Holmium laser sclerostomy.
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Biomedical subjects
Publications and source records attributed to E D Allen.
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A retrospective study was undertaken to assess the value of three-dimensional computed tomography (3-D CT) in evaluating craniofacial abnormalities. Over a 2-year period, 145 children evaluated with routine two-dimensional (2-D) CT had 3-D CT reformatted images assessing a variety of anomalies including craniosynostosis, midface clefts, trauma, and craniofacial syndromes. There were 62 females and 83 males ranging in age from 1 month to 17 years (median: 5 months). Both soft-tissue and bone algorithms were used. In all 145 cases, the 3-D CT images confirmed or provided additional information of depth perception, contours, volumes, and extent of an abnormality. This was especially important and useful in the settings of complex anomalies and preoperative planning. We concluded that 3-D CT reconstructed images in conjunction with routine 2-D CT should be an integral part of the examination in evaluating craniofacial abnormalities.
PURPOSE: To assess MR and pathologic characteristics of childhood intracranial meningiomas, comparing the radiographic findings with those observed in adult intracranial meningiomas. METHODS: Clinical records, MR and CT scans, and histology of eight children with intracranial meningiomas presenting for a period of 7.5 years were retrospectively reviewed. RESULTS: Boys equaled girls but predominated from ages 4 to 11 years. The ages ranged from 4 to 18 years. Two patients had radiation-induced meningiomas. Two children had multiple lesions; neither had neurofibromatosis. All solitary lesions were supratentorial. Other characteristics included: dural-based attachment (n = 6); large size (> 5 cm) (n = 4); cystic components (n = 3); and intraventricular location (n = 1). Histologic subtypes were: meningothelial (n = 4); transitional (n = 3); and fibroblastic (n = 1). Preoperative diagnoses of meningiomas were made in six cases based on overall imaging characteristics. CONCLUSIONS: Diagnosis of childhood intracranial meningiomas does not differ from that of adults radiographically, with the exception of larger tumor sizes.
Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.
Previous methods of in vivo gene transfer to differentiated neurons of the adult mammalian brain have been inefficient and associated with technical problems. We have therefore developed a model system of direct gene transfer using a replication-defective adenoviral vector containing a beta-galactosidase gene to transduce brain neurons. Following injection of purified high titre recombinant adenovirus into the caudate putamen of seven week old mice, lacZ activity was evident in neural components of the central nervous system (CNS) for at least 8 weeks post infection. The efficiency of adenoviral gene transfer was very high compared to other techniques, suggesting an attractive and efficient alternative for neuronal gene transfer in vivo.
We describe the use of a human bronchial xenograft model for studying the efficiency and biology of in vivo gene transfer into human bronchial epithelia with recombinant E1 deleted adenoviruses. All cell types in the surface epithelium except basal cells efficiently expressed the adenoviral transduced recombinant genes, lacZ and CFTR, for 3-5 weeks. Stable transgene expression was associated with high level expression of the early adenoviral gene, E2a, in a subset of transgene expressing cells and virtually undetectable expression of the late adenoviral genes encoding the structural proteins, hexon and fiber. These studies begin to address important issues that relate to safety and in vivo efficacy of recombinant adenoviruses for gene delivery into the human airway.
Currently, treatment for rheumatoid arthritis and other inflammatory arthropathies is often ineffective in ameliorating the progression of the disease, particularly the invasive destruction of cartilage and bone by rheumatoid synovium. Multiple aspects of this inflammatory process are mediated by the synovial lining cells (synoviocytes). Genetic modification of these cells in vivo represents a potential method for the treatment of these conditions. In this report, we describe a novel technique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection techniques. Purified high titer suspensions of a recombinant adenoviral vector containing the gene for Escherichia coli beta-galactosidase (AdCMVlacZ) were directly injected into the hind knees of New Zealand white rabbits. Synovial tissues were then examined for transgenic lacZ expression using a combination of in situ staining for beta-galactosidase activity, immunohistochemical staining, and transmission electron microscopy. High efficiency gene transfer and lacZ expression was observed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for > or = 8 wk after infection.
