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Biomedical subjects

L Blanch

Publications and source records attributed to L Blanch.

At least 37 records · Page 2Linked to original sources
PubMed1998

Identification of a common mutation (R245H) in Sanfilippo A patients from The Netherlands.

We have identified a common mutation (R245H) in the sulphamidase gene of Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA, MPS IIIA) patients from The Netherlands. Allele-specific oligonucleotide hybridization was used to determine the incidence of this mutation in 45 unrelated MPS IIIA patients from different regions of The Netherlands. R245H was present in 51 alleles, representing 56.7% of the total allelic population. Of 39 patients, for whom we have uniform clinical details, 13 MPS IIIA patients who were homozygous for this common mutation had a more uniform but severe clinical phenotype than the remaining 21 or 5 patients, containing respectively one or no R245H alleles. The R245H allele had a higher prevalence in western rather than eastern regions of The Netherlands.

Adolescent↗
PubMed1998

Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS.

Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs, limitation of airway pressure, allowing hypercapnia if necessary, is already used for ventilation of acute respiratory distress syndrome (ARDS). Whether a systematic and more drastic reduction is necessary is debatable. A multicenter randomized study was undertaken to compare a strategy aimed at limiting the end-inspiratory plateau pressure to 25 cm H2O, using tidal volume (VT) below 10 ml/kg of body weight, versus a more conventional ventilatory approach (with regard to current practice) using VT at 10 ml/kg or above and close to normal PaCO2. Both arms used a similar level of positive end-expiratory pressure. A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers. The two groups were similar at inclusion. Patients in the two arms were ventilated with different VT (7.1 +/- 1.3 versus 10.3 +/- 1.7 ml/kg at Day 1, p < 0.001) and plateau pressures (25.7 +/- 5. 0 versus 31.7 +/- 6.6 cm H2O at Day 1, p < 0.001), resulting in different PaCO2 (59.5 +/- 15.0 versus 41.3 +/- 7.6 mm Hg, p < 0.001) and pH (7.28 +/- 0.09 versus 7.4 +/- 0.09, p < 0.001), but a similar level of oxygenation. The new approach did not reduce mortality at Day 60 (46.6% versus 37.9% in control subjects, p = 0.38), the duration of mechanical ventilation (23.1 +/- 20.2 versus 21.4 +/- 16. 3 d, p = 0.85), the incidence of pneumothorax (14% versus 12%, p = 0. 78), or the secondary occurrence of multiple organ failure (41% versus 41%, p = 1). We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O.

Adolescent↗
PubMed1997

Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease.

OBJECTIVE: Inhalation of nitric oxide (NO) can improve oxygenation and decrease mean pulmonary artery pressure (MPAP) in patients with the acute respiratory distress syndrome (ARDS). It is not known whether inhaled NO exerts a similar effect in hypoxemic patients with chronic obstructive pulmonary disease (COPD). DESIGN: Prospective clinical study. SETTING: General intensive care unit in Sabadell, Spain. PATIENTS: Nine mechanically ventilated COPD patients (mean age 72 +/- 2 years; forced expiratory volume in 1 s 0.91 +/- 0.11 l) and nine ARDS patients (mean age 57 +/- 6 years; mean lung injury score 2.8 +/- 0.1). MEASUREMENTS AND RESULTS: We measured hemodynamic and gas exchange parameters before NO inhalation (basal 1), during inhalation of 10 ppm NO (NO-10), and 20 min after NO was discontinued (in basal 2) in the ARDS group. In the COPD group, these parameters were measured before NO inhalation (basal 1), during different doses of inhaled NO (10, 20, and 30 ppm), and 20 min after NO was discontinued (basal 2). A positive response to NO was defined as a 20% increment in basal arterial partial pressure of oxygen (PaO2). MPAP and pulmonary vascular resistance (PVR) decreased significantly, while other hemodynamic parameters remained unchanged after NO-10 in both groups. Basal oxygenation was higher in the COPD group (PaO2/FIO2 (fractional inspired oxygen) 190 +/- 18 mmHg) than in the ARDS group (PaO2/FIO2 98 +/- 12 mmHg), (p < 0.01). After NO-10, PaO2/FIO2 increased (to 141 +/- 17 mmHg, p < 0.01) and Qva/Qt decreased (39 +/- 3 to 34 +/- 3%, p < 0.01) in the ARDS group. There were no changes in PaO2/FIO2 and Qva/Qt when the NO concentration was increased to 30 ppm in the COPD group. In both groups, a correlation was found between basal MPAP and basal PVR, and between the NO-induced decrease in MPAP and in PVR. The NO-induced increase in PaO2/FIO2 was not correlated with basal PaO2/FIO2. In the ARDS group, six of the nine patients (66%) responded to NO and in the COPD group, two of nine (22%) (p = 0.05). CONCLUSIONS: NO inhalation had similar effects on hemodynamics but not on gas exchange in ARDS and COPD patients, and this response probably depends on the underlying disease.

