The mental health provider's view

What do we want from primary care physicians to make their care of our patients better and our jobs less difficult? We want reasonable access to primary care services, effective communication, reduction in excessive practice interference, and flexible collaboration.     

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.     

Radiation therapy in the management of desmoid tumors

Purpose: To evaluate the outcome of patients with extra-mesenteric desmoid tumors treated with radiation therapy, with or without surgery.

Methods and Materials: The outcome for 75 patients receiving radiation for desmoid tumor with or without complete gross resection between 1965 and 1994 was retrospectively reviewed utilizing univariate and multivariate statistical methods.

Results: With a median follow-up of 7.5 years, the overall freedom from relapse was 78% and 75% at 5 and 10 years, respectively. Of the total, 23 patients received radiation for gross disease because it was not resectable. Of these 23 patients, 7 sustained local recurrence, yielding a 31% actuarial relapse rate at 5 years. Radiation dose was the only significant determinant of disease control in this group. A dose of 50 Gy was associated with a 60% relapse rate, whereas higher doses yielded a 23% relapse rate (p < 0.05). The other 52 patients received radiation in conjunction with gross total resection of tumor. The 5- and 10-year relapse rates were 18% and 23%, respectively. No factor correlated significantly with disease outcome. There was no evidence that radiation doses exceeding 50 Gy improved outcome. Positive resection margins were not significantly deleterious in this group of irradiated patients. For all 75 patients, there was no evidence that radiation margins exceeding 5 cm beyond the tumor or surgical field improved local-regional control. Ultimately, 72 of the 75 patients were rendered disease-free, but 3 required extensive surgery (amputation, hemipelvectomy) to achieve this status. Significant radiation complications were seen in 13 patients. Radiation dose correlated with the incidence of complications. Doses of 56 Gy or less produced a 5% 15-year complication rate, compared to a 30% incidence with higher doses (p < 0.05).

Conclusions: Radiation is an effective modality for desmoid tumors, either alone or as an adjuvant to resection. For patients with negative resection margins, postoperative radiation is not recommended. Patients with positive margins should almost always receive 50 Gy of postoperative radiation. Unresectable tumors should be irradiated to a dose of approximately 56 Gy, with a 75% expectation of local control.