in freshly isolated intestinal mucosal cells, as well as in mucosal biopsies obtained from control, Crohn's disease, and ulcerative colitis patients. IL-1 alpha, IL-1 beta, and IL-1 ra were measured by specific non-cross-reacting radioimmunoassays and ELISA. A markedly significant decrease in the intestinal mucosal IL-1ra/IL-1 ratio was found in both Crohn's disease and ulcerative colitis patients when compared with control subjects (p < 0.01). The IL-1ra/IL-1 ratio correlated closely with the clinical severity of disease (r = -0.7846, p < 0.001). Furthermore, the observed decrease in the IL-1ra/IL-1 ratio was specific for IBD because a decreased IL-1ra/IL-1 ratio was not found in patients with self-limiting colitis. These results support the hypothesis that an imbalance between IL-1 and IL-1ra production is of pathogenic importance in chronic inflammatory diseases, including IBD.


Subject(s)
Colitis, Ulcerative/immunology , Crohn Disease/immunology , Interleukin-1/metabolism , Intestinal Mucosa/immunology , Sialoglycoproteins/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Cell Separation , Colitis, Ulcerative/etiology , Colitis, Ulcerative/pathology , Crohn Disease/etiology , Crohn Disease/pathology , Female , Humans , Interleukin 1 Receptor Antagonist Protein , Intestinal Mucosa/pathology , Male , Middle Aged
17.
J Clin Invest ; 94(1): 449-53, 1994 Jul.
Article in English | MEDLINE | ID: mdl-8040288

ABSTRACT

Administration of exogenous interleukin-1 receptor antagonist (IL-1ra) is effective in reducing the severity of disease in animal models of acute inflammation. However, the function of endogenous IL-1ra in this process, is not yet known. We investigated the pathophysiological role of IL-1ra in a rabbit model of formalin-immune complex colitis. This model has previously been shown to be IL-1 mediated and a reduction in disease severity is observed with exogenous IL-1ra treatment. Colonic IL-1ra was found to be elevated subsequent to IL-1, and exceeded IL-1 levels 10-fold. Peak levels of IL-1ra preceded both the resolution of colitis and a significant decrease in IL-1 production. Administration of specific neutralizing antibodies against rabbit IL-1ra increased mortality and prolonged intestinal inflammatory responses. A significant increase in IL-1 alpha colonic tissue levels was also measured as a result of exogenous anti-IL-1ra treatment. These studies are the first demonstration that endogenous IL-1ra may play an important role in regulating the host's inflammatory response by counteracting the deleterious and possibly lethal effects of IL-1 produced during acute inflammation.


Subject(s)
Colitis/etiology , Sialoglycoproteins/physiology , Animals , Colitis/immunology , Immune Sera/immunology , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/physiology , Male , Rabbits
18.
Gastroenterology ; 104(2): 588-94, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8425702

ABSTRACT

BACKGROUND: In cirrhotic patients with ascites, captopril has deleterious effects on renal function, which have been referred to as captopril-induced arterial hypotension. The effects of this drug on renal function in cirrhosis were evaluated using low-dose captopril, thereby avoiding any change in arterial pressure. METHODS: In a randomized, double-blind, placebo controlled, cross-over trial, the effects of 12.5 mg captopril on renal plasma flow, glomerular filtration rate (measured by radioisotopic techniques), and sodium excretion in healthy controls and cirrhotic patients with and without ascites were determined. RESULTS: In healthy subjects, captopril only induced a significant, 18% increase in renal plasma flow. In contrast, glomerular filtration rate significantly decreased in patients with (from 108 +/- 7 to 78 +/- 9 mL/min) and without ascites (from 102 +/- 4 to 88 +/- 3 mL/min), whereas renal plasma flow did not change. Urinary sodium excretion also significantly decreased in ascitic patients (from 43.8 +/- 4.4 to 30.6 +/- 3.8 mumol/min). CONCLUSIONS: These data suggest that angiotensin II contributes to maintain renal hemodynamics in cirrhosis with and without ascites.


