Biomedical subjects
Publications and source records attributed to K J Murphy.
Vertebroplasty is the percutaneous injection of bone cement into a symptomatic fractured vertebral body under fluoroscopic guidance. It is a safe and simple outpatient procedure. We discuss patient selection, the techniques, and the results based on our experience and that of our radiology colleagues.
One of the strongest advantages of CT angiography (CTA) lies in its unique ability to display simultaneously the anatomy of the vascular system and the topographic relationships existing between the vessels and the neighboring structures. The case we report, a 76-year-old man who underwent an intraventricular shunt placement complicated by a stroke, shows how this topographic assessment also provides important diagnostic information when vascular lesions resulting from an extrinsic compression mechanism are suspected.
Within the rat medial temporal lobe, transient modulations of neural cell adhesion molecule (NCAM) polysialylation have been observed to follow spatial learning. These have been attributed to neuroplastic events associated with the processing of information destined for long term memory consolidation. To determine if similar events are associated with avoidance learning, we investigated change in polysialylated cell number in the entorhinal, perirhinal, and piriform cortex, following acquisition of a passive avoidance task in the rat. Direct quantification of polysialylated neurons in layer II of these cortical regions revealed a significant increase in polysialylated cell frequency at 12 h following passive avoidance training. Unlike spatial learning, the increased expression of polysialylated neurons persisted for up to 24-48 h following training. In the more dorsal aspect of the perirhinal/entorhinal cortex, this increase was found to be specific to learning, as it was not observed in animals rendered amnesic with scopolamine. By contrast, change in polysialylated cell frequency in the ventral aspect of the medial temporal lobe was only partially reduced by amnesic doses of scopolamine. The persisting activation of NCAM polysialylation in the more dorsal aspects of the perirhinal and entorhinal cortex is suggested to reflect the need for more extensive synaptic alterations, as compared to those required for the consolidation of spatial learning. Moreover, the neuroplastic modulations observed in the more ventral regions of the entorhinal and perirhinal cortex appear to be a unique aspect of avoidance conditioning that reflects the activation of alternative learning strategies associated with motivational and/or contextual parameters of the task.
Fatty acid utilization is initiated by fatty acid-CoA ligase, which converts free fatty acids into fatty acyl-CoA esters. We have cloned previously the human long-chain fatty acid-CoA ligase 4 (FACL4), which is a central enzyme in controlling the free arachidonic acid level in cells and thereby regulating eicosanoid production. We report here the expression of this gene in tissues, particularly in different parts of the brain. We found that FACL4 encoded a 75 kDa enzyme and that there was a modified translation product expressed in the brain. FACL4 was expressed in early stages of development with a significant amount of FACL4 mRNA detected in an E7 mouse embryo. In addition, FACL4 was highly expressed in both adult and newborn mouse brain especially in the granule cells of the dentate gyrus and the pyramidal cell layer of CA1 in hippocampus, and the granular cell layer and Purkinje cells of the cerebellum.
Forty-six patients with single focal lesions (35 frontal, 11 nonfrontal) were administered the Wisconsin Card Sorting Test (WCST) under three conditions of test administration. The three conditions varied in the amount of external support provided via specificity of instructions. The WCST, while a multifactorial test, is specifically sensitive to the effects of frontal lobe damage if deficits in language comprehension and visual-spatial search are controlled. There is also specificity of functioning within the frontal lobes: patients with inferior medial frontal lesions, unilateral or bilateral, were not impaired on the standard measures although they had increased loss of set when informed of the sorting categories. Verbal instructions may provide a probe to improve diagnosis and prognosis, assessment of the potential efficacy of treatment, and the time frame of plasticity of specific cognitive operations.
In previous studies, we observed a transient increase in dendritic spine frequency in the molecular layer of the dentate gyrus at 6h following passive avoidance training [O'Malley A., O'Connell C. and Regan C. M. (1998) Neuroscience 87, 607-613]. To determine if a similar change is associated with spatial forms of learning, we have estimated time-dependent modulations of spine number in the dentate gyrus of the adult rat following water maze training. All animals exhibited significant reductions in the latency to locate the platform over the five training sessions of the single trial (median and interquartile ranges of 60, 8 versus 8, 3 s for trials 1 and 5, respectively) and this improved performance was retained just prior to killing at the 6h post-training time. The unbiased dissector stereological procedure was used to estimate spine number in serial pairs of ultrathin coronal sections obtained at a point 3.3 mm caudal of Bregma. This analysis revealed a significant learning-associated increase in spine number at the 6h post-training time (1.32+/-0.18 spines/microm(3)) as it was not observed in paired controls exposed to the water maze for a similar swim-time (0.66+/-0.11 spines/microm(3)). The increase was transient as spine number returned to control levels at the 72 h post-training time. These spine frequency changes are proposed to reflect increased synapse turnover rate and concomitant change in connectivity pattern in the processing of information for long-term storage.
