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Biomedical subjects

L Kangas

Publications and source records attributed to L Kangas.

At least 91 records · Page 5Linked to original sources
PubMed1985

Subrenal capsule assay in choosing cytostatics for gynaecological tumours.

The subrenal capsule assay (SRCA) was used to test the sensitivity of gynaecological tumours to chemotherapy. The total number of the assays was 95, ovarian cancer being the most often tested. Of the SRCAs 92% were evaluable. Of the 59 evaluable assays for ovarian cancer, 52% showed sensitivity, 41% intermediate sensitivity, and 7% resistance to chemotherapy. The previously treated tumours were less sensitive than the untreated ones (p less than 0.01). To the most often tested drug combinations, DOX (doxorubicin) + C (cyclophosphamide) + DDP (cisplatin), DOX + C + Tegafur, and C + V (vincristine), resistance was observed in 10-20% of the assays. However, there was marked interindividual variation. Twenty-five assays of the squamous cell carcinomas were evaluable. Of the tumours 28% were sensitive, 48% intermediately sensitive, and 24% were resistant. Five of 7 sensitive tumours were previously untreated. The combination of DDP and VP-16 (etoposide) was tested most often, followed by Bleo (bleomycin) as a single agent. DDP + VP-16 was significantly superior to Bleo (p less than 0.01). The results of the SRCA and the clinical outcome of the patients could be compared in 31 cases. An overall predictive accuracy rate of 81% was achieved. It was concluded that the SRCA has predictive value in determining chemotherapy responsiveness of gynaecological tumours.

Animals↗
PubMed1985

Clinical praxis and laboratory procedures in subrenal capsule assay (SRCA).

Subrenal capsule assay (SRCA) is a promising method in cancer research and in the selection of individual chemotherapy for cancer patients. The laboratory procedures of SRCA are as follows: on day zero 1 X 1 X 1 mm pieces of fresh human tumour are carefully prepared. The pieces are transferred by a trocar under the outer capsule of normal immunocompetent mice, one piece to each. The mice (about 30-40/test) are divided randomly into groups of at least five. The size of each piece (initial size) is measured in situ by a stereomicroscope fitted with an ocular micrometer. On days 1-5 cytostatics are administered to the animals. On day 6 the animals are killed and the final tumour size is measured. The difference between the final and initial tumour size describes the response of the tumour to the treatments. The critical point of the assay is the selection of the tumour fragment which has to be representative, as homogeneous as possible and contain living tumour cells. When the sample is in pieces of about 3 X 3 mm (4-5 tumour fragments are sufficient for the assay) in the culture medium, it may be stored in an ice bath or at room temperature for one day. During this time, though as rapidly as possible, the sample has to be delivered to a research laboratory where the SRCA is carried out.

Animals↗
PubMed1985

Morphology of transplanted tumours and drug induced regression in the subrenal capsule assay (SRCA) of mice and rats.

Specimens from freshly biopsied human mammary and ovarian tumours and DMBA-induced rat mammary tumours were transplanted under the renal capsule of normal, immunocompetent mice and rats. The growth of the tumour and the effects of chemotherapy to the host animals were evaluated by measuring the growth of the implanted tumour specimens. Morphological analysis of the tumours showed preserved histological structures and cellular function, as evidenced by the basement membrane component production seen using immunohistochemical stains and by the surface specialized structures, cell-to-cell contact and secretory activity observed in ultrastructural studies. Treatments with different types of drugs yielded tangible results within 6 days of transplantation, showing lymphoid infiltration and scar formation, but preserved vascular structures. The results suggest that tumours subjected to subrenal capsule assay retain their structure and function when transplanted, thus enabling the evaluation of their sensitivity to therapeutic manipulation.

Animals↗
PubMed1985

Response of ovarian cancer to combined cytotoxic agents in the subrenal capsule assay: Part I.

