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Biomedical subjects

A Pfeiffer

Publications and source records attributed to A Pfeiffer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of two anticholinergic drugs, trospium chloride and biperiden, on motility and evoked potentials of the oesophagus.

BACKGROUND: Anticholinergic drugs are known to impair the motor function of the oesophagus but their effects on the oesophageal afferent pathways are unknown. AIM: To determine the effects of a peripherally-acting (trospium chloride) and a centrally-acting (biperiden) anticholinergic drug on the motility and the evoked potentials of the oesophagus. METHODS: Nine healthy volunteers were randomized to receive 1.2 mg trospium chloride (TC), 5 mg biperiden (BIP) or saline i.v. Primary peristalsis was elicited by swallowing a 5 mL water bolus and secondary peristalsis by insufflation of 20 mL air, 10 times each. Oesophageal potentials were evoked by electrical stimulation in the distal and proximal oesophagus (30 stimulations at 0.4 Hz, two runs). RESULTS: Both anticholinergic drugs reduced by a similiar amount the contraction amplitudes (TC 17 mmHg, BIP 25 mmHg, saline 67 mmHg; P < 0.01) and the rate of secondary contractions (TC 60%, BIP 70%, saline 95%; P < 0.01). In contrast, only biperiden prolonged the latencies of the evoked potentials (N1 peak, distal oesophagus: BIP 191 ms, TC 102 ms, saline 101 ms; P < 0.01; P1 peak: BIP 322 ms, TC 161 ms, saline 144 ms; P < 0.01). CONCLUSIONS: Both anticholinergic drugs depress oesophageal motility, but only the centrally-acting anticholinergic drug biperiden modifies the oesophageal evoked potentials, suggesting a central cholinergic transmission of the oesophageal afferent pathways.

Adult↗
PubMed1998

Discrimination of irritable bowel syndrome by non-linear analysis of 24-h jejunal motility.

Conventional analysis of ambulatory longterm manometry of the small intestine has revealed abnormalities in patients with the irritable bowel syndrome (IBS). The aim was to use methods from non-linear dynamics, in particular the concepts of symbolic dynamics and entropy, in order to discriminate motility in IBS from healthy subjects. 24-h jejunal motility was recorded in 30 IBS patients and 30 healthy subjects. Computerized analysis of contraction amplitudes and intercontractile intervals was performed. Both time series were analysed by symbolic dynamics and entropy to quantify the degree of randomness inherent in the signal. During phase II IBS patients exhibited significantly increased entropies for the intercontractile intervals (IBS: 0.978 +/- 0.016, C: 0.965 +/- 0.020, P = 0.004) and for the contraction amplitudes (IBS: 0.978 +/- 0.008, C: 0.970 +/- 0.026, P = 0.05) compared with healthy subjects. In addition, a significantly increased mean contraction amplitude (mmHg) was found in patients (IBS: 25.2 +/- 4.8, C: 22.2 +/- 3.1, P = 0.003). Considering a combination of both parameters, a diagnostic accuracy of 82% was achieved. We conclude that phase II motility of the small intestine is more random in IBS than in health. Symbolic dynamics seems to be a promising new concept for the analysis of long-term gastrointestinal motility recordings.

Adult↗
PubMed1998

Different effects of white and red wine on lower esophageal sphincter pressure and gastroesophageal reflux.

BACKGROUND: White wine and beer induce gastroesophageal reflux (GER). We investigated the effects of white and red wine on lower esophageal sphincter pressure (LESP) and GER. METHODS: Twenty healthy volunteers received 300 ml white wine, red wine, or water together with a standardized meal. The LESP was continuously monitored with a Dent sleeve the 1st h postprandially, and the esophageal pH measured with a glass pH electrode. RESULTS: The LESP was decreased after intake of white wine (median, 14.9 mmHg; range, 5.6-19.5 mmHg) compared with red wine (20.4 mmHg; 13.1-22.3 mmHg; P < 0.05) and tap water (19.5 mmHg; 16.2-29.1 mmHg; P < 0.01). The fraction time esophageal pH <4 was increased after both alcoholic beverages compared with tap water (0.9%; 0.2-5.8%; P < 0.01 versus white wine, P < 0.05 versus red wine) with a greater fraction time after white wine (13.2; 0.3-58.1 ) than after red wine (2.3; 0.7-24.4; P < 0.05). The decreased sphincter pressure after white wine was accompanied by a change in the reflux pattern with increased 'stress reflux' and the occurrence of 'free reflux'. CONCLUSION: White wine and red wine exert different effects on LESP and GER.

Adult↗
PubMed1998

An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich's ataxia) gene.

