Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating... more
Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating baclofen withdrawal syndrome. To complete a preliminary study of IV baclofen in dogs. Single bolus IV doses (0.5, 2 and 3 mg/kg) as well as multiple dose regimens were evaluated. Sedation and clinical tolerability was assessed by modified Glasgow Coma Scale and Discomfort and Behaviour Scale. Baclofen concentration-time profiles following single IV boluses were best fit by a two-compartment model which was used to predict plasma concentrations for the multiple dose regimens. The mean distribution and elimination half-lives were 11 min and 222 min, respectively. Maximum clinical effect did not occur until approximately 120 min. The discomfort score increased proportionately with increased single IV bolus doses. Multiple dose regimens resulted in greater tha...
Research Interests: Pain, Pharmacokinetics, Medicine, Dogs, Humans, and 14 morePharmacology and Clinical pharmacy, Female, Animals, Male, Anesthesia, Sedation, Shell Half-Life, Baclofen, Pharmacodynamics, Biological Availability, Area Under Curve, Tolerability, discontinuation, and Pharmacology and pharmaceutical sciences
Sixty elementary schools in Minneapolis were asked to participate in a study to evaluate the most effective education method to increase booster seat knowledge and use in kindergarten-age children. School personnel selected one of the... more
Sixty elementary schools in Minneapolis were asked to participate in a study to evaluate the most effective education method to increase booster seat knowledge and use in kindergarten-age children. School personnel selected one of the following interventions: (1) written information, (2) parent education class and a free booster seat, or (3) student education and a free booster seat. Twenty schools participated, with 132 parents completing the telephone interview 3 to 6 months post-survey. Providing instructions to parent groups and teaching children in the classroom, along with providing an incentive booster seat, was shown to increase booster seat use. Providing information only was found to be ineffective. Pediatric and school nurses should focus their injury prevention efforts beyond written materials. Results indicate that presentations for children and their parents, along with incentives, can result in changes in behavior.
Research Interests:
The absorption of valproic acid administered by rectal suppository was studied in six male volunteers. Valproic acid was incorporated into a synthetic lipid base in our pharmacy. Each subject received 500 mg of valproic acid by rectal... more
The absorption of valproic acid administered by rectal suppository was studied in six male volunteers. Valproic acid was incorporated into a synthetic lipid base in our pharmacy. Each subject received 500 mg of valproic acid by rectal suppository and 500 mg of oral valproate sodium syrup one week apart; 13 blood samples were drawn to determine serum concentrations over 48 hours after administration of each formulation. Significant differences were evident in the amount absorbed, maximum serum concentration, and time to achieve maximum serum concentration between the oral and rectal formulations. Mean absorption after rectal suppository was 80%. Maximum serum concentration was 43.4 mg/L after oral administration and 29.2 mg/L after rectal suppository. The time to achieve maximum serum concentration was 1.0 hour after oral syrup and 3.1 hours after rectal suppository. Absorption of the rectal suppository was consistent and complete within 3 hours. The use of valproate sodium in rectal suppository form can be a more convenient and satisfactory method of administering valproic acid when the oral route is impossible. Dosage increases may be necessary, and serum concentrations should be monitored.
