Search PubMed⌕ Search

Biomedical subjects

K J Murphy

Publications and source records attributed to K J Murphy.

At least 55 records · Page 3Linked to original sources

A longitudinal study of psychological adjustment to familial genetic risk assessment for ovarian cancer.

OBJECTIVES: To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6-12 months later. METHODS: Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc. RESULTS: Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up. CONCLUSION: To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up (R = 0.33, P<0.02, R(2) = 11%).

Adaptation, Psychological↗

Sequential training in separate paradigms impairs second task consolidation and learning-associated modulations of hippocampal NCAM polysialylation.

As transient and time-dependent modulations of neural cell adhesion molecule polysialylation (NCAM PSA) are associated with morphofunctional change and required for the consolidation of spatial and nonspatial forms of learning, we determined the demands imposed on this system by sequential training in the Morris water maze followed by the passive avoidance paradigm. Animals trained in this manner had recall of the water maze but not the passive avoidance response as judged by their escape and avoidance latencies, respectively. Activation of NCAM PSA on dentate neurons at the 12-h post-training time suggested information processing; however, this was significantly less than that predicted for coincident acquisition of both tasks. When sequential training was separated by an interparadigm period of 2 h, an enduring NCAM PSA activation was observed which was indistinguishable from the sum of the expected activations for each individual task. These observations suggest that the NCAM PSA response may become saturated when alternate tasks are presented without an intervening period.

Analysis of Variance↗

Low-level lead exposure in the early postnatal period results in persisting neuroplastic deficits associated with memory consolidation.

Prospective studies in humans and experimental investigations in animals have correlated elevated perinatal blood lead levels with enduring behavioural and cognitive perturbations. Although deficits in neuroplastic events necessary for long-term memory consolidation have been observed during the postnatal period, there is little evidence that these persist into adulthood in the absence of continued lead exposure. To address this issue, we exposed Wistar rat pups to 400 mg of PbCI2/L via their dams' drinking water from postnatal day 1 to 30. At postnatal day 80, the animals were trained in a one-trial, step-through, light-dark passive avoidance paradigm. Prior postnatal lead exposure resulted in a significant decline in recall latency on posttraining day 5, an effect that was specific to the learned response as no obvious behavioural alterations were apparent in open-field studies. As recall was unaffected in the immediate 48-h posttraining period, this suggested an enduring impairment in events associated with long-term memory storage. To investigate this further, we determined the influence of prior lead exposure on the transient modulations of hippocampal neural cell adhesion molecule polysialylation state that occur in the 10-12-h posttraining period, a neuroplastic event associated with memory consolidation. Direct quantification of polysialylated dentate neurons revealed prior lead exposure to have no effect on basal number but to significantly delay and blunt the transient increase observed in control animals at the 12-h posttraining time. These findings confirm that lead exposure in the postnatal period results in enduring neuroplastic deficits most likely associated with reordering of connections in pathways subservient to memory consolidation.

Animals↗

In vitro models of intracranial arteriovenous fistulas for the evaluation of new endovascular treatment materials.

BACKGROUND AND PURPOSE: The purpose of this study was to create and test an in vitro model of intracranial arteriovenous fistulas (AVFs) that simulates the geometry of human vasculature and allows realistic testing of devices used in endovascular therapy. METHODS: The models were derived from corrosion casts of the main cervicocranial arteries and veins obtained from two nonfixed human specimens. Wax copies of the casts were produced and combined to create complex models simulating various types of intracranial AVFs. Wax assemblies were embedded with liquid silicone solidified into transparent blocks containing, after wax evacuation, hollow reproductions of the original vascular trees. The models were connected to a pulsatile pump and their compatibility with various imaging techniques and endovascular treatment materials was evaluated. RESULTS: The models were compatible with digital subtraction angiography, CT, MR imaging, and transcranial Doppler sonography. They provided a realistic endovascular environment for the simulation of interventional neuroradiologic procedures. CONCLUSION: Anatomically accurate and reproducible in vitro models of intracranial AVFs provide a valuable method for evaluating new endovascular treatment materials and for teaching purposes.

Aged↗

Kv1.1 channel antisense attenuates learning and modulation of dentate polysialylated NCAM.

The distribution and modulation of neural cell adhesion molecule polysialylation state (NCAM PSA) and the consequence of antisense inactivation of the Kv1.1 potassium channel was investigated following avoidance learning in mice. PSA immunoreactivity was most notable on cells at the inner denate border and in cortical layer II. Task acquisition resulted in a significant 30% transient increase in the frequency of dentate polysialylated neurons at the 12 h post-training time. In contrast, animals pretreated with the Kv1.1 antisense oligonucleotide exhibited both attenuated recall avoidance latencies and polysialylated cell frequency. As Kv1.1 is enriched on the dendrites of these granule-like cells, the attenuated polysialylation response is considered secondary to NCAM-mediated events during their transient synapse production in the 6-8 h post-training period.

