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Biomedical subjects

M R Delgado

Publications and source records attributed to M R Delgado.

15 recordsLinked to original sources
PubMed1996

Identification and molecular confirmation of a small chromosome 10q duplication [dir dup(10)(q24.2-->q24.3)] inherited from a mother mosaic for the abnormality.

We describe a family in which two siblings exhibited developmental delay, reduced muscle tone and mild muscle weakness. Cytogenetic evaluation demonstrated that both children had a tandem duplication of a small portion of the long arm of chromosome 10 [46,XX or XY,dir dup(10)(q24.2-->q24.3)], inherited from their clinically normal mother, who was found to be mosaic for the duplicated chromosome 10. Fluorescence in situ hybridization approaches, including total chromosome painting and the use of regional specific cosmid probes, were used to confirm the chromosome 10q origin of the duplicated material. This is the smallest confirmed duplication of this portion of chromosome 10 reported to date.

Child↗
PubMed1996

Effects of external fixation and limb lengthening on peripheral nerve function.

To identify factors affecting peripheral nerve function during limb lengthening, serial somatosensory evoked potentials studies were performed in 18 goats and correlated with gross appearance of the soft tissues at necropsy. In 15 goats, a 20% or 30% tibial lengthening was done using the Ilizarov apparatus at a rate of 0.75 mm per day and rhythm of 1, 4, or 720 times per day. Three animals served as frame/corticotomy controls. Seven lengthened and 2 control animals maintained normal somatosensory evoked potentials throughout the study. At necropsy, the peroneal and tibial nerves appeared grossly normal. In one control animal with irreversible loss of evoked potentials documented intraoperatively, peroneal nerve impalement by a transfixion wire was identified at necropsy. Eight lengthened animals experienced significant changes of peroneal nerve conduction. In 6 of these 8 animals, transfixion wires were found to be disrupting the nerve in some way. In the remaining 2 animals, no offending wires were identified, but there was extensive diffuse soft tissue fibrosis within the extremity. The rhythm of distraction did not have an important influence on evoked potential changes during the course of distraction. Although there was a correlation between the amount of lengthening performed and the degree of evoked potentials deterioration, the anatomic relationship between the wires and nerves was a more important factor in the development of these abnormalities.

Animals↗
PubMed1996

Discontinuation of antiepileptic drug treatment after two seizure-free years in children with cerebral palsy.

OBJECTIVE: The risk of seizure relapse after antiepileptic drug (AED) discontinuation in children has been reported to vary between 6% and 40%. It has been suggested that neurologic deficit and mental retardation are poor prognostic factors for seizure relapse after AED discontinuation. Because epileptic children with cerebral palsy (CP) have neurologic deficits, and many have mental retardation, it is important to know their risk for seizure relapse. METHODS: AED treatment was discontinued in 65 children with CP and histories of epilepsy after 2 seizure-free years. All of the patients were followed until they had seizure relapses or for at least 2 years without seizures after AEDs were stopped. Multiple factors were analyzed for possible association with seizure relapse. RESULTS: Twenty-seven patients (41.5%) had seizure relapses. Patients with spastic hemiparesis had the highest relapse rate (61.5%), and those with spastic diplegia had the lowest rate (14.3%). No other factor correlated significantly with the risk of seizure relapse. CONCLUSIONS: Discontinuation of AEDs in children with CP can, and should, be practiced when possible after patients have been seizure-free for at least 2 years. AED discontinuation in patients with spastic hemiparesis is significantly more likely to lead to seizure relapse than in patients with other CP types, but no other factor is yet known to increase the chance of relapse.

Adolescent↗
PubMed1995

Interactions of valproic acid with carbamazepine and its metabolites' concentrations, concentrations ratios, and level/dose ratios in epileptic children.

In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA.

Carbamazepine↗
PubMed1995

Interactions of phenobarbital and phenytoin with carbamazepine and its metabolites' concentrations, concentration ratios, and level/dose ratios in epileptic children.

