bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation
Authors: Chieppa  , Mansi  , Rinaldi  , Serio  , Nacci  , Montagnani  , Potenza  , De Salvia  , Mitolo  , Rinaldi  , Altomare  
Published: March 2003

BackgroundErythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects (‘off contraction’) of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC).Materials and methodsCumulative concentrations of erythromycin (1–20 μM) and motilin (0.05–1 μM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5–10 μM) and motilin (0.05–0.5 μM) were tested on their ability to affect the off‐contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1–5 Hz, 20 V, 1 msec pulse trains lasting 1 min).ResultsThe direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh‐induced contraction) in the basal tension, with no dose–response relationship. The off‐contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off‐contraction (about 30%).ConclusionsErythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS‐induced relaxation.
Characteristics of thyroid carcinomas in aging patients
Authors: Lin  , Chao  , Chen  , Weng  , Lin  
Published: March 2003

BackgroundTo investigate the clinical features of thyroid cancer in aging patients and to present the results of treatment. From this we can provide bases for earlier diagnoses and better treatment of thyroid malignancies in older patients.Materials and methodsIn this study a retrospective analysis was performed with 204 thyroid cancer patients aged 60 years or older (132 women, with a mean age of 68.3 ± 6.6 years; 72 men, with a mean age of 67.0 ± 5.3 years).ResultsOf the 204 patients, 142 had well‐differentiated thyroid carcinomas (96 papillary thyroid carcinomas, 43 follicular carcinomas, three Hürthle cell carcinomas) and three medullary carcinomas. Sixty‐nine (33.8%) of the 204 patients died after treatment. Of these, three patients died of causes not related to thyroid cancer. For well‐differentiated thyroid carcinomas, male gender, follicular carcinoma, and a larger tumour size indicated a poor prognosis. Of the 59 non‐well‐differentiated thyroid carcinomas, 39 were anaplastic thyroid carcinomas, nine metastatic cancers of the thyroid, seven lymphomas, and four squamous cell carcinomas. After treatment, 40 (67.8%) of the 59 patients died. In multivariant analysis of the differences in clinical parameters between aging and younger thyroid cancer patients, the current status, tumour size, follow‐up period, sex, and stage at diagnosis were independent factors. From this data the delayed diagnosis of aging patients with thyroid cancer was of note when compared with younger patients.ConclusionThyroid cancer in older patients is not a benign clinical disorder. Early diagnosis and urgent aggressive treatment are recommended courses of action for this type of cancer, especially for non‐well‐differentiated thyroid cancers.
Effect of tauroursodeoxycholic acid on bile acid‐induced apoptosis in primary human hepatocytes
Authors: Benz  , Angermüller  , Otto  , Sauer  , Stremmel  , Stiehl  
Published: March 2003

Background/aimsThe accumulation of endogenous bile acids contributes to hepatocellular damage during cholestatic liver disease. To evaluate the potential role of apoptotic cell death due to increased concentrations of bile acids, primary human hepatocytes were treated with hydrophobic and hydrophilic bile acids. Because the Fas receptor–ligand system may mediate apoptosis in human liver cells, the effect of toxic bile acids on hepatocellular Fas receptor expression was evaluated.Materials and methodsPrimary human hepatocytes were incubated with 50 and 100 μM glycochenodeoxycholic acid (GCDCA) and co‐incubated with equimolar concentrations of tauroursodeoxycholic acid (TUDCA). To evaluate cytolytic and apoptotic effects, morphological alterations, hepatocellular enzyme release, nuclear DNA fragmentation and hepatocellular Fas receptor expression were evaluated.ResultsApoptotic cell death was significantly increased after exposure to 50 μM GCDCA. Bile acid‐induced apoptosis was not accompanied by hepatocellular Fas receptor overexpression. Tauroursodeoxycholic acid reduced apoptosis, as indicated by a significant reduction of oligonucleosomal DNA cleavage. Fas receptor expression was not significantly affected by tauroursodeoxycholic acid. At higher concentrations, direct cytolytic cell destruction was observed.ConclusionPrimary human hepatocytes represent a suitable model to study bile acid‐induced apoptotic cell death. In these hepatocytes, already low bile acid concentrations might induce apoptotic cell death, which is not triggered by hepatocellular Fas receptor overexpression. Apoptotic DNA fragmentation was significantly reduced by co‐incubation with tauroursodeoxycholic acid. The reduction of bile acid‐induced apoptosis by ursodeoxycholic acid and its conjugates may contribute to the beneficial effects of these hydrophilic bile acids used for medical treatment of several cholestatic liver diseases.
Platelet factor 4 and β‐thromboglobulin in inflammatory bowel disease and giant cell arteritis
Authors: Vrij  , Rijken  , Van Wersch  , Stockbrügger  
Published: March 2003

