Biomedical subjects

R K Mulhern

Publications and source records attributed to R K Mulhern.

At least 55 records · Page 3Linked to original sources

PubMed1995

Family cohesion and expressiveness promote resilience to the stress of pediatric bone marrow transplant: a preliminary report.

The effect of perceived family environment as a determinant of adjustment in children undergoing bone marrow transplant (BMT) was assessed in a prospective, longitudinal study. Measures of patients' social competence, behavior problems, and self-esteem, along with perceived family conflict, cohesion, and expressiveness, were obtained before hospital admission for BMT and again in the period 6 to 12 months post-BMT. Significant declines were observed in post-BMT social competence and overall self-concept. Before BMT, perceptions of family conflict showed a moderate inverse correlation with patient adjustment, whereas family cohesion and expressiveness were unrelated or were weakly related with adjustment measures. In contrast, all pre-BMT family environment variables were highly predictive of adjustment post-BMT. Using a cross-lagged correlational approach, it was determined that perceived family cohesion and expressiveness act as protective factors, promoting resilience to the stresses of BMT, whereas family conflict acts directly as a risk factor that adversely affects adjustment regardless of stress level.

Adaptation, Psychological↗

PubMed1994

Quality of survival among children treated for brain stem glioma.

In order to describe the status of long-term survivors of brain stem glioma, neuropsychological and behavioral measures were obtained a median of 2.5 (range 1.5-5.6) years after diagnosis from 16 survivors of 51 consecutively diagnosed children with brain stem glioma between 1983 and 1991. Among 11 children with dorsally exophytic tumors, 7 were treated with surgery alone (SRG) and 4 received conventionally fractionated local cranial radiation therapy (CFRT; 54-56 Gy) to the brain stem following surgery, 3 of these because of recurrent disease. Five others with diffusely infiltrative brain stem tumors received hyperfractionated radiation therapy (HFRT; 70.2 Gy) to the brain stem; 4 following biopsy or limited resection and 1 without prior surgery. IQs of children in the CFRT (mean 89, SD 24.4) and HFRT (mean 85, SD 12.7) groups were not significantly different. Children in the SRG group had significantly higher IQs (mean 100, SD 11.0) and fewer neurologic deficits than those who had received CFRT or HFRT. However, after statistically controlling for severity of neurologic deficits, treatment had no effect on IQ. The severity of residual neurologic deficits accounted for 42% of the variance in IQ scores; children with fewer neurologic problems scored higher. Additional studies are required to evaluate the potential neuropsychological benefits of equivalent total doses of HFRT compared to CFRT.

Adolescent↗

PubMed1994

Medulloblastoma in very young children: outcome of definitive craniospinal irradiation following incomplete response to chemotherapy.

PURPOSE: To evaluate survival and neurodevelopmental outcomes following radiation therapy in infants and young children with residual or progressive medulloblastoma after primary chemotherapy. PATIENTS AND METHODS: Thirteen young patients (< or = 36 months old) with medulloblastoma were treated with preirradiation multiagent chemotherapy and maximal surgical resection. Patients were scheduled to receive radiation therapy at the time of documented disease progression or upon completion of chemotherapy with residual disease. All patients underwent neurodevelopmental evaluation at the time of diagnosis, before receiving radiation therapy, and at yearly intervals posttreatment. RESULTS: Two patients completed the scheduled chemotherapy with residual disease and received delayed radiation therapy. The remaining 11 patients had either local or leptomeningeal progression during chemotherapy (median time to progression, 5 months). Six patients had a complete response (CR) to radiation therapy, and three of these children are alive 48 to 104 months postdiagnosis. Of the five patients who had progressive disease (PD) during radiation therapy or residual imaging abnormalities after treatment, only one is alive (with stable enhancing leptomeningeal abnormalities) 48 months postirradiation. Two additional survivors were rendered disease-free by surgical resection before radiation therapy and are without evidence of disease at 91 and 107 months after diagnosis. Thus, six of 13 patients are alive at 48 to 107 months postdiagnosis. Neurodevelopmental scores tended to be below age norms at diagnosis; scores improved during chemotherapy, but then decreased during posttreatment follow-up evaluation. CONCLUSION: Radiation therapy appears to produce long-term disease-free survival in a proportion of very young patients who have progressive or residual medulloblastoma during or after primary chemotherapy. However, neurodevelopmental deficits are frequent among long-term survivors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Sibling adaptation to childhood cancer collaborative study: prevalence of sibling distress and definition of adaptation levels.

