Biomedical subjects

M J Sullivan

Publications and source records attributed to M J Sullivan.

At least 37 records · Page 2Linked to original sources

PubMed2000

Repression of CDK1 and other genes with CDE and CHR promoter elements during DNA damage-induced G(2)/M arrest in human cells.

Entry into mitosis is controlled by the cyclin-dependent kinase CDK1 and can be delayed in response to DNA damage. In some systems, such G(2)/M arrest has been shown to reflect the stabilization of inhibitory phosphorylation sites on CDK1. In human cells, full G(2) arrest appears to involve additional mechanisms. We describe here the prolonged (>6 day) downregulation of CDK1 protein and mRNA levels following DNA damage in human cells. This silencing of gene expression is observed in primary human fibroblasts and in two cell lines with functional p53 but not in HeLa cells, where p53 is inactive. Silencing is accompanied by the accumulation of cells in G(2), when CDK1 expression is normally maximal. The response is impaired by mutations in cis-acting elements (CDE and CHR) in the CDK1 promoter, indicating that silencing occurs at the transcriptional level. These elements have previously been implicated in the repression of transcription during G(1) that is normally lifted as cells progress into S and G(2). Interestingly, we find that other genes, including those for CDC25C, cyclin A2, cyclin B1, CENP-A, and topoisomerase IIalpha, that are normally expressed preferentially in G(2) and whose promoter regions include putative CDE and CHR elements are also downregulated in response to DNA damage. These data, together with those of other groups, support the existence of a p53-dependent, DNA damage-activated pathway leading to CHR- and CDE-mediated transcriptional repression of various G(2)-specific genes. This pathway may be required for sustained periods of G(2) arrest following DNA damage.

CDC2 Protein Kinase↗

PubMed2000

Role of the locus ceruleus in baroreceptor regulation of supraoptic vasopressin neurons in the rat.

The goal of this study was to identify the source of baroreceptor-related noradrenergic innervation of the diagonal band of Broca (DBB). Male Sprague-Dawley rats underwent sinoaortic denervation (SAD, n = 13) or sham SAD surgery (n = 13). We examined Fos expression produced by baroreceptor activation and dopamine-beta-hydroxylase immunofluorescence in hindbrain regions that contain noradrenergic neurons. Baroreceptors were stimulated by increasing blood pressure >40 mmHg with phenylephrine (10 microgram. kg(-1). min(-1) iv) in sham SAD and SAD rats. Controls were infused with 0.9% saline. Only the locus ceruleus (LC) demonstrated a baroreceptor-dependent increase in Fos immunoreactivity in dopamine-beta-hydroxylase-positive neurons. In a second experiment, normal rats received rhodamine-labeled microsphere injections in the DBB (n = 12) before phenylephrine or vehicle infusion. In these experiments, only the LC consistently contained Fos-positive cells after phenylephrine infusion that were retrogradely labeled from the DBB. Finally, we lesioned the LC with ibotenic acid and obtained extracellular recordings from identified vasopressin neurons in the supraoptic nucleus. LC lesions significantly reduced the number of vasopressin neurons that were inhibited by acute baroreceptor stimulation. Together, these results suggest that noradrenergic neurons in the LC participate in the baroreflex activation of the DBB and may thus be important in the baroreflex inhibition of vasopressin-releasing neurons in the supraoptic nucleus.

Animals↗

PubMed1999

Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation.

Relaxation of IGF2 imprinting occurs in Wilms tumours and many other cancers, but the mechanism of loss of imprinting (LOI) remains unknown. To investigate the role of altered DNA methylation in LOI, we examined the pattern of methylation of the human insulin-IGF2 region in Wilms tumours and the normal kidney. The analysis included regions homologous to three 'differentially methylated regions' of the mouse Igf2 gene (dmrs 0, 1 and 2). In tumours displaying normal IGF2 imprinting, and in the normal kidney, maternal allele-specific DNA methylation was identified spanning exons 2 and 3. This region is homologous to dmr 0, a site of maternal-specific differential methylation in the mouse. In Wilms tumours with relaxed imprinting or 11p15.5 LOH this region was unmethylated. No other differential methylation was identified. In particular, two sites of paternal methylation in the mouse (dmrs 1 and 2), and all three imprinted IGF2 promoters were not methylated in the kidney or in Wilms tumours. We postulate that LOI in Wilms tumours is associated with loss of maternal allele-specific methylation from a region located upstream of the imprinted IGF2 promoters. This region may contain cis acting sequences that coordinately influence imprinting.

