Biomedical subjects

B van den Berg

Publications and source records attributed to B van den Berg.

At least 37 records · Page 2Linked to original sources

PubMed1997

Controlled expiration in mechanically-ventilated patients with chronic obstructive pulmonary disease (COPD).

In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume.

Aged↗

PubMed1996

Localization of monoamine oxidases in human peripheral tissues.

Localization of monoamine oxidases (MAO) A and B and beta-adrenoceptors, was studied in aged human peripheral tissues (age 68-80 years) by quantitative autoradiography. The tissues analyzed were heart, lung, liver, kidney, spleen and duodenum. [3H]Ro41-1049 and [3H]lazabemide, two recently characterized selective radioligands were used to map MAO-A and MAO-B respectively. The regional pattern of distribution of MAO-A and MAO-B did not differ markedly, except in kidney and especially in duodenum. Highest levels of MAOs were measured in liver, and lowest in spleen. MAO-A was more abundant than MAO-B in lung and duodenal mucosa, and the reverse was true in myocardium. These results show marked differences in the abundance and patterns of distribution of MAOs, particularly MAO-B, in human and rodent peripheral tissues.

Aged↗

PubMed1996

Severe Legionnaire's disease requiring intensive care treatment.

BACKGROUND: Legionnaire's disease is well known as severe pneumonia requiring intensive care treatment in many cases. In this study the clinical course is described of patients admitted to the medical ICU of the University Hospital of Rotterdam for respiratory distress due to Legionnaire's disease. METHODS: From the register of admissions to the medical ICU all patients suffering from Legionnaire's disease were identified. All data on clinical signs and symptoms present on admission were collected. The circumstances in which the infections were contracted were sought, as well as the tests establishing the diagnosis. The occurrence of various organ failures and complications were noted, as were the causes of death on the ICU. RESULTS: From 1978 till 1995 the diagnosis of Legionella pneumonia was made in 17 patients admitted to the ICU: in 13 patients a community-acquired infection was established. As in 12 patients Legionnaire's disease was diagnosed on serological tests, it took several weeks before the diagnosis could be established in these patients. In all patients the circumstances predisposing to Legionnaire's disease were noted. Respiratory distress was present in all patients, ventilatory support was required in 14. Apart from this, both profound shock and renal failure were commonly encountered. As complications jaundice, rhabdomyolysis and polyneuropathy were frequently noted. Three patients died: 2 due to irreversible shock and 1 due to hospital-acquired sepsis. CONCLUSION: Legionnaire's disease can develop into life-threatening pneumonia requiring intensive care treatment in previously healthy subjects. As the clinical features are aspecific, careful search for predisposing circumstances such as recent travel or use of a contaminated water-supply is mandatory. As the diagnosis required positive serological tests in most patients, a considerable delay in diagnosis was noted. Despite the frequent occurrence of multiple organ failure, a favourable outcome can be anticipated in most cases.

Adult↗

PubMed1996

Native-like secondary structure in a peptide from the alpha-domain of hen lysozyme.

BACKGROUND: To gain insight into the local and nonlocal interactions that contribute to the stability of hen lysozyme, we have synthesized two peptides that together comprise the entire alpha-domain of the protein. One peptide (peptide 1-40) corresponds to the sequence that forms two alpha-helices, a loop region, and a small beta-sheet in the N-terminal region of the native protein. The other (peptide 84-129) makes up the C-terminal part of the alpha-domain and encompasses two alpha-helices and a 3(10) helix in the native protein. RESULTS: As judged by CD and a range of NMR parameters, peptide 1-40 has little secondary structure in aqueous solution and only a small number of local hydrophobic interactions, largely in the loop region. Peptide 84-129, by contrast, contains significant helical structure and is partially hydrophobically collapsed. More specifically, the region corresponding to helix C in native lysozyme is disordered, whereas regions corresponding to the D and 3(10) helices in the native protein are helical in this peptide. The structure in peptide 84-129 is at least partly stabilized by interactions between residues in the two helical regions, as suggested by further NMR analysis of three short peptides corresponding to the individual helices in this region of the native protein. CONCLUSIONS: Stabilization of structure in the sequence 1-40 appears to be facilitated predominantly by long-range interactions between this region and the sequence 84-129. In native lysozyme, the existence of two disulphide bonds between the N- and C-terminal halves of the alpha-domain is likely to be a major factor in their stabilization. The data show, however, that native-like secondary structure can be generated in the C-terminal portion of the alpha-domain by nonspecific and nonnative interactions within a partially collapsed state.

