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Biomedical subjects

V Hofmann

Publications and source records attributed to V Hofmann.

At least 37 records · Page 2Linked to original sources

Prognostic significance of agar and liquid cultures in AML patients before treatment, early postinduction and in remission.

In the present study, the growth and differentiation capacity of myeloid leukemic cells in agar and liquid cultures have been investigated in relation to their prognostic significance for treatment outcome and early detection of relapse. Prior to induction therapy, leukemic cells failed to differentiate and the colony or cluster number did not correlate with response to treatment. Seventeen to 42 days after induction, patients with BM cells producing greater than 10 colonies or greater than 30 clusters resp. had a high likelihood of achieving a complete remission. Cells from refractory patients had a significantly impaired differentiation capacity. During remission, a colony number greater than 50 was significantly associated with a high probability to remain in further remission for greater than 3 months. An impaired differentiation was significantly associated with the likelihood of relapsing within 3 months. In the light of these results, agar and liquid cultures appear to be useful for monitoring the effect of induction chemotherapy and detecting patients likely to relapse.

Agar↗

[Mycoplasma etiology of acute pancreatitis].

In a 10 year-old girl the clinical and laboratory findings led to the diagnosis of pancreatitis. At the same time an infection by mycoplasma pneumoniae was serologically stated. Since there could not be found another cause for pancreatitis, a relation between pancreatitis and infection by mycoplasms is very probable.

Child↗

[Effectiveness and toxicity of high-dosage Ara-C. Clinical observations in 10 cases and review of the literature].

Ten patients with acute myeloid leukemia were treated with a high-dose ara-c regimen (3 g twice daily for 6 days). 5 patients (50%) achieved a complete remission lasting for a median duration of 5 months. These patients had all achieved a complete remission following standard treatment with ara-c. High-dose ara-c was ineffective in 2 patients resistant to standard ara-c protocols. The most important side effects of high-dose ara-c were conjunctivitis and cerebellar symptomatology. In one case a severe diffuse encephalopathy with cerebellar predominance set in at a remarkably late stage (45 days after starting treatment). Our results and those of other authors suggest that treatment with high-dose ara-c should be used with caution.

Adolescent↗

[Multiple myeloma].

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Antineoplastic Combined Chemotherapy Protocols↗

Leukemic samples characteristics associated with clonogenic growth.

In this study, we attempted to delineate readily assessable characteristics from 100 leukemic samples associated with in-vitro growth. Successful growth defined as production of greater than 30 clusters and/or colonies per culture dish was obtained in 68% of samples. More than 10 colonies were found in 59% and greater than 30 colonies in 51% of cultures, respectively. Leukemic cells from patients previously treated with aggressive cytotoxic chemotherapy grew significantly better than cells from untreated patients, independently of the above definitions of cloning success. Cells from peripheral blood had a weak, albeit significant growth advantage over bone marrow cells (p = 0.032) when cluster growth was taken into account for growth success. When colony growth alone was used as criterium, no growth advantage was found. The morphological subtype and the proliferation kinetics prior to cell plating did not affect cloning success. A high labeling index had predictive value for subsequent growth, but only in bone marrow cells. By multivariate analysis, we found that treatment status was the most important factor correlated with in-vitro growth.

Analysis of Variance↗

Limitations of the salmonella/mammalian microsome assay (Ames test) to determine occupational exposure to cytostatic drugs.

Urine samples of nursing personnel working in medical oncology divisions of several Swiss hospitals were examined for mutagenic activity. Urine samples were concentrated 100 times following XAD-2 chromatography and mutagenicity was determined using the Salmonella/mammalian microsome assay (Ames test). Apart from the urine samples of patients treated with cytostatic drugs and urine samples of nurses who are cigarette smokers, no mutagenic activity could be found. Also following exposure to an increased and defined quantity of cytostatic drugs no mutagenicity could be recovered from the urine. Four different nurses worked with cyclophosphamide, methotrexate, 5-fluorouracil, adriamycin and cis-platinum for 3-4 hr without using any protection such as gloves, masks or a vertical laminar airflow hood. Aqueous extracts of filters, through which air was pumped during the whole experiment (a personal air-sampler was fixed near the face of the test persons), were non-mutagenic. Parallel to the mutagenicity test chemical analyses were also done. The methotrexate content was determined in serum samples and the aqueous filter extracts and urine samples were examined for cis-platinum. All chemical determinations were negative. With the aid of urine concentrates of a patient treated with sub-therapeutic doses of cyclophosphamide as well as with normal urine to which single small amounts of different cytostatics (adriamycin, cyclophosphamide, cis-platinum) were added, the detection limits for the corresponding cytostatic drugs were determined and found to be in the range of 2-10 mg for cyclophosphamide and approx. 10 micrograms for adriamycin. Cis-platinum was lost during the passage through the XAD-2 columns. With these results at hand the sensitivity of the hitherto preferably used method (Ames test) for the monitoring of exposure to cytostatic drugs must be seriously questioned.

