Biomedical subjects

J Doyle

Publications and source records attributed to J Doyle.

At least 37 records · Page 2Linked to original sources

PubMed2001

Highly optimized tolerance in epidemic models incorporating local optimization and regrowth.

In the context of a coupled map model of population dynamics, which includes the rapid spread of fatal epidemics, we investigate the consequences of two new features in highly optimized tolerance (HOT), a mechanism which describes how complexity arises in systems which are optimized for robust performance in the presence of a harsh external environment. Specifically, we (1) contrast global and local optimization criteria and (2) investigate the effects of time dependent regrowth. We find that both local and global optimization lead to HOT states, which may differ in their specific layouts, but share many qualitative features. Time dependent regrowth leads to HOT states which deviate from the optimal configurations in the corresponding static models in order to protect the system from slow (or impossible) regrowth which follows the largest losses and extinctions. While the associated map can exhibit complex, chaotic solutions, HOT states are confined to relatively simple dynamical regimes.

Journal Article↗

PubMed2001

Radioreceptor assays for sensitive detection and quantitation of saxitoxin and its analogues from strains of the freshwater cyanobacterium, Anabaena circinalis.

Toxic freshwater cyanobacteria can contaminate water supplies and adversely effect humans, agricultural livestock, and wildlife. Toxicity is strain-specific so morphological observations alone cannot predict the hazard level. Two microtiter plate based bioassays have emerged for measuring saxitoxin (STX) and its derivatives, commonly found in the freshwater cyanobacteria Anabaena and Aphanizomenon. They use radioactively labeled STX binding by sodium channels, STX's pharmacological target, or an unrelated protein, saxiphilin. These bioassays were challenged with extracts of toxic and nontoxic strains of Anabaena circinalis, and the results were compared with HPLC analysis. Both radioreceptor assays had detection limits of 2 microg STX equivalents (STXeq)/L, which is belowthe concentration proposed for a health alert, namely 3 microg STXeq/L. In all cases, statistically significant correlations existed between all toxicity measurements of the same extracts with the methods used herein. Sodium channel and saxiphilin assays however predicted less toxicity relative to HPLC analysis. The only exception to this was the equivalency observed between saxiphilin measurement and HPLC quantitation corrected for mammalian toxicity. Saxiphilin assay predicted toxicity in one strain was 3 orders of magnitude more than by sodium channel assay, and no STX was detected by HPLC. Lack of acetylcholinesterase inhibition showed this bioactivity was not anatoxin-a(S), a toxin also produced by this A. circinalis with some resemblance to the region of STX bound by saxiphilin. Presence of anatoxin-a(S) was predicted for another strain by this same acetylcholinesterase assay that, if confirmed by chemical analysis, would be the first report of anatoxin-a(S) in an Australian cyanobacterium.

Acetylcholinesterase↗

PubMed2001

A prospective comparison of octyl cyanoacrylate tissue adhesive (dermabond) and suture for the closure of excisional wounds in children and adolescents.

BACKGROUND: Recent studies suggest that the use of octyl cyanoacrylate tissue adhesive for closure of both traumatic lacerations and incisional surgical wounds results in a cosmetic outcome comparable to that achieved with conventional sutures. To date, no studies have looked at the use of tissue adhesive for higher-tension wounds, such as those created during cutaneous excisional procedures. OBJECTIVE: To compare the tissue adhesive octyl cyanoacrylate with standard suture for the closure of excisional wounds in children and adolescents. DESIGN: A prospective comparison with blinded assessment of cosmetic outcome. Twenty-eight wounds were closed with monofilament suture and 24 were closed with tissue adhesive. At approximately 2 months, photographs of the incisions were evaluated by 2 dermatologists blinded to the method of skin closure. SUBJECTS: Forty-two consecutive patients undergoing excisional dermatologic procedures at Children's Hospital, San Diego, Calif. These 42 patients had a total of 52 wounds that were evaluated. MAIN OUTCOME MEASURES: The cosmetic appearance of the wounds at 2 months, based on 2 validated wound scales: the Hollander Wound Evaluation Scale and a visual analog scale. RESULTS: There were no differences in early complications between the groups. The suture group scored higher on the visual analog scale (63.3 mm for suture vs 47.8 mm for tissue adhesive), and this difference was statistically significant (P =.02). The suture group also had a higher median score on the Hollander Wound Evaluation Scale, but this difference was not statistically significant (P =.09). CONCLUSION: The cosmetic outcome of cutaneous excisional surgery wounds closed with standard suturing was found to be superior to that of wounds closed with octyl cyanoacrylate.

