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F T Caldwell

Publications and source records attributed to F T Caldwell.

At least 19 recordsLinked to original sources
PubMed1999

The effect of indomethacin on the cytokine cascade and body temperature following burn injury in rats.

This study investigates the hypothesis that indomethacin's ability to prevent "fever" following burn injury in rats is mediated via decreased plasma concentrations of IL-6, the putative mediator of increased body temperature. Sprague-Dawley rats had radio transmitters and osmotic pumps containing indomethacin placed in the peritoneal cavity. Seven days later full thickness scald burns to 50% of the body surface area were produced. Following burn injuries, daily blood samples were obtained from a carotid catheter for assay of lipopolysaccharide (LPS), interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and IL-6. In addition, body temperature (T(B)) and activity index were obtained every five minutes by telemetry. There were four experimental groups: burn + indomethacin (B-In); burn + polyethylene glycol (Peg) (B-Peg); control + indomethacin (C-In); and control + Peg (C-Peg). Burned animals demonstrated a significant two-fold increase in plasma IL-1alpha levels (p=0.004) and a seven-fold increment in IL-6 (p=0.0001) through the 7th PBD, and indomethacin administration had no significant effect upon the cytokine plasma levels. There were no significant increases in IL-1beta, TNF-alpha or LPS in any group. Indomethacin eliminated the chronic increase in T(B) following burn injury, and this effect was not produced by changes in plasma levels of the endogenous pyrogens IL-1alpha and IL-6.

Analysis of Variance↗
PubMed1999

Vagotomy modifies but does not eliminate the increase in body temperature following burn injury in rats.

INTRODUCTION: Rats with burn injury to > or = 50% of the BSA demonstrate a significant increase in body temperature (T(B)) during light hours, and decrease of circadian variation in T(B). This study investigated the hypothesis that part or all of the signal for increased T(B) in rats with burn injury is transmitted to the central nervous system by way of afferent vagal fibers. METHODS: Four groups of animals were studied: Burn-Sham Vagotomy; Control-Sham Vagotomy; Burn-Vagotomy and Control-Vagotomy. Anesthetized animals had bilateral subdiaphragmatic vagotomy (VagX) or sham VagX performed, and AM radio transmitters were implanted in the peritoneal cavity for the purpose of recording T(B) and activity index (AI). Following a one week recovery period, burn animals received scald burns equal to 50.3 +/- 2.5% BSA. RESULTS: The main effect of VagX upon T(B) was a small but significant reduction in T(B) during dark hours. At least 87% of this decrease in post-burn T(B) was also present for the control vagotomy group. Vagotomy had no effect on the increase in T(B) for the burn groups during light hours. During dark hours, VagX significantly reduced T(B) in burns and controls, and burn injury significantly reduced activity. CONCLUSIONS: One may speculate that afferent vagal signals are partially responsible for maintenance of T(B), with or without burn injury, and that the major signal for increase in T(B) for animals with burn injury is not a neural one via afferent vagal pathways.

Afferent Pathways↗
PubMed1999

Humoral versus neural pathways for fever production in rats after administration of lipopolysaccharide.

BACKGROUND: These studies address the question of the relative roles of humoral and neural pathways in the genesis and control of the fever component of the acute phase response. METHODS: Two experiments were performed to examine the effect of vagotomy (VagX) on the febrile response to intraperitoneal (i.p.) and intra-arterial (i.a.) lipopolysaccharide (LPS), and plasma cytokine and LPS concentrations after intravenous (i.v.) or i.p. injections of LPS. In experiment 1, body temperature (T(B)) was obtained from unperturbed animals by using radio transmitters and telemetry after injection of LPS i.a. or i.p. In the second study, serial blood samples were obtained for cytokine and LPS assay after injection of LPS either i.v. or i.p. Colonic temperatures (T(C)) were obtained from indwelling thermistors. RESULTS: The maximal increments in T(B) for animals receiving LPS i.a. and i.p. with or without VagX were not different from one another: sham vagotomy (Sham-VagX) + LPS i.a., 1.20 +/- 0.26 degrees C; VagX + LPS i.a., 1.23 +/- 0.64 degrees C; Sham-VagX + LPS i.p., 1.45 +/- 0.27 degrees C; VagX + LPS i.p., 1.50 +/- 0.35 degrees C (F = 1.12, p = 0.36). Neither were the four resulting response curves for T(B) different from one another. Plasma levels of LPS, tumor necrosis factor-alpha, and interleukin-6 were significantly elevated at 45 minutes after LPS injection by either the i.v. or i.p. routes, preceding any increments in T(B), and were not effected by VagX. CONCLUSION: Fever development for animals receiving LPS in experiment 1 demonstrates a temporal relationship -- with increments in plasma levels of LPS and pyrogenic cytokines obtained in experiment 2 after administration of LPS either i.p. or i.v. Vagotomy had no discernible effect on the responses regardless of the route of administration of LPS.

