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The effects of chymopapain on prolapsed human intervertebral disc. A clinical and correlative histochemical study 总被引:1,自引:0,他引:1
Light and electron microscopy were used to demonstrate extensive matrix degradation in a failed chymopapain-treated disc as compared with an untreated degenerative control disc. Both specimens contained viable cells with patches of degenerative cells. There was a loss of disc height in the chymopapain-treated disc, but no improvement of symptoms. These results illustrated that even in well-circumscribed cases with documented disc protrusion into the spinal canal, the disc space narrowing following injection may aggravate the symptoms of nerve root entrapment, especially if a low-grade lateral recess stenosis is associated with the disc protrusion. The persistence or aggravation of symptoms probably is related to these anatomic considerations. The low level of enzyme activity in the injected area may or may not be correlated with the clinical response to treatment. 相似文献
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The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies. 总被引:4,自引:0,他引:4
Daniel A Hamstra Kuei C Lee Joseph M Tychewicz Victor D Schepkin Bradford A Moffat Mark Chen Kenneth J Dornfeld Theodore S Lawrence Thomas L Chenevert Brian D Ross Juri T Gelovani Alnawaz Rehemtulla 《Molecular therapy》2004,10(5):916-928
To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy. 相似文献
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Bradford L. Kirkman-Liff Ruud Lapre Tracy L. Kirkman-Liff 《The International journal of health planning and management》1988,3(2):89-109
The United States and the Netherlands are the focus for this comparative analysis of the evolutionary interaction between health planning and the political system, seen in the context of change in social and economic ideologies. While health planning in the USA started in 1946, it was the comprehensive health planning program in 1966 that created the form to be followed by Health Systems Agency effort in 1974: local, voluntary planning, coordinated by state agencies, supported by federal funding. Health planning in the Netherlands has moved through four distinct periods: a hospital construction period, starting during the post-war recovery; a hospital regionalization period, from 1971 through the late 1970s; a transition period from the late 1970s to 1982, during which several planning approaches were considered; and, the current comprehensive health and social services planning period. Today, federal support for health planning in the US has been eliminated as part of the current de-regulatory, competitive health care strategy. Health planning in the US is now an institutional activity, with less focus on community needs. Advocated changes in the Dutch planning approach incorporate ideas similar to past approaches in the US; but, a failed approach in one nation may work in another, if the underlying cultural and organizational characteristics are sufficiently different. 相似文献
6.
K Emancipator N Urankar-Nagy K A Leonard G Bradford S N Emancipator 《American journal of clinical pathology》1992,97(3):376-380
The authors used antibodies specific for creatine kinase MB isoenzyme (CK-MB) and myosin light chain-1 (MLC-1) for immunohistologic staining. At appropriate dilutions of antibody, frozen sections of human heart muscle were positive for both CK-MB and MLC-1, whereas sections of human skeletal muscle were negative for both proteins. Staining for both CK-MB and MLC-1 also was demonstrated in an immature teratoma. Furthermore, staining was localized to the rhabdomyosarcomatous elements within the teratoma; other components of the tumor did not stain for CK-MB or MLC-1. Biopsies of skeletal muscle revealed that regenerative, but not intact normal or degenerating, fibers also contained CK-MB and MLC-1. Immunohistologic stains for CK-MB and MLC-1 may be useful as tumor markers and as markers for regenerative muscle fibers. 相似文献
7.
Despite advances in the neuro-imaging of the brain stem, an accurate diagnosis of intrinsic lesions in this region requires tissue sampling and histological verification. We have performed a series of computer-directed stereotactic procedures in 12 patients with intrinsic brain stem lesions. A positive diagnosis was obtained in 11 cases and therapeutic intervention was possible in four. There was no operative mortality. Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, computer-directed stereotactic biopsy should be considered in all patients harbouring an intrinsic brain stem mass. 相似文献
8.
Roger E. Kelley MD Alireza Minagar MD Bradford J. Kelley Regina Brunson RVT 《Journal of neuroimaging》2003,13(1):85-87
Meningovascular syphilis is now quite uncommon, but there have been increasing reports in patients immunocompromised with human immunodeficiency virus. The response of syphilis affecting the central nervous system to antibiotic therapy remains a challenge. This is an even greater challenge in patients who have underlying compromise of the immune system. The authors present a 46-year-old male with recurrent stroke who was found to have cerebrospinal fluid compatible with syphilitic involvement of the central nervous system and a cerebral arteriogram, which revealed focal narrowing of the right middle cerebral artery. The baseline transcranial Doppler study demonstrated increased mean and peak flow velocity within the right middle cerebral artery. Despite a 10-day course of intravenous penicillin, with substantial improvement in the cerebrospinal fluid results, this flow velocity elevation persisted, in a remarkably consistent pattern, over a 4-month follow-up period. Thus, the involved vessel remained patent following treatment, but no clear resolution of the stenotic lesion was observed. 相似文献
9.
Josh W. McDonald Victor L. Roggli William D. Bradford 《Fetal and pediatric pathology》1994,14(3):505-511
We report a unique case of coexistingexogenous lipoid pneumonia, endogenous lipoid pneumonia (EU), and pulmonary alveolar proteinosis (PAP) in a 5-year-old patient with severe neurodevelop mental disease. The patient presented with gastroesophageal reflux and presumed chronic lung disease resulting from recurrent aspiration pneumonias and succumbed to respiratory failure. The autopsy showed lipid-laden macrophages and periodic acid-SchiJf9ositive granular matm'al i n alveolar spaces and multilamellated structures within both alveolar macrophages and extracellular debris.
These findings were similar to those in previous reports of coexisting E I P and PAP in the setting of gastroesophageal refux [I] . However, the present case diJfered by the presence of scattered large osmiophilic extracellular lipid vacuob. Besides strengthening the association between EIP and PAP and their relationship to gastroesophageal refux, this case suggests that t h q may arise together with exogenous lipoid pneumonia, through related mechanisms, in the setting of neurodevelopmental disease. 相似文献
These findings were similar to those in previous reports of coexisting E I P and PAP in the setting of gastroesophageal refux [I] . However, the present case diJfered by the presence of scattered large osmiophilic extracellular lipid vacuob. Besides strengthening the association between EIP and PAP and their relationship to gastroesophageal refux, this case suggests that t h q may arise together with exogenous lipoid pneumonia, through related mechanisms, in the setting of neurodevelopmental disease. 相似文献
10.