Adolescent↗

PubMed2001

Preventing recurrent depression using cognitive therapy with and without a continuation phase: a randomized clinical trial.

BACKGROUND: Cognitive therapy (CT) may reduce depressive relapse and recurrence when patients learn and use the associated skills. Reported relapse and recurrence rates after CT discontinuation vary widely. The factors that determine when CT is preventive remain unidentified. We developed continuation-phase CT (C-CT) to teach responders skills to prevent relapse. This is the first randomized trial comparing CT with and without a continuation phase in responders to CT who were vulnerable, given their history of recurrent unipolar depression. METHODS: Patients aged 18 to 65 years (n = 156) with recurrent DSM-IV major depressive disorder (MDD) entered 20 sessions of acute-phase CT (A-CT). Unmedicated responders (ie, no MDD and 17-item Hamilton Rating Scale for Depression score < or =9; n = 84) were randomized to either 8 months (10 sessions) of C-CT or control (evaluation without CT). Follow-up lasted an additional 16 months. A clinician blind to assignment evaluated relapse and recurrence (ie, DSM-IV MDD). RESULTS: Over an 8-month period, C-CT significantly reduced relapse estimates more than control (10% vs 31%). Over 24 months, including the CT-free follow-up, age of onset and quality of remission during the late phase of A-CT each interacted with condition assignment to influence durability of effects. In patients with early-onset MDD, C-CT significantly reduced relapse and recurrence estimates (16% vs 67% in control). When patients had unstable remission during late A-CT, C-CT significantly reduced relapse and recurrence estimates to 37% (vs 62% in control). CONCLUSIONS: Findings suggest that 8 months of C-CT significantly reduces relapse and recurrence in the highest-risk patients with recurrent MDD. Risk factors influenced the necessity for C-CT.

Adaptation, Psychological↗

PubMed2001

What is the role of impression management in adolescent cigarette smoking?

PURPOSE: This study examined the role of impression management in cigarette smoking by linking the constructs of self-monitoring, perceived success in impression management, self-esteem and social anxiety among nonsmokers (NS), occasional smokers (OS), and frequent smokers (FS). METHODS: High school students (N=243) in years 8-12 completed a questionnaire assessing the above-mentioned variables. Multivariate discriminant function analysis and a priori contrasts were used to analyze the data. RESULTS: In comparison to OS, FS and NS had the lowest levels of self-monitoring, perceived success in impression management and self-esteem, while having the highest levels of social anxiety. IMPLICATIONS: Cigarette use may serve an impression management function during adolescence and subsequently influences OS' level of smoking. Intervention programs need to give greater consideration to providing adolescents with alternative strategies for both social acceptance and the acquisition and maintenance of self-esteem.

Adolescent↗

PubMed2001

The utility of plasma polymerase chain reaction for human herpes virus-6 among pediatric bone marrow transplant recipients: results of a pilot study.

We evaluated the utility of plasma polymerase chain reaction (PCR) for surveillance of human herpes virus 6 (HHV-6) infection among pediatric bone marrow transplant (BMT) recipients. We used a prospective, non-interventional design involving a study group and controls. BMT recipients and healthy controls were evaluated. BMT subjects had HHV-6 PCR done biweekly for 12 weeks post transplantation, while a single PCR test was done on controls. For the PCR assay, EDTA blood was collected and DNA extracted from whole blood and cell-free plasma using standard procedures. The PCR was first performed on DNA from whole blood and if a positive result was obtained, the test was repeated on the DNA from the plasma. Thirty BMT recipients (13 autologous and 17 allogeneic) were enrolled, on whom a total of 156 PCR tests were performed, while six tests were done on six healthy controls. The median age of BMT subjects was 6.2 years (range 0.5-17.5 years). The median age of the control subjects was 6.6 years (range 2-10 years). Among asymptomatic BMT patients who had PCR surveillance, the positivity rate was 3.3% (1/30) on whole blood and 0% (0/30) on plasma. None of the six healthy subjects had a positive PCR test on whole blood. During the period of the surveillance study, 14 patients had diagnostic evaluations for HHV-6 disease because of clinical symptoms. Two of these patients were diagnosed with disease associated with HHV-6 (graft failure and encephalitis) and had positive PCR tests on whole blood and plasma and whole blood and cerebrospinal fluid, respectively. We conclude that despite the fact that HHV-6 seropositivity rates are high among children, the frequency of HHV-6 plasma PCR positivity is low in pediatric BMT subjects who are asymptomatic for HHV-6 disease. Given that a positive test on plasma is consistent with active infection, this increases the utility of the PCR test as a diagnostic aid in evaluating syndromes presumed to be due to HHV-6 in pediatric bone marrow transplant recipients.

