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Biomedical subjects

B Gustavsson

Publications and source records attributed to B Gustavsson.

At least 73 records · Page 4Linked to original sources

Aberrant expression of receptors for platelet-derived growth factor in an anaplastic thyroid carcinoma cell line.

Receptors for platelet-derived growth factor (PDGF) have previously only been found on cells of mesenchymal and glial origin. This study shows PDGF receptors on an anaplastic thyroid carcinoma cell line, C 643, that was found to express thyroglobulin mRNA, confirming its origin from thyroid epithelium. Northern blot analysis of poly(A)+ RNA hybridized with a human PDGF B-type receptor cDNA probe revealed a 5.4-kilobase transcript in the C 643 cells. The existence of receptor protein on the cell surface was shown by immunofluorescence microscopy with a PDGF receptor monoclonal antibody. Binding experiments with 125I-labeled dimeric forms of PDGF indicated that the cells contain B-, but not A-, type PDGF receptors. The addition of PDGF to C 643 membranes in the presence of [32P]ATP induced phosphorylation of the receptor. A polyclonal PDGF B-type receptor peptide antiserum was used to immunoprecipitate a receptor protein from metabolically labeled C 643 cells; the receptor was found to be 5-10 kDa larger than that in normal human fibroblasts. Removal of N-linked carbohydrates using endoglycosidase H resulted in deglycosylated receptor proteins of similar size in C 643 cells and fibroblasts, indicating differences in glycosylation patterns of the two receptor proteins. The aberrant expression of receptors might be crucial in tumor development by conferring a selective growth advantage to the cancer cells.

Blotting, Northern↗

Effects of dopamine on the portal circulation after therapeutic hepatic artery ligation.

The effects of exogenous dopamine (2, 4 and 6 micrograms.kg-1.min-1 i.v.) on the portal circulation were studied in six patients following therapeutic hepatic artery ligation. Portal blood flow (PBF) was measured by the continuous thermodilution technique. Portal venous pressure (PVP, n = 3) was monitored through the thermodilution catheter to allow derivation of preportal vascular resistance (PVR). Blood samples were taken through the portal venous catheter for measurement of dopamine. A significant increase in PBF and a decrease in PVR were observed during graded i.v. dopamine infusion. Thus, PBF was 961 +/- 119 ml.min-1 during control conditions and increased to 1446 +/- 221 ml.min-1 during the dopamine infusion at 6 micrograms.kg-1.min-1. No significant changes in mean arterial pressure or PVP were observed during dopamine administration. The pharmacokinetics of dopamine did not differ from that previously reported in patients with an intact arterial supply. In conclusion, our data indicate that exogenous dopamine consistently increases PBF by preportal vasodilation, also in patients with a surgically restricted hepatic arterial blood supply.

Adult↗

Inhibition of thymidylate synthase after administration of doxifluridine in a transplantable colon carcinoma in the rat.

Parameters for inhibition of thymidylate synthase (TS) in a DMH-induced transplantable rat colon carcinoma were studied after intraperitoneal administration of bolus doxifluridine (5'-dFUR) 200 mg/kg. Levels of 5'-dFUR, 5-fluorouracil (5-FU), fluorouridinediphosphate (FUDP), and fluorouridinetriphosphate (FUTP) were determined by use of high-performance liquid chromatography. Micromethods for analysis of 5-fluoro-2'-deoxyuridylate (FdUMP) and TS were used to study the in vivo intracellular pharmacokinetics of TS inhibition. Peak values of 5'-dFUR and 5-FU were found at 30 min and showed exponential declines with values close to zero at 5 hr. Substantial levels of FUDP and FUTP were found throughout the 24 h observation time. Peak FdUMP levels were modest compared to those observed after equimolar administration of 5-FU, but FdUMP persisted in amounts well above available binding sites on TS for the 24 h observation time. Reduction of free TS enzyme to undetectable levels (less than 0.05 pmol/g) lasted for 4 h, and at 24 h, there was still almost 70% enzyme inhibition. The total amount of TS (TStot) defined as free [3H]FdUMP-titrable enzyme (TSf) plus TS bound to FdUMP in a ternary complex (TSb) increased as a result of 5'-dFUR bolus injection from 15 to 50 pmol/g during the 24 hr observation time. We conclude from these data that 5'-dFUR is converted to 5-FU and subsequently to FdUMP, and the results suggest that 5'-dFUR exerts its cytotoxic effects through inhibition of TS and incorporation into RNA.

Animals↗

Concurrent allopurinol and 5-fluorouracil: 5-fluoro-2'-deoxyuridylate formation and thymidylate synthase inhibition in rat colon carcinoma and in regenerating rat liver.

