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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 109 records · Page 6Linked to original sources
PubMed1998

Reduced penetrance, variable expressivity, and genetic heterogeneity of familial atrial septal defects.

BACKGROUND: Secundum atrial septal defect (ASD) is a common congenital heart malformation that occurs as an isolated anomaly in 10% of individuals with congenital heart disease. Although some embryological pathways have been elucidated, the molecular etiologies of ASD are not fully understood. Most cases of ASD are isolated, but some individuals with ASD have a family history of this defect or other congenital heart malformations. METHODS AND RESULTS: Clinical evaluation of three families identified individuals with ASD in multiple generations. ASD was transmitted as an autosomal dominant trait in each family. ASD was the most common anomaly, but other heart defects occurred alone or in association with ASD in individuals from each kindred. Genome-wide linkage studies in one kindred localized a familial ASD disease gene to chromosome 5p (multipoint LOD score=3.6, theta=0.0). Assessment of 20 family members with the disease haplotype revealed that 9 had ASD, 8 were clinically unaffected, and 3 had other cardiac defects (aortic stenosis, atrial septal aneurysm, and persistent left superior vena cava). Familial ASD did not map to chromosome 5p in two other families. CONCLUSIONS: Familial ASD is a genetically heterogeneous disorder; one disease gene maps to chromosome 5p. Recognition of the heritable basis of familial ASD is complicated by low disease penetrance and variable expressivity. Identification of ASD or other congenital heart defects in more than one family member should prompt clinical evaluation of all relatives.

Adult↗
PubMed1998

[Smoking behavior of pregnant patients and mothers with young children].

The aim of the study is to analyse the smoking behaviour of pregnant women and mothers with young children and to identify sociodemographic factors for the nicotine consumption of these persons. Data basis are the national and regional health examination surveys of the German Cardiovascular Prevention Study (GCP). Included were 8385 females in the age group 25-40 years. 326 (3.9%) of these females were pregnant at the time of the survey, and 2538 (30.3%) were mothers with one or more children, aged up to 5 years. Smoking behaviour, family status, number and age of the children and other sociodemographic variables were determined with a self-administered standardised questionnaire. Altogether, 39.4% of the 8385 females reported that they were current smokers. The prevalence of smoking for females without young children was slightly higher (42.3%). 20.6% of all pregnant females were current smokers. For mothers in the lowest social class, the smoking prevalence was two times higher compared to mothers in the highest social class. Unmarried and divorced mothers yielded a very high smoking prevalence. These results suggest that there is a need for prevention and health promotion programs for pregnant females and young mothers. Special emphasis should be targetted at unmarried young mothers and mothers from socially disadvantaged population groups.

Adult↗
PubMed1998

Indirect MR arthrography: techniques and applications.

Indirect MR arthrography is a relatively new MR technique improving articular and periarticular contrast. It is achieved by injection of paramagnetic MR contrast media intravenously instead of intra-articular injection as in direct MR arthrography. After the injection exercising the joint results in considerable signal intensity increase within the joint cavity. Fat saturated MR sequences then yield arthrographic images. The method is less invasive than direct MR arthrography and first results showed comparable sensitivities and specificities for rotator cuff and glenoid labrum pathology. In this article the technique, established and potential future indications, drawbacks and limitations of the method are reviewed.

Contrast Media↗
PubMed1998

Estimation of outward currents in isolated human atrial myocytes using inactivation time course analysis.

The aim was to investigate outward currents in single, isolated, human, atrial myocytes and to determine the relative contribution of individual current components to the total outward current. Currents were recorded using the whole-cell patch-clamp technique at 36-37 degreesC. Individual outward current components were estimated from recordings of total outward current using a mathematical procedure based on the inactivation time course of the respective currents. This method allows estimation of outward currents without the use of drugs or conditioning voltage-clamp protocols to suppress individual current components. A rapidly activating and partially inactivating total outward current was recorded when myocytes were voltage clamped at potentials positive to -20 mV (peak current density 24. 0+/-0.97 pA/pF at +40 mV; n=107 cells, 33 patients). This total outward current comprised three overlapping currents: a rapidly inactivating, transient, outward current (Ito1) a slowly and partially inactivating current (ultrarapid delayed rectifier, IKur) and a third current component which most probably reflects a non selective cation current (not characterized). The average current densities at +40 mV were 8.92+/-0.44 pA/pF for Ito1 and 15.1+/-0.72 pA/pF for IKur (n=107 cells). Recovery from inactivation was bi-exponential for both currents and was faster for Ito1. A slowly activating delayed rectifier current (IK) was not found. The current densities of peak Ito1 and IKur varied strongly between individual myocytes, even in those from the same patient. The ratio IKur/Ito1 was 0.5-6.9 with a mean of 1.98+/-0.11 (n=107 cells), suggesting that IKur is the main repolarizing current. The amplitudes of the total outward current, Ito1 and IKur, and the ratio of the latter two were independent of patient age (16-87 years).

