Biomedical subjects

L Schut

Publications and source records attributed to L Schut.

At least 55 records · Page 3Linked to original sources

PubMed1990

Glycerophosphoethanolamine concentration is elevated in brain of patients with dominantly inherited olivopontocerebellar atrophy.

We measured the concentration of glycerophosphoethanolamine (GPEA), a membrane breakdown product, in autopsied brain of 10 patients with dominantly inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder. As compared with the controls, mean GPEA levels were significantly elevated by 37-69% in 11 of the 15 brain areas examined, including extracerebellar brain regions in which no neuronal cell loss could be detected by semiquantitative estimation. Our data suggest the possibility of altered membrane phospholipid metabolism in OPCA which could be a contributing factor in the neuronal cell death.

Adult↗

PubMed1990

Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors.

Thirty-six pediatric patients (ages 0.8-16.8 years) with recurrent intracranial ependymoma were treated for a total of 52 separate cases of relapse from 1970 to 1989. Therapy consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and five of these 12 who had initially been treated with surgery and chemotherapy alone were irradiated to full dose. The 2-year actuarial survival and progression-free survival (PFS) rates are 29% and 23%, respectively. Two-year survival after treatment of first relapse is 39%. Of the 52 cases, there have been 44 subsequent relapses (and one septic death), three of which have occurred in the five patients treated with definitive radiation. Twenty-seven relapses have occurred exclusively with local disease. Eight patients failed with disease outside as well as in the primary site. Survival was better for patients who had histologically benign lesions at relapse (53% versus 9%, P less than 0.02), and for patients in first versus subsequent relapse (p less than 0.005). Cisplatin and etoposide (VP-16) appeared to be the most active chemotherapeutic agents. The authors conclude that some patients with histologically benign ependymoma at first relapse may benefit from aggressive therapy, with occasional long-term, progression-free survival possible. Patients with malignant lesions, or patients who relapse a second time, are less likely to benefit from conventional therapy for a significant period of time.

Actuarial Analysis↗

PubMed1990

Results of treatment of children with recurrent medulloblastoma/primitive neuroectodermal tumors with lomustine, cisplatin, and vincristine.

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) are the most common posterior fossa tumors in childhood. Despite surgery and radiation therapy, 40% to 50% of children with PNET/MB will have recurrent disease. Various chemotherapeutic agents are transiently effective in recurrent PNET/MB, but long-lasting responses are rarely attainable. To increase the rate and duration of response in children with recurrent PNET/MB, the authors treated seven patients (ages 2-18 years; median, 10 years) with lomustine (CCNU) (100 mg/m2), cisplatin (CPDD) (90 mg/m2) and vincristine (VCR) (1.5 mg/m2; maximum, 2 mg) in a 6-week cycle for a maximum of eight cycles. Six of six evaluable patients responded to chemotherapy. Four patients had a complete response; three with complete disappearance of tumor by imaging studies; and one with eradication of extraneural disease for a median of 24 months from relapse (13-29 months). Overall disease-free survival was 18.5 months. All six patients have subsequently died of recurrent tumor. Major toxicities consisted of reversible bone marrow suppression (six of six), high frequency hearing loss (six of six) and decreased renal function (three of six). All patients required dosage modification for toxicity. A regimen of CCNU, VCR, and CPDD is effective therapy in children with relapsed PNET/MB and can produce relatively long-term disease control with good quality of life. Further investigation into the efficacy of this combination as adjuvant chemotherapy in newly diagnosed high-risk PNET/MB is now being performed.

Adolescent↗

PubMed1990

Pediatric brainstem glioma. Post-radiation clinical and MR follow-up.

Thirty-four pediatric patients, twenty with presumed and fourteen with biopsy or autopsy proven brainstem gliomas were imaged by CT and MR before radiation therapy. Twenty-eight patients received radiotherapy. Of these, eighteen fit the protocol for combined clinical and MR post-treatment evaluation. No cases of radionecrosis were seen at autopsy. This study shows that MR can demonstrate tumor response to radiation therapy, tumor progression prior to clinical deterioration, post-treatment cyst formation and hemorrhage. Although MR clinical correlation was not optimal on six week post-treatment evaluation, 4-10 month post-treatment MR scanning correlated well with clinical evaluation. MR appears useful in post-therapeutic monitoring of tumor response.

Adolescent↗

PubMed1990

Intracranial ependymomas in children.

Between 1970 and 1988, 51 children with intracranial ependymal tumors (33-infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors.

Adolescent↗

PubMed1990

Cavernous angioma presenting as atypical facial and head pain.

