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Biomedical subjects

M Yaster

Publications and source records attributed to M Yaster.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dopamine transporters are markedly reduced in Lesch-Nyhan disease in vivo.

Dopamine (DA) deficiency has been implicated in Lesch-Nyhan disease (LND), a genetic disorder that is characterized by hyperuricemia, choreoathetosis, dystonia, and compulsive self-injury. To establish that DA deficiency is present in LND, the ligand WIN-35,428, which binds to DA transporters, was used to estimate the density of DA-containing neurons in the caudate and putamen of six patients with classic LND. Comparisons were made with 10 control subjects and 3 patients with Rett syndrome. Three methods were used to quantify the binding of the DA transporter so that its density could be estimated by a single dynamic positron emission tomography study. These approaches included the caudate- or putamen-to-cerebellum ratio of ligand at 80-90 min postinjection, kinetic analysis of the binding potential [Bmax/(Kd x Vd)] using the assumption of equal partition coefficients in the striatum and the cerebellum, and graphical analysis of the binding potential. Depending on the method of analysis, a 50-63% reduction of the binding to DA transporters in the caudate, and a 64-75% reduction in the putamen of the LND patients was observed compared to the normal control group. When LND patients were compared to Rett syndrome patients, similar reductions were found in the caudate (53-61%) and putamen (67-72%) in LND patients. Transporter binding in Rett syndrome patients was not significantly different from the normal controls. Finally, volumetric magnetic resonance imaging studies detected a 30% reduction in the caudate volume of LND patients. To ensure that a reduction in the caudate volume would not confound the results, a rigorous partial volume correction of the caudate time activity curve was performed. This correction resulted in an even greater decrease in the caudate-cerebellar ratio in LND patients when contrasted to controls. To our knowledge, these findings provide the first in vivo documentation of a dopaminergic reduction in LND and illustrate the role of positron emission tomography imaging in investigating neurodevelopmental disorders.

Adolescent↗
PubMed1995

Preanesthetic medication of children with midazolam using the Biojector jet injector.

BACKGROUND: A rapid, dependable, and economical technique to atraumatically sedate children before anesthesia that does not prolong postanesthesia care unit time remains elusive. The Biojector jet injection system uses carbon dioxide rather than a needle to deliver an intramuscular injection. The dose-response relationship when midazolam is administered was studied using this jet injector. METHODS: Forty children (2.3 +/- 1.3 yr old) undergoing elective myringotomy and tube placement were randomly assigned to receive 0.05, 0.1, 0.15, 0.2, or 0.3 mg.kg-1 midazolam injected intramuscularly using the Biojector disposable syringe (0.006-inch orifice). Assessment of each child before, during, and 10 min after injection, on application of the anesthesia face mask, and every 15 min for 1 h after arrival to the postanesthesia care unit was made by an observer blinded to drug dosage. RESULTS: Face mask tolerance using doses > or = 0.1 mg.kg-1 midazolam was acceptable and statistically different from 0.05 mg/kg. Crying on injection tended to increase with increasing dose. All children were awake and arousable, meeting discharge criteria, after 30 min from arrival in the postanesthesia care unit. CONCLUSIONS: Midazolam (0.1-0.15 mg.kg-1) administered using jet injection effectively and rapidly produces sedation, in a manner acceptable to parents, without delaying postanesthesia care unit discharge.

Child, Preschool↗
PubMed1995

Pain relief.

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Administration, Buccal↗
PubMed1994

Interaction of fentanyl and nitrous oxide on peripheral and cerebral hemodynamics in newborn lambs.

