[Gemcitabine/cisplatin vs. MVAC. 5 year survival outcome of the phase III study of chemotherapy of advanced urothelial carcinoma in Germany]. / Gemcitabin/Cisplatin vs. MVAC. 5-Jahres-Ergebnisse der Phase-III-Studie zur Chemotherapie des fortgeschrittenen Urothelkarzinoms in Deutschland.

Of 405 patients with stage IV transitional cell carcinoma from an international multicenter phase III trial, 70 were randomized in Germany to receive either gemcitabine/cisplatin or standard MVAC systemic chemotherapy for locally advanced or metastatic urothelial cancer. Overall survival as the primary endpoint of the study was similar in both arms (median survival GC 15.4 months vs MVAC 16.1 months), as were tumor-specific survival and time to progressive disease. In the intent-to-treat analysis, the 5-year overall survival rate was 10% for patients randomized to GC and 18% randomized to MVAC. Tumor overall response rates (GC 54%, MVAC 53%) were similar. The toxic death rate was 0% in the GC arm and 3% (one patient) in the MVAC arm. Significantly more GC than MVAC patients experienced grade 3/4 anemia (GC 52%, MVAC 20%) with significantly more red blood cell transfusions in the GC arm.Significantly more GC than MVAC patients had grade 3/4 thrombocytopenia (GC 54%, MVAC 17%) without grade 3/4 hemorrhage or hematuria in either arm. More MVAC patients experienced grade 3/4 neutropenia (GC 56%, MVAC 61%, p=1.000), neutropenic or leukopenic fever (GC 0%, MVAC 10%, p=0.237), mucositis (GC 0%, MVAC 7%, p=0.495), and alopecia (GC 6%, MVAC 36%, p=0.004). GC represents a reasonable alternative for the palliative treatment of patients with locally advanced and metastatic transitional cell carcinoma. Sustained long-term survival was only found for patients with locally advanced cancer, lymphatic metastases, or solitary distant metastasis but not for visceral metastatic disease.

[Selected aspects of the life situation of elderly women and men in West and East Germany]. / Ausgewählte Aspekte der Lebenssituation älterer Frauen und Männer in West- und Ostdeutschland.

The current and future expected aging process of the population in Germany affects women more than men. This is equally true for West and East Germany. The demographic development in Germany will cause a confrontation with the problems of aging persons in our society to be ever more essential. This also includes the analysis of the living situation of older women and men. In this contribution two significant aspects of the living situation of older persons in West- and East Germany are being discussed; the income situation and household- and marital status structures. A German-German comparison shows that older women in the new federal states already have higher pension qualifying periods than women in the old federal states. Decisive causes for this are different personal labour force biographies. In total, the income situation of the elderly in East Germany is less favourable as a result of formerly no or at best, minimal possibilities for investments. In addition, it is evident (and this applies to all of Germany) that women have poorer financial starting positions for arranging their life situation in old age than do men. Additionally, there are more women than men who live alone in old age. One-person households of the aged are predominantly female households. Differences according to sex which are analyzed in the article result in different consequences for life in old age. Precisely what this might look like in the final analysis depends not only on the old people themselves, but also on the opportunities that the society in which they live provides for them.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril-induced bone marrow suppression in two cardiac patients with trisomy 21.

Neutropenia is an infrequent complication following administration of the angiotensin-converting enzyme (ACE) inhibitor, captopril. Most reports have been in adult patients, with rare reports in the pediatric population. We report two cases of neutropenia following captopril use in cardiac patients with trisomy 21. As this was not seen in patients without Down's syndrome, we postulate that patients with trisomy 21 have bone marrow which is "at risk" for suppression, and, thus warrant close evaluation while on such medications.

Lack of significant activity of 2'-deoxycoformycin alone or in combination with adenine arabinoside in relapsed childhood acute lymphoblastic leukemia. A randomized phase II trial from the Childrens Cancer Study Group.

Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children.

Molecular genetic studies in black families with sickle cell anemia and unusually high levels of fetal hemoglobin.

