The integrated system's view

Truly integrated systems in public sector settings have been few, and most of us are operating in uncharted waters. However, we can embark on this new effort with some eagerness and confidence that collaboration will contribute significantly to the care of our mutual patients.     

Cerebellar astrocytomas in children

Cerebellar astrocytomas, as a group, carry a more favorable prognosis than most other brain tumors, because these neoplasms generally are histologically benign and amenable to extensive resection. However, it is clear that a number of factors have an impact on prognosis. In particular, resection extent has been strongly associated with progression-free survival: patients undergoing gross total resection appear to have a substantially better prognosis than those undergoing incomplete resection. Brainstem invasion, which is the factor that most often precludes a complete resection, has also been associated with a less favorable prognosis. In addition, histological features indicative of malignancy are clearly associated with a poor outcome.In contrast to the above observations, which have been established convincingly in the literature, a number of issues regarding cerebellar astrocytomas remain unresolved. First, the correlation between histology and prognosis among patients with low-grade cerebellar astrocytomas is uncertain: in some series, pilocytic astrocytomas have been associated with a better prognosis than non-pilocytic tumors, but in other studies, no such relationship has been observed. Second, the role of radiotherapy after incomplete resection of a low-grade cerebellar astrocytoma remains problematic. In view of the lack of convincing data in this regard, many groups, including our own, defer radiotherapy until there is evidence of progressive disease that is surgically unresectable. Finally, the frequency of follow-up in patients with cerebellar astrocytomas remains largely empirical. Although most recurrences are detected within a few years after initial surgery, late recurrences are well known, which raises the question of when and if such patients should be regarded as cured of their disease. Long-term multi-institutional natural history studies are in progress to address the above issues.     

Expression of oncofetal antigens on murine sarcomas characterized for expression of endogenous MuLV.

A rabbit antiserum raised by repeated immunization with BALB/c fetuses obtained at 10-14 days of gestation was used to search for oncofetal antigens (OFA) in murine sarcomas which had previously been characterized for the expression of endogenous murine leukemia virus (MuLV). Iodinated protein A from staphylococcus aureus (IPA) was used to quantitate binding of the antiserum to cultured tumor or fetal cells or to saline extracts of tumors and fetuses. Use of the "antigen" extracts facilitated the assay: the extracts bound to plastic and served as targets for the binding assay, eliminating the need to establish tumors in culture. After absorbtion in vitro and in vivo with adult tissues the rabbit antiserum bound to day 10-14 fetal cells and extract but not to endogenous MuLV (BALB virus 1). The antiserum bound equally well to MuLV-negative and MuLV-positive sublines of MCA-induced sarcomas 1420 and 1414 but not to Moloney sarcoma cells and MCA-induced sarcoma 1386. Thus, the absorbed antiserum detects a class of common cross-reacting antigens which are serologically distinct from MuLV-associated antigens.     

Home care cost-effectiveness for respiratory technology-dependent children

We evaluated home care costs and the cost-effectiveness of home care vs alternative institutional care for respiratory technology-dependent children in a Medicaid Model Waiver Program. "Cost-savings" was measured as the difference between the established Medicaid reimbursable charges to enact an individualized care plan at a long-term care institution and the actual Medicaid reimbursements for home care. Ten patients--six dependent on mechanical ventilation and four with a tracheostomy who were receiving oxygen--were included in the analysis. The mean (+/- SD) annual home care costs were $109,836 +/- $20,781 for ventilator-dependent children and $63,650 +/- $12,350 for oxygen-dependent patients with a tracheostomy, representing annual savings of approximately $79,000 per patient and $83,000 per patient, respectively. The largest portion of home care reimbursements was for nursing care, accounting for 69.0% and 59.0% of the two patient groups. The full program (50 patients) has the potential for a savings of $4 million per year.     

Evidence that protein constituents of postsynaptic membrane specializations are locally synthesized: time course of appearance of recently synthesized proteins in synaptic junctions.

