Circadian rhythms: charting oral temperatures to spot abnormalities

1. A normal daily variation in body temperature is found in the elderly. Normal oral temperature in an older person is lower than in a younger person, and the temperature peaks in the early afternoon and is lowest in the early morning hours before awakening. 2. Elderly subjects may be more prone to hypothermia in the early morning hours when their body temperature is naturally lower. Bathing may cause the body temperature to drop up to 1 degree C and add to this risk. 3. Many factors should be considered when analyzing temperature data for the determination of fever. Time of day, as well as symptoms of infection, should be considered. 4. Disturbances in circadian temperature rhythms accompany central nervous system dysfunction and may be an early indicator of other illnesses.     

Influence of test temperature on biomechanical properties of all-inside meniscal repair devices and inside-out meniscus sutures--evaluation of an isolated distraction loading, worst-case scenario

Background

Studies on the biomechanical properties of meniscus repairs are usually performed at room instead of body temperature. However, various all-inside meniscal repair devices include bioabsorbable materials, which are mechanically sensitive to higher environmental temperatures. Therefore, we hypothesize that current test standards may systematically lead to a false overestimation of their performance.

Methods

In 84 cadaveric bovine lateral menisci, an artificial vertical lesion was repaired with different all-inside meniscal repair devices (FasT-Fix, FasT-Fix AB, RapidLoc, Meniscus Arrow, Meniscus Screw) compared to a vertical inside-out Ethibond Excel 2.0 suture loop. Maximum load-to-failure, stiffness, and failure mode were tested in a uniaxial distraction loading at 20 °C and 37 °C.

Findings

Most of the tested implants were not susceptible to the higher environmental test temperature with respect to maximum load-to-failure, stiffness, and failure mode. Only the RapidLoc showed a significantly decreased stiffness (- 28.1%) and a statistical trend to lower maximum load-to-failure (- 20.6%) at 37 °C compared to 20 °C.

Interpretation

20 °C environmental temperature seems to be an acceptable test condition for the most meniscal repair devices. However, if the bioabsorbable part of the implant is the weakest link, body temperature may be considered for testing to prevent false overestimation of the biomechanical properties. For future biomechanical in vitro testing of meniscal repair devices, this study may provide novel insight into biomechanical test protocols for considering the environmental test temperature as an influencing factor of the biomechanical properties of especially bioabsorbable meniscal repair devices.     

Temperature effects on free-thyroxine measurements: analytical and clinical consequences.

We compared the analytical and clinical performance of two free-thyroxine (FT4) assays--a solid-phase radioimmunoassay, Spectria, and a time-resolved fluoroimmunoassay, Delfia, both of them two-step methods--with the performance of a direct radioimmunoassay, Nichols, to measure FT4 concentration in equilibrium dialysate of undiluted serum. The three assays showed comparable analytical performance. We tested clinical utility in sera from 135 healthy subjects with and without thyroxine-binding abnormalities and in 61 patients with and without thyroidal illnesses. We found significant differences for FT4 measured by different assays in sera from the same euthyroid patients. To explain the differences, we studied the influence of temperature on performance and calibration. Most important was the neglected fact that the association constant for the binding of thyroxine to thyroxine-binding globulin decreases when the temperature rises from 20 to 37 degrees C, causing a doubling of FT4. The two-step assays, if performed at room temperature without a well-defined calibration, can give misleading FT4 concentrations. This is the case when sera from patients with thyroxine-binding abnormalities are measured against kit standards, made up in normal human sera. If an assay is to reflect the in vivo FT4 concentration at body temperature in all types of samples, it should be performed at body temperature. For practical reasons 37 degrees C is recommended, and reference values should be defined at 37 degrees C. The same might be valid for other free-hormone assays.     

Comparison of the Effects of Hypothermia at 33°C or 35°C after Cardiac Arrest in Rats

