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Biomedical subjects

M Aas

Publications and source records attributed to M Aas.

At least 37 records · Page 2Linked to original sources

Renal function related to different treatment modalities for malignant germ cell tumours.

The renal function was evaluated with 131I-Hippuran clearance in 171 patients with malignant germ cell tumours. Assessments were performed before treatment and at three fixed times afterwards within 5 years. The patients were treated with surgery only (20 patients), infra-diaphragmatic radiotherapy only (median midplane dose 36 Gy) (48 patients), cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus surgery (64 patients), cisplatin-based chemotherapy (total cisplatin dose greater than 850 mg) with or without surgery (23 patients) or cisplatin-based chemotherapy (total cisplatin dose 500-850 mg) plus infra-diaphragmatic radiotherapy (16 patients). No renal impairment was observed for patients treated with surgery only. In patients who received radiotherapy no change of the renal function occurred during the first year post-treatment. Three to five years after treatment discontinuation a statistically significant reduction within the normal range was observed in patients who were greater than 40 years at the time of irradiation. Cisplatin-based chemotherapy led to a statistically significant irreversible renal impairment for all the three groups. The greatest reduction was seen in patients who received the highest total cisplatin dose or who were treated with irradiation in addition to chemotherapy. The clinical significance of the observed nephrotoxicity is still unknown.

Adolescent↗

Early liver metastases in patients with medullary carcinoma of the thyroid gland.

In 13 patients who had been thyroidectomized for medullary carcinoma (MCT), basal and pentagastrin-stimulated immunoreactive calcitonin (iCT) concentrations were measured in a peripheral vein and concomitantly in hepatic veins as well as in the superior and inferior caval veins. The basal concentrations of iCT in serum from the antecubital vein ranged from normal values (less than 0.50 micrograms/1) to grossly elevated (greater than 100 micrograms/1). Intravenous pentagastrin injections (0.5 micrograms/kg) stimulated transiently calcitonin secretion in all patients and peak concentrations occurred in peripheral venous blood and in the inferior caval vein after 3 to 5 minutes. In all patients peak iCT values in the hepatic vein occurred at 1 to 2 minutes and were much higher than in samples taken from other veins. Only three patients showed metastases to liver as judged by conventional clinical and laboratory examinations. Two patients with nonthyroid, malignant disease did not show an increase in serum iCT concentration of hepatic veins. The authors conclude that MCT may spread early to the liver. The presence of liver metastases is an important prognostic factor in patient evaluation and can be demonstrated by measuring iCT in hepatic veins before and during pentagastrin stimulation.

Adult↗

High-dose cis-platinum combination chemotherapy in advanced nonseminomatous malignant germ cell tumours with emphasis on nephrotoxicity.

High-dose cis-platinum treatment (180 mg/m2 per cycle) in combination with VP16 and bleomycin was given to 14 patients with highly advanced nonseminomatous malignant germ cell tumours (total: 31 cycles). Cis-platinum was administered in infusions of 0.9% NaCl given daily for 3 days with 3-week intervals. An intensive hydration regimen (71 NaCl/day) provided a urinary output of at least 1000 ml/4 h. The response and side effects were evaluated. Ultimately 11 of 12 patients evaluable for treatment effect were rendered tumour-free and are alive with NED. All 14 patients were evaluable for toxicity; 2 developed life-threatening lung edema during the initial prehydration period and did not continue the high-dose cis-platinum schedule. After one to four cycles of high-dose cis-platinum treatment the 131I-Hippuran clearance was reduced by 28%. Decreased kidney function evaluated by 131I-Hippuran clearance was the reason for discontinuation of treatment in 5 patients. Patients with ureteric obstruction represented a high-risk group for reduction of kidney function. High-dose cis-platinum therapy is an intensive treatment demanding a high level of investment of resources, which has promising response rates in patients with highly advanced malignant germ cell tumours. Short-term clinically significant reduction of the kidney function can be avoided by intensive hydration of the patient.

Adolescent↗

Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5'-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month.

Eighteen patients with advanced solid cancer were treated with daily 5'-dFUrd infusions given over 1 h on days 1-5 of a 4-week cycle. Nine patients received 3 g/m2 5'-dFUrd daily and another nine patients 5 g/m2. One patient on 5 g/m2 5'-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1-2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m2 5'-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m2 group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5'-dFUrd and its metabolites 5-FU and 5'-dFUH2 have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5'-dFUrd at the end of the infusion approximated 500 mumol/l and 1000 mumol/l for the 3 g/m2 and 5 g/m2 group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5'-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2-3 compared with the direct injection of 5-FU. Monthly infusion of 5'-dFUrd 5 mg/m2 per day on days 1-5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5'-dFUrd 3 g/m2 per day on days 1-5 were well tolerated.

