Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 55 records · Page 3Linked to original sources

PubMed2004

Evidence for autoantibody-induced CD4 depletion mediated by apoptotic and non-apoptotic mechanisms in HIV-positive long-term surviving haemophilia patients.

It is believed that autoimmune phenomena and apoptosis contribute to CD4 depletion. We investigated 11 long-term (>20 years) HIV-infected haemophilia patients and 10 healthy controls. Using four-colour-fluorescence flow cytometry, we studied the proportions of CD3+CD4+ and CD3+CD4- blood lymphocytes that were CD95+, CD95L+, immune complex+ (IC+, consisting of IgM, IgG, C3d and/or gp120), and were viable or non-viable (propidium iodide+ = PI+). In addition, we studied viability of CD4+IgG+ patient lymphocytes using the apoptosis marker annexin and the permeability indicator 7-amino actinomycin D (7-AAD). HIV+ patients had a higher proportion of CD3+CD4+IgG+PI+ lymphocytes than healthy controls (median: 3.7%versus 0.3%; P = 0.00001). These non-viable IgG-coated lymphocytes might have been killed in vivo by ADCC or complement lysis; 9.1% of the circulating CD3+CD4+ blood lymphocytes were IgG+PI- (controls: 2.5%; P = 0.001). These viable IgG-coated lymphocytes might be targets for phagocytosis or anti-CD95 autoantibody-mediated apoptosis. Because HIV+ patients and healthy controls had similar proportions of PI+ or PI- CD3+CD4+ lymphocytes that carried CD95L on the surface, and because CD3+CD4+CD95L+ cells that were IgG+, C3d+ and/or gp120- were increased in HIV+ patients, the role of CD95L-induced apoptosis in long-term HIV-infected haemophilia patients remains unclear. The findings that HIV+ patients had higher proportions of CD3+CD4+CD95+ (PI+: 6.5%versus 1.4%; P = 0.00002; PI-: 55.8%versus 44.4%; P = 0.04) blood lymphocytes and that the proportion of CD4+IgG+Annexin+7-AAD- blood lymphocytes was associated inversely with peripheral CD4 counts (r = -0.636; P < 0.05) suggest that attachment of IgG to CD4+ blood lymphocytes (anti-CD95?) induces in some lymphocytes apoptosis with subsequent depletion of these IgG-coated apoptotic CD4+ lymphocytes from the circulation. We found supporting evidence for the contention that autoantibody-induced apoptotic and non-apoptotic mechanisms contribute to CD4 depletion in long-term HIV-infected haemophilia patients.

Adolescent↗

PubMed2004

Treatment patterns and cost-of-illness of severe haemophilia in patients with inhibitors in Germany.

To evaluate current treatment patterns and resource utilization as well as related cost in the management of severe haemophilia patients with inhibitors in Germany, a cost-of-illness study was conducted. Generally, data were generated by structured literature search. Missing data were collected by expert interviews. All data were validated by a panel of German experts in haemophilia care. In Germany, immune tolerance therapy (ITT) is first-line therapy in inhibitor management for children in the initial year after inhibitor development, particularly for high responders (HR). In adult HR patients ITT is applied but to a remarkably lower extent than in children. To treat bleeding episodes, factor VIII (FVIII) is first-line therapy in low responders (LR). For paediatric HR patients, bleeds are mainly treated with recombinant FVIIa (rFVIIa). In adult HR patients, activated prothrombin complex concentrate (aPCC) and rFVIIa are more equally distributed as treatment options. Treatment costs were calculated for paediatric patients (15 kg) and adult patients (75 kg) from third party payers' perspective. Cost for ITT ranges from Euro 70,290 (2 months; LR) to Euro 3 812,400 (24 months; with aPCC; HR) in a paediatric patient. For an adult patient ITT cost ranges from Euro 287,500 (6 months; LR) to Euro 17,253,000 (36 months; HR). For on average 12.5 acute bleeds, average annual treatment costs amount to Euro 77,000 for a child and Euro 354,000 for an adult. Assessing the results it has been taken into consideration that ITT can last longer and annual number of bleeds can be extremely higher than on average 12.5 episodes. This indicates more health care resource consumption in some patients.

Adult↗

PubMed2004

The in vitro quality of washed, prestorage leucocyte-depleted red blood cell concentrates.

