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Biomedical subjects

M Classen

Publications and source records attributed to M Classen.

At least 145 records · Page 8Linked to original sources
PubMed1993

Pertussis toxin-sensitive inhibition of glucagon-like peptide 1-stimulated acid production by epidermal growth factor and transforming growth factor alpha in rat parietal cells.

We have recently shown that the intestinal hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is a cAMP-dependent stimulant of rat parietal cell H+ production. Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha) are known to inhibit histamine-stimulated parietal cell function by reducing cAMP production in a pertussis toxin-sensitive manner. Pertussis toxin blocks Gi alpha, the inhibitory subunit of adenylate cyclase, thereby preventing inhibitors from acting via Gi alpha. Therefore, we used pertussis toxin as a tool to determine whether EGF and TGF alpha inhibit GLP-1-stimulated parietal cell function via Gi alpha. In enriched (76 +/- 4%) rat parietal cells [14C]aminopyrine accumulation and cAMP production were maximally stimulated by GLP-1-(7-36) amide (10(-8) and 10(-7) M, respectively) or by histamine (10(-4) and 10(-3) M, respectively). EGF and TGF alpha (10(-13)-10(-7) M) caused concentration-dependent inhibition of GLP-1-stimulated parietal cell function. Maximal inhibition (33% and 37% of the response to GLP-1-(7-36) amide was observed at 10(-8) M EGF and 10(-9) M TGF alpha, respectively. There was a close correlation (r = 0.83; P < 0.05; n = 7) between the inhibition by EGF and TGF alpha of [14C]aminopyrine accumulation and the fall in cAMP production in GLP-1-stimulated parietal cells. The identical concentrations of both growth factors which maximally reduced GLP-1-stimulated parietal cell function inhibited [14C]aminopyrine accumulation in response to histamine by approximately 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1993

[Endoscopic ultrasonography--an addition to pancreas diagnosis?].

Endoscopic ultrasonography (EUS) has been developed for high resolution imaging of the upper gastrointestinal tract and immediate surroundings, such as the pancreas and the biliary tract. The ultrasonic transducer at the tip of the instrument works with ultrasound frequencies of 7.5 MHz and provides delineation of small structures and lesions, but the ultrasonic penetration depth is not sufficient for visualization of organs such as liver, spleen and kidneys. In the diagnosis of pancreatic disease the advantages of EUS lie in the delineation of small endocrine and exocrine tumors of the pancreas, complementary to other procedures such as ultrasound, CT and ERCP. EUS is also the most accurate single diagnostic method in the local staging of pancreatic ampullary carcinoma, being superior to other modalities in the diagnosis of portal venous infiltration. The disadvantage of EUS is its poor ability to differentiate between malignant and focal inflammatory tumors of the pancreas. The role of EUS in the diagnosis of chronic pancreatitis has not yet been fully established.

Ampulla of Vater↗
PubMed1993

[The benefits and risks of percutaneous transhepatic cholangioscopy].

Percutaneous transhepatic cholangioscopy (PTCS) was undertaken in 101 patients (for diagnostic reasons in 64 and/or therapeutic reasons in 56) out of 167 consecutive patients (56 women, 45 men; mean age 64.2 [27-95] years) in whom percutaneous transhepatic drainage had been instituted. In all but one of 64 patients PTCS clearly defined stenoses which had been unclear in the cholangiogram. There was a 90% accuracy of histological diagnosis of biopsies obtained under vision in 60 cases. A malignant stenosis was seen in 19 of 25 cases (sensitivity 76%). Severe stenosis, not passable by contrast medium, were recanalized cholangioscopically in 14 of 15 cases. Biliary tract stones were completely removed by PTCS in 40 of 41 patients, by mechanical means (n = 4) or intracorporeal lithotripsy (n = 37). There were no complications from PTCS. It is concluded that PTCS can be performed safely and reliably in patients with functioning percutaneous transhepatic drainage. It provides the diagnosis of previously unclear cholangiographic findings as well as treatment of difficult biliary tract stenoses and/or ductal stones.

Adult↗
PubMed1993

p-ANCA as a diagnostic marker in ulcerative colitis.

