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Biomedical subjects

Asher Barak

Publications and source records attributed to Asher Barak.

15 recordsLinked to original sources

Long term nutritional rehabilitation by gastrostomy in Israeli patients with cystic fibrosis: clinical outcome in advanced pulmonary disease.

OBJECTIVES: Several studies have shown a linear correlation between nutritional status and pulmonary function in patients with cystic fibrosis. Our study aims were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on nutritional, clinical, and pulmonary parameters, and 2) To identify predicting factors for success of long-term nutritional rehabilitation. METHODS: Twenty-one Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from 1992 to 2001. All patients were pancreatic insufficient, and all carried severe mutations (W1282X in 62% of the patients). Anthropometric and clinical data were obtained for each patient: 0-12 months before and 6-12 months and 18-24 months after gastrostomy placement. Standard deviation scores (SDS) for height, weight, and body mass index as well as percent of height-appropriate body weight were calculated. RESULTS: The mean percent-of-predicted forced expiratory volume in 1 second (FEV1) decreased significantly during the first year of gastrostomy feeding (n = 16), from 44.2% +/- 13.9 to 41% +/- 13.3 (P = 0.05). However, during the second year of therapy (n = 10), a trend toward improvement was observed (from 39.4 +/- 12.1 to 41.4 +/- 16.1). Weight, and BMI z-scores as well as weight percent-of ideal body weight increased significantly. Height z-score for age decreased during the first year (from -1.9 +/- 1.3 to -2.1 +/- 1.4), However, a trend toward improvement was observed during the second year. A significant correlation was found between the change in weight z-score and height z-score during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P < 0.001) years. There was no difference between compliers and noncompliers regarding height, weight, and BMI either before or after gastrostomy placement. A significant correlation between age at insertion of gastrostomy and improvement in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related diabetes (n = 8) did not affect the response to supplemental feeding. CONCLUSIONS: We observed a trend toward improvement of pulmonary disease during the second year, and a significant improvement in weight, height, and BMI z-scores. Compliance, diabetes, and young age prior to tube insertion did not predict success of nutritional rehabilitation.

Adolescent↗

Characterization of human metapneumovirus infections in Israel.

Respiratory tract infections are a leading cause of morbidity and mortality worldwide. Even with the advancement of diagnostic tools, the causative agent of 20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly identified human respiratory virus, human metapneumovirus (hMPV), was discovered in young children in The Netherlands. To study the prevalence of hMPV infections in Israeli children, respiratory specimens from 388 hospitalized children less than 5 years of age were evaluated for the presence of hMPV RNA, which was present in 42 (10.8%) of these samples. All hMPV-positive samples were negative for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B, adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV activity was between the months February and April. Sequence analysis of 20 positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have circulated in central Israel during the study period. Moreover, three of the four known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples. Seroprevalence of hMPV in 204 patients from the central part of Israel revealed that 100% of the children are hMPV seropositive by the age of 5 years old. We conclude that hMPV is a common respiratory pathogen in Israel, while mixed infections of hMPV with RSV or Flu in hospitalized children are apparently rare.

Adolescent↗

Methacholine bronchial provocation measured by spirometry versus wheeze detection in preschool children.

BACKGROUND: Determination of PC20-FEV1 during Methacholine bronchial provocation test (MCT) is considered to be impossible in preschool children, as it requires repetitive spirometry sets. The aim of this study was to assess the feasibility of determining PC20-FEV1 in preschool age children and compares the results to the wheeze detection (PCW) method. METHODS: 55 preschool children (ages 2.8-6.4 years) with recurrent respiratory symptoms were recruited. Baseline spirometry and MCT were performed according to ATS/ERS guidelines and the following parameters were determined at baseline and after each inhalation: spirometry-indices, lung auscultation at tidal breathing, oxygen saturation, respiratory and heart rate. Comparison between PCW and PC20-FEV1 and clinical parameters at these end-points was done by paired Student's t-tests. RESULTS AND DISCUSSION: Thirty-six of 55 children (65.4%) successfully performed spirometry-sets up to the point of PCW. PC20-FEV1 occurred at a mean concentration of 1.70+/-2.01 mg/ml while PCW occurred at a mean concentration of 4.37+/-3.40 mg/ml (p < 0.05). At PCW, all spirometry-parameters were markedly reduced: FVC by 41.3+/-16.4% (mean +/-SD); FEV1 by 44.7+/-14.5%; PEFR by 40.5+/-14.5 and FEF25-75 by 54.7+/-14.4% (P < 0.01 for all parameters). This reduction was accompanied by de-saturation, hyperpnoea, tachycardia and a response to bronchodilators. CONCLUSION: Determination of PC20-FEV1 by spirometry is feasible in many preschool children. PC20-FEV1 often appears at lower provocation dose than PCW. The lower dose may shorten the test and encourage participation. Significant decrease in spirometry indices at PCW suggests that PC20-FEV1 determination may be safer.

