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Biomedical subjects

David Russell

Publications and source records attributed to David Russell.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cerebral microembolization during off-pump coronary artery bypass surgery with the Symmetry aortic connector device.

OBJECTIVE: The use of aortic connector systems for proximal vein grafts in off-pump coronary artery bypass grafting might minimize aortic manipulation by eliminating the need for partial aortic clamping. The objective of this study was to asses whether use of a Symmetry connector (St Jude Medical, Inc, St Paul, Minn) reduced intraoperative cerebral embolization. METHODS: Thirty-two consecutive patients underwent off-pump coronary artery bypass grafting. Sixteen patients received at least one mechanical proximal vein graft anastomosis with a Symmetry aortic connector system. Sixteen patients representing the control group underwent operations with standard suturing techniques using partial aortic clamping. During surgical intervention, all patients were monitored continuously with multifrequency transcranial Doppler scanning, which detected and differentiated cerebral emboli. RESULTS: There were significantly more cerebral emboli in the Symmetry group (median, 36) compared with the control group (median, 11; P = .027). This was due to a higher number of gaseous emboli in the Symmetry group than in the control group (median, 27 vs 8; P = .014), whereas there was no significant difference regarding the number of solid emboli (median, 7 vs 3; P = .139). CONCLUSION: Use of a Symmetry connector system during proximal vein graft anastomosis increased the number of emboli to the brain compared with a standard technique in coronary bypass surgery without cardiopulmonary bypass.

Aged↗
PubMed2005

Slow, medium, or fast re-warming following post-traumatic hypothermia therapy? An ultrastructural perspective.

It was hypothesized that rapid rather than slow re-warming following traumatic brain injury (TBI) and short-term hypothermia results in secondary, ultrastructural pathology. After stretch injury to the right optic nerve, adult guinea pigs were randomly allocated to one of six experimental groups. Either (1) sham (all procedures but not stretch-injured; n = 4); injured and (2) maintained at normal temporalis core temperature (38.5 degrees C) for 8 hours (n = 6); (3) cooled rapidly to 32.5 degrees C (temporalis temperature), maintained for 4 h and re-warmed to 38.5 degrees C at 1 degrees C rise every 10 min (fast; n = 6); (4) cooled and re-warmed at 1 degrees C rise every 20 min (medium; n = 6); (5) cooled and rewarmed at 1 degrees C rise every 40 min (slow; n = 6) before being killed 8 h after injury; and (6) uninjured animals (n = 6) cooled to 32.5 degrees C for 4 h and then re-warmed at 1 degrees C every 10 min before killing 4 h later. Tissue was processed for light immunocytochemistry (beta-APP and RMO-14) and ultrastructural stereology. In both uninjured and injured fast re-warmed animals, there was almost total loss of axonal microtubules (MT) and an increased number of neurofilaments (NF) within the axoplasm. In the former, there was also compaction of NF. The number of MT was reduced to 40% of control values, NFs were increased but were not compacted after medium rate re-warming. Following slow re-warming the axonal cytoskeleton did not differ from that in control animals. It is concluded that re-warming faster than 1 degrees C every 40 min following mild post-traumatic hypothermia induces secondary axonal pathology.

Actin Cytoskeleton↗
PubMed2005

A prospective 3-yr evaluation of tacrolimus-based immunosuppressive therapy in immunological high risk renal allograft recipients.

BACKGROUND: There have been no published data on use of the the newer immunosuppressants tacrolimus and mycophenolate mofetil (MMF) in high immunological risk renal transplantation. We therefore undertook a prospective study to systematically assess outcomes using these agents as part of an aggressive immunosuppressive regimen. METHODS: Fifty-nine high-risk renal allograft recipients were enrolled at 10 Canadian sites and given a regimen of: a biological induction agent, tacrolimus, MMF, and corticosteroids. Patients included 10 (17%) who had lost a previous graft to rejection <1 yr, 31 (53%) with a current panel reactive antibody (PRA) >30%, 47 (80%) with a historic PRA >50%, four (7%) who had a positive historical T-cell crossmatch with the current donor, and six (10%) with a current positive B-cell crossmatch. The mean peak PRA was 76 +/- 33%. RESULTS: The estimated 3-yr Kaplan-Meier patient and graft survival estimates were 89% and 75%, respectively. There were nine graft losses other than deaths with a functioning graft, of which six were preceded by delayed graft function (p = 0.01, chi2). Sixteen (27%) recipients experienced at least one episode of biopsy-confirmed acute rejection. Infections included cytomegalovirus in 16 patients, eight of whom had tissue-invasive disease. Only one malignancy occurred. CONCLUSIONS: The immunosuppressive strategy investigated is effective and displays a satisfactory safety profile in high immunological risk renal allograft recipients.

Adult↗
PubMed2005

Medication utilization behavior in patients receiving phosphodiesterase type 5 inhibitors for erectile dysfunction.

