Supporting patients with heart failure with digital therapeutics-A pilot study in Germany.

Objective: Continuous monitoring and targeted behavioral interventions have been shown to improve health status and quality of life for heart failure patients. Digital therapeutics offer the possibility to make more frequent monitoring and targeted behavioral interventions available for more people. Methods: We conduct a pilot study with 71 patients who were given a smartphone app and wearables for a 3-month period. Clinical indicators as well as patient-reported outcomes were collected at entry and exit examinations. Results: The New York Heart Association class remained stable or improved. Most quantitative outcome measures improved (6-minute walk test distance + 21 m, Kansas City Cardiomyopathy Questionnaire summary score + 6.0 points, European Heard Failure Self-care Behavior Scale summary score + 6.6 points, correct answers in the Atlanta Heart Failure Knowledge Test + 2.1), although the changes were mainly not significantly different from zero. There was no change in EQ-5D weight and 9-item Shared Decision-Making Questionnaire summary score. Conclusions: This before-after comparison shows that an app-based intervention can work as a digital therapeutic for heart failure patients.

Depressive symptoms, impaired glucose metabolism, high visceral fat, and high systolic blood pressure in a subgroup of women with recent gestational diabetes.

Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.

Physical fitness and plasma leptin in women with recent gestational diabetes.

AIMS/HYPOTHESIS: Low physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass. METHODS: Cross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3-16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011-16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann-Whitney U and t -test, Spearman correlation coefficient, multiple linear regression. RESULTS: Women pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3-29.9) vs. 30.0(26.6-34.1)ml/min/kg; total VO2peak: 1733(1552-2005) vs. 1970(1767-2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5-136.5) vs. 141.0(128.5-159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI). CONCLUSIONS/INTERPRETATION: Women with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels-independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation.

First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin's lymphomas.

BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of copanlisib, a phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors or non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Phase I dose-escalation study including patients with advanced solid tumors or NHL, and a cohort of patients with type 2 diabetes mellitus. Patients received three weekly intravenous infusions of copanlisib per 28-day cycle over the dose range 0.1-1.2 mg/kg. Plasma copanlisib levels were analyzed for pharmacokinetics. Biomarker analysis included PIK3CA, KRAS, BRAF, and PTEN mutational status and PTEN immunohistochemistry. Whole-body [(18)F]-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) was carried out at baseline and following the first dose to assess early pharmacodynamic effects. Plasma glucose and insulin levels were evaluated serially. RESULTS: Fifty-seven patients received treatment. The MTD was 0.8 mg/kg copanlisib. The most frequent treatment-related adverse events were nausea and transient hyperglycemia. Copanlisib exposure was dose-proportional with no accumulation; peak exposure positively correlated with transient hyperglycemia post-infusion. Sixteen of 20 patients treated at the MTD had reduced (18)FDG-PET uptake; 7 (33%) had a reduction >25%. One patient achieved a complete response (CR; endometrial carcinoma exhibiting both PIK3CA and PTEN mutations and complete PTEN loss) and two had a partial response (PR; both metastatic breast cancer). Among the nine NHL patients, all six with follicular lymphoma (FL) responded (one CR and five PRs) and one patient with diffuse large B-cell lymphoma had a PR by investigator assessment; two patients with FL who achieved CR (per post hoc independent radiologic review) were on treatment >3 years. CONCLUSION: Copanlisib, dosed intermittently on days 1, 8, and 15 of a 28-day cycle, was well tolerated and the MTD was determined to be 0.8 mg/kg. Copanlisib exhibited dose-proportional pharmacokinetics and promising anti-tumor activity, particularly in patients with NHL. CLINICALTRIALSGOV: NCT00962611; https://clinicaltrials.gov/ct2/show/NCT00962611.

Response to medical treatment in patients with Crohn's disease: the role of NOD2/CRAD15, disease phenotype, and age of diagnosis.

