Effects of temporary sacral nerve stimulation on gastrointestinal motility and function in patients with chronic refractory slow-transit constipation.

BACKGROUND: The efficacy of sacral nerve stimulation (SNS) on patients with chronic refractory slow-transit constipation is controversial and its mechanism of action on gastrointestinal motility and transit is not fully understood. The aim of this study was to document the effects of temporary SNS on the gastrointestinal and biliary tract motility and on gastrointestinal transit in patients with refractory slow-transit constipation. METHODS: This was a prospective interventional study. Patients with slow-transit chronic constipation, unresponsive to any conservative treatment, were enrolled between January 2013 and December 2018. Patients' quality of life [patient assessment of constipation quality of life (PAC-QOL) questionnaire], constipation scores (Cleveland Clinic Constipation Score) colonic transit time (CTT), orocecal transit time (OCTT), gastric and gallbladder kinetics, together with the assessment of the autonomic nerve function were evaluated before and during temporary SNS. RESULTS: 14 patients (12 females, median age 38 years, range 24-42 years) had temporary SNS. The Cleveland Clinic Constipation Score did not change compared to baseline (23 ± 3 vs 21.4; p = 070). The PAC-QOL did not improve significantly during the stimulation period. Gallbladder/stomach motility (half-emptying time) did not change significantly before and after SNS. OCTT was delayed at baseline, as compared to standard internal normal values, and did not change during SNS. CTT did not improve significantly, although in two patients it decreased substantially from 97 to 53 h, and from 100 to 65 h. CONCLUSIONS: Temporary SNS did not have any effect on upper/lower gastrointestinal motility and transit in patients with severe constipation.

Simvastatin increases AQP2 urinary excretion in hypercholesterolemic patients: A pleiotropic effect of interest for patients with impaired AQP2 trafficking.

We previously reported that statins improve the symptoms of X-linked nephrogenic diabetes insipidus (X-NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney-concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24-hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine-concentrating defects caused by defective AQP2 plasma membrane trafficking, like X-NDI.

Management of gallstones and its related complications.

The majority of gallstone patients remain asymptomatic; however, interest toward the gallstone disease is continuing because of the high worldwide prevalence and management costs and the development of gallstone symptoms and complications. For cholesterol gallstone disease, moreover, a strong link exists between this disease and highly prevalent metabolic disorders such as obesity, dyslipidemia, type 2 diabetes, hyperinsulinemia, hypertriglyceridemia and the metabolic syndrome. Information on the natural history as well as the diagnostic, surgical (mainly laparoscopic cholecystectomy) and medical tools available to facilitate adequate management of cholelithiasis and its complications are, therefore, crucial to prevent the negative outcomes of gallstone disease. Moreover, some risk factors for gallstone disease are modifiable and some preventive strategies have become necessary to reduce the onset and the severity of complications.

Biliary proteins and their redox status changes in gallstone patients.

BACKGROUND: Proteins might act as pronucleating agents of cholesterol crystallization in bile. However, little is known about the redox status of biliary proteins in humans and their interaction with crystallization of biliary cholesterol. MATERIALS AND METHODS: Gallbladder biles were obtained at cholecystectomy from 86 symptomatic patients with either cholesterol gallstones (32 multiple and 32 solitary stones) or pigment stones (n = 22), and studied for protein redox status [carbonyl and sulfhydryl (PSH) concentrations], total lipid and protein levels and cholesterol saturation index (CSI). First appearance of cholesterol crystals in ultrafiltered bile (crystal observation time, COT) was studied with polarizing light microscopy during 21 days. RESULTS: Patients with cholesterol stones had significantly shorter COT (3 days vs. >21 days, P < 0.05), higher CSI (149 +/- 10% vs. 97 +/- 7%, P < 0.05) and higher total biliary proteins (1.96 +/- 0.1 mg mL(-1) vs. 0.55 +/- 0.1 mg mL(-1), P < 0.05) than patients with pigment stones. Patients with cholesterol stones had significantly lower (P < 0.05) level of protein sulfhydryl concentrations (18 +/- 4 nmol mg(-1) protein vs. 49 +/- 16 nmol mg(-1) protein), while total lipid and carbonyl proteins concentrations were similar between cholesterol and pigment stone patients. Crystallization probability was influenced by the number/type of gallstones (multiple > solitary > pigment stones, P = 0.009) and total protein concentration (high > low levels, P = 0.004). COT was negatively correlated with total protein content (r = -0.45, P = 0.03). CONCLUSIONS: Biles with cholesterol stones show high CSI and total protein concentration, and rapid COT, which is even faster in patients with multiple stones and high protein concentration. Low PSH levels in cholesterol stone patients point to a biochemical shift, potentially able to affect cholesterol crystallization.