Adenocarcinoma↗

Lymphatic drainage from subcutaneous tissue in the foot and leg in the sitting human.

To determine how fast lymph is drained from the foot in the sitting, completely relaxed position, we injected 99mTc-labelled human serum albumin subcutaneously between the first and second toe of both feet in three subjects sitting with legs down. Radioactivity appeared in the calf within the first 30 s, in the thigh within 1 min and in the blood between 2 and 5 min after injection. A scintigram of the calves showed distinct strands of activity. Radioactivity was found in the inguinal lymph nodes and in no other lymph nodes. The radioactivity in the segments of the calf showed rhythmic variations. EMGs showed minimal muscular activity during the examination. We conclude that interstitial fluid is drained by way of the lymphatics against gravity and most probably as a result of the intrinsic contractions of the lymphatics.

Adult↗

Lymph drainage from the vulva.

Fifty-four patients with cervical cancer stage Ib were injected preoperatively with 99mTc-colloid in different areas of the vulva and three controls in the axilla. The radioactivity in the groins and the pelvis was measured with a scintillation camera and in the removed pelvic lymph nodes with a well counter. A low activity could be measured in the removed pelvic nodes of the controls indicating the radioactivity which had reached the pelvic nodes via the bloodstream. Clitoris and perineum had a bilateral lymph flow. In all the other patients the vast majority of the radioactivity was found in the ipsilateral lymph nodes. A significant, but small amount of activity was recorded in the contralateral nodes in 67% of the patients and in all patients injected in the anterior part of the labium minus. The medial external iliac lymph chain had an uptake of 73% of the total activity measured in the removed pelvic nodes. Only in 13% of the patients was the activity higher in the lateral than in the medial external iliac chain. Direct lymphatic pathway from the clitoris to the pelvic lymph nodes was not found. Anastomoses exist probably in 13 out of 42 patients between the presacral and/or common iliac nodes on both sides.

Adult↗

Pelvic lymphoscintigraphy with 99mTc-colloid in lymph node metastases.

Twenty-four patients with cervical cancer stage Ib were examined by pelvic lymphoscintigraphy with 99mTc-colloid prior to operation. Four of the patients had histologically verified lymph node metastases. No difference in the lymphoscintigrams was found between the patients with pelvic metastases and those without. The removed involved lymph nodes did not contain less radioactive colloid than the histologically normal nodes. In two involved lymph nodes the uptake of radioactivity was far above any of the noninvolved nodes.

Adult↗

Serum ferritin and bone marrow haemosiderin in patients with malignancies and in healthy controls.

Serum ferritin has been analysed and bone marrow haemosiderin evaluated in 306 patients with malignancies, mostly lymphomas, and in 46 healthy controls. Also haemoglobin, serum iron, transferrin and liver enzymes were analysed simultaneously. 60% of the patients had serum ferritin above normal values and 20% had values above 1000 micrograms/l. There was a good correlation between serum ferritin and bone marrow iron both in the patients and in the controls, r = 0.67 and r = 0.77, respectively. There was a negative correlation between serum ferritin and haemoglobin concentration in the patients and a positive correlation in the controls. In patients with Hodgkin's disease serum ferritin was related to the stage of the disease.

Bone Marrow↗

A mathematical model for the liver uptake and excretion of 99mTc-diethyl IDA.

A mathematical model for the liver uptake and excretion of 99mTc-diethyl IDA has been formulated and data from four patient studies have been fitted to the model, resulting in values for the model parameters. The model includes compartments for blood, extravascular space, hepatocytes, bile ducts, and kidneys. The parameter values obtained reflect a rapid exchange between blood and extravascular space and a significant reverse flow of the radiopharmaceutical from the liver to the blood.

Adult↗

Time of exchange of 131I-labeled albumin between plasma and peripheral lymph in man.

The passage from blood to peripheral lymph of 131I-labeled human serum albumin has been studied in 6 male patients (30-70 years) with malignancies without metastases. On the first day the concentration of radio-labeled albumin in the blood was kept almost constant by repeated i.v. injections. Lymph was collected continuously from a cannulated subcutaneous lymph vessel on the leg. Two hours after the first i.v. injection of radiolabeled albumin the lymph contained significant amounts of radioactivity in all patients. Equilibrium between radioactivity in blood and lymph was reached after 26 hrs. This indicates a long "wash out time" of unlabeled protein in the interstitial tissue from where lymph has been sampled.

