PubMed Health⌕ Search

Biomedical subjects

F Hoffmann

Publications and source records attributed to F Hoffmann.

At least 19 recordsLinked to original sources
PubMed2006

Multicenter-study of operative treatment of intraligamentous tears of the anterior cruciate ligament in children and adolescents: comparison of four different techniques.

Tears of the anterior cruciate ligament in skeletally immature patients were operated with four different methods and their outcome compared to each other. Sixty-eight patients (33 males, 35 females), mean 12.5 years, were treated in four different centers from 1984 to 2001. Twenty-eight patients underwent the ACL-reconstruction with hamstring grafts, 16 patients with bone-patella-bone autografts, 12 patients with quadriceps grafts and 12 patients with facia lata. The mean follow-up was 32 months. Postoperative evaluation included radiographs, KT-1000/2000 stability measurements, Lysholm score, The Tegner activity scale and IKDC score. Neither leg length discrepancy nor angular deformities were noted. Mean KT-1000 difference was 2.1 mm, mean postoperative Lysholm knee score 93.3, IKDC 87% normal or nearly normal. The Tegner index decreased from 6.6 to 5.7. In total, six patients developed instability due to an adequate trauma 1 year after the index operation. Two patients showed mild arthrotic changes. All but two patients were able to return to the same level of preoperative sports participation. None of the four methods studied showed major differences in outcome compared to the other. No growth disturbance could be noted.

Adolescent↗
PubMed2006

[New use of benzodiazepines and the risk of hip fracture: A case-crossover study].

Benzodiazepines appear to increase the incidence of hip fractures. Their role as a time-dependent risk factor remains unclear. We therefore conducted a case-crossover study to determine whether the new use of benzodiazepines is associated with a rise in hip fractures. We analysed 49 months of the statutory health insurance Gmünder Ersatzkasse (GEK) and enrolled all first hip fractures. The index date was the day of hospital admission. Exposure to new use of benzodiazepines was compared within the five periods preceding the index date. Out of 1630 subjects, 223 (13.7%) had at least one prescription of benzodiazepines in the preceding 150 days before the index date, 74 (4.5%) of them as a first prescription. The average age of the population was 79.8 years (SD: 7.7). Odds ratio (OR) of hip fracture was highest during the initial 5 days of new use (OR: 3.43; 95% CI 1.15-10.20) and then declined to a non-significant OR of 1.59 (95% CI 0.96-2.63) after 30 days. In conclusion, the start of a new benzodiazepine is associated with an increased risk of hip fractures. However, the population attributable risk (PAR) and, therefore, the percentage of preventable events is small (PAR: 0.55%; 95% CI 0.05-1.06%).

Age Factors↗
PubMed2006

[Incidence of hip fracture in Germany--person-related analysis of health insurance population].

BACKGROUND AND PURPOSE: An increasing number of hip fractures were reported world wide during the last decades. Up to now incidence data are rare for Germany. The aim of this study is to determine actual person-related age- and sex-specific rates of hip fractures in Germany. METHODS: The linkable and person-specific but non-identifying database of a German statutory health insurance company, Gmuender ErsatzKasse (GEK), was used. All subjects who were admitted to hospital with a primary diagnosis of hip fracture (ICD-10: S72.0-S72.2) in 2004 were identified. Incidence rate ratios (IRR), age- and sex-specific rates (per 1000 person-years) were calculated. Annual numbers of hip fractures for all persons covered by statutory health insurances (Gesetzliche Krankenversicherung- GKV) and the German population were estimated. RESULTS: The incidence of hip fracture increases exponentially with age. Hip fractures occur 129 times more often (IRR: 129.07; 95 % CI: 66.55 - 269.78) in women aged 90 - 94 years and 79 times more often (IRR: 78.97; 95 % CI: 30.02 - 185.87) in men aged 90 - 94 years compared to those aged 50 - 54 years. Approximately 101 037 (95 % CI: 91 779 - 110 294) persons are annually admitted to hospital in Germany due to this event. CONCLUSION: Hip fractures are common in the elderly and especially in women. Because of demographic changes and a possible secular trend an increasing number of hip fractures are to be expected in the future.

Adolescent↗
PubMed2006

Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children.

We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis.

Adolescent↗
PubMed2005

Posttraumatic anterior-inferior instability of the shoulder: arthroscopic findings and clinical correlations.