INTRODUCTION: A number of preference studies have been conducted with phosphodiesterase type 5 (PDE5) inhibitor medications demonstrating inconsistent findings. Additionally, limited information is available regarding real-world utilization patterns of PDE5 inhibitors. AIM: To evaluate treatment patterns using real-world data for patients initiating erectile dysfunction (ED) therapy with Viagra (sildenafil citrate), Levitra (vardenafil), or Cialis (tadalafil). METHODS: Patients with an initial prescription claim for sildenafil, vardenafil, or tadalafil were identified in NDCHealth's Intelligent Health Repository. Medication refills, medication switching, and dose titration were analyzed. Logistic regression on the odds of refilling initial PDE5 medications was conducted controlling for patient age, presence of common comorbidities, initial number of tablets, and copay. RESULTS: A higher percentage of patients receiving sildenafil (52%) refilled their ED medication during the study period than patients receiving vardenafil (30%) or tadalafil (29%) (P<0.001). A smaller percentage of patients in the sildenafil cohort (6.4%) switched medication than in the tadalafil (9.0%) or vardenafil (10.4%) cohorts (P<0.001); the difference between the tadalafil and vardenafil cohorts in switching medications was also significant (P<0.001). There were no statistically significant differences between cohorts in dose titration frequency, which was low in all three treatment cohorts. Using logistic regression, the odds of refilling initial PDE5 therapy was significantly lower for vardenafil (odds ratio [OR]: 0.39, 95% confidence interval [CI]: 0.38-0.40; P<0.0001) and tadalafil (OR: 0.38, 95% CI: 0.37-0.40; P<0.0001) compared with sildenafil. CONCLUSIONS: Patients who were initially prescribed sildenafil were significantly more likely to refill their medication and significantly less likely to switch medications during the study period compared with patients who were initially prescribed vardenafil or tadalafil. These findings may indicate greater treatment satisfaction in patients receiving sildenafil, although future prospective evaluation is required.

Adult↗
PubMed2004

Methods of detecting potential causes of vascular cognitive impairment after coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) is the most common major surgical procedure performed worldwide. Neuropsychological deficits are frequent following CABG occurring in up to 80% in the early postoperative period, 20-50% at 6 weeks and 10-30% of patients at 6 months. Transcranial Doppler monitoring is well suited for monitoring the brain during surgery. It has been shown that both solid and gaseous microemboli are frequent during, surgery especially during clamping and declamping of the aorta. This method can also monitor cerebral hemodynamics during surgery and alert the surgical team when a fall in perfusion pressure occurs. Magnetic resonance imaging (MRI) studies have found evidence which suggests increased water content in the brain following "on-pump" CABG. New postoperative cerebral lesions have also been found in many patients using diffusion-weighted MRI.

Aged↗
PubMed2004

Coronary artery bypass grafting (CABG) and cognitive decline: a review.

Coronary artery bypass grafting (CABG) is a worldwide used myocardial revascularization procedure, which despite the modern advantages still has a spectrum of complications. The relatively old age of the patients who undergo CABG and their widespread atherosclerotic disease are possible reasons for vascular sequels particularly those leading to neurological dysfunction. Immediate, early and late cognitive decline is a known- and well-defined outcome of CABG. Whereas a lot of data was collected through the last years regarding to neuropsychological dysfunction after CABG, nevertheless etiology and mechanisms of this phenomenon remain unresolved and they are probably multifactorial. Meticulously preoperative assessment of those patients with a potential risk of adverse neurocognitive outcomes can help clinicians to select the mode of revascularization and to better counsel patients about the risks and benefits of surgery versus more conservative kinds of treatment.

Alzheimer Disease↗
PubMed2004

Mechanical stress induces profound remodelling of keratin filaments and cell junctions in epidermolysis bullosa simplex keratinocytes.

The outer epidermal layer of the skin is an epithelium with remarkable protective barrier functions, which is subject to pronounced physical stress in its day-to-day function. A major candidate component for absorbing this stress is the K5/K14 keratin intermediate filament network. To investigate the part played by keratins in stress resilience, keratinocyte cell lines were subjected to mechanical stress. Repeated stretch and relaxation cycles over increasing time produced reproducible changes in the configuration of the keratin network. When wild-type cells were compared with cells carrying a keratin mutation associated with severe epidermolysis bullosa simplex-type skin fragility, the mutant keratin filaments were unable to withstand the mechanical stress and progressively fragmented yielding aggregates and novel ring structures. The cell junctions into which the keratin filaments are normally anchored also progressively disassembled, with all components tested of the cytoplasmic plaques becoming relocated away from the membrane and onto the keratin rings, while integral membrane receptors integrins and cadherins remained at the plasma membrane. The results suggest that maintenance of desmosomes and hemidesmosomes may require some tension, normally mediated by keratin attachments.

Cell Line↗
PubMed2004

Sexually dimorphic metabolism of branched-chain lipids in C57BL/6J mice.

