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Biomedical subjects

J R Adams

Publications and source records attributed to J R Adams.

At least 19 recordsLinked to original sources

Neuroimaging in Parkinson's disease.

Structural imaging studies often reveal relatively limited findings in Parkinsonian disorders, as the most profound changes are neurochemical and hence better revealed by functional studies such as PET or SPECT. However, newer magnetic resonance techniques such as spectroscopy, diffusion weighted imaging, diffusion tensor imaging and magnetization transfer have shown promise in differentiating between idiopathic Parkinson's and the atypical parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy. We review here recent advances in functional imaging as well as in structural studies of basal ganglia disorders. Functional studies may give insights into mechanisms underlying disease pathogenesis, as well as neurochemical alterations.

Diffusion Magnetic Resonance Imaging↗

Postoperative radiographs after open reduction and internal fixation of the mandible: are they useful?

Mandibular fractures are common in oral and maxillofacial departments in the UK. The aim of this study was to find out the national practice in preoperative and postoperative radiographic investigations for fractured mandibles and to audit their diagnostic capacity, including specificity and sensitivity to short-term complications. The audit took place over a 4-month period and involved 100 patients across the Northern region. Ninety percent of patients were reviewed up to discharge and five of these patients developed a short-term postoperative complication. The postoperative radiograph was diagnostic in only one of the five cases. Overall, postoperative radiographs had a sensitivity of 20% and a specificity of 5% in their ability to predict short-term postoperative complications.

Adolescent↗

Functional imaging in Tourette's syndrome.

The cause or causes of Tourette's syndrome (TS) remain unknown. Functional imaging studies have evaluated several implicated neurotransmitter systems and focused predominantly on the frequency or severity of tics. The results have been inconclusive and frequently contradictory with little light shed on pathogenetic mechanisms. However, metabolic derangements have been demonstrated within regions of the basal ganglia, limbic system and sensori-motor cortex and are in keeping with the concept of TS as both a motor and behavioral disorder. TS has long been regarded an involuntary movement disorder. However, many patients have stated that without the premonitory sensation, there would be no tics. For this reason, it has been suggested that the premonitory urge may be considered the involuntary component of TS and the performance of the tic merely a voluntary response. Future studies are needed to differentiate functional changes relating to urge from those associated with the performance of tics and tic suppression.

Brain Chemistry↗

Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein.

Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.

Agouti-Related Protein↗

Effect of organic matter addition to the pen surface and pen cleaning frequency on nitrogen mass balance in open feedlots.

Three finishing trials were conducted to determine the effects of dietary manipulation and management on N losses from open feedlots. In each experiment, 96 steers were assigned randomly to 12 nutrient balance pens. In Trial 1, calves were fed for 180 d during the winter/spring months; in Trial 2, yearlings were fed for 132 d in the summer. In Trials 1 and 2, N losses from pens were compared directly by adding OM to the pen surface or indirectly by feeding digestible ingredients designed to increase OM excretion. The dietary treatment (BRAN) included 30% corn bran (DM basis) replacing dry-rolled corn. Pens where OM was directly added received sawdust applications (SAWDUST) at a rate to match OM excretion from the BRAN diet. These two treatments were compared with a conventional, 75% dry-rolled corn diet (CON). Because CON and SAWDUST diets were identical, performance for both treatments was similar during Trials 1 and 2. The BRAN diet decreased (P < 0.10) gain efficiency during Trials 1 and 2 by 9.5% relative to CON. Fecal N excretion was greater (P < 0.01) for calves and yearlings when BRAN was fed compared with CON. Adding OM to the pen surface increased (P < 0.01) the amount of N in manure removed from pens and reduced (P < 0.10) N losses in Trial 1. Nitrogen losses were not significantly different among treatments in Trial 2. In Trial 3, calves were fed for 166 d during the winter/spring months. A 2 x 2 factorial design was used to evaluate pen cleaning frequency and diets similar to CON and BRAN. Pens were either cleaned monthly or once at the end of the feeding period. Daily DMI was greater (P = 0.01) and ADG was lower (P < 0.01) when cattle were fed BRAN compared with CON. Responses from all three trials indicate a negative effect of BRAN on gain efficiency. Dietary treatment and cleaning frequency interacted for N balance in the feedlot. Nitrogen losses decreased and manure N increased (P < 0.10) for cattle fed BRAN compared with CON when pens were cleaned monthly. Feeding BRAN did not affect total manure N, but resulted in higher N losses when pens were cleaned only once. For all trials, BRAN increased the amount of N remaining in composted manure. Adding OM to pen surfaces and/or cleaning pens more frequently may decrease N losses from open feedlot pens and from compost, although responses seem influenced by ambient temperature or season.

