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Foot ulcers associated with Diabetes mellitus require immediate attention due to risk of amputation if left untreated. Herein we focus on the mitigating risk factors and physiopathology of the diabetic foot, recounting our own surgical approach and revascularization procedures.

The objective of this work is to evaluate in a selection of patients with erectile dysfunction the influence of alcohol consumption and the response to alcohol abstinence with and without sildenafil association. Materials and Methods. In a population of 150 consecutive patients with erectile dysfunction we studied 50 patients aged between 22 and 77 years (mean 56±14 SD). These 50 patients were divided into three different treatment groups and were screened for three different levels of alcohol risk with two questionnaires. All patients were evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire before and after one month of treatment. Results. The 50 patients included 14 patients with high alcohol risk, 34 patients with low alcohol risk and only 2 patients with no alcohol risk. After one month, 29 patients responded to the therapy, and 21 did not respond. The IIEF questionnaire presented a statistically significant difference between the different risk groups before and after treatment (p≤0.05). All the patients were examined with a penile Doppler Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11 patients did not respond to therapies and 10 of them were at high alcohol risk. The alcohol consumption risk was directly correlated with PDV (p=0.00001; R=0.4). Conclusions. The results of this study demonstrated a significant relationship between alcohol consumption and erectile dysfunction. This underlines the important therapeutic issue of alcohol abstinence in treating patients with erectile dysfunction.

Renal artery aneurysms (RAA) are rare (general population incidence is 0.09%). At this time, the appropriateness of the type of intervention ‑ surgical or endovascular ‑ is based on single center experiences rather than large randomized trials. Endovascular therapy offers less morbidity but surgery has excellent long-term results. In reality, the choice of the treatment relies on the operative risk. A patient with a RAA and good surgical risk should be offered open surgery. If the patient is deemed to be at high risk from surgery then the choice of the type of endovascular treatment (stent grafting, coil/glue embolization, multilayer stenting) should be based on the location and shape of the RAA. RAA should be treated by surgeons/interventionalists who have demonstrated expertise in renal artery procedures.

The objective of this work is to evaluate in a selection of patients with erectile dysfunction the influence of alcohol consumption and the response to alcohol abstinence with and without sildenafil association. Materials and Methods. In a population of 150 consecutive patients with erectile dysfunction we studied 50 patients aged between 22 and 77 years (mean 56±14 SD). These 50 patients were divided into three different treatment groups and were screened for three different levels of alcohol risk with two questionnaires. All patients were evaluated with an International Index Erectile Dysfunction (IIEF) questionnaire before and after one month of treatment. RESULTS. The 50 patients included 14 patients with high alcohol risk, 34 patients with low alcohol risk and only 2 patients with no alcohol risk. After one month, 29 patients responded to the therapy, and 21 did not respond. The IIEF questionnaire presented a statistically significant difference between the different risk groups before and after treatment (p≤0.05). All the patients were examined with a penile Doppler Ultrasound. Only 10 of them had an abnormal diastolic peak velocity (PDV) and only 1 presented both pathologic systolic peak velocity (PSV) and PDV. These 11 patients did not respond to therapies and 10 of them were at high alcohol risk. The alcohol consumption risk was directly correlated with PDV (p=0.00001; R2=0.4). CONCLUSIONS. The results of this study demonstrated a significant relationship between alcohol consumption and erectile dysfunction. This underlines the important therapeutic issue of alcohol abstinence in treating patients with erectile dysfunction.

A lactose-free diet is commonly prescribed to subjects with hypolactasia. We tested the effectiveness of a single ingestion of tilactase (a beta-D-galactosidase from Aspergillus oryzae) in adults with hypolactasia, previously assessed by lactose H(2)-breath test.After measurement of orocecal transit time (OCTT, by lactulose H(2)-breath test) and lactose H(2)-breath testing plus placebo, a total of 134 subjects were positive to hypolactasia and underwent lactose H(2)-breath testing plus either low (6750 U) or standard (11,250 U) doses of tilactase. The appearance of gastrointestinal symptoms during the tests was monitored.OCTT was longer in malabsorbers (subjects without bloating, abdominal pain and/or diarrhoea, n = 25) than in intolerants (bloating, abdominal pain and/or diarrhoea, n = 109, P0.02). Malabsorbers had longer time to H(2) peak (P0.03), lower H(2) peak levels (P0.002) and smaller integrated H(2) excretion levels (P0.005) than intolerants. After tilactase ingestion, integrated H(2) levels were decreased by 75% (low dose) and 87% (standard dose) in malabsorbers, and by 74% (low dose) and 88% (standard dose) in intolerants. In the latter group, total symptom score were decreased by 76% (low dose) and by 88% (standard dose) (P0.0001).A single oral administration of tilactase is highly effective in decreasing symptoms and hydrogen excretion of hypolactasia assessed by lactose H(2)-breath test. If confirmed by long-term observations, ingestion of tilactase might be a better option than exclusion diets in intolerant subjects with hypolactasia.

