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Biomedical subjects

T Frieling

Publications and source records attributed to T Frieling.

At least 19 recordsLinked to original sources

[Systemic mast cell disease with gastrointestinal symptoms--a diagnostic questionnaire].

Systemic mast cell disease often becomes clinically manifest as a mast cell mediator activation syndrome with episodic or chronic nonspecific abdominal symptoms. As a result of genetic alterations, pathological mast cells have an increased proliferation rate as well as accumulation within different organs with consequential effect on gastrointestinal secretion, absorption, pain perception and motility caused by release of their mediators. These changes may not be detected in routine laboratory or imaging methods. This report describes how the diagnosis systemic mast cell disease can be established with a diagnostic questionnaire based on a synopsis of clinical findings relevant to a mast cell mediator activation syndrome.

Diagnosis, Differential↗

Selective expression of histamine receptors H1R, H2R, and H4R, but not H3R, in the human intestinal tract.

BACKGROUND AND AIMS: Histamine is known as a regulator of gastrointestinal functions, such as gastric acid production, intestinal motility, and mucosal ion secretion. Most of this knowledge has been obtained from animal studies. In contrast, in humans, expression and distribution of histamine receptors (HR) within the human gastrointestinal tract are unclear. METHODS: We analysed HR expression in human gastrointestinal tissue specimens by quantitative reverse transcription-polymerase chain reaction and immunostaining. RESULTS: We found that H1R, H2R, and H4R mRNA were expressed throughout the gastrointestinal tract, while H3R mRNA was absent. No significant differences in the distribution of HR were found between different anatomical sites (duodenum, ileum, colon, sigma, and rectum). Immunostaining of neurones and nerve fibres revealed that H3R was absent in the human enteric nervous system; however, H1R and H2R were found on ganglion cells of the myenteric plexus. Epithelial cells also expressed H1R, H2R and, to some extent, H4R. Intestinal fibroblasts exclusively expressed H1R while the muscular layers of human intestine stained positive for both H1R and H2R. Immune cells expressed mRNA and protein for H1R, H2R, and low levels of H4R. Analysis of endoscopic biopsies from patients with food allergy and irritable bowel syndrome revealed significantly elevated H1R and H2R mRNA levels compared with controls. CONCLUSIONS: We have demonstrated that H1R, H2R and, to some extent, H4R, are expressed in the human gastrointestinal tract, while H3R is absent, and we found that HR expression was altered in patients with gastrointestinal diseases.

Cells, Cultured↗

Relief of reflux symptoms after endoscopic gastroplication may be associated with reduced esophageal Acid sensitivity: a pilot study.

BACKGROUND AND STUDY AIMS: Although the new endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) lead to marked clinical benefit, the underlying mechanism of this is unknown. MATERIALS AND METHODS: In this prospective study, the effect of endoscopic gastroplication was investigated in six patients with GERD, who were assessed before and 4 weeks after treatment. The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI) consumption, reflux esophagitis, acid exposure, esophageal motility, lower esophageal sphincter pressure (LESP), and gastric emptying was measured. Esophageal acid sensitivity before and after treatment was investigated using a standardized acid provocation test, and compared with that of six age- and sex-matched healthy controls. RESULTS: Significant clinical benefit and discontinuation of PPI consumption after gastroplication was seen. Among the objectively measured parameters, only acid exposure was significantly reduced and gastric emptying significantly delayed. However, acid exposure remained pathologically high. Esophageal acid sensitivity was significantly reduced. The induction of heartburn and/or pain was abolished in four patients after gastroplication. In two patients the intensity of heartburn/pain was significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain significantly prolonged by 40% or 100%. CONCLUSION: These preliminary data suggest that the decrease of esophageal sensitivity to acid after endoscopic gastroplication is part of the mechanism responsible for the reduction of reflux symptoms.

Adult↗

[Antireflux therapy--more than acid reduction?].

