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Biomedical subjects

Georg Heinze

Publications and source records attributed to Georg Heinze.

17 recordsLinked to original sources
PubMed2003

Heterogeneous perfusion is a consequence of uniform shear stress in optimized arterial tree models.

Using optimized computer models of arterial trees we demonstrate that flow heterogeneity is a necessary consequence of a uniform shear stress distribution. Model trees are generated and optimized under different modes of boundary conditions. In one mode flow is delivered to the tissue as homogeneously as possible. Although this primary goal can be achieved, resulting shear stresses between blood and the vessel walls show very large spread. In a second mode, models are optimized under the condition of uniform shear stress in all segments which in turn renders flow distribution heterogeneous. Both homogeneous perfusion and uniform shear stress are desirable goals in real arterial trees but each of these goals can only be approached at the expense of the other. While the present paper refers only to optimized models, we assume that this dual relation between the heterogeneities in flow and shear stress may represent a more general principle of vascular systems.

Arteries↗
PubMed2003

Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage.

OBJECTIVE: To identify associations or interrelations between carriage of the methylenetetrahydrofolate reductase (MTHFR) C677T, the MTHFR A1298C, the factor V Leiden G1691A, the factor II prothrombin G20210A, the human platelet antigen (HPA) 1 C12548T, and the apolipoprotein (APO) B R3500Q polymorphisms and idiopathic recurrent miscarriage (IRM). DESIGN: Prospective case control study. SETTING: Academic research institution. PATIENT(S): One hundred forty-five women with a history of three or more consecutive pregnancy losses before 20 weeks gestation and 101 healthy postmenopausal women with at least two live births and no history of pregnancy loss. INTERVENTION(S): Peripheral venous punctures. MAIN OUTCOME MEASURE(S): Multiplex polymerase chain reaction was performed to identify the different alleles of six candidate genetic risk factors for IRM (MTHFR C677T, MTHFR A1298C, factor V Leiden G1691A, factor II prothrombin G20210A, HPA 1 C12548T, and the APO B R3500Q). RESULT(S): Allele and genotype frequencies of all polymorphisms were not significantly different between the study and the control groups. Also, no significant associations occurred between combinations of polymorphisms and the occurrence of IRM. CONCLUSION(S): Our data fall short of showing any significant association between single polymorphisms of the MTHFR, the Factor V Leiden, the Factor II Prothrombin, the HPA 1 and APO B genes or combinations of these polymorphisms and the occurrence of IRM.

Abortion, Habitual↗
PubMed2003

Comparing the importance of prognostic factors in Cox and logistic regression using SAS.

Two SAS macro programs are presented that evaluate the relative importance of prognostic factors in the proportional hazards regression model and in the logistic regression model. The importance of a prognostic factor is quantified by the proportion of variation in the outcome attributable to this factor. For proportional hazards regression, the program %RELIMPCR uses the recently proposed measure V to calculate the proportion of explained variation (PEV). For the logistic model, the R(2) measure based on squared raw residuals is used by the program %RELIMPLR. Both programs are able to compute marginal and partial PEV, to compare PEVs of factors, of groups of factors, and even to compare PEVs of different models. The programs use a bootstrap resampling scheme to test differences of the PEVs of different factors. Confidence limits for P-values are provided. The programs further allow to base the computation of PEV on models with shrinked or bias-corrected parameter estimates. The SAS macros are freely available at www.akh-wien.ac.at/imc/biometrie/relimp

Data Interpretation, Statistical↗
PubMed2003

Fixing the nonconvergence bug in logistic regression with SPLUS and SAS.

When analyzing clinical data with binary outcomes, the parameter estimates and consequently the odds ratio estimates of a logistic model sometimes do not converge to finite values. This phenomenon is due to special conditions in a data set and known as 'separation'. Statistical software packages for logistic regression using the maximum likelihood method cannot appropriately deal with this problem. A new procedure to solve the problem has been proposed by Heinze and Schemper (Stat. Med. 21 (2002) pp. 2409-3419). It has been shown that unlike the standard maximum likelihood method, this method always leads to finite parameter estimates. We developed a SAS macro and an SPLUS library to make this method available from within one of these widely used statistical software packages. Our programs are also capable of performing interval estimation based on profile penalized log likelihood (PPL) and of plotting the PPL function as was suggested by Heinze and Schemper (Stat. Med. 21 (2002) pp. 2409-3419).

Likelihood Functions↗
PubMed2003

Flow monitoring: performance characteristics of ultrasound dilution versus color Doppler ultrasound compared with fistulography.

