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Biomedical subjects

K Moser

Publications and source records attributed to K Moser.

At least 19 recordsLinked to original sources

Instability of the anticancer agent etoposide under in vitro culture conditions.

Degradation of etoposide is rapid under in vitro culture conditions. At pH 7.4 and 37 degrees C, the isomerisation of trans-etoposide to the inactive compound cis-etoposide has a half-life of 2 days in Dulbecco's modified Eagle's medium and results in the loss of 90% of the active drug within 1 week. As a consequence, prolonged incubations with etoposide in in vitro assays may lead to erroneous interpretations ignoring the real in vitro situation. The degradation is not influenced by organic compounds such as bovine serum albumin or amino acids but depends strongly on the pH value and, to a lesser degree, on the ionic strength of the medium. Therefore, we propose a mathematical correction based on the pH value so as to obtain the real exposure of cells to trans-etoposide during in vitro assays.

Cells, Cultured

Mucin-like cancer-associated antigen (MCA) compared with CA 15-3 in advanced breast cancer.

Mucin-like cancer-associated antigen (MCA), a new tumor marker using the mouse monoclonal antibody b-12 is thought to be of value in the management of patients with breast cancer. In this study sera from 191 female patients with breast cancer (112 with progressive disease [PD] and 79 with no evidence of disease [NED]) were analyzed for MCA levels and compared with those of cancer antigen 15-3 (CA 15-3) in single determination and in combination with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). A cut-off level of 14 U/ml for MCA seems to be more appropriate than the recommended 11 U/ml to distinguish between PD and NED in patients with breast cancer. Although there was a fairly good correlation of MCA to CA 15-3, MCA was inferior in sensitivity and specificity to CA 15-3. Patients with osseous metastases and those with more than one metastatic site showed higher MCA levels than patients with visceral or soft tissue metastases, a fact which was comparable to CA 15-3. Combining MCA and CA 15-3 resulted in a gain in specificity but marked loss of sensitivity. The combination of MCA and CEA results also in a loss of sensitivity whereas the combination of CA 15-3 and CEA showed an increased specificity and only a negligible loss of sensitivity. The combination of MCA with TPA is of little value in the follow-up of breast cancer, as is the combination of CA 15-3 with TPA. The combination of CA 15-3 with CEA can be still recommended for follow-up for early detection of metastases in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The clinical course of lung metastases from breast cancer.

The clinical course of 50 breast cancer patients whose first metastases were found in the lungs was investigated. 18 months after the start of primary treatment 50% of the patients had developed pulmonary metastases (range: 0-81 months). In 23% of patients a solitary, and in 68% more than one, lung metastases were detected. After a median time of 4 months, in 56% of patients the disease had spread to further organs with bone (25%) and liver (17%) being the most frequent sites. First line management of lung metastases employed surgery, endocrine treatment, chemotherapy or a combination of these modalities. In 24% of patients a complete response was achieved, and in 11% a partial response, with an overall response rate of 35%. Median survival from detection of lung metastases was 13 months (range 4-123+). Patients with only a solitary lung metastasis survived for a median of 11.5 months as compared to 10.5 months for patients with more than one pulmonary metastases. Patients with a disease-free interval of more than 18 months survived significantly longer than patients with a disease-free survival of 18 months or less.

Adult

Mortality in women in relation to their childbearing history.

With data from the Office of Population Censuses and Surveys' longitudinal study the mortality of currently married women aged under 60 in 1971 was investigated in relation to the number of liveborn children reported at the 1971 census, adjusting for their husbands' social class. Women who had never had children experienced a higher mortality from many causes of death than the parous women, and this was probably due, at least in part, to selective factors. When the analysis was confined to parous women mortality from diabetes mellitus and cervical cancer increased significantly and oesophageal cancer decreased significantly with increasing number of liveborn children. Mortality from all circulatory diseases and from hypertensive disease, ischaemic heart disease, and subarachnoid haemorrhage tended to rise with parity, though the trends were not statistically significant. Mortality from breast cancer decreased significantly with the number of liveborn children, but only when nullipara were included in the analyses. These data suggest that there may be residual and cumulative effects of childbearing which influence patterns of disease in the long term.

Adolescent

Toxicity and response to high-dose ifosfamide + mesna as salvage therapy for advanced breast cancer.