Because gastroesophageal reflux disease (GERD) is a motility disorder, acid reduction with proton pump inhibitors (PPI) remains a symptomatic therapy with a recurrence rate of over 90% after discontinuation of acid suppression. This "therapeutic dilemma" becomes obvious in patients not responding sufficiently to the conventional medication (therapy resistance, necessity of high PPI doses, volume reflux). In this manuscript we analyze additional factors that may play a role in the pathogenesis and interpretation of GERD. These additional factors include gastroesophageal motility and esophageal barrier functions as well as duodenogastroesophageal reflux and Helicobacter pylori infection. In addition, basic problems in interpretation of therapeutic success such as placebo effect, spontaneous remission of GERD, the role of sensory function and subjective interpretation of symptoms and the overlap between physiological and pathological reflux as well as functional disorders will be discussed.

Antacids↗

[Endoscopic ultrasound in routine clinical practice for staging adenocarcinomas of the stomach and distal esophagus].

PROBLEM: Endoscopic ultrasound (EUS) is an important diagnostic tool for determining the best therapeutic strategy (primary resection, neoadjuvant therapy or palliation only) to offer esophageal or gastric cancer patients. PATIENTS AND METHODS: In the present study (1992-2001),we evaluated the accuracy of EUS in adenocarcinomas of the distal esophagus and stomach and compared our results with pathologists findings as the gold standard. RESULTS: Of the 222 patients studied, the precise examination of 11% EUS was not completely possible due to severe tumor stenosis. The accuracy of EUS with respect to T, N+/- and TN+/- amounted to 51%, 65% and 34% in 131 patients with adenocarcinomas of the esophageal gastric junction and to 50%, 66% and 37% in 91 patients with adenocarcinomas located in the fundus, corpus or antrum of the stomach respectively. With respect to T-stage, the overstaging of tumors was more common than understaging, especially in pT2b-carcinomas. The subgroup analysis of the 131 EGJ adenocarcinoma patients showed that the results obtained by EUS were slightly better in type I (distal esophageal cancer) than in type II and III cardia carcinomas (proximal gastric cancer).When comparing two observation periods (1992-1996 and 1997-2001), the accuracy of endoscopic ultrasound staging was very similar in both periods for T-category (51% vs 49%) and N-category (63% vs 64%) as well as for combined TN-staging (36% vs 35%) respectively. CONCLUSIONS: In clinical routine examinations of adenocarcinomas of the stomach and the distal esophagus, the accuracy of EUS is not as good as the excellent results in the past--mostly obtained under study conditions--may suggest.

Adenocarcinoma↗

Expense and benefit of neoadjuvant treatment in squamous cell carcinoma of the esophagus.

BACKGROUND: The effectiveness of neoadjuvant treatment (NT) prior to resection of squamous cell carcinoma of the esophagus (SCCE) in terms of prolonged survival has not been proven by randomized trials. Facing considerable financial expenses and with concerns regarding the consumption of the patient's remaining survival time, this study aims to provide rationales for pretreating resection candidates. METHODS: From March 1986 to March 1999, patients undergoing resection for SCCE were documented prospectively. Since 1989, NT was offered to patients with mainly upper and middle third T3 or T4 tumors or T2 N1 stage who were fit for esophagectomy. Until 1993, NT consisted of chemotherapy. Since that time chemoradiation has also been applied. The parameters for expense and benefit of NT are costs, pretreatment time required, postoperative morbidity and mortality, clinical and histopathological response, and actuarial survival. RESULTS: Two hundred and three patients were treated, 170 by surgery alone and 33 by NT + surgery. Postoperative morbidity and mortality were 52% to 30% and 12% to 6%, respectively (p = n.s.). The response to NT was detected in 23 patients (70%). In 11 instances (33%), the primary tumor lesion was histopathologically eradicated. Survival following NT + surgery was significantly prolonged in node-positive patients with a median survival of 12 months to 19 months (p = 0.0193). The average pretreatment time was 113 +/- 43 days, and reimbursement for NT to the hospital amounted to Euro 9.834. CONCLUSIONS: NT did not increase morbidity and mortality. Expenses for pretreatment, particularly time and costs, are considerable. However, taking into account that the results are derived from a non-randomized study, patients with regionally advanced tumor stages seem to benefit, as seen by their prolonged survival.

Antineoplastic Combined Chemotherapy Protocols↗

Neural components of distension-evoked secretory responses in the guinea-pig distal colon.

