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Biomedical subjects

N Schmitz

Publications and source records attributed to N Schmitz.

At least 91 records · Page 5Linked to original sources

[Long-term results after tension-free inguinal hernia repair].

A total of 186 consecutive patients underwent open tension-free inguinal hernia repair, either on one or both sides. Overall, 220 hernias were repaired under local anesthesia conditions after intraoperatively classifying the size of the hernia. The follow-up investigation took place as planned in 165 hernias. The mean follow-up time was 15.5 months, with a range from 6.6 to 30. 8 months, and the follow-up rate was 75.0 %. During this first follow-up it was especially interesting to read the patients, self-assessment concerning their physical restrictions during the first month after the operation. Furthermore, we were interested in learning about the objective and subjective operation-linked consequences in the patients, inguinal region. Most patients (89.7 %) were able to do sports and drive their car; 86.1 % were able to manage their usual physical activity 4 weeks after the operation. Focusing on the operation site, patients complained about chronic unpleasant effects, such as mild pain (21.2 %), local hypoesthesia (12.1 %), weather-dependent changes in sensitivity (7.2 %), moderate pain (3.6 %), inguinal syndrome (1.8 %) and hyperesthesia (1.2 %). Persistent swelling in the parainguinal region was found in 1.8 % of the patients and only one recurrence was found (0.6 %). In the analysis we found that mild chronic pain was not related to the time period after the operation and the age or sex of the patient, but there was a correlation with the size of the hernia. Patients with small hernias significantly more often experienced chronic pain than patients with bigger hernias. These results suggest that open tension-free inguinal hernia repair according to Lichtenstein appears to be overtreatment in patients with small inguinal hernias.

Activities of Daily Living↗

[Feelings without speech or speech without feelings? Further evidence for the decoupling hypothesis of alexithymia].

The theoretical background of the present investigation was the decoupling hypothesis of alexithymia, which presumes for alexithymic individuals a dissociation of psychophysiological indicators of emotion from verbal cognitive awareness of one's emotional state. To study alterations in reactivity to emotionally distressing stimuli in alexithymic individuals, 12 high-alexithymic and 14 low-alexithymic subjects (separated by TAS) out of a general sample of 54 were investigated. All subjects were exposed to cognitive (CPT) and affect inductive (film sequences) distress. During stimulus exposition electrodermal activity (spontaneous fluctuations) was recorded. After stimulus exposition the subjects assessed their emotional reaction towards the film sequences (DAS). Concerning electrodermal activity no differences were found between high and low alexithymics under cognitive distress. In any case a significant autonomous arousal was registered. However, only the low alexithymic subjects but not the high alexithymics showed a significant increase of spontaneous fluctuations as expression of autonomous arousal during presentation of affect inductive stimuli. The altered psychophysiological reactivity found in high alexithymics in contrast to low alexithymic subjects was revealed specifically for the processing of emotional qualified stimuli. However, there was no difference between the groups in cognitive self assessment of emotional response towards the film sequences. The findings are discussed with reference to neurophysiological and psychodynamic models and the decoupling hypothesis of alexithymia.

Adult↗

Diagnosing mental disorders in primary care: the General Health Questionnaire (GHQ) and the Symptom Check List (SCL-90-R) as screening instruments.

BACKGROUND: The treatment of mental disorders in Germany is mainly done by primary care physicians. Several studies have shown that primary care physicians have difficulty in diagnosing these disorders. Recently, several self-report questionnaires have been developed that can be used as screening instruments to identify psychopathology in primary care settings and in the community. The aim of this paper was to investigate the screening properties of the General Health Questionnaire (GHQ-12) and the Symptom Check-List (SCL-90-R) in a primary care setting in Germany. METHOD: A randomly selected sample (n = 408) of adult outpatients from 18 primary care offices in Düsseldorf was screened using the German versions of the GHQ-12 and the SCL-90-R. A structured diagnostic interview (SCID) and an impairment rating (IS) were used as a gold standard to which both questionnaires were compared. Test performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: We found no difference in the performance of the general scores of the two questionnaires. Both instruments were able to detect cases. Complex scoring methods offered no advantages over simpler ones for the GHQ-12. ROC analysis confirmed that the SCL-90-R subscales "anxiety" and "depression" showed acceptable concurrent validity for the diagnostic groups anxiety and depression (according to DSM-III-R). CONCLUSIONS: GHQ-12 and SCL-90-R appeared to be useful tools for identifying mental disorders in primary care practice and research. The use of GHQ-12 or SCL-90-R, employed as a first step, supplemented by a second-stage interview, may enhance the detection rate of mental disorder in primary care settings.

