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PubMed1997

A comparison of the infusion pharmacokinetics and pharmacodynamics of cisatracurium, the 1R-cis 1'R-cis isomer of atracurium, with atracurium besylate in healthy patients.

We have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mg.kg-1 and 10 patients (Group A) were given atracurium 0.5 mg.kg-1. Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train-of-four had recovered to 5% of control, an infusion of cisatracurium 3 micrograms.kg-1.min-1 was started in Group C and an infusion of atracurium 10 micrograms.kg-1.min-1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train-of-four at 5% of control. The times to 90% and maximum depression of the first twitch of the train-of-four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high-performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non-linear Mixed Effects Model program. A two-compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans-trans group having the highest clearance (1440 ml.min-1) and the cis-cis group the lowest (499 ml.min-1). The clearance of cisatracurium (425 ml.min-1) is less than that of cis-cis atracurium and its elimination half-life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was one-fifth of that after atracurium.

Adult↗
PubMed1984

Plasma disappearance of ovine corticotrophin-releasing factor in man.

Disappearance of immunoreactive ovine corticotrophin-releasing factor (IR-oCRF) from plasma after a single intravenous injection of ovine corticotrophin-releasing factor (oCRF) was studied in man in the morning and evening. Synthetic oCRF (80 micrograms) was injected intravenously to four normal male volunteers at 0900 h or at 2200 h. Blood samples were drawn before and 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after the oCRF injection. Plasma IR-oCRF was measured by a specific radioimmunoassay for OCRF. Plasma concentrations of IR-oCRF after oCRF injections in the morning and in the evening did not differ significantly (P greater than 0.05). Disappearance of IR-oCRF was modelled with a two-exponent function by using a non-linear least squares computer program. The metabolic clearance rate, the apparent initial volume of distribution, the plasma half-life for the fast component and that for the slow component calculated from all eight tests in the morning and evening were 1.49 +/- 0.05 ml/min X kg, 44.4 +/- 1.7 ml/kg, 6.8 +/- 0.7 min and 46.2 +/- 2.3 min (mean +/- SEM), respectively. This relatively long half-life may be responsible for the prolonged biological effect of oCRF administered intravenously. There were no significant differences between parameters of IR-oCRF disappearance curves in the morning and those in the evening (P greater than 0.05).

Adult↗
PubMed1978

Cobalt hemoglobin: pH dependence of Adair constants and the Bohr effects.

Precise oxygen equilibrium curves have been obtained for cobalt hemoglobin at pH values from 5.5 to 8.2. The Hill plots are symmetric having asymptotes with slopes of unity. At pH 7.0, cobalt hemoglobin has p0.5 = 116 toor (15.45 kPa), pm = 117 torr (15.58 kPa) and a Hill coefficient of n = 1.72. The values of n decrease slightly with either decrease or increase of pH; the protein is almost non-cooperative at pH greater than 8.2. The Adair constants have been calculated with a non-linear least-squares program. From deltalnpm/deltapH a maximum of 2.5 Bohr protons was calculated at physiological pH values. The majority of alkaline Bohr protons are released after binding of the first and the third oxygen with maxima at pH 7.6 and 7.3, respectively. The acid Bohr effect was also observed with the majority of the protons taken up following the first and third oxygen bound. Smaller alkaline Bohr effects were obtained by differential titration and at higher pH than that calculated from oxygen equilibria. The discrepancy can be largely attributed to the binding of salt components to cobalt hemoglobin.

Cobalt↗
PubMed1991

Salivary excretion of mexiletine in normal healthy volunteers.

To investigate the kinetics and correlation between serum and saliva levels of mexiletine, serum (total and unbound) and saliva drug concentration-time courses have been analysed in five normal healthy volunteers after administration of a single oral dose (200 mg) of the drug. Mexiletine levels in saliva were always higher than those in serum. The drug concentration-time curve in each sample was analysed according to the non-linear least squares regression program MULTI, for a two-compartment model with first-order absorption. The saliva drug concentration in the post-absorption phase was found to be well correlated with either corresponding serum total or serum unbound drug level in four of the subjects. Although there was a large inter-individual variation in the ratio of saliva to serum drug concentrations as well as in the pharmacokinetic parameters, an almost consistent ratio was obtained in each individual.