The biological importance of the aquaporin family of water channels was recently acknowledged by the 2003 Nobel Prize for Chemistry awarded to the discovering scientist Peter Agre. Among the pleiotropic roles exerted by aquaporins in nature in both health and disease, the review addresses the latest acquisitions about the expression and regulation, as well as physiology and pathophysiology of aquaporins in the hepatobiliary tract. Of note, at least seven out of the thirteen mammalian aquaporins are expressed in the liver, bile ducts and gallbladder. Aquaporins are essential for bile water secretion and reabsorption, as well as for plasma glycerol uptake by the hepatocyte and its conversion to glucose during starvation. Novel data are emerging regarding the physio-pathological involvement of aquaporins in multiple diseases such as cholestases, liver cirrhosis, obesity and insulin resistance, fatty liver, gallstone formation and even microparasite invasion of intrahepatic bile ducts. This body of knowledge represents the mainstay of present and future research in a rapidly expanding field.

Angiotensin converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARB) are considered to be equally effective for patients with diabetic kidney disease, while only ACE-i have been shown to determine a significant reduction in the risk of all-cause mortality, predominantly cardiovascular, in these patients. Studies on the cardio-renal efficacy of combined therapy with ACE-i and ARB are not available or not conclusive, in a population with cardiovascular risk with micro- or macroalbuminuria. In this paper, we present the protocol of a randomized controlled clinical trial that will address the question. The LIRICO (Long-term Impact of RAS Inhibition on Cardiorenal Outcomes) study will evaluate the comparative efficacy for cardiovascular and renal outcomes of combined therapy with ACE-i and ARB versus monotherapy with ACE-i or ARB in micro/macroalbuminuric individuals at cardio-renal risk. The study will enrol 2100 patients allocated to monotherapy with ACE-i, ARB or combined treatment with ACE-i + ARB. The LIRICO study is a randomized comparative trial, with PROBE (Prospective Randomized Open Blinded End-Point) design. The study has been approved and funded by the Agenzia Italiana del Farmaco (AIFA) within the 2005 funding plan for independent research on drugs. Availability of funding for this study provides, for the first time in our Country, an opportunity to organize a collaborative national network of nephrology, internal medicine and diabetology outpatient clinics to develop a large multicentre trial collaboration. The results of this trial will establish the optimal therapy for micro/macroalbuminuric individuals with cardiovascular and renal risk.

The aim of this study was to evaluate the technical success and clinical outcome of surgical revascularization, angioplasty and/or stenting for renal artery stenosis (RAS) in patients with renovascular hypertension (RVH). The secondary aim was to identify independent negative predictors of blood pressure control after successful renal revascularization.From January 1998 to July 2006, we treated 97 cases of RAS in 83 RVH patients. Inclusion criteria were RASor =80% associated with hypertension refractory to medical control with at least three drugs including a diuretic. Therapeutic options were surgical revascularization in 15 cases (11 renal endarterectomies, 4 aortorenal bypasses) and endoluminal treatment in 82 (14 balloon angioplasties, 68 stents).Technical success was 100% for both surgical and endovascular procedures; 13 cases of restenosis (or =80%) were detected: 12 (14.6%) in the endoluminal group and one (6.6%) in the surgical group (P=0.68). During the follow-up period (average 37 months, range 6-94), blood pressure control improved in 43% of patients, disease stabilized in 37% and the natural course of RVH deteriorated in 20%. Multivariate Cox regression analysis showed that only a long history of antihypertensive drug use was a predictor of inefficacy of blood pressure control after revascularization (P0.04).The complete resolution of RVH associated with severe RAS appears unrealistic in several cases. Early and long-term results in terms of technical success and restenosis were acceptable and similar for surgical and endovascular renal intervention. An early diagnosis of RVH could improve the control of hypertension after successful renal revascularization.

The clinical aspects and the diagnostic features of gallstone disease are described. The natural history of silent gallstones is overviewed, and the risk of developing symptoms and complications is also discussed. The importance of colicky pain as a specific gallstone symptom is highlighted, and the role of both laboratory tests and diagnostic investigations for differential diagnosis is discussed. Finally, we describe the diagnostic features of gallbladder stone disease, including indications, sensitivity, specificity, and limitations of different test investigations under special circumstances.

Accidental aspiration of fuel in fire eaters can cause an acute chemical pneumonitis known as 'fire-eater's pneumonia". We report a case in a 29 year-old fire-eater. Six hours after aspiration of kerosene, he developed fever up to 39,5 degrees C, dyspnea, cough and chest pain. Chest radiograph showed infiltrates in the middle and lower parts of the lungs and left pleural effusion. He was treated with an antibiotic and antipiretic therapy and then with corticosteroids. The acute stage lasted four weeks and the patient recovered without sequelae within 3 months. Hazard related to main fuels used for fire eating is discussed.

