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Biomedical subjects

J Schipper

Publications and source records attributed to J Schipper.

At least 91 records · Page 5Linked to original sources

Hyperglycemia modulates gallbladder motility and small intestinal transit time in man.

The aim of the present study was to investigate the effect of acute hyperglycemia on (1) the intestinal phase of gallbladder contraction induced by the intraduodenal administration of emulsified fat, and (2) the small intestinal transit time measured by the lactulose breath hydrogen test. Six healthy volunteers were studied in random order during normoglycemia and hyperglycemia (blood glucose levels 15 mmol/liter). Gallbladder volumes were measured with ultrasonography. Administration of 1 and 2 g/hr of fat resulted in significant reductions in gallbladder volumes from 24 +/- 2 cm3 to 11 +/- 1 cm3 (P < 0.05) and 8 +/- 1 cm3 (P < 0.05), respectively during normoglycemia, and from 24 +/- 2 cm3 to 21 +/- 2 cm3 (P < 0.05) and 16 +/- 2 cm3, respectively (P < 0.05) during hyperglycemia. Compared to normoglycemia, the gallbladder contraction was significantly (P < 0.05) reduced during hyperglycemia. No significant differences in CCK secretion were observed between experiments. Small intestinal transit time during hyperglycemia (101 +/- 12 min) was significantly (P < 0.05) prolonged compared to normoglycemia (57 +/- 12 min). During hyperglycemia, basal PP levels and PP secretion in response to intraduodenal fat were significantly (P < 0.05) reduced compared to normoglycemia. It is concluded that (1) low doses of intraduodenal emulsified fat result in significant gallbladder contraction and CCK secretion, (2) acute hyperglycemia inhibits intraduodenal fat induced gallbladder contraction, (3) acute hyperglycemia does not affect the intraduodenal fat induced CCK secretion, (4) small intestinal transit is significantly prolonged during acute hyperglycemia, and (5) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Acute Disease↗

Hyperglycemia reduces gallbladder emptying and plasma hormone secretion to modified sham feeding and regular feeding.

The purpose of this study was to investigate the effect of acute stable hyperglycemia on gallbladder motility, plasma cholecystokinin level and pancreatic polypeptide secretion. Gallbladder emptying in response to modified sham feeding and regular feeding was determined in six healthy subjects on two separate occasions during normoglycemia (serum glucose = 5 mmol/L) and during hyperglycemia (serum glucose = 15 mmol/L). Pancreatic polypeptide secretion was determined as an indirect measure of cholinergic tone. Gallbladder contraction in response to sham feeding during hyperglycemia (9% +/- 2%) was significantly (p < 0.05) reduced compared with that in normoglycemia (22% +/- 1%). During hyperglycemia, gallbladder emptying after meal ingestion (29% +/- 9%) was significantly (p < 0.05) less than that in normoglycemia (60% +/- 10%). Sham feeding did not affect plasma cholecystokinin levels. Regular feeding induced significant (p < 0.05) increases in plasma cholecystokinin levels in both experiments. However, integrated postprandial plasma cholecystokinin secretion was significantly (p < 0.05) reduced during hyperglycemia compared with that in normoglycemia (29 +/- 5 pmol.60 min vs. 58 +/- 10 pmol.60 min). Modified sham feeding-and feeding-stimulated pancreatic polypeptide secretion during hyperglycemia (235 +/- 95 pmol.90 min and 1,035 +/- 267 pmol.60 min, respectively) were significantly (p < 0.05) less than levels seen in normoglycemia (434 +/- 71 pmol.90 min and 1,961 +/- 219 pmol.60 min, respectively). This study indicates that gallbladder emptying and plasma hormone secretion in response to sham feeding and regular feeding are affected by blood glucose levels.

Adult↗

Preclinical evidence on the psychotropic profile of fluvoxamine.

Serotonin (5-HT) reuptake inhibitors (SSRIs) such as fluvoxamine are interesting compounds. Initially launched as antidepressants, they have been found to be active in various psychiatric disorders besides depression, including obsessive-compulsive disorder, panic disorder, and eating disturbances. Preliminary data suggest their efficacy in alcohol and drug abuse, aggression, and posttraumatic stress disorder as well. Along with those clinical findings, new preclinical data have emerged. For example, fluvoxamine has demonstrated activity in various models of anxiety in rodents. Its anxiolytic activity can be clearly discriminated from that of the benzodiazepines. In the DRL 72-sec paradigm, fluvoxamine exhibits a good antidepressant profile, similar to those of imipramine and flesinoxan. Studies have shown that fluvoxamine does not down-regulate beta-adrenoceptors; apparently, that property is not a conditio sine qua non for antidepressant activity. Results of studies of the mechanism of action of fluvoxamine in which drug discrimination tests were performed with rats and pigeons suggest that the fluvoxamine stimulus is not (or is only to a very limited degree) dependent on activation of 5-HT1A receptors or 5-HT1B/1D receptors, or both. Experimentation is ongoing in those animal models.