Twenty-six cycles of high-dose ifosfamide + mesna (HD-IFO + M) were applied to seven female patients with advanced breast cancer refractory to prior treatment, using three different durations of continuous infusion (4, 24, and 48 h) every 3 weeks. To evaluate the most tolerable time schedule, the duration of the infusions was changed periodically in each patient. Toxicity was low in general, but continuous infusion of HD-IFO + M over 24 h appeared to be the best tolerated. One partial response lasting 27 weeks was achieved and four patients achieved stable disease lasting from 9 to 12 weeks.

Adult

[Sports-related fractures of the facial skull in Austria].

Details of injuries to the maxillo-facial region have been collected over a five year period. 635 fractures in this region were registered resulting from 24 different sports. Soccer was found as the most dangerous individual sport. There is no absolute safe kind of sport but we suggest that the number of fractures depends too on a local factor.

Athletic Injuries

[Interferon alpha 2C in the treatment of 2 patients with AIDS-associated Kaposi sarcoma].

Two patients with AIDS and histologically confirmed Kaposi's sarcoma were treated with 3 X 10(6) U/m2 interferon alpha 2C (rIFN alpha 2C) subcutaneously three times a week. In both cases remissions (7 weeks and more than 9 months) of the tumour lesions were achieved and in one case pretherapeutic moderate thrombocytopenia improved. The positive serum antibody titres to HTLV III-virus showed no conversion. Except for fever (below 39 degrees C) during the first two weeks of IFN treatment in both patients, therapy-requiring hypotonia, mild depression, leucopenia (WHO grade 1) and thrombocytopenia (WHO grade 2) in one patient, no side effects were observed. All the above-mentioned features were reversible after termination of treatment. Further studies to optimize the dosage of rIFN alpha 2C and its time schedule in the treatment of Kaposi's sarcoma in patients with AIDS are recommended.

Acquired Immunodeficiency Syndrome

Possible adverse effect of failed adjuvant chemotherapy on the prognosis of women receiving consecutive chemotherapy for recurrent breast cancer.

This study tried to evaluate the impact of adjuvant chemotherapy on the induction of chemoresistance in radically operated upon breast cancer patients. Remission rate, remission duration and survival of a group of women (n = 22) treated with combination chemotherapy (adriamycin and cyclophosphamide, AC) for recurrent breast cancer after failed adjuvant therapy (cyclophosphamide, methotrexate, fluorouracil, vinblastine) were retrospectively compared with the clinical data of non-pre-treated patients (n = 28) receiving the same regimen (AC). The two groups of patients were comparable with regard to their risk factors. In the group of women with prior adjuvant chemotherapy only 3 out of 22 had a partial response, lasting 3, 8, and 16 months; the median survival was 50 months. In the group without prior adjuvant therapy 3 complete and 7 partial remissions with a median remission duration of 15.5 months (range 2-54 months) were found; the median survival was 104 months. The percentage of objective responses among the non-pre-treated patients at 36% was almost significantly higher than that of the pretreated women with 14% (p less than 0.1). Responders to chemotherapy after relapse profited in terms of survival within the first 3 years after radical mastectomy, although no statistically significant difference was observed. The survival data shown assume a "shifting" of women from a group with better prognosis to a group with unfavourable prognosis following failed adjuvant chemotherapy.

Antineoplastic Combined Chemotherapy Protocols

Coupling of mitoxantrone to poly(I).poly(C) reduces absorption after intraperitoneal administration.

Coupling of mitoxantrone (M), an intercalating cytostatic, to macromolecular polynucleotides may reduce side effects after direct intraperitoneal chemotherapy by interfering with systemic absorption of M. We have administered free M (30 mg/m2) or M mixed with poly(I).poly(C) (90 mg/m2) intraperitoneally to 5 patients with peritoneal carcinosis (cross-over study): peak plasma levels (HPLC assay) were 62 +/- 12 versus 28 +/- 4 ng/ml (p less than 0.0025), AUC0-24h were 583 +/- 126 versus 481 +/- 57 ng X h/ml (p less than 0.025). Coupling of M to poly(I).poly(C) seems to reduce M absorption after intraperitoneal administration.

Absorption

Pulmonary angiography in severe chronic pulmonary hypertension.

