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Biomedical subjects

M Urban

Publications and source records attributed to M Urban.

At least 19 recordsLinked to original sources
PubMed2006

Detection of novel skeletogenesis target genes by comprehensive analysis of a Runx2(-/-) mouse model.

Runx2 is an essential factor for skeletogenesis and heterozygous loss causes cleidocranial dysplasia in humans and a corresponding phenotype in the mouse. Homozygous Runx2-deficient mice lack hypertrophic cartilage and bone. We compared the expression profiles of E14.5 wildtype and Runx2(-/-) murine embryonal humeri to identify new transcripts potentially involved in cartilage and bone development. Seventy-one differentially expressed genes were identified by two independent oligonucleotide-microarray hybridizations and quantitative RT-PCR experiments. Gene Ontology analysis demonstrated an enrichment of the differentially regulated genes in annotations to terms such as extracellular, skeletal development, and ossification. In situ hybridization on E15.5 limb sections was performed for all 71 differentially regulated genes. For 54 genes conclusive in situ hybridization results were obtained and all of them showed skeletal expression. Co-expression with Runx2 was demonstrated for 44 genes. While 41 of the 71 differentially expressed genes have a known role in bone and cartilage, we identified 21 known genes that have not yet been implicated in skeletal development and 9 entirely new transcripts. Expression in the developing skeleton was demonstrated for 21 of these genes.

Animals↗
PubMed2005

Improving the safety of laparoscopic cholecystectomy: the routine use of preoperative magnetic resonance cholangiography.

BACKGROUND: The aim of this study was to determine the value of routinely performed preoperative magnetic resonance cholangiography (MRC) in detecting common bile duct (CBD) stones in patients stated to undergo elective laparoscopic cholecystectomy. In addition, we used MRC to investigate possible variants of the cystic duct. METHODS: Magnetic resonance cholangiography was performed preoperatively in 773 patients (311 male and 462 female; median age 55 years, range 16-91) who had no clinical signs of cholestasis prior to undergoing elective laparoscopic cholecystectomy. In cases where the MRC was positive for CBD stones, endoscopic retrograde cholangiopancreatiography (ERCP) was then performed. A total of 532 patients were available for continuous postoperatively follow-up (median 54 months, range 36-85). In 462 patients (247 female, and 215 male), MR images were also reviewed for variants of the cystic duct. RESULTS: In 705 patients (91%), MRC was negative for CBD stones. In 64 patients (9%) MRC was positive. Of these patients, 47 (6%) had CBD stones on ERCP. In 12 patients (2%), MRC was false positive. In five cases (0.6%), ERCP had an inconclusive result postoperative follow-up (532 patients, or 69%) revealed evidence of CBD stones in three patients (10.4%) despite a preoperative negative MRC result. Anatomical variants in the course of the cystic duct and its confluence with the common bile duct were found in 27 of 462 patients (6%). CONCLUSIONS: Magnetic resonance cholangiography proved to be a reliable screening technique in the preoperative evaluation of patients with silent CBD stones. Imaging of the course of the cystic duct is possible in a high percentage of cases. Therefore, MRC can be recommended as a screening technique before laparoscopic cholecystectomy.

Adolescent↗
PubMed2005

Application of mouse monoclonal antibodies for identification of antigen regions of human thyroid peroxidase in adolescents with Graves' disease and non-toxic multinodular goiter by flow cytometry.

Thyroid peroxidase (TPO) is the major thyroid autoantigen recognized by serum autoantibodies from patients with Graves' disease (GD) or Hashimoto's thyroiditis directed to two immunodominant conformational regions termed A and B. The epitopes of human TPO have been defined using a panel of mouse monoclonal antibodies (mAbs). The aim of this study was to estimate the expression of chosen surface antigen regions of TPO (1, 18, 30, 64 epitopes) on thyroid cells in 15 patients with non-toxic multinodular goiter (NTMG) and 15 patients with GD. The thyrocytes were identified by indirect method: in the first stage we added mouse monoclonal autoantibodies specific for TPO regions and in the second stage we conjugated this complex with rabbit anti-mouse antibodies IgG (Fab')(2) with FITC. All investigations were performed by flow cytometry using Coulter EPICS XL apparatus. The percentages of thyrocytes with expression of epitopes 1, 18, 30, 64 TPO were measured in relation to the respective anti-TPO concentrations: 50-1600 microg/ml. The analysis of epitopes located in immunodominant regions (IDR) of TPO revealed higher percentages of thyrocytes in cases with GD in comparison to NTNG. The most predominant difference was observed for mAb 64 epitope (48 vs 7%, p < 0.019; 39 vs 5%, p < 0.017) at the concentration of 100-200 microg/ml mAbs. The expression of 18 epitope on thyrocytes was also statistically higher in Graves' patients than in the NTMG (14 vs 6%, p < 0.025) at concentration of 400 microg/ml mAbs. However, this expression was much less pronounced. In all the cases, the percentages of thyrocytes with epitopes 1 and 30 were in low detection (8-15% of positive cells). In conclusion, our findings suggest that the elevated expression of TPO epitopes 18 and 64 in young patients with thyroid autoimmune diseases increase stimulation and activation of thyroid cells during inflammatory reaction within the thyroid gland. In addition, predominant expression of 64 TPO epitope that recognizes B domain in GD patients could be a useful marker of the immune process in the thyroid gland.

