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Background Gemistocytes (GCs) are unique phenotype of reactive astrocytes. In diffuse low-grade gliomas, they are associated with grim prognosis. Less is known regarding their pathogenesis and prognostic significance in glioblastoma (GBM). Previous data on-neoplastic central nervous system (CNS) lesions has linked the presence of GCs with states of uncontrolled hyperglycaemia in diabetes mellitus type 2 patients. study purpose is to find a correlation between systemic metabolic features and the presence of GCs in patients with GBM.Also, to try and correlate between the presence of GCs, molecular changes, and use of anti-diabetic drugs on overall survival of GBM patients. Methods Electronic medical records from newly diagnosed GBM patients were retrospectively reviewed and extracted for demographic, clinical, metabolic, radiological and pathological variables with emphasis on different metabolic - related features. A statistic-based comparison was made between GBM patients with and without GCs for the same variables. We compared DM2 GC-GBM patients to DM2 non-GC GBM patients in a cohort of poorly controlled DM2 (i.e., HBA1C ≥ 8.0). A possible influence of metformin administration on OS of DM2 GBM patients, with and without GCs, and with and without TP53 mutations was investigated. Results A total of 220 patients with newly diagnosed GBM were included in the study. 14.5% were defined as GC-GBM (group 1, n=32) and 85.5% were defined as non-GC GBM (group 2, n=188). The incidence of DM2 was 25% in both groups. The rate of poorly-controlled DM2 was nearly as twice in group 1 than in group 2 (18.75% vs. 9.5%; p=0.130). In the DM2 GBM group, significant differences were found between DM2 GC-GBM (group 1a, n=9) and DM2 non-GC GBM (group 2a, n=49) patients with male gender predominance (89% vs. 50%, p=0.073) and obesity. Patients in group 1a were more likely to have weight ≥85kg (OR 6.16; 95% CI 1.3336 to 28.5147, p=0.0019) and had higher BMI values (mean BMI of 34.1±11.42 vs. 28.7±5.44 for group 1a and 2a respectively; OR= 1.095, 95%CI 1.053-1.207;p=0.034). Similar significant findings were in the poorly-controlled DM2 subgroup. None of the poorly-controlled DM2 GC-GBM patients were using insulin prior to diagnosis (0% vs. 61.10%, p=0.016). Survival analyses have shown trends for differences in overall survival between subgroups in correlation with presence of GCs, p53 mutations and use of metformin. Conclusion GBM patients with systemic metabolic factors that are associated with marked insulin resistance and are not using insulin at time of diagnosis are significantly more likely to have GCs in their initial pathology. This is a novel finding that may add to data on glucose metabolism in astrocytes and in astrocytes-associated tumors. The presence of GCs, molecular changes in the tumor, and under the influence of anti-diabetic drugs such as metformin, may affect the prognosis of different GBM subgroups.

Background Brain metastases are a common complication of non small cell lung cancer (NSCLC). Approximately 10 percent of newly diagnosed patients with advanced NSCLC have brain metastases. The purpose of this study was to determine whether using magnetic resonance imaging (MRI) for early screening of brain metastases can improve survival. Material and Methods A retrospective analysis of newly diagnosed stage IV NSCLC treated at Davidoff Cancer Center, Israel, between the years 2019-2020. Only patients who were neurologically asymptomatic were included in the study. The study population was divided into two groups. Group A included patients who underwent screening MRI within 12 weeks form diagnosis and group B included those who did not undergo screening MRI. Clinical and radiographic data were collected form the medical records. Results 379 patients were included in the study, of whom 170 underwent screening MRI. Of the patients who underwent screening MRI 54 were diagnosed with brain metastases. On univariate analysis screening MRI was correlated with better survival [group A median survival 24 month, group B median survival 18 month, p=0.003 HR 1.4 CI 1.12-1.75]. On multivariate analysis that included functional status (ECOG 0-2 compared to 3 and above) and age- screening MRI correlated with survival (p=0.04 HR 1.28 CI 1.02-1.6). Subgroup analysis according to molecular subgroup will be presented in the conference. Conclusion In this study screening MRI among stage IV NSCLC correlated with better survival even when adjusted to functional status and age.