BACKGROUND: Measurement of access blood flow is the preferred noninvasive screening test for hemodialysis arteriovenous (AV) fistula stenosis. However, performance characteristics of the 2 most frequently used ultrasound techniques compared with fistulography remain elusive. METHODS: We evaluated 59 hemodialysis patients with native forearm AV fistulae who underwent all 3 measurements in a prospective order: the ultrasound dilution technique (UDT), color Doppler ultrasonography (CDUS), and fistulography. Patients with angiographically diagnosed access stenosis underwent angioplasty and were followed up by means of monthly UDT measurements until restenosis occurred within the first 6 months. RESULTS: Both ultrasound techniques predicted access stenosis (P < 0.01). Performance was similar between both techniques, evaluated by receiver operating characteristic curves. Areas under the curve averaged 0.79 (95% confidence interval [CI], 0.66 to 0.91) for UDT and 0.80 (95% CI, 0.65 to 0.94) for CDUS. Correlation between measured UDT and CDUS blood flow rates was 0.37 (Spearman's rho, rho = 0.004). The calculated optimal cutoff value for the prediction of stenosis was 465 mL/min for the UDT and 390 mL/min for the CDUS technique. Access stenosis was diagnosed in 41 patients who subsequently underwent percutaneous angioplasty (PTA), which was successful in 34 patients. Restenosis occurred in 13 patients within the first 6 months after PTA. UDT access blood flow after PTA was significantly lower in these 13 patients compared with the other 21 patients. CONCLUSION: Our data suggest that blood flow monitoring of AV hemodialysis access by ultrasound provides a reasonable prediction of access stenosis and restenosis.

Adult↗
PubMed2003

Pathogenesis of bone loss in heart transplant candidates and recipients.

BACKGROUND: Heart transplantation (HTX) is associated with decreased bone mineral density and changes in bone metabolism. We conducted this study to evaluate the pathophysiology of bone metabolism in HTX candidates and recipients. METHODS: Thirty-six HTX recipients were compared with 36 HTX candidates concerning biochemical parameters of bone metabolism and bone mineral density. RESULTS: Osteocalcin, bone-specific alkaline phosphatase, cross-linked-N-telopeptide of type I collagen, estradiol, serum creatinine, and blood urea nitrogen concentrations were significantly higher, whereas the calcium-creatinine ratio, thyrotropin, thyroxine, and bone mineral density were significantly lower in HTX recipients than in HTX candidates. Compared with a control group, HTX candidates had decreased renal function and increased bone resorption, whereas HTX recipients additionally had increased alkaline phosphatase and osteocalcin levels. In HTX recipients, we found positive correlations between creatinine clearance and bone mineral density; daily and cumulative cortisone doses were not associated with bone mineral density. CONCLUSIONS: In HTX candidates, disturbances in bone metabolism with increased bone resorption may be caused partly by existing low-grade renal insufficiency, regular intake of loop diuretics, and restriction of mobility. In HTX recipients, immunosuppressive therapy-glucocorticoids and cyclosporine-seem to be responsible for changes in bone metabolism.

Adult↗
PubMed2003

Influence on fetal blood pH when adding amniotic fluid: an in vitro model.

OBJECTIVE: To assess the effect of contamination with amniotic fluid in different quantities on fetal capillary blood pH. DESIGN: In vitro model. SETTING: Department of Obstetrics, St Pölten Hospital. SAMPLE: Venous umbilical blood and amniotic fluid from 35 women who underwent amniotomy during labour. METHODS: Venous umbilical blood was mixed in vitro with amniotic fluid in diluted series (venous umbilical blood/amniotic fluid, 10:1 to 1:1). In every case two parallel runs of the dilution series in an inverted fashion were performed to rule out a possible time-dependent bias of the pH measurements. MAIN OUTCOME MEASURES: pH change in dilutions of umbilical venous blood with amniotic fluid: 10:1, +0.07 (0.02); 8:1, +0.08 (0.02); 6:1, +0.08 (0.03); 4:1, +0.07 (0.02); 2:1, +0.09 (0.03); 1:1, +0.12 (0.05); all P < 0.001. RESULTS: Amniotic fluid pH increases, whereas umbilical blood pH decreases slightly over time since collection. Dilutions of umbilical venous blood with amniotic fluid resulted in a significant pH rise. There was no significant difference between the two inversely performed dilution series. CONCLUSION: Amniotic fluid influences in vitro fetal venous blood pH immediately after contact. This observation indicates the possible masking of a fetus in distress by fetal scalp blood pH determination when amniotic fluid contaminates the sample.