Subject(s)
Captopril/pharmacology , Kidney/drug effects , Liver Cirrhosis/physiopathology , Aged , Captopril/administration & dosage , Double-Blind Method , Female , Glomerular Filtration Rate/drug effects , Hemodynamics/drug effects , Humans , Kidney/physiopathology , Male , Middle Aged , Renal Circulation/drug effects
19.
Ann Ital Med Int ; 8(1): 38-46, 1993.
Article in English | MEDLINE | ID: mdl-8485009

ABSTRACT

Refractory ascites, that is ascites which cannot be mobilized by low sodium diet and maximal doses of diuretics (up to 400 mg spironolactone or potassium canrenoate and 160 mg furosemide per day), occurs in 5% of cirrhotic patients with ascites. The development of refractory ascites is mainly related to the progression of arterial vasodilation-mediated vascular underfilling and to the imbalance between reduced synthesis of renal vasodilating factors (especially renal prostaglandins) and extreme activation of vasoconstricting systems. Further features include increased sodium reabsorption in the proximal tubule and altered pharmacokinetics and pharmacodynamics of diuretics. In patients with impaired renal function (as is the case for most patients with refractory ascites), the marked reduction of renal perfusion and glomerular filtration rate, with the consequent decrease of filtered sodium load, becomes the main pathogenetic factor. The principal therapeutic options for refractory ascites include repeated paracentesis and implantation of the LeVeen shunt. Paracentesis is a rapid and safe procedure to remove ascites, but it does not correct sodium retention. Ascites recurrence, therefore, may occur after a brief interval. The LeVeen shunt allows for better long-term control of ascites, but severe complications may supervene, and shunt occlusion is common. Neither therapeutic procedure improves survival. Different experimental therapeutic procedures have been proposed. Administration of ornipressin corrects hyperdynamic circulation and improves renal function. Thromboxane synthase inhibitors, by reducing renal synthesis of thromboxane A2, potentiate the diuretic and natriuretic response to furosemide. More invasive procedures, including portosystemic shunt and transjugular intrahepatic stent, are rarely used in the treatment of refractory ascites.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Ascites/etiology , Ascites/physiopathology , Ascites/therapy , Diuretics/therapeutic use , Drug Resistance , Hemodynamics , Humans , Kidney/physiopathology , Liver Cirrhosis/complications , Liver Cirrhosis/physiopathology , Natriuresis , Prognosis , Renal Insufficiency/etiology , Renal Insufficiency/physiopathology , Vasodilation
20.
Hepatology ; 16(1): 156-61, 1992 Jul.
Article in English | MEDLINE | ID: mdl-1618467

ABSTRACT

Plasma levels of brain natriuretic peptide, a recently identified cardiac hormone with natriuretic activity, were measured in 11 healthy subjects, 13 cirrhotic patients without ascites, 18 nonazotemic cirrhotic patients with ascites and 6 patients with cirrhosis, ascites and functional kidney failure. Plasma levels of brain natriuretic peptide were similar in healthy subjects and cirrhotic patients without ascites (5.56 +/- 0.65 and 7.66 +/- 0.68 fmol/ml, respectively). In contrast, cirrhotic patients with ascites, with and without functional kidney failure, had significantly higher plasma concentrations of brain natriuretic peptide (19.56 +/- 1.37 and 16.00 +/- 1.91 fmol/ml, respectively) than did healthy subjects and patients without ascites (p less than 0.01); no significant difference was found between the two groups of cirrhotic patients with ascites with respect to this parameter. In the whole group of cirrhotic patients included in the study, brain natriuretic peptide level was directly correlated with the degree of impairment of liver and kidney function, plasma renin activity and plasma levels of aldosterone and atrial natriuretic peptide. The results of this study indicate that brain natriuretic peptide is increased in cirrhotic patients with ascites and suggest that sodium retention in cirrhosis is not due to deficiency of this novel cardiac hormone.


Subject(s)
Liver Cirrhosis/blood , Nerve Tissue Proteins/blood , Alanine Transaminase/blood , Aldosterone/blood , Alkaline Phosphatase/blood , Ascites , Aspartate Aminotransferases/blood , Bilirubin/blood , Biomarkers/blood , Blood Pressure , Creatinine/metabolism , Diuresis , Electrolytes/blood , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/complications , Liver Cirrhosis/complications , Liver Cirrhosis/physiopathology , Liver Function Tests , Male , Middle Aged , Natriuretic Peptide, Brain , Prothrombin Time , Reference Values , Renin/blood
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