Antineoplastic Agents↗

[Possibilities of pre-, intra- and postoperative sonography in hydrocephalus].

Short-term repeat sonographic examinations of the brain were performed in 90 newborn and infants with ventricular dilatation. Changes in the ventricular configuration are pointers to the intracranial pressure. Measurement of the ventricular system must be performed in the same way as for estimating progressive ventricular dilatation. If a shunt is necessary, the ventricular tube can be positioned in the anterior horn of the lateral ventricle under ultrasound guidance. This will help to avoid complications which are due to a wrong position near the plexus or in a clot. Complications like overdrained ventricles, haemorrhages, shunts blocked in proximal or distal areas may be visible even before the appearance of clinical signs or symptoms. Comparative postoperative examinations allow an assessment of shunt function.

Cerebral Hemorrhage↗

[Sonographic follow-up studies in purulent meningitis and its complications in infancy].

In 29 newborns and 18 infants ill with meningitis the following characteristic signs visible by sonographic examination of the brain mostly indicated complications: increase of the leptomeningeal echogenicity, increase of the periventricular echogenicity in ventriculitis, alterations of the configuration of the ventricles, typical echos in the CNS-fluid by increased cell and protein content, alterations of the Plexus chorioideus caused by inflammation, membranes in the enlarged ventricular system. In the first year of life the sonographic examination of the brain is ideal for early diagnosis of possible complications in meningitis to change the therapeutic management without any loss of time.

Bacterial Infections↗

[Is the use of adriamycin (doxorubicin) limited by its cardiotoxicity?].

Adriamycin (doxorubicin), one of the most active cytotoxic antineoplastic agents, can cause heart failure. This side effect is dose-dependent, the frequency of heart failure being 3% at a cumulative Adriamycin dose of 400 mg/m2 and 18% at 700 mg/m2. It is assumed that Adriamycin, or other anthracycline derivatives, are still active when the cardiotoxic level is reached. In this retrospective study of 171 patients with various metastatic malignant tumors, the total dose of Adriamycin given to the patients and the reasons for withholding the treatment have been analyzed. Overall, among the 171 patients treated by Adriamycin-containing combination chemotherapy, 54 objective remissions (31%) were observed. Remissions were more frequent in untreated patients (52%) than in previously treated patients (20%). In 36 of 54 patients the disease progressed before the cumulative cardiotoxic level was reached. Adriamycin could be discontinued in only 18 patients still in remission. 8 of 171 patients received more than 450 mg/m2 Adriamycin without cardiotoxic side effects being observed. Among the 171 patients, cardiotoxicity probably related to anthracyclines developed in 5 cases (3%), in all cases at a level below 450 mg/m2. These results suggest that in most cases Adriamycin becomes inactive before the dose-limiting cumulative cardiotoxic level is reached.

Antineoplastic Combined Chemotherapy Protocols↗

[Effect of interferon-alpha 2 (E. coli) in hairy cell leukemia].

Recombinant interferon-alpha 2 (E. coli) produced a clinically significant improvement in hemoglobin, granulocytes and platelets in 7 of 8 patients with hairy cell leukemia. Response to treatment was already noticeable in the fourth treatment week. In one case without improvement after 120 days, treatment was stopped. So far only one complete remission has been documented. Because of the remarkable improvement in the peripheral blood values, the induction of a complete remission may not be the ultimate goal of interferon treatment. The side effects of this subcutaneous low-dose treatment consisted mainly of mild flu-like symptoms of short duration. The results obtained with recombinant interferon-alpha 2 confirm the initial observation by Quesada et al. with partially purified leukocyte-interferon. In our experience, these results are superior to those obtained in similar conditions with chlorambucil.

Adult↗

Hairy cell leukemia: kinetics and intercellular relationships of cells in leukemic colonies grown in a semisolid medium.

