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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 127 records · Page 7Linked to original sources
PubMed1990

Intestinal absorption of amiodarone in man.

The jejunal absorption rate of amiodarone and the influence of lipids on it were studied in human volunteers using the intestinal perfusion technique. A nutrient solution (Realmentyl, Sopharga Laboratories, France) with 300 mg of the drug was infused for 120 minutes at the ligament of Treitz. The segment tested was 25 cm long. Two caloric loads of the nutrient solution, 3.3 Kcal/min (solution A) and 1.3 Kcal/min (solution B), A containing total lipid and caloric load 2.5 times higher than B, were administered. Minor interindividual differences in amiodarone absorption rate were observed (20.2 to 31.7%) with solution A. Amiodarone absorption correlated with lipid absorption significantly. Since the maximal plasma concentrations of the drug and the area under the curve (AUC/24 hours) did not correlate with the amount of amiodarone absorbed, the wide fluctuations of amiodarone pharmacokinetics must mainly be due to amiodarone tissue distribution and metabolic pathway.

Administration, Oral↗
PubMed1990

Severe short bowel syndrome with a surgically reversed small bowel segment.

We report a case of short bowel syndrome (60 cm of jejunum anastomosed to the left colon) with reversal of the distal 15 cm of jejunum in a 21-year-old man. The nutritional absorptive capacity and digestive motility was studied for 18 months postoperatively. His absorptive capacity reached subnormal values allowing him oral nutritive autonomy and normal social life. The results of the manometric study suggested that the reversed segment delayed intestinal transit time. The prolonged contact of the chyme with the intestinal absorptive mucosa possibly increased its absorptive capacity. Our data and the literature reports suggest that reversal of a bowel loop could help wean patients from their dependence on parenteral nutrition.

Adult↗
PubMed1990

Human gastric mucosa expresses glandular M3 subtype of muscarinic receptors.

Five subtypes of muscarinic receptors have been distinguished by pharmacological and molecular biological methods. This report characterizes the muscarinic subtype present in human gastric mucosa by radioligand binding studies. The receptor density was 27 +/- 6 fmol/mg protein and the tritiated ligand N-methylscopolamine had an affinity of (KD) 0.39 +/- 0.08 nM (n = 11). The M1 receptor selective antagonist pirenzepine and the M2 receptor selective ligand AF-DX 116 had low affinities of 148 +/- 32 nM (n = 13) and 4043 +/- 1011 nM (n = 3) KD, respectively. The glandular M3 antagonists hexahydrosiladifenidol and silahexocyclium had high affinities of KD 78 +/- 23 nM (n = 5) and 5.6 +/- 1.8 nM (n = 3). The agonist carbachol interacted with a single low-affinity site and binding was insensitive to modulation by guanine nucleotides. Antagonist and agonist binding studies thus showed an affinity profile typical of M3 receptors of the glandular type.

Carbachol↗
PubMed1990

Increased epidermal growth factor receptors in gastric carcinomas.

The epidermal growth factor and the homologous alpha-tumor growth factor are mitogenic polypeptides that act by binding to the epidermal growth factor receptor. The present study investigated whether increased production of epidermal growth factor/alpha-tumor growth factor or increased density of epidermal growth factor receptors may occur in gastric carcinomas as compared with normal mucosa from the same individuals. Epidermal growth factor receptors were measurable by (125I)EGF-binding assays in 13 of 15 normal mucosas and in 15 of 15 carcinomas. The epidermal growth factor-binding capacity was significantly higher in carcinomas than in mucosa. A comparison of pairs of mucosa and carcinomas showed an increase of epidermal growth factor receptors in 9 of 15 carcinomas, no change in 3, and a decrease in 2 carcinomas. One mucinous adenocarcinoma contained extreme numbers of epidermal growth factor receptors (2445 fmol/mg protein) corresponding to a 320-fold increase over normal mucosa. Epidermal growth factor-like activity was increased in 2 of 22 carcinomas compared with mucosa. We conclude that relative overexpression of epidermal growth factor receptors occurs in a fraction of gastric carcinomas. Whether increased expression of epidermal growth factor receptors is associated with particular patterns of tumor progression needs to be investigated.

