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Biomedical subjects

Peter Lange

Publications and source records attributed to Peter Lange.

At least 37 records · Page 2Linked to original sources

Transfusion-free complex cardiac surgery with cardiopulmonary bypass in a 3.55-kg Jehovah's Witness neonate.

Complex cardiac surgery using cardiopulmonary bypass normally requires the transfusion of autologous blood components, particularly in neonates. This is predominately caused by the relatively high priming volume of the circuit with subsequent extreme hemodilution and the often extended and complex perfusions leading to progressive consumption of platelets and coagulation factors. We report on a strategy to minimize the cardiopulmonary bypass circuit and adjust the perfusion technique that resulted in transfusion-free correction of tetralogy of Fallot with an absent pulmonary valve and an aneurysm of the left pulmonary artery in a 3.55 kg Jehovah's Witness neonate boy.

Aneurysm↗

Tau, phospho-tau, and S-100B in the cerebrospinal fluid of children with multiple sclerosis.

Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins using specific enzyme-linked immunoabsorbent assays. In general, tau, phospho-tau, and S-100B protein levels did not differ significantly between groups. However, in a subgroup of nine children with multiple sclerosis, all of whom had prominent clinical symptoms at the time of lumbar puncture and radiologic disease activity, tau protein levels were significantly elevated when compared with other controls. These data indicate that axonal injury is not restricted to adult multiple sclerosis but can already occur in children with multiple sclerosis.

Adolescent↗

Outdoor activity and performance status as predictors of survival in hypoxaemic chronic obstructive pulmonary disease (COPD).

BACKGROUND: Performance status has been associated with survival in hypoxaemic chronic obstructive pulmonary disease (COPD) patients on long-term oxygen therapy. OBJECTIVE: To determine whether self-reported outdoor activity and performance status are independent predictors of survival in hypoxaemic COPD patients on long-term oxygen therapy. DESIGN, SUBJECTS AND MAIN MEASURE: In a prospective design, survival over an eight-year period was studied in 226 Danish patients on long-term oxygen therapy. They were subdivided according to self-reported mobility (+/-outdoor activity) and World Health Organization (WHO) performance status (score 0-4). RESULTS: A total of 148 patients (65.5%) reported outdoor activity. Compared to the immobile patients, those reporting outdoor activity had higher performance status, higher body mass index and lower duration of oxygen administration. In multivariate analyses adjusting for body mass index, gender and age, both poor performance status and lack of outdoor activity were associated with poor survival (p-levels 0.006 and 0.045, respectively). Lack of outdoor activity was associated with increased mortality (relative risk (RR) and 95% confidence interval of dying was 1.39 (1.01-1.91)) and significantly higher risk was found among those with age in the youngest tertile (less than 66.4 years), the relative risk of dying was 2.18 (1.20-3.95). CONCLUSIONS: This study shows that self-reported performance status and outdoor activity are independent predictors of survival in hypoxaemic COPD patients on long-term oxygen therapy. However, our study suggests that in the most elderly patients, outdoor activity does not predicting survival. Further studies are needed to determine whether interventions that facilitate outdoor activity (e.g., pulmonary rehabilitation) have an effect on survival in this group of patients.

Activities of Daily Living↗

Transfusion-free cardiopulmonary bypass in Jehovah's Witness patients weighing less than 5 kg.

Performing cardiac surgery on pediatric Jehovah's Witness patients is a great challenge for the surgical team and especially for the perfusionist. Jehovah's Witnesses reject blood transfusions on the grounds of their literal interpretation of passages of the Bible. In accordance with this belief, Jehovah's Witnesses feel that it is also forbidden to retransfuse autologous blood that has been separated from their own circulatory system. We report the use of cardiopulmonary bypass (CPB) during open-heart surgery in three infants with a body weight of 4.5 kg, 3.5 kg, and 3.1 kg, respectively, without transfusion of blood components. A small-volume CPB circuit with a priming volume of 200 mL, including the arterial line filter, was designed to decrease the degree of hemodilution. A dedicated pediatric heart lung machine console with remote pump heads and intensive blood conservation efforts allowed the operation without the use of donor blood. The CPB circuits were primed with crystalloid solution only. The procedures were performed in normothermia or in moderate hypothermia. Pre-CPB hemoglobin levels were 10.8 g/dL, 10.6 g/dL, and 8.5 g/dL. The hemoglobin concentrations measured during CPB ranged from 5.9 to 6.5 g/dL, 6.4 to 6.8 g/dL, and 5.5 to 5.9 g/dL, respectively. The patients did not receive any blood or blood products during their entire hospital stay.

