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PubMed1991

Combined chemical and mechanical effects on free radicals in UHMWPE joints during implantation.

An electron spin resonance (ESR) technique is employed to determine the free radical distribution in the articulating surfaces of retrieved acetabular cups and knee-joint plateaus (retrieved after more than 6 years of implantation). Similar measurements made on samples prepared from cyclically stressed and unstressed cups, and on samples following oxidations in nitric acid and intralipid solutions provided sufficient data to gain more knowledge about the combined chemical and mechanical effects on PE free radicals during implantation. In UHMWPE free radicals are primarily initiated by gamma-ray sterilization; however, during implantation, peroxy (scission type) free radicals are formed and reach a maximum concentration level (equilibrium state) due to oxidation by chemical (hemoglobin and/or synovial fluids) environment of the joints. Subsequently, due to frictional heating and stress in the loading zones, free radical reaction is accelerated and their number is reduced only in those areas. This is consistent with the observations of a temperature rise in acetabular cups during in vitro frictional wear stress tests and in vivo telemetry observations, as reported by others. Compared with the previously reported SEM micrographs the low-free-radical regions are correlated with high-wear areas and the high-free-radical regions with the low-wear areas.

Biocompatible Materials↗

PubMed1995

Screening for ovarian cancer: what are the optimal surrogate endpoints for clinical trials?

The inability to identify relevant markers for presymptomatic screening in early stage or "preinvasive" ovarian cancer has plagued investigators and clinicians facing the problems of early detection. The characteristic late stage of disease at initial presentation has hindered our understanding of the biologic progression and stepwise molecular alterations that result in ovarian carcinoma. To date, most screening studies have focused on identifying early anatomic changes using ultrasound or fluctuations in serum biomarkers such as CA-125. These screening methodologies have proven inadequate in both sensitivity and specificity for early stage ovarian cancer detection. Molecular analysis of ovarian carcinomas has revealed alterations in oncogenes and tumor suppressor genes associated with these tumors. The HER-2/neu oncogene, a member of the epidermal growth factor family, is amplified or overexpressed in approximately 25-30% of ovarian carcinomas. Significant data substantiate an important role for HER-2/neu in the pathophysiology of ovarian cancer. While potentially an attractive surrogate endpoint biomarker (SEB), serum HER-2/neu levels have not proven to be a useful screening modality. In response to the urgent need for improved early detection for ovarian cancer, our current research efforts include differential hybridization studies between normal and malignant ovarian epithelium to define potentially unique ovarian cancer antigens which may ultimately have utility; defining physical alterations that occur in malignant ovarian tissues using implanted telemetry systems; studies using positron emission tomography to detect changes in glucose metabolism between normal and malignant ovarian tissues; and screening studies using a 3-dimensional ultrasound unit to improve the accuracy of this technique in recognizing early neoplastic changes. By taking diverse approaches to tackle this problem, an improved understanding of ovarian carcinogenesis should translate into the identification of appropriate SEBs for early detection.

Biomarkers, Tumor↗

PubMed1992

Body temperature rhythm of the tree shrew, Tupaia belangeri.

The circadian rhythm of body temperature of the tree shrew Tupaia belangeri was studied by telemetry. The amplitude of the daily (or circadian) variation was found to be much larger than that of most endotherms (amplitude approximately 5 degrees C) and the bimodal shape of the rhythm differed from the cosine waveform that characterizes the temperature rhythms of most other species. In free-running conditions, as well as in the entrained state, the temperature rhythm remained synchronized to the rhythm of locomotor activity.

Animals↗

PubMed1997

Telemedicine: new technology = new questions = new exposures.

Cyberspace, telemetry, and virtual reality all refer to mankind's evolving ability to be in two places at once, without ever leaving one location. Now this ability has expanded into the world of medicine, with increased awareness of risk management concerns, and questions about where we go from here.