Adult↗
PubMed1990

Muscarinic receptors mediating acid secretion in isolated rat gastric parietal cells are of M3 type.

Five subtypes of muscarinic receptors have been identified by pharmacological and molecular biological methods. The muscarinic receptor subtype mediating acid secretion at the level of the parietal cell was unknown. Therefore, this study was performed to characterize muscarinic receptors on rat gastric parietal cells using the 3 subtype-selective antagonists hexahydrosiladifenidol and silahexocyclium, which have high affinity for glandular M3 subtypes, and AF-DX 116, which has high affinity to cardiac M2 receptors. The affinity of these antagonists was determined by radioligand binding experiments. In addition, their inhibitory potency on carbachol-stimulated inositol phosphate production was investigated. Inhibition of carbachol-stimulated aminopyrine uptake was used as an indirect measure of proton production. Both M3 antagonists, hexahydrosiladifenidol and silahexocyclium, had nanomolar affinities for parietal cell muscarinic receptors and potently antagonized inositol phosphate production with nanomolar Ki values. Silahexocyclium similarly antagonized aminopyrine accumulation while hexahydrosiladifenidol behaved as a noncompetitive antagonist. AF-DX 116 was a low-affinity ligand and a weak competitive antagonist at parietal-cell muscarinic receptors. It was concluded that muscarinic M3 receptors mediate acid secretion probably by activation of the phosphoinositide second messenger system in rat gastric parietal cells.

Animals↗
PubMed1990

Effect of fat-emulsion phospholipids on serum lipoprotein profile during 1 mo of cyclic total parenteral nutrition.

Changes in serum lipoprotein determined by selective precipitation were investigated in 11 adult patients during 1 mo of parenteral nutrition. Patients were divided into two groups that received a similar nutrient regimen except for Intralipid (IL) phospholipid, which was higher in group A (10% IL, n = 5) than in group B (20% IL, n = 6), 139 +/- 15 vs 71 +/- 0.5 mg.kg-1.d-1 (P less than 0.01). Lipoprotein X (LPX) detected soon after IL infusions were started reached its highest concentrations in group A. LPX concentrations correlated with phospholipid intakes on days 7 and 15 but not on day 29. Significant increases in the cholesterol and phospholipid content of low-density-lipoprotein-very-low-density-lipoprotein fractions were observed only in group A. It is suggested that these changes were induced by the twofold-higher intake of phospholipids in group A. With regard to the possible involvement of LPX in lipid overloading of the reticuloendothelial system and hepatocytes, administration of 20% IL seems preferable to 10% IL.

Adult↗
PubMed1990

Low diacylglycerol values in colonic adenomas and colorectal cancer.

The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis.

Adenocarcinoma↗
PubMed1990

Upper gastrointestinal porcine smooth muscle expresses M2- and M3-receptors.

The existence of 5 different mammalian subtypes of muscarinic receptors, named M1 to M5 has been established. This study was designed to characterize the subtypes of muscarinic receptors occurring in smooth muscle of the upper gastrointestinal tract. Displacement studies of [3H]N-methylscopolamine by the highly M2-selective ligand methoctramine revealed the presence of M2-receptors. The remaining sites had characteristics of M3-receptors. The ratio of M2- to M3-receptors varied from a predominance of M3-receptors in antral tissue over a predominance of M2-receptors in gastric corpus and ileal smooth muscle to the almost exclusive presence of M2-receptors in duodenal smooth muscle. Mucosa from all areas showed characteristics of M3-receptors without evidence for the occurrence of M2-receptors.

Animals↗
PubMed1990

[Modification of lipoxygenase products in bone by the linoleic acid content of the diet].

Eicosanoids are supposed to participate in the regulation of bone metabolism. 30 male white rats of the wistar strain were fed on a diet rich in linoleic acid (LA), on a diet poor in LA and on a pellet diet after 3 month up to an age of 5 month. The formation of leukotrienes (LT) C4, D4, and E4 from the proximal tibia metaphysis after LA rich diet has been compared to the formation from LA poor and pellet diet. LA rich diet increased the formation of LTC4, D4 and E4 in the proximal tibia metaphysis. The properties of eicosanoids as local mediators in the bone were discussed.