Research Interests:
Research Interests:
Despite significant advances in automatic garage door opener design, automatic garage door openers continue to severely injure or kill children. In this investigation, we sought to determine the frequency and circumstances of accidents... more
Despite significant advances in automatic garage door opener design, automatic garage door openers continue to severely injure or kill children. In this investigation, we sought to determine the frequency and circumstances of accidents that have caused severe injury or death to children. We also tried to develop a means by which homeowners can evaluate their door openers. We present the histories of three children severely injured or killed by automatic garage door openers. We reviewed national data of similar accidents primarily published by the US Product Safety Commission and Underwriters Laboratories. Also, we evaluated 50 automatic door openers for safety of operation. The reversing mechanisms of door openers were tested using a cardiopulmonary resuscitation mannequin, a roll of paper towels, and a block of wood. In the United States, at least 85 children have had permanent brain injury or have died since 1974 as a result of accidents involving automatic door openers. A review ...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating... more
Abrupt discontinuation of baclofen therapy is associated with a clinically serious withdrawal syndrome. Current treatment modalities are often ineffective. Intravenous (IV) baclofen is a potential method for preventing or treating baclofen withdrawal syndrome. To complete a preliminary study of IV baclofen in dogs. Single bolus IV doses (0.5, 2 and 3 mg/kg) as well as multiple dose regimens were evaluated. Sedation and clinical tolerability was assessed by modified Glasgow Coma Scale and Discomfort and Behaviour Scale. Baclofen concentration-time profiles following single IV boluses were best fit by a two-compartment model which was used to predict plasma concentrations for the multiple dose regimens. The mean distribution and elimination half-lives were 11 min and 222 min, respectively. Maximum clinical effect did not occur until approximately 120 min. The discomfort score increased proportionately with increased single IV bolus doses. Multiple dose regimens resulted in greater than proportionate discomfort scores based on total dose and were generally not as well tolerated. If projected for human use, our data suggests that initial IV baclofen doses will need to be reduced by approximately one-third of the usual oral dose, and clinicians should observe patients for several hours before administering subsequent doses.
Research Interests: Pain, Dogs, Humans, Female, Animals, and 5 moreMale, Shell Half-Life, Baclofen, Biological Availability, and Area Under Curve
Research Interests: Cognitive Science, Neurology, Phospholipids, Adolescent, Vibration, and 19 moreMovement disorders, Proprioception, Gait, Humans, Child, Female, Male, Reaction Time, Tremor, Electromyography, Hypertrophy, Clinical Sciences, Middle Aged, Adult, Time Factors, Peripheral nerves, Postural Balance, Syndrome, and Neurosciences
Research Interests:
ABSTRACT The case of an infant who presented twice with water intoxication due to excessive intake alone was discussed and a review of four similar cases in the pediatric literature was given. The transient nature of the condition was... more
ABSTRACT The case of an infant who presented twice with water intoxication due to excessive intake alone was discussed and a review of four similar cases in the pediatric literature was given. The transient nature of the condition was emphasized. In all cases, there was a remarkable uniformity of findings and hospital course. Maternal misjudgment or neglect was present in all cases, although why the children accepted an unsuitable diet was not fully answered. Finally, the pathophysiology and treatment of water intoxication were discussed.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
ABSTRACT The regaining of language skills in thirty children unconscious for ninety days or more following acquired brain injury is reported. Although language skills were limited in twenty-six children, four children with closed head... more
ABSTRACT The regaining of language skills in thirty children unconscious for ninety days or more following acquired brain injury is reported. Although language skills were limited in twenty-six children, four children with closed head injuries were sufficiently function al to be placed in mainstream classes. The recovery of language was correlated with cause of injury—children with closed head injuries were much more likely to regain lan guage. Ten children acquired language more than one year after injury, two at nearly four years after injury. In the four children who were most functional, initial language attempts were observed within 96 to 133 days after injury. Only children with closed head injuries regained higher language skills.
Research Interests:
Page 1. 41 Central Autonomic Dysfunction Following Acquired Brain Injury in Children 1 Linda E. Krach, MD, 2 Robert L. Kriel, MD, 3 William F. Morris, DO, 3 Bonnie L. Warhol, MD, and 4 Michael G. Luxenberg, PhD ... ' Mann-Whirney... more
Page 1. 41 Central Autonomic Dysfunction Following Acquired Brain Injury in Children 1 Linda E. Krach, MD, 2 Robert L. Kriel, MD, 3 William F. Morris, DO, 3 Bonnie L. Warhol, MD, and 4 Michael G. Luxenberg, PhD ... ' Mann-Whirney U-Wilcwun Rank Sum Test Page 3. 43 ...
