Integration of the social and behavioral sciences into the core medicine clerkship.
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Adult↗
Biomedical subjects
K Moser
Publications and source records attributed to K Moser.
Carcinoembryonic antigen (CEA) plasma level determination in the management of gastric cancer patients.
Carcinoembryonic antigen (CEA) levels of 161 patients with gastric cancer and of 12 patients with noncarcinomatous diseases of the stomach were retrospectively analyzed. In this study, we examined the correlation between CEA level and histologic type, T and N stage, and the value of the preoperative CEA determination for diagnosis, operability and prognosis for patients with gastric cancer. Summarizing our results: There exist significant higher CEA levels in patients with gastric cancer in comparison with patients with noncarcinomatous disease of the stomach (p less than 0.01), but the absolute CEA titer is not a reliable parameter for the prediction of the existence or absence of gastric cancer for the individual patient. A positive correlation between the CEA level and the histologic type in the subgroup of radically operable patients was found, the intestinal type having lower titers (p less than 0.05). The operability of two different histologic entities (diffuse or intestinal type) was equally high. No conclusion can be drawn from CEA plasma levels concerning the operability of the individual gastric cancer patient; on one hand, 30% of the patients with normal preoperative CEA titers could not be radically operated, whereas 34% of the patients with elevated preoperative CEA titers (greater than 5.0 ng/ml) had radical surgery. Furthermore, the absolute value of the preoperative CEA level does not predict the course of the disease, whereas continuously rising postoperative CEA levels are indicative of tumor progression.
Aged↗
[Surgical therapy of breast cancer: to operate radically or to preserve the breast?].
Surgical treatment, i.e. partial resection (R) versus modified radical mastectomy (M) in lymph node negative T1/2 patients and M versus the classical Halsted procedure (RM) in lymph node positive cases, as well as adjuvant treatment forms, namely chemotherapy (B) and chemoimmunotherapy (C) versus a control group treated by surgery only (A) have been evaluated in 241 patients with breast cancer follow up over a median observation time of 48 months. Whereas M showed significantly better results than R, no difference was detected between M and RM. The incidence of recurrence in the R group did not appear to be markedly reduced by cytotoxic treatment. In the same way, the data from a retrospective study on non-randomized patients treated by breast resection, showed a relatively high local recurrence rate (23.6%) at a median observation level of 10 years. Considering the various forms of surgical treatment for operable breast cancer by analysing the data from retrospective studies and prospective randomized trials from the literature as well as our own results, the only recommendation for the standard treatment of patients with primary operable breast cancer should be nothing less than modified radical mastectomy. Breast-conserving treatment forms should be tested only within the framework of controlled clinical trials.
Breast Neoplasms↗
[Glucose-6-phosphate dehydrogenase deficiency and other erythrocyte enzyme abnormalities].
Normal values of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glucosephosphate isomerase (GPI), pyruvate kinase (PK) and pyrimidine 5'-nucleotidase (P5N) have been determined in normocytes, reticulocytes, newborn cord erythrocytes, and leucocytes. Metabolic and clinical aspects of G6PD and the classification of its genetic variants are reviewed. Enzyme determinations and their variation in drug-induced haemolysis are critically presented. Extensive tables are published listing the drugs and compounds that can cause haemolysis in G6PD-deficient patients, as well as those preparations which may, probably, be administered safely. Clinical and biochemical data in patients with the inherited enzyme defects GR, GPI, PK, and P5N, as well as acquired deficiency of the last-mentioned in chronic lead intoxication, are reviewed in the light of our personal experience in this field.
5'-Nucleotidase↗
[Clinical experiences with high-dose methotrexate].
40 patients with various forms of malignant disease, who had already been subjected to conventional regimens of treatment, were treated between 1976 and 1981 at the Department of Chemotherapy, Vienna University, with high-dose methotrexate (MTX) as sole therapeutic agent. 18 patients received MTX in moderately high doses of 250 mg/m2 to 750 mg/m2 at 10-day intervals. 19 patients were treated with high doses of 5 to 15 g MTX at 10-day intervals. In 2 cases of severe malignant non-Hodgkin's lymphoma one patient received 2 X 1 g MTX with an interval of 19 days between doses and the other received a single dose of 5 g MTX by infusion. One patient with alveolar soft part cell sarcoma was given ultra-high therapy, with a cumulative dose of 205 g. None of the patients in the group given moderately high-dose MTX therapy, whereas three in the high-dose group had an objective remission. Objective remission was obtained neither in the two lymphoma patients nor in the ultra-high-dose treated case. Complications such as leucopenia and/or thrombopenia were found in 9%, reversible transaminase activity increases in 45%, as well as a decrease in creatinine clearance in 10% of the cases. Irreversible severe kidney insufficiency was found in none of the cases. One patient with lymphoma died as a result of severe toxic epidermiolysis with involvement of the gastrointestinal mucosa, whilst the other suffered from pulmonary complications in the form of the respiratory distress syndrome. On the basis of our experience the use of high-dose MTX therapy as an alternative method following trials of all conventional regimens is not recommended.
