PubMed Health⌕ Search

Biomedical subjects

H H Brackmann

Publications and source records attributed to H H Brackmann.

At least 19 recordsLinked to original sources
PubMed2006

[The modified Bonn Malmö protocol (MBMP) in the treatment of acquired haemophilia A].

BACKGROUND AND OBJECTIVE: Autoantibodies directed against clotting factors can induce life threatening bleeding with a mortality rate up to 22%. Although the incidence of the disease is low (1-4 x 10(-6)), costs of treatment due to long-term clotting factor substitution can be enormous. Aim of an optimal treatment strategy should be to control bleedings by a rapid and safe elimination of the inhibitor and reinducing long-term immune tolerance. PATIENTS AND METHODS: Treatment of 48 patients with acquired haemophilia A (m=20, f =28, age 61.3 (SD 16.4)), the largest patient collective world-wide, was monitored for a mean of 48 months. Three patients received only conservative treatment. 45 patients were treated intensively by a multimodal strategy including: 1. immunoadsorption for antibody elimination; 2. FVIII substitution; 3. intravenous immunoglobulin substitution and 4. immunosuppression. The times required for inhibitor elimination, factor VIII substitution and the duration of the MBMP were documented. RESULTS: In 45 patients with a high titre critical bleeding was controlled immediately after the initiation of MBMP. There were no deaths from bleeding or the treatment. Inhibitor levels decreased to undetectable levels within a median of 3 days (95% CI, 3-7 days), factor substitution was terminated within a median of 13 days (95% CI, 10-16 days) and the treatment was completed within a median of 15 days (95% CI, 13-17 days). The overall response rate for complete remission (CR) was 91%. When cancer patients were excluded, the CR rate was 97%. CONCLUSION: Considering the short duration and amount of factor VIII substitution, the short time of hospitalization and the long-term median follow up of 48 months without bleeding events, the MBMP appears to have a modifying effect on the immunological response.

Aged↗
PubMed2006

Successful pain treatment in arthropathic lower extremities by acupuncture in haemophilia patients.

Acupuncture is successfully used in the treatment of degenerative osteoarthritis. The treatment of haemophilic arthropathies can require strong painkillers with severe side-effects. Therefore, a special yet simple acupuncture technique was evaluated in the treatment of these joint problems. Twelve patients with a factor VIII activity<1% and at least one painful arthropathy in both lower extremities were included in this single-blinded study. The non-treated side served as a control. Treatment was assessed by a visual analogue scale (VAS) and an orthopaedic clinical examination. Only one needle was inserted at the rear fontanelle once per week and in 15 cycles. Ten of 12 patients showed an improvement of their pain perception. The average VAS could be reduced from 6.8 to 5.0. The side not receiving treatment showed a reduction from 4.1 to 4.0. No side-effects were observed. Even though interpretation of our data are limited due to the small patient numbers, significant improvement of the VAS after treatment suggests that acupuncture has a measurable positive effect in pain management for haemophilic arthropathy of the lower extremities.

Acupuncture Therapy↗
PubMed2005

Analysis of mRNA in hemophilia A patients with undetectable mutations reveals normal splicing in the factor VIII gene.

BACKGROUND: haemophilia A (HA) is characterized by partial or total deficiency of factor VIII (FVIII) protein activity. It is caused by a broad spectrum of mutations in the FVIII gene. Despite tremendous improvements in mutation screening methods, in about 2% of HA patients no DNA change could be found, even after sequencing the whole coding part of the FVIII gene including the flanking splice sites, as well as the promotor and the 3' UTR regions. OBJECTIVES, PATIENTS AND METHODS: In the present study we performed a detailed RNA analysis of three groups of patients. The first included control patients with known splicing defects, the second included two patients with already identified nucleotide changes close to splicing sites, that could potentially alter the normal splicing process, and a third group of 11 unrelated patients whose genomic DNA have already been screened for mutations by DHPLC and direct sequencing with no mutation being identified. RESULTS: Both candidate splice site mutations were shown to result in either skipping or alternative splicing of at least one exon, therefore these DNA changes must be considered as causal for the patients' HA phenotype. In contrast, no abnormalities on the RNA level were observed in any of 11 unrelated patients without mutations in the FVIII gene. CONCLUSIONS: These findings exclude mutations that could be located deep in the introns and affecting either normal splicing or lead to mechanisms causing some unknown rearrangements of the FVIII gene. In fact, our results point to the presence of still unknown factor(s) causing HA, which might be either allelic or in the close proximity of the FVIII gene or non-allelic associated with other genetic loci that are involved in the processing of the FVIII protein.

