[Breastfeeding Rates and Duration in Germany - A Systematic Review]. / Stillhäufigkeit und Stilldauer in Deutschland ­ eine systematische Übersicht.

Aim: 20 years after establishment of the National Breastfeeding Committee, the present work, based on published data on breastfeeding, is aimed at providing insight into the development of breastfeeding behaviour in Germany. Methods: To identify relevant publications, a comprehensive literature search was conducted in PubMed and Web of Science using the search terms "breast feeding" or "breastfeeding" in combination with "Germany". The publication period was limited to the period 1995-2014. Results: A total of 35 studies with data on breastfeeding for the birth cohorts of 1990-2012 were identified. Most of the data had been collected in regional or local surveys, often retrospectively. About 60% of the studies had been conducted with the primary aim of collecting data on breastfeeding or infant nutrition. Over the past 2 decades, breastfeeding rates were always relatively high at the beginning (72-97%). However, they declined significantly within the first 2 months, and by the age of 6 months, only about 50% of infants were still breastfed. Conclusion: Breastfeeding support and early assistance should be offered to a greater extent in order to achieve sustainable improvement of breastfeeding frequency and duration in Germany. Regarding the quality of data collected on breastfeeding, it seems crucial to implement standardised approaches to monitor breastfeeding in Germany.

[Molecular pathology of sarcomas. Update on the research group "Molecular Diagnosis of Sarcomas"]. / Molekularpathologie von Sarkomen. Erste Ergebnisse des Sarkomforschungsverbundes KoSar.

To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).

[Amphetamine misuse in suspected adult ADHS syndrome]. / Amphetaminmissbrauch bei angeblichem adultem Aufmerksamkeitsdefizit/Hyperaktivitätssyndrom.

Methylphenidate is increasingly used in adults with attention deficit/hyperactivity syndrome (ADHS). We report two cases of amphetamine misuse in patients with suspected ADH syndrome. In both cases the diagnoses had not been made in childhood. The interrelationship between substance use and adult ADHS is discussed.

[Public opinion on breast-feeding and infant nutrition: results of a questionnaire in North Rhine-Westphalia]. / Die Einstellung der Bevölkerung zum Stillen und zur Säuglingsernährung - Bevölkerungsbefragung in Nordrhein-Westfalen.

AIM: With the intention to create a basis for interventions on the promotion of breast-feeding, the public opinion on breast-feeding and infant nutrition in NRW was assessed. METHODS: A two-stage random sample of interviewees was drawn for a computer-assisted telephone survey (CATI). Methods applied on the selection of: 1. Households: 1.1. Gabler-Häder (n=1 811); 1.2. Onomastik (n=200); participants with a Turkish background of migration interviewed in German or Turkish language, alternatively: 2. Interviewees: Last Birthday method (n=2 011), age > or =18 years. RESULTS: Breast milk is the nutrition preferably recommended in the first six months, the knowledge of adjacent issues of infant nutrition has to be improved. The majority accepts supportive measures for breast-feeding. Different sources of information were assessed in Turkish and German participants. CONCLUSION: The survey supplies the background for the development of target group-specific information strategies which take specifically into account of issues attributable to ethnic differences and to reach the relatives and friends of young families, too.

Prediction of relapse of pediatric acute myeloid leukemia by use of multidimensional flow cytometry.

