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Biomedical subjects

J Short

Publications and source records attributed to J Short.

At least 19 recordsLinked to original sources

Reversible findings of restricted diffusion in 5-fluorouracil neurotoxicity.

A 35-year-old woman presented with neurotoxicity correlated to an i.v. regimen of 5-fluorouracil as episodes of acute confusional state and abnormalities of symmetrically restricted diffusion in the periventricular white matter and corpus callosum. On discontinuing the medication, the areas of severely restricted diffusion had entirely resolved, with minimal residual T2 signal abnormality. In this case, immediate discontinuation of the chemotherapeutic agent apparently reversed the patient's symptoms and findings on MRI. The scant information available in the published literature regarding this phenomenon is reviewed with regard to 5-fluorouracil.

Adult↗

The fragile X tremor ataxia syndrome in the differential diagnosis of multiple system atrophy: data from the EMSA Study Group.

The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS) associated with premutations in the FMR1 gene and the possibility of clinical overlap with multiple system atrophy (MSA) has raised important questions, such as whether genetic testing for FXTAS should be performed routinely in MSA and whether positive cases might affect the specificity of current MSA diagnostic criteria. We genotyped 507 patients with clinically diagnosed or pathologically proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we identified four patients carrying FMR1 premutations (0.94%). Within the subgroup of patients with probable MSA-C, three of 76 patients (3.95%) carried premutations. We identified no premutation carriers among 81 patients with pathologically proven MSA and only one carrier among 622 controls (0.16%). Our results suggest that, with proper application of current diagnostic criteria, FXTAS is very unlikely to be confused with MSA. However, slowly progressive disease or predominant tremor are useful red flags and should prompt the consideration of FXTAS. On the basis of our data, the EMSA Study Group does not recommend routine FMR1 genotyping in typical MSA patients.

Aged↗

Intracranial metastasis via transplacental (vertical) transmission of maternal small cell lung cancer to fetus: CT and MRI findings.

We present the computed tomography (CT) and magnetic resonance imaging (MRI) findings of brain metastases in an unusual case of a premature, 33-week gestational age neonate who was emergently delivered from a mother suspected of having lung cancer according to imaging performed during the third trimester of pregnancy. Owing to the presence of placental metastases noted after delivery, the fetus had initial screening with brain MRI and chest/abdomen CT as well as serial screening imaging studies during the first 5 months of life, all of which were apparently normal. However, serial examinations eventually revealed a cerebellar lesion that significantly improved after chemotherapy but recurred and enlarged within a few months. This lesion was later confirmed to be metastasis by subsequent biopsy and resection. More metastatic lesions were identified in the frontal and temporal lobes on follow-up MRI. In the setting of aggressive maternal malignancy (without known fetal primary malignancy) an intracranial mass can, on the exceedingly rare occasion, result from maternal high-grade malignancy and the neuroradiologist should be alerted to this phenomenon.

Adult↗

Comparison of three joint simulator wear debris isolation techniques: acid digestion, base digestion, and enzyme cleavage.

Quantification of ultrahigh molecular weight polyethylene (UHMWPE) wear debris remains a challenging task in orthopedic device analysis. Currently, the weight loss method is the only accepted practice for quantifying the amount of wear generated from a PE component. This technique utilizes loaded soak controls and weight differences to account for polymeric material lost through wear mechanisms. This method enables the determination of the amount of wear in the orthopedic device, but it provides no information about debris particulate size distribution. In order to shed light on wear mechanisms, information about the wear debris and its size distribution is necessary. To date, particulate isolation has been performed using the base digestion technique. The method uses a strong base, ultracentrifugation, and filtration to digest serum constituents and to isolate PE debris from sera. It should be noted that particulate isolation methods provide valuable information about particulate size distribution and may elucidate the mechanisms of wear associated with polymeric orthopedic implants; however, these techniques do not yet provide a direct measure of the amount of wear. The aim of this study is to present alternative approaches to wear particle isolation for analysis of polymer wear in total joint replacements without recourse to ultracentrifugation. Three polymer wear debris isolation techniques (the base method, an acid treatment, and an enzymatic digestion technique) are compared for effectiveness in simulator studies. A requirement of each technique is that the wear particulate must be completely devoid of serum proteins in order to effectively image and count these particles. In all methods the isolation is performed through filtration and chemical treatment. Subsequently, the isolated polymer particles are imaged using scanning electron microscopy and quantified with digital image analysis. The results from this study clearly show that isolation can be performed without the use of ultracentrifugation and that these methods provide a viable option for wear debris analysis.

Biocompatible Materials↗

Apolipoprotein E is upregulated in olfactory bulb glia following peripheral receptor lesion in mice.