Asthma↗

The role of computer games in measuring spirometry in healthy and "asthmatic" preschool children.

STUDY OBJECTIVES: To explore the role of respiratory interactive computer games in teaching spirometry to preschool children, and to examine whether the spirometry data achieved are compatible with acceptable criteria for adults and with published data for healthy preschool children, and whether spirometry at this age can assess airway obstruction. DESIGN: Feasibility study. SETTINGS: Community kindergartens around Israel and a tertiary pediatric pulmonary clinic. PARTICIPANTS: Healthy and asthmatic preschool children (age range, 2.0 to 6.5 years). INTERVENTION: Multi-target interactive spirometry games including three targets: full inspiration before expiration, instant forced expiration, and long expiration to residual volume. MEASUREMENTS AND RESULTS: One hundred nine healthy and 157 asthmatic children succeeded in performing adequate spirometry using a multi-target interactive spirometry game. American Thoracic Society (ATS)/European Respiratory Society spirometry criteria for adults for the start of the test, and repeatability were met. Expiration time increased with age (1.3 +/- 0.3 s at 3 years to 1.9 +/- 0.3 s at 6 years [+/- SD], p < 0.05). FVC and flow rates increased with age, while FEV1/FVC decreased. Healthy children had FVC and FEV1 values similar to those of previous preschool studies, but flows were significantly higher (> 1.5 SD for forced expiratory flow at 50% of vital capacity [FEF50] and forced expiratory flow at 75% of vital capacity [FEF75], p < 0.005). The descending part of the flow/volume curve was convex in 2.5- to 3.5-year-old patients, resembling that of infants, while in 5- to 6-year-old patients, there was linear decay. Asthma severity by Global Initiative for Asthma guidelines correlated with longer expiration time (1.7 +/- 0.4 s; p < 0.03) and lower FEF50 (32 to 63%; p < 0.001) compared to healthy children. Bronchodilators improved FEV1 by 10 to 13% and FEF50 by 38 to 56% of baseline. CONCLUSIONS: Interactive respiratory games can facilitate spirometry in very young children, yielding results that conform to most of the ATS criteria established for adults and published data for healthy preschool children. Spirometric indexes correlated with degree of asthma severity.

Airway Obstruction↗

Pregnancies and outcome in women with cystic fibrosis.

BACKGROUND: Along with the increased life expectancy in cystic fibrosis and the remarkable progress in its management and therapy, issues of female fertility and pregnancy are frequently raised. These include infertility, severity of lung disease, pancreatic insufficiency, poor nutritional status, glucose intolerance and diabetes, drug safety, and long-term maternal and neonatal outcome. OBJECTIVE: To describe the experience of our CF center in the management of CF pregnant woman from 1977 to 2004. METHODS: We analyzed 27 years of records (1977-2004) of the national CF registry of all CF women who wished to conceive and became pregnant. RESULTS: Eight CF women (mean age 24 +/- 4.5 years) who wished to conceive had 11 pregnancies and delivered 12 neonates. The pregestational results of forced expiratory volume per 1 second varied significantly among patients (59 +/- 23%), yet most (10/11) stayed stable throughout the pregnancy course. Maternal deterioration in CF condition occurred in only one mother, necessitating cesarean section. In 9 of the 11 pregnancies the women were pancreatic-insufficient. Of the 11 pregnancies, 2 CF women had diabetes mellitus and 3 developed gestational diabetes. One pregnancy occurred in a mother with a transplanted lung. Of the 12 neonates, 3 were preterm and one was born with esophageal atresia. No miscarriages, terminations or neonatal mortalities occurred. Although most of the CF mothers had FEV1 below 55% before pregnancy, the maternal and neonatal outcome was favorable and lung function tests generally remained stable. CONCLUSIONS: We conclude that pregnancy in CF is feasible with a positive maternal and neonatal outcome. Early participation of the CF physician in the wish of the CF woman to reproduce is required. The integration of an intensive multidisciplinary approach during pregnancy, which includes close follow-up of maternal and fetal condition by the various specialists, should ensure an optimal outcome.

