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Biomedical subjects

W A Hall

Publications and source records attributed to W A Hall.

At least 19 recordsLinked to original sources
PubMed1995

Maintaining accuracy in stereotactic radiosurgery.

PURPOSE: To provide the manufacture's specification for the base phantom of a commercially available stereotactic radiosurgery system so that its accuracy can be confirmed, and to describe a calibration device that allows the accuracy of the base phantom to be verified quickly and on a routine basis. Modifications to the target pointer system that make matching the pointer tips easier and less likely to damage the pointer tips are also described. METHODS AND MATERIALS: In stereotactic radiosurgery, spatial accuracy is the key factor for successful dose delivery. With some commercially available systems, this accuracy depends on the accuracy of the base phantom coordinate system, how closely the tip of the target pointer can be matched to the tip of the base phantom pointer, and how accurately the coordinates set on the isocentric subsystem match those set on the base phantom. Two major problems, usually overlooked when evaluating system accuracy are, first, the base phantom, which establishes the stereotactic coordinate system, is assumed to be completely accurate. This is a dangerous assumption because the base phantom is used frequently for routine patient treatments and for standard quality assurance tests. To exacerbate the problem, no independent device is provided with stereotactic systems to check the accuracy of the base phantom. Second, the accuracy of the isocenter coordinates set on the head support stand depends upon how closely the target pointer and the base phantom pointer can be aligned. The hardware provided with the system is difficult to use and easily leads to damage of the pointer tips. RESULTS: In this work, we provide the manufacturer's specifications for a popular stereotactic system, describe a device that can be used to check quickly and easily the accuracy of the base phantom, and describe a modification to the transfer pointer system that allows the pointer tips to be more easily aligned with reduced possibility of damage to the pointer tips. CONCLUSION: The methods and apparatus described in this paper should be useful to anyone using a base phantom for testing radiosurgery accuracy.

Equipment Design↗
PubMed1995

Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status.

BACKGROUND: The authors assessed cerebrospinal fluid (CSF) flow in patients with carcinomatous meningitis using technetium-99m-DTPA (Tc-99) ventriculography to determine the frequency of flow abnormalities, their reversibility with treatment, and the implications for successful therapy and survival. METHODS: Technetium-99m-DTPA flow studies were performed in 31 patients after placement of Ommaya reservoirs (Baxter, McGaw Park, IL). Two millicuries of Tc-99 were injected into the reservoir. Planar images of the head and entire spine were obtained after 10 and 30 minutes and after 1, 4, 6, and 24 hours. Follow-up studies were performed for 12 patients whose initial studies were abnormal or who developed complications of therapy. RESULTS: In 19 of the 31 patients (61%), ventricular-outlet, spinal, or convexity blocks were identified. In 11 of these 19 patients, focal radiotherapy to the site of the block restored normal flow. Survival among patients with initially normal, abnormal but correctable, and abnormal but uncorrectable CSF flow differed significantly (6.9, 13.0, and 0.7 months respectively; P < 0.001). Some patients who were treated intrathecally despite abnormal CSF flow experienced drug-related toxicity. CONCLUSIONS: Cerebrospinal fluid-flow blocks are common in patients with carcinomatous meningitis and may occur at the skull base, in the spinal canal, and over the convexities. These flow abnormalities often can be corrected with appropriately directed radiotherapy. If untreated, CSF tumor progression (protected site effect), neurotoxicity (high concentration effect), and systemic toxicity (reservoir effect) can occur, resulting in shortened survival and treatment-related morbidity. Therefore, intrathecal chemotherapy should be preceded by a radionuclide flow study and should be delayed if abnormal flow is documented until appropriate radiotherapy reestablishes normal flow.

Adolescent↗
PubMed1995

Multifocal enhancing magnetic resonance imaging lesions following cranial irradiation.

Radiation necrosis is a delayed complication of cranial irradiation, typically presenting as a single intracerebral mass that is radiographically indistinguishable from recurrent tumor. We describe 6 patients with a distinct radiographic syndrome of multifocal enhancing lesions on magnetic resonance images, and their variable clinical courses: some fluctuating, some spontaneously resolving, and some demonstrating fulminant progression to frank necrosis.

Adult↗
PubMed1995

Stereotactic radiosurgery for recurrent malignant gliomas.

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.

Actuarial Analysis↗
PubMed1995

In vitro and in vivo variation in transferrin receptor expression on a human medulloblastoma cell line.