A multisite collaborative study assessed the frequency and intensity of emotional/behavioral distress in siblings of children with cancer. A sample of 254 siblings, aged 4 to 18 years, and their parents completed interviews and self-report measures 6 to 42 (average 22.5) months after diagnosis of cancer in a brother or sister. Matched controls were obtained from respondents to the Child Health Supplement of the National Health Interview Survey administered in 1988 (CHS88). Before diagnosis, the prevalence of parent-reported emotional/behavioral problems among siblings was similar to that in the general population (7.7% vs 6.3%; p = not significant). After diagnosis, prevalence rose to 18% among siblings. When siblings were grouped according to the presence or absence of problems exacerbated by and/or arising after diagnosis, four levels of adaptation, consistent with scores on the Behavior Problem Scales from the CHS88, emerged. This differentiation may help explain inconsistencies in sibling response reported previously and provides a framework for investigating factors that enhance adaptation.

Adaptation, Psychological↗

PubMed1993

Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors.

BACKGROUND: Among patients with malignant brain tumors, infants and very young children have the worst prognosis and the most severe treatment-related neurotoxic effects. Therefore, in 1986, the Pediatric Oncology Group began a study in which postoperative chemotherapy was given in order to permit a delay in the delivery of radiation to the developing brain. METHODS: Children under 36 months of age with biopsy-proved malignant brain tumors were treated postoperatively with two 28-day cycles of cyclophosphamide plus vincristine, followed by one 28-day cycle of cisplatin plus etoposide. This sequence was repeated until the disease progressed or for two years in 132 children 24 months of age at diagnosis and for one year in 66 children 24 to 36 months of age at diagnosis. After this, the patients received radiation therapy. The response to the first two cycles of chemotherapy was measured in 102 patients with residual postoperative disease. RESULTS: The first two cycles of cyclophosphamide and vincristine produced complete or partial responses in 39 percent of the 102 patients who could be evaluated. The response rates were highest among patients with medulloblastomas, malignant gliomas, or ependymomas. Patients with brain-stem gliomas or embryonal tumors (primitive neuroectodermal tumors) had little or no response. The progression-free survival rate was 41 percent at one year for children who were 24 to 36 months old at diagnosis and 39 percent at two years for those under 24 months of age at diagnosis. Multivariate analysis identified embryonal tumors as a significant adverse prognostic feature (relative risk, 2.2; 95 percent confidence interval, 1.4 to 3.4) and complete resection as a favorable feature (relative risk, 0.33; 95 percent confidence interval, 0.20 to 0.54). Complete responses to chemotherapy were associated with a progression-free survival rate approaching that achieved with gross total resection. A comparison of cognitive evaluations obtained at base line and after one year of chemotherapy revealed no evidence of deterioration in cognitive function. CONCLUSIONS: Chemotherapy appears to be an effective primary postoperative treatment for many malignant brain tumors in young children. Disease control for one or two years in a large minority of patients permitted a delay in the delivery of radiation and, on the basis of preliminary results, a reduction in neurotoxicity. For patients who had undergone total surgical resection or who had a complete response to chemotherapy, the results are sufficiently encouraging to suggest that radiation therapy may not be needed in this subgroup of children after at least one year of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Chlorpromazine with and without lorazepam as antiemetic therapy in children receiving uniform chemotherapy.

