Biomedical subjects

L Schut

Publications and source records attributed to L Schut.

At least 19 recordsLinked to original sources

PubMed1992

Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy.

Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA.

Adult↗

PubMed1992

Vascular malformation with radiation vasculopathy after treatment of chiasmatic/hypothalamic glioma.

Chiasmatic/hypothalamic gliomas usually are histologically benign astrocytomas that may recur many years after diagnosis and treatment. Three children with chiasmatic/hypothalamic gliomas who were treated at the authors' institution returned 9.5, 11.5, and 2 years, respectively, after radiation therapy (RT) because visual and neurologic deterioration developed. Neuroradiographic studies, including arteriography in two of the patients, showed large mass lesions. These were presumed to be recurrence of tumor, and chemotherapy was administered. Pathologic examination of two children who died and of the third who had a biopsy revealed only a minimal amount of residual, histologically benign astrocytoma, whereas the bulk of the specimen consisted of numerous vessels of variable size. These probably represented incorporation of the rich vasculature in the chiasmal region into the tumor, which underwent degeneration secondary to RT. Radiographic methods did not distinguish progressive tumor growth from the vasculopathy and led to inappropriate clinical diagnoses and treatment.

Adolescent↗

PubMed1992

Choroid plexus carcinoma of childhood.

The presentation, growth patterns, and response to therapy of 11 consecutive children with choroid plexus carcinomas were analyzed, and the results were compared with the outcome reported in other series. Patients were a median of 26 months of age at diagnosis. Two patients had thalamic tumors, one had a posterior fossa primary, and the rest had ventricular lesions. Five of 11 (45%) children remain in continuous progression-free remission a median of 48 months from diagnosis. Four of the five in continuous remission had a "gross total" surgical resection, and only one received radiation therapy. Five of six patients with subtotal resections relapsed despite postoperative treatment with radiation therapy (three) and chemotherapy (one). The response to treatment with radiation therapy or chemotherapy at relapse was disappointing, with only one child (treated with etoposide) responding. In combination with other series, 11 of 14 children had prolonged progression-free survival after gross total resection (only two of whom received adjuvant therapy) compared with two of 20 after less than total resections, independent of the type of adjuvant therapy given. Adjuvant therapy for children with choroid plexus carcinomas is of unproven benefit, and this must be considered when analyzing innovative treatment trials for such children, especially for those with totally resected tumors. Patients with partially resected lesions fare poorly with present forms of treatment.

Child↗

PubMed1992

Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy.

Cognitive function and school achievement were studied prospectively over 3 to 4 years in 19 children treated for brain tumors with whole-brain radiotherapy; 14 of 19 also received adjuvant chemotherapy. For the group as a whole, mean IQ fell from a baseline of 104 to 92 at follow-up (p < 0.01). Age was inversely correlated with change in IQ over time (r = 0.71; p < 0.001). Children younger than 7 years at diagnosis had a mean IQ loss of 27 points, while children over 7 years at diagnosis showed no significant decrease in IQ. Decline in IQ occurred between baseline and year 2 of follow-up; none could be documented between years 2 and 4. All children younger than 7 years at diagnosis were receiving special education at follow-up; 50% of the children over 7 years at diagnosis were receiving supplemental educational services.

Adolescent↗

PubMed1992

Childhood meningiomas. Experience in the modern imaging era.

Twenty children with meningiomas (ages 18 months to 17 years) received initial therapy at the Children's Hospital of Philadelphia between January 1975 and June 1991, accounting for 2% of children with primary brain tumors seen during that time interval. All were verified histopathologically, and none had had prior irradiation. Fifteen were male and 5 female. Fifteen tumors were intracranial, all located supratentorially. Two of these also had a component within the optic canal. One tumor was entirely within the orbit. Four meningiomas arose within the spinal canal. Associated conditions were neurofibromatosis (NF) type I (1 patient), NF type II (2 patients), and a facial alveolar rhabdomyosarcoma (1 patient). A gross total resection as documented by postoperative scan and operative note was accomplished in 12 patients. Four of these relapsed, at a mean of 3.5 years from initial surgery. In 4 patients a near-total resection (> 90%) was performed. Of these, 2 progressed at 9 months and 1.5 years. One of these died of complications associated with reoperation. In 4 patients a partial resection (50-90%) was performed. Two of these progressed at 4 months and 1 year, and the other 2 have been followed for less than 2 years. Five patients received radiation therapy (RT). One patient received RT as adjunctive therapy after primary surgery because of papillary histology. The other 4 had RT following reoperation for recurrence at a mean of 1.5 years from diagnosis (range, 7 months to 2 years). These 4 patients remain alive and with stable disease at a mean of 6 years from diagnosis (range 2-8.8 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Striatal monoamine neurotransmitters and metabolites in dominantly inherited olivopontocerebellar atrophy.

