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H Kirchner

Publications and source records attributed to H Kirchner.

At least 19 recordsLinked to original sources
PubMed2003

[Assessment and implementation of guidelines].

The importance of guidelines increases continuously on the political level whereas on the user level reservations and uncertainty persist. Consequently guidelines are not considered as they should be. Guidelines will develop their effectiveness only if they are firmly implemented in the delivery process. Acceptance problems spring from problems in development and from aspects of dissemination and implementation not sufficiently considered so far. Therefore a lot of countries have developed quality criteria for guidelines and programmes for quality promotion. To further the use of guidelines in the care process aspects of dissemination and implementation have to be recognized even in the development process. This has not been recognized sufficiently so far. Implementation of guidelines is a systematic approach which has to be connected seamlessly with other activities (e. g. quality management). The implementation process should be accompanied and evaluated so that a continuous adjustment is possible. Most of the existing guideline programmes do not consider this sufficiently. The following contribution gives a survey of results and introduces means and instruments for assessment and implementation of guidelines.

Forecasting↗
PubMed2003

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

Administration, Inhalation↗
PubMed2002

Successful long-term erythrocytapheresis therapy in a patient with symptomatic sickle-cell disease using an arterio-venous fistula.

The use of long-term automated erythrocytapheresis via an arterio-venous fistula for the prevention of recurrent ischaemic stroke in a child with sickle-cell disease (SCD) has not been described previously. We report the successful use of this technique in a 13-year-old boy. A procedure was performed every 36 +/- 6 days, transfusing six units of donor packed red blood cells (RBCs) and discarding 1318 +/- 174 mL of exchanged erythrocytes (Hct 60%). After transfusion of 85 units over 17 months, there is no evidence for iron-overload, red cell alloimmunization, transfusion-transmitted infections, or other complications. Until now, no cerebrovascular ischaemia has been observed.

Adolescent↗
PubMed2002

[Current initiatives in Germany for translating national guidelines into reality - a survey].

The role of practice guidelines as a tool for quality management in health care is now widely accepted in Germany- not only by health professionals, but also in politics. The physicians' professional associations as well as health care authorities (physicians' self-governmental bodies) and parliament introduced several incentives and regulations, aiming at a regular use of guidelines in health care. Among these the German guideline clearinghouse with the systematic approach towards identification, dissemination, and implementation of best available evidence-based guidelines, as well as the country-wide implementation of disease management guidelines seem to be effective and efficient in quality management as well as in patient care management in the German health care system. The article gives an overview on background, procedures and barriers to country-wide implementation of clinical practice guidelines within a social security health care system.

Forecasting↗
PubMed2001

IL-2 in combination with IFN- alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial.

We conducted a prospectively randomized clinical trial to compare the efficacy and safety of subcutaneous interferon-alpha2a, subcutaneous interleukin-2 and intravenous 5-fluorouracil as home therapy against oral tamoxifen in 78 patients with progressive metastatic renal cell carcinoma. Treatment courses consisted of interferon-alpha2a 5 x 10(6) IU m(-2), day 1 weeks 1 + 4; days 1, 3, 5 weeks 2 + 3; 10 x 10(6) IU m(-2), days 1, 3, 5 weeks 5-8; interleukin-2 10 x 10(6) IU m(-2), twice daily days 3-5 weeks 1 + 4; 5 x 10(6) IU m(-2), days 1, 3, 5 weeks 2 + 3; and 5-fluorouracil 1000 mg m(-2), day 1 weeks 5-8. The tamoxifen group received tamoxifen 80 mg twice daily over 8 weeks. Among 41 patients treated with interleukin-2, interferon-alpha2a and 5-fluorouracil there were 7 complete (17.1%) and 9 partial responders (21.9%), with an overall objective response rate of 39.1% (95% CI, 24.2-55.5). An additional 15 patients (36.6%) were stable throughout therapy. The overall survival was 24 months (range 5-76+). In 37 patients receiving tamoxifen no objective remissions occurred. 13 patients (35.1%) had stable disease and 24 patients (64.9%) showed continued disease progression. The overall survival was 13 months (range 3-73+). In summary, this home-based therapy regimen of interferon-alpha2a, interleukin-2 and 5-fluorouracil demonstrated significant therapeutic efficacy in patients with progressive renal cell carcinoma when compared to hormonal therapy.

Adult↗
PubMed2001

Low-dose radiation is sufficient for the noninvolved extended-field treatment in favorable early-stage Hodgkin's disease: long-term results of a randomized trial of radiotherapy alone.