Research Interests:
The bioavailability of commercially available valproic acid (VPA) syrup was studied following rectal administration in both dogs and children. Six dogs were studied following both oral (PO) and rectal (PR) administration of a dilute VPA... more
The bioavailability of commercially available valproic acid (VPA) syrup was studied following rectal administration in both dogs and children. Six dogs were studied following both oral (PO) and rectal (PR) administration of a dilute VPA syrup given in a dose of 40 mg per kilogram. There was no significant difference (p greater than 0.1) in the area under the serum concentration-time curve (AUC) between the oral (201.1 mg L-1hr) and rectal 219.6mg L-1hr) routes of administration. Four children were given VPA syrup by the rectal route. In three patients on maintenance VPA therapy, absorption following rectal administration was similar to that following oral administration. In a fourth child, VPA serum levels following an initial rectal dose of 20 mg per kilogram reached a maximum of 42 mg per liter 2 hours after the drug was given. These results indicate that the bioavailability of a diluted VPA syrup given rectally is comparable to that following oral administration. Rectal administration of VPA syrup appears to be a satisfactory alternative when the oral route is unavailable.
Research Interests:
Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were... more
Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were receiving other antiepileptic drugs at the time of this study. The children with very high dose requirements were significantly lighter, shorter, and had less body surface area than the control group. Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group. In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%. We concluded that very high VPA dosages are sometimes required to achieve therapeutic serum drug concentrations and that this therapy occasionally improves seizure control. There were no adverse effects of very high dose therapy that required dosage reduction.
Research Interests:
To evaluate the effectiveness and safety of a single-dose treatment for acute repetitive seizure (ARS) episodes (e.g., clusters) administered in a nonmedical setting by caregivers. Patients with epilepsy may experience ARS episodes... more
To evaluate the effectiveness and safety of a single-dose treatment for acute repetitive seizure (ARS) episodes (e.g., clusters) administered in a nonmedical setting by caregivers. Patients with epilepsy may experience ARS episodes despite optimal anticonvulsant treatment. Such episodes require rapid treatment as medical emergencies. Typically, the patient is treated in an emergency medical setting with i.v. medication by trained medical personnel. The authors undertook a multicenter, randomized, parallel, double-blind study of a single administration of Diastat (diazepam rectal gel) for treating episodes of ARS. ARS episodes and treatment criteria were defined for each patient at the start of the study. Caregivers were taught to determine ARS episode onset, administer a predetermined dose of study medication, monitor outcome, count respirations, and record seizures and adverse events. A total of 29 centers enrolled 158 patients, of whom 114 patients had a treated ARS episode (Diastat, n = 56; placebo, n = 58). Diastat treatment reduced median seizure frequency (p = 0.029). More Diastat patients were seizure free post-treatment (Diastat, 55%; placebo, 34%; p = 0.031). Kaplan-Meier analysis of the time to the next seizure favored Diastat treatment (p < 0.007). The most common adverse event was somnolence. Administration of a single rectal dose of Diastat was significantly more effective than placebo in reducing the number of seizures following an episode of ARS. Caregivers could administer treatment safely and effectively in a nonmedical setting.
Research Interests:
ABSTRACT We studied the pharmacokinetics of valproic acid (VPA) in 37 children who were taking other antiepileptic drugs. Thirteen children were studied both after initial and while on maintenance valproic acid therapy. Significant... more
ABSTRACT We studied the pharmacokinetics of valproic acid (VPA) in 37 children who were taking other antiepileptic drugs. Thirteen children were studied both after initial and while on maintenance valproic acid therapy. Significant differences occurred between initial and maintenance therapy in the mean apparent volume of distribution and in apparent VPA clearance, whereas VPA half-life remained relatively constant. Analysis of data in the 13 children studied on two occasions demonstrated wide intrapatient variability of VPA pharmacokinetics. Children taking VPA together with other antiepileptic medications generally require higher doses of VPA given more frequently.
