Andreas J. Eherer

Effect of sildenafil on oesophageal motor function in healthy subjects and patients with oesophageal motor disorders

Background and aims: Sildenafil blocks phosphodiesterase type 5 which degrades nitric oxide (NO) stimulated 3`5`-cyclic monophosphate (cGMP), thereby relaxing smooth muscle cells in various organs. We used sildenafil as a tool to investigate the role of the NO-cGMP pathway in the oesophagus of healthy volunteers and patients with hypercontractile oesophageal motility disorders. Methods: Six healthy male volunteers participated in a randomised double blind study on two separate days before and one hour after oral intake of either sildenafil 50 mg or placebo. Oesophageal manometry was performed to determine vector volume of the lower oesophageal sphincter (LOS) and pressure amplitudes of the oesophageal body. Four of the volunteers underwent 12 hour ambulatory oesophageal manometry on two separate days, once with sildenafil 50 mg and once with placebo. An activity index for spontaneous swallowing was calculated for every hour of the study. Eleven patients with hypercontractile oesophageal motility disorders took part in an open study of the effect of 50 mg sildenafil on manometric features of their disorder and on the clinical response to sildenafil taken as required. Results: In healthy subjects, sildenafil significantly reduced LOS pressure vector volume and pressure amplitudes in the distal half of the oesophageal body. In three of four subjects the inhibitory effect of sildenafil lasted at least eight hours. In nine of 11 patients, manometric improvement after sildenafil was observed but only four had an improvement in oesophageal symptoms with sildenafil taken as required. Two of these four patients however experienced side effects and did not want to continue treatment. Conclusions: Sildenafil lowers LOS pressure and propulsive forces in the body of the oesophagus of healthy subjects as well as in patients with nutcracker oesophagus, hypertensive LOS, and achalasia. The effect of sildenafil on the oesophageal body may last for up to eight hours in healthy volunteers. A subset of patients with hypertensive LOS or nutcracker oesophagus may benefit from sildenafil but side effects are a limiting factor.

Anti-cardiolipin antibodies in patients with inflammatory bowel disease.

Elevated levels of anti-cardiolipin antibodiesare associated with an increased risk for venous andarterial thrombosis. In patients with inflammatory boweldisease thrombosis is a well known complication. We determined the prevalence of elevatedanti-cardiolipin antibodies in 136 patients withinflammatory bowel disease compared with 136 healthycontrols and analyzed thromboembolic complications inpatients with increased anti-cardiolipin antibodylevels. Anti-cardiolipin antibody titers weresignificantly elevated in patients with Crohns disease(5.7 units/ml) and ulcerative colitis (5.3 units/ml)compared to the control group (2.5 units/ml). We foundno correlation between disease activity andanti-cardiolipin antibody levels. Seven patients haddeep venous thrombosis in their history, in three ofthem this was complicated by pulmonary embolism. In onlytwo of the seven patients with deep venous thrombosiswere anti-cardiolipin antibody levels increased. Inconclusion, anti-cardiolipin antibody titers were significantly increased in patients withinflammatory bowel disease. Elevated anti-cardiolipinantibody levels appear to play no role in thepathogenesis of thromboembolic events in patients withinflammatory bowel disease.

Intraluminal capsaicin does not affect fluid and electrolyte absorption in the human jejunum but does cause pain

Background—Stimulation of sensory nerves with capsaicin regulates ion transport in the small intestine in animal experiments. Aim—To investigate whether sensory nerves that are stimulated by capsaicin administration influence fluid and electrolyte absorption in the human jejunum in vivo. Method—Intestinal perfusion studies were performed in 12 healthy subjects using a four lumen tube with a proximal occlusion balloon and a plasma-like electrolyte solution. After an initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) μg/ml capsaicin was added to the perfusate, and this was followed by a final control period. Rates of absorption of water, sodium, potassium, chloride, and bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable volume marker. Results—At all three concentrations of capsaicin there were no significant changes in water and electrolyte absorption as compared with control periods. Two subjects who received 10 μg/ml and the subject receiving 50 μg/ml experienced crampy abdominal pain. Conclusion—The results do not support the hypothesis that capsaicin sensitive afferent nerves are involved in the physiological regulation of net absorption or secretion across the human jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to abdominal pain.