Amino Acid Sequence↗

PubMed1996

Incorporation of an unnatural amino acid in the active site of porcine pancreatic phospholipase A2. Substitution of histidine by 1,2,4-triazole-3-alanine yields an enzyme with high activity at acidic pH.

The effect of the substitution of the active site histidine 48 by the unnatural 1,2,4-triazole-3-alanine (TAA) amino acid analogue in porcine pancreas phospholipase A2 (PLA2) was studied. TAA was introduced biosynthetically using a his-auxotrophic Escherichia coli strain. To study solely the effect of the substitution of the active site histidine, two nonessential histidines (i.e. His17 and His115) were replaced by asparagines, resulting in a fully active mutant enzyme (His-PLA2). In this His-PLA2 the single histidine as position 48 was substituted by TAA with an incorporation efficiency of about 90%, giving a mixture of His-PLA2 and TAA-PLA2. Based on the charge difference at acidic pH, both forms could be separated by FPLC, allowing for the purification of TAA-PLA2 free from His-PLA2. At pH 6, TAA-PLA2 has a fivefold reduced activity compared with His-Pla2. This reduced activity paralells a reduced rate of covalent modification with p-nitrophenacyl bromide of TAA-PLA2 compared with His-PLA2. Competitive inhibition gave comparable IC50 values for WT-PLA2, His-PLA2 and TAA-PLA2. These results indicate that the reduction in activity is not caused by a different affinity for the substrate, but more likely results from a reduced kcat value in TAA-PLA2. The enzymatic activities for native and mutant PLA2s were measured at different pH values. For WT-PLA2 and His-PLA2 the activity is optimal at pH 6 and is strongly deminished at acidic pH, with no observable activity at pH 3. In contrast, TAA-PLA2 is as active at pH 3 as at pH 6. Most likely, the decrease in activity observed for WT-PLA2 and His-PLA2 is caused by the protonation of the active site His48, which is the general base involved in the activation of the nucleophilic water molecule. In TAA-PLA2, however, the active site residue TAA48 is unprotonated at both pH 3 and 6 as a result of the low pKa of TAA compared with histidine.

Acids↗

PubMed1996

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt (TIPS).

We reported the case of a patient in whom severe, and ultimately fatal, pulmonary hypertension developed 1.5 yrs after transjugular intrahepatic portosystemic shunt (TIPS). Pulmonary artery pressures were not affected by 100% oxygen, prostacyclin or nifedipine. Postmortem examinations showed pulmonary and vascular abnormalities typical of pulmonary hypertension. Pulmonary artery pressures should be measured in each patient with otherwise not readily explained dyspnoea following transjugular intrahepatic portosystemic shunt.

Fatal Outcome↗

PubMed1996

Quinine pharmacokinetics in young children with severe malaria.

Children less than two years of age represent a substantial proportion of severe malaria cases in Africa. The standard treatment is parenteral quinine, but little is known about the pharmacokinetics and toxicity of quinine in this age group. We have studied the pharmacokinetics of quinine after intravenous (iv) and intramuscular (im) administration in a group of 20 children less then two years of age with severe malaria. A loading dose of 20 mg/kg of quinine dihydrochloride was followed by 10 mg/kg at 12-hr intervals. The im quinine was very rapidly absorbed, reaching high peak concentrations of 16.4 +/- 3.7 mg/L (mean +/- SD) in 1.1 +/- 0.4 hr. Mean peak levels after iv administration were also high (17.5 +/- 2.4 mg/L). Free quinine levels at 4 hr postadministration ranged from 0.27 to 1.89 mg/L (0.87 +/- 0.53 mg/L). At 2 hr and 4 hr after commencing treatment, an electrocardiogram showed a significant lengthening of the QRS interval compared with baseline (15.6 +/- 21.4%; P = 0.007 and 17.3 +/- 21.9%; P = 0.006 at 2 hr and 4 hr, respectively), whereas this was not observed in a control group of nine older children (age range = 24 months to 10 years) receiving the same im dosage regimen. Free and total quinine levels were not significantly correlated with changes in the QRS interval. Levels of alpha1-acid glycoprotein, which binds quinine within the circulation, did not differ between the younger and the older children. These findings raise the possibility that young children are more susceptible to quinine toxicity than older children, and indicate the need for further evaluation of quinine dosage regimens in this age group.

