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Biomedical subjects

R K Mulhern

Publications and source records attributed to R K Mulhern.

At least 73 records · Page 4Linked to original sources
PubMed1991

A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation.

To compare the late neuropsychologic toxicities of CNS prophylaxis for childhood acute lymphoblastic leukemia (ALL), longitudinal assessments were performed on three groups of patients: those who received repeated courses of moderate-dose (1 g/m2) intravenous (IV) and intrathecal methotrexate (IT MTX) without cranial irradiation (MTX group, n = 26), those who received IT MTX and 18 Gy cranial irradiation (18-Gy group, n = 23), and those who received IT MTX and 24 Gy cranial irradiation (24-Gy group, n = 28). All patients were free of CNS leukemia at diagnosis and had remained in continuous, complete remission 5 to 11 years (median, 7.4 years) following CNS prophylaxis. An analysis of serial intelligence quotient (IQ), achievement, and neuropsychologic studies revealed no significant influence of either age at CNS prophylaxis or CNS prophylaxis group on any neuropsychologic outcome measure. After adjusting for changes in IQ test versions that were necessitated by advancing patient age, no statistically significant declines in Verbal, Performance, or Full Scale IQs were noted for the three CNS treatment groups. However, comparisons of group means masked declines in individual children; 22% to 30% of children exhibited a clinically significant deterioration (greater than or equal to 15 points) in uncorrected IQ values over the study period. Female sex was associated with an increased risk of deterioration in Verbal IQ, but we were unable to identify risk factors associated with other declines in intellect and achievement. The inability to reliably predict individual patients at risk for clinically significant neuropsychologic toxicities on the basis of age at diagnosis or specific method of CNS prophylaxis suggests that other etiologic factors must be explored as the basis for these changes, such as ecologic factors and chemotherapy during the continuation phase of treatment.

Adolescent↗
PubMed1990

Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study.

Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.

Adolescent↗
PubMed1989

Long-term follow-up of parental adjustment following a child's death at home or hospital.

The adjustment of parents whose children had died from cancer 6 to 8 years earlier was assessed using structured interviews and standardized inventories. Forty parents had participated in a home hospice program during the terminal phase of their child's illness whereas 22 were parents of children who died in the hospital. Home care parents reported significantly stronger relationships with spouse and remaining children, firmer religious convictions, more adequate coping abilities, and less residual guilt than non-home care parents. On the Minnesota Multiphasic Personality Inventory (MMPI), non-home care parents exhibited more frequent indications of maladjustment including somatization, depression, and interpersonal problems. The results confirm that the more optimal adjustment of home care parents which was first reported 5 years earlier has been maintained. Support and expansion of pediatric home hospice programs are strongly encouraged in light of the positive results of our longitudinal studies.

Adaptation, Psychological↗
PubMed1989

Lorazepam pharmacodynamics and pharmacokinetics in children.

We evaluated the effects of low doses of lorazepam on episodic versus long-term memory, attention, and somatic and affective symptoms, as well as its pharmacokinetics, in a group of 16 children aged 2.8 to 14.2 years. Psychologic assessments of each child were performed twice before intravenous administration of lorazepam (0.03 mg/kg), and 1 1/2 hours and 24 hours after lorazepam; there were no significant changes in long-term memory, attention, or somatic symptoms. There was a significant decrease in affective symptoms at 1 1/2 hours (p = 0.011), with a trend toward decreased anxiety at 1 1/2 and 24 hours after lorazepam (p = 0.026 and 0.028, respectively). There was also a selective anterograde amnestic effect in 5 of 16 children after lorazepam (p = 0.06). Mean (+/- SD) lorazepam systemic clearance was 1.3 +/- 0.4 ml/min/kg, with a terminal half-life of 10.5 +/- 2.9 hours and an unbound clearance of 15.9 +/- 5.2 ml/min/kg. A group of healthy adult volunteers who were given lorazepam had a mean systemic clearance of 1.0 +/- 0.4 ml/min/kg, somewhat less than that of the children (p = 0.069). There were no significant differences in any lorazepam pharmacokinetic parameter between those children who did versus those who did not have changes in affective symptoms or amnesia. These data should be helpful in establishing the dose of lorazepam in children, as the drug becomes more widely used as an antiemetic, premedicant, and anticonvulsant agent.