The subrenal capsule assay in normal immunocompetent mice was used to test the responsiveness of ovarian cancer to combination chemotherapy. Of the assays, 42 were of untreated tumors and 19 of previously treated tumors. Fifty-nine (97%) of the assays were evaluable. The previously treated tumors were less sensitive than the untreated ones. Of the treated tumors 44% were sensitive, 33% intermediately sensitive, and 22% resistant versus 56, 44, and 0%, respectively, of the untreated tumors (P less than .01). Repeat assays for the tumors of seven patients were performed successfully after five to eight courses of therapy with the combination of doxorubicin, cyclophosphamide, and cisplatin. The responsiveness to this combination had weakened significantly (P less than .01); the response of only one tumor remained unchanged. The rates of resistance to the drug combinations doxorubicin-cyclophosphamide-cisplatin, doxorubicin-cyclophosphamide-tegafur, and cyclophosphamide-vincristine were 11, 10, and 21%, respectively; there was, however, considerable interindividual variation in tumor responses to these combinations. Of other combinations, hexamethylmelamine combined with 4-epidoxorubicin, aclarubicin, or chlorambucil and cisplatin had effect, whereas the combinations of cisplatin and etoposide and of tegafur and methotrexate or mitomycin were quite ineffective, as measured by the assay. The reliability of the subrenal capsule assay in normal immunocompetent mice is discussed, and it is concluded that the assay can be used to assess the response of ovarian cancer to chemotherapy, including multidrug therapy, without routine histologic control.

Aclarubicin↗
PubMed1985

Ultrastructural effects of alpha and gamma interferons and cytostatics on ovarian cancer cells in the subrenal capsule assay (SRCA).

Ovarian cancers from 9 patients were grown in the subrenal capsule assay for 6 days. Groups of five mice were treated with saline, alpha interferon, a combination of alpha and gamma interferons and 2 cytostatic drug combinations with and without alpha interferon. The histological evaluation suggested that the regression of drug-treated transplants measured with stereomicroscope can reliably be used as an indicator of drug effect. However, it is possible that in a few cases the control growth measured with preparation microscope is somewhat exaggerated due to inflammatory reactions induced by the grafts. At the ultrastructural level, the cell, nuclear and mitochondrial volumes were morphometrically evaluated. The cytostatic treatment caused marked degenerative changes with nuclear enlargement and cytoplasmic vacuolization of the tumour cells. Only small differences could be detected between the control groups and the interferon-treated groups. In these groups, the nuclear and cytoplasmic volumes were not significantly different, whereas the mitochondrial volume was larger in the interferon-treated cells.

Animals↗
PubMed1984

The subrenal capsule assay in mice. Prediction of rat tumor sensitivity to chemotherapy.

The predictive value of the subrenal capsule (SRC) assay for cancer chemotherapy was tested in five rat tumors. Tumor-bearing rats were used as controls. In order to simulate clinical chemotherapy, different dose regimens and drug combinations were used. All five tumors were evaluable in in the SRC assay. Taking into account cytotoxic drugs, 86% compatibility was obtained between the SRC assay and the rat model. Antitumor effect of three antiestrogenic compounds could not be predicted by the SRC assay. It is concluded that the SRC assay can be expected to have predictive value in the assessment of tumor sensitivity to single and combination chemotherapy based on experimental animal models.

Animals↗
PubMed1984

Midazolam versus atropine plus pethidine as premedication in children.

The effects of oral midazolam or intramuscular atropine and pethidine used as premedication in two groups of 35 children over 5 years of age were studied. There was some evidence that the anxiolytic effect of midazolam was rather better than that of atropine plus pethidine, but, in other respects, subjective assessments in the two patient groups were similar. Intramuscular atropine caused tachycardia and subjective side-effects, nevertheless children appear to require anticholinergics during premedication because of excessive salivary secretion, especially during extubation. Oral midazolam is a new anxiolytic drug which can be used as an alternative to existing premedicant drugs, but, in children, it should still be combined with an anticholinergic agent. No correlation between serum levels of midazolam or atropine and their clinical effects was found.

Administration, Oral↗
PubMed1984

Steroid receptors and response of ovarian cancer to hormones in vitro.

Oestrogen receptor (ER) and progesterone receptor (PR) content and the response in vitro to tamoxifen (T), medroxyprogesterone acetate (MPA) and to a combination of the two hormones were determined in 21 epithelial ovarian carcinomas. The response was assessed by the level of adenosinetriphosphate in the cells. ER and PR were detected in 62% and 57%, respectively, with significant variations between the different histopathological cancer types. ER and PR predicted the response in vitro in 62% of the tumours exposed to the combined hormones, and in 38% and 33% of those exposed to T and MPA, respectively. The value of steroid-receptor determinations in selecting the proper hormonal treatment in ovarian cancer is significantly reduced because of the high proportion of incorrect predictions.

Adult↗
PubMed1984

Steroid receptors and response of ovarian cancer to cytostatic drugs in vitro.

