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Biomedical subjects

J M Roelofs

Publications and source records attributed to J M Roelofs.

At least 19 recordsLinked to original sources

Gastric emptying and dyspeptic symptoms in the irritable bowel syndrome.

Many patients with irritable bowel syndrome (IBS) have symptoms suggestive of disturbances in gastric emptying, but so far no abnormalities in gastric emptying have been demonstrated in these patients. We studied gastric emptying of a solid meal with a 99mTc-labeled pancake in 16 healthy volunteers (8 women and 8 men; age, 20-33 years; mean age, 25 years) and 16 predominantly constipated IBS patients (10 women and 6 men; age, 17-43 years; mean age, 25 years). The incidence and severity of the symptoms nausea, vomiting, early satiety, and pain in the upper abdomen were scored. The duration of the lag phase of gastric emptying of the solid meal did not differ between the groups (controls, 16.6 +/- 4.7 min; IBS patients, 22.2 +/- 14.7 min). In normal subjects lag phase duration and emptying rate were correlated (r = 0.49, p greater than 0.05); in the IBS patients they were not. Post-lag gastric emptying of the solid meal was slower (p less than 0.01) in the IBS patients (0.58 +/- 0.24%/min) than in the control subjects (0.85 +/- 0.24%/min). No correlations were found, however, between the emptying rate and the severity of the upper abdominal symptoms. This study is the first to demonstrate that gastric emptying is delayed in IBS patients. This abnormality, however, appears not to be the major determinant of the upper abdominal symptoms often present in these patients.

Adolescent

Bone growth and remodeling after distraction epiphysiolysis of the proximal tibia of the rabbit. Effect of electromagnetic stimulation.

The effect of pulsed electromagnetic stimulation on bone formation was tested in a lower-limb-lengthening model in the rabbit. Limb lengthening was performed by distraction epiphysiolysis. A specially designed external distraction device allowed 10 mm of lengthening of the tibia. Coils to generate a pulsed electromagnetic field were clipped onto the distractor. Stimulation started after a distraction period of three weeks and was continuous for 18 weeks. A control group received the same treatment without stimulation. Bone formation in the elongated zone was evaluated by computed tomography, scintigraphy, and histology. Bone healing involved accretion of callus followed by a process of remodeling, resulting in the formation of a solid cortex. The formation of a diaphysislike structure at the original site of the metaphysis progressed from the distal end of the elongated zone upward. Electromagnetic stimulation had no effect on the rate or extent of bone formation and remodeling.

Animals

Effect of ICS 205-930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects.

The effects on gastric emptying of a solid meal of the specific 5-HT3-receptor antagonist ICS 205-930, 10 mg and 20 mg intravenously were assessed with a scintigraphic technique in 12 normals. The 50% emptying time was less, the lag phase was shorter and the post lag emptying rate was faster after 20 mg ICS 205-930 (p less than 0.02). After 10 mg ICS 205-930 the lag phase was significantly shorter compared with placebo (p less than 0.04). These results suggest that 5-HT3 receptors may be involved in the regulation of gastric emptying in man.

Adult

The pharmacokinetics of intradural morphine in major abdominal surgery.

The pharmacokinetics of intradural morphine used for major abdominal surgery were evaluated. Lumbar spinal fluid and plasma concentrations were measured at intervals after morphine 0.05 mg/kg had been injected intradurally in 21 patients scheduled for elective abdominal aortic surgery. The CSF morphine concentrations were fitted by a biexponential function. A non-compartmental model based on statistical moment theory was used for calculating the intradural morphine disposition. Mean residence time was 137 +/- 54.9 minutes, mean initial volume of distribution 15 +/- 5.49 ml, mean volume of distribution at steady-state 42 +/- 18.25 ml and mean clearance 0.34 +/- 0.18 ml/min (0.02 +/- 0.01 L/h). The moments of the morphine concentration-time curves and the pharmacokinetic parameters varied between the patients. They were not significantly different with regard to morphine dosage, or patient sex or age. Free morphine could not be detected in plasma. Morphine-3-glucuronide appeared in plasma at 5 minutes, increased to a maximum at 240 minutes and fell below the detection limit at about 16 hours after morphine administration. Possible clinical causes of interindividual variations in the CSF morphine concentrations and the pharmacokinetics of intradural morphine are discussed.

Adult

Computer aided analysis of electrical and mechanical activity of stomach and duodenum.

