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Biomedical subjects

I Schwarzinger

Publications and source records attributed to I Schwarzinger.

At least 91 records · Page 5Linked to original sources

Fertility, pregnancies and offspring complications after bone marrow transplantation.

Hormonal assessment including luteotropic hormone (LH), follicle stimulating hormone (FSH), testosterone (T), oestradiol and sex hormone binding globulin was performed 1-6 years after allogeneic, syngeneic and autologous bone marrow transplantation in nine patients with severe aplastic anaemia (SAA) and 14 patients with haematological malignancy (HM). Among nine allografted SAA patients, seven aged less than 26 years showed normal gonadal function while two women above 26 years had premature ovarian failure. All eight female patients transplanted for HM had premature ovarian failure. Among six male patients transplanted for HM, four have elevated FSH but normal LH and T levels, while two have normal LH, FSH and T levels or elevated LH and FSH levels but decreased T levels, respectively. Three patients transplanted for SAA (two female, one male), but none of those transplanted for HM, parented four healthy children. A high incidence of offspring complications was noticed, including (i) persistence of fetal circulation syndrome, (ii) erythroblastosis fetalis, and (iii) prolonged newborn icterus. One female patient transplanted for SAA had an abortion in the 25th week of gestation. These observations confirm previous reports on recovery of fertility, mainly in younger patients transplanted for SAA; there was, however, an unexpectedly high incidence of pre-, peri- and postpartum complications in the offspring of bone marrow graft recipients.

Adolescent↗

Azidothymidine (AZT) in the treatment of symptomatic HIV-1-infected hemophiliacs.

Twenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months. At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with interruption of treatment. Three patients developed severe leukopenia and 3 patients severe anemia during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was interrupted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of non-compliance. No significant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted. We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patients are comparable to those seen in other risk groups. AZT does not increase the bleeding tendency in this patient group.

Adolescent↗

Prognostic role of inducible ventricular tachycardia in patients with dilated cardiomyopathy and asymptomatic nonsustained ventricular tachycardia.

We studied the prognostic relevance of inducible ventricular tachycardia in 32 patients with dilated cardiomyopathy and spontaneous nonsustained asymptomatic ventricular tachycardia. Programmed ventricular stimulation included basic drive cycle lengths of 600, 500, 430, 370, 330 and 300 msec at single, double, and triple extrastimuli. Ventricular tachycardia (greater than or equal to 6 beats) was initiated in 7 patients (22%), with sustained monomorphic ventricular tachycardia being seen in 4 of them. During median follow-up of 21 months (13-44), 14 patients died. Sudden cardiac death occurred in two of the seven patients with inducible tachycardia and in only one of the 25 patients in whom it was not possible to induce tachycardia. Although patients with inducible tachycardia did not differ clinically from those in whom tachycardia could not be induced, the projected mean survival time was significantly shorter in those with inducible tachycardia (10 months vs. 32 months, P = 0.04). For late sudden cardiac death, the positive predictive value of inducible tachycardia was 28%. The negative predictive value was 96%. We conclude that induction of ventricular tachycardia by programmed stimulation might indicate poorer prognosis in patients with dilated cardiomyopathy.

Adult↗

[Invasive pulmonary aspergillosis: radiologic and magnetic resonance tomographic characteristics].

46 patients with invasive pulmonary aspergillosis (IPA) were investigated by chest radiographs (n = 46), plain film tomograms (n = 16), CT (n = 8) and MRI (n = 13). Radiologic characteristics of early IPA were nodular or patchy infiltrates in the upper lobes of all patients. Enlargement of the infiltrates and/or development of segmental/lobar consolidations were typical for fully developing IPA. Air crescent signs were seen in 40% of patients during or after bone marrow restitution. CT added additional information by visualisation of small pleural based infiltrates, demonstration of air crescents and identification of halo phenomena. MRI revealed the target character of nodular aspergillomas with hypointense centres and rims of higher signal intensity. A gadolinium-DTPA rim enhancement could be observed in almost all nodular lesions. Hyperintense areas in nodular and segmental infiltrates on T1-weighted images were interpreted as aging haemorrhage (methemoglobin) in aspergillus-induced haemorrhagic infarcts or in focal parenchymal bleeding.

Aspergillosis↗

Gamma-interferon in myelodysplastic syndromes: a pilot study.