BACKGROUND: Most patients receiving therapy for acute myeloid leukemia (AML) enter an interval in which leukemic blast cells cannot be detected by light microscopy (i.e., morphologic remission). However, many of these patients experience a subsequent relapse. Multidimensional flow cytometry, which allows the discrimination of antigens expressed on normal and malignant cells, can detect small numbers of cancer cells in bone marrow or peripheral blood specimens. This technique enables the detection of one leukemic blast cell among 10(3) to 10(2) normal regenerating hematopoietic cells. PURPOSE: We determined whether the presence of residual leukemic blast cells, identified in the bone marrow of pediatric patients with AML by use of multidimensional flow cytometry, would be predictive of subsequent leukemic relapse. METHODS: Multidimensional flow cytometry was performed on 205 marrow specimens collected throughout the course of treatment from 39 patients who had achieved morphologic remission. The analyses employed monoclonal antibodies directed against CD45 in combination with mixed pairs of monoclonal antibodies directed against 10 other antigens. A time-varying Cox regression analysis that controlled for sample time intervals, age, sex, morphologic classification of disease, and white blood cell count at diagnosis was used to relate the multidimensional flow cytometric results to the risk of relapse after achieving remission. Reported P values are two-sided. RESULTS: Thirty-five of the 39 patients had bone marrow specimens available from the time that first morphologic remission was achieved. Leukemic blast cells were detected in the specimens from 19 (54%) of these 35 patients. Twenty-five of the 35 patients did not receive an allogeneic (i.e., from a different genetic background) bone marrow transplant during first morphologic remission, and 13 of 14 with residual leukemic cells experienced a relapse at a median time of 153 days after diagnosis (range, 48-863 days). Nine of the 11 patients who did not receive an allogeneic bone marrow transplant and lacked evidence of leukemic blast cells at first morphologic remission relapsed at a median time of 413 days after diagnosis (range, 321-794 days). Among the 10 individuals who received an allogeneic bone marrow transplant during first morphologic remission, five were positive for leukemic blast cells and five were negative; one of these patients (positive for leukemic blast cells) experienced a relapse 265 days after diagnosis, and three others died of transplant-related complications. The estimated risk of relapse during intervals of multidimensional flow cytometric positivity (i.e., intervals of remission for which the immediately preceding cytometry measurement was positive) was 2.8 times greater than that during negative intervals (95% confidence interval = 1.1-7.0; P = .02). CONCLUSIONS AND IMPLICATIONS: Multidimensional flow cytometry identifies residual leukemia in more than half of the patients with AML who are in morphologic remission. The detection of leukemic blast cells in these patients by multidimensional flow cytometry is predictive of a more rapid relapse.

Feasibility, toxicity, and biologic response of interleukin-2 after consolidation chemotherapy for acute myelogenous leukemia: a report from the Children's Cancer Group.

PURPOSE: Although remission can be achieved in 80% of children with acute myelogenous leukemia (AML), many patients experience relapse. Because interleukin-2 (IL-2) can induce remission in patients with overt evidence of AML, we hypothesized that IL-2 given to patients in first remission after intensive consolidation chemotherapy might prevent relapse. This study sought to determine whether such an approach was feasible. PATIENTS AND METHODS: Twenty-one patients in complete remission received IL-2 after completion of treatment on Children's Cancer Group (CCG) protocol 2941. Recombinant IL-2 9 x 10(6) IU/m2 daily by continuous intravenous infusion (c.i.v.) was given for 4 days. After 4 days rest, IL-2 1.6 x 10(6) IU/m2 daily c.i.v. was resumed for 10 days. We monitored patients for toxicity and measured absolute lymphocyte count, the absolute count of cells that express CD56 and CD3 antigen, and soluble IL-2 receptor alpha-chain (sIL-2R alpha) levels before the start of IL-2 and after completion of each of the two courses of IL-2. RESULTS: Observed toxicities included fever (57%), vascular leak (48%), hypotension (38%), tachycardia (14%), rash (29%), septicemia (5%), thrombocytopenia (29%), elevated transaminase (14%), electrolyte disturbance (29%), and hyperglycemia (10%). No patient required cardiac pressors or transfer to an intensive care unit. All patients studied developed an increase in lymphocyte count, CD56 count, CD3 count, and sIL-2R alpha levels after treatment with IL-2. CONCLUSION: This schedule of IL-2 was reasonably well tolerated by children with AML in first remission. After treatment, increased levels of sIL-2R alpha were observed. CCG is conducting a randomized prospective trial to assess the efficacy of IL-2 to prevent the relapse of AML (CCG-2961).

United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.

PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.

