PubMed Health⌕ Search

Biomedical subjects

J Doyle

Publications and source records attributed to J Doyle.

At least 55 records · Page 3Linked to original sources
PubMed2000

Robust perfect adaptation in bacterial chemotaxis through integral feedback control.

Integral feedback control is a basic engineering strategy for ensuring that the output of a system robustly tracks its desired value independent of noise or variations in system parameters. In biological systems, it is common for the response to an extracellular stimulus to return to its prestimulus value even in the continued presence of the signal-a process termed adaptation or desensitization. Barkai, Alon, Surette, and Leibler have provided both theoretical and experimental evidence that the precision of adaptation in bacterial chemotaxis is robust to dramatic changes in the levels and kinetic rate constants of the constituent proteins in this signaling network [Alon, U., Surette, M. G., Barkai, N. & Leibler, S. (1998) Nature (London) 397, 168-171]. Here we propose that the robustness of perfect adaptation is the result of this system possessing the property of integral feedback control. Using techniques from control and dynamical systems theory, we demonstrate that integral control is structurally inherent in the Barkai-Leibler model and identify and characterize the key assumptions of the model. Most importantly, we argue that integral control in some form is necessary for a robust implementation of perfect adaptation. More generally, integral control may underlie the robustness of many homeostatic mechanisms.

Acclimatization↗
PubMed2000

Highly optimized tolerance: robustness and design in complex systems

Highly optimized tolerance (HOT) is a mechanism that relates evolving structure to power laws in interconnected systems. HOT systems arise where design and evolution create complex systems sharing common features, including (1) high efficiency, performance, and robustness to designed-for uncertainties, (2) hypersensitivity to design flaws and unanticipated perturbations, (3) nongeneric, specialized, structured configurations, and (4) power laws. We study the impact of incorporating increasing levels of design and find that even small amounts of design lead to HOT states in percolation.

Journal Article↗
PubMed2000

Surgical resident research in New England.

HYPOTHESIS: This study sought to determine the attitudes of general surgery residents in New England toward research and the factors that affect their research participation and productivity. DESIGN: Survey. SETTING: Eighteen of the 20 general surgery residency programs in New England. PARTICIPANTS: Four hundred fifty-nine surgical residents taking the American Board of Surgery In-Training Examination in 1999. MAIN OUTCOME MEASURES: Rationale for and amount of time spent in research and the number of publications. RESULTS: A majority of residents (61%) participated in research. Rationales for research participation included initiating an academic career (82%) and enhancing fellowship application prospects (83%). Personal debt was substantial, but had little influence on decisions regarding research. Gender was not a factor in the decision to participate in research, although women were more likely to cite a break from residency as a positive influence in their decision for doing research. Residents from larger programs (>25 residents) were more likely to participate in research, spend more time in research, and to publish an article than those from programs with fewer than 25 residents. CONCLUSIONS: Most surgical residents in New England plan to or participate in research and publish their work. Significant differences in the type, duration, and productivity of research exist between larger and smaller programs, and may reflect differing priorities among residents, or differences in the variety of research opportunities available.

Adult↗
PubMed2000

Assessment of systemic toxicity in children receiving chemotherapy with cyclosporine for sarcoma.

BACKGROUND: Overexpression of P-glycoprotein in malignant tumors has been associated with poor responses to chemotherapy. It appears biologically plausible that addition of the P-glycoprotein inhibitor cyclosporine (CsA) to standard chemotherapy may improve the outcome. The protective functions of P-glycoprotein in healthy tissues, however, have not been fully elucidated. Addition of CsA may lead to increased systemic chemotherapy toxicity, so we compared the rate and severity of chemotherapy-associated systemic toxicity in the presence and absence of CsA. PROCEDURE: Standard chemotherapy consisted of etoposide/ifosfamide (VP16/IFOS) cycles, alternating with vincristine/dactinomycin/cyclophosphamide (VAC) cycles. CsA was given at a median dose of 20 mg/kg with unaltered doses of the antineoplastic drugs. The analysis of toxicity was performed by comparing clinically significant toxicity events recorded during and after chemotherapy cycles with and without CsA. RESULTS: Toxicity-related hospital admissions occurred after 93% of VAC cycles with CsA compared to 40% of the cycles without CsA (P < 0. 0001); 29% of VP16/IFOS cycles with CsA led to admissions vs. 12% with non-CsA cycles (P = 0.04). Infections or fever and neutropenia were the main reasons for these admissions. Thirty-seven percent of the VAC cycles with CsA were complicated by culture-proved sepsis, which did not occur in cycles without CsA (P < 0.0001). Requirements for blood and platelet transfusions were greatly increased after VAC cycles with CsA compared to VAC cycles without CsA. CONCLUSIONS: The chemosensitizer CsA increases the systemic toxicity of VAC chemotherapy in patients with sarcomas. Future trials of chemotherapy with chemosensitizers will have to take into account a potential increase in systemic toxicity. Careful monitoring of chemotherapy-related toxicity becomes mandatory in such studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Comparative effects of extremely high power microwave pulses and a brief CW irradiation on pacemaker function in isolated frog heart slices.