Adult↗

A decade of spontaneous long-term course of psychogenic impairment in a community population sample.

BACKGROUND: Our epidemiological study demonstrates the spontaneous long-term course of predominantly psychosocially influenced ("psychogenic") disorders (neurotic spectrum disorders, personality disorders, stress reactions and somatoform disorders) in a representative community sample of the normal adult population of Mannheim, an industrial and university town in Germany. The natural spontaneous course of these disorders in a population sample over a long period remains largely unknown. METHOD: Beginning in 1979 (nt1 = 600) a random population sample was investigated three times over a mean period of approximately 11 years. The last follow-up study ended in 1994 (nt3 = 301). The follow-up sample was representative of the t1 sample. Psychodynamically trained and clinically experienced interviewers used a semi-structured interview and standardized clinical and psychometric instruments. Psychogenic impairment was assessed using a standardized expert rating (Impairment Score, IS). RESULTS: The mean sum-score of psychogenic impairment after 11 years exceeded the value at t1. The case rate (point prevalence, ICD diagnosis + clinical cut-off/IS) increased from 21.6% at t1 to 26.2% at t3 in the investigated follow-up sample. Intra-individual correlation of psychogenic impairment between t1 and t3 was high (r = 0.55). We found strong evidence for an unfavorable long-term course of psychogenic impairment and only a weak tendency (23.1%) for spontaneous remission of clinically relevant psychogenic impairment. Within a regression model clinical variables, childhood development conditions and personality traits at t1 predicted psychogenic impairment at t3. CONCLUSION: All clinical variables conclusively indicate an unfavorable spontaneous long-term course of psychogenic impairment. Together with the well-known high prevalence of psychogenic disorders in the normal population, this underlines the need for early therapeutic and preventive intervention.

Adult↗

Investigating the lysis of small-cell lung cancer cell lines by activated natural killer (NK) cells with a fluorometric assay for NK-cell-mediated cytotoxicity.

Activation of natural killer (NK) cells with interleukin-2 (IL-2) and IL-12 leads to an enhanced lysis of tumour cells. We investigated the ability of NK cells, with or without prior activation, to lyse a variety of small-cell lung cancer (SCLC) target cells. Specific lysis was measured with a fluorometric assay for NK-cell-mediated cytotoxicity: target cells were labelled with 3,3'-dioctadecyloxacarbocyanine, a green membrane dye. After co-incubation with NK cells, dead target cells were stained with propidium iodide, a red DNA dye that only penetrates dead cells. Of all eight SCLC cell lines tested, three were susceptible to lysis by non-activated NK cells, three were only susceptible to lysis by NK cells activated with IL-2 and IL-12 and two were not even susceptible to lysis by activated NK cells. The differences in target cell susceptibility showed no correlation with the expression of MHC-I on the surface of the target cells or with the expression of the adhesion molecules CD50, CD54, CD58 or CD102. Comparing the kinetics of the lysis of one SCLC cell line sensitive to non-activated NK cells and one sensitive only to activated NK cells, we found that maximum lysis of the former was obtained after 1 h, whereas significant lysis of the latter was only obtained after 4 h of incubation. This might be due to different mechanisms engaged in target cell lysis.

Carcinoma, Small Cell↗

The function of the chicken p34CDC2 protein kinase in fission yeast is cold sensitive for cell cycle progression through the G1 phase and temperature sensitive for traversal of mitosis.

