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Biomedical subjects

A D Mason

Publications and source records attributed to A D Mason.

At least 91 records · Page 5Linked to original sources

Rhythmic melatonin response of the Syrian hamster pineal gland to norepinephrine in vitro and in vivo.

Norepinephrine (NE, 10(-6) M) stimulated melatonin accumulation in the incubation medium of rat (but not Syrian hamster) pineals taken at the end of the light phase. However, NE elevated melatonin accumulation in the medium of pineals taken after 20 min of light exposure of animals of either species at 6 h into the 10-h dark phase. A dose response to 10(-7)-10(-5) M NE was observed in both the medium and pineals upon incubation of pineals taken from rats at 4 h into the light phase and from hamsters after 20 min light exposure at 6 h into the dark phase. Approximately 95% of the melatonin present was in the medium. The incubation time was 4 h in all cases. Subcutaneous injection of 1 microgram/g NE (either at the end of the light phase or after 30 min of light at 6 h into the dark phase) did not stimulate in vivo Syrian hamster pineal melatonin content determined 1 or 2 h after injection, whether the hamsters were placed in light or darkness after the injection. However, after 30 min of light beginning at 6 h into dark, injection of 5 micrograms/g desipramine (DMI, a blocker of catecholamine uptake into nerve endings) allowed a dramatic hamster pineal melatonin response to additional injection of 1 microgram/g NE, observed at 1 and 2 h in light after injection. A small effect of DMI alone was seen. DMI also potentiated the effect of NE (each 10(-6) M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night. No significant stimulatory effect of NE and/or DMI was seen in vivo or in vitro near the middle of the light phase. Measurement of melatonin in the incubation medium is a useful method for studying pineal function. The Syrian hamster pineal has rhythm of sensitivity to NE (sensitivity evident at night) and even at night is protected by neuronal uptake from circulating NE-induced stimulation of melatonin production. NE appears to be the neurotransmitter for stimulation of pineal melatonin production in the Syrian hamster. The sensitivity rhythm and uptake protection might provide specificity of control of the nightly melatonin signal by reducing the chance of a melatonin response during the day or a response to circulating catecholamines from general sympathetic stimuli.

Animals↗

Thermoregulatory and nonthermoregulatory heat production in burned rat.

Severely burned patients are hypermetabolic within their thermoneutral zone (TNZ), where there are no thermoregulatory demands on heat production. The rat has been used as a model of postburn hypermetabolism without clear evidence that it behaves in a similar way. Male rats (400-500 g; n = 34-39) were placed as a group in a respiration chamber and metabolic rates for the average rat were determined over 3-6 h at ambient temperatures between 9 and 36 degrees C. Colonic temperatures (Tco) and body weights were measured after each run. Animals were studied sequentially as normals (N), after clipping (C) and following 50% total body surface scald burns. Clipping increased the lower critical temperature (LCT) from 27.7 to 29.1 degrees C without affecting resting heat production (N = 42.6 +/- 0.5; C = 42.0 +/- 0.8 W/m2; mean +/- S.E.) or Tco (N = 36.6 +/- 0.1; C = 36.6 +/- 0.1 degrees C) in the TNZ. Injury increased LCT to 32.8 degrees C and the burned animals were hypermetabolic (47.2 +/- 0.6 W/m2; P less than 0.05 vs. N) and febrile (36.9 +/- 0.1 degrees C; P less than 0.05 vs. N) in the elevated TNZ. These metabolic and temperature responses of burned rats are limited in magnitude but are qualitatively similar to those of patients. The extra heat production in the TNZ reflects the basic metabolic cost of injury.

Animals↗

Serum melatonin after a single aqueous subcutaneous injection in Syrian hamsters.

A single injection of 25 micrograms melatonin was given subcutaneously in 0.1 ml saline either at 3 h into the light phase (morning) in female Syrian hamsters or at 1 h before the beginning of the dark phase (evening) in males (L/D 14/10 h). In both cases, the maximal mean serum values seen at 20 min after injection (50 ng/ml) were more than 1,000 times the normal nocturnal melatonin concentration. By 1 h after injection, serum melatonin had fallen to 10% (morning) or 4% (evening) of the respective 20-min value. The average half-times for plasma concentration during the second hour after injection were 14 min in the morning and 13 min in the evening. After either morning or evening injection, serum melatonin reached normal daytime concentration between 2 and 4 h after injection.

Animals↗

Evaluation of (1-sarcosine, 8-isoleucine) angiotensin II as a therapeutic agent for oleic acid-induced pulmonary edema.

