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Biomedical subjects

N Schmitz

Publications and source records attributed to N Schmitz.

At least 19 recordsLinked to original sources

Allogeneic stem cell transplantation after reduced-intensity conditioning in lymphoid malignancies.

Allogeneic stem cell transplantation (allo-SCT) is an effective therapeutic option for a wide range of hematological malignancies. The toxicity of the conditioning regimen and graft-versus-host disease (GVHD) occurring after the infusion of the graft remain the most important factors leading to high morbidity and mortality. Reduced-intensity conditioning regimens have recently been developed in an effort to reduce the toxicity associated with conventional allo-SCT while preserving the curative potential of the graft-versus-tumor (GVT) effect. Most patients with lymphoproliferative disorders are not ideal candidates for allo-SCT due to higher age at diagnosis, which together with the advanced stage of disease at the time of transplantation can lead to a high transplant-related mortality (TRM). Preliminary experience indicates that reduced-intensity allo-SCT is feasible in such patients. The immediate TRM is low in comparison with conventional procedures and overall results seem promising, thus indicating the existence of a GVT effect. Nevertheless, all series are still low in numbers and follow-up is too short to draw definitive conclusions. Acute and chronic GVHD remain a significant problem with incidences comparable to the conventional setting in some series. Thus, therapeutic strategies must be sought to decrease GVHD without abrogating the GVT effect.

Graft vs Host Disease↗

Psychological distress and socioeconomic status in single mothers and their children in a German city.

BACKGROUND: The proportion of single mothers in western countries is continuously growing. In contrast to other western countries, support programs in Germany especially for single mothers are rare. This study identifies for the first time in Germany within a large epidemiological sample different subgroups of higher distressed single mothers as important potential target groups for psychosocial support interventions. Facing limited resources, data about these subgroups are helpful to develop and establish specific support programs. METHOD: In a cross-section study, family status of a complete cohort of school beginners in Duesseldorf (N = 5178 children, aged 5-7 years) was screened within the school eligibility test (recruitment rate 97.5 %, N = 5048). Out of a total of 891 single mothers, 531 fulfilling inclusion criteria (speaking fluent German, not married, living together with the tested child, informed consent) were compared to a control group of married mothers out of the same sample (N = 278). Socioeconomic status, social network and psychological distress of mothers (SCL-90-R) and children (CBCL) were investigated. RESULTS: Socioeconomic status (income, education) of single mothers was lower while psychological distress (SCL-90-R) was elevated compared to the control group. Single mothers without additional personal support for their child, younger, as well as poor single mothers showed higher values of psychological distress. In sons of single mothers, increased behavior problems were found (CBCL). Of all children screened, 907 (18 %) lived in single-parent families. CONCLUSION: An increased psychological distress of single mothers and their sons could be shown for the first time in Germany within a large epidemiologic sample. This has implications for the planning of preventive interventions and evaluation of associations, e. g., between social variables and distress of single mothers and their children within longitudinal study designs.

Adult↗

An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation.

The role of allogeneic bone marrow transplantation in lymphoma remains uncertain. We have analyzed 1185 allogeneic transplants for lymphoma reported to the EBMT registry between 1982 and 1998 and compared the results with those of 14687 autologous procedures performed over the same period. Patients receiving allogeneic transplants were subdivided according to histology: low-grade non-Hodgkin's lymphoma (NHL) 231 patients; intermediate-grade NHL 147 patients; high-grade NHL 255 patients; lymphoblastic NHL 314 patients; Burkitt's lymphoma 71 patients; and Hodgkin's disease 167 patients. These patients received allogeneic transplants as their first transplant procedure. Actuarial overall survival (OS) at 4 years from transplantation was: low-grade NHL 51.1%; intermediate-grade NHL 38.3%; high-grade NHL 41.2%; lymphoblastic lymphoma 42.0% years; Burkitt's lymphoma 37.1%; and Hodgkin's disease 24.7% years. These outcomes are relatively poor because of the high procedure-related mortality associated with these procedures, particularly in patients with Hodgkin's disease (51.7% actuarial procedure-related mortality at 4 years). Multivariate analysis showed that for all lymphomas apart from Hodgkin's disease, status at transplantation significantly affected outcome. A matched analysis was performed: for all categories of lymphoma, OS was better for autologous than for allogeneic transplantation. Relapse rate was better in the allogeneic group for low-, intermediate- and high-grade, and lymphoblastic NHL. It was equivalent for Burkitt's lymphoma and worse in the allogeneic group for Hodgkin's disease. Allogeneic transplantation appears to be superior to autologous procedures in terms of producing a lower relapse rate. The toxicity of allogeneic procedures must however be reduced before this translates into an improvement in OS.

