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Biomedical subjects

D H Langer

Publications and source records attributed to D H Langer.

14 recordsLinked to original sources

Real-ear to coupler differences in children with grommets.

Real-ear to coupler differences (RECDs) are important for the selection of appropriate amplification characteristics for hearing impaired children. The aim of this study was to investigate the effects of patent grommets on RECDs in children. Subjects were 32 children aged between 4 and 7 years, 16 had a patent grommet in one or both ears as confirmed by otoscopy and large equivalent ear canal volumes on tympanometry. There was no evidence of middle ear pathology in the remaining 16 who comprised the control group. All real-ear and coupler measures showed good test-retest repeatability across the whole frequency range. The mean difference in RECDs between the two groups in the frequency range 0.125-0.75 kHz was 15 dB. The differences in RECDs were statistically significant (P < 0.01) for all frequencies below 0.75 kHz. There was a strong correlation between the mean RECD and equivalent ear canal volume at all frequencies between 0.125 and 0.5 kHz, and a moderate correlation at 0.75 kHz. Large inter-subject variability was found, with a maximum standard deviation of 6.6 dB at 4.0 kHz. Therefore, this study supports the need for individual RECD measures to be made, particularly for subjects with grommets, rather than using averaged transformation figures. It suggests that more low frequency gain should be given to hearing aid users with patent grommets to overcome the reduced SPL in the ear canal, due to leakage through the vented tympanic membrane.

Child↗

Valproic acid hepatic fatalities. II. US experience since 1984.

We have analyzed the usage pattern of valproate and the associated hepatic fatalities that have been reported in the 2 years since our first study evaluating US experience during the period 1978-1984. In this follow-up study (1985-1986), we have observed a nearly fivefold decrease in the incidence of hepatic fatality during a time when the overall use of valproate has increased significantly. The dramatically decreased incidence, from 0.93 per 10,000 (1/10,000) in 1978-1984 to 0.20 per 10,000 (1/49,000) in 1985-1986 appears to be due to changes in the prescribing patterns of physicians, prompted by greater awareness of low-risk versus high-risk patients. More patients are receiving valproate as monotherapy, considerably more low-risk patients are being treated with valproate, and fewer high-risk patients (0 to 2 years old) are being treated with valproate. During 1985-1986, no hepatic fatalities were reported in any patients above the age of 10 years, regardless of whether valproate was administered as monotherapy or polytherapy. The altered exposure pattern, with an increased use of monotherapy, appears to have had a positive impact on the number of hepatic fatalities (four among 198,000 patients treated during 1985-1986) and contributed to a decreased rate of valproate-associated hepatic fatality.

Adolescent↗

Side effects of valproate.

In the management of epilepsy, selecting an antiepileptic drug appropriate for each individual patient requires matching the patient's clinical needs with the agent's specific pharmacologic attributes. In many situations, the final choice of an antiepileptic drug is based upon an agent's side-effect profile. Because side-effect profiles emerge gradually as the number of patients treated expands from the thousands to the hundreds of thousands, it is helpful to periodically update our perspective of side effects of antiepileptic drugs. For valproate, the frequency of side effects has been reduced by monitoring serum levels, using improved formulations, and limiting use in patients who have been identified as having a high risk for the development of a serious side effect.

Behavior↗

Hepatic considerations in the use of antiepileptic drugs.

Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10-38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.

Anticonvulsants↗

Valproic acid hepatic fatalities: a retrospective review.

We reviewed all US cases of fatal hepatotoxicity coincident with valproate anticonvulsant therapy that were reported between 1978 and 1984. Thirty-seven hepatic fatalities were determined to have occurred coincident with the use of valproate. All but one patient had such other medical conditions as mental retardation, developmental delay, congenital abnormalities, and other neurologic diseases. The primary risk of fatal hepatic dysfunction (1/500) was found to be in children 0 to 2 years old receiving valproate as polytherapy. The risk declined with age and was low in patients receiving valproate as monotherapy (1/37,000). No hepatic fatalities occurred in patients above the age of 10 years receiving valproate as monotherapy.