Friedreich's ataxia is the most common hereditary ataxia and is frequently associated with disturbances of glucose metabolism. This autosomal recessive disease is caused by the decreased expression of a mitochondrial protein, frataxin, encoded by the X25 gene. Homozygous expansion of a GAA repeat in the first intron of X25 inhibits frataxin expression and is associated with clinical disease. We evaluated whether heterozygous expansions of the triplet repeat in the frataxin gene X25 may be associated with NIDDM in two genetically distinct populations--one in Germany (n = 358) and the other in the U.S. (n = 292)--using a polymerase chain reaction-based assay. Intermediate expansions (10-36 repeats), which are longer than normal but not sufficient for the appearance of the ataxia phenotype, were found in 24.7 and 27.3% of these two NIDDM cohorts compared with 7.6 and 6.3% of the matched control subjects (both P < 0.001). The odds ratios were 3.36 (95% CI 1.72-6.55) for the German group and 4.01 (2.08-7.74) for the U.S. group. Therefore, we conclude that the X25/frataxin GAA repeat polymorphism is associated with NIDDM in a frequency higher than any other mutation heretofore described. Further studies are needed to elucidate the possible role of frataxin in the pathogenesis of NIDDM.

Aged↗
PubMed1997

Deficiency of phosphofructo-1-kinase/muscle subtype in humans impairs insulin secretion and causes insulin resistance.

Non-insulin-dependent diabetes mellitus (NIDDM) is caused by peripheral insulin resistance and impaired beta cell function. Phosphofructo-1-kinase (PFK1) is a rate-limiting enzyme in glycolysis, and its muscle subtype (PFK1-M) deficiency leads to the autosomal recessively inherited glycogenosis type VII Tarui's disease. It was evaluated whether PFK1-M deficiency leads to alterations in insulin action or secretion in humans. A core family of four members was evaluated for PFK1-M deficiency by DNA and enzyme-activity analyses. All members underwent oral and intravenous glucose tolerance tests (oGTT and ivGTT) and an insulin-sensitivity test (IST) using octreotide. Enzyme activity determinations in red blood cells showed that the father (46 yr, body mass index [BMI] 22. 4 kg/m2) and older son (19 yr, BMI 17.8 kg/m2) had a homozygous, while the mother (47 yr, BMI 28.4 kg/m2) and younger son (13 yr, BMI 16.5 kg/m2) had a heterozygous PFK1-M deficiency. DNA analyses revealed an exon 5 missense mutation causing missplicing of one allele in all four family members, and an exon 22 frameshift mutation of the other allele of the two homozygously affected individuals. The father showed impaired glucose tolerance, and the mother showed NIDDM. By ivGTT, both parents and the older son had decreased first-phase insulin secretion and a diminished glucose disappearance rate. The IST showed marked insulin resistance in both parents and the older, homozygous son, and moderate resistance in the younger son. PFK1-M deficiency causes impaired insulin secretion in response to glucose, demonstrating its participation in islet glucose metabolism, and peripheral insulin resistance. These combined metabolic sequelae of PFK-1 deficiency identify it as a candidate gene predisposing to NIDDM.

Adult↗
PubMed1997

mRNA expression of ligands of the epidermal-growth-factor-receptor in the uterus.

Six different ligands of the epidermal-growth-factor receptor (EGFR) have been identified in the past. In some cervical squamous-cell carcinomas, an increased amount of proteins binding to the EGFR has been reported. In order to identify the mRNA of EGFR ligands (EGFRL), which might be overexpressed in cervical and endometrial cancers, we performed semi-quantitative reverse-transcription/polymerase chain reactions (RT-PCR) for all 6 EGFRL in RNA extracts of normal and malignant tissue samples of the human uterus. PCR products from RNA extracts of 83 patients were quantitated relative to the housekeeping gene and internal standard pyruvate dehydrogenase by analyzing the PCR kinetics of product synthesis. In extracts of normal cervix, the level of mRNA expression of the EGFRL was significantly higher than in endometrium. No significant difference was detected between normal cervix and cervical carcinomas. However, both in cervical and in endometrial cancers, mRNA expression was non-parametrically distributed and in some cervical cancers overexpression of transforming growth factor alpha (TGF-alpha), amphiregulin or EGF was observed. In endometrial cancers, mRNA levels of all EGFRL were higher than in normal endometrium. This increase was significant (p < 0.005) for TGF-alpha and amphiregulin. Thus, TGF-alpha mRNA is overexpressed in approximately 10% of cervical cancers and in the majority of endometrial cancers. Since TGF-alpha anti-sense therapy might represent a future strategy in such cancers, we also determined the absolute level of TGF-alpha mRNA expression by quantitative PCR using a cloned standard.