The existence of specific bioeffects due to high peak power microwaves and their potential health hazards are among the most debated but least explored problems in microwave biology. The present study attempted to reveal such effects by comparing the bioeffects of short trains of extremely high power microwave pulses (EHPP, 1 micros width, 250-350 kW/g, 9.2 GHz) with those of relatively low power pulses (LPP, 0.5-10 s width, 3-30 W/g, 9.2 GHz). EHPP train duration and average power were made equal to those of an LPP; therefore both exposure modalities produced the same temperature rise. Bioeffects were studied in isolated, spontaneously beating slices of the frog heart. In most cases, a single EHPP train or LPP immediately decreased the inter-beat interval (IBI). The effect was proportional to microwave heating, fully reversible, and easily reproducible. The magnitude and time course of EHPP- and LPP-induced changes always were the same. No delayed or irreversible effects of irradiation were observed. The same effect could be repeated in a single preparation numerous times with no signs of adaptation, sensitization, lasting functional alteration, or damage. A qualitatively different effect, namely, a temporary arrest of preparation beats, could be observed when microwave heating exceeded physiologically tolerable limits. This effect also did not depend on whether the critical temperature rise was produced by LPP or EHPP exposure. Within the studied limits, we found no indications of EHPP-specific bioeffects. EHPP- and LPP-induced changes in the pacemaker rhythm of isolated frog heart preparation were identical and could be entirely attributed to microwave heating.

Animals↗
PubMed2000

Matched unrelated bone marrow transplantation for combined immunodeficiency.

Bone marrow transplantation (BMT) from siblings is the treatment of choice for severe combined immunodeficiency (SCID). The objective of this study was to evaluate the efficiency of BMT from matched unrelated donors (MUD) in congenital immunodeficiencies when a sibling donor is unavailable. Sixteen consecutive patients with SCID (n = 9) and CID (n= 7), were referred for an unrelated donor search. Acceptable donors were found for all patients. Fifteen patients received busulfan and cyclophosphamide pretransplant conditioning. One patient had an early loss of graft and was reconditioned using cyclophosphamide and total body irradiation. The graft-versus-host disease (GVHD) prophylaxis used was methylprednisolone, cyclosporin A with or without methotrexate. Neutrophil engraftment was rapid and was achieved in all patients within a mean of 15.4 days. Only 13 episodes of fever were recorded shortly after BMT. GVHD of grade II or more was apparent in 2/9 (22%) of SCID patients and in 4/7 (57%) of CID patients. Overall survival was 75% with a mean follow-up of 47.4 months (range 18-101). Six out of nine SCID patients (67%) and 6/7 (86%) of CID patients are alive and well. Eleven patients had normal humoral immunity, and cell-mediated immunity as measured by flow cytometry and mitogenic responses, was intact in all patients. Intradermal candida skin test was positive in 9/10 patients tested. We conclude that BMT from MUD results in rapid engraftment and is therefore associated with a low rate of infection contributing to the improved survival rate. The protocol used is especially favorable for patients with combined immunodeficiency.

Anti-Bacterial Agents↗
PubMed2000

Improved survival in severe acquired aplastic anemia of childhood.

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.

Adolescent↗
PubMed2000

Effect of resident call status on ABSITE performance. American Board of Surgery In-Training Examination.

BACKGROUND: Long work hours that result in fatigue may adversely affect cognitive function. Chronically sleep-deprived surgical residents fear that being on call the night before sitting for a standardized test puts them at a potential disadvantage. We examined American Board of Surgery In-Training Examination (ABSITE) scores to assess the effect of call status on exam performance. METHODS: Results of the 1994 ABSITE for 424 residents in 15 New England general surgery programs were collected. We compared standard scores of residents for the total test, clinical management, and basic science components with resident call status (on/off) for the night before the exam. RESULTS: Differences were apparent in total test scores (mean: off, 496.1; on, 466.0; P <.03) and clinical management scores (mean: off, 504.3; on, 470.6; P <.02) (t test, Mann-Whitney U test). Multivariate analyses revealed that differences in postgraduate year level and training track were significant contributors to differences in scores in all test components (analysis of covariance). Call status was not a significant factor in score variation after adjusting for these 2 factors. CONCLUSIONS: Differences in ABSITE scores of residents were related to postgraduate year level and training track. Call status had no significant effect on ABSITE performance.