Animals↗

PubMed1999

The effects of disclosure on pain during dental hygiene treatment: the moderating role of catastrophizing.

Catastrophizers and non-catastrophizers were asked to disclose about their dental worries prior to undergoing dental hygiene treatment. It was hypothesized that the effects of emotional disclosure would vary as a function of the level of catastrophizing; where catastrophizers would be more likely than non-catastrophizers to show reductions in pain and emotional distress. The study also examined whether emotional disclosure influenced subsequent levels of catastrophizing and dental anxiety. Eighty undergraduate students were randomly assigned to a disclosure condition or a control condition prior to undergoing a scaling and root planing procedure. In the control condition, catastrophizers reported significantly more pain and emotional distress than non-catastrophizers. In the disclosure condition, catastrophizers and non-catastrophizers did not differ significantly in their pain and emotional distress. The interaction between condition and level of catastrophizing remained significant even when controlling for emotional distress and the emotional content of the thought records. While catastrophizers benefited from disclosure in regard to their immediate physical and emotional experience, their levels of catastrophizing and dental anxiety remained essentially unchanged. Theoretical and clinical implications of the findings are discussed.

Adult↗

PubMed1999

Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.

OBJECTIVES: The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF). BACKGROUND: Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF. METHODS: The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients. Aerobic capacities, myosin heavy chain (MHC) isoforms, enzymes, and capillary density were measured. RESULTS: The patients with CHF demonstrated a reduced peak oxygen consumption when compared to controls (15.0+/-2.5 vs. 19.8+/-5.0 ml x kg(-1) x min(-1), p <0.05). Using cell-specific antibodies to directly assess vascular density, there was a reduction in capillary density in CHF measured as the number of endothelial cells/fiber (1.42+/-0.28 vs. 1.74+/-0.35, p = 0.02). In CHF, capillary density was inversely related to maximal oxygen consumption (r = 0.479, p = 0.02). The MHC IIx isoform was found to be higher in patients with CHF versus normal subjects (28.5+/-13.6 vs. 19.5+/-9.4, p <0.05). CONCLUSIONS: There was a significant reduction in microvascular density in patients with CHF compared with the control group, without major differences in other usual histologic and biochemical aerobic markers. The inverse relationship with peak oxygen consumption seen in the CHF group suggests that a reduction in microvascular density of skeletal muscle may precede other skeletal muscle alterations and play a critical role in the exercise intolerance characteristic of patients with CHF.

Biopsy↗

PubMed1999

Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD.

This study was designed to further characterize peripheral skeletal muscle alterations in patients with chronic obstructive pulmonary disease (COPD) and to evaluate the possible relationship between myosin heavy chain (MyoHC) isoform expression and exercise tolerance in these individuals. MyoHC composition from biopsy of the vastus lateralis muscle was examined in 12 COPD patients (forced expiratory volume in one second (FEV1)=31+/-9% predicted, peak oxygen consumption (V'O2)=15+/-4 mL x kg(-1) x min(-1)) and 10 age-matched normal male subjects (peak V'O2=20+/-5 mL x kg(-1) x min(-1)). The proportion of MyoHC type I was smaller in COPD than in normals (27+/-17% versus 41+/-9%, p<0.05) with an increase in MyoHC type IIa (51+/-15% versus 39+/-9%, p<0.05) and the proportion of MyoHC type IIx being comparable between both groups. A significant relationship was found between peak V'Oo2 mL x kg(-1) x min(-1) and FEV1 % pred (r=0.91, p<0.0001) and the percentage of MyoHC type I (r=0.61, p=0.016). In stepwise multiple regression, only FEV1 % pred was found to be a significant determinant of peak V'O2 (p<0.0001). This variable explained 83% of the total variance of peak V'O2. In summary, this study showed considerable modifications in the phenotypic expression of the myosin heavy chain in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. An independent effect of myosin heavy chain expression on exercise capacity was not found. These results suggest that chronic inactivity and muscle deconditioning may not be the sole factors explaining peripheral muscle dysfunction in patients with chronic obstructive pulmonary disease.

Aged↗

PubMed1999

Intraoperative evaluation of tissue perfusion in high-risk patients by invasive and noninvasive hemodynamic monitoring.