Apolipoprotein E (apoE), a lipid transporting protein, has been postulated to participate in nerve regeneration. To better clarify apoE function in the olfactory system, we evaluated the amount and distribution of apoE in the olfactory bulb following olfactory nerve lesion in mice. Olfactory nerve was lesioned in 2- to 4-month-old mice by intranasal irrigation with Triton X-100. Olfactory bulbs were collected at 0, 3, 7, 21, 42, and 56 days postlesion, and both apoE concentrations and apoE distribution were determined. ApoE levels, as determined by immunoblot analysis, were twofold greater than normal during nerve degeneration at 3 days. ApoE levels remained elevated by approximately 1.5 times normal levels at 7 through 21 days after injury and returned to baseline by 56 days. Immunocytochemical studies supported these observations. ApoE immunoreactivity was prominent on the olfactory nerve at 3 days after lesion and decreased to baseline levels at later time periods. Double-labeling immunocytochemical studies confirmed that both reactive astroglia and microglia produced detectable amounts of apoE following the lesion. Return of apoE expression to baseline paralleled measures of olfactory nerve maturation as measured by olfactory marker protein. These data suggest that apoE increases concurrent with nerve degeneration. ApoE may facilitate efficient regeneration perhaps by recycling lipids from degenerating fibers for use by growing axons. The association of apoE genotype with dementing illnesses may represent a diminished ability to support a lifetime of nerve regeneration.

Animals↗

The simultaneous determination of diazepam and its three metabolites in dog plasma by high-performance liquid chromatography with mass spectroscopy detection.

A fast, sensitive and specific LC/MS/MS method for the simultaneous determination of diazepam and its three metabolites, oxazepam, temazepam and desmethyldiazepam, in dog plasma is described. The method consists of an automated 96-well solid phase extraction procedure and electrospray LC/MS/MS analysis. D(5)-Diazepam is used as the internal standard for all the compounds. Intra-day and inter-day assay coefficients of variations are less than 12.7%. The lower limit of quantitation (LLOQ) is 1 nM for each analyte, based on 0.1 ml aliquots of dog plasma. The analytical run time was 5 min. Linearity is observed over the range of 1--500 nM. This method has been used to support the discovery of pharmacokinetic studies.

Animals↗

Imaging of acute subarachnoid hemorrhage with a fluid-attenuated inversion recovery sequence in an animal model: comparison with non-contrast-enhanced CT.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) MR imaging sequences have been previously described in the evaluation of acute subarachnoid hemorrhage (SAH) in human subjects and have demonstrated good sensitivity. The purpose of this study was to evaluate a FLAIR sequence in an animal model of SAH and to compare the results with those obtained with non-contrast-enhanced CT. METHODS: SAH was experimentally induced in 18 New Zealand rabbits by injecting autologous arterial blood into the subarachnoid space of the foramen magnum. Nine animals had high-volume (1-2 mL) injections, and nine animals had low-volume (0.2-0.5 mL) injections. Four control animals were injected with 0.5 mL of saline. The animals were imaged with a FLAIR sequence and standard CT 2-5 hours after injection. Gross pathologic evaluation of seven of the animals was performed. Four blinded readers independently evaluated the CT and FLAIR images for SAH and graded the probability of SAH on a scale of 1 to 5 (1 = no hemorrhage, 5 = definite hemorrhage). RESULTS: Overall, the sensitivity of FLAIR was 89%, and the sensitivity of CT was 39% (P <.01). In animals with a high volume of SAH, the sensitivity of FLAIR was 100%, and the sensitivity of CT was 56%. In animals with a low volume of SAH, the sensitivity of FLAIR was 78%, and the sensitivity of CT was 22%. The specificity of FLAIR in animals without SAH was 100%, and the specificity of CT was 100%. The average reader score for FLAIR was 3.8, and that for CT was 2.2 (P <.001). Reader scores for FLAIR were higher than those for CT in 94% (P <.01) of animals with SAH and in 25% of animals without SAH (P >.05). Seven animals underwent gross pathologic examination, and all had blood in the subarachnoid space around the brain stem. CONCLUSION: FLAIR was more sensitive than CT in the evaluation of acute SAH in this model, especially when a high volume of SAH was present. This study provides a model for further experimentation with MR imaging in the evaluation of SAH. These findings are consistent with those of current clinical literature, which show FLAIR to be an accurate MR sequence in the diagnosis of SAH.

Acute Disease↗

Consultant appraisals. With due respect.

Consensus is needed on which management competencies should be included in doctors' appraisals. One trust employed management consultants to find out the views of senior doctors, managers, directors and patients. Common themes included concern for standards, effective use of information, openness, integrity and insight. The results will be used to guide future recruitment.

Clinical Competence↗

Apolipoprotein E immunoreactivity in human and mouse olfactory bulb.

We evaluated the distribution of apolipoprotein E (apoE) immunoreactivity in mouse and human olfactory bulbs. ApoE immunoreactivity was present in the olfactory nerve and around the glomeruli. Immunoreactivity was seen in somata that appeared to be glial. No neuronal staining was seen. The apoE immunoreactivity was also present in the mouse olfactory bulb subependymal layer. The specificity of immunoreactivity was confirmed with apoE-deficient mice (apoE gene knock-out mice, apoE KO) which did not display any immunoreactivity. The presence of apoE around glomeruli and nerve suggest that apoE is associated with the continuous degeneration and regeneration processes that occur in the olfactory nerve. Experimental manipulation of the olfactory nerve may be a useful technique to determine the functions of apoE in a well-defined neural system.

