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Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 235 records · Page 13Linked to original sources

Functional dyspepsia: how could a biliary dyspepsia sub-group be recognized? A methodological approach.

Functional dyspepsia (FD) includes a heterogeneous group of patients suffering from a variety of different conditions. The Dyspepsia Project has been implemented in 14 GI Units since 1984, in order to epidemiologically test the discriminating power of the Working Teams definitions and of standardized questionnaires. Five per cent of admitted subjects were subclassified as sphincter of Oddi dysfunction or biliary dyspepsia (BD), defined as biliary pain associated or not to bilirubin or alkaline phosphatase elevation, in the abscence of ultrasonographic evidence of gallstone disease or bile duct dilatation. The more useful symptoms in favour of the diagnosis of biliary dyspepsia were found to be pain in the right hypochondrium, radiating to the shoulder, or to the back, initiated by food, and eventually associated with constipation, or epigastric postprandial discomfort. Interestingly, symptoms suggesting biliary dyspepsia are partially shared by dysmotility-like dyspepsia. The placebo response in functional dyspepsia is variable, between 6 and 80% of patients, reflecting variations in the kind and severity of the diseases in different studies. That represents a considerable difficulty in evaluating drug efficacy, even in the case of biliary dyspepsia. A therapeutic double-blind trial in functional dyspepsia using tauro-ursodeoxycholic acid is discussed.

Adult↗

[Segmental rehabilitation in cardiac failure: short and long-term results].

Many patients with chronic cardiac failure may benefit from exercise rehabilitation. However, the usual protocols, which may lead to haemodynamic disturbances or induce arrhythmias, are rarely applicable in the most severe cases. Therefore, the authors developed a protocol of segmental rehabilitation where the same muscle groups as in global readaptation are involved, but successively and not simultaneously. This study included 25 patients in the NYHA class III. Many parameters were analysed before and after forty sessions. Although the resting isotopic ejection fraction (0.26 +/- 0.1 vs 0.27 +/- 0.11; p = NS), oxygen consumption at the ventilatory threshold (14.3 +/- 3.5 vs 18.3 +/- 5.2 ml/kg/min; p = NS) or at peak effort (17.4 +/- 4.7 versus 18.3 +/- 5.2 ml/kg/min, p = NS) were unchanged, three other parameters were significantly improved: the duration of exercise (9.2 +/- 2.4 vs 10.4 +/- 3.4 min; p < 0.02) maximum work load (3 046 +/- 1 510 vs 3 992 +/- 2 482; p < 0.01) and muscular force (151 +/- 35 versus 220 +/- 41 kg; p < 0.0001). In addition, after a follow-up period of 43 +/- 18 months, a close inverse relationship was observed between the gains obtained in terms of duration of exercise and maximum work load and the number of hospital readmissions. Similarly, the 10 patients having undergone rehabilitation with this protocol had 11.7 times fewer hospital readmissions than the other 15. Segmental rehabilitation would therefore seem to be a safe technique for patients with severe cardiac for significantly increasing exercise capacity and lowering the number of readmissions to hospital.

Aged↗

MR of cerebral abnormalities concomitant with primary intracerebral hematomas.

PURPOSE: To determine whether arteriolar vessel wall degeneration in primary intracerebral hematomas might be associated with ischemic brain lesions and clinically silent (apparently intracerebral) previous hemorrhages. METHODS: The MR images of 120 consecutive patients (mean age, 60 years; age range, 22 to 84 years) with their first stroke caused by a primary intracerebral hematoma were reviewed retrospectively for coexisting ischemic damage and previous bleeds. RESULTS: Early confluent to confluent white matter hyperintensities, lacunes, or infarction were present in 83 (69%) of the patients, and 39 (33%) had had previous hemorrhages consisting of microbleeds or old hematomas. Extensive white matter hyperintensities and lacunes were most frequent in patients with thalamic primary intracerebral hematomas. There was no relationship between the frequency of old hemorrhages and the location of subsequent primary intracerebral hematomas. CONCLUSION: Clinically silent ischemic lesions and previous hemorrhages are a common finding on MR images of patients with primary intracerebral hematoma. They may therefore serve as evidence of diffuse microangiopathy with a possible increased risk for cerebral hemorrhage.

Adult↗

[Isoflurane anesthesia in rabbits in a closed anesthetic system].

