Biomedical subjects

C Becker

Publications and source records attributed to C Becker.

At least 19 recordsLinked to original sources

PubMed2007

Biowaiver monographs for immediate release solid oral dosage forms: isoniazid.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing isoniazid as the only active pharmaceutical ingredient (API) are reviewed. Isoniazid's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. Isoniazid is "highly soluble" but data on its oral absorption and permeability are inconclusive, suggesting this API to be on the borderline of BCS Class I and III. For a number of excipients, an interaction with the permeability is extreme unlikely, but lactose and other deoxidizing saccharides can form condensation products with isoniazid, which may be less permeable than the free API. A biowaiver is recommended for IR solid oral drug products containing isoniazid as the sole API, provided that the test product meets the WHO requirements for "very rapidly dissolving" and contains only the excipients commonly used in isoniazid products, as listed in this article. Lactose and/or other deoxidizing saccharides containing formulations should be subjected to an in vivo BE study.

Biological Availability↗

PubMed2006

Color Doppler, power Doppler and B-flow ultrasound in the assessment of ICA stenosis: Comparison with 64-MD-CT angiography.

The purpose of this study is to investigate the diagnostic potential of color-coded Doppler sonography (CCDS), power-Doppler (PD) and B-flow ultrasound in assessing the degree of extracranial internal carotid artery (ICA) stenosis in comparison to CT-angiography (MD-CTA). Thirty-two consecutive patients referred for CTA with 41 ICA-stenoses were included in this prospective study. MD-CTA was performed using a 64 row scanner with a CTDIvol of 13.1 mGy/cm. In CTA, CCDS, PD and B-flow, the degree of stenosis was evaluated by the minimal intrastenotic diameter in comparison to the poststenotic diameter. Two radiologists performed a quantitative evaluation of the stenoses in consensus blinded to the results of ultrasound. These were correlated to CTA, CCDS, PD and B-flow, intraoperative findings and clinical follow-up. Grading of the stenoses in B-flow ultrasound outperformed the other techniques in terms of accuracy with a correlation coefficient to CTA of 0.88, while PD and CCDS measurements yield coefficients of 0.74 and 0.70. Bland-Altman analysis additionally shows a very little bias of the three US methods between 0.5 and 3.2 %. There is excellent correlation (coefficient 0.88, CI 0.77-0.93) with 64-MD-CTA and B-flow ultrasound in terms of accuracy for intrastenotic and poststenotic diameter. Duplex sonography is useful for screening purposes.

Aged↗

PubMed2006

Transstadial and transovarial persistence of Babesia divergens DNA in Ixodes ricinus ticks fed on infected blood in a new skin-feeding technique.

Although Babesia divergens is the the principal confirmed zoonotic Babesia sp. in Europe, there are gaps in our knowledge of its biology and transmission by the tick Ixodes ricinus. In order to reproduce the part of the parasite cycle that occurs in the vector, an in vitro animal skin feeding technique on blood containing in vitro cultivated B. divergens was developed. Parasite DNA was detected in all samples of salivary glands of nymphs and adults that had fed on parasitized blood as larvae and nymphs, respectively, indicating acquisition as well as a transtadial persistence of B. divergens. PCR performed on eggs and larvae produced by females that had fed on parasitized blood demonstrated the existence of a transovarial transmission of the parasite. Gorging B. divergens infected larvae on non-infected gerbils showed persistance of the parasite over moulting into the resulting nymphs. These results indicate that the parasitic stages infective for the vector (i.e. the sexual stages) can be produced in vitro. To our knowledge, this is the first report of artificial feeding of I. ricinus via membrane as well as in vitro transmission of B. divergens to its vector. The opportunities offered by the use of such a transmission model of a pathogen by I. ricinus are discussed.

Animals↗

PubMed2006

Magnetically tuned spin dynamics resonance.

We present the experimental observation of a magnetically tuned resonance phenomenon in the spin mixing dynamics of ultracold atomic gases. In particular, we study the magnetic field dependence of spin conversion in F=2 (87)Rb spinor condensates in the crossover from interaction dominated to quadratic Zeeman dominated dynamics. We discuss the observations in the framework of spin dynamics as well as matter wave four wave mixing. Furthermore, we show that the validity range of the single mode approximation for spin dynamics is significantly extended at high magnetic field.

Journal Article↗

PubMed2006

Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders.

Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p. The LAMB2 gene, which was recently reported as mutated in Pierson syndrome (microcoria-congenital nephrosis syndrome; OMIM #609049), was located in the linkage interval. Sequencing of all coding exons of LAMB2 revealed a novel homozygous missense mutation (R246Q) in both affected children. A different mutation at this codon (R246W), which is highly conserved through evolution, has recently been reported as causing Pierson syndrome. Subsequent LAMB2 mutational screening in six additional families with congenital nephrotic syndrome revealed compound heterozygosity for two novel missense mutations in one family with additional nonspecific ocular anomalies. These findings demonstrate that the spectrum of LAMB2-associated disorders is broader than previously anticipated and includes congenital nephrotic syndrome without eye anomalies or with minor ocular changes different from those observed in Pierson syndrome. This phenotypic variability likely reflects specific genotypes. We conclude that mutational analysis in LAMB2 should be considered in congenital nephrotic syndrome, if no mutations are found in NPHS1, NPHS2, or WT1.

Child, Preschool↗

PubMed2006

Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids.

Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation.

Animals↗

PubMed2006

[Recurrent acute pancreatitis during pravastatin-therapy].

Acute pancreatitis can rarely be caused also by drugs. Several substances from different drug classes have been associated with the occurrence of acute pancreatitis. Regarding the class of the hydroxymethylglutaryl-CoA-reductase-inhibitors (statins) case-reports have been published in the literature in association with each individual statin. We present a 60-years-old male who developed twice an acute pancreatitis while being treated with pravastatin. Because some case reports describe the reoccurrence of acute pancreatitis after exposure to a different statin, recommendations for further therapy remain complex. There are also case reports of pancreatitis associated with fibrates and information on rare adverse reactions associated with ezetimibe is sparse.

Acute Disease↗

PubMed2006

[Lymphadenopathy and constitutional symptoms. Progress of a low-grade follicular lymphoma?].

Atypical presentation of Churg-Strauss syndrome includes lymph-node and parenchymatous organ involvement which mimics the clinical presentation of lymphoproliferative disorders.A 54-year old man with a history of a low-grade follicular lymphoma presented with rapidly growing abdominal lymph-nodes and hepatic, renal and pulmonary infiltrations. CT guided biopsies to verify either lymphoma or infections showed eosinophilic, necrotizing, granulomatous vasculitis leading to the diagnosis of atypical Churg-Strauss syndrome. Within a few days of cyclophosphamide and prednisone treatment the clinical presentation improved and imaging studies detected regression of all manifestations during follow-up.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

[Do injuries of the upper extremity in geriatric patients end up in helplessness? A prospective study for the outcome of distal radius and proximal humerus fractures in individuals over 65].

In a prospective study 104 patients >or=65 years with distal radius fractures (DRF; n=52) and proximal forearm fractures (PHF; n=52) were followed up for a period of 4 months after injury. As an inception- cohort study, influence on treatment pattern was not part of the examination. A total of 53% of the DRF and 74% of the PHF patients underwent surgery. There were no significant changes in the ability of daily living management (IADL) with either fracture form. Functional outcome was better in PHF than DRF patients. PHF patients showed a high incidence in "fear of falling" throughout the whole study, whereas fear of falling rose significantly in DRF patients. 4% of DRF and 9.6% of PHF patients died during the observation period, while 6% of DRF and even 17% of PHF patients had to give up their own housekeeping. One third of both patient groups did not receive physiotherapy. In only 12% of DRF and 6% of PHF patients was osteoporosis treated. In both groups of patients there was a significant worsening in the ability of walking after injury, leading to two or more new falls in 24% of DRF and 28% of PHF patients.

Accidental Falls↗

PubMed2006

Congenital hepatic arteriovenous malformation: an unusual cause of neonatal persistent pulmonary hypertension.

Congenital hepatic arteriovenous malformations are rare anomalies, which typically present in infancy with congestive heart failure, anemia, and hepatomegaly. Morbidity and mortality is high if the condition is not recognized and treated promptly. Hepatic arteriovenous malformation associated with persistent pulmonary hypertension of the newborn has been reported in two cases in the literature. We report a neonate who was referred for management of persistent pulmonary hypertension and was subsequently diagnosed with a large hepatic arteriovenous malformation. He underwent coil embolization following which pulmonary hypertension resolved.

Arteriovenous Malformations↗

PubMed2006

Effectiveness of physical training on motor performance and fall prevention in cognitively impaired older persons: a systematic review.

OBJECTIVE: To determine whether older cognitively impaired people benefit from physical training with regard to motor performance or fall risk reduction and to critically evaluate the methodologic approach in identified randomized controlled intervention trials. DESIGN: Published randomized controlled intervention trials from 1966 through 2004 were identified in PubMed, CINAHL, Gerolit, and the Cochrane Central Register of Controlled Trials according to predefined inclusion criteria and evaluated by two independent reviewers using a modified rating system for randomized controlled intervention trials developed by the Cochrane Library. RESULTS: There were 11 randomized controlled intervention trials that met the predefined inclusion criteria. There was a large heterogeneity regarding methodology, sample size, type of intervention, study outcomes, and analyses. We found conflicting evidence regarding the effect of physical training on motor performance and falls in older people with cognitive impairment. However, a considerable number of the studies had methodologic limitations, which hampered the evaluation of the effectiveness of training. CONCLUSIONS: The randomized controlled intervention trials showed only limited effectiveness of physical training in patients with cognitive impairment. More studies with adequate sample size, sensitive and validated measurements, and higher specificity for the types of intervention targeting subgroups of patients with different degrees of cognitive impairment are required to give evidence-based recommendations.