BACKGROUND AND OBJECTIVES: No data are currently available on the quality of washed prestorage leucocyte-depleted red blood cell concentrates (RCCs). MATERIALS AND METHODS: Five groups of RCCs stored in additive solution (SAG-M) were washed. The groups differed in the age of RCCs (2-5 days or 11-15 days), the temperature during the washing procedure and a 6-h storage period (4 degrees C or room temperature) and the washing solution (saline, SAG-M or 5% albumin). We measured ATP, 2,3-diphosphoglycerate (2,3-DPG), haemolysis, blood cell count, Na(+), K(+), pH, pO(2), pCO(2) and lactate, before and after the washing procedure and hourly during the 6-h postwash storage period. RESULTS: The erythrocyte ATP content increased by 2-13%, relative to the baseline value, during the washing procedure. The 2,3-DPG level decreased by 15-35% in 2-6-day-old RCCs and by 30-40% in 11-15-day-old RCCs (relative to baseline values) during the washing procedure. In RCCs that were washed and stored at room temperature, and in 2-week-old RCCs, a further decrease in 2,3-DPG of up to 40%, relative to the baseline value, was observed during the 6-h postwash time-period. CONCLUSIONS: Washing of RCCs stored in SAG-M results in a considerable, significant loss of erythrocyte 2,3-DPG, especially in older RCCs. This loss increases in during a 6-h storage period postwash, even at 4 degrees C. This loss of erythrocyte quality might well outweigh the benefits of washed SAG-M RCCs during massive transfusion in neonates.

2,3-Diphosphoglycerate↗

PubMed2004

Cross sectional study of automated blood pressure measurements throughout pregnancy.

OBJECTIVE: To generate reliable new reference ranges for pregnancy blood pressure from a large population. DESIGN: A prospective cross sectional study. SETTING: Obstetric outpatient clinic, Zurich University Hospital. SAMPLE: Accurately dateable singleton pregnancies (Caucasian: n= 3234; Asian [predominantly from Sri Lanka, Thailand and the Philippines]: n= 577; Black n= 212). METHODS: Between January 1996 and February 2000 blood pressure was determined in 4023 pregnant women using an oscillometric automated device (Dinamap) according to British Hypertension Society recommendations. Women receiving antihypertensive medication were excluded. MAIN OUTCOME MEASURE: Blood pressure. RESULTS: Only the means of duplicate measures at the booking visit (5-42 weeks) were used in the analysis. Mean blood pressure decreased from early to mid pregnancy before increasing to levels 4 mmHg higher at term than in early pregnancy. Values >130/80 and <90/50 mmHg were above the 95th and below the 5th centiles, respectively. Parity, age and body mass index were significant determinants in Caucasians. Blood pressure was slightly lower in Asians and Blacks. CONCLUSIONS: The current World Health Organisation definition of high diastolic blood pressure (>or=90 mmHg on two occasions) reflects values >2 standard deviations from the mean. This may be too conservative as threshold for detecting women at risk of pre-eclampsia. Further studies are required to determine the prognostic implications of gestational values >or=95th centile (>or=130/80 mmHg) and <or=5th centile (<or=90/50 mmHg).

Adult↗

PubMed2004

Human recombinant DNA-derived antihemophilic factor in the treatment of previously untreated patients with hemophilia A: final report on a hallmark clinical investigation.

BACKGROUND: Development of recombinant factor VIII (rFVIII) replacement therapy represents a milestone in the treatment of hemophilia A. OBJECTIVE: The objective of this long-term, multicenter study was to assess the safety, efficacy and rate of inhibitor formation of rFVIII (Kogenate) in the treatment of hemophilia A in a group of previously untreated patients (PUPs). PATIENTS AND METHODS: Between January 1989 and October 1997, 102 evaluable patients (mean age 3.9 years) were treated with rFVIII as sole therapy for prophylaxis against bleeding or for hemorrhage. Patients with mild hemophilia were treated for > or =2 years, while those with moderate or severe hemophilia were treated for > or =5 years or 100 exposure days. RESULTS: All patients responded well to therapy, so that 82% of bleeding episodes required a single infusion for treatment. Only four mild drug-related adverse events were recorded during the study for an overall rate of 0.03% (4/13 464 infusions). No viral seroconversions were observed. The inhibitor incidence in PUPs with severe hemophilia was 29% (19/65). Overall, inhibitory antibodies developed in 21 patients (20.6%). Inhibitor titers were low (<10 Bethesda Units) in nine of the 21 patients despite continued episodic treatment with rFVIII and transient in eight patients receiving episodic treatment (seven low titer, one high titer). Eight high-titer inhibitor patients were treated with immune-tolerance induction therapy; five had successful outcomes. CONCLUSIONS: The observed incidence of inhibitor formation is similar to studies of PUPs receiving plasma-derived FVIII. These results demonstrate the safety and efficacy of rFVIII in long-term treatment of hemophilia A.

