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C T Simons

Publications and source records attributed to C T Simons.

24 records · Page 2Linked to original sources
PubMed1997

Febrile responsiveness of vagotomized rats is suppressed even in the absence of malnutrition.

The repeatedly observed attenuation of fever in vagotomized rats has been accepted as evidence of an essential role of vagal afferents in the transduction of pyrogenic signals from the periphery to the brain. If, however, the general condition of a vagotomized animal is poor (the usual case) and accompanied by malnutrition and body mass loss (common complications of vagotomy), the febrile responsiveness can be suppressed not because of the lack of vagal afferentation, but rather secondarily to a malnutrition-associated thermogenic incompetence. In the present study, we addressed this dilemma. Male Wistar rats were subjected to subdiaphragmatic vagotomy (or sham surgery) and, 24 days later, catheterized in the jugular vein. Postsurgically, the rats were closely watched and fed highly palatable food. Their febrile responsiveness [colonic (Tc) and tail skin (Tsk) temperature responses] to Escherichia coli lipopolysaccharide (LPS: 1 microgram/kg i.v.) was tested on day 27 postvagotomy. To verify the completeness of vagotomy, each rat was food deprived for 24 h and then euthanized; its stomach's evacuatory function was assessed by weighing the organ. One month postsurgery, both food consumption and body mass of the vagotomized rats (33 +/- 2 g/day and 313 +/- 4 g, respectively) were similar to the control values (30 +/- 1 g/day and 315 +/- 8 g). In the sham rats, LPS induced a monophasic Tc rise of 0.5 +/- 0.3 degree C at 70 min postinjection (peak), preceded by a fall in Tsk. Neither this Tsk fall (tail skin vasoconstriction) nor the resultant fever occurred in the vagotomized rats; at 70 min, Tc change was -0.1 +/-0.1 degree C. The gastric mass (4.1 +/- 0.5 g in the vagotomized vs. 1.8 +/- 0.1 g in sham rats) indicated the effectiveness of vagotomy. In sum, although the vagotomy-associated malnutrition was successfully prevented with special perioperative care, the vagotomized animals still did not respond to LPS with fever. Malnutrition is, therefore, unlikely to constitute the main reason of the febrile irresponsiveness of vagotomized rats.

Animals↗
PubMed1997

Cold defense mechanisms in vagotomized rats.

Subdiaphragmatically vagotomized rats cannot mount a febrile response to pyrogens and are believed to have severe thermoregulatory deficiencies. We addressed the issue of thermoeffector competence of vagotomized rats by asking three questions. In Expt. 1 we asked, can vagotomized rats readily recruit tail skin vasoconstriction in the course of a moderate cold exposure? In Expt. 2 the question was, can brown adipose tissue (BAT) thermogenesis readily be activated in vagotomized rats (e.g., in response to a tail pinch)? In Expt. 3, we investigated the question: can vagotomized rats elevate their body temperature in response to ephedrine (a drug of high hyperthermizing potential) to the same extent as sham-operated controls? Rats were vagotomized or sham operated and implanted with a catheter into the jugular vein and a thermocouple into the interscapular BAT. To prevent the common complications of vagotomy, special perioperative care was given. During experiments, colonic, tail skin, and BAT temperatures (Tc, Tsk, and TBAT, respectively) were measured. The vagotomized animals were well nourished and had a body mass (325 +/- 6 g) similar to that of the controls (338 +/- 6 g). In Expt. 1, in response to external cooling (15 degrees C, 1 h), the vagotomized (n = 30) and sham-operated (n = 31) rats recruited tail skin vasoconstriction at close values of both Tc (37.84 +/- 0.08 and 37.97 +/- 0.07 degrees C) and Tsk (33.16 +/- 0.17 and 33.18 +/- 0.18 degrees C, respectively). In Expt. 2, tail pinch-associated stress in vagotomized rats resulted in a sharp rise in the TBAT-Tc gradient by 0.3-1.0 degree C. In Expt. 3, ephedrine administered intravenously (whether in a 5 or 35 mg/kg dose) evoked similar hyperthermic responses in the vagotomized and sham-operated rats: a moderate (approximately 2.5 degrees C) Tc rise in the low dose and a "supramaximal" (approximately 5.0 degrees C) rise in the high dose. In sum, the answer to all three questions asked is yes. Vagotomized rats, at least when well nourished, exhibit no signs of thermoeffector deficiency. It is, therefore, not effector incompetence but rather vagal deafferentation per se that can explain the febrile irresponsiveness of vagotomized rats.

