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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 55 records · Page 3Linked to original sources

Land-use dynamics in a southern Illinois (USA) watershed.

The Cache River of southernmost Illinois is used as a case study for developing and demonstrating an approach to quantitatively link (1) national agricultural policy and global agricultural markets, (2) landowner's decisions on land use, (3) spatial patterns of land use at a watershed scale, and (4) hydrologic impacts, thus providing a basis to predict, under a certain set of circumstances, the environmental consequences of economic and political decisions made at larger spatial scales. The heart of the analysis is an estimation, using logistic regression, of the affect of crop prices and Conservation Reserve Program (CRP) rental rates on farmland owner's decisions whether to reenroll in the CRP or return to crop production. This analysis shows that reasonable ranges for crop prices (80%-150% of 1985-1995 values) and CRP rental rates (0-125% of 1985-1995 rates) result in a range of 3%-92% of CRP lands being returned to crop production, with crop prices having a slightly greater effect than CRP rental rates. Four crop price/CRP rental rate scenarios are used to display resulting land-use patterns, and their effect on sediment loads, a critical environmental quality parameter in this case, using the agricultural non point source (AGNPS) model. These scenarios demonstrate the importance of spatial pattern of land uses on hydrological and ecological processes within watersheds. The approach developed can be adapted for use by local governments and watershed associations whose goals are to improve watershed resources and environmental quality.

Agriculture↗

Antagonism of PI 3-kinase-dependent signalling pathways by the tumour suppressor protein, PTEN.

The tumour suppressor protein, PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a member of the mixed function, serine/threonine/tyrosine phosphatase subfamily of protein phosphatases. Its physiological substrates, however, are primarily 3-phosphorylated inositol phospholipids, which are products of phosphoinositide 3-kinases. PTEN thus antagonizes PI 3-kinase-dependent signalling pathways, which explains to a large extent its tumour suppressor status. We have examined the kinetic behaviour, substrate specificity and regulation of PTEN both in vitro and in a variety of cellular models. Although PTEN can utilize both phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)] and its water-soluble headgroup, inositol 1,3,4,5-tetrakisphosphate, as substrates, it displays classical features of interfacial catalysis, which greatly favour the lipid substrate (by as much as 1000-fold as judged by K(cat)/K(m) values). Expression of PTEN in U87 cells (which lack endogenous PTEN) and measuring the levels of all known 3-phosphorylated lipids suggests that phosphatidylinositol 3,4-bisphosphate and PtdIns(3,4,5)P(3) are both substrates, but that phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate are not. PTEN binds to several PDZ-domain-containing proteins via a consensus sequence at its extreme C-terminus. Disruption of targeting to PDZ-domain proteins selectively blocks some PTEN functions, but not others, suggesting the existence of spatially localized, functionally dedicated pools of signalling lipids. We have also shown recently that PTEN expression is controlled at the transcriptional level and is profoundly upregulated by peroxisome proliferator activated receptor gamma agonists, thereby providing possible implications for these drugs in diabetes, inflammation and cancer.

Animals↗

Radiographic features of a lateral extracapsular wire suture in the canine cranial cruciate deficient stifle.

Radiographs of 74 dogs (84 stifles) presented with a cranial cruciate ligament rupture and surgically treated using a lateral extracapsular wire (LEW) were reviewed. A strand of orthopaedic wire was surgically placed caudally around the lateral fabella and through a predrilled hole in the tibial crest. At six week follow-up, the LEW was broken at least once in 26 of 33 stifles, predominantly in the area of the lateral fabella. In five stifles, the LEW had slipped off the fabella and was displaced distally along the gastrocnemius muscle. Six months after surgery, the LEW was often broken at several sites. LEW migration was rare. Osteolysis and sclerosis at the site of LEW penetration through the tibial crest occurred in about two-thirds of the stifles examined.

Animals↗

Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment.

Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end-stage Alzheimer's disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimer's disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron-specific nuclear protein (NeuN). Stereological counts of NeuN-immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 +/- 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0.0003) and mild or moderate Alzheimer's disease (46.06%; p < 0.0017) displayed significant losses of layer II entorhinal cortex neurons relative to those with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimer's disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimer's disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimer's disease.

Aged↗

Public health importance of vascular dementia and Alzheimer's disease with cerebrovascular disease.