INTRODUCTION: The main purpose of our study was to evaluate intra-articular lesions in glenohumeral-instability with arthroscopy and correlate them with clinical findings as well as history of instability. MATERIAL AND METHODS: In this prospective multi-centre study, we evaluated arthroscopic findings in 303 patients with posttraumatic anterior-inferior instability of the shoulder. The study cohort was divided into 2 groups: patients with a history of one dislocation (Group 1, n=61, 20.1%) and patients with a history of more than one dislocation (Group 2, n=242, 79.9%). RESULTS: In Group 1, 37 patients had an IGHL-lesion, 31 a MGHL-lesion and 41 a Hill-Sachs lesion. In Group 2, 182 patients had an IGHL-lesion, 172 a MGHL-lesion and 203 a Hill-Sachs lesion. The percentage of lesions in Group 2 (IGHL-75.2%, MGHL-71.1%, Hill-Sachs-83.9%) was significantly higher than in Group 1 (IGHL-60.7%, MGHL-50.8%, Hill-Sachs-67.2%, P=0.0233, P=0.0026, and P=0.0033, respectively). Within Group 2 we found significantly more Hill-Sachs-lesions with a history of an increasing number of recurrences (P=0.0436). We also found an increase of IGHL- and MGHL-lesions with an increasing number of recurrences, but this difference was not significant. The distribution of lesion types of the anterior labrum-ligament complex showed no significant difference between the two groups, apart from a higher incidence of ALPSA-lesions within Group 2 (34.7% versus 18.0% in Group 1). The results of this study show that recurrences after primary posttraumatic anterior-inferior shoulder dislocation cause increasing ligamental damage as well as increasing Hill-Sachs lesions within the gleno-humeral joint. CONCLUSION: Thus we conclude that early surgical stabilization after posttraumatic anterior-inferior shoulder dislocation is necessary to prevent increasing damage within the shoulder joint.

Adolescent↗
PubMed2005

No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome.

Hyper-IgE syndrome is a rare primary immunodeficiency of unknown etiology characterized by recurrent infections of the skin and respiratory system, chronic eczema, elevated total serum IgE, and a variety of associated skeletal symptoms. Recent reports about susceptibility to pyogenic bacterial infections and high IgE levels in patients and animals with defects in toll-like receptor (TLR) signaling pathways prompted us to search for TLR signaling defects as an underlying cause of hyper-IgE syndrome. Blood samples from six patients with hyper-IgE syndrome were analyzed for serum cytokine levels, intracellular cytokine production in T cells after stimulation with PMA/ionomycin, and cytokine production from peripheral blood mononuclear cells stimulated by TLR ligands and bacterial products including LPS (TLR4), peptidoglycan (TLR2), PolyIC (TLR3), R848 (TLR7/8), CpG-A, and CpG-B (TLR9), zymosan and heat killed Listeria monocytogenes. All results were compared to data from healthy controls. A reduction in IFN-gamma, IL-2, and TNF-alpha producing T cells after PMA stimulation suggested a reduced inflammatory T cell response in patients with hyper-IgE syndrome. Increased serum levels of IL-5 indicated a concomitant Th2 shift. However, normal production of cytokines (TNF-alpha, IL-6, IL-10, IFN-alpha, IP-10) and upregulation of CD86 on B cells and monocytes after TLR stimulation made a defect in TLR signaling pathways highly unlikely. In summary, our data confirmed an imbalance in T cell responses of patients with hyper-IgE syndrome as previously described but showed no indication for an underlying defect in toll-like receptor signaling.

Adolescent↗
PubMed2004

Long-term pharmacokinetics of amprenavir in combination with delavirdine in HIV-infected children.

Five heavily pretreated HIV-infected children were put on amprenavir and delavirdine plus two nucleoside inhibitors to reverse transcriptase to boost amprenavir levels and to use the antiretroviral activity of a non-nucleoside reverse transcriptase inhibitor. No data are available about this combination in children. It w;as well tolerated, and the median reduction in viral load was 1.5 log after 18 months. Delavirdine boosted amprenavir trough levels more than 10-fold, and delavirdine trough levels remained i several fold above susceptible HIV strains.

Adolescent↗
PubMed2003

[Effect of topical dexamethasone treatment on antigen-presenting cells in murine corneas].