PURPOSE: Factors influencing response to medications in Crohn's disease (CD) patients are not fully understood. We aimed to evaluate the relationships between NOD2/CARD15 mutations, disease phenotype and age of CD diagnosis and response to medical treatment with systemic steroids, azathioprine (AZA) or 6-mercaptopurine (6-MP), and infliximab. METHODS: A retrospective medical records analysis was made of patients previously tested for the CD-associated NOD2/CARD15 mutations. Harvey- Bradshaw score was used to assess remission or response to therapy. RESULTS: CD-associated NOD2/CARD15 mutations were not related to the rate of steroids dependency or clinical response to AZA/6-MP and infliximab. Steroid dependency was associated with colonic involvement. Thirty-three of 127 (26%) patients with colonic disease were steroid dependent, compared with 7/72 (9.7%) patients with isolated small bowel disease (ISBD), (p = 0.009). ISBD was mildly associated with a better remission/response to AZA/6-MP treatment. Disease behavior and age of diagnosis were not related to response to therapy. CONCLUSIONS: Response to treatment with systemic steroids, AZA/6-MP and infliximab are not related to NOD2/CARD15 mutations, age of diagnosis and disease behavior. Patients with colonic disease have higher rates of steroid dependency.

Phase I study of the novel, fully synthetic epothilone sagopilone (ZK-EPO) in patients with solid tumors.

BACKGROUND: Sagopilone (ZK-EPO) is a fully synthetic microtubule-stabilizing agent that has demonstrated high antitumor activity in preclinical models. This first-in-human phase I study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxic effects (DLTs) of 3-weekly sagopilone treatment. PATIENTS AND METHODS: A total of 52 patients with advanced solid tumors received a 30-min infusion of escalating doses of sagopilone (0.6-29.4 mg/m(2)) every 3 weeks. Nine additional patients were recruited to a 3-h infusion arm (16.53- or 22.0-mg/m(2) dose) to assess the incidence of neuropathy with prolonged infusion. RESULTS: The MTD was established as 22.0 mg/m(2). DLTs comprised peripheral sensory neuropathy (PNP), infection, hyponatremia, diarrhea, and central ataxia. PNP was the most common grade 3 event, with a similar incidence in the 30-min and 3-h arms. Hematologic adverse events were rare and of low intensity. One confirmed partial response (PR) and one unconfirmed PR were reported in the 30-min arm, and a further unconfirmed PR was observed in the 3-h arm. Eleven patients achieved disease stabilization. Sagopilone showed high levels of tissue binding and no obvious serum accumulation in both arms. CONCLUSIONS: These data demonstrate that sagopilone therapy is feasible and well tolerated. The recommended dose for phase II studies is 16.53 mg/m(2), once every 3 weeks.

Weekly administration of sagopilone (ZK-EPO), a fully synthetic epothilone, in patients with refractory solid tumours: results of a phase I trial.

BACKGROUND: Epothilones are a novel class of microtubule-stabilising agents, and sagopilone is a fully synthetic epothilone that has shown marked in vivo and in vitro preclinical activity. METHODS: This phase I, open-label study investigated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of weekly sagopilone. Twenty-three patients with malignancy resistant or refractory to standard treatment were enrolled into this study evaluating sagopilone doses from 0.6 to 7.0 mg m(-2). RESULTS: The incidence of drug-related haematological adverse events (AEs) was low, with two grade 3 events observed. Nonhaematological AEs were generally mild and reversible; increased gamma-GT was the only grade 4 event and grade 3 events comprised peripheral neuropathy (n=2), diarrhoea (n=1) and fatigue (n=1). Two grade 3 events were DLTs (diarrhoea and peripheral neuropathy at 7.0 mg m(-2)). The MTD of weekly sagopilone was therefore established as 5.3 mg m(-2). Stable disease was the best overall response (n=3). Microtubule bundle formation in peripheral blood mononuclear cells increased post-treatment, peaking after 1 h. Sagopilone disposition was similar across treatment courses and showed rapidly decreasing serum concentrations after infusion end and a long terminal disposition phase with no obvious accumulation in the serum, probably reflecting a fast uptake into tissues followed by a slow release. CONCLUSION: Weekly administration of sagopilone could represent an alternative to the 3-weekly administration currently evaluated in phase II trials.

Nonalcoholic fatty liver disease in overweight children and adolescents.