We have analyzed the safety of doing pulmonary angiography in 67 consecutive patients with moderate-to-severe primary pulmonary hypertension or hypertension secondary to chronic thromboembolic occlusions of the pulmonary arteries. The average (+/- SD) pulmonary arterial systolic and diastolic pressures were 74 +/- 19 and 34 +/- 10 mm Hg, respectively. Fourteen patients had a right ventricular end-diastolic pressure of 20 mm Hg or more. Selective left and right main pulmonary artery injections were done using ionic contrast agents in 56 patients and nonionic contrast agents in 11. No major rhythm disturbances or systemic hypotension requiring therapy occurred, and there were no deaths. Thrombotic occlusions of the pulmonary arteries were identified in 52 patients and confirmed in all 42 of those who had a thromboendarterectomy. At autopsy, 3 of the 15 patients who had normal angiograms were found not to have had thrombotic occlusions. We conclude that pulmonary angiography can be done safely despite the presence of severe pulmonary hypertension and right ventricular failure, and that the procedure leads to the identification of chronic, major-vessel thromboembolic pulmonary hypertension that may be alleviated by thromboendarterectomy.

Adolescent

Assessment of the human tumor cloning assay for urologic malignancies with special emphasis on bladder cancer.

Specimens of different urologic malignancies such as cancer of the bladder, renal pelvis, prostate, testis and renal cell carcinomas were sent to our laboratory for cultivation with the clonogenic assay. Of the 62 samples--biopsies, bladder barbotages and effusions--48% were considered to be evaluable; the others had to be excluded from evaluation because of negative histologic/cytologic findings, insufficient cell viability, inadequate tumor material, or contamination. All test procedures were done using a slightly modified human tumor cloning assay originally described by Hamburger and Salmon [Science 197: 461-463, 1977]. Overall growth was seen in about one third of all tumors cultivated; the mean colony count being 13 +/- 8, the mean cloning efficiency 0.0026%. About one third of bladder cancer specimens and half of the renal cell carcinomas showed colony growth. No correlation between tumor stage or grade and the overall colony growth rate in vitro was seen. Furthermore, it was impossible to correlate the growth rate in vitro and the overall survival of the patients included in the study.

Biopsy

Long-term effects of nitrendipine on hemodynamics and oxygen transport in patients with cor pulmonale.

Recent studies have suggested that vasodilators may acutely improve pulmonary hemodynamics in patients with chronic obstructive pulmonary disease and cor pulmonale, but the effects of long-term therapy have not been assessed. We evaluated the hemodynamic and gas exchange effects of nitrendipine, a calcium channel blocker with a cardiovascular profile similar to nifedipine, acutely and after five days and six weeks of therapy in eight patients with stable COPD and cor pulmonale. After six weeks, nitrendipine significantly decreased both mean pulmonary artery pressure (40.4 +/- 10.3 to 31.2 +/- 6.6 mm Hg, p less than 0.01) and pulmonary vascular resistance (6.8 +/- 3.9 to 3.0 +/- 1.1 units, p less than 0.01), while cardiac index increased (2.4 +/- 0.8 to 3.6 +/- 1.0 L/min/m2, p less than 0.001). Despite a fall in arterial PO2 (53.1 +/- 18.7 to 45.5 +/- 11.3 mm Hg, p = NS), systemic oxygen transport increased by over 30 percent (843 +/- 284 to 1,111 +/- 373 ml/min, p less than 0.05). Systemic arterial pressure, pulmonary capillary wedge pressure, and heart rate were unchanged. Despite these hemodynamic changes, three patients died from complications of their underlying disease while receiving long-term therapy after eight, nine, and ten months. These preliminary findings suggest that long-term vasodilator therapy can result in persistent hemodynamic improvement in some patients with cor pulmonale secondary to COPD, although the impact of this form of therapy on survival remains to be clarified.

Aged

The human tumour cloning assay in the management of breast cancer patients.

A tumour cloning system was used to cultivate breast cancer specimens. Fifty-six percent of 87 samples were adequate for evaluation, showing clonal growth in about one third (35%). Effusions yielded significantly better growth than solid specimens, the median colony numbers being 64 and 18 respectively. An attempt was made to examine whether there was any association between parameters accepted as prognostic factors for breast cancer and clonal growth in vitro. No correlation was found between preoperative tumour burden, histopathologic grading, menopausal status or overall survival and clonal growth in vitro, whereas we observed an inverse trend between progesterone receptor content of the tumours and their growth potential (P less than 0.01). In those few cases where in vitro and in vivo data could be compared, a high accuracy of the predicted sensitivities was found with respect to chemotherapy, but not in relation to hormonal treatment. A statistically significant higher overall chemosensitivity was associated with the absence of oestrogen receptors (P less than 0.01).

Breast Neoplasms

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.

Biopsy