Biomedical subjects

K Fischer

Publications and source records attributed to K Fischer.

At least 19 recordsLinked to original sources

PubMed2007

Pegylated interferon and ribavirin combination therapy for chronic hepatitis C in patients with congenital bleeding disorders: a single-centre experience.

Chronic hepatitis C is a major comorbidity in patients with haemophilia. Although the current state-of-the-art therapy consists of pegylated interferon (PegIFN) and ribavirin, there are no reports of the efficacy of this combination in the haemophilia population. The aim of this study was to assess the response and side-effects of PegIFN and ribavirin in patients with inherited bleeding disorders. Patients with chronic hepatitis C were treated with PegIFN alpha-2b (1.5 microg kg(-1) week(-1)) and ribavirin (800-1200 mg day(-1)) for 24 (genotype 2 and 3) or 48 weeks (genotype 1) and followed for an additional 24 weeks. In total, 56 patients were enrolled: 31 (55%) had genotype 1, 12 (21%) genotype 2, and 13 (23%) genotype 3. Ten patients (18%) were HIV co-infected and seven (13%) had been previously treated with IFN-alpha with or without ribavirin. The overall response was 55%. In HIV-negative and treatment-naïve patients, the sustained virological response was 70%. Successful treatment was associated with genotypes 2 and 3, absence of HIV, absence of previous IFN treatment, and decrease of hepatitis C virus load at weeks 4 and 12. Although many side-effects occurred, only a minority (11%) discontinued therapy for this reason. Dose reduction of PegIFN was required in 28% and of ribavirin in 35% of patients. Overall, 22% of patients developed a depression requiring antidepressant drugs and one patient developed psychosis. In conclusion, PegIFN and ribavirin is effective in patients with inherited bleeding disorders. Treatment is safe, but severe side-effects may occur and warrant close monitoring during therapy.

Adolescent↗

PubMed2006

Realized correlated responses to artificial selection on pre-adult life-history traits in a butterfly.

We use artificial selection experiments targeted on egg size, development time or pupal mass within a single butterfly population followed by a common-garden experiment to explore the interactions among these life-history traits. Relationships were predicted to be negative between egg size and development time, but to be positive between development time and body size and between egg size and body size. Correlated responses to selection were in part inconsistent with these predictions. Although there was evidence for a positive genetic correlation between egg and body size, there was no support for genetic correlations between larval development time and either egg size or pupal mass. Phenotypic correlations among the three target traits of selection gave comparable results for the relationships between egg mass and development time (no association) as well as between egg mass and pupal mass (positive association), but not for the relation between development time and pupal mass (negative phenotypic correlation). In summary, correlated responses to selection as well as phenotypic correlations were rather unpredictable. The impact of variation in acquisition and allocation of energy as well as of the benign conditions used deserve further investigation.

Animals↗

PubMed2006

Identification of heavy metal-induced genes encoding glutathione S-transferases in the arbuscular mycorrhizal fungus Glomus intraradices.

Arbuscular mycorrhizal fungi are able to alleviate the stress for plants caused by heavy metal contamination of soil. To analyze the molecular response of arbuscular mycorrhizal fungi to these pollutants, a subtractive cDNA library was constructed using RNA from Glomus intraradices extraradical hyphae of a root organ culture treated with a mixture of Cd, Zn, and Cu. Screening by reverse Northern blot analysis indicated that, among 308 clones, 17% correspond to genes up-regulated by heavy metals. Sequence analysis of part of the clones resulted, amongst others, in the identification of six genes putatively coding for glutathione S-transferases belonging to two different classes of these enzymes. Expression analyses indicated that the genes are differentially expressed during fungal development and that their RNA accumulation dramatically increases in extraradical hyphae grown in a heavy metal-containing solution.

Daucus carota↗

PubMed2006

[The hand assisted transperitoneal laparoscopic donor nephrectomy].

From December 2004 to May 2005 we performed hand assisted laparoscopic donor nephrectomy in 13 female and seven male patients. The median age was 37 years. As immunosuppressant drug, we consistently used tacrolimus, mycophenolate mofetil, methylprednisolone and a monoclonal antibody. The median surgical time was 138 min (range 113-180), and the median warm ischemic time was 87 s (range 63-150). These results are comparable to the surgical and warm ischemic times for open donor nephrectomy. The hospitalization period of the donors was between 5 and 7 days. Renal function and acute-phase parameters showed a transient increase during and after the operation. Most of the patients reached the baseline levels at day 3 and 4, respectively. Together with the clinical data, these findings verify the minimal invasiveness of laparoscopic donor nephrectomy. In the future, this surgical method will probably be the procedure of choice.