Vascular dementia (VaD) refers to a heterogeneous group of conditions that include all dementia syndromes resulting from ischaemic, haemorrhagic, anoxic or hypoxic brain damage. VaD is the second most common cause of dementia in the elderly after Alzheimer's disease. Persons with VaD are at greater risk of morbidity and mortality compared with those without dementia or those with Alzheimer's disease, and appear to be at greater risk of institutionalisation. Despite the importance of the problem posed by VaD, few placebo-controlled, double-blind, randomised clinical trials have been conducted. Although dementia may result solely from the accumulation of brain damage from cerebrovascular disease (CVD), recent data suggest that VaD often results from a combination of both CVD and Alzheimer's disease ('mixed' dementia). This raises the possibility that persons with VaD may respond to medications that are commonly used to treat Alzheimer's disease.

Alzheimer Disease↗

An epidemiological case-control study of migraine and its associated comorbid conditions.

BACKGROUND: The economic impact of migraine to society has been well documented. However, few studies have identified the risk of migraine-specific comorbid conditions to explain the higher healthcare resource utilization by migraineurs. Because comorbidity has the potential to increase treatment costs, estimating its risks and its economc impact becomes imperative.OBJECTIVES: To estimate the risk for migraine by presence of a defined set of comorbidities, and to quantify the association of estimated healthcare costs between the case-control groups with and without comorbidity.METHODS: A matched case-control was designed using data from 1998 Idaho Medicaid claims. Cases were identified by physician-diagnoses and migraine-specific medication use. A 1:1 matching was performed on age, race, gender, and residence. Presence of comorbidity was determined by ICD-9 diagnostic categories. Total healthcare resource utilization was estimaed for all physician, hospital (inpatient and outpatient), and emergency services, including prescription medicines paid by Idaho Medicaid. Multivariate logistic regression was used to compute the odds ratio controlling for the matching variables. Multiple-regression models were used to quantify the association of total healthcare costs.RESULTS: Migraine patients were approximately five times more likely (Odds Ratio = 5.34; Confidence Interval(95%)-4.38 to 6.52) than their controls to be diagnosed with comorbid condition(s). A model with variables of age, gender, presence of comorbidity and migraine, explained approximately 21% of the variance in healthcare utilization (p < 0.05).CONCLUSIONS: Migraine patients are at a higher risk for defined comorbid conditions resulting in significantly higher healthcare costs as compared to non-migraine patients.

Journal Article↗

Characterization of chromosome 1 abnormalities in malignant melanomas.

Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanomas. Specific breakpoints are reported for malignant melanomas throughout the chromosome but especially at 1p36 and at several sites throughout 1p22-q21. In addition, partial deletions and loss of heterozygosity have been found on 1p indicating the possible location of tumor suppressor genes. Here we have characterized the involvement of chromosome 1 in a series of seven malignant melanoma cell lines. Initial chromosome painting studies revealed that six of the cell lines had chromosome 1 rearrangements. Deletions involving 1p10-32, 1q11-44, and 1q25-44 were observed. The other rearrangement breakpoints included three in the 1q10-p11 region with the rest at 1p36, 1p34, 1p32, 1p31, 1p12-13, 1q21, and 1q23. The breaks at 1q10-p11 were investigated further using an alpha-satellite 1 centromere probe and yeast artificial chromosomes (YACs) from the region. Two of the 1q10-p11 breaks mapped in the centromeric region, while the others mapped to variable sites. This suggests that the role of these rearrangements in the pathogenesis of melanomas does not involve the alteration of specific oncogenes in the breakpoint region. During the YAC mapping a previously undetected, small (<1 Mbp) del(1)(p10p11) was identified. This deletion lies within minimal overlapping deleted regions reported in head and neck as well as breast carcinomas and it could therefore facilitate the isolation of a carcinoma-associated tumor suppressor gene.

Chromosome Aberrations↗

Development of methods to assess the effects of xenobiotics in outdoor artificial streams.

Two collaborative research projects were designed to develop and validate methods for determining the chronic effects of xenobiotics in freshwater ecosystems. The work reported here focuses on the development of methods for measuring effects on fish, invertebrates, and algae in outdoor artificial streams. 3,4-Dichloroaniline (3,4-DCA), has been used as a reference xenobiotic in two artificial stream experiments. The first used five stream channels: a control and treatments ranging from 70 to 2400 microg/liter. The second used eight stream channels--a control and treatments ranging from 0.45 to 4700 microg/liter and four coupled, 510-liter-capacity, downstream ponds-a control and treatments of 1.7, 37, and 820 microg/liter. Effects on the biota of the stream channels and the downstream ponds were examined using a range of sampling techniques and in situ toxicity tests.