The Quality Guide, a strategic tool for any nephrologist wishing to initiate a quality policy in his own renal unit, describes to the organisation of total quality management. This article gives a short description of a Quality Guide in Nephrology and Dialysis. According to ISO 9004:2000 Norms, the Quality Guide can be subdivided into four sections: Managerial Accountability, Resource Management; Implementation of Services; Analysis, Evaluation and Continuous Quality Improvement. The quality cycle begins by identifying the customers, who added to the resources constitute the input that will be transformed by the service into output (results). By measuring customer satisfaction the results will be evaluated and analyzed to allow continuous improvement of the service. In conclusion, the drafting of the Guide by all staff members involved has a twofold value: it organizes the quality management within the renal unit and certifies the quality level guaranteed to the customer.

Erythrocyte membrane modifications in patients with cholestasis are supposed to reflect those of hepatocytes.Erythrocyte membrane composition (cholesterol, phospholipids, fatty acids, protein sulphydrils and carbonyls) was assessed and related to the stage of liver disease in patients with primary biliary cirrhosis before and after 1 year of ursodeoxycholate treatment.Compared with controls, patients showed lower levels of protein sulphydrils (28.9 +/- 7.1 vs. 65.6 +/- 1.8 nmol mg(-1) prot) and accumulation of carbonyls (4.7 +/- 1.7 vs. 1.4 +/- 0.1 nmol mg(-1) prot). Phosphatidylethanolamine level was lower in stage III-IV cirrhosis while phosphatidylcholine and cholesterol levels were higher; as a consequence the phosphatidylcholine/sphingomyelin ratio was higher than in controls (4.25 +/- 0.55 in the I-II stage and 2.89 +/- 0.44 in the stage III-IV vs. 1.61 +/- 0.30). These changes were particularly evident in patients with more advanced stages of liver disease. Protein sulphydrils and carbonyls, phosphatidylethanolamine and cholesterol levels correlated (P0.05) with the histological stage of the liver disease, serum and membrane cholesterol levels were significantly related (r=0.66, P0.05). One year of ursodeoxycholate administration was accompanied by major changes of the membrane lipid composition, partial reversal of protein oxidation, and improvement of serum parameters.This study indicates that major alterations in protein status and lipid composition occur in erythrocyte membrane of patients with primary biliary cirrhosis. These changes were more pronounced in patients with advanced liver disease. Ursodeoxycholate was able to revert in part serum and erythrocyte alterations, especially in patients with early stages of liver disease.

Fatty accumulation per se does not appear to affect liver function; however, interest has recently renewed to fatty liver because of the clinical relevance of non alcoholic steato-hepatitis (NASH) and for the increased risk of post-transplant failure in grafted livers with steatosis. Clinical and experimental studies have doubtless demonstrated that oxidative stress ensues in steatotic livers. Mitochondria represent the preferential target of the oxidative injury associated to fatty degeneration and show reduced content of glutathione, higher levels of oxidative products and damages to enzymes involved in the process of ATP synthesis, which become more evident under stressing conditions. Although obese patients with fatty liver are advantaged by weight loss, clinical and experimental observations suggest that fatty livers poorly tolerate excessive food deprivation. These observations represent the rationale for treatment strategies based on the supplementation of antioxidants and energetic substrates rather than solely a diet restriction. This review focuses on data emerging from a series of investigations performed in rats with fatty livers induced by a choline-deficient diet, which resembles human steatosis due to an excessive intake of carbohydrates, and aims to give the cue for the development of therapeutic options able to preserve hepatic function after transplantation of steatotic organs.

In rodents, interleukins administration induces intestinal changes similar to those found in inflammatory bowel disease. We investigated the effects of in vivo subchronic treatment with IL-1 beta and IL-6 on rat colonic mucosa and circular smooth muscle.We evaluated transmucosal electrical parameters (Ussing chambers) and early changes of in vitro direct contractility induced by carbachol and tachykinins. Alterations in excitatory and inhibitory neurotransmission were studied with electrical field stimulation (EFS).Treatment with interleukins induces inflammation proved by fever, early signs of colonic histological damage and changes in mucosal ion transport. Concentration response-curve to carbachol was significantly lower in treated rats (P0.02) with significant difference in Emax between control (1.67+/-0.17 g) and treated preparations (1.20+/-0.13 g) (P0.05). Concentration response-curve to NK2 agonist was significantly lower in the treated rats (P0.005) with a significant difference in Emax between the control (0.26+/-0.04 g) and treated preparations (0.12+/-0.02 g) (P0.02). None of the drugs used induces changes in EC50. The contractile reflex response to electrically induced distension was significantly higher in the treated rats and more reduced after administration of atropine. Adding NK2 receptor antagonist resulted in a further reduction being observed in the treated and control rats (P=NS). Relaxation by EFS on cholinergic tone was not different between treatments, although pretreatment with L-NNA resulted in greater relaxation in the treated (-21.7%) than in the control rats (-14.8%).Early inflammation induced by a subchronic treatment with ILs causes changes in mucosal ionic transport parameters, a reduction in the direct contractile response, and an alteration in the neurotransmission (by an enhancing cholinergic component) that may affect the physiological pattern of colonic motility and the sensory reflex.

