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Biomedical subjects

T Duke

Publications and source records attributed to T Duke.

At least 19 recordsLinked to original sources

Cooperativity of myosin molecules through strain-dependent chemistry.

There is mounting evidence that the myosin head domain contains a lever arm which amplifies small structural changes that occur at the nucleotide-binding site. The mechanical work associated with movement of the lever affects the rates at which the products of ATP hydrolysis are released. During muscle contraction, this strain-dependent chemistry leads to cooperativity of the myosin molecules within a thick filament. Two aspects of cooperative action are discussed, in the context of a simple stochastic model. (i) A modest motion of the lever arm on ADP release can serve to regulate the fraction of myosin bound to the thin filament, in order to recruit more heads at higher loads. (ii) If the lever swings through a large angle when phosphate is released, the chemical cycles of the myosin molecules can be synchronized at high loads. This leads to stepwise sliding of the filaments and suggests that the isometric condition is not a steady state.

Adenosine Diphosphate↗

Auditory sensitivity provided by self-tuned critical oscillations of hair cells.

We introduce the concept of self-tuned criticality as a general mechanism for signal detection in sensory systems. In the case of hearing, we argue that active amplification of faint sounds is provided by a dynamical system that is maintained at the threshold of an oscillatory instability. This concept can account for the exquisite sensitivity of the auditory system and its wide dynamic range as well as its capacity to respond selectively to different frequencies. A specific model of sound detection by the hair cells of the inner ear is discussed. We show that a collection of motor proteins within a hair bundle can generate oscillations at a frequency that depends on the elastic properties of the bundle. Simple variation of bundle geometry gives rise to hair cells with characteristic frequencies that span the range of audibility. Tension-gated transduction channels, which primarily serve to detect the motion of a hair bundle, also tune each cell by admitting ions that regulate the motor protein activity. By controlling the bundle's propensity to oscillate, this feedback automatically maintains the system in the operating regime where it is most sensitive to sinusoidal stimuli. The model explains how hair cells can detect sounds that carry less energy than the background noise.

Animals↗

Suspected tolazoline toxicosis in a llama.

Clinical signs of tolazoline toxicosis developed in a 4-year-old llama that received 2 doses of tolazoline hydrochloride to reverse xylazine-induced sedation. The full first dose (4.3 mg/kg [2.0 mg/lb] of body weight) was erroneously injected i.v., and the second dose was administered half i.v., half i.m. 45 minutes later, because the llama became weak and recumbent. Signs of anxiety, hyperesthesia, profuse salivation, and tachypnea were the first detectable clinical signs of tolazoline toxicosis. Convulsions, hypotension, gastrointestinal tract hypermotility, and diarrhea also developed. The llama was treated successfully with i.v. administration of diazepam, phenylephrine, and lactated Ringer's solution supplemented with potassium chloride and oxygen administered via nasal insufflation. We suggest that the maximum dose of tolazoline administered at any one time to llamas not exceed 2 mg/kg (0.91 mg/lb). Furthermore, tolazoline should be administered slowly i.v. or i.m. to reduce the risk of adverse reactions.

Adrenergic alpha-Agonists↗

Sorting biomolecules with microdevices.

Micro- and nanofabrication techniques have provided an unprecedented opportunity to create a designed world in which separation and fractionation technologies which normally occur on the macroscopic scale can be optimized by designing structures which utilize the basic physics of the process, or new processes can be realized by building structures which normally do not exist without external design. Since microfabrication is exceedingly sophisticated in its development, it is possible to design and construct highly creative microdevices which allow one to probe specific aspects of biological objects. We give examples of uses of micro- and nanofabrication which, as opposed to simply shrinking the size of the vessels or tubes used in macroscopic lab environments, utilize our understanding of the physics of the process to take advantage of fabrication technologies.

Animals↗

An exercise intervention for advanced cancer patients experiencing fatigue: a pilot study.

Fatigue is reported by advanced cancer patients to be their most prevalent and distressing symptom. Despite this, few interventions have been developed and tested to manage this debilitating symptom. This paper describes a pilot study undertaken to test the effects of a 28-day exercise intervention on levels of fatigue in advanced cancer patients. All participants were able to increase their activity levels with no increase in reported fatigue. Furthermore, a trend was noted in all patients toward increased quality of life scores and decreased anxiety scores. All participants described a sense of satisfaction in attaining increased activity levels. These preliminary pilot results suggest that patients who initially report the highest levels of fatigue may achieve the largest decrease in fatigue scores. These findings provide support for the suitability of this intervention for the palliative care population and justify the importance of further hypothesis testing.

Activities of Daily Living↗

Meningitis or madness: a delicate balance.

A child with meningitis who developed a psychosis 2 weeks after commencing treatment with antituberculous therapy is described here. The psychosis resolved with cessation of isoniazid, but the meningitis returned. The meningitis was treated by re-introduction of daily doses of isoniazid, but the psychosis recurred. Successful treatment of the meningitis, with minimal psychotic symptoms, eventually was achieved using isoniazid at 48 h dose intervals. The psychosis resolved completely after completion of therapy for tuberculous meningitis and cessation of isoniazid. This is the first case of isoniazid-associated psychosis reported in a child.

Antitubercular Agents↗

The ventricular assist device as a bridge to cardiac transplantation.

Congestive heart failure is occurring in the United States at an increasing rate. Transplantation remains the treatment of choice for end-stage heart failure. Prolonged waiting time and decreased availability of suitable organs has increased the necessity for a device to act as a bridge to transplantation to keep patients alive during the waiting period. Ventricular assist devices have become an accepted and proven option for patients whose condition deteriorates to the point that waiting for an available donor organ is a mortal risk. With proper patient selection and timely device insertion, these patients can remain stable until a donor organ becomes available.