The formation of FdUMP and the inhibition of TS were studied in a subcutaneously growing transplantable rat colon carcinoma and in regenerating rat liver following bolus administration of 5-FU, with or without HPP pretreatment. In tumor, peak levels of FdUMP at 30 min following bolus 5-FU, 100 mg/kg, averaged 4931 +/- 587 pmol/g. Pretreatment with HPP, 50 mg/kg, 24 h and 1 h before 5-FU, reduced the peak FdUMP level to 2085 +/- 387 pmol/g. The inhibition of TS by 5-FU treatment was greater than 95% by 30 min, and after 48 h residual enzyme inhibition averaged 40%. No effect on TS inhibition by 5-FU treatment could be observed as a result of HPP pretreatment. The levels of TStot increased linearly after 5-FU treatment and doubled within 48 h. In regenerating rat liver, neither FdUMP levels nor TS inhibition, studied at 1 h after bolus 5-FU, were affected by HPP pretreatment.

Adenocarcinoma↗

Cardio-pulmonary elimination of 5-fluorouracil after bolus injection in the hepatic artery.

Theoretically, administration of 5-fluorouracil (5-FU) into the hepatic artery should improve the clinical response rate by high tumor cell extraction of the drug. However, previous studies in animals and man have also found a major extrahepatic elimination route for 5-FU. In the present study of 7 patients with primary and secondary liver cancer, we have found indications that a considerable elimination of 5-FU takes place in the cardio-pulmonary circuit. Thus, the mean AUC in the hepatic vein was 7185 mumol X min X l-1 and 3792 in a peripheral vein.

Adult↗

Primary gastrointestinal lymphoma incidence, clinical presentation, and surgical approach.

During a 5-year period, 15 cases of primary gastrointestinal lymphoma, corresponding to 14% of the non-Hodgkin's lymphomas, were diagnosed in a population of 200,000. Most patients had a short duration of symptoms--less than 3 months--and a clinical picture dominated by abdominal pain. All patients were laparotomized and six patients presented with an acute abdomen and were subjected to emergency operations. In seven cases, gastrointestinal malignancy was not suspected preoperatively. The patients were treated with a combination of surgery, cytostatic therapy, and/or radiotherapy. Cases with localized disease had a favorable prognosis, seven of nine patients being alive 31 to 70 months after diagnosis. A statistically significant difference in median survival was also noted between patients with lymphomas of low-grade and high-grade malignancy (70+ vs. 10.5 months).

Abdomen, Acute↗

Portal blood flow in man during graded positive end-expiratory pressure ventilation.

The cardiovascular response to graded PEEP ventilation (5-10 cm H20) was studied peroperatively in patients undergoing cholecystectomy (n = 8) or hepatic tumour surgery (n = 3). Portal blood flow was measured by the continuous thermodilution technique and cardiac output, in a sub-group of the patients, by impedance cardiography. A parallel reduction in cardiac output and portal blood flow was demonstrated in patients undergoing cholecystectomy as the result of the application of PEEP. Thus, ventilation with 5 cm H2O of PEEP elicited a 17% decrease in cardiac output and a 26% decrease in portal blood flow. During 10 cm H2O of PEEP cardiac output decreased by 22% and portal blood flow by 32%. However, there were no significant changes in preportal tissue perfusion pressure by the application of PEEP and preportal vascular resistance increased by 22% and 30%, respectively. This indicates that a vasoconstrictor response, elicited by PEEP, in the preportal tissue is the predominating mechanism for the observed decrease in portal blood flow. Systemic oxygen transport decreased by 214 ml/min during PEEP ventilation, but preportal tissue oxygen utilization was not significantly changed due to a concurrent increase (2.9%; p less than 0.05) in oxygen extraction.

Adolescent↗

Estimation of central venous pressure by measurement of proximal axillary venous pressure using a "half-way" catheter.

The pressure in the proximal axillary vein (AVP) was compared with central venous pressure (CVP) in eight patients during and after elective abdominal surgery. Both pressures were recorded from soft, elastic, polyurethane catheters inserted in the basilic or cephalic veins ("half-way" catheters), punctured at the fossa cubiti (AVP), and via the right jugular vein (CVP). The AVP and CVP were recorded simultaneously using hydrostatic, conventional disposable venous pressure measurement sets. The measurements were performed during intermittent positive pressure ventilation with positive end-expiratory pressure from 0 to 7.5 cmH2O (0-0.74 kPa), as well as during spontaneous breathing. During both controlled and spontaneous respiration, small mean differences (0.2-1.0 cmH2O) (0.02-0.1 kPa), and a highly significant (P less than 0.001) positive correlation between CVP- and AVP-values were found. An increase of 1 cmH2O (0.10 kPa) in the CVP was associated with an increment of practically identical order (0.99-1.04 cmH2O) (0.10-0.11 kPa) in the AVP. The results suggest that monitoring of the AVP by a basilic "half-way" catheter produces diagnostic information similar to that from the measurement of the CVP from subclavian, external or internal jugular, as well as "long-way" brachial catheter, with no risk of the major mechanical complications which accompany the use of the latter catheters.