OBJECTIVE: To investigate the prevalence and characteristics of non-alcoholic fatty liver disease (NAFLD) and identify predictors for NAFLD in an overweight paediatric population. METHODS: The study group included 58 overweight (BMI-SDS 3.37 +/- 1) patients aged 8-18 years attending the paediatric obesity clinic. They underwent a clinical and biochemical work-up and liver ultrasonography. Grading of liver steatosis severity was done according to discrepancy in ultrasonographic liver-kidney densities. RESULTS: The prevalence of NAFLD was 60.3%. There was a highly significant (p = 0.004) association between severity of obesity and the presence or absence of liver steatosis. The study cohort was divided into three groups: group 1 (patients with normal ultrasonographic liver structure and normal liver enzymes), group 2 (patients with ultrasonographic fatty liver and normal liver enzymes) and group 3 (patients with ultrasonographic fatty liver and elevated liver enzymes). The BMI-SDS was significantly higher in group 3 compared to group 1 (4.2 +/- 1.1 vs. 2.8 +/- 0.9, p < 0.001). The rate of obesity complications was more prevalent in group 3 compared to groups 1 and 2 (p < 0.001). The insulin resistance index was higher in group 3 compared to group 1 (0.75 +/- 0.2 vs. 0.47 +/- 0.3, p < 0.05). CONCLUSIONS: The prevalence of NAFLD in our study cohort was high (60.3%). Patients with steatosis and elevated liver enzymes had a higher risk for obesity complications. Measurements of liver enzymes alone are insufficient, and liver ultrasonography is required for early identification of NAFLD.

Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukaemia and its link to treatment response.

AIMS: To characterize alemtuzumab pharmacokinetics and its exposure-response relationship with white blood cell (WBC) count in patients with B-cell chronic lymphocytic leukaemia (CLL). METHODS: Nonlinear mixed effects models were used to characterize plasma concentration-time data and WBC count-time data from 67 patients. Logistic regression was used to relate summary measures of drug exposure to tumour response. RESULTS: Alemtuzumab pharmacokinetics were best characterized by a two-compartment model with nonlinear elimination where V(max) (microg h(-1)) was [1020 x (WBC count/10 x 10(9) l(-1))(0.194)], K(m) was 338 microg l(-1), V(1) was 11.3 l, Q was 1.05 l h(-1) and V(2) was 41.5 l. Intersubject variability (ISV) in V(max), K(m), V(1) and V(2) was 32%, 145%, 84% and 179%, respectively. The reduction in WBC over time was modelled by a stimulatory loss indirect response model with values of 18.2 for E(max), 306 microg l(-1) for EC(50), 1.56 x 10(9) cells l(-1) h(-1) for K(in) and 0.029 per h for K(out). The probability of achieving a complete or partial response was >/=50% when the maximal trough concentration exceeded 13.2 microg ml(-1) or when AUC(0-tau) exceeded 484 microg h(-1) ml(-1). CONCLUSIONS: Alemtuzumab displayed time- and concentration-dependent pharmacokinetics with large interpatient variability, both in pharmacokinetics and pharmacodynamics, which was probably reflective of differences in tumour burden among patients. A direct relationship between maximal trough concentrations and clinical outcomes was observed, with increasing alemtuzumab exposure resulting in a greater probability of positive tumour response.

The origin of MDMA ("ecstasy")--separating the facts from the myth.

MDMA (3,4-methylenedioxy-N-methylamphetamine), better known as "Ecstasy", is a synthetic drug with psychedelic and stimulant effects which has gained great popularity. It is closely tied to the underground scene, but has also been used therapeutically as an adjunct to psychotherapy. Both scientific as well as newspaper articles communicate faulty or incomplete information on the origin of MDMA and the role of the German pharmaceutical-chemical company Merck in its development. One of the most common misconceptions is that the substance was synthesized with the goal of creating an anorectic but was not marketed by Merck because of side effects. It was our aim to clarify the circumstances of MDMA's discovery at Merck. An interdisciplinary working group conducted a comprehensive analysis of the original documents in Merck's historical archive in Darmstadt, Germany. It could be revealed that MDMA was in fact mentioned for the first time in files from 1912, but not under this name. In the lab journals it was called "Methylsafrylamin". In a patent certificate it was mentioned only with its chemical structure. Merck applied for this patent to protect an alternative chemical method for synthesizing the styptic hydrastinine, not appetite suppressants. MDMA was not the key substance in this patent, only a precursor. Archive documents revealed that Merck's scientists did not perform basic pharmacological tests with MDMA (now called "Safrylmethylamin") before 1927. These tests were halted for economic reasons. In the 1950s, primitive toxicological studies were conducted but MDMA was not tested in humans.

Improving health outcomes among individuals with HIV, mental illness, and substance use disorders in the Southeast.