We prospectively studied the efficacy and adverse effects of chlorpromazine (30 mg/m2 given intravenously) plus lorazepam (0.04 mg/kg given intravenously) versus chlorpromazine alone in a controlled, double-blind, randomized, parallel-design investigation in 25 children (1.5 to 17.3 years of age) with acute lymphoblastic leukemia. Response to other antiemetics in eight children refusing random assignment to treatment was also evaluated. All children were receiving intravenous infusions of teniposide plus cytarabine, the pharmacokinetics of which were characterized for each of the one to four courses. There were no differences between the 11 patients randomly assigned to receive chlorpromazine alone and the 14 randomly assigned to receive lorazepam plus chlorpromazine in the number of emesis episodes (6.0 vs 5.9; p = 0.53), frequency of dystonic reactions (3% vs 5%), or akathisia (13 vs 10%). The only serious adverse event, symptomatic hypotension, occurred in a boy receiving chlorpromazine plus lorazepam. An exploratory pharmacodynamic analysis revealed that the only variable that correlated with vomiting was cytarabine 1 1/2-hour plasma concentration (p = 0.007). Children who received either chlorpromazine plus lorazepam or chlorpromazine alone had fewer episodes of vomiting than those who received "conventional" antiemetic therapy (6.0 vs 8.6; p = 0.01). We conclude that the severity of emesis is related to the plasma concentration of cytarabine; that intravenously administered chlorpromazine is as effective as chlorpromazine plus lorazepam in preventing chemotherapy-induced vomiting; and that the potential for adverse effects with the addition of lorazepam may be a disadvantage.

Adolescent↗

PubMed1993

Factors associated with social and behavioral problems among children recently diagnosed with brain tumor.

Compared the psychological adjustment of 81 children with brain tumors to that of 31 control children with various malignancies not involving the central nervous system. Both groups exhibited significantly increased frequencies of elevations on one or more age- and gender-corrected Social Competence and Behavior Problems scales of the Child Behavior Checklist (CBCL) relative to normative expectations. Comparison of the Brain Tumor and Cancer Control groups revealed no significant differences on any CBCL scale. Among children diagnosed with brain tumors, stepwise multiple regression analyses revealed that low child IQ, residence in a single-parent family, moderate to severe disfigurement, low SES, tumor location, and severe functional impairment were associated with decreased Social Competence scores. Elevated Behavior Problems scores were associated with younger maternal age at the child's birth, tumor location, and residence in a single-parent family. Results reinforce the need to consider complex relationships between demographic characteristics of the child's family, type of brain damage, and the cosmetic and functional status of the child in determining acute psychological adjustment of brain-damaged children.

Adaptation, Psychological↗

PubMed1993

Patterns of memory dysfunction among children surviving temporal lobe tumors.

We compared the cognitive functioning of seven children with left and seven children with right temporal lobe tumors one year or more following completion of medical intervention (surgical resection + radiation therapy). No differences were found between the two groups with respect to verbal IQ, performance IQ.full scale IQ, verbal minus performance IQ, or verbal comprehension, perceptual organization, or freedom from distractability factor scores. After adjusting memory test results for variance attributable to general intelligence, three children with left and four children with right temporal tumors exhibited specific auditory-verbal memory dysfunction; five of these children had concurrent visual-verbal memory dysfunction. Children receiving radiation therapy to the tumor were at significantly greater risk for verbal memory problems. Reading and spelling achievement were significantly correlated with verbal memory performance. Inconsistent association between cerebral hemisphere of tumor and type of cognitive deficit may be related to the relatively slow progression of the tumor and regional interventions such as radiation therapy. Nevertheless, the results of the present report suggest that the majority of children diagnosed with temporal lobe tumors are at increased risk for memory dysfunction and academic failure.

Journal Article↗

PubMed1993

Chemotherapy induced nausea and emesis in pediatric cancer patients: external validity of child and parent emesis ratings.

