Cystatin C as an endogenous marker of glomerular filtration rate in renal transplant patients.

BACKGROUND: Serum creatinine is the most common endogenous marker used to estimate the glomerular filtration rate (GFR). However, creatinine depends considerably on muscle mass, and its tubular secretion increases, especially in chronic renal failure. Cystatin C is a 13-kD protease inhibitor which is produced by all nucleated cells and is independent of muscle mass and sex. Cystatin C is eliminated by glomerular filtration and metabolized by proximal tubular cells. Its measurement has been proposed as an alternative and more sensitive marker of GFR than creatinine in patients with slight to moderately decreased GFR. METHODS: We investigated serum cystatin C levels in comparison with creatinine as a single measurement for estimation of GFR in 173 patients after renal transplantation. GFR was calculated as creatinine clearance according to standard equations. RESULTS: Serum creatinine correlated well with cystatin C (r = 0.84; p < 0.0001). No significant differences were obtained for the comparison of the linear correlation of 1/creatinine with creatinine clearance (r = 0.77; p < 0.0001) and for the linear correlation of 1/cystatin C with creatinine clearance (r = 0.73; p < 0.0001). However, we found a significant advantage of cystatin C in detecting a clinical relevant reduction of kidney function (GFR <70 ml/min; p = 0.0047, McNemar test). CONCLUSION: Cystatin C is an alternative marker for the assessment of GFR in renal allograft recipients that may be superior to creatinine.

Prediction of the lower esophageal sphincter pressure after oral molsidomine by sydnonimine plasma concentrations.

BACKGROUND/AIMS: Recent studies suggest that endogenous nitric oxide decreases lower esophageal sphincter pressure (LESP). Substances leading to the formation of nitric oxide, such as molsidomine, decreases the human LESP. It is not yet clear whether this reduction is related to plasma concentrations of molsidomine, the nitrate-active substance sydnonimine (SIN-1) or to serum concentrations of nitrate/nitrite (NOx) as a stable end-product of volatile nitric oxide. METHODOLOGY: We performed a double blind controlled crossover trial in 8 healthy male volunteers. Plasma concentrations of molsidomine, SIN-1 and serum concentrations of NOx as well as esophageal manometry were determined. RESULTS: Mean basal LESP was significantly decreased from 25.4 +/- 2.8 mmHg to 21.9 +/- 2.7 mmHg and 21.4 +/- 2.6 mmHg 2 and 3 hours after molsidomine administration, respectively (mean +/- SEM; n = 8; p < 0.05). The maximum decrease of LESP from the baseline within 1-4 hours after molsidomine administration was 7.6 +/- 1.5 mmHg (mean +/- SEM; n = 8; p < 0.01). The decrease of the LESP correlated significantly with plasma concentrations of SIN-1 (r = -0.53; p = 0.002). NOx levels remained unchanged. CONCLUSIONS: Molsidomine decreases the LESP and plasma concentrations of the active metabolite SIN-1 may predict the potency of molsidomine to lower LESP. NOx was useless as a control metabolite to measure the LESP in response to molsidomine in healthy volunteers.

Effect of omeprazole treatment on plasma concentrations of the gastric peptides, xenin, gastrin and somatostatin, and of pepsinogen.

The peptide xenin 25 is a gastric mucosal constituent like gastrin, somatostatin and pepsinogen. Gastrin and pepsinogen plasma concentrations increase when the secretion of gastric acid is reduced by proton pump inhibitors. In the present investigation, treatment with omeprazole led to an increase in fasting and postprandial plasma concentrations of xenin, gastrin and pepsinogens A and C (P < 0.05, in each instance), whereas somatostatin plasma levels remained unchanged. Because subcutaneous injection of pentagastrin did not raise xenin plasma concentrations, a direct effect of gastrin on xenin production seems unlikely. This study indicates that xenin plasma concentrations are regulated by intragastric pH, as are those of gastrin and pepsinogen.

Cholestasis associated with mesalazine therapy in a patient with Crohn's disease.

BACKGROUND/AIMS: Mesalazine is a widely prescribed medication, developed as an alternative to sulfasalazine in the treatment of inflammatory bowel disease. In contrast to sulfasalazine, there are only a few case reports on its causing hepatic injury. We here report on a patient with cholestasis after mesalazine therapy for Crohn's disease of the ileum. METHODS/RESULTS: The patient, a 30-year-old man, developed clinical signs of severe hepatic injury 4 months after treatment with mesalazine (4 g/day) including biopsy-proven hepatocellular cholestasis with minimal focal mononuclear inflammatory infiltration. Contrary to previous reports, no symptoms of generalized hypersensitivity were seen. The patient's illness was resolved by discontinuing the mesalazine treatment and he recovered completely in 40 days. CONCLUSIONS: This case reinforces the possibility of a causal relationship between mesalazine treatment and toxic hepatic injury without systemic hypersensitivity.

Effect of omeprazole on Helicobacter pylori urease activity in vivo.