Research Interests:
The relationship of the initial phenobarbital dose to weight, gestational age, blood level, and seizure control was studied in 39 neonates. The blood proportional to the dosage per kilogram, and was not related to weight or gestational... more
The relationship of the initial phenobarbital dose to weight, gestational age, blood level, and seizure control was studied in 39 neonates. The blood proportional to the dosage per kilogram, and was not related to weight or gestational age. Seizures remitted only at blood phenobarbital concentrations above 16.9 micrograms per milliliter. Therapeutic levels can be achieved by the intravenous or intramuscular administration of 16 to 23 mg per kilogram of phenobarbital.
Research Interests:
Research Interests: Pediatrics, Traumatic Brain Injury, Coma, Humans, Child, and 8 moreFemale, Hormones, Male, Infant, Menarche, Sex Factors, Motor Skills, and Diabetes Insipidus
A case of trisomy 14q mosaicism is described and compared with three other similar reported cases. The clinical picture is characterised by severe developmental retardation, failure to thrive, and somatic abnormalities including skeletal... more
A case of trisomy 14q mosaicism is described and compared with three other similar reported cases. The clinical picture is characterised by severe developmental retardation, failure to thrive, and somatic abnormalities including skeletal asymmetry, high arched or cleft palate, and low set dysplastic ears. The present chromosome imbalance probably resulted from dissociation of a balanced 14q15q translocation with subsequent formation of a 14q isochromosome.
Research Interests:
A patient with Down's syndrome was found to have 47,XX,+18/47,XX,+21 mosaicism. Chromosome 18 trisomy was found only in 18% of lymphocytes and not in skin fibroblasts. A likely interpretation is double nondisjunction in a single... more
A patient with Down's syndrome was found to have 47,XX,+18/47,XX,+21 mosaicism. Chromosome 18 trisomy was found only in 18% of lymphocytes and not in skin fibroblasts. A likely interpretation is double nondisjunction in a single lymphocyte precursor of a trisomy 21 embryo. A brief review of other cases of mitotic multiple nondisjunction and double aneuploid mosiacism is presented.
Research Interests:
ABSTRACT A new microtiter method for determining serum neutralizing antibodies for measles is described. The test can be read macroscopically by the pattern of hemagglutination. The results obtained by the microtest compare well with... more
ABSTRACT A new microtiter method for determining serum neutralizing antibodies for measles is described. The test can be read macroscopically by the pattern of hemagglutination. The results obtained by the microtest compare well with those obtained in tube neutralization tests. Philadelphia strain 26 was technically the most satisfactory of the three measles strains evaluated for use in microneutralization tests.
Research Interests:
Parenteral phenytoin solution (Dilantin) was given rectally three times a day for three days to two beagle dogs. This was well tolerated, with no evidence of mucosal irritation noted either on endoscopic nor on rectal mucosal biopsy. When... more
Parenteral phenytoin solution (Dilantin) was given rectally three times a day for three days to two beagle dogs. This was well tolerated, with no evidence of mucosal irritation noted either on endoscopic nor on rectal mucosal biopsy. When given in this manner, phenytoin is absorbed to a limited degree in canines. Parenteral phenytoin solution can be safely administered rectally, despite a pH of 12. Further study in normal volunteers is needed to assess the usefulness of this route of administration in situations in which the oral and/or parenteral route of administration is unavailable.
Research Interests:
Research Interests:
Research Interests:
The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in dogs. Doses of carbamazepine, 20 mg/kg, were given to six dogs. The routes of administration were oral tablet, oral... more
The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in dogs. Doses of carbamazepine, 20 mg/kg, were given to six dogs. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, as indicated by the area under the serum concentration-time curve between the oral and rectal suspensions. The notable differences between the oral suspension and the rectal suspension were in the maximum serum concentration achieved and the time to achieve this maximum serum concentration. This is due to a prolonged absorption of carbamazepine given rectally, which may limit the ability to achieve therapeutic serum concentrations rapidly. Carbamazepine suspension given rectally may be a satisfactory alternative when administration by the oral route is not possible.