Children's and parent's subjective ratings of the frequency and severity of nausea and emesis were assessed among 33 children with acute lymphoblastic leukemia receiving identical chemotherapy. Parents were trained to record the frequency of the child's actual emesis episodes during chemotherapy. Although parent and child ratings of nausea were significantly correlated, children generally rated their nausea and emesis as more frequent and more severe than did their parents. Parent ratings showed inadequate external validity when compared with behavioral observations. Children with greater anxiety and higher subjective ratings subsequently exhibited more frequent episodes of emesis by observation, suggesting that their perceptions of symptoms based on previous chemotherapy experiences may predict emesis during different chemotherapy. In a stepwise multiple regression analysis, antiemetic regimen and the child's anxiety as rated by the parent combined to account for approximately 47% of the variance in number of episodes of emesis. These findings are discussed in the context of factors limiting validity of parent and child reports of children's symptomatology with implications for future epidemiologic and intervention research.

Adolescent↗

PubMed1992

Neuropsychological status of children treated for brain tumors: a critical review and integrative analysis.

The literature on the neuropsychological status of children with primary brain tumors was reviewed to identify English-language publications reporting the results of standardized, quantitative measures of patient function. The 22 studies that met these review criteria, representing 544 patients, were evaluated to assess the relationship between traditional risk factors (age at diagnosis, tumor location, radiation therapy, and time since completion of treatment), as well as subsequent intellectual development, academic achievement, psychosocial adjustment, and neuropsychological status. The impact of other potentially salient factors, such as seizures and sensory and motor deficits, was evaluated when possible. Despite inconsistent reporting of demographic and treatment-related effects across studies which precluded formal meta-analysis, we were able to confirm the primary importance of radiation therapy volume and age at treatment on IQ. No effects were detected for tumor location. Younger children treated with cranial (whole brain) irradiation showed a 14-point deficit in IQ as compared with their older counterparts. No significant differences were noted between older children receiving local or cranial irradiation, although both groups had IQ levels 12-14 points lower than those not irradiated. The high-risk groups identified in this study require increased clinical surveillance. Definitive evaluation of potential risk factors for neuropsychological impairment will depend on more complete reporting of relevant patient characteristics and interinstitutional studies.

Adolescent↗

PubMed1992

Deterioration of intellect among children surviving leukemia: IQ test changes modify estimates of treatment toxicity.

This study assessed the association of young age at treatment, cranial irradiation, and time since treatment with intellectual deterioration among 49 long-term survivors of childhood leukemia. Ss had been randomized to receive low-dose cranial radiation therapy or high-dose chemotherapy. Longitudinal assessments of intellect were conducted. No significant effects of treatment group or age at treatment were detected. A small but statistically significant decline in mean full-scale IQ was noted over time (M = -3.6). Reanalysis with IQ test version included as a covariate eliminated IQ declines found initially. Results suggest (a) that there has been reduced toxicity of these methods of treatment and (b) that the magnitude and direction of error introduced by changing tests may approximate the magnitude of adverse effects on IQ from treatment.

Age Factors↗

PubMed1992

Maternal depression, assessment methods, and physical symptoms affect estimates of depressive symptomatology among children with cancer.

Investigated the incidence of depressive symptoms and their covariates in a sample of 99 children undergoing treatment for cancer and their mothers. Although the prevalence of depressive symptoms falling within the clinical range was low (7 to 8%), classification of these children was highly dependent upon the informant and instrument used. Interrater reliabilities did not differ from chance levels. Separate multiple regression analyses of the mother's and nurse's ratings of the child's level of depression, the child's self-report on the Child Depression Inventory, and the mother's responses to the Child Behavior Checklist depression scales revealed different statistical models for each method of assessment. However, increased severity of the mother's self-report of depressive symptoms on the Beck Depression Inventory, which was predicted by low perceived social support and hospitalization of her child, was associated with higher levels of child depression on all child- and parent-report measures. Parental adjustment, sociodemographic, and medical factors as well as methods of assessment must be addressed by models explaining the etiology of depressive symptoms among pediatric oncology patients.