BACKGROUND: The ability of opioids to produce complete general anesthesia is controversial. Nitrous oxide (N2O) is often added to fentanyl-based anesthetics to produce unconsciousness and amnesia. The addition of N2O may adversely affects fentanyl's hemodynamic stability and safety. The purpose of this study was to determine the physiologic consequences of combining N2O with fentanyl in newborn animals. METHODS: The effects of 50% nitrous oxide in oxygen (O2), and 50% N2O in O2 combined with 3,000 micrograms/kg fentanyl, on cerebral and peripheral hemodynamics were studied in seven unanesthetized newborn lambs, in whom catheters were previously inserted. After a control period, lambs were placed in a hood in which inspired gas concentrations were controlled and which minimized external stimuli. After 30 min of breathing room air, the lambs breathed 50% N2O in O2 for an additional 30 min. The lambs were then given 3,000 micrograms/kg fentanyl by intravenous bolus and by infusion (1,000 micrograms.kg-1 x h-1) for 60 min while continuing to breathe 50% N2O in O2. RESULTS: All animals responded to pain (tail clamp) and alerted to sound when breathing room air or when N2O was used alone. Adding fentanyl to the N2O abolished all responses to pain, but not to sound. Additionally, fentanyl produced immediate apnea necessitating tracheal intubation and mechanical ventilation. Mean arterial pressure and heart rate increased 27% and 23%, respectively, after fentanyl administration, intubation, and ventilation. It did not change over the course of the fentanyl infusion. Cerebral blood flow, O2 consumption, and O2 delivery did not change when N2O was administered alone or in combination with fentanyl. Splanchnic blood flow was unaffected by treatment over time. Renal blood flow decreased by 21% after fentanyl administration, but was unaffected by N2O alone. Right and left ventricular blood flow increased (47% and 26%, respectively) after fentanyl administration, intubation, and ventilation, but not when N2O was administered alone. CONCLUSIONS: Fentanyl (3,000 micrograms/kg) when combined with 50% N2O in O2 produced a plane of general anesthesia in newborn lambs in which the behavioral responses to painful stimuli were abolished. The response to sound was never eliminated, nor was cerebral oxygen consumption decreased. The combination of 50% N2O in O2, 3,000 micrograms/kg fentanyl, tracheal intubation, and mechanical ventilation did not depress heart rate, blood pressure, or blood flow to any of the major organs, except the kidneys.

Anesthesia, General↗
PubMed1994

Epidural analgesia in the management of severe vaso-occlusive sickle cell crisis.

OBJECTIVES: To determine whether continuous epidural analgesia could effectively decrease pain and thereby improve the management of severe vaso-occlusive crisis in children with sickle cell disease who were unresponsive to conventional analgesic therapy. DESIGN: Retrospective observational study. SETTING: A tertiary care hospital with a large pediatric sickle cell patient referral population. PATIENTS: The study describes nine children in 11 painful vaso-occlusive crises, unresponsive to high-dose systemic opioids, nonsteroidal anti-inflammatory drugs, and adjunctive measures, who underwent continuous epidural analgesia to control pain. OUTCOME MEASURES: Subjective pain scores, arterial oxygen saturation monitoring, and plasma lidocaine levels. METHODS: Placement of an epidural catheter for the administration of a continuous infusion of local anesthetic, alone, or in combination with fentanyl, in the management of vaso-occlusive crisis. RESULTS: An initiation of epidural analgesic therapy, 8 of 9 patients reported severe pain (8 to 10 on a scale of 0 to 10, 0 = no pain, 10 = the worst pain they ever experienced). Analgesic was immediate (pain score 0 to 2) in 8 of 9 patients, and continuously effective in 9 of 11 crises. Five patients required either the addition of fentanyl or changing the local anesthetic from lidocaine to bupivacaine to maintain analgesia for 2 to 5 days. In 7 of 9 patients, oxygen saturation dramatically increased from 87 to 95% to 99 to 100% after epidural analgesia was initiated. In all patients, plasma lidocaine levels ranged from 1.1 to 4.6 mg/L and dose-related toxicity did not occur. One patient developed hypotension secondary to high sympathetic blockade (T-4), one had an inadvertent dural puncture during insertion of the catheter, one had the epidural catheter removed for fever, and one achieved analgesia only transiently. There were no other complications, and epidural analgesia was not associated with sedation, respiratory depression, or limitation of movement. All epidural catheters were cultured on removal, and colonization did not occur. CONCLUSIONS: Epidural analgesia with local anesthetics administered alone or in combination with fentanyl effectively and safely treats the pain of sickle cell vaso-occlusive crisis unresponsive to conventional pain management and does so without causing sedation, respiratory depression, or significant limitation on ambulation. Furthermore, early treatment of painful crisis with this technique may improve oxygenation, a critical factor in the evolution of further sickling.

Analgesia, Epidural↗
PubMed1993

Disposition and respiratory effects of intrathecal morphine in children.