In studies of gastroduodenal motility several imaging techniques and also recordings of signals of implanted transducers are used. Combination of methods and prolonged observation times produce so much information that an automatic analysis is advantageous, the more so because more complex parameters can be analysed. Using a desktop computer, it is possible to analyse long time-series of antral and duodenal signals, obtained with implanted electrodes and strain gauges. The developed program can discriminate between the signal and the majority of artefacts. An easy manual interaction on the computer display enables the operator to either accept or adjust the indicators of recognized signals. The times of occurrence and the amplitudes of the detected peaks are retained for further analysis e.g. production of histograms of interval time, amplitude, antroduodenal time lag, or calculation of coordination parameters.

Animals

The effect of changes in dietary sodium content on complaints and clinical parameters of volume depletion in patients with a permanent ileostomy.

In seven patients with an ileostomy the volume and electrolyte composition of ileal effluent and urine were studied at the end of 7-day periods on a free diet (mean total sodium excretion 180 mmol/day) and on diets with a fixed sodium content ranging from 120 to 350 mmol/day. At the same time, complaints were scored and the plasma aldosterone concentration, renal aldosterone excretion, and ileal transmucosal potential difference were determined. On a free diet, all of the patients had one or more complaints. These tended to disappear when intake was increased. Changes in dietary sodium led to only minor changes in the volume and composition of the ileal effluent. Significant associations were found between sodium intake and complaints, the urinary sodium/potassium ratio, plasma aldosterone concentration, and aldosterone excretion. The ileal transmucosal potential difference showed the same tendency. Mean sodium intake on a free diet appeared to be suboptimal. The well-being of many ileostomists can be improved by increasing the dietary sodium intake to a level higher than 250 mmol/day.

Adult

Gastric emptying and postprandial symptoms after Billroth II resection.

Gastric emptying was studied in 18 symptomatic and 16 asymptomatic patients after Billroth II (BII) resection (without vagotomy) and the possible relationships between emptying and postprandial symptoms in these patients were assessed. The BII patients were compared with 20 nonoperated patients who had duodenal ulcer disease and 16 healthy subjects. Gastric emptying of two test meals (a semisolid porridge meal and a solid pancake meal) was measured with a radionuclide technique. The major difference between the BII patients and control subjects and duodenal ulcer patients was an increased rate of emptying of the semisolid meal in the first 5 minutes after meal consumption. The percentage of the meal remaining in the stomach at 5 minutes after completion was significantly less in the symptomatic (45.3% +/- 4.3%) than in the asymptomatic BII patients (79.4% +/- 2.6%). A positive correlation was demonstrated between the initial emptying rate of semisolids and the intensity of postprandial nausea (p less than 0.01), vomiting (p less than 0.05), and vasomotor symptoms (p less than 0.001). The duration of the lag phase for solid and semisolid meals was shorter in BII patients than in healthy subjects but was as short in nonoperated duodenal ulcer patients. The duration of the lag phase for solid food in the BII patients correlated positively with the score for postprandial epigastric pain (p less than 0.001). The rate of emptying of the solid meal was lower in symptomatic BII patients (28.1% +/- 3.6% per hour) than in asymptomatic patients (47.8% +/- 7.2% per hour) and correlated with the severity of postprandial fullness and nausea. The emptying of the solid meal was inversely related to the initial emptying rate of the semisolid meal (p less than 0.05). Therefore, the results of this study support the assumption that many of the postprandial symptoms occurring after BII resection reflect alterations in gastric emptying. Some of the emptying abnormalities present after BII resection may be related to duodenal ulcer disease rather than to the surgical procedure.

Adolescent

Does the metabolite uracil arabinoside inhibit cytosine arabinoside (Ara-C) penetration into the cerebrospinal fluid during high-dose Ara-C therapy?

A patient with acute leukaemia was treated with i.v. 2-h infusions of Ara-C at a dose of 3.0 g/m2 every 12 h. During 6 d of therapy the concentrations of the metabolite Ara-U in the CSF reached rather high levels of between 60 and 70 mumol/l from d 2-6 due to high levels of Ara-U in the plasma. The concentration of Ara-C in the CSF after the first infusion was 10.8 mumol/l. After repetitive doses on d 2-6 the drug concentrations increased from about 3 mumol/l just before infusion to about 8 mumol/l at the end of infusion, indicating inhibition of Ara-C influx into the CSF during prolonged treatment. We suggest that the high levels of Ara-U in the plasma interfere with Ara-C transport across the blood-brain barrier.

