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Gerald Holtmann

Publications and source records attributed to Gerald Holtmann.

30 records · Page 2Linked to original sources
PubMed2004

G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia.

BACKGROUND & AIMS: In patients with functional dyspepsia, altered alpha-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein beta 3 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein beta 3 subunit genotypes with functional dyspepsia. METHODS: In study A, abdominal symptoms were assessed in 67 patients with unexplained, upper abdominal symptoms and 259 consecutive blood donors with and without abdominal symptoms. In study B, a further 56 patients with functional dyspepsia and 112 age- and sex-matched healthy controls from a blood donor population study were evaluated. Genomic DNA was isolated from buccal swabs and genotyping of the C825T polymorphisms was performed by polymerase chain reaction and restriction analysis. RESULTS: In the blood donors with no abdominal symptoms in study A (controls, n = 161), genotype distribution was 17 TT, 77 TC, and 67 CC. In blood donors and patients with unexplained abdominal symptoms, genotype distribution was 22 TT, 54 TC, and 89 CC (P = 0.007 vs. controls). In study B, the genotype distribution in functional dyspepsia patients was 4 TT, 18 CT, and 34 CC compared with 4 TT, 62 CT, and 46 CC in the controls (P < 0.02). Combining studies A and B, the odds ratio (OR) adjusted for age and sex for upper abdominal symptoms associated with the CC genotype was 2.2 (95% confidence interval [CI]: 1.4-3.3), compared with subjects with TC and TT genotype carrying an allele. CONCLUSIONS: Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms.

Abdominal Pain↗
PubMed2004

Are there alterations of neuroendocrine and cellular immune responses to nutrients in women with irritable bowel syndrome?

OBJECTIVES: The goal was to investigate the neuroimmune axis in irritable bowel syndrome (IBS) by analyzing the neuroendocrine and cellular immune responses to nutrient load. METHODS: In the fasting state and 20, 40, 70, and 100 min following nutrient load, blood samples were collected and cardiovascular recordings were accomplished in 15 female IBS patients and 15 healthy women. Plasma norepinephrine, prolactin, cortisol, and growth hormone were analyzed, and blood pressure and heart rate responses were measured. The distribution of peripheral leukocytes and lymphocyte subpopulations and the in vitro production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) after whole blood stimulation with in lipopolysaccharide (LPS) were analyzed. RESULTS: IBS patients demonstrated significantly greater postprandial increases in plasma norepinephrine and systolic blood pressure (p < 0.05), but no cortisol response. A postprandial redistribution of circulating leukocytes and lymphocyte subpopulations was observed in both groups, including significant increases in the numbers of leukocytes and granulocytes and significant decreases in the numbers of monocytes, T-cells, and natural killer (NK) cells (all p < 0.05). However, IBS patients demonstrated significantly greater postprandial increases in leukocytes and granulocytes, while changes in the numbers of monocytes and NK cells were significantly diminished (all p < 0.05). Patients also failed to show the postprandial decrease in the in vitro TNF-alpha production observed in controls. Postprandial norepinephrine concentrations were negatively correlated with NK cell numbers in IBS patients (r= 0.58, p < 0.05) but not controls. CONCLUSIONS: IBS may involve an autonomic hyper-responsiveness to visceral stimuli, which occurs throughout the entire gut, is independent of acutely perceived GI symptoms, and does not necessarily involve HPA axis activation. Women with IBS show altered cellular immune responses to food intake, which may at least in part be mediated by adrenergic mechanisms. Thus, autonomic disturbances may have implications for cellular immune function along the neuroendocrine-immune axis in patients with IBS.

Adult↗
PubMed2003

Serum ferritin and survival of renal transplant recipients: a prospective 10-year cohort study.

Increased serum ferritin is frequent in renal transplant recipients. This reflects iron overload due to blood transfusions given to treat renal anaemia. Previous studies suggested excess mortality in non-renal transplant recipients with iron overload. We hypothesized that serum ferritin levels above 1100 ng/ml may be associated with increased long-term mortality in renal transplant recipients. Twenty consecutive renal transplant recipients with high levels of serum ferritin and 20 renal transplant recipients with normal serum ferritin levels, matched for age and gender, were prospectively studied for 10 years. Nine patients (45%) with increased serum ferritin died during follow-up, compared to four controls (20%). Univariate and multivariate analysis identified multiple blood transfusions (>40 units) prior to transplantation as being associated with higher mortality in renal transplant recipients (risk ratio (RR): 3.1, confidence interval (CI): 1.1-9.2; P=0.03). These data suggest that serum ferritin levels above 1100 ng/ml due to multiple blood transfusions causing iron overload is a relevant factor that increases mortality.

Adult↗
PubMed2003

Papillomatosis confined to the distal biliary tract--a rare cause of obstructive jaundice: report of a case.

