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Biomedical subjects

E Heinonen

Publications and source records attributed to E Heinonen.

At least 73 records · Page 4Linked to original sources

Nandrolone decanoate added to tamoxifen in the treatment of advanced breast cancer.

Since 1980 we have been carrying out a prospective randomized trial comparing tamoxifen with the combination of tamoxifen plus nandrolone decanoate in advanced breast cancer. The tamoxifen dose is 30 mg daily and the nandrolone decanoate dose 100 mg i.m. once a week for four weeks and thereafter every other week. 98 post-menopausal patients have been evaluated for the response. The number of patients is 49 in both groups. The overall response rates (CR + PR) to tamoxifen and tamoxifen plus nandrolone decanoate were not significantly different; in the tamoxifen group the response rate was 49% and in the combination group 45%. The mean time to progression in tamoxifen group is over 13 months and in tamoxifen plus nandrolone decanoate group over 12 months. Our results do not suggest a synergistic effect from combining tamoxifen and nandrolone decanoate treatments. The response rates to tamoxifen at different sites of metastases were as follows: bones 47%, soft tissues 56%, and viscera 48%. The respective figures with the combination therapy were 36%, 64%, and 40%. Both treatments were well tolerated and in no patient was withdrawal of the therapy necessary. Mild virilization and hoarseness were experienced by all patients treated with nandrolone decanoate. Side-effects associated with tamoxifen were rare, although five patients experienced nausea and two had hot flushes.

Aged↗

Depolarization of the mitochondrial membrane potential increases free cytosolic calcium in synaptosomes.

Intracellular calcium transients in synaptosomes, isolated from the guinea pig brain, were measured using entrapped metallochromic indicator arsenazo III. Addition of 1 microM carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP) increased rapidly the absorbance of the entrapped arsenazo III, indicating an increase in the cytosolic free calcium. The FCCP-induced increase in cytoplasmic free Ca2+ was not blocked by 200 microM verapamil, while the increment in calcium caused by 40 microM veratridine was verapamil-sensitive. The absorbance changes induced by FCCP were not significantly increased when the extracellular potassium concentration was elevated from 5.4 to 50 mM. These data indicate that in nerve endings of mammalian brain, cytoplasmic free calcium, which is essential for the release of transmitter, is increased on depolarization of major intracellular calcium buffers, mitochondria.

Animals↗

Adjuvant postoperative radiotherapy, chemotherapy, and immunotherapy in stage III breast cancer.

One hundred twenty pathologically confirmed operable Stage III (T3N0-2) 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 node areas and chest wall. Chemotherapy consisted of 6 cycles of Adriamycin (doxorubicin) (45 mg/m2), vincristine (1.2 mg/m2) intravenously, and cyclophosphamide (200 mg/m2 for 5 days) perorally every 4 weeks. Peroral levamisole, 150 mg a day, 2 days weekly, was given as an immunotherapy. The 3-year results are described in this article. The effect of levamisole on the prognosis cannot be evaluated yet because of the short follow-up period. The disease-free survival was almost equal in each patient group, however, some benefit was achieved by levamisole (a shift of disease-free survival from 12 to 18 months). The patients receiving radiotherapy alone had the poorest prognosis: 68% had a recurrent tumor, and 57% were alive. In the chemotherapy group, the figures were 53% and 72%, respectively. Patients who received a combined treatment had the best prognosis: 13% had a recurrent tumor, and 90% survived 3 years. There was a statistically significant difference in the recurrence rate between any single therapy and the combined treatment (radiotherapy to combined treatment, P less than 0.001, chemotherapy to combined treatment, P less than or equal to 0.01 chi-square test). In overall survival, a statistically significant difference was reached between radiotherapy and combination treatment groups (P less than 0.01, chi-square test). Radiotherapy gave a good local control of the tumor, and chemotherapy decreased the number of metastases. The nonmetastatic axillary lymph node status and secondary amenorrhea or severe menstrual disturbances were of positive prognostic value. The side effects due to radiotherapy and chemotherapy were moderate and tolerable. The dose of Adriamycin had to be reduced only in four patients. All of the patients receiving chemotherapy had a transient total alopecia. Three of them had nonlethal arrhythmias, and one had skin rash. Levamisole was found very toxic with 9 cases of transient agranulocytosis, leading to the discontinuation of immunotherapy in 22 of 59 patients. Our results show that radiotherapy controls the tumor only locally and chemotherapy systematically, but the best patient-saving results are achieved with a combination of radiotherapy and chemotherapy. The disease-free and overall survival are statistically significant, and favor the combined therapy.

Adult↗

Oestrogen and progesterone receptors and disease-free interval in primary breast cancer.

Oestrogen and progesterone receptor assays were performed in 286 women with primary breast cancer, and the patient group was followed up for a minimum of 24 months. Of the 263 patients belonging to clinical stages I-III and serving as the population used for calculation of disease-free interval only 1.9% received postoperative endocrine treatment and 6.5% chemotherapy. No significant relationship between the presence or concentrations of oestrogen or progesterone receptor and the disease-free interval was observed. It is therefore possible that the positive relationship between these variables reported in some investigations reflects an influence by adjuvant endocrine measures.

