Gastric electrical stimulation results in improved metabolic control in diabetic patients suffering from gastroparesis.

AIMS/HYPOTHESIS: Symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. Gastric electrical stimulation (GES) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. However, the effect of GES on metabolic control has not been assessed yet. METHODS: We performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy GES on symptoms, gastric emptying (measured scintigraphically), and metabolic control (HbA1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. RESULTS: Seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. No therapy-associated adverse events occurred. Weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. Gastric retention rates improved significantly from 83 % (2 h) and 38 % (4 h) to 35 % (2 h)/14 % (4 h) and 25 % (2 h)/17 % (4 h) at 6 and 12 months, respectively. HbA1c values were lowered in all 17 subjects; initially, all HbA1c values were above 7.5 %; at 6 and 12 months, mean values had significantly decreased from 8.6 % to 6.2 % and 6.5 %, respectively. CONCLUSIONS/INTERPRETATION: Gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. This study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by HbA1c, a surrogate marker of the risk of diabetic complications.

Gastric electrical stimulation in intractable symptomatic gastroparesis.

BACKGROUND: The treatment of gastroparesis remains unsatisfactory despite prokinetic and anti-emetic drugs. Gastric electrical stimulation has been proposed as a therapeutic option. We have assessed the effect of gastric electrical stimulation on symptoms, medical treatment, body weight and gastric emptying in patients with intractable symptomatic gastroparesis in a non-placebo-controlled study. METHODS: In this multicenter study, 38 highly symptomatic patients with drug-refractory gastroparesis were enrolled. Patients first received temporary electrical stimulation using percutaneous electrodes. The 33 responders to temporary stimulation then underwent surgical implantation of a permanent stimulator. Severity of vomiting and nausea was assessed before and after stimulation. Patients were reassessed 3, 6, and 12 months after permanent implantation. RESULTS: With stimulation, 35/38 patients (97%) experienced >80% reduction in vomiting and nausea. This effect persisted throughout the observation period (2.9-15.6 months, 341 patient-months). Gastric emptying did not initially change, but improved in most patients at 12 months. At 1 year, the average weight gain was 5.5% and 9/14 patients initially receiving enteral or parenteral nutrition were able to discontinue it. CONCLUSION: Electrical stimulation of the stomach has an immediate and potent anti-emetic effect. It offers a safe and effective alternative for patients with intractable symptomatic gastroparesis.

[Fulminant liver failure after administration of the herbal antidepressant Kava-Kava]. / Fulminantes Leberversagen nach Einnahme des pflanzlichen Antidepressivums Kava-Kava.

HISTORY AND CLINICAL FINDINGS: A 60 year-old woman was admitted to hospital because of jaundice, fatigue, weight loss over several months and icteric skin. Because of progressive liver failure, concomitant renal failure and progressive encephalopathy she was transferred to an intensive care unit. INVESTIGATIONS: Biochemical tests revealed acute liver failure with high levels of total and conjugated bilirubin (30 mg/dl) as well as aspartate aminotransferase (921 IU/l) and alanine aminotransferase (1350 IU/l) concentrations. Prothrombin time was less than 10 %. Serological tests could rule out viral hepatitis, metabolic or autoimmune causes of liver failure. On abdominal computed tomography and ultrasonography no pathological changes were detected. Above all portal vein thrombosis, ascites, focal lesions of the liver and extrahepatic cholestasis could be excluded. Liver histology showed extensive hepatocellular necrosis with intrahepatic cholestasis. TREATMENT AND CLINICAL COURSE: The patient's physical condition deteriorated. She had to be intubated because of respiratory insufficiency and encephalopathy stage IV. Because of progressive liver failure under conservative treatment the patient received an orthotopic liver transplant 11 days after admission. CONCLUSIONS: The exclusion of other causes and the histological diagnosis made Kava-Kava as the cause of acute liver failure most likely. This is the 18th case of Kava-Kava induced liver failure reported to the European regulatory authorities.

Expression of decorin and biglycan in rat gastric tissue: effects of ulceration and basic fibroblast growth factor.