Computer Communication Networks↗

PubMed2003

Effects of ATP-sensitive K+ channel openers and tolterodine on involuntary bladder contractions in a pig model of partial bladder outlet obstruction.

AIMS: To compare in vivo the efficacy, potency, and bladder-vascular selectivity of ATP-sensitive potassium channel openers (KCOs), YM934 and (-)-cromakalim to a muscarinic antagonist, tolterodine in a novel partial outlet obstructed pig model. METHODS: Partially obstructed female Landrace pigs were implanted with telemetry transmitters to allow the continuous measurement of intravesical, abdominal and arterial pressures. A subcutaneous port catheter was used to adjust bladder volume. Bladder and arterial pressure were simultaneously monitored under isoflurane anesthesia before and after increasing i.v. doses of test compounds. RESULTS: Under anesthesia, voiding was completely inhibited, but spontaneous, nonvoiding bladder contractions were observed with mean amplitude of 16 +/- 1 cm H(2)O, duration of 35 +/- 2 seconds, and intercontraction interval of 43 +/- 4 seconds (n = 25). YM934 and (-)-cromakalim both caused dose-dependent decreases in bladder contraction area under the curve (AUC) with effective doses to inhibit AUC by 35% of 3.6 and 14.9 nmol/kg, i.v., respectively. However, concomitant reductions in mean arterial pressure of 12 and 13% were also observed. Tolterodine did not inhibit spontaneous bladder contractions at doses up to 100 nmol/kg, i.v. corresponding to plasma concentrations up to 41 ng/mL. CONCLUSIONS: The superior efficacy of KCOs to inhibit spontaneous bladder contractions relative to tolterodine support the hypothesis that KCOs may provide an alternate therapeutic mechanism to treat symptoms of overactive bladder if bladder-vascular selectivity can be sufficiently improved. The minimally invasive model described herein appears useful in the preclinical evaluation of potential therapeutics targeted to treat the overactive bladder.

Adenosine Triphosphate↗

PubMed1997

Distribution and activity of male harbour seals during the mating season

Little is known about male reproductive strategies in aquatically mating pinnipeds. To study the mating patterns of harbour seals, Phoca vitulinaVHF telemetry was used to relate the distribution and behaviour of adult males to the distribution of females during the summer pupping and mating season. Prior to July males occupied large and variable ranges. At the beginning of July, males decreased their mean range size, but continued to spend much of their time in the water where they made characteristic short dives. Acoustic recordings in the presence of several radiotagged males suggested that these short dives were associated with underwater vocal displays. Throughout July, males varied in the geographical areas which they used to perform these displays. Some individuals were found in the water around haul-out sites; others were located on foraging grounds, up to 50 km from pupping sites, and some were consistently located displaying on transit routes between these two areas. This study supports previous suggestions that vocalizations and diving displays may be associated with male mating behaviour, but suggests that males may display over a much wider geographical area than was previously recognized. This system of dispersed but small display territories is suggestive of lekking. However, further research on the distribution of the clumping of displaying males is required to confirm this.

Journal Article↗

PubMed1998

Circadian rhythms in the Zucker obese rat: assessment and intervention.

Body temperature (Tb) and activity were recorded by telemetry in obese and lean Zucker rats in light-dark (LD), constant dark (DD) and constant light (LL). In LD, obese rats, by comparison with lean rats, exhibited a 2-4-h phase advance and attenuated amplitude of Tb and activity rhythms. These differences persisted on the first day of DD, and thus were not due to differential sensitivity to masking effects of light. In LL, obese and lean rats exhibited similar free-running periods, thus the phase advance in LD was also not due to a short intrinsic period. In LD, obese rats exhibited more diurnal food intake and a reduced LD intake ratio. To assess the role of diurnal feeding in weight gain, one group of obese rats was fed ad libitum, and another fed only at night. Food intake did not differ significantly between groups, but ad libitum fed rats gained 23% more weight (60 g) over 60 days, suggesting that excessive diurnal feeding may contribute adversely to body weight regulation in this animal model of obesity.