Heritable cancer risk assessment is an increasingly common method of deriving valuable information relevant to deciding on appropriate screening regimens and preventive treatments. Assessments of heritable risk typically include familial-genetic evaluation, where analyses relate family pedigree to cancer risk, and DNA testing, where analyses indicate genetic mutations associated with cancer risk (e.g., BRCA1/BRCA2 mutations) or their absence. In this paper we report on the psychological responses of women given familial-genetic evaluations for ovarian cancer risk. The baseline and 6 to 12 follow-up assessments of an initial clinic-attending cohort of 65 women are compared with the baseline and 9 to 12 follow-up assessments of a second clinic-attending cohort of 60 women. Sizeable differences were found in the prevalence of clinically significant depression in these two physician or self-referred populations, as assessed by the Center for Epidemiological Studies Depression scale and in the mean scores. Hypotheses accounting for these differences are discussed.
Quinolate acid phosphoribosyltransferase (QPRTase), a key enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis, also plays an important role in ensuring nicotinic acid is available for the synthesis of defensive pyridine alkaloids in Nicotiana species. In this study, cDNAs for QPRTase were characterized from N. rustica and N. tabacum. Deduced proteins from both cDNAs are almost identical and contain a 24 amino acid N-terminal extension, not reported in other QPRTases, that has characteristics of a mitochondrial targeting sequence. In N. tabacum and N. sylvestris, both of which contain nicotine as the major pyridine alkaloid, QPRTase transcript was detected in roots, the site of nicotine synthesis, but not in leaves. QPRTase transcript levels increased markedly in roots of both species 12-24 h after damage to aerial tissues, with a concomitant rise in transcript levels of putrescine N-methyltransferase (PMT), another key enzyme in nicotine biosynthesis. In N. glauca, however, in which anabasine represents the major pyridine alkaloid, QPRTase transcript was detected in both leaf and root tissues. Moreover, wound induction of QPRTase but not PMT was observed in leaf tissues, and not in roots, 12-24 h after wounding. Southern analysis of genomic DNA from the Nicotiana species noted above, and also several others from within the genus, suggested that QPRTase is encoded by a small gene family in all the species investigated.
OBJECTIVE AND IMPORTANCE: The frequent association of dural arteriovenous fistulae (DAVFs) and dural sinus thrombosis may render the treatment of these complex lesions difficult. We report a case of DAVF eradicated by recanalization of the chronically thrombosed transverse sinus (TS) and sigmoid sinus followed by balloon angioplasty and stent deployment at the site of the fistula. CLINICAL PRESENTATION: A 52-year-old man presented with a Type IV DAVF of the left TS with widespread white matter changes secondary to venous hypertension. Arterial feeders arose from the left internal carotid, external carotid, and vertebral arteries. The distal segment of the left TS, the left sigmoid sinus, and the proximal segment of the right TS were occluded. Reverse flow was observed in the deep venous system and in the superior sagittal sinus. INTERVENTION: Endovascular access was gained through the left internal jugular vein. Mechanical recanalization of the thrombosed left TS and sigmoid sinus was followed by balloon angioplasty and placement of six overlapping stents extending from the TS to the proximal internal jugular vein. Angiograms performed after surgery showed resaturation of antegrade venous drainage as well as complete eradication of the fistulous connections. The patient was discharged with an improving clinical CONCLUSION: Recanalization of a chronically occluded dural venous sinus through a jugular approach is feasible. In addition to eradicating cerebral venous hypertension by reestablishing antegrade venous drainage, balloon angioplasty and stent deployment at the DAVF site produced complete closure of the fistula. This may prove to be a new therapeutic strategy for management of DAVF.
The authors evaluated a mechanically detachable platinum coil system intended for neurovascular use. The introduction characteristics, ease of delivery, ease of retrieval, and detachability were studied with fluoroscopic guidance with in vitro silicone models. All the coils passed easily through the microcatheter. The detachment maneuver occurred within 20 seconds with 20 or fewer rotations of the pusher wire. One of 229 coils detached prematurely but only after deliberate and extreme manipulation. The detachment system is safe, reliable, and consistent and will be useful for interventional neuroradiologists.
BACKGROUND AND PURPOSE: Several recent studies have shown that sonographic contrast agents may affect transcranial Doppler evaluation of the arterial peak systolic velocity (PSV). Some investigators reported an increase in PSV, and others reported no change in PSV compared with baseline values. This study was conducted to determine the effect of sonographic contrast agent on PSV measured in normal middle cerebral arteries. METHODS: Continuous spectral Doppler sonography was performed on the right middle cerebral artery of 20 participants with angiographically proven normal intracranial vasculature. Videotaping was performed in each case from the initiation of the administration of contrast medium until the effect of the contrast agent on the PSV subsided. The PSV values were normalized for each participant, were pooled, and were plotted as a function of time. RESULTS: PSV increased in all participants after the administration of contrast material; the mean maximum increase was 24+/-7.4% (mean +/- standard deviation) (range, 15-36%). The mean duration of PSV increase was 320+/-97 s (range, 165-465 s). CONCLUSION: The middle cerebral artery PSV increased substantially after the administration of contrast material. This effect needs to be considered if velocity thresholds developed for disease detection without the use of contrast materials are used when contrast agents are administered.