Female↗
[Analgesic effect of tramadol in patients with malignant diseases].
The new synthetic opioid Tramadol [1-(m-Methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexane-1-ol] was examined in 30 patients with different malignant diseases. An excellent or sufficient pain relief could be found in 86%. Only 14% of all patients did not respond. The analgetic effect throughout the day could be observed in most cases (92%) after the application of maximally 200 mg/die. Optimal or moderate subjective tolerance was found in 95% of all cases. Fatigue (65.8%), dryness of the mouth (68.4%), dizziness (14.3%) and perspiration (12.2%) were the main side effects. For this reason Tramadol can be recommended as a highly useful analgesic drug in the treatment of tumor induced pain.
Adult↗
[Mitoxantrone in the primary treatment of metastasizing breast cancer].
25 females (57.7 +/- 11.1 years) and 1 male (71 years) with histologically verified metastasizing breast cancer were submitted to mitoxantrone therapy. Secondary tumours were found in following organ systems: bone: 19 cases; lung: 13 cases; liver: 6 cases; skin: 5 cases; locoregional and nodal: 5 cases; brain: 1 case. All patients showed normal bone marrow and heart function before commencement of treatment. Mitoxantrone was given in form of a 30-minute infusion at a dosage of 14 mg/m2. In 4 patients dosage was increased to 20 mg/m2. Treatment cycles were repeated every 3 weeks according to peripheral blood counts. All patients were cardiologically monitored throughout the study by means of electrocardiogram, systolic time interval measurement and radionuclide angiography. The mean observation period was 169 +/- 98 days. The response of the patients was as follows: 1 complete remission, 5 partial remissions, 4 unchanged disease and 16 progressive disease. Side effects were normally mild; only nausea, leucopenia and moderate hair loss were of clinical relevance. Cardiac decompensation was not observed. No significant electrocardiographic alterations were found throughout the study. Results of systolic time interval measurements (PEPI, PEP:LVET) and radionuclide angiography (LVEF) gave evidence of moderate depression of heart function. In view of the optimal benefit/risk ratio of mitoxantrone this drug could be used in combined modality treatment schedules in metastasizing breast cancer.
Aged↗
[Monitoring of cardiac function during doxorubicin therapy in metastasized breast cancer. Measuring systolic time interval].
Assessment of systolic time interval represents an uncomplicated, sufficiently precise and cheap possibility in clinical practice of cardiac monitoring during treatment with doxorubicin (adriamycin) if the ratio between pre-ejection period interval (PEPI) and left ventricular ejection time interval (LVETI) ("Weissler index") for evaluation of left ventricular cardiac function is used. In an investigation of 352 female patients with metastatic carcinoma of the breast statistically ascertained dose-response relationships could be established as regards electrocardiographic disorders of repolarisation and the systolic time interval (P less than 0.001). Pre-irradiated patients showed more ECG changes (P less than 0.001) and higher PEPI : LVETI values (P less than 0.001) than patients without prior irradiation. There was no general influence of cytostatic treatment on systolic and diastolic blood pressure values. The upper limit of a therapeutic risk in evaluation of the systolic time interval for cardiac monitoring of doxorubicin treatment should be 0.45-0.50 for PEPI : LVETI. Above this borderline value precise cardiac evaluation including invasive methods should be attempted if continuation of treatment is indicated. This regime could help prevent the occurrence of life-threatening cardiac crises during treatment with doxorubicin.
Breast Neoplasms↗
[Preventable side effects of chemotherapy].
During the last years antineoplastic chemotherapy provided the possibility to cure many patients suffering from a malignant tumor and to improve their quality of life. Like every powerful remedy cytostatic drugs show side effects, which must be taken into consideration. Advantages and risks of cancer chemotherapy have to be considered carefully in each individual treatment schedule. The definition of the upper limit of therapeutic risk for each individual patient in order to avoid life-threatening situations is of principal importance. This can be accomplished by introduction of methods which can measure actual functional conditions and by the definition of a threshold-level in order to establish contraindication. Paul Ehrlich introduced the term "therapeutic index" in antibacterial chemotherapy. This term should express the ratio between risk and benefit of a drug and its application in the still very young field of antineoplastic chemotherapy should be considered. Since every treatment of a patient with cytostatic drugs represents a very significant interference with the patient's life, very strict indication- and and contraindication-criteria have to be applied.