Using the Stephens anaesthetic apparatus-which is a closed system with an in-circuit, nonprecision vaporizer-and isoflurane as anaesthetic gas, 18 rabbits were anaesthetized and showed sufficient hypnosis, analgesia, and muscle relaxation during bone surgery. Induction of anaesthesia was achieved with intravenous propofol and all rabbits were intubated afterwards. During the following isoflurane inhalation anaesthesia the mean arterial blood pressure decreased considerably (compared to control measures before induction), the heart rate remained the same or showed a slight increase, and the respiratory rate decreased. The arterial pO2 decreased corresponding to the respiratory depression after propofol induction and increased again during spontaneous ventilation with 100% oxygen. The changes in arterial pCO2 and pH were representative for a rise in the CO2-stimulation threshold. A moderate metabolic acidosis could be seen due to preanaesthetic excitement of the animals. Recovery time was short (between one and 11 minutes) and no signs of excitation could be detected. The consumed volume of isoflurane was 0.80 ml/kg BW/h.

Anesthesia, Closed-Circuit↗

Cholecystokinin enhances the acoustic startle response in rats.

The present study examined the effects of the neuropeptide cholecystokinin (CCK) on neurones of the caudal pontine reticular nucleus (PnC), which mediates the acoustic startle response (ASR) in rats. Electrophysiological experiments revealed an excitatory effect of CCK on acoustically responsive neurones in the PnC. On the behavioural level, CCK also enhanced the ASR. Since the PnC is not only an obligatory relay station of the brain circuit mediating the ASR, but also receives modulatory input from brain areas involved in the expression of fear and anxiety, the enhancement of the ASR by CCK could be interpreted as an anxiogenic-like effect of this peptide.

Acoustic Stimulation↗

Glycine receptors in the caudal pontine reticular formation: are they important for the inhibition of the acoustic startle response?

The present paper sought to test the hypothesis that inhibitory glycine receptors (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are involved in the inhibition of the acoustic startle response (ASR) in rats. First we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR on PnC neurons by immunocytochemical labeling using an antibody against the alpha 1 subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting phenomena, short-term habituation and prepulse inhibition, after microinjections of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist beta-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor beta-alanine had a measurable influence on any of the parameters of the ASR investigated (amplitude, short-term habituation, prepulse inhibition). In contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR amplitude. The systemic administration of strychnine did not impair prepulse inhibition. The human 'startle disease' (hyperekplexia), an exaggerated startle response, is caused by a defect of the alpha 1 subunit of the inhibitory GlyR, but it is unclear at which site in the central nervous system this defect ultimately leads to the symptoms of hyperekplexia. Our data indicate that a blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats, suggesting that deficient GlyRs in the PnC might not be involved in the etiology of the human 'startle disease'. We conclude that the inhibitory GlyRs on PnC neurons are not necessary for the inhibition of the ASR and believe that they are involved in another behavioral context.

Animals↗

Magnetic resonance imaging cerebral abnormalities and neuropsychologic test performance in elderly hypertensive subjects. A case-control study.

OBJECTIVE: To search for a morphologic basis of cognitive impairment possibly associated with arterial hypertension using magnetic resonance imaging and a demanding neuropsychologic test battery. DESIGN: Case-control comparison with age, length of education, presence of diabetes, and presence of cardiac disease as matching criteria. SETTING: Austrian Stroke Prevention Study. SUBJECTS: A total of 89 hypertensive subjects and 89 control subjects from a subset of 272 volunteers with no neurologic symptoms undergoing extensive diagnostic workup in a large-scale stroke prevention study among randomly selected elderly community members. MAIN OUTCOME MEASURES: Focal brain abnormalities and size of ventricles and cortical sulci as assessed by magnetic resonance imaging and neuropsychological test scores. RESULTS: Hypertensive subjects more commonly showed areas of white matter hyperintensity and moderately severe ventricular enlargement compared with controls. While no differences were noted between the investigational groups in test results of memory capacity and conceptualization, hypertensive subjects tended to perform worse when assessed for attentional and visuopractical skills. These differences became significant when comparing the brain-damaged subsets of patients and controls with their counterparts without cerebral changes. The pattern and extent of neuropsychologic deficits was similar in hypertensive and normotensive subjects with abnormal magnetic resonance imaging scans. CONCLUSION: Our data strongly suggest the high rate of brain abnormalities among hypertensive subjects as the cause of their subtle neuropsychological dysfunction.

Aged↗

Development of a parenterally administrable hydrosol preparation of the "third generation platinum complex" [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II). Part 1. Preparation and studies on the stability and antitumor activity.

The development of a galenical formulation for poorly water soluble dichloroplatinum(II) complexes suitable for the parenteral administration in cancer chemotherapy is described. The procedure, which we elaborated for [(+/-)-1,2-bis(4-fluorophenyl)ethylenediamine]dichloroplatinum(II) (rac-4F-PtCl2), is based on the reaction of a soluble diaquaplatinum(II) salt with sodium chloride in water in the presence of pluronic F 68 as stabilizer and results in a sufficiently stable colloidal solution (i.e. hydrosol). In contrast to the poorly water soluble synthetic rac-4F-PtCl2, which was ineffective towards the hormone sensitive MXT-M-3.2 breast cancer of the mouse, its hydrosol formulation proved to be highly active and was very well tolerated.