Administration, Inhalation↗
PubMed1997

Short-term effects of prone position in critically ill patients with acute respiratory distress syndrome.

OBJECTIVE: Changing the position from supine to prone is an emerging strategy to improve gas exchange in patients with the acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the acute effects on gas exchange, hemodynamics, and respiratory system mechanics of turning critically ill patients with ARDS from supine to prone. DESIGN: Open, prospective study. SETTING: General intensive care units. PATIENTS: 23 patients [mean age 56 +/- 17 (SD) years] who met ARDS criteria and had a Lung Injury Score > 2.5 (mean 3.25 +/- 0.3). INTERVENTIONS: The decision to turn a patient was made using a protocol based on impaired oxygenation despite the use of positive end-expiratory pressure and a fractional inspired oxygen (FIO2) of 1. MEASUREMENTS AND RESULTS: We measured gas exchange and hemodynamic variables in all patients and in 16 patients calculated respiratory system compliance when they were supine and 60 to 90 min after turning them to a prone position. This latter position was remarkably well tolerated and no clinically relevant complications or events were detected either during turning or while prone. The partial pressure of oxygen in arterial blood (PaO2)/FIO2 ratio improved from 78 +/- 37 mm Hg supine to 115 +/- 31 mm Hg prone (p < 0.001), and intrapulmonary shunt decreased from 43 +/- 11 to 34 +/- 8% (p < 0.001). Cardiac output and other hemodynamic parameters were not affected. Respiratory system compliance slightly improved from 24.7 +/- 10.2 ml/cmH20 supine to 27.8 +/- 13.2 ml/cmH20 prone (p < 0.05). An improvement in PaO2/FIO2 of more than 15% from changing from supine to prone was found in 16 patients (responders). Responders had more hypoxemia (PaO2/FIO2 70 +/- 23 vs 99 +/- 53 mm Hg in non-responders, p < 0.01), more hypercapnia (partial pressure of carbon dioxide in arterial blood (70 +/- 27 vs 64 +/- 9 mm Hg, p < 0.01) and a shorter elapsed time to the onset of ARDS and turning to the prone position (11.8 +/- 16 vs 32.8 +/- 42 days, p < 0.01). CONCLUSIONS: Turning critically ill, severely hypoxemic patients from the supine to the prone position is a safe and useful therapeutic intervention. Our data suggest that prone positioning should be carried out early in the course of ARDS.

Adult↗
PubMed1997

Clinical evaluation of a new orthosis, the 'walkabout', for restoration of functional standing and short distance mobility in spinal paralysed individuals.

The Walkabout orthosis is a relatively new device for assisted standing and mobility in spinal paralysed individuals. The design, with a medially-mounted single-axis hinge joint linking two knee-ankle-foot orthoses, is quite different to other currently available orthoses which have laterally positioned hip joints such as the Reciprocal Gait Orthosis or Hip Guidance Orthosis. Twenty-five spinal cord injured patients were fitted and trained with the Walkabout orthosis and followed up regularly for just under 2 years on average. Sixty percent of all the patients fitted have incorporated use of the Walkabout orthosis into their lifestyles. Maintenance of joint mobility and psychological benefits were the most important outcomes of Walkabout usage. Loss of thoraco-lumbar mobility was found to be a limiting factor in successful use of the Walkabout orthosis in patients without active hip flexion. Patient selection criteria should include demonstrated spinal stability without significant deformity, controlled muscle spasm, less than 5 degrees of hip or knee flexion contracture, achievable neutral ankle position, mobility of the thoraco-lumbar spine into lateral flexion, good upper limb strength, and motivation with realistic expectations.

Adult↗
PubMed1997

Molecular defects in Sanfilippo syndrome type A.