Animal Feed↗

Widespread occurrence of a domestic dog mitochondrial DNA haplotype in southeastern US coyotes.

Sequence analysis of the mitochondrial DNA control region from 112 southeastern US coyotes (Canis latrans) revealed 12 individuals with a haplotype closely related to those in domestic dogs. Phylogenetic analyses grouped this new haplotype in the dog/grey wolf (Canis familiaris/Canis lupus) clade with 98% bootstrap support. These results demonstrate that a male coyote hybridized with a female dog, and female hybrid offspring successfully integrated into the coyote population. The widespread distribution of this haplotype from Florida to West Virginia suggests that the hybridization event occurred long ago before the southeastern USA was colonized by coyotes. However, it could have occurred in the southeastern USA before the main front of coyotes arrived in the area between male coyotes released for sport and a local domestic dog. The introgression of domestic dog genes into the southeastern coyote population does not appear to have substantially affected the coyote's genetic, morphological, or behavioural integrity. However, our results suggest that, contrary to previous reports, hybridization can occur between domestic and wild canids, even when the latter is relatively abundant. Therefore, hybridization may be a greater threat to the persistence of wild canid populations than previously thought.

Animals↗

Using faecal DNA sampling and GIS to monitor hybridization between red wolves (Canis rufus) and coyotes (Canis latrans).

The US Fish and Wildlife Service's (USFWS) Red Wolf Recovery Program recognizes hybridization with coyotes as the primary threat to red wolf recovery. Efforts to curb or stop hybridization are hampered in two ways. First, hybrid individuals are difficult to identify based solely on morphology. Second, managers need to effectively search 6000 km(2) for the presence of coyotes and hybrids. We develop a noninvasive method to screen large geographical areas for coyotes and hybrids with maternal coyote ancestry by combining mitochondrial DNA sequence analysis of faeces (scat) and geographic information system (GIS) technology. This method was implemented on the Alligator River National Wildlife Refuge (1000 km(2)) in northeastern North Carolina. A total of 956 scats were collected in the spring of 2000 and 2001 and global positioning system (GPS) coordinates were recorded. Seventy-five percent of the scats were assigned to species and five coyote/hybrid scats were detected. Placement of scat location coordinates on a map of the experimental population area revealed that four of the coyote/hybrid scats were detected within the home ranges of sterilized hybrids. The other coyote/hybrid scat indicated the presence of a previously unknown individual. We suggest this method be expanded to include more of the experimental population area and be optimized for use with nuclear markers to improve detection of hybrid and back-crossed individuals.

Animals↗

Influence of bone invasion and extent of mandibular resection on local control of cancers of the oral cavity and oropharynx.