Clinical, hematologic, and molecular genetic studies are reported for five families with SS patients having unusually high fetal hemoglobin (Hb F) levels (mean 28.3%, range 19-42%). Some of the individuals were symptom-free and one was not anemic. However, some were symptomatic despite a very high Hb F. Neither the Hb F level nor the F cell distribution entirely explained the variation in clinical severity. Molecular genetic studies identified the Senegal haplotype with the associated -158 G gamma (C----T) mutation in two of the five families. The -202 G gamma (C----G) mutation was not found in any of the individuals studied. Sequencing of the gamma-globin gene promoters to detect genetic high F determinants not detectable by restriction digestion was not performed. All AS parents and AS siblings demonstrated elevated F cells when the Senegal/-158 G gamma (C----T) mutation was present with either the beta S or beta A allele. Double heterozygosity for two different high F determinants in some SS patients is suggested by the studies in at least one family. Discordance among siblings in clinical and hematologic manifestations in two families provides additional evidence for loci regulating Hb F cell production which are not linked to the beta-globin gene clusters.

Case report 730. Malignant large cell lymphoma of tibial epiphysis.

We present a case of primary lymphoma of bone arising in the proximal tibial epiphysis of a 16-year-old boy. To the best of our knowledge, primary lymphoma of bone has not been described previously as a mimicker of chondroblastoma. This case report is intended to increase awareness among clinicians and radiologists that primary lymphoma of bone can present with a long clinical prodrome and initially benign radiographic appearance. Early recognition of this unusual presentation will (hopefully) increase the likelihood of cure. However, it is recognized that in children, primary lymphoma of bone is a rare diagnosis and associated with a poor prognosis unless aggressive treatment is utilized [8].

[The women of the German Democratic Republic in the mirror of demography (a retrospective look)]. / Frauen der DDR im Spiegel der Demographie (ein Ruckblick).

PIP: A review of demographic trends in East Germany over the period of its existence from 1950 to 1989 is presented. The emphasis is on how social and economic conditions affected the fertility and mortality of women. The authors note that fertility remained relatively high, although below replacement level, despite widespread female labor force participation. They suggest that social policies designed to ensure compatibility between employment and motherhood may have contributed in this area. Increases in female life expectancy are also noted, but at lower levels than in other developed countries.^ieng

[Forecasts of population trends in the German Democratic Republic yesterday and today]. / Prognosen fur die Bevolkerungsentwicklung der DDR gestern und heute.

PIP: Population forecasts for East Germany are presented. Aspects considered include population size, fertility, geographic distribution of the population, immigration, and age structure. The discrepancy between forecasts made in 1968 and actual trends is noted, and the socioeconomic impact of such trends is discussed.^ieng

Biphenotypic leukemic lymphocyte precursors in CD2+CD19+ acute lymphoblastic leukemia and their putative normal counterparts in human fetal hematopoietic tissues.