Adult↗

Long-term non-invasive positive pressure ventilation among cystic fibrosis patients awaiting lung transplantation.

BACKGROUND: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF patients with end-stage lung disease. OBJECTIVES: To determine the role of NIPPV in CF patients awaiting lung transplantation. METHODS: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode. RESULTS: The patients' mean age at initiation of BiPAP was 15 years (range 13-40 years) and the mean duration of BiPAP usage was 8 months (range 3-16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m2). Blood pH, PaCO2, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage. CONCLUSIONS: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.

Adolescent↗

Endobronchial adrenaline: should it be reconsidered? Dose response and haemodynamic effect in dogs.

BACKGROUND: Tracheal drug administration is a route for drug delivery during cardiopulmonary resuscitation when intravenous access is not immediately available. However, tracheal adrenaline (epinephrine) injection has been recently shown to be associated with detrimental decrease in blood pressure. This was attributed to exaggerated early beta2 mediated effects unopposed by alpha-adrenergic vasoconstriction. We hypothesized that endobronchial adrenaline administration is associated with better drug absorption, which may abolish the deleterious drop of blood pressure associated with tracheal drug administration. OBJECTIVE: To determine haemodynamic variables after endobronchial adrenaline administration in a non-arrest canine model. DESIGN: Prospective, randomized, laboratory study. METHODS: Adrenaline (0.02, 0.05, 0.1 mg/kg) diluted with normal saline was injected into the bronchial tree of five anaesthetized dogs. Injection of 10-ml saline served as control. Heart rate, blood pressure and arterial blood gases were monitored for 60 min after drug instillation. The protocol was repeated after 1 week. RESULTS: Adrenaline at a dose of 0.02 mg/kg produced only a minor initial decrease in diastolic (from 90 +/- 5 to 78 +/- 3 mmHg, P=0.05), and mean blood pressure (from 107 +/- 4 to 100 +/- 3 mmHg, P=0.05), in all dogs. This effect lasted less then 30 s following the drug administration. In contrast, higher adrenaline doses (0.05 and 0.1 mg/kg) produced an immediate increase in diastolic (from 90 +/- 5 to 120 +/- 7 mmHg; and from 90 +/- 5 to 170 +/- 6 mmHg, respectively), and mean blood pressure (from 107 +/- 4 to 155 +/- 10 mmHg; and from 107 +/- 4 to 219 +/- 6 mmHg, respectively). All adrenaline doses resulted in an immediate increase in systolic blood pressure and pulse. Endobronchial administration of saline (control) affected none of the haemodynamic variables. CONCLUSIONS: In a non-arrest model, endobronchial adrenaline administration, as opposed to the effect of tracheal adrenaline, produced only a minor decrease in diastolic and mean blood pressure. We suggest that endobronchial adrenaline administration should be investigated further in a CPR low-flow model when maintaining adequate diastolic pressure may be crucial for survival.

Animals↗

Tracheal epinephrine or norepinephrine preceded by beta blockade in a dog model. Can beta blockade bestow any benefits?

Tracheal epinephrine (adrenaline) has been associated with two major deletorious side effects: increased heart rate (HR) and an initial decrease of blood pressure (BP). This prospective randomized animal study compared the haemodynamic responses to tracheally administered epinephrine or norepinephrine (nor adrenaline) alone versus each after pretreatment with propranolol for ameliorating those two untoward effects associated with epinephrine administration. Five anaesthetized mongrel dogs underwent 25 experiments of tracheal epinephrine or norepinephrine (0.02 mg/kg diluted with normal saline to 5 ml total volume) with or without an I/V non-selective beta-blocker (propranolol 0.1 mg/kg) pretreatment, and served as their own controls. Tracheal epinephrine alone produced a rise in both diastolic and mean arterial BP and an increase of HR. Tracheal norepinephrine alone produced the largest increase of diastolic and mean BP but this change was associated with a significant tachycardia (from 37 to 72/m, P<0.001). While both epinephrine or norepinephrine after pretreatment with propranolol produced a significant increase in both diastolic (from 106 to 166 mmHg and from 118 to 169 mmHg, respectively) (P<0.01) and mean BP (from 122 to 183 mmHg and from 133 to 188 mmHg, respectively) (P<0.01), only propranolol-pretreated tracheal epinephrine yielded a significant decrease in HR (from 52 to 33/m, P=0.002). Pretreatment with a beta-blocker protected against the deleterious tachycardia associated with epinephrine or norepinephrine and, by doing so, may improve the myocardial oxygen supply-and-demand balance. At the same time, the pretreatment augmented the relatively mild diastolic BP increase associated with the beta-adrenergic effect of epinephrine.