Effect of neuropeptide Y on jejunal water and ion transport in humans

Neuropeptide Y is a neurotransmitter in enteric and postganglionic sympathetic neurons. In animal models of intestinal water and ion transport, neuropeptide Y decreases stimulated secretion but has no consistent effect on basal transport. In the present study, the effect of neuropeptide Y on jejunal water and electrolyte transport in healthy volunteers was investigated under basal conditions and during intestinal secretion induced by intraluminal administration of prostaglandin E2. The triple-lumen tube technique was used for perfusion of the small intestine with a plasmalike electrolyte solution containing polyethylene glycol as a nonabsorbable volume marker. After an initial control period (saline IV) neuropeptide Y was administered IV at a dose of 400 pmol.kg-1.h-1. Neuropeptide Y significantly increased net absorption of water, sodium, potassium, and chloride under basal conditions. The peptide significantly reduced the secretion of these electrolytes induced by an intraluminal prostaglandin E2 concentration of 5 mumol/L and reduced net water secretion by 36%. The results of the current study suggest that neuropeptide Y can change intestinal water and ion transport from secretion toward absorption.

Effect of cholera toxin on the human jejunum.

In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents.

Gastric adenocarcinoma mimicking achalasia in a 15-year-old patient: a case report and review of the literature.

Although adenocarcinoma of the cardia is extremely rare in adolescent patients, the endoscopist should be alert to this disease in patients of any age with dysphagia, even if symptoms, and results of a barium study, upper endoscopy, and esophageal manometry are suggestive of primary achalasia, especially if family history is negative for achalasia. In addition, secondary achalasia should be suspected in patients who do not respond to therapy with botulinum toxin within 2 months. Because none of the mentioned tests can distinguish between primary achalasia and secondary forms due to carcinoma of the cardia, biopsy specimens should be obtained. It appears that, although there is a minimal risk for complications, a diagnostic procedure such as biopsy would be appropriate when the information obtained could be essential. In some cases EUS can be an additional diagnostic tool, because lesions of the submucosa and the surrounding area can be identified by EUS.

Absorption of hydrolysed bovine serum albumin from the human jejunum over a 6-hour period

Objective: Quantitative assessment of intestinal absorption of total and single amino acids in a hydrolysed bovine serum albumin solution over a 6‐h period. Design: Ten healthy volunteers underwent segmental jejunal perfusion using a multilumen tube assembly with a proximal occluding balloon. Prehydrolysed bovine serum albumin served as protein source. In one set of experiments we used a washout phase before the equilibration period to eliminate any contents present in the test segment. In another set we started directly with the equilibration period. Absorption rates of total and single amino acids were measured over a period of 6h. Results: Absorption rates remained constant throughout this period and there was no significant difference in absorption rates whether a washout phase was used or not. Absorption rates of total amino acids ranged from 6.4±1.9 (mean±SEM) to 10.7±0.7 g/h and 30 cm, when a washout phase was used. Percentage absorption of the perfusion load per hour was 24±7% to 40±2% with a washout phase. Although a highly concentrated perfusion load was used there was a correlation (r=0.66, P<0.05) between absolute concentration in the perfusion solution and the amount of individual amino acid absorbed. Individual amino acids showed a wide range of percentage absorption. Percentage absorption of 50% or more of the perfusion load was seen for alanine, phenylalanine, arginine, leucine, methionine and tyrosine. The highest absorption rate was seen for methionine with 86%, the lowest for cysteine with 3%. Conclusion: When hydrolysed bovine serum albumin is used, amino acid absorption is constant over a period of 6h in the human jejunum. A washout phase has no influence on total and single amino acid absorption.

Effect of pantoprazole on reflux-associated laryngitis: A placebo-controlled crossover study

Effect of Pantoprazole on Reflux-Associated Laryngitis: A Placebo-Controlled Crossover Study Andreas J. Eherer, Dept of Internal Medicine, KarI-Franzens Univ, Graz Austria; Walter Habermann, Dept of Oto-Rhino-Laryngology, KarI-Franzens Univ, Graz Austria; Heinz F. Hammer, Dept of Internal Medicine, Kari-Franzens Univ, Graz Austria; Karl Klasler, Gerhard Friedrich, Dept of Oto-Rhino-Laryngology, KarI-Franzens Univ, Graz Austria; Guanter J. Krejs, Dept of Internal Medicine, KarI-Franzens Univ, Graz Austria