Absorption↗

PubMed1995

Solution structure of porcine pancreatic phospholipase A2.

The lipolytic enzyme phospholipase A2 (PLA2) is involved in the degradation of high-molecular weight phospholipid aggregates in vivo. The enzyme has very high catalytic activities on aggregated substrates compared with monomeric substrates, a phenomenon called interfacial activation. Crystal structures of PLA2s in the absence and presence of inhibitors are identical, from which it has been concluded that enzymatic conformational changes do not play a role in the mechanism of interfacial activation. The high-resolution NMR structure of porcine pancreatic PLA2 free in solution was determined with heteronuclear multidimensional NMR methodology using doubly labeled 13C, 15N-labeled protein. The solution structure of PLA2 shows important deviations from the crystal structure. In the NMR structure the Ala1 alpha-amino group is disordered and the hydrogen bonding network involving the N-terminus and the active site is incomplete. The disorder observed for the N-terminal region of PLA2 in the solution structure could be related to the low activity of the enzyme towards monomeric substrates. The NMR structure of PLA2 suggests, in contrast to the crystallographic work, that conformational changes do play a role in the interfacial activation of this enzyme.

Animals↗

PubMed1995

Solution structure of porcine pancreatic phospholipase A2 complexed with micelles and a competitive inhibitor.

The three-dimensional structure of porcine pancreatic PLA2 (PLA2), present in a 40 kDa ternary complex with micelles and a competitive inhibitor, has been determined using multidimensional heteronuclear NMR spectroscopy. The structure of the protein (124 residues) is based on 1854 constraints, comprising 1792 distance and 62 phi torsion angle constraints. A total of 18 structures was calculated using a combined approach of distance geometry and restrained molecular dynamics. The atomic rms distribution about the mean coordinate positions for residues 1-62 and 72-124 is 0.75 +/- 0.09 A for the backbone atoms and 1.14 +/- 0.10 A for all atoms. The rms difference between the averaged minimized NMR structures of the free PLA2 and PLA2 in the ternary complex is 3.5 A for the backbone atoms and 4.0 A for all atoms. Large differences occur for the calcium-binding loop and the surface loop from residues 62 through 72. The most important difference is found for the first three residues of the N-terminal alpha-helix. Whereas free in solution Ala1, Leu2 and Trp3 are disordered, with the alpha-helical conformation with the alpha-amino group buried inside the protein. As a consequence, the important conserved hydrogen bonding network which is also seen in the crystal structures is present only in the ternary complex, but not in free PLA2. Thus, the NMR structure of the N-terminal region (as well as the calcium-binding loop and the surface loop) of PLA2 in the ternary complex resembles that of the crystal structure. Comparison of the NMR structures of the free enzyme and the enzyme in the ternary complex indicates that conformational changes play a role in the interfacial activation of PLA2.

Animals↗

PubMed1995

NMR structures of phospholipase A2 reveal conformational changes during interfacial activation.

It has long been proposed that the higher activity of phospholipase A2 (PLA2) for substrates presented as multimolecular aggregates compared to dispersed molecules (interfacial activation) arises due to a conformational change in the enzyme. X-ray studies have, however, failed to identify any such change. Here we report the solution structures of porcine pancreatic PLA2 both free and as a ternary complex with micelles and a competitive inhibitor. Important differences between these structures indicate that conformational changes may play an important role in the mechanism of interfacial activation in PLA2s.

Amino Acid Sequence↗

PubMed1995

Effect of continuous positive airway pressure (CPAP) in patients with chronic obstructive pulmonary disease (COPD) depending on intrinsic PEEP levels.