Eight patients with myelodysplastic syndrome (MDS; RA = 1, RAEB = 2, RAEB-t = 4, CMML = 1) received three cycles of recombinant gamma-IFN administered in 2-week intervals, each consisting of a 14-day period of subcutaneous injections at a daily dose of 0.1 mg/m2. Neither a complete nor a partial remission could be obtained. There was only one definite improvement consisting in a rise of hemoglobin level from 7 to more than 12 g/dl. Two minor improvements were due to a slight rise of platelet counts. Three patients developed acute leukemia under treatment with gamma-IFN. Our data suggest that gamma-IFN administered according to the treatment schedule as used in our trial has only a minimal beneficial effect in patients with MDS.

Adult↗

Prognostic significance of surface marker expression on blasts of patients with de novo acute myeloblastic leukemia.

The prognostic significance of the expression of surface membrane antigens on the blasts of 123 consecutive patients with de novo acute myeloblastic leukemia (AML) was evaluated. For this purpose, reactivity of monoclonal antibodies (mAbs) CLB-ERY3 (antiblood-group H antigen), VIM-D5 (CD15), WT1 (CD7), MY7 (CD13), MY9 (CD33), VID-1 (antihuman leukocyte antigen locus DR [anti-HLA DR]), VIM-2 (CDw65L), VIM-13 (CD14), 63D3 (CD14) and anti-TdT with leukemic blast cell populations was prospectively analyzed with respect to the rates of complete remission (CR), continuous complete remission (CCR), and survival. The overall rate of CR was 65%, the 6-year rates of overall CCR and survival were 23% and 13%, respectively (median period of patient observation, 30 months). Of all Abs tested, four (CLB-ERY3, MY7, anti-TdT, and VIM-D5) were found to be of prognostic value. Reactivity of CLB-ERY3, MY7, and anti-TdT was predictive for CR (CLB-ERY3+, 43% v CLB-ERY3-, 73%, P less than .02; MY7+, 59% v MY7-, 91%, P less than .003; TdT+, 28% v TdT-, 71%, P less than .001, respectively) and probability of survival (significantly lower survival rates: CLB-ERY3+, P less than .02; MY7+, P less than .03; and TdT+ cases, P less than .001, respectively). Reactivity of VIM-D5 was significantly associated with a higher probability of CCR (P less than .01). Our results confirm earlier reports on the prognostic significance of expression of CD13 and TdT in AML and indicate CLB-ERY3 (antiblood-group H antibody) and VIM-D5 (CD15) as further markers predictive for the clinical outcome in patients with de novo AML.

Adolescent↗

[Interferon therapy in hematologic neoplasms].

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.

Hematologic Diseases↗

[High dosage and intermediate dosage cytosine arabinoside in the treatment of secondary leukemias].

Patients with secondary acute myeloid leukaemia (AML) following treatment with alkylating agents and/or radiation show a poor response to standard induction therapy. Between 1983-1987 8 consecutive patients were treated with high-dose cytosine arabinoside (HD-ARA C; 3 g/sqm twice daily for 6 days) or intermediate-dose cytosine arabinoside (ID-ARA C; 0.5 g/sqm twice daily for 6 days). Complete remission was achieved in 3 patients (HD-ARA C: 2/3l; ID-ARA C: 1/5) and partial remission in 3 patients (ID-ARA C: 3/5). One patient (HD-ARA C) died during prolonged aplasia, one patient (ID-ARA C) proved refractory to treatment. The respective duration of remission in the 3 responsive patients was 3, 7 and 8 months. The probability of survival of the whole group was 50% after 12 months and 25% after 24 months. Our results confirm the efficacy of monotherapy with ARA C in the treatment of secondary AML. Consolidation therapy with ID-ARA C for 4 days seems to prolong remission.

Adult↗

Recombinant alpha-interferon (alpha-IFN) for progressive hairy-cell leukemia (HCL): a study in previously untreated nonsplenectomized patients.