The protein kinase p34cdc2 is required at the onset of DNA replication and for entry into mitosis. The catalytic subunit and its regulatory proteins, notably the cyclins, are conserved from yeast to man. This suggests that the control mechanisms necessary for progression through the cell cycle in fission yeast are conserved throughout evolution. This work describes the characterization of a fission yeast strain that is dependent for cell cycle progression on the activity of the p34CDC2 protein kinase from chicken. The response of the chicken p34CDC2 protein kinase to cell cycle components of fission yeast was examined. Cells expressing the chicken p34CDC2 protein divide at reduced size at 31 degrees C. Cells are temperature sensitive at 35.5 degrees C and die as a result of mitotic catastrophe. This phenotype can be rescued by delaying cell cycle progression at the G1-S transition by adding low concentrations of hydroxyurea. Schizosaccharomyces pombe cells that are dependent on chicken p34CDC2 are cold sensitive. At 19 degrees C to 25 degrees C cells arrest in the G1 phase, while traversal of the G2-M transition is not blocked at low temperature. Expression of chicken p34CDC2 in the cold-sensitive G2-M mutant cdc2A21 suppresses the G1 arrest.

Animals↗

Molecular cloning and characterization of a birch pollen minor allergen, Bet v 5, belonging to a family of isoflavone reductase-related proteins.

BACKGROUND: Birch pollen is a major cause of pollinosis and is responsible for cross-reactive oral allergies to fruits, nuts, and vegetables. The major allergen, Bet v 1, has been extensively characterized, and 3 minor allergens, Bet v 2, Bet v 3, and Bet v 4, have been cloned and sequenced. Recently, another birch pollen protein with an apparent mass of 35 kd was described as a new IgE-binding protein in birch pollen with cross-reacting homologues in plant foods. OBJECTIVE: The aim of this study was to determine the primary structure of the 35-kd birch pollen allergen and to investigate its immunologic properties. METHODS: On the basis of a known complementary DNA fragment, a PCR strategy was applied to obtain the full-length nucleotide sequence of the coding region. The protein was expressed as His-Tag fusion protein in Escherichia coli and purified by Ni-chelate affinity chromatography. Nonfusion protein was obtained by cyanogen bromide treatment of the fusion protein. IgE-binding characteristics and potential allergenicity were investigated by immunoblot, immunoblot inhibition analysis, rat basophil leukemia-cell mediator release assay, and basophil histamine release and compared with those of natural (n) Bet v 5, recombinant (r)Bet v 1, and rBet v 2. RESULTS: Recombinant Bet v 5 has a mass of 33 kd, an isoelectric point of 9.0, and sequence identity of 60% to 80% to isoflavone reductase homologue proteins from various plants. On immunoblots the recombinant Bet v 5 bound IgE from 9 (32%) of 28 sera from patients allergic to birch pollen with a CAP class of at least 3; Bet v 1 was detected by 89% of these patients. IgE immunoblot and inhibition experiments showed that nBet v 5 and rBet v 5 shared identical epitopes. A rabbit antiserum raised against pea isoflavone reductase and patients' IgE reacted with Bet v 5 and proteins of similar size in several vegetable foods, including exotic fruits. A similar reaction pattern was obtained with 2 Bet v 5-specific mAbs. Furthermore, Bet v 5 triggered a dose-dependent mediator release from rat basophil leukemia 2H3 cells passively sensitized with murine anti-birch pollen IgE and from basophils of a Bet v 5-reactive subject with birch pollen allergy. In contrast, no mediator release could be induced from basophils of a subject who was monosensitized to Bet v 1. CONCLUSIONS: This 33-kd protein, designated as Bet v 5, is a new minor allergen in birch pollen and may be responsible for pollen-related oral allergy to specific foods in a minority of patients with birch pollen allergy. Amino acid sequence comparison and immunoreactivity to anti-isoflavone reductase serum indicate that Bet v 5 is related to isoflavone reductase, a protein family that is involved in plant defense reactions.

