Evolving traumatic cerebellar hematoma.
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Brain Hemorrhage, Traumatic↗
Biomedical subjects
N W Thomas
Publications and source records attributed to N W Thomas.
Cauda equina sarcoidosis. Brief report of a special case.
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Aged↗
The strange association of pneumosinus dilatans and arachnoid cyst: case report and review of the literature.
BACKGROUND: The authors present the case of a 71-year-old man with dramatic pneumosinus dilatans adjacent to a large, symptomatic, fronto-temporal arachnoid cyst. METHOD: The literature on pneumosinus dilatans and its association with arachnoid cyst is reviewed. FINDINGS: Pneumosinus dilatans may be either idiopathic, a reaction to an adjacent meningioma, or an 'ex-vacuo' response to cerebral volume loss and intracranial hypotension. It is also found with large arachnoid cysts and is probably under-recognised in this context. The co-existence of an expansile intradural lesion with changes in the skull base that tend to reduce the intracranial volume is puzzling, and has not yet been fully explained. Differences in the relative timing of paranasal sinus and arachnoid cyst growth, and the 'temporal agenesis' theory of arachnoid cyst formation have been proposed but do not account for all the features of this unusual association. INTERPRETATION: Pneumosinus dilatans is a useful and under-recognised indicator of the presence and chronicity of a variety of intracranial pathologies. Its association with arachnoid cyst is paradoxical, and a new explanation is offered as to how this may arise.
Aged↗
Spinal meningioma after treatment for Hodgkin disease. Case report.
Long-term survivors of Hodgkin disease may develop second primary tumors caused by the mutagenic effects of radio- and chemotherapy. The authors describe the case of a 35-year-old woman who presented with an unusual meningioma of the cervical spine 9 years after undergoing combined-modality treatment for Hodgkin disease. To the authors' knowledge, this is the first report of spinal meningioma as a complication of such therapy. Whereas radiation-induced intracranial meningiomas are well described in the literature, treatment-induced meningiomas of the spine have not been widely recognized.
Adult↗
Depression of glutathione content, elevation of CYP2E1-dependent activation, and the principal determinant of the fasting-mediated enhancement of 1,3-dichloro-2-propanol hepatotoxicity in the rat.
The influence of fasting (18 hours) on the hepatotoxicity of 1,3-dichloro-2-propanol (1,3-DCP) and on various hepatic parameters has been assessed in the rat. Fasting produced an enhancement of the hepatotoxicity which was associated with alterations in a variety of hepatic parameters when measured relative to protein content, most notably glutathione (GSH) levels (decrease) and CYP2E1-mediated enzyme activity (increase), two parameters previously identified as being important determinants to the toxicity. Fasting also decreased the liver weight normalized to body weight. When this was taken into account, total liver CYP2E1-mediated enzyme activity was not significantly altered whereas the total liver GSH level was markedly reduced following fasting. These results imply that the reduction in hepatic GSH is the principal determinant of the enhanced susceptibility to 1,3-DCP hepatotoxicity following fasting.
Animals↗
Up-regulation of microsphere transport across the follicle-associated epithelium of Peyer's patch by exposure to Streptococcus pneumoniae R36a.
Transport of antigens through the follicle-associated epithelium (FAE) of Peyer's patch (PP) is the critical first step in the induction of mucosal immune responses. We have previously described that short-term exposure to Streptococcus pneumoniae R36a induced dramatic morphological alterations of the FAE in rabbit PP. These results prompted us to investigate whether the pneumococci-induced modifications were accompanied by enhanced ability of the FAE to transport antigens. We addressed this problem by evaluating the ability of the FAE to bind, internalize, and transport fluorescent polystyrene microparticles, highly specific to rabbit M cells, after exposure to S. pneumoniae. Quantitative study revealed a marked increase in the number of microspheres in PP tissues exposed to S. pneumoniae compared to tissues exposed to either phosphate-buffered saline or Escherichia coli DH5alpha as controls. No sign of bacterially induced damage to the epithelial barrier was observed. Further confocal microscopy analysis of the FAE surface showed that a significant increase in the number of cells that showed both morphological and functional features of M cells took place within pneumococci-treated PP tissues. These data provide the first direct evidence that the FAE-specific antigen sampling function may be manipulated to improve antigen and drug delivery to the intestinal immune system.