Acute-Phase Reaction↗
PubMed1998

Studies on the mechanism of fever after intravenous administration of endotoxin.

BACKGROUND: The sequential events in fever production after intravenous administration of lipopolysaccharide (LPS) remain unsettled and controversial. Vessels of the organum vasculosum laminae terminalis (OVLT) lack the tight junctions of the blood-brain barrier and allow substances of high molecular weight to enter the interstitium but not the neuropil. The present studies investigate the hypothesis that the OVLT is needed for fever production after intravenous administration of LPS in the rat. METHODS: Electrolytic lesions were produced in the OVLT of rats. After recovery, left carotid and right atrial catheters were inserted, and 24 hours later calorimetry was performed. Blood was drawn for baseline assay for cytokines and LPS after which LPS was given intravenously, with studies continued for 5 hours, and additional blood samples were drawn at 90 and 300 minutes. RESULTS: The maximal increment in rectal temperature for the sham lesion LPS group (1.25 +/- 0.44 degrees C) was significantly greater than for the sham-saline (-0.05 +/- 0.46 degrees C) and the lesion-LPS groups (0.35 +/- 0.45 degrees C) for minutes 120 to 300. Ninety minutes after LPS administration, serum levels of interleukin (IL)-6, tumor necrosis factor-alpha, and LPS were significantly elevated (p < 0.0001) above baseline for the sham-LPS and lesion-LPS groups. IL-1beta serum levels remained below detection levels. CONCLUSION: Large lesions of the OVLT prevent and/or attenuate fever due to LPS even though tumor necrosis factor-alpha and IL-6 are greatly increased in serum. IL-1beta does not seem to be an endogenous humoral mediator in this model.

Animals↗
PubMed1997

Manipulation of the inflammatory response to burn injury.

BACKGROUND: Burn injury is characterized by hypermetabolism and protein catabolism. Endotoxin, derived from either wound or gut, may participate in this response. METHODS: Eleven seriously burned patients were treated with the endotoxin-binding agent polymyxin B and underwent partitional calorimetry and nitrogen balance studies. The data from theses patients were compared with data from 28 contemporary, similarly burned patients who did not receive polymyxin B. RESULTS: Elevated levels of circulating endotoxin were not consistently detected in either group. Interleukin-6 was elevated and correlated with rectal temperature and nitrogen excretion in both groups. Administration of polymyxin B produced no change in metabolic rate but produced a significantly more positive nitrogen balance and was associated with a prompt reduction in interleukin-6 levels. CONCLUSIONS: These data support the hypothesis that endotoxin plays a role in the postburn protein catabolism but not in the hypermetabolic response. This protein catabolic response is statistically associated with circulating interleukin-6 levels, suggesting a possible role for interleukin-6 in postinjury protein wasting.

Adolescent↗
PubMed1995

Effect of adrenal medullectomy on responses in heat production, plasma catecholamines and body temperature of burned rats to changes in the temperature of the hypothalamus.

