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Biomedical subjects

J Lange

Publications and source records attributed to J Lange.

At least 145 records · Page 8Linked to original sources
PubMed1985

Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse.

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a rapid and long-lasting reduction of both 3,4-dihydroxyphenylalanine (dopamine, DA) and noradrenaline (NA) in mouse brain, as observed histo- and neurochemically. The depleting effects were more pronounced after repeated MPTP administration and the most marked reductions were observed after 2 X 50 mg MPTP/kg s.c., when DA in striatum and NA in frontal cortex were reduced by greater than 90% 1 week after MPTP. Mice with such catecholamine depletions were markedly sedated and almost completely immobilized. The behavioural syndrome after MPTP resembled that seen after reserpine, a monoamine-depleting drug. MPTP also caused a long-lasting reduction of catecholamine uptake in striatal DA and cortical NA nerve terminals and reduced tyrosine hydroxylase activity in these regions. There was no evidence that MPTP caused any marked DA and NA cell body death. MPTP given acutely transiently elevated serotonin levels. The results are compatible with a neurotoxic action of MPTP on both DA and NA nerve terminals. The nigro-striatal DA and the locus coeruleus NA neurone systems appeared to be most susceptible. Synthesis and utilization of residual striatal DA and cortical NA were increased, as often observed in partially denervated monoamine-innervated brain regions. Both DA and NA showed a gradual recovery, which took months to become complete and may have been related to a regrowth of catecholamine nerve terminals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1985

On the differential affinities of two anticancer analogues to their target.

The aim of the present study was to compare the pharmacokinetics of 5-fluorouracil (FU) and 5-fluoro-2-deoxyuridine (FUDR) during intra-arterial infusion. For this purpose 10 patients with widespread metastatic disease of the liver received implantable hepatic arterial catheters through the gastroduodenal artery. The patients were given FU (7.5 mg/kg) and FUDR (0.75 mg/kg) respectively via the hepatic catheter; drugs were administered for 30 min at a constant infusion rate. Blood samples were drawn from the hepatic vein after the end of the intra-arterial infusion. An established HPLC method was used to determine drug plasma levels. The patients who were on the FU infusion protocol during the first week showed mean FU plasma levels of 10 micrograms/ml, whereas FUDR plasma levels in the same patients, treated in the second week, were about 1 microgram/ml. Apparently hepatic removal was equally effective, with 97% of FU and with 96% of FUDR being extracted from the plasma. Kinetic consideration of the these data, however, suggested significantly differing affinities--on analogy with enzyme kinetics--of active facilitated transport mechanisms towards FUDR (KD = 4.2 X 10(-2)) and towards FU (KD = 64.2 X 10(-2)).

Adenocarcinoma↗
PubMed1985

[Experiences with therapeutic whole-body hyperthermia].

Therapeutic whole body hyperthermia (WBH) as an additional therapy in the treatment of cancer has been known for a long time and is beginning to attain acceptance. In a clinical study 28 patients were treated 70 times with WBH at a core temperature of 41.8 degrees C. Hyperthermia was induced and maintained with an extracorporal circuit (ECC). Patients were anaesthesized with nitrous oxygen, enflurane and fentanyl. Therefore artificial ventilation was mandatory. Invasive monitoring was used to control vital functions. The effect of WBH includes a rise in cardiac output and heart rate as well as a decrease in total vascular resistance and mean arterial pressure. Pulmonary function almost remains constant. A raised oxygen consumption is compensated by a rise of oxygen availability. In consequence of an augmented perspiratio insensibilis and the ECC, close observation of fluid and electrolyte balance is necessary. According to our experience the small number of complications and problems allows the treatment with WBH even of patients with a high risk of anaesthesia.

Adolescent↗
PubMed1984

Evidence for high affinity [3H] imipramine binding sites in human lung.

