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Biomedical subjects

G Willems

Publications and source records attributed to G Willems.

At least 91 records · Page 5Linked to original sources

Quantitative study of the growth of experimental hepatic tumors in rats by using magnetic resonance imaging.

Precise estimation of the volume and growth rate of hepatic metastases would represent an important step forward not only in clinical oncology but also for the evaluation of experimental treatments in animal models. In the present study, an original method of volumetry of hepatic metastatic tumors in vivo has been tested in rats using magnetic resonance imaging (MRI). Three different hepatic tumor models mimicking liver metastases were established in syngeneic BDIX rats by injection of DHD/K12 rat colon cancer cells either directly under the liver capsule or via the portal system. The liver tumor volumes were estimated in vivo by using MR imaging of the liver and summing the individual tumor volumes in the sequential MR liver sections. The values of the tumor volumes measured by MRI were compared with those determined by a classical method of water displacement in vitro after killing the animals and excising the tumors. At 3 weeks after tumor implantation, liver tumors as small as 1 mm in diameter could be detected by MRI. The difference between the tumor volumes estimated by MRI in vivo and those measured by water displacement in vitro was 9% for single liver tumors and 16% for multiple liver tumors. Close correlation between the values of the tumor volumes measured by MRI and those determined by water displacement was observed in solitary liver tumors (r = 0.985, p less than 0.01) as well as in multiple liver tumors (r = 0.985, p less than 0.01), indicating the high accuracy of MRI volumetry for liver tumors. Estimation of the liver tumor volumes by MRI in the same animals at successive time intervals made it possible to construct tumor growth curves and to calculate tumor growth parameters. These data suggest that MRI volumetry represents an effective means of evaluating the efficacy of experimental treatments in small animals and may have potentially important applications in clinical patients.

Animals↗

In vitro vibrational wear under small displacements of dental materials opposed to annealed chromium-steel counterbodies.

In vitro vibrational wear tests were performed on 17 composites and one amalgam with human enamel as a reference. The specimens were fixed on a computer-controlled X-Y translation table that generated an oscillatory movement under small displacements. The dental material specimens were in permanent contact with an annealed chromium-steel counterbody. The tests were performed in ambient air of normal humidity at room temperature under non-lubricated sliding conditions. The friction between the counterbody and each of the various materials was measured on-line. After completion of the tests, the wear volumes were determined by contactless profilometry, and the wear pattern was studied with SEM. The simple vibrational test used in this study allowed a fast classification of different dental materials in terms of the relative wear on either the specimen or the counterbody material. The ratio of the wear volume of the counterbody versus the wear volume of the dental material specimen was used to accurately classify the materials according to their in vitro wear behavior, especially when this ratio was related to the total wear volume of the dental material specimen and the counterbody. From an analysis of the wear behavior of the both contacting materials, it became obvious that neither the wear of the dental materials nor of the chromium-steel counterbody appears to correlate with either the inorganic filler hardness, the intrinsic surface roughness, the surface hardness or the Young's modulus of the dental materials.

Chromium Alloys↗

A classification of dental composites according to their morphological and mechanical characteristics.

The on-going search for a biologically acceptable restorative material has brought a confusing variety of composites on the dental market. In the present study, commercially available composites are categorized as a function of their mean particle size, filler distribution, filler content, Young's modulus, surface roughness, compressive strength, surface hardness, and filler morphology. Out of this information, it can be concluded that the materials of choice for restoring posterior cavities at present are the Ultrafine Compact-Filled Composites because their intrinsic surface roughness, Young's modulus and, indirectly, their filler content, compressive strength, and surface hardness are comparable to the same properties of enamel and dentin. The Ultrafine Midway-Filled Composites seem to be very satisfactory materials for anterior use.

Composite Resins↗

Vitamin status in patients with acute pancreatitis.

The serum levels of 6 vitamins were prospectively evaluated in 20 patients with acute biliary pancreatitis and in 20 patients with acute alcoholic pancreatitis. Twenty healthy subjects acted as controls. There were no statistically significant differences in the levels of vitamin B12 and D among the groups. Patients with alcoholic pancreatitis had significantly lower levels of vitamins A, E (p < 0.01) and C (p < 0.001) than those of the control group. Plasma levels of vitamin K were decreased or undetectable in 6 patients with biliary and 3 with alcoholic pancreatitis. The pathophysiological and clinical implications of this abnormal vitamin status in patients with acute pancreatitis are unknown. Nevertheless, multi-vitamin supplementation seems justified, especially in patients affected by alcoholic pancreatitis. Vitamin K should be administered in both types of pancreatitis when blood coagulation tests are disturbed.