Data collected over the past 8 years on the radiological appearance of common pediatric primary brain neoplasms are presented. An emphasis is placed on the newer radiological imaging modality of magnetic resonance imaging (MRI). Part I of this article emphasized the clinical evaluation of these brain neoplasms. Three hundred eighty-five children with known brain neoplasms ranging in age from newborn to 18 years were evaluated with one or all of the following radiological modalities: MRI, computed tomography (CT), water-soluble myelography (WSM), WSM with CT, and angiography. Contrast-enhanced MRI and CT scans both were accurate in delineating these brain neoplasms although MRI provided better resolution and delineation than CT. Angiography provided information on the vascularity of the neoplasms and their relationship to prominent arterial and venous structures. Water-soluble myelography with CT and gadolinium-enhanced MRI of the spine were equally accurate in demonstrating metastatic spread to the spinal canal and spinal cord. Magnetic resonance imaging with gadolinium was more accurate than CT with contrast in demonstrating recurrent or residual neoplasm at the operative site and metastatic spread to the brain. Magnetic resonance imaging with gadolinium is the best radiological modality to fully evaluate pediatric brain neoplasms.
In Part I of this article, we present our data collected over the past 8 years on the clinical evaluations of pediatric brain tumors with an emphasis placed on the more common neoplasms. Our data consists of 385 children ranging in age from newborn to 18 years. The majority of children presented with signs of raised intracranial pressure (including nausea, vomiting, and headaches), seizures or other focal neurologic deficits. Five percent of our children presented to outlying hospitals with symptoms that retrospectively turned out to be due to brain neoplasms but were misdiagnosed as "gastroenteritis," "viral upper respiratory tract infection," or even viral meningitis. These delays in diagnosis can cause serious negative outcomes for these patients and can be avoided through more careful neurologic and ophthalmologic examination at the time of first presentation. Central nervous system neoplasms are not uncommon in children and any child presenting with nausea, vomiting, and headaches should raise the suspicion of a primary brain tumor and should receive both a thorough neurologic exam and screening for papilledema. If papilledema is present, these children should be referred for proper neuroradiologic evaluation (which will be addressed in Part II.
OBJECTIVE: To describe the varied characteristics seen in patients with cystic fibrosis who develop chronic abscess formation secondary to unrecognized appendicitis. DESIGN: Patient series. SETTING: Cystic Fibrosis Care Centers in Columbus, Ohio, and Tucson, Ariz. PARTICIPANTS: Five patients with cystic fibrosis who developed chronic abdominal abscesses secondary to occult appendicitis are described. Two patients developed fistula formation with purulent fluid drainage before diagnosis. One patient developed an extensive psoas abscess. Another presented with prolonged fever of unknown origin. These patients were identified by retrospective review of the past 20-year experience at two Cystic Fibrosis Care Centers. CONCLUSIONS: Development of chronic abdominal abscess related to unrecognized appendicitis is a rare but important complication in patients with cystic fibrosis. Prompt diagnosis depends on physician familiarity with the varied presentations of this entity. Diagnostic abdominal computed tomography and/or ultrasonography should particularly be considered when patients with cystic fibrosis present with pain, mass, or drainage from the right flank; prolonged fever; a limp; or failure of suspected meconium ileus equivalent syndrome to respond promptly to cathartic measures.
Because removal of monocytes from their natural milieu may alter their subsequent immune response patterns, we have compared the production of interleukin-1 beta (IL-1-beta) and tumor necrosis factor alpha (TNF-alpha) by cultured human whole blood to that by purified monocytes. IL-1-beta was released in a dose-dependent fashion by whole blood after stimulation with lipopolysaccharide. Immunofluorescence studies indicated that monocytes were the main producers of IL-1-beta in whole blood cultures. On a per monocyte basis, after stimulation with 10 micrograms/ml lipopolysaccharide, much more IL-1-beta was released by cultured whole blood (56.2 +/- 8.3 ng/10(6) monocytes) than by purified mononuclear cells maintained in tissue culture medium (7.1 +/- 2.6 ng/10(6) monocytes). However, maintaining purified mononuclear cells in autologous plasma restored IL-1-beta release to levels observed in whole blood cultures. IL-1-beta release by whole blood peaked at 9 to 12 hours, in contrast to release of TNF-alpha, which peaked at 6 hours. In parallel with protein production, IL-1-beta messenger RNA levels peaked later and were more sustained than TNF-alpha messenger RNA levels. These experiments suggest that plasma augments the stimulatory effect of endotoxin and that IL-1-beta and TNF-alpha have differing kinetics in whole blood.
A rational approach to the development of gene therapies for cystic fibrosis requires a better understanding of the cellular targets for gene transfer in the airway epithelium. We have used recombinant retroviruses to study the dynamics and lineage relationships of a regenerating rat tracheal epithelium. Primary cultures of tracheal epithelial cells were exposed to lacZ-transducing retroviruses and subsequently seeded into denuded trachea that were implanted into BALB/c (nu/nu) mice. The grafts developed a fully differentiated mucociliary epithelium containing large clones of lacZ-expressing cells with virtually all cell types represented within each clone. These data are most consistent with gene transfer into a putative progenitor cell that is capable of extensive self renewal and pleuripotent development. Vector-specific variation in transgene expression was noted in the various cell types.