Adult↗
PubMed2003

Microbial invasion of the amniotic cavity at birth is associated with adverse short-term outcome of preterm infants.

AIMS: To determine the frequency and clinical significance of microbial invasion of the amniotic cavity at the time of delivery in preterm infants. METHODS: Prospective cohort study during June 2001 and January 2002. Preterm infants < 33 + 6 weeks of gestation who had amniotic fluid and placental tissue sampled for culture during cesarean section were included. RESULTS: Of a total of 80 neonates, 42 had negative culture results, 22 had growth of Ureaplasma urealyticum, and 16 had growth of other pathogens. Isolation of Ureaplasma urealyticum was associated with a decreased risk of developing hyaline membrane disease after birth but a more than 20 times increased risk of developing chronic lung disease. Patients with growth of other pathogens had a significantly higher mortality than patients with negative culture results. CONCLUSIONS: Isolation of miroorganisms from the amniotic cavity at birth is associated with an adverse outcome of the preterm infant. In the light of extremely small numbers of positive blood cultures in preterm infants after birth, we consider it reasonable to recommend routine culturing of amniotic cavity tissues/fluid obtained during cesarean section in order to increase the identification rate of pathogens potentially involved in the pathogenesis of perinatal infections.

Chorioamnionitis↗
PubMed2002

A solution to the problem of separation in logistic regression.

The phenomenon of separation or monotone likelihood is observed in the fitting process of a logistic model if the likelihood converges while at least one parameter estimate diverges to +/- infinity. Separation primarily occurs in small samples with several unbalanced and highly predictive risk factors. A procedure by Firth originally developed to reduce the bias of maximum likelihood estimates is shown to provide an ideal solution to separation. It produces finite parameter estimates by means of penalized maximum likelihood estimation. Corresponding Wald tests and confidence intervals are available but it is shown that penalized likelihood ratio tests and profile penalized likelihood confidence intervals are often preferable. The clear advantage of the procedure over previous options of analysis is impressively demonstrated by the statistical analysis of two cancer studies.

Breast Neoplasms↗
PubMed2002

Systemic effects of low-intensity laser irradiation on skin microcirculation in patients with diabetic microangiopathy.

Low-intensity laser irradiation has been shown to induce wound healing in conditions of reduced microcirculation, which is in part explained by systemic effects. We therefore investigated such a potential systemic effect of low-intensity laser irradiation on skin blood circulation in patients with diabetic microangiopathy. Patients with diabetic microangiopathy were randomized to receive either a single helium-neon (HeNe, 632.8 nm) low-intensity laser irradiation with a dose of 30 J/cm(2) or a sham irradiation over the forefoot region in a double-blind, placebo-controlled clinical study. Skin blood circulation by means of temperature recordings over forefoot regions was detected by infrared thermography. Following a single transcutaneous low-intensity laser irradiation, a rise in skin temperature in both feet of the subjects in the laser group was noted, whereas in both feet of the subjects in the placebo group a drop in skin temperature occurred. The baseline-adjusted skin temperature 15 min after the end of the irradiation was significantly higher in the laser-treated forefeet compared to the placebo-"treated" forefeet (p < 0.0001); the baseline-adjusted difference in the temperature was 1.94 +/- 0.35 degrees C. Simultaneously, the baseline-adjusted skin temperature was significantly higher in the laser-untreated forefeet compared to the placebo-"untreated" forefeet (P < 0.0001); the baseline-adjusted difference was 1.70 +/- 0.33 degrees C. Our data show a significant increase in skin circulation due to athermic laser irradiation in patients with diabetic microangiopathy and point to the possibility of inducing systemic effects.

Adult↗
PubMed2002

SAS and SPLUS programs to perform Cox regression without convergence problems.

When analyzing survival data, the parameter estimates and consequently the relative risk estimates of a Cox model sometimes do not converge to finite values. This phenomenon is due to special conditions in a data set and is known as 'monotone likelihood'. Statistical software packages for Cox regression using the maximum likelihood method cannot appropriately deal with this problem. A new procedure to solve the problem has been proposed by G. Heinze, M. Schemper, A solution to the problem of monotone likelihood in Cox regression, Biometrics 57 (2001). It has been shown that unlike the standard maximum likelihood method, this method always leads to finite parameter estimates. We developed a SAS macro and an SPLUS library to make this method available from within one of these widely used statistical software packages. Our programs are also capable of performing interval estimation based on profile penalized log likelihood (PPL) and of plotting the PPL function as was suggested by G. Heinze, M. Schemper, A solution to the problem of monotone likelihood in Cox regression, Biometrics 57 (2001).