High fecal deoxycholate levels may promote colonic cancer. Phospholipids protect against bile salt-induced cytotoxicity. We therefore aimed to examine whether the dietary phospholipid sphingomyelin could decrease hyperproliferation induced by deoxycholate. In CaCo2 cells, hyperproliferation (by bromodeoxyuridine assay), phosphorylation state of cellular proteins, and apoptosis with concomitant caspase-3 activity were evaluated after incubation with 50-500 microM deoxycholate, with or without sphingomyelin. At 2 and 4 hr of incubation, deoxycholate induced dose-dependent apoptosis, with concomitant caspase-3 activation. At 16 hr, apoptosis had decreased markedly, but there was dose-dependent hyperproliferation (with changed phosphorylation status of cellular proteins) at this time point. Sphingomyelin dose-dependently reduced deoxycholate-induced apoptosis and hyperproliferation. In conclusion, sphingomyelin reduces deoxycholate-induced hyperproliferation and apoptosis. These findings may have implications for colonic cancer prevention by dietary modification.

Patients with colonic inertia, the most severe form of chronic functional constipation, may present with a more diffuse panenteric motility disorder. We describe a case of a woman with severe longstanding colonic inertia associated with chronic functional dyspepsia and defective gastric, gallbladder and small intestinal motility, as confirmed by several diagnostic tests including two breath tests with the 13C-stable isotope. A subclinical form of authonomic sympathetic neuropathy was diagnosed, providing a possible pathophysiological explanation for the presence of simultaneous multiple motility defects of the gastrointestinal tract.

Transient alterations of gallbladder morphology and dynamics have been reported in patients with during acute hepatitis A. The presence of dyspepsia also suggests involvement of gastric motility. During a 60-day follow-up, we investigated gallbladder and gastric motility in relation to dyspepsia in acute viral hepatitis A patients. Twenty patients were assessed at referral (day 0) and at days 7, 21, 42 and 60 and compared with 20 healthy volunteers. Gallbladder morphology and motility and gastric motility were assessed in the fasting and postprandial period by functional ultrasonography using a liquid test meal. Dyspeptic symptoms were scored. At day 0, fasting gallbladder volume was 5.9 +/- 1.3 mL, 32.6 +/- 4.6 mL, and 21.5 +/- 1.9 mL (mean +/- SE) in patients with gallbladder sludge (n = 7), without sludge (n = 13) and controls, respectively (P0.05 in sludge vs. no sludge and controls; P0.05 in no sludge vs. controls, ANOVA). Small fasting gallbladder volume in patients with sludge increased and sludge disappeared within 7 days. At day 0, patients with sludge also had increased thickness of fasting gallbladder wall and increased serum transaminase levels compared with patients without sludge and controls. Gallbladder contraction was similar in patients and controls. However, patients had delayed gastric emptying, which positively correlated with dyspepsia score. Gallbladder morphological changes observed in the acute phase of hepatitis A are transient and are associated with hepatocellular damage. Gastric emptying is delayed during the first week of disease and is associated with dyspeptic symptoms.

The interplay between contraction and relaxation in the gall-bladder muscularis leads to appropriate gall-bladder emptying and refilling during fasting and in the postprandial state in vivo. Several studies in both human and animal models have focused on cellular and molecular events in the gall-bladder wall in health and disease in vitro. Principal methods to study gall-bladder smooth muscle function include receptor binding studies (at the level of plasmamembranes or histological sections), phase contrast microscopy (at the level of isolated smooth muscle cells), and tensiometry (at the level of smooth muscle strips or the whole gall-bladder). At a very early stage, cholesterol gallstone disease is characterized by exposure of the gall-bladder wall to excess of biliary cholesterol and the cytotoxic effect of the bile salt deoxycholate. On a long-term basis, a form of gall-bladder leiomyopathy develops with defects involving the mechanisms of signal transduction at the level of plasmamembranes. The end-stage result is pathological contraction and/or relaxation of smooth musculature, impaired gall-bladder motility and gall-bladder stasis, all key factors in the pathogenesis of biliary cholesterol crystallization and gallstones.