Allergens↗

Anxiety moderates cardiovascular responses to painful stimuli during sphygmomanometry.

Sphygmomanometry is the most common technique of blood pressure (BP) determination. We were interested in the role of anxiety as a predictor of BP changes induced by painful stimuli during sphygmomanometry. We studied 141 normotensive healthy subjects who were asked to complete a State-Trait-Anxiety-Inventory (STAI) prior to the experiment. BP was determined continuously and non-invasively using a Finapres device (Penaz-technique) and by arm sphygmomanometry. Five sphygmomanometric measurements took place, during the fourth the arm cuff was inflated to 300 mmHg (unpredictable to the subject), the others were done with a pressure of 175 mmHg. State and trait anxiety (STAI X1 and X2) correlated positively with diastolic BP changes during inflation of the arm cuff (state anxiety: r = 0.26, P < 0.05; trait anxiety: r = 0.20, P < 0.05). Our results suggest that anxiety may have an impact on cardiovascular responses following painful stimuli.

Adult↗

OX40-deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL Responses after virus infection.

OX40, a member of the TNF receptor superfamily, is expressed on activated T cells and implicated in stimulation of T cells and T-dependent humoral responses. We generated OX40-/- mice and found that the formation of extrafollicular plasma cells, germinal centers, and antibody responses was independent of OX40. After infection with LCMV and influenza virus, OX40-/- mice retain primary and memory cytotoxic T cell responses with normal expansion and decline of specific CTL. In contrast, CD4+ T cell proliferation and the number of IFN-gamma-producing CD4+ T cells were reduced in OX40-/- mice. Moreover, the number of CD4+ T cells infiltrating the lungs of influenza virus-infected OX40-/- mice was reduced. These results define a unique role of OX40 in the generation of optimal CD4+ T cell responses in vivo.

Animals↗

Autografting of highly purified peripheral blood progenitor cells following myeloablative therapy in patients with lymphoma: a prospective study of the long-term effects on tumor eradication, reconstitution of hematopoiesis and immune recovery.

In a prospective study, we have investigated CD34+ selection of peripheral blood progenitor cells (PBPC) for autotransplantation in patients with lymphoma. Twenty-six consecutive patients (10 follicular lymphomas, seven mantle cell lymphomas, seven B-CLL, two immunocytomas) were mobilized using chemotherapy plus G-CSF. Sufficient numbers of PBPC could be collected from 24 patients and were immunoselected with the semiautomated Isolex 300 (n = 17) or the fully integrated Isolex 300i (n = 7) devices. The selection products were assayed by PCR amplification of clonal CDRIII or t(14;18) rearrangements for residual tumor cell content. Residual disease and long-term hematopoietic and immune recovery were studied by assessing the following parameters at 3, 6, and 12 months post-transplant: CDRIII or t(14;18) PCR, platelet count, lymphocyte subsets, serum IgG, serum IgA, and measles titer. With the Isolex 300 device 26% (10-65) of input CD34+ cells were recovered with a median purity of 89.2% (49.4-98.9) after CD34+ selection. The Isolex 300i device allowed significantly better recoveries (46% (22-86)) and purities of CD34+ cells (98.8% (92.2-99.2)). The overall purging efficacy was 3.2 (0.6-5.1) log. Twenty patients have been reinfused with CD34+ selected grafts after myeloablative preparation. Rapid engraftment occurred in all patients. With a median follow-up of 28 (19-42) months, 14 patients are alive without clinical or molecular evidence of disease recurrence, whereas five have relapsed and one additional patient shows persistent presence of the disease-specific molecular marker without clinical progression. Cellular and serological parameters of hematopoietic and immune functions were largely normal at 12 months post-transplant including the measles titer which was present in all patients. Kinetics of immunohematopoietic recovery were similar to those of 12 control patients who had received unmanipulated PBPC during the same time period except for the recovery of CD4+ CD45RA+ T cells which was significantly delayed in the CD34+ group. During the first year post-transplant, transient monoclonal or oligoclonal gammopathies were observed in seven of 16 study patients. We conclude that CD34+ selection with the Isolex system allows preparation of highly purified CD34+ fractions and effective tumor cell depletion. The CD34+ products can be reinfused safely after myeloablative treatment and result in sustained hematopoietic and immune recovery. The fact that all patients retained their specific measles immunity suggests that myeloablative treatment with reinfusion of highly purified CD34+ PBPC is not immunoablative.