Breast Neoplasms↗

Facilitation of transmission at the crayfish neuromuscular synapse by a convulsant phenol.

The effects of the convulsant drug 4-Cl phenol on synaptic transmission were studied in the opener muscle of the crayfish walking leg. 4-Cl phenol was found to increase the amplitude of the excitatory postsynaptic potential without affecting the resting potential or input resistance of the muscle fiber. The drug did not change the frequency of spontaneous miniature postsynaptic potentials in K+-depolarized fibers. The postsynaptic voltage response to bath-applied glutamate (the excitatory transmitter compound) was decreased while the Cl(-) -conductance increase related to the action of bath-applied gamma-aminobutyric acid (the inhibitory transmitter) was not affected. In the light of previous results obtained on crayfish axons it is concluded that convulsant phenols induce an increase in the evoked release of transmitter by increasing the duration of the presynaptic depolarization through a block of voltage-dependent potassium channels.

Action Potentials↗

Qualitative measurements of cytosolic calcium ion concentration within isolated guinea pig nerve endings using entrapped arsenazo III.

If arsenazo III is present during homogenization of brain this metallochromic indicator is entrapped within subsequently isolated synaptosomes. A large proportion of the entrapped indicator is released upon addition of digitonin to disrupt the synaptosomal plasma membrane. A similar proportion of [3H]sucrose is also trapped within synaptosomes if present in the homogenization medium, suggesting that homogenization causes a transient opening of the nerve ending as it is chopped off from the axon. Addition of the ionophore A23187 or depolarization of the plasma membrane by adding veratridine, gramicidin or increasing external K+ changes the absorbance of the entrapped dye, with peaks of absorbance around 600 and 650 nm, typical of the arsenazo III-Ca2+ complex. The response to veratridine is inhibited by the Ca2+-channel antagonist, verapamil, while that of A23187 is unaffected. The present method provides a sensitive technique for measurements of changes in cytosolic calcium ion concentrations within nerve endings.

Animals↗

Adriamycin extravasation: surgical treatment and possible prevention of skin and soft-tissue injuries.

In a material consisting of approximately 6,000 injections of Adriamycin during a 2-year period, eleven moderate and five severe extravasation injuries have been observed. Even a small leakage of the drug may cause a permanent lesion. The most serious injuries were caused by large doses and on the dorsum of the hand. Plastic surgical operations were successfully performed in the severe cases. An active surgical intervention after primary neutralization of the extravasated Adriamycin is recommended.

Adult↗

Differential sensitivity of A and C nerve fibres to long-acting amide local anaesthetics.

The differential sensitivities of A beta, A delta and C fibres of rat vagus nerve to bupivacaine, etidocaine and AL-381 were studied in vitro. In A beta fibres, at 35-37 degrees C, 50 mumole litre-1 of the drugs had similar effects on the action potential amplitude, while at greater concentrations (100 and 200 mumole litre-1) the greatest mean depression of amplitude was seen with etidocaine (n.s.). AL-381 had the most marked effect on the A delta potentials, and it appeared that it was about twice as potent as the others in blocking these fibres. Etidocaine 100 mumole litre-1 was more depressant than the same dose of bupivacaine. The C fibres were blocked most rapidly by AL-381, while etidocaine had the least effect.

Action Potentials↗

Value of liver and spleen aspiration biopsy in malignant diseases when these organs show no signs of involvement in sonography.

To determine whether an aspiration biopsy of liver and/or spleen is likely to reveal a clinically silent malignant infiltration, fine-needle aspiration biopsies were carried out in 180 patients with a diagnosed malignancy in whom neither the liver nor the spleen gave signs of involvement in sonography. Few, if any, findings were positive in patients with cancer or Hodgkin's disease. In non-Hodgkin lymphoma, about 25% of the biopsies were positive for malignancy or aroused suspicion of malignancy. We conclude that fine-needle aspiration biopsies of the liver and spleen may be of value in the clinical follow-up of non-Hodgkin lymphoma.

Adolescent↗

A spin label study on the effect of dibutyryl cyclic AMP on synaptic plasma membranes isolated from rat brain.

The fluidity of the deep layer of the lipid bilayer and the mobility of sulphydryl (-SH) groups of synaptic plasma membranes, isolated from rat brain and spin-labelled with a doxyl derivative of stearic acid and with a nitroxide derivative of maleimide, respectively, were studied using electron spin resonance (ESR) techniques. Dibutyryl cyclic AMP (db-cAMP) and adenosine triphosphate (ATP) had no effect on the fluidity of the deep layer of the lipid bilayer of synaptic plasma membranes. While protein dephosphorylation was inhibited by Zn2+, db-cAMP together with ATP increased the mobility of -SH groups above the value obtained with db-cAMP alone.

Adenosine Triphosphate↗

Tigason (etretinate) in prevention of recurrence of superficial bladder tumors. A double-blind clinical trial.

