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Biomedical subjects

E Heinonen

Publications and source records attributed to E Heinonen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Changes of the membrane potential in striatal synaptoneurosome, synaptosome and membrane sac preparations induced by glutamate, kainate and aspartate as measured with a cyanine dye DiS-C2-(5).

The effects of glutamate, kainate and aspartate on the membrane potential of striatal synaptoneurosome, synaptosome and membrane sac preparations were studied by using a potential sensitive cyanine dye DiS-C2-(5). Excitatory amino acids glutamate and aspartate had a depolarizing effect on synaptoneurosomes. 7.9 microM glutamate and 2.8 microM aspartate produced a half-maximal response. Depolarizations induced by glutamate and aspartate were dependent on the concentration of extracellular sodium ions, a maximal response occurred at around 40 mM of external Na+. Kainate induced a dual effect on synaptoneurosomes. In a standard Na+-based medium a hyperpolarization, likely due to inhibition of a presynaptic sodium-dependent glutamate uptake, predominated over a postsynaptic kainate receptor-mediated depolarization that was observed when electrogenic glutamate uptake was inhibited. This interpretation was supported by results obtained with synaptosome and membrane sac preparations. In a standard Na+-based medium kainate had a hyperpolarizing effect on synaptosomes while in the membrane sac preparation kainate induced a depolarization.

Animals↗
PubMed1989

Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy.

Reduced respiratory sinus arrhythmia, measured as heart rate variability, is a reliable indicator of autonomic nervous dysfunction, reflecting a damage in vagal cardiac control. The authors studied the heart rate variability (HRV) of nine children treated for acute lymphoblastic leukemia during the different phases of cytostatic treatment utilizing heart rate processing techniques with a computer. The indices of HRV as well as the spectral components of heart rate were examined with special relation to vincristine administration. The heart rate variability was significantly reduced during the vincristine induction phases as compared to the consolidation and maintenance phases without vincristine administration. In particular, the respiratory components of the HRV during deep breathing tests were significantly reduced during vincristine treatment. The authors conclude that the measurement of the HRV is a suitable method for monitoring transient autonomic neuropathy, which these results show to be a frequent complication of vincristine treatment.

Adolescent↗
PubMed1989

Phase II evaluation of peroral carmofur, cyclophosphamide, and hexamethylmelamine as a second-line therapy in advanced epithelial ovarian carcinoma.

A prospective phase II study was performed to evaluate the effect and tolerability of a peroral combination chemotherapy consisting of hexamethylmelamine, cyclophosphamide, and carmofur in patients with epithelial ovarian cancer previously heavily treated by cisplatin-based chemotherapy but no longer responding to it. Of the 27 patients 1 showed a clinical complete remission lasting 15+ months and 4 a partial remission of 6+ to 21 months. A further 7 patients had an unchanged situation of 4 to 13+ months. The median survival of the nonresponders was 3 months. The side effects were tolerable, mostly nausea and vomiting. Only 4 of 27 patients suffered from severe vomiting causing discontinuation of the therapy. The peroral ambulatory chemotherapy prolonged markedly the overall survival of about one-half of the patients with ovarian cancer who previously failed to respond to cisplatin-based chemotherapy.

Administration, Oral↗
PubMed1989

Selegiline and levodopa in early or moderately advanced Parkinson's disease: a double-blind controlled short- and long-term study.

Selegiline 10 mg per day was compared to placebo as an adjunct to levodopa treatment in this double-blind study of early or moderately advanced Parkinson's disease. Thirty-eight patients completed an initial cross-over trial comprising two treatment periods, each of eight weeks, with a four weeks' wash-out period between them. Thirty of the patients continued in a long-term, double-blind parallel trial with a mean duration of 16 months (range 6-30 months). Selegiline treatment allowed a significant reduction of the necessary daily levodopa dose in both parts of the study and of the daily dosing frequency in the long-term investigation. In spite of this reduction of levodopa dose, an improvement was noted in tremor during the short-term selegiline periods. The side-effects were slight and related to dopamine effects and disappeared after reduction of levodopa-dose. The results support the use of selegiline as an early adjunctive treatment in Parkinson's disease.