Journal Article↗

Marginal adaptation of four tooth-coloured inlay systems in vivo.

This study investigates the margin quality of four different tooth-coloured inlay systems using computer-aided quantitative margin analysis under scanning electron microscopy. Three types of restorations involved chairside procedures using a commercial CAD-CAM apparatus: one type of inlay restoration was milled from preformed glass ceramic blocks, the other two inlay types were milled from preformed porcelain blocks. The fourth system was based on an experimental indirect composite inlay system. Each inlay type was luted with its respective dual-curing luting composite, which was supplied with the system. After 6 months of clinical service, all four systems revealed a significant percentage of submargination indicating occlusal wear of the luting composite. The porcelain inlays and the composite inlays luted with their respective experimental luting composite showed the best marginal adaptation. Luted glass ceramic inlays, in particular, suffered from a significantly higher percentage of inlay margin fractures (9 per cent) and marginal openings (4 per cent) than the other systems. A possible explanation is that the glass ceramic subsurface structure at the inlay-lute interface was weakened by etching with ammonium bifluoride.

Acid Etching, Dental↗

Marginal accuracy of CAD/CAM inlays made with the original and the updated software.

The software driving the Cerec CAD/CAM system has recently been updated. In this study, the marginal accuracy of computer-machined porcelain inlays was determined using the original and the updated software. Two types of MOD cavities in Frasaco resin teeth were prepared with either sharp or rounded box corners. The distance of the occlusal and proximal marginal interface was determined using a measuring microscope. The mean occlusal interfacial distance was 52 microns for both programs. Only the box corners showed a significantly larger space, of which the mean value was approximately 200 microns. The updated version improved the marginal accuracy at the box corners. Further reduction of the interfacial distance was accomplished by rounding the sharp box corners.

Bicuspid↗

Unilateral vagal denervation suppresses omeprazole-induced trophic effects on the denervated side of the rat stomach.

In several experimental animals treatment with large doses of the proton pump inhibitor omeprazole leads to hypergastrinemia and with time to trophic effects in the acid-producing part of the stomach, most notably an increased density of the histamine-producing enterochromaffin-like (ECL) cells. The trophic effects are thought to reflect the increase in circulating gastrin. In the present study unilateral vagal denervation in the rat partly suppressed the tropic effects seen in the denervated side of the stomach but not those in the intact side after treatment with omeprazole for 10 weeks. Unilateral vagal denervation significantly reduced the proliferative stimulus of omeprazole on the ECL cells in the denervated part of the stomach. Thus, an intact vagal innervation appears to be essential for the capacity of the oxyntic mucosa, including the ECL cells, to respond to elevations in serum gastrin. We suggest that gastrin and the vagus interact to maintain trophic control of the oxyntic glands.

Animals↗

Reversibility of the cell kinetic changes induced by omeprazole in the rat oxyntic mucosa. An autoradiographic study using tritiated thymidine.

Both oxyntic mucosal progenitor cells and enterochromaffin-like (ECL) cells are under the trophic control of gastrin. We studied the effect of discontinuing omeprazole-induced hypergastrinemia on cell proliferation and ECL cell function in the rat oxyntic mucosa. All rats had hypergastrinemia after 16 days' omeprazole administration, and the proliferation rate of both progenitor and ECL cells was increased, whereas it was decreased 5 days after withdrawal of omeprazole. Circulating gastrin had normalized by then. The proliferative activity of the progenitor cells returned to normal within 10 days, whereas that of the ECL cells remained suppressed for at least 20 days. The histidine decarboxylase activity of the ECL cells changed in parallel with their proliferative activity. These data suggest either a down-regulation of membrane receptors or the involvement of still unknown inhibitors of mitotic activity and ECL cell function in the oxyntic mucosa.

Animals↗

Somatostatin analogue RC-160 inhibits the growth of transplanted colon cancer in rats.