Alopecia↗
[Pharmacokinetics and acute signs of cardiac toxicity during doxorubicin therapy].
Doxorubicin (Adriamycin) has shown impressive activity in the treatment of a broad spectrum of malignant tumours. Chronic irreversible cardiac myopathy is the usual cumulative dose-limiting toxicity with this anthracycline antibiotic. In this study acute cardiac reactions following doxorubicin infusions (60 mg/m2) were registered by means of ECG Holter monitoring and measurement of systolic time intervals. The PEPI as well as the PEP/LVET ratio were found to be significantly increased, with a peak at 6 hours following drug infusion (p less than 0.001). This observation proves the occurrence of transient myocardial dysfunction during doxorubicin treatment. Pharmacokinetic data showed good correlation between the electrocardiographic changes and the tissue distribution of the drug. Doxorubicin-related ventricular arrhythmias were observed in only 2 out of 6 cases. Repeated acute myocardial damage by doxorubicin infusions is considered to be the cause of chronic cardiomyopathy with long-term administration.
Adult↗
Indication of reduced doxorubicin-induced cardiac toxicity by additional treatment with antioxidative substances.
The influence of antioxidative substances on doxorubicin-induced cardiac toxicity was studied in C 57 BL mice. Tocopherol (500 mg/kg), glutathione (1000 mg/kg), cysteamine (15 mg/kg) and L-cysteine (1000 mg/kg), injected i.p. 24 h before doxorubicin treatment (15 mg/kg i.p.) were able to reduce malonaldehyde production in cardiac tissues significantly. SH-containing substances with high reducing activity, such as vitamin E, could be a useful tool in clinical trials to prevent doxorubicin induced cardiac damage.
Animals↗
Noninvasive methods for the early detection of doxorubicin-induced cardiomyopathy.
Ninety-eight female patients (mean age 54 years) who underwent doxorubicin therapy because of metastatic breast cancer were submitted to radionuclide angiography at rest. Left ventricular ejection fractions (LVEFs) were found to decrease significantly with the increasing cumulative doxorubicin dosage. Patients with prior local radiotherapy showed lower LVEFs at the same dosage level than nonirradiated patients, but the difference was not statistically significant. In a further study, 52 patients (mean age 56 years) were followed up regularly for their history and systolic time intervals prior to each doxorubicin treatment course. Before starting treatment, LVEF values were normal in all cases. Fifteen of these patients complained of dyspnea at some time during the treatment period before the critical cumulative dosage level of 550 mg/m2 was reached. Nine of these 15 patients showed an increase of the PEPI:LVETI ratio (greater than or equal to 0.40) and 12 patients a decrease of the LVEF values at rest at the same time. The rest of the patients did not complain of cardiac symptoms and did not show any significant alterations in systolic-time-interval measurements until the borderline dosage level (550 mg/m2) was attained. To evaluate myocardial function with greater accuracy, these 15 patients were submitted to right-heart catheterization and radionuclide angiography at rest and during exercise. As a result, doxorubicin treatment had to be discontinued in three of these patients because of heart failure of stage III or IV and treatment with methyl digoxin and nifedipine was started. In these three patients cardiotonic medication could produce more or less complete cardiac recompensation. We conclude from our findings that signs of stage-III heart failure in radionuclide angiography performed while the patient is at rest and exercising should be regarded as the upper limit of the therapeutic risk, where further doxorubicin treatment is contraindicated. Cardiotonic medication during cytostatic courses should be avoided, however, because the true functional condition of the myocardium could be masked during a potentially cardiotoxic therapy.
Adult↗
Acute cardiac toxicity in patients after doxorubicin treatment and the effect of combined tocopherol and nifedipine pretreatment.
In two groups of female patients with metastatic breast cancer who had all been pretreated with doxorubicin (350 mg/m2), acute cardiac effects following i.v. doxorubicin bolus injection (60 mg/m2) were recorded on the basis of systolic time intervals (STI). In six patients who received doxorubicin only the ratio between the heart-beat-corrected preejection period and left ventricular ejection time (PEPI:LVETI) as well as the PEP index were found to be significantly increased with a peak at 6 h following drug infusion (P less than 0.001). Another six patients received an identical chemotherapeutic regimen and, in addition, a combination of tocopherol (200 mg i.m. 6 h before treatment) and nifedipine (60 mg p.o. daily from 2 days before doxorubicin infusion). In the pretreatment group, the PEPI:LVETI ration and PEP index remained unchanged during the posttreatment period. Pharmacokinetic analysis of drug concentrations in the plasma revealed a significantly accelerated distribution and elimination of doxorubicin after combined tocopherol and nifedipine pretreatment, although no statistically significant differences could be found in calculated drug levels in the peripheral compartment between both treatment groups. Our results indicate that acute cardiac reactions reflected by changes in STI values can be prevented by combined tocopherol and nifedipine pretreatment.
