Standing thoracoscopy in the diagnosis of lymphosarcoma in a horse.
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Animals↗
Biomedical subjects
T Russell
Publications and source records attributed to T Russell.
Transoral resection of odontoid process fragment in a rheumatoid patient using Coblation electrosurgery.
A new technique is described for the removal of ligaments and soft tissue during a transoral resection of the odontoid process in a patient with rheumatoid arthritis. The technique employed is Coblation, a form of electrosurgery that operates at lower temperatures than conventional electrosurgical technique and, therefore, produces less collateral damage.
Arthritis, Rheumatoid↗
Genetic composition of human immunodeficiency virus type 1 in cerebrospinal fluid and blood without treatment and during failing antiretroviral therapy.
Human immunodeficiency virus (HIV) infection of the central nervous system (CNS) is a significant cause of morbidity. The requirements for HIV adaptation to the CNS for neuropathogenesis and the value of CSF virus as a surrogate for virus activity in brain parenchyma are not well established. We studied 18 HIV-infected subjects, most with advanced immunodeficiency and some neurocognitive impairment but none with evidence of opportunistic infection or malignancy of the CNS. Clonal sequences of C2-V3 env and population sequences of pol from HIV RNA in cerebrospinal fluid (CSF) and plasma were correlated with clinical and virologic variables. Most (14 of 18) subjects had partitioning of C2-V3 sequences according to compartment, and 9 of 13 subjects with drug resistance exhibited discordant resistance patterns between the two compartments. Regression analyses identified three to seven positions in C2-V3 that discriminated CSF from plasma HIV. The presence of compartmental differences at one or more of the identified positions in C2-V3 was highly associated with the presence of discordant resistance (P = 0.007), reflecting the autonomous replication of HIV and the independent evolution of drug resistance in the CNS. Discordance of resistance was associated with severity of neurocognitive deficits (P = 0.07), while low nadir CD4 counts were linked both to the severity of neurocognitive deficits and to discordant resistance patterns (P = 0.05 and 0.09, respectively). These observations support the study of CSF HIV as an accessible surrogate for HIV virions in the brain, confirm the high frequency of discordant resistance in subjects with advanced disease in the absence of opportunistic infection or malignancy of the CNS, and begin to identify genetic patterns in HIV env associated with adaptation to the CNS.
AIDS Dementia Complex↗
Initial effects of anti-pronation tape on the medial longitudinal arch during walking and running.
OBJECTIVES: To investigate the effect of an augmented LowDye taping technique on the medial longitudinal arch of the foot during dynamic tasks such as walking and jogging, and to elucidate the relation between tape induced changes in static and dynamic foot posture. METHODS: Seventeen subjects (mean (SD) age 27 (5.8) years) who were asymptomatic and exhibited a navicular drop greater than 10 mm were studied. Medial longitudinal arch height standardised to foot length during standing and at mid-stance of walking and jogging was measured from digital video images taken before and after the application of an anti-pronation taping technique. A no tape control condition was also included. RESULTS: Compared with the no tape control condition, tape produced a significant mean (SD) increase in the medial longitudinal arch height index of 0.031 (0.015), 0.026 (0.014), and 0.016 (0.017) during standing, walking, and jogging respectively (p < 0.05). The relative increase in medial longitudinal arch height represents an anti-pronation effect. The tape induced changes in the medial longitudinal arch height measured during standing correlated strongly with those measured during walking and jogging (Pearson's r = 0.7 and 0.76 respectively). CONCLUSIONS: The augmented LowDye tape was effective in controlling pronation during both static and dynamic activity. Tape induced changes in static foot posture paralleled those during walking and jogging.
Adult↗
An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function.
