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Biomedical subjects

G Paret

Publications and source records attributed to G Paret.

At least 19 recordsLinked to original sources

[FK506 (tacrolimus) does not increase hepatic damage due to hypoperfusion].

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver. Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

Animals↗

The role of dextromethorphan in pain control.

PURPOSE: To review the clinical benefits of dextromethorphan (DM) in pain management, describe its neuropharmacological properties. SOURCE: A Medline search was made for experimental and clinical data on DM use from 1967 to date using keywords nociception, acute and chronic pain control, N-methyl-D-aspartate, antagonists, dextromethorphan. PRINCIPLE FINDINGS: The 930 DM citations mostly described its antitussive, metabolic and toxicological aspects, animal studies and its possible role in minimizing post-brain ischemia complications in humans. The use of DM in acute pain revealed eight original studies involving 443 patients, as well as two preliminary reports and our own unpublished data on 513 patients. Most of the 956 patients had general anesthesia. Eight studies (154 patients) and one case report dealt with chronic pain management. This N-methyl-D-aspartate (NMDA) receptor antagonist binds to receptor sites in the spinal cord and central nervous system, thereby blocking the generation of central acute and chronic pain sensations arising from peripheral nociceptive stimuli and enabling reduction in the amount of analgesics required for pain control. DM attenuated the sensation of acute pain at doses of 30-90 mg, without major side effects, and reduced the amount of analgesics in 73% of the postoperative DM-treated patients. Studies in secondary pain models in healthy volunteers and in various types of chronic pain showed DM to be associated with unsatisfactory pain relief. CONCLUSION: DM attenuates acute pain sensation with tolerable side effects. Its availability in oral form bestow advantages over other NMDA antagonists.

Animals↗

Repeat computed tomographic scan within 24-48 hours of admission in children with moderate and severe head trauma.

OBJECTIVE: To asses the yield and contribution of a routine predetermined repeat head computed tomographic (CT) scan within 24-36 hrs in pediatric patients with moderate to severe head trauma. DESIGN: Records review. SETTING: Five pediatric intensive care units. PATIENTS: We reviewed the charts of 173 consecutive pediatric patients with moderate to severe head trauma (Glasgow Coma Scale score of < or = 11) that survived the first 24 hrs after being admitted to five Israeli trauma centers. Clinical data collected included status at admission, at the time between the first and second CT scans, and after the second scan. Head details of the first, second, and, if performed, third CT scan were collected. Treatment strategy during each period was recorded, including any change in treatment after each CT scan. MEASUREMENTS AND MAIN RESULTS: A total of 47 (27%) of the second CT scans showed new lesions including six intracranial hemorrhages, 17 cases of worsening brain edema, and 18 newly diagnosed brain contusions. However, none of these findings necessitated surgical intervention or any change in therapy. Of the 67 patients who underwent a third CT scan, two cases required surgical intervention because of new findings in the third CT. CONCLUSIONS: A second routine prescheduled head CT scan within 24-36 hrs after admission in pediatric patients with moderate to severe head trauma is unlikely to yield any change in therapy. Clinically and intracranial pressure-oriented CT scan may better select and diagnose patients who require changes in therapy, including surgery. Studies aimed to determine the ideal timing for the second are warranted.

Adolescent↗

Problematic intubation in soldiers: are there predisposing factors?

Attempts by a combat medical officer to secure the airway of a multiple-injury patient in the field may frequently end in failure. The recurrence of such failures, despite Advanced Trauma Life Support training, is perplexing; therefore, we studied the prevalence of clinical criteria that could predispose active soldiers to difficult intubation. Such known anatomical features and the Mallampati classification were assessed by experts in 250 soldiers at a military outpatient clinic of the Israel Defense Forces. It was found that most soldiers had normal airways. Limitations of head and neck movement, or in opening the mouth, were not observed. Other risk factors were noted in only a small percentage of the study population. Mallampati classes I and II were noted in 40% and 31%, respectively. No statistically significant differences between young (18-21 years) and older (40-44 years) soldiers were found. It was concluded that difficult intubations among soldiers are unlikely to be associated with anatomical causes. Complicated scenarios and deficient skills of the physicians are the most important factors that contribute to in-field failures to secure airway control. Several recommendations to remedy this situation are offered.

