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Biomedical subjects

C S Simpson

Publications and source records attributed to C S Simpson.

30 records · Page 2Linked to original sources
PubMed1998

Correlation of waiting time with adverse events in patients admitted for nonelective permanent pacemaker implantation.

OBJECTIVE: To determine the effect of a dedicated permanent pacemaker implantation procedure room on waiting time and waiting time-related morbidity. DESIGN: Retrospective chart review. SETTING: Two tertiary care teaching hospitals in southern Ontario; one with a dedicated procedure room (centre B) and one without (centre A). PATIENTS: Two hundred and fourteen consecutive patients who required permanent pacing urgently or emergently. METHODS: Charts were examined retrospectively at centre A (131 patients) and centre B (83 patients) to determine the waiting time for and the number of preoperative adverse events in nonelective permanent pacemaker implantation. RESULTS: Patients in centre A waited a mean of 4.5 +/- 3.0 days while patients in centre B waited a mean of 1.9 +/- 1.6 days (P = 0.0001). Centre A patients experienced a total of 57 adverse events that were likely or possibly related to the waiting period, while patients at centre B experienced eight such events (P < 0.0001). Thirty-three per cent of the centre A patients experienced at least one adverse event, while 8% of centre B patients experienced at least one adverse event (P < 0.00001). Of the centre A patients who waited for more than six days (26 patients), 58% had at least one adverse event, compared with 26% of those who waited less than six days (105 patients, P = 0.0009). CONCLUSIONS: Delays in implanting nonelective permanent pacemakers are strongly associated with an increase in adverse events. Measures to shorten the waiting time are likely to result in a reduction in morbidity in conjunction with a beneficial impact on health care resource utilization.

Humans↗
PubMed1995

Stimulation of zif/268 gene expression by basic fibroblast growth factor in primary rat striatal cultures.

The presence of basic fibroblast growth factor (bFGF) in the basal ganglia, and its known neurotrophic activity, has created interest in its possible role as an agent to attenuate striatal neurodegeneration. However, little information is available on the mechanisms through which bFGF might exert a long-term influence on striatal function. Primary cultures of embryonic rat striatal neurones were used to ascertain whether bFGF can alter the pattern of striatal gene expression. Treatment of cultures with bFGF (500 pM) resulted in a dramatic increase in the levels of zif/268 mRNA within 45 min. This induction was attenuated by the tyrosine kinase inhibitor genistein (100 microM), but not by its inactive structural analogue genistin (100 microM). The induction of zif/268 mRNA was found to occur in non-neuronal cells, with no increase in mRNA levels being observed in neurones. A similar induction was noted for another putative transcription factor, jun B, although no induction of the related factor jun D could be detected. These results show that bFGF can induce immediate-early gene expression in striatal cultures, and therefore that this may provide a mechanism, mediated by non-neuronal cells, which allows bFGF to cause a long-term change in striatal neurochemistry.

Animals↗
PubMed1995

Induction of c-fos and zif/268 gene expression in rat striatal neurons, following stimulation of D1-like dopamine receptors, involves protein kinase A and protein kinase C.

Changes in the level of dopaminergic activity in the rat striatum lead to the induction of a number of immediate-early genes, including c-fos and zif/268. These immediate-early genes are thought in turn to alter the rate of transcription of downstream genes. There is evidence that the dopaminergic activation of the c-fos and zif/268 genes in the striatum in vivo is linked to stimulation of D1-like dopamine receptors. We have used primary cultures of embryonic rat striatal neurons to identify the intracellular pathways involved in this response. Dopamine (10 nM-5 microM) caused a marked increase in the levels of c-fos mRNA and zif/268 mRNA in cultured striatal neurons, an effect that was reproduced by the D1-like dopamine receptor agonist SKF38393 (10 nM-5 microM). These actions were attenuated by the D1-like antagonist SCH23390 (1 microM) but not by the D2-like antagonist eticlopride (1 microM). The D2-like agonist quinpirole did not increase zif/268 mRNA above basal levels at concentrations up to 5 microM, but caused a slight increase in the levels of c-fos mRNA. The stimulation of c-fos mRNA levels caused by 1 microM SKF38393 was reduced by 45% following pretreatment with the selective protein kinase A inhibitor KT5720, and by 87% following pretreatment with the selective protein kinase C inhibitor calphostin C. The stimulation of zif/268 mRNA levels caused by 1 microM SKF38393 was reduced by 90% following pretreatment with KT5720, but was not significantly affected by pretreatment with calphostin C. In addition, the actions of SKF38393 to stimulate the expression of both immediate-early genes were attenuated by coadministration of quinpirole. These results suggest that SKF38393 acts on striatal neurons to stimulate c-fos expression predominantly through protein kinase C, but also partially through protein kinase A. Conversely, SKF38393 induces zif/268 expression through protein kinase A. The ability of quinpirole to antagonize the actions of SKF38393 on cultured neurons is consistent with the presence of both D1-like receptors on the same neuronal population.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Basic fibroblast growth factor induces c-fos expression in primary cultures of rat striatum.