We measured the levels of the monoamine neurotransmitters and metabolites in striatum of 14 patients with end-stage dominantly inherited olivopontocerebellar atrophy (OPCA). On average, dopamine levels were reduced in putamen (-53%), caudate (-35%), and nucleus accumbens (-31%). However, individual patient values showed a wide variation, indicating that mild to moderate striatal dopamine loss is a common but not constant feature of OPCA. Seven patients had marked putamen dopamine loss (-62% to -81%) but without evidence of correspondingly severe substantia nigra cell damage; this suggests the possibility of a "dying-back" phenomenon in which nerve terminal loss precedes cell body degeneration. Severe substantia nigra cell loss with almost total (-95% to -99%) putamen and caudate dopamine depletion was present in two patients; however, none of the 14 patients had had a clinical diagnosis of parkinsonism or was receiving antiparkinsonian medication. Mean striatal serotonin levels were normal, whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were elevated by 47% to 63%; this suggests increased activity of raphe dorsalis serotonin neurons innervating the striatum, which might aggravate the functional consequences of the dopamine deficit.

Biogenic Amines↗

PubMed1992

Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age.

Head injury in the youngest age group is distinct from that occurring in older children or adults because of differences in mechanisms, injury thresholds, and the frequency with which the question of child abuse is encountered. To analyze some of these characteristics in very young children, the authors prospectively studied 100 consecutively admitted head-injured patients 24 months of age or younger who were drawn from three institutions. Mechanism of injury, injury type, and associated injuries were recorded. All patients underwent ophthalmologic examination to document the presence of retinal hemorrhages. An algorithm incorporating injury type, best history, and associated findings was used to classify each injury as inflicted or accidental. The results confirmed that most head injuries in children younger than 2 years of age occurred from falls, and while different fall heights were associated with different injury types, most household falls were neurologically benign. Using strict criteria, 24% of injuries were presumed inflicted, and an additional 32% were suspicious for abuse, neglect, or social or family problems. Intradural hemorrhage was much more likely to occur from motor vehicle accidents and inflicted injury than from any other mechanism, with the latter being the most common cause of mortality. Retinal hemorrhages were seen in serious accidental head injury but were most commonly encountered in inflicted injury. The presence of more serious injuries associated with particular mechanisms may be related to a predominance of rotational rather than translational forces acting on the head.

Accidental Falls↗

PubMed1991

Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas?

Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory.

Brain Neoplasms↗

PubMed1991

Quinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy.

We measured the activities of the enzymes responsible for the metabolism of the excitotoxin quinolinic acid, 3-hydroxyanthranilate oxygenase and quinolinic acid phosphoribosyltransferase, in autopsied brain of 11 patients with olivopontocerebellar atrophy. In cerebellar cortex, severe Purkinje cell loss was evident but with relative preservation of granule cells. As compared with the control subjects (n = 14), mean activity of 3-hydroxyanthranilate oxygenase was normal in cerebellar cortex from the patients with olivopontocerebellar atrophy, whereas quinolinic acid phosphoribosyltransferase activity was markedly increased (+92%, p less than 0.02). No significant changes in enzyme activities were found in samples from occipital cortex. Increased quinolinic acid phosphoribosyltransferase activity may represent a mechanism, in the degenerating cerebellum, to protect quinolinic acid-sensitive granule cells in patients with olivopontocerebellar atrophy.

Adult↗

PubMed1991

Brain amino acid reductions in one family with chromosome 6p-linked dominantly inherited olivopontocerebellar atrophy.