Recurrent headache is a common pediatric problem. As the differential diagnosis of headache is extensive, physicians rely on the mode of presentation to focus any investigation. A report of an adolescent in whom atypical facial and head pain caused by a preexisting cerebellar cavernous angioma is presented. Facial pain and headache resolved following excision of the tumor.

Child↗

PubMed1990

Medulloblastomas.

It is obvious that the past decade has witnessed considerable progress in the management of children with medulloblastoma. Better surgical technique has led to more aggressive surgery with less morbidity. The use of staging has led to reduction in radiation therapy doses in some patients and will, it is hoped, lead to better neuropsychological outcome. The use of adjuvant chemotherapy in high-risk patients is delaying recurrence. It remains unknown, however, whether the patient with a medulloblastoma is ever "cured." Certainly, in the future, control of this tumor will depend on new therapeutic modalities, which will be developed on the basis of a better understanding of the biology of these primitive tumors. A better understanding of tumor immunology, cytogenetics, and biochemistry is a goal for the future.

Adolescent↗

PubMed1989

Cerebellar [3H]inositol 1,4,5-trisphosphate binding is markedly decreased in human olivopontocerebellar atrophy.

We examined the behaviour of [3H]inositol-1,4,5-trisphosphate (IP3) binding in autopsied cerebellar and cerebral cortex of 10 neurologically normal controls and 8 patients with end-stage olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder characterized histologically by severe degeneration of Purkinje cells. [3H]IP3 binding to normal human cerebellar cortex was 6-15 times higher than in cerebral cortex. As compared with the controls, mean [3H]IP3 binding to cerebellar cortex was markedly reduced by 61% in the OPCA patients whereas levels were normal in frontal and occipital cortices. Since the Purkinje cell dendrite receives neuronal input from granule cells and climbing fibers utilizing glutamate and aspartate, respectively, as neurotransmitters, the reduced IP3 binding in OPCA cerebellar cortex may reflect a loss of Purkinje cells containing these excitatory amino acid receptors linked to the phosphatidylinositide second messenger system. Our data suggest that in humans, IP3 receptors may be highly localized to the Purkinje cell dendrite.

Adult↗

PubMed1989

Suprasellar germinomas in childhood. A reappraisal.

Germinomas in childhood may arise in both the suprasellar and pineal region, and outcome has been reported to be worse for suprasellar germinomas with a 5-year survival rate of 20% as compared to 60% for pineal germinoma. To determine the factors impacting on outcome, the results of a uniform treatment approach were evaluated and included primary surgical debulking (PSD) and systemic craniospinal axis radiation (CSRT) for suprasellar germinomas. Between 1976 and 1985 ten consecutive patients (seven females, three males) with the pathologically confirmed diagnosis of suprasellar germinoma were treated. Outcome was compared to four male patients with pineal germinoma treated over the same time period and series of patients reported in the literature. At diagnosis the mean age of patients with suprasellar germinoma was 13.9 years (range, 8.9 to 9.4 years). Symptoms were present for a mean of 18 months (range, 2 to 72 months) prior to diagnosis and included diabetes insipidus, anterior pituitary dysfunction, decreased vision, headache, vomiting, and diplopia. Staging studies, including myelography (n = 4) and cerebrospinal fluid cytology (n = 7), disclosed dissemination in only one child. Surgical treatment included biopsy in three cases, partial resection in five, and total resection in two; no permanent postsurgical complications were noted. The mean radiation therapy dose to the tumor site was 4953 cGy (range, 4400 to 5250 cGy) and to the spine 3354 cGy (range, 3000 to 4000 cGy). Patients were followed for a mean period of 5.1 years (range, 1.9 to 10.5 years). One patient with SG who did not receive treatment initially developed a pineal tumor after diagnosis; she was treated with PSD and CSRT and is asymptomatic 5 years later. All the remaining patients are alive and remain disease-free. Surgical resection and CSRT results in excellent disease control for children with suprasellar germinomas, and outcome is similar to those patients with pineal germinoma.

Adolescent↗

PubMed1989

Non-Alzheimer-type pattern of brain cholineacetyltransferase reduction in dominantly inherited olivopontocerebellar atrophy.

We recently reported reduced activity of the cholinergic marker enzyme cholineacetyltransferase (ChAT) in several brain regions of patients with dominantly inherited olivopontocerebellar atrophy (OPCA). To document the regional extent of these changes we performed a comprehensive examination of the behavior of ChAT throughout both cerebral cortical and subcortical brain areas in 5 patients from one large OPCA pedigree. As compared with the controls, mean ChAT activities in OPCA were reduced by 39 to 72% in all (n = 27) cerebral cortical areas examined and in several thalamic subdivisions, caudate head, globus pallidus, red nucleus, and medial olfactory area. In contradistinction to findings in Alzheimer's disease (AD), mean ChAT levels in OPCA amygdala and hippocampal subdivisions were either normal or only mildly reduced. The lack of severe disabling dementia in our OPCA patients compared with AD patients having a similar cortical cholinergic reduction could be explained by an absence of either a marked cholinergic loss in amygdala or hippocampus or significant loss of noncholinergic cerebral cortical and limbic neurons as occurs in AD brain. We suggest that this and other OPCA pedigrees having a cortical cholinergic reduction represent a unique model for the study of behavioral consequences of a more selective cerebral cortical cholinergic lesion rather than a limbic cholinergic lesion.

