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Biomedical subjects

D Russell

Publications and source records attributed to D Russell.

At least 19 recordsLinked to original sources
PubMed2001

A pilot study of steroid-free immunosuppression in the prevention of acute rejection in renal allograft recipients.

BACKGROUND: Corticosteroids have been a mainstay of rejection prophylaxis for several decades, despite the multiple adverse effects of long-term use, including weight gain, hyperlipidemia, diabetes, hypertension, and bone disease. The detrimental effect of steroids on the metabolic profile begins in the early posttransplantation period, and the complete avoidance of steroids in transplantation would therefore be optimal. We hypothesized that the addition of mycophenolate mofetil (MMF) and a humanized monoclonal anti-CD25 antibody (daclizumab) to a cyclosporine (CsA microemulsion)-based immunosuppression protocol would permit transplantation without steroids. METHODS: Steroid-free renal transplantation was attempted in 57 patients treated with daclizumab, MMF, and CsA. Twenty-eight patients received kidneys from living donors; the remaining 29 received cadaveric grafts. RESULTS: At 1 year, patient and graft survival were 95% and 89%, respectively. Fourteen patients (25%) experienced rejections, of which 13 were readily reversed with steroids; 1 patient required OKT3. Mean serum creatinine at 12 months for patients not experiencing rejection was 149+/-58 micromol/L, compared with 158+/-102 micromol/L for those experiencing rejection. Five patients required hospitalization for infection; no patients developed lymphoproliferative disease. At baseline, 17 patients required 3 or more antihypertensive medications, compared with 2 patients at 1 year. Three of 43 nondiabetic patients developed diabetes during the study. There was no significant reduction in lumbar or femoral bone density. CONCLUSIONS: On the basis of these positive results, we believe steroid avoidance with this immunosuppressive regimen merits further study.

Acute Disease↗
PubMed2001

Van't Hoff and calorimetric enthalpies from isothermal titration calorimetry: are there significant discrepancies?

The enthalpy of a reaction is most often determined through one of two means; it can be determined directly using calorimetry or indirectly by measuring the temperature dependence of the equilibrium constant (i.e., the van't Hoff method). Recently, discrepancies have been noted between the enthalpy measured by calorimetry, and the enthalpy determined by the van't Hoff method,. This has been suggested to indicate that the binding reaction is more complex than the simple one-to-one binding model used to describe the data. To better understand possible discrepancies between and, we have undertaken both experimental studies using isothermal titration calorimetry to measure the binding energetics of Ba(2+) binding 18-crown-6 ether and 2'-CMP binding RNase A, along with a simulation of a system involving a molecule in conformational equilibrium coupled with binding. We find that when experimental setup and analysis are correctly performed, no statistically significant discrepancies between and exist even for the linked system.

Barium↗
PubMed2001

Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts.

OBJECTIVE: To investigate whether a computer vision system is comparable with humans in detecting early retinal lesions of diabetic retinopathy using color fundus photographs. METHODS: A computer system has been developed using image processing and pattern recognition techniques to detect early lesions of diabetic retinopathy (hemorrhages and microaneurysms, hard exudates, and cotton-wool spots). Color fundus photographs obtained from American Indians in Oklahoma were used in developing and testing the system. A set of 369 color fundus slides were used to train the computer system using 3 diagnostic categories: lesions present, questionable, or absent (Y/Q/N). A different set of 428 slides were used to test and evaluate the system, and its diagnostic results were compared with those of 2 human experts-the grader at the University of Wisconsin Fundus Photograph Reading Center (Madison) and a general ophthalmologist. The experiments included comparisons using 3 (Y/Q/N) and 2 diagnostic categories (Y/N) (questionable cases excluded in the latter). RESULTS: In the training phase, the agreement rates, sensitivity, and specificity in detecting the 3 lesions between the retinal specialist and the computer system were all above 90%. The kappa statistics were high (0.75-0.97), indicating excellent agreement between the specialist and the computer system. In the testing phase, the results obtained between the computer system and human experts were consistent with those of the training phase, and they were comparable with those between the human experts. CONCLUSIONS: The performance of the computer vision system in diagnosing early retinal lesions was comparable with that of human experts. Therefore, this mobile, electronically easily accessible, and noninvasive computer system, could become a mass screening tool and a clinical aid in diagnosing early lesions of diabetic retinopathy.

Aged↗
PubMed2001

William Hunter's casts of the gravid uterus at the University of Glasgow.