Animals↗

The acute outcome of tibioperoneal vessel angioplasty in 417 cases with claudication and critical limb ischemia.

A non-randomized, consecutive series of 417 first procedure tibioperoneal vessel angioplasty (TPVA) cases were analyzed to determine if angioplasty were an alternative revascularization technique for critical limb ischemia (CLI) and claudicants patients. TPVA was performed on 312 patients (70% male; age 66 +/- 10 years) with success attained in 406/417 cases (96%) of 605/657 lesions (92%): [461/469 stenoses (98%) and 144/188 occlusions (77%) *(P < 0.05)]. Claudication and CLI patients had similar rates of success. In claudication patients clinical success was 130/133 (98%); lesion success was 197/208 (92%); stenosis was 148/151 (98%); and occlusion was 49/57 (86%). In CLI patients clinical success was 270/284 (95%); lesion success was 408/449 (91%); stenosis was 313/318 (98%); and occlusion was 95/131 (73%). We conclude that TPVA is an effective revascularization technique for obstructed tibioperoneal vessels, with excellent success in stenotic (98%) and reasonable results in occluded vessels (77%). These data demonstrate TPVA effectiveness in CLI patients and in carefully selected claudicants with appropriate indications (severe, lifestyle limiting claudication) and readily amenable anatomy, and TPVA for CLI patients appears to be an effective revascularization technique.

Acute Disease↗

Nefiracetam prevents propofol-induced anterograde and retrograde amnesia in the rodent without compromising quality of anesthesia.

BACKGROUND: Propofol is a short-acting intravenous anesthetic agent. However, cognitive function remains depressed for several hours thereafter. We have evaluated the ability of nefiracetam, a novel cognition-enhancing agent, to alleviate propofol-induced amnesia in a rodent model of learning. METHODS: Rats were trained in a one-trial, step-through, light-dark passive avoidance paradigm. Propofol (10 and 75 mg/kg) was administered by the intraperitoneal route at 15 min before training and separately at increasing times in the immediate 0-6 h post-training period (100 and 150 mg/kg). Nefiracetam, 9 mg/kg, was administered by the intraperitoneal route 1 h before training. Animals were tested for recall at the 12 h post-training time, and after their killing, immunocytochemistry was used to determine the increase in hippocampal neuronal polysialylation, an event associated with memory consolidation. Induction and duration of anesthesia induced by propofol was determined using tail pinch and pedal withdrawal reflexes. RESULTS: Propofol-induced anterograde amnesia occurred in a dose-dependent manner. Induction of retrograde amnesia required a higher dose of propofol, which anesthetized the animals and was effective only in the immediate 3-h post-training period. In the absence of any evident effect on the onset or duration of anesthesia, nefiracetam prevented both forms of propofol-induced amnesia and preserved the learning-associated changes of neuronal polysialylation state. CONCLUSIONS: The ability of nefiracetam to prevent propofol-induced anterograde and retrograde amnesia is proposed to be indirect and to result from modulation of gene transcription in a manner that initiates a cascade of events involving protein synthesis leading to synaptic growth associated with the formation of the long-term memory trace.

Amnesia↗

Spinal cord infection: myelitis and abscess formation.

PURPOSE: Our purpose was to describe the MR findings and evolution of spinal cord abscess and to define those MR features that allow differentiation of cord infection from other intramedullary abnormalities. METHODS: We retrospectively reviewed the MR studies of all patients in whom intramedullary spinal cord abscess was proved either by blood or cerebrospinal fluid culture or by serologic examination at our institution between January 1988 and January 1996. The study group included four adults and two children, 7 to 74 years old (mean age, 38 years). RESULTS: Initial MR studies showed intramedullary high signal on T2-weighted sequences with poorly defined marginal enhancement on T1-weighted images. On follow-up contrast-enhanced T1-weighted studies, the lesions had well-defined enhancing margins with central low signal intensity. After the initiation of therapy, T2 signal abnormalities decreased markedly and contrast-enhanced studies showed ring enhancement. These T1 findings resolved with treatment over serial studies in four patients. The organisms identified were Streptococcus milleria, S pyogenes, atypical mycobacteria, Mycobacterium tuberculosis, and Schistosoma mansoni (both children). CONCLUSION: A characteristic sequence of imaging findings aids in the differentiation of cord infection from other intramedullary lesions.