PURPOSE: Three open-label, multicenter trials were conducted to evaluate the efficacy and safety of single-agent Mylotarg (gemtuzumab ozogamicin; CMA-676; Wyeth Laboratories, Philadelphia, PA), an antibody-targeted chemotherapy agent, in patients with CD33-positive acute myeloid leukemia (AML) in untreated first relapse. PATIENTS AND METHODS: The study population comprised 142 patients with AML in first relapse with no history of an antecedent hematologic disorder and a median age of 61 years. All patients received Mylotarg as a 2-hour intravenous infusion, at a dose of 9 mg/m(2), at 2-week intervals for two doses. Patients were evaluated for remission, survival, and treatment-emergent adverse events. RESULTS: Thirty percent of patients treated with Mylotarg obtained remission as characterized by 5% or less blasts in the marrow, recovery of neutrophils to at least 1,500/microL, and RBC and platelet transfusion independence. Although patients treated with Mylotarg had relatively high incidences of myelosuppression, grade 3 or 4 hyperbilirubinemia (23%), and elevated hepatic transaminase levels (17%), the incidences of grade 3 or 4 mucositis (4%) and infections (28%) were relatively low. There was a low incidence of severe nausea and vomiting (11%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Many patients received Mylotarg on an outpatient basis (38% and 41% of patients for the first and second doses, respectively). Among the 142 patients, the median total duration of hospitalization was 24 days; 16% of patients required 7 days of hospitalization or less. CONCLUSION: Administration of the antibody-targeted chemotherapy agent Mylotarg to patients with CD33-positive AML in first relapse induces complete remissions with what appears to be a favorable safety profile.

Coculture with dendritic cells promotes proliferation but not cytotoxic activity of gamma/delta T cells.

T cells bearing the gamma9/delta2 T cell receptor (TCR) have recently raised interest as non-MHC restricted effector cells against multiple myeloma. They are described to be stimulated by phosphoantigens without the need of antigen presenting cells. However, in the past a positive effect of cells of the monocyte lineage on activation of gamma/delta T cells has been shown. Monocyte derived dendritic cells (DC) are professional antigen presenting cells widely investigated as stimulators of alpha/beta T cells. But only little is known about the interaction of gamma/delta T cells and monocyte derived DC. Here, we investigated the effect of coculture of mature DC unpulsed or pulsed with ibandronate on the proliferation and cytotoxic activity of isolated gamma/delta T cells. After coculturing monocyte derived DC with isolated gamma/delta T cells, proliferation of gamma/delta T cells was enhanced as determined by the (3)H thymidine uptake assay. Also, IFN-gamma secretion was increased after coculture with DC. As DC are well known to induce activation of alpha/beta T cells we investigated whether the cytotoxic activity of gamma/delta T cells could be increased by coculture with DC. We found no difference in cytotoxic activity of gamma/delta T cells alone or cocultured with unpulsed or pulsed mature DC. Also, sensitizing of myeloma cells by addition of ibandronate could not increase lysis by gamma/delta T cells. In conclusion, monocyte derived DC are capable of stimulating proliferation and secretion of IFN-gamma of gamma/delta T cells but do not exert an effect on cytotoxic activity of gamma/delta T cells against myeloma cells.

Cell surface expression of the multidrug resistance P-glycoprotein (P-170) as detected by monoclonal antibody MRK-16 in pediatric acute myeloid leukemia fails to define a poor prognostic group: a report from the Childrens Cancer Group.

Expression of the multidrug resistance (MDR-1) gene product, P-glycoprotein (P-170), and the stem cell antigen, CD34, at diagnosis were determined using monoclonal antibodies (MoAbs) MRK-16 and 12.8 respectively, in 130 pediatric acute myeloid leukemia (AML) patients entered onto Childrens Cancer Group (CCG) study CCG-2891. Fluorescein isothiocyanate (FITC) as a second step reagent was employed for the measurement of P-170 expression since it is commonly used in clinical laboratories. Nine of 30 (30%) infant ( < 1 year of age) de novo specimens expressed P-170 at levels > or = 20% of control cells. In contrast, eight of 100 (8%) AML samples from older children ( > or = 1 year of age) expressed the multidrug resistance surface protein at diagnosis. With the exception of one infant, all de novo samples that expressed P-170 also expressed CD34. Pediatric patients of any age with positive P-170 expression using MoAb MRK-16 with a FITC-conjugated second step reagent fared no worse than remaining patients treated on the same treatment with regard to induction failure, incidence of relapse, event-free survival, or overall survival. Further investigation is necessary to determine whether P-170 assay systems with greater sensitivity will distinguish pediatric AML patients with poor prognosis.

Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin).

We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101 patients > or =60 years of age with acute myeloid leukemia (AML) in untreated first relapse in three open-label trials. Mylotarg is administered as a 2-h intravenous infusion at 9 mg/m(2) for two doses with 14 days between doses. The overall remission rate was 28%, with complete remission (CR) in 13% of patients and complete remission with incomplete platelet recovery (CRp) in 15%. Median survival was 5.4 months for all patients and 14.5 months and 11.8 months for patients achieving CR and CRp, respectively. CD33 antigen is present on normal hematopoietic progenitor cells; thus, an expected high incidence of grade 3 or 4 neutropenia (99%) and thrombocytopenia (99%) was observed. The incidences of grade 3 or 4 elevations of bilirubin and hepatic transaminases were 24% and 15%, respectively. There was a low incidence of grade 3 or 4 mucositis (4%) and infections (27%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Mylotarg is an effective treatment for older patients with CD33-positive AML in first relapse and has acceptable toxicity.

Non-malignant neutropenia.

Neutropenia occurs when the production of neutrophils by the bone marrow is outpaced by utilization in the periphery. Abnormalities of hematopoietic stem-cell development and decreased proliferation of neutrophil precursors in the marrow can reduce production of neutrophils. Conversely, decreased neutrophil survival in the peripheral circulation can also give rise to neutropenia. Non-malignant neutropenia of acute onset can be caused by infection, antibody-mediated destruction, or an idiosyncratic reaction to a drug. Severe chronic neutropenia is a global, descriptive term for several disorders of varied etiologies in which neutrophil levels are consistently or recurrently at levels less than 0.5 x 10(9)/L. Despite this heterogeneity of origin, administration of recombinant human granulocyte colony stimulating factor to individuals with severe chronic neutropenia results in an increase in neutrophil counts in most patients associated with a significantly improved quality of life.

Understanding and exploiting nature's chemical arsenal: the past, present and future of calicheamicin research.

The enediyne antitumor antibiotics are appreciated for their novel molecular architecture, their remarkable biological activity and their fascinating mode of action and many have spawned considerable interest as anticancer agents in the pharmaceutical industry. Of equal importance to these astonishing properties, the enediynes also offer a distinct opportunity to study the unparalleled biosyntheses of their unique molecular scaffolds and what promises to be unprecedented modes of self-resistance to highly reactive natural products. Elucidation of these aspects should unveil novel mechanistic enzymology, and may provide access to the rational biosynthetic modification of enediyne structure for new drug leads, the construction of enediyne overproducing strains and eventually lead to an enediyne combinatorial biosynthesis program. This article strives to compile and present the critical research discoveries relevant to the clinically most promising enediyne, calicheamicin, from a historical perspective. Recent progress, particularly in the areas of biosynthesis, self-resistance, bio-engineering analogs and clinical studies are also highlighted.

Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukaemia in first relapse.

Gemtuzumab ozogamicin (CMA-676, Mylotarg, an antibody-targeted chemotherapy agent, was recently approved by the FDA for the treatment of patients with CD33+ acute myeloid leukaemia (AML) in first relapse who are 60 years of age or older and who are not considered candidates for other types of cytotoxic chemotherapy. In combined Phase II studies of 142 patients with CD33+ AML in first relapse, gemtuzumab ozogamicin monotherapy was associated with a 30% overall response rate. While treated patients had relatively high incidences of myelosuppression, grade 3 or grade 4 hyperbilirubinaemia (23%) and elevated hepatic transaminases (17%), the incidences of grade 3 or grade 4 mucositis (4%) and infections (28%) were low compared with what might be expected in association with conventional chemotherapeutic treatment. In contrast with the usual in-patient administration of cytarabine and anthracycline-containing induction regimens, a large number of patients were treated with gemtuzumab ozogamicin as outpatients (38% and 41% for the first and second doses, respectively). Two prognostic factors for patients with AML in first relapse, age and duration of complete remission, had relatively little effect on response rates to gemtuzumab ozogamicin. Preliminary data in pediatric patients also suggest the immunoconjugate to be reasonably well tolerated. Studies of gemtuzumab ozogamicin in combination with anthracycline and cytarabine are underway. Gemtuzumab ozogamicin, administered to patients with CD33+ AML in first relapse, has shown overall response rates comparable to conventional agents and a safety profile that appears to be favourable.

