Search PubMed⌕ Search

Biomedical subjects

D Russell

Publications and source records attributed to D Russell.

At least 73 records · Page 4Linked to original sources

Enhanced tyrosine phosphorylation of striatal NMDA receptor subunits: effect of dopaminergic denervation and L-DOPA administration.

Sensitization of striatal N-methyl-D-aspartate receptors (NMDAR) has been linked to events leading to the motor response changes associated with the administration of dopaminomimetics to parkinsonian animals and patients. To determine whether tyrosine phosphorylation of NMDAR subunits contributes to the apparent long-term enhancement in synaptic efficacy of these receptors, we examined the effect of unilateral nigrostriatal dopamine system ablation with 6-hydroxydopamine followed by twice-daily treatment with l-DOPA on the phosphorylation state of rat striatal NR2A and NR2B subunits. Three weeks of intermittent l-DOPA administration produced a shortening in the duration of the rotational response to dopaminergic challenge and other changes mimicking those occurring in patients with Parkinson's disease. Concurrently, tyrosine phosphorylation of NR2A and especially of NR2B subunits increased ipsilateral to the lesion (20+/-5% and 46+/-7% of intact striatum, respectively; p<0.01) without attendant changes in subunit protein levels. Selective blockade of NR2B subunits with ACEA 10-1244, but not of NR2A subunits with MDL 100,453, reversed the l-DOPA-induced response alterations. The intrastriatal injection of a tyrosine kinase inhibitor, genistein, at a dose (2.0 microg) that normalized the response shortening, attenuated the NR2A and NR2B phosphorylation increase by about 12% and 24%, respectively (p<0.01). Taken together, these results suggest that augmented tyrosine phosphorylation of NR2B subunits, alone or in combination with the smaller rise in NR2A subunit phosphorylation, contributes to the apparent enhancement in striatal NMDAR sensitivity and thus to the plastic alterations in dopaminergic responses in l-DOPA-treated parkinsonian rats.

Animals↗

Influence of guidewire and catheter type on the frequency of cerebral microembolic signals during left heart catheterization.

Cerebral embolization is a serious complication during diagnostic heart catheterization. To date there have been no studies to determine whether the technique and the catheter type influence the frequency of cerebral microembolic signals (MES's) during left ventricular catheterization. Twenty-two patients had a leading straight tip guidewire protruding 5 to 10 cm outside the coronary catheters when the latter was advanced over the aortic arch (group A), whereas in 21 patients the guidewire was withdrawn in the descending part of the aorta (group B). Transcranial Doppler of the left middle cerebral artery was performed to monitor the number of cerebral MES's. When a protruding guidewire was used to advance the coronary catheters over the aortic arch, MES's were detected in 86% of the patients compared with 29% when the catheters were advanced without a guidewire (relative risk = 4.6, p = 0.00001). The number of MES's per patient also was significantly higher when a guidewire was used (median 9 vs 0) (p = 0.000004). In group A, a higher number of MES's was detected when a right Judkins catheter was advanced over the aortic arch than when a left Judkins catheter was advanced (median 6.5 vs 1) (p = 0.0005) and in patients who previously had a myocardial infarction than in those who had not (median 1 1 vs 4) (p = 0.007). This study strongly suggests that the risk of embolization is greater when straight tip guidewires are used to advance catheters over the aortic arch during left ventricular heart catheterization, especially in patients with a history of myocardial infarction.

Adult↗

[Cerebral microembolism detected by transcranial Doppler ultrasonography].

The clinical diagnosis of brain embolism has traditionally been based on evidence suggesting a potential embolic source. However, it is now possible to detect circulating cerebral microemboli by means of transcranial Doppler ultrasound. We explain the theory behind microembolus detection, and discuss initial clinical experience of this method. During invasive cardiovascular investigations and surgery this method can warn the physician that microemboli are entering the cerebral circulation, and preventive measures can be taken. Cerebral microemboli are quite often detected in stroke prone patients, and their presence probably indicates increased risk of stroke. In the acute phase of ischemic stroke, microembolus detection may help to decide the etiology and the source of the emboli. When microemboli are detected in cases of acute embolic stroke, serial detections can be performed which, in future studies, might be of help when evaluating the effect of the treatment.

Humans↗

Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.

BACKGROUND: There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. METHODS: The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up. RESULTS: No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035). CONCLUSIONS: Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.

Administration, Oral↗

Isolation and characterization of 26- and 30-kDa rat liver proteins immunoreactive to anti-sterol carrier protein-2 antibodies.