Aim: To describe our experience in treating vitreoretinal involvement of primary central nervous system lymphoma, by intravitreal injections of methotrexate (MTX). Methods: Patients with suspected intraocular lymphoma underwent a diagnostic vitrectomy. Samples were sent for cytology, genetic evaluation and for interleukin level measurements. Treatment protocol included injection of 400 μg/0.1 ml MTX intravitreally twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months, for a total of 25 injections. Data were collected from the patients’ records and included, inter alia, response to intravitreal MTX measured by time to disappearance of vitreal cells and retinal infiltrates, changes in visual acuity, and clinical recurrence rate. Results: In the past 10 years we have treated 44 eyes of 26 patients; seven patients had monocular involvement, and 19 binocular. Six patients were initially diagnosed as having a non-responsive uveitis, and 16 with either CNS or systemic lymphoma with later involvement of the eye. Four patients had systemic lymphoma; one of them was found to have CNS lymphoma after the ocular involvement. Three patients had T cell lymphoma, and the rest had B cell lymphoma. Clinical remission was reached after 6.4 (3.4) (2–16) injections of MTX (mean (SD) (range)), with 95% of the eyes needing 13 injections or less to be cleared of malignant cells. None of the patients had an intraocular recurrence. Among the side effects, the most common was corneal epitheliopathy, which usually appeared after the third injection and began to subside when the intervals between injections increased. Conclusions: Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.

In view of the demanding instruction and training requirements associated with cochlear implantation, patients with cognitive impairments have typically been considered to be poor candidates for this procedure. This presumption persists in part because experience and research in this area are limited. We describe our experience with implanting cochlear devices in 2 patients who had significant psychological impairments; 1 patient had experienced a severe brain injury, and the other had paranoid schizophrenia. Nevertheless, both patients were able to follow the implant training program, and they experienced different degrees of improvement in their hearing. We discuss our preoperative evaluations of these patients and the key factors that led to our decision to proceed with surgery.

Aim: To determine the incidence and characteristics of maculopathy associated with blood–brain barrier disruption (BBBD) which is used in treating primary central nervous system lymphoma (PCNSL). Methods: Files of all 56 patients with PCNSL, with or without intraocular lymphoma (IOL), treated at Hadassah University Hospital during the years 1997–2007 were reviewed. Data on 46 patients for whom we had documentation of ocular examination were studied. Those who were alive at the time of the data collection were invited for further evaluation of the presence or absence of maculopathy. The patients were divided into four groups according to treatment protocol. Group 1: systemic intravenous chemotherapy; Group 2: systemic intravenous chemotherapy and intravitreal methotrexate (MTX); Group 3: systemic intra-arterial (IA) chemotherapy and BBBD; Group 4: systemic IA chemotherapy, BBBD, and intravitreal MTX. Results: Of the 23 patients of Groups 1 and 2 who were not treated by BBBD, none developed maculopathy. Of those 23 patients who were treated by BBBD, 12 of 17 (70.5%) in Group 3 and three of six (50%) in Group 4, for a total of 15 of 23 (65.2%) developed maculopathy. The maculopathy did not significantly affect visual acuity in any of them. Conclusions: BBBD may cause maculopathy in almost two-thirds of patients treated for PCNSL, without affecting significantly the visual acuity. Intravitreal injection of MTX, according to the protocol which we apply, is not associated with maculopathy.

Purpose: Vitreoretinal involvement occurs in approximately one-quarter of patients with primary CNS lymphoma (PCNSL), and in some patients with systemic lymphoma who may later develop CNS lymphoma. The traditional method for treating vitreoretinal lymphoma, which is the common type of intraocular lymphoma, is by external beam radiation, or intravenous or intrathecal chemotherapy; however, recurrences are common. We describe our ten years of experience in treating vitreoretinal involvement of PCNSL by intravitreal injections of methotrexate (MTX). Methods: Biopsy-proven vitreoretinal lymphoma has been treated by intravitreal injections of 400 μg/ml methotrexate. According to our protocol, injections are administered twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months for a total of 25 injections. Results: Forty-four eyes of 26 patients have been treated; 7 patients had monocular involvement and 19 binocular. Twenty-three patients had B-cell lymphoma and 3 patients had T-cell lymphoma. In all patients remission of the intraocular lymphoma was achieved after 6.1 + 3.5 injections (range 2 – 16 injections). None of the patients had an intraocular recurrence. Among the side effects, the most common were conjunctival hyperemia and corneal epitheliopathy, which usually subsided when the interval between the injections increased. Conclusions: In our experience, treatment by intravitreal injections of methotrexate provides complete remission of vitreoretinal lymphoma with, so far, no recurrences and with bearable side effects, and can be considered as alternative treatment to radiotherapy and systemic or intrathecal chemotherapy.