BACKGROUND: Detection of Helicobacter pylori infection in clinical routine is based either on the direct visualization of the bacterium in gastric biopsies by histology or microbiology or on the demonstration of urease activity in gastric biopsies and by the labelled-urea breath test (UBT). Omeprazole has a strong inhibitory effect on H. pylori urease activity in vitro, but its effect in vivo and thus its influence on urease-based diagnostic procedures has not been investigated systematically. AIM: To investigate whether omeprazole is able to inhibit H. pylori urease activity in vivo and, if so, at which doses. PATIENTS: Eighteen patients with H. pylori associated chronic gastritis were studied. METHODS: H pylori diagnosis was based on histology, rapid urease test and culture from antral biopsies. Following a positive H. pylori diagnosis patients received omeprazole 20mg (n = 6), 40mg (n = 6) and 80mg (n = 6) once daily for 5 days and 13C-UBT was performed on day 1, 3 and 5, 30min after each omeprazole administration. The 13C-UBT was performed with 200ml 0.1 N citric acid as test drink and 75mg 13C-urea. Breath samples were collected before and 30 min after 13C-urea administration. RESULTS: A significant inhibition of urease activity was observed only under high dose omeprazole administration (80 mg/day), and the 13C-UBT turned negative in three (50%) of these patients after 5 days therapy. CONCLUSION: Short-term omeprazole administration reduces H. pylori urease activity only at doses as high as 80 mg/day. A direct inhibition of enzyme activity as well as a reduction in the number of viable H. pylori bacteria may be responsible for this omeprazole-mediated reduction in urease activity. Urease-based diagnostic procedures for H. pylori are not suitable for patients under omeprazole therapy depending on the dose and duration of therapy.

Effect of human gastrin-17 with and without acid suppression on human esophageal motility.

The putative role of gastrin for the regulation of esophageal motility is a matter of debate. Accordingly it was the aim of this study a) to examine if physiological postprandial plasma levels of human gastrin-17 (hG-17) can affect esophageal motility, especially the pressure of the lower esophageal sphincter (LESP), and b) to assess the contribution of augmented acid secretion during gastrin infusion. In a first series of experiments postprandial plasma gastrin levels were determined in 8 healthy volunteers following the ingestion of a mixed meal. Gastrin rose from a baseline of 21 +/- 2 pg/ml to 67 +/- 8 pg/ml and returned almost to basal levels within 120 minutes. In a second experimental series the effect of i.v. synthetic human gastrin-17 (hG-17) was studied in 17 volunteers. At a lower dose of 0.75 ng/kg/min hG-17 increased plasma gastrin to 62 +/- 7 pg/ml while a higher dose of 1.5 ng/kg min elicited a supraphysiological increase to 119 +/- 11 pg/ml. Infusion of hG-17 caused a significant increase of the LESP from 19.0 to 25.8 mmHg (p < 0.05, low dose) and from 18.5 mmHg to 23.3 mmHg (p < 0.05, high dose) when compared to the effect of i.v. saline. To exclude effects of augmented acid secretion during hG-17 infusion the experiments were repeated after complete blockade of acid secretion with famotidine 40 mg i.v. After famotidine pretreatment hG-17 caused a similar increase of LESP from 20.1 to 25.9 mmHg (low dose) and from 19.9 to 24.1 mmHg (high dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Double blind placebo controlled study on the effect of the nitric oxide donor molsidomin and the 5-HT3 antagonist ondansetron on human esophageal motility.

The aim of the present study was to investigate the effects of acute administration of the NO-donor molsidomin (2 mg) and the 5-HT3 antagonist ondansetron (8 mg) on esophageal motility and lower esophageal sphincter pressure (LESP) in 10 healthy volunteers by stationary side hole manometry in a double-blind placebo controlled study design. LESP, contraction amplitudes (5, 10, 15 cm above the LES) and propagation velocity (10-15 cm above the LES) for dry and wet swallows were analysed and additional blood samples were taken for determination of plasma levels of VIP and gastrin. Molsidomin significantly decreased basal LESP from 16.8 +/- 1.6 mmHg to 11.4 +/- 1.0 mmHg, while ondansetron had no influence. Molsidomin also reduced contraction amplitudes of dry swallows (saline 61.9 +/- 7.2 mmHg, molsidomin 40.1 +/- 8.1 mmHg), while it did not influence contraction amplitudes of wet swallows. Ondansetron had no effect on contraction amplitudes. Both substances did not influence propagation velocity of wet swallows, while they reduced propagation velocity of dry swallows significantly (saline 3.9 +/- 0.4 cmls, ondansetron 3.1 +/- 0.2 cm/s, molsidomin 3.1 +/- 0.2 cmls). There were no effects on plasma levels of gastrin or VIP. These data strongly suggest a possible therapeutic role of molsidomin in the treatment of esophageal motility disorders. Effects of ondansetron have to be further evaluated in patients with disturbed esophageal motility.

Drug-induced dysphagia.

Dysphagia describes the disability or problems in swallowing a wet or dry bolus properly and is normally associated with an impaired transport of the bolus. Dysphagia can be accompanied by a pain sensation in the chest mostly caused by impaction of the food bolus in the esophagus. Odynophagia describes only the status of painful swallowing without an impairment of the swallow and transport function. Drug-induced dysphagia can be caused in two different ways. First as a normal drug side effect of the pharmacological action of the drug or as a complication of the therapeutic action of the drug. The normal drug side effect is most likely in drugs that affect smooth or striated muscle function or the sensitivity of the mucosa. The drug effect on smooth muscle function that causes dysphagia can be inhibitory or excitatory. Dysphagia is a common clinical symptom in patients with reduced perception of the pharyngeal mucosa which leads to an subjective impairment of swallowing. Dysphagia caused by a complication of the therapeutic action of a drug includes viral or fungal esophagitis in patients treated with immunosuppressive drugs or cancer therapeutic agents, or antibiotics and immunological reactions to certain drugs such as erythema exsudativa multiforme or Stevens-Johnson syndrome. Second, drug-induced dysphagia can be due to medication-induced esophageal injury (MIEI). In most cases this mucosal injury appears to be the direct result of prolonged contact of a potentially caustic drug with the esophageal mucosa. This form of medication-induced esophagitis is most likely to be found in elderly patients and patients with esophageal motility disorders.(ABSTRACT TRUNCATED AT 250 WORDS)