The application of continuous positive airway pressure (CPAP) is known to reduce inspiratory work of breathing in intubated patients with chronic obstructive pulmonary disease (COPD). This effect is caused by a decrease in elastic work related to a reduction in intrinsic PEEP. The aim of this study was to relate the decrease in inspiratory work due to CPAP to the intrinsic PEEP levels obtained during spontaneous breathing without positive pressure. Ten intubated patients with COPD who had been ventilated for acute respiratory failure were studied. Intrinsic PEEP was determined during tracheal occlusions performed at end-expiration when the patient was breathing without positive airway pressure. Inspiratory work was computed during breathing through a circuit with a CPAP of 0.5 kPa and the same circuit without positive pressure. Intrinsic PEEP-levels ranged from 0.26 to 1.31 kPa. Compared to spontaneous breathing without positive pressure, CPAP reduced the total inspiratory work per liter of ventilation (Wltot) from 1.42 +/- 0.48 to 1.24 +/- 0.50 J.1-1 (means +/- SD P < 0.01). This decrease was found to be related to the intrinsic PEEP-levels; the largest reductions were found in the patients with an intrinsic PEEP-level close to the CPAP-level applied. In intubated patients with COPD, the decrease in Wltot due to a CPAP of 0.5 kPa was found to be related to the intrinsic PEEP-levels present when no positive airway pressure was applied. The intrinsic PEEP measured during tracheal occlusions could be used to estimate the effect of CPAP in these patients.

Aged↗

PubMed1995

Detection of flow limitation during tidal breathing by the interruptor technique.

In patients with airflow obstruction, flow limitation can be established in various ways. Using body plethysmography, flow limitation is assumed when expiratory flow decreases whilst alveolar pressure increases at the same time. During forced expiration, flow limitation can be established by means of the flow interruptor technique; flow limitation is assumed when, after release of an occlusion, a spike flow superimposed on the ongoing alveolar flow (delta peak flow) is detected. In this study, the flow interruptor technique was applied to detect flow limitation during tidal breathing. The results were compared to those obtained with the body plethysmograph. The expiratory flow pattern, post-interruption, was analysed in 33 subjects; 11 patients with airflow obstruction and flow limitation established with the body plethysmograph (AO+); 11 patients with airflow obstruction without flow limitation (AO-); and 11 healthy volunteers. Mean spike areas were 27.6 +/- 18.3, 4.6 +/- 2.3 and 3.4 +/- 2.0 mL for the AO+, AO- and control group, respectively, showing a highly significant difference between the AO+ patients and the other groups. Also, significantly higher delta peak flows were found in the AO+ patients compared to the other groups. No differences in delta peak flows or spike areas could be established between patients without flow limitation and controls. We conclude that the interruptor technique may be a useful means of assessing flow limitation during tidal breathing.

Adolescent↗

PubMed1994

[Criteria for and results of liver transplantation in patients with acute liver insufficiency].

OBJECTIVE: Evaluation of the results of emergency liver transplantation in patients with acute liver failure. DESIGN: Analysis of 25 patients with acute liver failure. SETTING: University Hospital Rotterdam Dijkzigt. METHOD: Twenty-five patients with acute liver failure were admitted to the Intensive Care Unit in January 1989-May 1993. Patients were selected for emergency liver transplantation according to the Clichy criteria (presence of confusion or coma and factor V activity less than 20-30%). RESULTS: Liver transplantation was indicated in 17 patients and performed in 13. The 1-year survival rate in patients with a liver transplant was 85%. Four patients with an indication for liver transplantation, but who could not be transplanted died. All 8 patients without an indication for emergency liver transplantation survived. CONCLUSION: Survival after liver transplantation for acute hepatic failure is now about 80%; the Clichy criteria appear to be helpful in selecting patients with acute hepatic failure for liver transplantation.

Adolescent↗

PubMed1994

High fat, low carbohydrate, enteral feeding in patients weaning from the ventilator.

OBJECTIVE: To study whether high fat, low carbohydrate enteral nutrition could reduce VCO2 in patients during ventilator support and weaning from the ventilator in order to facilitate the weaning process. DESIGN: prospective, randomized controlled study. SETTING: Medical ICU of a university hospital. PATIENTS: 32 ventilator-dependent patients with a prospect of weaning from mechanical ventilation. INTERVENTIONS: high fat feeding administered to 15 patients and standard isocaloric feeding administered to 17 patients, both in a dosage of 1.5 times basal metabolic rate. MEASUREMENTS AND RESULTS: Respiratory and metabolic measurements were obtained both during mechanical ventilation and weaning procedures. High fat feeding was associated with significantly lower RQ values compared with standard feeding; the mean (+/- SEM) RQ values during mechanical ventilation amounted to 0.91 +/- 0.01 and 1.00 +/- 0.02 and during weaning to 0.72 +/- 0.02 and 0.86 +/- 0.02 for high fat and standard nutrition respectively (both p-values < 0.001). High fat feeding reduced the CO2-excretion both during mechanical ventilation and weaning, but only the decrease during weaning proved to be significant; the mean (+/- SEM) CO2-excretion amounted to 0.177 +/- 0.010 and 0.231 +/- 0.011 1/min STPD for the high fat and standard feeding respectively (p < 0.01). No significant differences were found in the PaCO2 during weaning between the two feeding groups. CONCLUSION: High fat, low carbohydrate enteral feeding significantly reduced the RQ values in ventilated patients with decreases in VCO2, but in this study failed to reduce PaCO2 during weaning from the ventilator.