Activity Cycles↗

PubMed2000

Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion.

Postischemic hypothermia provides long-lasting neuroprotection against global cerebral ischemia in adult rats and gerbils. Studies indicate that hypothermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. However, no study has examined long-term outcome following postischemic hypothermia in adult animals. Furthermore, most studies examined only brief hypothermia (e.g., 3 h). Since previous studies may have overestimated long-term benefit and have likely used suboptimal durations of hypothermia, we examined whether prolonged cooling would attenuate infarction at a 2-month survival time following middle cerebral artery occlusion (MCAo) in rats. Adult male Wistar rats were implanted with telemetry brain temperature probes and later subjected to 30 min of normothermic MCAo (contralateral to side of probe placement) or sham operation. Ischemia was produced by the insertion of an intraluminal suture combined with systemic hypotension (60 mm Hg). Sham rats and one ischemic group controlled their own postischemic temperature while another ischemic group was cooled to 34 degrees C for 48 h starting at 30 min following the onset of reperfusion. The infarct area was quantified after a 2-month survival time. Normothermic MCAo resulted in almost complete striatal destruction (91% loss +/- 12 SD) with extensive cortical damage (36% +/- 16 SD). Delayed hypothermia treatment significantly reduced cortical injury to 10% +/- 10 SD (P < 0.001) while striatal injury was marginally reduced to 79% loss +/- 17 SD (P < 0.05). Delayed hypothermia of only 34 degrees C provided long-lasting cortical and striatal protection in adult rats subjected to a severe MCAo insult. These results strongly support the clinical assessment of hypothermia in acute stroke.

Analysis of Variance↗

PubMed1996

The myocardial lesions produced by the potassium channel opener aprikalim in monkeys and rats are prevented by blockade of cardiac beta-adrenoceptors.

Aprikalim is a potent, specific, and selective opener of ATP-sensitive K+ (KATP) channels. By virtue of this pharmacological property, aprikalim affords cardioprotection in experimental models of ischemia/reperfusion injury, and, at higher doses, also causes peripheral or coronary vasodilatation. Direct-acting peripheral vasodilators can cause myocardial lesions, particularly in rats and dogs. However, unexpectedly, aprikalim produced this effect also in monkeys. Thus, the primary aim of this investigation was to assess whether in monkeys these myocardial lesions were the direct or indirect consequence of the vascular effects of aprikalim. Cynomologus monkeys were given the beta-adrenoceptor antagonist nadolol (2 mg/kg p.o., twice daily) for 4 consecutive days. On the third and fourth day of the experiment, they received aprikalim (1 mg/kg p.o.). In another series, two monkeys carrying telemetry transmitters for blood pressure and heart rate measurements were also given aprikalim or its vehicle. Finally, aprikalim (1 mg/kg p.o. for 2 days) or its vehicle was administered to rats which were concurrently treated with the beta-adrenoceptor antagonist atenolol (5 mg/kg s.c.) or its vehicle. In cynomologus monkeys, aprikalim produced focal and multifocal myocardial necrosis of minimal to moderate intensity in or near the papillary muscles of the left ventricle. These effects were abrogated by nadolol. Similarly, necrotic lesions were caused by aprikalim only in those rats which had not been pretreated with atenolol. In monkeys, aprikalim produced a marked and long-lasting decrease in aortic blood pressure, accompanied by an even more prolonged tachycardia. These results demonstrate that aprikalim can produce myocardial necrosis not only in rats but also in monkeys. To our knowledge, this is the first time that such adverse effects are reported for a vasodilator in monkeys. More importantly, these effects were prevented by blocking cardiac beta-adrenoceptors. Thus, the myocardial lesions produced by aprikalim may be attributed to its profound and prolonged hemodynamic effects.