The Hunterian Collection at the University of Glasgow possesses 11 plaster casts showing the pregnant uterus. Three correspond to Plates I, IV, and VI of Hunter's The Anatomy of the Gravid Uterus Exhibited in Figures (1774), progressive stages of dissection of the same specimen. A further three casts show consecutive stages of dissection of a uterus containing a fetus presenting by the breech. The other specimens show a normal pregnancy at about 6 months, a normal full-term uterus with the fetal head becoming engaged, a breech presentation with placenta previa and the umbilical cord around the fetal neck, and an obstructed labor with distended bladder and colon. The 10 on display show realistic coloring and are mounted on black wooden stands. An 11th specimen, amateurishly painted, is not on display. The casts differ in their style; some show only the abdomen, pelvis, perineum, and thighs, others show the full torso. They also differ in the amount of detail shown. The first three casts show the cut femur and muscles at the transected ends of the thighs, also shown in some of the plates in the Gravid Uterus. Although these features enhance the artistic impact of both the engravings and the casts, the authors are unconvinced that Hunter deliberately used them to achieve this, as has been claimed.

Adult↗
PubMed2001

The appearance of retinopathy and progression to proliferative retinopathy: the WHO Multinational Study of Vascular Disease in Diabetes.

AIMS/HYPOTHESIS: We aimed to estimate incidences of any retinopathy and proliferative diabetic retinopathy (PDR) by direct ophthalmoscopy and relate them to baseline risk factors in re-examined diabetic survivors from 10 centres of the WHO Multinational Study of Vascular Disease in Diabetes. METHODS: After a mean follow-up of 8.4years (11.7 years in Oklahoma), 2877 (71.6%) survivors were resubmitted to standardised direct ophthalmoscopy as at baseline. The presence of any retinopathy and PDR were recorded at each centre and their incidence estimated in those without retinopathy and PDR at baseline. The independent associations of these incidences with baseline risk factors are expressed as odds ratios derived from multiple logistic regression analyses, within individual centres (which included fasting plasma glucose in 8 and triglyceride in 5) and in pooled data. RESULTS: Of the 4662 original patients, 465 (10.4%) of those without and 77 (43.0%) of those with baseline PDR had died (p < 0.001). Any retinopathy was newly reported at follow-up in 47.7 % and PDR in 9.7 % of those free of them at baseline, with reported incidences varying substantially among centres. Incident retinopathy appeared earlier in the known course of diabetes but incidence rates rose more slowly with duration in patients with Type II (non-insulin-dependent) diabetes mellitus than in those with Type I (insulin-dependent) diabetes mellitus. In pooled data and in some individual centres, any retinopathy incidence gave significantly positive odds ratios with age, diabetes duration, systolic pressure, plasma cholesterol, BMI, insulin treatment and proteinuria, and with fasting plasma glucose in the centres where it was measured. Positive odds ratios for PDR were similarly obtained for age, duration, insulin treatment, cholesterol, proteinuria and fasting glycaemia. Smoking status odds ratios were negative for both outcomes. CONCLUSION/INTERPRETATION: Incidence of ophthalmoscopically ascertained any retinopathy varied about twofold and of PDR about threefold among centres. Although, in part attributable to differences between observers, variation in incidence in all centres and in some cases within centres was associated with a number of baseline risk factors. Such associations are not likely due to observer variation or selection biases and emerged despite the imprecision of clinical ophthalmoscopy. Improved detection and control of these risk factors should reduce the impact of diabetic retinopathy and its consequences.

Age Factors↗
PubMed2001

The incidence of visual impairment and its determinants in the WHO Multinational Study of Vascular Disease in Diabetes.

AIMS/HYPOTHESIS: Incidence of severe visual impairment and the ultimate prevalence of all grades of impairment were estimated in the 10 centres of the WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participating in the follow-up. METHODS: Visual function was ascertained at follow-up in 2994 (77.9 %) of the 3845 eligible participating survivors of the 4709 originally recruited for the WHO MSVDD using the same baseline enquiry method. The associations between incident severe visual impairment, follow-up prevalence of all grades of impairment and baseline risk factors were examined by univariate and stepwise multiple logistic regression analysis. RESULTS: Overall, 8.4 year incidence of severe visual impairment was 1.94 % and showed statistically significant univariate correlations with age at diagnosis, diabetes duration, systolic blood pressure, fasting blood glucose and cholesterol, insulin treatment and strongly with baseline retinopathy. Baseline retinopathy, systolic pressure and cholesterol were statistically significant in multivariable analysis. Differences between centres (0.3% to 3.45%) were not significant. Ultimate prevalence of all grades of impairment differed between centres and within almost all of them was correlated in multivariable analysis with baseline retinopathy and proteinuria. CONCLUSION/INTERPRETATION: Comparisons of incident severe visual impairment between centres are restricted by selective mortality, low incidence rates and relatively small numbers in each centre but before retinopathy, baseline systolic pressure and cholesterol predicted severe visual impairment. Follow-up prevalence of all degrees of impairment varied among centres and were associated with prior retinopathy and renal disease at baseline.

