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Biomedical subjects

J P Allen

Publications and source records attributed to J P Allen.

At least 19 recordsLinked to original sources
PubMed1979

Rapid metabolism of phenytoin: a method of calculating proper dosage.

The optimal dosage of phenytoin can be accurately determined by a pharmacokinetic method. By plotting the rate of administration of phenytoin acid against the apparent plasma clearance rate, we estimated the maximum rate of metabolism and the serum concentration at which the rate of metabolism was one half the maximum rate for phenytoin and then applied the Michaelis-Menten equation to optimize the dosage of phenytoin in a 48-year-old man with uncontrolled idiopathic generalized seizures and increased metabolism of phenytoin. The patient became seizure free on a regimen of 650 mg of phenytoin daily and experienced no side effects of phenytoin over-dosage. The pharmacokinetic technique described is simple to use and can be applied in an outpatient clinic.

Dose-Response Relationship, Drug↗
PubMed1979

Phenytoin cumulation kinetics.

Four male subjects were given phenytoin orally in single or twice-daily doses. Subjects were on 2 or 3 different dosing rates from 260 to 600 mg phenytoin sodium daily. Predose blood samples were obtained almost daily. The resulting serum levels, measured by gas-liquid chromatography, ranged from 1 to 18 micrograms/ml. Serum phenytoin concentration-time data were fit to a 1-compartment open model with zero-order input and Michaelis-Menten elimination. The resulting computer-generated parameter estimates (Vmax, 5.28 to 8.41 mg/kg/day; Km, 0.83 to 4.18 mg/1; Vd, 0.74 to 0.97 1/kg) are in agreement with the ranges of values in the literature. The time course of phenytoin cumulation is compatible with the presence of a major elimination pathway exhibiting Michaelis-Menten kinetic behavior.

Administration, Oral↗
PubMed1979

Transient erythrocytosis during the neonatal period: possible neurologic compications.

Transient erythrocytosis during the neonatal period may result in serious complications. Among the well recognized problems are respiratory distress, acute heart failure, and death. Little attention has been ascribed to the neurologic complications of a high hematocrit level in the neonatal period. This report describes four pediatric patients with neurologic deficits presumably due to transiently high hematocrit levels during the neonatal period. The neurologic findings in these patients were consistent with the general diagnosis of cerebral palsy. We hypothesize that they may be representative of a group of patients with seizures, structural central nervous system defects, and/or mental retardation secondary to transient erythrocytosis. Moreover, prompt recognition and treatment of this hematologic finding may prevent the immediate or late appearance of such neurologic findings.

Cerebral Palsy↗
PubMed1979

Rapid melatonin transients.

Two normal male subjects exhibited rapid pulses of melatonin concentration in plasma, apparently unrelated to stages of sleep and undisturbed with spontaneous waking during the night. Pulse intervals of approximately 8 and 12 min., respectively, for subjects 1 and 2, were associated with excursions of 35% and 33% of the nadir or 28% and 26% of the mean value. The pulses were detected with a 2.5 min. sampling interval.

Adult↗
PubMed1978

Overnight plasma profiles of melatonin and certain adenohypophyseal hormones in men.

Melatonin levels exhibited a day-night rhythm with highest levels at night. Nocturnal plasma melatonin concentrations were unrelated to sleep stages, whereas secretion of GH was temporally related to slow wave sleep. Levels of corticotropin rose in the later sleep cycles. We found no relationship between endogenous nocturnal melatonin and adenohypophyseal hormone levels. The results indicate that in young men nocturnal levels of melatonin are controlled separately from those of LH, PRL, corticotropin, and GH.

Adrenocorticotropic Hormone↗
PubMed1977

Individualization of phenytoin dosage regimens.

Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis-Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady-state phenytoin serum concentrations resulting from different daily doses: The observed steady-state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p less than 0.02). The average deviation between observed and predicted levels was 0.04 mug/ml (range, +/- 3.2 mug/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r= 0.360, p less than 0.05). The average deviation was --3 mug/ml (range, 3.9 to --11.3 mug/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.

Adolescent↗
PubMed1977

Frequency analysis of the EEG in children with sickle cell disease.

An automated technique for EEG frequency analysis was employed in the study of nine children with sickle cell disease. Quotients, Q(1) (delta+theta/alpha+beta) and Q(2) (theta/alpha+8), were calculated from the computed power in each frequency range. Recordings from occipital-parietal and temporal-frontal areas resulted in a higher Q(1) for sickle cell disease patients than for reported normals (p<.002 and p<.05 respectively). Q(2) value from the occipital-parietal sites were also higher for the sickle cell group (p<.05).The technique reported here lends itself to serial studies in appropriate patient groups and suggests the possibility of an organic basis for some of the results found.

Adolescent↗
PubMed1976

Nyctohemeral variation and suppressibility of plasma ACTH in various stages of Cushing's disease.

In order to define nyctohemeral plasma ACTH secretory patterns, frequency plasma ACTH samples were obtained in seven patients with untreated Cushing's disease (i.e. pituitary-dependent Cushing's syndrome), five Cushing's patients treated by bilateral adrenalectomy, four of whom had Nelson's syndrome, and one patient with 21-hydroxylase deficiency (congenital adrenal hyperplasia). A nyctohemeral rhythm of plasma ACTH concentration was apparent in the one patient with the adrenogenital syndrome but not in those with Nelson's syndrome or Cushing's disease. The effect of graded doses of dexamethasone, 2,8 or 32 mg per 24 h period, on plasma ACTH concentrations was studied in patients with untreated or treated Cushing's disease or Nelson's syndrome. In all of these hypercorticotrophic states, the mean plasma ACTH concentraton was not significantly affected by the smallest dose of dexamethasone, was partially suppressed by the intermediate dose, and further suppressed by the largest dose. In contrst, the patient with congenital adrenal hyperplasia and elevated plasma ACTH concentrations showed complete suppression of plasma ACTH levels following the smallest dose of dexamethasone. These findings indicate that there is resistance to ACTH suppression by dexamethasone in all stages of Cushing's disease and suggest that negative feedback of glucocorticoids may be involved in the pathogenesis of this disease.

Adrenalectomy↗
PubMed1976

Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.

Adenoma, Acidophil↗