The poor prognosis associated with pediatric central nervous system tumors such as medulloblastoma has led to the development and investigation of a variety of new treatment techniques. Therapeutic agents include targeted-toxin conjugates or immunotoxins that show significant in vitro activity against many brain tumors. Transferrin receptors (TRs) are specific, cell-surface antigens that are expressed preferentially on brain tumors rather than on normal human brain tissue. This antigen has been successfully targeted in human and nonhuman brain tumors in vitro and in vivo. In this study, when TRs were used as a target in the DAOY human medulloblastoma-derived cell line in vitro, a significant level of expression was confirmed by testing the sensitivity to different immunotoxins. To ensure the relevance of the in vitro data to the in vivo situation, we also analyzed TR expression in DAOY tumors growing in athymic mice and rats. Immunocytochemistry, immunohistochemistry, immunobead binding, immunofluorescence, 125iodine-transferrin binding, and Northern blot analysis were used to compare TR expression in DAOY cells in vitro and in vivo. All in vitro assays demonstrated significant TR expression, whereas in vivo, the TR expression was negligible in the DAOY tissue. The results caution against extrapolating in vitro antigen and receptor expression data directly to the in vivo situation. Using a transferrin-toxin conjugate in a nude rat model of leptomeningeal carcinomatosis, we achieved therapeutic efficacy, despite demonstrating reduced TR expression on tumor tissue. With respect to clinical efficacy, the reduced expression of TR on DAOY medulloblastoma in vivo may be less significant than expected because of the extreme potency of immunotoxins observed in central nervous system tumors.

Animals↗
PubMed1994

Nude rat models for human tumor metastasis to CNS. Procedures for intracarotid delivery of cancer cells and drugs.

Models for hematogenous spread of human cancer to the central nervous system (CNS) were established by injecting human tumor cells into the internal carotid artery of nude rats. With 4 out of 10 cell lines, belonging to four different tumor types, metastases developed in all injected animals. Tumor growth manifested clinically as neurological symptoms which appeared after a median latency ranging from 19-87 days for the different tumors. The H-146 and DMS-273 small cell lung cancers and the LOX melanoma almost exclusively gave meningeal tumors, whereas with FEMX-I melanoma cells bone metastases in the skull dominated. For these tumor types a correlation was found between the capacity for experimental metastasis formation and the s.c. tumorigenicity. In agreement with clinical experience, none of the 2 sarcoma and 2 glioblastoma lines gave CNS metastases. With a modified microsurgical technique, allowing for repeated ipsilateral intracarotid injections, we analyzed the drug concentrations obtained in tumor and surrounding brain tissue after i.v. treatment with doxorubicin. The concentration in the LOX tumor reached therapeutic levels and was approximately 100 x higher than in normal brain tissue, both with and without intraarterial pretreatment with arabinose. In the same model, the tissue concentrations of 9.2.27-abrin immunotoxin 10 min after intracarotid injection were examined. Although the levels were low, a tumor to brain concentration ratio of up to 9 was achieved. The data demonstrate that clinically relevant tumor models can be established with the techniques described, and these models may successfully be used to evaluate the pharmacokinetics and effect of intravenous or intraarterial therapy.

Animals↗
PubMed1992

Comparison of the experience of women and men in dual-earner families following the birth of their first infant.

This paper describes an extension of the concept of "redefining roles" developed from an initial study that described the experience of eight women in dual-earner families following the birth of their first infant. A second study used redefining roles as a springboard and described the experience of ten men. Although constant comparative analysis generated a core variable in both studies best described as "redefining roles," the two groups redefined their roles somewhat differently. When the women redefined their roles, they took on multiple roles, experienced role strain, and reduced role strain. The men monitored and limited role strain. The implications for nursing practice are outlined.

Adult↗
PubMed1992

Metastatic carcinoid tumor to the orbit and brain.

Carcinoid tumors constitute an uncommon source of metastatic lesions to the brain. We report the case of a 63-year-old man who initially sought treatment for proptosis 15 years before coming to our attention with a metastatic intracerebral left parietal carcinoid. The pathological features of the exenterated orbital mass were interpreted as undifferentiated carcinoma, and a lesion of the left lower lobe of the lung that had been removed 6 years earlier had been reported as metastatic malignant melanoma. The long duration between the initial diagnosis and the onset of neurological symptoms brought into question the original diagnosis, which, in retrospect, was most consistent with metastatic carcinoid. Staining for cytokeratin, neuron-specific enolase, and synaptophysin in the absence of staining for S-100 and HMB-45 supported the revised pathological diagnosis. Metastatic intracerebral carcinoid from an unrecognized bronchogenic source is a rare event, particularly after an orbital metastasis, but should be suspected when the clinical course is inconsistent with the more common causes of metastatic disease.