We examined cellular relationships and cytokinetics of hairy cells in colonies formed in an in vitro cloning system. Cells in small colonies and at the periphery of larger ones were separated by wide, irregular intercellular spaces. Cells in the core of large colonies were elaborately intertwined by their cytoplasmic processes and so densely packed that their intercellularity was greatly reduced. Cell labeling with 3H-thymidine revealed indices ranging from less than 1% to 35%. The combination of autoradiography with a stain for tartrate-resistant acid phosphatase showed that the enzyme was not expressed by cells in S-phase. The cellular relationships of hairy cells in colonies grown in this system closely mimic those of their in vivo counterparts in the spleen and bone marrow.

Acid Phosphatase↗

Ultrasonic diagnosis of the spleen.

The sonographic presentation of the spleen may be difficult and is seldom requested. Main indications for special investigation are traumatic lesions, malignant diseases, such as Hodgkin's or non-Hodgkin's lymphomas, and changes in portal hypertension.

Cysts↗

Clinical experience with preoperative chemotherapy for osteosarcoma.

Since 1978 preoperative chemotherapy has been administered to 15 consecutive patients with osteosarcomas in Zurich. Preoperative chemotherapy was acceptably well tolerated and did not impair surgical procedures. Our retrospective analysis confirmed that the extent of necrosis after preoperative chemotherapy is of biological importance for the further course of the disease. Patients with extensive necrosis had better relapse-free survival and longer overall survival than those with little necrosis.

Antineoplastic Combined Chemotherapy Protocols↗

Drug selection for perioperative chemotherapy.

A wide variety of tumor types can be successfully grown with the clonogenic assay. However, few tumor types perform adequately for routine drug sensitivity testing, e.g., ovarian carcinoma and malignant melanoma. Because of insufficient in vitro growth, the cloning system cannot help substantially in indicating active substances for epidemiologically frequent tumors that usually have a poor prognosis, such as colorectal cancers and non-small cell lung and breast cancers. The degree of in vitro cell kill that would correspond to complete eradication of micrometastases is unknown. The identification of individual patients sensitive to a given antineoplastic agent becomes more difficult as the tumor becomes more refractory to treatment. At this moment, the clonogenic assay appears most promising for trials dealing with the treatment of ovarian adenocarcinoma.

Cell Count↗

Effects of 13-cis retinoic acid and Ara-C on differentiation and proliferation of non-promyelocytic acute myelogenous leukemia.

An alternative to a cell-kill strategy for eradication of acute myelogenous leukemia, is to restore normal differentiation. Vitamin A derivatives demonstrate differentiation-inducing activity both in vitro and in vivo on promyelocytic leukemic cells. We tested the ability of 13-cis retinoic acid to reduce proliferation and induce differentiation in 10 samples from patients with acute non-promyelocytic leukemia. DNA synthesis and leukemia colony formation were affected to varying degrees by a prolonged exposure to the vitamin A compound. Morphologically and cytochemically no differentiation was determined either after 48 h in suspension cultures or 7 additional days in semi-solid cultures. Alkaline leukocyte phosphatase, a biochemical marker of differentiation, was significantly increased in five samples. DNA synthesis in these samples was significantly reduced as compared to samples failing to express alkaline leukocyte phosphatase following 13-cis retinoic acid treatment. DNA synthesis of these same 5 samples was also strongly inhibited by Ara-C. Expression of alkaline leukocyte phosphatase following 13-cis retinoic acid exposure may be a useful indicator for cells amenable to 13-cis retinoic acid or Ara-C treatment.

Adult↗

Hairy cell leukemia. Ultrastructural and cytochemical evaluation of leukemic colonies grown in a semi-solid medium.

We examined the fine structure and enzymatic activity of cells composing colonies grown from blood and/or spleen of eight patients with hairy cell leukemia. Mononuclear cells (MNC) were plated over an agar layer in a medium containing methylcellulose and leukocyte-conditioned medium. After 7-10 days incubation colonies were harvested for cytologic study. Colony cells possessed a euchromatic nucleus with an occasional nucleolus. Their cytoplasm contained a prominent Golgi region, numerous mitochondria and small vesicles, many short strands of rough endoplasmic reticulum (RER) and an infrequent phagosome. Well-developed ribosome-lamella complexes and what may have been their intermediate forms appeared in colony cells from three patients. Strong activity for tartrate-resistant acid phosphatase, localized in the RER, nuclear envelope and some Golgi vesicles, was evident in 50-95% of all colony cells. Our results indicate that a high proportion of MNC forming colonies in this culture system maintain the characteristic morphology and cytochemical activity of hairy cells.

Acid Phosphatase↗