Aged↗
PubMed1987

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer. II. 5-year results and influence of levamisole.

One hundred twenty pathologically confirmed operable Stage III breast cancer patients were randomized to receive either postoperative radiotherapy or chemotherapy, or a combination of these, with or without levamisole immunotherapy. Radiotherapy was given to regional lymph nodes and chest wall. Chemotherapy consisted of six cycles of vincristine, doxorubicin, and cyclophosphamide. Radiotherapy provided local and chemotherapy systemic control over the tumor, but the best patient-saving results were achieved with a combination of radiotherapy and chemotherapy. This clinical trial was commenced in 1976, and the first 60 of 120 patients also received oral levamisole, 150 mg/day, on 2 consecutive days weekly as immunotherapy. All patients were followed for at least 5 years. At this stage levamisole seems to increase disease-free and overall survival in all three treatment arms (radiotherapy, chemotherapy, combined treatment). Significance is reached in disease-free survival (P = 0.035) and overall survival, adjusted for all other treatment modalities (P = 0.019).

Aged↗
PubMed1987

Intracellular free magnesium in synaptosomes measured with entrapped eriochrome blue.

The free Mg2+ concentration within synaptosomes has been measured with an entrapped Mg2+ indicator, eriochrome blue. Ionophores gramicidin and A23187 slowly increased the absorbance of the entrapped dye. Calibration of the dye response in a Na+-based medium gave a value around 0.3 mM for the internal free Mg2+ concentration at 1 mM external Mg2+. The replacement of Na+ by choline increased this value to around 0.65 mM. Depolarisation with a high K+ concentration or depletion of intrasynaptosomal ATP with FCCP and iodoacetate did not affect the level of intracellular free Mg2+ concentration. An elevation of the external Ca2+ concentration significantly reduced internal Mg2+ to about 0.1 mM. Ca2+ had no significant effect when Na+ was replaced by choline. The results indicate that the intrasynaptosomal Mg2+ activity is partially regulated by a Na+-Mg2+ exchange mechanism which does not directly require ATP as an energy source.

Adenosine Triphosphate↗
PubMed1987

Ionic dependence of membrane potential and glutamate receptor-linked responses in synaptoneurosomes as measured with a cyanine dye, DiS-C2-(5).

Membrane potentials of particles present in a subcellular brain preparation, called synaptoneurosomes, have been monitored by measurement of changes in the absorbance of a cyanine dye, DiS-C2-5. The membrane potential of the particles seems to be dependent on both Cl- and K+ diffusion potentials, as judged from dependence of the absorbance changes on the K+ equilibrium potential across the membrane in the presence of Ba2+ or when Cl- was replaced with gluconate. The apparent high Cl- permeability of the membrane preparation was reduced in the presence of picrotoxin, a finding suggesting endogenous activation of receptor-linked Cl- channels. Glutamate and kainate caused depolarization of the membranes present in the preparation. This effect was only seen if K+ channels had been blocked in the presence of Ba2+ or 4-aminopyridine. No responses were observed with other glutamate receptor agonists (quisqualate or N-methyl-D-aspartate). The membrane potential of particles present in conventional synaptosomal preparations neither had a high Cl- permeability nor reacted to glutamate or kainate in the present conditions. The results suggest that synaptoneurosome preparations may be used for functional studies on postsynaptic neurotransmitter receptor-linked membrane potential changes with optical probes of membrane potential.

Animals↗
PubMed1987

Autonomic neuropathy and vibration exposure in forestry workers.

The variation in heart rate (HRV) at rest and during deep breathing (6 cycles a minute) of 88 professional lumber jacks was studied using a computer technique. The traditional indexes of HRV (CV, CVS, MEAN) were calculated and the spectral components of the HRV were also computed. There was a significant difference (p less than 0.001) between the HRV indexes during the deep breathing test in those with the shortest (CV = 10.1 +/- 1.1) and those with the longest (CV V 6.2 +/- 0.4) exposures to vibration. The values of the HRV indexes decreased with age, but multiple regression analysis showed that the total exposure time to vibration had an independent negative association with the HRV. There were significant differences in all the frequency bands (frequency related power, FRP) of the heart rate between those with the longest and those with the shortest exposures. The HRV during a deep breathing test is associated with the activity of the parasympathetic nervous system and is decreased in autonomic neuropathies. Our results suggest that prolonged exposure to the vibration caused by a chain saw has a negative effect on the parasympathetic activity and thus causes autonomic dysfunction.