DNA Mutational Analysis↗
PubMed2003

Long-term follow-up after osteotomy for haemophilic arthropathy of the knee.

In this study the long-term value of corrective osteotomy around the knee was evaluated by means of clinical and radiographic parameters. Between 1974 and 1984 we performed 52 corrective osteotomies in the vicinity of the knee on patients affected by haemophilic arthropathy. Forty-two patients (45 osteotomies) were adequately followed-up at an average 11.6 years postoperatively. Using the clinical score of the Advisory Committee of the World Federation of Haemophilia, 38 patients showed a postoperative improvement, five remained clinically unchanged and two showed deterioration. Range of motion of the knee joint did not significantly improve postoperatively. The radiographic Pettersson score showed only a marginal decrease by an average 0.003 points at the time of follow-up. Only one patient needed subsequent joint replacement of both knees, on the left side 13 years after osteotomy and on the right side 8 years after osteotomy. Even in cases of marked radiographic joint destruction, corrective osteotomy shows acceptable long-term clinical results, underlining the feasibility of this management option in the treatment of haemophilic arthropathy of the knee. Although moderate cartilage degenerations in the femoropatellar complex and in the contralateral compartment can be tolerated, this therapy should primarily be contemplated for those patients where damage is unicompartmental and a corresponding axial deviation is found. Particularly the younger patient can benefit from this treatment option in that joint replacement may possibly wholly be avoided or at least postponed to a later stage of life.

Adolescent↗
PubMed2003

Haemophilic arthropathy of the hip in children--prognosis and long-term follow-up.

The aim of this study was to report on the long-term follow-up of haemophilic children with avascular femoral head necrosis and to determine whether radiographic findings at initial diagnosis have any prognostic value. Seven patients with avascular necrosis of the femoral head were clinically and radiographically observed over a period of 5-50 years. The average age of patients at first diagnosis was 7.1 years. At follow-up, three of seven patients claimed to have occasional mild pain in the affected hip, four of seven showed loss of range of motion in the hip joint and two of seven patients showed a limp. Only one patient was clinically completely inconspicuous. The radiographically measured caput-collum-diaphysis angle at follow-up was pathologic in four cases and in one case a lateral subluxation of the femoral head was found. There was marked deformation of the femoral head in three of seven cases and a further two hips showing slight incongruency. Owing to the small patient-number, a statement concerning the prognostic value of defined radiographic signs cannot be made. As expected, the more 'risk signs' radiographically found, the higher the likelihood that patients will suffer arthrosis at a later stage. We propose that a clear distinction between haemophilic arthropathy of the hip and Legg-Calvé-Perthes disease should be made. In cases where radiographic changes are also found in the vicinity of the acetabulum, it is indicative for haemophilic arthropathy.

Child↗
PubMed2003

[Significance of mutation analysis in patients with haemophilia A].

Haemophilia A represents the most frequent hereditary bleeding disorder in humans. The disease is caused by mutations within the factor VIII gene leading to decreased or absent factor VIII activities with a bleeding tendency depending on the degree of factor VIII deficiency. Nowadays, the causative mutations can be routinely detected and have substantially improved diagnostic and understanding of the pathophysiology of haemophilia A. Identification of the gene defects in haemophilic families have enabled fast and save carrier diagnosis. The correlation of the genetic defects with the clinical course revealed that the type of mutation represents the most important genetic predisposing factor for inhibitor formation, the most severe complication of treatment with factor VIII concentrates. Mitigated clinical courses of haemophilia A were shown to be due to special types of mutations or the presence of concomitant thrombophilic mutations. Molecular models of the factor VIII protein allowed to investigate the effects of specific mutations thus giving new insights in the structure/function relationship of the factor VIII molecule. These findings might promote the development of novel recombinant factor VIII concentrates with higher efficacy, longer half life and reduced immunogenicity.

Exons↗
PubMed2003

[The national GTH haemophilia registry as database within the scope of the German human genome project].

The Committee of Haemophilia of the GTH has established a central registry for all German centers treating patients with haemophilia. The intention was to establish a suitable system for collecting and analyzing epidemiological data relevant to bleeding disorders. The registry provides the database within the scope of the German Human-Genome-Project. The set goal is the complete molecular characterization of the genetic mutations on chromosome X of haemophilia A patients in Germany and subsequent correlation with the phenotype. An electronic network is applied for communication. A Java-application was developed for online electronic data acquirement by the participating centers. Offline data entry and sending encrypted data carriers is possible, too. A high level of security is assured by personalized access. Data are anonymized and scrambled by secure encoding. The concept was confirmed by the official data security offices. A considerable improvement for the epidemiological sciences and a better basis on therapy for patients with bleeding disorders is expected. Furthermore the registry is available for other scientific projects.