BACKGROUND: The extent and duration of respiratory depression after opioid administration are poorly defined in infants and children. METHODS: The disposition and respiratory effects of intrathecal morphine were studied in ten patients (ages 4 months-15 yr) after repair of craniofacial defects. Morphine, 0.02 mg/kg, was administered intrathecally before the end of surgery. Postoperatively, we determined the minute ventilation (VE) in response to increasing partial pressure of end-tidal carbon dioxide (PETCO2) during carbon dioxide rebreathing. The slope (VE/PETCO2) and intercept (VE at PETCO2 60 mmHg, VE 60) of the carbon dioxide response curve were calculated at 6, 12, and 18 h after morphine administration. Cerebrospinal fluid (CSF) and blood were analyzed for morphine concentration by radioimmunoassay. RESULTS: Mean VE/PETCO2 decreased from a preoperative value of 35.1 +/- 3.7 to 16.3 +/- 2.8 ml.kg-1 x min-1 x mmHg-1 at 6 h after morphine, and remained depressed to 23.4 +/- 2.9 and 23.5 +/- 3.3 ml.kg-1 x min-1 x mmHg-1 at 12 h and 18 h, respectively, compared to preoperatively). The infants' (n = 3) VE/PETCO2 at 6 h were 21, 4, and 27 ml.kg-1 x min-1 x mmHg-1. Mean VE 60 decreased from 874 +/- 125 to 276 +/- 32 ml x kg-1 x min-1 at 6 h, but then recovered at 12 and 18 h to 491 +/- 68 and 567 +/- 82 ml.kg-1 x min-1, respectively. The infants' VE 60 at 6 h were 350, 142, and 245 ml.kg-1 x min-1. Mean CSF morphine concentration was 2,860 +/- 540 ng/ml at 6 h, and decreased to 640 +/- 220 and 220 +/- 150 ng/ml at 12 and 18 h, respectively. CONCLUSIONS: Intrathecal morphine, 0.02 mg/kg, depressed the ventilatory response to carbon dioxide for up to 18 h concomitant with increased CSF morphine concentrations. Infants (4-12 months of age) did not exhibit greater ventilatory depression than did children (2-15 yr of age).

Administration, Inhalation↗
PubMed1991

Preinduction of anesthesia in children with rectally administered midazolam.

The authors evaluated the efficacy of rectally administered midazolam for preinduction (i.e., premedication/induction) of anesthesia in 67 pediatric patients, ASA physical status 1 or 2, undergoing a variety of elective surgical procedures. In phase 1, 41 children weighing 12 +/- 3 kg (range 7-20 kg) and 31 +/- 16 months (range 8-67 months) of age (mean +/- SD) received midazolam, 0.4-5.0 mg.kg-1, in an attempt to produce unconsciousness. Only one child lost consciousness (4.5 mg.kg-1). However, at all doses, inhalational induction of anesthesia was facilitated because children were tranquil and calmly separated from their parent(s). There were no clinically significant changes in arterial blood pressure, heart rate, oxyhemoglobin saturation, and end-tidal carbon dioxide concentration, 10 min after drug administration. In phase 2, 26 children weighing 17 +/- 4 kg (range 10-26 kg) and 44 +/- 19 months (range 17-84 months) months of age undergoing tonsil and/or adenoid surgery were studied to determine the optimal sedative dose of rectally administered midazolam. Patients received 0.3, 1.0, 2.0, or 3.0 mg.kg-1 of midazolam in a randomized, double-blind fashion. One third (3 of 9) of patients receiving 0.3 mg.kg-1 struggled during mask induction. All patients receiving greater than or equal to 1.0 mg.kg-1 were adequately sedated (P less than 0.008). Discharge from the postanesthesia care unit (PACU), however, was delayed (greater than 60 min) in children receiving greater than or equal to 2.0 mg.kg-1 (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Rectal↗
PubMed1989

Prediction of successful primary closure of congenital abdominal wall defects using intraoperative measurements.

To determine whether intragastric pressure (IGP) and central venous pressure (CVP) would reliably predict successful primary closure of congenital abdominal wall defects (omphalocele/gastroschisis) in newborn infants, we developed the following prospective intraoperative management protocol. Following a temporary trial of fascial closure, infants who had an IGP less than 20 mm Hg or an increase in CVP of less than 4 mm Hg were primarily closed. If IGP was greater than 20 mm Hg or if CVP increased by more than 4 mm Hg, the temporary closure of the abdomen was reopened and a prosthetic silo was placed. Ten infants who were less than 24 hours old and averaged 2.7 kg (range, 1.4 to 4.2 kg) and 37-weeks gestation (range, 32 to 41 weeks) were studied. Eight infants met criteria for primary closure. Their IGP averaged 14 +/- 4 mm Hg (+/- SD) (range, 8 to 19 mm Hg), and their increase in CVP averaged 1 +/- 2 mm Hg (range, -2 to 3 mm Hg). In the two infants who required staged repair, IGP averaged 25 +/- 1 mm Hg (+/- SD) (range, 24 to 25 mm Hg), and the increase in CVP averaged 7 +/- 1 mm Hg (range, 6 to 8 mm Hg). All patients were anesthetized with fentanyl (12.5 micrograms/kg) and paralyzed with metocurine (0.3 mg/kg) intraoperatively. There were no postoperative complications in either group of patients related to increased intraabdominal pressure, and all patients were extubated within 48 hours of the initial surgery. We conclude that the intraoperative measurement of changes in IGP and CVP can serve as a guide to the operative management of congenital abdominal wall defects and can reliably predict successful outcome following repair.

Abdominal Muscles↗