Aneurysm models were used to study the density of packing after coil embolization. Platinum coils were introduced until the point of minimally dense packing, indicated by aneurysmal circulatory exclusion. Packing was continued up to the point of maximal density, indicated by protrusion into the parent artery. Volumetric ratios (coil volume/aneurysmal volume) were calculated for minimally and maximally dense packing. Maximally dense packing ratios were a little higher than the minimally dense ratios, but less than 37%.
We report the case of a 72-year-old man with bilateral intrathoracic carotid bifurcations associated with a Klippel-Feil anomaly. The left and right carotid bifurcations were located at levels corresponding to the second and fourth thoracic vertebrae, respectively. A possible association between low carotid bifurcation and the Klippel-Feil anomaly is suggested.
Based on experience, published data, and published series, the authors recommend the use of vertebroplasty for painful destructive vertebral lesions. In the authors' opinion, the greatest difficulty lies in denying the treatment to patients with advanced metastatic disease, where other surgical or medical treatments may have greater morbidity and mortality. The few complications reported have been related to excessive PMMA injection, underlining the need for excellent imaging conditions to control the cement injection.
The omega 3 polyunsaturated fatty acids have had a major impact on thinking in medicine in the last twenty years. The parent fatty acid in the omega 3 fatty acid family is alpha-linolenic acid (ALA) which is an essential fatty acid found in high concentrations in certain plant oils, such as flaxseed oil, walnut oil and canola oil. Several longer chain or derived omega 3 fatty acids are formed from alpha-linolenic acid and these are mainly found in fish, fish oils and from other marine organisms. The main marine omega 3 fatty acids are eicosapentaenoic acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). It is of interest that DHA is specifically localised in the retina and the brain in humans and other mammals. The longer chain omega 3 fatty acids are rapidly incorporated into cell membrane phospholipids where it is regarded they influence the metabolism/metabolic events within the cells. The mechanisms by which these changes occur include alteration in the fluidity of membranes such that there are subtle changes in receptor function, alteration in cell signalling mechanisms, membrane-bound enzymes, regulation of the synthesis of eicosanoids, and regulation of gene expression. In this chapter, we report a comparison between the composition of the oil derived from the New Zealand Green Lipped Mussel (Lyprinol') and two other oils rich in omega 3 fatty acids, namely flaxseed oil and tuna oil. The main lipid classes in Lyprinol' were sterol esters, triglycerides, free fatty acids, sterols and phospholipids while triglycerides were the main lipids in the other two oils. The main omega 3 fatty acids in Lyprinol' were EPA and DHA, while in flaxseed oil and tuna oil the main omega 3 fatty acids were ALA and DHA, respectively. The main sterols in Lyprinol' were cholesterol and desmosterol/brassicasterol, while in flaxseed oil and tuna oil the main sterols were beta-sitosterol and cholesterol, respectively. Epidemiological observations, populations' studies and basic research indicate the possibility of influencing the outcome of cardiovascular disease, inflammatory disorders and neural function by ingestion of the omega 3 polyunsaturated fatty acids.
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Modulation of neural cell adhesion molecule polysialylation (NCAM PSA) state has been proposed to underlie morphofunctional change associated with consolidation of memory in the rodent, and its age-dependent decline to be related to impaired cognitive function. To establish whether this may be a human correlate of cognitive decline, we determined the age-dependent expression of PSA in the human hippocampal dentate gyrus using postmortem tissue derived from individuals who exhibited no obvious neuropathology. As in the rodent, PSA immunoreactivity in the 5-month human infant was associated mainly with a population of granule-like cells and their mossy fibre axons. Cell numbers were maximal during the first 3 years of life but declined by an order of magnitude between the second and third decades and remained relatively constant thereafter and was restricted to the granule cell layer/hilar border. In contrast to the rodent, diffuse immunostaining was observed in the inner molecular layer; however, as development advanced, this became relocated to the outer molecular layer from 2 years of age onwards. In addition, numerous polysialylated hilar neurons became evident at 2-3 years of age and remained constant until the eighth decade of life. These findings suggest NCAM polysialylation to play a crucial developmental role within a period concluding with adolescence, and that an attenuated NCAM PSA-mediated neuroplasticity continues throughout the human lifespan. The importance of the developmental phase of NCAM PSA expression in the emergence of schizophrenia is discussed.
OBJECTIVE: We report a case of metastatic ovarian granulosa cell tumor in the mediastinum with a 2-year disease-free interval after treatment with radiotherapy and review the literature regarding the use of radiotherapy in recurrent and metastatic granulosa cell tumor. METHODS: The patient's medical records, histological slides, and radiological films were reviewed. The pertinent references were obtained using a Medline search and cross-references. RESULTS: A patient with Stage 1A granulosa cell tumor developed a recurrence in the retroperitoneum 10 years after initial surgery. She was treated with chemotherapy followed by surgical resection. She subsequently developed metastatic tumor in the mediastinum which responded completely to radiotherapy. She has remained disease free for 2 years since the completion of radiotherapy. CONCLUSION: Radiotherapy is a treatment option that should be considered in localized recurrent or metastatic granulosa cell tumor that is not amenable to surgery as it can potentially control the disease for several years.