Adult↗

PubMed1989

Isochromosome 17q in primitive neuroectodermal tumors of the central nervous system.

We have prepared karyotypes from 22 primitive neuroectodermal tumors (PNETs) from pediatric patients ranging in age from 10 months to 16 years. Twenty-one cases were newly diagnosed, primary, posterior fossa tumors. One case was a recurrent tumor in a patient previously treated with radiation. Cytogenetic results were obtained from direct preparations and/or short-term (1-10 day) culture. Three tumors had apparently normal karyotypes. Nineteen tumors demonstrated numerical and/or structural abnormalities. The most frequent structural chromosomal changes were deletions and nonreciprocal translocations. Four tumors contained double minutes. Several chromosomes appear to be nonrandomly involved in PNETs. These include chromosomes 5, 6, 11, 16, 17, and a sex chromosome. The most consistent change, however, was an i(17q), present in one-third (8/22) of the cases. Strikingly, in three of these eight tumors, the i(17q) was the only structural abnormality observed. An i(17q) is not specific for pediatric PNETs, as it is also seen in leukemias and other solid tumors. However, in PNETs it may be a primary change related to tumor development and/or progression. Clinically, there was no correlation of the cytogenetic findings with histologic features of the tumors, size of the tumor, extent of metastasis, or surgical resection.

Adolescent↗

PubMed1989

The role of radiation therapy in the management of childhood craniopharyngioma.

Between 1965 and 1986, 31 children were treated for craniopharyngioma at the Children's Hospital of Philadelphia. Total removal was attempted in all patients. Some patients received radiation therapy following subtotal removal. Of the patients whose first resection was subtotal, five received radiation and seven did not. Four of the 5 patients who were radiated (80%) are stable (median 89 months, range 42-155 months) and one recurred at 42 months, failed salvage with total removal, and subsequently died of disease. Of the seven who were not irradiated, all had recurrences (median 12 months, range 3-192 months) and one died of disease. Nineteen patients initially had total removal and none received adjuvant radiation. One patient died postoperatively. Of the 18 remaining patients, 6 had recurrences (median 24 months, range 7-100 months) and 12 (66%) are stable (median 42 months, range 9-133 months). One of these stable patients died of endocrine complications 24 months after initial surgery. Fourteen of the 31 patients recurred. Two died with recurrence and one required no further treatment. Eleven had second resections following initial surgical removal. Seven of these 11 went on to receive radiation and four did not. All seven who were radiated are stable (median 33 months, range 1-228 months); whereas 1 of the 4 who were not radiated recurred again at 18 months. This patient had a third resection followed by radiation therapy and is now stable at 20 months. After initial surgery (and before radiation, when given) 26 of 31 patients had panhypopituitarism, 4 had partial deficits, and 1 was normal. Severe diencephalic syndrome, loss of visual acuity, and intellectual deficits were no more frequent in patients treated with total removal, subtotal removal, and in patients who received radiation. We conclude that radiation has an important role following subtotal removal and for salvage treatment after initial surgery. Aggressive attempt at total removal does result in prolonged progression-free survival in some patients. Extensive resections may result in significant mortality and endocrine morbidity. This review suggests that subtotal removal and radiation results in outcomes at least as favorable as treatment with total removal alone.

Adolescent↗

PubMed1989

Magnetic resonance imaging of lipomyelomeningocele and tethered cord.

The operative and magnetic resonance image (MRI) findings of 25 patients with the diagnosis of lipomyelomeningocele and/or tethered cord were compared. Postoperative MRI scans of eight patients, five of whom were in stable condition, were also compared with the preoperative studies. In this review there was one false negative MRI scan and four MRI scans in which the relationship of the lipoma to the conus or filum was not demonstrated accurately. In six patients, incidental intramedullary cystic lesions at the conus were identified by MRI scan. All eight postoperative (1 month to 2 years) scans demonstrated no change in the level of the conus from the preoperative study. MRI is an accurate screening modality in the initial diagnosis of occult spinal dysraphism. MRI was not useful in the postoperative evaluation of lipomyelomeningocele and the tethered cord, since the caudal, posterior displacement of the conus was unchanged in all studies.