Adult↗
PubMed2001

Mouse BAC ends quality assessment and sequence analyses.

A large-scale BAC end-sequencing project at The Institute for Genomic Research (TIGR) has generated one of the most extensive sets of sequence markers for the mouse genome to date. With a sequencing success rate of >80%, an average read length of 485 bp, and ABI3700 capillary sequencers, we have generated 449,234 nonredundant mouse BAC end sequences (mBESs) with 218 Mb total from 257,318 clones from libraries RPCI-23 and RPCI-24, representing 15x clone coverage, 7% sequence coverage, and a marker every 7 kb across the genome. A total of 191,916 BACs have sequences from both ends providing 12x genome coverage. The average Q20 length is 406 bp and 84% of the bases have phred quality scores > or = 20. RPCI-24 mBESs have more Q20 bases and longer reads on average than RPCI-23 sequences. ABI3700 sequencers and the sample tracking system ensure that > 95% of mBESs are associated with the right clone identifiers. We have found that a significant fraction of mBESs contains L1 repeats and approximately 48% of the clones have both ends with > or = 100 bp contiguous unique Q20 bases. About 3% mBESs match ESTs and > 70% of matches were conserved between the mouse and the human or the rat. Approximately 0.1% mBESs contain STSs. About 0.2% mBESs match human finished sequences and > 70% of these sequences have EST hits. The analyses indicate that our high-quality mouse BAC end sequences will be a valuable resource to the community.

Animals↗
PubMed2001

Ventricular fibrillation during off-pump coronary artery bypass grafting: transcranial Doppler and clinical findings.

A 73-year-old male developed ventricular fibrillation which lasted for 2 min and 24 s, during off-pump coronary artery bypass grafting. Cerebral hemodynamics were assessed by continuous transcranial Doppler monitoring. Ventricular fibrillation resulted in an immediate fall in cerebral blood flow velocities to almost zero with only slight fluctuations. This was then followed by a pronounced reactive hyperperfusion. Cerebral magnetic resonance imaging examinations and detailed neurological and neuropsychological evaluations were performed before and at 3 and 12 months after surgery. No evidence of cerebral damage was found.

Aged↗
PubMed2001

Prey detection in selective plankton feeding by the paddlefish: is the electric sense sufficient?

The long rostrum of the paddlefish Polyodon spathula supports an extensive array of ampullary electroreceptors and has been proposed to function as an antenna for detecting planktonic prey. Evidence in support of this hypothesis is presented in experiments that preclude the use of other sensory mechanisms for plankton detection. Paddlefish swimming in a recirculating observation chamber are shown to feed normally in the dark when prey-related chemical and hydrodynamic sensory cues are masked or attenuated. Specifically, we demonstrate that the spatial distribution of plankton captured by paddlefish is little changed when the plankton are individually encapsulated in agarose, when a high background concentration of plankton extract is added to the chamber, when the nares are plugged and under turbulent water flow conditions. Paddlefish also discriminate between encapsulated plankton and 'empty' agarose particles of the same size. Although capture distributions differed somewhat under certain conditions, the general pattern and effectiveness of prey capture were not disrupted by these procedures. These results support the conclusion that paddlefish, as zooplanktivores, rely on their passive electric sense for prey detection.

Animals↗
PubMed2001

Pyrethroid resistance and mechanisms of resistance in field strains of Helicoverpa armigera (Lepidoptera: Noctuidae).

Pyrethroid resistance was found in 54 field strains of Helicoverpa armigera collected between 1995 and 1999 from 23 districts in seven states of India. LD50 values of the field strains ranged from 0.06 to 72.2 microg/larva with slopes of 0.5-3.1. Resistance was highest in regions where pyrethroid use was frequent (four to eight applications per season). Resistance to deltamethrin was exceptionally high with resistance ratios of 13,570 and 27,160 in two strains collected during February 1998 in central India. Resistance to cypermethrin, fenvalerate and cyhalothrin also was high with resistance ratios of >1,000 in four strains collected from central and southern India. Resistance ratios were below 100 in >50% of the strains tested. Pyrethroid resistance was high in strains collected from the districts in Andhra Pradesh where a majority of the cotton farmer suicide cases in India were reported. Resistance to pyrethroids appeared to have increased over 1995-1998 in most of the areas surveyed. Studies carried out through estimation of detoxification enzyme activity and synergists indicated that enhanced cytochrome p450 and esterase activities were probably important mechanisms for pyrethroid resistance in field strains. Pyrethroid nerve insensitivity also was found to be a major mechanism in some parts of the country where the use of pyrethroids was high. The information presented illustrates the importance of proper insect management programs to avoid the consequences associated with improper insecticide use.