Little is known about gallbladder motility in patients with black pigment stones when compared to cholesterol gallstone patients, or about their relationship to biliary composition, crystallization and stone characteristics.Fasting and postprandial gallbladder volumes were studied by ultrasonography in 49 gallstone patients with pigment (n = 14) or cholesterol (n = 35) stones and 30 healthy controls. After cholecystectomy stone composition, gallbladder wall inflammation, cholesterol saturation index and appearance of platelike cholesterol crystals in bile were evaluated in gallstone patients.Fasting gallbladder volume was significantly (P0.05) increased in cholesterol stone patients (31.7 +/- 1.9 mL) but not in pigment stone patients (21.9 +/- 3.1 mL), compared to controls (21.0 +/- 1.5 mL). Postprandial emptying was delayed in patients (half-emptying time: 31 +/- 2 min, 35 +/- 3 min, 24 +/- 2 min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05) and incomplete (residual volume: 43.2 +/- 2.7%, 40.0 +/- 4.3%, 15.8 +/- 1.6% min in cholesterol stone patients, pigment stone patients and controls, respectively, P0.05). The inflammation of the gallbladder wall was mild or absent in all cases. Biliary cholesterol saturation index was 152.3 +/- 8.5% and 92.9 +/- 4.8% in patients with cholesterol and pigment stones, respectively (P0.01). Whereas cholesterol crystals never appeared during 21 days in biles from patients with pigment stones, crystal observation time in patients with cholesterol gallstone was 5 days (median) and was significantly shorter in patients with multiple (4 days) than in patients with solitary (12 days) cholesterol stones (P = 0.0019).Patients with black pigment stones who do not have excess cholesterol and do not grow cholesterol crystals in bile have decreased gallbladder emptying, although to a lesser extent than patients with cholesterol stones. Thus, gallbladder stasis is likely to put a subset of subjects at risk for the formation of pigment gallstones, and pathogenic mechanisms need to be further investigated.

In the last year at the Department of Surgery of the University of Siena two patients presenting a clinical feature of intestinal infarct have been operated. In these patients a wide intestinal resection has been performed. After this surgical operation, a patient had a residual tract of 40 cm of bowel and the other 50 cm. It was not possible during operation to preserve the Bauin valve in a case; in the other, this valve has been sacrificed during a previous operation for cecal neoplasm. In the postoperative period, patients were transferred temporarily in the intensive care unit, and after some days they returned to the department where total parenteral nutrition with progressive decreasing mixture in calories over time was administered. Enteral nutrition was also started and the quantity of water, calories and azote was slavly increased. In a second time an oral diet was started up to completely weaning from parenteral and then enteral nutrition. At present, these patients are enlisted in quarterly follow-up and are completely stabilized. They are independent from artificial nutrition and they have a good quality of life.

The primum movens in cholesterol gallstone formation is hepatic cholesterol hypersecretion and chronic supersaturation of bile. A cascade of events will then include: (i) multiple biochemical defects: increased total biliary proteins (and qualitative shift to cholesterol crystallization-promoting factors), increased proportions of hydrophobic bile salts, increased mucin secretion, and rapid nucleation/crystallization of cholesterol from cholesterol-enriched biliary vesicles; (ii) multiple motility defects: impaired gallbladder contractility in vitro and gallbladder stasis in vivo, delayed intestinal transit. A genetic predisposition (together with environmental factors) might also be important. Therapy should be offered to patients with symptomatic gallstones. Cholecystectomy remains the only radical therapy for cholelithiasis. For a subgroup of patients with symptomatic, uncomplicated cholesterol stones who are unwilling to undergo surgery, or who have a significant surgical risk, alternative non-invasive therapies include: (i) oral litholysis of small stones by bile salts, (ii) fragmentation of 1-3 medium-sized stones by extracorporeal shock-wave lithotripsy, and (iii) topical dissolution of multiple stones by methyl tertbutyl ether. A major disadvantage of all non-surgical therapies, however, is the 50% recurrence rate of stones at 5 years. A number of prokinetic agents can improve gallbladder and/or intestine transit, two important contributing factors in gallstone disease. In selected patients, administration of these agents might enhance the clearance of cholesterol crystals/gallstones or might impede/delay gallstone formation and recurrence.

We describe the role of US, in the diagnosis of LMPR and in differentiating LMPR from other renal disease, such as hydronephrosis and parapelvic cysts. In 10 patients mild to moderate hydronephrosis showed at the US, bilateral in 8 cases, was not confirmed at IVP and CT scan evaluation. Instead, compression of the collecting system by multiple cysts arising from the renal sinus was revealed by CT scan in 8 cases and by IVP in 2. At the U.S. the profile of the calices appeared irregular, differing from the features of hydronephrosis; furthermore calices were adjacent each other, separated only by a thin membrane. All patients were asymptomatic. The examination of the cystic liquor and wall, obtained percutaneously or during surgical procedures, showed the lymphatic origin of them. We cannot provide definitive data regarding how to differentiate LMPR from hydronephrosis at U.S.. In asymptomatic patients the U.S. evidence of dilated calices with irregular profile and thin membrane separating each other, can strongly suggest the diagnosis of LMPR.