Functional magnetic resonance imaging (fMRI) was used to investigate the hypothesis that schizophrenia is associated with a dysfunction of prefrontal brain regions during motor response inhibition. Generic brain activation of six male medicated patients with schizophrenia was compared to that of seven healthy comparison subjects matched for sex, age, and education level while performing 'stop' and 'go-no-go' tasks. No group differences were observed in task performance. Patients, however, showed reduced BOLD signal response in left anterior cingulate during both inhibition tasks and reduced left rostral dorsolateral prefrontal and increased thalamus and putamen BOLD signal response during stop task performance. Despite good task performance, patients with schizophrenia thus showed abnormal neural network patterns of reduced left prefrontal activation and increased subcortical activation when challenged with motor response inhibition.
Adult↗
G2 phase cell cycle arrest in human skin following UV irradiation.
The contribution of the short wavelength ultraviolet (UV) component of sunlight to the aetiology of skin cancer has been widely acknowledged, although its direct contribution to tumour initiation or progression is still poorly understood. The loss of normal cell cycle controls, particularly checkpoint controls, are a common feature of cancer. UV radiation causes both G1 and G2 phase checkpoint arrest in vitro cultured cells. In this study we have investigated the cell cycle responses to suberythemal doses of UV on skin. We have utilized short-term whole organ skin cultures, and multi parameter immunohistochemical and biochemical analysis to demonstrate that basal and suprabasal layer melanocytes and keratinocytes undergo a G2 phase cell cycle arrest for up to 48 h following irradiation. The arrest is associated with increased p16 expression but no apparent p53 involvement. This type of organ culture provides a very useful model system, combining the ease of in vitro manipulation with the ability to perform detailed molecular analysis in a normal tissue environment.
Bromodeoxyuridine↗
NMDA receptor antagonist AP5 and nitric oxide synthase inhibitor 7-NI affect different phases of learning and memory in goldfish.
The present study investigated the amnestic effects of N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and nitric oxide (NO) synthase inhibitor 7-NI in avoidance conditioning in goldfish. The results showed that both AP5 and 7-NI, without impairing performance processes, produced anterograde amnesia when given before training. Furthermore, 7-NI produced retrograde amnesia when given immediately following training while AP5 did not. Thus, AP5 and 7-NI affected different phases of learning and memory.
2-Amino-5-phosphonovalerate↗
Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks.
Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.
Adult↗
A medical center's experience with managing specialty bed usage.
The focus of this case study was the escalating use of specialty beds at a large military medical center. Members of a multidisciplinary task force looked at current use of specialty beds, clinical appropriateness of past decisions regarding use of these beds, and education of staff members. They concluded that specialty beds were being ordered randomly from multiple vendors without the benefit of sound clinical decision making. The task force narrowed the types of beds used from 16 to only 7, limited the number of primary bed vendors to two and placed them under contract, educated staff regarding proper selection of specialty beds, and established a protocol specifying WOC nurses and physicians as responsible personnel for ordering specialty beds. These efforts resulted in a marked decline in the use of specialty beds, better patient clinical outcomes, and a sizable cost reduction.
Beds↗
Effect of polyunsaturated fatty acid (PUFA) supplementation on intestinal inflammation and necrotizing enterocolitis (NEC) in a neonatal rat model.
Inasmuch as long-chain polyunsaturated fatty acids (PUFA, metabolites of the essential n-3 and n-6 fatty acids) are known to modulate inflammation, we hypothesized that supplementation of formula with these compounds would prevent necrotizing enterocolitis (NEC) and intestinal inflammation in our neonatal rat model. Newborn rats were stressed with asphyxia and formula feeding, and randomly assigned to control formula, control with PUFA supplementation, and PUFA with nucleotides. Animals were followed for 72--96 h and assessed for death, gross and histologic NEC, intestinal apoptosis, endotoxemia, and intestinal mRNA synthesis of phospholipase A(2)-II (rate-limiting enzyme for platelet activating factor production), platelet activating factor receptor, and inducible nitric oxide synthase. We found that PUFA reduced the incidence of death and NEC compared with the other groups (NEC 8 of 24 versus 17 of 24 control and 13 of 23 PUFA + nucleotides, p < 0.05). Furthermore, PUFA reduced plasma endotoxemia at 48 h (25 +/- 4 EU/mL versus 276 +/- 39 EU/mL in control and 170 +/- 28 EU/mL in PUFA + nucleotide), intestinal phospholipase A(2)-II expression at 24 h, and platelet activating factor receptor expression at 48 h. Formula supplementation had no effect on apoptosis of intestinal epithelium or intestinal inducible nitric oxide synthase expression. Addition of nucleotides with PUFA abrogated the beneficial effects of PUFA on intestinal inflammation. We conclude that PUFA reduces the incidence of NEC and intestinal inflammation in a neonatal rat model.