Adolescent↗

PubMed2001

Probiotic bacteria enhance murine and human intestinal epithelial barrier function.

BACKGROUND & AIMS: The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T(84) monolayers. METHODS: IL-10 gene-deficient and control mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T(84) monolayers. RESULTS: Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor alpha and interferon gamma and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. CONCLUSIONS: Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.

Animals↗

PubMed2001

Measurement of paralytic shellfish toxins in molluscan extracts: comparison of the microtitre plate saxiphilin and sodium channel radioreceptor assays with mouse bioassay, HPLC analysis and a commercially available cell culture assay.

This study compared five methods of measuring paralytic shellfish toxins (PSTs) including the long-used mouse lethality bioassay, a commercially available cell culture test (MIST Quantification kit), HPLC analysis, and two newly developed radioreceptor assays utilizing mammalian sodium channels and saxiphilin. Methods were challenged with toxic shellfish extracts prepared according to the AOAC official method. The best correlations between predicted toxicity values being 0.9 or better, were those between HPLC analysis when compared with both radioreceptor assays and the mouse lethality bioassay, as well as that between the saxiphilin and the sodium channel radioreceptor assays. In all cases, statistically significant correlations existed between the toxicity measurements of the same extracts. The ratios between some methods were not unitary as measured by the slopes of the regression lines used for correlation analyses. HPLC analysis predicted more toxicity than all of the bioassays. The saxiphilin assay underestimated toxicity relative to the mouse bioassay, the MIST kit determinations and the sodium channel assay. The sodium channel assay predicted there to be less toxicity than the mouse bioassay and the MIST kit. Of all of the techniques used, the MIST kit correlation with the mouse bioassay was nearest to one. Each method possesses differentt virtues and it may be that a multi-method approach would harness the benefits of each method for various aspects of a shellfish testing regime.

Amphibian Proteins↗

PubMed2001

Assesing the potential for struvite recovery at sewage treatment works.

Struvite in wastewater treatment plants was identified as early as 1939. Problems with struvite formation date back to the 1960s when it was noticed at the Hyperion treatment plant, Los Angeles. Operators at the plant noticed crystalline deposits on the underside of post digestion screens. The digested sludge stream was diluted and it was thought the problem was solved, until five years later when the normal gravity flow of digested sludge had decreased to such a stage that pumping was required. This paper reports the findings of a series of experiments undertaken to identify the potential of recovering struvite from sludge liquors. Seven sludge treatment works (STW) have been investigated including one detail. A number of the works has the potential to form over 100 mg l(-1) of struvite.

Hemostatics↗

PubMed2001

Cost of treatment for onychomycosis. Data from a 9-month observational study.

OBJECTIVES: To estimate component and total costs of treatment and to examine differences in cost and cost effectiveness between oral antifungal medication and local therapy for patients with toenail onychomycosis. DESIGN: Prospective, observational study of patients with onychomycosis who visited dermatologists and podiatrists in the US. Physicians provided data on clinical management, disease severity, nail improvement and resource utilisation. Patients completed questionnaires on resource utilisation and symptoms at base-line, 4 and 9 months. To estimate costs, reported utilisation was multiplied by unit costs expressed in 1997 US dollars ($US) and derived in 2 ways: first, using Medicare fees; and second, using standard physician fees. RESULTS: After adjustment for key demographic and clinical variables, participants receiving oral medication had higher total costs based on standard fees ($US794 vs $US575) and medication costs ($US564 vs $US109), lower procedure costs ($US0 vs $US122) and physician visit costs ($US200 vs $US330), and greater clinical effectiveness as measured by global improvement rating (86 vs 35%) and Toenail Symptom Index (94 vs 49%). For participants receiving oral medication, 90% of total costs were incurred during the first 4 months of follow-up, whereas for those receiving local therapy, costs were more evenly distributed throughout the study period. Incremental cost-effectiveness analysis showed $US304 to $US491 per additional case improved with oral medication over a 9-month timeframe. Extrapolation of these results using 2 time-points (months 4 and 9) suggested that cost equivalence would be reached 17 to 21 months following the initiation of treatment. CONCLUSIONS: During 9 months of follow-up in patients with toenail onychomycosis, the use of oral antifungal medication resulted in superior patient outcomes, but at higher total cost compared with local therapy.

