Biomedical subjects

R Lenzhofer

Publications and source records attributed to R Lenzhofer.

At least 37 records · Page 2Linked to original sources

PubMed1984

[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↗

PubMed1983

[Significance of laboratory chemical parameters for the detection of metastases in breast cancer].

The diagnostic value of 7 laboratory parameters for the detection of metastases was investigated in 136 patients with verified breast carcinoma after mastectomy. The post-operative interval was 6 to 80 months (means = 27.5). 61 patients had multiple metastases as determined by physical examination, X-rays, computertomography, sonographic and scan procedures, while the other 75 patients had no evidence of metastases. Carcinoembryonic antigen (CEA), alkaline phosphatase (AP) and lactate dehydrogenase (LDH) proved to be reliable parameters for the presence of metastases; the combination of these 3 parameters had a sensitivity of 73.0% and a specificity of 94.7% in the detection of metastases. The additional determination of gamma-glutamyltranspeptidase (gamma-GT), blood sedimentation rate (BSR), C-reactive protein (CRP) and serum iron (Fe) increased the sensitivity of metastases detection to 83.8%, but the specificity decreased to 46.2%.

Adult↗

PubMed1983

[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↗

PubMed1983

Plasmapheresis in the treatment of myasthenia gravis.

Between 1978 and 1980, 10 patients with myasthenia gravis underwent treatment by plasmapheresis. Of these, 7 responded to plasma exchange. Pre- and post-exchange anti-acetylcholine receptor antibody concentrations were found to be a useful parameter for intraindividual comparisons, but failed to correlate with the stage of the disease. Anti-acetylcholine receptor antibody assays cannot be replaced by determinations of IgG and globulin concentrations. In view of the potential risks and of the high cost factor, plasmapheresis should be reserved for particularly severe cases for obtaining transient clinical improvement in life threatening situations.

Adult↗

PubMed1983

[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↗

PubMed1983

[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↗

PubMed1983

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↗

PubMed1983

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↗

PubMed1983

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↗

PubMed1983

[Selective toxicity of cytostatic agents: studies on the cardiotoxicity of doxorubicin, its pathogenesis and contraindications].

In the past few years the medical treatment of malignant diseases has steadily increased in scope and importance. However, the tumor regimens described in the textbooks still are rather schematic recommendations, which are inadequately tailored to the needs of the individual case. Current tumor therapy is based on the results of the statistical analysis using empirical data collected in randomized trials. While patients can today be given a statistical value which expresses their computed chance of a cure versus that of a defined population, there is still no generally valid method which could serve as a rational basis for individualized counselling. But cytostatic chemotherapy has yet another major shortcoming: the collective assessment of toxicity, which is related to one of the basic properties of cytostatic drugs, i.e. their extremely low therapeutic index. Many of the side effects of cytostatics may cause severe irreversible, at times even fatal, organ dysfunction. Consequently, the definition of the therapeutic risks involved on the basis of an objective identification of potential organ toxicity is a major challenge. "Surgery without a knife", as K.H. Spitzy has called chemotherapy, should be subjected to objective criteria for its indications and contraindications so that patients can truly benefit from what are become increasingly aggressive measures. The principle of weighing the benefits desired in the individual case against the potential risks involved in a specific treatment, which Paul Ehrlich postulated for antibacterial chemotherapy, should also be applied to cytostatic chemotherapy with a view to facilitating the decision for or against therapy in borderline cases. The present contribution which is designed to shed light on the cardiotoxicity of doxorubicin should be interpreted in light of this situation. Pathogenetic aspects and animal experiments on drug-induced lipid peroxidation will be discussed and clinical trials on both acute and chronic doxorubicin cardiotoxicity will be reviewed. Special attention will be paid to the tolerable risks of this special form of toxicity and cardiologic methods currently available for patient monitoring will be critically assessed. In summary, the studies produced the following results: A. Pathogenesis Treatment of C 57 B1 mice with doxorubicin increases the production of malonic dialdehyde in the myocardium. Enhanced malonic dialdehyde production can largely be suppressed by the additional administration of anti-oxidants (tocopherol, glutathione, cysteamine, cysteine).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗

PubMed1983

[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↗

PubMed1983

[Doxorubicin-induced cardiomyopathy: hemodynamic studies for evaluating the limit of therapeutic risk].

