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Biomedical subjects

W D Hirschmann

Publications and source records attributed to W D Hirschmann.

At least 19 recordsLinked to original sources

Aplastic crisis as a complication of congenital dyserythropoietic anemia type II.

A transient aplastic crisis (TAC) is a well-known complication in all types of chronic hemolytic anemia but only 2 cases of such an event were described in congenital dyserythropoietic anemias (CDAs). Here, we report a third case, and by retrospective chart review of 78 cases we found evidence of TAC in 8 further patients with CDA II, with serological evidence of previous human parvovirus B19 (B19V) infection in all but one. Although B19V infection results in TAC in only a minority of patients with CDA, physicians responsible for these patients should be aware of such a potentially life-threatening complication. Testing for B19V-specific IgG is recommended in patients with CDA to estimate the risk of a possible future aplastic crisis.

Adolescent↗

Remission induction therapy: the more intensive the better?

Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.

Acute Disease↗

Left main coronary stenosis by a mediastinal lymphoma.

A 50-year-old patient presented with a 3-month history of chest pain, a pathological result on electrocardiogram stress test, and signs of coronary heart disease on myocardial scintigraphy. Coronary angiography showed an isolated, moderate tubular stenosis of the left main coronary artery. Coronary bypass surgery was carried out, and intraoperative examination revealed a mediastinal lymphoma which caused the stenosis of the left main artery by external compression.

Antineoplastic Combined Chemotherapy Protocols↗

Fluorouracil versus folinic acid/fluorouracil in advanced colorectal cancer--preliminary results of a randomized trial.

Patients with advanced colorectal cancer were randomized to receive either fluorouracil (5-FU) 370 mg/m2 IV days 1 to 5 followed by weekly applications of 5-FU 600 mg/m2 or the same doses of 5-FU preceded by folinic acid 200 mg/m2. Because of toxicity, the weekly 5-FU dose in the combination treatment schedule was reduced to 500 mg/m2 in the course of the study. As of November 1990, 135 patients entered the study; 71 have received combination therapy, and 64 monotherapy. Sixty-three and 59 patients, respectively, are included in the present interim analysis. The two groups are well matched for age, performance status, site of disease, number of metastatic sites, and biochemical parameters. Treatment results are evaluable in 118 patients. Thirty percent receiving combination treatment and 20% receiving monotherapy achieved a complete or partial remission. There is no survival time difference between the groups. However, time to progression is superior in the combination treatment group (median 26 weeks compared with 13 weeks). The main toxicity was diarrhea during the weekly therapy. This was especially true for patients receiving combination treatment before the reduction of 5-FU dosage. In contrast to only four of 56 patients with monotherapy, 14 of 39 with the combination treatment at the initial dosage had severe diarrhea with two treatment-related deaths in this latter group. By reduction of 5-FU dosage during the weekly therapy severe diarrhea could be clearly reduced with only one of 18 patients suffering from diarrhea of World Health Organization grade 3. Other toxicity was usually mild. In conclusion, a prolongation of time to progression could be achieved by combination treatment of folinic acid and 5-FU, which was well tolerated when the weekly dose of 5-FU did not exceed 500 mg/m2.

Colorectal Neoplasms↗

[Ciprofloxacin in the treatment of Legionnaires' disease].

Case report on a granulocytopenic patient suffering from acute myeloid leukaemia and legionnaire's disease as a complication. Under therapy with ciprofloxacin (2 x 200 mg/die) the symptoms decreased within five days; hence, ciprofloxacin seems to be a good alternative to erythromycin and rifampicin in the therapy of legionnaire's disease in immunodeficient patients.

Antibodies, Bacterial↗

[T-cell lymphoma associated with sprue].

A 47-year-old woman, known to have coeliac disease, developed bouts of fever, up to 39 degrees C, with loss of weight and treatment-resistant diarrhoea, as well as swelling of the submandibular, axillary and inguinal lymph nodes. Tests revealed a pancytopenia (haemoglobin 8.8 g/dl, leucocytes 500/microliter, platelets 19,000/microliter), and a reduction of the Quick value to 39%. Computer tomography demonstrated extensive abdominal lymphomas. The patient's general condition quickly deteriorated, hypoproteinaemia developed (total protein 4.6 g/dl) with peripheral oedema, ascites and pleural effusion. She died before the suspected diagnosis of coeliac disease-associated malignant lymphoma could be confirmed. Autopsy demonstrated a highly malignant, pleomorphic, primary abdominal non-Hodgkin lymphoma, immunohistologically a T-cell lymphoma.

Abdominal Neoplasms↗

[Beta interferon therapy in hairy cell leukemia].

Eleven patients with histologically proven hairy-cell leukemia were treated for 2 to 6 months with a natural beta-interferon (beta-IFN) preparation (3 X 4 million units week i.v.). Three of the eight evaluable patients experienced a partial response, two a minor response, and three no improvement. A reduction of the hairy-cell infiltration of the bone marrow was observed in one patient. Typical IFN side-effects with flu-like symptoms were noted. These results demonstrate that IFN-beta has some clinical efficacy in hairy-cell leukemia.

Adult↗

Long term follow-up of remission patients in adult acute leukemia.

31 adults suffering from acute leukemia were followed for a period of more than 5 years after achieving complete remission. Maintenance chemotherapy consisted of antimetabolite treatment (mercaptopurine + methotrexate) as well as COAP reinduction every 3 months. Chemotherapy was stopped if the first complete remission lasted for 3 years ("long term remission"). This was the case in 8 out of 31 remission patients (26%). Analysis of hematological parameters at diagnose for long term remission patients revealed that the initial leukocyte count was of prognostic significance.

Acute Disease↗

Remission induction and remission maintenance in adult acute nonlymphocytic leukemia employing a modified cytostatic (COAP) regimen.

Thirty adult patients suffering from acute nonlymphocytic leukemia (ANLL) were treated according to a modified COAP regimen. Vincristine, cyclophosphamide, and prednisone were given by push injection, while cytosine arabinoside was infused over periods of 8 h. Nineteen patients (63%) achieved complete remission. Remission maintenance therapy consisted of 6-mercaptopurine daily and methotrexate twice weekly. Later in the study, COAP consolidation and reinduction was added, which improved the median duration of complete remission from 7 to 24 months. Comparison of the results with the literature shows that the modified COAP regimen is one of the most effective treatment schedules for adult ANLL.

Acute Disease↗

[Clinical problems of optimum bioavailability, in particular in cytostatic therapy (author's transl)].

The clinical application of cytostatic drugs requires knowledge of their biochemistry, pharmacology, pharmacokinetics as well as their action at the cellular level within the generation cycle. The principles apply to tumor cells as well as to normal, rapidly proliferating tissues. The intensive research on cancer treatment all over the world is leading to a rapid accumulation of experimental data about the action of single cytostatic drugs in tissue culture and on transplantable animal tumor systems, especially in rodents. Clinical chemotherapy in human malignancies today preferentially uses combinations of different cytostatics. Inumerable combinations of drugs are available, especially if variations in respect to drug dose and intervals of drug application are taken into consideration. The experimental basis for such combinations of drugs and drug interactions is scanty. Using the pyrimidine analog cytosine arabinoside and the two antibiotics daunorubicin and doxyrubicin (adriamycin) as examples, it is demonstrated that information on the pharmacolinetic behaviour of cytostatic drugs is a prerequisite for their success in clinical application, but is on its own insufficient to predict the tumor response.

Animals↗