Fasting and postprandial gallbladder volumes have been measured by sonography both in healthy subjects and gallstone patients ingesting: (a) tauroursodeoxycholic acid; (b) ursodeoxycholic acid; (c) placebo. Each bile salt was given at a dose of 10 mg kg-1. Sonography was repeated in gallstone patients fed tauroursodeoxycholic acid or ursodeoxycholic acid (10 mg kg-1 day-1) for 1 month. Gallstone patients had gallbladder stasis (increase in fasting and residual volumes) and decreased postprandial emptying. Acute ingestion of tauroursodeoxycholic acid or ursodeoxycholic acid did not modify postprandial gallbladder emptying in both groups of subjects. After one month's therapy with tauroursodeoxycholic acid or ursodeoxycholic acid, fasting gallbladder volume further increased in gallstone patients, although gallbladder emptying remained unchanged. Thus, therapeutic doses of tauroursodeoxycholic acid or ursodeoxycholic acid do not acutely modify postprandial gallbladder emptying in either healthy subjects or gallstone patients. Chronic treatment with either bile salts results in an increase in fasting gallbladder volume without interfering with the extent of postprandial gallbladder emptying.

To evaluate whether a low dose of oral cholestyramine improves gallbladder emptying in gallstone patients.Gallbladder volumes were assessed by sonography in 36 patients with cholesterol gallstones and 18 healthy controls. On three different days subjects ingested: 1) test meal alone, 2) test meal plus cholestyramine (4 g), and 3) cholestyramine alone (4 g).Fasting gallbladder volume (mean +/- SE, 25.9 +/- 1.8 ml and 19.2 +/- 1.3 ml for patients and controls, respectively, p0.05) and postprandial gallbladder residual volume (48.7 +/- 3.9% and 21.6 +/- 2.8% of fasting volume in patients and controls, respectively, p0.001) were larger in patients than controls, indicating impaired gallbladder emptying. Gallstone patients were divided into 19 "contractors" and 17 "hypocontractors" (residual gallbladder volume smaller or greater than mean +/- 2 SD of controls). Compared with the test meal alone, the addition of cholestyramine induced a further decrease of residual volume in contractors (from 30.4 +/- 2.1% to 19.8 +/- 1.9%, p0.001), hypocontractors (from 69.3 +/- 3.9% to 56.7 +/- 7.4%, p0.05), and controls (from 21.6 +/- 2.8% to 5.0 +/- 1.0%, p0.0004). Two hours after test meal plus cholestyramine gallbladder volume was still markedly reduced in both patients and controls. Fasting gallbladder volume 24 h after test meal plus cholestyramine was decreased in patients and in controls. The ingestion of cholestyramine alone initiated gallbladder evacuation comparable to that of test meal in both contractors and hypocontractors.A low dose of cholestyramine in combination with test meal induces a considerable decrement of gallbladder volume compared with test meal alone in gallstone patients. Cholestyramine alone causes a decrease of gallbladder volume which is comparable to that observed in response to test meal alone.

A prospective blind study was performed to compare sonographic with postoperative findings of gallstone burden in 34 patients (10 males, 24 females; mean age 52 years). Gallstone size was assessed in single calculi (n = 15) by measuring the largest diameter by ultrasonography (US). The ellipsoid algorithm was used to estimate US volume for both single and multiple gallstones. After cholecystectomy, diameters were measured in single stones; stone volume was assessed by the ellipsoid formula (single stones) and fluid displacement (single and multiple stones). Stone volumes assessed by the ellipsoid formula and fluid displacement correlated closely (r = 0.98; p0.0001, n = 15). In the case of single gallstones, the mean length assessed by US was 25.3 +/- 3.2 mm and compared well with the value measured "in vitro" (24.8 +/- 3.1 mm). A highly significant and positive relationship existed between the sonographic size and the true stone size (r = 0.93; p0.0001, n = 15). Stone volumes assessed "in vivo" and by fluid displacement were comparable and correlated for both single (US: 6.6 +/- 1.3 vs fluid displacement: 5.8 +/- 1.4 ml; r = 0.79; p0.0005, n = 15) and multiple stones (US: 3.8 +/- 0.8 vs fluid displacement: 3.7 +/- 0.8 ml; r = 0.85; p0.0001, n = 19).(ABSTRACT TRUNCATED AT 250 WORDS)

Crystalline lactulose (Laevolac Cristalli, CAS 4618-18-2), a pure form of the disaccharide widely employed in the therapy of complications of liver cirrhosis, was administered, after a pharmacological wash-out of 10 days and following a randomized design, to 10 cirrhotic patients for 30 days at the dosage of 60 g/d, while another 10 subjects with similar characteristics received no treatment. Besides the parameters usually monitored for the evaluation of liver function and state of hepatic encephalopathy, immunological patterns such as lymphocyte subpopulations CD3, CD4, CD8, CD16(NK), CD25 and antibacterial activity against Ty2 strain of Salmonella typhi were evaluated. At the end of the study (day 30) a significant decrease of blood ammonia was observed, as expected, only in the group treated with lactulose with respect to the control group, as well as a significant increase of CD16 and antibacterial activity (1/3); an enhanced level of CD25, although not significant, was also noticed in the treated group with respect to the control group. These findings seem to show an effect of activation on cell-mediated immune system depressed during liver cirrhosis, produced by lactulose. Further studies are needed to confirm these data and to clarify the possible mechanisms involved.