Aniline Compounds↗

Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure.

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

Adult↗

DLA-DQA1 polymorphisms in dogs defined by sequence-specific oligonucleotide probes (SSOP).

Several recent studies have identified DNA sequences for alleles of the DLA-DQA1 locus in the dog. To date, 10 DQA1 alleles have been reported. No data exists on the frequencies of these alleles within the general dog population, nor is there any indication of whether alleles are breed specific. We have addressed this issue by establishing a molecular-based sequence-specific oligonucleotide probing (SSOP) method to identify all published DQA1 alleles and have used these methods to type a large number of dogs. Oligonucleotide probes were designed to detect all the polymorphic sites in exon 2. This allowed assignment at the allele level. Three hundred and thirty dogs were typed for DQA1. All but two of the published DQA1 alleles were identified in these animals. One new allele was identified, and confirmed by DNA cloning and sequencing. This typing method provides a powerful tool for generating data that will be essential for studies investigating the genetic relationships between different breeds.

Animals↗

Identification of further DLA-DRB1 and DQA1 alleles in the dog.

Three novel DLA-DRB1 alleles and one novel DQA1 allele have been identified in a panel of 367 dogs. These were suggested by unusual reaction patterns found in sequence specific oligonucleotide probing (SSOP) data. Four new alleles were confirmed using DNA cloning and sequencing.

Alleles↗

Prevalence of tuberculosis infection among homeless young people in central and eastern Sydney.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection among homeless young people (aged 12-25 years) in central and eastern Sydney. METHODOLOGY: A cross-sectional survey was conducted in 16 youth refuges and four drop-in centres in Central and Eastern Sydney Health Areas and at the Cellblock Youth Health Centre, Glebe and the Kirketon Road Centre, Darlinghurst, New South Wales (NSW). Participants completed a questionnaire and underwent Mantoux testing. RESULTS: One hundred and forty-one young people completed questionnaires and 139 received a Mantoux test; 112 (80. 6%) had their Mantoux read and 10 (8.9%) were Mantoux positive (95% confidence interval 3.6-14.2). None of the risk factors examined were found to be associated with increased risk for TB infection. CONCLUSIONS: In this sample of homeless young people in central and eastern Sydney, the Mantoux positivity rate appears to be higher than the general population in NSW, but they would not currently be considered a high-risk group for TB infection.

Adolescent↗

The public health applications of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom.

BACKGROUND: In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990. METHODS: The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested. RESULTS: The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C). CONCLUSIONS: Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.

Confidentiality↗

Medical practice and manuscripts in Byzantium.

Scholars, past and present, have belittled Byzantine medicine for its perceived static and derivative nature. Applied to the medicine of the centuries immediately before and after the year 1000, these criticisms, though apparently sustainable, fail to recognize its underlying vigour. It was a practical craft medicine, and one which used elements of magic and religion to compensate for the intractability of the many diseases that were not amenable to medicine. These centuries were a time when hospitals flourished in Byzantium, and this paper assembles and describes some of the manuscripts that can be associated with them. The influence of islamic medicine, which had hitherto borrowed from Byzantium, is also examined. If the Byzantine medicine of this period could not claim great originality or innovation, it had none the less distilled what was best and most useful from the long and often complex medical writings of antiquity, ensured its transmission, and preserved much from earlier times that would otherwise now be lost.

Byzantium↗

Radial carpal bone fractures in 15 dogs.

Between 1977 and 1992, 15 adult dogs were presented to the Universities of Bristol, Glasgow, Liverpool and London with fractures of the radial carpal bone which had occurred without a known episode of violent trauma. Eleven of the dogs were boxers and the other breeds affected were a Pharaoh hound, rottweiler, springer spaniel and a greyhound. The condition was bilateral in three cases. Eleven dogs were treated surgically by cast immobilisation (four cases), fragment removal (one case), lag screw fixation (three cases), pan-carpal arthrodesis (one case) and lag screw reduction followed by pan-carpal arthrodesis (two cases). The remaining four dogs were treated conservatively with rest and tactical use of non-steroidal anti-inflammatory drugs. Follow-up periods ranged from two months to 11 years. Varying degrees of lameness, which tended to be exacerbated by exercise, persisted in all cases. The radial carpal bone appears to have at least three separate centres of ossification which eventually fuse; their planes of fusion correspond approximately to the two main fracture lines. These areas of fusion could be weak points within the radial carpal bone.

Animals↗