Acute-Phase Proteins↗

PubMed2006

Diagnostics and therapy of lymphoceles after kidney transplantation.

Lymphocele incidence after kidney transplantation is as high as 18%. We retrospectively studied the therapy of 42 lymphoceles that occurred in our clinic between 1990 and 2005, focusing on possible predisposing factors for their formation and the results of several therapy variants: conservative, operative, percutaneous puncture, and laparoscopic or open marsupialization. There was no connection between lymphocele formation and the following parameters: the extent to which the iliac vessels had been prepared, the materials used for the preparation, or whether clips or ligatures were applied. Lymphoceles may originate either from the lymphatic system of the recipient or the transplanted kidney. The most sensible measures to prevent their occurrence therefore seems to be to restrict the transplant bed to the smallest permissible level with careful ligature of the lymphatic vessels in the area of the kidney hilus. Treatment for lymphoceles should start with minimally invasive measures. We use the following algorithm in our clinic: puncture to differentiate between urinoma/lymphocele and to test for bacterial infection, sclerotization (200 mg doxycyclin), and finally marsupialization if persistent. The choice of operative technique depends on the location. This algorithm resulted in a relapse rate of 9.5% during the postoperative observation period of up to 15 years.

Diagnosis, Differential↗

PubMed2006

The chitinase allergens Der p 15 and Der p 18 from Dermatophagoides pteronyssinus.

BACKGROUND: House dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae cause allergic disease in humans as well as in dogs. In geographical regions where the two mite species coexist, they both elicit specific immunoglobulin (Ig E) responses in humans whereas dogs preferentially react to D. farinae extracts. In dogs the main IgE binding is directed to the D. farinae chitinase allergens Der f 15 and Der f 18 and not to the groups 1 and 2 allergens as found for humans. Although the IgE response of humans to Der f 18 has been investigated there is no report on Der f 15-specific IgE in humans. OBJECTIVE: This study aimed to characterize the chitinase allergens Der p 15 and Der p 18 of D. pteronyssinus and to find out whether they are important allergens for humans. METHODS: cDNA was cloned by a polymerase chain reaction strategy from D. pteronyssinus libraries using primers based on conserved chitinase sequences. IgE binding to the recombinant polypeptides was measured by immunosorbent assay. Mice were immunized with the polypeptides and cross-reactivity examined. RESULTS: Two variants of Der p 15 were isolated, encoding mature proteins of 58.8 and 61.4 kDa. The amino acid sequences had 90% identity to Der f 15. The cDNA for Der p 18 encoded a mature protein of 49.2 kDa with 88% sequence identity to Der f 18. Der p 15-specific IgE was detected in 70% and Der p 18-specific IgE in 63% of a panel of 27 human allergic sera. CONCLUSIONS: The D. pteronyssinus chitinases Der p 15 and Der p 18 show a high frequency of binding to IgE in allergic human sera. They are therefore potentially important allergens for humans as well as dogs.

Amino Acid Sequence↗

PubMed2006

Pain and functional limitations in patients with severe haemophilia.

Patients with severe haemophilia often experience pain caused by haemophilic arthropathy, and it is known that pain acts as a predictor of disability. The role of pain in functional limitations in these patients, however, has not been systematically investigated. The aim of this study was to describe pain as experienced by patients with haemophilia and to address the role of pain in subsequent functional limitations. Seventy-eight adult patients (18-70 years) with severe haemophilia completed one questionnaire on pain and one on self-perceived functional abilities. Two-thirds of the patients suffered from more than one painful joint, the ankle being mentioned most frequently (n=43). Analgesics were used by 36% of the patients indicating having pain. Six of 10 most frequently mentioned pain descriptors were of evaluative nature. Evaluative qualities of pain were associated with pain intensity, which in turn was associated with the impact of pain on daily life. Pain outcomes, after adjusting for age and treatment modality, explained 3-22% of the variance in self-perceived functional abilities. Data on radiological joint damage (Pettersson scores) were retrieved for a subgroup of 28 younger patients on prophylaxis and no significant correlations with pain parameters were found. Over two-thirds of the patients with severe haemophilia had one or more painful joints. Pain plays a small, but significant role in functional limitations. In the identified subgroup, arthropathy, as measured by the Pettersson score, seemed to have no role in pain experience. Promoting analgesic use might decrease the impact of pain on functional limitations.