Abscess↗

Psychological impact of screening for familial ovarian cancer: reactions to initial assessment.

OBJECTIVES: To assess the psychological impact on women attending a familial ovarian cancer screening clinic. STUDY METHODS: 157 women referred for screening completed an investigator designed questionnaire, the Spielberger State Trait Anxiety Scale and the Centre for Epidemiological Studies Depression Scale prior to the screening interview and an eight-item questionnaire post-assessment. RESULTS: 95.4% saw the screening as valuable. Thirty-one point four percent of all patients scored about the cutoff point for depression. Sixteen percent exhibited high levels of anxiety. Fifty-six point four percent of patients accurately perceived their risk. Twenty-one point five percent of those who accurately perceived themselves as being at high risk had high anxiety and 40.6% reported significant depressive symptoms. Of the 26.5% of patients who overestimated their risks, 40.0% reported significant depressive symptoms and 22.6% were anxious. Of the 17.1% who minimized their risk, none were anxious (0.0%), and only 15.8% were depressed. CONCLUSION: Attendees at a familial ovarian cancer screening clinic may have high levels of depression and anxiety.

Adult↗

Influence of nefiracetam on NGF-induced neuritogenesis and neural cell adhesion molecule polysialic acid expression: in vivo and in vitro comparisons.

Previously, the ability of co-administered nefiracetam to reverse scopolamine-induced learning deficits has been attributed to the preservation of a transient increase in neural cell adhesion molecule (NCAM) polysialylation state during a late phase of memory consolidation (Doyle et al., J. Neurosci. Res., 31 (1992) 513-523). Using the PC-12 pheochromocytoma cell model, we now demonstrate nefiracetam pre-exposure to significantly enhance nerve growth factor-induced neuritogenesis and NCAM polysialylation, but not prevalence, in a dose-dependent manner with maximal effects being observed at the lowest dose (0.1 microM) examined. As the memory-associated increase in NCAM polysialylation in vivo is associated with a defined group of neurons at the dentate hilar/granule cell layer border (Regan and Fox, Neurochem. Res., 20 (1995) 521-526), the effect of chronic nefiracetam exposure in vivo was evaluated. Once-daily, intraperitoneal administration of either 3 or 9 mg/kg nefiracetam to adult male Wistar rats for 40 days significantly increased the number of hippocampal dentate polysialylated neurons only at the highest dose evaluated, suggesting it to prevent their age-dependent decline. These results are consistent with nefiracetam facilitating early induction events of long-term memory consolidation processes involving NCAM polysialylation state.

Aging↗

Adult claustrophobia, anxiety and sedation in MRI.

The purpose of this study was to identify the proportion of adult patients at our institution who require sedation to tolerate MR imaging. We also wished to identify whether the type of study and patient age or sex was associated with a variation in the use of sedation. A total of 939 patients, 18 years of age or older, underwent MR imaging at a large university hospital during a randomly selected 7-week period. Age, sex, type of study, number of prior MRI's, and use of sedation were identified in this group. Patients requiring sedation were compared by these criteria to all non-sedated members over 18 years of age in the cohort who acted as a control. Of the 939 patients 134 (14.3%) required oral sedation, i.v. sedation, or general anesthesia to tolerate MRI. This group was 35.8% male, 64.1% female (control group 48.1% male, 51.9% female). Of those requiring sedation, 89 patients (66.4%) were having brain MRI (male n = 29 or 32.6%, female n = 60 or 67.4%). In the control group 461 patients (57.3%) were having brain MRI (male n = 209 or 45.3%, female n = 252 or 54.6%). The mean age of the sedated group was 60.75 (range 19-91). The non-sedated group had a mean age of 67.3 (range 28-93). The sedated group had undergone a mean of 1.56 prior MR studies (range 0-16); the control group had a mean of 0.9 prior studies (range 0-7). Sedation was more commonly utilized in women than men, in patients having brain MRI, and in patients who had undergone prior MRI procedures. The identification of a population having the greatest need for sedation may aid in the development and selection of methods of stress reduction which will result in greater patient comfort, reduction in motion artifact, and fewer prematurely terminated studies.

Abdomen↗

Power Doppler: it's a good thing.