Adolescent↗

PubMed1989

A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results.

As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties. After CRT, children with brain tumors also demonstrated a fall in a wide range of achievement scores and an increased need, over time, for special help in school. The 2-year results of this study suggest that children with brain tumors treated with CRT are cognitively impaired and that these deficits worsen over time. The younger the child is at the time of treatment, the greater is the likelihood and severity of damage. These children, although not retarded, have a multitude of neurocognitive deficits which detrimentally affects school performance. New treatment strategies are needed for children with malignant brain tumors.

Adolescent↗

PubMed1988

Late recurrence of primitive neuroectodermal tumor/medulloblastoma.

The period of risk for recurrence of primitive neuroectodermal tumor/medulloblastoma (PNET/MB) is not clearly defined. With current treatment since more than 50% of children with PNET/MB can be expected to survive for at least 5 years after diagnosis, determining the evidence of "late" recurrence is of increasing concern. Collins has stated that patients with embryonal tumors who survive, disease free, for a period of time equal to the age at diagnosis plus 9 months can be declared cured. This, so-called Collins' law has been applied to patients with PNET/MB. To determine the incidence of "late" recurrence, factors which impact on recurrence and applicability of Collins' law, the authors studied all patients diagnosed with PNET/MB at the Children's Hospital of Philadelphia, Hospital of the University of Pennsylvania, Philadelphia, and Geisinger Medical Center, Danville, Pennsylvania, between 1970 and 1984. For the 44 patients in this study, the disease-free survival at 5, 10, and 12 years was 54%, 41% and 30%, respectively. For children surviving 5 years, the actuarial survival at 10 years was 75% and at 12 years, 51%. Age, sex, dose of radiotherapy, chemotherapy, or extent of surgery were not predictive of late relapse. Recurrence in three of seven patients (43%) occurred outside the "period of risk" as predicted by Collins. It appears that the "period of risk" for recurrent central nervous system tumors after PNET/MB is as yet undefined and probably indefinite.

Actuarial Analysis↗

PubMed1988

Results of the treatment of children with recurrent gliomas with lomustine and vincristine.

Gliomas comprise over 50% of all childhood brain tumors. Treatment of recurrent childhood gliomas has been disappointing and the effectiveness of therapy has been difficult to judge because of the variable natural history of the disease. Information gathered recently has suggested that treatment with [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea)] (CCNU) and vincristine (VCR) after radiotherapy is effective in prolonging survival in children with newly diagnosed anaplastic gliomas. The authors have used these same drugs--CCNU (100 mg/m2) and VCR (1.5 mg/m2 up to a maximum dose of 2 mg)--in 6-week cycles for a maximum of eight cycles in children with recurrent gliomas. To date, 15 patients have been treated; five patients had malignant gliomas and ten low-grade gliomas. Three children showed improvement, five had stable disease, and seven had progressive disease. Of the five patients with malignant gliomas, four progressed within two cycles of treatment and one had stable disease for 7 months on treatment and then relapsed. Seven of ten children with low-grade gliomas benefitted from treatment and six remain in continuous remission a median of 16 months after initiation of therapy. Three of these children are off all therapy 21, 30, and 30 months after treatment, respectively. Therapy was well tolerated and toxicity consisted primarily of reversible bone marrow suppression. The authors conclude that CCNU and VCR chemotherapy is effective in children with recurrent low-grade gliomas and can result in relatively long-term disease stabilization. In limited experience of the authors, it is not of benefit in children with recurrent anaplastic lesions.

Adolescent↗

PubMed1988

Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update.

Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long-term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1988

Cognitive deficits in olivopontocerebellar atrophy: implications for the cholinergic hypothesis of Alzheimer's dementia.

A cerebral cortical cholinergic reduction in dominantly inherited olivopontocerebellar atrophy (OPCA) was recently described. Although the magnitude of the cholinergic reduction was similar to that observed in Alzheimer's disease (AD), none of the OPCA patients was reported to have been demented. We now describe a comprehensive neuropsychological assessment of 11 patients from one of the OPCA pedigrees which we examined biochemically. Detailed neuropsychological testing disclosed previously unrecognized deficits in verbal and nonverbal intelligence, memory, and frontal system function which were positively correlated with the severity of cerebellar ataxia. However, our OPCA patients appeared to be at most only mildly disabled by their cognitive impairment and scored within or close to the normal range on a simple mental status screening examination. This, as well as an absence of any aphasia, apraxia, or agnosia, contrasts with the profile and severity observed in advanced AD dementia, characterized by a similar cortical cholinergic deficit. This finding also suggests that cholinergic reduction may explain only part of the pathophysiology underlying the dementia of AD.

Adult↗