Adolescent↗

Invasive meningococcal disease: patient and strain characteristics set new challenge for prevention and control.

Differences in the course of invasive meningococcal disease, in prevalence, case-to-carrier ratio, geographical pattern, age distribution and antibiotic resistance have been related to major serogroups and their serotypes. The relationships between Neisseria meningitidis serogroups and clinical manifestation, outcome and patient characteristics are assessed. All hospitalized patients in six major hospitals in central Israel with a verified meningococcal disease during 1990-1994 were included (n = 66). Their personal and clinical data and the results of bacteriological and serological tests of their blood and cerebrospinal fluid (CSF) were recorded. Meningococci were isolated from both blood and CSF, from blood alone, and from CSF alone in 60.6%, 18.2%, and 21.2% of the cases, respectively. The highest proportion of isolations were from infants < 1 year (34.8%), followed by children aged 1 to 5 years (25.8%). Serogroup B prevailed in 62.1%, while groups C and W135 accounted for 28.8% and 9.1%, respectively. Serogroup B predominated in children < 1 year, while in patients aged 5-22 years, C strains were the major pathogen (P < 0.001). Serogroup B accounted for 93% of the cases of meningitis, 58% of meningococcemia and 42% of fulminant meningococcemia, while group C strains were the major cause of fulminant meningococcemia (50%). The overall case fatality rate was 7.6%: fulminant meningococcemia 8.3%, and meningococcemia 10%. It was concluded that N. meningitidis group C continues to account for almost a third of the cases of meningococcal disease and is the major cause of fulminant meningococcemia.

Adolescent↗

Atropine pharmacokinetics and pharmacodynamics following endotracheal versus endobronchial administration in dogs.

Emergency endotracheal and endobronchial drug administration provide an effective alternative for intravenous drug delivery during cardiopulmonary resuscitation. The purpose of the present study was to determine the immediate pharmacokinetic and pharmacodynamic properties of atropine following administration by either of these routes. Atropine (0.02 mg/kg) was given to seven anaesthetized mongrel dogs. Each dog was studied twice: once when atropine was injected into the endotracheal tube, and on another day when atropine was given via a flexible catheter wedged into a peripheral bronchus. Plasma atropine concentrations and blood gases were measured during 60 min following drug administration. Both routes of atropine administration differed significantly in three measures: the maximal atropine concentration (Cmax) was significantly higher with the endobronchial administration 40.0 +/- 7.8 ng/ml compared to 23.9 +/- 5 ng/ml endotracheally (P = 0.008); atropine's elimination (t1/2beta) half-life was significantly longer with the endobronchial route (39.3 +/- 5.2 min vs. 28.0 +/- 7.9 min; P = 0.05); Endobronchial administration resulted in an increase of 16% in heart rate, beginning immediately after drug delivery and peaking after 5 min. Other pharmacokinetic parameters were not significantly different. We conclude that endobronchial administration of atropine has a clear advantage over the endotracheal route.

Animals↗

Adapting prognostic respiratory variables of ARDS in children to small-scale community needs.

PURPOSE: The clinical literature on the incidence and subsequent mortality of adult respiratory distress syndrome (ARDS) has come primarily from the experiences of large tertiary referral centers, particularly in Western Europe and North America. Consequently, very little has been published on the incidence, management, and outcome of ARDS in smaller community-based intensive care units. We aimed to delineate early clinical respiratory predictors of death in children with ARDS on the modest scale of a community hospital. MATERIALS AND METHODS: A retrospective chart review of children with ARDS needing conventional mechanical ventilation admitted to our pediatric intensive care unit from 1984 to 1997. The diagnosis of ARDS was based on acute onset of diffuse, bilateral pulmonary infiltrates of noncardiac origin and severe hypoxemia defined by partial pressure of oxygen <200 mm Hg during positive end-expiratory pressure (PEEP) of 6 cm H2O or greater for a minimum of 24 hours. Demographic, clinical, and physiological data including PaO2/ FIO2, A-aDo2, and ventilation index were retrieved. RESULTS: Fifty-six children with ARDS aged 8 +/- 5.5 years (range, 50 days to 21 years) were identified. The mortality rate was 50%. Early predictors of death included the peak inspiratory pressure (PIP), ventilation index, and PEEP on the third day after diagnosis: Nonsurvivors had significantly higher PIP (35.3 +/- 10.5 cm H2O vs 44.4 +/- 10.7 cm H2O, P < .001), PEEP (8 +/- 2.8 cm H2O vs 10.7.0 +/- 3.5 cm H2O, P < .01), and ventilation index (49.14 +/- 20.4 mm Hg x cm H2O/minute vs 61.6 +/- 51.1 mm Hg cm H2O/minute) than survivors. In contrast, PAO2/FIO2 and A-a DO2 were capable of predicting outcome by day 5 and thereafter. CONCLUSIONS: A small-scale mortality outcome for ARDS is comparable to large tertiary referral institutions. The PIP, PEEP, and ventilation index are valuable for predicting outcome in ARDS by the third day of conventional therapy. The development of a local risk profile may assist in decision-making of early application of supportive therapies in this population.