(1-Sarcosine, 8-isoleucine) angiotensin II was assessed as a therapeutic agent for acute respiratory distress syndrome with oleic acid pulmonary edema in sheep used as an experimental model. Under general anesthesia with controlled mechanical ventilation with 100% oxygen, 32 sheep received oleic acid (0.075 ml/kg) intravenously. After oleic acid infusion, 20 animals were treated with continuous intravenous infusion of the angiotensin II analogue; nine received 300 ng/kg/min, six received 600 ng/kg/min, and five received 2000 ng/kg/min. Cardiopulmonary measurements were repeated every 30 minutes for 270 minutes. According to time-integrated PaO2, six of 15 animals of the groups given 300 and 600 ng/kg/min (43%) did not respond to the treatment. All animals responded in the group given 2000 ng/kg/min. Animals in the latter group had lower Qs/Qt, PaCO2, and airway resistance than had the control animals. Elevation of pulmonary vascular resistance was limited and mean arterial blood pressure was well maintained. These results reveal that (1-Sar, 8-Ile) angiotensin II is effective in the treatment of oleic acid-induced pulmonary edema.

1-Sarcosine-8-Isoleucine Angiotensin II↗

Microbial colonization in a new intensive care burn unit. A prospective cohort study.

Renovation of an existing intensive care burn facility required closure for ten months. An interim eight-bed open intensive care ward (B) was established in a burn convalescence ward. The renovated unit (A) contained nine single-bed intensive care rooms and seven intermediate-level care beds in four rooms. Patients admitted to unit A were treated as a cohort. The first 25 admissions to unit A and the last 25 admissions to ward B meeting the inclusion criteria were compared. Microbial colonization was monitored by a fixed protocol of admission and multiple weekly sputum, wound, stool, and urine cultures. During intensive care, both cohorts exhibited the same incidence of gram-negative wound, sputum, and urine colonization. Occurrence of antibiotic-resistant organisms was the same. No evidence of bacterial cross-contamination was observed between A and B. A continuation of Providencia stuartii and Pseudomonas aeruginosa (type 15) endemics occurred in B. The collected data demonstrate that the A cohort was colonized with new, similar but distinct gram-negative organisms and indicate that cohort separation may be a practical way of eliminating endemic resistant gram-negative organisms from burn units.

Adult↗

Twenty-five year review of Pseudomonas aeruginosa bacteremia in a burn center.

The incidence of Pseudomonas aeruginosa bacteremia was examined in 5,882 burn patients consecutively admitted over a 25-year period to one burn center. The population examined had an average burn size of 33.8% of the body surface and an average age of 26.3 years. Pseudomonas aeruginosa bacteremia occurred in 540 patients. These patients had an average burn size of 54.2% and average age of 28 years. Mortality was 77%. Bacteremia with other organisms occurred during hospitalization of all but 128 of the 540 patients. Comparison of predicted mortality based on burn size and age to observed mortality showed Pseudomonas aeruginosa bacteremia to be associated with a 28% increase in mortality. Examination of mortality as a function of time showed no significant change over the 25-year period. The incidence of Pseudomonas aeruginosa colonization and infection was examined in 400 recently admitted burn patients. Colonization occurred in 107 and 34 infections were recorded in 27 of the colonized patients.

Adult↗

Nonthyroidal control of metabolism after burn injury: possible role of glucagon.

The endocrine basis for control of metabolism in nonthyroidal illness is not yet understood. Burn injury is associated with reduced serum concentrations of thyroid hormones and with resting hypermetabolism. One index of severity is total burn size (TBS, % body surface). After overnight fasting and recumbency, resting metabolic rate (MR, O2 consumption) was measured weekly and plasma was sampled for determination of glucose, total cholesterol, triglycerides, insulin, glucagon, somatostatin, growth hormone, norepinephrine, epinephrine, and cortisol in 28 burned men, 17-23 years old, TBS 2%-85%, including 8 controls with minimal injury (TBS less than or equal to 7.5%). MR was elevated in proportion to burn size mainly in the first week then declined toward normal. Growth hormone was not changed. Two multiple regression analyses (validated by random partitioning of data) determined which plasma variables independently reflected residual variation in MR: without TBS entered as a variable, high MR was associated with elevated glucose, cortisol, and glucagon, and low cholesterol (cumulative r2 = 0.79); with TBS entered, high MR was associated with greater TBS, elevated norepinephrine, and again high glucagon and low cholesterol (r2 = 0.81). Resting metabolism after burn injury is controlled not by the thyroid but may be controlled by a set of antiinsulin hormones that does not include growth hormone, but possibly includes glucagon.

Adolescent↗

Upper airway sequelae in burn patients requiring endotracheal intubation or tracheostomy.