OBJECTIVE: Although invasive monitoring has not been effective in late stages after organ failure has occurred, early postoperative monitoring revealed differences in survivor and nonsurvivor patterns and provided goals for improving outcome. We searched for the earliest divergence of survivor and nonsurvivor circulatory changes as an approach to earlier preventive therapy. The aim was to describe the intraoperative time course of circulatory dysfunction in survivors and nonsurvivors among high-risk elective surgery patients using both the thermodilution pulmonary artery catheter (PAC) and multicomponent noninvasive monitoring. DESIGN: Prospective intraoperative description of circulatory dysfunction. SETTING: University-run county hospital. PATIENTS: Two hundred nine consecutively monitored high-risk elective surgery patients. MEASUREMENTS AND MAIN RESULTS: We evaluated the data of high-risk elective surgery patients using both PAC and multicomponent noninvasive monitoring. The latter consisted of the following: a) an improved bioimpedance method for estimating cardiac output; b) the standard pulse oximetry to screen for pulmonary problems; c) transcutaneous oxygen and carbon dioxide tension sensors to evaluate tissue perfusion; and d) routine noninvasive blood pressure and heart rate. The current noninvasive impedance cardiac output estimations closely approximated those of the thermodilution method; r2 = .74, p < .001; the precision and bias was -0.124 +/- 0.75 L/min/m2. Outcome measures included intraoperative description of circulatory patterns of high-risk surgical patients who survived compared with nonsurvivors. Hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen, high transcutaneous carbon dioxide tensions, low oxygen delivery, and low oxygen consumption developed intraoperatively gradually over time; the abnormalities were more pronounced in the nonsurvivors than in the survivors. CONCLUSIONS: The survivors had slightly higher mean arterial pressure, cardiac index, and mixed venous oxygen saturation, as well as significantly higher oxygen delivery, oxygen consumption, transcutaneous oxygen tension, and transcutaneous oxygen tension/FIO2 ratios, than did the nonsurvivors. The data suggest that blood flow, oxygen delivery, and tissue oxygenation of the nonsurvivors became inadequate toward the end of the operation. Noninvasive monitoring provides similar information to that of the PAC; both approaches revealed low-flow and poor tissue perfusion that were worse in the nonsurvivors. The continuous on-line real-time displays of hemodynamic trends facilitate early recognition of acute circulatory dysfunction.

Carbon Dioxide↗

PubMed1998

Catastrophizing, anxiety and pain during dental hygiene treatment.

OBJECTIVES: This study examined the relations between catastrophizing, dental anxiety, and pain during dental hygiene treatment. METHODS: Participants were 78 (32 men, 46 women) consecutive referrals to the Dalhousie University Dental Clinic. All patients were scheduled for a scaling procedure performed by senior dental hygiene students. Following treatment, patients completed the Pain Catastrophizing Scale and the Dental Anxiety Scale - Revised, and were asked to rate the degree of pain they experienced during the scaling procedure. RESULTS: Regression analyses revealed that age and the rumination subscale of the Pain Catastrophizing Scale were significant predictors of pain, even when controlling for gender, and oral hygiene status. CONCLUSIONS: The findings suggest that excessive focus on pain sensations may be one of the mechanisms by which catastrophizing leads to increased pain. The clinical challenges will be to develop cost- and time-effective means of identifying individuals who catastrophize and to implement interventions to reduce their level of distress.

Acute Disease↗

PubMed1998

Fos expression following isotonic volume expansion of the unanesthetized male rat.

Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation (P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.

Animals↗

PubMed1998

Metabolic and hemodynamic responses of lower limb during exercise in patients with COPD.

Premature lactic acidosis during exercise in patients with chronic obstructive pulmonary disease (COPD) may play a role in exercise intolerance. In this study, we evaluated whether the early exercise-induced lactic acidosis in these individuals can be explained by changes in peripheral O2 delivery (O2). Measurements of leg blood flow by thermodilution and of arterial and femoral venous blood gases, pH, and lactate were obtained during a standard incremental exercise test to capacity in eight patients with severe COPD and in eight age-matched controls. No significant difference was found between the two groups in leg blood flow at rest or during exercise at the same power outputs. Blood lactate concentrations and lactate release from the lower limb were greater in COPD patients at all submaximal exercise levels (all P < 0.05). Leg D02 at a given power output was not significantly different between the two groups, and no significant correlation was found between this parameter and blood lactate concentrations. COPD patients had lower arterial and venous pH at submaximal exercise, and there was a significant positive correlation between venous pH at 40 W and the peak O2 uptake (r = 0.91, P < 0.0001). The correlation between venous pH and peak O2 uptake suggests that early muscle acidosis may be involved in early exercise termination in COPD patients. The early lactate release from the lower limb during exercise could not be accounted for by changes in peripheral O2. The present results point to skeletal muscle dysfunction as being responsible for the early onset of lactic acidosis in COPD.