Animals↗

Analysis of thyroid stimulating hormone-receptor mutations by temperature-gradient gel electrophoresis.

Somatic mutations in the genes for G-protein-coupled receptors which regulate intracellular levels of cyclic AMP have been found in several regions coding for the receptors of melanocyte-stimulating hormone, adrenaline, luteinizing hormone, rhodopsin and thyrotropin. The mutations found in the thyroid-stimulating hormone (TSH) receptor are restricted to cells of hyperfunctioning thyroid adenomas and other thyroid tumors. They are thought to lead to a constitutive activation of the receptor independent of TSH. We have developed a temperature-gradient gel electrophoresis (TGGE) assay starting with the amplification of a part of exon 10 of the TSH-receptor gene to screen tissue of thyroid tumours. TGGE allows the detection of point mutations even if there are only a few cells with somatic mutations in tissue sections.

Adenoma↗

Conditioned pleasure attenuates the startle response in rats.

The acoustic startle response of rats was found to be attenuated if elicited in the presence of a conditioned stimulus predicting reward. During conditioning, animals received a total of 21 pairings of light with palatable food and sucrose solution, whereas controls received food and sucrose in the absence of light. The amplitude of the acoustic startle response was significantly reduced in the presence of light in conditioned animals, but not in controls. It is assumed that a conditioned response to light is the activation of a central state of pleasure. We therefore suggest that "pleasure-attenuated startle" reflects a mechanism by which a defensive or aversive response is attenuated during a pleasant, hedonic state.

Acoustic Stimulation↗

Large and small splice variants of collagen XII: differential expression and ligand binding.

Collagen XII has a short collagenous tail and a very large, three-armed NC3 domains consisting primarily of fibronectin type III repeats. Differential splicing within this domain gives rise to a large (320 kD) and a small (220 kD) subunit; the large but not the small can carry glycosaminoglycan. To investigate whether collagen XII variants have distinct expression patterns and functions, we generated antibody and cDNA probes specific for the alternatively spliced domain. We report here that the large variant has a more restricted expression in embryonic tissue than the small. For example, whereas the small variant is widespread in the dermis, the large is limited to the base of feather buds. Distinct proportions of mRNA for the two variants were detected depending on the tissue. Monoclonal antibodies allowed us to separate collagen XII variants, and to show that homo- and heterotrimers exist. Collagen XII variants differ in ligand binding. Small subunits interact weakly with heparin via their COOH-terminal domain. Large subunits have additional, stronger heparin-binding site(s) in their NH2-terminal extra domain. In vivo, both large and small collagen XII are associated with interstitial collagen. Here we show biochemically and ultrastructurally that collagen XII can be incorporated into collagen I fibrils when it is present during, but not after, fibril formation. Removal of the collagenous domain of collagen XII reduces its coprecipitation with collagen I. Our results indicate that collagen XII is specifically associated with fibrillar collagen, and that the large variant has binding sites for extracellular ligands not present in the small variant.

Alternative Splicing↗

Gastroduodenal toxicity of different nonsteroidal antiinflammatory drugs.

Although the etiologic relation between nonsteroidal antiinflammatory drug (NSAID) use and gastrointestinal lesions is well documented, newly introduced NSAIDs deserve a fresh examination for their risk/benefit ratio. To estimate the association between consumption of ketorolac and the occurrence of gastroduodenal lesions, we conducted a case-control study. The study population comprised 600 outpatients with a confirmed endoscopic diagnosis of ulcer and erosion in 1991 and 1992 and 6,000 community controls matched by age and sex. We retrieved the prescription history through a computerized prescription monitoring system. We defined exposure to each study drug as "current" (month of endoscopy and preceding month), "recent" (second or third month preceding endoscopy). and "past" (fourth to sixth month preceding endoscopy). Current users of NSAIDs showed a 30% increase in the incidence of gastroduodenal lesions [odds ratio (OR) = 1.3; 95% confidence interval (CI) = 0.98 - 1.8] after adjustment for recent or past use of any NSAID, recent or past gastrotoxic therapy, recent or past use of gastroprotective drugs, and recent or past use of any other drug. Among NSAIDs, ketorolac was the only one showing a distinctly elevated risk of gastroduodenal lesions (OR = 4.2; 95% CI = 1.9-9.4). Current use of any NSAID was associated with almost a doubling of risk for ulcer alone (OR = 1.9; 95% CI = 1.3-3.0); no elevation in risk was found for erosions. The adjusted relative risk for ulcer associated with current use of ketorolac was 9.8 (95% CI = 3.4-28.10. Recent and past use of NSAIDs does not increase the risk of ulcer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Efficacy of rifaximin in the treatment of symptomatic diverticular disease of the colon. A multicentre double-blind placebo-controlled trial.