The effect of Tigason (etretinate) in the prevention of the recurrence of superficial bladder tumors (Ta-T1, grade 0 papilloma and grade 1 and 2 carcinoma) was studied in 30 patients in a double-blind, placebo-controlled study. Before beginning treatment, the bladder was cleared from all visible tumors by electrocoagulation or TUR. The duration of treatment ranged from 10 to 26 months. The overall preventive effect was significantly better (p less than 0.01) in Tigason-treated patients than in patients given placebo. Tigason was more effective in preventing the recurrence of grade 1 and 2 carcinoma than placebo. On grade 0 papilloma this difference was not so marked. Side effects were common and disturbing at high doses (50 mg/day), but Tigason was well tolerated at the final maintenance dose (25 mg/day). The results obtained from this first clinical study with Tigason in the prevention of recurrence of superficial bladder tumors are promising.

Aged↗

Effects of dopamine and dibutyryl cyclic adenosine monophosphate on delayed release of transmitter at the rat neuromuscular junction.

The effects of dopamine and dibutyryl cyclic adenosine monophosphate (db-cAMP) on delayed release of transmitter were studied in vitro in the phrenic nerve-diaphragm muscle preparation in the rat using intracellular recording techniques. Dopamine at 1 X 10(-4) mol 1(-1) prevented the initial facilitation of delayed release of transmitter. This inhibitory phase was transformed into a transient facilitation of delayed release. We observed that dopamine hyperpolarized muscle fibres by about 9%. Thus motor nerve terminals may also have been hyperpolarized by dopamine; however, it is unlikely that this hyperpolarization explains the observed effects on delayed release of transmitter. Db-cAMP at 1 X 10(-3) mol 1(-1) predominantly augmented delayed release of acetylcholine. These effects of dopamine and db-cAMP on delayed release of transmitter are discussed in terms of a modulation of calcium fluxes in the presynaptic nerve terminal.

Acetylcholine↗

Independent release of supranormal acetylcholine quanta at the rat neuromuscular junction.

This electrophysiological study deals with the occurrence and with the mode of release of unusually large miniature end-plate potentials at the rat neuromuscular junction during physiological conditions. A specific limit for the normal miniature end-plate potential amplitude at each cell studied was determined after fitting the observed frequency-amplitude histogram to a Gaussian distribution. The relative abundance of giant miniature end-plate potentials was 4.15% at room temperature. The occurrence of giant miniature end-plate potentials was temperature dependent. The percentage of giant miniature end-plate potentials was 5.8% and 0.61% at 35 degrees C and at 16 degrees C, respectively. The amplitude-independence of the intervals between miniature end-plate potentials was demonstrated at room temperature as well as at 35 degrees C and at 16 degrees C. The results of this study show that giant miniature end-plate potentials are produced by acetylcholine packets which are released independently and that they are not a consequence of the synchronous release of several normal-sized quanta. Moreover, the results indicate that during physiological conditions a minor but regular proportion of the spontaneous release of acetylcholine is made up of larger packets, which produce miniature end-plate potentials of supranormal amplitude.

Acetylcholine↗

Effect of prostaglandin E1, dopamine and dibutyryl cyclic AMP on the fluidity of synaptosome membranes.

The membrane fluidity of synaptosomes, isolated from rat brain and spin-labelled with doxyl derivatives of stearic acid, was studied using electron spin resonance techniques. Prostaglandin E1 fluidized while dopamine ordered both the surface and intermediate lipid layers of the synaptosome membranes. At corresponding concentrations these substances have been shown to modulate synaptic transmission. A possible thermal phase transition of the membrane lipid bilayer was observed at about 35 degrees C (the abrupt change in the Arrhenius plot). Dopamine abolished this thermal change. Dibutyryl cyclic AMP had no significant membrane effects.

Alprostadil↗

Differential nerve block by bupivacaine and 2-chloroprocaine. An experimental study.

The differential blocking effect of bupivacaine and 2-chloroprocaine was studied on isolated rabbit cervical sympathetic trunks (B and C fibres) and phrenic nerves (A fibres). The B fibres (myelinated, preganglionic) were more sensitive than C fibres (unmyelinated, postganglionic) to nerve block by bupivacaine and 2-chloroprocaine, as assessed by changes in action potential amplitude and latency. The blocking action of both bupivacaine and 2-chloroprocaine caused a decrease in amplitude in the B fibres approximately twice as great as that produced in the C fibres. In similar experimental conditions, the fastest conducting A fibres (myelinated, motor) were least affected. Bupivacaine 200 mumol litre-1 completely blocked all B fibres in 7 min and C fibres in 10 min. The average action potential amplitude of A fibres at that time was 78%. 2-Chloroprocaine 300 mumol litre-1 completely blocked B fibres in 4 min and C fibres in 15 min. At 15 min the average action potential amplitude of the A fibres was still approximately 35%. Although these two local anaesthetics differ structurally and physico-chemically, the rates of block of the different fibres were in the same order in vitro.

Action Potentials↗