Adult↗

Surface morphology of unused and used Hydromer-coated intravenous catheters.

Hydromer-coated polyurethane (Erythroflex) catheters, unused, or intravenously inserted for 2-20 days, were studied by scanning electron microscopy (SEM). Both unfixed and fixed (2% glutaraldehyde in phosphate buffer), and air-or critical-point dried (CPD) specimens were investigated. The catheter segments were sputter-coated with approx. 20 nm gold and studied at an accelerating voltage of 20 kV. The specimens were examined for surface depositions, thickness and structure of the Hydromer layers, and occurrence of adhering and embedded bacteria. The outer Hydromer layer showed, in the unused specimens, scratches and fissures, as well as adhering foreign bodies. In used specimens, the layer was swollen, with cracks (like "dried earth"), and, occasionally, amorphous substances and coccoid bacteria were seen adhering. Damage to the layer, or even its total disappearance was also noted in some specimens. The inner (luminal) Hydromer layer was, in unused specimens, clean and slightly wavy. In used catheters, it was thicker, possibly swollen, with small, isolated or agglomerated protrusions, like a "lunar landscape". Adhering platelets and amorphous substances were also occasionally seen. The results suggest that the Hydromer is a fragile material in both its dry and wet forms. Thus, the Hydromer-coated catheters should neither be stored in flexible packs, nor inserted by the Seldinger technique. The findings do not support the belief that the Hydromer-coating can prevent either thrombus formation, or intraluminal occlusion of the in-situ catheters.

Catheters, Indwelling↗

"Half-way" venous catheters. II. Anatomoradiological basis.

In order to develop a "half-way" venous catheter for clinical use, anthropometric (n = 200), radiographic (n = 101), and phlebographic (n = 44) investigations were undertaken to determine the lengths, diameters, and morphology of the basilic and cephalic veins from fossa cubiti to the lateral edge of the first rib. The lengths of basilic and cephalic veins varied from 25 to 45 cm, exceeding 40 cm in approximately 5% of cases. Catheter lengths to be inserted were correlated ("r" = 0.6-0.7) with body heights, accurately estimated by 1/5 of the body height (cm) plus 2 cm for the basilic vein, and 4 cm for the cephalic vein. The cephalic veins have small proximal end diameters (mean = 6 mm), and present terminal arches of 2-3 cm. These are connected by a rich anastomotic network to the superficial cervical veins. The basilico-axillary courses are regular with gradually increasing diameters (mean = 16 mm), but in some observations, with the arms maximally abducted, the axillary veins presented accentuated folds. With these considerations, we recommend the insertion of the "half-way" catheters by basilic approach with the patient's arm in 90 degree abduction. The axillosubclavian length (mean = 18.5 cm) ensures wide limits for accurate placement of the "half-way" catheter tips when a basilic approach is used. Further, their large diameters (16-19 mm) make flotation of the soft catheters probable.

Adolescent↗

"Half-way" venous catheters. III. Tip displacements with movements of the upper extremity.

Directions and sizes of displacement of "half-way" catheter tips with movements of the upper extremities were investigated in thoracic radiographs in 21 patients (10 women and 11 men), 28-88 years old. Ten catheters were inserted by basilic, and 11 by cephalic veins punctured at the fossa cubiti. Catheter tip positions were related to the lateral edge of the first rib. The tip position with the patient's arm in 90 degree abduction was considered as the reference point. Displacements caused by maximal flexion of the forearm, maximal adduction of the upper extremity, and maximal elevation of the brachium plus maximal flexion of the forearm were studied. With all movements and venous approaches there were significantly more medial than lateral displacements (P less than 0.001). The medial displacements varied from 0.2-5.0 cm, and the lateral ones from 0.5-1.8 cm. Location of the "half-way" catheter tips in the proximal axillary vein, at the lateral edge of the first rib, is recommended. As found previously, this may be obtained by inserting a catheter length representing 1/5 of the patient's height. Such a location inhibits harbouring of the "half-way" catheter tips in the jugular veins with movement in the upper extremities. Furthermore, estimation of central venous pressures by axillary venous pressures is not affected.

Adult↗

"Half-way" venous catheters. IV. Clinical experience and thrombogenicity.