Acidosis, Lactic↗

PubMed1998

Multicenter study of noninvasive monitoring systems as alternatives to invasive monitoring of acutely ill emergency patients.

BACKGROUND: Recent reports showed lack of effectiveness of pulmonary artery catheterization in critically ill medical patients and relatively late-stage surgical patients with organ failure. Since invasive monitoring requires critical care environments, the early hemodynamic patterns may have been missed. Ideally, early noninvasive hemodynamic monitoring systems, if reliable, could be used as the "front end" of invasive monitoring to supply more complete descriptions of circulatory pathophysiology. OBJECTIVES: To evaluate the accuracy and reliability of noninvasive hemodynamic monitoring consisting of a new bioimpedance method for estimating cardiac output combined with arterial BP, pulse oximetry, and transcutaneous PO2 and PCO2; we compared this system of noninvasive monitoring with simultaneous invasive measurements to evaluate circulatory deficiencies in acutely ill patients shortly after hospital admission where invasive monitoring was not readily available. We also preliminarily explored early differences in temporal hemodynamic patterns of survivors and nonsurvivors. DESIGN AND SETTING: Prospective comparison of simultaneous invasive and noninvasive measurements of circulatory function with retrospective analysis of data in university-run county hospitals, university hospitals and affiliated teaching hospitals, and a community private hospital. PATIENTS: We studied 680 patients, including 139 severely injured or hemorrhaging patients in the emergency department (ED), 129 medical (nontrauma) patients on admission to the ED, 274 high-risk surgical patients intraoperatively, and 138 patients recently admitted to the ICU. RESULTS: A new noninvasive impedance device provided cardiac output estimations under conditions in which invasive thermodilution measurements were not usually applied. There were 2,192 simultaneous bioimpedance and thermodilution cardiac index measurements; the correlation coefficient, r = 0.85, r2 = 0.73, p < 0.001. The precision and bias was -0.124+/-0.75 L/min/m2. Both invasive and noninvasive monitoring systems provide similar information and identified episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous O2, high transcutaneous CO2, and low oxygen consumption before and during initial resuscitation. The limitations of noninvasive systems were described. CONCLUSIONS: Noninvasive monitoring systems gave continuous displays of physiologic data that provided information allowing early recognition of low flow and poor tissue perfusion that were more pronounced in the nonsurvivors. Noninvasive systems may be acceptable alternatives where invasive monitoring is not available.

Adult↗

PubMed1998

What hurts during dental hygiene treatment.

PURPOSE: The purpose of this study was to examine clients' pain reports for routine clinical procedures during dental hygiene treatment, and to examine the degree to which physical and psychological variables contribute to pain. METHODS: A convenience sample consisting of 53 (18 male, 35 female) undergraduate students enrolled at Dalhousie University participated as dental hygiene clients. Before treatment, the demographics, dental anxiety, and pain catastrophizing of students were measured. During procedures, dental status was measured. Following procedures, the amount of pain associated with procedures was recorded. Data was analyzed using an SPSS/PC statistical package. RESULTS: Most procedures were associated with little or no pain. However, probing and scaling were associated with greater pain. Furthermore, 25 percent of the sample reported their pain was > or = 7/10 on at least one dental hygiene procedure. Dental status measures and treatment difficulty did not correlate with pain. Individuals higher in dental anxiety and pain catastrophizing reported greater pain. Multiple regression showed that all predictor variables combined to account for approximately 1/3 of the variance in pain reports. CONCLUSION: On average, clinical dental hygiene treatment is associated with low levels of pain, but approximately 25 percent of subjects experienced at least one of the seven procedures as being moderately to severely painful. Findings illustrate the need for effective pain management that may be physiologically or psychologically based. Interventions geared toward reducing anxiety and pain catastrophizing may be useful additions to the curriculum of dental hygiene programs.

Adult↗

PubMed1998

Fos-like immunoreactivity in the medulla after acute and chronic angiotensin II infusion.