P-ANCA that do not react with myeloperoxidase (MPO) have been claimed to serve as a useful diagnostic marker in the differential diagnosis of inflammatory bowel disease (IBD). Therefore, in this study we determined the frequency of MPO-negative-p-ANCA in patients with inflammatory bowel disease and correlated the presence with intestinal and extra-intestinal disease manifestation. In 44 out of 65 (68%) sera from patients with ulcerative colitis (UC) but in only 14 of 66 (21%) with Crohn's disease (CD) MPO-negative-p-ANCA were detected whereby colonic involvement and extraintestinal manifestations seemed to be important. There was no correlation to therapy, activity, sex, age, extent and duration of disease. Moreover, the sera did not exhibit significant reactivity in ELISAs testing for Cathepsin G-, Lactoferrin-, Myeloperoxidase-, Elastase- or Proteinase 3- specificity.

Adult↗
PubMed1993

The gastroenterologist's approach to dysphagia.

In the gastroenterological diagnostic armamentarium, dysphagia is considered as an important symptom for diseases of the esophagus. Concerning the history of illness, symptoms such as retrosternal pain and heartburn are often associated with gastroesophageal reflux disease. Morphological changes of the mucosa can be diagnosed by flexible endoscopy and radiographic examinations. Investigation with 24-h pH monitoring, manometry, and pharmacological tests is necessary for the diagnosis of functional disorders. Additionally, dysphagia can be associated with multiple internal diseases, including muscular diseases such as dermatomyositis, progressive systemic sclerosis, as well as lupus erythematosus. Difficulties in swallowing associated with hypo- and hyperthyroidism can also be interpreted as muscular lesions. Metabolic disorders such as alcoholism, and diabetes mellitus can be the cause of dysphagia. Increasing importance in the differential diagnosis of dysphagia is attached to infections of the upper GI tract. Especially in immunocompromised patients, infections of Candida albicans, mycobacterias, herpes, varicella zoster, and cytomegaloviruses can produce dysphagia and odynophagia. The differential diagnosis of the "angina-like chest pain" has to differentiate between cardiac disease and a noncardiac genesis. Therefore, besides the cardiac diagnostic investigation, endoscopy, radiography, and manometry are often indicated.

Deglutition Disorders↗
PubMed1993

The value of endoscopy and endosonography in the diagnosis of the dysphagic patient.

The value of endoscopy in dysphagia is limited in the diagnosis of motility disorders and small structures, webs, and hiatal hernias. Endoscopy is of special use for the clarification of an organic cause of dysphagia. Intraluminal tumors can be seen and in a high percentage of cases be definitely diagnosed by taking biopsies; a malignant degeneration in Barrett's esophagus is detectable by endoscopy in 89.1% of cases. Gastroesophageal reflux disease can be diagnosed on endoscopy as it leads to an endoscopically visible inflammatory reaction; however, normal findings on endoscopy cannot exclude reflux disease. Endoscopy is the method of choice in the diagnosis of nonreflux esophagitis, especially Candida and viral esophagitis. A further advantage of endoscopy is the fact that a microscopic diagnosis can be obtained and endoscopic treatment can be performed simultaneously. Submucosal or extramural lesions can be missed by endoscopy. Endosonography, the combination of endoscopy and ultrasonography (EUS) yields additional information in diagnosing submucosal and extramural lesions of the esophagus which is missed by other imaging procedures. One of the main advantages of EUS is the detection of small and submucosal lesions. The most important indication is the local staging of esophageal carcinomas; the accuracy of endosonography in determining the depth of infiltration ranges between 79% and 92%. The detection of paraesophageal lymph nodes is successful in 60%-82%, although EUS cannot differentiate benign from malignant lymph nodes. Submucosal tumors can be visualized by endosonography and their size, echopattern, and the layers of origin can be determined with high accuracy. Further indications for EUS are the exclusion of focal lesions in achalasia or peptic strictures.

Deglutition Disorders↗
PubMed1993

Effect of bombesin antagonist D-Phe6-BN(6-13)OMe on vagally induced gastrin release from perfused rat stomach.