The aim of this paper was to evaluate the influence of bone invasion on treatment outcome among patients with cancers of the oral cavity and oropharynx and to determine whether or not outcome was influenced by the extent of mandibular resection. A review of 127 prospectively documented patients who were treated with marginal or segmental resection for oral (n = 110) and oropharyngeal (n = 17) cancers was undertaken. There were 97 males and 30 females with a median age of 61 years. Clinical T stages were: T1 17 patients, T2 33, T3 22, T4 55. Median followup was 4 years. A total of 94 patients underwent marginal resections and 33 underwent segmental resections. Histological bone invasion was present in 17 patients (16%) in the marginal resection group and 21 patients (64%) in the segmental group (P<0.05). Soft tissue surgical margins were positive in 11 patients (12%) in the marginal group and in seven patients (21%) in the segmental group (P=not significant). Local control did not correlate significantly with T stage, the extent of mandibular resection or the presence of histological bone invasion, but was significantly influenced by positive soft tissue margins (P<0.01). Among patients with bone invasion, the local control rate was higher following segmental resection when compared to marginal resections (87% vs 75%) but this was not statistically significant. Survival was significantly influenced by positive soft tissue margins but not bone invasion or the type of resection. We conclude that bone invasion alone did not predict for local control or survival rates among patients with oral and oropharyngeal cancers. Involved soft tissue margins were highly predictive of local recurrence and decreased survival. Conservative resection of the mandible is safe as long as marginal mandibulectomy does not lead to compromise of soft tissue margins. Segmental resection should be reserved for patients extensive bone invasion or those with limited invasion in a thin atrophic mandible.

Adult↗

Pharmacoeconomics of therapy for ITP: steroids, i.v.Ig, anti-D, and splenectomy.

Factors that influence the choice of therapeutic option in treating idiopathic thrombocytopenic purpura (ITP) include cost, toxicity, and efficacy of the agent. Today the most commonly used agents for treating ITP include glucocorticoids, intravenous immunoglobulin (i.v.Ig), anti-D, and splenectomy. Splenectomy cannot be avoided in some instances, but i.v.Ig, and anti-D offer viable treatment alternatives in many cases. i.v.Ig and anti-D are both equally efficacious; however, anti-D therapy may come with lower cost to the patient and the healthcare system. Thus, in treating patients with ITP, clinical and economic considerations should be considered when choosing among the various treatment options.

Adult↗

A comparative economic analysis of pegylated liposomal doxorubicin versus topotecan in ovarian cancer in the USA and the UK.

BACKGROUND: Economic information is necessary for rational decision-making in health care. Many European countries require financial impact statements prior to drug approval, and many health care organizations in the USA consider cost-effectiveness when making formulary decisions. We report the findings and discuss the policy implications of an economic evaluation based on an international, randomized controlled trial of salvage therapy for epithelial ovarian cancer, wherein topotecan and pegylated liposomal doxorubicin (PLD) were found to have similar efficacy but differing toxicities. PATIENTS AND METHODS: Direct costs to the payer were estimated for 235 North American and 239 European trial participants who had relapsed or failed platinum-based therapy. Unit costs were obtained from national sources or previously reported economic analyses. Sensitivity analyses were also performed. RESULTS: Total cost per person in the topotecan arm was 12,325 dollars (95% CI 9445 dollars to 15,415 dollars; P >0.05) higher in the USA-based analysis and 2909 dollars (95% CI 779 dollars to 3415 dollars; P <0.05) higher in the UK-based analysis than for PLD. Pegylated liposomal doxorubicin was cost saving over a wide range of assumptions. The main differences (per person) in toxicity management following PLD compared with topotecan in Europe were for blood transfusions (1190 dollars versus 181 dollars, respectively) and hospitalizations (1197 dollars versus 280 dollars, respectively). In North America, differences were mainly for granulocyte colony stimulating factors (1936 dollars versus 419 dollars micro g, respectively), erythropoietin (3493 dollars versus 308 dollars, respectively) and blood transfusions (1346 dollars versus 140 dollars, respectively). CONCLUSIONS: Policy makers who evaluate pharmacoeconomic studies should consider international differences in health care delivery. Cost assessments based on information obtained from one country may not be relevant for policy makers in a different country.

Adult↗

Clinical trials: are they a good buy?