Adult↗

PubMed1992

Long-term survivors of leukemia treated in infancy: factors associated with neuropsychologic status.

PURPOSE: Because of concerns about late toxicities of treatment among infants diagnosed with acute lymphoblastic leukemia (ALL), and especially the effects of cranial radiation therapy (CRT), we compared the functional and neuropsychologic status of 26 long-term survivors of ALL who were diagnosed in the first 24 months of life versus 26 children who were treated previously for Wilms' tumor. PATIENTS AND METHODS: Of the children with ALL, CNS prophylaxis included no CRT in six, 18 Gy CRT in five, 20 Gy CRT in seven, and 24 Gy CRT in five. Three additional children experienced CNS relapse and received total CRT doses of 24, 40, and 44 Gy. All children received neuropsychologic testing; children with ALL also participated in diagnostic imaging studies. RESULTS: As a group, the children who were treated for ALL did not differ significantly from those who were treated for Wilms' tumor on objective measures of global functional status. However, children treated for ALL had a significantly lower mean intelligence quotient (IQ) (87 v 96), poorer performance on four of six measures of visual and auditory memory, lower achievement with regard to arithmetic skills, and a greater frequency of special educational intervention than those who were treated for Wilms' tumor. IQ and auditory memory performance in the ALL group was correlated inversely with time since the completion of therapy and total CRT dose. CONCLUSIONS: These results reinforce the contemporary trend of prophylactic CRT omission in very young children except for those who are at risk for CNS relapse. For infants and very young children who require CRT, evidence is presented that supports the approach for the delay of CRT until the child is older.

Adolescent↗

PubMed1992

Oral ketamine premedication to alleviate the distress of invasive procedures in pediatric oncology patients.

This study prospectively evaluated the efficacy of oral ketamine in alleviating procedure-related distress in pediatric oncology patients. Ketamine (10 mg/kg) was administered orally to 35 children and adolescents, ranging in age from 14 months to 17 years (mean = 6.5 years). Procedure-related distress was evaluated by using parent/clinician ratings and the Observational Scale of Behavioral Distress (OSBD-R). Eighty-seven percent of children were sedated within 45 minutes. Clinician and parent ratings were similar, with 77% rating procedural distress as low (0 to 3). The OSBD-R scores were low throughout all phases of the study. Although this study was neither randomized nor placebo-controlled, statistical comparison of the OSBD-R scores of the patients who received oral ketamine with those of historical controls (from a study previously performed at the same institution but using intravenous midazolam) showed significantly less distress (P < .001) during the procedure in children who received oral ketamine. Additionally, OSBD-R scores of the patients who received oral ketamine were significantly lower (P < .001) during all phases than those of the saline placebo group in the other study. No cardiorespiratory side effects related to ketamine were noted. The majority of patients showed recovery from sedation within 2 hours following the procedure. In conclusion, oral ketamine effectively alleviated procedure-related distress in pediatric oncology patients.

Administration, Oral↗

PubMed1991

Midazolam premedication for pediatric bone marrow aspiration and lumbar puncture.

The ability of midazolam, a benzodiazepine, to reduce the distress associated with lumbar puncture and bone marrow aspiration was examined in 23 children with acute lymphocytic leukemia. Patients were randomized to receive 0.2 mg/kg midazolam HCl or placebo intravenously 3-5 min before the procedures, under double-blind conditions. Based on prior experiences, children in both groups anticipated severe pain from these procedures. Postprocedure pain ratings by patients were markedly reduced in the midazolam but not the placebo group. Both physicians and parents judged the midazolam group as significantly less distressed than controls during and after the procedures. Trained observers recorded significantly fewer pain- and anxiety-related behaviors in the midazolam group immediately before and after, but not during the procedures. The amnestic effects of midazolam, confirmed in a visual recall/recognition test, appear to account for the decreased pain ratings since the behavioral manifestations were similar in the two groups. There were no adverse drug reactions or significant changes in vital signs. Midazolam warrants further investigation as a premedication for painful diagnostic and treatment procedures in children with cancer.