Adolescent↗

Pharmacokinetics of endobronchial tolazoline administration in dogs.

Tolazoline is a potent vasodilator of arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in the systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endobronchial tolazoline to determine the relationship between endobronchial tolazoline administration, plasma concentration, and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endobronchially to seven dogs, and its serum concentration and the hemodynamic parameters were monitored for 270 min postdelivery. It was found that 15 sec after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 9.3+/-8.0 microg x mL(-1) The volume of distribution was 1657+/-321 mL x kg(-1) after 1 2.4+/-1 6.6 min. The extent of tolazoline absorption was 319+/-38 microg x min(-1) mL(-1). The total body clearance was 10.9 +/-4.8 mL x min(-1) x Kg(-1) and the elimination half-life was 156+/-81 min. Endobronchial tolazoline produced an initial short-lived decrease in the mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endobronchial tolazoline a significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. We conclude that an endobronchial bolus dose of tolazoline is effectively absorbed, produces measurable pharmacological effects, and may be beneficial in the therapy of persistent pulmonary hypertension of the newborn.

Absorption↗

Endotracheal tolazoline: pharmacokinetics and pharmacodynamics in dogs.

Tolazoline is a potent vasodilator of both arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36; 13.16) microg/ml. The extent of tolazoline absorption was 305 (148;453) microg/ min/ml. The volume of distribution was 3.4 (1.6;7.4) 1/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.

Animals↗

Advanced trauma life support (ATLS) courses: should training be refocused towards rural physicians?

Recently there has been an increase in the number of courses designed to improve the theoretical knowledge and practical skills of health workers for immediate emergency management under life-threatening conditions. However, the numbers of applicants for these courses far exceed the available places. Priorities should be reviewed to solve the current shortfall. The purpose of this study was to compare the improvement in basic knowledge associated with the advanced trauma life support (ATLS) programme for paediatricians practising in a metropolitan area, with those practising in rural hospitals. This should facilitate proper use of the limited existing resources for training of physicians. A retrospective, comparative analysis of the impact of the ATLS courses for pediatricians was assessed by analysing scores of multiple choice tests before and after the programme. The study group comprised all Israeli paediatricians (n = 72) who completed the course during 1996. Performance was compared between paediatricians working in major, level I (n = 39) and rural, level II trauma centres (n = 33). After the course, all paediatricians improved their scores; those in level I trauma centres improved their mean precourse scores from 72 +/- 13.6 to 85 +/- 5.4, while those working in level II trauma centres improved from 67 +/- 12.4 to 85 +/- 5.0. The impact of the course was reflected in the net and proportional gains. Both were higher for paediatricians working in level II trauma centres, compared with those working in metropolitan trauma centres. Furthermore, the net gain was significantly higher (p < 0.05). Efforts should be made to increase the participation of paediatricians practising in rural level II trauma centres in trauma care courses. Further research should address the applicability of these results for recruiting primary care physicians to the ATLS courses.

Education, Medical, Continuing↗

Long term neurological outcome of herpes encephalitis.

Twenty eight children with herpes simplex encephalitis were followed up for a mean of 5.5 years. Two children died and 26 survived, of whom 16 were left with no neurological sequelae and 10 had persistent neurological sequelae. Mean (SD) Glasgow coma score was significantly lower in the patients with neurological sequelae (7.7 (1.5)) and the patients who died (4.5 (0.7)), compared with the patients without neurological sequelae (11 (1.7)).

Acyclovir↗

Early prediction of neurological outcome after falls in children: metabolic and clinical markers.