Administration, Oral↗
PubMed2000

Time normalization of voice signals using functional data analysis.

The harmonics-to-noise ratio (HNR) has been used to quantify the waveform irregularity of voice signals [Yumoto et al., J. Acoust. Soc. Am. 71, 1544-1550 (1982)]. This measure assumes that the signal consists of two components: a harmonic component, which is the common pattern that repeats from cycle-to-cycle, and an additive noise component, which produces the cycle-to-cycle irregularity. It has been shown [J. Qi, J. Acoust. Soc. Am. 92, 2569-2576 (1992)] that a valid computation of the HNR requires a nonlinear time normalization of the cycle wavelets to remove phase differences between them. This paper shows the application of functional data analysis to perform an optimal nonlinear normalization and compute the HNR of voice signals. Results obtained for the same signals using zero-padding, linear normalization, and dynamic programming algorithms are presented for comparison. Functional data analysis offers certain advantages over other approaches: it preserves meaningful features of signal shape, produces differentiable results, and allows flexibility in selecting the optimization criteria for the wavelet alignment. An extension of the technique for the time normalization of simultaneous voice signals (such as acoustic, EGG, and airflow signals) is also shown. The general purpose of this article is to illustrate the potential of functional data analysis as a powerful analytical tool for studying aspects of the voice production process.

Data Interpretation, Statistical↗
PubMed2006

Investigating the relation between placement of Quit antismoking advertisements and number of telephone calls to Quitline: a semiparametric modelling approach.

STUDY OBJECTIVES: Quitline-an antismoking advertising and a telephone helpline service-is an effective public health intervention strategy for tobacco control. The objective of this short report is to model the relation between placement of antismoking advertisements and calls to Quitline on a given day. METHODS/DESIGN: Data on daily Quitline antismoking advertisements, television target audience rating points (TARPS), and calls to Quitline Victoria were studied for the period 1 August 2000 and 31 July 2001. The outcome-calls to Quitline-is a count and thus assumed to follow a Poisson distribution. Generalised partial linear models were used to model the logarithm of mean daily calls as a non-parametric function of time and a linear parametric function of the day of week, number of advertisements, and TARPS. MAIN RESULTS: Peak calls to Quitline Victoria occurred during Monday to Wednesday with around three times as many calls compared with Sunday. Both placement of Quitline advertisements (p<0.001) and an increase in TARPS (p<0.001) on a given day significantly increased the number of calls made to Quitline Victoria. The model adequately captured fluctuations in call volume and diagnostics showed no model inadequacy. CONCLUSIONS: In this short report the emphasis is on modelling the parametric components-day of week, placement of advertisements, and TARPS on call volume. The dynamics of the underlying time trend in call volume is captured in a non-parametric component. Future analysis of hourly data would provide additional information to assess different media buying strategies that might increase call volume.

Adult↗
PubMed1975

Computer Diagnosis of Breast Thermograms.

A computer-based technique was developed for the automated diagnosis of breast thermogram. Eighty-five thermograms were digitized and analyzed, and 23 parameters computed for each thermogram. A statistical decision program, based on a linear discriminant analysis technique, classified the thermograms into normal and abnormal categories. The accuracy of classification was evaluated by several techniques and found to be comparable to that of trained thermographers.

Breast Neoplasms↗
PubMed2005

Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women.

OBJECTIVE: Hormone therapy use has been positively associated with mammographic density in several studies. However, few studies have examined the association between endogenous hormone levels and mammographic density. Therefore, we evaluated the relationship of endogenous sex hormones, insulin-like growth factor (IGF), and lipids with mammographic density in 88 overweight, postmenopausal women not taking hormone therapy. METHODS: Percent density and dense area were evaluated as continuous measures using a computer-assisted program. We used multiple linear regression to evaluate the associations of sex hormones, IGF, and cholesterol with mammographic density, adjusting for confounders, including adiposity. We evaluated stratification by history of hormone therapy use (former versus never) and hormone therapy latency (<5 versus > or = 5 years). RESULTS: Among former hormone therapy users, mammographic density was inversely associated with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02), androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar associations when we limited the analyses to women who had used hormone therapy within the past 5 years. We also noted positive associations of mammographic density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03) among former hormone therapy users. No associations were noted among women who had never used hormone therapy. CONCLUSIONS: These results suggest that there is an inverse relationship between endogenous sex hormones and mammographic density in postmenopausal women among former users of hormone therapy. This is not consistent with the hormone therapy literature and should be confirmed in larger studies.

