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Biomedical subjects

T Duke

Publications and source records attributed to T Duke.

At least 19 recordsLinked to original sources
PubMed2001

Physical basis of two-tone interference in hearing.

The cochlea uses active amplification to capture faint sounds. It has been proposed that the amplifier comprises a set of self-tuned critical oscillators: each hair cell contains a force-generating dynamical system that is maintained at the threshold of an oscillatory instability, or Hopf bifurcation. While the active response to a pure tone provides frequency selectivity, exquisite sensitivity, and wide dynamic range, its intrinsic nonlinearity causes tones of different frequency to interfere with one another in the cochlea. Here we determine the response to two tones, which provides a framework for understanding how the ear processes the more complex sounds of speech and music. Our calculations of two-tone suppression and the spectrum of distortion products generated by a critical oscillator accord with experimental observations of basilar membrane motion and the nervous response. We discuss how the response of a set of self-tuned oscillators, covering a range of characteristic frequencies, represents the structure of a complex sound. The frequency components of the stimulus can be inferred from the timing of neural spikes elicited by the vibrating hair cells. Passive prefiltering by the basilar membrane improves pitch discrimination by reducing interference between tones. Our analysis provides a general framework for examining the relation between the physical nature of the peripheral detection apparatus and psychophysical phenomena such as the sensation of dissonance and auditory illusions.

Cochlea↗
PubMed2001

Near-field scanner for moving molecules.

We have fabricated using electron beam nanolithography a fixed slit near-field optical scanning device which uses near-field fluorimetry to achieve 200 nm spatial resolution of objects moving over the slits. We explore the basic physics of operating narrow slits in the waveguide cutoff mode and present data from the passage of extended double-stranded DNA molecules passing over the slits as a first example of how this device can be used to do ultrahigh spatial resolution mapping of long polymers.

Algorithms↗
PubMed2001

Hypoxaemia in children with severe pneumonia in Papua New Guinea.

OBJECTIVES: To investigate the severity and duration of hypoxaemia in 703 children with severe or very severe pneumonia presenting to Goroka Hospital in the Papua New Guinea highlands; to study the predictive value of clinical signs for the severity of hypoxaemia, the predictive value of transcutaneous oxygen saturation (SpO2) and other variables for mortality. DESIGN: Prospective evaluation of children with severe or very severe pneumonia. SpO2 was measured at the time of presentation and every day until hypoxaemia resolved. Children with a SpO2 less than 85% received supplemental oxygen. By comparing with a retrospective control group for whom oxygen administration was guided by clinical signs, we evaluated whether there was a survival advantage from using a protocol for the administration of oxygen based on pulse oximetry. We determined normal values for oxygen saturation in children living in the highlands. RESULTS: In 151 well, normal highland children, the mean SpO2 was 95.7% (SD 2.7%). The median SpO2 among children with severe or very severe pneumonia was 70% (56-77); 376 (53.5%) had moderate hypoxaemia (SpO2 70-84%); 202 (28.7%) had severe hypoxaemia (SpO2 50-69%); and 125 (17.8%) had very severe hypoxaemia (SpO2 < 50%). Longer duration of cough or the presence of hepatomegaly or cyanosis predicted more severe degrees of hypoxaemia. After 10, 20 and 30 days from the beginning of treatment, respectively 102 (14.5%), 38 (5.4%) and 19 (2.7%) of children had persistent hypoxaemia; 46 children (6.5%) died. Predictors of death were low SpO2 on presentation, severe malnutrition, measles and history of cough for more than 7 days. The mortality risk ratio between the 703 children managed whose oxygen administration was guided by the use of pulse oximetry and the retrospective control group who received supplemental oxygen based on clinical signs was 0.65 (95%CI 0.41-1.02, two-sided Fisher's exact test, P = 0.07). CONCLUSION: There is a need to increase the availability of supplemental oxygen in smaller health facilities in developing countries, and to train health workers to recognise the clinical signs and risk factors for hypoxaemia. In moderate sized hospitals a protocol for the administration of oxygen based on pulse oximetry may improve survival.

Child, Preschool↗
PubMed2000

The immature-to-total neutrophil ratio (IT ratio) is a sensitive indicator of sepsis after paediatric cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) causes a systemic inflammatory response syndrome (SIRS) with activation of neutrophils (increased immature-to-total neutrophil ratio, IT ratio). Does an additional inflammatory response induced by sepsis further increase the IT ratio, so that it can still be used as an indicator of sepsis? In 160 children we analysed retrospectively the IT ratios from the day before CPB to the 10th day after the operation (controls). The 95% confidence limits of the controls were plotted against postoperative day and compared with the IT ratio courses in all children of a 4-year period who developed sepsis during the first 10 days after CPB. All septic children (n = 9) had IT ratios above the upper 95% confidence limits of the controls on the day of positive culture or on the following day. The IT ratio remains a sensitive indicator of sepsis even after CPB.

Cardiopulmonary Bypass↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