In view of the demanding instruction and training requirements associated with cochlear implantation;,patients with cognitive impairments have typically been considered to be poor candidates for this procedure. This presumption persists in part because experience and research in this area are limited. We describe our experience with implanting cochlear devices in 2 patients who had significant psychological impairments; 1 patient had experienced a severe brain injury, and the other had paranoid schizophrenia. Nevertheless, both patients were able to follow the implant training program, and they experienced different degrees of improvement in their hearing. We discuss our preoperative evaluations of these patients and the key factors that led to our decision to proceed with surgery.

The aim of this study was to determine the safety and efficacy of intraarterial chemotherapy with osmotic opening of the blood-brain barrier (BBB) for the treatment of malignant brain tumors when administered across multiple centers.Patients with primary central nervous system lymphoma (PCNSL), primitive neuroectodermal tumor (PNET), germ cell tumor, cancer metastasis to the brain, or low or high grade glioma were eligible. Prior to entry, magnetic resonance imaging or computed tomography brain scan, medical history, neurologic status, and Karnofsky performance status were reviewed at the coordinating center. Standardized anesthesia and intraarterial catheterization guidelines were followed by a multidisciplinary team at each center. Between March 1994 and November 1997, 5 universities treated 221 adult patients with intraarterial chemotherapy with or without osmotic opening of the BBB (2464 procedures).Of evaluable patients with PCNSL, 40 of 53 (75%) achieved complete response (CR). All evaluable patients with PNET (n = 17), metastatic disease (n = 12), or germ cell tumor (n = 4) achieved stable disease (SD) or better. Of 57 evaluable patients with glioblastoma multiforme, 45 (79%) achieved SD or better. Asymptomatic subintimal tear occurred in 11 of 221 patients (5%), pulmonary embolism in 6 of 221 (2.7%), and renal toxicity in 4 of 221 (1.8%). One patient with extensive glioma expired within 48 hours after treatment.Using standard guidelines and protocols, intraarterial chemotherapy with or without osmotic opening of the BBB is feasible across multiple centers with a low incidence of catheter-related complications. In patients with chemotherapy-sensitive tumors, such as PCNSL, PNET, germ cell tumor, and cancer metastasis to the central nervous system, enhanced delivery results in a high degree of tumor response, with an efficacy profile that is reproducible across multiple centers.

Hemangioendothelioma is an uncommon vascular tumor that falls between hemangioma and angiosarcomas in behavior and appearance. These tumors may occur anywhere in the body, even very rarely in the b...

Malignant subarachnoid deposits complicate both primary central nervous system (CNS) tumors and systemic neoplasms. Although the pathophysiology of symptoms and signs can not be separated by the category of primary tumors that seeds the leptomeninges, the approach to therapy is not similar in primary CNS tumors and in systemic neoplasms. Standard therapy for subarachnoid seeding in primary CNS tumors include conventional or high doses of systemic chemotherapy with various combinations of radiotherapy given either to limited fields or to the whole neuroaxis. Direct administration of chemotherapy to the CSF is not being used. In contrast, whenever a systemic tumor seeds the subarachnoid space the standard approach includes intensive intra-CSF chemotherapy, radiotherapy to limited or extended CNS fields and various combinations of systemic chemotherapy. The published experience with the conventional therapy is reviewed and is critically analyzed. Evidence indicating that high dose systemic chemotherapy can replace intra-CSF treatment in some subgroups are also reviewed and the rationale for this approach is specified. Recent experience in which intra-CSF therapy was prospectively eliminated from the treatment protocol of leptomeningeal metastases of solid tumors reveals that the response rate and survival are similar to those obtained by protocols that differed only by the inclusion of intra-CSF chemotherapy. Patients who were treated by radiotherapy alone combined with systemic chemotherapy but without the intra-CSF therapy were spared the high rate of early and delayed complications directly related to intra-CSF therapy. Still, treatment outcome did not differ. Therefore, future research efforts and prospective clinical trials should investigate the best chemotherapeutic schedules and their sequencing with radiotherapy or with more intensive complementary systemic chemotherapy schemes. Newly designed drugs with long circulation time and improved CNS penetration may serve for this purpose.