Animals↗
PubMed1989

Human HT-29 colon carcinoma cells contain muscarinic M3 receptors coupled to phosphoinositide metabolism.

Five different muscarinic receptor subtypes can be distinguished by the differences in their amino acid sequence, the coupled signal transduction system, pharmacological binding properties and activation of ionic fluxes. The present study served to characterize the binding profile of muscarinic receptors in human colon carcinoma cells (HT-29) using selective muscarinic antagonists. The affinities of the compounds were compared with their potency to inhibit cholinergically-activated phosphoinositide metabolism. Pirenzepine displaced [3H]N-methyl-scopolamine binding and inhibited inositolphosphate (IP) release with potencies typical of those of non-M1 receptors. The M3 subtype-selective antagonists sila-hexocyclium and hexahydro-sila-difenidol had high affinity to the muscarinic receptors in HT-29 cells (KD = 3.1 nM and 27 nM, respectively) and inhibited IP release at nanomolar concentrations. The M2 receptor antagonists, AF-DX 116 and methoctramine, had low antimuscarinic potencies. Our results demonstrate that HT-29 human colon carcinoma cells contain an apparently pure population of M3 receptors. These cells could serve as a model system for further investigations concerning regulatory and signal transduction mechanisms associated with glandular muscarinic M3 receptors.

Carbachol↗
PubMed1989

Facilitation of ACTH secretion by morphine is mediated by activation of CRF releasing neurons and sympathetic neuronal pathways.

Exogenously applied opioid agonists have a stimulatory effect on adrenocorticotropic hormone (ACTH) secretion. The present experiments were designed to examine the mechanisms involved in the stimulatory effect of the mu-receptor agonist morphine on ACTH release in chronically cannulated, freely moving, non-stressed rats. Morphine (7.5 mg/kg, i.v.) treatment was followed by a significant increase in plasma levels of ACTH. Pretreatment with the peripheral ganglionic blocker chlorisondamine (3 mg/kg, i.p.) attenuated the response to morphine. The morphine stimulatory effect was also partially inhibited if the rats were pretreated with a specific antiserum to corticotropin-releasing factor (CRF). In rats given both CRF antiserum and chlorisondamine, the plasma ACTH levels remained unchanged after morphine application. These findings indicate that morphine stimulates the release of ACTH by activating both CRF-secretion and peripheral sympathetic neuronal pathways.

Adrenocorticotropic Hormone↗
PubMed1989

[Entropion in newborn lambs].

The Entropion in newborn lambs could be proved so far in 8 sheep-breeds and 7 cross-breeds out of 33 flocks in the Federal Republic of Germany. In our patients the Entropion was found at the lower eyelid only. The owners of the animals often mistake the Entropion for an ophthalmia. An early diagnosis and an early beginning of the therapy keep the expenditure of treatment small and shorten the period of treatment; therefore examination is commendable within a short time after birth. Female lambs get clearly more often affected than male ones (Gynecotropia). In small pure-bred flocks with only one breeding-ram (and also in breeds with a limited population) the percentage of suffering lambs is higher than in large and crossed flocks with several rams and in large populations (except the breed "Heidschnucke"). In agreement with the literature it must be supposed that different genes are responsible for the Entropion. The selection of ill animals and those which are suspected of transmitting the disposition is evidently appropriate to lower the number of attacks of illness within a population considerably. All 47 affected eyes of 32 lambs were treated. Low degrees of Entropion were healed by repeated manual eversion plus application of antibiotic eye-ointment. In middle and high degrees of Entropion the application of Michel-wound-clamps on 23 of 26 eyes was successful; antibiotic eye-ointment was applied here, too; additionally these lambs prophylactically got 2000 I.U. of Tetanus-antitoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Epidermal growth factor receptors and epidermal growth factor-like activity in colorectal mucosa, adenomas and carcinomas.