Adolescent↗
PubMed1989

Neuropsychological status of children with acute lymphoblastic leukemia treated for central nervous system relapse.

Approximately 10% of children treated with contemporary therapy for acute lymphoblastic leukemia (ALL) will experience an isolated relapse in the central nervous system (CNS). From 5 to 25% of this group will become long-term survivors, but only after additional, more aggressive therapy. A review of the limited number of studies of children surviving treatment for CNS relapse disclosed a strikingly higher incidence of intellectual impairment than was found in similarly treated patients who remain in complete remission. Specific risk factors for this complication included the number of courses of cranial irradiation, a young age at treatment, increasing time since treatment, neuropathological changes apparent on abnormal computed tomography scans of the brain, and seizures. The methodological problems inherent in neurobehavioral research in childhood acute lymphoblastic leukemia are critically reviewed and suggestions for future studies are offered. Children with a CNS relapse should be serially evaluated for psychoeducational performance to facilitate early intervention in cases of learning difficulties.

Child↗
PubMed1989

Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy.

In an effort to reduce the severity of late neurotoxicities associated with cranial irradiation, 14 infants and young children with malignant brain tumors were given preirradiation chemotherapy for 2 to 22 months (median, 8 months). Prospective neurodevelopmental evaluations were routinely conducted and now extend from 35 to 60 months (median, 41 months) postdiagnosis, and 10 to 52 months (median, 31 months) postirradiation in the 12 surviving children. At the initiation of chemotherapy, less than one fourth of the patients displayed normal performance status or mental functioning on age-corrected tests; the majority remained stable or declined while receiving chemotherapy. Declining mental development and adaptive behavior were noted in six patients following radiation therapy with only two patients now functioning in the normal range for age. The analysis suggests that neurodevelopmental progress is a function of multiple factors, including neurologic and sensorimotor deficits associated with the tumor, surgical intervention, and chemotherapy that antedated radiation therapy. This implies that delaying irradiation will not necessarily improve the patients' functional status. Whether the interval of postponement of irradiation evidenced in this sample will translate into an ultimately better quality of life remains unknown. Given the probable interaction of multiple risk factors, well-controlled prospective clinical trials are needed to definitively analyze this issue.

Auditory Perception↗
PubMed1989

Social competence and behavioral adjustment of children who are long-term survivors of cancer.

Relatively little is known about the special needs of long-term survivors of childhood cancer or the factors that make this growing population vulnerable to chronic psychologic disorders. We therefore surveyed 183 children who had been treated for cancer at St Jude Children's Research Hospital and were free of the disease for greater than or equal to 2 years after completing therapy. Parental responses to the Child Behavior Checklist, a standardized inventory of social competence and behavioral problems, were analyzed in relation to demographic and medical variables, as well as the children's appearance and functional status. School-related problems and somatic complaints of undetermined origin were increased fourfold relative to age- and gender-adjusted rates for peer groups in the general population. The presence of functional but not cosmetic impairments increased the risk of academic and adjustment problems. An older age at evaluation, treatment with cranial irradiation, and residence in a single-parent household were also associated with an increased risk of psychologic problems. General pediatricians must eventually assume responsibility for the extended follow-up care of children who have survived a malignancy. Their awareness of the high-risk groups described in this report should facilitate more timely identification of problems and referral of the children to appropriate services.

Achievement↗
PubMed1988

Brain tumors in the very young child. Postoperative chemotherapy in combined-modality treatment.

Twelve consecutively diagnosed children with brain tumors, ages 7 to 27 months, were treated by a combined-modality approach featuring aggressive surgical resection followed by chemotherapy and delayed irradiation. Patients received multiple clinical neurologic examinations and psychological evaluations, as well as diagnostic imaging studies, to monitor the efficacy of chemotherapy and toxic effects of therapy. Six of the eight children with residual tumor evident postoperatively on computed tomography scans had objective responses to chemotherapy. The efficacy of chemotherapy was further demonstrated by the lack of disease progression for 7 months or longer in eight children, seven of whom remain free of tumor 19 to 57 months (median, 28 months) from the date of diagnosis. The neurologic status of ten patients improved during treatment. Developmental progress was normal in two, low average in three, and frankly deficient in four of ten children formally evaluated. These results indicate that postoperative chemotherapy, added to a regimen of surgical resection and delayed irradiation, prolong survival with only minimal short term neurotoxicity in the majority of very young children with malignant brain tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Late effects of antileukemic treatment.