The influence of gender, age, body size, cholelithiasis, and obesity on fasting gallbladder volume (GBV) was investigated by real-time ultrasonography in a general population cohort of subjects whose ages were between 30 and 69 yr, living in Bari, a Southeastern Italian city. Of the 2076 subjects analyzed, 1246 (60%) were males and 830 (40%) were females (mean age 50 yr). Among them, 1703 subjects were healthy, 108 had gallstones, and 265 were obese. Fasting GBV in healthy individuals was larger in males (M) than in females (F) [M, 18.7 +/- 0.3 (SEM) ml vs. F, 17.0 +/- 0.3 ml; p less than 0.001] and obese (M, 23.4 +/- 1.5 ml vs. 19.7 +/- 0.9 ml; p less than 0.05). The trend was similar in gallstone patients, but it was not statistically significant (M, 23.0 +/- 2.0 ml vs. F, 18.8 +/- 1.5 ml; t = 1.64). Gallbladder size correlated positively with body size in the lean healthy population (p less than 0.01), increased with age in healthy nonobese males (p less than 0.01), and was smaller in healthy males than in males with gallstones (0.01 less than p less than 0.02) and obese, in both sexes (p less than 0.01). We conclude that fasting GBV 1) is larger in lean healthy and obese males than females, 2) increases with age in lean males and with body size in healthy lean females, and 3) is greater in patients with gallstones and in obese subjects, and this might partially account for the defective gallbladder motor function reported in these patients.

The effects of niperotidine, a novel histamine H2-receptor antagonist, on nocturnal gastric acid secretion in healthy volunteers, have been investigated. Twenty subjects were randomly assigned to the placebo (M:F = 7:3; Age 34 +/- SD3 yrs) or to the niperotidine-treated group (M:F = 7:3; Age: 37 +/- 6 yrs) in which 460 mg were administered at 22.00. Intragastric acidity was assessed by means of 24-hour pH-measurement (10.00-22.00) using sensitive antimony monocrystalline electrodes. The percentage of daytime gastric acidity (prandial and interprandial) was similar in both groups (median; interquartile range): placebo group 87.5; 69.5-90.1 vs niperotidine 85.8; 59-89.1. Niperotidine increased the intragastric pH during the period 22.00-10.00. The percentage of time above pH 4 was higher in the treated group (28.4; 14.8-50.7% vs 7.4; 1.4-10.7%; p less than 0.02). The duration of niperotidine action was 5 to 7 hours. The nocturnal pH frequency curve after niperotidine was shifted toward alkaline values with a decrease of acidity in the pH range 1-2 (p less than 0.04). We conclude that a bedtime dose of niperotidine inhibits nocturnal gastric acid secretion in healthy subjects.

The effect of a novel CCK-antagonist (lorglumide, CR 1409) was evaluated by "in vitro" tensiometric studies on 16 human (gallstone patients) and 12 guinea pig gallbladder smooth muscle strips. In the animal experiments, increasing doses of lorglumide (0.2-6.5 uM) caused a rightward shift of the dose-response curves of CCK-OP, with an increase of the ED50 from 8.2 nM +/- 1.62 SEM, n = 12; to 100 nM +/- 12, n = 4) without affecting the maximal effect (Emax). Schild plot gave an affinity constant of 7.19. In human gallbladders, the effect of lorglumide was also present (ED50 increased from 47 nM +/- 8 SEM, n = 16; to 300 nM +/- 10 SEM, n = 4) coexisting with a large inter-sample variation for CCK-OP ED50s and maximal contractions, most likely due to the histological changes of the wall in chronic cholecystitis. The affinity constant was similar to that found in animal experiments. We confirm the studies previously reported in animals on the existence of a competitive antagonism of lorglumide on CCK gallbladder receptors. Moreover, our results on gallbladders from gallstone patients show that lorglumide is a highly effective antagonist of CCK-induced contractions despite the presence of chronic cholecystitis. Our study might help for a better comprehension of the role of these new anti-CCK drugs in the treatment of biliary pain.

The Authors describe an optimized procedure for the isolation of rat pancreatic acini and the preliminary results concerning the functional characterization of the cells. Isolation is carried out by two sequential digestive steps in a KREBS modified medium containing collagenase, separated by an intermediate step in which acini separation is fostered by incubation in a Ca++ free medium containing the Ca++ chelator EDTA. Final separation is obtained through the application of mechanical forces by aspirating the suspension in plastic pipettes. The choice of the collagenase, the duration and the entity of the mechanical dissociation strength are the main modifications to the classic procedure and allow to obtain a very high yield of cells maintaining their ability to secrete enzymes for a long period (6-7 hours). Functional characterization is completed mainly by the determination of the amylase release stimulated by increasing doses of cholecystokinin.

A fluorimetric method for the study of intracellular Ca++ metabolism in rat pancreatic acini is described. Following previous reports on the utilization of the new intracellularly trapped fluorescent dye fura2 in human lymphocytes, the authors point out the relevance of the cellular and fura2 concentration as critical issues for an accurate evaluation of Ca++ homeostasis. A dose-response curve to both carbamoylcholine and cholecystokinin is reported, demonstrating the ability of the cells to respond to hormonal stimulation with a transient Ca++ peak. The almost complete absence of noise in the recorded traces allow to carry out an evaluation of the intracellular mechanism related to Ca++ mobilization with a very high sensitivity.