Anticoagulants↗

Catheter visualization with resonant markers at MR imaging-guided deployment of endovascular stents in swine.

PURPOSE: To evaluate resonant circuits as markers for magnetic resonance (MR) imaging-guided placement of nitinol stents. MATERIALS AND METHODS: The study was approved by the institutional animal research committee and complied with National Institutes of Health guidelines for care and use of laboratory animals. Resonant circuits similar to catheter markers used at conventional angiography were placed proximally and distally to a nitinol stent in a stent delivery system. Resonant circuits were tested in vitro and in vivo for signal intensity levels that would enable visualization during MR imaging-guided stent deployment. Experiments were conducted by using real-time imaging with a 1.5-T unit. Stents (n = 9) were deployed in the vena cava (n = 2), abdominal aorta (n = 2), isthmus of the aorta (n = 2), and carotid (n = 2) and iliac (n = 1) arteries in five pigs. After intervention, the site of the stent was investigated with balanced fast field-echo MR imaging and contrast material-enhanced MR angiography. Blood flow velocities were measured in the stent lumen and next to the stent with velocity-encoded cine MR imaging. Level of agreement was determined with Bland-Altman analysis. RESULTS: During all interventions, resonant circuits provided highly visible MR signal that allowed fast and reliable visualization of the stent delivery system. Borders of loaded stents were clearly marked, which allowed precise stent placement in all experiments. Balanced fast field-echo MR imaging and contrast-enhanced MR angiography provided information about immediate postintervention position. Positions depicted on MR images were found accurate at postmortem examination. Results of Bland-Altman analysis showed good agreement between blood flow velocities measured in and next to the stent lumen, with a mean difference of -9 cm/sec +/- 5 (standard deviation). CONCLUSION: Resonant circuits are well suited for use at deployment of endovascular stents.

Alloys↗

Magnetic resonance imaging analysis of right ventricular pressure-volume loops: in vivo validation and clinical application in patients with pulmonary hypertension.

BACKGROUND: The aims of this study were to validate MRI-derived right ventricular (RV) pressure-volume loops for assessment of RV myocardial contractility and then to apply this technique in patients with chronic RV pressure overload for assessment of myocardial contractility, ventricular pump function, and VA coupling. METHODS AND RESULTS: Flow-directed catheters were guided under MR fluoroscopy (1.5 T) into the RV for invasive pressure measurements. Simultaneously, ventricular volumes and myocardial mass were assessed from cine MRI. From sampled data, RV pressure-volume loops were constructed, and maximal ventricular elastance indexed to myocardial mass (E(max_i)) was derived by use of a single-beat estimation method. This MRI method was first validated in vivo (6 swine), with conductance techniques used as reference. Bland-Altman test showed good agreement between methods (E(max_i)=5.1+/-0.5 versus 5.8+/-0.7 mm Hg x mL(-1) x 100 g(-1), respectively; P=0.08). Subsequently, the MRI method was applied in 12 subjects: 6 control subjects and 6 patients with chronic RV pressure overload from pulmonary hypertension. In these patients, indexes of RV pump function (cardiac index), E(max_i), and VA coupling (E(max)/E(a)) were assessed. In patients with pulmonary hypertension, RV pump function was decreased (cardiac index, 2.2+/-0.5 versus 2.9+/-0.4 L x min(-1) x m(-2); P<0.01), myocardial contractility was enhanced (E(max_I), 9.2+/-1.1 versus 5.0+/-0.9 mm Hg x mL(-1) x 100 g(-1); P<0.01), and VA coupling was inefficient (E(max)/E(a), 1.1+/-0.3 versus 1.9+/-0.4; P<0.01) compared with control subjects. CONCLUSIONS: RV myocardial contractility can be determined from MRI-derived pressure-volume loops. Chronic RV pressure overload was associated with reduced RV pump function despite enhanced RV myocardial contractility. The proposed MRI approach is a promising tool to assess RV contractility in the clinical setting.

Adolescent↗

Assessment of vascular invasion in pancreatic head cancer with multislice spiral CT: value of multiplanar reconstructions.