Adolescent↗

Concentrations of lead in blood, hair and saliva of German children living in three different areas of traffic density.

Lead contents in hair, whole blood and saliva were determined for 245 healthy children (121 male, 124 female, age: 8-10 years) from three residential areas of Düsseldorf (North-Rhine-Westphalia, Germany) with different traffic densities. The geometric mean for the lead content in hair was found to be 0.87 microg/g (range: 0.2-9.9 microg/g) for the entire test group. While the levels of lead in hair in the suburban population were significantly lower than in the two city centre populations, no significant difference concerning the lead content in hair could be detected in the latter. The geometric mean for lead concentration in whole blood amounted to 25.0 microg/l (range: 8.0-154 microg/l). There was no significant difference between the sub-groups. The lead concentrations found in saliva were rather low (range: < 1.5-47.0 microg/l). Of the values, 89% were below the detection limit of 1.5 microg/l. Due to reduced levels of lead in fuel, the present study exposes that the amount of lead in the children examined has further decreased compared to preceding surveys. The correlation between the lead content in hair and the road traffic density was not corroborated by the findings with regard to amounts of lead found in blood, indicating that residual lead from fuel does not result in a substantial burden of lead found in the whole body. In contrast to levels of lead found in blood, levels of lead found in hair may be influenced more by environmental conditions. Saliva is not a suitable material for biological monitoring with respect to lead exposure in children.

Air Pollutants↗

[Specific countertransference experience and interpersonal problem description in psychodynamic psychotherapy].

In psychodynamic psychotherapy, countertransference and its professional use is seen as an important means to identify central difficulties of patients. The present study examines the correspondence of countertransference and interpersonal difficulties in 30 therapist-patient couples in day hospital psychodynamic psychotherapy. Interpersonal problems were recorded using the inventory of interpersonal problems (IIP) and countertransference was measured using the impact message inventory (IMI). Correspondence was measured as the correlation of IIP data from the patients and IMI data from the therapists. Data were collected at the start of therapy, after 4 weeks of treatment, and at the end of treatment. Over the course of the therapy, an increase in the correspondence of interpersonal problems as reported by patients and countertransference could be observed, starting with r = 0.22 at the beginning of therapy and continuing through r = 0.47 after 4 weeks to r = 0.58 at the end of therapy. The mean correlation was slightly above that of a control group of 20 nonclinical couples associated for at least 6 months.

Adult↗

Idiotype protein-pulsed dendritic cells produce strong anti-myeloma effects after syngeneic stem cell transplantation in mice.

Dendritic cell (DC) vaccination represents an interesting immunotherapeutic option in the treatment of several malignancies. In multiple myeloma (MM) patients, vaccination with autologous idiotype (Id) protein-pulsed DC is feasible, but their antitumoral effectiveness was rather limited. To improve the therapeutic potential of DC therapy, we studied the immunological effects of syngeneic peripheral blood stem cell transplantation (PBSCT) given in conjunction with Id-loaded DC. Balb/c mice were inoculated i.p. with 5 x 10(5) of HOPC myeloma cells (Balb/c origin). Animals were immunized with three injections of 5 x 10(5) DC pulsed with the IgG2a(HOPC) or with a control immunoglobulin (Ig(control)). Some experimental groups of myeloma-bearing animals received total body irradiation (7.5 Gy) and a subsequent transplant of 2 x 10(7)syngeneic peripheral blood progenitor cells (PBPC) followed by DC therapy beginning at day 10 post transplant. Animals receiving DC therapy or syngeneic PBPCT alone neither induce long-term survival nor tumor-specific CTL reactivity in vitro. In marked contrast, combination of syngeneic PBPC transplantation and subsequent DC therapy resulted in 78% survival after a follow-up of 180 days. In addition, this treatment modality conferred a generation of Id peptide-specific CD8-mediated T cell reactivity. These data provide a rationale for DC-based vaccination in multiple myeloma patients administered post syngeneic transplantation.