Adult↗

Clinical results with 131I-toluidine blue and triple radionuclide subtraction for preoperative localization of enlarged parathyroid glands.

Clinical results from the application of a triple radionuclide subtraction study for preoperative localization of enlarged parathyroid glands are presented in this paper. A scintillation camera image was recorded after i.v. injection of 131I-toluidine blue. The contributions to this image from activity in the thyroid gland and in blood were determined after recording of additional images (obtained after injection of 99mTcO4- and 113mIn, respectively) using an iterative computer algorithm that also provides an estimate for a uniform background. Subtraction of these contributions gives an image that may be interpreted as an image of the selective accumulation of 131I-toluidine blue in the parathyroids. One or more enlarged glands were correctly localized in 17 of 21 cases, but in four cases there were only false positives. In ten cases the correctly localized glands weighed 900 mg or less.

Adult↗

Association between HLA and red cell antigens. VII. Survival studies of incompatible red blood cells in a patient with HLA-associated haemagglutinins.

Serum from a multitransfused patient with bladder papilloma was examined. The serum contained anti-Kell as well as polyspecific, cytotoxic HLA antibodies and HLA-associated haemagglutinins. The HLA haemagglutinins were demonstrated by the Auto Analyzer method and reacted predominantly with red blood cells (RBC) from HLA-A28-positive individuals, and were distinctly weaker with all other test cells. Survival studies with 51Cr-RBC from an HLA-A28-positive, Kell-negative donor with strong A28 RBC reactivity were performed. A small component of the RBC showed clearly reduced survival time, while the main component showed nearly normal survival.

ABO Blood-Group System↗

A computer algorithm for triple radionuclide subtraction studies applied for preoperative localization of enlarged parathyroid glands.

This paper presents a computer algorithm for triple radionuclide subtraction studies and its application to preoperative localization of enlarged parathyroid glands. In the clinical examination procedure, 131I-toluidine blue was used as the principal radionuclide, 99mTcO4 and 113mIn were used to obtain additional images of the thyroid and the blood distribution respectively. A scintillation camera with a pinhole collimator and connected to a digital data aquisition system was used to record the images. Subtraction of uniform background, thyroid and blood contributions to the principal image is done automatically in the computer program. The results from a clinical study is used to illustrate the method.

Computers↗

The intracellular localization of long-chain acyl-CoA synthetase in brown adipose tissue.

1. The acyl-CoA synthetase activity in brown adipose tissue of cold-exposed guinea pig has been studied by measuring the rate of palmitoylcarnitine formation in the presence of excess carnitine palmitoyltransferase. 2. The rate of palmitoylcarnitine formation in the mitochondria was found to be 161 plus or minus 64 nmol.mg-minus-1. min-minus-1 (n=9). 3. In the absence of added palmitate and bovine serum albumin a total of 35 plus or minus 1 nmol endogenous fatty acids.mg-minus-1 were activated with three different mitochondrial preparations. 4. Three different experimental approaches have been used to study the subcellular localization of the enzyme: (a) conventional differential centrifugation (De Duve, C., Pressman, B.C., Gianetto, R., Wattiaux, R. and Appelmans, F. (1955) Biochem. J. 60, 604-617) (B) the determination of the sediterm of different marker enzymes (Slinde, E. and Flatmark. T. (1973) Anal. Biochem. 56, 324-340) and (c) the determination of the stoichiometry between the activities of these enzymes sedimented at higher centrifugal effects. 5. Throughout all fractionation procedures, the long-chain acyl-CoA synthetase follows strictly the amine oxidase generally considered to be exclusively located on the mitochondrial outer membrane.

Adipose Tissue, Brown↗

Subcellular localization of hexadecanedioic acid activation in human liver.

The activation of hexadecanedioic acid has been studied in subcellular fractions of human liver. The activation capacity in a total homogenate of human liver was found to be 0.5 micro mole/min/g wet wt of tissue, about 10% of that for palmitic acid. Hexadecanedioic acid was activated by the mitochondrial and microsomal fractions. The mitochondrial enzyme is probably localized outside the inner mitochondrial compartment. The subcellular distribution of the hexadecanedioic acid activation was almost identical with the distribution of palmitic acid activation. Hexadecanedioic and palmitic acids seemed to compete for the same enzyme.

Acid Phosphatase↗