Burn (B) and control (C) rats with and without adrenal medullectomy (Adx) 9-11 days postburn underwent warning and cooling of the preoptic anterior hypothalamus (POAH) during calorimetry at 22 degrees and 28 degrees C ambient. Blood was drawn for catecholamine assay during each displacement of the POAH temperature (Thy). The heat production (Hp) for the AdxB group at 22 degrees and 28 degrees C was not different from the Hp for the sham AdxB group (80 +/- 4 vs 86 +/- 8 at 22 degrees C, 58 +/- 8 vs 64 +/- 7 W/m2 at 28 degrees C) in spite of there being no detectable circulating epinephrine (E) for the AdxB groups. Cooling of the POAH of the AdxB 22 degrees C group, however, did not induce a further increment in Hp, in contrast to all other groups. Thy demonstrated good significant negative linear correlation with Hp for all groups. The resulting slopes were not significantly different from one another, indicating no difference in thermal sensitivity of the POAH between the groups. In four of eight groups plasma norepinephrine (NE) demonstrated positive correlation with Hp and in five of eight groups negative correlation with Thy, Plasma E values did not correlate with Hp and demonstrated negative correlation with Thy in two of four possible groups. These data show that postburn hypermetabolism is not dependent on E in the rat and suggest that NE may be calorigenic in burned rats.

Adrenal Medulla↗
PubMed1995

Effect of alpha adrenergic blockade on thermoregulation in adrenal demedullated burned rats.

This study in burned rats studied at two ambient temperatures (22 degrees and 28 degrees C) and housed at 28 degrees C was designed to investigate the role of catecholamines in the maintenance of thermal homeostasis following burn injury. Two weeks prior to burn or sham burn, animals underwent adrenal medullectomy or sham adrenal medullectomy. Between postburn days 9 and 13, simultaneous direct and indirect calorimetry was performed following administration of 2mg/kg of phentolamine (alpha adrenergic blocking agent) via a carotid arterial line. Following administration of phentolamine, heat production and body temperature decreased and heat loss increased immediately. The cooling slopes for the burn groups were significantly steeper than for the control groups, within ambient temperatures. Within ambient temperatures, the presence or absence of the adrenal medulla had no discernible effect on the cooling slope of the burns or the controls. The burned animals cooled 1.9-3.5 times faster at 22 degrees than at 28 degrees C, and controls cooled 2.0-3.9 times faster at 22 degrees than at 28 degrees C. Phentolamine produced a several-fold increase in serum concentrations of both norephinephrine (NE) and epinephrine (E), indicating a gross overlap in alpha and beta adrenergic receptor utilization for E and NE. The progressive cooling of the adrenal demedullated burn group at 22 degrees C following phentolamine administration seems to indicate that norepinephrine is calorigenic for rats under these experimental circumstances. These experimental results indicate a relatively non-essential role for catecholamines in the maintenance of thermal homeostasis within the thermal neutral zone in the rat.

Adrenal Medulla↗
PubMed1995

Retrospective evaluation of admission criteria for paediatric electrical injuries.

In the medical community, the practice of admitting all electrical burns for 24-48 h of observation, monitoring and laboratory evaluation is widespread. This retrospective review of paediatric electrical burns was conducted to determine which patients may safely be treated as outpatients. Retrospective analysis of all paediatric burns admitted between 1980 and 1991 identified 35 patients with electrical injuries. Patients were divided into two groups for analysis: those burned by exposure to household voltages (120-240 V; n = 26) and those exposed to high voltages, in excess of 1000 V (n = 9). The majority of household electrical injuries occurred secondary to contact with the household 120 V (21/26). Contact with an extremity accounted for the largest number of these injuries (18/26). The mouth was the second most frequent site of injury (7/26). Most of these patients (20/26) had < 1 per cent BSA burn. No patient in the household-voltage group had an arrythmia that required treatment, nor were there any identified examples of compartment syndrome or other vascular complications. Seven patients did require minimal skin grafting. No deaths occurred in either group. The patients in the household-voltage group were significantly younger. High-voltage electrical injuries occurred in an older patient population and required more aggressive care and surgical intervention. This was evident at the time of initial evaluation. Based on these data, healthy children with small partial-thickness electrical burns and no initial evidence of cardiac or neurovascular injury do not appear to need hospital admission.

Adolescent↗
PubMed1992

Control of the hypermetabolic response to burn injury using environmental factors.