The effect of somatostatin analogue RC-160 on the growth of DHD/K12 rat colon cancer has been investigated in vivo as well as in vitro. Twenty syngeneic BDIX rats with s.c. implanted tumors were divided randomly into 2 groups. The rats from each group received a daily s.c. injection of either RC-160 (100 micrograms/kg/day) or injection vehicle as control for 37 days starting from the day of tumor inoculation. Tumor volumes were measured every 3-4 days. At the end of the treatment, the mean tumor volume was 504.5 +/- 97.0 mm3 in the control group and 177.8 +/- 60.5 mm3 in the RC-160 treated group (p less than 0.01). The tumor volume doubling time was calculated to be 11 days in the control group and 13.5 days in the RC-160 group, respectively. The tumor growth delay time was 18 days. Using bromodeoxyuridine labelling in vivo, the mean labelling index in the tumors was decreased by 35% (p less than 0.01) after RC-160 treatment. Total protein and total DNA contents in the tumors were decreased by 70.1% (p less than 0.05) and 68.7% (p less than 0.05), respectively. The data indicate that somatostatin analogue RC-160 inhibits the growth of DHD/K12 colon cancer in vivo. In 2 studies in vitro, DHD/K12 cells were cultured for 72 hr with RC-160 and natural somatostatin-14 (S-S-14) at concentrations ranging from 62.5 ng/ml to 2,000 ng/ml. Tumor-cell growth was measured spectrophotometrically by the crystal violet staining assay. No direct effect on tumor cell growth in vitro was observed with either RC-160 or S-S-14, possibly because of the loss of somatostatin receptors in previous passages of the DHD/K12 cell line.

Adenocarcinoma↗

Radiopacity of composites compared with human enamel and dentine.

A 99.5 per cent pure aluminium step-wedge served as reference for evaluating the radiopacity of 55 anterior and posterior composites. The radiopacity of all materials evaluated was compared with the radiopacity of human enamel and human dentine of equivalent sample thickness. Seventeen composites exhibited a radiopacity significantly greater than that of enamel. Some composites intended for posterior use lack the radiopacity required for posterior composite restorations.

Analysis of Variance↗

The surface roughness of enamel-to-enamel contact areas compared with the intrinsic roughness of dental resin composites.

The purpose of this study was to determine the surface roughness of enamel-to-enamel contact areas in order to provide a standard for comparison with surface characteristics of commercially available composite restorative materials. In addition, the inherent surface roughness of resin composites was evaluated profilometrically after a toothbrush abrasion procedure. A one-sided t-test analysis was performed to outline significant differences between the surface roughness value of enamel facets and that of the respective composite samples. A surface roughness of 0.64 +/- 0.25 micron (mean +/- S.D.) was found for the enamel-to-enamel contact areas.

Bicuspid↗

Treatment of high-output gastric fistulas with omeprazole.

Two patients with high-output gastrocutaneous fistulas were treated with total parenteral nutrition and gastric antisecretory drugs. IV administration of omeprazole decreased acid output in one patient in a rapid and significant way, resulting in the spontaneous healing of the fistula after eight days of treatment. In the second patient, omeprazole caused a marked reduction in the acidity of the fluid in the fistula, which also closed without surgical operation. The long-standing decrease in acid output induced by intravenous omeprazole may be very useful for promoting spontaneous closure of high-output gastrocutaneous fistula.

Gastric Fistula↗

Hepatic artery ligation with and without portal infusion of 5-FU. A randomized study in patients with unresectable liver metastases from colorectal carcinoma. The E.O.R.T.C. Gastrointestinal Cancer Cooperative Group (G.I. Group).

The aim of this multicentric prospective randomized clinical trial was to study the efficacy of hepatic artery ligation (HAL) with and without portal infusion (PI) of 5-FU in patients with liver metastasis of colorectal origin. Seventy-four patients were randomized. Sixty-seven were fully evaluable. Thirty-five patients were eligible in the HAL + PI of 5-FU group and 32 in the HAL alone group. The 5-FU infusion had to be discontinued for technical reasons in 13 patients. Complications of HAL were relatively high, including four hepatic failures (WHO grading greater than 2). Side effects of chemotherapy were limited. Five patients out of 30 had a partial response (WHO criteria) and one patient had a complete response in the group treated by HAL and PI of 5-FU. Only one patient had a partial response in the HAL alone group. Median survival for both groups was 12 months. Median time to progression for both groups was 6 months. This study did not show any advantage of delivery using the portal route in addition to hepatic artery ligation in terms of progression nor in survival of patients.

Adenocarcinoma↗

Continuous flow and the prothrombinase-catalyzed activation of prothrombin.