Sanfilippo A syndrome (mucopolysaccharidosis type IIIA, MPS-IIIA) is an autosomal recessive neurodegenerative disorder due to an enzymatic defect of the lysosomal enzyme sulphamidase (EC 3.10.1.1) required for the degradation of heparan sulphate. In this study, molecular defects in the sulphamidase gene of MPS-IIIA patients were investigated in a group of 10 patients of Australian and American origin. The entire coding region of the sulphamidase gene was RT-PCR amplified and one polymorphism (R456H), four novel mutations (S66W, R245H, E447K, 1307 del 9) and one previously described mutation (1284 del 11) were identified by direct PCR sequencing. R245H was present in six patients including one severely affected homozygote. In three of the other patients with R245H, second mutant alleles were identified as S66W, 1284 del 11 and E447K, respectively. S66W was also detected in another patient where the other mutant allele remains undefined. In addition, 1307 del 9 was also detected in a patient with the other mutant allele remaining undefined. Allele specific oligonucleotide hybridisation was used to determine the incidence of these in a population of 26 MPS-IIIA patients (Australian and American) and 60 normal controls (Australian). R245H represented 27% (14/52 alleles) in this total patient population, while the other three changes ranged from 1.9 to 9.6% (1-5 of 52 alleles). The sequence variant, R456H, was shown to be polymorphic as it was present in 55% of normal and 38% of patient alleles. The total combined incidence of these five is 46% of alleles. This is the first study of the molecular defects in MPS-IIIA patients and will greatly assist the development of molecular analysis for MPS-IIIA patients and studies concerned with genotype to phenotype relationships.

Age of Onset↗
PubMed1997

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation.

Several indices of ventilatory heterogeneity can be identified from the expiratory CO2 partial pressure or CO2 elimination versus volume curves. The aims of this study were: 1) to analyse several computerizable indices of volumetric capnography in order to detect ventilatory disturbances; and 2) to establish the relationship between those indices and respiratory system mechanics in subjects with normal lungs and in patients with acute respiratory distress syndrome (ARDS), both receiving mechanical ventilation. We studied six normal subjects and five patients with early ARDS mechanically ventilated at three levels of tidal volume (VT). Respiratory system mechanics were assessed by end-expiratory and end-inspiratory occlusion methods, respectively. We determined Phase III slopes, Fletcher's efficiency index, Bohr's dead space (VD,Bohr/VT), and the ratio of alveolar ejection volume to tidal volume (VAE/VT) from expiratory capnograms, as a function of expired volume. Differences between normal subjects and ARDS patients were significant both for capnographic and mechanical parameters. Changes in VT significantly altered capnographic indices in normal subjects, but failed to change ventilatory mechanics and VAE/VT in ARDS patients. After adjusting for breathing pattern, VAE/VT exhibited the best correlation with the mechanical parameters. In conclusion, volumetric capnography, and, specifically, the ratio of alveolar ejection volume to tidal volume allows evaluation and monitoring of ventilatory disturbances in patients with adult respiratory distress syndrome.

Adult↗
PubMed1996

Structure and sequence of the human sulphamidase gene.

Sanfilippo A syndrome (MPS-IIIA) is a mucopolysaccharide lysosomal storage disorder caused by a deficiency in the lysosomal enzyme, sulphamidase (EC 3.10.1.1), which is required for the degradation of heparan sulphate. A genomic clone containing the entire sulphamidase gene was isolated from a chromosome 17-specific gridded cosmid library. The structure of the gene and the sequence of the exon/intron boundaries and the 5' promoter region were determined. The sulphamidase gene is split into 8 exons spanning approximately 11 kb.

Base Sequence↗
PubMed1996

Clinical consequences of the implementation of a weaning protocol.