PURPOSE: To show that radiotherapy (RT) dose to the noninvolved extended field (EF) can be reduced without loss of efficacy in patients with early-stage Hodgkin's disease (HD). PATIENTS AND METHODS: During 1988 to 1994, pathologically staged patients with stage I or II disease who were without risk factors (large mediastinal mass, extranodal lesions, massive splenic disease, elevated erythrocyte sedimentation rate, or three or more involved areas) were recruited from various centers. All patients received 40 Gy total fractionated dose to the involved field areas but were randomly assigned to receive either 40 Gy (arm A) or 30 Gy (arm B) total fractionated dose for the clinically noninvolved EF. No chemotherapy was given. RT films were prospectively reviewed for protocol violations and recurrences retrospectively related to the applied RT. RESULTS: Of 382 recruited patients, 376 were eligible for randomized comparison, 190 in arm A and 186 in arm B. Complete remission was attained in 98% of patients in each arm. With a median follow-up of 86 months, 7-year relapse-free survival (RFS) rates were 78% (arm A) and 83% (arm B) (P =.093). The upper 95% confidence limit for the possible inferiority of arm B in RFS was 4%. Corresponding overall survival rates were 91% (arm A) and 96% (arm B) (P =.16). The most common causes of death (n = 27) were cardiorespiratory disease/pulmonary embolisms (seven), second malignancy (six), and HD (five). Protocol violation was associated with significantly poorer RFS. Nonirradiated nodes were involved in 42 of 52 reviewed relapses, infield areas in 18, marginal areas in 17, and extranodal sites in 16. CONCLUSION: EF-RT alone attains good survival rates in favorable early-stage HD. The 30-Gy dose is adequate for clinically noninvolved areas. Protocol violation worsens the subsequent prognosis. Relapse patterns suggest that systemic therapy can reduce the 20% long-term relapse rate.

Adolescent↗
PubMed2001

Different immune patterns in melancholic and non-melancholic major depression.

The search for immune patterns in major depression has thus far resulted in ambiguous findings, probably because patient samples are psychiatrically heterogeneous. We therefore focused on a detailed classification of subtypes of major depression, comparing patients with melancholic and non-melancholic major depression. Inpatients suffering from acute major depression were diagnosed and subclassified according to DSM IV criteria. Cell counts were determined by FACS analysis and morphology. Cytokine production (IL-2, IFN-gamma, IL-10) upon mitogen stimulation was measured by ELISA in a whole blood assay. Non-melancholic patients showed increased counts of leukocytes, lymphocytes and NK-cells in the acute stage of disease and after two and four weeks of treatment. Their lymphokine production was unchanged compared to that of healthy controls. Melancholic patients on the other hand demonstrated normal cell counts but a decreased production of IL-2, IFN-gamma and IL-10 during the acute stage of disease followed by a normalization with clinical improvement. Melancholic and non-melancholic patients showed different immune patterns. Classifying melancholic and non-melancholic patients is helpful towards the identification of immune characteristics typical for these diseases.

Adult↗
PubMed2001

Inflammatory markers in major depression and melancholia.

BACKGROUND: There is evidence that patients with major depression (MD) also suffer an inflammatory immune reaction. However, the results remain ambiguous. This could be due to the psychiatrically heterogeneous patient samples investigated in many published studies. Since melancholic depression is psychopathologically and possibly etiologically different from non-melancholic MD, we focused on investigating immune parameters in these two subgroups. METHODS: 43 in-patients suffering from acute major depression were diagnosed, sub-classified according to DSM IV criteria, and compared to 43 matched healthy controls. Cell counts were determined by morphology, and acute phase proteins [c-reactive protein (CRP), alpha(2)-macroglobulin (A2M), haptoglobin (HP)] were measured by laser nephelometry. Cytokine production (IL-1beta) upon mitogen stimulation was measured by ELISA in a whole blood assay. RESULTS: Non-melancholic patients showed increased monocyte counts and A2M serum concentrations in the acute stage of disease and after 2 and 4 weeks of treatment. Melancholic patients demonstrated a decreased monocyte count upon admission and after 4 weeks of treatment. HP levels and IL-1beta production were unchanged in all studied subjects. LIMITATIONS: Medication of the patients varied. The differentiation between melancholic and non-melancholic depression was performed clinically and was not performed using any standardized instrument. CONCLUSION: Melancholic and non-melancholic patients show different immune patterns. This differentiation might clarify immunological findings in MD and point towards etiological factors that are involved in the development of various subtypes of MD.