During aging, protein synthesis undergoes decremental changes in many organs and tissues. In the pancreas, as well as in other exocrine glands, the rate of protein synthesis declines with age. However, it is unknown whether this decline is related to intrinsic aging changes which affect the secretory cell function. In this study, we compared the ability of pancreatic acinar cells to synthesize amylase and its messenger RNA (mRNA) in response to insulin treatment of young and old rats rendered diabetic with streptozotocin (STZ). In STZ-induced diabetic rats, amylase protein and its mRNA levels were reduced drastically in the pancreas of young and old groups. Injections of these diabetic rats with insulin increased pancreatic amylase mRNA contents significantly in both young and old rats. Insulin also increased proportions of amylase protein synthesis in the pancreas of both age groups. These results indicate that the pancreatic cells remain effective during aging in their transcriptional activity for functional amylase mRNA in response to an exogenous stimulus of insulin.
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Two cases of Graves ophthalmopathy (GO) are presented, both of which required orbital decompression. The indications for orbital decompression and techniques used are discussed and the advantages of inferior orbitotomy presented.
Previous studies have shown that amylase levels are reduced significantly in the pancreas and parotid gland of diabetic rats and that insulin reverses this effect and increases the secretory protein levels. In the pancreas, these changes in amylase protein levels are accompanied by parallel changes in amylase mRNA levels. In the present study, the effects of diabetes and subsequent insulin treatments on contents (per cell) of amylase protein and its mRNA in parotid glands were compared in rats rendered diabetic with an injection of a beta-cell toxin, streptozotocin (STZ). Both amylase protein and its mRNA contents were reduced significantly in diabetic rats, compared with control rats, and this reduction was reversed following insulin injections of diabetic rats. In insulin-injected diabetic rats, amylase protein contents increased before a detectable increase in amylase mRNA levels was seen. The mRNA contents of a non-secretory protein, actin, did not change during diabetogenesis or subsequent insulin treatments. The reductions in parotid contents of amylase and its mRNA in diabetic rats and the reversal of these changes by insulin are similar to those changes that occur in the pancreas under the same conditions. However, the magnitude of these changes in parotid glands was much smaller than in the pancreas, and the effect of insulin on amylase mRNA synthesis was not as immediate as in the latter gland.
The relationship between acute alterations of tissue Ca++ and the development of acute renal failure and lethal renal tubular cell injury in the kidney was studied. Nephrotoxicity was induced by HgCl2, and its course was modified by prior saline drinking. Both a semiquantitative scale measuring the extent of lethal tubule cell injury and a computerized assessment of numbers of nuclei in Feulgen stained sections of cortex were used for morphologic analysis. The 2 methods agreed very closely with each other, indicating the utility of an automated computerized approach as a rapid, quantitative adjunct for the assessment of lethal cell injury in the kidney. Increases of blood urea nitrogen during 12-24 hr after HgCl2 were associated with increasing extent of lethal cell injury in both saline and water drinking rats. Striking progressive increases of renal cortical Ca++ developed. In both water and saline drinking rats, the increases in tissue Ca++ were significantly associated with increasing blood urea nitrogen levels and extent of lethal cell injury as determined morphologically. However, similar degrees of increased blood urea nitrogen and extensive lethal cell injury were accompanied by substantially lower tissue Ca++ levels in saline drinking rats than in water drinking rats, indicating an independent effect of saline drinking to ameliorate the increases in tissue Ca++ occurring during lethal cell injury in this model. These data provide further insight into the relationship between structural and functional changes during HgCl2 nephrotoxicity and establish the utility of an automated computerized morphometric method for assessing the extent of lethal cell injury.
The induced dissociation of stacks of annulate lamellae in multinuclear cells of P3J, a Burkitt's lymphoma cell line, is described. The multinuclear cells form as a portion (15-25%) of the population when growth of P3J is prevented by high concentrations (100-200 micrograms/ml) of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis. All cells in the population form stacks of annulate lamellae when incubated in DFMO and when the action of DFMO is reversed by the addition of putrescine, the annulate lamellae disappear. However, unlike the typical (uninucleate) cells in the population, the multinucleate ones do not divide following the addition of putrescine. During dissociation, the annulate lamellae fragment into small segments of cisternae and vesicles of various sizes. Although some of the electron-dense pore material is dispersed in the cytoplasm, much is retained with the vesicular elements that form.