1. Using a Ussing chamber and neuronal retrograde tracing with 1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) we characterized the afferent and efferent neuronal pathways which mediated distension-evoked secretion in the guinea-pig distal colon. 2. Acute capsaicin application (10 microM) to the serosal site of the Ussing chamber evoked a secretory response which was blocked by tetrodotoxin (1 microM), the combined application of the NK1 and NK3 receptor antagonists CP-99,994-1 and SR 142801 (1 microM), and by combined application of atropine (10 microM) and the VIP receptor antagonist VIP(6-28) (10 microM). Functional desensitization of extrinsic primary afferents by long-term application of capsaicin significantly diminished distension-evoked secretion by 46 %. 3. After functional desensitization by capsaicin, serosal application of gadolinium (100 microM) inhibited the distension-evoked chloride secretion by 54 %; the L-type Ca(2+) channel blocker nifedipine (1 microM) and the 5-HT(1P) receptor antagonist renzapride (1 microM) had no effect. The combination of atropine and VIP(6-28) or the combination of NK1 and NK3 receptor antagonists almost abolished distension-evoked secretion. 4. The secretory response evoked by electrical field stimulation, carbachol (1 microM) or VIP (1 microM) was not attenuated by gadolinium. Field stimulation-evoked chloride secretion was not affected by blockade of NK1 and NK3 receptors. 5. Twelve per cent of DiI-labelled submucosal neurones with projections to the mucosa were immunoreactive for choline acetyltransferase, substance P and calbindin and very probably represented intrinsic primary afferent neurones. 6. Distension-evoked chloride secretion was mediated by capsaicin-sensitive extrinsic primary afferents and by stretch-sensitive intrinsic primary afferent neurones. Both the extrinsic and intrinsic afferents converge on common efferent pathways. These pathways consist of VIPergic and cholinergic secretomotor neurones that are activated via NK1 and NK3 receptors.

Afferent Pathways↗

Association between duplex Doppler sonographic flow pattern in right hepatic vein and various liver diseases.

PURPOSE: The aim of this study was to evaluate the association between the Doppler sonographic waveforms in the right hepatic vein and various liver diseases. METHODS: We performed Doppler sonography of the right hepatic vein in 225 individuals (189 patients with liver disease and 36 control subjects). Patients were categorized on the basis of their histologic diagnosis: cirrhosis (n = 122), fibrosis (n = 23), fatty liver disease (n = 11), metastatic liver disease (n = 8), and noncirrhotic liver disease with neither fatty infiltration nor metastases (n = 25). The waveforms of the hepatic veins were categorized as type 1, triphasic; type 2, biphasic; or type 3, flat. RESULTS: Type 1 waveforms were found in 100% of the control subjects and in patients with each of the various liver diseases, including 40% of those with cirrhosis. Type 2 waveforms were not found in control subjects or in patients with either fatty infiltration or metastatic liver disease. Type 2 waveforms were, however, found in 16% of patients with cirrhosis, 13% of patients with fibrosis, and 4% of patients with other noncirrhotic liver diseases. Type 3 waveforms were found in 43% of patients with liver cirrhosis, 13% of patients with liver fibrosis, 27% of patients with fatty liver disease, and 50% of patients with metastatic liver disease. In contrast, type 3 waveforms were not found in any control subjects or in patients with other noncirrhotic liver diseases without fatty liver or metastases. CONCLUSIONS: Type 3 waveforms in the right hepatic vein are suggestive of liver cirrhosis, although they may also occur in patients with fibrosis, fatty liver disease, or metastatic liver disease.

Adult↗

Effect of balloon compliance on symptomatic success of pneumatic dilation in achalasia patients.

