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Biomedical subjects

P K Duffner

Publications and source records attributed to P K Duffner.

At least 55 records · Page 3Linked to original sources
PubMed1983

Late effects of treatment on the intelligence of children with posterior fossa tumors.

This retrospective pilot study was undertaken to evaluate the late effects of treatment on intelligence in a population of children with posterior fossa tumors. Ten children with posterior fossa tumors treated with radiation and chemotherapy received intellectual evaluations at least one year following diagnosis. Six children had medulloblastomas, one child had a fourth ventricular ependymoma, two children had brainstem gliomas, and one child had a recurrent cerebellar astrocytoma. Children with supratentorial tumors were specifically excluded from the study in order to eliminate the possible influence of the tumor on intellectual functioning. Four children had had intelligence testing in school prior to treatment of their tumor. In each case results following treatment revealed a deterioration of full scale IQ of at least 25 points. Six children did not have prior testing; of these, two had IQ's less than 20. Overall, 50% of the patients had IQ's of less than 80 and 20% had IQ's of greater than 100. Furthermore, four children with normal intelligence (IQ greater than 80) have learning problems requiring special classes. Thus, of the ten children evaluated, all have either dementia, learning disabilities, or evidence of intellectual retardation. This study suggests that aggressive treatment of children with brain tumors may improve survivals but may be associated with significant long-term disabilities.

Adolescent↗
PubMed1983

Long-term effects of treatment on endocrine function in children with brain tumors.

Fourteen children with brain tumors received endocrine evaluations at least one year following completion of cranial irradiation. Treatment consisted of operation (13 patients), craniospinal irradiation (6), whole brain irradiation (5), posterior fossa irradiation (3), and chemotherapy (10). Endocrine evaluation included bone age roentgenography and measurement of growth hormone (using sequential arginine and insulin stimulation), thyroxine, thyroid-stimulating hormone, plasma cortisol, testosterone, prolactin, and urinary follicle-stimulating hormone and luteinizing hormone. Ten of 12 children (83%) had abnormal responses to both tests of growth hormone stimulation. All growth hormone-deficient patients treated prior to puberty and tested at least 2 years following completion of cranial irradiation had decelerated linear growth. Results of thyroid function tests were abnormal in 4 patients: 2 patients had evidence of primary hypothyroidism, and 2 showed secondary or tertiary hypothyroidism. Two patients had inadequate cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone and luteinizing hormone, serum prolactin, and serum testosterone levels were appropriate for age in all patients.

Adolescent↗
PubMed1983

Visual-evoked responses in children with optic gliomas, with and without neurofibromatosis.

Gliomas of the optic pathway are considered to be slowly growing, potentially benign neoplasms. Association of this tumor with neurofibromatosis has been well established. We have recently evaluated 7 children with putative evidence of optic glioma, 6 of whom had additional evidence of neurofibromatosis. All children had CT scans and visual-evoked responses. CT scan allows anatomic assessment of the optic nerve mass while evoked responses offer the possibility of identifying functional abnormalities in the optic pathway. It is felt that both these modalities will add in the early diagnosis of optic gliomas and help to further establish the true natural history of this tumor.

Adolescent↗
PubMed1983

Incontinence of urine and stool following treatment in infancy for embryonal rhabdomyosarcoma.

A vaginal rhabdomyosarcoma which occurred in an 11-month-old infant was treated with conservative surgical excision, radiation therapy and chemotherapy. The long-term sequelae of this therapy included rectal stenosis, which required surgical correction, and urinary incontinence. The patient may have had fewer long-term complications if a more aggressive surgical procedure had been performed at the time of diagnosis because a gross and microscopically complete excision would have obviated the need of postoperative pelvic irradiation. Strong consideration of total surgical excision should be given to infants with pelvic rhabdomyosarcoma.

Fecal Incontinence↗
PubMed1982

Referral patterns of childhood brain tumors in the state of Connecticut.