The epidermal growth factor (EGF) and alpha-tumor growth factor are mitogenic proteins which bind to the EGF-receptor and may play a role in carcinogenesis or tumor progression. Our study investigated whether colorectal carcinomas and adenomas express altered levels of EGF-receptors or overproduce EGF-like activity by comparing histologically normal mucosa to carcinomas resected from the same patients. EGF-receptors were characterized by radioligand binding studies. Carcinomas contained unchanged or decreased levels of EGF-receptors in 13/16 and moderately increased levels in 3/16 patients as compared to normal mucosa. Adenomas obtained from 2 patients with familial polyposis coli and from a third patient with a coincident carcinoma had similar numbers of EGF-receptors as normal mucosa. EGF-like growth factors, in contrast, were significantly elevated in carcinoma extracts as compared to extracts from normal mucosa of the same patients. Adenomas did not contain elevated levels of EGF-like activity. We conclude that increased expression of EGF-receptors is infrequent in colonic adenocarcinomas. Increased production of EGF-like growth factors may frequently occur but seems to be associated with tumor progression rather than with premalignant lesions as represented by adenomas.

Adenomatous Polyposis Coli↗
PubMed1989

Stimulation of inositol phosphate and diacylglycerol production by RHC 80267, a diacylglycerol-lipase inhibitor, in rat gastric parietal cells: effects on hydrogen ion secretion.

RHC 80267, on inhibitor of diacylglycerol lipase, was used to investigate the role of diacylglycerol in acid secretion by isolated rat gastric parietal cells. Unexpectedly, RHC 80267 stimulated the production of inositol phosphates in [3H]inositol-prelabeled cells and increased levels of 32P-labeled phosphatidic acid to the same degree as did carbachol. RHC 80267 increased diacylglycerol to a greater extent than did carbachol, and additionally decreased levels of [3H]arachidonic acid. This suggests that RHC 80267 stimulated phospholipase C and inhibited diacylglycerol lipase in parietal cells. RHC inhibited [14C]aminopyrine uptake, a measure of acid secretion, stimulated by carbachol or by simultaneous addition of carbachol and dibutyryl-cAMP. These data support the model that the diacylglycerol/protein kinase C branch of the phosphoinositide system is inhibitory to acid secretion.

Aminopyrine↗
PubMed1989

Legionella infection of the colon presenting as acute attack of ulcerative colitis.

A 42-yr-old woman with long-standing ulcerative colitis of the descending colon, sigmoid, and rectum presented with bloody diarrhea, tenesmus, and high fever. Endoscopic findings were compatible with an acute attack of ulcerative colitis, which proved to be resistant to systemic corticosteroid treatment. In the presence of an acute abdomen with ascites and double-contoured colonic wall, hemicolectomy was performed. Postoperatively, high temperature, hyponatremia, and elevated liver enzyme levels persisted. Pleural effusions developed. Antibodies to Legionella pneumophila serogroup 3 were detected in the serum. Erythromycin therapy induced rapid improvement. In a massive submucosal edema of the affected colon, L. pneumophila of the same serogroup was demonstrated by direct immunofluorescence staining.

Acute Disease↗
PubMed1989

Clinical implications of the epidermal growth factor receptor in the squamous cell carcinoma of the uterine cervix.

The clinical implications of the epidermal growth factor (EGF) and its receptor (EGF-R) were studied in 52 squamous cell carcinomas of the uterine cervix. In comparison to 40 biopsies of the normal cervix EGF-R capacity was significantly increased in the carcinomas, while the affinity was unchanged. The amount of EGF-like substances extracted from the tumors was increased in patients with lymph node metastases, in whom 5-year survival is reduced. Irrespective of tumor stage patients with a very high level of EGF-R (greater than 100 fmole/mg protein) were more likely to have recurrences later or to die from disease: recurrence or death occurred in 5 of 7 patients with high capacity and in 2 of 45 patients with low capacity. Our data suggest that the level of EGF-R is indicative of the biological aggressiveness of cervical carcinomas.

Adult↗