The effects of phenytoin (PHT) or phenobarbital (PB) comedication on the concentrations, concentration ratios, and level/dose ratios of carbamazepine (CBZ) and its metabolites were investigated. The hetero-induction effects of CBZ metabolism by PHT or PB were clearly demonstrated. Serum CBZ level/dose ratios in patients with CBZ polytherapy were decreased while CBZ-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H) concentrations were increased as compared with those of patients receiving CBZ alone. The concentration ratios of CBZ-H/CBZ and CBZ-E/CBZ were also greater in patients receiving CBZ+PHT or CBZ+PB than in patients receiving CBZ alone. In addition, positive correlations between serum PHT concentration and CBZ-H/CBZ or CBZ-E/CBZ concentration ratios were observed. There were no significant differences in CBZ-H/CBZ-E concentration ratios, the free fractions of CBZ and its metabolites, and CBZ-E or CBZ-H level/dose ratios among the three groups of patients. Because this approach investigates the in vivo relation between the substrates and products of the enzymes involved in CBZ biotransformation, more detailed information about the drug interactions was obtained. The results suggest that the PHT has a potent induction effect on CBZ epoxidase, whereas PB is a moderate inducer.

Biotransformation↗
PubMed1995

Tuberous sclerosis.

Tuberous sclerosis complex is a disorder of cellular differentiation and proliferation that is inherited as an autosomal dominant trait with variable penetrance and a high spontaneous mutation rate. Lesions occur in the brain, skin, kidneys, heart, and other organs. Recent studies suggest genetic heterogeneity, with at least two gene loci on chromosomes 9, 16, and perhaps 11.

Cell Differentiation↗
PubMed1994

The influence of polytherapy on the relationships between serum carbamazepine and its metabolites in epileptic children.

The influence of polytherapy on the relationships between the age, weight, carbamazepine (CBZ) dose, total clearance, and intrinsic clearance, with concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) are investigated. Three groups of patients with CBZ monotherapy, or receiving CBZ polytherapy by taking CBZ and valproic acid (VPA) or CBZ plus other antiepileptic drugs (AEDs) were studied. The significant correlations between serum CBZ concentrations and CBZ dose in patients taking CBZ alone were no longer significant in patients with polytherapy, and the positive associations between serum CBZ-E concentrations and CBZ dose were lost in patients with CBZ + VPA. Only the concentrations of CBZ-H had significant correlations with CBZ dose in all three groups of patients. Results from this relationship study indicate a heteroinduction effect of other AEDs on CBZ metabolism, and a relatively weak influence on CBZ-E elimination. Data also suggest that there is a block in the biotransformation from CBZ-E to CBZ-H in patients taking CBZ + VPA, presumably caused by the inhibition effect of VPA on epoxide hydrolase. Therapeutic drug monitoring of CBZ will benefit from the knowledge obtained from the relationship study.

Aging↗
PubMed1994

Improved therapeutic monitoring of drug interactions in epileptic children using carbamazepine polytherapy.

Drug interactions in epileptic children with carbamazepine (CBZ) polytherapy were investigated by analysis of total and free CBZ and its metabolites simultaneously. Heteroinduction effects of CBZ metabolism by other antiepileptic drugs (AEDs), including phenytoin (PHT), phenobarbital (PB), or primidone (PRM), were clearly demonstrated. Serum CBZ level/dose ratios in patients taking CBZ plus other AEDs were decreased while CBZ-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11-dihydro-CBZ (CBZ-H) concentrations were significantly increased compared to patients with CBZ alone. Concentration ratios of CBZ-H/CBZ and CBZ-E/CBZ were also significantly higher in patients taking CBZ plus other AEDs. Interactions between CBZ and valproic acid (VPA) involved both protein binding displacement and metabolic inhibition. Patients taking CBZ plus VPA showed significantly increased free fractions of CBZ and CBZ-E and substantially increased serum CBZ-E concentrations and CBZ-E level/dose ratios, while CBZ-H/CBZ-E concentration ratios were decreased compared with patients on CBZ alone. Since this approach investigates the in vivo relationship between substrates and products of the enzymes involved in CBZ biotransformation (the ratios between CBZ and its metabolites), detailed information about the activities of the enzymes may be obtained. This approach appears to be a practical way to improve the monitoring of CBZ metabolism influenced by various physiological or pathological conditions and achieve a better understanding of the drug interactions under different drug regimens (coadministered inhibitor or inducer). This principle may also be adopted for other drugs with similar metabolic characteristics.