Adolescent↗
PubMed1998

L-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot.

OBJECTIVE: The aim was to investigate the electrophysiological properties of the L-type calcium current (ICa,L) in ventricular myocytes at a physiological temperature (36-37 degrees C) isolated from children undergoing surgical repair of tetralogy of Fallot. METHODS: ICa,L was recorded with the patch-clamp technique in the single electrode whose-cell mode at a physiological calcium concentration (1.8 mmol/l) at 36-37 degrees C. RESULTS: Under these conditions, maximum current density averaged -5.80 +/- 0.45 pA/pF. ICa,L showed a bell-shaped current-voltage relationship: the current activated at -37.7 +/- 1.36 mV, peaked at +9.41 +/- 1.60 mV and reversed at +57.7 +/- 2.12 mV (n = 17). At +10 mV, time to peak of ICa,L was 5.23 +/- 0.46 ms. Membrane potentials for half-maximal steady-state activation and inactivation of ICa,L were -6.02 and -20.4 mV, respectively, the slope factors were 7.16 mV for steady-state activation and 6.49 mV for steady-state inactivation. ICa,L did not completely inactivate and showed a big window current between -45 and +40 mV. The inactivation of ICa,L showed a biexponential time course with a fast time constant ranging from 9.11 to 12.9 ms and a slow time constant ranging from 60.9 to 220 ms between -30 and +30 mV. Only the slow time constant showed a pronounced voltage dependency. The recovery from inactivation of ICa,L was biphasic with a fast time constant of 60.7 ms and a slow time constant of 619 ms. beta-Adrenergic stimulation with isoprenaline (1 mumol/l) increased the ICa,L density from -5.71 +/- 1.55 to -13.8 +/- 1.96 pA/pF (142%; P < 0.05) at +10 mV. CONCLUSIONS: The present study demonstrates that most of the electrophysiological properties of ICa,L in ventricular myocytes isolated from children with tetralogy of Fallot resemble those of adult ventricular cells. The existence of a big calcium window current could be involved in the occurrence of early afterdepolarizations which could lead to the high incidence of arrhythmias after surgical repair of tetralogy of Fallot.

Adrenergic beta-Agonists↗
PubMed1998

Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study.

Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.

3-Iodobenzylguanidine↗
PubMed1998

Isolation and transplantation of autologous peripheral CD34+ progenitor cells highly purified by magnetic-activated cell sorting.

Peripheral stem cells were mobilized and collected in 26 pediatric patients with malignant diseases. A total of 47 leukaphereses were performed in the 26 patients. The mean number of nucleated cells collected was 4.5 +/- 2.6 x 10(8)/kg and the number of CD34+ progenitors collected was 6.7 +/- 6.8 x 10(6)/kg. CD34-positive selection was performed using a two-step method of magnetic-activated cell sorting (MACS) in 24 patients or a combination of an immunoaffinity column and MACS in two patients. The purity of the positively selected CD34+ progenitors was 98.8 +/- 0.7% and the number of isolated CD34+ cells was 6.5 +/- 5.9 x 10(6)/kg. Thus, the mean recovery of CD34+ cells was 93 +/- 10%. In 22 of the 26 patients, high-dose chemotherapy was performed with subsequent reinfusion of the highly purified CD34+ cells. In all 22 patients, a normal hematopoietic reconstitution was seen with a mean time of 12.4 +/- 2.7 days to reach >0.5 x 10(9)/l neutrophils (range 8-19 days). The time to reach independence from platelet transfusion was 31.6 +/- 17.0 days (range 16-78 days). There were no transplant-related deaths. In summary, we have shown that mobilized peripheral CD34+ progenitors can be highly purified with a good recovery, and that reinfusion of these cells after high-dose chemotherapy results in a rapid, complete and sustained engraftment. We conclude that this method can be used for purging in any CD34-negative malignancies and for autologous T and B cell depletion in the treatment of autoimmune diseases with high-dose immunoablative therapy.

Adolescent↗
PubMed1998

Neuroretinal rim width ratios in morphological glaucoma diagnosis.