Ten nonsplenectomized patients (5 males, 5 females) with hairy-cell leukemia were treated with recombinant alpha-IFN. The median age of patients was 54 years (32-76 years). The time between diagnosis and onset of treatment ranged from 1-120 months. Initially the patients received 5 x 10(6) I.U. daily by intramuscular or subcutaneous injections for 10 weeks. Thereafter the dose of IFN was reduced to 5 x 10(6) I.U. 3 x weekly and after 6 months to 5 x 10(6) I.U. 2 x weekly for at least 6 months. The median time of patient follow-up is 23 months (4-28 months). Three complete remissions were achieved after 3-24 months and five partial remissions after 4-18 months. One patient showed improvement after 3 months, and one patient died from cerebral hemorrhage after 5 weeks. In eight of ten patients peripheral blood cell counts normalized after a median of 7 months (1.5-11 months). A marked reduction in spleen size was observed in all seven patients who had splenomegaly at study entry. Two of three patients who interrupted therapy have relapsed after 2 and 6 months. We conclude that alpha-interferon is an effective method of first-line treatment in patients with HCL.

Adult↗

Skeletal involvement in hairy cell leukemia.

The clinical and radiographic aspects of two patients with destructive bone lesions, complicating the course of hairy cell leukemia are presented. The findings are compared with those of 27 previously published cases. The most prominent features of this rare skeletal disorder are osteolysis and widespread or localized demineralisation with predilection for the femoral head and neck. Localized persisting pain is the leading clinical symptom in all cases. Magnetic resonance imaging is helpful in evaluating the extent of bone marrow infiltration and demonstrates focal areas of decreased signal intensity in sites of radiographically detectable bone destruction as well as in bones that appear normal on plain films.

Bone Neoplasms↗

[Electrophysiologic study in patients with syncope of unknown cause].

Electrophysiologic studies were performed in 51 patients with syncopes of unexplained origin. 25 patients (49%) had organic heart disease. Electrophysiologic testing included determination of corrected sinus node recovery time, AV-nodal effective refractory period, AH- and HV-intervals, and AV-nodal Wenckebach rate. During programmed right ventricular stimulation, 1-3 premature stimuli were used. 26 patients (53%) had an abnormal outcome that strongly suggested an arrhythmogenic cause of the reported syncopes. In ten patients (20%), corrected sinus node recovery time was prolonged; AV-nodal conduction disturbance was manifest in two patients (4%); reversibility with atropine was shown in one patient. Six patients (12%) had an infrahisian conduction delay with an HV-interval longer than 70 ms. Eight patients (15.6%) had either symptomatic ventricular tachycardias (n = 4), AV-nodal reentry tachycardias (n = 2), or inducible symptomatic rapid atrial fibrillation (n = 2). In one additional patient, ventricular tachycardias could not be reinitiated after ending tricyclic antidepressant drug medication. The diagnostic yield of the electrophysiologic study was not influenced by the presence of organic heart disease. Patients with prolonged corrected sinus node recovery time, prolonged HV-interval, and irreversible AV-conduction delay underwent pacemaker implantation (n = 17). Patients with rapid response to programmed stimulation received antiarrhythmic medication, the efficacy of which was assessed by serial electrophysiologic testing until non-inducibility was obtained. The mean follow-up period was 11 months (1-31 months). Overall 2-year mortality was 17%. In 4/5 patients, death was unrelated to the cause of syncope.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Allogeneic bone marrow transplantation in acute myeloid leukemia (AML): results in 14 patients].

Between February 1982 and August 1986 14 patients with AML (median age 24 years, range 10-41) underwent allogeneic bone marrow transplantation. 9 patients were grafted in first complete remission, 4 in first relapse, 1 in second relapse and 1 patient with refractory AML. Conditioning consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad). The patients received methotrexate (n = 12) or methotrexate and cyclosporine (n = 2) for prevention of graft versus host disease. Of the 14 patients, 7 are alive, 7 patients died. Causes of death were recurrence of leukaemia (n = 2), veno occlusive disease of the liver (n = 1), CMV-pneumonitis (n = 1), septicaemia (1), cerebral haemorrhage (1), acute graft versus host disease of the gut (1), necrotizing encephalopathy (n = 1). 7 patients are alive between 124 and 1784 days (median 671) in continuous complete remission. All patients but 1 have a Karnofsky-index of more than 80%.

Adolescent↗

[Bone marrow transplantation in chronic myeloid leukemia--experiences in 16 patients].