Equipment Design↗

Nucleated red blood cells after cardiopulmonary bypass in infants and children: is there a relationship to the systemic inflammatory response syndrome?

In a retrospective case control study we aimed to evaluate whether infants and children with nucleated red blood cells (NRBCs) in their peripheral blood smears after cardiopulmonary bypass (CPB) had longer bypass times than controls without NRBCs. On review of a 3-year period, 58 children with NRBCs after CPB (and without NRBCs prior to CPB) were identified (cases). A random sample of 100 children without NRBCs after CPB over the same period served as controls. The median age (range) of the children with NRBCs and without NRBCs was 0.6 years (2 days to 20 years) and 1.4 years (2 days to 16 years), respectively (p = 0.03). The children with NRBCs had a significantly longer bypass time than the controls (mean, standard deviation (SD): 114 min, 50 vs 79 min, 46 min; p < 0.0001). For the patients with postoperative polychromasia alone, the mean CPB time (111 min, SD 46 min) was also significantly longer than the respective time in the controls (p < 0.001). Markers of organ dysfunction (renal failure, use of inotropic support, time of endotracheal intubation, stay in intensive care unit and stay in hospital) were significantly more frequent/longer in the NRBC group. Post-CPB release of NRBCs is associated with longer CPB time. This alteration may be part of the CPB-related systemic inflammatory response syndrome.

Adolescent↗

Intravenous regional anesthesia (Bier block) in a dog.

Intravenous regional anesthesia was used in an adult dog as part of a balanced approach to general anesthesia for amputation of the 4th digit of its right hind limb. It allowed the concentration of isoflurane to be reduced to 0.5%.

Amputation, Surgical↗

The effect of opioid and acepromazine premedication on the anesthetic induction dose of propofol in cats.

The median effective dosage (ED50) for induction of anesthesia with propofol was determined by using the up-and-down method in 31 unpremedicated cats, in 30 cats premedicated with butorphanol, 0.4 mg/kg body weight (BW), and acepromazine, 0.1 mg/kg BW, intramuscularly, and in 30 cats premedicated with morphine, 0.2 mg/kg BW, and acepromazine, 0.1 mg/kg BW, intramuscularly. The dose required for a satisfactory anesthetic induction in 50% of unpremedicated cats (ED50) was 7.22 mg/kg BW and of premedicated cats was 5.00 mg/kg BW. The reduction in dose was statistically significant in both premedicated groups compared with no premedication. There was no significant difference in ED50 between premedication regimes. Cyanosis was the most common adverse effect observed in all groups following anesthetic induction with propofol.

Acepromazine↗

Separation techniques.

The past two years have seen continued development of capillary electrophoresis methods. The separation performance of flowable sieving media now equals, and in some respects exceeds, that provided by gels. The application of microfabrication techniques to separation science is gaining pace. There is a continuing trend towards miniaturization and integration of separation with preparative or analytical steps. Innovative separation methods based on microfabrication technology include electrophoresis in purpose-designed molecular sieves, dielectric, trapping using microelectrodes, and force-free motion in Brownian ratchets.

Biocompatible Materials↗

Sequencing in nanofabricated arrays: a feasibility study.

The feasibility of using nanofabricated arrays as electrophoretic chambers for DNA sequencing is investigated. A specific array design, consisting of rows of closely spaced posts, separated by longer open spaces, is proposed. Molecules driven through the array by an electric field get hooked over obstacles at successive rows and their progress through the device is delayed as a consequences. The dependence of the delay time on molecular size is derived. Numerical evaluation indicates that a device of modest dimensions, operating at high fields, can rapidly resolve oligonucleotides containing several hundred bases.

DNA↗

Early markers of major adverse events in children after cardiac operations.

OBJECTIVES: The purpose of this study was to determine the physiologic variables that predict major adverse events in children in the intensive care unit after cardiac operations. METHODS: A cohort observational study was conducted. At the time of admission to the intensive care unit and 4, 8, 12, and 24 hours later the following variables were recorded: mean arterial pressure, heart rate, cardiac index, oxygen delivery, mixed venous oxygen saturation, base deficit, blood lactate, gastric intramucosal pH, carbon dioxide difference (the difference between arterial carbon dioxide tension and gastric intraluminal carbon dioxide tension), and toe-core temperature gradient. Major adverse events were prospectively identified as cardiac arrest, need for emergency chest opening, development of multiple organ failure, and death. RESULTS: Ninety children were included in the study; 12 had major adverse events and there were 4 deaths. Blood lactate level, mean arterial pressure, and duration of cardiopulmonary bypass were the only significant, independent predictors of major adverse events when measured at the time of admission to the intensive care unit. The odds ratio (95% confidence intervals) for major adverse events if a lactate level was greater than 4.5 mmol/L was 5.1 (1.2 to 21.1), for admission hypotension 2.3 (0.5 to 9.8), and for a cardiopulmonary bypass time greater than 150 minutes 13.7 (3.3 to 57.2). Four hours after admission lactate and carbon dioxide difference, and 8 hours after admission lactate and base deficit, were independently significant predictors. The odds ratios for major adverse events if the blood lactate level was greater than 4 mmol/L at 4 and 8 hours were 8.3 (1.8 to 38.4) and 9.3 (1.9 to 44.3), respectively. At no time in the first 24 hours were cardiac output, oxygen delivery, mixed venous oxygen saturation, toe-core temperature gradient, or heart rate significant predictors of major adverse events. CONCLUSIONS: In the context of our current treatment strategies, the duration of cardiopulmonary bypass and blood lactate level, measured in the early postoperative period, were the best predictors of impending major adverse events.

Blood Pressure↗