BackgroundAs platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and β‐thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis.Patients and methodsIn a prospective study, the platelet count, platelet factor 4 and β‐thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation.ResultsPlatelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and β‐thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non‐inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and β‐thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and β‐thromboglobulin. However, even after 12 months of follow‐up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and β‐thromboglobulin were significantly higher than the levels of the controls.ConclusionPlatelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and β‐thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre‐thrombotic state of disease.
Ultrastructural changes of human cardiac atrial nerve endings in diabetes mellitus
Authors: Schramm  , Wagner  , Nellessen  , Inselmann  
Published: March 2003

BackgroundAutonomic neuropathy resulting from long‐term diabetes mellitus may affect heart innervation. However, so far diabetes induced morphological changes of cardiac nerves are not well‐known. In this study human cardiac atrial tissue from diabetic patients was analysed by electron microscopy for structural alterations as a result of diabetic neuropathy.MethodsIn coronary bypass surgery, an edge of the right auricle was routinely resected for reason of extracorporal circulation. Thin cardiac tissue sections of 100 nm were studied by electron microscopy. Atrial tissue samples were collected from 5 patients with long‐standing diabetes (for at least 8 years) and compared to atrial tissue samples from 5 patients without diabetes, equally undergoing coronary bypass surgery.ResultsIn all atria‐free nerve endings with unmyelinized, axons were observed. Cross sections of 479 axons from diabetic patients were compared to 419 axons of nondiabetic patients. The number of altered axons was significantly higher in cardiac tissue of diabetic patients (32%) in comparison to normal subjects (17%). In diabetic patients, 20% of the intra‐axonal mitochondria were condensed or hydropic, whereas in nondiabetic patients only 4% of the mitochondria were altered. Membrane fragments were present in 21% of the axons in atria of diabetic patients compared to 10% in nondiabetic subjects. Only in cardiac axons from diabetic patients there were lamellar bodies, dissolved axoplasma and junctions between neighbouring axons in a minor number. Few vacuoles were present in axons of both groups.ConclusionIn myocardial atrial‐free nerve fibre bundles of diabetic patients, the amount of degenerative changes was higher in comparison to atrial cardiac tissue from nondiabetic subjects. These morphological alterations may indicate manifestation of diabetic neuropathy and might contribute to the impairment of autonomic neural control affecting the heart in long‐standing diabetes mellitus.
Effect of hemipancreatectomy and of pancreatic diversion on the tolerance to a glucose load in humans
Authors: Battezzati  , Zerbi  , Perseghin  , Caumo  , Terruzzi  , Di Carlo  , Luzi  
Published: March 2003