Animals↗
PubMed1996

First and second phases of biphasic fever: two sequential stages of the sickness syndrome?

We hypothesized that the systemic inflammatory response undergoes two consecutive stages, each characterized by different nonspecific sickness patterns. To test this hypothesis, we studied thermal, nociceptive, and motor responses to lipopolysaccharide (LPS) in 43 unanesthetized, habituated, and lightly restrained male Wistar rats previously implanted with a catheter in the jugular vein. Escherichia coli LPS was injected intravenously in a dose of 0, 0.1, 1, 10, 100, or 1,000 micrograms/kg. Colonic temperature (Tc) was measured with a thermocouple. Changes in nociception were assessed by tail flick latency (TFL) to a noxious heat stimulus. Motor activity was evaluated using an observation-based activity score (AS). The two lowest doses were apyrogenic. The next dose induced a monophasic fever with a maximal Tc rise of 0.9 +/- 0.2 degrees C at 108 +/- 11 min post-LPS. The next two higher doses caused biphasic fevers with the first and second peaks of 0.7 +/- 0.1 and 1.4 +/- 0.1 degrees C (10 micrograms/kg) and 0.7 +/- 0.1 and 1.4 +/- 0.2 degrees C (100 micrograms/kg) occurring at 60 +/- 6 and 165 +/- 17 min and at 45 +/- 3 and 141 +/- 6 min, respectively. The highest dose of LPS resulted in a Tc fall (nadir, -0.6 +/- 0.1 degree C at 83 +/- 6 min). Two different sickness patterns were exhibited. The first (high Tc, low TFL and high AS) occurred during the monophasic fever and the first (early) phase of the biphasic fevers, and it was termed the early phase syndrome. The second pattern (high or low Tc, high TFL, and low AS) developed during the second (late) phase of the biphasic fevers and LPS-hypothermia (endotoxin shock), and it was termed the late phase syndrome. Occurring at different stages of the systemic inflammatory response and developing through different coping patterns [fight/flight (energy expenditure) vs. depression/withdrawal (energy conservation)], the two syndromes represent two different types of adaptation to infection and have different biological significance. Viewing sickness as a dynamic entity is justified clinically. Such a dynamic approach to the problem resolves several contradictions in the current concept of sickness.

Animals↗
PubMed1993

Survival after severe brain injury in the aged.

OBJECTIVE: We studied the impact of age on outcomes for patients with severe blunt brain injury. DESIGN: Inception cohort, retrospective study, cost-benefit analysis. SETTING: Level 1 trauma center. PATIENTS: Ninety consecutive patients aged 60 years or older were compared with 79 randomly selected patients aged 20 to 40 years, all with Glasgow Coma Scale scores of 5 or less. These patients were admitted from January 1, 1983, to September 1, 1991. Patients who died less than 6 hours after admission to the hospital, had cranial gunshot wounds, or had no structural brain injury on computed tomographic scans were excluded, leaving 42 elderly and 50 younger patients for the final analysis. MAIN OUTCOME MEASURES: Mortality rates and quality of survival as measured by the Glasgow Outcome Scale scores. RESULTS: There were no differences between the older and younger patients in admission Glasgow Coma Scale score, Revised Trauma Score, Injury Severity Score, or Abbreviated Injury Scale 1 score. Resuscitation, neurosurgical interventions, and adequacy of nutritional support were equivalent. Elderly patients had a higher incidence of brain confusion and more frequently had multiple brain lesions. Thirty-three (79%) of the 42 elderly patients died in the hospital. Death was attributed to secondary organ failure in 33% of these elderly patients. In-hospital mortality was 36% for younger patients, all of whom died of brain injury. On the basis of the Glasgow Outcome Scale, only one elderly survivor made a favorable recovery (2%) compared with 38% of young patients. Total charges per favorable outcome were $1,540,971 for the elderly compared with $154,155 for the young. CONCLUSIONS: Elderly patients experienced higher mortality, had poorer functional recovery, more frequently died of secondary organ failure, and consumed more resources per favorable outcome than did younger patients with similar injury profiles despite equivalent treatment efforts.

Adult↗