The aim of the present study was to evaluate the effect of the bombesin antagonist D-Phe6-BN(6-13)OMe (BN-antagonist) on vagally stimulated gastrin release from the isolated rat stomach, which was perfused via the celiac artery with Krebs-Ringer buffer. Vagal stimulation was performed for 10 minutes with 1 ms, 10 V and 10 or 2 Hz, respectively. Gastrin secretion increased significantly during stimulation with 10 and 2 Hz. BN-antagonist was added to the perfusate at the concentration of 10(-6) M, which induced a significant reduction of vagally stimulated gastrin release at 10 Hz (619 +/- 65 vs. 252 +/- 62 pg/10 min, p < 0.05), but not at 2 Hz (564 +/- 117 vs. 493 +/- 113 pg/10 min, p > 0.05). In contrast, atropine (10(-7) M) reduced significantly the gastrin response at 2 Hz (270 +/- 78 pg/10 min, p < 0.01), but not at 10 Hz (446 +/- 87 pg/10 min, p > 0.05). The combination of BN-antagonist and atropine elicited an inhibition of vagally stimulated gastrin release similar to each substance when given alone. Basal gastrin release was not changed by the BN-antagonist. The present data suggest, that in the rat stomach endogenously released bombesin-related peptides contribute to the noncholinergic stimulation of gastrin release at higher stimulation frequencies (10 Hz), however, bombesin-related peptides are not involved, when lower stimulation frequencies (2 Hz) are employed. At both stimulation frequencies additional mechanisms are activated which are noncholinergic and not related to bombesin peptides.

Animals↗
PubMed1993

Differential effects of selective neurokinin agonists on phasic and tonic activity in rat ileal longitudinal muscle.

To test the hypothesis that different neurokinin receptors might be involved in the generation of either phasic or tonic muscular activity, selective ligands for the 6 neurokinin-1-receptor, [Sar9, Met(O2)]-SP, the neurokinin-2-receptor, [Nle10]-NKA4-10, and the neurokinin-3 receptor, [beta Asp4,MePhe7]-NKB4-10, were used to evaluate the excitatory effects of these agonists in the longitudinal rat ileal muscle in vitro. The excitatory effect was analyzed as total response (area under the curve) and as tonic or phasic (area under or within the peaks) activity. Substance P (SP, relative amount of phasic activity in comparison to total activity: 3 x 10(-8) M 87%, 3 x 10(-6) M 30%) and the neurokinin-2-receptor selective agonist [Nle10]-NKA4-10 (N-NKA: 3 x 10(-8) M 67%, 3 x 10(-6) M 59%) caused both tonic and phasic responses, with the percentage of phasic responses decreasing at higher concentrations. The neurokinin-1-receptor selective agonist [beta Ala4, Sar9, Met(O2)]-SP4-11 caused a predominantly tonic response with only a small phasic component (10(-8) M 27.1% 10(-6) M 13.8%). The selective neurokinin-3 receptor agonist [beta Asp4, MePhe7]-NKB4-10 caused a predominantly phasic motor response (SM-SP: 3 x 10(-8) M 98%, 3 x 10(-6) M 87%). Tetrodotoxin (TTX 10(-6) M), omega-conotoxin (CTX 10(-7) M) and atropine (10(-6) M) had no significant influence on the contractile responses to all four peptides, indicating a direct action on the smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Prospective multicentre study of risk factors associated with delayed healing of recurrent duodenal ulcers (RUDER). RUDER Study Group.

Risk factors for delayed duodenal ulcer healing during treatment with ranitidine (300 mg daily) were examined in a multicentre German study of 1923 patients with endoscopically proved, recurrent duodenal ulceration. Healing rates, per protocol, were 39.5% at two weeks, 70.9% at four weeks, and 93.2% at eight weeks. Prospective testing of five, predefined risk factors indicated that smoking (p = 0.0039) was associated with a decreased healing rate at two weeks. Frequent prior recurrence (p = 0.464), a heavy physical workload (p = 0.145), and psychological stress (p = 0.062) were not associated with a decreased healing rate and there were too few patients at risk to allow assessment of the effect of regular NSAID intake. Exploratory analysis identified prior slow healing, a large ulcer, multiple ulcers, and prior ulcer complications, in addition to smoking, as markers of slow healing. In the absence of these risk factors, the mean healing time was 3.3 weeks (95% confidence interval 3.0, 3.5), rising to 3.7 weeks (3.5, 3.9) for one, 4.4 weeks (4.1, 4.7) for two, and 5.1 weeks (4.5, 5.6) for three to five risk factors. Delayed duodenal ulcer healing is associated with multiple factors whose effect is cumulative; for patients with two or more of five easily identified risk factors, more than four weeks' treatment with a histamine H2 receptor antagonist is required to achieve ulcer healing.