Basic fibroblast growth factor (bFGF) is present in the rat striatum in vivo, where evidence suggests it may have a long-term trophic role in supporting the survival of striatal neurones. To examine the possibility that these effects of bFGF might be mediated by induction of neuronal gene expression, we have investigated the ability of bFGF to stimulate expression of the immediate-early gene c-fos in primary cultures of embryonic rat striatum. The basal levels of c-fos mRNA were low in both neurones and glia in culture. Application of 500 pM bFGF resulted, within 45 min, in a 11-fold increase in the c-fos hybridisation signal in the non-neuronal cells. No significant induction of c-fos mRNA was detected in the striatal neurones at this time. The induction in non-neuronal cells was blocked by the tyrosine kinase inhibitor genistein (100 microM), but not by its inactive structural analogue genistin (100 microM). These results represent a novel mechanism whereby bFGF can exert prolonged effects on striatal function, and indicate that the increases in striatal c-fos gene expression induced by bFGF occur primarily in non-neuronal cells.

Animals↗
PubMed1994

Neuronal expression of protease-nexin 1 mRNA in rat brain.

Protease-nexin 1 (PN1), also known as glia-derived nexin, is a protease inhibitor secreted by cultured fibroblasts and glioma cells, with postulated roles in regeneration and the regulation of neurite outgrowth. In this study we have localised the sites of PN1 gene expression in rat brain using in situ hybridisation. As expected, cultured cortical astrocytes contained relatively high levels of PN1 mRNA. However, the mRNA localisation in rat brain suggested that the primary sites of synthesis in the CNS are neuronal. Relatively high levels of PN1 mRNA were found in the olfactory nerve layer of the olfactory bulb, in layer V of the cerebral cortex, in magnocellular neurones of the basal forebrain, and in scattered neurones of the striatum. The results show that PN1 gene expression occurs in discrete populations of neurones in the brain, and suggest that these neurones may therefore play a role in the local regulation of neurite outgrowth.

Amyloid beta-Protein Precursor↗
PubMed1994

Phenotypic characterisation of rat striatal neurones in primary culture.

The aim of this study was to determine to what extent the neuronal phenotypes present in primary cultures of rat striatal neurones correspond to those present in vivo. A large percentage of cultured striatal neurones contained relatively high levels of proenkephalin mRNA. In addition, a high level of expression was found for the prosomatostatin mRNA. Protachykinin mRNA and proneuropeptide Y mRNA were also expressed, but at a comparatively low level. No prodynorphin mRNA could be detected. Considerable numbers of neurones were also found to express NADPH-diaphorase activity, while a smaller number of neurones were positive for acetylcholinesterase. The NADPH-diaphorase and the acetylcholinesterase could be detected both in cell bodies, and in neuronal processes contacting groups of neighbouring neurones. Since nitric oxide does not require synaptic specialisations to exert its intercellular actions, this provides strong evidence that NADPH-positive neurones communicate with other cells in primary culture. These observations demonstrate that when striatal neurones are grown in primary culture, a range of neurochemical phenotypes are present which correspond closely to those present in the mature striatum in vivo. Together with the evidence for cell-cell interactions, this suggests that primary striatal cultures will provide a suitable model to study the molecular mechanisms controlling striatal function.

Animals↗
PubMed1994

Haloperidol and fluphenazine induce junB gene expression in rat striatum and nucleus accumbens.