Targeted therapy of acute myeloid leukemia with monoclonal antibodies and immunoconjugates.

Traditional chemotherapy for acute leukemia often causes life-threatening toxic effects due to a lack of specificity for hematopoietic cells. Monoclonal antibodies and fusion proteins that target cell surface antigens on leukemic blasts are being evaluated for their cytotoxic effects and as a means of delivering chemotherapeutic agents or radiation directly to malignant cells. It is hoped that this strategy might selectively ablate malignant cells without many of the toxic effects commonly associated with conventional chemotherapy. In acute myeloid leukemia (AML), the cell surface antigens CD33 and CD45 are especially suitable targets. Although CD33 is expressed on AML blast cells from about 90% of patients, normal hematopoietic stem cells lack this antigen, as do essentially all nonhematopoietic tissues. For that reason, anti-CD33 antibodies have been created to target malignant myeloid and immature normal cells selectively while sparing normal stem cells. Anti-CD33 antibodies have also been used to deliver radiation or a cytotoxic agent directly to leukemic cells. Since the vast majority of leukemias and normal stem cells express the cell surface antigen CD45, another targeting approach allows the delivery of myeloablative radiation to bone marrow and spleen, common sites of leukemic involvement. Consequently, 131I-labeled anti-CD45 antibody has been combined with traditional preparative regimens for patients receiving bone marrow transplantation for acute leukemia. Finally, fusion proteins such as those combining diphtheria toxin with granulocyte-macrophage colony-stimulating factor (GM-CSF) to target the GM-CSF receptor are now being evaluated in clinical trials. Both unconjugated and conjugated antibodies have shown promise in early clinical trials, and may represent appealing therapeutic alternatives for patients with AML.

Targeted therapies for high-risk acute myeloid leukemia.

Approximately half of children with acute myeloid leukemia (AML) can be cured with contemporary chemotherapy regimens; however, various forms of drug resistance pose considerable obstacles for curing the remaining patients. Recent advances in immunology, cytogenetics, and cellular and molecular biology have provided new insights into fundamental biological differences between leukemic myeloid blasts and their normal counterparts. This article focuses on new technologies involving: (1) antibody- or growth factor-mediated targeting of antigens or growth factor receptors found on AML blasts and restricted sub-groups of normal cells, (2) pharmacologic targeting of the pathologic t(15;17) translocation of acute promyelocytic leukemia with all-trans retinoic acid, (3) pharmacologic and immunologic targeting of mutant RAS oncogenes and related aberrant signaling in AML blasts, and (4) targeting of pathological signaling of the Bcr-Abl oncoprotein and c-kit tyrosine kinase in myeloid leukemias. These advances herald an exciting new era of AML-specific therapies.

Expression of sialosyl-T and disialosyl-T antigens in erythroid cells.

Expression of T, sialosyl-T and disialosyl-T antigens on normal blood and bone marrow cells as well as transformed cells was examined using specific monoclonal antibodies and multidimensional flow cytometry. Both anti-sialosyl-T (QSH1) and anti-disialosyl-T (QSH2) monoclonal antibodies aggregated erythrocytes. The anti-disialosyl-T antibody was specific for the erythroid lineage and did not react with neutrophils, monocytes or T-lymphocytes, while the anti-sialosyl-T antibody reacted with erythroid cells and a subset of T-lymphocytes. The developing erythroid cells in bone marrow showed coordinate expression of glycophorin A and the two carbohydrate chains, sialosyl-T and disialosyl-T. Analysis of neoplastic cells showed that the anti-disialosyl-T antibody only reacted with glycophorin A-positive blasts from erythroleukemia (FAB M6) patients (4/4) and one patient with chronic myeloid leukemia in erythroblastic transformation (CMLET). Leukemic blasts from these patients demonstrated coordinate quantitative expression of glycophorin A and disialosyl-T. The anti-sialosyl-T antibody reacted with glycophorin A-positive blasts from FAB M6 patients (4/4) and one CMLET patient; however, the antibody also reacted with glycophorin A-negative blasts from one FAB M6 and the one CMLET patients and transformed cells from other types of leukemia. The anti-T monoclonal antibody (HH8) did not react with any of the other cells tested. These results indicate that glycophorin A and disialosyl-T expression are tightly linked during normal erythroid development and erythroid leukemogenesis.