Biomarkers, Tumor↗
PubMed1992

Immunotoxins and central nervous system neoplasia.

The poor prognosis associated with central nervous system (CNS) malignancy has led investigators to seek new, innovative treatment modalities. Immunotoxins, carrier molecules linked to toxic agents, combine high specificity for tumor-associated antigens with extreme potency. The rationale for both the development of these compounds and for their application to CNS neoplasia is explained. This report discusses the design and construction of immunoconjugates, using toxins that differ in their mechanism of action bound to ligands directed against various antigens. A comparison is made between the in vitro efficacy of standard chemotherapy and immunotoxins in glioblastoma- and medulloblastoma-derived cell lines. A review is included of the results of experiments in animals with leptomeningeal neoplasia, where prolongation of survival following intrathecal administration of immunotoxins has been reported. The obstacles encountered in clinical trials with other types of cancer are addressed and approaches to optimize the use of these novel agents in the context of treating malignant disease of the CNS are suggested.

Animals↗
PubMed1992

In vitro efficacy of transferrin-toxin conjugates against glioblastoma multiforme.

The cytotoxic activity of immunotoxins constructed with human diferric transferrin (Tfn) as the carrier ligand and an abrin variant Pseudomonas exotoxin A (PE) and the diphtheria toxin mutant cross-reacting material (CRM) 107 as the toxin moieties were studied in vitro. Three malignant human cell lines, the glioblastomas multiforme SNB19 and SF295 and the LOX melanoma, and a nonhuman control murine melanoma cell line B16 were assessed. The presence of transferrin receptors on the cell lines was confirmed by direct 125I-Tfn binding assays. The 50% protein synthesis inhibitory concentration (IC50) values for all cell lines demonstrated that Tfn-abrin variant and Tfn-PE had comparable potency and were both more effective than Tfn-CRM 107. Monensin, a carboxylic ionophore, potentiated the effect of Tfn-abrin variant against glioma cells approximately 35-fold with IC50 values of 4.0 x 10(-13) M and 4.7 x 10(-12) M for SNB19 and SF295, respectively. Cytotoxic activity of Tfn-abrin variant (with or without monensin) and Tfn-PE was correlated with the degree of Tfn receptor expression measured on the cell lines. The exquisite in vitro cytotoxicity of Tfn-abrin variant and Tfn-PE immunotoxins against glioma and melanoma cells warrants further in vivo evaluation and future consideration of these agents for potential clinical application against glioblastoma multiforme and leptomeningeal neoplasia.

ADP Ribose Transferases↗
PubMed1992

Infections in neurologic surgery. The intraventricular use of antibiotics.

Intraventricular antibiotic therapy appears to be a useful treatment modality in those CSF infections in which systemic therapy may fail. Consideration should be given to using this form of treatment when infecting organisms are only sensitive to antibiotics with poor penetration of the CSF (e.g., aminoglycosides and vancomycin) and for cases in which intravenous therapy has failed to sterilize the CSF, toxicity from systemic therapy precludes further increases in dosages, and shunts or other CSF hardware might be expected to reduce the efficacy of systemic therapy by providing a foreign body to harbor organisms. Shunts or reservoirs that are infected may be successfully sterilized with IVT therapy alone or in conjunction with systemic therapy, but this has a lower success rate than cases in which the shunt is removed. There is a wealth of clinical experience with IVT vancomycin and gentamicin that suggests that they are relatively safe. Until more data are available on other aminoglycosides and newer antibiotics, these two agents should be considered the antibiotics of choice for IVT therapy. In situations in which the organism is sensitive to both vancomycin and gentamicin, vancomycin should be used in view of the documented neurotoxicity seen with gentamicin. When gentamicin resistance occurs, amikacin and tobramycin are appropriate alternatives. The high risk of epilepsy with the penicillins and cephalosporins makes them less suited for IVT therapy, although the newer cephalosporins have some promise for IVT therapy. CNS fungal infections can be treated effectively with IVT amphotericin B but with a high risk of significant toxicity. Miconazole appears to be safer than amphotericin B but there is less clinical experience with this drug. Table 1 summarizes the dosages, indications, and toxicity of those antibiotics commonly used for intraventricular administration, which have been reported previously.

Anti-Bacterial Agents↗
PubMed1992

Neurosurgical infections in the compromised host.