Adult↗

Myeloablative radiochemotherapy followed by reinfusion of purged autologous stem cells for Waldenström's macroglobulinaemia.

Waldenström's macroglobulinaemia (WM) is an incurable lymphoproliferative disorder. The purpose of this study was to investigate the role of autologous peripheral blood stem cell transplantation (ASCT) for the treatment of WM. Seven patients (untreated or after first-line therapy) with symptomatic WM underwent two or three cycles of Dexa-BEAM chemotherapy + G-CSF with stem cell harvesting and proceeded to total body irradiation and high-dose cyclophosphamide followed by reinfusion of ex-vivo B-cell-depleted stem cells. Engraftment was prompt, and procedure-related deaths did not occur. A strong reduction or normalization of BM infiltration and serum IgM levels occurred in all evaluable patients, but immunofixation electrophoresis revealed persistent paraproteinaemia in five of them. With 3-30 months of follow-up, all patients are alive without clinical or serological signs of disease progression. This pilot trial shows for the first time that high-dose radiochemotherapy with purged stem cells is effective and may improve the course of patients with WM. In the majority of cases, however, complete eradication of the disease does not appear to be possible with ASCT alone.

Adolescent↗

Secondary leukaemia and myelodysplasia after autografting for lymphoma: results from the EBMT. EBMT Lymphoma and Late Effects Working Parties. European Group for Blood and Marrow Transplantation.

Between 1978 and 1996 more than 7500 lymphoma transplants have been reported to the European Bone Marrow Transplantation (EBMT) Lymphoma Registry. This has been examined to establish the incidence of secondary leukaemia and myelodysplasia and to relate this to possible prognostic factors. 131 centres representing 4998 patients responded to a questionnaire. This identified 66 patients with post transplant myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML). The actuarial risk for MDS/AML at 5 years post-transplant (+/-95% CI) was 4.6% (3.1-6.8) for Hodgkin's disease and 3.0% (2.0-4. 3) for non-Hodgkin's lymphoma. Multivariate analysis for all patients demonstrated an effect of age at transplant, radiotherapy at conditioning, number of transplants and interval between diagnosis and transplant as risk factors. For patients with NHL, grade of histology was important (low grade > intermediate or high-grade); for Hodgkin's disease, female sex was identified as a risk factor. These findings suggest that the incidence of MDS/AML may not be greater following an autograft than after conventional chemotherapy.

Adolescent↗

Psychometric properties of the General Health Questionnaire (GHQ-12) in a German primary care sample.

OBJECTIVE: The aim of this investigation was to examine the psychometric properties of the German 12-item General Health Questionnaire (GHQ-12) in a primary care sample. METHOD: A sample (n = 421) of adult out-patients was screened using the GHQ-12. A standardized clinical interview (SCID) was conducted with all screened patients. Reliability, validity and factor analysis of the GHQ-12 were evaluated. Item characteristics were examined using item characteristics curves. Item bias analysis was performed using contingency tables. RESULTS: The German version of the GHQ-12 is a reliable instrument and performed well in detecting cases of psychological disorders. Factor analysis replicated the findings of earlier studies. Item characteristics curves and item bias analysis indicated that the individual items should be assessed carefully. One item was biased in relation to age, while another item showed a low positive response rate. CONCLUSION: The GHQ-12 as a whole is a reliable questionnaire and can be a useful screening tool in primary care.

Adult↗

High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party.

PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy.

Adolescent↗