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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

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

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

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

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

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

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

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

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

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

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

Neuropathology of pediatric liver transplantation.

We reviewed the clinical histories and autopsy records of 35 pediatric patients (ranging in age from 9 months to 18 years) who underwent orthotopic liver transplantation using ciclosporin and corticosteroids for immunosuppression. At the time of death, 19 children (54%) had encephalopathy, 16 (46%) were lethargic or in coma, 10 (29%) had seizures, and 10 were normal. Neuropathological lesions were found on postmortem examination in all 35 patients. Vascular lesions such as infarction, ischemia, thrombosis, and hemorrhage were the most common neuropathological findings (86%) followed by infectious processes (29%). Candida albicans (2 patients) and Aspergillus fumigatus (3 patients) were the only offending organisms identified, both causing meningoencephalitis. Alzheimer type II astrocytes, a characteristic feature of chronic liver disease, were the single most common autopsy finding (69%). Central pontine myelinolysis was seen in 3 children and basilar artery thrombosis affected 1 child. Neurological complications and their subsequent neuropathology are a significant cause of morbidity and mortality after pediatric liver transplantation. Vascular insults, electrolyte abnormalities, and infections that involve the central nervous system are directly related to liver function and the immunosuppression necessary to maintain graft viability. Only with continued observation after surgery combined with rapid medical and surgical treatment can we hope to improve the prognosis following liver transplantation in the pediatric population.

Adolescent

Recanalization of spinal arteriovenous malformations following embolization.

Recently, therapeutic embolization has been advocated as the treatment of choice for arteriovenous malformations (AVM's) of the spine. However, no study has established lasting benefit from this procedure or determined the incidence of recanalization, as occurs with cerebral AVM's. In this study, six patients were followed periodically after complete obliteration of their AVM's by particulate embolization was shown by immediate arteriography. The study group included three men (aged 59 to 72 years) with spinal dural arteriovenous (AV) fistulas and three women (aged 27 to 38 years) with intramedullary glomus-type spinal cord AVM's. The patients were treated by embolization with 100- to 1000-microns diameter polyvinyl alcohol particles. Clinical improvement, most commonly manifesting as increased lower-extremity strength, occurred in all patients after embolization. However, recurrent symptoms, including weakness, numbness, and urinary incontinence, occurred within 2 and 8 months in two of the three patients with dural AV fistulas and within 2 months in two of the three patients with glomus AVM's, prompting radiological reevaluation. Spinal arteriography revealed recanalization of the AV fistulas and spinal AVM's in five patients. Magnetic resonance (MR) imaging demonstrated a signal-void area caused by intramedullary AVM's. This area disappeared after embolic occlusion, but recurred after delayed recanalization, indicating restored flow through the AVM. Embolization provides only temporary treatment for many spinal AVM's. After embolic occlusion, delayed reassessment with arteriography and/or MR imaging is indicated, particularly if the symptoms persist or recur. Surgical excision of spinal AVM's provides the only therapeutic means to eliminate flow through the AVM permanently in most patients, and should be considered the treatment of choice when feasible.

Aged

Diagnosis of tethered cords by magnetic resonance imaging.

Thirty children presented with signs and/or symptoms of tethered spinal cord, 13 in association with spina bifida occulta and 17 after myelomeningocele repair. Preoperative magnetic resonance imaging (MRI) of 27 children showed tethering (27), intradural fat (17), distal syrinxes (8), and thickened filum terminale (2). There was an excellent correlation between MRI and the surgical findings. Postoperative MRI was obtained within 1 year after operation in 14 children; spinal cord ascent was seen on only four studies and retethering was suspected on five studies. We consider MRI the procedure of choice to diagnose a tethered cord because this technique accurately defines anatomical relationships without risk to the patient. In addition, we conclude that cord ascent is seen less often than expected and that retethering may occur, especially to cadaveric dura mater.

Adolescent

Touch preparations in the rapid intraoperative diagnosis of central nervous system lesions. A comparison with frozen sections and paraffin-embedded sections.

Cytologic preparations provide a rapid, simple method for intraoperative diagnosis of central nervous system (CNS) lesions. Details of cellular morphology are defined sharply, avoiding artifacts often introduced by the frozen section technique. In 100 neurosurgical biopsies performed between 1984 and 1986, touch preparations and cryostat (frozen) sections were made at the time of surgery for preliminary intraoperative diagnosis. To assess the accuracy of each of the diagnostic methods used independently, slides obtained with each of the two techniques were later reviewed retrospectively with appropriate clinical and radiological data, but without knowledge of the final neuropathological diagnoses. When compared with the final diagnoses, intraoperative diagnoses were confirmed in 95 cases. The diagnoses based on cytologic and frozen section techniques were compared with the final diagnoses based on paraffin sections. Touch preparation diagnosis was confirmed by paraffin sections in 76 cases; in 18 additional cases a clinically useful, but nonspecific diagnosis (benign versus malignant, glial versus nonglial) was established by touch preparation. In five cases with firm or rubbery tumors, insufficient cells were imprinted for reliable evaluation, and no definitive diagnoses could be made. Specific cryostat diagnoses were confirmed by paraffin sections in 88 cases; nonspecific diagnoses were made in 11 cases. A single incorrect diagnosis was obtained with each technique. When the two techniques were used together, a specific and accurate diagnosis was achieved in 95 cases. Touch preparations were superior to frozen sections for evaluating soft or highly cellular tumors and for preliminary diagnosis from a minute surgical specimen (i.e., stereotactic biopsy).(ABSTRACT TRUNCATED AT 250 WORDS)

Central Nervous System Diseases

Nocardial brain abscess: diagnostic and therapeutic use of stereotactic aspiration.

Three cases of nocardial brain abscess are presented. All three patients were receiving immunosuppressive therapy at the time of diagnosis. Two patients had cardiac transplantation and the third had periarteritis nodosa. The patients presented with generalized seizures or focal weakness. Accurate localization of the intracerebral mass lesion was obtained from computed tomography (CT) scans, but CT-guided stereotactic aspiration was required for diagnosis and treatment in every case. After Nocardia asteroides was seen on Gram's stain and subsequently identified by culture, appropriate antibiotic therapy was initiated. Both heart transplant patients survived in good neurological condition. We believe that stereotactic aspiration followed by prolonged antibiotic therapy may significantly improve the outcome of patients with nocardial brain abscess.

Adult