Accidental Falls↗

PubMed2006

'UroMaix' scaffolds: novel collagen matrices for application in tissue engineering of the urinary tract.

Reconstruction of bladder and ureter tissue is indicated in cases of injury, stenosis, infection or tumor. Substitution by ileum, colon or pure synthetic polymers generates a variety of complications. Biohybrid tissue mimicking structural and functional attributes of the multilayered wall architecture of the urinary conduit may be the solution to current problems. This study reports on porcine urinary tract cells isolated and placed on UroMaix matrices with different degrees of cross-linking produced from highly purified type I collagen from medically approved porcine tissue. A patented procedure revealed membrane structures composed of a dense fibrous side and an open fibrous side. These scaffolds with the porcine urinary tract cells were incubated in a batch culture system for up to 14 days. Cell growth and topographical orientation were examined. Urothelial cells showed maximum attachment and a significant increase of living cells on the dense fiber layer of UroMaix-1. No attachment of urothelial cells occurred on the other prototypes. Smooth muscle cells showed similar behavior within the open fiber layer of all UroMaix matrices. Both urothelial and smooth muscle cells retained their phenotypes as demonstrated by the immunostaining of epithelial cytokeratin 18 and the smooth muscle myosin heavy chain respectively. Thus we could show that UroMaix scaffolds support the attachment and proliferation of urinary tract cells. The elastomeric properties of the collagenous matrices promise attractive applications in the tissue engineering of the urinary tract with its high mechanical demands.

Animals↗

PubMed2006

Gait analysis and WOMAC are complementary in assessing functional outcome in total hip replacement.

OBJECTIVE: To investigate the correlation between objective and subjective evaluation of patients with total hip replacement. DESIGN: Prospective preliminary trial comparing the Western Ontario and McMaster University questionnaire (WOMAC) and gait analysis preoperatively and three months postoperatively. SETTING: A German academic orthopaedic centre specializing in total hip replacement surgery. SUBJECTS: Seventeen patients (median age 70 years) with hip osteoarthritis. INTERVENTION: All patients had had a primary unilateral total hip replacement. MAIN MEASURES: WOMAC questionnaire to assess self-perceived health status and gait analysis to determine objective gait parameters. RESULTS: Performance of walking as well as subjective judgement of health status improved following surgery (gait speed P = 0.0222; stride length P = 0.038; stance phase ratio P = 0.0466; WOMAC P < 0.0001). However, the correlation between gait parameters and WOMAC was poor (r = -0.27 or less). Correlation between changes of walking parameters and WOMAC was bad to good (r = 0.01 to r = -0.72). CONCLUSION: The WOMAC questionnaire might not reflect walking performance. The addition of gait analysis is recommended to gain objective information about the quality of gait.

Aged↗

PubMed2005

[Prediction of serious cardiovascular events by determining coronary artery calcification measured by multi-slice computed tomography].

BACKGROUND: The efficacious prophylaxis of myocardial infarction requires an accurate identification of patients at risk. Conventional risk stratification is often insufficient for this. We therefore examined the predictive value of coronary calcifications for future cardiovascular events. METHODS: We determined the extent of coronary calcification by multi-slice computed tomography in 924 patients (443 men, 481 women, aged 59.4 +/- 18.7 years) after coronary artery disease had been excluded by coronary angiography. To quantify coronary calcifications the volume score was calculated. After an observation period of 36 months was calculated the incidence of coronary revascularisation, myocardial infarction, and cardiac death. RESULTS: During the observation period the event rates for coronary revascularization (5.4 %/ year vs. 2.9 %/ year), myocardial infarction (3.8 %/ year vs. 1.8 %/ year), and cardiac death (2.1 %/ year vs. 1.0 %/ year) in patients with volume scores above the 75th percentile were significantly higher compared to the total study group. Correspondingly the scores in patients with revascularization (397 +/- 187), myocardial infarction (412 +/- 176), and cardiac death (422 +/- 184) were significantly higher compared to patients without cardiovascular events (218 +/- 167). In addition future cardiovascular events were excluded in patients without coronary calcifications. CONCLUSIONS: By determining coronary calcifications it was possible to identify patients at risk for myocardial infarction could be identified. Future cardiovascular events could not be observed in patients without coronary calcifications.

Calcinosis↗

PubMed2005

Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis.