Aged↗
PubMed1998

Relationship between growth and the pattern of tooth initiation in alligator embryos.

The temporal and spatial patterns in which teeth are initiated in the growing jaws of embryos are constant for a species but different for different species. The sources of the patterns have been explained in two ways. First, they are the outcome of reactions between molecules created at stationary targets and those which diffuse through embryonic tissues (e.g., Edmund, 1960). Second, Osborn (1978) supposed that the patterns mirror the way a (mixed) population of parent cells, the tooth clone, grows. Westergaard and Ferguson (1986, 1987, 1990) concluded, from their observations of the sequence of tooth initiation in alligators, that the complicated sequences in which 20 teeth are initiated in each tooth quadrant could not be explained by jaw growth. The present study attempts to refute this criticism by means of measurements made from the raw data published by Westergaard and Ferguson. These data reveal that new teeth, here called primary teeth, are added at a constant rate at the back of the jaw. Interstitial growth of the cells between primary teeth creates space for secondary teeth in secondary regions. The secondary regions increase in length exponentially with time. The sequence in which teeth are initiated in the growing secondary regions was found to be the same in every part of the upper and lower jaws. It was accurately reproduced by a computer program based on a linear contraction rate of inhibitory zones and exponential growth of secondary regions. The results suggest that the posterior progress zone in alligator embryos grows about 125 microm a day. Newly initiated tooth germs are surrounded by an inhibitory zone about 250 microm in diameter. These zones contract from 20 to 30 microm a day until they are about 170 microm in diameter. The sequences in which tooth positions are initiated in embryos may be more the result of the pattern in which cells escape from molecules that inhibit induction rather than the pattern in which cells create molecules that initiate induction.

Alligators and Crocodiles↗
PubMed2001

Interaction of diphenyltin(IV) dichloride with some selected bioligands.

The interaction of diphenyltin(IV) with selected bioligands having a variety of model functional groups were investigated using the potentiometric technique. The hydrolysis constants of diphenyltin(IV) cation and the step-wise formation constants of the complexes formed in solution were calculated using the non linear least-squares program MINIQUAD-75. The participation of different ligand functional groups in binding to organotin is discussed. The concentration distribution of the various complex species was evaluated as a function of pH.

Algorithms↗
PubMed2002

PCR-based detection of a rare linear DNA in cell culture.

The described method allows for detection of rare linear DNA fragments generated during genomic deletions. The predicted limit of the detection is one DNA molecule per 10(7) or more cells. The method is based on anchor PCR and involves gel separation of the linear DNA fragment and chromosomal DNA before amplification. The detailed chemical structure of the ends of the linear DNA can be defined with the use of additional PCR-based protocols. The method was applied to study the short-lived linear DNA generated during programmed genomic deletions in a ciliate. It can be useful in studies of spontaneous DNA deletions in cell culture or for tracking intracellular modifications at the ends of transfected DNA during gene therapy trials.

Journal Article↗
PubMed1990

Effect of glucocorticoids on alpha 1-adrenergic receptor binding in rat vascular smooth muscle.