Power Doppler is a new method of ultrasound flow imaging the utility of which is currently under investigation. This technique creates a flow map based on the integrated power of the Doppler spectrum, rather than mean Doppler frequency. Power Doppler imaging is inherently more sensitive in terms of flow detection than standard color Doppler imaging; therefore, power Doppler can display flow for situations in which color Doppler is ineffective and can even display tissue perfusion in highly vascular organs such as the kidneys. Furthermore, power Doppler is not effected by aliasing, nor is it effected by blooming in the same way as color Doppler, which has deleterious effects on color Doppler flow images. The control of blooming with power Doppler may be of great importance in the clinical application of echo-enhancing agents. This review article discusses in detail the technological advantages and disadvantages of power Doppler flow imaging. In addition, it provides a synopsis of the preliminary research studies that have been conducted to date with respect to the clinical applications of power Doppler.

Animals↗

Use of intravenous contrast material in transcranial sonography.

RATIONALE AND OBJECTIVES: The appearance of the intracranial vasculature was compared on power and color Doppler ultrasound (US) scans obtained with and without a microbubble contrast agent. MATERIALS AND METHODS: Nine patients (three men, six women) aged 42-70 years (mean age, 53 years) participated in the study. Seven patients underwent both color Doppler US and power Doppler US before and after intravenous administration of contrast agent, and two underwent only color Doppler US. All patients had previously undergone cerebral angiography. RESULTS: Before contrast material was administered, power Doppler US was more sensitive than color Doppler US in the detection of intracranial vessels (P < .05); neither technique depicted the entire circle of Willis in eight of nine patients. Postcontrast power Doppler US depicted more vascular segments than postcontrast color Doppler US (P < .01) or precontrast power Doppler US (P < .01). Use of intravenous contrast material enabled the entire circle of Willis to be evaluated from a single temporal bone acoustic window with both power Doppler US and color Doppler US in all patients. Contrast-enhanced power Doppler US depicted vessels not shown by enhanced color Doppler US. CONCLUSION: Contrast-enhanced power Doppler US depicted more vessels, better demonstrated specific vascular segments, and provided better vascular definition of the intracranial vasculature than contrast-enhanced color Doppler US or unenhanced power Doppler US.

Adult↗

Spatial learning activates neural cell adhesion molecule polysialylation in a corticohippocampal pathway within the medial temporal lobe.

Transient and time-dependent modulations of neural cell adhesion molecule (NCAM) polysialylation in the dentate gyrus of the rodent hippocampus are a feature of spatial and nonspatial forms of learning. In the hippocampal formation, polysialic acid immunoreactivity was localized to granule-like cells and their mossy fibre axons. We now demonstrate the latter to extend to the CA3 region where apparent recurrent and Schaffer collaterals were labelled. The axons of the CA1 pyramidal cell layer were immunopositive, as was the subiculum that they innervate. Layers I and III of the entorhinal cortex stained intensely for polysialic acid; however, these were not visible in the more lateral aspect of this region and were replaced by a single band of immunopositive neurons that extended to include the perirhinal and piriform cortices. After Morris water maze training, the number of polysialylated neurons within the entorhinal cortex exhibited a two- to threefold increase at the 10-12-h posttraining time with respect to that observed immediately after training. This increase was task specific, as no change was observed in freely swimming animals or those required to locate a visible platform. These results suggest the presence of a corticohippocampal pathway involved in the eventual consolidation of memory.

Age Factors↗

Renal transplant evaluation with power Doppler sonography.

This study was performed to determine if the marked variation we had previously noted in the power Doppler sonographic appearance of renal transplants correlated with disease, 22 renal transplants were scanned with power Doppler at 5 MHz, with biopsies being taken within 1 h in 17 kidneys and within 48 h in four other kidneys. Biopsy was not performed in one kidney with distal ureteral obstruction. Biopsy results were complex with many coexistent abnormalities; classification was based upon the predominant abnormality. Cortical vascularity was subjectively evaluated as normal, decreased or markedly decreased, and graded as 0, 1 or 2, respectively, and was compared with biopsy results, serum creatinine levels and resistive index. Cortical vascularity gradings were: 0 (12 cases); 1 (7 cases); and 2 (3 cases). The large number of disease categories (cellular rejection, 11 cases; vascular rejection, 5 cases; IgA nephropathy, 1 case; cyclosporin toxicity, 3 cases; obstruction, 1 case; and lupus nephropathy, 1 case) in relation to the number of vascular grades and number of kidneys precluded statistical analysis of cortical vascularity for rejection. However, vascularity did not appear to correlate with rejection, the three severest cases of vascular rejection having normal (grade 0) vascularity. There was no statistically significant correlation of vascular grade with creatinine levels or resistive index. In conclusion, subjective analysis of the power Doppler sonographic appearance of renal transplants does not appear to aid in their evaluation.

Adolescent↗