Adolescent↗

PubMed2003

Search criteria and rules for comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry analysis of airborne particulate matter.

Direct thermal desorption-gas chromatography-time-of-flight mass spectrometry (DTD-GC-TOFMS) and comprehensive two-dimensional (2D) gas chromatography-time-of-flight mass spectrometry (GC x GC-TOFMS) was applied for characterisation of semi-volatile organic compounds (SVOC) in fine particulate matter (PM), with a diameter of up to 2.5 microm (PM2.5), from ambient air in Augsburg, Germany. DTD-GC-TOFMS measurements on the SVOC in PM2.5 are done on a daily basis (time series over several years). The data will be used in an epidemiological study questioning the influence of SVOC in PM2.5 on ambient aerosol related health effects. The outcome of the first measurements periods is that the organic inventory in the ambient aerosol can undergo drastic fluctuations, e.g. due to meteorological influences or specific emission sources. This includes also the large fraction of chromatographically not resolved peaks (unresolved carbonaceous matter (UCM)). The UCM fraction contains about 70% of the SVOC mass in PM2.5. GC x GC-TOFMS is a suited technique to study the nature of the yet unidentified compounds forming the UCM. The considerably increased chromatographic resolution in GC x GC allows separation of many UCM compounds while the TOFMS supplies mass spectral data of all separated compounds. However, the data sets are getting enormously complex. In a typical PM2.5 sample from Augsburg more than 15,000 peaks can be detected. Thus, it is important to classify the observed GC x GC peaks by rational means. A classification procedure based on GC x GC retention times and the fragmentation patterns is suggested. With a preliminary classification procedure it is already possible to group compounds with some certainty into substance classes. After some further development, this approach can be used for classifying GC x GC data, e.g. for environmental and epidemiological studies.

Aerosols↗

PubMed2003

Resonance-enhanced multiphoton ionization and VUV-single photon ionization as soft and selective laser ionization methods for on-line time-of-flight mass spectrometry: investigation of the pyrolysis of typical organic contaminants in the steel recycling process.

A newly conceived compact and mobile time-of flight mass spectrometer (TOFMS) for real-time monitoring of highly complex gas mixtures is presented. The device utilizes two selective and sensitive soft ionization techniques, viz., resonance-enhanced multiphoton ionization (REMPI) and single-photon ionization (SPI) in a (quasi)-simultaneous mode. Both methods allow a fragmentationless ionization. The REMPI method selectively addresses aromatic species, while with SPI applying vacuum ultaviolet light (118 nm) in principle all compounds with an ionization potential below 10.5 eV are accessible. This provides comprehensive information of the chemical composition of complex matrixes. The combustion and pyrolysis behavior of five organic materials typically used in steel processing in China was studied. The trace amounts of organic compounds in the gas phase during combustion and pyrolysis were monitored selectively and sensitively by real-time SPI/REMPI-TOFMS. The measurements were carried out at several constant temperatures in the range from 300 to 1190 degrees C in both synthetic air and nitrogen. Timely resolved mass spectra reveal the formation and subsequent growth of aromatic molecules. At lower temperatures, highly alkylated PAHs predominate, while at temperatures above 800 degrees C, the more stable benzene and PAHs without side chains prevail. Potential hyphenation of SPI/REMPI-TOFMS to methods of thermal analysis is discussed.

Journal Article↗

PubMed2003

Functional outcome with special attention to the DASH questionnaire following callus distraction and phalangization of the thumb after traumatic amputation in the middle one-third.