Samples of 21 ovarian cancers were assayed for oestrogen receptor (ER) and progesterone receptor (PR) content, and the response in vitro to treatment with a combination of doxorubicin, diacetyldian hydrogalactitol and cisplatin was determined. The number of living cells after drug exposure was estimated by a new ATP-bioluminescence method and the tumours were considered responsive if cell survival was less than or equal to 50% of the value in a corresponding control culture. Of the 16 tumours that responded to drug exposure, nine were ER-positive, seven ER-negative and eight were PR-positive, eight PR-negative. The mean percentages of surviving cells ranged from 22.2% in PR-negative tumours to 30.9% in PR-positive tumours. There were no differences in the response rates or in the degree of response to the cytostatics in terms of either receptor status or tumour histology. The results were also compared with those obtained in the same tumour samples exposed to hormones, tamoxifen and medroxyprogesterone acetate. The average response of all tumours was better to cytostatics than to hormones (P less than 0.05); this was particularly marked in the ER-negative tumours. Cytostatics may be preferable to hormones as the primary drug treatment for ovarian cancers but steroid-receptor determinations appear not to help in formulating the optimum drug treatment.

Adult↗
PubMed1984

Bioluminescence of cellular ATP: a new method for evaluating cytotoxic agents in vitro.

Rat Walker 256 carcinosarcoma, human MCF-7 cell line and a specimen of ovarian serous cystadenocarcinoma were cultured in vitro and exposed to different cytostatic drugs. The drug effects were evaluated by bioluminescence, i.e., by measuring the levels of adenosine triphosphate (ATP), the basic energy source of the living cells. The intracellular ATP was released by TCA or NRS -reagent, and the ATP levels were measured directly from an aliquot of the growth medium without any extraction or precipitation steps. ATP level was significantly correlated with cell number, viability, [3H]-thymidine incorporation and stem cell assay. The most important advantages of bioluminescence method was speed, technical simplicity and good sensitivity (about 500 cells/sample easily quantitated, the results are seen directly within a few seconds) and flexibility (any cell line and drug may be studied by many different test designs). ATP method obviously describes the "well- being" of the cultured cells. According to our experience, the ATP-bioluminescence method is a powerful alternative to any other cell growth estimation method in vitro. It can be used especially in primary screening of the cytostatic activity of any known or unknown substance as well as in attempts to select an individual drug therapy for patients with cancer.

Adenosine Triphosphate↗
PubMed1984

Use of atropine in connection with oral midazolam premedication.

The clinical significance of intramuscular premedication with 0.01 mg/kg of atropine in a procedure involving oral benzodiazepine premedication (15 mg midazolam the evening before surgery and on the morning of surgery) was investigated in a double-blind study. As far as sedation, apprehension, excitement, dizziness, emesis, and headache were concerned, there were no significant differences between group 1 (atropine) and group 2 (placebo) patients; however, both during and after anesthesia patients in group 1 had less excessive salivary secretion (especially during extubation). As a result of sympathetic overactivity, patients in group 1 had an increased heart rate and an increased incidence of supraventricular tachycardia. In group 1 intravenous infusion proved more difficult, and in addition, the patients complained more of subjective side effects (dry mouth). There was no significant correlation between the radioimmunologically measured serum concentrations and the clinical effects of atropine measured just before the induction of anesthesia. Substantial interindividual differences were found in these serum levels. From the anesthetist's viewpoint, atropine has both beneficial effects (antisecretory) and unwanted effects (cardiovascular effects). For the patient atropine caused only subjective unwanted effects. Midazolam, a new short-acting, sedative benzodiazepine derivatives, can be used without atropine as an oral premedicant.

Administration, Oral↗
PubMed1984

[Comparative study of the oral administration of flunitrazepam with oral pentobarbital and intramuscular administration of atropine and pethidine (meperidine) as premedication].

Thirty-four patients were allocated at random to treatment with 1 mg of flunitrazepam, orally, the night before operation, and 1 mg on the morning of operation (Group 1), and another 34 to treatment with 100 mg of pentobarbital, orally, the night before operation, followed by intramuscular atropine (0.01 mg/kg)+pethidine (meperidine 1 mg/kg) on the morning of operation (Group 2). The patients in both groups slept equally well. As far as apprehension and excitement (= anxiolytic effect) just before induction of anaesthesia were concerned, oral flunitrazepam proved to be markedly better than i.m. atropine+pethidine. There were no significant differences in cardiovascular variables between the two groups. From the anaesthesiologist's point of view, atropine had beneficial antisecretory effects, but, from the patients point of view, it caused only a subjective unwanted effect (dry mouth). In our opinion, oral flunitrazepam is a useful alternative agent for routine premedication. However, when used without i.m. atropine, excessive salivary secretion in some patients may occur and be disturbing, especially during extubation.