Adrenergic beta-Antagonists↗

PubMed2002

A life-supporting technique of renal allotransplantation in Macaca fascicularis to evaluate novel immunosuppressive drugs in nonhuman primates.

BACKGROUND: The use of nonhuman primates in preclinical transplantation studies is becoming more common. This report details complete procedures developed for a successful life-supporting kidney allotransplantation program using the cynomolgus monkey (Macaca fascicularis). MATERIALS AND METHODS: All transplants were performed in wild-caught, ABO-matched, MLR-mismatched adult males. Transplant procedures were staggered: an animal first served as a donor, was allowed to recover for 4 weeks, and was subsequently used as a recipient. The kidney was flushed in situ while the aorta was briefly cross-clamped. The graft was implanted heterotopically end-to-side in the right iliac fossa using microsurgical techniques. An ureteroneocystostomy was constructed; a telemetry probe was inserted into the aorta, and the remaining native kidney was removed. RESULTS: Sixty-two transplants were performed in 6.9 +/- 0.1 kg animals. Operating times in the donor and recipient were 126 +/- 3 and 166 +/- 5 min, respectively. The cold ischemia time was 55 +/- 1 min. There were no intraoperative deaths. Postoperative complications were observed in six (9.7%) monkeys and consisted of one early renal arterial thrombosis and five ureteral complications (two of which were successfully repaired). Transplants were ultimately successful in 93.6% (58/62) of cases. Immediate kidney function was satisfactory, with a mean serum creatinine of 1.7 +/- 0.2 mg/dL and a mean urine output of 140 +/- 15 ml on postoperative day 7. CONCLUSION: Life-supporting kidney transplantation in cynomolgus macaques is a demanding operation that requires great attention to details. Precise surgical techniques, telemetric monitoring, ultrasound surveillance, and aggressive, early, postoperative fluid resuscitation produced a 94% success rate.

Animals↗

PubMed1993

In vivo metabolism of chloroform in B6C3F1 mice determined by the method of gas uptake: the effects of body temperature on tissue partition coefficients and metabolism.

Mice exposed to various chemicals have been shown to respond by decreasing their core body temperature. To examine what effect such a response might have on the determination of in vivo metabolism, core body temperatures of B6C3F1 mice were recorded with temperature telemetry devices during exposure to chloroform (CHCl3) in a closed, recirculating chamber (100 to 5500 ppm). Significant decreases in body temperature occurred in all mice exposed to greater than 100 ppm CHCl3, with the greatest decrease of 14 degrees C occurring at 5500 ppm. A starting CHCl3 concentration of 4000 ppm had no effect on the 7-ethoxycoumarin O-deethylase (ECOD) activity or P450 levels determined at the end of a 5-hr gas uptake exposure. A physiologically based pharmacokinetic (PB-PK) model was developed to describe the effects of decreased body temperature on the analysis of metabolic data. In vitro ECOD activity as a measure of in vivo P450 metabolism was determined for temperatures ranging from 24 to 40 degrees C. In vitro enzyme activity decreased linearly from a maximum at 37 degrees C to one-third of this activity at 24 degrees C. A linear equation describing this enzymatic activity-temperature correlation was incorporated into the PB-PK model structure to describe decreases in metabolic activity resulting from decreases in core body temperature. In vitro blood/air and tissue/air partition coefficients were determined for CHCl3 at temperatures ranging from 24 to 40 degrees C. All blood/air and tissue/air partitions increased with decreasing temperature, while the tissue/blood partition coefficients calculated from the tissue/air and blood/air partitions decreased with decreasing temperature. Adding these temperature corrections to the model greatly improved the overall fit of the gas uptake curves at all concentrations. Incorporation of a first-order metabolic rate constant was also required to provide an adequate representation of the data at high concentrations. The analysis of gas uptake data by the use of a PB-PK computer model is a very powerful technique for determining in vivo metabolism of many volatile compounds, but the incorporation of significant deviations from a generally used model structure (i.e., Ramsey-Andersen model) to account for shortcomings of the model's ability to adequately analyze a gas uptake data set should be based on data collection when possible.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1996

The pineal complex and melatonin affect the expression of the daily rhythm of behavioral thermoregulation in the green iguana.