Acute and chronic angiotensin (Ang) II hypertension are reported to have different mechanisms that involve differential contributions of the peripheral vasculature and the nervous system. Acute Ang II hypertension is mediated primarily by Ang acting at vascular smooth muscle, whereas chronic Ang II hypertension appears to have a neural component. In our experiments, the transition from a peripheral to a neural effect occurs over 10 hr of Ang II infusion in rats. To identify the role of the central nervous system in this transition, we measured Fos immunoreactivity, an indicator of neural activity, in the nucleus of the solitary tract (NTS), caudal ventrolateral medulla (CVL) and rostral ventrolateral medulla (RVL) in normal, sinoaortic denervated (SAD) and sham SAD rats after 2- or 18-hr Ang II infusion (50 ng/kg/min intravenously). Vehicle (5% dextrose) was infused in normal rats as control. Comparable increases in arterial pressure were produced by 2- and 18-hr Ang II infusion in all groups. Fos was increased in the NTS in sham SAD rats by 2- and 18-hr Ang II infusion (P < .05 vs. vehicle control). In the CVL, only 2-hr Ang II infusion was associated with increased Fos in normal and sham SAD rats (P < .05 vs. vehicle control) but not in SAD rats. In the RVL, 18-hr Ang II infusion elevated Fos in all groups (P < .05 vs. vehicle control). Activation of NTS during Ang II infusion is baroreceptor mediated and independent of infusion duration. Acute Ang II infusion produced a baroreceptor-mediated activation of the CVL, a region associated with baroreflex sympathoinhibition. Chronic Ang II infusion produced a baroreceptor-independent activation of the RVL, a brain area associated with sympathoexcitation, suggesting a centrally mediated increase in sympathetic outflow that may be associated with chronically infused Ang II.

Angiotensin II↗

PubMed1997

Role of right ventricular and pulmonary functional abnormalities in limiting exercise capacity in adults with congenital heart disease.

This study evaluates right ventricular (RV) and pulmonary function during exercise in adults with congenital heart disease (CHD). Thirty-one patients with CHD involving the right side of the heart underwent symptom-limited bicycle exercise testing with simultaneous expired gas analysis and measurement of RV ejection fraction (EF). Twenty-one age-matched normal controls underwent the identical exercise protocol. Maximal oxygen consumption was lower in the CHD than in normal controls (19.5 +/- 6.4 vs 30.5 +/- 0.8 ml/kg/min, p = 0.0001 patients vs controls). Both heart rate (156 +/- 25 vs 171 +/- 13 beats/min, p = 0.01) and oxygen pulse (9.3 +/- 3.7 vs 12.3 +/- 3.7 ml/beat, p = 0.01), an indirect measure of stroke volume, were found to be lower in the CHD group at peak exercise. Pulmonary dysfunction was evidenced in the CHD group by decreased forced expiratory volume, forced vital capacity and maximum voluntary ventilation, and by a higher ventilation/expired carbon dioxide ratio at peak exercise (37.2 +/- 6.9 vs 33.0 +/- 5.4, p = 0.02), suggesting an increase in dead space ventilation. Maximal oxygen consumption was lower in patients whose RVEF decreased with exercise (17.6 +/- 5.4 vs 22.8 +/- 6.4 ml/kg/min, p = 0.03 "decrease RVEF" group vs "increase RVEF" group). Maximal oxygen consumption correlated with the change in RVEF only in the group whose RVEF decreased with exercise (r = 0.5, p = 0.03). In the group that had increased RVEF with exercise, maximal oxygen consumption correlated with forced expiratory volume (r = 0.7, p = 0.02). Thus, adults with CHD have a reduced functional capacity compared with normal controls. This phenomenon appears to be associated with both RV and pulmonary abnormalities.

Adult↗

PubMed1997

Promoting wellness in cardiac rehabilitation: exploring the role of altruism.

Coronary artery disease continues to be the primary cause of mortality in the United States. Recent studies have significantly advanced the ability to improve outcomes in this disorder by demonstrating that intensive risk factor modification programs with diet, lipid-lowering drugs, exercise, and psychosocial interventions can reverse atherosclerosis and reduce events by 40% to 60%. Of all the interventional arms, psychosocial interventions have been the least studied despite research demonstrating that depression and social isolation are potent risk factors for events in patients with coronary artery disease. The few studies that have examined psychosocial interventions in patients with coronary artery disease have demonstrated a reduction in mortality and recurrent events, suggesting that this treatment strategy may be beneficial. Use of volunteer, patient-driven support groups may provide a cost-effective way to improve social support and enhance altruism in patients with coronary artery disease. Although the psychophysiology of altruism is not well defined, it is possible that altruistic activities might have positive health benefits in patients with coronary artery disease. Studies are needed to explore the roles of low-cost, patient-driven support programs in improving psychosocial functioning and outcomes in patients with coronary artery disease.