BACKGROUND: The small chondroitin/dermatan sulphate proteoglycans decorin and biglycan participate in organizing the network of collagen fibrils and interact with non-collagenous matrix proteins. In addition, via interactions with cytokines they are directly or indirectly involved in signalling, growth and cell differentiation. We aimed to analyse their expression in normal gastric tissue and during gastric ulcer healing. METHODS: Proteoglycan expression was studied by immunohistochemistry and in situ hybridization in acetic acid-induced gastric ulcers in rat during early phases and during chronic ulceration. The effects of treatment with an acid stable mutein of FGF-2 (bFGF) were also studied. RESULTS: In normal gastric tissue, both proteoglycans were most strongly expressed in the submucosal layer. However, some epithelial cells were positive for biglycan and, surprisingly, also for decorin. In the early phase after ulcer induction exclusively decorin became induced in the muscularis mucosae, while biglycan became detectable in this layer only after 2 weeks. There was no up-regulation of either proteoglycan in other layers, nor could an effect of FGF-2 treatment be seen. CONCLUSIONS: The expression of decorin could be observed for the first time in epithelial cells. Decorin, but not biglycan, appears as an early phase reactant in the muscularis mucosae in accordance with its putative role during angiogenesis and the prevention of apoptosis.

Enhancement in the protective qualities of gastric mucus with combination therapy of ebrotidine and amoxicillin for H. pylori eradication.

1. Gastric mucus from Helicobacter pylori-positive patients with active chronic gastritis type B, before and after successful combination therapy consisting of the H2 receptor antagonist ebrotidine (400 mg) and amoxicillin (1,000 mg) administered b.i.d., in the morning and at bedtime for a period of 2 weeks followed by administration of ebrotidine alone for the subsequent 4 weeks, was assessed for the changes in physicochemical properties associated with the mucosal protective potential and anti-H. pylori activity. 2. The results of physicochemical measurements revealed that eradication of H. pylori associated with the successful therapy for active chronic gastritis type B with ebrotidine-amoxicillin was accompanied by a 36% increase in gastric mucus hydrogen ion retardation capacity, a 1.5-2.1-fold increase in mucus gel viscosity and a 2.4-fold increase in its hydrophobicity. 3. The beneficial changes brought about by the ebrotidine-amoxicillin therapy in the physical properties of gastric mucus were also manifest in a 2.7-fold enhancement in the proportion of the high-molecular-weight polymeric mucin form responsible for the maintenance of gastric mucus gel integrity. 4. Moreover, assays of H. pylori aggregating titer of gastric mucus revealed that the successful combination therapy with ebrotidine and amoxicillin led to a 3.8-fold increase in mucin anti-H. pylori activity. 5. The results demonstrate that combination therapy with ebrotidine and amoxicillin for H. pylori eradication leads to a marked improvement in the protective qualities of gastric mucus essential for the preservation of mucosal integrity and enhances the inherent mucosal defense against H. pylori infection.

Analysis of a protein kinase C-alpha mutation in human pituitary tumours.

It is generally accepted that protein kinase C-alpha (PKC-alpha) is an important enzyme in the cellular regulation of growth and differentiation by phosphorylating proteins. Recent studies have described a point mutation of PKC-alpha (position 908 of the genetic sequence, codon GAC becoming GGC) in invasive human pituitary tumours which leads to an exchange of amino acids in the protein. We investigated 11 human pituitary tumours to evaluate the data obtained previously. cDNA was subcloned and up to ten individual clones were sequenced from each tumour, resulting in 85 clones analyzed in total. All of the pituitary adenomas showed a normal wild-type sequence of PKC-alpha DNA. Even if the tumour was 'invasive' (infiltration of the dura mater) no mutation at position 908 of the sequence was found. Moreover, using Western blot analyses we did not observe any differences in PKC-alpha protein expression in invasive as compared with noninvasive pituitary adenomas. Until now we have been unable to confirm the data of other investigators, suggesting that mutated PKC-alpha is an inconsistent feature of invasive pituitary tumours.

[Acute sigmoid diverticulitis--current diagnosis]. / Akute Sigmadiverticulitis--aktuelle Diagnostik.