Administration of neuroleptics such as haloperidol to rats is known to induce the expression of the immediate-early genes (IEGs) c-fos and zif/268 in striatal neurones. Another IEG, junB, is of interest because it may be involved in the suppression, rather than the enhancement, of downstream gene transcription. In this study, rat striatal tissue was assayed for IEG expression by in situ hybridisation, after the injection of haloperidol (1 mg/kg) or fluphenazine (3 mg/kg). In addition to c-fos mRNA and zif/268 mRNA, neurones in both the striatum and nucleus accumbens were found to contain high levels of junB mRNA, after treatment with either haloperidol or fluphenazine. The proportion of striatal neurones expressing junB mRNA strongly suggests that induction occurs in striatal projection neurones. A significant increase in the levels of the mRNA encoding another IEG, junD, was also detected after haloperidol treatment. The atypical neuroleptic clozapine (3 mg/kg) did not induce the expression of any of these IEGs in striatal tissue. The results show additional complexity in the pattern of IEG induction after neuroleptic administration and suggest that junB is involved in mediating some of the effects of neuroleptics on striatal gene expression.

Animals↗
PubMed1989

Medical and surgical management of early Q wave myocardial infarction. I. Effects of surgical reperfusion on survival, recurrent myocardial infarction, sudden death and functional class at 10 or more years of follow-up.

To define the outcome of patients given medical or surgical therapy for Q wave myocardial infarction, 387 patients were followed up for 10 to 13 years (mean 11.4). On study entry the groups had similar distributions for variables such as mean age, gender, previous myocardial infarction, abnormal creatine kinase activity, area of infarction, number of vessels diseased and clinical classification. The hospital mortality rate of the medical versus surgical group was 11.5% (23 of 200) versus 5.8% (11 of 187) (p = 0.07). Early reperfusion (that is, less than or equal to 6 h) resulted in a lower mortality rate than did medical therapy--2% (2 of 100) versus 11.5% (23 of 200) (p less than 0.05)--whereas the hospital mortality rate with late reperfusion was 10.3% (9 of 87). The long-term mortality rate of the medical and surgical groups was 41% (82 of 200) versus 27% (51 of 187) (p = 0.0007) with use of an adjusted Cox proportional hazards model. In the survivors, the differences between medical and surgical groups in recurrent myocardial infarction, mortality associated with reinfarction and sudden death were prospectively followed and evaluated by the life table method. Recurrent myocardial infarction was not prevented by surgical reperfusion or medical therapy (23% in both groups), however, the mortality rate in patients with recurrent infarction was higher in the medical therapy group--36.6% (15 of 41) versus 17.5% (7 of 40) (p = 0.04). The mortality difference did not depend on early or late surgical reperfusion. In the in-hospital survivors, the incidence of sudden death was 17.5% in the medical (31 of 177) versus 7.4% (13 of 176) in the surgical group (p = 0.01). This difference was much more pronounced in the early reperfusion group. Functional class was significantly lower than that for medical therapy in the early reperfusion but not the late reperfusion group. Thus, in comparable groups given medical and surgical therapy for acute myocardial infarction and followed up for greater than or equal to 10 years, surgical reperfusion appears to offer improved longevity in selected cases (when implemented early) but does not prevent recurrent myocardial infarction. The associated mortality with recurrent myocardial infarction is less as is the incidence of sudden death. Finally, lower functional class occurs most often in patients given early reperfusion.

Acute Disease↗
PubMed1986

Coronary arteriographic findings soon after non-Q-wave myocardial infarction.