Chromosomes, Human, X↗
PubMed2002

[Do polymorphisms of the SDF1 and CCR2b genes modify the course of hepatitis C or HIV/HCV co-infection?].

BACKGROUND AND OBJECTIVE: Complementary to the CCR5-Delta32 mutation polymorphisms in the genes of CCR2b (CCR2b-V64 I) and stromal derived factor (SDF)-1 (SDF-1 3'A) affect the course of the human immunodeficiency virus (HIV) infection. While the CCR5-Delta32 mutation is also increased in chronic hepatitis C virus (HCV) infection it is unclear, whether the CCR2b-V64 I and the SDF-1 3'A polymorphisms also are associated with chronic HCV infection. METHODS: We analyzed the frequencies of the CCR2b-V64I and SDF1 - 3'A mutation in patients with HIV/HCV coinfection (n = 130), HIV infection (n = 105), HCV infection (n = 153) and 112 healthy blood donors. We stratified each group into homozygous mutations, heterozygous mutations and homozygous wild types, respectively. The resulting subsets were compared with respect to HIV and HCV loads, CD4 and CD8 cell counts. RESULTS: The mutant SDF1 - 3'A allele was found at 20.3 % frequency in patients with HCV infection and at 20.4 % frequency in patients with HIV/HCV coinfection, respectively. It was present in 27.1 % of the patients with HIV infection and 27.9 % of the healthy controls (not significant). The number of SDF-1 3) A homozygous patients was highest in patients with HIV/HCV coinfection and significantly different compared to the Hardy-Weinberg equilibrium (p = 0.010, chi (2) = 9.15). However, CD4- and CD8-cell counts or viral loads were not affected by this mutation. The frequency of the CCR2b-V64 I allele was similar in all patient groups. However, CCR2b-V64 I heterozygous patients showed HIV loads that were threefold lower than in CCR2b wildtype patients (22.9 x 103 vs. 6.4 x 103 copies/ml, not significant). Furthermore, hepatitis C viral loads were reduced roughly by 30 %. CONCLUSION: These results suggest that the SDF1 - 3'A and CCR2b-V64I mutations do not affect the course of HCV and HIV/HCV infection in the same manner as does the CCR5-Delta32 mutation.

Adolescent↗
PubMed2002

[Recurrent spontaneous hemorrhage in a patient with light chain immunocytoma].

The 48-year-old female patient was sent to our clinic for further evaluation of a spontaneous decrease of prothrombin- and prolongation of the bleeding-time. She presented in good conditions with an enlargement of cervical lymphnodes and the history of a monoclonal plasmacyte dyscrasia. The laboratory results revealed a pronounced decrease of prothrombin-time, a prolonged activated partial thromboplastin-time, a decrease of factor VII and X activity and a light chain paraprotein. The histological examination of the bone marrow led to the diagnosis of an immunocytoma and a medullar amyloidosis. For the aim of influencing the coagulopathy the patient was treated with chemotherapy. However, she developed severe bleedings. Further haemostaseological tests presented an amyloidosis-associated decrease of factor VII and X, an acquired von Willebrands disease, an acquired thrombozytopathy and a lupus-like anticoagulans. Under substitution of factor VIII-von Willebrand-factor-complex and chemotherapeutic treatment a stabilisation over several years was achieved till the patient died due to an amyloid-associated acute pancreatitis.

Amyloidosis↗
PubMed2002

Defective human T-cell leukaemia virus type 1 (HTLV-1) genomes: no evidence in serologically indeterminate german blood donors but new type detected in established cell lines.

Individuals reactive in antibody screening tests (ELISA) and with one or more reactions to HTLV-1 proteins on Western blotting, but lacking the criteria of a confirmed HTLV infection, are not exceptional in regions with a low prevalence of HTLV-1/-2 infections. PCR analysis of these indeterminate samples, using "diagnostic" pol and tax sets of primers, give negative results. However, expression of HTLV-1 defective proviruses with internal deletions undetectable by PCR with diagnostic primers could have taken place. Seven German HTLV-1 ELISA-reactive blood donors, who showed reactivity also in Western blots against several viral proteins, and twenty haemophiliacs, were examined by nested PCR and/or PCR/Southern hybridisation with primers designed for detection of HTLV-1 defective proviruses. No HTLV-1-specific amplification products were obtained. However, HTLV-1 defective proviruses with large internal deletions were detected in four out of five cell lines established from symptomatic HTLV-1 cases and two in HUT-102 cells. In two amplicons, short inverted rRNA sequences between gag and env fragments of HTLV-1 defective proviruses were revealed. These results do not exclude the presence of defective HTLV-1 proviruses in individuals with indeterminate serology although this is unlikely.