This study was performed to establish the relative efficiency of occlusive dressings and variable ambient temperature (group I) versus no dressings and variable ambient temperature (group II) versus no dressings and electromagnetic heaters (group III) for controlling the postburn hypermetabolic response. Fifteen burn patients and five normal controls (group IV) were studied when subjectively comfortable using partitional calorimetry, after which each patient was cold stressed by sequentially decreasing external energy support, and repeating calorimetry studies and serial plasma catecholamine assays. The percentage increase in heat production above predicted normal values was significantly increased for all groups when cold (C) versus neutral (N) (group I: [N] 24 +/- 24 versus [C] 49 +/- 25%; group II: [N] 46 +/- 35 versus [C] 74 +/- 47%; group III: [N] 21 +/- 20 versus [C] 78 +/- 25%; group IV: [N] -9 +/- 12 versus [C] 16 +/- 10%, p less than 0.05 all comparisons). Plasma catecholamine values did not increase significantly when patients were subjectively cold. These studies do not support the role of catecholamines as the primary mediator in the cause of the postburn hypermetabolic response. Using the patients' subjective comfort status as a guide for external energy support, it is possible to greatly reduce but not to eliminate the hypermetabolic response to burn injury.

Adult↗
PubMed1992

Ibuprofen lowers body temperature and metabolic rate of humans with burn injury.

A group of 15 burned children and young adults with large burns (mean, 41% +/- 15% BSA) were administered ibuprofen (40 mg/kg for 3 days). Each patient served as his or her own control in this crossover study (with and without ibuprofen). Paired calorimetric and temperature studies and urinary nitrogen measurements were performed. No nitrogen-sparing effect was identified for this dose of ibuprofen. However, patients demonstrated a statistically significant reduction in average rectal temperature (0.67 degrees C decreases) (p less than 0.01) and in metabolic rate (11.4% decreases) (p less than 0.01) while taking ibuprofen. Linear regression analysis of the reduction in temperature versus the reduction in metabolic rate yielded a statistically significant correlation (p less than 0.01) with a slope of 13.6% reduction in metabolic rate per degree centigrade reduction in the 72-hour average rectal temperature. These results support the hypothesis that ibuprofen attenuates the hypermetabolic response to thermal injury by blunting the temperature elevation that is usually seen.

Adolescent↗
PubMed1990

Effect of early feeding on the postburn hypermetabolic response in rats.

The effect of early enteral feeding on the hypermetabolic response following burn injury in a rat burn model has been investigated. The rates of heat production and partitioned heat loss were determined on the fourteenth postburn day for five treatment groups: I) burn, fed rat chow ad libitum starting 2 hours postburn; II) burn, fed by gastrostomy beginning 2 hours postburn; III) burn, fed by gastrostomy, delayed until 72 hours postburn; IV) controls, fed by gastrostomy 2 hours post anesthesia; and V) controls, fed rat chow ad libitum 2 hours post anesthesia. Gastrostomy feedings delivered 175 kcal/kg.day. The mean rates of heat production and heat loss for the three burn groups did not differ significantly whether rats were fed chow ad libitum, or by gastrostomy early or late. Contrary to previous studies using a guinea pig model, method and timing of feeding in this burned rat model had no significant effect on the postburn increment in the rate of heat loss and the corresponding increment in the rate of heat production.

Animals↗
PubMed1988

Surgical complications of thermal injury.

Aggressive control of intragastric pH in the burn patient has essentially eliminated upper gastrointestinal bleeding. The recent spectrum of complications in the thermally injured patient has shifted. Vascular occlusion and missed associated injury were the most frequent early complications in this review. Those complications occurring late in the course were attributed to sepsis originating in the burn wound. The common diagnostic error was to blame the burn injury for the patient's signs and symptoms. A high index of suspicion of an occult process must be exercised when caring for the burn patient who has burn shock with a decreasing hematocrit value or a compartment syndrome that does not respond to escharotomy or fasciotomy or the septic patient with a clean burn wound.

Adolescent↗
PubMed1988

The effect of early feeding on postburn hypermetabolism.