Acute sigmoid diverticulitis may present in different forms. Firstly, symptomatic diverticulosis and acute diverticulitis have to be differentiated to allow for the proper selection of treatment. In the initial phase of diagnostic procedures in addition to clinical features a few laboratory data, plain X-ray films of the abdomen and abdominal ultrasound are helpful to obtain information about the potential presence of perforation, abscess, tumor masses and the structure of the colonic wall. Computed tomography is capable to answer most of the questions in the diagnostic work-up of acute diverticulitis. On the other hand, contrast barium enema provides little additional information and should be considered as contraindicated in acute diverticulitis. If at all, water-soluble contrast media should be employed. Endoscopy has its place in the differential diagnostic evaluation of severe bleeding and suspected tumor, but should be reserved for these limited indications.

Acupuncture inhibits vagal gastric acid secretion stimulated by sham feeding in healthy subjects.

In a prospective randomised study, the effect of acupuncture on sham feeding stimulated gastric acid secretion was investigated. In eight healthy volunteers (five men, three women, mean (SEM) age 26.3 (4.7) years) various methods of acupuncture were performed. Apart from the sham procedure, the acupuncture was performed at the classic acupuncture points. Electroacupuncture reduced gastric acid secretion expressed as median (range) significantly during the first 30 minute period to 1.6 (0-5.2) mmol compared with 3.8 (2.3-14.5) mmol (p < 0.05) during control period (sham feeding without acupuncture). Inhibition of gastric acid secretion by electroacupuncture was also significant during the second 30 minute period (0.2 (0-5.6) v 3.6 (0.3-9.1) mmol; p < 0.05) and for peak acid output (0.8 (0.2-5.1) v 7.6 (3.4-12.1) mmol; p < 0.05). Transcutaneous electrical nerve stimulation also resulted in significant reduction of gastric acid secretion during the first 30 minute period (1.0 (0-3.6) mmol v 3.8 (2.3-14.5) mmol; p < 0.05), and peak acid output (3.6 (1.2-12.0) v 7.6 (3.4-12.1) mmol; p < 0.05). The classic needle acupuncture, laser acupuncture, and sham acupuncture had no significant effect on gastric acid secretion. This study shows firstly that in healthy volunteers, only the versions of acupuncture using more pronounced stimulation (electroacupuncture, transcutaneous electrical nerve stimulation), but not those with only mild stimulation of the nerves (classic needle acupuncture, laser acupuncture), and secondly only acupuncture performed at defined points lead to significant reduction in gastric acid secretion.

Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis.

The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851 +/- 361 ng/ml in group A versus 840 +/- 348 ng/ml in group B; after the 5th infusion it was 2,005 +/- 588 ng/ml in group A versus 2,463 +/- 1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582 +/- 308 ng/ml in group A versus 379 +/- 170 ng/ml in group B; P less than 0.05) and in the elimination half life (8.5 +/- 2.6 h in group A versus 6.1 +/- 1.1 h in group B; P less than 0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.

[Drug testing today]. / Arzneimittelprüfung heute.

According to the new West German drug legislation, new drugs will only be registered if their quality, effectiveness and safety is ensured. Safety means a favourable ratio of therapeutic value and risk of side-effects. Effectiveness can usually be verified most objectively in adequate and well-controlled clinical investigations (phase II and phase III of drug evaluation), which are preceded by pharmacological and toxicological experiments in animals and preliminary pharmakokinetic and pharmakodynamic studies in volunteers (phase I). In phase III and IV, rare but important adverse drug effects are looked for.

Effect of lysine-acetylsalicylate on serum gastrin levels.

The effect on serum gastrin levels of lysin-acetylsalicylate (LAS), water soluble derivative of acetylsalicylic acid, was investigated in mice. Intragastrically administered LAS did not at all alter serum gastrin values while--when given via the intravenous route--LAS not earlier than at the very high dose of 450 mug/g caused a short-lived significant increase in serum gastrin. These results are in keeping with the view that salicylates do not owe their potential ulcerogenic properties to stimulation the gastrin-gastric secrection mechanism.