PURPOSE: Concern that clinical trials may be too costly has been used to justify traditionally restrictive insurer policies regarding clinical trials. Additionally, fear of insurer reimbursement denial can be a significant barrier to clinical trial participation. In this study, we reviewed the empirical data on costs of clinical trials versus standard care and summarized the current status of policy initiatives related to clinical trial insurance reimbursement. METHODS: Electronic and print data sources were searched for studies on the costs of oncology clinical trials. Information on policy initiatives for clinical trial reimbursement was obtained from the American Society of Clinical Oncology, the American Society of Hematology, and the Coalition of National Cancer Cooperative Groups and from searches of World Wide Web sites. RESULTS: Five pilot studies provided information for 377 patients on phase II/III clinical trials matched with controls on standard care. Cost estimates ranged from 10% lower to 23% higher costs/charges for clinical trials in comparison to standard medical care. Medicare, 14 states, and several private insurers now cover the costs of patient care in "qualifying" clinical trials. CONCLUSION: Findings from small pilot studies suggest that phase II and III clinical trials result in at most modest increases in cost over standard treatment costs. Also, an increasing number of policy makers have decided to support clinical trial reimbursement initiatives. It is hoped that economic data from large observational studies will facilitate widespread and permanent decisions that support reimbursement for phase I, II, and III clinical trial participation.

Clinical Trials as Topic↗

Evaluation and appraisal of randomized controlled trials in myeloma.

PURPOSE: To critically appraise therapeutic innovations tested in randomized controlled trials (RCTs) in multiple myeloma from 1966-1998. DESIGN: We performed a comprehensive search to identify published RCTs in multiple myeloma. Quality dimensions of the design, conduct, analysis and reporting of each trial were assessed. RESULTS: We identified 136 RCTs reported in 114 papers. Overall, therapeutic efforts in multiple myeloma resulted in a 5% absolute gain in five-year survival at a cost of a 0.35% increase in treatment related deaths. Hence on average a patient enrolled in a RCT in myeloma is 14 (5/35) times more likely to be helped than harmed. However, when the RCTs were critically appraised for key quality dimensions of trials' conduct, we found that only 7%) of the trials (10 of 136) were analyzed according to intention-to-treat (ITT), 9% (12 of 136) reported a power analysis (beta error), 32% (35 of 111) adequately concealed treatment allocation, 78% (106 of 136) provided a detailed description of patient withdrawals, and 83%) (19 of 22) of the double blind RCTs had appropriately described methodology. CONCLUSIONS: Therapeutic innovations tested through RCTs have improved the outcomes of patients with multiple myeloma. However, the quality of RCT reporting and methodology in multiple myeloma could be substantially improved. Most therapeutic strategies in multiple myeloma are based on modest quality, low power evidence. Despite these shortcomings our findings suggest patients may often clinically benefit from enrollment in clinical trials when available. Patients on average received modest benefit from innovative therapies tested in RCTs at little additional risk of side effects.

Humans↗

A comparison of sampling and analysis methods for low-ppbC levels of volatile organic compounds in ambient air.

A carefully designed study was conducted during the summer of 1998 to collect samples of ambient air by canisters and compare the analysis results to direct sorbent preconcentration results taken at the time of sample collection. Thirty-two 1 h sample sets were taken, each composed of a "near-real-time" sample analyzed by an autoGC-MS XonTech 930/Varian Saturn 2000 system, and Summa and Silco canisters. Hourly total non-methane organic carbon (TNMOC), ozone, and meteorological measurements were also made. Each canister was analyzed on the autoGC-MS system for a target list of 108 volatile organic compounds (VOCs) and on a manual cryosampling GC-FID system. Comparisons were made between the collection and analysis methods. Because of the low sample loading (150-250 ppbC TNMOC), these comparisons were a stringent test of sample collection and analysis capabilities. The following specific conclusions may be drawn from this study. Reasonable precision (within 15% mean difference of duplicate analyses from the same canister) can be obtained for analyses of target VOCs at low-ppbC concentrations. Relative accuracy between the GC-MS and GC-FID analysis methods is excellent, as demonstrated by comparisons of analyses of the same canisters, if measurements are sufficiently above the detection limits. This is especially significant as the GC-MS and GC-FID were independently calibrated. While statistically significant differences may be observed between the results from canister and near-real-time samples, the differences were generally small and there were clear correlations between the canister results and the near-real-time results. Canister cleanliness limits detection below the EPA Method TO-14 acceptance standard of 0.2 ppbv (0.2-2 ppbC for target analytes).