The effect of early enteral feeding upon postburn hypermetabolism was studied on the fourteenth postburn day using five groups of rats. Feeding methods and treatments for the groups were: I) rat chow ad libitum at 2 hours postburn (PB); II) fed early by gastrostomy at 2 hours PB; III) fed late by gastrostomy at 72 hours PB; IV) fed early by gastrostomy--shaved control; V) rat chow ad libitum--shaved control. Gastrostomy feedings delivered 175 kcal/kg.day. The rates of heat production and heat loss did not differ significantly between any of the burn groups, whether fed ad libitum, or early or late by way of gastrostomy. The burned rats fed ad libitum gained significantly more weight than the rats fed late by gastrostomy. Contrary to previous studies using a guinea pig model, method and timing of feeding had no demonstrable effect on the postburn increment in heat loss and the secondary increment in heat production following thermal injury in rats.

Animals↗
PubMed1988

The effect of staged burn wound closure on the rates of heat production and heat loss of burned children and young adults.

The sequential metabolic studies of nine severely burned patients were examined retrospectively. Information analyzed included heat production (M), partitioned heat loss (HL), the percentage of the body surface area open wound (% open wound) and skin (TS) and rectal (TR) temperatures. The reduction in the hypermetabolic response correlated with the number of days postburn (DPB), % open wound, average body temperature (TB = 0.8TR + 0.2TS) and evaporative heat loss (EV) (r = 0.62, 0.55, 0.56, 0.63, respectively). However, decrements in metabolic rate between sequential studies correlated only with the change in % open wound and the change in EV (r = 0.41 and 0.49, respectively). While changes in heat loss are not capable of predicting all of the variation in metabolic rate, burned patients demonstrate an increase in heat production largely secondary to the inability to conserve heat effectively in the periphery. This response is compounded by an altered central thermoregulation.

Adolescent↗
PubMed1987

Beneficial effects of a hypertonic solution for resuscitation in the presence of acute hemorrhage.

Crystalloid solutions such as Ringer's lactate have become the standard for initial volume replacement after hemorrhage. Although the relative merits of blood, colloid, and crystalloid have been extensively studied, little attention has been directed toward determining the optimal composition of the crystalloid solution. Based on the beneficial properties of hypertonic lactated saline solution in burn resuscitation, we have extended its use to acute hemorrhage. Using an awake canine model analogous to the clinical situation, we compared hypertonic lactated saline solution with Ringer's lactate solution for resuscitation in the presence of acute blood loss. The hypertonic lactated saline solution group required less fluid to restore and maintain cardiac output and blood pressure while maintaining better urine output. Although the Ringer's lactate solution group had increased shunt function indicative of pulmonary dysfunction, the shunt function in the hypertonic lactated saline solution group did not differ from that in the control group. Serum sodium and osmolality values were higher in the hypertonic lactated saline solution group, but at no time did they approach toxic levels.

Acute Disease↗
PubMed1987

The effect of rapid resuscitation upon cardiac index following thermal trauma in a porcine model.

Minipigs were divided into four experimental groups: nonburned control (C); burn, minimal resuscitation (MR); burn, standard resuscitation (SR); and burn, rapid resuscitation (RR). Resuscitation was begun 30 minutes postburn and hemodynamics were measured through 24 hours postburn. At 30 minutes postburn, the three burn groups demonstrated a significant decrease in cardiac index % (CI%). At 1 1/2 hours postburn, the RR group CI% was significantly greater than for the SR group and not significantly different from that of controls. At 2 hours postburn, fluid was abruptly decreased in the RR group and the salutary effect on CI promptly dissipated. In this model, the early decrement in CI following thermal injury is responsive to rapid resuscitation, concluding that the etiology of decreased CI following thermal trauma is at least partially due to inadequate volumes of fluid administration in the early postburn period.

Animals↗
PubMed1987

Hypocupremia in a major burn.

Trace element deficiency in burns is an area which apparently has not been investigated. We recently encountered a severely burned patient with profound copper depletion. Neuropsychiatric symptoms and delayed healing may have been secondary to this deficiency. Further study is needed to clearly delineate the role of acquired copper deficiency in recovering burned patients.

Adolescent↗