OBJECTIVE: To determine the influence of dexamethasone treatment on APCs and the time of graft survival of MHC-disparate grafts. METHODS: Flatmounts of the ocular surface prepared with EDTA and tangential frozen sections of the remaining corneal stroma from untreated eyes of normal mice (n=6) and from eyes treated for 7 days with dexamethasone ( n=6) were immunohistologically examined for content of F4/80+ and MHC II+ cells.Furthermore, corneas of C(3)H mice without and with 7-day dexamethasone eye drop treatment (n=8) were grafted into BALB/c mice receiving the same treatment. RESULTS: The number of positive cells within the epithelial flatmounts showed a dramatic reduction in the dexamethasone-pretreated group (p<0.01 compared to the untreated control group). The number of positive cells in the corneal stroma remained unchanged. The grafts of untreated control mice survived 16+/-4 days, the treated grafts 16+/-3 days. CONCLUSIONS: Most investigators assume that normal murine corneas contain no APCs such as macrophages and Langerhans cells. For the first time we were able to detect APCs in flatmounts of the ocular surface and frozen sections of corneal stroma. Our investigations show that, in contrast to the ocular surface, the number of F4/80+ cells in the corneal stroma is not influenced by dexamethasone treatment. Transplantation of corneas containing donor-derived APCs promotes acute rejection (direct pathway of allorecognition).Thus,dexamethasone treatment did not prolong the time of allograft survival.

Administration, Topical↗
PubMed2003

[Tissue typing in perforating corneal transplantation].

The demand for matched corneal grafts has risen rapidly over the last years. One reason for this is the change in the judgement of the value of tissue and especially HLA typing for prevention of an immune reaction in perforating corneal transplantation. Besides HLA or major antigens, there are other immunologically relevant tissue surface molecules such as the non-MHC antigens of which blood groups and minor antigens are the most important. With regard to effective cost-benefit and waiting time-benefit analyses, differentiated matching strategies are needed to assure optimized utilization and allocation of the still unsatisfactory number of available corneal grafts. With special matching strategies, such as the calculation of the individual waiting time, the consideration of split, non-MHC and HLA antigens, additional HLA loci as well as so-called "permissible" and "taboo" mismatches, much more has to be taken into account in the future than just the numerical correspondence of HLA antigens. This will make it possible to turn from a pure numerical approach to a functional matching strategy. This review summarizes the discussion and different matching strategies, possibilities and limitations of HLA and tissue typing in perforating corneal transplantation.

Blood Group Antigens↗
PubMed2002

Effect of antiretroviral triple combinations including the protease inhibitor nelfinavir in heavily pretreated children with HIV-1 infection.

BACKGROUND: In this retrospective study the effect of antiretroviral triple therapy including the protease-inhibitor nelfinavir (NFV) on CD4-cells and viral load (VL) in heavily pretreated HIV-infected children was evaluated. PATIENTS AND METHODS: 20 children (<18 years) were included. Median duration of antiretroviral pretreatment was 27 months (range, 7 65), median initial VL was 4.7 log subset 10 (3.2 6.1) and median relative CD4-cells was 17.5% (3 33). Patients were put on combinations with NFV because of treatment failure (increasing VL), intolerance to prior therapy with PIs or adherence problems with prior indinavir. Viral load (RT-PCR, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks. RESULTS: Median viral load decreased 1.2 log(10) (-1.3 2.5), 0.9 log(10) (-0.8 - 2.5) and 0.4 log(10) (-0.5 - 3.0) after 12, 24 and 36 weeks. The VL of 2 patients was below the detection limit (50 copies/ml) after 24 weeks. The relative CD4-cell count increased from a median of 17.5% to 22%, 23% and 25% after 12, 24 and 36 weeks, respectively. Side effects of NFV were usually mild. WHO grade 1 or 2 diarrhea occurred in 70% and moderate elevations of triglycerides in 40% of the patients. At 48 weeks 18/20 patients had to be switched to other combinations due to virological failure. CONCLUSIONS: In children with intensive prior antiretroviral therapy combination therapy including NFV lead to a modest short-term reduction of the VL and increase in CD4-cells. However, the long-term antiretroviral effect was poor.

Adolescent↗
PubMed2002

Effect of antiretroviral combination therapies including efavirenz in heavily pretreated HIV-infected children.