Adolescent↗
PubMed2005

Efficacy of the fully human monoclonal antibody MOR102 (#5) against intercellular adhesion molecule 1 in the psoriasis-severe combined immunodeficient mouse model.

BACKGROUND: Psoriasis is considered as a chronic immune-mediated disease characterized by inflammation and proliferation of the epidermis. OBJECTIVES: Targeting intercellular adhesion molecule 1 (ICAM-1) is an attractive therapeutic option as this molecule is critically involved in leucocyte adhesion and extravasation as well as in lymphocyte activation. METHODS: We have selected the fully human monoclonal antibody MOR102 (#5) against ICAM-1 from the Human Combinatorial Antibody Library (HuCAL). This antibody, as human IgG4 [corrected] was tested for its ability to interfere with lymphocyte activation and adhesion in vitro as well as for its antipsoriatic efficacy in vivo using the psoriasis-severe combined immunodeficient (SCID) mouse model. RESULTS: The antibody demonstrated efficient inhibition of lymphocyte adhesion to ICAM-1 in vitro, with an IC(50) of approximately 0.4 microg mL(-1) (3 nmol L(-1)). In addition, MOR102 (#5) reduced lymphocyte proliferation in mixed lymphocyte cultures by approximately 50%. The in vivo efficacy of MOR102 (#5) was tested on grafts derived from lesional skin of patients with chronic plaque-stage psoriasis transplanted on to SCID mice. Intraperitoneal injection of 10 mg kg(-1) of MOR102 (#5) antibody every alternate day over a period of 4 weeks resulted in reconstitution of orthokeratotic differentiation and a significant (P < 0.05) reduction in epidermal thickness as well as marked reduction in the inflammatory infiltrate. Therapeutic activity may be related to the targeting of ICAM-1 on keratinocytes and thus preventing efficient activation of local T cells. CONCLUSIONS: Based on the efficacy of the fully human monoclonal antibody MOR102 (#5) shown in vitro as well as in vivo in the psoriasis-SCID mouse model, initiation of clinical studies is indicated.

Animals↗
PubMed2005

Intrinsic constraint of unlinked total elbow replacements--the ulnotrochlear joint.

BACKGROUND: Many unlinked total elbow replacement designs with radically differing articular geometries exist, suggesting that there is no consensus regarding an optimal design. A feature inherent to the articular design is the intrinsic constraint afforded to the joint by the implant. Our aim was to compare the intrinsic constraints of unlinked implants with that of the normal ulnotrochlear joint. METHODS: We tested twelve cadaveric ulnotrochlear joints with a custom-made multiple-axis materials testing machine. With compressive loads ranging from 10 to 100 N, the joints were moved in either valgus or varus directions at 90 degrees of flexion. The ulnotrochlear components from a single example of five medium-sized unlinked elbow replacements (Ewald, Kudo, Pritchard ERS, Sorbie-Questor, and Souter-Strathclyde) were also tested. The recorded measurements included the torques and forces, angular displacement, and axial displacement of the humerus relative to the ulna. RESULTS: In general, the peak torque and the constraint ratio significantly increased with increasing compressive load for the implants as well as for the normal elbow. In valgus displacement, the Souter-Strathclyde implant had the highest and the Sorbie-Questor had the smallest peak torque and the Souter-Strathclyde had the highest and the Ewald had the smallest constraint ratio. In varus displacement, the Kudo had the highest and the Ewald had the smallest peak torque and constraint ratio. CONCLUSIONS: The constraint ratio is a characteristic that is useful for describing elbow joint behavior and for comparing the behavior of implants with that of the human elbow. Of the unlinked implants tested, the Souter-Strathclyde and Kudo prostheses most closely approximated the behavior of the human elbow joint. Implants that resemble the human elbow in appearance do not replicate normal behavior consistently, whereas other implants that do not resemble the human elbow closely do not deviate markedly from human behavior. Thus, much basic information about elbow form and function is needed to improve the performance of total elbow prostheses.