Analysis of Variance↗

Liver cirrhosis and portal hypertension in cystic fibrosis.

OBJECTIVES: Liver disease is the second cause of death in cystic fibrosis. The most deleterious complication of liver disease is portal hypertension, which has an estimated prevalence of up to 8%. Portal hypertension may manifest itself by splenomegaly, hypersplenism, gastro-oesophageal bleeding and ascites. The aim of our study was to determine the prevalence, risk factors and invasive management of portal hypertension at our centre. METHODS: One hundred and fifty patients with cystic fibrosis were followed up between 1975 and 2000 in the national cystic fibrosis centre in Israel. Forty patients (27%) had liver disease. All underwent clinical evaluation and laboratory and imaging studies. RESULTS: Portal hypertension was diagnosed in 10 patients (7%), of whom eight were male. The mean age at diagnosis was 11 years (range, 4-17 years). All had severe mutations of the cystic fibrosis transmembrane conductance regulator gene (the CFTR gene), pancreatic insufficiency, meconium ileus or distal intestinal obstruction syndrome and variceal bleeding. Seven patients underwent sclerotherapy to control acute bleeding. Four underwent portosystemic shunting (functioning up to 37 years). Two patients with severe lung and liver disease underwent transjugular intrahepatic portosystemic shunting, which provided bleeding control, but both died while waiting for lung/liver transplantation. One patient underwent liver transplantation due to liver failure and still had good liver and lung function 10 years later. CONCLUSIONS: Portal hypertension is more common among Israeli patients with cystic fibrosis. The unique genetic composition of our population may explain this phenomenon. Risk factors include male gender, pancreatic insufficiency, severe CFTR mutations, meconium ileus and meconium ileus equivalent. Sclerotherapy is the main option to control oesophageal variceal bleeding, while portosystemic shunts offer a prolonged alternative treatment for refractory bleeding. A transjugular intrahepatic portosystemic shunt and liver transplantation may also be effective, but further research is required in order to establish their role.

Adolescent↗

Should vasopressin replace adrenaline for endotracheal drug administration?

OBJECTIVE: Arginine vasopressin was established recently as a drug of choice in the treatment of cardiac arrest and in retractable ventricular fibrillation; however, the hemodynamic effect of vasopressin following endotracheal drug administration has not been fully elucidated. We compared the effects of endotracheally administered vasopressin vs. adrenaline on hemodynamic variables in a canine model, and we investigated whether vasopressin produces the same deleterious immediate blood pressure decrease as did endotracheal adrenaline in the canine model. DESIGN: Prospective controlled study. SETTING: Animal laboratory in Tel-Aviv University, Israel. SUBJECTS: Five adult mongrel dogs weighing 6.5-20 kg. INTERVENTIONS: Dogs were anesthetized; each dog was intubated orally, and both femoral arteries were cannulated for the measurement of arterial pressure and for sampling blood gases. Each dog was studied four times, 1 wk apart, by using the same protocol for injection and anesthesia: endotracheal placebo (10 mL NaCl 0.9%,), endotracheal vasopressin (1 units/kg), endobronchial adrenaline (0.1 mg/kg), and endotracheal adrenaline (0.1 mg/kg). Following placebo, vasopressin, and adrenaline instillation, five forced manual ventilations were delivered with an Ambu bag. Each dog was its own control. MEASUREMENTS AND MAIN RESULTS: Following placebo or drug administration, heart electrocardiography and arterial pressures were continuously monitored with a polygraph recorder for 1 hr. Endotracheal vasopressin produced an immediate increase of diastolic blood pressure (from 83 +/- 10 mm Hg [baseline] to 110 +/- 5 mm Hg at 1 min postinjection). This response lasted >1 hr. In contrast, both endotracheal and endobronchial administration of adrenaline produced an early and significant (p <.05) decrease in diastolic and mean blood pressures. The diastolic blood pressure increase from 85 +/- 10 mm Hg to 110 +/- 10 mm Hg took an ill-afforded 55 secs following endotracheal adrenaline. Diastolic blood pressure was significantly (p <.05) higher following vasopressin compared with adrenaline administration in both routes. CONCLUSIONS: Vasopressin accomplishes its hemodynamic effect, particularly on diastolic blood pressure, more rapidly, vigorously, and protractedly and to a significant degree compared with both endotracheal and endobronchial adrenaline. Evaluation of the effects of endotracheal vasopressin in a closed chest cardiopulmonary resuscitation model is recommended.