"Half-way", Secalon-Seldy, soft venous catheters, 40 cm long, were inserted by basilic (n = 90) and cephalic (n = 31) veins at the fossa cubiti in 121 patients (71 men and 50 women) aged between 19 and 88 years whose heights varied from 152-197 cm. The inserted catheter lengths approximated 1/5 of the patient's height. Sixty-five per cent of 106 radiologically investigated catheter tips were located proximally in the axillary veins, and 34% distally in the subclavian veins. The duration of catheterization varied from 1 to 44 (mean 9 +/- 7) days (means +/- 1 s.d.). Perfect function was recorded in 93 of 121 catheters. No serious, but some minor complications were registered such as temporary interruption of infusion flow with movements of the arm (n = 12), partial or total catheter occlusion (n = 16), leakage of the infusate at the insertion site (n = 1), and pain along the vein during infusion (n = 2). Five patients (4%) developed thrombophlebitis 2-.10 days after insertion. Pull out phlebographies at catheter withdrawal (4-35 days after insertion) were performed in 36 patients. Radiological thrombi were small and similar to those recorded in another 53 phlebographies of "long-way" brachial catheters of similar stiffness. Neither local infection nor episodes of sepsis were registered over a period of 1,081 catheter days. "Half-way" catheters proved able to take over all the functions of both peripheral and central venous catheters, lacking the frequent complications (phlebitis and infection) of the former, and the serious mechanical complications (pneumothorax, vein perforations, and injuries of the ductus thoracicus, nerves, arteries, and heart) of the latter.

Adult↗

Intravesical high dose 5-fluorouracil instillations combined with allopurinol--a therapeutic alternative in the treatment of multiple bladder tumors.

Chemical cystitis and systemic toxic effects limit the therapeutic use of intravesical cytotoxic agents against bladder tumors. In our series 1,000 mg. 5-fluorouracil could be instilled 2 hours daily, 5 days per week for 5 weeks if 100 mg. allopurinol were given 3 times daily simultaneously. After 6 weeks all patients were macroscopically free of tumors. Another instillation was performed because of recurrences within 6 months in 3 patients. This preliminary report of 5 patients with multiple superficial transitional cell bladder tumors shows that a combined treatment of high dose 5-fluorouracil instillation and simultaneous oral allopurinol will abolish temporarily all tumor tissue without signs of general absorption or chemical cystitis. The observation time is too short to predict definitive cure.

Allopurinol↗

Material thrombogenicity in central venous catheterization III. A comparison between soft polyvinylchloride and soft polyurethane elastomer, long, antebrachial catheters.

Soft venous catheters, 36 made of polyurethane (PU) and 37 made of polyvinylchloride (PVC), were inserted in 73 patients via basilic and cephalic veins punctured at the cubital fossa, and compared regarding their thrombogenicity. The mean duration of catheterization was 12.5 days. Two patients with PU- and six patients with PVC-catheters developed clinical thrombophlebitis 4-36 days after insertion. The radiological thrombi were rather small with both PU- and PVC-catheters in both peripheral and central veins with no significant difference between the catheters. Also, the incidence of thrombosis and the rate of catheter occlusions were similar. The surface topography of the PVC-catheters was relatively smoother, but less uniform than that of the PU-catheters. Platelet adhesion in vitro to the catheter surfaces, expressed as ATP-concentration in relation to catheter area after contact with human blood, was relatively low with both catheters. The results suggest that soft PU- and PVC-catheters have a similar thrombogenicity.

Adolescent↗

Effects of hydralazine on liver blood flow in normovolemic dogs.

The effects on liver blood flow caused by hydralazine were studied in 14 dogs. Hepatic artery and femoral artery blood flow were estimated with an electromagnetic flow meter. Total hepatic blood flow (THBF) was measured by 133Xenon clearance. Cardiac output (CO) was determined by intravenous injection of Cardio-Green. After 0.2 mg/kg of hydralazine total hepatic blood flow increased by 57%. The hepatic artery blood flow increased by 82% and portal blood flow by 58%. Cardiac output increased by about 50%, while total peripheral vascular resistance decreased. The results further suggest that hydralazine increases portal blood flow. Also the ratio THBF : CO increased. These findings together indicate a hydralazine-induced redistribution of cardiac output with a relatively increased proportion provided to the liver.

Animals↗

Dynamics of thrombophlebitis in central venous catheterization via basilic and cephalic veins.

The incidence distribution of thrombophlebitis after central catheterization via basilic and cephalic veins was investigated, using 227 catheters made of various plain or heparin-coated materials and with differing stiffness and surface structures. The platelet-adhesion stimulating properties were measured in vitro. Thrombophlebitis showed similar incidence patterns with all catheter types. The maximum incidence of venous reaction was found one to ten days after catheter insertion (central tendency 3-8 days with a peak at 5 days). After ten days the risk of thrombophlebitis fell significantly. The results supported the view that central venous catheters inserted via basilic or cephalic veins should not be withdrawn or exchanged as prophylaxis against thrombophlebitis, at any rate when long-term catheterization is intended. For conclusive comparisons between catheter materials regarding induction of clinically apparent thrombophlebitis, all the patients in the trial should be catheterized for ten days or more, unless symptoms of venous reaction arise earlier.

Adolescent↗