Acute-Phase Proteins↗
PubMed2001

S-100B is increased in melancholic but not in non-melancholic major depression.

BACKGROUND: Recent evidence suggests that neurodegeneration may be involved in the pathophysiology of major depression. The astroglial peptide S-100B was shown to be increased in many diseases causing neuronal cell damage or degeneration. METHOD: S-100B plasma levels were determined in 28 patients with major depression and 28 matched healthy controls using an immunofluorometric sandwich assay. RESULTS: Patients suffering from melancholic depression showed significantly increased S-100B levels compared to healthy controls while non-melancholic patients demonstrated normal levels. LIMITATIONS: Medication of patients varied. The differentiation between melancholic and non-melancholic patients was performed clinically without using a standardized instrument. CONCLUSIONS: Neurodegeneration or axonal remodeling may be involved in the pathogenesis of melancholic depression.

Adult↗
PubMed2001

Dose escalation of cytotoxic drugs using haematopoietic growth factors: a randomized trial to determine the magnitude of increase provided by GM-CSF.

BACKGROUND: The magnitude of chemotherapy dose escalation made possible by the use of recombinant haematopoietic growth factors has not been quantified in a randomized trial. PATIENTS AND METHODS: Patients with refractory or relapsing Hodgkin's disease were randomized to receive the Dexa-BEAM regimen with escalating etoposide doses supported by placebo or granulocyte-macrophage colony-stimulating factor (GM-CSF). Using an adaptive sampling method independently in both arms, the etoposide dose was escalated until the maximal tolerated dose for the first cycle was reached. RESULTS: Thirty patients were randomized to GM-CSF and thirty to placebo. The etoposide dose could be escalated considerably in both treatment arms. Maximal etoposide dose for the first cycle was 1920 mg/m2 for patients receiving GM-CSF and 1160 mg/m2 for patients receiving placebo (P = 0.045 one-sided), corresponding to a 65% higher etoposide dose and a 13% higher dose intensity with GM-CSF. Dose-limiting events were similar in both arms, consisting mainly of prolonged neutropenia and consecutive infections. Treatment efficacy was not different in the two treatment groups. CONCLUSIONS: While GM-CSF permits a somewhat higher dose escalation than placebo, the increase in dose intensity provided by GM-CSF is small. The use of CSF for interval reduction rather than dose escalation is the more effective strategy for dose intensification.

Adolescent↗
PubMed2001

Results of vitrectomy and the no-touch-technique using autologous adjuvants in macular hole treatment.

BACKGROUND: Anatomic and functional results of macular holes using vitrectomy and platelet-concentrate (PC) or autologous whole blood (WB) were investigated without peeling any epiretinal membrane in order to minimize retinal trauma. METHODS: 44 patients with macular holes stage II, III and IV underwent a vitrectomy with removal of posterior cortical vitreous (in stage II and III) and C2F6 gas endotamponade. No peeling of any epiretinal membrane or the ILM was performed. In 14 patients autologous WB was injected and in 30 patients autologous PC. The mean follow-up time was 9.3 months. RESULTS: An anatomic closure was observed in 36.4% of patients in the WB-group and in 93.9% of patients in the PC-group. SLO-microperimetry showed a reduction of absolute scotomas in 80% of the WB- and in 75% of the PC-group. In the WB-group 1 retinal detachment and 1 branch vein occlusion occurred; in the PC-group 3 retinal detachments, 1 central artery occlusion, 1 macular pucker, 1 cystoid macular edema, 1 late reopening and 1 secondary glaucoma were observed. In both groups no endophthalmitis occurred. CONCLUSION: If autologous platelet concentrate is available, high anatomic success rates can be achieved without aggressive membrane removal, which may cause retinal damage. Autologous whole blood cannot be recommended as an alternative adjunct for the treatment of macular holes without membrane removal.

Adult↗
PubMed2001

Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation.

For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3(+) lymphocytes, a consistent reconstitution associated with an increase in CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+) helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4(+) subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFNgamma synthesis.

Adult↗
PubMed2001

Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology.