Although the existing literature suggests that the sterol carrier protein-2 (SCP-2) gene has only two initiation sites encoding for a 58- and a 15-kDa protein, respectively, this does not explain the profusion of other putative SCP-2-related proteins detectable on Western blotting. Two of these additional anti-SCP-2 immunoreactive proteins, 13.2 and 46 kDa, appear due to proteolytic processing of the two gene transcripts. However, the origin of additional immunoreactive rat liver proteins near 26 and 30 kDa is unclear. The latter proteins were consistently detected on Western blotting by three independent types of polyclonal antisera: anti-13.2-kDa SCP-2, anti-synthetic peptide from the amino-terminus of the 13.2-kDa SCP-2, and Protein A affinity-purified anti-synthetic peptide to the amino-terminus of 13.2-kDa SCP-2. To resolve whether the 26- and 30-kDa proteins are SCP-2 gene products, each protein was isolated from rat liver and purified to homogeneity as indicated by Tricine-SDS polyacrylamide gel electrophoresis, isoelectric focusing, and/or mass spectroscopy. Their masses, determined by MALDI-TOF mass spectroscopy, were 25.7 and 29.8 kDa, respectively. However, the mass spectral data were not consistent with either protein being an SCP-2 gene product. Peptide mass mapping of the 25.7-kDa protein revealed identity to the rat 25,784.79-Da glutathione-S-transferase. Furthermore, neither the mass nor the amino acid composition of the 29.8-kDa protein correlated with any SCP-2 gene product or dimerized SCP-2 gene product. A database search of the amino acid composition identified the protein as rat carbonic anhydrase. In summary, although the 26- and 29.8-kDa proteins may share some common epitopes with the 13.2-kDa SCP-2, they were not SCP-2 gene products.

Amino Acid Sequence↗

Extracellular levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid measured by microdialysis in the corpus striatum of conscious AS/AGU mutant rats.

The AS/AGU rat is a mutant derived from the Albino Swiss (AS) strain. It is characterized by an ungainly, staggering gait, hind limb rigidity, whole body tremor and, in older animals, difficulty in initiating movement. As and AS/AGU males aged three, six and nine months (n=6 per group) were used to estimate the levels of dopamine and its metabolites in the extracellular fluid of the caudate-putamen. The results indicate a profound loss of dopamine in the extracellular fluid at all age points examined, together with an increase in the concentration of the metabolite 3,4-dihydroxyphenylacetic acid. It is suggested that these changes reflect a defect of dopaminergic neuron function which may underlie the motor disorder seen in these animals.

3,4-Dihydroxyphenylacetic Acid↗

Role of echocardiography in systemic arterial embolism. A review with recommendations.

The ability of echocardiography to diagnose sources of embolism and the role of the examination in the prediction of thromboembolism are reviewed. In addition, the yield of transthoracic (TTE) and transoesophageal echocardiography (TEE) is analysed in patients with suspected embolism and guidelines are proposed for performing echocardiography in this setting. In general, echocardiography is reliable for diagnosing sources of embolism and this applies in particular to TEE in the case of atrial, valvular, and aortic abnormalities. However, the method is useful for predicting embolism in a few cases only. There is a substantial risk in the event of mobile or protruding thrombi, but screening for these and other markers of thromboembolism seems to be unproductive in most groups of risk patients. Yet, in the presence of atrial fibrillation, echocardiography may be helpful in defining patients with an otherwise normal heart and low risk of embolism--and in defining the relatively rare patient with a clinically low-risk profile but moderate-to-severe left ventricular systolic dysfunction and a high risk of embolism. TEE-guided conversion of atrial fibrillation without weeks of preceding anticoagulation may prove useful, after further investigation. The risk of embolism in relation to the size and mobility of valvular vegetations has remained controversial. In patients with suspected recent embolism, TTE results in less than 5% new therapeutic consequences. In those with a normal TTE, the yield of TEE seems to be equally low. We therefore recommend a selective strategy: TTE and TEE can be omitted when a cardiac source of embolism appears from the clinical setting and in most patients with an obvious predisposition to cerebrovascular disease. However, in the latter cases TTE should be performed if indicated by the clinical situation, e.g. in the presence of fever and murmur. TTE is also recommended when there are no obvious markers of primary vascular disease. To preclude very rare sources of embolism (e.g. atrial thrombi despite sinus rhythm), supplementary TEE is recommended in younger patients in whom primary vascular disease is very unlikely. The diagnosis by TEE of common conditions such as atrial septal aneurysms and patent foramen ovale cannot, however, be taken as proof of the mechanism of a systemic arterial occlusive event; thus it is difficult to change therapy on the basis of such diagnoses.

Algorithms↗

Air-filled ultrasound contrast agents do not damage the cerebral microvasculature or brain tissue in rats.