Animals↗
Quantitative outcome and radiographic comparisons between laminectomy and laminotomy in the treatment of acquired lumbar stenosis.
OBJECTIVE: The objective of this study was to conduct a comparative quantitative analysis of outcomes, radiographic findings, and magnetic resonance imaging results after laminectomy or laminotomy was performed for patients with lumbar stenosis. Such as analysis had not previously been conducted. METHODS: Twenty-six patients with no exclusion criteria who were treated surgically for acquired stenosis at the Division of Neurological Surgery at The Ohio State University from 1990 to 1993 were studied retrospectively. At follow-up examinations, each patient completed a detailed questionnaire that included visual analog scales, functional assessments, and the medical outcome study short form health survey, SF-36. Each patient underwent plain static and dynamic radiography that detailed vertebral body sagittal listhesis and rotation and magnetic resonance imaging that evaluated dural sac compression. RESULTS: The mean follow-up duration was 36.7 months. Good outcome was defined by the presence of three criteria: no greater than mild leg pain (Grades 0-4), the ability to walk more than one block without developing lower extremity pain, and the ability to walk without assistance devices. Fifty-eight percent of the patients who had undergone laminectomies and 50% of the patients who had undergone laminotomies had good outcomes. All were judged to have had adequate decompression. The average maximum postoperative listhesis was 17.3 +/- 9.9% in the laminectomy group and 17.6 +/- 12.5% in the laminotomy group. In contrast to some previous studies, pre- or postoperative listhesis was not statistically related to outcome in either group. Patients in each poor outcome category seemed to have worse comorbid medical conditions than did patients in the good outcome category. The SF-36 measurements of poor functioning because of health factors and bodily pain correlated somewhat with poor outcomes in the patients who had undergone laminectomies. In patients who had undergone laminotomies, the only statistically significant finding among the outcome groups was the effect of poor emotional health on activity for the patients with poor outcomes. CONCLUSION: This study indicates that laminotomy can adequately decompress lumbar canal stenosis, that laminectomy and laminotomy have the same degree of postoperative listhesis, and that the quantitative outcome of any treatment for lumbar stenosis is dependent not only on surgical factors but also on comorbid physical and psychological factors.
Adult↗
Low-dose diethyldithiocarbamate attenuates the hepatotoxicity of 1,3-dichloro-2-propanol and selectively inhibits CYP2E1 activity in the rat.
The effect of low doses of diethyldithiocarbamate (DEDC) on hepatic cytochrome P450-dependent enzyme activity and 1,3-dichloro-2-propanol (DCP) hepatotoxicity in the rat have been investigated. DEDC at a dose of 5 mg/kg selectively inhibited enzyme markers for CYP2E1 activity, and provided substantial protection against DCP hepatotoxicity. At a higher dose (25 mg/kg), DEDC also inhibited an enzyme marker for CYP1A2 activity and provided complete protection against DCP hepatotoxicity. It is concluded: (a) that DEDC at a dose of 5 mg/kg is a selective CYP2E1 inhibitor in the rat in vivo; and (b) that DCP hepatotoxicity is mediated principally by CYP2E1, with a possible contribution from CYP1A2.
Animals↗
Further studies on the lobar heterogeneity in response to coumarin-mediated hepatotoxicity.
A randomized sampling protocol coupled with quantitative morphometry has been used to evaluate the inter-lobe variation in centrilobular hepatic necrosis in the mouse, and periportal hepatic necrosis in the beta-naphthoflavone-induced rat, both in response to treatment with coumarin. The results of these studies indicate a random inter-lobe variation in xenobiotic-mediated hepatotoxicity.
Animals↗
Meningiomas of the cerebellopontine angle. A report of 41 cases.
A retrospective study of the surgical management of 41 cerebellopontine angle (CPA) meningiomas was performed. All patients were treated by a single surgeon (TTK) over a 25 year period (1967-1992). There were 13 males, 28 females with a median age of 53.5 years. The median follow-up after surgery was 9 years (range 2-20.4 years). Tumours were classified anatomically into six groups (lateral, midpetrosal, petroclival, internal auditory meatal, Meckel's cave and inferior). Only the petroclival tumours posed difficulties with complete resection (achieved in 7 out of 16) and for most of them a transtentorial transpetrous approach was used. In other groups, complete resection was achieved in all patients. There were four recurrences (two mid-petrosal, one petroclival, one internal auditory meatal), three of which had complete macroscopic resection at the initial operation.