Animals↗
PubMed2001

Bioinformatics: use in bacterial vaccine discovery.

Bioinformatics has now become a common laboratory name for groups studying genomic sequences. It is composed of many different, yet interrelated scientific fields such as genomics, proteomics, and transcriptional profiling. The availability of complete genomic sequences, especially prokaryotic organisms, allows one to rapidly identify, analyze, and clone genes of interest. For bacterial vaccine discovery, one can "mine" the genomic sequence for potential surface targets using various algorithms, characterize these gene targets, and produce primers for cloning, all before one enters the wet laboratory. This review will focus on various genomic mining tools/algorithms available for predicting open reading frames and their associated annotation (if known), physical and functional characterization, and cellular localization. Finally, examples are given of how all of this is being used for the identification of potential bacterial vaccine candidates.

Animals↗
PubMed2001

Carbamate and organophosphate resistance in cotton pests in India, 1995 to 1999.

Monitoring for organophosphate and carbamate resistance was carried out on five major insect pests of cotton collected from 22 cotton-growing districts across India. Resistance was monitored in Helicoverpa armigera (Hübner) and Pectinophora gossypiella (Saunders) for the period 1995-1999 and for Spodoptera litura (Fabricius), Earias vittella (Fabricius) and Bemisia tabaci (Gennadius) in a survey conducted during the 1997-98 cropping season. Of the 53 field strains of H. armigera, only four were found to exhibit resistance to quinalphos, the highest 15-fold, whereas all 16 field strains tested were found to be resistant to monocrotophos. Similarly, out of 40 field strains tested, only eight were found to express appreciable resistance to methomyl. Resistance in P. gossypiella to quinalphos was high in the majority of the strains tested. Of the seven strains of E. vittella tested, two strains from northern India exhibited > 70-fold resistance to monocrotophos. Of the 11 S. litura strains tested, only four were found to exhibit resistance factors of 10 to 30-fold to quinalphos and monocrotophos. All of the B. tabaci field strains exhibited resistance to methomyl and monocrotophos and susceptibility to triazophos. Practical implications for pest control resulting from the observed patterns of cross-resistance between quinalphos, monocrotophos and methomyl are discussed.

Animals↗
PubMed2000

MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.

MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.

Animals↗
PubMed2000

Pharmacological analysis of extracellular dopamine and metabolites in the striatum of conscious as/agu rats, mutants with locomotor disorder.

The as/agu rat is a spontaneously occurring mutation which exhibits locomotor abnormalities, reduced tyrosine hydroxylase levels in the substantia nigra and lower extracellular levels of dopamine. The animal could represent a model of some human locomotor disorders. High-potassium medium evoked a 460% rise of dopamine levels in control rats but double this in mutants. Amphetamine increased extracellular dopamine by 710% in controls and 1480% in mutants. Clorgyline produced a small increase of dopamine levels in controls but an 1170% increase in mutants. The uptake inhibitor nomifensine increased dopamine levels by 910% in controls but only 270% in mutants. After treatment with benserazide plus L-DOPA, an acute injection of L-DOPA evoked a release of dopamine which was twice as large in the as/agu rats compared with controls. The results show reduced extracellular dopamine in as/agu rats when the locomotor disorder is apparent, but there has been little loss of tyrosine hydroxylase. The responses to drugs are qualitatively different from those obtained using 6-hydroxydopamine.Overall, the effects of compounds affecting aminergic neurons suggest that one possible mechanism for the neuronal abnormality in as/agu rats is a defective regulation of dopamine release from striatal terminals.

Amphetamine↗
PubMed2000

The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system.

The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only 10-20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.

Animals↗
PubMed2000

Capturing the paradigm shift in HIV treatment: changing attitudes in the choice of combination antiretroviral drugs by high HIV caseload Australian GPs (1996-1997).

The use of combination antiretroviral therapy for HIV infection is a rapidly changing field. To assess the impact of recent studies on prescribing patterns, two surveys of 21 high HIV caseload Australian GPs were undertaken in June 1996 and June 1997 to plot changes in the choice of combination antiviral therapy. Of the 17 GPs who responded to the survey in each year, the number of HIV-infected patients seen at their practices were estimated to be 5,061 in 1996 and 5,912 in 1997. In 1996, 40% of their patients were estimated to be on antiretroviral therapy compared to 60% in 1997 (p < 0.05). In 1996, most GPs preferred using dual combination therapy (59%); whereas in 1997, triple combination therapy was preferred (82%). Between 1996 and 1997, there was a significant change by high caseload Australian GPs in the choice of antiretroviral drugs with many combinations being preferred prior to presentation of efficacy data for those combinations, or recommendation through national guidelines.

Anti-HIV Agents↗