Animals↗
Ultraviolet radiation induces p16CDKN2A expression in human skin.
The loss of the tumor suppressor gene product p16 in melanoma is well documented, although the normal physiological function of p16 in skin melanocytes is unknown. In this report, we demonstrate that when human skin was irradiated with suberythemal doses of UV radiation, levels of p16 were dramatically increased by 16 h postirradiation, peaking at 24 h, and declining by 72 h. p16 was expressed in the nucleus and cytoplasm of melanocytes and keratinocytes within the epidermis, and the pattern of p16 expression within the epidermis was dependent on the penetrative ability of the different UV wavebands. The existence of a UV-induced response pathway involving up-regulated p16 expression may provide a mechanism linking the loss of p16 and UV exposure with the development of melanoma.
Cyclin-Dependent Kinase Inhibitor p16↗
Cardiovascular safety of fexofenadine HCl.
Fexofenadine HCl is the acid metabolite of terfenadine (Seldane). The effect of this recently approved nonsedating antihistamine on the corrected QT interval (QTc) was evaluated in dose-tolerance, safety, and drug-interaction studies with healthy volunteers, and in clinical studies in patients with seasonal allergic rhinitis (SAR). Twelve-lead electrocardiographic data were collected once before and after dosing or serially throughout these studies. Outliers were defined as QTc > 440 ms with a > or = 10 ms increase from baseline. The recommended fexofenadine HCl dose is 60 mg twice daily. Fexofenadine HCl doses up to 800 mg once daily or 690 mg twice daily for 28 days resulted in no dose-related increases in QTc. Longer term studies indicated no statistically significant QTc increases compared with placebo in patients receiving fexofenadine HCl 80 mg twice daily for 3 months, 60 mg twice daily for 6 months, or 240 mg once daily for 12 months. Interaction studies showed no significant increases in QTc when fexofenadine HCl 120 mg twice daily was administered in combination with erythromycin (500 mg 3 times daily) or ketoconazole (400 mg once daily) after dosing to steady state (6.5 days). Clinical trials in patients with SAR (n = 1,160) treated with 40, 60, 120, or 240 mg twice-daily fexofenadine HCl or placebo indicated no dose-related increases in QTc and no statistically significant increases in mean QTc compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, we conclude that fexofenadine HCl has no significant effect on QTc, even at doses > 10-fold higher than that is efficacious for SAR.
Double-Blind Method↗
Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model.
BACKGROUND & AIMS: Neonatal necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants partly caused by intestinal bacterial proliferation. Because bifidobacteria are thought to reduce the risk for intestinal disturbances associated with pathogenic bacterial colonization, we hypothesized that exogenous bifidobacterial supplementation to newborn rats would result in intestinal colonization and a reduction in the incidence of neonatal NEC. METHODS: Newborn rat pups were given Bifidobacterium infantis (10(9) organisms per animal daily), Escherichia coli, or saline control and exposed to the NEC protocol consisting of formula feeding (Esbilac; 200 cal. kg(-1). day(-1)) and asphyxia (100% N(2) for 50 seconds followed by cold exposure for 10 minutes). Outcome measures included stool and intestinal microbiological evaluation, gross and histological evidence of NEC, plasma endotoxin concentration, intestinal phospholipase A(2) expression, and estimation of intestinal mucosal permeability. RESULTS: Bifidobacterial supplementation resulted in intestinal colonization by 24 hours and appearance in stool samples by 48 hours. Bifidobacteria-supplemented animals had a significant reduction in the incidence of NEC compared with controls and E. coli-treated animals (NEC, 7/24 B. infantis vs. 19/27 control vs. 16/23 E. coli; P < 0.01). Plasma endotoxin and intestinal phospholipase A(2) expression were lower in bifidobacteria-treated pups than in controls, supporting the role of bacterial translocation and activation of the inflammatory cascade in the pathophysiology of NEC. CONCLUSIONS: Intestinal bifidobacterial colonization reduces the risk of NEC in newborn rats.