Leptomeningeal metastases are common in patients with metastatic systemic cancer or certain primary brain tumors. They may be unsuspected clinically and may be missed by cerebrospinal fluid (CSF) cytology. We undertook a retrospective study of the diagnostic value of gadolinium enhanced spinal MR imaging in patients with known or at high risk for leptomeningeal metastases (LM).Ninety-six gadolinium enhanced MR examinations of the whole spine were performed in 61 patients (26 primary central nervous system tumors, 20 solid tumors and 15 lymphoproliferative neoplasms). All patients had detailed neurological evaluation and concomitant CSF examination.Sixty-one MR's (62%) were positive, mostly in the lumbar spine. MR's were positive in 92% of patients with positive initial CSF cytology and in 60% of patients with negative CSF cytology. The MR examination was positive in 49% of those without clinical findings related to the spinal region. It showed disease beyond the symptomatic level in 42% of patients with spinal symptomatology. Multi-level spinal involvement was present in 57% of positive MR exams.Enhanced spinal MR is sensitive for the detection of neoplastic spinal seeding. It detects LM in about 50% of high risk patients with negative initial CSF cytology or no spinal symptoms.

We evaluated the role of serotonin (5-HT) in neoplastic cord compression in paraplegic rats harboring a thoracolumbar epidural tumor. We measured serotonin and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the C-1 to C-7, T-1 to T-6, T-7 to T-12, and T-13 to L-3 spinal segments of tumor-free and tumor-bearing rats. In normal controls, a consistent rostral-to-caudal gradient for 5-HT and 5-HIAA was evident, but the 5-HIAA/5-HT ratio remained constant. In paralyzed rats, 5-HT levels were unchanged, but the 5-HIAA/5-HT ratio was elevated, especially in the compressed segments. Treatment with either dexamethasone or indomethacin delayed onset of paraplegia but had no effect on 5-HT metabolism. Blocking 5-HT receptors by cyproheptadine, evaluated 30 hours after onset of paralysis and treatment, resulted in a reduction in the high water content, vascular permeability, and prostaglandin E2 synthesis in the compressed cord. Early administration of cyproheptadine effectively delayed the onset of paraplegia. These data indicate that receptor-activated serotonergic mechanisms participate in the disruption of the blood-spinal cord barrier and that these effects can be manipulated pharmacologically.

Water content and specific gravity were measured in the cervical, high thoracic, thoracic, and lumbar segments in an experimental model of neoplastic epidural spinal cord compression in rats harboring a thoracolumbar tumor. Increased content of water was observed only in the compressed lumbar cord segments of paralyzed rats (P less than 0.04). A progressive increase in specific gravity values of the compressed segments accompanied the increasing severity of neurological dysfunction (P less than 0.003 in paraplegic rats). Electron microscopy of the compressed cord revealed enlarged interstitial spaces, myelin breakdown, and extravasated blood cellular elements. Treatment with dexamethasone (10 mg/kg q 12 hr x 3) failed to reduce the increased content of water, but corrected specific gravity changes. Treatment with indomethacin (10 mg/kg q 12 hr x 3) reduced both elevated water content and specific gravity values back to normal levels. In untreated animals, the interval between the first neurological sign (limp tail) and paraplegia was 2.8 +/- 0.34 days (mean +/- SE). Treatment with dexamethasone lengthened this period by 28.6% (P less than 0.05); treatment with indomethacin lengthened it by 66.4% (P less than 0.005). We conclude that, because the specific gravity measurements in this model reflect complex pathophysiological processes, their translation into water content values is not advisable. Pharmacological intervention with indomethacin compares favorably with dexamethasone in reduction of spinal cord edema and in delaying the onset of paraplegia.

Two patients with dermatomyositis were treated with methotrexate, given intravenously. They were unresponsive to corticosteroids. The patients were bedridden and paralysed and one seemed to be in the terminal phase of the disease. The response to courses of methotrexate treatment was satisfactory and sustained over a 2-year follow-up period; muscle enzyme studies indicate that the muscle disease is no longer active. Although steroid therapy alone may be effective, its usefulness is unpredictable and may lead to dependence and undesirable side effects. Our experience with these two patients suggests that a combination of the two drugs may be justified as initial treatment in severe cases.