Providing behavioral treatment for mental health and substance use disorders among HIV-infected individuals is critical because these disorders have been associated with negative outcomes such as poorer medication adherence. This study examines the effectiveness of an integrated treatment model for HIV-infected individuals who have both substance use and mental disorders. Study participants (n = 141) were recruited through routine mental health and substance abuse screening at tertiary Infectious Disease clinics in North Carolina. The study participants received integrated mental health and substance abuse treatment for one year and were interviewed at three-month intervals. Using linear regression analyses, we detected statistically significant decreases in participants' psychiatric symptomatology, illicit substance use, alcohol use, and inpatient hospital days. Participants also reported fewer emergency room visits and were more likely to be receiving antiretroviral medications and adequate psychotropic medication regimens at follow-up. No changes in sexual risk, physical health, or medical adherence were detected after treatment participation. This integrated treatment model offers an option for treating HIV-infected individuals with mental health and substance use disorders that can be adapted for use in a variety of psychiatric and medical treatment settings.

Does distance affect utilization of substance abuse and mental health services in the presence of transportation services?

Long travel times have been identified as a significant barrier to accessing mental health and other critical services. This study examines whether distance to treatment was a barrier to receiving outpatient mental health and substance abuse care for HIV-positive persons when transportation was provided. Data from a cohort of HIV-positive persons who participated in a year-long substance abuse and mental health treatment programme were examined longitudinally. Transportation, which included buses, taxis, and mileage reimbursement for private transportation, was provided free of charge for participants who needed this assistance. Nearly three-quarters (74%) of participants utilized the transportation services. No statistically significant differences in retention in, or utilization of, the mental health and substance abuse treatment programme were identified by distance to the treatment site. This analysis demonstrated that increased distance to care did not decrease utilization of the treatment programme when transportation was provided to the client when necessary. These results provide preliminary evidence that distance to substance abuse and mental health services need not be a barrier to care for HIV-positive individuals when transportation is provided. Such options may need to be considered when trying to treat geographically dispersed individuals so that efficiencies in treatment can be attained.

Association of unmet needs for support services with medication use and adherence among HIV-infected individuals in the southeastern United States.

Unmet needs for services, such as housing and psychiatric treatment, are relatively common among HIV-infected individuals; however, the effects of different types of unmet needs on health-care outcomes are not well understood. This study describes unmet psychosocial needs and their relationship with health-care outcomes among individuals receiving HIV care in the southeastern US (n=526). We used multivariate logistic regression to examine the association of seven categories of unmet needs with HIV medication use and adherence. Most participants (84.5%) reported at least one service need in the past year. Nearly half (47%) of participants with service needs reported that at least one need was not met. Participants with one or more unmet needs were less likely to be taking any HIV medications (p = 0.007) and reported poorer medication adherence (p=0.013). The specific unmet needs for benefits (including Social Security, health insurance and prescription coverage) (p = 0.006) and a support group (p=0.040) were associated with being less likely to be taking any HIV medications. Unmet need for mental health-related counseling was associated with poorer medication adherence (p=0.003). Study findings regarding the high level of unmet need and the association of unmet need with poorer outcomes illustrate the importance of interventions to address these needs.

Clinical and laboratory characteristics of non-E. coli urinary tract infections.

Comparison of the clinical and laboratory characteristics of infants and children with urinary tract infection caused by E. coli (n = 107) or other pathogens (n = 32) yielded a significantly higher association of non-E. coli disease with urinary tract anomalies, younger age, and previous antibiotic treatment. Underlying urinary tract anomalies were noted in 18 patients, of whom 14 (77%) were infected by non-E. coli pathogens. The most frequent anomaly was grade 3-4 vesicoureteral reflux (50%), followed by hydronephrosis (22.7%), ureteropelvic junction obstruction (9%), hypospadias (4.5%), pinpoint meatus (4.5%), and dysplastic kidney (4.5%).

Expression of poliovirus receptor-related proteins PRR1 and PRR2 in acute myeloid leukemia: first report of surface marker analysis, contribution to diagnosis, prognosis and implications for future therapeutical strategies.