Blood Donors↗
PubMed2002

Long-term follow-up after intertrochanteric varus osteotomy for haemophilic arthropathy of the hip.

In view of an increasing tendency in prosthetic management of haemophilic arthropathy, we intended to evaluate the efficacy of corrective osteotomy of the hip, specifically taking long-term clinical and radiographic results into consideration. Eleven hips affected by haemarthropathy in nine patients suffering from severe haemophilia A were treated with an intertrochanteric varus osteotomy. The average follow-up period was 15 small middle dot4 years. The preoperative clinical score of the Advisory Committee of the World Federation of Haemophilia was 5 small middle dot3 points (range 4-7) and the Pettersson score was 6 small middle dot4 points (range 2-10). The average WFH score at follow-up had increased to 3 small middle dot6 points. Seven hips showed clinical improvement, two hips showed a postoperative deterioration while a further two hips remained unchanged. The Petterson score increased to an average of 7 small middle dot7 points. Here the radiographs of six patients indicated postoperative deterioration, three remained unaltered and two showed improvement. Our study cannot conclusively answer whether intertrochanteric varus osteotomy for haemophilic arthropathy of the hip is always a feasible alternative to joint arthroplasty. The decision for or against this procedure must be individually assessed and the patient must be thoroughly informed about the advantages and disadvantages of both procedures.

Adolescent↗
PubMed2002

Clinical and radiographic scores in haemophilic arthropathies: how well do these correlate to subjective pain status and daily activities?

Haemophilic patients who reached adulthood before the establishment of prophylactic treatment frequently show multiple and substantial arthropathies. The aim of this study was to determine to what extent haemophiliac's subjective impairment due to arthropathies correlates with objective clinical and radiographic parameters. By means of a questionnaire and a visual analogue scale, we consulted 79 haemophiliacs concerning their joint-pain status, how these were treated and to what extent their daily activities had been affected. Using a scoring system suggested by the Advisory Committee of the World Federation of Haemophilia, clinical evaluation was performed. Radiographs of 60 patients were assessed by means of the Petterson scale. The results were statistically compared. We found a significant correlation between pain intensity and clinical pathology as well as between pain intensity and radiographic joint damage for both knees and for the right ankle. The number of painful joints correlated well with the number of clinically/radiographically affected joints. The more pronounced the objective damage to joints, the more frequently patients claimed to have constant pain, depressive episodes and a dependency on pain-relieving medication. The more pronounced the objectively assessed damage to the knee and ankle joint, the higher the likelihood that the patient suffers from severe joint pain and reduction of activity. Treatment of painful symptoms from arthropathies is often insufficient. Scores and questionnaires may help to define the haemophiliacs pain status more clearly, thereby offering a possibility of assessment and long-term observation.

Activities of Daily Living↗
PubMed2001

Hemophilia.

Explore the source record for details and available documents.

Factor VIII↗
PubMed2001

Pain status of patients with severe haemophilic arthropathy.

Patients with severe haemophilia A growing up before the establishment of prophylactic treatment frequently developed significant haemarthropathies. The goal of the following study was to clarify the role of haemarthropathic pain for haemophilic patients. Furthermore, we aimed to determine to what degree daily activities are influenced by the impairment and which therapeutic modalities are used in pain management. Using a questionnaire we consulted 71 haemophiliacs concerning their complaints and how they were treated in 1999 (average age 43 years; range 21-63 years). The pain in the large joints and spine and the effect of specific treatment was estimated by a visual analogue scale. On average, there were four joints with major pain and 0.5 with minor pain. The most frequent sources of pain were the ankle joints (45%), followed by the knee (39%), spine (14%) and elbow (7%). Fifty percent of all patients complained of pain throughout the day if no treatment was applied. In 29% of patients, pain persisted after application of factor VIII (FVIII), while 12% claimed that pain still remained after use of FVIII and pain killers. Restriction in activities of daily life was reported by 89% of the group and 85% reported on an impact of pain on their mood. Patients primarily used FVIII to decrease pain, followed in frequency by use of anti-inflammatory drugs, orthopaedic footwear, liniments and bandages. Haemophilic patients with haemarthropathy are chronic pain patients. By means of the questionnaire, it is possible to reveal the 'silent' sufferers. Sufficient pain treatment is essential so as to increase the patient's quality of life and avoid inadvertent abnormal postures possibly resulting in increased loading of joints and subsequent bleeding episodes.