Animals↗

[Evaluation of visual field defects, motility disorders and diplopia within the scope of accident insurance law].

Visual Field: The determination of the level of compensation for loss of integrity is based on the Goldmann Perimetry. In case of concentric loss of the visual field the SUVA Tables 1989 are used. Hemi- and Quadrantanopsias are still evaluated according to the Rintelen Tables from 1954. No guidelines are available for the evaluation of central and paracentral skotomas. It is uncertain if automatic perimetry can be used routinely in the future for the evaluation of visual function. Motility Disorders and Diplopia: The evaluation of functional loss caused by diplopia is very difficult. Therefore a big variation of 5-30% has been determined. It is up to the specialist to evaluate the extent of the damage. In this study we looked for a correlation between the objective findings and the subjective complaints. Such a correlation could not be found so that an arbitrary classification depending on the extent of the diplopia must be recommended. This would create an analogy to the evaluation of the loss of visual acuity and visual field where no freedom is left to the judgement of the physician. Some reflections are given on the sense and benefit of the unique Swiss law concerning compensation for loss of integrity.

Diplopia↗

Abdominal ultrasound as a reliable indicator for conclusive laparotomy in blunt abdominal trauma.

The purpose of this study was to evaluate the ability of abdominal ultrasound (US) to detect intra-abdominal injuries that required surgical repair. We therefore retrospectively reviewed 353 patients with nontrivial blunt abdominal trauma. All patients underwent abdominal evaluation as part of our routine trauma protocol within the first minutes of arrival at our emergency center. Hemoperitoneum and intraperitoneal parenchymal damage were correctly identified by US with a sensitivity of 92.8%, and a specificity of 100%. Accuracy was 99.4%, the positive predictive value was 100%, and the negative predictive value was 99.4% (prior probability of disease was 7.65%). We believe that abdominal US should be considered an important tool and an integral part in the work-up of major trauma victims.

Abdominal Injuries↗

Effect of acute hyperglycaemia on gall bladder contraction induced by cholecystokinin in humans.

This study examined the effect of acute hyperglycaemia, induced by intravenous glucose, on gall bladder motility. Six healthy volunteers were studied in random order on three occasions during normoglycaemia and hyperglycaemia with blood glucose concentrations stabilised at 8 and 15 mmol/l. Gall bladder volumes, measured with ultrasonography, were studied before and during infusion of stepwise increasing doses of cholecystokinin (CCK-33; 0.25, 0.5, and 1.0 IDU.kg-1.h-1). Each dose was given for 30 minutes. Pancreatic polypeptide (PP) secretion was determined as an indirect measure of cholinergic tone. Infusion of CCK-33 resulted in significant dose dependent reductions in gall bladder volume in all three experiments. Compared with normoglycaemia the gall bladder contraction was significantly (p < 0.05) reduced during infusion of 0.25 and 0.5 IDU kg-1.h-1 CCK-33 in the 8 mmol/l hyperglycaemic experiment, and during infusion of 0.25, 0.5, and 1.0 IDU kg-1.h-1 CCK-33 in the 15 mmol hyperglycaemic experiment. During hyperglycaemia basal plasma PP concentrations and PP secretion in response to CCK-33 were significantly (p < 0.05) reduced. It is concluded that blood glucose concentrations affect gall bladder motility, that an acute hyperglycaemia at 8 and 15 mmol/l reduces the gall bladder responsiveness to CCK-33 in a dose dependent manner, and that hyperglycaemia reduces basal and CCK-33 stimulated plasma PP concentrations, suggesting impaired cholinergic activity during hyperglycaemia.

Adult↗

Effect of loxiglumide and atropine on erythromycin-induced reduction in gallbladder volume in human subjects.