Increasing numbers of childhood ALL survivors have increased the need to assess the physical and psychosocial functioning of this group in a careful manner. This article reviews data on the frequency and types of second malignancies, structural and functional changes in the central nervous system, endocrine effects on growth and reproduction, and psychosocial aspects of development. Most long-term survivors of ALL do not have serious or life-threatening medical problems; however, medical and psychosocial problems may not be insignificant and may require coordinated management over prolonged periods.

Antineoplastic Agents↗
PubMed1988

Cognitive processing of children with Williams syndrome.

The Illinois Test of Psycholinguistic Abilities was administered to 22 children with Williams syndrome and to 22 children with non-specific development disabilities, matched for age, sex and global intelligence. Visual processing abilities significantly differentiated the two groups. The children with Williams syndrome had substantially more problems with visual reception, visual closure and visual memory tasks. They appeared to adhere more rigidly than controls to a global deployment of visual attention. Their visual processing difficulties were not related to the level of mental ability. Visual reception, closure and memory scores correctly classified 82 per cent of the children with Williams syndrome and 68 per cent of the controls. Instructional and remedial programs are needed for these children.

Aortic Valve Stenosis↗
PubMed1988

Psychologic and neurologic function following treatment for childhood temporal lobe astrocytoma.

Seven school-aged children treated for temporal lobe astrocytomas with surgical resection and irradiation were prospectively tested to evaluate their intellectual, academic, personality, and neurologic status after therapy. At their most recent follow-up examination, neuropsychologic functioning was adequate in only two patients. The other five children manifested either intellectual deterioration, learning disability, mental retardation, or psychopathology. These deficits were associated with poor postoperative performance status, inadequate seizure control, tumor recurrence, and younger age at diagnosis. No pattern of intellectual, academic, or personality dysfunction emerged in association with left- versus right-hemisphere tumors.

Achievement↗
PubMed1988

Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation.

Previous studies have found that CNS prophylaxis of children with leukemia, especially young children receiving cranial irradiation, causes neuropsychologic deficits. In the present study, 40 children in continuous complete remission from acute lymphocytic leukemia (ALL) were given a battery of tests to assess memory functioning 5 years after CNS prophylaxis. All children were free of CNS disease at diagnosis and had been randomly assigned to receive CNS prophylaxis with either 1,800 cGy cranial irradiation (CRT) plus intrathecal (IT) methotrexate (MTX) or IT MTX plus intravenous (IV) high-dose MTX (HDMTX). No treatment- or age-related differences were seen on 16 standardized memory measures. However, scores of the combined sample were significantly lower than age-corrected norms on a test of visual-spatial memory and on four scales of verbal memory. Differences in methods or intensity of CNS prophylaxis and study group selection criteria are proposed to explain our findings and to resolve discrepancies with previous reports. The long-term neuropsychological sequelae in these survivors of ALL may be attributable to some common factor, such as the disease itself or systemic and IT chemotherapy.

Child↗
PubMed1988

Feasibility and efficacy of preirradiation chemotherapy for pediatric brain tumors.

Preirradiation chemotherapy is a potentially important component of combined treatment for brain tumors; however, concerns over its side effects and antitumor activity have impeded its evaluation in clinical trials. To determine the feasibility of administering such therapy to children, we assessed the responses of 38 brain tumor patients (median age, 2 years) to 12 weeks of combination chemotherapy given after surgical resection but before irradiation. Transient myelosuppression was noted in all patients, but was not associated with infections or complications of surgical wounds. The ability of the patients to perform activities of daily life, as rated with the Karnofsky performance scale, was either improved (n = 14) or unchanged (n = 18) at the end of the evaluation period. In the remainder of the group, functional deterioration was clearly related to causes other than drug treatment. Prior chemotherapy did not compromise the delivery of radiation except for a brief interruption of spinal irradiation in 3 patients. Objective responses to chemotherapy, defined as a greater than 50% decrease in tumor masses, occurred in 16 of the 31 patients who had subtotal resections; only 6 patients in the entire group showed disease progression during the 12 weeks of drug administration. We conclude that chemotherapy of the type used in this study is well tolerated and produces beneficial effects in children with brain tumors.