Adolescent↗

PubMed1991

High risk of recurrent stroke after discontinuance of five to twelve years of transfusion therapy in patients with sickle cell disease.

Although long-term transfusion therapy is at least 90% effective in preventing recurrent strokes after an initial cerebrovascular accident in patients with sickle cell disease, it is unknown how long transfusion therapy should be continued. To address this question, we prospectively discontinued transfusions in 10 patients with sickle cell disease whose median duration of transfusion therapy after an initial stroke was 9 1/2 years (range 5 to 12 years). Before the transfusions were discontinued, patients were examined by cerebral angiography, magnetic resonance imaging of the head, neuropsychologic testing, electroencephalography, and a complete neurologic examination. Within 12 months after transfusion therapy was stopped, 5 of 10 patients had had an ischemic event. Three events caused relatively mild deficits in the same areas as those originally affected. Two were associated with massive intracranial hemorrhage, including one on the contralateral side of original involvement. An additional patient died suddenly of unknown causes. Of the four remaining patients, three declined to resume transfusion and are relatively well at greater than or equal to 18 months after therapy was stopped. The studies performed before transfusions were stopped were not predictive of recurrent stroke. The risk of recurrent cerebrovascular accident in this group was significantly greater than the estimated risk of 10% in patients who are receiving long-term transfusion therapy (p = 0.002). This adverse outcome suggests that patients with sickle cell disease who have had a stroke must receive long-term transfusion indefinitely or a suitable therapeutic alternative must be devised.

Adult↗

PubMed1991

Parental report of everyday cognitive abilities among children treated for acute lymphoblastic leukemia.

Compared ratings of everyday cognitive functioning made by parents of leukemic children to ratings made by parents of normal control and learning disabled (LD) children. The leukemic children had been randomly assigned to one of two CNS prophylaxis treatments, one including cranial irradiation and intrathecal methotrexate and another including only intrathecal methotrexate and intermediate dose infusions of methotrexate. Leukemic children were rated significantly worse than controls in areas related to schooling and academic skills. The type of CNS prophylaxis was not discriminated by parent ratings. LD children were rated as significantly worse than either of the two groups in all areas of cognitive functioning. Leukemic and LD children were both rated as having poor academic skills. Leukemic children missed significantly more school than control and LD children, and their poor ratings on academic skills were partially attributed to academic deprivation. These results suggest that studies should control for academic deprivation when evaluating the neuropsychological outcome of CNS prophylactic treatment and that reintegration and normalization programs should be designed to address the intellectual problems resulting from missed academic experiences.

Adolescent↗

PubMed1991

Subtle neuropsychological deficits in children with sickle cell disease.

Forty-three children and adolescents (8-16 years old) with sickle cell disease (SCD) and no overt neurologic dysfunction were evaluated with the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT), and an age-appropriate version of the Luria-Nebraska Neuropsychological Battery (LNNB). Thirty similar-aged siblings were controls. WISC-R performance and full-scale IQs were lower (p less than 0.05) for patients than sibling controls. No significant differences were seen on the WRAT. Patients with SCD missed more school days than controls (p less than 0.001) but did not differ from controls in academic performance or the proportion in special education. On the LNNB, scores for patients and controls 13 years and older did not differ. However, young patients had significantly elevated (abnormal) scores compared with controls on the following scales: expressive speech, writing, reading, arithmetic, memory, and pathognomonic. The possibility that subtle neuropsychological deficits in younger patients with SCD reflect either subclinical strokes or a predisposition for strokes merits further investigation in a large multi-institution study.

Adolescent↗