Adult↗
Restrictive ventilatory pattern in precapillary pulmonary hypertension.
Patients with precapillary pulmonary hypertension (PPH) have classically been reported to have normal pulmonary mechanical function. We reviewed spirometric data from 8 patients with primary pulmonary hypertension and from 17 patients with chronic thromboembolic pulmonary hypertension. All patients had undergone right heart catheterization and pulmonary angiography. Five of the 8 patients with primary pulmonary hypertension demonstrated a severe restrictive ventilatory pattern with a mean vital capacity (VC) of 50.4% predicted and a mean total lung capacity (TLC) of 64.3% predicted. Five of the 17 patients with chronic thromboembolic pulmonary hypertension manifested a restrictive pattern with a mean VC of 68.0% predicted and a mean TLC of 75.3% predicted. We conclude that restrictive ventilatory defects occur more frequently than previously described in patients with PPH. The physiologic mechanism responsible for the restrictive ventilatory pattern is not clear.
Adult↗
[Hepatic tumors].
In this paper aspects concerning epidemiology, pathophysiology, laboratory diagnosis and treatment modalities of primary hepatomas and secondary tumors of the liver are discussed. As results obtained with conventional chemotherapy are unsatisfying special emphasis is put on the new therapeutic methods of intraarterial and intravenous cytostatic perfusion via hepatic artery and portal vein respectively. Additionally our own clinical and laboratory datas are presented.
Angiography↗
[Pilot studies with aclacinomycin in patients with breast cancer or gastrointestinal tumors].
Aclacinomycin (ACM), a new anthracycline antibiotic compound, was given intravenously q x 3 to 6 weeks in a dosage of 4 x 60 mg/4 days to 10 patients with metastasizing breast cancer and 5 patients with gastric carcinoma. Breast cancer patients, prior to ACM had extensive cytotoxic and hormonal treatments, gastric cancer patients received ACM as a first chemotherapeutic tumor treatment. No life-threatening hematologic toxicities could be noticed. All patients experienced moderate to severe gastrointestinal toxicities. No patient had considerable hair loss. 4 patients showed clinical signs of cardiac dysfunction: 1 ECG changes, 4 developed edema of lower extremities, 2 developed pericardial effusion. Moreover, 1 patient developed significant elevation of the pulmonary capillary wedge pressure (PCW) and prolongation of the systolic time intervals indicating pulmonary congestion grade I to II (Braunwald). No significant increase in heart volume was registered. Clear signs of cardiotoxicity could be demonstrated in patients pretreated with adriamycin exclusively. In animal experience, ACM had been reported as less cardiotoxic as compared to adriamycin. Present studies seem to indicate ACM being considerably cardiotoxic at relatively low cumulative dosages. Among the 15 patients there was one with metastatic breast cancer pretreated with adriamycin and resistant to that drug in whom partial remission was achieved. The other patients did not objectively respond to ACM therapy. 3 out of 5 patients with gastric cancer had stabilisation of the disease but no objective response.
Aclarubicin↗
Clinical and experimental aspects of hormone receptors in breast carcinoma patients.
Estrogen (ER) and progesterone (PgR) receptor contents were determined in 214 patients with primary mammary carcinoma. Premenopausal and postmenopausal females (43 and 48%, respectively) were found to be ER and PgR positive. ER levels between 100 and 500 fmol/mg protein were observed in 37% postmenopausal and 14% premenopausal patients, respectively. ER distribution between lymph node-positive and -negative patients did not differ significantly. Subjects without detectable ER had recurrences earlier than did subjects with ER. On the other hand, no differences in recurrence rates were noted when PgR-positive and -negative patients were compared. In addition, the determination of ER did not permit selection of patients for adjuvant cytotoxic chemotherapy. Furthermore, the action of tamoxifen was investigated in the rat pituitary as a model system. Tamoxifen was found to act as antiestrogen at the level of transcription by inhibiting the accumulation of estrogen-stimulated preprolactin mRNA. Combined data suggest that patients with positive lymph nodes and positive receptors may benefit from combined endocrine plus cytotoxic adjuvant chemotherapy.
Animals↗
[Recent developments in chemotherapy of malignant diseases].
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Anthraquinones↗