[3H] imipramine exhibits both saturable and high affinity binding sites in human lung with a maximal number of binding sites of 7.50 pmoles/mg protein and a dissociation constant of 1.74 nM. Displacement studies indicate that these sites can be considered as specific of imipramine, tricyclic compounds and also monoamine uptake inhibitors:fluoxetine and nisoxetine. Atypical antidepressants were inactive as ligands of main known receptors.

Antidepressive Agents↗
PubMed1984

MR-tomography in the diagnosis of malignant soft-tissue tumours.

Nine patients with malignant, peripheral soft-tissue tumours were examined using a 0.35 T MR equipment. In 7 cases in which tumour presence was surgically verified, a definite identification as well as an exact determination of tumour extension was achieved using MR. The various tumours exhibited a particularly high degree of contrast when using a T2-weighted Spin-Echo-(SE) as well as the T1-weighted Inversion-Recovery-(IR) mode. The T1- and T2-relaxation times of the soft-tissue malignancies evaluated in this study were markedly longer than those obtained for normal tissue. In 2 patients within the collective, a definite exclusion of tumour recurrence was possible.

Adolescent↗
PubMed1983

[Extracorporeally induced whole-body hyperthermia in conventionally incurable malignant tumor patients].

Whole body hyperthermia was produced in 14 patients with conventionally incurable malignant disease. The technique consisted of arteriovenous shunting involving extracorporeal circulation with heat exchange during general anaesthesia. A temperature of 41.8 degrees C was maintained for periods of 6 hours. After achieving hyperthermic temperatures treatment was enlarged by administration of 5-fluorouracil (1000 mg) in patients with colorectal carcinoma and by dacarazine (200 mg/m2) in patients with malignant melanoma. In 5 out 6 patients with stage IV colorectal carcinoma stabilisation of the disease was seen for an average of 10 months. In contrast, progression of the disease was seen in patients with malignant melanoma and mean survival was only 5 months. These preliminary results in a small number of patients indicate that 1. induction and maintenance of whole body hyperthermia is clinically possible, 2. technical requirements are considerable, however feasible, 3. different tumours react differently to treatment.

Adolescent↗
PubMed1983

[Cyto-diagnosis of cystic ovarian tumours].

The value of aspiration cytology of cystic ovarian tumours was studied, as an aid to the differential diagnosis between functional ovarian cysts and cystic ovarian tumours. In 158 women age 14 age 77 the cystic ovarian tumour was aspirated by laparoscopy or at laparotomy and the contents of the cyst were centrifuged and the sediment investigated by papanicolaou cytology. The findings of the smears showed direct or indirect cytological criteria for a cystic ovarian tumour. In 47 cystic neoplasms verified by microscopic examination the cytological diagnosis showed conclusive evidence of a neoplasm in 27 cases. In 7 cases the cytology was suspicious of a neoplasm. In 36 cases the differential diagnosis between cystic tumour and functional cyst was supplemented by radio-immuno-assay for estradiol in the aspirated contents of the cysts. Values over 500 picomol/litre are suggestive of a follicle are corpus luteum cyst.

Adolescent↗
PubMed1983

Biovailability and pharmacokinetics of femoxetine.

The availability of trans-(+)-3-[(4-methoxy-phenoxy)methyl]-1-methyl-4-phenylpiperidine (femoxetine, HCl; 500 mg) from an enteric coated tablet and from a water solution, respectively, have been compared in a single dose, cross-over study using six healthy volunteers. The tablet gave a longer lag time and a slower absorption rate than the solution. The mean availability of the tablet was 71% (range 12-150%), relative to the availability of the solution in five of the subjects. During a multiple dose study, where the same six volunteers took 400-600 mg (as tablets) per day for a week, no change in the kinetic parameters was observed and no discrepancy between the parameters obtained in the single dose study and the ones from the multiple dose study was seen within each subject. A high first pass effect is presumed to be the main reason for the relatively great inter-individual variations. The formation and elimination rate of an active metabolite, norfemoxetine, were very similar in three of the four subjects for whom the rates could be calculated.

Adult↗