The use of multiplanar reconstructions (MPRs) generated from multislice spiral CT (MSCT) data sets in the preoperative assessment of vascular invasion in pancreatic cancer was evaluated. Forty patients underwent biphasic high-resolution MSCT prior to surgery for pancreatic head cancer. Image reconstruction included thin-slice axial, sagittal and coronal MPRs as well as an MPR perpendicular to the course of a major peripancreatic vessel in proximity to the tumor. CT criteria for vascular invasion were: (1) circumferential involvement >180 degrees and (2) vessel narrowing. Imaging findings of 52 vessels were correlated with surgical and histopathological reports. Regarding the CT criterion circumferential involvement, vascular invasion was demonstrated on axial MPRs with a sensitivity and specificity of 58 and 97%. For the assessment with coronal and sagittal MPRs sensitivity was only 47%. Vascular invasion was recognized best on perpendicular MPRs with a sensitivity, specificity and accuracy of 74, 97 and 88%, respectively. Vessel narrowing was a less reliable CT criterion for vascular invasion, mainly due to the lower specificity of 91% obtained with each available MPR. Thin-slice MPRs oriented perpendicularly to a possibly invaded vessel exactly depict the grade of circumferential involvement and thus have the capability to improve the assessment of vascular invasion in pancreatic cancer.

Adenocarcinoma↗

Beneficial effect of matching at the HLA-A and -B amino-acid triplet level on rejection-free clear graft survival in penetrating keratoplasty.

OBJECTIVE: The beneficial effect of human leukocyte antigen (HLA) matching on long-term prognosis in penetrating keratoplasty is now unequivocal but has to be weighed against the additional waiting period on an individual basis. HLAMatchmaker is a molecularly based algorithm for histocompatibility determination that can identify immunologically acceptable mismatches and thus potentially reduce time on the waiting list dramatically without negatively affecting prognosis. METHODS: The HLAMatchmaker algorithm (triplet-string matching) was applied on each of 545 normal-risk keratoplasties for which complete HLA type was known at split-level resolution. Two homogeneous groups were defined. Group I consisted of the 147 penetrating keratoplasties with up to 13 triplet-string mismatches (the typical upper limit of foreign in case of a single HLA-A or HLA-B allele mismatch) and was compared to the remaining 398 patients with more triplet mismatches (group II) using the Kaplan-Meier method and log-rank statistics. Analysis of clear graft survival on the basis of conventional HLA-A and HLA-B matching was performed as well. Reduction of time on the waiting list as compared to conventional HLA-A and HLA-B matching was predicted individually. RESULTS: Triplet-string matching yielded 85% rejection-free clear graft survival 3 years after penetrating keratoplasty in group I but only 76% in group II (P<0.05), whereas conventional HLA-A and HLA-B matching did not result in any statistically significant reduction of immune reactions because of lack of statistical power (P=0.08). Triplet-string matching (13 mismatches accepted) reduces median time on the waiting list by 80%. CONCLUSIONS: Triplet-string matching seems to improve mid- to long-term prognosis in penetrating keratoplasties while simultaneously reducing time on the waiting list in most cases. It should thus be considered for histocompatibility determination in penetrating keratoplasty.

Aged↗

Diastolic left ventricular function in preterm infants with a patent ductus arteriosus: a serial Doppler echocardiography study.

In very low birth weight neonates, a left-to-right shunt via persistent ductus arteriosus (PDA) may interact with diastolic left ventricular function, but specific changes of Doppler parameters have yet to be reported. In a serial transmitral Doppler study, we investigated the impact of a PDA on diastolic function parameters. Twenty-two patients with and without PDA were examined on day 3.8+/-1 and day 14+/-2 after birth. By the first examination, 13 out of 22 patients had a PDA; by the second examination, the number was still 8 out of 22. Peak early and atrial flow velocities (44.8+/-15 and 50.1+/-13 cm/s, respectively) were higher (p<0.05) for neonates with PDA compared to those with closed duct (30.9+/-6 and 34.2 cm/s, respectively). Isovolumic relaxation time (IVRT) was shorter in neonates with PDA (45+/-7 ms, N=21) compared to those with a closed duct (55.3+/-5 ms, N=23) (p<0.01). IVRT correlated inversely with cardiac index (R=-0.79, p<0.01). All observed changes reversed to the normal range after closure of the PDA. When premature infants with a PDA experience a preload challenge, early and atrial peak velocities increase and IVRT shortens significantly. This coincidence of elevated transvalvular pressure differences and decreased IVRT in neonates with immature diastolic function can best be explained as a result of left atrial pressure elevation. Consequently, pulmonary venous pressure must be elevated, with its inherent effect on pulmonary capillary physiology. Thus, the monitoring of left ventricular diastolic function adds significant information to the care of preterm infants with a PDA.

Blood Gas Analysis↗

Doppler-derived parameters of diastolic left ventricular function in preterm infants with a birth weight <1500 g: reference values and differences to term infants.