Proportional Hazards Models↗
PubMed2002

Uveal and capsular biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses.

PURPOSE: To evaluate the long-term response of 6 types of 3-piece intraocular lenses (IOLs) by assessing the cellular reaction on the anterior IOL surface, the behavior of posterior and anterior capsule fibrosis, and flare. SETTING: Department of Ophthalmology, Medical School, University of Vienna, Vienna, Austria. METHODS: One hundred eighty eyes were prospectively randomized to receive 1 of 6 IOLs: hydrophilic acrylic Hydroview (Bausch & Lomb) or MemoryLens (ORC); hydrophobic acrylic AcrySof MA60BM (Alcon) or AMO Sensar AR40 (Allergan); hydrophobic silicone CeeOn 920 or CeeOn 911A (Pharmacia). The patients had standardized cataract surgery, postoperative medication, and follow-up. One year after surgery, 155 eyes were assessed. The cellular reaction was evaluated by specular microscopy of the anterior IOL surface. Anterior and posterior capsule opacification (PCO) was assessed semiquantitatively by biomicroscopy. Flare was measured with a Kowa FC-1000 laser flare-cell meter. RESULTS: Regarding uveal biocompatibility, the hydrophobic acrylic IOLs showed the highest incidence of late foreign-body cell reaction (AcrySof, 30%; AR40, 17%) followed by the hydrophilic acrylic (MemoryLens, 8%; Hydroview, 4%) and silicone (CeeOn 920, 4%; CeeOn 911A, 0%) (P =.0044). In all cases, the cellular reaction was low grade and clinically insignificant. Regarding capsular biocompatibility, some eyes developed lens epithelial cell (LEC) outgrowth on the anterior IOL surface. The highest incidence was in the hydrophilic acrylic group (Hydroview, 85%; MemoryLens, 27%) followed by the hydrophobic acrylic (AcrySof, 4%; AR40, 3%). No silicone IOL had LECs on the anterior surface. The difference among IOL groups was significant (P =.0001). Anterior capsule opacification was more predominant in the hydrophobic IOL groups. Posterior capsule opacification of the central 3.0 mm area was lowest in the groups with a sharp-edged optic (CeeOn 911A, AcrySof) followed by the round-edged silicone (CeeOn 920), hydrophobic acrylic (AR40), and hydrophilic acrylic IOLs (P =.0001). There was a significant difference in flare between the AR40 lens and the Hydroview, MemoryLens, CeeOn 911A, and CeeOn 920 (P <.004). There was no statistically significant difference in the postoperative cell count at 1 year. The power calculation showed that the sample size was sufficient. CONCLUSIONS: The differences in cellular reaction, although clinically mild in normal eyes, indicate that there were more giant cells with hydrophobic acrylic IOLs and an increased tendency toward LEC outgrowth with hydrophilic lenses. The incidence of PCO was lowest in the hydrophobic IOL groups, especially in groups with a sharp-edged optic. Second-generation silicone IOLs with a sharp edge had good uveal and capsular biocompatibility 1 year after surgery.

Acrylic Resins↗
PubMed2002

Small carbon monoxide formation in absorbents does not correlate with small carbon dioxide absorption.

UNLABELLED: In this study we sought to determine whether an absorbent in which little carbon monoxide (CO) forms has a correspondingly small capacity to absorb carbon dioxide (CO(2)). Completely dried samples (600 g) of Baralyme (A), Drägersorb 800 (B), Drägersorb 800 Plus (C), Intersorb (D), Spherasorb (E), LoFloSorb (F), Superia (G), and Amsorb (H) were exposed to a flow of 0.5% (A-H; n = 4-5) and 4% isoflurane (F-H; n = 3) in pure oxygen at 5 L/min for 60 min. Downstream CO concentration, temperature, and isoflurane concentration were recorded every 60 s to calculate CO formation and isoflurane loss. The CO(2) absorption capacity of each brand was determined by passing 5.1% CO(2) in oxygen (flow, 250 mL/min) through untreated samples (30 g; n = 5) until the outlet CO(2) concentration reached 0.5%. CO formation was largest in absorbents containing potassium hydroxide (A and B) and negligible in absorbents not containing any alkali hydroxide (F-H). The outlet temperature correlated with CO formation, but the isoflurane loss did not. The duration of CO(2) absorption also did not correlate with CO formation. We conclude that absorbents that allow only very little CO formation are not necessarily poor CO(2) absorbents. IMPLICATIONS: In an in vitro study, carbon dioxide (CO(2)) absorption capacity and possible carbon monoxide (CO) formation were tested in different absorbent brands. Absorbents with very small CO formation are not necessarily poor CO(2) absorbents.