Cloning, Molecular↗
PubMed1997

Effect of ethanol on postprandial duodenojejunal motility in humans.

The effect of ethanol on postprandial small bowel motility was investigated in eight healthy volunteers using perfusion of nutrient solutions (17% proteins, 59% carbohydrates, 24% lipids) into the descending duodenum (5 ml/min for 120 min). An ethanol-containing solution (4% w/v, 4.06 kcal/min, 1190 mosmol/kg) was compared with the corresponding ethanol-free solution (2.64 kcal/min, 160 mosmol/kg) and another ethanol-free hyperosmolar solution adapted in caloric load and osmolality (4.06 kcal/min, 1160 mosmol/kg). Motility was recorded with a data logger and six pressure transducers at 3-cm intervals around the duodenojejunal flexure. Clustered contractions (27 +/- 4/hr) migrating aborally through the whole recording segment were the predominant motor pattern with ethanol compared with the ethanol-free (10 +/- 2/hr; P < 0.01) and the ethanol-free hyperosmolar solution (6 +/- 3/hr; P < 0.001). Other motility parameters with ethanol were not different from the ethanol-free solution, whereas the ethanol-free hyperosmolar solution showed a much less intense motor response. We conclude that ethanol does modify human postprandial duodenojejunal motility by inducing propagative motor patterns.

Adult↗
PubMed1997

The effect of decaffeination of coffee on gastro-oesophageal reflux in patients with reflux disease.

BACKGROUND: Patients with reflux disease often complain of heartburn after ingestion of coffee. Induction of gastro-oesophageal reflux has been demonstrated by pH-metry following the intake of coffee in healthy volunteers. The reflux was reduced when the coffee had undergone a decaffeination process. The aim of this study was to investigate the effect of decaffeination of coffee on reflux in patients with reflux disease. METHODS: Seventeen reflux patients underwent two osesophageal 3-h pH measurements. The patients received, in a double-blind study design in a randomized order, 300 mL of either regular or decaffeinated coffee together with a standardized breakfast. The fraction time oesophageal pH < 4 was calculated during the three postprandial hours. RESULTS: For regular coffee the fraction time was calculated to a median of 17.9% with a range of 0.7-56.6%. The fraction time was significantly reduced to 3.1% (0-49.9%) after ingestion of decaffeinated coffee. CONCLUSION: The amount of gastro-oesophageal reflux induced by the intake of regular coffee in patients with reflux disease can be reduce by the decaffeination of coffee.

Aged↗
PubMed1997

Ambulatory long-term jejunal manometry in diabetic patients with cardiac autonomic neuropathy.

Concerning alteration of small bowel motility in diabetic patients with autonomic neuropathy controversial data were obtained with stationary manometry and over a limited period of time. The aim of our study was to examine ambulatory 24 h jejunal motility in 15 diabetic patients with cardiac autonomic neuropathy compared with data obtained in 50 healthy controls. Twenty-four hour motility was recorded in the proximal jejunum with a portable datalogger and tube-mounted miniature pressure sensors. Diurnal and nocturnal fasting motility and the motor response to a standardized evening meal of 600 kcal were evaluated by visual and computer-aided analysis. The following abnormalities were found during fasting motility (n = number of patients): absence of phase III over 24 h (n = 2), retrograde migration or simultaneous occurrence of phase III (n = 5). During postprandial motility irregular bursts with tonic baseline elevation (n = 3) and contraction frequencies below the range of controls (n = 8) occurred. Furthermore patients exhibited an inversion of the normal relationship between phase I and phase II during nocturnal MMC-cycles, and discrete clustered contractions were diminished (P < 0.01) in the fasting and digestive state. All patients showed at least one abnormal manometric finding. We conclude that small bowel motility in diabetic autonomic neuropathy is characterized by disturbances in the generation and aboral migration of phase III, an altered circadian variability of the MMC cycle and by postprandial hypomotility.

Adult↗
PubMed1997

Circulating tumor necrosis factor alpha is elevated in male but not in female patients with type II diabetes mellitus.