Adult↗
PubMed1993

Laser lithotripsy of difficult bile duct stones under direct visual control.

Biliary laser lithotripsy was performed under direct visual control in 35 consecutive patients not amenable to routine endoscopy. The patients had 1-50 (median 1) bile duct stones with the greatest diameter of the largest stone being 9-42 mm (median 20 mm). Conventional endoscopic treatment had failed because of an inaccessible papilla (16 patients), biliary strictures (seven patients), and impaction or large size of calculi (12 patients). Twelve patients, depending on their anatomical condition, underwent peroral cholangioscopy by means of a mother-babyscope system. Percutaneous cholangioscopy was initially carried out in 23 patients, 7-20 days (median 10 days) after creation of a transhepatic fistula. Pulsed dye laser (32 patients) or alexandrite laser (three patients) lithotripsy was applied under an appropriate direct visual control in all cases. Complete stone disintegration succeeded in 33 of 35 patients. All resultant fragments passed the papilla within a mean number of 1.3 treatment sessions. Peroral cholangioscopic lithotripsy failed in two cases. One patient successfully underwent percutaneous laser treatment and the other patient was referred to surgery. Fever, temporary haemobilia, or a subcapsular liver haematoma were seen in a total of eight patients during establishment of the cutaneobiliary fistula. A 95 year old patient who had been admitted with septic cholangitis died because of cardiorespiratory failure 5 days after bile duct clearance. It is concluded that laser lithotripsy performed under a direct visual control is an effective and safe procedure for the non-surgical treatment of difficult bile duct stones. Ductal clearance can usually be achieved in a single treatment session when the papilla and the stones are accessible by the peroral route. Percutaneous cholangioscopic lithotripsy is more time consuming but highly effective even in patients with a difficult anatomy, bile duct strictures, or intrahepatic calculi. This approach should be limited, however, to cases not amenable to retrograde procedures because the creation of the cutaneobiliary fistula is not without risks.

Aged↗
PubMed1993

Nitric oxide as putative nonadrenergic noncholinergic inhibitory transmitter in the opossum sphincter of Oddi.

The sphincter of Oddi has a typical nonadrenergic noncholinergic inhibitory innervation; however, the transmitter of this inhibition has not been identified. The aim of the present study was to evaluate whether metabolites of the L-arginine--nitric oxide synthase pathway mediate neural inhibition in the sphincter of Oddi of the opossum. Electrical field stimulation at various frequencies (3, 5, and 10 pulses/s), performed in the presence of guanethidine (10(-6) M) to exclude adrenergic responses, caused a slight, but significant excitatory response of the sphincter of Oddi. The responses were more pronounced at the duodenal side of the sphincter of Oddi than on the hepatic side. When the electrical field stimulation was repeated after blockading muscarinic receptors, using atropine (10(-6) M), a potent inhibitory response was obtained. The inhibitory response to each of the various stimulation parameters was similar. Addition of L-arginine methyl ester (L-NAME, 2 x 10(-4) M) abolished and reversed the inhibitory effect of electrical field stimulation, resulting in a potent stimulatory effect. Higher frequencies (5 and 10 pulses/s) were more potent in causing a stimulatory response than lower frequencies (3 pulses/s). The excitatory effect of electrical field stimulation was blocked or reversed to inhibition when the amino acid L-arginine (2 x 10(-3) M) was added to the bath. In a second series of experiments, the inhibitory effect of electrical field stimulation in the presence of atropine and guanethidine was not prevented after the addition of methylene blue (5 x 10(-5) M), a substance that, in vascular smooth muscle, has been demonstrated to block cyclic GMP dependent inhibitory responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic Fibers↗
PubMed1993

Intracellular pH-regulating ion transport mechanisms in parietal cell basolateral membrane vesicles.