This study was undertaken to investigate the effect of erythromycin, a motilin agonist with prokinetic activity, on fasting gallbladder volume. To evaluate the mechanism of action of erythromycin on gallbladder motility, erythromycin (3.5 mg/kg.20 min, intravenously) was infused on three separate occasions: during cholinergic blockage with atropine (0.005 mg/kg.hr), during cholecystokinin receptor blockade with loxiglumide (10 mg/kg.hr) and during saline solution infusion (control). Atropine, loxiglumide and saline solution infusions were started 3 hr before administration of erythromycin and were continued for 3 hr thereafter. Gallbladder volumes (measured by ultrasonography), plasma cholecystokinin levels (radioimmunoassay) and plasma pancreatic polypeptide levels (radioimmunoassay) were determined at regular intervals for 6 hr in six healthy volunteers. During the 3-hr infusion before administration of erythromycin, both loxiglumide and atropine significantly increased gallbladder volumes--from 18 +/- 2 to 37 +/- 3 cm3 (p less than 0.05) and from 17 +/- 3 to 24 +/- 2 cm3 (p less than 0.05), respectively--whereas saline solution did not significantly affect gallbladder volume. During control saline solution infusion, erythromycin induced prolonged gallbladder contraction that was significant (p less than 0.05) between 60 and 180 min and reached a maximum of 45% +/- 8% at 150 min. Plasma cholecystokinin levels were not affected by erythromycin. Erythromycin induced a significant (p less than 0.05) increase in plasma pancreatic polypeptide levels, from 12 +/- 1 pmol/L to 34 +/- 3 pmol/L. Loxiglumide did not prevent the erythromycin-induced reduction in gallbladder volume. Atropine markedly reduced the effect of erythromycin, causing slight but significant (p less than 0.05) gallbladder volume reductions (18% +/- 4%) between 150 and 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Magnetic resonance imaging of Achilles tendon xanthomas in familial hypercholesterolemia.

The demonstration of tendon xanthomas is helpful in diagnosing heterozygous familial hypercholesterolemia, but in many patients lipid may accumulate without clinical abnormality being present. We investigated the possibility of detecting the lipid element with magnetic resonance (MR) imaging in seven patients with familial hypercholesterolemia and six controls. Although the mean relative signal intensities measured on long TR/TE spin echo sequences of the tendon were significantly higher in patients than in controls, the lack of such elevation does not rule out the presence of such lesions. In vitro measurements indicated that the signal intensity of triglycerides was quenched by cholesterolesters. The anatomic findings of MR imaging were compared with those of ultrasonography (US), showing excellent correlation in measurements between MR images and US [r(S) = 0.95 and 0.97 respectively]. MR imaging and US provide equal information on the anatomy of the Achilles tendon; as an abnormally increased signal intensity within the xanthoma on MRI was found in only a minority of our patients, the value of MRI in the demonstration of Achilles tendon xanthomas is limited when using conventional T1 and T2 spin echo sequences.

Achilles Tendon↗

The value of increased end diastolic velocity during penile duplex sonography in relation to pathological venous leakage in erectile dysfunction.

In 58 patients 23 to 71 years old (mean age 49.5 years) with suspected vasculogenic erectile dysfunction diagnosed on the basis of repeated negative reactions to intracavernous pharmacological stimulation (rigidity less than 60% when measured with the RigiScan* device) pharmacocavernosometry and duplex Doppler measurements were performed. The end diastolic velocity in the 24 patients without venous leakage ranged from 0 to 21 cm. per second (mean 7.5 +/- 6.3, standard deviation). The end diastolic velocity in the 34 patients with venous leakage ranged from 0 to 26 cm. per second (mean 9.0 +/- 6.7). In 23 of the 58 patients a peak systolic velocity of less than 25 cm. per second was found, which is an indication of arterial disease. Of 35 patients with a normal peak systolic velocity 15 were in the group without and 20 were in the group with leakage. In the group with a normal peak systolic velocity no statistically significant difference was found in end diastolic velocity between patients with and without leakage. We conclude that the end diastolic velocity during color Doppler analysis of patients with negative reactions on intracavernous pharmacological stimulation does not provide a good indication of potential pathological venous leakage.

Adult↗

Cell adhesion in invasion and metastasis.

Metastatic cells exhibit considerable flexibility in their adhesive interactions with other cells or components of the extracellular matrix. This review will describe the involvement of specific adhesion receptors, extracellular matrix molecules and cell dissociating cytokines in the metastatic cascade. We will particularly focus on disturbance of intercellular adhesion as a prerequisite for the release of invasive cells from carcinomas. We suggest that cell dissociation in these tumours is accomplished by loss of function or expression of the epithelial cell adhesion molecule E-cadherin, and through the activity of cell motility factors such as the scatter factor.

Animals↗

Species differences in the distribution of central 5-HT1 binding sites: a comparative autoradiographic study between rat and guinea pig.