Adolescent↗

Evidence of lack of abuse or dependence following pemoline treatment: results of a retrospective survey.

Pemoline is recognized as an efficacious and safe therapeutic agent for children suffering from Attention Deficit Disorder (ADD). A review of adverse experience reports submitted to the manufacturer suggests that Cylert (brand of pemoline) has a limited potential for abuse or dependence. Drug dependence studies in animals have demonstrated that pemoline is not self-administered in naive nor cocaine-dependent animals. Human experience indicates that, despite the fact that the drug has been available in the U.S. since 1975, use is limited and is increasing slowly. A review of the literature revealed no published case reports of euphoria, abuse, dependence or withdrawal. While there have been a few reports of tolerance, it is possible that these were a reflection of inadequate dosing rather than actual tolerance to the drug's therapeutic effects. During the 10 years that Cylert has been available in the United States, there have been only four reports of withdrawal reactions and no reported cases of dependence. Reports of intentional overdose of Cylert are minimal, with no reports involving abuse via the intravenous route.

Adolescent↗

Differential effects of selected dopaminergic agents on locomotor activity in normotensive and spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) exhibit a significantly higher level of spontaneous locomotor activity than age-matched normotensive controls (WKY). The direct-acting dopamine agonists, apomorphine and pergolide, produced a biphasic effect on locomotor activity levels in normotensive controls. Low doses of these agonists decreased activity levels, while higher doses of these agonists dramatically stimulated activity. In marked contrast to these results was the effect observed in the SHR, in which these agonists at all doses tested decreased activity. Amphetamine, a dopamine releaser, stimulated activity levels in both the WKY and SHR; however, the magnitude of the increase was somewhat attenuated in the SHR.

Amphetamine↗

Urinary phenethylamine response to d-amphetamine in 12 boys with attention deficit disorder.

Urinary phenethylamine (PEA), an endogenous amine similar to amphetamine in both molecular structure and pharmacological properties, was studied in 12 boys with attention deficit disorder with hyperactivity. d-Amphetamine and placebo were given for 14 days each in a counterbalanced crossover design; double-blind teacher behavior ratings and motor activity measurements were also obtained. Excretion of PEA, phenylacetic acid, creatinine, and d-amphetamine were measured. PEA was significantly increased and phenylacetic acid was unchanged after d-amphetamine administration, and change in PEA excretion correlated significantly with d-amphetamine excretion. There was no significant relationship between either clinical response to drug and change in PEA or phenylacetic acid excretion.

Attention Deficit Disorder with Hyperactivity↗

Dopamine receptor supersensitivity and schizophrenia: a review.

Advances in knowledge of brain neurochemistry have lent impetus to the biological study of schizophrenia. A prominent example is the dopamine hypothesis. Increasing additions to and refinements of neurochemical knowledge, particularly the study of receptors, have continued to support biological hypotheses of schizophrenia. A recently proposed hypothesis is that schizophrenic patients suffer from dopamine receptor supersensitivity at certain phases of their illness. The present article selectively reviews data that are relevant to this refinement of the dopamine hypothesis.

Adenylyl Cyclases↗

Childhood obsessive-compulsive disorder.

The authors collected clinical diagnostic, neurophysiological, electrophysiological, and biochemical data on 9 adolescents who had primary obsessive-compulsive disorder. The results indicate considerable descriptive validity of the syndrome in childhood and its independence from obsessional traits; however, all of the children had a history of major depressive disorder, and their sleep EEG measures resembled those of young adults with primary depressive disorder. The patients' families did not have a more consistent pattern of anxiety disorder or any other psychiatric disorder than do families of adult obsessive patients. Psycholinguistic test results showed a lack of normal laterality, which has been reported for other psychiatric illness.

Adolescent↗