BackgroundAbrupt discontinuation of baclofen can result in a potentially severe withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate, resulting in a critical need to develop an alternative method to prevent or... more
BackgroundAbrupt discontinuation of baclofen can result in a potentially severe withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate, resulting in a critical need to develop an alternative method to prevent or treat this withdrawal syndrome.ObjectiveTo evaluate the safety profile and pharmacokinetics of oral (PO) and investigational intravenous (IV) baclofen formulations at clinically relevant doses.DesignRandomized, open‐label, dose‐escalation, crossover study.SettingContract Research Organization (CRO).MethodsThree cohorts of 12 healthy adults received single doses of PO baclofen (10 mg, 15 mg or 20 mg) and 10‐minute infusions of IV baclofen (7.5 mg, 11.5 mg, or 15 mg) with a minimum 48‐hour wash‐out period. The third cohort also received a 60‐minute infusion of 15 mg IV baclofen after an additional 48‐hour wash‐out period.Main Outcome MeasuresSubjects were observed in a CRO for 24 hours after each dose of baclofen, and were assessed for nystagmus, atax...
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Excerpt To the editor: The surreptitious use of insulin (1) and oral hypoglycemic agents (2, 3) are recognized causes of hypoglycemia. Recently, Aderka and Pinkhas (4) reported a case of hypoglycem...
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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.
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A method for determination of serum-neutralizing antibody titers to rhinovirus type 16 and coxsackievirus type A-4 in human diploid cells (WI-38) grown in Microtiter plates is described. A good correlation was observed when comparing... more
A method for determination of serum-neutralizing antibody titers to rhinovirus type 16 and coxsackievirus type A-4 in human diploid cells (WI-38) grown in Microtiter plates is described. A good correlation was observed when comparing neutralization tests in WI-38 and other cells. The WI-38 Microtiter method is relatively simple and economical. It is suitable for those laboratories which are required to conduct large-scale serological evaluation of antibodies for rhinoviruses and coxsackie A viruses. This system also can be used for cytomegalovirus and varicella-zoster virus, which grow relatively slowly.
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To determine the relative bioavailability of lamotrigine (LTG) chewable dispersible tablets after rectal administration. Two-period, crossover study with a 2-week washout between dosing periods. Clinical research center. Twelve healthy... more
To determine the relative bioavailability of lamotrigine (LTG) chewable dispersible tablets after rectal administration. Two-period, crossover study with a 2-week washout between dosing periods. Clinical research center. Twelve healthy adult volunteers. One hundred milligrams of a LTG chewable dispersible tablet was administered by oral and rectal routes. Plasma samples were collected before and up to 120 hours after drug administration. The samples were analyzed for LTG by high-performance liquid chromatography, and the relative bioavailability was determined. Drug concentrations were lower after rectal than after oral administration. The relative bioavailability (F = AUC(rectal)/AUC(oral)) was 0.52 +/- 0.23 (SD). Drug prepared from LTG chewable dispersible tablets is absorbed rectally, although not to the same extent as when given orally. Rectal administration of suspension of these tablets can be an acceptable route of administration.
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A prospective study was performed of antiepileptic drug levels in 14 boys resident in a pediatric chronic care facility. Blood samples and 24-hour urine collections were obtained monthly. During febrile illness (temperature greater than... more
A prospective study was performed of antiepileptic drug levels in 14 boys resident in a pediatric chronic care facility. Blood samples and 24-hour urine collections were obtained monthly. During febrile illness (temperature greater than 101 degrees F for more than 24 hours), six additional blood samples and two urine collections were obtained for each child. During 8 of 10 febrile illnesses, phenytoin (PHT) decreased more than 40% from pre-illness baseline. Mean PHT level before illness was 16.7 (+/- 4.5 micrograms/ml) and during illness, 8.2 (+/- 3.6 micrograms/ml), significantly lower (p less than 0.001). Neither PHT binding nor absorption was altered by illness, so the most probable cause of the drop in PHT levels was induction of the hepatic oxidative enzyme system.
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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.
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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.
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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.
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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.