We measured the levels of aspartate, glutamate, gamma-aminobutyric acid (GABA), and other amino acids in autopsied brain of 6 patients from one family (Pedigree S) with dominantly inherited olivopontocerebellar atrophy. A previous demonstration of reduced aspartate concentration in plasma of affected members of this family suggested the possibility of a generalized disorder of amino acid metabolism affecting the brain. As compared with the control levels, mean levels of aspartate and glutamate were markedly reduced by about 70 and 40%, respectively, in the degenerated cerebellar cortex from the patients. Since the cerebellar aspartate reduction likely exceeds the amount that could be explained by neuronal loss, other factors such as abnormal aspartate metabolism, neurotransmitter turnover, or both are probably involved. Mean aspartate, glutamate, and GABA levels were also reduced by about 10 to 30% in most of the 16 examined extracerebellar brain areas in which no or, at most, mild neuronal cell loss was observed by semiquantitative estimation. Concentrations of taurine, glutamine, and omicron-phosphoethanolamine were normal in all brain areas examined. Our biochemical data provide support to the presence of a generalized, but quantitatively mild, disturbance in amino acid metabolism in patients with olivopontocerebellar atrophy from Pedigree S. The regionally widespread amino acid reductions in the brain, of as yet unknown pathophysiological significance, could be due to a failure of one or more enzymes involved in aspartate and glutamate metabolism.

Adult↗

PubMed1991

Congenital forms of intracranial teratoma.

Intracranial teratoma in the newborn is a well-recognized but infrequent entity. We describe two such cases: one with a massive intracranial teratoma replacing the cerebral hemispheres and the other, a smaller tumor extending into the orbit. Forms of congenital intracranial teratoma and theories of pathogenesis and management are briefly discussed.

Brain Neoplasms↗

PubMed1991

Distribution of bacteria in the operating room environment and its relation to ventricular shunt infections: a prospective study.

In order to study the distribution of bacteria in the operating room environment, cultures were obtained during 111 unselected shunt operations throughout a 10-month period. After routine skin preparation, bacteria were collected by placing Millipore filters on the patient's prepped skin underneath the drapes, on top of the drapes in the operative field, and/or on the sterile instrument table, and left in place for the duration of the case. In 48 patients, full-thickness skin biopsies taken at the initial incision were cultured in lieu of skin surface cultures. Perioperative cerebrospinal fluid cultures and subsequent shunt infections were monitored. Of the 288 environmental (skin and surfaces) cultures, 24 were positive (20 coagulase-negative Staphylococcus and 4 Staphylococcus aureus). Positive cultures were found in 15 of 111 drape cultures (13.5%), 7 of 77 instrument table cultures (9.1%), and 2 of 97 skin cultures (2.1%). Positive environmental cultures were not correlated with the surgeon, length of case, time of day, or type of shunt operation, but were more likely to occur in a room other than the designated neurosurgical operating room. There was a correlation between the occurrence of positive environmental cultures and positive cerebrospinal fluid cultures, although the organisms were not always the same. Coagulase-negative Staphylococcus was the most common organism isolated from all sites. We conclude that bacteria most often associated with shunt infections are airborne in the operating room, rather than originating from the patient's skin, and are distributed in the highest concentration near the surgical team.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Selective delayed alternation deficits in dominantly inherited olivopontocerebellar atrophy.

In order to characterize more completely the nature of the frontal lobe-type cognitive changes in patients with dominantly inherited olivopontocerebellar atrophy (OPCA) we administered two tasks sensitive to frontal system dysfunction, delayed alternation (DA) and delayed response (DR), to 12 patients from one OPCA family. Affected members from this family have previously been shown to have a marked and widespread cerebral (including frontal) cortical cholinergic reduction as severe as that observed in Alzheimer's disease. Performance on DA, but not on DR, was significantly impaired in the OPCA patients compared to that in the controls. We suggest that the DA deficits in OPCA could be a consequence of a loss of cholinergic innervation to orbitofrontal or possibly temporal cortical areas and/or damage to the integrity of the cerebello-frontal neuronal connections.

Adult↗

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↗