AIMS: To evaluate the inferior to temporal neuroretinal rim width ratio and superior to temporal rim width ratio as measures of rim shape for diagnosis of glaucoma. METHODS: Colour stereo optic disc photographs of 527 normal subjects, 100 ocular hypertensive individuals with normal visual fields, and 202 open angle glaucoma patients with a mean perimetric defect of less than 10 dB were morphometrically evaluated. Eyes with an optic cup area of < 0.2 mm2 were excluded. RESULTS: In the normal subjects, inferior to temporal rim width ratio (1.67 (SD 0.53)) was significantly (p < 0.0001) higher than superior to temporal rim width ratio (1.56 (0.49)). Both ratios were significantly (p < 0.0001) higher the more vertically the optic disc was configured. In the normal eyes, both ratios were statistically independent of disc size, rim area, refractive error, age, and sex. With the differences being more marked for the inferior to temporal ratio than for the superior to temporal ratio, both rim width ratios were significantly (p < 0.005) lower in the ocular hypertensive group than in the normal group. Despite the high significance of the differences, diagnostic power of the inferior ratio and the superior ratio was 59% and 58%, respectively, indicating a marked overlap between the groups. CONCLUSIONS: Abnormally low inferior to temporal and superior to temporal rim width ratios can indicate glaucomatous optic nerve damage in some ocular hypertensive eyes. Being independent of optic disc size and ocular magnification, the rim width ratios may be taken as one among other variables for the ophthalmoscopic optic disc evaluation, taking into account, however, a pronounced overlap between normal eyes and ocular hypertensive eyes.

Adolescent↗
PubMed1998

Optic disc morphology in pigmentary glaucoma.

AIM: To evaluate the morphology of the optic nerve head in eyes with pigmentary glaucoma. METHODS: Colour stereo optic disc photographs of 62 patients with pigmentary glaucoma and 566 patients with primary open angle glaucoma were morphometrically evaluated. By prestudy selection, mean visual field defect and neuroretinal rim area were not significantly different between the two groups (p = 0.89 and p = 0.45). RESULTS: The pigmentary glaucoma group did not vary significantly (p > 0.10) from the primary open angle glaucoma group in size and shape of the optic disc, configuration of neuroretinal rim, depth of optic cup, area of alpha zone of parapapillary atrophy, diameter of retinal vessels at the disc border, and frequency of disc haemorrhages and localised retinal nerve fibre layer defects. The beta zone of parapapillary atrophy was slightly, but not statistically significantly (p = 0.06), smaller in the pigmentary glaucoma group. The mean maximal intraocular pressure and mean intraocular pressure amplitude were significantly (p < 0.001) higher in the pigmentary glaucoma group. CONCLUSIONS: In contrast with the characteristic morphology of the anterior segment and despite significantly higher intraocular pressure peaks and a larger pressure amplitude, eyes with pigmentary glaucoma compared with eyes with primary open angle glaucoma do not show a pathognomonic morphology of the optic disc and retinal nerve fibre layer. The slightly smaller beta zone of parapapillary atrophy may correspond to higher intraocular pressure in pigmentary glaucoma.

Adult↗
PubMed1998

Osteogenic sarcoma: noninvasive in vivo assessment of tumor necrosis with diffusion-weighted MR imaging.

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for detecting tumor necrosis in an animal model of osteogenic sarcoma. MATERIALS AND METHODS: Twelve rats with osteogenic sarcoma underwent T1-weighted unenhanced and gadolinium-enhanced spin-echo and diffusion-weighted spin-echo MR imaging. Histologic correlation was performed. Signal intensities, T2 relaxation times, normalized apparent diffusion coefficients, and relative signal intensity increases were calculated. RESULTS: On diffusion-weighted images, necrotic tumor showed low signal intensity (mean normalized apparent diffusion coefficient, 0.46 +/- 0.20 [1 standard deviation]), indicating rapid diffusion of water molecules as a result of loss of membrane integrity, while viable tumor showed high signal intensity (mean normalized apparent diffusion coefficient, 0.16 +/- 0.05; P < .0001). Differences in the T2 relaxation times and relative signal intensity increases between viable and necrotic tumor were not statistically significant. CONCLUSION: Normalized apparent diffusion coefficients are more accurate in differentiating between viable and necrotic tumor than are T2 relaxation times or relative signal intensity increases on contrast-enhanced images. Signal intensity overlap between viable and necrotic tumor on gadolinium-enhanced images may be caused by the small molecular size of the agent, which permeates the interstitial space freely, thereby also enhancing necrosis. Diffusion-weighted MR imaging depicts differences in diffusion and, ultimately, in membrane integrity between viable and necrotic tumor and may be used to monitor tumor viability during treatment.

Animals↗
PubMed1998

Advances in MR imaging of pediatric musculoskeletal neoplasms.