BACKGROUND AND AIMS: In a recent open trial we have shown the efficacy of long term intermittent administration of a poorly absorbable antibiotic (rifaximin) in obtaining symptomatic relief in uncomplicated diverticular disease of the colon. The aim of this double-blind placebo-controlled trial was to test our previous observations. METHODS: One hundred and sixty-eight outpatients with symptomatic uncomplicated diverticular disease were treated with fibre supplementation (glucomannan 2 g/day) plus rifaximin 400 mg b.d. for 7 days every month (84 patients), or with glucomannan 2 g/day plus placebo two tablets b.d. for 7 days every month (84 patients). Clinical evaluation was performed at admission and at three-month intervals for 12 months. RESULTS: After 12 months, 68.9% of the patients treated with rifaximin were symptom-free or mildly symptomatic, compared to 39.5% in the placebo group (P = 0.001). Symptoms such as bloating and abdominal pain or discomfort were primarily affected by antibiotic treatment when compared with placebo (P < 0.001). CONCLUSION: Rifaximin appears to be of some advantage in obtaining symptomatic relief in diverticular disease of the colon when compared with fibre supplementation alone.

Adult↗

Prevention of NSAID-induced gastroduodenal mucosal injury: meta-analysis of clinical trials with misoprostol and H2-receptor antagonists.

In order to provide a systematic overview of the available information on the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury, we performed a meta-analysis based on all the in extenso published randomized clinical trials comparing H2-blockers or misoprostol to placebo for the prevention of NSAID-induced gastrointestinal mucosal injury in arthritis patients or normal subjects. The main endpoints after NSAID therapy were considered the number of subjects developing gastric ulcer, or clinically relevant gastric lesions (i.e. more than 10 erosions or 1 ulcer), or duodenal ulcer, or clinically relevant duodenal lesions (i.e. more than 10 erosions or 1 ulcer). The total number of patients studied was 1,955, and that of normal subjects was 715. Results were analyzed by the DerSimonian and Laird method, as well as by the Peto one. The data available from the trials suggest that misoprostol prevention is of benefit in patients under NSAID treatment for the prevention of NSAID-induced gastroduodenal mucosal injury. The effect of prevention is statistically significant with both methods, and ranges from -42% (duodenal ulcer) to -79% (gastric ulcer). The prevention estimates for gastric and duodenal erosions are in between. H2-blockers seem to be less effective: prevention is not indeed demonstrable for the more relevant lesions, like gastric and duodenal ulcer.

Anti-Inflammatory Agents, Non-Steroidal↗

[Prognosis and predictive factors of mortality in patients with inoperable coronary disease].

In the period between September 1979 and December 1986, 105 out of 2,178 consecutive patients with coronary artery disease (men 93, women 12; age : 58.1 +/- 10 years; previous myocardial infarction : 67%) were considered inoperable because of poor distal coronary circulation (84.8%), left ventricular dysfunction (3.8%) or both (11.4%). Fifty-four clinical, ergometric and angiographic parameters were examined at inclusion. The mean follow-up was 69 +/- 40.2 months (1 to 146 months). The Kaplan Meier 10 year survival rate was 43%. Only 25% of the population remained free of major cardiac events. Multivariate analysis showed that only the coronary angiographic score had a significant predictive value. The authors conclude that the long-term prognosis of these patients is poor. Some did undergo coronary bypass surgery secondarily, and their prognosis was good, suggesting that revascularisation, even if only partial and at high risk, should be considered.

Adult↗

The effects of cyanide on the extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 5-hydroxyindoleacetic acid and inositol phospholipid breakdown in the brain.

The effects of sodium cyanide on the extracellular levels of dopamine and the main brain metabolites of dopamine and 5-hydroxytryptamine were studied in awake, freely moving rats using microdialysis technique. Already 20 min after the administration of cyanide (2 mg/kg; ip) the extracellular level of striatal dopamine was increased and after 40 min an enhancement of the homovanillic acid level was observed. Slight but significant decreases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid were also observed. The increased extracellular levels of dopamine and homovanillic acid could indicate an increased release of dopamine. An alternative explanation could be an extracellular leakage of dopamine due to neuronal damage caused by cyanide. Cyanide has also been reported to induce marked changes in cytosolic brain Ca2+. We examined the effect of cyanide on inositol phospholipid breakdown in rat cerebral cortex and pig striatum in vitro. This breakdown was not affected by sodium cyanide and appears therefore not to be responsible for the reported changes of cytosolic Ca2+ induced by sodium cyanide.

3,4-Dihydroxyphenylacetic Acid↗