[Somatostatin-analogue treatment of severe esophagitis after gastrectomy]. / Behandlung einer schweren ulzerösen Refluxösophagitis nach Gastrektomie mit einem Somatostatinanalogon.

This article presents a case of successful treatment of severe erosive esophagitis, which developed after total gastrectomy. The patient suffered from a poorly differentiated, diffuse gastric carcinoma with subtotal gastric outlet obstruction, accompanied by Helicobacter pylori-associated type b gastritis. A few weeks after Helicobacter eradication followed by successful surgery, swallowing of nutrition became impossible due to severe erosive esophagitis. Histologically there was no evidence of tumor infiltration in this organ. After numerous unsuccessful attempts using established conventional pharmacotherapy options, the problem could be solved by daily subcutaneous somatostatin-analogue (octreotide) injections. The patient started to eat again, and endoscopically/histologically the severe inflammation significantly improved. Attempts to reduce the daily injections, undertaken by the patient, resulted in relapses within a few days. Octreotide was well tolerated by the patient.

[Coronary risk factors in chronic hemodialysis patients]. / Koronare Risikofaktoren bei chronisch hämodialysierten Patienten.

BACKGROUND: In contrast to persons with normal renal function, coronary risk factors or indicators until yet could not clearly be defined in renal insufficiency. PATIENTS AND METHODS: 30 patients under chronic hemodialysis therapy were investigated; 15 patients with severe coronary artery disease and 15 patients with normal coronary angiogram were compared. Numerous factors of the manner of living (diet, smoking behaviour etc.) were registered and glucose and lipid metabolism, hemostatic and fibrinolytic system as well as blood pressure level were investigated. RESULTS: Besides higher HDL-cholesterol and tissue plasminogen activator (TPA) levels in patients without coronary heart disease, no significant difference could be found between both groups. The higher HDL levels were mainly due to the higher percentage of women in the coronary healthy group. There was no evidence of insulin resistance as a major pathogenic factor in the group with coronary heart disease. The blood pressure levels were not significantly different in both groups. CONCLUSION: Our quantitative examination of accepted or suspected coronary risk factors revealed no entity which turned out to be a reliable risk indicator for practical purposes.

[Symptomatic therapy with famotidine in non-erosive gastro-esophageal reflux. Results of an open multicenter study]. / Symptomatische Therapie mit Famotidin bei nicht-erosiver gastro-ösophagealer Refluxkrankheit. Ergebnisse einer offenen multizentrischen Studie.

180 patients suffering from frequent heartburn and endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis entered an open, multicentre study to evaluate the 6-week safety profile and efficacy on symptom relief of famotidine (CAS 76824-35-6, Pepdul mite), a potent and long-acting H2-receptor antagonist. By week 6 the cumulative percentage of patients with defined response, that is complete relief of heartburn in 5 days and only mild discomfort in the remaining 2 days of a week, reached 68.9%, whereas the cumulative percentage of patients with complete relief of heartburn within a week reached 52.7%. Throughout the evaluation period famotidine relieved nighttime heartburn better than daytime heartburn. More than 75% of the responders remained without recurrence. Even the non-responders experienced a 60-70% reduction of heartburn severity assessed using scores. Antacid consumption was reduced from 18 tablets (median) in week 0 to 5 tablets in week 6. 90% of the patients reported at week 6 excellent (67.2%) or moderate (22.8%) symptomatic improvement. No serious adverse events attributable to famotidine occurred. It is concluded that in patients with non-erosive gastro-oesophageal reflux disease famotidine therapy, 20 mg twice daily, is highly effective in reducing reflux disease symptoms.

Regulation of adrenergic receptors in the rat kidney.

Chronic daily application of (+/-)-isoprenaline induced a selective-down regulation of beta-adrenoceptors in the kidney: the concentration of [3H]dihydroalprenolol binding sites was significantly lowered by isoprenaline treatment while [3H]prazosin and [3H]rauwolscine binding, representing alpha 1- and alpha 2-adrenoceptors, respectively, was not markedly altered. Since the proportion of high- and low-affinity sites for the non-selective alpha- but relatively beta 1-selective agonist (-)-noradrenaline remained constant and since in [3H]dihydroalprenolol competition experiments the high- and low-affinity site ratio fitted well to the beta 1/beta 2 relation, determined independently by employing ICI 118551 as a beta 2-selective ligand, a parallel decrease of both beta 1- and beta 2-adrenoceptor density can be concluded.

Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis.

N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acetate on left ventricular function in hemodialysis patients.

Two approaches were chosen to assess the controversially debated influence of acetate on the heart in dialysis patients: (1) To separate acetate effects from influences of dialysis, acetate was infused in 12 chronic dialysis patients with normal systolic function on a dialysis-free day, and left ventricular (LV) function was assessed by LV pressure/volume loops. Hyperacetatemia (3-5 mmol/l) resulted in a decrease in LV preload (LV end-diastolic pressure decreased from 16 +/- 3 to 10 +/- 4 mm Hg, p < 0.01) but had no influence on LV contractility. (2) In 8 dialysis patients without cardiac disease, isovolemic acetate or bicarbonate dialysis was performed. During both procedures, there were comparable changes in serum electrolytes as well as in echocardiographic parameters. LV contractility measured by velocity of circumferential fiber shortening increased during acetate and bicarbonate dialysis (1.47 +/- 0.22 to 1.77 +/- 0.29, p < 0.01; 1.47 +/- 0.21 to 1.70 +/- 0.22 circ/s, p < 0.01). It is concluded that mild hyperacetatemia does not influence LV contractility and that dialysis-induced changes in serum electrolytes are responsible for the increase in LV contractility during dialysis. However, the pronounced acetate effect on LV preload implies considerable therapeutic implications.

Catecholamines and thrombocyte alpha 2-adrenoceptors in patients with acute myocardial infarction.

In 28 patients with first myocardial infarction plasma catecholamines and thrombocyte alpha 2-adrenoceptors were studied. The first determination (by HPLC and radioligand binding, respectively) was performed immediately after hospital admission and 6 weeks later. In the acute phase of myocardial infarction plasma adrenaline and noradrenaline levels were high. No significant differences in thrombocyte alpha 2-adrenoceptors and plasma concentrations of adrenaline and noradrenaline were observed between diabetic and non-diabetic patients. In three non-surviving patients only the affinity of the alpha 2-adrenoceptor to the radioligand was decreased (P less than 0.05), the relatively high catecholamine levels failed to reach statistical significance. Six weeks after hospital admission, adrenaline plasma levels were significantly decreased in diabetic and non-diabetic patients, while noradrenaline was only lowered in non-diabetic patients (P less than 0.05). Only in this group did the receptor number (BMAX) show a significant elevation 6 weeks after hospital admission. We conclude that, in acute myocardial infarction, alpha 2-adrenoceptors mainly interact with noradrenaline. Accordingly, no adrenoceptor alteration occurred in diabetic patients, who showed only a decrease in adrenaline but not in noradrenaline plasma concentrations 6 weeks following myocardial infarction. The different patterns in diabetic and non-diabetic patients suggest an alteration of catecholamine metabolism in diabetes mellitus.

Time course of alpha 2-adrenoceptor desensitization induced by adrenaline infusion in man.

After a rapid increase in infusion rate of adrenaline to elevate the initial heart rate by more than 15%, a continuous infusion was sustained in order to maintain elevated adrenaline plasma levels. At the end of the first phase of the experiment, the thrombocyte alpha 2-adrenoceptor number (determined by radioligand binding) was significantly lowered. After the second part of the experiment, a further significant decrease in the density of binding sites was observed, while elevated adrenaline plasma levels were kept constant. The decrease in the number of binding sites was accompanied by a slight increase in affinity of the radioligand. Serum potassium concentration significantly decreased during the experiment, while other serum electrolytes showed no significant alterations.