During detailed immunophenotypic analyses of marrow blasts from 336 acute lymphoblastic leukemia (ALL) patients, a very small percentage of cases reactive with B-cell-directed as well as T-cell-directed monoclonal antibodies (MoAbs) were identified. Five ALL cases were biphenotypic since they coexpressed CD2 (Tp50) and CD19 (Bp95) antigens at the single-cell level. The composite immunophenotype of these biphenotypic ALL cases was [TdT+HLA-ABC+CD2+CD3-CD10+CD13-CD14-CD16-CD19+CD20+ ++-CD21-CD33-CD34+Bgp95-C mu- slg-]. Low-molecular-weight B-cell growth factor (LMW-BCGF), recombinant interleukin-2 (rIL-2), and rIL-3 stimulated the proliferative activity of biphenotypic leukemic lymphocyte precursors without inducing differentiation. In the presence of the phorbol ester TPA, leukemic blasts from two cases differentiated along the B precursor pathway to the [CD2-CD10+CD19+CD20+C mu+slg-] pre-B cell stage. Biphenotypic ALL cases did not share a common configuration and gene rearrangement pattern of the immunoglobulin heavy chain genes or T-cell receptor (TCR) genes. Three cases had rearranged C mu genes but germline TCR genes, one case showed rearrangement of both C mu and TCR genes, and the remaining case had rearranged TCR genes but germline C mu genes. All five patients attained prompt remission after standard induction chemotherapy. Three to four years after initial diagnosis, four patients are now off chemotherapy and remain alive in their first remission. One patient relapsed at 3 years, 7 months, but promptly achieved complete remission after reinduction chemotherapy and remains in second remission off chemotherapy greater than 3 years after her reinduction therapy. With two-color immunofluorescence staining techniques and multiparameter flow cytometric analyses, we identified a small population of CD2+CD19+ lymphoid cells in fetal livers (FLs) and fetal bone marrows (FBMs), which may represent the putative normal counterparts of biphenotypic ALL blasts. A CD2+CD19+ normal biphenotypic lymphoid precursor cell line, designated FL 8.2 CD2+, was established from an FL of 8-weeks of gestational age by Epstein-Barr virus (EBV)-induced blastoid transformation. The composite immunophenotype of FL 8.2 CD2+ cell line was [TdT+HLA-ABC+HLA-DR+ CD2+CD5-CD7-CD10+/-CD13-CD19+CD20-CD21+ CD22+CD33-CD34+/-Bgp95-CDw40+C mu-slgD-slgM-]. FL 8.2 CD2+ cells showed germline patterns of immunoglobulin heavy-chain joining region, heavy-chain constant region, kappa light-chain constant region genes, and TCR beta-chain genes. Cross-linking of CD2 as well as CD19 antigens on FL 8.2 CD2+ cells caused an increase of intracellular ionized calcium.(ABSTRACT TRUNCATED AT 400 WORDS)

Primary peripheral neuroepithelioma of the orbit with intracranial extension.

A 7-year-old girl with clinical signs limited to moderate unilateral proptosis of 2 weeks duration and ipsilateral disc edema was found to have a contiguous orbital and subfrontal intracranial tumor best characterized as a peripheral neuroepithelioma by recent studies. Previously this tumor would have been called an extraosseous Ewing's sarcoma. The tumor had a significant lobular component on either side of the orbital roof. The patient is still alive 24 months posttreatment with multimodal excisional surgery, radiation, and chemotherapy.

Heterogeneity of cultured leukemic lymphoid progenitor cells from B cell precursor acute lymphoblastic leukemia (ALL) patients.

Colony assays were performed for 50 patients with B cell precursor acute lymphoblastic leukemia (ALL). Blast colony formation was observed for 33 patients, and the plating efficiency (PE) showed a marked interpatient variation, which indicates a pronounced biological heterogeneity at the level of leukemic progenitor cells. Notably, the mean PE of leukemic B cell precursors from patients with a pseudodiploid or near-diploid karyotype with structural chromosomal abnormalities (SCA) was significantly higher than the mean PE of normal diploid or hyperdiploid cases. All patients who had SCA involving 7p13, 11q23-24, or 12p11-13, and patients with a Philadelphia chromosome had high PE values. The S phase percentage, expression of CD19 antigen, and relapse status were also correlated with PE. Significantly, colony blasts had slightly different surface marker profiles in each case and were common ALL antigen negative in 33% of cases, which indicates the existence of a marked immunological heterogeneity at the level of leukemic progenitor cells.

Depression of cardiac function by bisantrene.

Bisantrene is a newer anthracycline derivative currently being investigated in phase 2 trials. One presumed advantage of bisantrene is that it is purportedly free of cardiotoxic effects. However, bisantrene apparently precipitated congestive heart failure after a single intravenous infusion in a young boy, prompting our study of a second child who remained asymptomatic but had transient declines in cardiac function after receiving bisantrene. Since bisantrene may acutely depress myocardial contractile function, further investigation is necessary.

Hypercalcemia associated with immunoreactive parathyroid hormone in a malignant rhabdoid tumor of the kidney (rhabdoid Wilms' tumor).