Animals↗
Cardiovascular safety of fexofenadine HCl.
BACKGROUND: Certain first- and second-generation H1-receptor antagonists are associated with prolongation of the corrected QT interval (QTc) and, in rare instances, with ventricular dysrhythmias, including torsades de pointes ventricular tachycardia. OBJECTIVE: To assess the effect of fexofenadine HCl, a new non-sedating antihistamine, on QTc. METHODS: Dose-tolerance, safety, and drug-interaction studies with healthy volunteers; and clinical efficacy studies with seasonal allergic rhinitis patients were conducted. Twelve-lead ECG data were collected pre- and postdosing or serially throughout these studies. Outliers were defined as QTc >440 msec with a >/=10 msec increase from baseline. RESULTS: Fexofenadine HCl at single doses up to 800 mg q.d. (once daily) and multiple doses up to 690 mg b.d. for 28 days in healthy volunteers resulted in no increases in QTc (recommended dose range is 120-180 mg daily); QTc changes were similar to placebo. Compared with placebo, there were no statistically significant QTc increases in patients receiving fexofenadine HCl 80 mg b.d. for 3 months, 60 mg b. d. for 6 months, or 240 mg q.d. for 12 months. No statistically significant increases in QTc were detected when fexofenadine HCl 120 mg b.d. was administered in combination with erythromycin (500 mg t. d.) or ketoconazole (400 mg q.d.) after dosing to steady-state (6.5 days). In seasonal allergic rhinitis patients (n = 1160) treated with 40, 60, 120, or 240 mg b.d. fexofenadine HCl for 2 weeks, there were no dose-related increases in QTc and no significant increases in mean QTc compared with placebo. Frequency and magnitude of QTc outliers with fexofenadine HCl and placebo were similar in all studies. No case of fexofenadine-associated torsades de pointes has been observed in controlled trial experience with more than 6000 patients. CONCLUSION: Fexofenadine HCl has been investigated more extensively for possible electrophysiological effects than any other antihistamine. Fexofenadine HCl has no significant effect on QTc, even at doses much higher than those used in clinical practice.
Dose-Response Relationship, Drug↗
Assessment of QTc prolongation for non-cardiac-related drugs from a drug development perspective.
It is increasingly likely that non-cardiac-related drugs will need to be routinely analyzed for their ability to prolong cardiac repolarization. This leads to potential problems for drug companies in general and statisticians in particular. A number of issues immediately arise in regard to answering the question, "Does drug X prolong cardiac repolarization?" These include identifying what is the desired outcome, what is the dependent variable, and what analysis method should be used. The purpose of this article is bring to to light some of the issues regarding the analysis of QTc data, the advantages and disadvantages of these analysis methods, and some general recommendations.
Cardiotonic Agents↗
Pharmacokinetics, pharmacodynamics, and tolerance of single- and multiple-dose fexofenadine hydrochloride in healthy male volunteers.
