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.

[Use of antibacterial chemotherapy. A historical comparison]. / Nutzen der antibakteriellen Chemotherapie. Ein historischer Vergleich.

The real breakthrough to successful antibacterial chemotherapy was caused by the development of sulfonamides and penicillin. Subsequently numerous other antibiotics were developed and successfully applied. Whilst both the percentage share as well as the resistance pattern with different bacterial strains has remained more or less stable in Europe as well as in the US over the past ten years, staphylococci, especially Staphylococcus epidermidis, appear to increase consistently. This fact can above all be seen with blood cultures. Within the Viennese clinical material, the staphylococcal share increased between 1984 and 1989 from 40 to 48%, with material from intensive care units from 42 to 60% and at the burn care unit up to almost 90% with S. epidermidis counting for the largest share. The resistance pattern has hardly changed. The lethality of patients with staphylococcal sepsis only depended on the timing of treatment: even with targeted treatment starting within two days from onset of clinical symptoms we lost 29%, when therapy was started later, lethality increased to 50%, and without treatment to 90%. Only fast diagnosis can help to fully utilize the benefits offered by antibacterial chemotherapy.

[Effect of major epidemics on cultural awareness]. / Einfluss grosser Seuchen auf das Kulturbewusstsein.

Mankind has been stricken with "major" epidemic diseases throughout its history. The most serious among them immediately threaten man's life e.g. plague, cholera, smallpox, typhus, and dysentery, besides, there are others which take a slower course e.g. lues, leprosy, leishmaniasis, tuberculosis, and malaria. Yet, the "lesser" epidemic diseases like diphtheria, scarlet fever, mumps, pneumococcosis, influenza, and most recently AIDS may also turn into "major" ones. Originally, man exclusively depended on his genetic makeup for protection, and being particularly prone to attacks of disease he was subject to natural selection. Thus, only one human species survived, the homo sapiens. Interbreeding achieved biologic adaptation and created a balanced genetic polymorphism. Advancing in his degree of civilization, man formed groups, developed clothing, fire, houses, and tools, and his increasing cultural awareness allowed him to migrate from the tropical climates to more temperate, and less disease-infested zones. Immigration and wars, and the accompanying infections jeopardized and diminished entire populations and eradicated highly developed cultures like that of the American Indians. The plague, coming from Asia, and lues, from America, as well as cholera, influenza, and smallpox spread around the whole globe. Fear and terror led to irrational conclusions and triggered persecutions. The attitude of accepting disease as a God-sent fate (Hiob), or a God-sent punishment suppressed reasonable measures against disease. The necessary official measures have increasingly restricted liberty, and this patronizing treatment needs to be opposed with a higher sense of responsibility. Medical art has developed from more healing towards prophylactic and predictive medicine, which prognosticates the individual susceptibility to particular infections, and other risk factors.

[Can meta-medicine bridge the gap between para-medicine and so-called school medicine?]. / Kann eine Metamedizin zwischen der Paramedizin und der sogenannten Schulmedizin eine Brücke schlagen?

The concept of metamedicine is analogous to the concept of metaphysics. According to Kants perception, medicine has its origin in the human mind ("Gemüt") which is the source of all kinds of arts. Controversally to Kant, Fichte established I and non-I as a subject-object relationship. School philosophy, psychology and biology tend to banish the "subject" into mysticism but it comes up again in modern physics. Medicine as "art of healing" can only happen between subjects (physician and patient). Considering "metamedical" points of view, it cannot exist without the I/you respectively the you/I relationship. Following Plato, this means "loving-science" and is common to all kinds of medicine.

[Responsibility in medicine--from the dialog viewpoint]. / Verantwortung in der Medizin--aus dialogischer Sicht.

The rapid progress in modern medicine puts a strong strain on the question of trust and responsibility within the doctor-patient-relationship. More control has increasingly been demanded but has not provided any satisfying solutions so far. No clear point of view can be discerned in the present discussion about responsibility. Responsive, communicative, relational and distributive models are the topics of discussion. Still they can't serve as arguments for the responsibility for something as well as the being responsible to somebody as claimed by Hans Jonas. Acknowledging the subjectivity of responsibility a position of dialogue ought be taken. Martin Buber as well as Ferdinand Ebner consider the "Though" in opposition to the "I" on the ontological level as being symmetric and autonomous which reaches further then the sociological, psychological and legal position. Bubner as well as Ebner furthermore provide an analogy to the human "I-Though-relationship" and the relationship between men and the eternal and absolute "Though". Thus they reason responsibility and consciousness. "Ethics speaks primarily to the right and wrong in human relationships".

[Clinical microbiology and chemotherapy in the spirit of Escherich]. / Klinische Mikrobiologie und Chemotherapie im Sinne Escherichs.

One hundred years ago Billroth and Escherich were engaged with microbiological investigations. They are representative of intimate relationship between clinic and microbiological laboratory. In 1979 the Department of Chemotherapy was founded and this tradition was resumed and continued.

[Has the rate of resistant staphylococci increased recently? (author's transl)]. / Resistente Staphylokokken neuerlich im Vormarsch?

In clinical material sent to the Clinic for Chemotherapy and the Institute of Hygiene of Vienna University between 1973 and 1978, Staphylococcus aureus was isolated from 0.9-2.3% and 4.2-11.9% respectively. The rate of resistance of the clinic material to oxacillin increased from 0.8 to 16.0%, to cephalothin from 3.3 to 30.5%, to gentamicin from 0.0 to 43.3%, and to erythromycin from 0.8 to 40.2%. In material sent to the Institute of Hygiene the rate of resistance to oxacillin was stable at 13.8%, and to cephalothin remained fairly constant at 2.4%. On the other hand, the rate of resistance to gentamicin increased from 0.5 to 48.5%, and to erythromycin from 19.8 to 56.9%. The reasons for these alarming increases in resistance and the conclusions which should be drawn are discussed.

[Monitoring of cardiac function during doxorubicin therapy in metastasized breast cancer. Measuring systolic time interval]. / Uberwachung der Herzfunktion bei Doxorubicintherapie des metastasierten Mammakarzinoms.

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.

[Aminopenicillin rashes - a multicentric prospective study (author's transl)]. / Aminopenicillin-Exantheme - eine multizentrische, prospektive Studie.

538 patients, admitted to the hospitals participating in this study for a variety of indications for antibacterial therapy, were treated by the ampicillin-analogue Epicillin. 42 patients (7.8%) who developed exanthem underwent detailed clinical and immunological investigation. Exanthems were scored according to the form of application and doses of Epicillin as well as to the morphology and time of onset of the exanthem. A variety of serological tests were performed: 1. total IgE (RIST), 2. presence of penicilloyl-specific IgE (RAST), 3. penicilloyl-reactive antibodies using an antiglobulin-haemagglutination-tests. In addition, PHA-induced lymphocyte transformation was studied in 10 patients with exanthems. 38/42 patients developed transient monomorphic morbiliform or scarlatiniform exanthems. 4. exanthems were classified as urticarial or polymorphic. In contrast to the 38 patients, the latter also were positive in the serological tests as it is observed in patients with IgE-mediated penicillin allergy.