BACKGROUND: Pneumatic dilation is the standard non-surgical treatment of achalasia. The dilation devices in use differ in their physical properties, particularly with regard to balloon compliance. PATIENTS AND METHODS: 35 achalasia patients (18male, 20-82 years, median 45 years) diagnosed by accepted criteria were prospectively and randomly assigned to 39 dilation procedures by either a low compliance dilation device (LCDD, polyethylene balloon, Rigiflex(trade mark), Microvasive Boston Scientific, USA, n = 18) or a high compliance dilation device (HCDD, latex balloon, Rüsch Inc., Germany, n = 17). Individual complaints were graded by a standardized questionnaire before treatment and prospectively after a median of 3 and 13 months. Furthermore, the patients' readiness to retrospectively re-consent (treatment satisfaction) and treatment complications were recorded. RESULTS: Patient groups did not differ with regard to age, sex, number of previous dilations, and duration of follow-up (Mann-Whitney U-test, p > 0.05). 2 patients were excluded from follow-up, with one individual (HCDD) having suffered a dilation-related perforation (2.6 %) and another subject (LCDD) having not been able to re-contact. Initial and post-treatment symptom scores as well as treatment complications were similar in both treatment groups (p > 0.05). Treatment satisfaction was 90 % for the LCDD and 82 % for the HCDD group at first control, and 89 % and 87 % at second control, respectively (p > 0.05). In both patient groups, dilation therapy best improved the symptom "dysphagia" (Wilcoxon rank sum test, p < 0.05). CONCLUSIONS: Achalasia patients' satisfaction of dilation treatment is high, with their dysphagia benefiting most from therapy. Low and high compliance balloon devices did not differ from each other with regard to symptomatic efficacy and safety in forceful dilation of these individuals.

Adult↗

[Jejunum diverticulosis--a rare cause of gastrointestinal hemorrhage].

In this case report the diagnostic difficulties of massive intestinal hemorrhage caused by diverticula of the small intestine are demonstrated. After resuscitation of the patient by transfusion of 8 units of packed red cells the segment of the jejunum bearing the diverticula was resected. There was no complication until discharge nor was any recurrent bleeding or functional disorder of the bowel reported during follow-up. The clinical presentation, the different value of diagnostic tools and the therapy are discussed.

Diagnosis, Differential↗

Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous flow in patients with cirrhosis.

PURPOSE: The aim of the study was to evaluate the usefulness of color Doppler sonography in the detection of spontaneous portosystemic shunts and abnormal blood flow direction in the portal vein in patients with cirrhosis. METHODS: Patients were 67 men and 42 women (mean age, 53 +/- 14 years) with cirrhosis confirmed by liver biopsy. All patients underwent abdominal gray-scale and color Doppler sonographic evaluations to detect the presence of spontaneous portosystemic shunts and to analyze portal vein blood flow direction. RESULTS: Spontaneous portosystemic shunts were found in 41 patients (38%), most often as splenorenal shunts (21%) and patent umbilical veins (14%). Less frequent were gastric collaterals, gallbladder varices, collaterals to thrombotic portal veins, mesoiliac shunts, and portorenal shunts to the right kidney. The presence of shunts was associated with that of esophageal varices (p < 0.01), ascites (p < 0.01), and inversion of portal flow (p < 0. 001) but not with splenomegaly. The direction of portal venous flow was normal (hepatopetal) in 80 patients (73%), hepatofugal in 10 (9%), and bidirectional in 7 (6%); 12 patients (11%) had partial portal vein thrombosis. CONCLUSIONS: Portosystemic shunts and the direction of portal venous flow are important features in the sonographic diagnosis of portal hypertension.

Adult↗

[Therapy of fecal incontinence in elderly patients: Study of a home biofeedback training program].

UNLABELLED: The increased prevalence of urinary and fecal incontinence is one of the most important factors in the loss of independence and mobility in the elderly population. It is also one of the major reasons for elderly people to give up their household and move into a nursing home. Anorectal biofeedback therapy is a very effective treatment for fecal incontinence. However, due to the increased immobility of elderly people, ambulatory biofeedback training programs which require the participants to leave their homes and travel to the next available outpatient clinic on a regular basis, especially when depending on public transportation, may prove particularly difficult for elderly, incontinent subjects. Supervised home biofeedback training programs may offer an alternative for those patients, who are motivated enough and not mentally impaired. Two different age groups of women (between 49 and 63; and between 65 and 78 years old) suffering from fecal incontinence due to external anal sphincter impairment, received a supervised home biofeedback program, after extensive anorectal diagnostics including manometry. The program focused on improving voluntary sphincter contraction. After an average of 9 months, anorectal manometry was repeated, and anal resting and squeeze pressure as well as minimal rectal perception threshold were determined. There was no effect on anal resting pressure and rectal perception. However, anal maximum squeeze pressure as well as squeeze pressure over 10 s was substantially increased with no difference between the age groups. CONCLUSION: Supervised home biofeedback for sphincter insufficiency was effective in improving the voluntary contraction of the anorectum in both age groups. Therefore, biofeedback home training programs may offer an alternative to ambulatory programs for those individuals, who are not mobile enough to regularly attend an outpatient clinic.