Cognition↗
PubMed2000

Age effects on the temporal evolution of isometric and swallowing pressure.

BACKGROUND: The tongue plays a key role in bolus propulsion through the oropharyngeal chamber. In this study, possible age effects on the magnitude and timing of lingual pressure generation were analyzed. METHODS: Oral pressure was measured during isometric and swallowing tasks for 10 elderly (mean age = 81 years) and 10 young (mean age = 51 years) subjects. Three trials each of the isometric task and swallows of three different boluses (3 ml semisolid, 3 ml liquid, and 10 ml liquid) were performed by each subject. The timing and magnitude of isometric and swallowing pressure generation along with the pattern of the swallowing pressure waveform were analyzed. RESULTS: Whereas maximum lingual isometric pressures decreased with age (p < .001). no significant age difference was found for swallowing pressure. Time taken to reach peak pressure also was reduced with age in both the isometric task and swallows of liquid boluses (p < .05), while no significant age effect was found for semisolid swallows. Finally, only elderly subjects showed a pattern of liquid swallowing pressure generation in which multiple lingual gestures were required to reach peak pressure (termed "pressure building"), a pattern demonstrated by both young and elderly groups for semisolids. CONCLUSIONS: Decreased lingual strength with age combined with unchanging swallowing pressure leads to a decreased "pressure reserve," perhaps leaving older individuals more at risk for dysphagia resulting from insults directly or indirectly to the swallowing system. Additionally, swallowing is generally "slowed" with age, apparently due to both central and peripheral factors, and this change may have an impact on bolus flow outcomes.

Aged↗
PubMed2000

Prostate cancer: MR imaging and thermometry during microwave thermal ablation-initial experience.

Percutaneous interstitial microwave thermoablation of locally recurrent prostate carcinoma was continually guided with magnetic resonance (MR) imaging. Phase images and data were obtained with a rapid gradient-echo technique and were used to derive tissue temperature change on the basis of proton-resonance shift. Thermally devitalized regions correlated well with the phase image findings. MR imaging-derived temperatures were linearly related to the fluoroptic tissue temperatures. MR imaging can be used to guide thermoablation.

Aged↗
PubMed2000

Influence of parental gender and self-reported health and illness on parent-reported child health.

BACKGROUND: Although there is clear evidence of the influence of parental factors on child health outcomes, the influence of parental perceptions of their health and illness on the reporting of child health remains primarily unknown. OBJECTIVES: To examine relationships between parents' reporting of their own health and illness with the reporting of their children's health and illness. METHOD: We surveyed parents of a representative population-based sample of children aged 5 to 18 years. One parent of each child completed a written questionnaire including the Child Health Questionnaire, a subjective measure of functional health and well-being, and an assessment of self-reported parental health and illness. Logistic regression models were used to examine relationships between parent and child health and illness. MAIN RESULTS: 5340 parents responded (86% mothers, 14% fathers). After adjusting for confounding effects, parents self-reporting poor health had increased odds of reporting their children with poor health (odds ratio: 7.5), although the effect was modified by parent gender. There were increased odds of mothers with self-reporting poor global health reporting their children with poor global health and illness (odds ratio: 9.0 and 2.5, respectively) that were not observed for fathers. CONCLUSIONS: A mother's self-reported health is strongly associated with her reporting of her child's health; this was not observed for fathers. These results suggest that parental gender should be considered as a mediating factor in the reporting of child health.

Adolescent↗
PubMed2000

The dual diagnosis facility: a renewed engagement with the psychiatry of intellectual disability?

A case study of a pilot residential facility for intellectually disabled adults who also suffer the effects of mental illness I presented in the context of the emergent debate surrounding the issue of dual diagnosis and co-morbidity. The innovative role of nurses in the establishment if this new service is discussed in terms of the beginning of a renewed engagement with the psychiatry of intellectual disability and it's implications for nursing practice and practice arrangements.

Child↗
PubMed2000

Probing for nasolacrimal duct obstruction with intravenous propofol sedation.