Adult↗
PubMed1986

Measurement of cytoplasmic, free magnesium concentration with entrapped eriochrome blue in nerve endings isolated from the guinea pig brain.

Cytoplasmic, free Mg2+ was measured spectrophotometrically using an intrasynaptosomally entrapped Mg2+-indicator, Eriochrome blue (EB). Addition of the ionophore A23187 or disruption of the synaptosomal plasma membrane with digitonin caused an increase in absorbance of entrapped EB with a maximum at 551 nm, which is typical for the Mg2+-EB complex. A conversion of absorbance changes to levels of free Mg2+ concentrations was performed after disruption of synaptosomal plasma membranes by digitonin. The results indicated that the internal, free Mg2+ increased from 0.34 to 2.2 mM when the extracellular Mg2+ concentration was increased from 1 to 5 mM. The low values of cytoplasmic, free Mg2+ concentrations suggest the presence of effective regulatory mechanisms in the nerve endings.

Animals↗
PubMed1986

Quantitative measurements of the cytosolic Ca2+ activity within isolated guinea pig nerve-endings using entrapped arsenazo III and quin2.

The absorbance changes of intrasynaptosomally entrapped arsenazo III have been converted into values of free Ca2+ concentration by correcting for the nonlinear response of arsenazo III at different concentrations of the dye as well as for changes in internal pH. An average resting value for free Ca2+ concentration around 0.4 microM is obtained. Depolarization with veratridine or gramicidin increases this value to around 3 microM. Measurements of cytosolic free Ca2+ with the quin2 method gives much lower values in similar conditions. The release of prelabelled [14C]noradrenaline from the nerve-endings is maximally activated when the internal free Ca2+ concentration rises as measured with arsenazo III to about 4 microM when titrated with increasing concentrations of ionophore A23187.

Aminoquinolines↗
PubMed1986

Effects of repeated bupivacaine administration on sciatic nerve and surrounding muscle tissue in rats.

The effects of repeated administration of 0.5% bupivacaine or saline into the sciatic notch of rats were studied by light microscopy, electron microscopy and a neurophysiological technique. Very severe myositis, including local necrosis, developed in six of 12 rats treated twice daily with 1 ml bupivacaine for either 3 or 7 days. A 3-h infusion of 1.5 ml 0.5% bupivacaine resulted in minor injury to muscle tissue. A marked degree of disruption and vacuolization of myelin sheaths was evident in nerves exposed to bupivacaine for 3 days. Lymphocyte accumulation was confined to the area surrounding the nervous tissue in 7 of 10 of the preparations from rats treated for 3 days or by a 3-h infusion. No histological changes were detected in nerve and muscle tissue from the opposite extremity exposed to saline. After a recovery period of 3 weeks, no differences in the nerve or muscle histology were seen between samples from bupivacaine- or saline-treated animals. The amplitude of the compound action potential of sciatic nerves was, however, significantly lower after bupivacaine treatment (7 days, 1 ml twice daily). Thus, impaired function may continue despite the lack of histological intraneural injury.

Animals↗
PubMed1986

Effects of haemodialysis on heart rate variability in chronic renal failure.

The influence of haemodialysis (HD) on the heart rate variability (HRV) was investigated in nine non-diabetic patients on maintenance haemodialysis. The R-R intervals were measured in recordings during spontaneous quiet breathing and during controlled deep breathing before and after a single HD session. The HRV was expressed as the standard deviation of the mean R-R interval in 3 min ECG recordings. Heart rate variability is the irregularity in the heart rate mainly caused by autonomic control mechanisms. The long-term HRV during quiet breathing was statistically significantly (p less than 0.05) higher after the HD than before. The HRV in the intermediate frequency range of 0.075-0.125 Hz was also significantly increased by the HD. This suggests that some metabolic agents interfering with the heart rate regulation are removed by the haemodialysis, and as a result a better function of the autonomic cardiac control is achieved in uraemic patients.