Objectives: Hypothermia of 32°C–34°C induced after resuscitation from cardiac arrest improves neurologic recovery, but the optimal depth of cooling is unknown. Using a rat model, the authors tested the hypothesis that cooling to 35°C between hours 1 and 24 after resuscitation would improve neurologic outcome as much as cooling to 33°C.
Methods: Halothane-anesthetized rats ( n = 38) underwent 8 minutes of asphyxial cardiac arrest and resuscitation. Cranial temperature was maintained at 37°C before, during, and after arrest. Between one and 24 hours after resuscitation, cranial temperature was maintained at 33°C, 35°C, or 37°C using computer-controlled cooling fans and heating lamps. Neurologic scores were measured daily, and rats were killed at 14 days for histologic analysis. Neurons per high-powered field were counted in the CA1 region of the anterior hippocampus using neuronal nuclear antigen staining.
Results: After 14 days, 12 of 12 rats (100%) cooled to 33°C, 11 of 12 rats (92%) cooled to 35°C, and ten of 14 rats (71%) cooled to 37°C survived, with hazard of death greater in the rats cooled to 37°C than in the combined hypothermia groups. Neurologic scores were worse in the rats cooled to 37°C than in the hypothermia groups on days 1, 2, and 3. Numbers of surviving neurons were similar between the groups cooled to 33°C and 35°C and were higher than in the group cooled to 37°C.
Conclusions: These data illustrate that hypothermia of 35°C or 33°C over the first day of recovery improves neurologic scores and neuronal survival after cardiac arrest in rats. The benefit of induced hypothermia of 35°C appears to be similar to the benefit of 33°C.     

The effect of preactivation vial temperature on the acoustic properties of Definity™

Definity^TM is a widely available clinically approved ultrasound contrast agent. The manufacturer’s instructions indicate that the refrigerated vial should be allowed to reach room temperature prior to its 45 s mechanical agitation activation process. Activation results in vial heating and it has been previously observed that “smaller” bubbles are formed later in this process (>10 s) when the vial temperature is elevated. The objective of this work was to examine the effects of preactivation vial temperature on the size distribution, frequency dependent attenuation (1.5–27 MHz) and nonlinear imaging performance of Definity^TM. Experiments were conducted with vials at refrigerator temperature (2°C), room temperature (22°C) or 37°C at the outset of the activation procedure. The size distributions were found to be strongly dependent on preactivation vial temperature and the attenuation results indicated considerable differences in the frequency response of the agent, most notably the appearance of a peak at 4 MHz for the 2°C case. Nonlinear imaging results performed using a 1–5 MHz transducer probe with a wall-less vessel phantom indicated that 2°C vials produced a signal enhancement 5.1 dB greater than for 22°C Definity^TM (p < 0.05). These results, therefore, indicate that not permitting the vial to reach room temperature has a considerable impact on the imaging performance of Definity^TM. Conversely, activating a cooled vial can provide a means by which to improve contrast enhancement when using low frequency clinical transducers.     

A simple method of maintaining chilled saline in the prehospital setting

Objective

Mild therapeutic hypothermia has been shown to improve neurologic outcomes after sudden cardiac arrest. Therapeutic hypothermia should be started as soon as return of spontaneous circulation occurs. However, saline is difficult to keep chilled in the prehospital environment. We sought to determine whether a cooler and ice packs could keep saline cold under prehospital conditions.

Methods

In phase 1 of the experiment, two 1000-mL bags of prechilled 0.9% normal saline were placed in a cooler with 3 ice packs. An additional bag of 1000-mL 0.9% normal saline remained outside the cooler as a control. Over 9 consecutive days, we measured the ambient air temperature and the temperature of each bag of saline every 4 hours. In phase 2 of the experiment, the cooler was kept sealed, and the temperature of the saline was measured after 24 hours.

Results

The mean temperatures over 24 hours ranged as follows: ambient temperature, 24°C to 27.2°C; bottom bag, 0.6°C to 3.5°C; top bag, 1.4°C to 5.7°C; and control bag, 9.8°C to 26.8°C. A t test was used to compare the chilled saline against the control bag. Statistical significance (P < .05) was achieved at all times. In phase 2 of the experiment, after 24 hours, 100% of the bottom bags and 93% of the top bags were less than 6°C.

Conclusions

Our data demonstrate that saline can be kept chilled in ambulances for 24 hours using ice packs and coolers. The estimated cost is less than $50.00 per ambulance. Using coolers and ice packs is an inexpensive way for emergency medical service agencies to initiate prehospital hypothermia.     

Therapeutic hypothermia induction via an esophageal route--a computer simulation

Objectives

Mild therapeutic hypothermia has been shown to improve outcomes after adult cardiac arrest but remains underused. Development of easier methods than currently exist to induce therapeutic hypothermia may help increase use of this treatment. We developed a mathematical model to evaluate the potential to induce mild therapeutic hypothermia through the esophagus.

Methods

Using a finite element mathematical modeling software package incorporating Pennes Bioheat equation, we predicted the changes in body temperature that would occur with placement of an esophageal cooling device containing recirculating chilled water at 10°C.