Falls are the foremost reason for non-fatal injuries and are second only to motor vehicle accidents in causing accidental death. The purpose of this study was to identify the clinical and metabolic predictors of the outcome of head injury caused by falls from a height. Medical records of 61 children who had been admitted to the paediatric intensive care unit from 1990 to 1993 after falling from a height were reviewed retrospectively. Outcomes were categorised as good, moderate, severe, and poor. Glasgow coma scores, pupillary responses, brain oedema, and midline shift are significantly associated with poor outcome (p < 0.05). Metabolic markers associated with poor outcome included hyperglycaemia and hypokalaemia. Children with a poor outcome had, at admission, significantly higher glucose concentrations compared with children with good outcomes (mean SD): 20.0 (7.1) v 9.31 (4.0) mmol/l, p < 0.01), and lower potassium concentrations compared with children with good, moderate, and severe outcomes (mean (SD): 2.8 (0.4) v 3.7 (0.4) mmol/l, p < 0.001, 3.5 (0.3) mmol/l, p < 0.01, and 3.41 (0.3) mmol/l, p < 0.05, respectively). These findings allow for an early allocation of effort and resources to children injured from such falls.

Accidental Falls↗

Abnormal visual evoked potentials in children with "Alice in Wonderland" syndrome due to infectious mononucleosis.

Visual illusions characterized by distortion of form, size, reciprocal position of objects, movement, or color, labeled as "Alice in Wonderland" syndrome, were discussed in children with infectious mononucleosis, as well as in other clinical conditions, such as migraine, epilepsy, use of certain hallucinogenic drugs, etc. The purpose of our study was to investigate for the first time visual evoked potential results in children with "Alice in Wonderland" syndrome associated with infectious mononucleosis. Five children with "Alice in Wonderland" syndrome associated with infectious mononucleosis underwent visual evoked potential studies during and after their clinical symptoms. Visual evoked potential results during the disease demonstrated statistically significant high amplitudes of P100-N145 in all children compared to the control group. A few weeks later, repeated studies after the resolution of the complaints were normal. Since the same findings can be observed in patients with migraine, we postulate that a common pathophysiologic underlying abnormality, which can cause transient focal decreased cerebral perfusion, could be involved in the disease process of these two conditions.

Adolescent↗

Acute respiratory distress syndrome in children: a 10 year experience.

BACKGROUND: Acute respiratory distress syndrome is a well-recognized condition resulting in high permeability pulmonary edema associated with a high morbidity. OBJECTIVES: To examine a 10 year experience of predisposing factors, describe the clinical course, and assess predictors of mortality in children with this syndrome. METHODS: The medical records of all admissions to the pediatric intensive care unit over a 10 year period were evaluated to identify children with ARDS. Patients were considered to have ARDS if they met all of the following criteria: acute onset of diffuse bilateral pulmonary infiltrates of non-cardiac origin and severe hypoxemia defined by < 200 partial pressure of oxygen during > or = 6 cm H2O positive end-expiratory pressure for a minimum of 24 hours. The medical records were reviewed for demographic, clinical, and physiologic information including PaO2/forced expiratory O2, alveolar-arterial O2 difference, and ventilation index. RESULTS: We identified 39 children with the adult respiratory distress syndrome. Mean age was 7.4 years (range 50 days to 16 years) and the male:female ratio was 24:15. Predisposing insults included sepsis, pneumonias, malignancy, major trauma, shock, aspiration, near drowning, burns, and envenomation. The mortality rate was 61.5%. Predictors of death included the PaO2/FIO2, ventilation index and A-aDO2 on the second day after diagnosis. Nonsurvivors had significantly lower PaO2/FIO2 (116 +/- 12 vs. 175 +/- 8.3, P < 0.001), and higher A-aDO2 (368 +/- 28.9 vs. 228.0 +/- 15.5, P < 0.001) and ventilation index (43.3 +/- 2.9 vs. 53.1 +/- 18.0, P < 0.001) than survivors. CONCLUSIONS: Local mortality outcome for ARDS is comparable to those in tertiary referral institutions in the United States and Western Europe. The PaO2/FIO2, A-aDO2 and ventilation index are valuable for predicting outcome in ARDS by the second day of conventional therapy. The development of a local risk profile may allow early application of innovative therapies in this population.

Acute Disease↗