BACKGROUND: Nasolacrimal duct obstruction occurs in 5% to 6% of neonates. Many studies advocate the probing of nasolacrimal duct obstruction under general inhalational anesthesia in patients at a late age (12 to 13 months) because a high percentage will resolve spontaneously. Others support early surgical intervention in patients aged younger than 6 to 9 months without anesthesia. We present late nasolacrimal duct probing under intravenous propofol sedation as an alternative approach to the treatment of nasolacrimal duct obstruction with a decrease in cost and time compared with probing under general inhalational anesthesia. METHODS: We made a retrospective review of patient charts of children who underwent nasolacrimal duct probing with intravenous propofol sedation from April 1996 to September 1997. Procedure time and cost of procedure were compared for patients who had probings under propofol sedation to patients who had probings under general anesthesia. RESULTS: A total of 22 patients (31 eyes) underwent nasolacrimal duct probing with propofol sedation; the patients' ages ranged from 11.5 to 39 months (average age, 17.8 months). Twenty-six (84%) of 31 eyes had resolution of the symptoms. The average total time for procedure under propofol sedation was 10.5 minutes, compared with 43.6 minutes under general inhalational anesthesia. The average total recovery time under propofol sedation was 13.6 minutes, compared with 121.1 minutes with general inhalational anesthesia. The cost of probing under propofol sedation was one third less than the cost of probing under general inhalational anesthesia. DISCUSSION: Late probing for nasolacrimal duct obstruction under intravenous propofol sedation is comparable in efficacy to late probing under general inhalational anesthesia with a shorter time for the procedure and decreased expense.

Anesthesia, Intravenous↗
PubMed1999

Effect of pulsed dexamethasone therapy on tolerance of intravenously administered lipids in extremely low birth weight infants.

We investigated the effect of dexamethasone on parenteral lipid tolerance in 7-day-old extremely low birth weight infants (n = 28) in a randomized, double-blind trial. Serum triglycerides were measured before and after 3 days of dexamethasone or placebo treatment. Infants treated with dexamethasone responded with higher triglyceride concentrations and greater sensitivity to incremental increases in the intravenous lipid dose.

Dexamethasone↗
PubMed1999

The effect of induced mood states on performance profile areas of perceived need.

The performance profile technique is now widely used by a range of sports scientists, usually as the first step in implementing a training programme. The aim of this study was to examine the effect of altered mood states on areas of perceived need for an individual identified by the performance profile. Sixty-seven university sports science students (30 females, 37 males) participated in the study. They completed their performance profile and a shortened version of the Bi-polar Profile of Mood States before and after four separate mood manipulation treatments (happy, sad, neutral, control). The participants were allocated at random to one of four groups and completed the treatments in a counterbalanced order. Mood manipulation checks identified that both the happy and sad manipulations were successful. Profile areas of perceived need, identified through discrepancies in an individual's perceptions of ideal and current state, were not affected by the sad and neutral manipulations or by the control condition. However, areas of perceived need were significantly lower after the happy mood manipulation than before the treatment. Our results show that asking individuals to complete their profiles when in a happy mood state is likely to affect judgements and result in an underestimation of perceived need for improvement.

Adult↗
PubMed1999

Highly optimized tolerance: a mechanism for power laws in designed systems.

We introduce a mechanism for generating power law distributions, referred to as highly optimized tolerance (HOT), which is motivated by biological organisms and advanced engineering technologies. Our focus is on systems which are optimized, either through natural selection or engineering design, to provide robust performance despite uncertain environments. We suggest that power laws in these systems are due to tradeoffs between yield, cost of resources, and tolerance to risks. These tradeoffs lead to highly optimized designs that allow for occasional large events. We investigate the mechanism in the context of percolation and sand pile models in order to emphasize the sharp contrasts between HOT and self-organized criticality (SOC), which has been widely suggested as the origin for power laws in complex systems. Like SOC, HOT produces power laws. However, compared to SOC, HOT states exist for densities which are higher than the critical density, and the power laws are not restricted to special values of the density. The characteristic features of HOT systems include: (1) high efficiency, performance, and robustness to designed-for uncertainties; (2) hypersensitivity to design flaws and unanticipated perturbations; (3) nongeneric, specialized, structured configurations; and (4) power laws. The first three of these are in contrast to the traditional hallmarks of criticality, and are obtained by simply adding the element of design to percolation and sand pile models, which completely changes their characteristics.

Journal Article↗