BackgroundThe role of the pattern, quantity and site of insulin secretion in the tolerance to a glucose challenge is not fully evaluated in humans because it is difficult to obtain appropriate clinical models.DesignTo address this issue, we studied subjects with reduced pancreatic mass (hemipancreatectomized, HEMI), systemic insulin delivery (pancreas transplant recipients, PTX), and two control groups (healthy, CON; and with uveitis on the same immunosuppression as PTX, UVE), with an hyperglycaemic clamp (study 1, + 4.2 mmol L−1), using a repeat experiment (study 2) with a fixed glucose infusion, calculated to increase by 35% that in study 1.ResultsIn study 1, CON increased glucose uptake to 20 ± 3 μmol kg−1 min−1 after a biphasic insulin response. In study 2, CON further increased the glucose uptake via an increment in prehepatic insulin secretion that stimulated insulin sensitivity without changes in peripheral insulin and glucose concentrations. HEMI and PTX had 35% less glucose uptake in study 1, compared to CON, and increased glucose concentrations (+ 1.6 mmol L−1) in study 2. UVE had an intermediate defect. The causes of intolerance were different: HEMI had a defective first‐phase insulin secretion (50% peripheral insulin concentrations) but maintained insulin sensitivity; PTX had normal peripheral insulin but only one‐third of the insulin sensitivity of CON.ConclusionsHemipancreatectomy and systemic insulin delivery impair first‐phase insulin secretion; second‐phase peripheral insulinization (HEMI); insulin sensitivity (PTX); and a mechanism evidentiated in study 2 of CON that increases insulin sensitivity in response to prehepatic insulin secretion (both groups). Failure of these mechanisms is largely compensated by hyperglycaemia.
A novel hyperglycaemic clamp for characterization of islet function in humans: assessment of three different secretagogues, maximal insulin response and reproducibility
Authors: Fritsche  , Stefan  , Hardt  , Schützenauer  , Häring  , Stumvoll  
Published: March 2003

BackgroundCharacterization of beta‐cell function in humans is essential for identifying genetic defects involved in abnormal insulin secretion and the pathogenesis of type 2 diabetes.Materials and methodsWe designed a novel test assessing plasma insulin and C‐peptide in response to 3 different secretagogues. Seven lean, healthy volunteers twice underwent a 200 min hyperglycaemic clamp (10 mmol L−1) with administration of GLP‐1 (1.5 pmol . kg−1 . min−1) starting at 120 min and an arginine bolus at 180 min. We determined glucose‐induced first and second‐phase insulin secretion, GLP‐1‐stimulated insulin secretion, arginine‐stimulated insulin response (increase above prestimulus, ΔIarg) and the maximal, i.e. highest absolute, insulin concentration (Imax). Insulin sensitivity was assessed during second‐phase hyperglycaemia. On a third occasion 6 subjects additionally received an arginine bolus at > 25 m
m blood glucose, a test hitherto claimed to provoke maximal insulin secretion.ResultsInsulin levels increased from 46 ± 11 p m to 566 ± 202 p
m at 120 min, to 5104 ± 1179 p
m at 180 min and to maximally 8361 ± 1368 p
m after arginine (all P < 0.001). The within subject coefficients of variation of the different secretion parameters ranged from 10 ± 3% to 16 ± 6%. Except for second‐phase which failed to correlate significantly with ΔIarg (r = 0.52, P = 0.23) and Imax (r = 0.75, P = 0.053) all phases of insulin secretion correlated with one another. The insulin concentration after the arginine bolus at > 25 m
m glucose (n = 6) was 2773 ± 855 p
m vs. 7562 ± 1168 p
m for Imax (P = 0.003).ConclusionThis novel insulin secretion test elicits a distinct pattern of plasma insulin concentrations in response to the secretagogues glucose, GLP‐1 and arginine and is highly reproducible and can be used for differential characterization of islet function.
Effect of gemfibrozil on peripheral atherosclerosis and platelet activation in a pig model of hyperlipidemia
Authors: Royo T. , Alfón J. , Berrozpe M. , Badimon L. 
Published: March 2003

