[A case of rare side effects of certain antidepressive drugs]. / Ein Fall von seltenen Nebenwirkungen gewisser Antidepressiva.

Because of a depressive syndrome, a 39-year-old patient received 20 mg fluoxetine per day. Approximately 4 weeks later, treatment with this drug was stopped after the patient had complained of worsening tremor, particularly of the upper extremities. In addition, accommodation difficulties and problems with word-finding had appeared shortly before. The symptoms became worse after fluoxetine had been discontinued. Treatment of the side effects with piperiden and bromazepam brought about no real improvement in the patient's condition. The passive tremor with a frequency of approximately eight per second mainly suggests an extrapyramidal-parkinsonian cause. Five weeks after treatment with fluoxetine had been discontinued, owing to the persistence of the depressive syndrome the patient received maprotiline and clomipramine by infusion in a private hospital. After 2-3 days the patient complained of headaches and had a slightly raised temperature. After 7 days maprotiline and clomipramine were discontinued completely. During the fever there was no leucocytosis, so that a drug fever was diagnosed. These rare side effects are discussed.

Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethality.

Doxorubicin is an anticancer agent widely used in the treatment of human cancer. The major limitation of this drug governing the cell-killing effect appears to be its poor penetration into a tumor mass. We have studied the effects of hyaluronidase on the penetration and cell-killing effect of doxorubicin using multicellular tumor spheroids (MTS). MTS approximately 500 microns in diameter were produced by a liquid-overlay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed to hyaluronidase for various lengths of time; this was followed by a 1-h resting interval and a subsequent 1-h exposure to doxorubicin. MTS and monolayer cells were then trypsinized to a single-cell suspension and subjected to clonogenic assay. Hyaluronidase at a concentration of 25 U/ml or 250 U/ml was nontoxic to the monolayer cells. For PC-10 MTS, pretreatment with 25 U/ml hyaluronidase for 24 h and 72 h resulted in approximately 20% increases in Doxorubicin cell killing at the median (IC50) dose as compared to doxorubicin alone. HEp-2 MTS were more sensitive to the hyaluronidase pretreatment. Thus, a 1-h exposure to the enzyme produced a 40% increase in doxorubicin-induced cell death at the IC50 dose. A fluorescence microscopic study revealed that a 1-h exposure of MTS to doxorubicin produced doxorubicin fluorescence only in the one or two outer layers of MTS. When MTS were pretreated with hyaluronidase, there was enhanced penetration of doxorubicin fluorescence into the MTS core. Hyaluronidase-induced enhancement of Doxorubicin penetration and its cell-killing effect is dependent on the exposure time and tumor cell origin. These data suggest that anecdotal reports of hyaluronidase-enhanced activity of preclinical chemotherapy deserve a controlled trial.

[Placebo action and alternative medicine]. / Placebowirkung und Alternativmedizin.

Experimental and clinical data concerning placebo effects on pain states and other subjective symptoms are summarized, and show that placebo treatment and psychotherapy are identical. The drugs used by anthroposophical physicians, homeopaths, phytotherapists and therapists attempting to "normalize" the intestinal bacterial flora are in fact pure or impure placebos. Since official medicine is well aware of the scientific basis and favourable results of placebo treatment in psychosomatic and self-limiting diseases, it does not appear necessary to integrate varieties of alternative medicine into graduate and postgraduate medical training.

Therapeutic leukopheresis of acute myelo-monocytic leukemia in pregnancy.

Cytopheresis techniques have proven useful in the provision of platelets and granulocytes for transfusion to the pancytopenic patient. Mechanical cell removal has been applied to the treatment of chronic myelocytic and lymphocytic leukemias and the Sezary syndrome. We have treated a 16-year-old pregnant acute myelomonocytic leukemia (AMML) patient for 12 weeks solely with the use of intensive leukopheresis utilizing batch processing centrifugation and packed red cell transfusions. The patient presented with a white blood cell count of 54,000/mm3 with 64% myelomonoblasts, a platelet count of 45,000/mm3, marked gingival hyperplasia, and splenomegaly. Patient had a normal spontaneous delivery of a 2.5-kg male infant without complications. At the time of delivery, 12 weeks later, the white blood count had fallen to 4,9000/mm3 with 8% blasts and the platelet count had risen to over 100,000/mm3. Gingival hyperplasia decreased and the patient felt well. We have treated an additional small group of patients with acute myelogenous leukemia (AML) with high white counts with short term intensive leukopheresis followed by chemotherapy with promising results.