Data from the Connecticut Tumor Registry (1968-1979) were analyzed to determined whether referral patterns influenced survival rates in children with brain tumors. Two-hundred-seventy-eight children with brain tumors were identified. Less that one-third of the children received all their treatment at university cancer centers. An actuarial analysis of survival rates revealed that children with medulloblastomas treated solely at university cancer centers had projected five-year survival rates of 7.4%. Children with medulloblastomas treated solely at community hospitals had projected five-year survival rates of 29%. Children with brainstem gliomas treated at university cancer centers had projected five-year survival rates of 40% whereas of those children treated at community hospitals only one patient was alive at 13 months. No major differences in survival were identified among children with other tumor types. These data suggest that children with certain types of brain tumors may fare better when treated at university cancer centers.

Adolescent↗
PubMed1982

An improved high-pressure liquid chromatographic assay for secobarbital in serum.

A high-pressure liquid chromatographic method for the analysis of secobarbital in serum was developed. Secobarbital was extracted from buffered serum (pH 5.5) with a solvent mix of hexane-ether-n-propanol. 5-(4-Methylphenyl)-5-phenylhydantoin was added as an internal standard. Separation of secobarbital and internal standard from serum constituents and other drugs was achieved on a 5-mum C-18 reversed-phase column using an acetonitrile-phosphate buffer (pH 4.4) mobile phase. The eluent was monitored at 195 nm. The sensitivity limit of the assay was approximately 0.02 microgram/ml with 0.5 ml of serum sample. The application of this method to pharmacokinetic studies in pediatric patients was demonstrated.

Child, Preschool↗
PubMed1982

Rectal absorption and disposition of secobarbital in epileptic children.

The absorption and disposition of rectally administered secobarbital was studied in ten epileptic children, ages 2-13 yrs. Five subjects received secobarbital rectally in solution, and the other five received secobarbital suppositories. Concentration of secobarbital in serum was serially determined during 48 hrs after a single rectal dose of about 5 mg/kg. The rate of absorption of secobarbital, as measured by the time to reach peak serum concentration, was much more rapid from the solution than the suppository (0.92 +/- 0.47 hr vs 4.60 +/ 2.30 hr). The peak serum concentration of secobarbital in the solution group was consistently higher than in the suppository group (2.26 +/- 0.37 micrograms/ml vs 1.35 +/- 0.24 microgram/ml). None of the individual peak serum concentrations exceeded 3 micrograms/ml, which is well below the previously reported minimum toxic concentration of secobarbital (ie, 6 microgram/ml). The elimination half-life of secobarbital varied over a wide range, from 2.7 to 13.5 hr, and is, on the average, shorter than estimates previously reported for adult volunteers or poly-drug abusers. Also, the mean elimination half-life did not differ between the solution and the suppository groups. The extent of rectal absorption of secobarbital, as assessed by the area under the serum concentration time curve, was not significantly different between the solution and the suppository treatments. If rectal secobarbital is considered for treatment of prolonged seizure, a rectal solution may offer a more rapid and consistent onset of action than with the suppository preparation.

Adolescent↗
PubMed1981

Prognostic indicators in hemiparetic cerebral palsy.

In an attempt to define prognostic indicators of intelligence and seizures in the hemiparetic cerebral palsy population, birth histories, electroencephalograms, and computerized tomographic (CT) scans were reviewed in 52 children with hemiparetic cerebral palsy. Cases were excluded when the hemiparesis might have been related to events beyond the neonatal period, such as meningitis, trauma, focal seizures, tumor, or vascular insults. Detailed neurological histories and examinations were done in all patients. Intellectual evaluations, electroencephalograms, and CT scans were obtained. There was no significant relationship of birth history to subsequent seizure development or mental retardation. In contrast, findings in electroencephalograms and CT scans correlated well with the development of seizures and abnormal intelligence. Children who shared anatomical abnormalities of commissural pathways, association pathways, or cerebral cortex were found to have a much higher incidence of seizures and abnormal intelligence.