Severe hypercalcemia occurred in a child with metastatic disease from a rhabdoid tumor of the kidney. Because there was no evidence of skeletal involvement by tumor, an investigation of the cause for hypercalcemia was undertaken. A greatly elevated serum concentration of immunoreactive parathyroid hormone (iPTH) was documented. This together with the observation of histologically normal parathyroid glands and the immunohistologic demonstration of parathyroid hormone within tumor cells supports the hypothesis of ectopic iPTH production by the tumor. The concurrence of an unusual metabolic complication with an infrequently encountered tumor variant is notable.

Juvenile features in adult-type chronic granulocytic leukemia.

Philadelphia chromosome (Ph1) positive, or "adult-type," chronic granulocytic leukemia (CGL) differs in many clinical and laboratory aspects from PH1-negative, or "juvenile," CGL. Because of these differences, the disorders have been considered two distinct disease entities. We present a child with Ph1-positive CGL whose disease has several features more characteristic of the Ph1-negative syndrome. This case demonstrates that the chromosomal anomaly in CGL is not always predictive of phenotypic expression in this disease.

Mode of action of the IgG inhibitor of erythropoiesis in transient erythroblastopenia of children.

Twelve cases of transient erythroblastopenia of childhood (TEC) have been studied to evaluate their marrow cell erythropoiesis in vitro and the effect on it of their serum or IgG. The number of colony-forming units-erythroid (CFU-E) and burst-forming units-erythroid (BFU-E) in the bone marrow of nine cases was extremely variable and did not allow any conclusion regarding the pathogenesis of this anemia. An IgG inhibitor of growth of erythroid colonies or bursts was detected in 8/12 cases. This IgG inhibitor had no effect on the growth of granulocyte-macrophage colonies. Further studies on its mode of action indicated that the IgG did not have antierythropoietin antibody properties and did not affect the mature erythroblasts, as shown by a lack of inhibition of their responses to erythropoietin and by the lack of a cytotoxic effect on 59Fe-labeled erythroblasts. In four cases, preincubation studies demonstrated a direct effect of the IgG on the CFU-E, which was complement-mediated in three cases and complement-independent in one case. In two other cases, the IgG suppressed the growth of normal BFU-E only without affecting the growth of CFU-E. The IgG inhibitor was no longer present after the erythroblastopenia had remitted. These studies demonstrate that in the majority of cases of TEC, an IgG suppressor of erythropoiesis in vitro is present. Its mode of action is heterogeneous regarding its requirement for complement. Its target cells are the earlier or later erythroid progenitors, BFU-E or CFU-E, but not the differentiated erythroblasts.

Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils.

Human neutrophils exposed to chemotactic concentrations of zymosan-activated serum (ZAS) and a formylated chemotactic peptide (FMLP, 10(-7)--10(-9) M) were markedly enhanced in their ability to generate superoxide (O2-) upon stimulation with either sodium fluoride or phorbol myristate acetate (PMA). For both fluoride and PMA, enhancement was characterized by a decrease in the lag from stimulation to initiation of superoxide release and by an increase in the rate of superoxide generation--representing faster activation and increased activity of O2- generating enzyme, respectively. Chemotactic concentrations of casein, normal serum, and casein-treated serum enhanced the activity, but not the rate of activation, of the fluoride-stimulated superoxide generating system. This effect on activity was not so impressive as that obtained with FMLP or ZAS. The mechanisms by which FMLP enhanced responsiveness to fluoride and PMA were found to be different. Optimal enhancement for fluoride-stimulated responses required extracellular Ca++. Extracellular glucose, but not extracellular Ca++, was required for enhancement of FMLP of PMA-stimulated responses. A similar glucose requirement could not be demonstrated for chemotactic peptide enhancement of the superoxide-generating system stimulated by fluoride. Fluoride and PMA apparently activate the neutrophil O2- generating enzyme by pathways that are not identical. However, responsiveness of the enzyme to both agents is susceptible to modulation by cellular responses to chemotactic peptides.