To evaluate the therapeutic risk of doxorubicin therapy in terms of drug-induced cardiomyopathy, 75 female patients with metastasizing breast cancer (mean age: 60 +/- 7 years) were submitted to right heart catheterization at rest and on exercise: 37 of these patients underwent postoperative adjuvant radiotherapy; 38 patients were not pretreated. The hemodynamic profile of these patients was compared to that of eight healthy volunteers. Prior to doxorubicin therapy irradiated patients showed myocardial dysfunction characterized by significantly elevated pulmonary wedge pressures (PCP) on exercise (p less than 0.005). In the course of doxorubicin therapy a significant decrease in myocardial function could be observed at 500 mg/m2 cumulative dose in irradiated patients (p less than 0.05) and at 600 mg/m2 in non-irradiated patients (p less than 0.001). According to the hemodynamic classification of Reindell and Roskamm, after reaching a cumulative doxorubicin dose of less than 300 mg/m2, previously irradiated breast cancer patients showed a risk of developing stage III heart failure equal to that shown by nonirradiated patients after 400-500 mg/m2. It may be concluded that adjuvant radiotherapy can produce myocardial damage. Irradiated patients show a higher risk of developing doxorubicin-induced cardiomyopathy than nonirradiated patients. The limit of therapeutic risk should be established at stage III heart failure because cardiac failure can still be improved by treatment involving glycosides and a vasodilator.

Aged↗

PubMed1982

[Gluten-sensitive enteropathy and intestinal non-Hodgkin lymphoma (author's transl)].

The case report is presented of a patient with gluten sensitive enteropathy who subsequently developed an intestinal non-Hodgkin lymphoma. When steatorrhoea or diarrhoea develops in a patient with abdominal lymphoma, these symptoms are often attributed to progression of the lymphoma or to chemotherapy of the lymphoma. Since there is an established relationship between gluten-sensitive enteropathy and intestinal lymphoma, the differential diagnosis of steatorrhoea or diarrhoea developing in the course of malignant intestinal lymphoma must include gluten-sensitive enteropathy as well. In the investigation for gluten-sensitive enteropathy HLA typing can be used as a screening test in addition to routine malabsorption tests and small bowel biopsy

Adult↗

PubMed1982

Natural killer cell activity in patients with multiple sclerosis: interferon and plasmapheresis.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) were studied for natural killer (NK) cell activity and reactivity to interferon. NK activity determined at the same time in a 4-hr chromium-51 release assay using K562 target cells was significantly lower in MS patients than in controls. In-vitro treatment of MS lymphocytes with interferon resulted in only a slight increase in NK activity, while NK activity of normal individuals was markedly augmented by interferon. Leukopheresis of MS patients gave a rapid decrease in cytotoxic activity, which returned to pretreatment levels by 24 hrs. These results are consistent with the hypothesis of an immune deficit in multiple sclerosis.

Adult↗

PubMed1982

Duration of the hypotensive effect of guanfacine.

Guanfacine given intravenously causes a brief rise in blood pressure. This is followed by a sustained decrease of blood pressure, accompanied in one case by a marked orthostatic effect. In addition to its lowering effect on blood pressure, guanfacine also reduces heart rate. The duration of action for up to 72 h is due to the long half-life of the drug. The main side effects observed are fatigue and sedation.

Adult↗

PubMed1982

[Diagnosis of colitis in Behçet's syndrome (author's transl)].

A case report is given of a patient with Behçet's syndrome presenting with relapsing diarrhea and genital ulcers; similar cases from the literature are discussed. Neither the radiological nor the colonoscopic symptoms are typical in Behçet's syndrome and thus do not allow differentiating it from other forms of colitis. For that reason all forms of colitis accompanied by extraintestinal lesions, especially genital ulceration, should give rise to the suspicion of Behçet's syndrome.

Adult↗

PubMed1981

[Case report of a patient with intermittent fever, leucopenia and terminal fungal sepsis (author's transl)].

A fatal case of disseminated candidiasis with deep organ involvement is reported. The patient was employed as a radiologist for several decades and already showed X-ray-induced bone marrow damage at the onset of the disease. He suffered for several years from an unknown granulomatous systemic bacterial infection and had been treated with antimicrobial agents with varying degrees of success. Regarding prophylaxis of systemic Candida infections it is concluded that prolonged medication with glucocorticoids and antibiotics should be combined with the oral administration of antimycotic drugs in order to prevent invasion by potentially pathogenic fungi.

Anti-Bacterial Agents↗

PubMed1981

Failure of somatostatin to influence experimental tumor cell growth in vivo and in vitro.

The influence of somatostatin on tumor cell growth was studied in vivo in mice (sarcoma 180 ascites tumor and Lewis lung tumor) and in vitro on nontransformed and polyoma-transformed cell lines. 4 or 20 micrograms/100 g of cyclic somatostatin and 4 micrograms/100 g of linear protamin Zn-bound somatostatin were injected s.c. twice daily in the in vivo study. Cyclic somatostatin (1, 4 or 10 micrograms/ml) was added twice daily to the cell cultures. Somatostatin administration influenced neither the survival of animals nor the growth rate of cultured cell lines.

Animals↗