Animals↗

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Sub-Committee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders. Major changes have occurred since the last report in 1998. Haemopoietic stem cell transplantation today includes allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged, such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. Other indications, such as autologous transplantation for breast cancer have been challenged. An updated report with revised tables and operating definitions is presented here.

Adult↗

Mercury concentrations in urine, scalp hair, and saliva in children from Germany.

Mercury levels measured in urine, hair, and saliva of 245 German children (8-10 years old) are reported. Mercury concentrations in urine ranged between <0.1 and 5.3 microg/l [geometric mean (GM) 0.26 microg/l or 0.25 microg/g creatinine; median for both, 0.22 in microg/l and microg/g, respectively]. Using multiple linear regression analysis, two predictors have been found accounting for 25.3% of the variance of mercury levels in urine: the number of teeth with amalgam fillings (23.2%) and the number of defective amalgam fillings (2.1%). The mercury content in hair ranged from <0.06 to 1.7 microg/g (GM 0.18 microg/g; median 0.18 microg/g). The frequency of fish consumption, the smoking habits of the parents, and the age of the children accounted for 20.4% of the variance of mercury levels in hair. The correlation between the hair mercury content and urine mercury concentration was low (r=0.297). Mercury levels in saliva ranged between <0.32 and 4.5 microg/l (median 0.16 microg/l). The mercury concentration in saliva was below the limit of quantification of 0.32 microg/l in more than 70% of the samples. Mercury analysis in urine is suitable to estimate mercury exposure due to amalgam fillings, whereas hair mercury better reflects mercury intake by fish consumption. Up to now, saliva does not seem to be a suitable tool to monitor the mercury burden, at least not at low exposure levels.

Animals↗

A time-limited, problem-orientated psychotherapeutic intervention in Type 1 diabetic patients with complications: a randomized controlled trial.

AIMS: To examine the effects of a time-limited, problem-orientated psychotherapeutic intervention on self-defined psychological problems and metabolic control in Type 1 diabetic patients with microvascular complications. DESIGN: Randomized wait-list controlled trial with a follow-up of 6 months. SETTING: Out-patient clinic of a university diabetes centre. PARTICIPANTS: Forty-six Type 1 diabetic patients with intensified insulin therapy and presence of microvascular diabetic complications. Twenty-four patients were randomly allocated to the intervention group and 22 patients to the control group. INTERVENTION: Participation in a structured, problem-orientated, time-limited psychotherapeutic intervention (IG). The control group (CG) patients received routine diabetes care in a specialized diabetes university clinic. OUTCOME MEASURES: Degree of change of three self-defined main psychological and psychosocial problems (no. 1, no. 2 and no. 3) on a 1-10 graded scale and glycosylated haemoglobin HbA1c values. RESULTS: Two patients (one in each group) died during the study period. All remaining patients were followed for 6 months. Problem scores were high at baseline in both groups: IG/CG (mean values, standard deviation in parentheses): problem no. 1, 7.8 (2.0)/8.3 (1.7); problem no. 2, 7.7 (2.3)/7.6 (1.8); and problem no. 3, 7.7 (2.3)/7.4 (2.6). At follow-up, all problems were significantly lower in the intervention group (IG) when compared with the CG: IG/CG: problem no. 1, 4.3 (2.9)/6.8 (3.0), P = 0.03; problem no. 2, 3.9 (2.4)/5.8 (2.8), P = 0.03; problem no. 3, 4.7 (2.4)/6.8 (2.4), P = 0.02. Mean HbA1c decreased in the intervention group by 0.6 (1.2)% and increased in the control group by 0.1 (0.7)%, P = 0.016. In patients with suboptimal metabolic control, i.e. HbA1c > 8%, mean HbA1c decreased by 1.0 (1.2)% in the IG and increased by 0.1 (0.7)% in the CG, P = 0.011. CONCLUSION: A time-limited, structured, problem-orientated psychotherapeutic intervention decreases the severity of psychological problems and improves metabolic control in Type 1 diabetic patients with microvascular complications and self-management of intensified insulin therapy.

Adult↗

Survival and freedom from progression in autotransplant lymphoma patients is independent of stem cell source: further follow-up from the original randomised study to assess engraftment.