Aged↗
PubMed2005

[Infrared pupilometry measured by digital photography].

BACKGROUND: Pupil size is mainly controlled by the action of parasympathetic and sympathetic nerves. Measurement of pupil size and reaction to light are important in both experimental and clinical settings. METHODS AND RESULTS: We have established infrared pupilometry using a commercially available digital camera and a calculation with standard computer software. Volunteers were habituated in a dark room for five minutes before pupil evaluation. Pupil measurement was repeated three times and the diameter was calculated according to the following formula: D(mm)=30/S(pix)*D(pix), where D(pix) and D(mm) represent the pupil size in pixels and millimetres, respectively, and S(pix) was the length in pixels of a 30 mm standard. Our method was validated by the measurement of the diameter of calibration circles printed on a white sheet of paper. Deviation from the actual size was less than 3%. We also compared the results of pupil size obtained by our method, with the results of the pupilometer Pupillscan II measurement. The relative difference between the two methods was always less than 5%. The applicability of the method was illustrated by measurement of the pharmacodynamic effect of the single dose of tramadol (100 mg p.o.) in seven volunteers, compared with control placebo-treated volunteers. CONCLUSIONS: The proposed method is precise and sensitive enough to be used for pupil size determination.

Adult↗
PubMed2005

The role of the therapeutic team in shaping eating habits and lifestyle in children with dietary calcium deficiency.

PURPOSE: Assessment of the effect of low-calcium diet on bone mineral content in children and adolescents. MATERIAL AND METHODS: The study involved 89 children (49 girls and 40 boys) aged 5-18 years, in whom diseases affecting bony metabolism had been excluded. Children with a history of dietary calcium content below 500 mg/day were recruited. The study group was divided according to age: group I, age 5-9 years (children before puberty); group II, age 9-15 years (early puberty); group III, 15-18 years (late puberty). Dual energy X-ray absorptiometry (DEXA) was used for densitometric measurements. Bone mineral density (BMD) was assessed in the whole skeleton (total BMD), in vertebrae L2-L4 (spine BMD) in g/cm2 and as Z-score. Concentrations of Ca, Ca2, P, activity of alkaline phosphatase (AP) and its bony isoenzyme were determined in the serum. RESULTS: Total bone mass below 5th percentile (according to the norm for age and gender) was found in 56.98% of the children involved in the study. A significant reduction was noted in the spine mineral mass in boys (p < 0.01) as compared to girls (0.731 +/- 0.17 g/cm2 and 0.835 +/- 0.19 g/cm2, respectively). The lowest mean Z-score (-1.850) was observed in group III as compared to group I (-1.194) (p < 0.01) and group II (-1.201) (p < 0.05). There were statistically significantly positive correlations between total and spine BMD and BMI. The correlation coefficient was r = 0.56 and r = 0.41 (p < 0.001), respectively. CONCLUSIONS: In the majority of the children (c. 60%), a reduction in bone mineral content was found. The lowest Z-score (-1.850) was revealed in the oldest children, which may disturb the process of reaching the optimum level of the peak bone mass.

Adolescent↗
PubMed2004

Short- and long-term reproducibility of autonomic measures in supine and standing positions.

Autonomic nervous tests and heart rate variability (HRV) have been used to assess cardiac autonomic function and to evaluate long-term prognosis. The aim of this study was to evaluate the short- and long-term reproducibility of HRV parameters and autonomic nervous tests according to body position (supine or standing). The study group consisted of 26 healthy subjects. Autonomic nervous tests and HRV were performed twice during the day and the results were averaged. The protocol was then repeated 3 days after each examination and also after 6 and 24 months. Autonomic nervous tests included deep breathing, Valsalva manoeuvre and isometric muscle exercise (handgrip), as well as blood pressure and heart rate in response to standing. ECG recordings were taken for 10 min during spontaneous breathing for HRV analysis. We found that the reproducibility of some parameters of the autonomic nervous test were independent of body position [E/I ratio (heart rate response to deep breathing)], whereas other parameters were dependent on body position (Valsalva manoeuvre and blood pressure response to sustained handgrip). In addition, within-day measurements of those parameters varied from non-reproducible (Valsalva ratio, handgrip and blood pressure response to standing) to moderately reproducible [E/I ratio and 30/15 ratio (heart rate response to standing)]. Among the HRV parameters, we found that total power (TP), low (LF)- and high (HF)-frequency were reproducible not only for measurements made within the same day, but also during short- and long-term observations, and only the LF/HF ratio was dependent on body position. We conclude that only a few autonomic nervous tests are reproducible in the short- and long-term. Because HRV parameters obtained during spontaneous respiration showed high reproducibility for measurements made within the same day as well as in the short- and long-term, they should be used instead of autonomic nervous tests when long-term observations are carried out in a healthy population.