BACKGROUND: In this retrospective study the effect of antiretroviral combination regimens including the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) on viral load (VL) and CD4-cell count in heavily pretreated HIV-infected children was investigated. DESIGN: The data of 15 children (< 16 years) were evaluated during a treatment period of at least 52 weeks. Patients received a median of 4 prior antiretroviral regimens and were changed to combinations with EFV because of renewed increasing VL. METHODS: Viral load (Amplicor, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks. RESULTS: The median reduction of the viral load for the total study population was 1.9 log10 (0.8 - 4.7), 2.3 log(10) (0.5 - 4.7) and 2.6 log(10) (0-4.7) after 12, 24 and 52 weeks, respectively. After 24 weeks 7/15 children and after 52 weeks 9/15 patients had reductions of the VL below the detection limit. The median increase of CD4-cells in the study population during the treatment period were 104 cells/microl (189-969), 220 cells/microl (170-831) and 321 cells/ml (162-574) after 12, 24 and 52 weeks, respectively. CONCLUSIONS: In children with intensive prior antiretroviral therapy and multiple therapeutic failures with PI-containing regimens, combination therapy including EFV resulted in an excellent antiretroviral efficacy. After 52 weeks 9/15 patients had persistent reductions of the VL below 50 copies/ml, although none of these children reached this level of viral suppression during their multiple prior protease inhibitor-containing regimens.

Adolescent↗
PubMed2002

[Immunomodulation after keratoplasty by CTL4-Ig and anti-CD154 antibodies].

BACKGROUND: The immunoreaction after corneal transplantation is caused by the T cell receptor interacting with the major histocompatibility complex (MHC) receptor of the antigen-presenting cell. The signal is amplified by the CD4 receptor and the costimulatory signal interactions of CD28-B7 and CD40-CD154. We investigated the influence of costimulatory signal blocking on corneal transplant survival in mice. METHODS: Seven groups of 6 BALB/c mice received an orthotopic corneal transplant from C3H mice differing in minor and major MHC and were postoperatively treated as follows: (1) 80 micrograms of CTLA4 fusion protein intraperitoneally (i.p.) for 6 days; (2) 50 microliters of PBS i.p. for 6 days; (3) 1 mg of Solu-Decortin H i.p. for 5 days + dexamethasone AT 0.1% for 35 days; (4) therapy (3) + 50 micrograms of CTLA4 fusion protein i.p. for 6 days; (5) CTLA4-Ig as in (1) + 15 micrograms of anti-CD154 subconjunctivally (s.c.) on days 0, 2, 4, 6, and 8; (6) CTLA4-Ig as in (1) + 25 micrograms of anti-CD154 s.c. for 9 days; and (7) 25 microliters of PBS s.c. for 9 days. RESULTS: All animals had an immunoreaction on the following days: (1) day 18 +/- 3.1; (2) day 13.6 +/- 1.6; (3) day 48 +/- 6.6; (4) day 65 +/- 41; (5) day 23.5 +/- 8.5; (6) day 16.2 +/- 3.6; (7) day 13.8 +/- 2.7. CONCLUSION: The significant prolongation of transplant survival achieved by corticosteroids alone (P < 0.001) is again significantly increased by combining them with CTLA4-Ig (P < 0.001). Specific immunotherapy combined with nonspecific steroid therapy may also improve clinical corneal transplantation results. Compared to the two control groups, CTLA4-Ig and anti-CD154 only influenced transplant survival at a low dosage (P < 0.001).

Abatacept↗
PubMed2001

Engineering regulable Escherichia coli beta-galactosidases as biosensors for anti-HIV antibody detection in human sera.

The activity of engineered, peptide-displaying enzymes is modulated by binding to specific anti-peptide antibodies. This new concept of a quantitative antibody detection system allows test kits to be set up for fast diagnosis of infectious diseases. To develop a quick and homogeneous assay for the detection of human immunodeficiency virus (HIV) infection, we have explored two acceptor sites of the bacterial Escherichia coli beta-galactosidase for the accommodation of HIV antigenic peptides. Two overlapping epitopes (namely P1 and P2) from the gp41 envelope glycoprotein, contained in different sized peptides, were inserted in the vicinity of the enzyme active site to generate a set of hybrid, enzymatically active beta-galactosidases. Regulable enzymes of different responsiveness to monoclonal antibody binding were generated with both acceptor sites tested. These biosensors were also sensitive to immune sera from HIV-infected patients. Modeling data provide insight into the structural modifications in the vicinity of the active site induced by peptide insertion that strongly affect the responsiveness of the engineered proteins through different parameters of their catalytic properties.