OBJECTIVE: To analyze the clinical and economic consequences of the implementation of a weaning protocol in patients mechanically ventilated (MV) for more than 48 h. DESIGN: Comparative study. SETTING: General intensive care unit (ICU) in a county hospital covering 360000 inhabitants. PATIENTS: 51 patients weaned by a fixed protocol were studied prospectively and compared with 50 retrospective controls. MEASUREMENTS: The following variables were assessed: Acute Physiology and Chronic Health Evaluation (APACHE) II score, age, cause of respiratory failure, type of extubation (direct extubation or extubation using a weaning technique), number of days on MV before the weaning trial, weaning time, total duration of MV, complications (reintubations and tracheostomies), length of ICU stay, and mortality. RESULTS: The groups were comparable in terms of age, APACHE II score, and main cause of acute respiratory failure. Number of days on MV up to the weaning trial were similar in the two groups (8.4 +/- 7.7 in the protocol group vs 7.5 +/- 5.5 in the control group, NS). Most of the patients (80%) in the protocol group were directly extubated without a weaning technique, unlike the control group (10%) (p < 0.01). When a weaning technique was used, the weaning time was similar in both groups (3.5 +/- 3.9 days vs 3.6 +/- 2.2 days in the control group). Duration of MV was shorter in the protocol group (10.4 +/- 11.6 days) than in the control group (14.4 +/- 10.3 days) (p < 0.05). As a result, the ICU stay was reduced by using the weaning protocol (16.7 +/- 16.5 days vs 20.3 +/- 13.2 days in the control group, p < 0.05). We found no differences in reintubation rate (17 vs 14% in the control group) and need for tracheostomies (2 vs 8% in the control group). CONCLUSION: The implementation of a weaning protocol decreased the duration of MV and ICU stay by increasing the number of safe, direct extubations.

APACHE↗
PubMed1996

Use of capnography to detect hypercapnic episodes during weaning from mechanical ventilation.

OBJECTIVE: To evaluate the relationship between PaCO2 and end-tidal CO2 tension (PetCO2) before weaning and during a weaning trial and to determine the ability of PetCO2 to identify clinically relevant episodes of hypercapnia. DESIGN: Open, prospective study. SETTING: General intensive care unit. PATIENTS: 30 critically ill patients (mean age 63 +/- 2 years; Acute Physiology And Chronic Health Evaluation (APACHE) II of 18.4 +/- 3) who underwent a weaning trial during the recovery phase of acute respiratory failure requiring mechanical ventilation (MV) (8.9 +/- 1 days on MV). INTERVENTIONS: Weaning trial consisted of 2 h breathing on 5 cmH2O of Continuous Positive Airway Pressure (CPAP). MEASUREMENTS AND RESULTS: Arterial blood gas values, PetCO2 register and pulse oximetry determinations were recorded in assist/control ventilation before CPAP, after 1 h on CPAP and after 2 h on CPAP (immediately before extubation) or immediately before returning to assist/control mode in patients who failed the weaning trial. Clinically relevant hypercapnic episodes were described as: (1) an increment in PaCO2 > 42 mm Hg in previously normocapnic patients and (2) an increment of > 8 mm Hg from previous PaCO2 in previously hypercapnic patients. Changes in PaCO2 and changes in PetCO2 between MV and the first and second hour of CPAP showed a significant correlation (r = 0.74; p < 0.01). Clinically relevant hypercapnic episodes were detected by increments of > 3 mm Hg in PetCO2 with a sensitivity of 82%, a specificity of 76% and a negative predictive value of 94%. The area under the receiver operating characteristic curve for increments in PetCO2 was 0.90. CONCLUSIONS: Capnography provided good assessment of hypercapnic episodes during weaning, although the high number of false positives may result in arterial blood sampling in patients who do not present with ventilation failure.

APACHE↗
PubMed1996

Ventilatory factors affecting inhaled nitric oxide concentrations during continuous-flow administration.

PURPOSE: Inhaled nitric oxide has been reported to be useful in acute respiratory distress syndrome and other lung diseases characterized by pulmonary hypertension and hypoxemia. The best site to inject the NO is still controversial, as is whether it can be affected by changes in ventilatory settings. The objective of this study was to examine the impact of various ventilator settings (tidal volume [Vt], inspiratory-to-expiratory [I:E] ratio, added dead space) in the final NO concentrations reached when NO is administered as a continuous flow near the endotracheal tube. METHODS: A test lung model was ventilated using a ServoVentilator 300 Siemens with square wave flow. A continuous flow of NO was administered between the Y piece and the endotracheal tube. The flow was adjusted with an NO precision flowmeter (range, 0.2 to 1.5 L/min) attached to a cylinder containing 800 ppm of NO. Actual NO concentrations in the lung model were measured by chemiluminescence (NOX 2000; Seres). The effects of changing Vt (from 300 to 1300 mL) and I:E ratio (from 1:4 to 2:1) and the addition of dead space (100 mL) were examined. RESULTS: At each step of the study, the measured NO concentration was higher than predicted. Biases from predicted NO concentration due to tidal volume were 17% at 1,300 mL Vt, 21% at 1,100 mL Vt, 25% at 900 mL Vt, 28% at 700 mL Vt, 35% at 500 mL Vt, and 48% at 300 mL Vt. Changes in I:E ratio induced increases in No concentration of 4% at 2:1, 5% at 1:1, 22% at 1:2, and 31% at 1:4. The addition of dead space enhanced these differences: 62% at 2:1, 104% at 1:1, 230% at 1:2, and 322% at 1:4. CONCLUSION: According to our lung model, continuous-flow administration of NO near the endotracheal tube is influenced strongly by changes in ventilatory settings.