Altruism↗

PubMed1997

Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure.

To explore further alterations in skeletal muscle in chronic heart failure (CHF), we examined myosin heavy chain (MHC) isoforms from biopsies of the vastus lateralis in nine male patients with class II-III (CHF) (left ventricular ejection fraction (LVEF) 26 +/- 11%, peak oxygen consumption (peak VO2) 12.6 +/- 2 mL.kg-1.min-1) and nine age-matched sedentary normal males (NL). The relative content of MHC isoforms I, IIa, and IIx was determined by gel electrophoresis as follows: The normal sedentary group (NL) had a higher percent of MHC type I when compared with the patients (NL 48.4 +/- 7% vs CHF patients 24 +/- 21.6%, P < 0.05, no difference between MCH IIa (NL 45.1 +/- 10.5% vs CHF 56.0 +/- 12.5%), and CHF patients had a higher relative content of MHC type IIx than did the normal group (NL 6.5 +/- 9.6% vs CHF 20.0 +/- 12.9%, P < 0.05. Three of nine patients had no detectable MHC type I. In patients relative expression of MHC type I (%) was related to peak VO2 (r = 0.70, P < 0.05). Our results indicate that major alterations in MHC isoform expression are present in skeletal muscle in CHF. These alterations parallel previously reported changes in fiber typing that may affect contractile function i skeletal muscle and possibly exercise performance. The absence of MHC type I in some CHF patients suggests that skeletal muscle changes in this disorder are not solely a result of deconditioning, buy may reflect a specific skeletal muscle myopathy in this disorder.

Adult↗

PubMed1997

Usefulness of ictal and interictal 99mTc ethyl cysteinate dimer single photon emission computed tomography in patients with refractory partial epilepsy.

PURPOSE: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in approximately 90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for approximately 6 h. facilitating the performance of ictal studies. METHODS: In a prospective, open-label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of 99mTc-ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal 99mTc-ECD SPECT. RESULTS: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases. CONCLUSIONS: 99mTc-ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc-ECD are similar to those reported with 99mTc-HMPAO. Because 99mTc-ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.

Adult↗

PubMed1997

Non-voltage-gated Ca2+ influx through mechanosensitive ion channels in aortic baroreceptor neurons.

The mechanisms underlying mechanotransduction in baroreceptor neurons (BRNs) are undefined. In this study, we specifically identified aortic baroreceptor neurons in primary neuronal cell cultures from nodose ganglia of rats. Aortic baroreceptor neurons were identified by labeling their soma with the fluorescent dye 1,1'-dioleyl-3,3,3',3'-tetramethylin-docarbocyanine (DiI) applied to the aortic arch. Using Ca2+ imaging with fura 2, we examined these BRNs for evidence of Ca2+ influx and determined its mechanosensitivity and voltage dependence. Mechanical stimuli were produced by ejecting buffer from a micropipette onto the cell surface with a pneumatic picopump, producing a shift in the center of mass of the cell that was related to intensity of stimulation. Ninety-three percent of DiI-labeled neurons responded to mechanical stimulation with an increase in [Ca2+]i. The magnitude of the increases in [Ca2+]i was directly related to the intensity of the stimulus and required the presence of external Ca2+. The trivalent cations Gd3+ or La3+ in equimolar concentrations (20 mumol/L) eliminated the K(+)-induced rises in [Ca2+]i, demonstrating that both trivalent cations are equally effective at blocking voltage-gated Ca2+ channels in these baroreceptor neurons. In contrast, the mechanically induced increases in [Ca2+]i were blocked by Gd3+ (20 mumol/L) only and not by La3+ (20 mumol/L). Stretch-activated channels (SACs) have been shown in other preparations to be blocked by Gd3+ specifically. Our data demonstrate that (1) BRNs, specifically identified as projecting to the aortic arch, have ion channels that are sensitive to mechanical stimuli; (2) mechanically induced Ca2+ influx in these cells is mediated by a Gd(3+)-sensitive ion channel and not by voltage-gated Ca2+ channels; (3) the magnitude of the Ca2+ influx is dependent on the intensity of the stimulus and the degree and duration of deformation; and (4) repeated stimuli of the same intensity result in comparable increases in [Ca2+]i. We conclude that mechanical stimulation increases Ca2+ influx into aortic BRNs independent of voltage-gated Ca2+ channels. The results suggest that Gd(3+)-sensitive SACs are the mechanoelectrical transducers in baroreceptors.

Animals↗