Activities of Daily Living↗
PubMed2001

Transient loss of T-cell reactivity in a patient with hepatitis C virus reinfection.

BACKGROUND/AIMS: Self-limited acute hepatitis C virus (HCV) infection with spontaneous recovery is only rarely observed in clinical practice. All existing studies correlate strong cellular immune responses to the recovery from HCV infection. CASE REPORT: Here, we present a 49-year-old haemophiliac, who had successfully recovered from an acute hepatitis, which was classified retrospectively as HCV infection based on his antibody profiles. This patient was reinfected with HCV 18 years later from an exogenous source, and successfully recovered from this reinfection within 2 months. After his first hepatitis the patient displayed strong cellular responses against recombinant HCV proteins. During reinfection, T-cell proliferation was markedly reduced, while HCV antibody titres increased. However, E2 antibodies were consistently not detectable. T-cell proliferation returned to the pre-reinfection level only several months after loss of viraemia. DISCUSSION: Our observations resulted in the unexpected finding that our patient cleared HCV reinfection despite an apparent loss of his pre-existing T-cell reactivity in the peripheral blood.

Hemophilia A↗
PubMed2000

A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor.

The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma of patients with mild/moderate hemophilia A are poorly understood. In such patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr, Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated with reduced binding of fVIII to von Willebrand factor (vWf). For each patient plasma, the specific activity of mutated fVIII was close to that of normal fVIII. Scatchard analysis showed that the affinity for vWf of recombinant Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII mutants was reduced 8-fold, 80-fold, and 3-fold, respectively, when compared with normal fVIII. Given the importance of vWf for the stability of fVIII in plasma, these findings suggested that the reduction of fVIII binding to vWf resulting from the above-mentioned mutations could contribute to patients' low fVIII plasma levels. We, therefore, analyzed the effect of vWf on fVIII production by Chinese hamster ovary (CHO) cells transfected with expression vectors for recombinant B domain-deleted normal, Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII. These 3 mutations impaired the vWf-dependent accumulation of functional fVIII in culture medium. Analysis of fVIII production by transiently transfected CHO cells indicated that, in addition to the impaired stabilization by vWf, the secretion of functional Ile2098Ser and Arg2150His fVIII was reduced about 2-fold and 6-fold, respectively, by comparison to Ser2119Tyr and normal fVIII. These findings indicate that C1-domain mutations resulting in reduced fVIII binding to vWf are an important cause of mild/moderate hemophilia A.

Animals↗
PubMed2000

Intra-articular hyaluronic acid in the treatment of haemophilic arthropathy of the knee. Clinical, radiological and sonographical assessment.

Hyaluronic acid has been used successfully in the treatment of osteoarthritis since 1989. There is no experience in haemophiliacs in larger study groups. In a prospective study, 20 patients (21 knees) with haemophilic arthropathy of the knee received 20 mg hyaluronic acid by intra-articular injection for 5 consecutive weeks. Assessment included clinical scores, X-ray, magnetic resonance imaging (MRI) and biomechanical motion analysis before and 3 months after the first injection. The score of the WFH advisory committee and the Aichroth score for special evaluation of the knee were used. After an average period of 26 months, the World Federation of Hemophilia (WFH) score, the Aichroth score and the visual analogue scale were evaluated again. All patients had pain caused by their arthropathy, nine of them had positive antibodies to human immunodeficiency virus, and 15 had chronic hepatitis C. The mean WFH score was 8.1 points, the Petterson score was 7.3 points and the Aichroth score was 38 points (maximum 55 points). The WFH score decreased to 7.3 points, the Aichroth score improved to 40 points and the subjective assessment measured with a visual analogue scale improved from 5.3 to 3.7 points. No differences from MRI controls were detected. After 3 months, 14 of 20 patients improved subjectively, particularly in longer walking distance, stair-climbing or initial pain. These positive aspects were limited by arthropathy in adjacent joints. After 26 months 10 patients still are benefiting for up to 31 months follow-up. The average WFH score was 7.3 points, the Aichroth score 39 points, the visual analogue scale 4.0 points. We recommend hyaluronic acid for haemophilic arthropathy of the knee when regular conservative therapy has failed and operative treatment is not feasible.

Activities of Daily Living↗