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Intranasal therapy has been proposed as an alternative for the management of seizure emergencies. The bioavailability, dose proportionality and tolerability of a supersaturated intranasal formulation of diazepam (DZP) solubilized in a... more
Intranasal therapy has been proposed as an alternative for the management of seizure emergencies. The bioavailability, dose proportionality and tolerability of a supersaturated intranasal formulation of diazepam (DZP) solubilized in a glycofurol-water cosolvent system was investigated. Eight healthy volunteers were randomized into a single-blind, three-way crossover study to compare 5 and 10mg intranasal DZP doses of the investigational formulation with a 5mg dose of a DZP solution (DZP injectable, 5mg/mL) administered intravenously. Treatments were separated by a two-week washout period. Plasma samples for DZP analysis were collected pre-dose and at regular intervals up to 48h post-dose and assayed by HPLC. Visual analog scales (VAS) were used to assess tolerability (1-tolerable; 10-extremely intolerable) and pain (1-no pain; 4-extreme pain) at predefined time points. Following the 5 and 10mg doses, the median t(max) were 20 and 30min and the mean C(max) were 134.3+/-62 and 247.6+/-61ng/mL. Estimated bioavailability was 75% for both doses. Pain scores of 2 and 2.3 were observed following the 5 and 10mg doses; tolerability scores were 4.4 and 4.7. Pain and tolerability scores returned to baseline within 10h. Our formulation provided reasonable bioavailability, but was not well tolerated.
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Research Interests: Epilepsy, Treatment, Pharmacokinetics, Adolescent, Humans, and 17 moreDesign method, Female, Male, Statistical Significance, Fructose, Bioavailability, Clinical Sciences, Aged, Middle Aged, Adult, Analysis of Variance, Side Effect, Gestation, Biological Availability, Area Under the Curve, Cross-Over Studies, and Area Under Curve
ABSTRACT We reviewed the incidence of external leakage from feeding gastrostomies in 8 patients who received valproate sprinkle (VPA-S). We also identified a control group of 31 children with feeding gastrostomies who were also cared for... more
ABSTRACT We reviewed the incidence of external leakage from feeding gastrostomies in 8 patients who received valproate sprinkle (VPA-S). We also identified a control group of 31 children with feeding gastrostomies who were also cared for in our clinic, but who did not receive VPA-S. All patients in both groups have had their feeding gastrostomy greater than or equal to 6 months. Four of 8 children who received VPA-S through feeding gastrostomies developed problems with recurrent external leakage. The incidence of external leakage in our control group of children who had not received VPA-S was 2 in 31 (6.4%). We hypothesize that the external leakage is caused by adherence of the undissolved VPA-S particles to the exterior of the tube, preventing close approximation of the tube to the gastrostomy stoma. In most cases, VPA-S could continue to be administered and the problem of leakage reduced if the tubes were more frequently changed and/or a larger size were used. Complications with either leakage or occlusion were noted in all patients with the button feeding tube who had received VPA-S. Because of the especially high complication rate associated with administration of VPA-S in children with the "button" feeding tubes, we discourage VPA-S administration to children with that device.
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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.
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Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest... more
Search by Subject Search using Medical Subject Headings (< b> MeSH</b>), a controlled vocabulary for indexing life sciences content.< br/> Note that some records do not have MeSH. These include Patents and the latest PubMed and PubMed Central records.
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OBJECTIVES: 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... more
OBJECTIVES: 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.METHODS: 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.RESULTS: 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 of circumstances of the accidents illustrates that accidents are caused both by use of the openers by children and by faults in design. Most accidents have occurred when children have found access to the activation devices and have been entrapped under closing doors that failed to reverse. However, in one case, an adult activated the opener and left the premises before the door completely closed. Our evaluation of 50 garage door openers showed that although 88% percent reversed when encountering a block of wood, 40% failed to reverse when coming down on a supine, child-sized cardiopulmonary resuscitation mannequin.CONCLUSIONS: Automatic garage door openers pose a serious risk of severe injury or death to children. It is probable that many doors would not reverse if they came down on a young child. Therefore, we have devised a way for homeowners to test their door openers that closely mimics our evaluations using the mannequin by using a large roll of paper towels. If the door fails to reverse using this test, we suggest that homeowners disconnect their openers and operate the doors manually until the openers are serviced or replace their automatic openers with one that meets the latest Underwriters Laboratory standards. We also have other recommendations regarding the safe operation of the doors, including improving the safety standards for openers in apartment complexes. Compliance with these recommendations should reduce the number of injuries to children caused by garage door openers.