The activation of prothrombin by prothrombinase was investigated in a continuous flow system at 25 degrees C. A glass capillary, containing a continuous phospholipid bilayer attached to the interior surface, was first perfused with factor Va. The factor Va bound to the phospholipid surface functioned as sites for the formation of prothrombinase, when subsequently a factor Xa and prothrombin containing solution was perfused. Under the conditions used, steady-state rates of prothrombin activation were attained after 4 to 15 min. The rates of prothrombinase formation increased with increasing factor Xa concentrations and flow rates, which is compatible with the assembly of prothrombinase being dependent on the flux of factor Xa to the phospholipid-bound factor Va. As long as factor Xa and prothrombin were present in the fluid phase the assembly of prothrombinase was apparently irreversible; during at least 20 min no loss of activity occurred. The steady-state rate of prothrombin activation was dependent on the surface concentration of prothrombinase, at 1.0 microM prothrombin and a shear rate of 82 s-1 the average rate was 870 mol thrombin/min per mol prothrombinase. In contrast to test tube experiments it was observed that in this flow system, the formation of alpha-thrombin is favoured above the formation of meizothrombin (des fragment 1).

Adsorption↗

Heparin-stimulated inhibition of factor IXa generation and factor IXa neutralization in plasma.

Generation and inhibition of activated factor IXa was studied in factor XIa-activated plasma containing 4 mmol/L free calcium ions and 20 mumol/L phospholipid (25 mol% phosphatidylserine/75 mol% phosphatidylcholine). Interference of other (activated) clotting factors with the factor IXa activity measurements could be avoided by using a highly specific and sensitive bioassay. Factor IXa generation curves were analyzed according to a model that assumed Michaelis-Menten kinetics of factor XIa-catalyzed factor IXa formation and pseudo first order kinetics of inhibition of factor XIa and factor IXa. In the absence of heparin, factor IXa activity in plasma reached final levels that were found to increase with increasing amounts of factor XIa used to activate the plasma. When the model was fitted to this set of factor IXa generation curves, the analysis yielded a rate constant of inhibition of factor XIa of 0.7 +/- 0.1 min-1 and a kcat/Km ratio of 0.29 +/- 0.01 (nmol/L)-1 min-1. No neutralization of factor IXa activity was observed (the estimated rate constant of inhibition of factor IXa was 0). Thus, in the absence of heparin, the final level of factor IXa in plasma is only dependent on the initial factor XIa concentration. While neutralization of in situ generated factor IXa in normal plasma was negligible, unfractionated heparin dramatically enhanced the rate of inactivation of factor IXa (apparent second order rate constant of inhibition of 5.2 min-1/per microgram heparin/mL). The synthetic pentasaccharide heparin, the smallest heparin chain capable of binding antithrombin III, stimulated the inhibition of in situ generated factor IXa, but sevenfold less than unfractionated heparin (k = 0.76 min-1 per microgram pentasaccharide/mL). We found that free calcium ions were absolutely required to observe an unfractionated heparin and pentasaccharide-stimulated neutralization of factor IXa activity. Factor XIa inhibition (psuedo first order rate constant of 0.7 min-1) was not affected by unfractionated heparin or pentasaccharide in the range of heparin concentrations studied.

Activation Analysis↗

Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome.

In patients with multiple endocrine neoplasia type 1 (MEN-1), gastrinomas are common and thought to occur predominantly in the pancreas. We describe eight patients with MEN-1 and hypergastrinemia (seven with the Zollinger-Ellison syndrome) in whom we searched for neuroendocrine tumors in the pancreas and duodenum. Tumors were found in the proximal duodenum in all eight patients: solitary tumors (diameter, 6 to 20 mm) in three patients and multiple microtumors (diameter, 2 to 6 mm) in the other five. Paraduodenal lymph-node metastases were detected in four patients. Immunocytochemical analysis revealed the presence of gastrin in all the duodenal tumors and in their lymph-node metastases. In contrast, no immunoreactivity for gastrin was present in the endocrine tumors found in the seven pancreatic specimens available for study, except for one tumor with scattered gastrin-positive cells. In four of the six patients whose duodenal gastrinomas were removed, serum gastrin levels returned to normal; in the other two patients gastrin concentrations decreased toward normal. We conclude that in patients with MEN-1 and the Zollinger-Ellison syndrome, gastrinomas occur in the duodenum, but the tumors may be so small that they escape detection.

Adult↗