In this study, we compared the localization of central 5-HT1 binding sites of rat and guinea pig. The 5-HT1B sites were absent in the guinea pig brain. Good correlations were found between species in the regional distribution of 5-HT1 sites labelled with [3H]5-HT (r = 0.73), 5-HT1A sites labelled with [3H]8-OH-DPAT (r = 0.87), and 5-HT1B versus 5-HT1D sites labelled with [3H]5-HT in the presence of ipsapirone and DOI (r = 0.76). Despite the overall similarities, species differences were observed in many brain regions. The CA1/CA2 fields of the hippocampus and the dorsal subiculum displayed significantly more 5-HT1A receptor binding in guinea pig than in rat. Conversely, the 5-HT1A binding in dorsolateral septum, cingulate cortex and laminae IV-V of the neocortex, was more pronounced in rat. Areas almost exclusively containing 5-HT1B or 5-HT1D sites, such as the ventral pallidum, globus pallidus and substantia nigra, expressed markedly more [3H]5-HT binding in rat as compared to guinea pig, while the opposite occurred in claustrum, dorsal endopiriform nucleus, lateral geniculate nucleus, and superficial grey layer of the superior colliculus. The implications of the species differences are illustrated by the binding of [3H]eltoprazine. The distribution of [3H]eltoprazine binding sites showed a good correlation with that of the 5-HT1B sites in rat (r = 0.89), and with that of the 5-HT1A sites in guinea pig (r = 0.97). The data give rise to the possibility that differences in the presence and distribution of 5-HT1 receptor sites are related to species differences in behavioural, neurochemical and physiological responses to drugs with 5-HT1 receptor affinity.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effects of atrial natriuretic factor, nitroprusside and acetylcholine on cGMP immunostaining in the isolated perfused rat kidney.

In the present study the localization of the cGMP production in response to the vasodilators acetylcholine (ACh) and sodium nitroprusside (SNP) and to atrial natriuretic factor (ANF) was studied in the isolated perfused rat kidney using cGMP immunocytochemistry. After ACh (0.3 microM) infusion increased cGMP immunoreactivity was found in kidney interlobar and segmental arteries and in glomeruli. SNP (1 microM) and ANF (0.01 microM) elevated cGMP staining in the same elements of the kidney as ACh. In the glomeruli ACh and SNP stimulated cGMP production in mesangial cells whereas ANF stimulated cGMP production in mesangial cells whereas ANF stimulated cGMP production in epithelial cells (podocytes). However, SNP at higher doses (10 microM) stimulated cGMP production not only in glomeruli, but also in interstitial cells throughout the cortex. In addition SNP and ANF increased cGMP production in the medulla.

Acetylcholine↗

8-hydroxy-2-(di-N-propylamino)tetralin increases the activity of adenylate cyclase in the hippocampus of freely-moving rats.

The present study was designed to examine the effects of intraperitoneal (i.p.) administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on the efflux of cyclic adenosine monophosphate (cAMP) in the extracellular fluid of the dorsal hippocampus, using in vivo microdialysis. One week after implantation of the guide, probes were inserted in conscious rats and perfused with Ringer solution. Steady basal levels of cAMP (2.9 +/- 0.1 pmol/ml, n = 74 rats) were obtained after at least three hours of stabilisation. The 8-OH-DPAT dose-dependently increased the basal efflux of cAMP, which was most apparent between 20-40 min after the injection. The largest dose of 8-OH-DPAT (1 mg/kg) tested, induced a maximum response of approximately 50%, whereas injections of saline did not alter the efflux of cAMP. Treatment with (+/-)pindolol (10 mg/kg) did not significantly affect the basal efflux of cAMP, whereas it markedly inhibited the increase in levels of cAMP, induced by 0.5 mg/kg 8-OH-DPAT (injected 40 min later). Simultaneous behavioural observations demonstrated that (+/-)pindolol also attenuated various components of the 8-OH-DPAT-induced behavioural syndrome. Addition of 3-isobutyl-1-methylxanthine (IBMX), forskolin or noradrenaline, to the perfusion fluid, strongly enhanced the levels of cAMP in the extracellular fluid from the hippocampus. Injection of 8-OH-DPAT (1 mg/kg) during perfusion with IBMX induced a similar increase in levels of cAMP, as under normal perfusion conditions. However, 8-OH-DPAT did not significantly alter the efflux of cAMP, when probes were perfused with either forskolin or forskolin and IBMX.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

Postsynaptic 5-HT1 receptors and offensive aggression in rats: a combined behavioural and autoradiographic study with eltoprazine.