Adult↗
PubMed2004

Tobacco attributable deaths in South Africa.

BACKGROUND: In mid 1998, a question "Was the deceased a smoker five years ago?" was introduced on the newly revised South African death notification form. DESIGN: A total of 16,230 new death notification forms from 1998 have been coded, and comparison of the prevalence of smoking among those who died of different causes was used to estimate, by case-control comparisons, tobacco attributed mortality in South Africa. Cases comprised deaths from causes known (from other studies) to be causally associated with smoking, and controls comprised deaths from medical conditions expected to be unrelated to smoking. Those who died from external causes, and from diseases strongly related to alcohol consumption, were excluded. SUBJECTS: Reports were available from 5340 deceased adults (age 25+), whose smoking status was given by a family member. RESULTS: Significantly increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0), other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart disease (OR 1.7, 95% CI 1.2 to 2.3). CONCLUSION: If smokers had the same death rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8% of all adult deaths in South Africa (more than 20 000 deaths a year) were caused by smoking.

Adult↗
PubMed2004

Acceptability and utilisation of voluntary HIV testing and nevirapine to reduce mother-to-child transmission of HIV-1 integrated into routine clinical care.

OBJECTIVES: Use of nevirapine for prevention of mother-to-child transmission (PMTCT) of HIV-1 has been routine clinical care at Coronation Women and Children's Hospital since April 2000. We assessed the effect of regular audit and targeted interventions on the utilisation of the PMTCT programme. METHODS: Review of antenatal cards and hospital records of women discharged following delivery, in three time periods between October 2000 and February 2002. Following the initial audit an intervention was implemented to eliminate weaknesses in our PMTCT service. Following the second audit the hospital became a pilot site for the Gauteng PMTCT programme. RESULTS: In the initial audit 53.2% of women (159/299) were tested for HIV and received their results, while 56% (14/25) of identified HIV-infected women, and 16% (4/25) of their infants, received nevirapine. By the third audit 74.3% of women (266/358) received their results, and 86% (43/50) of HIV-positive women and 74% (37/50) of newborns were documented to have received nevirapine. In all three audits over 90% of women initiating antenatal care at the hospital were tested for HIV, while women who initiated care at district community clinics were less likely to receive testing. CONCLUSIONS: Ongoing audit has been important for targeting obstacles to detection of HIV-infected women and documented nevirapine uptake by women and infants. Rates of HIV testing and nevirapine use have increased significantly. Voluntary counselling and testing for HIV and use of nevirapine are acceptable to pregnant women in our setting. Roll-out of the pilot programme to district community clinics is essential for further improvement.

Anti-HIV Agents↗
PubMed2003

[Fluorescence cystoscopy using 5-aminolevulinic acid].

BACKGROUND: Fluorescence diagnosis has an increasing importance in different medical fields. In the presented paper, comparison of cystoscopy in white light with fluorescence cystoscopy after intravesical administration of 1 g of 5-aminolevulinic acid is presented. METHODS AND RESULTS: From the group of 63 persons examined, no difference between findings in white and blue light was found in 39 cases. In 21 patients more pathological spots were found in blue light (10 cases) or, in agreement with histology, pathology was detected in the blue light only (11 cases). CONCLUSIONS: The intravesical administration of 5-aminolevulinic acid had no side effects. Our study has definitely proved the advantages of fluorescence cystoscopy.

Administration, Intravesical↗
PubMed2002

[Lumbar meningeal enhancement after surgery in the posterior cranial fossa: a normal finding in children?].

PURPOSE: Spinal meningeal Gd-DTPA enhancement after cranial surgery is a known observation of a not well understood underlying mechanism. This paper demonstrates that this MRI finding is a normal meningeal reaction to subarachnoid hemorrhage, which should not be mistaken for metastatic spread. MATERIAL AND METHODS: Three pediatric patients were examined by MRI for metastatic spread of malignant infratentorial tumors along the spinal canal two to nine days after the removal of the primary cerebral lesion. The findings were compared with a control group that underwent cranial surgery (cyst resection or fenestration of the posterior cranial fossa) without major bleeding into the subarachnoid space. Unenhanced and enhanced sequences were obtained to prove that the high signal within the CSF is caused by an abnormal Gd-DTPA uptake and not by methemoglobin. RESULTS: Meningeal enhancement was observed in all patients with intraoperative bleeding resembling subarachnoid masses on enhanced T 1 -weighted images. This was not present in any patient of the control group. This finding lasts for approximately two weeks. CONCLUSION: The meningeal enhancement renders immediate postoperative studies inconclusive for the detection of metastatic spread. Consequently, the obligatory tumor staging along the spinal canal should ideally be done prior to the resection of a cerebral tumor.