Adolescent↗
PubMed1994

Influence of sex, age, weight, and carbamazepine dose on serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites.

We have conducted a comprehensive study in a group of epileptic children (25 boys and 30 girls) receiving carbamazepine (CBZ) monotherapy. The influence of sex, age, weight, and CBZ daily dose on serum CBZ, carbamazepine-10,11-epoxide (CBZ-E), and trans-10,11-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) concentrations, concentration ratios, and level/dose ratios were investigated. Compared with girls, boys required significantly larger CBZ dose and showed higher CBZ apparent clearances and lower level/dose ratios of CBZ and its metabolites. There were no significant differences between boys and girls in serum concentrations, concentration ratios, and free fractions of CBZ and its metabolites, although there were trends that boys had slightly higher concentration ratios. The relationship analysis suggested that there was a dose-dependent autoinduction of CBZ metabolism, and CBZ metabolism was decreased as patients mature, as measured by weight and age. Age showed a significant positive relationship with the free fractions of CBZ and its metabolites, indicating decreased protein binding of CBZ and its metabolites with the increase of age. Serum CBZ concentration is not a reliable index of CBZ dose, as there is only a weak correlation between them. Serum CBZ-H concentration showed strong positive correlations with CBZ dose and might be a valuable index in assessing patient compliance. The influence of sex, body weight, age, and CBZ dose on CBZ and its metabolites should be taken into consideration in further clinical studies.

Aging↗
PubMed1994

Thrombocytopenia secondary to high valproate levels in children with epilepsy.

We reviewed the frequency of valproate-induced thrombocytopenia in children with epilepsy in our institution. Sixty-four (21%) of 306 children taking valproate developed thrombocytopenia. Thirty-two of these 64 patients had at least one platelet count lower than 100 x 10(3)/mm3. Eight patients developed signs of bleeding. Low platelet levels were typically noted in patients with serum valproate levels of over 140 micrograms/mL, and reduction of the medication dose usually resulted in a prompt increase in the number of platelets. Only one patient developed thrombocytopenia unrelated to high serum drug levels, and her platelet count did not improve until the drug was discontinued. Neither the age of the patient nor the use of additional antiepileptic medication correlated with the platelet count. However, duration of valproate use was related. These data suggest that, although valproate may cause thrombocytopenia via more than one mechanism, by far the most common factor is the presence of high valproate levels. Thus, the medication can be safely lowered in most patients with thrombocytopenia rather than discontinued altogether. Platelet counts should probably be monitored more carefully in patients known to have higher drug levels.

Carbamazepine↗
PubMed1994

Somatosensory evoked potential evaluation of acute nerve injury associated with external fixation procedures.

The effects of different mechanisms of acute nerve injury on peripheral nerve function during K wire application and 1 stage limb lengthening were evaluated prospectively in 24 goats using somatosensory evoked potentials. Stable somatosensory evoked potential recordings throughout 3-day experiments were obtained in animals with wires placed at a distance from or directly adjacent to a nerve but without producing any tension or pressure. Complete loss of the peroneal nerve somatosensory evoked potentials occurred if this nerve was perforated by wire, underwent excessive pressure by wire, or had been over-stretched due to acute 10% limb lengthening. Acute distraction resulted only in peroneal nerve dysfunction, while the tibial nerve was relatively unaffected. Although somatosensory evoked potential changes were not specific for the type of injury produced and the time of waveform disappearance varied, significant somatosensory evoked potential changes (> 50% amplitude reduction, > 10% latency delay or both) were seen within the first 15 minutes after injury in 90% of the cases. The somatosensory evoked potential changes did not reverse if the offending wire or distraction was left in place for the full duration of the experiment. Variable nerve conduction recovery was observed in all animals who had the insult removed immediately after the somatosensory evoked potentials disappearance. The greatest improvement occurred after discontinuation of nerve distraction. The worst somatosensory evoked potential waveform recovery was noted in animals with nerve perforation. Intraoperative somatosensory evoked potential monitoring proved to be a reliable and useful technique for earlier detection of acute nerve injury during external fixation procedures.