Transmitral flow parameters in preterm and term infants were compared in order to study differences in signal expression and temporal dynamics of left ventricular diastolic function. In 63 preterm infants between 26 and 33 weeks of gestation and 102 term infants, a Doppler survey was performed during 6 months after birth. Early and atrial filling-time velocity integrals and peak velocities were significantly lower in the preterm neonates. Atrial filling parameters reached the level observed in term infants by 2 months of age. Peak early filling velocity was still lower for 2-month-old preterms and attained the term infants' level by 3 months of age. Preterm infants continued having high atrial filling fraction (AFF) (0.51+/-0.07) during 2 months after birth, while in term infants the fraction decreased continuously from 0.41+/-0.06 to 0.37+/-0.05. Isovolumic relaxation time (IVRT) was the only parameter without differences between preterm and term infants, and it decreased from 54+/-7 ms in neonates to 41+/-4 ms over 3 months. Stroke volume passing the mitral valve doubled in preterm (4+/-1 to 7.9+/-1.5 ml/cm2), but increased by only 37% (6.9+/-1.6 to 9.5+/-2.2 ml/cm2) in term infants. Our observations show that the maturational period of diastolic function appears prolonged in preterm infants. As preterm infants have to cope with a higher physiologic preload augmentation during growth, part of the delay in parameter changes might be caused by preload stress rather than by persistence of functional impairment. Although doing well under physiological conditions, preterm neonates may be at higher risk for diastolic dysfunction than term infants when an additional preload challenge is encountered.

Diastole↗

Diagnostic performance of MR arthrography in the assessment of superior labral anteroposterior lesions of the shoulder.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of MR arthrography in the assessment of superior labral anteroposterior (SLAP) lesions of the shoulder with emphasis on the classification of SLAP lesions. MATERIALS AND METHODS: Two hundred sixty-five MR arthrograms including 68 MR arthrograms of patients with arthroscopically proven SLAP lesions of the shoulder and 197 MR arthrograms of patients with an intact superior labrum and biceps anchor were retrospectively reviewed in random order. MR arthrography was performed using triplanar T1-weighted spin-echo sequences and a coronal oblique T2-weighted fast spin-echo sequence. MR arthrograms were evaluated by two radiologists with agreement by consensus, and the results were compared with arthroscopic findings. RESULTS: Of 68 SLAP lesions, seven (10%) were arthroscopically classified as type I, 41 (60%) as type II (including 20 type II lesions with coexisting Bankart lesions [29%]), 14 (21%) as type III, and six (9%) as type IV. Compared with arthroscopy as the gold standard, MR arthrography showed a sensitivity of 82% and a specificity of 98% for the overall detection of SLAP lesions. MR arthrographic grading and arthroscopic grading were concurrent in 45 (66%) of 68 arthroscopic diagnoses. Of the surgically confirmed SLAP lesions, involvement of the biceps insertion and SLAP type II lesions with coexisting Bankart lesions were assessed correctly in 75% and 95% of cases, respectively. CONCLUSION: MR arthrography is a highly effective method for the detection of SLAP lesions, but this technique is limited in the classification of different types of SLAP lesions. However, for preoperative planning MR arthrography provides accurate information about the stability of the biceps insertion and the presence of associated anteroinferior labral injuries.

Adolescent↗

Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene.

The functional consequences of an in vivo heterozygous insertion mutation in the human facilitated glucose transporter isoform 1 (GLUT1) gene were investigated. The resulting frameshift in exon 10 changed the primary structure of the C-terminus from 42 in native GLUT1 to 61 amino acid residues in the mutant. Kinetic studies on a patient's erythrocytes were substantiated by expressing the mutant cDNA in Xenopus laevis oocytes. K(m) and V(max) values were clearly decreased explaining pathogenicity. Targeting to the plasma membrane was comparable between mutant and wild-type GLUT1. Transport inhibition by cytochalasin B was more effective in the mutant than in the wild-type transporter. The substrate specificity of GLUT1 remained unchanged.

Amino Acid Sequence↗

Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease.

BACKGROUND: Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra) in pre- and postoperative children with increased PVR because of CHD. METHODS AND RESULTS: 12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3+/-1.0 Wood Units*m2) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (FiO2=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, P<0.05, and 25.8% versus 14.6% in the post op patient group, P=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Qs/Qt=16.5+/-4.7% to 25.5+/-18.2% P=0.04). CONCLUSIONS: Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.

3',5'-Cyclic-GMP Phosphodiesterases↗

[Diet and lung cancer].

Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and large well-designed original articles were preferred to form the basis of the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and in persons who have never smoked. Vitamin A, C and E supplements and beta-carotene offer no protection against the development of lung cancer. On the contrary, in two major randomised intervention trials beta-carotene supplement has resulted in increased mortality. Smoking remains by far the leading cause of lung cancer and the adverse effects can only be slightly alleviated by a healthy diet.

Diet↗