Daily variation in the body temperature of the green iguana (Iguana iguana) was studied by telemetry in laboratory photo-thermal enclosures under a 12Light:12Dark (L:D) photoperiod. The lizards showed robust daily rhythms of thermoregulation maintaining their body temperatures (Tb) at higher levels during the day than during the night. Some animals maintained rhythmicity when kept in constant darkness. On light:dark cycles parietalectomy produced only a transient increase of median Tb in the first or second night following the operation. Pinealectomized lizards on the other hand maintained their body temperatures as significantly lower levels during the day and at significantly higher levels during the night than did sham-operated or intact lizards. This effect was apparently permanent, since one month after pinealectomy lizards still displayed the altered pattern. Plasma melatonin levels in intact animals were high during the night and low during the day and were unaffected by parietalectomy. Pinealectomized lizards showed low levels of plasma melatonin during both the day and the night. A daily intraperitoneal injection of melatonin in pinealectomized animals given a few minutes after the light to dark transition decreased the body temperatures selected by the lizards during the night and increased the body temperatures selected during the following day. Control injections of saline solution had no effect. The significance of these results is discussed in relation to the role of the pineal complex and melatonin in the mediation of thermoregulatory behavior.

Animals↗

PubMed1993

Changes in carotid blood flow and electrocardiogram in humans during and after walking on a treadmill.

Blood flow velocity in the common carotid artery and the electrocardiogram were measured simultaneously by telemetry in seven male subjects during 20-min walking on a treadmill at an exercise intensity corresponding to a mean oxygen uptake of 26.0 (SD 2.9) ml.kg-1.min-1. The mean cardiac cycle was shortened from 0.814 (SD 0.103) s to 0.452 (SD 0.054) s during this exercise. Of this shortening, 73% was due to shortening of the diastolic period and 27% to shortening of the systolic period. In the relatively small shortening of the mean systolic period [from 0.377 (SD 0.043) s to 0.268 (SD 0.029) s], the isovolumetric contraction time was shortened by 56%. During exercise, the heart rate (fc) increased by 79.4% [from 74.3 (SD 9.3) beats.min-1 to 133.3 (SD 14.8) beats.min-1], and the peak blood velocity (S1) in the common carotid artery increased by 56.1% [from 0.82 (SD 0.10) m.s-1 to 1.28 (SD 0.11) m.s-1]. After exercise, the S1 decreased rapidly to the resting level. The fc decreased more slowly, still being higher than the initial resting level 5 min after exercise. The diastolic velocity wave and the end-diastolic foot decreased during exercise. The blood flow rate in the carotid artery increased transiently by 13.5% at the beginning of exercise [from 5.62 (SD 0.63) ml.s-1 to 6.38 (SD 0.85) ml.s-1] and by 26.5% at the end of the exercise period [from 5.62 (SD 0.63) ml.s-1 to 7.11 (SD 1.34) ml.s-1].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

Dietary linolenic acid-mediated increase in vascular prostacyclin formation.

To define vascular effects of an enhanced dietary alpha-linolenic acid intake, 28 spontaneously hypertensive rats were fed a 3% sunflowerseed oil (44% linoleic acid) diet; in 3 groups (7 rats each), the diet was supplemented with 1, 2.5 or 5% linseed oil containing 62% alpha-linolenic acid. alpha-Linolenic acid was incorporated up to 12% in the aorta of the 5% linseed oil group. The eicosapentaenoic acid content was not significantly increased. The content of arachidonic acid and docosatetraenoic acid was moderately reduced in rats fed 5% linseed oil. The generation of 6-keto-PGF1 alpha (degradation product of prostacyclin) assessed by HPLC/electrochemical detection was, however, markedly increased (p < 0.05) in rats fed 2.5 and 5% linseed oil. The minor prostanoids TXB2, PGE2 and PGF2 alpha were not significantly altered. The high systolic and diastolic blood pressure of SHR monitored by radio telemetry was more effectively reduced (p < 0.05) in the light, i.e. sleep, cycle. An increased prostacyclin formation and lowered vascular arachidonic acid content associated with enhanced dietary alpha-linolenic acid intake would thus be expected to prove beneficial in the prevention of vascular disorders.