Na(+)-H+ and Cl(-)-base exchangers on the parietal cell have been demonstrated by several authors. Controversy exists concerning a basolateral Na(+)-HCO3- cotransporter in the parietal cell. To clarify this issue, we prepared highly enriched basolateral membrane (BLM) and apical-tubulovesicular membrane (to serve as negative controls) vesicles from rabbit fundic mucosa. Na(+)-H+ exchange was demonstrated by measuring pH gradient-driven amiloride-sensitive 22Na+ uptake and Na+ gradient-driven proton uptake into voltage-clamped BLM but not into apical-tubulovesicular vesicles. Anion exchange was demonstrated by measuring 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)-inhibitable influx of 36Cl- into Cl(-)- or HCO3(-)-loaded voltage-clamped BLM vesicles. Na(+)-HCO3- cotransport was assessed by comparing HCO3(-)-driven 22Na uptake with uptake driven by an identical pH gradient. No significant difference was found between 22Na uptake in the presence and absence of HCO3-; 1 mM amiloride inhibited 22Na uptake > 90% in both conditions, whereas 2 mM DIDS had no effect. In BLM vesicles prepared from rabbit renal cortex, however, a HCO3- gradient stimulated 22Na uptake much more than an equivalent pH gradient, and DIDS inhibited this HCO3- gradient-driven 22Na uptake. This indicates that our experimental setup was suitable to detect a Na(+)-HCO3- cotransporter if present. Our data suggest that the parietal cell BLM contains Na(+)-H+ exchangers and Cl(-)-HCO3- exchangers but no Na(+)-HCO3- cotransporter.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1993

Effect of galanin on food intake in rats: involvement of lateral and ventromedial hypothalamic sites.

Galanin has previously been reported to elicit feeding in satiated animals when injected into the hypothalamic paraventricular nucleus. It is not known, however, 1) whether this action is due to activation of feeding signals or suppression of satiety signals or both or 2) whether other hypothalamic regions such as the lateral hypothalamus (LH) or the ventromedial hypothalamus (VMH) are involved in this action. The effects of galanin on food intake were therefore examined in satiated and in fasted rats both after intracerebroventricular injection (0.1, 1, and 10 micrograms/10 microliters) and after microinjection (1 and 5 micrograms/0.5 microliters) into the LH and VMH. Twenty minutes after intracerebroventricular injection, galanin significantly and dose dependently augmented food intake by up to sevenfold in freely feeding rats and by up to 79% in fasted animals. The galanin-induced augmentation of cumulative food intake up to 2 h after injection was due to the initial increase in food consumption during the 0 to 20-min interval. This suggests that galanin acts by activation of feeding behavior and not by suppression of satiety signals in these fasted animals, in which satiety signals are presumably not initially operative. Twenty minutes after intrahypothalamic injections into both the LH and VMH, galanin (5 micrograms) significantly increased food consumption, fivefold in freely feeding rats and 30-35% in fasted rats. Thus stimulation of feeding by centrally injected galanin also involves loci within the LH and VMH.

Animals↗
PubMed1992

[Laparoscopic cholecystectomy: ERCP as standard preoperative diagnostic technique].

In a prospective study 250 patients with proven cholelithiasis and clinical, biochemical and ultrasound indications for laparoscopic cholecystectomy (LC) underwent endoscopic retrograde cholangiography (ERCP) and (if bile-duct stones had been shown) endoscopic papillotomy (EPT). The biliary system was demonstrated in 229 patients (91.6%). Biliary tract stones were confirmed in 18 of 68 patients in whom they had been suspected clinically. In addition, ERCP revealed small stones in the bile-duct in eight of 154 patients with normal biochemical results and unremarkable ultrasound imaging, and in seven patients bile-duct anomalies which required EPT or open cholecystectomy. However, in retrospect five of the patients with cystic duct anomalies could have been treated by LC. The complication rate of ERCP/EPT was 3.2%. It is concluded from these results that, in view of the cost and potential risk to the patient, ERCP before LC can be limited to patients suspected of having bile-duct stones, even though small stones may be missed.

Adolescent↗