Air Pollutants↗

Genomic context modulates insulator activity through promoter competition.

Chromatin insulators regulate gene expression by preventing inappropriate enhancer-promoter interactions. Our previous study showed that insulators do not merely function as rigid blockers, rather their activities are quantitative and selective. We have investigated the factors and mechanisms that determine the effectiveness of the suHw insulator in transgenic Drosophila. We show that the suHw-mediated blockage of the AE1 enhancer from a downstream promoter depends on the ability of the promoter to compete for AE1. Promoters that are highly competitive for the enhancer are blocked less effectively. Moreover, blockage of AE1 from its cognate ftz promoter can range from virtually complete to non-detectable, depending on the property of the neighboring upstream promoter. A highly competitive neighboring promoter enhances the suHw-mediated blockage, whereas a less competitive promoter reduces the insulator effectiveness. The influence on insulator effectiveness by both the interacting and the neighboring competing promoters correlates with their ability to compete for the enhancer, which was previously shown to depend on core promoter sequences. Our findings suggest a mechanism at the level of gene organization that modulates insulator effectiveness through promoter competition. The dependence of insulator function on its cis contexts may provide it with more regulatory flexibility while imposing organizational restraints on eukaryotic gene complexes.

Animals↗

Pricing, profits and pharmacoeconomics--for whose benefit?

In today's troubled healthcare climate, it is not uncommon to run across headlines like: 'Health insurance premiums increasing by 10 percent to 30 percent across the country.' This particular New York Times article went on to explain that this premium price hike, the third consecutive double digit increase in 3 years, is driven largely by escalating pharmaceutical costs. The pharmaceutical industry has largely been vilified in the media and in the recent presidential debates, for fueling healthcare inflation and setting what many perceive to be 'unfair' prices in light of the profit margins on their life-saving products. A report released by the Congressional Research Service found that after tax, profits for the pharmaceutical industry averaged 17% of sales, compared with 5% for all other industries. The White House has added its voice to the popular discontent with notices such as this one reported in the New York Times: 'There is a rising tide politically in this country of strong antagonism against the pharmaceutical industry on the dimension of prices. (Without expanded access to insurance) price controls are an inevitable outcome.' Although the prospect of price control remains dubious in America's entrenched laissez-faire economy, David Kessler, former head of the FDA and the Dean of the Yale School of Medicine, described the situation as a 'powder keg,' stating 'the current system is simply not sustainable'. Although there does not appear to be an immediate solution to this escalating crisis, this editorial will examine pharmaceutical pricing, industry profits and the role of pharmacoeconomic analyses amidst the chaos.

Costs and Cost Analysis↗

The uncertainty principle and industry-sponsored research.

BACKGROUND: Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle. METHODS: We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding. FINDINGS: Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.

Bias↗

Further characterization of the gonad-specific virus of corn earworm, Helicoverpa zea.

The gonad-specific virus (GSV) is a DNA virus infecting the reproductive tracts of adults of both sexes of the corn earworm, Helicoverpa zea, causing severe tissue deformities leading to sterility. Atypical occlusion bodies containing large concentrations of virions embedded in a granular matrix were seen in the lumen of the oviduct and the bursa copulatrix of infected females. The virus, transmitted by both sexes, was successfully propagated in vivo and in tissue culture. The GSV genome is about 225 kb in size, with no apparent similarity to the nucleopolyhedrovirus type species, AcMNPV, genomic DNA, as determined by Southern hybridization. PCR amplification of GSV genomic DNA with primers derived from the highly conserved polyhedra gene of several baculoviruses indicated no similarity. GSV at 10(-2) female equivalents (based on virus obtained from the bursa copulatrix and oviducts of one infected female) injected into a newly emerged female and mated to a normal male resulted in >95% agonadal progeny. However, at lower doses, some of the adult progeny looked normal but apparently carried a low level of the virus that could be responsible for sustenance of infection in a given colony, as well as in nature.

Animals↗