Administration, Oral↗
PubMed1983

Optimising mitomycin C activity during intravesical instillation.

Walker 256 carcinosarcoma was shown to be sensitive to mitomycin C in vitro. In order to make practical recommendations for the clinical intravesical use of mitomycin C, this cell line was used to evaluate the activity of mitomycin C under different conditions. Mitomycin C loses its antitumour activity rapidly at pH's below 6. At higher pH's (up to 10) mitomycin C is stable and suitable for intravesical application. To secure a sufficiently high pH in the bladder during intravesical treatment, phosphate buffer 0.05 M with a pH of 7.4 is recommended. Constituents of urine very little decrease the activity of buffered mitomycin C during a 2 h application. Prednisolone, which has been suggested to prevent the harmful chemical cystitis, has no inhibitory effect on the activity of mitomycin C.

Animals↗
PubMed1983

Placental transfer and maternal midazolam kinetics.

Midazolam was given in a single 15-mg oral dose as a sedative the evening before elective cesarean section. Twelve hours later, levels of this new benzodiazepine were measureable in the fetomaternal entity in only one of 13 cases. After 15 mg midazolam orally or 0.05 mg/kg midazolam intramuscularly 15 to 60 min before elective cesarean section, there was evident transfer of drug into the placenta, but transfer took place more slowly than with diazepam. On the basis of kinetics derived from maternal serum concentrations after oral, intramuscular, or intravenous dosing, midazolam appears to have a rapid onset and short duration of action, which was also evident from subjective assessments by the patients. There was wide interindividual variation in the gastrointestinal absorption of midazolam in full-term pregnant women. Clinically, midazolam nevertheless seemed to be very useful for nocturnal sedation before elective cesarean section; it ensures a mean duration of sleep of about 6 hr and there are virtually no detectable levels of drug in the fetomaternal entity the next morning.

Adolescent↗
PubMed1983

Antidiuretic hormone concentrations following midazolam premedication.

Midazolam given orally the night before and on the morning of operation had a distinct subjective pre-operative sedative effect as compared with placebo. Patients receiving midazolam also experienced less apprehension and excitement before surgery, but in relation to quality of sleep, the difference between the two groups was not statistically significant. Antidiuretic hormone (ADH) concentrations were determined just before induction of anaesthesia and were significantly lower in the midazolam group (2.14 pg/ml, SD 0.96) than in the placebo group (3.07 pg/ml, SD 1.73). Our results show that midazolam is a useful sedative anxiolytic oral premedicant, which appears to prevent initiation of a stress reaction before induction of anaesthesia.

Anti-Anxiety Agents↗
PubMed1983

Effects of alpha and gamma interferons and cytostatics on ovarian cancer in the subrenal capsule assay.

Ovarian cancers from seven patients were grown in the subrenal capsule assay for 6 days in normal mice and for 12 days in nude mice. Groups of 5 mice received the following daily treatments: 1) saline 2) 6 x 10(5)IU of human leukocyte interferon (IFN-alpha) 3) 3 x 10(3)U of human IFN-gamma 4) 6 x 10(5)IU of IFN-alpha and 3 x 10(3)U of IFN-gamma 5) cytostatic drug combination (doxorubicin, cyclophosphamide, cis-platinum). The cytostatic drug combination had stronger antitumor activity than the interferons. The combination of alpha and gamma interferons was more effective than either interferons alone. The same trend was seen both in normal and nude mice.

Aged↗
PubMed1982

The effect of antidiuretic hormone, indomethacin and naproxen on prostaglandin synthesis of experimentally infected and healthy kidneys.

The authors studied the effect of indomethacin and naproxen on the changes of renal prostaglandin E and F2 alpha concentration in experimental kidney infection, as well as the action of arginine-vasopressin in healthy rats. Naproxen proved to be an effective inhibitor of prostaglandin synthesis, as did indomethacin. In control animals an increased prostaglandin E and F2 alpha synthesis was observed caused by arginine vasopressin. It is supposed that ADH--depending on its concentration--has a metabolic modulator role in prostaglandin synthesis, which raises the possibility of a self-regulatory mechanism of water reabsorption.

Animals↗