INTRODUCTION: Aim of this retrospective study was to obtain a functional outcome following callus distraction and phalangization of the thumb after traumatic amputation in the middle one-third. MATERIALS AND METHODS: From January 1998 to June 2001, 12 patients were treated in a staged procedure starting with corticotomy and continuous distraction (1 mm/day) of the first metacarpal bone using a unilateral external fixator device. After distraction until day 31 (range 25-35 days), the first metacarpal bone was stabilized with a plate, and phalangization was performed. RESULTS. At follow-up 1 year after surgery, the thumb was lengthened to 25-35 mm (average 28 mm) in all but 1 patient. In 1 patient a bone graft from the iliac crest had to be interposed. Pinch grip improved by 45%; grip strength improved by 55%. The function/symptom score from the DASH questionnaire was 25 points (range 16-38 points). In a 'pick-up test' all patients were able to pick up a pencil, they were able to write and could hold a full cup of water. Nine patients were able to pick up a paper clip, and 8 patients could hold a 1-liter bottle of water. CONCLUSION: Callus distraction can be considered a suitable procedure to reconstruct an amputated thumb levelled at the middle one-third. Additional phalangization proved essential as it deepened the first web space, enabling good motion and grasp. Callus formation was delayed in elderly patients, but adequate lengthening and bone healing also occurred in this age group. The procedure will not be as beneficial in cases of osteoarthritis of the trapezometacarpal joint or when coverage of the stump is insufficient. The DASH questionnaire is very helpful in evaluating the effect of thumb reconstruction on the entire upper limb.

Adolescent↗

PubMed2003

Malignant conversion of florid oral and labial papillomatosis during topical immunotherapy with imiquimod.

We report a case of a 61-year-old woman suffering from florid oral papillomatosis with a squamous-cell cancer of the floor of the mouth, which was removed by scalpel surgery combined with a radical neck dissection in 1996. Between 1996 and 2000 several histologically benign papillomatous lesions of mouth and lips were removed with laser and electrosurgery. However, the lesions recurred. In July 2000 hyperkeratotic, wart-like lesions were present at the lower and upper lips and at the right angle of the mouth and the adjacent oral mucosa. Overnight treatment with a topical 5% imiquimod cream on a Monday-Wednesday-Friday schedule was initiated. However, due to severe irritation and pain the application had to be reduced to 4 h per night, three times a week, followed by a therapy-free interval of 2 weeks. Despite this treatment consisting of four cycles of 3 weeks (1 week treatment and 2 weeks pause), the lesions increased markedly in size. A biopsy taken from the tumorous lesion from the right angle of the mouth proved to be a squamous-cell carcinoma. The tumors of the labial and oral mucosal sites as well as the right submandibular lymph nodes were removed by wide scalpel excision. The lips were reconstructed by plastic surgery. 24 months after surgical intervention no recurrence nor metastasis to lymph nodes or distal sites were observed.

Aminoquinolines↗

PubMed2003

[Clinical and molecular genetic analysis of monozygotic twins displaying stapes gusher syndrome (DFN3)].

BACKGROUND: DFN3 ( "stapes gusher") is the most frequent form of X-linked hearing impairment. It accounts for up to 0.5% of all cases of severe childhood hearing disorders. PATIENTS AND METHODS: Monozygotic twins with suspected stapes gusher syndrome, their mother, and control individuals were analyzed clinically and genetically. RESULTS: The clinical investigations confirmed a DFN3 phenotype in both brothers who displayed all typical symptoms. A molecular genetic investigation of the POU3F4 gene, which plays an essential role in the development of DFN3, was also performed. No chromosomal aberrations within the coding region of POU3F4were detected. Since several authors have described mutations in the 5' untranslated region of the gene also resulting in a DFN3 phenotype, we screened this area by microsatellite analysis and detected a double deletion localized in the critical interval. This is the first description of a double deletion in the non-coding region of POU3F4 leading to DFN3 phenotype. CONCLUSION: Interestingly, in spite of having an identical genotype, the twins displayed significant phenotypic differences. This underlines the importance of exogenous factors in the development of inherited pathological processes.

Audiometry, Pure-Tone↗

PubMed2003

[Reference values in pregnancy].

The body of pregnant women demonstrates in many ways different functions compared to non pregnant women. In order to assess lab results of antenatal tests the knowledge of physiologic and pathophysiologic changes are essential. This article reviews the state of the art in terms of reference values during pregnancy enriched with own results. Of special value for the practitioner are such reference values and curves for the circulatory system, kidney function, hematologic changes, plasma components and weight gain.