Astrocytoma↗
PubMed2001

The enigma of the old poet: did the child Wienke in Theodor Storm's novella "Der Schimmelreiter" (1888) have phenylketonuria?

We report a probable case of phenylketonuria in a figure from "Der Schimmelreiter", a novella by German author Theodor Storm (1817-1888), published in 1888. The child Wienke, daughter of the story's protagonist, Hauke Haien, displays symptoms of phenylketonuria. Storm's description of this child, its physiognomy, and increasing mental retardation, lead us to believe that Storm in fact described a case of phenylketonuria, a condition not reported until Følling's description in 1934.

Child↗
PubMed2001

Ultrasonographic and clinical appearance of a 22-week-old fetus with Brachmann-de Lange syndrome.

The diagnosis Brachmann-de Lange or Cornelia-de Lange syndrome is based on the characteristic facial appearance and other malformations. Prenatal ultrasonographic diagnosis has been made occasionally usually confirmed by clinical photographs of third trimester fetuses with distinctly recognizable hair anomalies (synophrys, low anterior and posterior hairlines, and hypertrichosis). However, at 22 weeks of gestation, these highly characteristic signs fail to support the clinical diagnosis. We report on pre- and post-natal findings in a 22-week-old female fetus with Brachmann-de Lange syndrome. The facial Gestalt was already characteristic and the associated upper limb malformations (bilateral monodactyly and ulnar agenesis) supported the diagnosis. The prenatal ultrasound images demonstrated a grossly abnormal facial profile (a protruding and overhanging upper lip and severe retrognathia) highly suggestive of Brachmann-de Lange syndrome. The recurrence risk is estimated &#1%. The recognition of Brachmann-de Lange syndrome in second trimester fetuses is essential for genetic counselling and reassurance of parents contemplating future reproduction.

Adult↗
PubMed2001

Mesomelic campomelia, polydactyly and Dandy-Walker cyst in siblings.

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib-polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy-Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations.

Abnormalities, Multiple↗
PubMed2001

The large increase in incidence of Type I diabetes mellitus in Poland.

AIMS/HYPOTHESIS: A rising incidence of Type I (insulin-dependent) diabetes mellitus in different countries in Europe during the last decade has been recently reported. However, in the early 1990s, Poland was reported to have a stable low incidence of this disease. This study aimed to estimate the annual incidence of Type I diabetes in a north-eastern region of Poland (Białystok region) and investigate if it is associated with age, sex, urban rural differences and the season of disease onset. METHODS: A register of patients with Type I diabetes using two independent sets of data sources was established in 1994 as part of the EURODIAB TIGER programme. The primary data sources were paediatric and internal medicine divisions of the hospitals in the Białystok province and the secondary were outpatient diabetic clinics in the region. The degree of ascertainment was 98.5 % for the combinated data sources. RESULTS: We found a significant rising trend in the incidence of Type I diabetes in children under 15 years of age (in 1998 the incidence was approximately twice as high as in 1994). Increasing incidence rates were observed in the rural areas but not in urban populations. Seasonal variation in the incidence was also found, with a peak in winter and nadir in summer. CONCLUSIONS/INTERPRETATION: These results show that the north-eastern region of Poland is an area with a moderate rather than a low risk of Type I diabetes. Our observations confirm the important role of environmental and socio-economic factors or both in the pathogenesis of Type I diabetes.

Adolescent↗
PubMed2001

MR imaging of the knee in marathon runners before and after competition.

OBJECTIVE: To evaluate the findings in MRI-studies of the knee in recreational long-distance runners after competition and to assess the reversibility of the findings. DESIGN AND PATIENTS: Eight recreational long-distance runners underwent MRI studies of the knee before, immediately after and 6-8 weeks after taking part in the Vienna City Marathon. The studies were evaluated regarding alterations of pre-existing lesions and new pathological findings. RESULTS: In six runners without major pre-existing alterations no negative effects were experienced. In one runner with pre-existing grade III alterations of the menisci, signs of progressive osteoarthritis were experienced 2 months after the competition. In all other cases increased meniscal signal alterations and minor signal changes in the bone marrow after the race were transitory. CONCLUSION: In healthy individuals no negative long-term-effects were experienced. Pre-existing high-grade lesions of the menisci might be a predisposing risk for osteoarthritis, triggered by the stress of long-distance running.

Adult↗