Between January 1983 and December 1986 16 patients (8 f, 8 m, median age 31.5 years, 14-41) with chronic myelocytic leukaemia (CML) received bone marrow grafts from their HLA compatible sibling donors. 11 patients were in the chronic and 4 in the accelerated phase. 1 patient was in lymphatic blast crisis. The patients were pretreated with busulfan (n = 15, total dose: 100-1000 mg, median: 225), mitobromitol (1 pat.), hydroxyurea (2 pats.), pre-irradiation of the spleen with 800 rad (1 pat.) and one patient had received 3 cycles of vincristin and prednisolone. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad, lung 800 rad). The prophylaxis against graft versus host disease (GVH-D) consisted of methotrexate (MTX) in 14 patients and of MTX in combination with cyclosporin-A in 2. At present (January 15th 1987) 9 patients survive 30 to 1210 days (median 1009) post graft (6/11 grafted in chronic, 2 of 4 in accelerated phase and 1/1 grafted in blast crisis. The causes of death were interstitial pneumonitis (CMV-associated, 2 pats.), venoocclusive disease of the liver (2 pats.), acute GVH-D and septicemia (2 pat.) and relapse (1 pat.). The Karnovsky score of 8/9 survivors is 100%, one patient has a score of 70% due to chronic GVH-D. Bone marrow transplantation for CML bears a high risk of early mortality but offers the unique option of permanent eradication of leukaemic haemopoiesis with subsequent long term survival.

Adolescent↗

Incidence of inhibitors in patients with severe and moderate hemophilia A treated with factor VIII concentrates.

Recent data published on the prevalence of inhibitors to factor VIII in hemophiliacs on treatment show great variations, with prevalence rates ranging from 3.6 to 14.2%. We have studied the cumulative risk of inhibitor development in a cohort of 62 patients with hemophilia A. All patients were born after 1960, were natives of the Vienna area, had a factor VIII activity of less than 5%, and were treated at least once. Using the method of Cutler and Ederer, the cumulative risk of inhibitor development was found to be 24% at the age of 25 years. Most inhibitors developed between the ages of 3 and 7 years. The current prevalence of F VIII inhibitors in the group of patients studied is 17.5%. It is concluded that prevalence data underestimate the true risk of inhibitor development.

Adult↗

Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone).

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.

Anemia, Aplastic↗

The Häma-COM laboratory data management system (LDS): tailor-made computerization of the individual working procedures arising in a hematology laboratory with a high throughput of pathologic samples.

A laboratory data management system (Häma-COM) is presented that is individually adaptable to the different working procedures arising in a hematology laboratory. The Häma-COM can be easily integrated into a hospital and/or another laboratory computer system, providing the facilities of total electronic data transfer between the referring institutions and the laboratory. The system is based on a network of personal computers running Novell Network software and coordinates two hematology analyzers (NE-8000, R-1000) and several microscopic work stations. The entire information provided by the hematology analyzers including scatterplots and histograms is captured by the system, whereby automated results are validated and worklists for further sample workup are created. Corrections of and/or additions to automated analysis results might be directly entered into the system from the respective microscopic working places. The Häma-COM system minimizes the administrative workload without interfering with the individual laboratory organization.

Blood Cell Count↗

Comparison of karyotype analysis and RT-PCR for AML1/ETO in 204 unselected patients with AML.

The chromosomal translocation t(8;21) (q22;q22) is often associated with acute myeloid leukemia with maturation (AML-M2) and can be detected by a reverse transcription-polymerase chain reaction (RT-PCR) for the AML1/ETO fusion mRNA. We investigated the prevalence of t(8;21) and AML1/ETO in 204 unselected patients with AML and compared the results of cytogenetic analysis with these of RT-PCR. Fifteen of 204 AML patients (7.4%) showed a t(8;21) in karyotype analysis. In 17 of 204 patients (8.3%) AML1/ETO was detected by RT-PCR. All patients who had a t(8;21) in conventional karyotyping also showed the gene rearrangement in molecular analysis, including one patient with a three-way translocation t(5;8;21). AML1/ETO was also detected in two AML patients lacking the t(8;21) cytogenetically. One had a normal diploid karyotype bone marrow (BM) at diagnosis; she has now been in CCR for 12 months. The second patient showed a complex chromosomal anomaly involving chromosome 21, but without a typical 8;21 translocation (BM in relapse). He died in relapse after an overall survival of 60 months. These data indicate that the results of karyotyping and RT-PCR are not completely identical, and molecular biology identifies approximately an additional 5-10% of AML1/ETO positive cases. The clinical relevance of our findings will have to be evaluated with larger patient numbers.

Acute Disease↗

Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT-PCR: implications for a monitoring schedule and for treatment decisions.

Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.

Acute Disease↗