Beneficial effects of oral tilactase on patients with hypolactasia.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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, P < 0.02). Malabsorbers had longer time to H(2) peak (P < 0.03), lower H(2) peak levels (P < 0.002) and smaller integrated H(2) excretion levels (P < 0.005) 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) (P < 0.0001). CONCLUSION: 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.

Gallstone disease: Symptoms and diagnosis of gallbladder stones.

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.

Changes of gallbladder and gastric dynamics in patients with acute hepatitis A.

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 (P < 0.05 in sludge vs. no sludge and controls; P < 0.05 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.

[Paraneoplastic syndromes of the central nervous system]. / Sindromi paraneoplastiche del sistema nervoso centrale.

Paraneoplastic syndromes of central nervous system are rare neurologic syndromes caused by cancer but not secondary to metastases. The physiopathologic mechanisms underlying these syndromes are still under debate. We report the biological and clinical features of the most frequent paraneoplastic syndromes involving the central nervous system. Their early clinical identification might be an useful marker of an otherwise unknown visceral malignancy. Furthermore, they might also be suggestive for the particular type of cancer present. Once, therefore, the diagnosis of these paraneoplastic syndromes has been established, an appropriate evaluation for the asymptomatic neoplasm in cancer-free individuals or investigation for the malignancy recurrences in oncologic patients might be performed.

Standards for diagnosis of gastrointestinal motility disorders. Section: ultrasonography. A position statement from the Gruppo Italiano di Studio Motilità Apparato Digerente.

Ultrasonography is a non-invasive, relatively easy, validated and reproducible technique. We assessed the usefulness of functional ultrasonography to study disorders of gastro-oesophageal tract, gallbladder and pancreatic duct. Oesophagus Oesophagus and the gastro-oesophageal junction can be visualized in children up to 5 years old. Ultrasonography shows 100% sensitivity and 87.5% specificity compared to ambulatory pH-metry for gastro-oesophageal reflux disease diagnosis. Stomach Ultrasonography can be used to estimate whole gastric volume, antral area or diameters, antro-pyloric volume, transpyloric flow in fasting state and in response to test meal. Gallbladder Ultrasonography is reliable to estimate volume in fasting state and in response to test meal or exogenous stimulus. For both stomach and gallbladder, indications might include the study of healthy subjects and of pathophysiologically relevant conditions such as dysmotility-like dyspepsia, suspicion of delayed gastric emptying, diabetes mellitus, gallstone disease and effect of drugs either delaying or accelerating motility. Common bile duct Ultrasonography can be used to estimate interprandial and postprandial common bile duct diameter in patients with clinical suspicion of common bile duct obstruction in fasting state and in response to test meal or exogenous stimuli. Although functional ultrasonography is used mainly for research purposes, its simplicity makes it appealing for clinical use to assess gastrointestinal motility in health and disease.

Gallbladder motility and cholesterol crystallization in bile from patients with pigment and cholesterol gallstones.

BACKGROUND: 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. DESIGN: 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. RESULTS: Fasting gallbladder volume was significantly (P < 0.05) 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, P < 0.05) 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, P < 0.05). 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 (P < 0.01). 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). CONCLUSIONS: 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.