RATIONALE AND OBJECTIVES: Air microemboli may damage the cerebral microvasculature. The aim of this study was to evaluate the safety of ultrasound contrast agents composed of air microspheres with regard to cerebral damage when administered into the arterial system (ie, when not filtered by the capillary system of the lungs). METHODS: Three experimental methods were used in 75 rats after injection of either Albunex, Echovist, or Levovist into the left heart ventricle. The alkaline phosphatase (ALP) method to demonstrate small segmental brain capillary and arteriolar dilatations (SCADs), intravenous injections of Evans blue and fluorescence microscopy to detect increased vascular permeability (blood-brain barrier damage), and histologic examination of the brain to detect microinfarction. Intracardiac injections of saline, air, and corn oil were used as controls. RESULTS: Brain microinfarcts and SCADs formation of the brain microvasculature occurred only after control injections with corn oil. None of the brains from animals that received ultrasound contrast agent showed gross discoloration, as an indication of increased vascular permeability, with the Evans blue/fluorescence microscopy method. Definite leakage of Evans blue occurred only after large doses (150 microL) of air. CONCLUSIONS: This study indicates that ultrasound contrast media composed of air microspheres do not cause lesions of the brain microvasculature or parenchyma.

Albumins↗

Intravenous anaesthesia: manual infusion schemes versus TCI systems.

Propofol was first used to induce and maintain anaesthesia in the early 1980s. Several infusion regimens were described, some based on pharmacokinetic predictions. Advances in computing technology subsequently have allowed the development of portable target controlled infusion devices, with drugs delivered to achieve specific predicted target blood propofol concentrations. Assessments of propofol target controlled infusion systems in clinical practice and comparisons of 'Diprifusor' target controlled infusion systems with manual infusion are reviewed here.

Anesthesia, Intravenous↗

Evaluating motor function in children with Down syndrome: validity of the GMFM.

The Gross Motor Function Measure (GMFM) was developed and validated originally by Russell and colleagues as an evaluative assessment of gross motor function in children with cerebral palsy (CP). The present study reports the results of reliability and validity testing of the GMFM for use with children with Down syndrome (DS). One hundred and twenty-three children with DS were assessed twice over a 6-month period, using the GMFM and the motor scale of the Bayley Scales of Infant Development - second edition (BSID-II). In addition to the usual method of scoring the GMFM using only observed motor behaviours (standard score), parent reports of children's activities not seen by the assessor on the day of testing were also obtained and a second score (reported score) was calculated for each GMFM assessment. Test-retest and interrater reliabilities were excellent (all >0.90). Observed correlations between change on GMFM and judgements of change made independently by parents, intervenors, and masked video raters were lower than hypothesized. However, the pattern of change scores in predefined age and severity subgroups supported the contention that the GMFM was able to detect differential amounts of change as predicted. The GMFM was shown to be relatively more responsive to change in gross motor function than the motor scale of the BSID-II. The 'reported' scores on the GMFM demonstrated better evidence of reliability, validity, and responsiveness than the standard scoring method and this approach is recommended for use when assessing children with DS.

Child↗

Association between intraoperative cerebral microembolic signals and postoperative neuropsychological deficit: comparison between patients with cardiac valve replacement and patients with coronary artery bypass grafting.

OBJECTIVES: To examine the association between intraoperative cerebral microembolic signals (MES) and postoperative neuropsychological deficit in patients with valve replacement (VR) and patients with coronary artery bypass grafting (CABG). METHODS: Neuropsychological examination (10 tests) was performed 1-2 days before and 2 months after surgery (VR (n=26) and CABG (n=14)). The intraoperative number of cerebral MES were monitored from the right middle cerebral artery using transcranial Doppler. RESULTS: A higher number of cerebral MES were detected in VR patients with neurological deficit (6/26) compared with those without deficit (20/26) (MES median number 2083 v 645, p=0.04). No such difference was found in patients with CABG (2/14 v 12/14) (MES median number 50 v 112, p=0.2). CONCLUSION: A high number of MES were detected in patients with VR with neuropsychological deficit. In patients with CABG with such a deficit, a low number of MES were detected. This difference in number may be explained by relatively more gaseous emboli in the first and more solid in the second. However, the results in the patients with CABG should be interpreted with caution due to the few patients in this subgroup.

Adult↗

Consensus on microembolus detection by TCD. International Consensus Group on Microembolus Detection.

Transcranial Doppler ultrasound is capable of detecting microembolic material, both gaseous and solid, within the intracranial cerebral arteries. To avoid discrediting this promising and exciting new technique, experts in this field met in January 1997 in Frankfurt, Germany, to discuss the limitations and problems of embolus detection and to determine guidelines for its proper use in clinical practice, as well as in scientific investigations. In particular, the authors suggest that studies report the following parameters: (1) ultrasound device, (2) transducer type and size, (3) insonated artery, (4) insonation depth, (5) algorithms for signal intensity measurement, (6) scale settings, (7) detection threshold, (8) axial extension of sample volume, (9) fast Fourier transform (FFT) size (number of points used), (10) FFT length (time), (11) FFT overlap, (12) transmitted ultrasound frequency, (13) high-pass filter settings, and (14) recording time. There was agreement that no current system of automatic embolus detection has the required sensitivity and specificity for clinical use.

Humans↗