Analysis of Variance↗

PubMed1994

Arteether administration in humans: preliminary studies of pharmacokinetics, safety and tolerance.

The recently developed artemisinin derivative arteether was administered by intramuscular injection to healthy male subjects in a single dose (n = 23) and a multiple dose study (n = 27). The drug was well tolerated. Clinical, neurological, electrocardiographic and biochemical monitoring did not reveal significant toxicity. Apart from some increase in eosinophil numbers, no haematological abnormality was seen. Preliminary pharmacokinetic data showed a long elimination half life of 25-72 h and marked accumulation in the multiple dose study.

Adolescent↗

PubMed1991

Multicentre comparison of the Novo Biolabs immunometric CK-MB assay with four established methods.

The analytical performance of a new immunometric CK-MB assay from Novo Biolabs was evaluated in three hospitals. Comparisons were made with another immunometric assay, an immune inhibition/precipitation technique, an immune inhibition method, and a column separation method. The Novo assay exhibited good precision (CV 3-7%) at all concentration levels tested (6-150 micrograms/L) and was found to be linear over the range 0-200 micrograms/L. Comparison of the Novo kit with the other methods using patients' sera showed acceptable correlation between the methods over a wide concentration range (r = 0.96-0.99). We conclude that the assay is a useful adjunct to the specific measurement of CK-MB, particularly in routine laboratories with a high throughput of such determinations.

Creatine Kinase↗

PubMed1991

Effects of PEEP on respiratory mechanics in patients with COPD on mechanical ventilation.

We studied the effects of positive end-expiratory pressure (PEEP) applied by the ventilator on respiratory mechanics in ventilated patients with chronic obstructive pulmonary disease (COPD). Airway pressures, relaxed expiratory flow-volume curves and end-expiratory volumes (EEV) were measured. In all patients investigated without PEEP applied by the ventilator, an intrinsic PEEP level (PEEPi) and a concavity in the flow-volume curve was present. Ventilator-PEEP caused a significant decrease in PEEPi in all patients (p less than 0.01). In patients in whom ventilator-PEEP exceeded PEEPi, significant increases occurred in airway pressures and EEV (p less than 0.05) and moreover the shape of the flow-volume curve was changing. In patients in whom the level of ventilator-PEEP was below the PEEPi level, no significant changes in airway pressures, EEV or flow-volume curves were found. We conclude: 1) PEEP applied by the ventilator can reduce PEEPi in ventilated patients with COPD without significant changes in airway pressures, EEV or flow-volume curves. 2) Expiratory flow-volume curves can be used to estimate the effects of ventilator-PEEP on EEV.

Aged↗

PubMed1990

Prenatal and perinatal factors in the etiology of cerebral palsy.

Among 19,044 children born to mothers with monitored pregnancies and followed medically for at least 5 years, 41 (0.2%) had cerebral palsy that was not the result of a progressive disease or of a neural tube defect. All children without cerebral palsy were entered as controls subjects in the analysis. Significant prenatal or gestational predictors of cerebral palsy were a severe or nonsevere birth defect other than cerebral palsy or its sequelae, low birth weight, low placental weight, abnormal fetal position, and premature separation of the placenta. Maternal antecedents of cerebral palsy were unusually long or unusually short intervals between pregnancies and unusually long menstrual cycles. Perinatal risk factors were delayed crying as a measure of birth asphyxia and abnormal delivery. Children who had seizures within 48 hours of birth were at high risk for the development of cerebral palsy. Seventy-eight percent of children with cerebral palsy did not have birth asphyxia, and the 22% who did had other prenatal risk factors that may have compromised their recovery.

Birth Intervals↗