Results

Patient temperature under the simulated conditions decreased from 37°C to 33°C in approximately 40 minutes. Distribution of body temperature was not uniform in our model, with the skin surface and extremities showing a greater temperature decrease than in the patient's core.

Conclusions

Our computer simulations suggest that inducing mild therapeutic hypothermia via an esophageal route is feasible.     

Assessment of Effects of a Radiofrequency Energy Field and Thermistor Location in an Electrode Catheter on the Accuracy of Temperature Measurement

Accurate measurement of temperature at the interface of the delivery electrode and the tissue during transcatheter delivery of radiofrequency energy (RFE) for ablation would provide better control of lesion production. Electromagnetic energy fields can affect the accuracy of temperature measurement with thermistors. An electrode probe was fabricated with a thermistor and an optical sensor in the center of the delivery electrode. Simultaneous temperature measurements during RFE delivery to cardiac tissue in the 37°C bath showed good agreement between the sensors, indicating that the RFE field did not cause errors in thermistor temperature measurements with the electrode probe used. A second electrode probe was designed to determine optimal thermistor location. It was constructed using two thermistors with identical temperature-resistance curves. One thermistor protruded through a hole in the side of the delivery electrode and was thermally isolated from it. The other thermistor was bonded to the inner surface of the electrode with heat conductive epoxy. The electrode was placed in contact with cardiac tissue in a 37°C bath of flowing saline with the protruding thermistor centered in the area to be heated. Temperatures measured at steady state during RFE delivery with the protruding thermistor were consistently higher than those of the inner wall thermistor, ranging from 1.8°C difference at 46°C to 8.3°C difference at 75°C interface temperature. The thermistor must be in contact with the tissue and thermally isolated from the delivery electrode for accurate determination of electrode/tissue interface temperature.     

Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI

The purpose of this study is to determine the diagnostic accuracy of MRI-based high-dimensional pattern classification in differentiating between patients with Alzheimer's disease (AD), Frontotemporal Dementia (FTD), and healthy controls, on an individual patient basis. MRI scans of 37 patients with AD and 37 age-matched cognitively normal elderly individuals, as well as 12 patients with FTD and 12 age-matched cognitively normal elderly individuals, were analyzed using voxel-based analysis and high-dimensional pattern classification. Diagnostic sensitivity and specificity of spatial patterns of regional brain atrophy found to be characteristic of AD and FTD were determined via cross-validation and via split-sample methods. Complex spatial patterns of relatively reduced brain volumes were identified, including temporal, orbitofrontal, parietal and cingulate regions, which were predominantly characteristic of either AD or FTD. These patterns provided 100% diagnostic accuracy, when used to separate AD or FTD from healthy controls. The ability to correctly distinguish AD from FTD averaged 84.3%. All estimates of diagnostic accuracy were determined via cross-validation. In conclusion, AD- and FTD-specific patterns of brain atrophy can be detected with high accuracy using high-dimensional pattern classification of MRI scans obtained in a typical clinical setting.     

Errors in body temperature assessment related to individual variation, measuring technique and equipment

Errors in body temperature measurement might seriously influence the evaluation of an individual's health condition. We studied individual variation, measurement technique and the equipment used when assessing body temperature. In the first part of the study, three volunteers performed repeated measurements for five mornings. In the second part, the morning rectal, oral, ear and axillary temperatures were measured once in 84 men and women (19-59 years). The repeated measurements showed a daily temperature difference of 0.1-0.4 degrees C in rectal and oral temperatures, 0.2 degrees C-1.7 degrees C in the ear and 0.1-0.9 degrees C in the axillary temperatures. In the sample of 84 subjects, men and postmenopausal women had a lower mean body temperature compared to premenopausal women. The mean deviation between rectal temperature, and oral, ear and axillary temperatures, respectively, was > 0.5 degrees C, with a large individual variation. In conclusion, in order to improve the evaluation of body temperature, the assessment should be based on the individual variation, the same site of measurement and no adjustment of oral, ear or axillary temperatures to the rectal site.     

Hypothermia associated with autonomic dysreflexia after traumatic spinal cord injury

Individuals with traumatic upper thoracic and cervical spinal cord injuries are at increased risk for the development of both thermoregulatory dysfunction and autonomic dysreflexia. It is unclear, however, what effect reflex autonomic sympathetic outflow has on thermoregulatory dysfunction during episodes of autonomic dysreflexia. The following case of an individual with C5 tetraplegia and both thermoregulatory dysfunction and autonomic dysreflexia illustrates the profound effects that the autonomic nervous system may have on body temperature in individuals at risk for this complication.     