Adult↗

PubMed2001

A retrospective analysis comparing the costs and cost effectiveness of amlodipine and enalapril in the treatment of hypertension.

A comparison of treatment costs and cost effectiveness was performed retrospectively by using patient-level data from a randomized, controlled, one-year clinical trial of amlodipine and enalapril in the treatment of mild-to-moderate hypertension. Unit costs of amlodipine and enalapril were applied to the daily dosages of individual patients to calculate the total costs and average costs per patient in each treatment group in the clinical trial on an intent-to-treat basis. Efficacy rates were used to calculate the average treatment costs per success in blood pressure control. Although not statistically significant, amlodipine treatment resulted in a higher efficacy (89.5%) vs. enalapril (85.2%). The average costs per amlodipine-treated patient were consistently lower (-$112.30) than for the enalapril-treated patient by week 50. Treatment with amlodipine resulted in an average cost per success of $609 per patient compared with $772 per enalapril-treated patient. A sensitivity analysis revealed that, in the treatment of mild-to-moderate hypertension over the 50-week treatment period, amlodipine would remain less costly than enalapril, with a decrease in the cost of enalapril of up to 17%, and would remain more cost effective, with a 21% decrease in the cost of enalapril.

Amlodipine↗

PubMed2001

The cost-effectiveness of doxazosin for the treatment of hypertension in type II diabetic patients in the UK and Italy.

The objective of this analysis was to assess the cost-effectiveness of achieving 'tight control' versus 'less tight control' of blood pressure, as defined in the UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and Italy. The effect of including doxazosin in a 'tight control' combination therapy was analysed. Given doxazosin's positive impact on lipid levels in addition to its antihypertensive effect, it is hypothesised that treatment including doxazosin will reduce the incidence of macrovascular complications. For each country, a Markov model was constructed to simulate macrovascular outcomes of patients on various drug combinations. Transitional probabilities were based on the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of the cohort and the lipid-lowering properties of doxazosin using Framingham risk equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867 Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent when included in a combination therapy in the treatment of hypertension in the diabetic populations of the UK and Italy.

Antihypertensive Agents↗

PubMed2001

Exceptionally high-rate nitrification in sequencing batch reactors treating high ammonia landfill leachate.

The nitrogen removal capacity of a suspended culture system treating mature landfill leachate was investigated. Leachate containing high ammonium levels of 300-900 mg N/L was nitrified in a bench scale sequencing batch reactor. Leachate from four different landfills was treated over a two year period for the removal of nitrogen. In this time, a highly specific nitrifying culture was attained that delivered exceptionally high rates of ammonia removal. No sludge was wasted from the system to increase the throughput and up to 13 g/L of MLSS was obtained. Settleability of the purely nitrifying biomass was excellent with SVI less than 40 mL/g, even at the high sludge concentrations. Nitrification rates up to 246 mg N/(L h) (5.91 g N/(L d)) and specific nitrification rates of 36 mg N/(gVSS h) (880 mg N/(gVSS d)) were obtained. The loading to the system at this time allowed complete nitrification of the leachate with a hydraulic retention time of only 5 hours. Following these successful treatability studies, a full-scale plant was designed and built at one of the landfills investigated.

Ammonia↗

PubMed2001

Sequencing batch reactor technology: the key to a BP refinery (Bulwer Island) upgraded environmental protection system--a low cost lagoon based retro-fit.

BP Refinery (Bulwer Island) Ltd (BP) located on the eastern Australian coast is currently undergoing a major expansion as a part of the Queensland Clean Fuels Project. The associated wastewater treatment plant upgrade will provide a better quality of treated effluent than is currently possible with the existing infrastructure, and which will be of a sufficiently high standard to meet not only the requirements of imposed environmental legislation but also BP's environmental objectives. A number of challenges were faced when considering the upgrade, particularly; cost constraints and limited plot space, highly variable wastewater, toxicity issues, and limited hydraulic head. Sequencing Batch Reactor (SBR) Technology was chosen for the lagoon upgrade based on the following; SBR technology allowed a retro-fit of the existing earthen lagoon without the need for any additional substantial concrete structures, a dual lagoon system allowed partial treatment of wastewaters during construction, SBRs give substantial process flexibility, SBRs have the ability to easily modify process parameters without any physical modifications, and significant cost benefits. This paper presents the background to this application, an outline of laboratory studies carried out on the wastewater and details the full scale design issues and methods for providing a cost effective, efficient treatment system using the existing lagoon system.

Bioreactors↗

PubMed2001

The health economic impact of antidepressant usage from a payer's perspective: a multinational study.