Adolescent↗
PubMed1988

Acute lymphoblastic leukemia: long-term psychological outcome.

Children diagnosed with acute lymphoblastic leukemia (ALL) now have an excellent chance for a medical cure. Nearly 90% can expect to attain an initial remission and the majority of those will remain disease-free. There is increasing concern about the long-term consequences of ALL and its treatment on the psychological adjustment of the survivor. This article selectively reviews the available literature on the neuropsychological and psychosocial adjustment of long-term survivors of ALL. The risk of neuropsychologic deficiencies among children who have remained in continuous remission has been the focus of conflicting findings, while the risk among those who have survived CNS relapse is clearly elevated. Generally, long-term survivors of childhood cancer have a 30-40% risk of school-related problems. Moreover, children treated for ALL with cranial irradiation have 3-4 times the risk of school problems relative to those who are not irradiated. Early identification of problems would facilitate referrals for appropriate intervention and hopefully minimize future difficulties.

Adaptation, Psychological↗
PubMed1987

Intellectual and academic achievement status after CNS relapse: a retrospective analysis of 40 children treated for acute lymphoblastic leukemia.

We determined the intellectual and academic status of 40 children with acute lymphoblastic leukemia who had experienced a primary isolated relapse in the CNS by analyzing the results of psychoeducational tests administered a median of 6.1 years after the relapse. Mean scores for full-scale IQ (87.5), verbal IQ (86.7), performance IQ (90.3), as well as academic achievement in reading (89.8), spelling (83.9), and mathematics (83.5) were significantly below normal expectations for age. Twenty percent of the group were mentally retarded and were receiving special educational assistance. The best clinical predictors of full-scale IQ were the number of radiation therapy courses, age, and the presence or absence of cerebral pathology as measured by computed tomography (CT). Children who were younger at the time of treatment, who received two courses of radiation therapy, and who had clinical seizures and structural abnormalities of the brain as detected by CT had the poorest psychological outcome. Although the psychoeducational consequences of CNS relapse and its attendant treatment are significant, these must be balanced by consideration of the relatively low probability of long-term survival without aggressive therapy. Recognition of this type of delayed morbidity with systematic surveillance and prompt attempts at rehabilitation may decrease or at least minimize these sequelae.

Achievement↗
PubMed1986

Serial neuropsychological studies of a child with acute lymphoblastic leukemia and subsequent glioblastoma multiforme.

A 10-year-old boy had a right posterior parietal glioblastoma 5 years after completing treatment for acute lymphoblastic leukemia. Interim findings included seizures, leukoencephalopathy, diffuse mineralizing microangiopathy, and abnormal changes in neuropsychological test performance, which, in retrospect, provided information about the location of the tumor. This case highlights unusual sequelae of childhood leukemia and its treatment, as well as the value of neuropsychological procedures in assessing functional status and integrity of the brain.

Brain Neoplasms↗
PubMed1986

The subacute effects of CNS prophylaxis for acute lymphoblastic leukemia on neuropsychological performance: a comparison of four protocols.

We report an assessment of the intellectual functioning after one year of therapy of 117 children treated for acute lymphoblastic leukemia (ALL) who were assigned to one of four protocols for central nervous systems (CNS) prophylaxis. These protocols were (a) 2400 rad cranial irradiation plus concurrent intrathecal methotrexate (i.t. MTX), (b)i.t. MTX alone, (c) 1800 rad cranial irradiation plus concurrent i.t. MTX, and (d) a protocol for high-risk patients that included intensive systemic chemotherapy plus 2400 rad delayed irradiation. Neuropsychological evaluation consisted of the Wechsler intelligence scales, the Wide Range Achievement Test, and selected tests from the Halstead-Reitan Neuropsychological Battery administered one year after diagnosis. All patients performed in the average range on measures, although the high-risk patients performed marginally worse than did the others. In general, our results do not support previous reports that cranial irradiation results in early adverse neuropsychological sequelae.

Journal Article↗