Glucocorticoids are known to have marked effects on blood pressure regulation, predominantly through altering cardiovascular sensitivity to noradrenaline. However, the molecular mechanisms underlying this action remain unclear. As part of our studies into these we have measured alpha 1-adrenergic receptor binding using the ligand [3H]prazosin in plasma membrane fractions of aortas prepared from control, adrenalectomized and dexamethasone-treated adrenalectomized rats. In controls there were 50 +/- 8 (S.E.M.; n = 6) fmol alpha 1-adrenergic receptors/mg membrane protein (Bmax) with a dissociation constant (Kd) of 0.52 +/- 0.10 nM (n = 6). Adrenalectomy 8 days before tissue preparation caused a 40% decrease in Bmax and a 60% decrease in Kd. Dexamethasone replacement after adrenalectomy returned these values close to those of controls. Noradrenaline competed for the [3H]prazosin-binding sites. Computer analysis by a non-linear curve-fitting program (LIGAND) showed that noradrenaline binding was to a heterogeneous population of high- and low-affinity receptors with Kd values of 1.87 +/- 0.73 microM and 0.48 +/- 0.12 mM (n = 5) respectively. Guanosine thiotriphosphate (GTP[S]) caused the conversion of high-affinity to low-affinity binding, consistent with the model of the high-affinity sites being coupled to a G protein. After adrenalectomy, noradrenaline binding was to a homogeneous population of low-affinity receptors; hence, the effect of GTP[S] was no longer apparent, suggesting that under these conditions the alpha 1-adrenergic receptors were unable to couple to a G protein. The two-site model of binding and GTP[S] effect was returned by dexamethasone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed2001

PDL: a definition language for trend pattern representation and detection in medicine.

This paper proposes a pattern definition language, PDL, to effectively represent and manipulate trend patterns to support medical decision making in time-critical domains. Based on a modified version of SDL, a shape definitional language introduced by Agrawal, PDL extends the expressive power of SDL in the temporal domains. PDL also permits irregular length of elementary patterns to be matched in the query. This paper describes the syntax and the semantics of PDL, as well as illustrating how it can be applied in a time-critical medical domain.

Critical Care↗
PubMed2002

The operating version of the Eye Tracker, a system to measure saccadic eye movements.

The operating version of the Eye Tracker, a transducer and system using a technique to bounce infrared light off the eye to measure saccadic eye movements in any X-Y position is presented in this paper. Discussed is the method of reading and analyzing eye movement data using a 24-channel infrared optoelectronic array and computer algorithms that utilize a linear regression model to interpret and determine eye location, the 24-channels used to ensure accurate reading of eye position. Accuracy is also maintained by a signal processing system that attenuates incident light as well as ambient light. Also discussed is a novel method of mounting the infrared array on hemispherical shaped eyepieces that in turn are mounted on goggles styled after an ophthalmologist's test frames that is comfortably worn and adjustable in size to fit any subject. A computer controlled, wall mounted light bank facilitates targeting for eye movements. The Eye Tracker is built to meet standards of a professional medical device manufacturer following typical mechanical, electrical, and safety techniques unique to device packaging.

Diagnosis, Computer-Assisted↗
PubMed1977

[Electronic measuring and calculating devices for arcogrammetric model diagnosis and for the interpretation of teleradiographs].

A newly developed method to mesure different parameters from plaster models of the teeth, from dental radiographs and from cephalometric X-rays by means of a 4-K minicomputer and on-line linear transducers are described. Programs in connection to Arcogrammetrics [Herren] are presented. The electronic devices allow storage of these parameters in order to make drawings of the actual dental arches and of predicted arches, as well as to trace growth and/or progress in orthodontic treatment.

Cephalometry↗
PubMed1980

Acyl-CoA synthetase in rat liver peroxisomes. Computer-assisted analysis of cell fractionation experiments.

The subcellular distribution of the acyl coenzyme A synthetases of rat liver was reinvestigated in order to determine whether part of this activity occurs in peroxisomes. Rat liver was fractionated by differential centrifugation and by equilibrium density centrifugation. Acyl-CoA synthetase was assayed using a new, simple extraction procedure on three substrates: palmitate, laurate, and octanoate. Comparison of the resulting synthetase distributions with the distributions of marker enzymes for peroxisomes, mitochondria, and endoplasmic reticulum demonstrated the presence of some synthetase activity in each of the three organelles. These trimodal synthetase distributions were evaluated quantitatively by means of a computer program that calculated optimal linear combinations of marker enzymes using a least squares criterion. Peroxisomes were found to contain 7% of the liver's palmitoyl-CoA synthetase activity and 6% of its lauroyl-CoA synthetase activity, but no demonstrable octanoyl-CoA synthetase activity. The remainder of these activities are divided between the mitochondria and endoplasmic reticulum, in a manner that agrees with previous studies. The chain length specificity of the synthetase(s) of each organelle appears to be unique. The absolute activity of the peroxisomal palmitoyl-CoA synthetase is sufficient to maintain maximal peroxisomal beta-oxidation. Clofibrate treatment of the rats caused a 2.6- to 3.1-fold increase in the liver's total acyl-CoA synthetase activities. The subcellular distribution was not greatly affected by this drug treatment.