BackgroundGemfibrozil has been shown to have beneficial effects in the primary and secondary prevention of atherosclerosis. However, a platelet pro‐activating effect induced by the drug has been reported.Material and methodsWe analysed the effect of hyperlipidemia and its treatment with gemfibrozil on platelet‐fibrinogen binding and the development of early fibrinogen‐rich vascular lesions in a porcine model of atherosclerosis. Polyclonal antibodies were raised against purified pig fibrinogen and intact platelets. Two groups of animals were fed a cholesterol/saturated fat‐enriched diet for 50 days; one group was treated with gemfibrozil and the other with placebo.ResultsThe hyperlipidemic diet induced a significant increase in total cholesterol; this was prevented by gemfibrozil (P < 0.05). The increase in platelet‐fibrinogen binding induced by hypercholesterolemia was mildly reduced in the gemfibrozil treated animals. Histological analysis of aortic vascular wall (abdominal aorta at the iliac bifurcation) from hyperlipidemic animals showed early lesions with fibrinogen infiltration; the lesions were reduced in the fibrate‐treated animals.ConclusionsGemfibrozil delayed the development of peripheral atherosclerotic plaque, normalised the impaired lipid profile induced by the hyperlipidemic diet and did not show a functionally detectable platelet pro‐activating effect able to increase platelet‐fibrinogen binding.
Phospholipid composition in late infantile neuronal ceroid lipofuscinosis
Authors: Granier L.‐A. , Langley K. , Leray C. , Sarlieve L. L. 
Published: March 2003

Neuronal ceroid lipofuscinosis (NCL) is a relatively common group of inherited neurodegenerative disorders characterised by the accumulation of autofluorescent lipopigments (ceroid) similar to lipofuscin. Because of this property, studies have concentrated on fatty acid metabolism and lipid peroxidation.In the present study, the fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and the molecular species compositions of diacylglycerophosphocholine (diacyl GPC), diacylglycerophosphoethanolamine (diacyl GPE) and alkenylacyl GPE (plasmalogens) were investigated in cultured skin fibroblasts from three patients with a confirmed diagnosis of the late infantile form of the disease (LINCL, CLN2) and three healthy age‐matched controls.Relatively minor differences in the fatty acid compositions of PC and PE were observed between patients and controls. However, dimethyl acetals of plasmalogens were found to be 40% higher in the patients compared to in the controls. Control and LINCL fibroblasts displayed only slight differences in the molecular compositions of diacyl GPE and diacyl GPC. In contrast, compared with normal cells, LINCL fibroblasts had higher levels of alkenylacyl GPE species containing both 18 : 1 and polyunsaturated fatty acids, but lower levels of species with 16 : 0 or 18 : 0 in the sn‐1 position.The molecular composition of PC and PE subclasses in skin fibroblasts of healthy subjects and patients suffering from LINCL is here described for the first time. While few differences are noticeable in the fatty acid composition of PC and PE and the molecular species distribution of diacylGPC and diacylGPE, the alkenylacyl GPE (or ethanolamine plasmalogens) were found to differ significantly between patients and healthy controls.
Elevated apolipoprotein B‐48 and remnant‐like particle–cholesterol in heterozygous familial hypercholesterolaemia
Authors: Dane‐Stewart C. A. , Watts G. F. , Mamo J. C. L. , Dimmitt S. B. , Barrett P. H. R. , Redgrave T. G. 
Published: March 2003

Apolipoprotein B‐48 (apoB‐48) is a marker of triglyceride‐rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB‐48 may predict postprandial lipaemia. Remnant‐like particle–cholesterol (RLP‐C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB‐48 and RLP‐C levels.The fasting plasma concentrations of apoB‐48 and RLP‐C were measured in 15 subjects with heterozygous FH and 15 age‐ and sex‐matched, normolipidaemic subjects. ApoB‐48 was determined using SDS‐PAGE and a western blotting/enhanced chemi‐luminescence technique. RLP‐C was measured using an immuno‐separation assay. Serum apolipoprotein B‐100 (apoB‐100) levels were measured using immmunonephelometry; lipids were assayed enzymatically.Compared with controls, FH subjects had significantly elevated plasma concentrations of apoB‐48 (29·3 median, 16·7–45·1 mg L−1 range vs. 12·8, 7·3–28·6; P < 0·001) and RLP‐C (16·2, 1·5–114·3 mg dL−1 vs. 8·5, 5·0–13·5; P = 0·003), as well as serum total apoB‐100 (1·9, 1·3–2·6 g L−1 vs. 1·0, 0·3–1·3; P < 0·001), LDL‐cholesterol (8·1, 4·6–10·4 mmol L−1 vs. 3·5, 2·4–4·4; P < 0·001) and triglyceride (1·5, 0·6–5·6 mmol L−1 vs. 1·0, 0·4–1·8; P = 0·018). There was no significant difference in HDL cholesterol.The findings suggest that patients with heterozygous FH have elevated plasma concentrations of TRL remnants, including those of intestinal origin. This may be a consequence of decreased clearance of these particles by the LDL‐receptor.
Low frequency of p53 and ras mutations in bile of patients with hepato‐biliary disease: a prospective study in more than 100 patients
Authors: Müller P. , Ostwald C. , Püschel K. , Brinkmann B. , Plath F. , Kröger J. , Barten M. , Nizze H. , Schareck W. D. , Hauenstein K. , Liebe S. , Löhr J. M. 
Published: March 2003