Animals↗

Reversal of digital clubbing after lung transplantation in cystic fibrosis patients: a clue to the pathogenesis of clubbing.

Digital clubbing is a common sign in cystic fibrosis (CF) and in a variety of other diseases. However, its pathogenesis remains obscure. In diseases other than CF, regression of clubbing has been noted after cure of the underlying disease. The aim of this study was to assess whether clubbing is reversible in CF patients after lung transplantation. Digital clubbing was investigated in 3 CF patients, prior to and after lung transplantation. Distal phalangeal depth (DPD) and interphalangeal depth (IPD) of the index finger were measured using a skinfold caliper, and the DPD/IDP ratio was calculated. The mean DPD/IDP ratio was 1.08 +/- 0.05 prior to transplantation and 1.00 +/- 0.06, 0.96 +/- 0.06, 0.92 +/- 0.04, and 0.89 +/- 0.07 at 3, 6, 12, and 24 months after transplantation, respectively. In all 3 patients, the DPD/IDP ratio was greater than 1 before transplantation. In 2 patients, this ratio decreased to less than 1 within 3 months, and in the third patient within 9 months after surgery. We conclude that digital clubbing is reversible in CF patients who undergo lung transplantation. Regression was usually noted during the first 3 months posttransplantation. This could be explained either by adequate inactivation of a circulating clubbing-inducing molecule by the normal transplanted lungs, or by removal of the diseased lungs in which this presumably causative substance was produced.

Adult↗

Endotracheal epinephrine: a call for larger doses.

UNLABELLED: Endotracheal administration of epinephrine 0.02 mg/kg (twice the IV dose) is recommended when IV access is unavailable during cardiopulmonary resuscitation. The standard IV dose has been considered too small for the endotracheal route by causing a detrimental decrease of arterial blood pressure (BP), presumably mediated by the beta-adrenergic receptor unopposed by alpha adrenergic vasoconstriction. We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase BP. After injecting normal saline (control), saline-diluted epinephrine (0.02, 0.035, 0.1, 0.2, and 0.3 mg/kg) was injected into the endotracheal tube of five anesthetized dogs at least 1 wk apart. Arterial blood samples for blood gases were collected before and at 14 time points up to 60 min after the drug administration. Heart rate and arterial BP were continuously monitored with a polygraph recorder. Only the 0.3 mg/kg dose successfully caused an increase in BP, observed 2 min after administration, and lasting for 10 min. An early decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. IMPLICATIONS: We conducted a prospective, randomized, laboratory comparison of increasing doses of endotracheal epinephrine to ascertain the yet undetermined optimal dose of endotracheal epinephrine that would increase arterial blood pressure (BP). A decrease in BP was obviated only at a dose equivalent to 10-fold the currently recommended one. Clinical studies using larger doses of endotracheal epinephrine and their use as first-line therapy in cardiac arrest are warranted.

Animals↗

Postnatal management of resolving fetal lung lesions.

OBJECTIVES: Lung lesions are increasingly diagnosed since the advent of routine prenatal ultrasound. These lesions seem to involute in 15% to 30% of cases. Postnatal evaluation is frequently limited, particularly when repeated ultrasound or initial chest radiographs are normal. As careful follow-up or resection may be required, accurate diagnosis is essential. The objective of this study was to determine whether prenatal lung lesions that seem to resolve are still present when evaluated more closely. METHODS: We followed 24 cases of prenatally diagnosed lung lesions at our center, using repeated chest radiographs and chest computerized tomography (CT). RESULTS: Some lesions caused mild mediastinal shift, but none showed hydrops fetalis. In 7 cases, the last prenatal ultrasound was negative. In 15 cases, initial postnatal chest radiograph was normal and in only 4 of these, the lesion was seen on later chest radiographs. This apparently high rate of resolution was, however, misleading. In 22 of the 23 cases in which CT was performed, lung cysts or lobar overinflation was clearly demonstrated. CONCLUSIONS: Apparent involution of lung lesions on serial prenatal ultrasounds or neonatal chest radiograph can be misleading. We strongly recommend repeated radiographs and chest CT for definitive diagnosis in all cases.

Cysts↗