Animals↗
PubMed2005

Design and testing of low intensity laser biostimulator.

BACKGROUND: The non-invasive nature of laser biostimulation has made lasers an attractive alternative in Medical Acupuncture at the last 25 years. However, there is still an uncertainty as to whether they work or their effect is just placebo. Although a plethora of scientific papers published about the topic showing positive clinical results, there is still a lack of objective scientific proofs about the biostimulation effect of lasers in Medical Acupuncture. The objective of this work was to design and build a low cost portable laser device for stimulation of acupuncture points, considered here as small localized biosources (SLB), without stimulating any sensory nerves via shock or heat and to find out a suitable method for objectively evaluating its stimulating effect. The design is aimed for studying SLB potentials provoked by laser stimulus, in search for objective proofs of the biostimulation effect of lasers used in Medical Acupuncture. METHODS: The proposed biostimulator features two operational modes: program mode and stimulation mode and two output polarization modes: linearly and circularly polarized laser emission. In program mode, different user-defined stimulation protocols can be created and memorized. The laser output can be either continuous or pulse modulated. Each stimulation session consists of a pre-defined number of successive continuous or square pulse modulated sequences of laser emission. The variable parameters of the laser output are: average output power, pulse width, pulse period, and continuous or pulsed sequence duration and repetition period. In stimulation mode the stimulus is automatically applied according to the pre-programmed protocol. The laser source is 30 mW AlGaInP laser diode with an emission wavelength of 685 nm, driven by a highly integrated driver. The optical system designed for beam collimation and polarization change uses single collimating lens with large numerical aperture, linear polarizer and a quarter-wave retardation plate. The proposed method for testing the device efficiency employs a biofeedback from the subject by recording the biopotentials evoked by the laser stimulus at related distant SLB sites. Therefore measuring of SLB biopotentials caused by the stimulus would indicate that a biopotential has been evoked at the irradiated site and has propagated to the measurement sites, rather than being caused by local changes of the electrical skin conductivity. RESULTS: A prototype device was built according to the proposed design using relatively inexpensive and commercially available components. The laser output can be pulse modulated from 0.1 to 1000 Hz with a duty factor from 10 to 90%. The average output power density can be adjusted in the range 24-480 mW/cm2, where the total irradiation is limited to 2 Joule per stimulation session. The device is controlled by an 8-bit RISC Flash microcontroller with internal RAM and EEPROM memory, which allows for a wide range of different stimulation protocols to be implemented and memorized. The integrated laser diode driver with its onboard light power control loop provides safe and consistent laser modulation. The prototype was tested on the right Tri-Heater (TH) acupuncture meridian according to the proposed method. Laser evoked potentials were recorded from most of the easily accessible SLB along the meridian under study. They appear like periodical spikes with a repetition rate from 0.05 to 10 Hz and amplitude range 0.1-1 mV. CONCLUSION: The prototype's specifications were found to be better or comparable to those of other existing devices. It features low component count, small size and low power consumption. Because of the low power levels used the possibility of sensory nerve stimulation via the phenomenon of shock or heat is excluded. Thus senseless optical stimulation is achieved. The optical system presented offers simple and cost effective way for beam collimation and polarization change. The novel method proposed for testing the device efficiency allows for objectively recording of SLB potentials evoked by laser stimulus. Based on the biopotential records obtained with this method, a scientifically based conclusion can be drawn about the effectiveness of the commercially available devices for low-level laser therapy used in Medical Acupuncture. The prototype tests showed that with the biostimulator presented, SLB could be effectively stimulated at low power levels. However more studies are needed to derive a general conclusion about the SLB biostimulation mechanism of lasers and their most effective power and optical settings.

Acupuncture Points↗