Purpose Hemolysis is a frequent adverse effect of ribavirin (RBV). Oxidative stress has been suggested to play a role, but mechanisms and predictive risk factors are unknown. Methods: Markers of redox status were determined in erythrocytes from hepatitis C infected patients with and without G6PD-deficiency before and during RBV treatment, and erythrocytes were incubated with RBV and dipyridamole, diethylmaleate or glutathione ester. Results: 5 out of 30 patients developed major RBV-induced hemolysis, which was associated with a more pronounced increase in thiobarbituric acid reactive substances (+22.5 vs. +9.4 nmol/gHb, p

The contribution of echotomography in the surgical approach to intra-abdominal masses is illustrated through description of several clinical observations. In order to effect frontal reconstruction of ultrasonic seriography, the authors used a manual-scanning B echotomograph probe working in the range of grays. This technic afforded detection of the intraperitoneal and extraperitoneal abdominal masses under investigation as well as precise definition of their location, size, and nature. Because of its rapidity and painlessness, echotomography should be adopted as firstchoice procedure for the diagnostic exploration of intraabdominal masses. Frontal reconstruction enables the surgeon to verify the topography of said masses with remarkable precision, and hence to plan surgery more intelligently.

Calcitonin (CT) is a 32 amino acidic polypeptide hormone which has been found in almost all species and whose effects are mainly concerned with calcium and phosphorous homeostasis. Three preparations are employed for therapeutic uses: salmon (sCT), porcine (pCT) and human CT (hCT). The sCT is the most powerful one and in human volunteers a strong relaxing effect has been shown on gallbladder (GB) basal volume and emptying in response to a meal, intraduodenal instillation of a liquid meal and i.v. cholecystokinin (CCK) infusion. Our study was aimed at investigating if a direct sCT effect could be demonstrated on smooth muscle strips from guinea pig GBs "in vitro" (organ bath). Isometric contractions were measured in response to maximal doses of acetylcholine (ACh: 10(-4) M), KCl (80 mM) and cholecystokinin octapeptide (CCK-OP: 10(-6) M), in absence and in presence of four doses of sCT (1 x 10(-9), 1 x 10(-8), 1 x 10(-7) and 1 x 10(-6) M). sCT did not affect the initial strip basal tone. ACh, CCK-OP and KCl caused, as expected, a powerful contraction of the strips, but no effect was shown when each of the sCT doses was administered before ACh (1.28+ 0.69 SEM without sCT vs 1.28g+ 0.69 with sCT; n = 6) and CCK-OP (1.46g+ 0.19 without sCT vs 1.46g+ 0.19 with sCT; n = 8) or 5 min after the induced KCl contraction. On the basis of these preliminary results, we conclude that no evidence of a direct sCT effect was found on guinea pig GBs when considering either basal smooth muscle tone or isometric contraction in response to ACh, KCl and CCK-OP. Further studies are therefore required to clarify the influence of CT on GB dynamics in vivo and to elucidate its the physiological significance.

In order to verify the influence of the adrenergic system on the gallbladder contraction the Authors studied the effect of isometeptene, a sympathomimetic drug active on beta receptors, on gallbladder emptying. The gallbladder was studied on 6 subjects using a real-time (linear array) equipment with a 3,5 MHz transducer. In fasting subjects the gallbladder emptying was obtained by a fatty meal. In the next day the fatty meal stimulation was associated with the administration of isometeptene. The mean values +/- S.D. of the follow parameters were evaluated: -gallbladder basal volume -gallbladder residual volume both after fatty meal and after the association with isometeptene -gallbladder maximum emptying percentage in two experiences. The results show that the isometeptene doesn't inhibit significantly the gallbladder emptying induced by a fatty meal.

The use of inert plastic (Prolene mesh, 0,027 inches in thickness fournited by Ethicon) as preperitoneal prosthesis in repair of incisional hernias and inguinal hernia recurrencies has been investigated in 28 patients operated upon then 1977 to 1984. In 9 patients the inguinal approach was used with one recurrence (11%). In 9 patients the posterior approach through a midline incision has been used with two recurrences (22%). In 10 patients with incisional hernias there was only one recurrence (10%). Total recurrences rate was 14%. Most recurrences occur in patients operated from 1977 to 1980 (40%). Patients operated in the last period from 1980 to 1984 had no recurrences.

The investigation methods of gallbladder physiology in normal man are usually limited because often they are invasives and hazardous (radiations). The gallbladder size was accurately evaluated by US with study "in vitro". The variations in gallbladder-size measurements in the same observer and among many observers by US, demonstrate that Real-Time ul-ultrasonography is a simple, accurate, non-invasive and potentially valuable mean in the study of gallbladder motility.