BACKGROUND: Fexofenadine is a selective, nonsedating H1-receptor antagonist that relieves symptoms of allergic conditions. METHODS: Two randomized, double-blind, parallel-group, placebo-controlled dose-escalation studies were performed in healthy men to determine the maximum tolerated oral dose, pharmacokinetics, pharmacodynamics, and safety of fexofenadine hydrochloride. In the first study, 87 subjects (6 in the active drug group and 2 in the placebo group) received single oral doses of fexofenadine hydrochloride ranging from 10 to 800 mg or placebo. In the second study, 32 subjects (3 in the active drug group and 1 in the placebo group) received multiple fexofenadine hydrochloride doses ranging from 20 to 690 mg or placebo twice daily for 28 1/2 days. Serial plasma and urine samples were collected. Fexofenadine concentrations were determined by HPLC and fluorescence. Wheal and flare response to intradermal histamine was used to evaluate antihistaminic activity. RESULTS: Fexofenadine hydrochloride was rapidly absorbed, reaching peak concentrations in 0.83 to 1.33 hours. Single-dose mean concentration ranged from 46 to 6383 ng/mL, and steady-state maximum plasma concentration ranged from 58 to 4677 ng/mL. Mean area under the plasma concentration-time curve was approximately proportional to dose. Oral clearance, renal clearance, and cumulative percent of drug excreted in urine were similar after single and multiple doses and were generally constant over the dose range studied. Inhibition of skin wheal and flare was shown for single doses of 40 mg and higher and for all multiple doses. No fexofenadine dose-related trends or apparent differences from placebo were found for any safety parameter. CONCLUSIONS: Fexofenadine hydrochloride was well tolerated at oral doses up to 11 times the recommended therapeutic dose. In addition, fexofenadine hydrochloride showed significant antihistaminic activity and dose-proportional pharmacokinetics over a wide dosing range.
Administration, Oral↗
Attributions for positive life events predict recovery from depression among psychiatric inpatients: an investigation of the Needles and Abramson model of recovery from depression.
The authors investigated whether attributions for positive life events predict decreases in hopelessness and depressive symptoms among clinically depressed adults. Measures of attributional style, attributions for recent events, depressive symptoms, dysfunctional attitudes, hopelessness, and life events were administered to 52 depressed psychiatric inpatients treated with antidepressant medication; the measures were readministered 12 and 24 days later. Results indicated that (a) internal, stable, global attributions for recent positive events mediated a significant association between attributional style for positive life events and decreased hopelessness; (b) decreases in hopelessness mediated a significant association between internal, stable, global attributions for recent positive events and decreases in depressive symptom levels; and (c) depressotypic cognitions were not associated with decreases in either hopelessness or depressive symptom levels.
Adolescent↗
Immunolocalization of cytoplasmic and myelin mcalpain in transfected Schwann cells: II. Effect of withdrawal of growth factors.
We have examined the reversal of the regulatory effect of growth factors on calpain/calpastatin activity in transfected Schwann cells (tSc) after their subsequent withdrawal. Removal of nerve growth factor (NGF) or cyclic adenosine monophosphate (cAMP) from tSc resulted in a smaller loss of mu calpain (37%) and mcalpain (36.5 %) activity compared to treated cells from which the growth factors were not withdrawn. The mu calpain activity increased approximately 12% following withdrawal of acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) at 24 hr, while the increased mcalpain activity was more than 30-40% compared with that of cells that were continuously treated. The activity of both isoforms returned to their normal levels (untreated) at 48-72 hr following withdrawal of various growth factors, including NGF, cAMP, aFGF, bFGF, platelet-derived growth factor aa (PDGFaa), and PDGFbb. The inhibitory activity of calpastatin was greater than control following withdrawal of NGF, cAMP, PDGFaa, or PDGFbb at 24 hr and this inhibitory activity was less with treatment by aFGF and bFGF. The control activity was restored at 48 hr following withdrawal of these factors. The intensity of the cytoplasmic calpain immunoreactivity was significantly decreased in the nuclear and non-nuclear regions of the cytoplasm, respectively, following withdrawal of cAMP at 144 hr. Removal of bFGF from the medium resulted in an increase of cytoplasmic calpain immunoreactivity in the nuclear regions and cytoplasm, while there was dramatic loss of myelin calpain immunoreactivity from both the nuclear region and cytoplasm. The changes in calpain activity and immunoreactivity in tSc following withdrawal of growth factors suggest that release of calpain from membrane to cytosol may be regulated by these factors.
Animals↗