Based on the findings of a patient with recurrent obstructive jaundice due to papillomatosis of the distal bile duct, we herein describe the diagnostic difficulties and therapeutic options in this very rare disease. Endoscopic retrograde cholangiopancreatography and, in particular, cholangioscopy are the imaging procedures of choice if biliary papillomatosis is suspected. Due to the tendency of such patients to demonstrate malignant transformation and develop biliary cirrhosis with septic complications, an early and radical surgical resection is recommended in rare cases of localized papillomatosis. This approach may offer the only chance of a cure although the potential risk of multifocal recurrence cannot be ruled out. When considering a radical resection, intraoperative cholangioscopy is strongly recommended to confirm any localized papillomatosis and rule out any diffuse papillomatosis of the entire biliary tract.

Adenoma↗
PubMed2003

GERD 2003 -- a consensus on the way ahead.

Gastroesophageal reflux disease (GERD) has in recent times become an important public health issue owing to the considerable health care resources utilized in its management, its deleterious effect on quality of life and the increasing prevalence of a relatively rare complication of reflux disease - esophageal adenocarcinoma. We review here the major current challenges in the field of reflux disease and its complications, and provide some approaches that may be useful in management. The issues to be faced include the very limited comprehension of the reasons behind the increasing prevalence of the disease, difficulties in correlating symptoms with objective data of pathological gastroesophageal reflux and the relatively unsophisticated tools we are employing to investigate the underlying pathophysiology. It is certain that the lack of well-defined and characterized methodologies to compare the effects of therapy require the development of more effective questionnaire-type analytic tools. In regard to treatment, there is little doubt that the widely prescribed proton pump inhibitors have dose-equivalent efficacy and are the most highly effective agents capable of suppressing acid, controlling many of the symptoms of GERD and healing erosions. Nevertheless, many patients continue to experience symptoms on withdrawal or at night. Pharmacological agents that can effectively increase lower esophageal sphincter pressure or promote motility are as yet unavailable. Although the introduction of laparoscopic techniques has resulted in a modest revival in surgical intervention using a variety of 'wrap-type' operations, the indications are few and the procedure is associated with a significant morbidity and even mortality especially if the expertise of the surgeon is an issue. Endoscopic techniques of regulating reflux are at this time experimental and not applicable to the general population. Intestinal metaplasia in the lower esophagus is probably very common. Whether and how to, first, screen for, and then, perform surveillance in Barrett's esophagus remains highly problematic and contentious.

Barrett Esophagus↗
PubMed2003

Time-resolved three-dimensional MR imaging of gastric emptying modified by IV administration of erythromycin.

OBJECTIVE: The aim of our study was to assess the effect of IV erythromycin on gastric emptying and subsequent small-bowel filling using three-dimensional (3D) MR imaging in both healthy subjects and patients with functional dyspepsia. SUBJECTS AND METHODS: Six healthy volunteers and six patients with symptoms of functional dyspepsia ingested 10 mL of gadopentetate dimeglumine mixed into 500 mL of a liquid nutrient. On two separate days, gastric emptying was determined using 3D volume measurements that were obtained every 5 min for as long as 25 min on 3D T1-weighted gradient-echo MR imaging with and without the use of IV erythromycin. Gastric volumes and filling of the small bowel were quantified on the 3D data sets using semiautomatic software. RESULTS: Delineation of the bright gastric lumen proved easy. After 25 min, a significant decrease in gastric volumes could be seen in examinations performed with and without erythromycin. In healthy volunteers, gastric volumes decreased significantly more after the administration of erythromycin. In three patients with functional dyspepsia, MR imaging revealed reduced rates of gastric emptying. The administration of erythromycin resulted in a significantly faster rate of gastric emptying in two of those three patients. CONCLUSION: Three-dimensional MR imaging is a feasible method of assessing gastric volumes and diagnosing delayed gastric emptying. In patients with reduced rates of gastric emptying, 3D MR imaging may be an appropriate tool with which to monitor therapeutic approaches, such as the use of prokinetic agents like erythromycin.

Adult↗
PubMed2002

Do changes in visceral sensory function determine the development of dyspepsia during treatment with aspirin?

BACKGROUND & AIMS: We hypothesized that the development of dyspeptic symptoms during treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) would be linked to alterations in gastric mechanosensory function and gastric emptying. METHODS: In the first study, gastric mechanosensory thresholds (barostat technique) and gastric emptying ((13)C-octanoic breath test) were measured and endoscopy was performed at entry and after 5 days of treatment with aspirin (500 mg 3 times daily) in 8 patients with functional dyspepsia (initially without symptoms) and 8 healthy controls. In a second, double-blind, placebo-controlled, cross-over study, 6 new patients with functional dyspepsia and 6 controls were started with either placebo or aspirin for 5 days. Sensory thresholds were tested after the fifth day of aspirin or placebo treatment. Abdominal symptoms were assessed daily. RESULTS: In the first study, 6 of 8 patients and 3 of 8 controls, and in the second trial 6 of 6 patients and 1 of 6 healthy subjects, developed dyspepsia on aspirin (P < 0.005 patients vs. healthy subjects). No symptoms occurred during placebo treatment. Lanza scores were not associated with symptoms. After aspirin, sensory thresholds increased in both studies in subjects without development of symptoms (by 25.9% +/- 7.9%, and 31.0% +/- 4.1%, respectively, all P < 0.05), whereas there was no significant increase in subjects who developed symptoms (-11.2% +/- 5.3% and -3.4% +/- 13.4%, all P > 0.4). Neither thresholds nor symptoms were linked with the severity of mucosal damage, baseline gastric emptying (t1/2), or changes of gastric emptying (all P > 0.4). CONCLUSIONS: Failure to increase sensory thresholds during treatment with aspirin is associated with the development of dyspepsia.