Adult↗

PubMed2003

Application of single-particle laser desorption/ionization time-of-flight mass spectrometry for detection of polycyclic aromatic hydrocarbons from soot particles originating from an industrial combustion process.

Combustion-related soot particles were sampled in situ from the stoker system of a 0.5 MW incineration pilot plant (feeding material was wood) at two different heights over the feed bed in the third air supply zone. The collected particles were re-aerosolized by a powder-dispersing unit and analyzed by a single-particle laser desorption/ionization (LDI) time-of-flight mass spectrometer (aerosol-time-of-flight mass spectrometry, ATOFMS). The ATOFMS instrument characterizes particles according to their aerodynamic size (laser velocimetry) and chemical composition (LDI mass spectrometry). Chemical species from the particles are laser desorbed/ionized by 266 nm Nd:YAG laser pulses. ATOFMS results on individual 'real world' particles in general give information on the bulk inorganic composition. Organic compounds, which are of much lower concentrations, commonly are not detectable. However, recent off-line laser microprobe mass spectrometric (LMMS) experiments on bulk soot aerosol samples have emphasized that organic compounds can be desorbed and ionized without fragmentation in LDI experiments from black carbonaceous matrices. This paper reports the successful transfer of the off-line results to on-line analysis of airborne soot particles by ATOFMS. The detection of polycyclic aromatic hydrocarbons from soot particles is addressed in detail. The results are interpreted in the context of the recent LMMS results. Furthermore, their relevance with respect to possible applications in on-line monitoring of combustion processes is discussed.

Air Pollutants↗

PubMed2003

[Cutaneous xanthomas associated with minocycline-induced cholestatic jaundice].

Minocycline is an effective treatment of acne vulgaris, especially for inflammatory forms. Prescription rates have increased in recent years accompanied by a number of reports concerning drug-induced side effects. An otherwise healthy woman developed an erythema multiform-like rash and and toxic hepatic damage causing cholestatic jaundice following long-term minocycline use. Unusual cutaneous lipid deposition also developed. Minocycline-induced side effects are reviewed.

Acne Vulgaris↗

PubMed2003

[Long-term results after a modified Sauvé-Kapandji procedure. Report on 105 post-traumatic cases].

A modified Sauvé-Kapandji procedure was performed on 105 patients for a painfully limited range of motion and arthritis of the distal radioulnar joint following distal fracture of the radius ( n=81), the radius and ulna in the distal one-third ( n=18) and of the forearm shaft ( n=6). After an average of 8 years all patients were followed up clinically (motion, strength, pain) and radiographically (union of the arthrodesis, carpal translation, radioulnar distance). Rotation of the forearm had been improved by 53%. The amount of strength lay by 70% in comparison to the contralateral side. In 97% of the patients pain could be reduced. In all cases the arthrodesis had fused completely. An ulnar drift of the carpus was observed in 5% of the patients, and 74% of the patients showed radiological signs of approximation of the proximal ulnar stump to the radius. This reduction of the radioulnar distance amounted to less than 3 mm in 65% of the patients and lay between 3 and 5 mm in 29% of the patients. In none of the cases was direct contact between the ulna and the radius encountered.

Adult↗

PubMed2003

Oxygen-regulated expression of TGF-beta 3, a growth factor involved in trophoblast differentiation.

The transforming growth factor-beta 3 (TGF-beta 3) is involved in oxygen-dependent differentiation processes during placental development and pregnancy disorders. However, the importance of oxygen partial pressure for the regulation of TGF-beta 3 expression is presently unclear. We and others presented preliminary evidence that the hypoxia-inducible factor-1 (HIF-1) confers TGF-beta 3 transcription but it was unknown whether this occurred directly or indirectly. To analyze how HIF-1 regulates TGF-beta 3 gene transcription, we cloned and sequenced the mouse TGF-beta 3 promoter region. Multiple putative HIF-1 binding sites (HBSs) were identified, many of which co-localized with two G+C rich CpG islands 5' to the TGF-beta 3 transcription start site. A 6.8 kb fragment of the TGF-beta 3 promoter induced reporter gene expression under hypoxic conditions or when treated with an iron chelator known to stabilize and activate the HIF-1 alpha subunit. Deletion of a 2.4 kb fragment upstream of the distal CpG island abolished inducibility of reporter gene expression. Two HBSs (HBS1 and HBS6) that bound the HIF-1 protein could be identified within this 2.4 kb fragment. These results suggest that TGF-beta 3 gene expression is directly regulated by HIF-1.