During a period of 11 1/2 months, 41 of 217 adult burn patients admitted to the U.S. Army Institute of Surgical Research Burn Center required endotracheal intubation or tracheostomy for management of the airway and/or ventilatory assistance. Permanent upper airway sequelae were recorded and related to presence of inhalation injury, duration of tube placement, cuff pressure, and pulmonary compliance. An "inhalation injury scoring system" based upon history, physical examination, bronchoscopic findings, and abnormalities at 133xenon lung scan correlated well with postinjury alteration in compliance and subsequent sequelae. Significant inhalation injury was found in 35 patients. Seventeen of the study patients survived (Group I) and 24 patients expired (Group II). Group I patients were screened for permanent airway sequelae by fiberoptic bronchoscopy, xeroradiograms, and spirometry undertaken an average of 11 weeks after extubation or decannulation. Four patients developed tracheal stenosis and five patients had significant tracheal scar granuloma formation. Sequelae were generally more frequent and more severe after tracheostomy than after translaryngeal intubation, and duration of tube placement and presence of a tracheal stoma were the most important etiological factors in permanent damage. For initial respiratory support, we favor the use of translaryngeal (nasotracheal) tubes for periods up to 3 weeks. Fiberoptic bronchoscopic examination is the most reliable follow-up method for detecting anatomic damage in such patients. Spirometry can be used as a noninvasive screening test and xeroradiograms are helpful in assessing the degree of tracheal stenosis.

Adolescent↗

Reduced serum T4 and T3 and their altered serum binding after burn injury in rats.

Total T4 and T3 concentrations are often suppressed in burned patients. To investigate the significance of such changes, we have characterized serum T4 and T3 after full-thickness scald burns (60% body surface under anesthesia) of 270-gm male Sprague-Dawley rats housed in a light:dark cycle of 14:10 hr. Groups (N = 9-15) of BURN, SHAM (anesthesia, fur clipped, no burn) and CON (controls) were sacrificed on postburn days 8 and 14. T4 and T3 (radioimmunoassay), free indices (FT4I and FT3I = respective total T4 or T3 X in vitro charcoal T3 uptake, T3U), and free concentrations (FT4 and FT3 = total T4 or T3 X respective equilibrium dialyzable fraction, T4DF or T3DF) were not different between CON and SHAM. Compared to SHAM, mean T4 and FT4I (by about 48% of respective SHAM means on both days), TT3 (by 36, 43%), and FT3I (by 38, 45%) (days 8, 14) were suppressed in BURN (all p less than 0.001). T4DF (both days) and T3DF (day 14) were significantly elevated in BURN, demonstrating a deficit in serum binding, but T3U was not. FT4 (by 26, 22%) and FT3 (by 33, 34%) (day 8, 14) were significantly lower in BURN. On either day, covariance analyses (BURN vs. combined CON + SHAM) correlated FT4I or FT3I with respective FT4 or FT3 (all p less than 0.001, slopes not different in BURN vs. CON + SHAM), but the lower FT4I and FT3I in BURN significantly overestimated (all p less than 0.001) the depression of respective FT4 and FT3 in BURN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Frozen section technique to evaluate early burn wound biopsy: a comparison with the rapid section technique.

The importance of early diagnosis and treatment of burn wound infection has prompted many efforts to use frozen section technique for processing burn wound biopsies, most of which have been unsuccessful. A frozen section technique which facilitates quick, reliable evaluation of biopsies was developed, and has been used in the evaluation of 169 biopsies over a period of 18 months. The frozen section technique takes 30 minutes compared with 4 hours for the rapid section method. Comparison of diagnoses made using both methods for each of the 169 biopsies produced a 96% coincidence. Each discrepant diagnosis was corrected by the rapid technique approximately 3 1/2 hours after the frozen section diagnosis. The frozen section technique is a generally accurate and rapid means of assessing the microbial status of a burn wound and diagnosing invasive infection. Permanent sections produced by rapid section technique should always be examined to confirm the frozen section diagnosis.

Biopsy↗

Pineal function in burns: melatonin is not a marker for general sympathetic activity.

Burn injury in humans or rats is a model of marked elevation of general sympathetic activity for weeks, manifested in part by increased heart rate, metabolic rate, core temperature, and plasma and urinary catecholamines. Plasma melatonin was sampled at 2-h intervals for 24 h in 9 control subjects and 11 patients with severe burn injury. Daytime melatonin was not different between the groups, but nighttime values were significantly lower in the burn patients. A nocturnal surge was still significant in the patients. Resting heart rate and rectal temperature were elevated in the burn patients. In male Sprague-Dawley rats, pineal melatonin content did not differ between controls and those with an experimental burn at 4 h into the light phase nor during the nocturnal surge. Male Syrian hamsters with burns had lower daytime pineal melatonin content than did controls, but the nocturnal surge in pineal melatonin was not significantly different between groups, nor was daytime morning serum melatonin. Sympathetic activity appears partitioned, with that controlling melatonin (nocturnal surge) regulated independently. In agreement with our previous findings in other models, melatonin is not a marker for general sympathetic activity, even following severe burn injury.