Absorption↗
PubMed2002

Failure of BCL-2 up-regulation in proximal tubular epithelial cells of donor kidney biopsy specimens is associated with apoptosis and delayed graft function.

SUMMARY: In renal transplantation, postischemic acute renal failure (ARF) develops in more than 20% of patients. We investigated whether tubular epithelial cells obtained from donor kidneys without subsequent ARF express a different pattern of survival genes, compared with cells from kidneys exhibiting ARF. Donor kidney biopsy specimens were obtained before transplantation from eight recipients of cadaveric kidneys with primary graft function (CAD-PF), eight patients with biopsy-proven ARF without rejection (CAD-ARF), and eight recipients of living donor kidneys with primary graft function (LIV). One thousand proximal tubular epithelial cells per biopsy specimen were isolated by laser capture microdissection. Quantitative analysis of apoptosis and the apoptosis regulatory genes Bcl-2, Bcl-xL, and Bax were performed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling staining and real-time PCR, respectively. Primary cultures of human proximal tubular epithelial cells served as calibrator. The number of apoptotic cells was significantly higher in CAD-ARF compared with LIV and CAD-PF (1.5 +/- 1.1% [p < 0.05] vs. 0.3 +/- 0.2% vs. 0.4 +/- 0.2%; mean +/- SD). The apoptosis inhibitors Bcl-2 and Bcl-xL were significantly up-regulated in renal tubular cells of recipients without ARF compared with CAD-ARF. The ratios of Bcl-2/GAPDH normalized to calibrator were as follows: LIV 48 +/- 30, CAD-PF 38 +/- 55, and CAD-ARF 5 +/- 7 (p < 0.05). The corresponding ratios for Bcl-xL were as follows: LIV 6 +/- 6, CAD-PF 5 +/- 3, and CAD-ARF 1 +/- 1 (p < 0.05). No difference in the expression of the proapoptotic Bax could be observed. These data suggest that failure of proximal tubular cells to respond to injury by up-regulation of survival factors from the Bcl-2 family contributes to postischemic ARF in patients after cadaveric renal transplantation.

Apoptosis↗
PubMed2002

Chlamydia pneumoniae in carotid artery atherosclerosis: a comparison of its presence in atherosclerotic plaque, healthy vessels, and circulating leukocytes from the same individuals.

BACKGROUND AND PURPOSE: There is growing clinical and experimental evidence that infections with Chlamydia pneumoniae might contribute to the development and progression of atherosclerosis. However, studies detecting the pathogen in atherosclerotic lesions examined either only atherosclerotic vessels or control vessels without atherosclerosis obtained from a different group of individuals. We analyzed atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins, and circulating leukocytes from the same individual patients for the presence of C pneumoniae. METHODS: From each of 46 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis, these samples were analyzed by nested polymerase chain reaction for C pneumoniae-specific DNA. Furthermore, we determined IgA and IgG titers specific for the pathogen and plasma levels of C-reactive protein in these patients. RESULTS: C pneumoniae DNA was detected in 86.9% of the leukocytes and in 82.6% of the atherosclerotic plaques but in only 6.5% of the saphenous veins. In 85% of patients who also had leukocytes positive for C pneumoniae, the atherosclerotic plaques were positive and the saphenous veins were negative. The presence of C pneumoniae-specific DNA in leukocytes significantly coincided with the presence of the respective DNA in the plaques of the carotid arteries (P=0.0002). No association between the presence of C pneumoniae and specific IgA or IgG levels was seen. C-reactive protein levels were significantly higher in patients with chlamydia-positive atherosclerotic plaques and with positive leukocytes than in patients with negative plaques of the carotid arteries or negative leukocytes, respectively (P<0.01, P<0.05). CONCLUSIONS: Our observation of >80% incidence of C pneumoniae in atherosclerotic plaques of the carotid artery does not prove causality between an infection with the pathogen and the development of atherosclerosis. It must be emphasized, however, that >90% of apparently healthy saphenous veins were negative for C pneumoniae. Given the structural and functional differences between veins and arteries, careful interpretation of our results regarding a possible causative role of C pneumoniae seems warranted.

Aged↗