Adult↗

Comparison of the effects of aging on 5-HT7 and 5-HT1A receptors in discrete regions of the circadian timing system in hamsters.

The circadian timekeeping system exhibits many functional changes with aging, including a loss of sensitivity to time cues such as systemic injections of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In order to elucidate the neurochemical mechanisms responsible for this age-related loss of sensitivity of the circadian pacemaker to serotonin agonists, the present study used quantitative autoradiography to determine whether aging decreases serotonin receptor populations in male Syrian hamsters. Four neuroanatomical regions that regulate circadian timekeeping were studied (the suprachiasmatic nuclei [SCN], the lateral geniculate nuclei [LGN], and the median raphe nucleus [MRN] and dorsal raphe nucleus [DRN]). The specific binding of [3H]8-OH-DPAT to serotonin7 (5-HT7) and serotonin1A (5-HT1A) receptors was investigated by competitive inhibition with ritanserin and pindolol, respectively. The results showed that the SCN, IGL, MRN, and DRN of the male Syrian hamster exhibited specific binding of [3H]8-OH-DPAT to both the 5-HT7 and 5-HT1A receptors, and that the latter receptor subtype is more abundant in all of these regions. At 17-19 months of age, a 50% decrease in 5-HT7 receptors was found in the DRN but not in any other regions. No significant age-related changes in 5-HT1A receptors were observed in any regions examined. The finding that a marked decrease in 5-HT7 receptors occurs in the DRN at the age previously characterized by loss of sensitivity to 8-OH-DPAT suggests that this region and this receptor subtype play important roles in 8-OH-DPAT induction of circadian phase shifts in vivo and that they constitute an important locus of aging in the circadian timing system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Quantitation of the changes in splenic architecture during the rejection of cardiac allografts or xenografts.

BACKGROUND: The spleen plays a central role in the generation of both cellular and antibody responses during graft rejection. Although changes in lymphocyte function have been extensively analyzed in vitro, there have been limited attempts at quantitating the structural changes in the lymphoid compartments within the spleen during graft rejection. METHODS: We describe here a means of quantitating the histological changes in the spleen using immunohistochemical techniques and computerized image analysis. RESULTS: Allograft rejection at 6 days after transplant is characterized by a threefold increase in the T cell-rich areas of the periarteriolar lymphoid sheaths (PALs). The follicular areas are enlarged and germinal centers appear in 55% of the white pulp regions. Acute xenograft rejection, 4 days after transplant, is specifically accompanied by a 2.3-fold increase in the marginal zone (MZ) and an increase in the numbers of B cells in the red pulp of the spleen. The expansion of both PALs and follicular/germinal centers during xenograft rejection is comparable to that observed during allograft rejection. We also investigated the effect of two immunosuppressants, leflunomide and cyclosporine, on the spleen of rats with hamster hearts. Leflunomide, which prevents acute xenograft rejection, prevented the increase in PALs and significantly reduced the areas comprising the MZ and follicles. Cyclosporine, which does not alter the tempo of xenograft rejection and only partially inhibited xenospecific antibody production, inhibited the increase in PALs and the appearance of germinal centers, while permitting a modest increase in the area of MZ and follicles. CONCLUSIONS: These observations collectively suggest that both T cell-dependent and T cell-independent responses are stimulated by the transplanted xenograft. However, the T cell-independent responses that initiate xenograft rejection are characterized by very modest increases in the area of MZ and follicles within the white pulp of the spleen.

Animals↗

Redesigning ambulatory care business processes supporting clinical care delivery.

The first step in redesigning the health care delivery process for ambulatory care begins with the patient and the business processes that support the patient. Patient-related business processes include patient access, service documentation, billing, follow-up, collection, and payment. Access is the portal to the clinical delivery and care management process. Service documentation, charge capture, and payment and collection are supporting processes to care delivery. Realigned provider networks now demand realigned patient business services to provide their members/customers/patients with improved service delivery at less cost. Purchaser mandates for cost containment, health maintenance, and enhanced quality of care have created an environment where every aspect of the delivery system, especially ambulatory care, is being judged. Business processes supporting the outpatient are therefore being reexamined for better efficiency and customer satisfaction. Many health care systems have made major investments in their ambulatory care environment, but have pursued traditional supporting business practices--such as multiple access points, lack of integrated patient appointment scheduling and registration, and multiple patient bills. These are areas that are appropriate for redesign efforts--all with the customer's needs and convenience in mind. Similarly, setting unrealistic expectations, underestimating the effort required, and ignoring the human elements of a patient-focused business service redesign effort can sabotage the very sound reasons for executing such an endeavor. Pitfalls can be avoided if a structured methodology, coupled with a change management process, are employed. Deloitte & Touche Consulting Group has been involved in several major efforts, all with ambulatory care settings to assist with the redesign of their business practices to consider the patient as the driver, instead of the institution providing the care.

Ambulatory Care↗