The cytokine tumor necrosis factor alpha (TNF alpha) was proposed to mediate obesity related insulin resistance upon production in fat cells and to participate in tissue remodelling leading to vascular complications upon being released by macrophages. To assess its putative role in diabetes we determined plasma levels of TNF alpha in 105 adult humans. Male nondiabetic subjects had significantly lower TNF alpha levels than female controls (4.4 +/- 0.3, n = 17 vs. 6.6 +/- 1.0 pg/ml, n = 13; p = 0.049). Men with NIDDM had elevated TNF alpha (6.7 +/- 0.6 pg/ml, n = 34) compared to nondiabetic subjects (4.4 +/- 0.3 pg/ml, n = 17; p = 0.012). Such a difference was not apparent in women. Levels of TNF alpha were correlated with serum triglyceride levels in male controls (r2 = 0.64; p = 0.007) but not in NIDDM. Neither body mass index nor glycosylated hemoglobin correlated with TNF alpha in any of the groups. The presence of retinopathy (p = 0.046) but not of neuropathy or nephropathy or macroangiopathy was associated with significantly elevated plasma TNF alpha. We conclude that plasma levels of TNF alpha are sex-dependent and that increased TNF alpha occurs in male but not female NIDDM and may participate in the development of diabetic complications.

Aged↗
PubMed1997

Effect of erythromycin on postprandial gastroesophageal reflux in reflux esophagitis.

UNLABELLED: The macrolide antibiotic erythromycin has recently been reported to exert profound prokinetic properties. The aim of the study was to investigate the effect of erythromycin on postprandial gastroesophageal reflux in patients with reflux esophagitis. METHODS: In 16 patients with reflux esophagitis (according to Savary and Miller: grade I, n = 8; grade II, n = 4; grade III/IV, n = 4) two pH measurements, with and without erythromycin, were performed for three postprandial hours after lunch. Erythromycin was administered in a dose of 3.5 mg/kg intravenously just prior to lunch. RESULTS: With erythromycin, the median fraction time esophageal pH < 4 was significantly decreased (7.6% versus 18.1%; P < 0.05). This decrease was the result of a diminished frequency of reflux episodes (19 vs 25; P < 0.05) and a shortening of the median reflux duration (0.7 min vs 1.1 min; P < 0.05). CONCLUSIONS: Intravenous administration of erythromycin decreases postprandial gastroesophageal reflux in patients with reflux esophagitis.

Adult↗
PubMed1997

Effect of smoking on the results of esophageal pH measurement in clinical routine.

Because data on the effects of smoking on gastroesophageal reflux are controversial, we evaluated the effect of smoking on the results of esophageal 24-hour pH-metry in clinical routine. Participants were 280 consecutive patients with symptoms suggestive of reflux disease, 78 smokers, and 202 nonsmokers. Of the smokers, 45 actually smoked during the pH measurement and 33 abstained from smoking. The frequency of reflux episodes, the fraction of time pH was < 4, and the percentage of abnormal 24-hour pH-metry results were compared among actual smokers, abstaining smokers, and nonsmokers. In actual smokers, the effect of smoking on gastroesophageal reflux was further analyzed by comparing the reflux frequency and the fraction of time that pH was < 4 for a 10-minute period before, during, and after smoking. We found no difference in reflux frequency and fraction of time that pH was < 4 among actual smokers, abstaining smokers, and nonsmokers, regardless of a normal or an abnormal pH-metry result. The percentage of patients with a pH-metry result indicating disease was similar in the three groups, at 53%, 52%, and 50%, respectively. Gastroesophageal reflux was not increased during smoking a cigarette or in the postsmoking period compared with the presmoking period. Neither being a smoker nor actually smoking a cigarette had a negative influence on gastroesophageal reflux. Thus smoking or abstaining from smoking does not modify the results of pH-metry in clinical routine.

Diagnostic Tests, Routine↗
PubMed1997

Identification and characterization of microsatellites in Norway spruce (Picea abies K.).

Norway spruce (Picea abies) genomic libraries were screened for presence of dinucleotide AC/GT and AG/CT microsatellites (or simple sequence repeats). On average, one (AG)n microsatellite every 194 kb and one (AC)n microsatellite every 406 kb were found. Forty-six positive clones were sequenced and primers flanking 24 AG microsatellites and 12 AC microsatellites diesigned. Only seven (20%) of them produced the expected single-locus polymorphic pattern when used to amplify Norway spruce DNAs. The other primer pairs gave either multiple bands or bad amplification, or a single monomorphic fragment. Such a small proportion of successful primer pairs was attributed to the high level of complexity of the Norway spruce genome. Dot blot analysis of the clones showed that many of them contained repetitive DNA and that those giving the single-locus polymorphic patterns usually corresponded to single-copy sequences. A family of repetitive DNA that contained AG repeats was identified and was present in about 40,000 copies per haploid genome. Simple Mendelian inheritance was observed for all the polymorphisms tested. The average number of alleles was 13, ranging from 6 to 22, and the expected heterozygosity was 0.79 when seven microsatellites were used to genotype a panel of 18 trees representing different populations. Compared with isozymes, microsatellites are about five times more informative and could provide an extremely valuable source of markers for genome mapping and genetic diversity studies.