Aged↗

Color doppler sonography avoids misinterpretation of the "parallel channel sign" in the sonographic diagnosis of cholestasis.

PURPOSE: The intrahepatic "parallel channel sign" on gray-scale sonograms is generally interpreted as representing dilated bile ducts, but it may also be caused by enlargement of intrahepatic arteries. This study was performed to evaluate the incidence of misinterpretation of the parallel channel sign without color Doppler sonography and the characteristics of patients in whom misinterpretation of the parallel channel sign is likely to occur. METHODS: A total of 1,100 patients were examined by sonography. All patients with a parallel channel sign on gray-scale sonograms underwent color Doppler sonography. In addition, laboratory values related to cholestasis were measured. RESULTS: The parallel channel sign was observed in 57 patients (5.2%). In 35 (61%) of these patients, color Doppler sonography revealed blood flow in both lumina, indicating that the parallel channel sign was not caused by enlarged bile ducts. Eighty-six percent of this group had nonbiliary liver disease; the enlarged hepatic artery branches were associated with liver cirrhosis in 63% of this group. Color Doppler sonography confirmed that the other 22 patients (39%) had an enlarged intrahepatic bile duct. CONCLUSIONS: Use of color Doppler sonography can help avoid misinterpretation of the parallel channel sign, especially in patients with nonbiliary liver disease.

Cholestasis↗

Different tachykinin receptors mediate chloride secretion in the distal colon through activation of submucosal neurones.

We investigated the role of tachykinin receptor subtypes on secretory responses in the guinea-pig distal colon using Ussing chamber experiments and intracellular recordings from submucosal neurones. Choline acetyltransferase (ChAT) and vasoactive intestinal polypeptide (VIP) were demonstrated in submucosal neurones by immunohistochemistry. In Ussing chamber experiments substance P (SP), the NK1-receptor agonist [SAR9,Met(O2)11]-SP and the NK-3-receptor agonist (MePhe7)-NKB increased dose-dependently short-circuit currents. The NK-2-receptor agonist (betaAla8)-NKA(4-10) had no effect. Responses to 1-100 nM SP, [(SAR9,Met(O2)11]-SP and (MePhe7)-NKB were tetrodotoxin-sensitive but hexamethonium-insensitive. While (MePhe7)-NKB-responses were atropine-sensitive at all concentrations, the atropine sensitivity of the secretory responses to SP and [SAR9,Met(O2)11]-SP dramatically decreased with increasing concentrations. [SAR9,Met(O2)11]-SP and (MePhe7)-NKB effects were blocked by the selective NK-I and NK-3 antagonists CP-99,994-1 (1 microM) and SR 142801 (1 microM), respectively. Combination of both antagonists blocked the SP-response. SR 142801 also suppressed the response to [SAR9,Met(O2)11]-SP. Desensitization with [SAR9,Met(O2)11]-SP significantly decreased (MePhe7)-NKB-responses but not vice versa. In intracellular recordings 90% of submucosal neurones were activated by both ISAR9,Met(O2)11]-SP and (MePhe7)-NKB as indicated by membrane depolarisation and enhanced spike discharge. These effects were tetrodotoxin-resistant and potentiated by atropine. NK-1-and NK-3-mediated responses occurred equally in ChAT-positive and in VIP-positive neurones. The results suggest the importance of NK-1- and NK-3-receptors on cholinergic and non-cholinergic submucosal neurones for secretory processes in the guinea-pig distal colon.

Action Potentials↗