Catheter Ablation of Atrial Fibrillation in the Elderly

The incidence and prevalence of atrial fibrillation (AF) increase with age. Catheter ablation has been suggested to improve the quality of life of patients with AF. However, in order to expand the indications for AF ablation to the elderly, several important questions should be answered as to whether safety and efficacy of AF ablation in elderly patients are similar to those in younger populations, whether the AF mechanisms in elderly patients are similar to those in younger patients so that the same ablation techniques can be used in both groups, and whether anticoagulation strategies should be the same for elderly patients as for younger patients after AF ablation. Recent studies reported that the risk of complications from AF ablation did not vary with age, nor was the AF recurrence rate age-dependent for any type of AF, suggesting that the AF mechanisms in elderly patients were similar to those in younger patients. On the other hand, the feasibility of discontinuation of anticoagulation in the elderly after successful AF ablation has not been established since it is difficult to be certain whether AF has been truly cured and since many elderly people are likely to be considered as high-risk based on their CHADS₂ score. In addition, the elderly patients who have been included in published trials of AF ablation may not represent an unselected population of individuals in this age group. Randomized trials of catheter ablation will be necessary before this procedure can be promoted for wider use in the elderly.     

Domains of Chronic Low Back Pain and Assessing Treatment Effectiveness: A Clinical Perspective

Nonspecific chronic low back pain (CLBP) is a common clinical condition that has impacts at both the individual and societal level. Pain intensity is a primary outcome used in clinical practice to quantify the severity of CLBP and the efficacy of its treatment; however, pain is a subjective experience that is impacted by a multitude of factors. Moreover, differences in effect sizes for pain intensity are not observed between common conservative treatments, such as spinal manipulative therapy, cognitive behavioral therapy, acupuncture, and exercise training. As pain science evolves, the biopsychosocial model is gaining interest in its application for CLBP management. The aim of this article is to discuss our current scientific understanding of pain and present why additional factors should be considered in conservative CLBP management. In addition to pain intensity, we recommend that clinicians should consider assessing the multidimensional nature of CLBP by including physical (disability, muscular strength and endurance, performance in activities of daily living, and body composition), psychological (kinesiophobia, fear‐avoidance, pain catastrophizing, pain self‐efficacy, depression, anxiety, and sleep quality), social (social functioning and work absenteeism), and health‐related quality‐of‐life measures, depending on what is deemed relevant for each individual. This review also provides practical recommendations to clinicians for the assessment of outcomes beyond pain intensity, including information on how large a change must be for it to be considered “real” in an individual patient. This information can guide treatment selection when working with an individual with CLBP.     

Activities of enzymes in plasma should be measured at 37 degrees C.

There are considerable differences of opinion as to the most desirable temperature at which activities of enzymes in plasma should be measured. Debate centers around 25 degrees C because of its widespread use in physico-chemical measurements, 30 degrees C because of its supposed technical convenience, and 37 degrees because of its physiological significance. There is, however, widespread agreement that the activities of intracellular enzymes, and of enzymes having a natural function in plasma, be measured at 37 degrees C. Perhaps because estimations of the activities of those enzymes in plasma that have leaked from damaged tissues have been subject to almost continuous modifications, temperature has simply become just another variable to take into account. In this article I describe the relevance of a temperature near 37 degrees C to the activities of all enzymes in man, intracellular and extracellular. I conclude that 37 degrees C is to be favored as the temperature for assaying all parameters in human biochemistry affected by temperature. These include not only enzyme activities but also pH, blood-gas equilibria, binding data, and, in fact, all kinetic activities in the body.     

Population pharmacokinetic modelling of carbamazepine in epileptic elderly patients: implications for dosage

BACKGROUND: Proper use of antiepileptic drugs in the elderly involves knowledge of their pharmacokinetics to ensure a patient-specific balance between efficacy and toxicity. However, populations of epileptic patients on chronic carbamazepine (CBZ) therapy which have been studied have included data of relatively few elderly patients. AIMS: The aim of the present study was to evaluate the population pharmacokinetics of CBZ in elderly patients on chronic monotherapy. METHODS: We have used the non-parametric expectation maximization (NPEM) program in the USC*PACK collection of PC programs to estimate individual and population post-induction pharmacokinetics of CBZ in epileptic elderly patients who received chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly and 35 younger patients with epilepsy. As a 'historical control' we used previously published population modelling results from 99 young epileptic patients on chronic CBZ monotherapy. In that control group, TDM was performed in the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in the present study, and the same PK population modelling software was used for data analysis. RESULTS AND CONCLUSIONS: A poor correlation was found between daily CBZ dose and serum concentrations in the elderly patients (r=0.2, P=0.25). Probably statistically significant difference in the median values of the CBZ metabolic rate constant (P<0.001) between elderly and relatively young epileptic patients was found. Our results showed that age-related influences in CBZ pharmacokinetics in elderly patients should be considered in the optimal planning of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ dosages lower than those based on the median population PK parameter values obtained from younger patients. The present population model is also uniquely well suited for the new 'multiple model' design of dosage regimens to hit target therapeutic goals with maximum precision.     

Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked hyperthermia in humans

The vanilloid receptor TRPV1 has been identified as a molecular target for the treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1 antagonists have been considered for therapeutic evaluation in such diseases. During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist, we found that TRPV1 blockade elicited marked, but reversible, and generally plasma concentration-dependent hyperthermia. Similar to what was observed in rats, dogs, and monkeys, hyperthermia was attenuated after repeated dosing of AMG 517 (at the highest dose tested) in humans during a second Phase I trial. However, AMG 517 administered after molar extraction (a surgical cause of acute pain) elicited long-lasting hyperthermia with maximal body temperature surpassing 40 °C, suggesting that TRPV1 blockade elicits undesirable hyperthermia in susceptible individuals. Mechanisms of AMG 517-induced hyperthermia were then studied in rats. AMG 517 caused hyperthermia by inducing tail skin vasoconstriction and increasing thermogenesis, which suggests that TRPV1 regulates vasomotor tone and metabolic heat production. In conclusion, these results demonstrate that: (a) TRPV1-selective antagonists like AMG 517 cannot be developed for systemic use as stand alone agents for treatment of pain and other diseases, (b) individual susceptibility influences magnitude of hyperthermia observed after TRPV1 blockade, and (c) TRPV1 plays a pivotal role as a molecular regulator for body temperature in humans.     

Bildgebende Diagnostik der Brustwirbelsäule

In addition to the clinical examination, various imaging techniques are employed to reach a diagnosis regarding the region of the thoracic spine. These procedures aid in objectifying different processes exhibiting structural pathology. The primary questions to be answered concern degeneration, inflammation, aftereffects of trauma, or tumors. It is not easy in every case to distinguish between what can still be considered a normal finding or age-appropriate image and a pathological process that is already clinically relevant. For routine clinical practice, however, competence in dealing with individual techniques is also necessary from the aspect of functional medicine to obtain the maximum level of information. Attention is called to the fact that it is essential to formulate the clinical indication as precisely as possible when requesting an imaging examination.     

Effect of Mao-bushi-saishin-to on infection of ofloxacin resistant bacteria and of unknown origin

When seven elderly patients with fever due to bacterial infection failed to respond to ofloxacin 300 mg/day for 3 days, we prescribed Mao-bushi-saishin-to for 7 days. Bushi, one of the components of Mao-bushi-saishin-to, is a complex of various alkaloids, which is known to stimulate the conducting system of the heart, so half of the standard dose was prescribed for these patients. We assessed changes in the patients' body temperatures and serum C-reactive protein concentrations. As a result, the patients' body temperatures all fell to under 37 degrees C and C-reactive protein levels decreased from an average of 3.06 mg/dl to an average of 0.36 mg/dl (P< 0.02). In cases where a fever does not decrease through dosage of an antibiotic such as ofloxacin after about 3 days, half of the standard dose of Mao-bushi-saishin-to for 7 days should be considered as a complementary therapy.     

Urinary dysfunction and urodynamics in the elderly

As the elderly population continues to grow, it is important to consider some of the normal changes inherent with the aging process, as well as to understand common urologic disorders that may occur in this population. Urodynamic clinicians should be aware of some special considerations when working with this group of individuals. The purpose of this article is to describe common urologic conditions in the elderly and correlate these conditions with typical urodynamic findings.     

Expert witness testimony: the ethics of being a medical expert witness

Giving testimony as an expert witness in court carries numerous ethical obligations, which are rarely delineated by the individuals who seek such testimony or even known to those who provide it. Because most expert medical witness testimony about the performance of physicians requires that a witness be medically licensed, and because verdicts based on expert testimony directly influence the standard of care that will be applied in the future, providing medical testimony legitimately can be considered to come within the realm of the practice of medicine. Testifying as an expert in legal matters should be undertaken with the same degree of integrity as the practice of medicine and is rightfully subject to the same degree of scrutiny and regulation.