Adult↗
PubMed1986

Reactivity of autonomic nervous control of heart rate in diabetes mellitus and juvenile rheumatoid arthritis.

Autonomic cardiac control of children with diabetes mellitus (DM, n = 12), juvenile rheumatoid arthritis (JRA, n = 12) and healthy controls (n = 12) was studied by a procedure consisting of a deep breathing test and an intermittent tilting test. Frequency selective entrainment of HR could be produced by tilting and deep breathing. No statistically significant intergroup differences were detected in the patterns of average heart rate (HR), overall or beat-to-beat heart rate variability (HRV) or HRV spectra. The DM group had an 8% higher HR and a limited short-term HRV response in relation to HR throughout the whole test procedure compared to controls. This increased HR causes an extra load to the cardiovascular system. We conclude that in spite of elevated HR and changed short-term chronotropic HR control in DM no features of autonomic failure could be detected in children with JRA.

Arthritis, Juvenile↗
PubMed1986

Sarcomas of the uterus: a clinicopathologic study of 119 patients.

This series consists of 119 uterine sarcoma patients treated at the University of Helsinki Central Hospital during the 20-year period of 1958 to 1977. It comprises the three main histologic varieties: leiomyosarcomas, 51 patients; mixed müllerian sarcomas, 45 patients; and endometrial stromal sarcomas, 23 patients. The clinicopathological features that could have had a bearing on prognosis were examined retrospectively. The clinical stage at the time of primary treatment was the main prognostic factor. Other important factors were the degree of histologic differentiation and the mitotic activity. The overall five-year survival rate for patients with leiomyosarcomas was 39%; for mixed müllerian sarcomas, 33%; and for endometrial stromal sarcomas, 61%. The ten-year survival figures were 27, 14, and 37%, respectively. Some features of the diagnosis, the natural history, and the different methods of treatment of these diseases are discussed.

Adult↗
PubMed1985

Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients.

Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.

Breast Neoplasms↗
PubMed1985

Levamisole in the treatment of stage II breast cancer. Five-year follow-up of a randomized double-blind study.

The effect of levamisole combined with postoperative radiotherapy in Stage II breast cancer was investigated in a double-blind randomized study comprising 72 patients. All patients were followed for at least 5 years. Disease-free survival was slightly prolonged in the levamisole group as a whole. Among postmenopausal patients, levamisole significantly increased both disease-free and total survival (P = 0.003) and P = 0.008, respectively). The levamisole group also showed fewer distant metastases as the first sign of recurrence. Levamisole treatment was associated with a risk of granulocytopenia and agranulocytosis (10%), but, as in the authors' previous studies, this seemed to be totally reversible and did not worsen the prognosis.

Actuarial Analysis↗
PubMed1985

Dependence of cytoplasmic calcium transients on the membrane potential in isolated nerve endings of the guinea pig.

The relation of changes in internal, free Ca2+, measured with arsenazo III, to the membrane potential, measured with the cyanine dye di-S-C2(5) or 86Rb+ distribution ratio, was studied in isolated guinea pig cortical nerve endings. Depolarization of the plasma membrane with veratridine or gramicidin as well as addition of ionophore A23187 led to an increase in cytosolic Ca2+. Only the response to veratridine was inhibited by tetrodotoxin. The dependence of the depolarization-induced increase in intraterminal, free Ca2+ on the membrane potential between about -50 to 0 mV was sigmoidal. A maximal increase in cytosolic Ca2+ was reached when the membrane potential was depolarized from the resting level, about -64 mV, to about -40 mV. These results show that in isolated nerve endings the activation of voltage-sensitive Ca2+ channels concomitantly leads to an increase in cytosolic, free Ca2+. Comparison of the results of the present study with the previous electrophysiological observations indicate that Ca2+ channels in synaptosomes, presynaptic nerve terminals of the squid giant synapse and cardiac cells have essentially similar voltage dependency.

Animals↗