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Rectal administration of antiepileptic drugs may be a useful alternative route when oral administration is not possible due to illness, surgery, or status epilepticus. Although parenteral administration often replaces oral administration... more
Rectal administration of antiepileptic drugs may be a useful alternative route when oral administration is not possible due to illness, surgery, or status epilepticus. Although parenteral administration often replaces oral administration in these circumstances, there is not always a desirable intravenous line available or repeated intramuscular injections may not be practical. The purpose of this study was to determine the relative bioavailability and time course of absorption of the commercially available parenteral phenobarbital sodium solution administered rectally in comparison with the same preparation given intramuscularly. Seven healthy adult volunteers were given phenobarbital 5 mg/kg intramuscularly and rectally five weeks apart. Eighteen blood samples were drawn over 288 hours. Pharmacokinetic parameters following intramuscular versus rectal administration were the following: area under the curve 5916 vs. 5253 mumol.h/L; half-life 112 vs. 113 h; time to maximum concentration 2.1 vs. 4.4 h; and maximum serum concentration 36.2 vs. 31.4 mumol/L. Mean relative bioavailability for rectal phenobarbital was 90 percent. Therefore, the parenteral phenobarbital sodium solution given rectally is well absorbed and provides a useful alternative route of administration.
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AbstractAbrupt 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
AbstractAbrupt 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.ObjectivesTo complete a preliminary study of IV baclofen in dogs.MethodsSingle 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.Key findingsBaclofen 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.ConclusionsIf 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.
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In our experience, accidents involving all-terrain vehicles are an increasingly frequent cause of brain injury in children. The risk associated with operation of these vehicles is not fully appreciated and should be better publicized. We... more
In our experience, accidents involving all-terrain vehicles are an increasingly frequent cause of brain injury in children. The risk associated with operation of these vehicles is not fully appreciated and should be better publicized. We believe that it is possible to delineate several steps that could significantly reduce the risk to the pediatric population without curtailing the recreation altogether. Although construction design has promised to produce safer vehicles, our experience has shown that extreme injury is still possible with the newer four-wheel machine.
Research Interests: Pediatrics, Adolescent, Coma, Humans, Child, and 5 moreRECREATION, Female, Male, Facial Injuries, and Brain injuries
A case is reported of scoliosis in a boy with epilepsia partialis continua, an unusual disorder with virtually constant episodes of seizures of only part of the body. The scoliosis appeared to be due to the seizure disorder. The epilepsy... more
A case is reported of scoliosis in a boy with epilepsia partialis continua, an unusual disorder with virtually constant episodes of seizures of only part of the body. The scoliosis appeared to be due to the seizure disorder. The epilepsy seriously inhibited conventional scoliosis management. The patient&#39;s scoliosis problem was finally solved by salvage surgery and intensive seizure medication supervision. Scoliosis management in complex seizure disorders presents special and unusual problems.
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... EPIDEMIOLOGIC OBSERVATIONS OF VIRUS INFECTIONS IN A CLOSED POPULATION OF YOUNG CHILDREN1 THOMAS C. CESARIOr ROBERT L. KRIEL,&quot; GLYN G. CALDWELL.4 LARRY E. DAVIS5 AND TOM DY CHIN0 ... for their technical assistance, and Dr.... more
... EPIDEMIOLOGIC OBSERVATIONS OF VIRUS INFECTIONS IN A CLOSED POPULATION OF YOUNG CHILDREN1 THOMAS C. CESARIOr ROBERT L. KRIEL,&quot; GLYN G. CALDWELL.4 LARRY E. DAVIS5 AND TOM DY CHIN0 ... for their technical assistance, and Dr. Herta Wulff, ...