Alleles↗
PubMed1997

Insulinoma cells contain an isoform of Ca2+/calmodulin-dependent protein kinase II delta associated with insulin secretion vesicles.

The Ca2+/calmodulin dependent protein kinase II (CaM kinase II) is thought to play an important part in glucose-stimulated insulin secretion. To determine which of the known subtypes (alpha, beta, gamma, delta) occur in insulin-secreting cells, we amplified all types of CaM kinase II by RT-PCR and found the beta3-, gamma-, delta2- and delta6-subtypes in RINm5F insulinoma cells. None of the other 8 delta-subtypes was present. Antibodies generated against the bacterially expressed association domain of the delta2-subtype recognized the recombinant gamma and delta-subtypes. In INS-1 and RINm5F cells, as well as freshly isolated rat islets, only a 55-kDa protein corresponding in size to the delta2-subtype expressed in NIH3T3 fibroblasts was detected. The delta2-subtype therefore appears to represent the predominant subtype of CaM kinase II present in insulin secreting cells. The enzyme was primarily associated with cytoskeletal structures, and very little was present in the soluble compartment or detergent soluble fraction in INS-1- or RINm5F-cells. An analysis of its subcellular distribution was performed by sucrose and Nycodenz density gradient fractionation of INS-1 cells and detection of CaM kinase II delta by immune blots. The enzyme codistributed with insulin used as a marker for secretory granules but not with the lighter synaptic-like microvesicles detected with an antibody against synaptophysin, plasma membranes (syntaxin 1), lysosomes (arylsulfatase), or mitochondria (cytochrome c oxidase). CaM kinase II delta2 thus is identified as the subtype associated with insulin secretory granules and is likely to be involved in insulin secretion.

Animals↗
PubMed1997

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.

Adenoma↗
PubMed1997

Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown.

Chronic hyperglycemia may cause growth factor alterations that are likely to participate in tissue remodeling typical for diabetic late complications. However, few details of such events are known. The ocular vitreous fluid allows studies of growth factor levels in human eyes (after vitrectomy). The vitreous is highly inert and protected by the blood-retina barrier and thus probably reflects growth factor production by the normal retina. Vitreous from patients with proliferative diabetic retinopathy (PDR) was compared with vitreous obtained from patients with nonproliferative eye disease and with vitreous from patients without diabetes but with marked neovascular proliferations due to ischemia. This design permits us to distinguish diabetes-related from non-diabetes-related alterations. Insulin-like growth factor I (IGF-I), IGF-II, IGF binding protein 2 (IGFBP-2), and IGFBP-3 were elevated 3- to 13-fold in nondiabetic retinal ischemia and 1.5- to 3-fold in PDR, indicating that the changes were not restricted to diabetes. These changes may partially be explained by leakage of serum into the vitreous, since IGFs and IGFBPs are 20- to 50-fold higher in serum than in vitreous, and vitreous protein content was 1.5-fold elevated in PDR subjects and 5-fold in ischemia patients compared with control subjects. TGF-beta is a proposed antiangiogenic factor in the eye. TGF-beta2 was the predominant subtype in vitreous, and its total amount was not altered in PDR patients. More importantly, the active fraction of TGF-beta was decreased by 30 and 70% in PDR and nondiabetic retinal ischemia patients, respectively. Since plasmin may control TGF-beta activation, the serum protein alpha2-antiplasmin was measured and found to be significantly elevated to 150 and 250% of control values in PDR and ischemia patients, respectively. Thus, influx of serum proteins due to microvascular disturbances and hypoxia is proposed as a possible cause for vitreous alterations of IGF-I and of active TGF-beta. These changes seem to occur late in the sequence of events leading to PDR and are not specific for diabetes, but they were also observed in other diseases characterized by retinal hypoxia.

Blood-Retinal Barrier↗
PubMed1997

Effect of a German Poison Control Center on health care cost reductions in harmless exposure cases.

To evaluate the effect of a German Poison Control Center (PCC) service on health care cost reduction in cases of harmless exposures, a prospective telephone survey of 200 callers were asked which medical aid would have been sought if no PCC service had been available. Calculation of savings was based on the total number of calls and standardized fees for medical treatment. Savings in costs for health insurance in these cases was 20 to 50% of the annual PCC budget. The cost effectiveness of this German PCC for this patient group was lower than for North American PCCs. Cost effectiveness might be improved by making efforts to increase the number of public calls.

Cost-Benefit Analysis↗