Adult↗
Particle uptake and translocation across epithelial membranes.
Oral delivery of drugs and vaccines has many advantages over other routes of administration. For example, for vaccination, enteric delivery may result in the induction of a mucosal immune response against pathogens which colonise and invade the mucosa. However, the oral delivery of peptide or protein drugs or antigens is beset with problems, such as gastrointestinal breakdown of labile molecules, low level of macromolecular absorption and, for vaccines, the poor immune response usually elicited by orally administered soluble antigens. Investigations are therefore in progress to develop means of increasing intestinal absorption and decreasing digestion of orally administered molecules. Molecules can be incorporated into biodegradable microparticles to reduce the effect of gut secretions and to enable the absorption of bioactive agents in an unaltered form. The uptake of microparticulates through the gut wall is accepted as a true biological phenomenon but the mechanism and route of uptake have not been established. Furthermore, in general, only small numbers of microparticles are translocated across epithelial membranes, possibly making these systems inappropriate for drug or vaccine delivery. This paper reviews particle uptake across the gastrointestinal tract and describes studies carried out to determine whether a humoral response can be elicited following oral administration of an antigen associated with biodegradable poly(DL lactide-coglycolide) microparticles. The use of lipid delivery vehicles to enhance microparticle uptake and the selective transport of microspheres across M cells is also described.
Administration, Oral↗
Lobar variation of carbon tetrachloride hepatotoxicity in the rat.
The lobar variation in carbon tetrachloride-induced liver damage in the rat has been assessed by use of a systematic random sampling protocol and quantitative morphometry. A random inter-animal lobar variation in severity of damage was apparent, in contrast with the results obtained previously in which sampling bias, small animal numbers, and lack of fully quantitative measurement were apparent. The route of administration (oral vs. i.p.) did not influence these findings.
Administration, Oral↗
Selective transport of microparticles across Peyer's patch follicle-associated M cells from mice and rats.
M cells are specialized structures in the Peyer's patch follicle-associated epithelium capable of taking up bacteria, viruses and other pathogens for later presentation to the gut-associated lymphoid tissue. The present work studies how coating microspheres with different proteins affects their ability to be taken up by M cells under near physiological conditions in vivo. The later appearance of microspheres in intestinal lymph has also been measured by flow cytometry. The protein preparations used in these experiments included bovine serum albumin (bSA), human immunoglobulin G (hIgG), secretory immunoglobulin A (hIgA), bovine growth hormone (bGH) and bGH complexed with an IgG antibody raised against bGH (bGH-Ab). Selectivity in binding of these microspheres to M cells, determined by confocal microscopy, was bGH < bSA < hIgG (mice) and bGH < bGH-Ab (rats and mice). A similar selectivity was seen for microsphere entry into M cells (bGH < bSA < hIgG; bGH < bGH-Ab). The appearance of protein-coated microspheres in rat mesenteric lymph showed a similar selectivity to that found for binding and entry into M cells (bGH < bGH-Ab). This latter selectivity was also found for hIgA-coated microspheres (bSA < hIgA). Preservation of transport selectivity throughout transcytosis highlights the unique importance of the M cell surface as being the primary site determining which type of antigen can be presented subsequently to the gut immune system. The possibility that this is a transient or phasic property of the M cell surface and that this could have physiological relevance is also discussed.
Animals↗
Aspects of the design and delivery of microparticles for vaccine applications.
Mortality and morbidity data continue to indicate there is a compelling need for the derivation of a new generation of vaccine delivery systems that can be usefully applied via injection and also mucosally. One technology that has potential for design as an effective vaccine delivery system is the formulation of biodegradable microparticles from the polymers and poly lactide co-glycolide (PLGA) in particular. The potential advantages of the delivery of vaccines within such microparticles is discussed. The potential for eliciting and optimising immunity after the mucosal delivery of biodegradable microparticles is also discussed.
Administration, Inhalation↗
Timing of postoperative intracranial hematoma development and implications for the best use of neurosurgical intensive care.