A multinational decision analytic model was developed to examine the treatment of major depressive disorder (MDD) in 10 European and American countries. Input to the model was obtained from a meta-analysis of current clinical trial data obtained from the published literature, and local clinical and health economic experts in each market. The patient- and policy-level impact of MDD treatment was measured in each of the 10 markets. The total expected cost per patient for treating MDD with venlafaxine XR during the six-month acute phase of MDD was the lowest expected cost in nine of the 10 countries studied, resulting in savings to the primary payer in almost all markets. As well as the cost savings, the higher efficacy and lower rate of dropout found for venlafaxine XR translate to a greater number of symptom-free-days (SFDs) per patient. The results of this investigation show that use of venlafaxine XR in most settings across Europe and the Americas will have a favourable impact on healthcare payer budgets and the overall mental health of MDD patients.

Acute Disease↗

PubMed2001

Comparison of rheumatoid arthritis care costs in patients starting therapy with leflunomide versus etanercept.

OBJECTIVE: To identify differences in rheumatoid arthritis (RA) care costs and utilization among patients receiving therapy with leflunomide (LEF) or etanercept (ETA). STUDY DESIGN: A retrospective cohort analysis of patients diagnosed with RA and starting treatment with LEF or ETA. METHODS: Patients diagnosed with RA and receiving newly prescribed LEF or ETA in 1998 were identified from a database containing patient-level medical and pharmaceutical claims. Patients were subsequently observed for 6 months. RA-related treatment charges during the observation period were compared between cohorts. RESULTS: A total of 527 LEF- and 281 ETA-treated patients were identified. The 2 cohorts were comparable with respect to demographics, comorbid conditions, and concomitant medication use, although LEF recipients were, on average, older than ETA recipients (mean age 52.97 versus 48.43 years; P < .0001). ETA recipients had higher mean 6-month postdiagnosis charges than LEF recipients ($7722.01 +/- $5285.20 versus $3301.84 +/- $4054.75; P < .0001). This difference was primarily related to differences in RA-related pharmacy charges ($5877.78 +/- $2237.68 versus $1877.23 +/- $1258.05; P < .0001). CONCLUSIONS: Compared with charges in the ETA group, RA care costs in the LEF group were significantly lower during the 6 months after the initiation of therapy. The difference in mean total RA-related charges was attributable mainly to the difference in RA-related pharmacy charges.

Adolescent↗

PubMed2001

Single or double plating for nonunion of the clavicle.

Between January 1982 and January 1999, 684 patients presented with a fracture of the clavicle to the accident and emergency departments of the Tamside and Bury District General Hospitals. Twenty patients (3%) subsequently developed symptomatic nonunion of the clavicle. The original injury resulted from a road traffic accident in 13 patients, from a fall on an outstretched hand in five patients, and two patients had sports related injuries. Mean age of the patients was 39 years (range, 17 to 76 years). Mean time from injury to surgery was 2.5 years (range, 6 months to 8 years). Fifteen patients underwent open reduction and internal fixation of the nonunion of the clavicle with a single plate (DCP or AO plate) and in the remaining five patients two plates were used. The clavicle went on to unite both clinically and radiographically in all patients. Mean time for clinical recovery of symptoms was 4 weeks (range, 3 to 15 weeks) and mean time for radiological union was 17 weeks (range, 15 to 35 weeks). The Constant score component for pain rose from a preoperative score of 0.71 to 13.8 +/- 3.5 (p < 0.0001, paired t-test). There was significant improvement for the level of activity of daily living from a preoperative score of 2.95 +/- 1.63 to 19.0 +/- 3.9. (p < 0.0001, paired t-test). The Imatani score for shoulder function rose from a preoperative score of 56.75 +/- 5.9, to a postoperative score of 98.39 +/- 4.0. No complications related to surgery were noted in the immediate postoperative period. Three patients required removal of the metal work. After removal of the plates there were no refractures of the clavicle. In conclusion, single or double plating of the clavicle is an effective technique in dealing with nonunions of both middle and distal thirds of the clavicle.

Adult↗

PubMed2000

Power laws, highly optimized tolerance, and generalized source coding

We introduce a family of robust design problems for complex systems in uncertain environments which are based on tradeoffs between resource allocations and losses. Optimized solutions yield the "robust, yet fragile" features of highly optimized tolerance and exhibit power law tails in the distributions of events for all but the special case of Shannon coding for data compression. In addition to data compression, we construct specific solutions for world wide web traffic and forest fires, and obtain excellent agreement with measured data.

Journal Article↗