Adult

Integrated image and X-ray microanalysis of hepatic lysosomes in a patient with idiopathic hemosiderosis before and after treatment by phlebotomy.

Morphometrical and X-ray elemental information was extracted from Scanning Transmission Electron Microscopy (STEM) images of hepatic lysosomes of a patient with idiopathic hemosiderosis before and after treatment by phlebotomy. The elements of interest were iron, stored in pathological quantities in hepatic lysosomal structures and cerium, used as a capture ion after a cytochemical reaction to detect acid phosphatase activity in the lysosomal structures. Morphologically the lysosomal structures are heteromorph and the elements iron and cerium are heterogeneously distributed. With "reduced raster" (= reduced scanning area) analysis at 16 X 16 pixelpoints (integrating image and X-ray microanalysis), a marked difference in the area of the cross sectioned lysosomal structures before and after treatment could be demonstrated. Simultaneously the difference in the relative orientation of the elements iron and cerium before and after phlebotomy could be visualized. Chelex ion exchange beads, loaded with 11.5% w/w iron, and coembedded with the tissue blocks, were used as an internal standard. A mean iron peak to background ratio was obtained and a factor, converting ratio to absolute iron concentration, was calculated. The same calculation procedure, now per pixelpoint, was followed for the hepatic lysosomal structures. A marked difference in iron concentration in the individual lysosomal structures was observed before and after treatment by phlebotomy.

Bloodletting

Electrical stimulation of bone growth with direct current.

Electrical stimulation of osteogenesis was studied in rabbit femora in: (A) a transcortical electric field with a cortex-depolarizing or hyperpolarizing orientation derived from an intramedullary electrode and a ring-shaped counter electrode encircling the femoral shaft; and (B) an electric field derived from an electrode located in the medullary canal and the counter electrode in the abdominal wall. Electrodes were made of platinum. A direct current of 20 microA was applied during six weeks. Contralateral femora with dummy electrodes served as controls. Results were analyzed by optical densitometry of roentgenograms and histomorphometry of histologic slides. Under the conditions of these experiments bone growth was not stimulated by applying a cortex-depolarizing electric field. Significant stimulation of bone growth was only observed at an intramedullary cathode, when the anode was placed at a distance.

Animals

The distribution of (5E)-(10S)-10,19-dihydroercalciol and its metabolites in serum of rats.

The distribution of radioactivity in serum of male rats (275 g) after oral administration of tritium labelled (5E)-(10S)-10,19-dihydroercalciol (dihydrotachysterol2) has been studied as a function of time and dose level. Nine distinct radioactive substances, chromatographing in the range between calciol and calcitriol, could be demonstrated. No attempt was made to establish chemical structures. After a single dose of 1.84 nmol, (5E)-(10S)-10,19-dihydroercalciol is very rapidly metabolized to more polar forms. The time course of appearance, ranging between 30 min and 1 day after administration, and the polarity of these substances indicated that they might be formed in sequence. The highest serum concentrations of the major substances occurred between 2 h and 10 h after administration, but compared with the dosage they were very low. In response to daily administration the concentrations of the major substances achieved steady-state levels within 1-4 days. The metabolism of (5E)-(10S)-10,19-dihydroercalciol was apparently not affected by its nutritional status at the dose level studied. After single administration of progressively increasing doses, ranging from 1.84 nmol to 1.84 mumol, the relative increments of the concentrations of the major substances rose in proportion to the relative increases of the dosage. The mechanisms responsible for the appearance of these substances in serum were found to be closely related. At dose levels up to 18.4 nmol feedback control was apparently absent.

Administration, Oral

Distribution of dendritic reticulum cells in follicular lymphoma and reactive hyperplasia. Light microscopic identification and general morphology.

Reactive and neoplastic follicles in lymph nodes showing changes of (1) follicular hyperplasia and (2) follicular lymphoma were examined for the presence of dendritic reticulum cells (DRC). These cells could be identified under the light microscope after comparing electron microscopical sections with subsequent 1 micro sections of reactive germinal centres. Quantitative light microscopical evaluation showed that DRC, both mononuclear and binuclear forms, were less numerous in neoplastic follicular structures than in reactive follicles. Before determining the frequency of binucleated DRC in follicular tissue their morphology was studied first in cell suspensions. DRC isolated by enzymatic treatment of tonsils and reactive lymph nodes were morphologically identical and contained one, or at most two, nuclei arranged in a typical doublet formation. Stereological calculations - made on three dimensional models of nuclear complexes prepared from serial tissue sections - indicated that 51 to 68% of DRC in reactive germinal centres were binucleated, whereas in neoplastic follicles this figure is 18 to 23%. The multinucleated giant cell forms of DRC described by others result from complex formation with other DRC or lymphoid cells. The smaller number of DRC and the lower frequency of binucleated DRC in follicular lymphomas suggest that differentiation of DRC from stromal cells is less complete in these neoplasms. The ability to identify DRC reliably by light microscopy offers a new means to define the difference in frequency of DRC. This may be of practical value in distinguishing reactive germinal centres from neoplastic follicles.