S100B, a calcium-binding protein produced by astroglial cells, is a marker of astroglial cellular integrity. It has been shown to be increased in acute brain damage and neurodegeneration. A recent study showed increased S100B levels in medicated acutely psychotic patients with schizophrenia. The study presented here included 26 drug-free patients with acute schizophrenia and 26 matched healthy controls. S100B blood concentrations were determined using a quantitative immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS was used to investigate psychopathology. Unmedicated schizophrenic patients showed significantly increased S100B levels compared to matched healthy controls. After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15 patients the levels remained increased. These patients showed significantly higher PANSS negative scores upon admission and after 6 weeks of treatment. Schizophrenic patients display a loss of astroglial integrity which is not caused by neuroleptic medication. Continuously increased S100B levels are associated with negative symptomatology.

Adult↗
PubMed2001

The effect of moderate hypovolaemia on microcirculation in healthy older blood donors.

Compensation for acute blood loss requires cardiovascular integrity. In older people, asymptomatic cardiovascular impairment is common. In these subjects, even moderate blood loss is often treated by external volume replacement although its benefits are not clear. We investigated the effect of 450 ml of blood loss on the microcirculation and compensatory mechanisms in healthy older blood donors. Red blood cell count, plasma viscosity and protein concentration were measured. Plasma volume replacement was calculated using haematocrit. We measured microcirculation tissue perfusion by laser Doppler fluxmetry prior to, during and after blood donation. Blood loss was immediately accompanied by a median rapid water shift of 208 ml (interquartile range 134-298 ml). Haemodilution led to a decrease in haematocrit, protein and plasma viscosity. We observed no changes in cutaneous microcirculation. Moderate blood loss is tolerated in older cardiovascularly asymptomatic patients without having an impact on microcirculation. This may reduce the need for external volume replacement.

Aged↗
PubMed2001

A novel RT-PCR for reliable and rapid HCV RNA screening of blood donations.

BACKGROUND: The objective of this work was to develop a novel and highly sensitive RT-PCR method that is suitable for HCV RNA screening of blood donations according to the criteria released by the Paul Ehrlich Institute, the federal licensing agency of Germany, for routine HCV NAT. STUDY DESIGN AND METHODS: RNA was prepared from plasma pools of up to 20 single blood donations using an automated nucleic acid isolation system (NucliSens Extractor, Organon Teknika). For reverse transcription, amplification, and simultaneous detection of PCR products, a novel approach based on the TaqMan technology was developed. Glyceraldehyde-3-phosphate dehydrogenase messenger RNA, which is detectable in human plasma, was coamplified in each reaction as an internal positive control. RESULTS: The HCV genotypes and subtypes 1a, 1b, 2a, 2b, 2c, 2i, 3a, 4, and 5a were detected in parallel with comparable amplification efficiency. The 95-percent detection limit related to the WHO HCV RNA standard preparation was calculated to be 389 IU per mL of plasma of the single blood donation. Total CVs (%) were <4. The screening of up to 180 blood donations took 5 hours; as a rule, the blood components could be released on the day of donation. CONCLUSION: The TaqMan HCV RT-PCR is an almost completely automated, highly sensitive, specific, and rapid method that is reliable for HCV RNA screening of blood donations. It allows a closed-tube HCV RNA detection without risk of contamination by PCR products.

Blood Donors↗
PubMed2001

A 5-year follow-up on antibody response after diphtheria and tetanus vaccination in hemodialysis patients.

Chronic renal failure is associated with a T-cell-dependent immune defect. In the past, various studies have focused on the insufficient immune response to vaccination of hemodialysis patients. An impaired vaccination response rate has been reported for vaccines against hepatitis B, influenza, tetanus, diphtheria, and others. However, no data exist on the long-term success of vaccination against tetanus and diphtheria in these patients. The aim of the present study is to investigate seroresponse to tetanus and diphtheria vaccination over a 5-year period. Antibody levels were determined by enzyme immunoassay. Antidiphtheria antibody levels of 31 hemodialysis patients were determined 5 years after vaccination. After 5 years, 10 of 31 patients (32%) had a protective antibody level against diphtheria (>/=0.1 IU/mL), whereas 12 months after vaccination, 26 of 71 patients (37%) were protected. Also, mean antibody levels significantly decreased. Furthermore, antitetanus antibody levels of 21 patients simultaneously vaccinated against tetanus and diphtheria were investigated. After 5 years, 15 of 21 patients (71%) were protected compared with 46 of 71 patients (65%) in the hemodialysis collective studied after 12 months. In the interval between 1 and 5 years after vaccination, significantly more patients in the initial nonresponder group had died than in the responder group; therefore, the overall protection rate observed in vaccinated patients increased. Our results provide evidence that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid. Therefore, detection of individual antibody concentrations may be indicated to decide on revaccination.

Antibodies, Bacterial↗