Despite the importance of branched chain lipid oxidation in detoxification, almost nothing is known regarding factors regulating peroxisomal uptake, targeting, and metabolism. One peroxisomal protein, sterol carrier protein-x (SCP-x), is thought to catalyze a key thiolytic step in branched chain lipid oxidation. When mice with substantially lower hepatic levels of SCP-x were tested for susceptibility to dietary stress with phytol (a phytanic acid precursor and peroxisome proliferator), livers of phytol-fed female but not male mice i). accumulated phytol metabolites (phytanic acid, pristanic acid, and Delta-2,3-pristanic acid); ii). exhibited decreased fat tissue mass and increased liver mass/body mass; iii). displayed signs of histopathological lesions in the liver; and iv). demonstrated significant alterations in hepatic lipid distributions. Moreover, both male and female mice exhibited phytol-induced peroxisomal proliferation, as demonstrated by liver morphology and upregulation of the peroxisomal protein catalase. In addition, levels of liver fatty acid binding protein, along with SCP-2 and SCP-x, increased, suggesting upregulation mediated by phytanic acid, a known ligand agonist of the peroxisomal proliferator-activated receptor alpha. In summary, the present work establishes a role for SCP-x in branched chain lipid catabolism and demonstrates a sexual dimorphic response to phytol, a precursor of phytanic acid, in lipid parameters and hepatotoxicity.

Animals↗
PubMed2004

Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia.

PURPOSE: We reviewed the physiological and pathogenic role of dihydrotestosterone (DHT), evidence for the beneficial effects of decreasing DHT through 5alpha-reductase inhibition and the effects of altering the androgen balance with these agents. MATERIALS AND METHODS: A review of the relevant literature was done using published studies identified from the MEDLINE database. RESULTS: The androgens DHT and testosterone have complementary roles in male physiology. Each is mediated through the intracellular androgen receptor. It has been hypothesized that DHT may provide an amplification mechanism for testosterone, which could be a beneficial adaptation in men with low circulating testosterone. The recognition of the central role of DHT in benign prostatic hyperplasia (BPH) has changed the way the disease is viewed and has led to the introduction of 5alpha-reductase inhibitors, which can prevent and retard the progression of BPH by suppressing DHT synthesis. The 5alpha-reductase inhibitors decrease prostate volume. In doing so they improve symptoms and urinary flow, and decrease the risks of acute urinary retention and the need for BPH related surgery. The predominant drug related adverse events with 5alpha-reductase inhibitors are reproductive events, that is typically decreased libido, impotence and ejaculatory dysfunction. These events occur in a minority of men and tend to decrease with a longer treatment duration. CONCLUSIONS: DHT appears to have an obligatory role in the development of BPH. The role of 5alpha-reductase inhibitors in the treatment of BPH has been firmly established with an adverse events profile that is suitable for long-term use.

5-alpha Reductase Inhibitors↗
PubMed2004

Effects of FGF9 on embryonic Sertoli cell proliferation and testicular cord formation in the mouse.

Proliferation and cord formation by embryonic Sertoli cells are pivotal events involved in testis morphogenesis. A number of growth factors have been implicated in mediating these events. However, the exact level of involvement and importance of each as yet remains elusive. We have adopted an in vitro approach to assess developing mouse Sertoli cells, whereby they are cultured in the presence or absence of fibroblast growth factor (FGF9) and/or extracellular matrix (ECM) gel, since previous studies have shown that ECM gel aids Sertoli cell differentiation. The present findings corroborate this effect, but in addition demonstrate that in the presence of FGF9 (10 ng/ml), cells undergo greater proliferation than those cultured on gel alone. They also display a differentiated epithelial phenotype, with appositional contact of cell membranes in cord-like aggregations. In addition we have shown that cultured Sertoli cells generally express a smaller truncated, nuclear form of the FGFr3, although in the presence of FGF9 and absence of gel, the larger, cytoplasmic form of the receptor is also expressed. Immunolocalisation of FGFr3 in Sertoli cells of whole testes revealed a temporal expression pattern profile, with high levels being abundant in the embryonic testicular cords and at puberty, but an absence in adult Sertoli cells. Our findings suggest that FGF9 plays an important role in proliferation and organisation of embryonic Sertoli cells during testis morphogenesis.

Animals↗
PubMed2004

Functional analysis and treatment of inappropriate sexual behavior.

The results of a functional analysis showed that inappropriate sexual behaviors exhibited by a 9-year-old boy who had been diagnosed with traumatic brain injury were maintained by positive reinforcement in the form of social attention. An intervention consisting of functional communication training and extinction resulted in reduced levels of inappropriate sexual behaviors.

Aggression↗
PubMed2003

Comparison of cerebral embolization during off-pump and on-pump coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury. At least 1% to 5% will suffer a stroke, and at 3-months postoperatively approximately 30% are reported to have cognitive impairment assessed by neuropsychologic testing. In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced. The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization. METHODS: This was a prospective and randomized study of two comparable groups with regard to age, sex, years of education, preoperative cognitive functioning, and surgical characteristics. Fifty-two patients (29 off-pump) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery. Preoperative and postoperative clinical, cerebral magnetic resonance imaging, and neuropsychologic examinations were also carried out. RESULTS: There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery (16.3 [range 0 to 131] versus 90.0 [range 15 to 274], p < 0.0001). No significant difference with regard to the incidence of neuropsychologic performance (decline in 29% off-pump, 35% on-pump) or neuroradiologic findings at 3 months was found, and there was no association between the number of cerebral microemboli and cognitive outcome. CONCLUSIONS: This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization. A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population.

Aged↗