Cell Count

Thyroid function and bone turnover.

The mechanism of thyroid action on bone was studied in 15 patients with thyrotoxicosis and 14 patients with hypothyroidism. The patients were studied twice: when they were thyrotoxic or hypothyroid and when they had returned to a euthyroid state. Parameters of bone turnover showed a decrease when hyperthyroid patients became euthyroid: serum calcium (2.51 +/- 0.04 vs 2.38 +/- 0.03 mmol/l, P less than 0.05), acid phosphatase (11.7 +/- 0.7 vs 8.3 +/- 0.4 U/l, P less than 0.01), alkaline phosphatase (124 +/- 11 vs 98 +/- 8 U/l, P less than 0.05), the calcium/creatinine ratio (1.03 +/- 0.31 vs 0.43 +/- 0.07, P less than 0.01) and the hydroxyproline/creatinine ratio in the urine (69.9 +/- 12 vs 20.7 +/- 2.4, P less than 0.01). These parameters showed an increase when hypothyroid patients became euthyroid: serum calcium (2.36 +/- 0.03 vs 2.48 +/- 0.04 mmol/l, P less than 0.01), alkaline phosphatase (60 +/- 4 vs 84 +/- 8 U/l, P less than 0.05) and the hydroxyproline/creatinine ratio in the urine (15.9 +/- 4.3 vs 25.3 +/- 3.2, P less than 0.05). Changes in the calcium regulating hormones, parathyroid hormone, calcitonin and vitamin D metabolites, were not observed when hyperthyroid patients became euthyroid. When hypothyroid patients were treated a decrease in serum levels of 1.25-dihydroxyvitamin D (32.6 +/- 4.6 vs 17.9 +/- 2.5 ng/l, P less than 0.01) was observed. Serum growth hormone levels decreased when hypothyroid patients became euthyroid (4.3 +/- 0.5 vs 2.6 +/- 0.4 mU/l, P less than 0.01). The possible mechanisms of thyroid action on bone are discussed. The presented findings are in accordance with a direct effect of thyroid hormones on bone in thyrotoxicosis. An additional factor could be somatomedin, that might also be involved in changes in bone turnover in hyper- and hypothyroidism.

Acid Phosphatase

A rapid method for preparing undecalcified sections of bone for autoradiographic investigation with short-lived radionuclides.

To prepare sections of undecalcified bone suitable both for autoradiography with short-lived radionuclides such as 99m-technetium (t 1/2 = 6 hr) and for normal histology, rapid processing is necessary. By modifying the routine technique of embedding in plastic, sections can be obtained within 6 hours. The most important modification concerns the temperature used for the different steps in the process. The procedure has been used to localize 99mTc labeled methylene diphosphonate for skeletal scintigraphy.

Animals

Kinetics of intravenously administered heparin in normal humans.

Heparin of five commercially available brands was used to study the disappearance of heparin anticoagulant activity in normal humans. The drug was administered intravenously by bolus injection and by continuous infusion. Heparin anticoagulant activity was determined by two assays: a diluted activated partial thromboplastin time (APTT) and an assay based on inactivation of bovine factor Xa, using a clotting system. After a bolus injection, the data fitted neither single exponential nor zero-order clearance. In semilogarithmic plots, heparin anticoagulant activity disappeared according to a slightly convex curve almost always preceded by a rapid initial loss of heparin anticoagulant activity. This disappearance profile was observed with all heparin regardless of the brand or assay system. Heparin anticoagulant activity estimated by the APTT disappeared faster than heparin anticoagulant activity estimated by the anti-Xa activity in the first phase. As expected, higher anticoagulant levels with the anti-Xa assay than with the APTT were also found on continuous infusion in normals as well as in patients treated for deep vein thrombosis or pulmonary embolism. The experimental data suggested a model based on the combination of a saturable and a linear clearance mechanism. These experimental data provide reliable guidelines for adjustment of the dose of heparin in single patients.

Adult