Previous studies have led to the hypothesis that some protein constituents of postsynaptic membrane specializations are locally synthesized near postsynaptic sites. The present study focuses on one prediction of this hypothesis, specifically, that if some proteins of the postsynaptic membrane specialization are locally synthesized, then the delay between synthesis and assembly into synaptic junctional membrane could be short. We evaluate the time course of appearance of recently synthesized protein in synaptic junctions by pulse-labeling hippocampal slices maintained in vitro with radiolabeled protein precursors, and then isolating subcellular fractions enriched in synaptic plasma membranes (SPM) and synaptic junctional complexes (SJC). We report that there is no evidence of a delay in the appearance of recently synthesized proteins in SPM and SJC fractions. Labeled proteins could be detected as early as 15 min after the initiation of the pulse-labeling period, and the extent of labeling increased monotonically thereafter. The labeling could not be accounted for by contamination of synaptic membrane fractions with other membranes, because the relative specific activity of the SPM and SJC fractions was the same or higher than that of the less pure fractions from which these synaptic fractions were derived. One-dimensional PAGE-fluorography was used to provide an initial characterization of which proteins were labeled in SJC fractions. We found that the most prominent labeled bands were at apparent molecular weights of approximately 43-44, 55-56, and 60 kd, with more lightly labeled bands at about 38 and 116 kd. In some preparations, there was a labeled doublet at about 36-38 kd. There were also other lightly labeled bands at other molecular weights. These bands were much less heavily labeled than the bands at 43-44, 55-56, and 60 kd, however. There was little labeling in the molecular weight range of the "major psd protein" (the alpha subunit of CAM-kinase), although there was diffuse labeling throughout the 45-52 kd region. These results are consistent with the hypothesis that some of the protein constituents of the postsynaptic junctional complex are synthesized by polyribosomes which are selectively localized beneath synaptic junctions.     

Correlation of neurosurgical subspecialization with outcomes in children with malignant brain tumors

OBJECTIVE: This study was performed to evaluate the association between the type of neurosurgeon (general or pediatric) and either the extent of tumor removal or the frequency of complications in children undergoing malignant brain tumor resections. METHODS: Data were analyzed from three recent Children's Cancer Group studies: two on medulloblastomas/primitive neuroectodermal tumors and one on malignant gliomas. Neurosurgeons were classified as general neurosurgeons, as designated pediatric neurosurgeons in their institutions, or as members of the American Society of Pediatric Neurosurgeons (ASPN), which requires pediatric neurosurgical experience and practice standards. RESULTS: Data forms from 732 children were analyzed; 485 were from children with medulloblastomas/primitive neuroectodermal tumors, and 247 were from children with malignant gliomas. Operations were performed by 269 neurosurgeons, including 213 general neurosurgeons, 29 designated pediatric neurosurgeons, and 27 ASPN members. The mean number of operations per surgeon was 1.8, 4.9, and 7.6 for general neurosurgeons, designated pediatric neurosurgeons, and ASPN members, respectively. There was a significant relationship between the extent of tumor resection or the amount of residual tumor and the type of neurosurgeon. Designated pediatric neurosurgeons and ASPN members were more likely to remove more than 90% of the tumor and to leave less than 1.5 cc of residual tumor than were general neurosurgeons (P<0.05). In these studies, the probability of extensive tumor removal correlated with the number of operations the neurosurgeon performed (P<0.01). Neurological complications occurred in the following proportion of cases: general neurosurgeons, 23%; designated pediatric neurosurgeons, 32%; and ASPN members, 18%. CONCLUSION: Pediatric neurosurgeons are more likely than general neurosurgeons to extensively remove malignant pediatric brain tumors. In these tumors, extent of removal has been demonstrated to influence survival.     

Communicating oesophageal duplication

Oesophageal duplications are rare congenital abnormalities. Most of them do not communicate with the oesophageal lumen. We present a very uncommon finding of communicating oesophageal duplication in which the connection between the oesophagus and its duplicate portion was demonstrated by CT.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.