Complete occlusion of the infarct-related coronary artery is a frequent finding soon after Q-wave (transmural) myocardial infarction. We performed coronary arteriography to study the frequency of total coronary occlusion and of angiographically visible collateral vessels in 341 patients within one week of non-Q-wave myocardial infarction. In this cross-sectional study, 192, 94, and 55 patients underwent coronary arteriography within 24 hours of peak symptoms, between 24 and 72 hours after peak symptoms, and between 72 hours and seven days after peak symptoms, respectively. In the three groups, total occlusion of the infarct-related vessel was found in 26 percent (49 of 192), 37 percent (35 of 94), and 42 percent (23 of 55) of the patients, respectively (P less than 0.05). The presence of visible collateral vessels increased in parallel: 27 percent (52 of 192), 34 percent (32 of 94), and 42 percent (23 of 55), respectively (P less than 0.05). The frequency of subtotal occlusion (i.e., greater than or equal to 90 percent stenosis) decreased inversely: 34 percent (65 of 192), 25.5 percent (24 of 94), and 18 percent (10 of 55), respectively (P less than 0.05). Thus, in contrast to Q-wave infarction, total coronary occlusion of the infarct-related vessel is infrequently observed in the early hours of non-Q-wave infarction, but it increases moderately in frequency over the next several days. These cross-sectional data suggest that non-Q-wave infarction may be related to a preserved but marginal blood supply, which sufficiently disrupts the relation between the supply of and the demand for myocardial oxygen to cause tissue necrosis.

Cardiac Catheterization↗
PubMed1983

Coronary arteriographic findings in acute transmural myocardial infarction.

To describe the coronary arteriographic findings during early transmural myocardial infarction and to define the prevalence of coronary thrombosis by arteriography, we performed coronary arteriography and left ventriculography within 24 hours from symptom onset of transmural myocardial infarction in 517 patients. The coronary arteriographic findings included total and nontotal coronary occlusion with and without coronary thrombosis. Coronary spasm or severe stenosis in the affected vessel were discovered in a minority of patients. The coronary arteriographic characteristics of thrombus included persistent staining of intraluminal material by the contrast material, local retention of the contrast agent in the involved coronary artery, and intracoronary filling defect occurring mostly in nontotal occlusion. Of the 517 patients, 368 were studied within 6 hours of symptom onset, 85 within 6-12 hours and 64 within 12-24 hours. There was a systematic difference between total coronary occlusion and coronary thrombosis in each group. This was determined by arteriographic findings (judged positive or negative) relative to surgical findings. Both total coronary occlusion and coronary thrombosis were more prevalent in the early treatment (within 6 hours from symptom onset) group. Total occlusion and thrombosis declined significantly in the 6-12- and 12-24-hour groups. These data suggest that thrombus is encountered by arteriography and confirmed by surgical exploration within the first 6 hours from symptom onset of transmural infarction in approximately 80% of patients. Coronary thrombosis by coronary arteriography decreases in parallel with total coronary occlusion during the first 24 hours after acute transmural infarction, suggesting that coronary spasm or thrombus formation with subsequent recanalization are important in the evolution of transmural infarction. Despite many factors involved in the pathogenesis of transmural myocardial infarction, coronary thrombosis appears to be the final common pathway converting chronic coronary disease to acute myocardial infarction in the majority of patients.

Cardiac Catheterization↗
PubMedDate not supplied

Dynamic changes in NADPH-diaphorase staining reflect activity of nitric oxide synthase: evidence for a dopaminergic regulation of striatal nitric oxide release.

In fixed tissue, neuronal NADPH-diaphorase staining results from nitric oxide synthase (NOS) activity. Neuronal NOS only synthesizes nitric oxide once activated by the binding of Ca2+/calmodulin. We show here that neuronal NADPH-diaphorase staining is also dependent on Ca2+/calmodulin, implying that only activated NOS is detected. In addition, in bovine pulmonary endothelial cells, carbachol and bradykinin dramatically and rapidly increase the intensity of NADPH-diaphorase staining. Furthermore, administration of MK801, an NMDA antagonist, decreases neuronal NADPH-diaphorase staining. This suggests that the intensity of the NADPH-diaphorase staining is related to the level of enzyme activation at the moment of tissue fixation. The potential of exploiting this observation to detect cellular activation of NOS is illustrated by the observations that the intensity of NADPH-diaphorase staining in rat striatal neurones is decreased following systemic treatment with the D1-like dopamine receptor antagonist SCH23390, and increased by the D2-like antagonist eticlopride. These results therefore provide strong evidence that the NADPH-diaphorase reaction can be used to monitor NOS activity at a cellular level of resolution, and reveal a dopaminergic regulation of NOS activity in the striatum mediated by D1-like and D2-like dopamine receptors.

Animals↗