Activities of Daily Living↗

PubMed2006

Prevention and treatment of musculoskeletal disease in the haemophilia population: role of prophylaxis and synovectomy.

Prophylaxis is defined as primary (started before the onset of joint damage) or secondary (started after the onset of joint damage). The aim of primary prophylaxis is to prevent recurrent bleeding into joints and the development of chronic arthropathy in later life. When started early, and at most after two joint bleeds, the result is predictably excellent if there is compliance with the primary prophylaxis regimen. In order to decrease the need for central venous access devices to assure reliable venous access, a number of centres start primary prophylaxis with once weekly infusions with dose-escalation based on frequency of joint bleeding. A major unanswered question is whether primary prophylaxis can be safely discontinued in adolescents/young adults and if so, when. A promising predictor for the milder bleeding phenotype in persons with severe haemophilia is a later onset of joint bleeding. Once joint damage has occurred as a result of recurrent bleeding, secondary prophylaxis can only retard, but not prevent, ongoing joint damage. Other strategies to decrease recurrent bleeding from target joints include surgical synovectomy (ideally performed using an arthroscopic technique), radionuclide synovectomy and chemical synovectomy. These interventions have very good outcomes when performed by an experienced team. Given the very high cost of factor concentrates required for programmes of prophylaxis prospective studies that document benefits to the child and family, e.g. quality of life are to be encouraged.

Hemarthrosis↗

PubMed2006

Treatment of chronic hepatitis C in patients with haemophilia: a review of the literature.

Chronic hepatitis C is a major cause of morbidity and mortality in haemophilia patients. In contrast to studies in the general population, the studies of antiviral therapy in haemophilia patients are limited and often include small numbers of patients. A review of the literature was performed to assess the efficacy of interferon (IFN)-based therapy for patients with haemophilia chronically infected with hepatitis C virus (HCV). Studies were identified by electronic searches (Medline, Embase) and hand searches in references of key articles. Data of the included studies were pooled, and responses to therapy were stratified according to treatment regimen, HIV co-infection status, and treatment history. The main outcome was a sustained virological response (SVR) defined as absence of HCV RNA both at the end of treatment and 24-week post-treatment. Thirty-five studies were identified that included 1151 patients. After pooling the data of included patients, the SVR in HIV-negative treatment naïve patients was 22% for IFN monotherapy, 43% for IFN and ribavirin, and 57% for pegylated IFN and ribavirin, respectively. Re-treatment with IFN and ribavirin of those who failed to respond to previous IFN monotherapy was successful in 33%. In HCV/HIV-coinfected patients, response to IFN monotherapy was 8% and to IFN combined with ribavirin 39%. Responses to IFN-based therapy in patients with haemophilia have been improved over time and are nowadays approximately 50-60%. However, data on haemophilic HCV/HIV-coinfected patients and in patients who failed to respond to previous therapy are limited and future studies in these specific patient population are necessary.

Antiviral Agents↗

PubMed2006

Do mothers producing large offspring have to sacrifice fecundity?

We artificially selected on egg size in a butterfly to study the consequences for fecundity, reproductive effort and offspring fitness. Correlated responses in either pupal mass, larval or pupal development time were virtually absent. Offspring size was positively related to fitness, but only partly traded off against fecundity. Rather, total reproductive effort (measured as fresh mass), egg water content and the decline of egg size with female age increased in the large-egg selected lines compared to either small-egg or control lines. Accounting for these effects showed that reproductive investment (in dry mass) was in fact similar across lines. Such mechanisms may enable increased investment in (early) offspring without a reduction in their number, revealing a much more complex picture than a simple trade-off between offspring size and number. Substantial variation among replicates suggests that there are different underlying mechanisms for change, rather than any single, unitary pathway.

Animals↗

PubMed2006

Hereditary hydrocephalus in laboratory-reared golden hamsters (Mesocricetus auratus).