BACKGROUND AND AIMS: The imbalance between effector and regulatory T cells plays a central role in the pathogenesis of inflammatory bowel diseases. In addition to the thymus, CD4+CD25+ regulatory T cells can be induced in the periphery from a population of CD25- T cells by treatment with transforming growth factor beta (TGF-beta). Here, we analysed the in vivo function of TGF-beta induced regulatory T (Ti-Treg) cells in experimental colitis. METHODS: Ti-Treg cells were generated in cell culture in the presence or absence of TGF-beta and tested for their regulatory potential in experimental colitis using the CD4+CD62L+ T cell transfer model. RESULTS: Ti-Treg cells significantly suppressed Th1 mediated colitis on CD4+CD62L+ T cell transfer in vivo, as shown by high resolution endoscopy, histology, immunohistochemistry, and cytokine analysis. Further analysis of in vivo and in vitro expanded Ti-Treg cells showed that exogenous interleukin 2 (IL-2) was crucial for survival and expansion of these cells. CONCLUSION: Our data suggest that regulatory Ti-Treg cells expand by TGF-beta and exogenous IL-2 derived from effector T cells at the site of inflammation. In addition to Tr1 and thymic CD4+CD25+ T cells, peripheral Ti-Treg cells emerge as a class of regulatory T cells with therapeutic potential in T cell mediated chronic intestinal inflammation.

Adoptive Transfer↗

PubMed2005

[Metformin-associated lactic acidosis in a patient with pre-existing risk factors].

Lactic acidosis is a serious clinical situation associated with a high case fatality rate. Lactic acidosis is particularly found in conditions with an insufficient supply of oxigen in the tissue. Other causes for lactic acidosis can be hepatic or renal insufficiency. For the therapy of overweight patients with type 2 diabetes metformin is the first choice if diet and physical training have been ineffective. Metformin, however, has the potential to increase serumlactate. Therefore its ability to cause lactic acidosis is controversely discussed. We present a 64-year-old female patient with metformin-associated lactic acidosis. She had several pre-existing risk factors to develop a lactic acidosis. On her referral to the hospital she suffered from acute renal failure which is considered to be a contraindication for the use of metformin.

Acidosis, Lactic↗

PubMed2005

IL-6 signaling promotes tumor growth in colorectal cancer.

Recent investigations support an important role for TGF-beta in the development of colorectal cancer. However, the molecular consequences of TGF-beta signaling in the colon remains incompletely understood. In a recent study in Immunity, we analyzed the role of TGF-beta in a murine model of colon cancer. Using transgenic mice overexpressing TGF-beta or a dominant negative TGF-beta receptor II under control of the CD2 minigene, we show that TGF-beta signaling in tumor infiltrating T lymphocytes regulates the growth of dysplastic colon epithelial cells, as determined by histology and a novel system for high resolution chromoendoscopy in vivo. At the molecular level, TGF-beta signaling in T cells regulated STAT-3 activation in tumor cells via IL-6. IL-6 signaling required tumor cell derived soluble IL-6R rather than membrane bound IL-6R and suppression of such TGF-beta-dependent IL-6 trans-signaling prevented tumor progression in vivo. Similar to these observations in mice, here we show that human colon cancer tissue expressed only low amounts of membrane bound IL-6R. In contrast, expression and activity of the matrix metalloproteinase TACE were increased. In summary, our data provide novel insights into the role of TGF-beta signaling in colorectal cancer and suggest novel therapeutic approaches for colorectal cancer based on an inhibition of TGF-beta-dependent IL-6 trans-signaling.

ADAM Proteins↗

PubMed2005

Evaluation of a fall detector based on accelerometers: a pilot study.

As falls and fall-related injuries remain a major challenge in the public health domain, reliable and immediate detection of falls is important so that adequate medical support can be delivered. Available home alarm systems are placed on the hip, but have several shortcomings. A fall detector based on accelerometers and placed at head level was developed, as well as an algorithm able to distinguish between activities of daily living and simulated falls. Accelerometers were integrated into a hearing-aid housing, which was fixed behind the ear. The sensitivity of the fall detection was assessed by investigation into the acceleration patterns of the head of a young volunteer during intentional falls. The specificity was assessed by investigation into activities of daily living of the same volunteer. In addition, a healthy elderly woman (83 years) wore the sensor during the day. Three trigger thresholds were identified so that a fall could be recognised: the sum-vector of acceleration in the xy-plane higher than 2 g; the sum-vector of velocity of all spatial components right before the impact higher than 0.7 m s(-1); and the sum-vector of acceleration of all spatial components higher than 6 g. The algorithm was able to discriminate activities of daily living from intentional falls. Thus high sensitivity and specificity of the algorithm could be demonstrated that was better than in other fall detectors worn at the hip or wrist at the same stage of development.

Acceleration↗