Animals↗

PubMed2003

Closed reduction transarticular Kirschner wire fixation versus open reduction internal fixation in the treatment of Bennett's fracture dislocation.

Thirty two patients with fracture dislocations of the base of the thumb metacarpal with a single large fracture fragment (Bennett's fracture) were either treated by open reduction and internal fixation or closed reduction and percutaneous transarticular Kirschner wiring. All were assessed at a mean follow up of 7 (range 3-18) years. Patients with an articular step off more than 1mm were excluded. The type of treatment did not influence the clinical outcome or the prevalence of radiological post-traumatic arthritis. The percutaneous group had a significantly higher incidence of adduction deformity of the first metacarpal. This was attributed to Kirschner wire placement near the fracture line or in the compression zone of the fracture, resulting in loss of reduction. This however did not result in an inferior outcome.

Adult↗

PubMed2003

Short- and long-term swimming exercise training increases myocardial insulin-like growth factor-I gene expression.

UNLABELLED: OBJECTIVES. We investigated the effect of short- and long-term swimming exercise, with or without insulin-like growth factor (IGF)-I administration, on the expression of myocardial IGFs and contractile proteins. METHODS: Sprague-Dawley male rats (n=36) were subjected to swimming exercise for 2 or 6 weeks. IGF-I (0.5mg/rat) was administered continuously for 1 week, using alzet osmotic pumps. Control groups remained sedentary. IGF-I, IGF-I receptor (IGF-IR), IGF-II, skeletal alpha-actin (sk-actin), and beta myosin heavy chain (beta MHC) mRNAs were measured using Northern blot analysis and RT-PCR. RESULTS: A significant 2-fold increase in myocardial IGF-I mRNA was found after 2 and 6 weeks of swimming in both IGF-I treated and untreated rats (p<0.001). IGF-IR mRNA was significantly (p<0.05) increased after 6 weeks of training only in the IGF-I treated animals. IGF-II mRNA remained unchanged at all time points. While beta MHC mRNA was significantly decreased (p=0.003) at 2 and 6 weeks, sk-actin mRNA remained unchanged. CONCLUSIONS: Short- and long-term swimming exercise training increase myocardial expression of IGF-I mRNA. Exogenous administration of IGF-I, during the first week of the exercise session, did not produce any effect on myocardial IGF-I but was associated with increased IGF-IR signal after the long-term exercise training. These data suggest a relationship between IGF-I expression and cardiac adaptation to exercise training.

Actins↗

PubMed2003

[Clinical long-term outcome after Kapandji-Sauvé procedure].

PURPOSE: The present study was designed to evaluate long-term outcome of upper extremities and subjective self-assessment of patient disability after a Kapandji-Sauvé procedure by means of the DASH score. PATIENTS AND METHOD: Between 1986 and 1996, a modified Kapandji-Sauvé procedure was performed in 117 patients with painfully limited forearm rotation and arthrosis of the distal radioulnar joint (DRUJ). Of the 117 patients, 73 women and 32 men, whose ages at operation ranged from 22 to 74 years (average, 58 years) were retrospectively reviewed clinically and radiologically eight years (range, five to twelve years) after the operation. The DASH questionnaire was used in 43 patients. RESULTS: The mean DASH score was 28 points (range, 0 to 53 points). The mean score in part A was 1.9 points, in part B 1.8 points. Worst outcomes were noted for activities requiring the exertion of force. Pain was reduced in 97 % of the patients. Forearm rotation and grip strength improved in all patients. CONCLUSION: Our clinical findings suggest that the Kapandji-Sauvé procedure is indicated in symptomatic, non-reconstructable disorders of the DRU-joint with or without ulnocarpal impaction syndrome. The DASH questionnaire provides a general view of functional outcome after the Kapandji-Sauvé procedure, though rotation is absolutely necessary to evaluate the success of the operation.

Adult↗