Cerebral Palsy↗
PubMed1981

Extraneural metastases in childhood brain tumors.

Although extraneural metastases are known to occur with primary tumors of the central nervous system, they are considered a rarity. Large autopsy series have placed the frequency at 0.4 to 0.5%. At the Roswell Park Memorial Institute, 36 children with brain tumors have been treated with a combination of surgery, radiotherapy, and chemotherapy in the past 12 years. We recently reviewed the autopsies obtained on 15 of these children and found that 4 (26%) had extraneural metastases. An additional child, who was not autopsied, had extraneural extension diagnosed during life. This inordinately high incidence of metastases outside the nervous system in children with aggressively treated brain tumors raises questions about their cause. The prolonged survival of these patients may have allowed growth of sufficient generations of extracranial metastatic cells for the extraneural disease to become clinically significant. Another possibility is that chemotherapy may alter the patients' immune system and thus promote extracranial tumor growth. As larger numbers of childhood brain tumors are managed with multimodality therapy, it may be possible to evaluate the extent to which treatment allows intracranial neoplasms to spread outside the nervous system.

Adolescent↗
PubMed1981

Salivary concentrations and plasma protein binding of carbamazepine and carbamazepine 10,11-epoxide in epileptic patients.

1. The relationships between saliva, free and total plasma concentrations of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) were studied in 24 chronically medicated epileptic patients. Four patients were taking CBZ alone, while 20 were taking one or more additional anticonvulsant drugs. 2. The free fraction of CBZ in plasma ranged from 0.19 to 0.33 (mean 0.24) while the saliva:plasma (S:P) concentration ratios ranged from 0.20 to 0.35 (mean 0.27). The free fraction of CBZ-EP in plasma ranged from 0.16 to 0.50 (mean 0.32), while the S:P ratios ranged from 0.14 to 0.70 (mean, 0.43). The plasma protein binding and S:P ratios of these compounds appeared to be independent of age, sampling time and concurrently administered anticonvulsant drugs. 3. Significant linear relationships between saliva and total plasma concentrations and between saliva and free plasma concentrations were observed for both compounds (P less than 0.001). However, salivary concentrations of CBZ and CBZ-EP were significantly more reliable as predictors of their respective free plasma concentrations than of their respective total plasma concentrations (P less than 0.01). 4. It is concluded that measurement of CBZ and CBZ-EP in the saliva of chronically medicated epileptic patients provides a more reliable estimate of the pharmacodynamically active, free concentrations of these compounds in plasma.

Blood Proteins↗
PubMed1981

Primitive neuroectodermal tumors of childhood. An approach to therapy.

Primitive neuroectodermal tumors are found in the cerebrum of children and young adults. The are clinically highly malignant and have rapid course from diagnosis to death. Their microscopic pathology reveals 90% to 95% nondifferentiation, frequent mitoses, and small dark cells with no observable cytoplasm. This paper discusses the treatment of three children with this tumor with a combination of surgery irradiation, and combination chemotherapy. The results of this approach are compared with previous reports in the literature. The average survival in this series is 24 months versus approximately 8 months reported in the literature.

Adolescent↗
PubMed1980

Multimodality therapy for medulloblastoma.

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 were in their second and third recurrences. Three remain in remission. The median duration of response was 18.8 months, and median time from start of chemotherapy to death was 32 months using the Kaplan-Meier technique. In addition, 9 other patients with newly diagnosed medulloblastoma were treated with craniospinal radiation and the same adjuvant chemotherapy as above. The first 5 patients also received intraventricular methotrexate and/or intravenous BCNU during radiotherapy. The toxicity in the 5 patients was very severe. There were three toxic deaths, one death from cancer; one patient survives disease-free, but he is demented. With the discontinuance of intraventricular methotrexate and the postponement of myelo-suppressive chemotherapy until after the completion of radiotherapy, the regimen has been well tolerated. All 4 patients treated this way remain alive, well, and disease-free at intervals up to 36 months. We conclude that recurrent medulloblastomas are sensitive to multiagent chemotherapy and that prolonged remissions may occur. With primary adjuvant chemotherapy, extreme caution with myelo-suppressive drugs must be exercised during the period of craniospinal radiotherapy. We also do not recommend the use of intraventricular methotrexate. When these two criteria were followed, the preliminary results with adjuvant chemotherapy appear encouraging.