Amino Acid Sequence↗
PubMed2001

Kinetic model of in vivo folding and inclusion body formation in recombinant Escherichia coli.

Aggregation of misfolded proteins can reduce the yield in recombinant protein production. The underlying complex processes are additionally influenced by cellular physiology. Nevertheless, a lumped-parameter model of kinetic competition between folding and aggregation was sufficient to track properly the specific concentration of a human protein produced in E. coli and its partitioning into soluble and insoluble cell fractions. Accurate estimation of the protein-specific parameters required informative experiments, which were designed using the Fisher information matrix. The model was employed to calculate the influence of the specific glucose uptake rate in high-cell-density cultivation of E. coli on accumulation and aggregation of the recombinant protein. Despite its simplicity, the model was flexible and unbiased concerning unidentified mechanisms. Assuming an exponentially decreasing production rate, the irreversible aggregation step was found to follow first order kinetics, while assuming a constant production rate with simultaneous degradation, the model predicted transient aggregation only. Implications for strain and process development are discussed.

Escherichia coli↗
PubMed2001

On-line estimation of the metabolic burden resulting from the synthesis of plasmid-encoded and heat-shock proteins by monitoring respiratory energy generation.

Human basic fibroblast growth factor (hFGF-2) was produced in high-cell density cultures of recombinant Escherichia coli using a temperature-inducible expression system. The synthesis rates of proteins were followed by two-dimensional gel electrophoresis of the (35)S-methionine-labeled proteom. After temperature induction of hFGF-2 synthesis, the rate of total protein synthesis per biomass increased by a factor of three, mainly as a result of the additional synthesis of hFGF-2 and heat-shock proteins. The synthesis rates of heat-shock proteins and constitutive plasmid-encoded proteins increased after the temperature upshift also in the control strain without hFGF-2 gene but followed time profiles different from the producing strain. The energy demand for the extra synthesis of plasmid-encoded and heat-shock proteins resulted in an elevated respiratory activity and, consequently, in a reduction of the growth rate and the biomass yield. A procedure was developed to relate the energy demand for the additional synthesis of these proteins to the generation of energy in the respiratory pathway. Specific energy production was estimated based on on-line measurable rates of oxygen consumption, or carbondioxide evolution and growth, respectively. In this way, the metabolic burden resulting from the synthesis of plasmid-encoded and heat-shock proteins was quantified from on-line accessible data.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2001

Contribution of lymphatic drainage system in corneal allograft rejection in mice.

PURPOSE: To modulate aqueous outflow via the uveoscleral pathway and to determine its influence on corneal graft survival in mice. METHODS: BALB/c mice received corneal transplants from C3H mice and were placed randomly in three treatment groups: saline, pilocarpine or latanoprost. Three further groups received adjuvant systemic and topical corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection. RESULTS: Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection. CONCLUSION: Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.

Animals↗
PubMed2001

Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria.

Zinc mesoporphyrin (ZnMP) is a potent inhibitor of heme oxygenase (HO) and represses 5-aminolevulinic acid synthase (ALAS). These properties make it a potential candidate for treatment of inducible acute hepatic porphyrias, diseases characterized by neurovisceral symptoms, and massive ALAS induction. Effects of intraperitoneal ZnMP (2.5-10 micromol/kg/d) and heme arginate (3-6 mg/kg/d) on plasma levels of 5-aminolevulinic acid (ALA), on messenger RNA (mRNA), and activity of hepatic ALAS and HO were studied in porphobilinogen deaminase-deficient mice treated with phenobarbital (100 mg/kg/d) to induce ALAS. ZnMP (5 micromol/kg/d) led to a significant reduction of plasma ALA levels to 31% of controls (P < .01) by lowering the activity of hepatic mitochondrial and cytosolic ALAS to 29% and 25% of controls, respectively (P < .03). ZnMP decreased the mRNA levels of hepatic ALAS to 53% (P < .03) of controls and this repression was more pronounced than that achieved with heme arginate. In contrast to heme arginate, ZnMP led to a significant reduction of HO activity. We conclude that the combined effect of ZnMP on highly induced ALAS and on HO may be of potential benefit for human acute hepatic porphyrias and therefore merits further in vivo investigations addressing questions raised by this study.

5-Aminolevulinate Synthetase↗