Peripheral blood progenitor cells (PBPCs) have become the stem cell source of choice in autologous transplantation. In a prospective randomised trial, we previously demonstrated that autologous transplantation using filgrastim-mobilised PBPCs resulted in faster haematopoietic recovery with shorter hospitalisation and reduced platelet transfusions compared to bone marrow transplant (BMT). This study is a follow-up analysis evaluating the long-term clinical outcome. Seventy-two patients with advanced Hodgkin's disease or high-grade lymphoma were randomised to receive either filgrastim-mobilised PBPCs (n = 37) or bone marrow (n = 35) after BEAM chemotherapy. Fourteen patients withdrew from the study before commencing high-dose chemotherapy. Fourteen of the 58 patients who received treatment with chemotherapy and transplant have died, 6 (19%) in the ABMT arm and 8 (30%) in the PBPC transplant (PBPCT) arm. Twenty-five patients (81%) in the ABMT arm and 17 (63%) in the PBPCT arm, who received treatment, were in complete remission at the date of last follow-up. Progression-free survival and overall survival (OS) were similar for both arms (OS 81% at 46 months for ABMT versus 63% for PBPC; p = 0.38). Further prospective studies with larger number of patients need to be done to assess which source of stem cells may translate into a long-term clinical benefit for the patient.

Adolescent↗

Role of allogeneic stem cell transplantation in relapsed or refractory Hodgkin's disease.

Little information is available regarding allogeneic stem cell transplantation (alloSCT) and Hodgkin's disease (HD). Autologous stem cell transplantation (autoSCT) is usually preferred to alloSCT due to its widespread availability, lack of the immunological problems intrinsic to the development of graft-versus-host disease (GvHD), and the infrequent bone marrow involvement present in HD patients undergoing high-dose chemotherapy/radiotherapy. AlloSCT has been associated with a high transplant-related mortality (TRM) in patients with HD due to a high incidence of GvHD and of fatal infectious events after transplantation. The poor outcome of these patients after alloSCT may reflect in part the advanced status of the disease at transplantation and the poor performance status of the patient population allografted. Furthermore, the high TRM present in t h e conventional alloSCT setting hasnever allowed a proper evaluation of a possible graft-versus-Hodgkin's effect. In an effort to reduce the TRM associated with alloSCT, low-intensity regimens have been developed; the curative potential of these protocols would rely on the graft-versus-leukemia effect of the allogeneic infusion more than in the conditioning regimen per se. Although the number of HD patients allografted with reduced-intensity protocols is low and the follow-up still short, TRM seems lower than in the conventional allograft setting despite a similar incidence of acute GvHD (aGvHD). Overall and progression-free survival seem promising, and patients developing aGvHD after transplantation or donor lymphocyte infusions seem to be at a lower risk of relapse than those not presenting this complication.

Disease Progression↗

[Interstitial lung disease in a patient given gemcitabine].

The differential diagnosis between infectious complications and tumor progression is sometimes difficult in patients given cytotoxic drugs. We report a case of diffuse interstitial lung disease induced by gemcitabine, a new agent used for the treatment of advanced-stage non-small-cell lung cancer.

Aged↗

Second German consensus on immunogenetic donor search for allotransplantation of hematopoietic stem cells.

The present paper summarizes the results of the second German consensus meeting on immunogenetic donor search for allotransplantation of hematopoietic stem cells held in Essen in November 1999 under the auspices of the German Society for Immunogenetics (DGI) and the German Working Party for Blood and Marrow Transplantation (DAG-KBT). Immunogeneticists and transplant physicians from all over the country agreed to update the national standards for: (1) search strategy including the role of unrelated and extended family donor search after unsuccessful core family donor search, (2) histocompatibility loci to be typed, (3) histocompatibility typing techniques to be used (HLA serology vs DNA-based HLA typing, cellular tests, serum cross-match), and (4) acceptable HLA mismatches in the context of a defined underlying disease, donor type, and conditioning regimen.

Aging↗

High-dose therapy and autologous stem-cell transplantation versus conventional-dose consolidation/maintenance therapy as postremission therapy for adult patients with lymphoblastic lymphoma: results of a randomized trial of the European Group for Blood and Marrow Transplantation and the United Kingdom Lymphoma Group.