A colony of golden hamsters had an ongoing problem with hydrocephalus. In an attempt to clear the colony of the problem, new breeders from another supplier had been purchased. At termination of a behavioral study, the brain was collected from 35 animals (four of which had died with hydrocephalus during the study) and was examined macroscopically and by light microscopy. Although no animals manifested obvious behavioral changes, 31 of 35 (88.6%, 13/15 males and 18/20 females in control and manipulated groups) had hydrocephalus. Twenty-five animals had macroscopically identifiable hydrocephalus, and six had hydrocephalus identified microscopically. Neither teratogenic concentrations of metals nor mycotoxins were detected in tissues or food, and sera from breeders tested negative for antibodies to Sendai virus, reovirus 3, and lymphocytic choriomeningitis virus. Trial matings of breeders expected to produce hydrocephalic offspring resulted in affected offspring, and mating of breeders expected to produce normal offspring resulted in normal or less-affected offspring. Hydrocephalus was confirmed retrospectively in some breeders. Hereditary hydrocephalus appears to be widespread in hamster stocks in Central Europe. Affected animals do not manifest signs of disease and usually die without obvious premonitory signs. Despite severe hydrocephalus, the animals can breed, and animal handlers do not identify motor deficits or abnormal behavioral activity. This entity is unlike the previously described, hereditary hydrocephalus of hamsters that is phenotypically identifiable and usually is lethal before they attain breeding age.

Animals↗

PubMed2005

Inter-observer reliability in the assessment of heterotopic ossification: proposal of a combined classification.

We applied four published classifications for assessment of heterotopic ossification after total hip arthroplasty (Arcq, Brooker, DeLee and Della Valle [1, 2, 5, 6]. The average incidence of heterotopic ossification varied from 19.8% to 27.7%. The inter-observer reliability of the various classifications was determined by Cohen's Kappa statistic. Kappa values ranged from 0.897 for Arcq's to 0.814 for Brooker's classification. In order to increase the reliability and consistency, we propose a new classification system combining Brooker's and Della Valle's classifications. This new classification preserves the high reliability of Della Valle's system and is comparable to previous publications since it includes Brooker's criteria.

Aged↗

PubMed2005

[Economisation of research -- or: what price deception?].

According to the accepted credo of German science policy the organization of research has to be reshaped to fit the needs of the national economy better than it did so in the past. This is seen as a conditio sine qua non to help German corporations to prevail in the global competition as well as to protect national welfare. The author argues that reorganizing research on a strictly mission-oriented line under economic imperatives will partly suspend the code of science in favor of the code of economy. The focal aim of science, which is to reach at the most reliable information in a methodical and impartial way, will be partly replaced by the aim to reach at the best sellable information in any way which is cheap and profitable. The probability that any information which might endanger the market performance of a product is clandestinely kept under cover by the selling corporation will be greatly enlarged. Expert knowledge necessary to uncover the truth will be mainly interest bound and no longer be freely available. Knowledge perceived to be irrelevant for economy, although possibly being of great intrinsic interest, and even knowledge which might become an essential part of a culture's identity, will be lost on its search for an investor. The great danger is that this applies also to important parts of basic science potentially providing the foundations for future technologies. Externalities such as these could be called the costs of economization, or: the costs of untruth.

Ethics, Research↗

PubMed2005

Can long-term prophylaxis for severe haemophilia be stopped in adulthood? Results from Denmark and the Netherlands.

Prophylaxis is the treatment of choice for children with severe haemophilia. As prophylaxis is especially important during the period of growth, the need for continued prophylaxis in adulthood should be considered. The aim of this study was to describe the incidence and outcome of stopping prophylaxis in patients with severe haemophilia who were offered prophylaxis during childhood. All patients with severe haemophilia (factor VIII/IX <0.01 IU/ml), born 1970-80, treated in two Danish and one Dutch treatment centre were studied. Data on discontinuation of prophylaxis, treatment, joint bleed frequency, clinical scores and radiological scores were collected. Eighty patients were studied. Median follow-up was 19 years (range 7-29). A total of 35% of patients discontinued prophylaxis at a median age of 21.5 years [interquartile range (IQR) 18.4-24.4], experiencing only three joint bleeds per year (IQR 1.4-8.7). Median clinical scores were similar in patients who discontinued prophylaxis [4 points (IQR 0-6)] and those who continued [3 points (IQR 1-6)], as were median Pettersson scores at 13 (IQR 1-24) vs. 13 points (IQR 5-23) respectively. In conclusion one-third of young adults with severe haemophilia on a prophylactic regimen discontinued prophylaxis in early adulthood, while maintaining a low joint bleed frequency and similar arthropathy after 4 years.