Adolescent↗
PubMed1979

Cystic fibrosis with brain abscess.

A 21-year-old patient with cystic fibrosis developed bilateral brain abscesses due to anaerobic Streptococcus. This rare association presents an interesting etiologic study.

Adult↗
PubMed1979

Combination chemotherapy in recurrent medulloblastoma.

Five children with recurrent medulloblastomas were treated with Vincristine, BCNU, Methotrexate and Dexamethasone. All five patients responded to therapy. Two of the patients are alive and well 30 and 48 months later; one died of disease 19 months after first recurrence; one developed a further recurrence at 18 months but responded to additional chemotherapy and is alive; and the fifth patient developed a second recurrence after 28 months but has responded to repeat chemotherapy and radiotherapy and is now asymptomatic. These results support the concept that medulloblastomas are sensitive to chemotherapy and suggest that chemotherapy should be considered in cases of recurrent medulloblastomas. In addition, the importance of trials now in progress which employ both adjuvant chemotherapy and radiotherapy in newly diagnosed medulloblastomas is apparent.

Adolescent↗
PubMed1979

Computed tomography and childhood seizure disorders.

Computerized tomography (CT) was performed on 256 children with seizure disorders. The incidence of abnormal scans was closely related to seizure type, and permitted separation of patients into a low-yield and a high-yield group. Low-yield groups included children with idiopathic generalized seizures, children in whom both the neurologic examination and electroencephalogram (EEG) were normal, and children with a generalized seizure of unknown etiology in whom the neurologic examination and the EEG were normal. The high-yield groups included children with partial seizures with elementary symptomatology, partial seizures with complex symptomatology, generalized seizures with known etiology, neonates with seizures, and children whose seizures began as neonates. The overall incidence of abnormalities in the entire group was 33 percent. An abnormal neurologic examination increased the incidence of abnormal CT scans to 64 percent. EEGs were abnormal in 65 percent of the children, but only focal slowing resulted in a significant increase in the incidence of abnormal CT scans. Seven children (2.7 percent) had intracranial abnormalities requiring surgery. If the neurologic examination and EEG were normal, the yield of abnormal CT scans was only 5 percent of the total.

Adolescent↗
PubMed1979

Liquid-chromatographic assay of diazepam and its major metabolites in plasma.

We describe a method for simultaneous quantitation of diazepam and its metabolites, N-desmethyldiazepam and oxazepam, by reversed-phase liquid chromatography with ultraviolet detection at 254 nm. After extraction with chloroform at pH 11.0, the organic extract is evaporated, and the residue is reconstituted in a small volume of mobile-phase and chromatographed. Concentrations as low as 12 to 20 microgram/L can be detected after extraction of only 250 microL of plasma. The maximum within-day and day-to-day coefficients of variation for each compound at concentrations of 50, 250, and 1000 microgram/L are 8.0 and 10.3%, respectively. Of 14 commonly used anticonvulsant, sedative, and psychotherapeutic drugs, only carbamazepine and lorazepam may interfere with analysis for oxazepam or N-desmethyldiazepam, or both. Total chromatography time for a single sample is less than 10 min. Applicability of the method to diazepam disposition studies in children is illustrated.

Chromatography, High Pressure Liquid↗
PubMed1978

Central core disease in one of identical twins.

A case of central core disease in one of identical twins is presented. The light and electron microscopic pathology is reviewed. We believe that these entities are not genetic in this sibship and may be an example of isolated maturational arrest of non-specific aetiology.

Arthrogryposis↗