Granulocytopenia, cellular and humoral mediated immune dysfunction are predisposing factors to the development of CNS infections in immunosuppressed patients. Brain abscess formation in the compromised host is most commonly caused by enteric bacilli, the bacterium N. asteroides, the fungus Aspergillus fumigatus, or the parasite T. gondii. Mucor and the JC virus cause invasive encephalitis in this patient population. CT and MR imaging have greatly aided in the diagnosis of intracranial lesions because of these agents. Stereotactic biopsy-aspiration for diagnosis and to relieve mass effect combined with systemic antimicrobial therapy is the treatment of choice for intracerebral abscess in the compromised host. Organ rejection and chronic immunosuppressive therapy can complicate surgical intervention in these patients. Only with a high index of suspicion, an aggressive approach to diagnosis, and rapid vigorous therapy may we hope to alter the clinical course in this difficult group of patients.

Brain Abscess↗
PubMed1991

Central nervous system germinomas. A review.

The germinoma represents a less malignant form of germ cell tumor. Depending on the individual's age, this neoplasm constitutes approximately 0.1% to 3.4% of all intracranial tumors. The embryologic origin remains a mystery; however, current theories implicate an aberration in primordial germ cell migration. Clinical presentation depends on tumor location and may involve endocrine, hypothalamic, visual, and cognitive dysfunction. In evaluating midline intracerebral masses, it is imperative that one be aware of the various radiologic appearances, endocrinologic changes, and chemical markers that help to distinguish germinomas from other neoplasms that appear in the pineal, suprasellar, and periventricular regions. Only through the careful evaluation of all available studies can the physician institute appropriate therapies such as biopsy, radiation, and chemotherapy. This article focuses on the epidemiology, embryology, clinical presentation, means of diagnosis, treatment, and outcome of this rare neoplasm.

Brain Neoplasms↗
PubMed1990

Subarachnoid-pleural and subarachnoid-mediastinal fistulae.

Subarachnoid-pleural fistula and subarachnoid-mediastinal fistula are rare complications of chest trauma. One case each of subarachnoid-mediastinal fistula and subarachnoid-pleural fistula is described. Both patients were young children who suffered severe longitudinal distraction injuries to their thoracic spine and exhibited complete cord transection without radiographic evidence of vertebral column injury. Progressive mediastinal widening and enlarging pleural effusion in the absence of angiographic evidence of aortic injury suggested the diagnosis of an intrathoracic cerebrospinal fluid fistula. Myelograms identified the site of spinal cord rupture and cerebrospinal fluid leakage. The diagnosis, management, and outcome of these rare fistulae are discussed.

Brain Diseases↗
PubMed1990

Epidermal growth factor receptors on ependymomas and other brain tumors.

Epidermal growth factor receptor (EGFR) and transferrin receptor levels were determined in 14 intracranial neoplasms (four glioblastomas multiforme, four medulloblastomas, four ependymomas, one cerebellar astrocytoma, and one acoustic neurinoma) and in four samples of "normal" brain tissue. A competitive radioreceptor assay with 125I-epidermal growth factor and 125I-transferrin was performed using the primitive neuroectodermal tumor-derived TE-671 tissue-culture cell line as a standard. Epidermal growth factor receptors were present on TE-671 cells, all four ependymomas, and two of the four glioblastomas multiforme. The number of EGFR's per cell for ependymomas were estimated to range from 1000 to 6000. Transferrin receptors were detected on TE-671 cells, two of the four medulloblastomas, and one of the four glioblastomas multiforme. A cell surface binding assay, performed directly on the rat ependymal cell monolayer, was also analyzed. The identification of EGFR's on ependymomas and TR's on medulloblastomas suggests that malignant central nervous system tumors that spread by cerebrospinal fluid pathways may be treatable by intrathecal antibody-toxin conjugates. The presence of EGFR's on all of the ependymomas may reflect a role of the receptor in the malignant phenotype of this tumor.

Animals↗
PubMed1989

Central nervous system infections in heart and heart-lung transplant recipients.

Infections, a major cause of morbidity and mortality in immunosuppressed heart and heart-lung transplant recipients, frequently involve the central nervous system and can produce devastating neurologic sequelae. Between 1980 and 1987, a total of 363 heart transplant and 54 heart-lung transplant recipients at the University of Pittsburgh sustained 13 intracranial infections two to 143 weeks after transplantation. Computed tomography demonstrated well-defined Nocardia and Aspergillus abscesses in four patients. Cerebrospinal fluid was normal in all cases studied, including in those patients in whom culture confirmed meningitis. Computed tomography-guided stereotactic surgery was used to diagnose and aspirate two nocardial brain abscesses. The prognosis for patients with central nervous system infections was related to their overall condition at the time of diagnosis. Both patients with nocardial abscesses and one patient with Listeria leptomeningitis survived, but all ten other patients died because of extensive multisystem infectious complications.

Adolescent↗