Animals↗
PubMed1985

Bromocriptine: problems with low-dose de novo therapy in Parkinson's disease.

Twenty Parkinson's disease patients, who had not yet received levodopa, were treated with low-dose bromocriptine. At a mean daily bromocriptine dose of 13.2 mg, 13 patients (65%) improved and had a 32% reduction in the combined score for tremor rigidity and bradykinesia. Adverse effects were frequent, and 25% of the patients were taken off the drug because of nausea or vomiting. After 30 months follow-up, only three patients continued on bromocriptine alone. Ten patients were eventually maintained on low-dose bromocriptine and levodopa-carbidopa, and a clear synergistic effect of bromocriptine in this drug combination was documented in eight patients. Low-dose bromocriptine does not replace levodopa as initial therapy for Parkinson's disease. The potential long-term benefit of the early use of combined low-dose levodopa-dopamine agonist therapy needs to be further studied.

Adult↗
PubMedDate not supplied

Intraoperative SSEP monitoring during external fixation procedures in the lower extremities.

The efficacy of somatosensory evoked potentials (SSEPs) to detect acute peripheral nerve injury during external-fixator application in the lower extremities was evaluated in 40 children with 42 Ilizarov surgical procedures. The study included patients who were either clinically normal or who had preexisting neuropathy but consistent and reliable SSEP responses preoperatively. SSEPs were recorded from the popliteal fossa and lumbar regions after alternating stimulation of the peroneal and posterior tibial nerves at the ankle. SSEP changes due to anesthesia, Ilizarov apparatus application, and other intraoperative variables are described. Significant deterioration or total loss of SSEP response during surgery occurred in four cases. Two of these patients were normal preoperatively and had symptoms of neurologic deficit postoperatively; the other two had exacerbations of pre-existing neuropathy. In general, the peroneal nerve was at greater risk for injury during surgery. SSEP monitoring proved to be technically feasible in external-fixation procedures on the lower extremities and may be a practical tool for detection of intraoperative nerve compromise.

Acute Disease↗
PubMedDate not supplied

A comprehensive study of the relation between serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites with age, weight, dose, and clearances in epileptic children.

We made a comprehensive study of the relation between age, weight, carbamazepine (CBZ) dose, total clearance (TC), and intrinsic clearance (IC) and concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11- dihydro-carbamazepine (CBZ-H) in a group of epileptic children receiving CBZ monotherapy. Body weight and age showed negative correlations with TC, IC, CBZ dose, and CBZ-E/CBZ and CBZ-H/CBZ concentration ratios, and had positive relation with CBZ, CBZ-E, and CBZ-H level/dose ratios. These results indicate decreased CBZ metabolism with patient maturity. Correlations between CBZ dose with TC, IC, and the concentration ratios of CBZ-E/CBZ, CBZ-H/CBZ-E, and CBZ-H/CBZ were positive. CBZ dose also had negative associations with CBZ and CBZ-E level/dose ratios, indicating dose-dependent autoinduction of CBZ metabolism. Our data suggest that weight, age, and CBZ dose have less influence on epoxide-hydrolase activities than on epoxidase activities. The CBZ-E/CBZ concentration ratio can be used as an indicator of the degree of autoinduction of CBZ metabolism, even in patients receiving CBZ monotherapy.

Adolescent↗