The present study was designed to assess whether the antiaggressive effects of eltoprazine are mediated via presynaptic and/or postsynaptic 5-HT1 receptors. We describe the effects of central 5-HT depletion 1) on the behaviour of resident TMD-S3 rats in a territorial situation, 2) on the efficacy of eltoprazine to inhibit offensive aggression, and 3) on the 5-HT1A, 5-HT1B and 5-HT1C receptor binding in brains of rats previously used in behavioural studies. Male resident rats were given combined 5,7-dihydroxytryptamine (5,7-DHT) injections into the dorsal and median raphe nuclei. Two to four weeks after the lesions, rats were confronted with an intruder Wiser rat in their home cage for a 10-min period. The 5,7-DHT treatment resulted in a modest reduction of offensive behaviour, while having no effects on other social and nonsocial behaviours. Oral administration of eltoprazine (1 mg/kg) specifically reduced offensive aggression in both sham- and 5,7-DHT-lesioned animals, leaving social interest and exploration intact or even increasing it. A low dose (0.3 mg/kg) of eltoprazine did not affect the behavioural repertoire of sham-operated rats, whereas this dose significantly reduced offense behaviours in the 5,7-DHT-lesioned residents. Quantitative autoradiographic studies 5 weeks after 5,7-DHT treatment revealed a significant increase in radioligand binding to 5-HT1A, 5-HT1B and 5-HT1C sites in many brain regions studied, except for the raphe nuclei where [3H]8-OH-DPAT binding to 5-HT1A sites was markedly reduced. The concentrations of 5-HT and 5-HIAA in frontal cortex were reduced to approximately 10% of controls. The results indicate that serotonin has a stimulatory rather than an inhibitory influence on offensive aggressive behaviour. Central 5-HT depletion does not prevent the antiaggressive effects of eltoprazine, indicating a role for postsynaptic 5-HT1 receptors in the modulation of offensive aggression. The 5,7-DHT-induced overall upregulation of 5-HT1A, 5-HT1B and 5-HT1C binding sites suggests that these three receptor subtypes receive a tonic serotonergic influence. It is conceivable that this postsynaptic 5-HT1 receptor supersensitivity is reflected by the increased efficacy of eltoprazine to inhibit offensive aggression.

5,7-Dihydroxytryptamine↗

Transvaginal sonography and abnormal ovarian appearance in menstrual cycle disturbances.

Transvaginal ultrasound examinations were performed in 37 oligo- or a-menorrheic women to describe ovarian changes and potential correlations with clinical and some biochemical features of polycystic ovarian syndrome (PCOS). Findings were compared between the right and left ovary and between each of three subsequent examinations of the same ovary. In any one ovary, no significant difference was found between mean ovarian volume, stroma echogenicity, mean follicle number and size. Correlation between ovarian volume and follicle number was strong in all examinations. Follicle number in both ovaries correlated significantly with ovarian stroma echogenicity and some biochemical markers of PCOS. These observations validate the usefulness of transvaginal sonography in demonstrating numerous correlations in menstrual cycle disturbances. The strong necessity to reevaluate sonographic criteria of PCOS is highlighted.

Adult↗

Dominant and recessive genes involved in tumor cell invasion.

The past year has been the discovery and further analysis of several genes and protein products that are critically involved in the generation of invasive and metastatic tumor cells. Like oncogenes and tumor suppressor genes, the genes responsible for invasive and metastatic phenotypes can function in a dominant or recessive fashion. In this review, particular emphasis will be given to the dominantly acting genes encoding the cell adhesion molecule CD44 and the motility factor scatter factor, and the recessively acting genes encoding the cell adhesion molecule E-cadherin and nm23.

Amino Acid Sequence↗

Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging.

Renal dysfunction has been recognized as an adverse effect of indomethacin treatment and is probably secondary to impairment of renal blood flow. We therefore evaluated renal artery blood flow velocity in 15 premature infants with a symptomatic ductus arteriosus before and during the first 12 hours after a single intravenous dose of 0.1 mg/kg of indomethacin. Renal artery blood flow velocity was measured serially by color-Doppler flow imaging and used as a qualitative measure of true renal blood flow. Indomethacin administration led to a sharp decrease in peak systolic flow velocity and temporal mean flow velocity of the renal artery. This effect was maximal at 10 minutes after indomethacin dosing; the flow velocities showed a slow recovery, reaching baseline values again at 2 hours after indomethacin dosing. We conclude that indomethacin can affect renal blood supply in the premature infant for a period of at least 1 hour after indomethacin treatment.

Blood Flow Velocity↗