6-Ketoprostaglandin F1 alpha↗

PubMed1995

Neuroimaging studies in children with temporal lobectomy.

Twenty-eight children with intractable seizures who subsequently underwent a temporal lobectomy were studied by electroencephalogram (EEG), prolonged video EEG telemetry, computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) for the localization of epileptogenic foci. MRI showed abnormalities indicating epileptogenic foci in 21/25 patients and a increased signal intensity in 7/11 patients with mesial temporal sclerosis (MTS). SPECT showed corresponding abnormalities in 17/22 patients, including an interictal decrease in regional cerebral blood flow corresponding to the epileptogenic zone in 15. CT showed localized abnormalities in 16/28. All 12 patients with benign, slow-growing neoplasms showed an abnormality on CT scan. In children, MRI is essential in localizing epileptogenic abnormalities, especially MTS and cortical dysplasia. SPECT contributes to the localization of epileptogenic foci, which are often coincident with EEG abnormalities, particularly in single pathology. CT depicts benign neoplasms with calcification in the temporal lobe, which are likely to provoke complex partial seizures.

Adolescent↗

PubMed1981

On the prediction of epileptic seizures.

In 12 epileptic patients suffering from "absences" 8-channel EEG was recorded by telemetry. The autoregressive model was applied to the signal and the prediction coefficients being the basis for calculation of the poles of the predictor. The location of the poles in the z- and s-planes was described as a function of time for 0.1 s steps along the pre-seizure EEG. In 10 of the 12 patients, and in 25 of the 28 recorded seizures this presentation of the poles of the predictor showed specific pattern linked with the occurrence of the seizure. The trajectory of the "most mobile pole" during the pre-seizure period could aid in the prediction of the seizure by several seconds.

Adolescent↗

PubMed1982

Evaluation of tension and compression forces in the canine femur in vivo.

In order to verify the existence of tension and compression forces from the cortical surface of canine femora, rosette strain gauges and a radio telemetry system were used to observe the animals during normal locomotion. Surface strain measured from the lateral cortical surface was consistently in tension whereas surface strain measured from the medial cortical surface was in compression. This data supported in vitro work which showed that eccentric loading of bone results in the convex side of bone being in tension and the concave side of bone being in compression.

Animals↗

PubMed1977

Effect of exercise on systemic blood pressure and heart rate in horses.

Carotid loops were prepared in 3 horses several months prior to the experiments. Systemic blood pressure was recorded at rest and during exercise by insertion of a plastic cannula into the carotid artery. The pressure transducer was fixed at the neck of the animal. The blood pressure signal was transmitted by telemetry. When the horses were standing under the rider, the following results were obtained: heart rate 38 +/- 5 beats-min-1, systolic pressure 115 +/- 15, disstolic pressure 83 +/- 10, mean pressure 97 +/- 12, and pulse pressure 32 +/- 9 mm Hg. During steady gallop at a mean speed of 548 +/- 90 m-min-1, heart rate rose to 184 +/- 23 beats-min-1, systolic pressure to 205 +/- 23, diastolic pressure to 116 +/- 12, mean pressure to 160 +/- 20 and pulse pressure to 89 +/- 19 mm Hg. These values remained stable throughout the exercise period of 5-6 min. When the horses were exercised at stepwise increasing speed from walk through trot to gallop, both the mean arterial blood pressure and the pulse pressure rose in proportion to the running speed.

Animals↗