Adolescent↗

PubMed2005

Effects of haemophilic arthropathy on health-related quality of life and socio-economic parameters.

Although prophylactic treatment is advised for all children with severe haemophilia, the optimal regimen is still under discussion. Should all joint bleeds be prevented, or can a limited amount of arthropathy be tolerated in adulthood without loss of quality of life? To answer this question, the effect of haemophilic arthropathy on health-related quality of life (HRQoL) needs to be quantified. In a retrospective study, the effect of arthropathy on HRQoL and socio-economic parameters was assessed in a single-centre cohort of 96 patients with severe and moderate haemophilia with a minimum age of 13 years. Arthropathy was measured by the radiological Pettersson score of the elbows, knees and ankles (maximum: 78 points). HRQoL was assessed by the Short Form 36 (SF36), measuring eight domains of health. Labourforce participation and medical consumption were assessed using a separate questionnaire. Patients were studied at a mean age of 28.6 years (range: 13-54), the mean time between evaluation and the last Pettersson score was 0.4 years (SD: 1.1). The overall median Pettersson score was 13 (range: 0-78). There was a trend towards lower quality of life with increasing Pettersson scores and age, especially in the physical domains of the SF36. An age-adjusted analysis showed that arthropathy had a small but significant effect on HRQoL in the domain of 'physical function' of the SF36, but not on its other domains, or on labourforce participation and medical consumption. Thus suggesting that the SF36 can be used to assess the effects of haemophilic arthropathy, especially in the domain of 'physical function'.

Adolescent↗

PubMed2005

Hepatitis C infection among Dutch haemophilia patients: a nationwide cross-sectional study of prevalence and antiviral treatment.

Hepatitis C is a major co-morbidity among patients with haemophilia who received inadequately or non-virus-inactivated clotting factor concentrates before 1992. The objectives of this study were to investigate the prevalence of hepatitis C and the use of antiviral therapies during the last decade among patients with haemophilia in the Netherlands. We performed a cross-sectional study and a questionnaire was sent to all 1519 patients known with haemophilia in the Netherlands between 2001 and 2002. The study population for the present study consisted of 771 patients who had received clotting factor products before 1992 of whom 638 reported their hepatitis C status. In total, 441 of the 638 (68%) patients ever had a positive test for hepatitis C virus (HCV); 344 patients (54%) had a current infection, and 97 (15%) had cleared the virus. Among 344 patients currently HCV infected, 111 (32%) had received treatment for hepatitis C, while 34% (33/97) of patients with an infection in the past had been treated for hepatitis C. In 2002 the prevalence of hepatitis C among patients with haemophilia who received clotting factor products before 1992 was 54%. The majority of patients with a current HCV infection had not been treated with antiviral therapy.

Adolescent↗

PubMed2005

Variability in clinical phenotype of severe haemophilia: the role of the first joint bleed.

To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968-1985 (n = 91), or 1985-2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968-1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4-1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment.

Adolescent↗

PubMed2005

The evolutionary genetics of egg size plasticity in a butterfly.

Abstract The evolution of phenotypic plasticity requires that it is adaptive, genetically determined, and exhibits sufficient genetic variation. For the tropical butterfly Bicyclus anynana there is evidence that temperature-mediated plasticity in egg size is an adaptation to predictable seasonal change. Here we set out to investigate heritability in egg size and genetic variation in the plastic response to temperature in this species, using a half-sib breeding design. Egg size of individual females was first measured at a high temperature 4 days after eclosion. Females were then transferred to a low temperature and egg size was measured after acclimation periods of 6 and 12 days respectively. Overall, additive genetic variance explained only 3-11% of the total phenotypic variance, whereas maternal effects were more pronounced. Genotype-environment interactions and cross-environmental correlations of less than unity suggest that there is potential for short-term evolutionary change. Our findings strengthen the support for the adaptive nature of temperature-mediated plasticity in egg size.

Adaptation, Physiological↗