This study records the incidence and timing of postoperative hematomas in neurosurgical patients and analyzes the best use of neurosurgical intensive care. In 2305 patients undergoing freehand or stereotactic biopsy, elective or emergency craniotomy, or posterior fossa surgery, 50 (2.2%) developed a hematoma. Clinical deterioration as a result of postoperative hematoma occurred within 6 hours of surgery in 44 patients and more than 24 hours after surgery in six patients. Although patients undergoing posterior fossa surgery or emergency craniotomy warrant longer periods of intensive-care observation, patients having elective supratentorial operations can safely be transferred to a neurosurgical ward for observation, provided they have regained their preoperative neurological status by 6 hours postsurgery.
Cerebral Hemorrhage↗
Comparison of in vivo and in vitro rat hepatic toxicity of coumarin and methyl analogues, and application of quantitative morphometry to toxicity in vivo.
The rat hepatic toxicity of coumarin and methyl analogues (3-,4-methyl coumarin and 3,4-dimethylcoumarin) has been determined in vivo and in vitro (freshly-isolated cells). Coumarin at a dose of approximately 1 mmol/kg produced clear histological evidence of centrilobular necrosis, while the methyl analogues at an equivalent dose were much less toxic. By use of a systematic random sampling protocol and quantitative morphometry it was determined that there was a lobar variation in the extent of hepatic damage but that this exhibited random inter-animal variation. The order of cytotoxicity in vitro was identical to that observed in vivo. In hepatocytes depleted of glutathione the toxicity of all four compounds was increased. This was particularly marked for the 3-methyl analogues, such that the order of toxicity was different to that observed in vivo and in hepatocytes not depleted of glutathione.
Animals↗
Nasal absorption in the rat. III. Effect of lysophospholipids on insulin absorption and nasal histology.
The intranasal absorption enhancing and histological effects of a range of lysophospholipids has been investigated in the rat. Blood glucose levels fell rapidly following the administration of insulin (8 IU/kg) in combination with lysophosphatidylcholines (LPC; 0.625% w/v) which had ten or more carbon groups in their fatty acid chain. The effect of the LPC-caproyl (C6) was comparable to that of an unenhanced insulin formulation; the enhancing effect of LPC-decanoyl (C10) was similar to that of an LPC-palmitoyl/stearoyl (C16/C18) for similar concentrations. The effect of LPC-decanoyl was reduced with concentration but was still significant at 0.2% w/v (5mM). Lysophosphatidylglycerol (LPG) had a marked insulin absorption enhancing effect even at 0.0625% w/v. The histological effects of LPC-caproyl were similar to those of an unenhanced insulin formulation, while co-administration of LPC-decanoyl resulted in evidence of epithelial interaction. LPG (0.5% w/v) resulted in similar histological changes as LPC (0.625% w/v) (1), but at 0.0625% w/v no significant changes in epithelial integrity were observed. The length of the fatty acid residue of lysophospholipids was identified as an important factor for intranasal absorption enhancing activity. The nature of the polar head group may also have an influence. Increased insulin absorption was not necessarily accompanied by severe disruption of the nasal epithelium. Careful selection of lysophospholipid type and concentration may enable therapeutic drug levels to be achieved via the nasal route without prohibitive toxic effects.
Absorption↗
Species differences in the hepatotoxicity of coumarin: a comparison of rat and Mongolian gerbil.
The acute hepatic effects of coumarin (2H-1-benzopyran-2-one) in male Wistar rats and Mongolian gerbils has been compared. A single dose of coumarin (125 mg/kg, intraperitoneally (i.p.)) was hepatotoxic to rats within 24 h as assessed by its effects on a variety of hepatic parameters. Coumarin-induced hepatotoxicity was associated with significant increases in relative liver weight, plasma alanine and aspartate aminotransferase activities and hepatic non-protein sulphydryl groups. Cytochrome P-450 content and 7-ethoxycoumarin O-deethylase and glucose 6-phosphatase activities were significantly lower in coumarin-treated compared with control rats. Centrilobular necrosis was only observed in two out of six rats at this dose, but was present in all four coumarin-treated rats when the dose was increased to 150 mg/kg. In contrast to the effects observed in the rat, no evidence was found for coumarin-induced hepatotoxicity in gerbils following a single i.p. dose of 125 mg/kg. These data indicate that the gerbil is less sensitive to the hepatotoxic effects of coumarin than the rat.
Animals↗