New developments in the treatment of acute myeloid leukemia.

Curative therapy for acute myeloid leukemia (AML) remains unsatisfactory. However, three recent advances may play an important role in determining how AML is treated in the near future. First, the development of targeted antibody therapy using the anti-CD33-calicheamicin conjugate (gemtuzumab ozogamicin, Mylotarg) represents a novel targeted approach to the killing of leukemia cells. Second, modern molecular methods have improved our ability to identify minimal residual disease (MRD) in patients who appear to be in remission. These methods will allow physicians to tailor therapy, offering, for example, more intensive therapy to patients who harbor MRD. Lastly, the development of microarray gene expression technology allows for the simultaneous study of thousands of genes. With this technology, we may determine the genes responsible for the biological properties of treatment response and relapse in leukemia patients.

Cell surface receptor-targeted therapy of acute myeloid leukemia: a review.

Combination chemotherapy produces remissions in patients with acute myeloid leukemia (AML). However, the majority of patients ultimately relapse and die with cytotoxic drug resistant blasts. Novel agents which circumvent resistance are needed. One such class are AML-cell surface targeted proteins. These genetically engineered polypeptides are hybrid molecules composed of two moieties--a haptophore which triggers AML cell binding and a toxophore which kills the cell. The haptophore or ligand portion consists of a monoclonal antibody or antibody fragment or a cytokine. These peptides react with cell surface receptors or antigens on AML cells. The haptophore is genetically or chemically linked to the toxophore. The toxophore may consist of an antibody Fc domain which triggers antibody-dependent cell cytotoxicity, a DNA-damaging cytotoxic drug, a radionuclide or a protein synthesis-inactivating peptide toxin. The toxophore may provide a cell death signal that overcomes standard resistance phenotypes. Further, the targeting provided by the haptophore may reduce normal tissue toxicities. This review describes some of the properties of the cell surface molecular targets, the reactive haptophores and toxophores and how these functional peptides have been optimally combined to kill leukemic blasts in patients with AML.

Pancreatic contrast enhancement with Mn-bis pyridoxal ethylene diamine diacetic acid and the influence of a hormonal stimulation of the pancreas in pigs.

RATIONALE AND OBJECTIVES: Pancreatic and hepatic contrast enhancement after different modes of administration of Mn-bis pyridoxal ethylene diamine diacetic acid (Mn-DPDP) and the influence of the hormones secretin and cholecystokinin on the uptake of this new contrast agent were studied by using magnetic resonance (MR) imaging and atomic absorption spectroscopy (AAS) examinations carried out on 13 young domestic pigs. METHODS: Mn-DPDP was administered either as bolus injection or 30-min infusion. The course of contrast enhancement was noted. MR imaging was carried out with or without pancreatic stimulation. The Mn content in pancreatic and hepatic tissue was analyzed by using AAS. RESULTS: Mn-DPDP caused a significant increase (66 +/- 40.1%) in pancreatic signal intensity, an increase in hepatic signal intensity (78 +/- 23.0%), and a significantly higher Mn content on tissue samples of both organs. The results showed a wide individual range. With infusion of Mn-DPDP, pancreatic enhancement was slower, with a peak at 82 +/- 34 min compared with 54 +/- 51 min following bolus injection. The Mn content of both hepatic and pancreatic tissue determined by AAS seemed to be higher after infusion. An incomplete washout of Mn after 24 hr was demonstrated. Hormonal stimulation of the pancreas further increased pancreatic signal intensity but did not influence hepatic contrast enhancement. CONCLUSION: Infusion is the method of choice for administering Mn-DPDP because it causes an increase in hepatic signal intensity but does not change pancreatic enhancement. Although pancreatic hormonal stimulation intensifies enhancement, the increase is not statistically significant, and this practice will not contribute to day-to-day clinical practice.