PURPOSE: To determine whether a combination of high-dose therapy and autologous stem-cell transplantation (ASCT) is superior to conventional-dose consolidation and maintenance chemotherapy as postremission therapy in adults with lymphoblastic lymphoma. PATIENTS AND METHODS: One hundred nineteen patients were entered onto this prospective randomized trial from 37 centers. Patients received standard remission induction therapy, and responding patients were randomized either to continue with a conventional consolidation/maintenance protocol (CC) or to receive high-dose therapy and ASCT. In some centers, patients with HLA-identical sibling donors were registered on the trial but proceeded to allogeneic bone marrow transplantation (BMT) without randomization. RESULTS: Of the 119 patients entered, 111 were assessable for response to induction therapy. The overall response rate was 82% (56% complete response, 26% partial response). Of the 98 patients eligible for randomization, 65 were randomized, 31 to ASCT and 34 to CC. Reasons for failure to randomize included patient refusal (12 patients), early progression or death on induction therapy (eight patients), excessive toxicity of induction regimen (six patients), and elective allogeneic BMT (12 patients). With a median follow-up of 37 months, the actuarial 3-year relapse-free survival rate is 24% for the CC arm and 55% for the ASCT arm (hazards ratio = 0.55 in favor of the ASCT arm; 95% confidence interval [CI], 0.29 to 1.04; P =.065). The corresponding figures for overall survival are 45% and 56%, respectively (hazards ratio = 0.87 in favor of the ASCT arm; 95% CI, 0.42 to 1.81; P =.71). CONCLUSION: The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.

Adolescent↗

Event-by-event fluctuations of the Kaon-to-Pion ratio in central Pb+Pb collisions at 158 GeV per nucleon.

We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine nonstatistical fluctuations, which could be related to a first- or second-order QCD phase transition. Such fluctuations are shown to be very small.

Journal Article↗

The motion aftereffect: more than area V5/MT? Evidence from 15O-butanol PET studies.

The motion aftereffect is a perceptual phenomenon which has been extensively investigated both psychologically and physiologically. Neuroimaging techniques have recently demonstrated that area V5/MT is activated during the perception of this illusion. The aim of this study was to test the hypothesis if a more broadly distributed network of brain regions subserves the motion aftereffect. To identify the neuronal structures involved in the perception of the motion aftereffect, regional cerebral blood flow (rCBF) measurements with positron emission tomography were performed in six normal volunteers. Data were analysed using SPM96. The motion-sensitive visual areas including area V5/MT were activated in both hemispheres. Additionally, the lateral parietal cortex bilaterally, the right dorsolateral prefrontal cortex, the anterior cingulate cortex and the left cerebellum showed significant increases in rCBF values during the experience of the waterfall illusion. In a further reference condition with identical attentional demand but no perception of a motion aftereffect elevated rCBF were found in these regions as well. In conclusion, our findings support the notion that the perceptual illusion of motion arises exclusively in the motion-sensitive visual area V5/MT. In addition, a more widespread network of brain regions including the prefrontal and parietal cortex is activated during the waterfall illusion which represents a non-motion aftereffect-specific subset of brain areas but is involved in more basic attentional processing and cognition.

Adult↗

High-dose therapy and autologous stem-cell support for chemosensitive transformed low-grade follicular non-Hodgkin's lymphoma: a case-matched study from the European Bone Marrow Transplant Registry.

PURPOSE: To assess the outcome of high-dose therapy with autologous stem-cell support in patients with histologic transformation of low-grade follicular non-Hodgkin's lymphoma (NHL) and identify significant prognostic factors, as well as to compare survival of these patients with that of patients with matched low-grade and de novo high- or intermediate-grade NHL undergoing the same procedure. PATIENTS AND METHODS: Fifty patients with transformed low-grade NHL have been reported to the European Bone Marrow Transplant registry. Outcome from high-dose therapy and significant prognostic factors were analyzed. Their survival was also compared with that of 200 patients with matched low-grade NHL and 200 patients with matched de novo high- or intermediate-grade NHL by a case-matched analysis. RESULTS: The procedure-related death rate among the 50 transformed NHL patients was 18%. Overall survival (OS) and progression-free survival (PFS) rates were 51% and 30% at 5 years, respectively. Median PFS time was 13 months. Raised lactate dehydrogenase levels at transformation (P =.0031) was identified as the only adverse significant predictor of PFS on multivariate analysis. A subgroup of patients with residual chemosensitive disease who attained complete remission after high-dose therapy had the best outcome, with an OS at 5 years of 69%. A comparison with matched patients with low-grade disease and with de novo high- or intermediate-grade lymphoma showed no significant difference in OS (P =.939 and P =.438, respectively). CONCLUSION: Patients with chemosensitive transformed lymphoma should be seriously considered for high-dose therapy and autologous stem-cell support.

Adult↗