The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato‐biliary disease.We investigated 118 consecutive patients, aged 24–89 with the following clincal diagnoses: choledocho/cholecystolithiasis (28), cholangiocellular carcinoma (21), gall bladder tumor (8), liver metastasis (3), autoimmune disease (8), chronic pancreatitis (16), pancreatic carcinoma (11), papillary disease (4), hepatic cirrhosis (6), cholangitis (2), anomalies (2), and normal (9). Bile was aspirated during routine endoscopic retrograde cholangio pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). DNA was prepared freshly from a native aliquot. p53 mutations were detected by polymerase chain reaction (PCR) for exons 5 through 8 followed by TGGE. PCR for ras mutations was performed as RFLP–PCR with sequencing.In four cases, mutations in p53 could be found in exons 6 and 7. Twenty‐two samples showed ras mutations; ras mutations were found in choledocholithiasis (4/28), bile duct (5/21), gall bladder (3/8) and pancreatic (1/11) carcinoma, liver metastasis (3/3), ulcerative colitis (2/3), PSC (1/2), and chronic pancreatitis (1/16). Cytology was clearly positive in seven cases, suspicious in three other, inconclusive in six, and negative in the rest. The molecular analysis resulted in a sensitivity of 33% and specificity of 87%, respectively, for the diagnosis of a malignant condition.PCR for p53 and ras mutations may aid the diagnosis of primary and secondary (metastatic) hepatobiliary disease if a malignant condition of the bile ducts and the liver is suspected and cytology is inconclusive or negative. However, the incidence of p53 and ras mutations in bile seems less frequent than in other malignant conditions of the gastrointestinal tract and the pancreas and lower than in tissue, leaving a poor sensitiviy and specificity. Nevertheless, the presence of a p53 and/or ras mutation per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or inconclusive.
Phospholipase C activity of Helicobacter pylori is not associated with the presence of the cagA gene
Authors: Bode G. , Barth R. , Song Q. , Adler G. 
Published: March 2003

Background Knowledge about the possible role of phospholipase C (PLC) activity of microbial pathogens in the development of disease is increasing. Recently attention has focused on investigating PLC activity elaborated by Helicobacter pylori, but the role of this enzyme in H. pylori pathogenesis is still unknown. The aim of this study was to correlate PLC‐activity of H. pylori on the basis of the cagA status with the clinical diagnosis of the patients.Materials and methods Helicobacter pylori was isolated from patients with gastritis (G; n = 38), duodenal ulcer (DU; n = 15), gastric ulcer (GU; n = 11) and gastric cancer (GC; n = 12). Polymerase chain reaction primers DZ3/R009 which amplified a 1350‐bp fragment were used to detect the cagA gene. PLC activity was determined using p‐nitrophenylphosphorylcholine as substrate.Results Of the strains, 60% were cagA+ and 40% were cagA−. All strains showed PLC activity (2·20 ± 0·91 U mg−1 protein). PLC activity showed no association with the cagA status: cagA+ (2·21 ± 1·03 U mg−1 protein), cagA− (2·18 ± 0·79 U mg−1 protein). Patients with GU had the highest PLC activity (2·77 ± 1·26 U mg−1 protein) and patients with GC had the lowest activity (1·8 ± 0·57 U mg−1 protein).Conclusions Although PLC activity was present in all strains tested, it may only have pathological importance in patients with GU. However, the extent of PLC activity was independent of the presence of the cagA gene.