Adult↗
PubMed2002

Effect of transient chemically induced colitis on the visceromotor response to mechanical colorectal distension.

BACKGROUND: Acute mucosal inflammation may initiate alterations of visceral sensory function. However, experimental studies on the potential effects of a transient inflammation on visceral sensitivity are lacking. METHODS: We performed colorectal distensions with a barostat device in fasted, conscious, male Lewis rats (n = 20) and assessed the nociceptive response (visceromotor response; VMR) to tonic colorectal distension (CRD) (60 mmHg/3 min) by abdominal-wall electromyography. Measurements were taken before and 3, 5 and 14 days after induction of a transient and self-limiting colitis by instillation of trinitrobenzenesulphonic acid (TNB)/ethanol (or saline as control). Tissue samples from paired controls were obtained to assess histological tissue alterations. RESULTS: TNB/ethanol but not saline induced an acute colitis, with most severe histological lesions occurring 5 days after instillation. After 14 days, there was no histological evidence for persisting mucosal alterations. Five days after induction of TNB/ethanol colitis, the VMR to CRD reached a transient increase (P < 0.05 v. baseline), which returned to baseline levels by day 14. In control experiments (rectal saline instillation), the VMR to CRD decreased significantly compared with baseline values (P < 0.05). CONCLUSION: Following an acute colitis due to single colorectal instillation of TNB/ethanol, histological changes are associated with an enhanced nociceptive response to CRD.

Animals↗
PubMed2002

MR colonography with barium-based fecal tagging: initial clinical experience.

PURPOSE: To assess a strategy for fecal tagging with barium sulfate as an inexpensive tagging agent in conjunction with magnetic resonance (MR) colonography in patients suspected of having colorectal lesions. MATERIALS AND METHODS: Twenty-four patients suspected of having colonic lesions because of rectal bleeding, positive fecal occult blood test results, or altered bowel habits underwent MR colonography and subsequent conventional colonoscopy. A 200-mL dose of a barium sulfate-containing contrast agent was ingested with each of four low-fiber meals, beginning 36 hours before the examination. For MR colonography, the colon was filled with tap water. Gadobenate dimeglumine was injected intravenously. Images were acquired 75 seconds after gadobenate dimeglumine administration by using only a T1-weighted three-dimensional gradient-echo sequence. Images were reviewed by two radiologists blinded to conventional colonoscopic data. By using colonoscopy as the reference standard, sensitivity and specificity of MR colonography were determined for detecting colorectal masses. RESULTS: On the basis of MR colonography, 15 polyps of 5-20 mm and 10 carcinomas were detected and later confirmed with conventional colonoscopy. Conventional colonoscopy depicted three additional lesions less than 8 mm in diameter. Thus, sensitivity of MR colonography was 89.3% (25 of 28) for lesions and 91.7% (22 of 24) for patients. CONCLUSION: Barium-tagged MR colonography obviates bowel cleansing and depicts all lesions exceeding 8 mm in diameter.

Adult↗
PubMed1993

Functional dyspepsia. Current treatment recommendations.

Symptoms of functional dyspepsia are frequent; the prevalence of dyspepsia (defined as pain or discomfort centred in the upper abdomen) in the general population approaches 25%. By definition, patients with functional dyspepsia do not have a structural or biochemical explanation for their symptoms. Disorders of function (e.g. delayed gastric emptying) are detectable in a proportion of patients but remain poorly understood. Nevertheless, the current rationale for drug treatment is based on altering pathophysiological mechanisms which are believed to be associated with the development of symptoms. Although the placebo response rates approach 60%, prokinetics, acid-suppressing agents and bismuth-containing compounds have been shown to be significantly better than placebo in reducing symptoms. Antacids are widely used, but no controlled study has been able to demonstrate a significant benefit over placebo. The efficacy of sucralfate is uncertain. Rational guidelines on which drug should be used for a given patient are lacking, although approaches based on symptom profiles have been proposed; the duration of treatment needed to achieve long-lasting relief of symptoms is also poorly defined. Identifying optimal treatment for the individual patient, therefore, continues to be largely a trial and error process. Further research efforts are needed to elucidate the pathophysiological basis of functional dyspepsia so that specific therapy can be tailored to underlying pathophysiological disturbances.

Cisapride↗