[The morphological and functional integrity of cryo-preserved leukocytes]. / Untersuchungen zur morphologischen und funktionellen Integrität kryokonservierter Leukozyten

Human peripheral blood lymphocytes were frozen by a simplified method which is described. Light and electron microscopic investigations of the frozen-thawed cells showed no significant morphological changes compared to the fresh cells; comparison of E-rosette formation and nonspecific acid esterase activity before and after cryoconservation afford evidence of a possible slight change in the percent relationship of T- and B-cells, whereas thymidine uptake values within normal range after stimulation with PHA and homologous cells demonstrate the functional integrity of the lymphocytes.

[HL-A B27 associated rheumatic disease]. / "HL-A B27 associated rheumatic disease"

Report on a HL-A B27 positive female patient with the typical cardiac lesion occasionally found inankylosing spondylitis, peripheral arthritis, and acute anterior uveitis but without clinical or radiological evidence of spine or sacroiliac joint involvement. The concept of "HL-A B27 associated disease", including ankylosing spondylitis as well as Reiter's disease or other forms of seronegative rheumatic diseases, is suggested.

[Demonstration of skeletal metastases using the bone marrow biopsy and the radiographic skeletal survey within the scope of pretherapeutic diagnosis in bronchial carcinoma]. / Nachweis von Skelettmetastasen mit Hilfe der Knochenmarksbiopsie und des röntgenologischen Skelettstatus im Rahmen der prätherapeutischen Diagnostik beim Bronchialkarzinom

In the course of pretherapeutic diagnostics of bronchogenic carcinoma, bone marrow biopsy revealed in ten out of 116 patients (9%) and radiographic skeletal survey in 16 out of 62 patients (26%) metastases to the skeleton. The two methods are complementary with reference to anaplastic and oat-cell carcinomas. On account of our experiences, we never fail to control the skeleton before the beginning of a local curative therapy in bronchial carcinoma.

Course and prognosis of 86 episodes of diabetic coma. A five year experience with a uniform schedule of treatment.

The admission data and the course of 58 episodes of severe diabetic ketoacidotic coma and of 28 episodes of non-ketotic coma are compared. The non-ketotic patients were older; initial blood glucose, osmolarity, blood urea and serum sodium concentration were higher than in the ketotic patients. Treatment in the first 24 hrs consisted of similar amounts of insulin in both coma forms, the presence of acidaemia did not increase the insulin needs. Acidaemia was corrected only when pH was below 7.20. The disadvantages of alkali therapy are emphasized. A comparison of the age groups of survivors and those patients who died within 72 hrs showed an increase in mortality with age. However, the mortality rates from ketotic and non-ketotic coma were similar in the age groups above 50 years. On admission, blood glucose, osmolarity and blood urea were higher in the fatal cases. Blood urea was the most important indicator of a fatal outcome. The response of blood glucose to insulin was impaired in the subsequently fatal cases. Insulin was given in "moderate" doses by constant infusion. The use of "small" doses is discussed. Early mortality was 14% in the ketotic and 29% in the non-ketotic cases. The most frequent causes of death were circulatory failure of undetermined origin, infections and thromboembolic complications.

[Acute myeloid leukemia following treatment of IgA-paraproteinemia with alkeran]. / Akute myeloische Leukämie nach Alkeran-Therapie einer IgA-Paraproteinämie

Report on a 74-year-old patient who developed acute myeloid leukemia 16 months after diagnosis of IgA paraproteinemia. He had received a total dose of 1.4-1.5 g melphalan. The possible etiologic role of melphalan in the development of acute leukemia is discussed.