Cartilaginous fetal bones from rat preserved by deep freezing procedures were compared to comparable fresh bones with regard to the following parameters: chemical composition, water and uronic acid contents; cell viability measured by the rate of proteoglycan synthesis; mineralization-ossification status by calcium binding; matrix integrity by the release of uronic acid containing substances; and biological activity as transplants inducing the formation of bone. The transplanted material was chemically analyzed and checked for its rate of proteoglycan synthesis. The quality of the formed bone was similar whether isogeneic or allogeneic, fresh or cryopreserved bone was employed as transplant material. Evidently those various fetal bones may be of clinical value whenever the need for replacement of massive bone loss arises. Although the viability and the cartilaginous nature of the graft are critical, the isogeneity and freshness are of a quantitative advantage only. These biochemical observations were confirmed by roentgenological and histological evaluations of the grafts. An optimal cryopreserving procedure and tests for examining bone candidates for successful grafting are described.

The posterior approach for varus rotational osteotomy of the hip with the patient prone is relatively bloodless, provides excellent visualization of the osteotomy site, and facilitates insertion of internal fixation devices. We performed this operation on 100 hips in fifty-nine patients. All but one of the osteotomies healed within eight weeks and there was one infection.

Nearly 20% of patients with neoplastic involvement of the vertebral column develop spinal cord compression, and in 8% this is the initial manifestation of cancer. Important determinants of functional prognosis are: 1) tumor biology, 2) pretreatment neurologic status, and 3) tumor location within the spinal canal and the therapy employed. Future efforts should be invested in manipulation of the last two determinants. Delay in neurologic deterioration may be achieved by pharmacologic manipulation of the deleterious pathophysiologic processes operating in the compressed spinal cord, as recently demonstrated in experimental animal models. Use of modern neuro-imaging techniques (metrizamide myelography combined with computed tomography, and/or magnetic resonance imaging) will accurately define tumor extent and location. Radiotherapy is indicated in highly or moderately radiosensitive tumors. Surgery is reserved for the following situations: diagnosis in doubt, previous radiation exposure, radioresistant tumors, neurologic deterioration during irradiation, and the presence of spinal instability or bone compression of the neural structures. The location of the compressing tumor will dictate the surgical approach--a vertebral body resection in an anterior or anterolateral tumor and a laminectomy in a posterior or posterolateral deposit. Modern instrumentation techniques for spinal column stabilization or vertebral body replacement will allow immediate painless ambulation and a better quality of life for these patients.

We are presenting our experience with vertebral body resection in forty-seven operative procedures in forty patients with a malignant epidural tumor. The indication for surgery was neural relapse after previous radiotherapy in eighteen procedures, the need for a tissue diagnosis in sixteen, a radioresistant tumor in seven, neural deterioration while receiving radiotherapy in five, and a pathological fracture-dislocation in one. In thirty-three procedures (70 per cent) the level of compression was in the thoracic spine. Replacement of the resected vertebral bodies was achieved by anterior instrumentation and the use of methylmethacrylate in twenty-one procedures (45 per cent), while bone-grafting, cement, and instrumentation in various combinations were used in the remainder. Before surgery all of the patients had some neural deficit. The patient was still able to walk prior to twelve (26 per cent) of the procedures, was paraparetic prior to twenty-three (49 per cent), and was paraplegic prior to twelve (26 per cent). Bowel and bladder dysfunction was present before twenty-five (53 per cent). The outcome of only forty-four procedures could be evaluated because three patients died postoperatively. The patient was able to walk following thirty-five (80 per cent) of the procedures, was paraparetic after eight (18 per cent), and was still paraplegic after one. The patient regained normal sphincter control after forty-one (93 per cent) of the procedures. Three (6 per cent) of the procedures were followed by the death of the patient, and complications occurred after five (11 per cent) of the procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Edema formation and prostanoid production (prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in a model of neoplastic epidural cord compression (NSCC) in rats harboring a thoracolumbar tumor. Tumor-free and tumor-bearing animals were randomized for three treatments at 12-hour intervals with saline, dexamethasone (10 mg/kg i.p.), or indomethacin (10 mg/kg i.p.). Increase in water content was observed only in the compressed lumbar cord segments of paralyzed rats; the cervical and thoracic segments did not differ from controls. The rate of release of prostaglandins was evenly distributed along the spinal segments in tumor-free rats. In tumor-bearing rats, a consistent significant increase in PGE2 production was found in the compressed lumbar segment in the presence of neurological dysfunction: early (limp tail), P less than 0.05; paraplegia, P less than 0.001. A significantly elevated PGE2 synthesis preceded the increase in water content by 2 to 3 days. A 2-fold increase in TXB2 was detected in only one of three experiments, and synthesis of 6-keto-PGF1 alpha was elevated to 4 times the normal value (P less than 0.005) in two of three experiments. Dexamethasone failed to inhibit prostaglandin synthesis in the spinal cord of normal controls or paralyzed rats, whereas in nonneural tissues (liver, uterus) it reduced synthesis of the three metabolites by at least 50%, thus demonstrating a differential effect on central nervous system (CNS) vs. non-CNS tissues. Dexamethasone also failed to reduce the increased water content of the compressed segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinal fluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis--a CT scan and a myelogram. We report a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. We believe that radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer. We therefore are extending our studies to validate this possibility.