Humans↗
PubMed1996

Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B).

Sanfilippo B syndrome is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes results in degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. In order to clone the deficient gene, we purified the enzyme from human placenta and obtained amino acid sequence information. Alignment of one of the CNBr generated internal peptides to sequence from the database revealed the chromosomal location of the gene in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence was used to clone the cDNA coding for alpha-N-acetylglucosaminidase and analyse its gene structure. The gene is fully contained in the 5' upstream flanking region of the gene for 17-beta-hydroxysteroid-dehydrogenase and interrupted by five introns. The cDNA clone has a length of 2575 bp and encodes a protein of 743 amino acids. Chinese hamster ovary cells transfected with the cDNA construct show alpha-N-acetylglucosaminidase activity about 17-fold over background. This will allow correction studies with NAG deficient Sanfilippo B cell lines and facilitate the development of enzyme replacement therapy for these patients.

Acetylglucosaminidase↗
PubMed1995

[Selective pulmonary vasodilator effect of inhaled nitric oxide in a patient with pulmonary thromboembolism].

The increase in pulmonary vascular resistences in acute pulmonary thromboembolism (APT) is the consequence of anatomical obstruction and pulmonary artery constriction. The administration of inhaled nitric oxide (NO) may be therapeutically useful in acute pulmonary hypertension by APT given its limited vasodilator effect on pulmonary circulation. A patient with APT in whom this selective vasodilator effect was observed is presented. The authors suggest that the administration of inhaled NO may be a potentially beneficial coadjuvant therapy in acute pulmonary hypertension induced by APT.

Administration, Inhalation↗
PubMed1995

Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia.

OBJECTIVE: To determine whether continuous subglottic aspiration prevents nosocomial pneumonia in mechanically ventilated patients. DESIGN: A randomized, controlled, blinded study. SETTING: Medical-surgical intensive care unit. PATIENTS: 190 patients who were admitted to the intensive care unit during a 33-month period and whose condition suggested the need for prolonged intubation (> 3 days). INTERVENTION: 76 patients were randomly allocated to receive continuous aspiration of subglottic secretions, and 77 control patients were allocated to receive usual care. MEASUREMENTS: The numbers of cases of ventilator-associated pneumonia, ventilated days, days in intensive care unit, and deaths were recorded. The amount of subglottic secretions aspirated daily and surveillance cultures in the subglottic secretions were also obtained periodically. Etiologic diagnosis was based on the quantitative culture of secretions obtained by protected specimen brush or bronchoalveolar lavage. RESULTS: The incidence rate of ventilator-associated pneumonia was 19.9 episodes/1000 ventilator days in the patients receiving continuous aspiration of subglottic secretions and 39.6 episodes/1000 ventilator days in the control patients (relative risk, 1.98; 95% CI, 1.03 to 3.82). This difference was due to a significant (P < 0.03) reduction in the number of gram-positive cocci and Haemophilus influenzae organisms in the patients receiving continuous aspiration. However, no differences were observed in the number of Pseudomonas aeruginosa or Enterobacteriaceae organisms. Episodes of ventilator-associated pneumonia occurred later in patients receiving continuous aspiration (12.0 +/- 7.1 days) than in the control patients (5.9 +/- 2.1 days) (P = 0.003). The same microorganisms isolated from protected specimen brush or bronchoalveolar lavage cultures in patients with ventilator-associated pneumonia were previously isolated from cultures of subglottic secretions in 85% of cases. No significant differences in outcome were found. CONCLUSIONS: The incidence of nosocomial pneumonia in mechanically ventilated patients can be significantly reduced by using a simple method that decreases the chronic microaspirations through the cuff of endotracheal tubes.

Aged↗