Plasma catecholamines and alpha 1-adrenoceptor function in hemodialysis-associated hypotension.

alpha 1-Adrenoceptor function and plasma catecholamine levels were investigated in chronically hemodialyzed patients with and without hemodialysis-induced hypotension. In the interdialytic period blood pressure responses as well as the mydriasis after topical application of the alpha 1-selective agonist phenylephrine were not significantly different in patients with or without hypotension during dialysis, although patients with hypotension were more susceptible to miosis induced by the muscarinergic agonist carbachol. In the normotensive group the blood pressure increasing effect of phenylephrine was attentuated after 120 min of hemodialysis therapy. Plasma noradrenaline levels were not significantly different in both groups and did not change significantly during hemodialysis, while plasma dopamine was significantly increased in the hypotensives. Thus, evidence for a pathophysiological role of a postsynaptic alpha-adrenoceptor dysfunction in hemodialysis-induced hypotension was lacking.

Influence of an uremia-associated serum factor on CNS alpha 2-adrenoceptors.

The action of blood serum from uremic rats and chronically hemodialyzed patients was investigated for effects on alpha 2-adrenoceptors labeled with 3H-clonidine. Compared to blood sera of rats and patients with normal kidney function, uremic serum significantly inhibited specific 3H-clonidine binding. In saturation experiments the density and affinity of alpha 2-adrenoceptors for 3H-clonidine was lowered by uremic serum. Heating, or trypsin or lipase treatment of the serum did not affect this phenomenon. The effect of the patient's serum could likewise be demonstrated after hemodialysis treatment. The presence of an allosteric regulating substance for clonidine binding to adrenoceptors could at least partially explain the altered and attenuated action of this drug in renal insufficiency.

Catecholaminergic and muscarinergic receptors in chronic experimental uremia.

In chronic uremic rats the density of alpha 1- and alpha 2-adrenoceptors in the cerebral cortex was significantly increased while beta-adrenoceptors and muscarinergic receptors in heart and brain as well as cardiac alpha 1-adrenoceptors were unchanged. Only the binding of the alpha 2-selective ligand 3H-clonidine was inhibited by uremic serum. In isolated left ventricular muscle strips dose-effect curves of (-)-noradrenaline and (+/-)-dobutamine were not significantly different in uremic and control animals whereas the negative inotropic action of the muscarinergic agonist carbachol was attenuated.

Cardiac glycoside receptors in clinical and experimental states of chronic renal failure.

To investigate the mechanisms leading to decreased cardiac glycoside sensitivity in uremia, digitalis receptors were characterized by [3H]-ouabain binding to mononuclear leucocytes of chronically hemodialyzed patients and to cerebral cortex membranes of partially nephrectomized rats. There were no statistically significant differences in receptor density and affinity between uremic patients and healthy control persons and between partially nephrectomized and sham operated rats. [3H]-Ouabain bound with high affinity to intact mononuclear leucocytes and to cerebral cortex membranes. However, the affinity to the cerebral cortex membrane preparation was markedly higher.

Adenylate cyclase and alpha-2-adrenoceptors in thrombocytes of chronic uremic patients.

Thrombocyte adenylate cyclase regulation and alpha-2-adrenoceptors have been studied in uremic patients as well as in healthy controls. Stimulation of adenylate cyclase activity by PGE1 and forskolin as well as inhibition by (+/-)-epinephrine was not significantly different between both groups. Additionally, there was no evidence of an alteration of the thrombocyte alpha-2-adrenoceptor density, determined by 3H-rauwolscine binding as suggested by others.

Interactions of heparin with alpha-2-adrenoceptors.

The interactions of the anticoagulant Heparin with the alpha-2-adrenoceptor in rat brain cortex membranes were investigated. Binding experiments with 3H-Clonidine were performed in both the absence and presence of Heparin. 1 uM Na-Heparin caused a significant decrease in the maximal number of binding sites (Bmax) from 129.4 fmol/mg protein to 93.7 fmol/mg protein with an associated decrease in affinity (KD = 0.79 pM vs. KD = 1.53 pM) of these binding sites. Addition of Na+-Heparin to 3H-Clonidine (3.1 nM) labelled membranes inhibited 50% of specific 3H-Clonidine binding (IC50) at a concentration of 0.95 uM. Based on our findings we conclude that the simultaneous long term administration of Na-Heparin and the antihypertensive agonist Clonidine should be regarded under consideration of the inhibitory effect of Na-Heparin to the alpha-2-adrenoceptors.