We report 98 consecutive patients with leptomeningeal metastases from lymphoma and other solid tumors. Of 90 who had non-CNS primary tumors, 71 had a life expectancy of at least 2 months from their systemic disease and were treated according to a protocol including radiotherapy to the symptomatic areas of the CNS and chemotherapeutic agents (usually MTX) administered into the CSF. Eight patients with meningeal spread from CNS tumors received craniospinal irradiation and/or systemic or intra-CSF chemotherapy. Of those treated according to the protocol, 30 had lymphoma, 25 of whom achieved a CR and 4 a PR; 27 had breast carcinoma, 9 of whom achieved a CR and 6 a PR; 14 had other solid tumors, 7 of whom achieved a CR and 2 a PR. Median survival was 8 months (range 1 to 87+) in patients with lymphoma and 3 months (range 1 to 40) in breast carcinoma patients. Long-term survivors were seen in these groups. Treatment complications occurred in 30% of patients, resulting in 4 deaths. The indications for aggressive therapy of leptomeningeal metastases and means to reduce its toxicity are discussed.

A fusiform longitudinal hemorrhagic necrosis of the spinal cord is described in a patient with spinal cord compression caused by metastases from an adenocarcinoma of the prostate. The lesion extended from the D3 down to L2 level with maximal involvement of the D7-D8 segments. The shape, location, and distribution of the lesion and its prominent hemorrhagic component corresponded to Jellinger's category of cylindrical liquefaction necrosis, probably due to venous obstruction. The multiple thrombi found in epidural veins supported such a pathogenic mechanism, which although extremely rare has been reported previously in five cases.

In the September-October 1986 issue of Physician Executive, we discussed the application of strategic business units (SBUs) to health care. SBUs are those corporate entities that market similar products to one or more target populations with similar characteristics. Examples of SBUs in health care are obstetrics, cardiology, orthopedics, etc. When the services within each SBU are linked together, they might resemble a vertically integrated health care system. In the case of obstetrics, a woman may have contact with physicians, a hospital, home care nurses, house-cleaning services, birthing teachers, and maternity clothing boutiques. Each of these are products/services within the SBU of obstetrics. Strategy development by SBU implies an external focus on the marketplace in terms of the specific mission of the SBU (clinical specialty). It also implies responding to the needs of consumers for whom the historical and present divisiveness between hospitals and physicians is immaterial and irrelevant. In this article, we will focus on ways to stabilize the relationship between hospitals and physicians within an SBU context in order to compete more successfully as a team in today's health care environment.

Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinal fluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis--a CT scan and a myelogram. We report a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. We believe that radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer. We therefore are extending our studies to validate this possibility.

The posterior approach for varus rotational osteotomy of the hip with the patient prone is relatively bloodless, provides excellent visualization of the osteotomy site, and facilitates insertion of internal fixation devices. We performed this operation on 100 hips in fifty-nine patients. All but one of the osteotomies healed within eight weeks and there was one infection.

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Ths structure of the health care delivery system continues to evolve, old organizational types taking new forms and new entities joining in a sometimes helter-skelter array. What is missing is order and purpose. Most health care organizations have not yet asked the critical questions, "What business are we in?" and "Who are our customers?" The authors suggest that what is needed is a strategic business unit approach to the process of business development.

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with "spontaneous" meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.