MR imaging has evolved as the most important diagnostic test for local staging of primary bone and soft tissue tumors, for monitoring response to chemotherapy, and for detecting postoperative tumor recurrence. MR imaging provides accurate preoperative staging of local tumor extent and helps to obtain adequate safety margins, prerequisites for successful limb-salvage surgery. Postcontrast MR imaging studies are helpful for evaluating the presence or absence of tumor necrosis during chemotherapy. Dynamic MR imaging after intravenous bolus administration of Gd-DTPA or other paramagnetic contrast media is particularly useful for assessing response to chemotherapy. Diffusion-weighted MR imaging is a new technique that is potentially capable of detecting and quantitating the amount of tumor necrosis after chemotherapy or radiation therapy.

Adolescent↗
PubMed1998

Magnetic resonance imaging of knee cartilage repair.

Cartilage injury resulting in osteoarthritis is a frequent cause of disability in young people. Osteoarthritis, based on either cartilage injury or degeneration, is a leading cause of disability in the United States. Over the last several decades, much progress has been made in understanding cartilage injury and repair. Magnetic resonance (MR) imaging, with its unique ability to noninvasively image and characterize soft tissue, has shown promise in assessment of cartilage integrity. In addition to standard MR imaging methods, MR imaging contrast mechanisms under development may reveal detailed information regarding the physiology and morphology of cartilage. MR imaging will play a crucial role in assessing the success or failure of therapies for cartilage injury and degeneration.

Cartilage, Articular↗
PubMed1997

Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts.

BACKGROUND: Basiliximab is an interleukin-2 receptor (IL-2R; CD25) chimeric monoclonal antibody for immunoprophylaxis against acute rejection in renal transplantation. Its pharmacokinetics were characterized in a multicenter open-label, prospective dose-escalation study to identify a single-dose regimen providing IL-2R-saturating serum concentrations in the critical first posttransplant month. METHODS: Thirty-two recipients of primary, mismatched cadaver kidneys were enrolled: 20 men and 12 women, who were 47+/-11 years old and weighed 65+/-12 kg. The immunosuppression regimen consisted of steroids and azathioprine from day 0 and cyclosporine from day 10. Basiliximab was infused over 30 min as a single dose preoperatively. RESULTS: Thirty patients were evaluable for basiliximab pharmacokinetics: 24 received 40 mg and 6 received 60 mg. Basiliximab was well tolerated without evidence of cytokine-release syndrome, hypersensitivity reactions, or anti-idiotype antibody response. Peak concentration and area under the concentration curve increased proportionally with dose. Postinfusion concentrations declined in a biphasic manner with a terminal half-life of 6.5+/-2.1 days. Weak, widely dispersed correlations were noted between body weight versus distribution volume (r=0.29) and versus clearance (r=0.45), suggesting no clinical relevance for weight-adjusted dosing. There were no apparent gender-related differences in basiliximab disposition. Previous phase II data indicated that serum concentrations in excess of 0.2 microg/ml are sufficient to saturate IL-2R epitopes on circulating T lymphocytes. Concentrations were above this threshold for 26+/-8 days (range 16 to 46) at the 40-mg dose level and for 32+/-11 days (range 22 to 51) at the 60-mg dose level. CONCLUSIONS: Total basiliximab doses of 40-60 mg were well tolerated, nonimmunogenic, and estimated to provide immunoprophylaxis to cover the first posttransplant month.

Adult↗
PubMed1997

Cytotoxic T lymphocyte changes after HLA-DR match and HLA-DR mismatch blood transfusions.

In the present study, we analyzed transfusion-induced cytolytic T lymphocyte (CTL) changes in patients who received either a one-HLA-DR-match or a zero-HLA-DR-match pretransplant blood transfusion. Twenty-four nonimmunized naive patients awaiting kidney transplantation received one planned, HLA-typed blood transfusion. The frequencies of CTL precursors (CTLp) directed against blood donor cells and controls were evaluated before and sequentially at days 7, 28, and 60 after transfusion. Results showed that sharing one HLA-DR between donor and recipient did not prevent CTL sensitization. Indeed, (1) An increase of donor-specific CTLp frequencies was observed in 8 of 11 patients who received a zero HLA-DR match (71%), as well as in 9 of 13 patients who received a one-HLA-DR-match (69%) transfusion. (2) This increase occurred with similar kinetics in the two groups, as it was highly significant 7 days after transfusion (P=0.002 and P=0.0035 in the first and second groups, respectively) but transient; CTLp frequencies returned to pretransfusion levels by day 60 after transfusion in both groups. (3) Finally, the magnitude of this increase was similar in the DR-match and DR-mismatch groups. Thus, if it is confirmed, in clinical practice, that one DR match between the blood donor and the patient would improve the tolerance effect of pretransplant blood transfusion, this phenomenon is unlikely to be related to the prevention of CTL sensitization.

Blood Donors↗