Poliovirus receptor-related (PRR) proteins belong to the Nectin-adhesion molecules' group, are expressed on endothelial cells and on CD34(+) stem cells and mediate the organization of endothelial and epithelial junctions. There is evidence to suggest, that those receptors could have a role in leukemia. We have studied the expression of PRR molecules PRR1 and PRR2 on mononuclear bone marrow (BM) cells of 55 patients with acute myeloid leukemia (AML) at first diagnosis by FACS-analysis using directly Phycoerythrin-labeled markers (PRR1 clone R1.302.12; PRR2 clone R2.477.1) in combination with other Fluorescein conjugated antibodies to evaluate the blast phenotype in AML. The leukemic gate included blasts and residual monocytes and lymphocytes. A case was defined as positive, if more than 20% of the gated cells expressed the regarding receptor. We could demonstrate, that on average 35% PRR1(+) or 45% PRR2(+) cells in AML were found. Within FAB-types we observed a high PRR1 expression in cases with M3 and M4 and lowest expressions in M0 and M5; a high PRR2 expression was found in cases with M3, M4, M5 and M1 and lowest expressions in M0 and M2. Separating our patients' cohorts in cytogenetic risk groups we could detect a significant higher proportion of PRR1(+) cases (73% vs. 25% of cases, P = 0.009) or PRR1(+) cells (57% vs. 18% of cases, P = 0.001) in the cytogenetic favorable risk vs. poor risk group (75% vs. 32% PRR2(+) cases). Moreover cut-off-values with a maximum probability for a significant differentiation between cases with higher or lower levels of these markers could be found: cases with >78% PRR1(+) and cases with >77% PRR2(+) cells were characterized by a tendency for longer relapse free survival times. Qui-square analyses showed, that 3 of 4 cases with FAB-type M3 (P = 0.03) or a favorable karyotype (P = 0.04) were found in the group with >7% PRR1(+) cells, due to only few cases available a similar correlation, however, could not be found in cases with >78% PRR2(+) cells. We can conclude, that blasts in AML regularly express PRR1 and PRR2. Cases with a high expression of PRR1 or PRR2 are characterized by a more favorable prognosis. With respect to the individual PRR-status the benefit of biological response modifiers as priming agents, differentiation mediators or factors influencing cellular metabolisms inducing factors can be discussed under a new point of view.

Barriers to accessing HIV/AIDS care in North Carolina: rural and urban differences.

Many HIV-positive individuals face multiple barriers to care and therefore frequently experience unmet medical and support services needs. Rural areas often lack the infrastructure to support the delivery of comprehensive HIV services; however, few studies have examined service barriers faced by rural residents with HIV/AIDS, particularly in the South where two-thirds of people living with HIV/AIDS in rural areas reside. We surveyed North Carolina HIV/AIDS case managers (N = 111) employed at state-certified agencies regarding barriers to medical and support services that influence medication adherence for their rural and urban-living clients. For each of the seven barriers assessed (long travel for care, HIV-related stigma, and a lack of transportation; HIV-trained medical practitioners; housing; mental health services and substance abuse treatment), a substantial proportion of case managers (29-67%) reported it was a 'major problem'. For five of the seven barriers, rural case managers were significantly more likely to identify the barrier as a 'major problem'. Multivariate analysis revealed that rural case managers and case managers with more female clients reported a greater number of barriers. Because unmet medical and support service needs may result in poorer outcomes for HIV-positive individuals, barriers to these services must be identified and addressed, particularly in rural areas which may be highly underserved.

High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML).

Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80 proportions and lower CD86 proportions compared to the "nonresponder" group. Whereas cases with more than 15% CD80(+) cells had a significantly lower probability for relapse-free survival, only cases with more than 65% CD86(+) were characterized by a significantly lower probability for relapse-free survival. Expression profiles of CD11a and CD58 were not associated with specific FAB types or prognostically relevant groups. We can conclude: (1) Expression of costimulatory molecules in AML is very variable. This reflects the great diversity of immunophenotypes in AML. (2) CD56 is mainly expressed in monocytic subtypes of AML. CD56(+) subtypes of AML seem to be a separate entity with a worse prognosis independent of the karyotype. (3) High expression of some costimulatory molecules correlates with a worse prognosis concerning relapse-free survival times.

[Special clinical manifestations of Helicobacter pylori infection in children and adolescents].

During the period 1989-1996, we retrospectively investigated 104 children and adolescents with Helicobacter pylori infection diagnosed by gastroscopy. The median age was 12.11 +/- 3.31 years, 55% were female and 45% male. The chief complaint of 92% of the children was abdominal pain, mainly epigastric. The typical macroscopic finding was nodular gastritis. The most common microscopic picture was chronic superficial gastritis with lymphatic follicles and the presence of Helicobacter pylori. We demonstrated correlation between these gastroscopic and histological findings. Children who suffered from peptic ulcer were older than those with nodular gastritis. Most of the Helicobacter pylori positive patients were treated with triple drug therapy. The combination of drugs changed throughout the years according to the newly accepted strategies in the treatment of Helicobacter pylori. The majority of children reported a decrease in symptoms on completion of therapy. Urea breath test was an efficient and convenient method for the follow-up of patients with Helicobacter pylori infection.