Adult↗

Hormonal changes in burned hamsters.

Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone.

Animals↗

Alterations of mental status and thyroid hormones after thermal injury.

In 16 burn patients, mean values for serum T4 and T3, their T3 uptake-derived free indices (FT4I and FT3I) and dialysis-derived free concentrations (FT4 and FT3) were depressed (all P less than 0.001) compared to respective means in 13 normal subjects. In the patients, the free hormone indices were relatively more depressed below control values than were the free hormone concentrations. However, within the group of burn patients, variation in FT4I reflected that of FT4 (r = 0.91), and variation in FT3I reflected that of FT3 (r = 0.93). We then studied serum T4, T3, and their free indices in 134 patients (burn size, 6-96% of the skin area), including 45 nonsurvivors, none of whom received steroid, dopamine, or iodine treatment. At each sampling, the level of obtundation (LO) was determined on a 6-point scale from normal to deep coma. Whereas initially low mean FT4I values rose in survivors, they remained lower in nonsurvivors than in survivors until death in the nonsurvivors. In nonsurvivors, mean LO worsened in the first week and remained worse than that in survivors until death. Multiple regression analyses showed that for a given age or burn size, nonsurvival was better correlated with lower T4 or FT4I than with T3 or FT3I, but was even more closely correlated with worse LO (P less than 0.001). Exclusion of data obtained within 24 h of narcotic or tranquilizer doses did not weaken the relationship of nonsurvival with LO and FT4I. Nonsurvival after burn injury was associated with reduced T4, FT4I, and mental status for up to weeks before death, this association being independent of treatment with drugs acting on mental status or thyroid function.

Burns↗

Replacement therapy with modified immunoglobulin G in burn patients: preliminary kinetic studies.

Suppression of serum immunoglobulin G for periods ranging from days to weeks following thermal injury may enhance the risk of infection in burn patients. In an initial trial, we attempted to determine whether intravenous pulses of Immunoglobulin G (IgG) will establish and maintain normal serum IgG concentrations in this interval. The levels of endogeneous serum IgG in eight control patients, mean total burn size 45 percent body surface area (no IgG infusions), were measured by radial immunodiffusion on various postburn days. Commercially available reduced alkylated IgG (5 percent Gamimune, Cutter Biological, Berkeley, California) was infused in doses of 500 mg/kg twice per week in four patients (total burn size 32 percent) and once per week in five patients (total burn size 47 percent), beginning during the first postburn week. Circulating IgG was measured prior to each infusion and at three postinfusion times: (1) 15 minutes (peak), (2) one day, and (3) either day 3, 4, or 6. Surgery or blood transfusions prior to one of these time points invalidated kinetic analysis of some infusions. Exponential two-point decay constants for total serum IgG after each of 24 infusions were calculated separately for early (day 0-1) and later (day 1-3 or 1-4) postinfusion intervals and assessed by stepwise regression analysis to determine sources of variation in decay. Early decay was seen to be faster with larger burn size after accounting for variation of decay with preinfusion and peak IgG values. Later decay was not related to burn size. Maltose, a constituent of the IgG preparation, was detectable in serum for only four to eight hours after each infusion and may have contributed to a 20 percent increase in total serum glucose between four and eight hours postinfusion. Mean serum IgG in patients given infusions twice weekly was in the normal range after one infusion, about a week earlier than in untreated patients. Such infusions maintained normal IgG levels.

Agammaglobulinemia↗

Increased susceptibility to infection related to extent of burn injury.

A model of burn wound sepsis in which the mortality caused by infection was significantly greater after a 60% total body surface area (TBSA) burn than after a 30% TBSA burn was developed in the rat. In rats that sustained a 60% TBSA burn (30% partial plus 30% full thickness), the 30% TBSA partial-thickness burn that was inoculated with Pseudomonas aeruginosa strain 59-1244 developed invasive wound infection (greater 10(5) colony-forming units per gram of tissue). Infection did not develop in rats that had a 30% TBSA partial-thickness burn inoculated, without additional injury. The additional burn in the rats with a 60% TBSA burn seemed to affect the development of infection in the partial-thickness wound and the overall outcome by a mechanism other than by infection of the full-thickness wound itself. Autopsy confirmed that mortality was caused by sepsis.

Animals↗

Topical chlorhexidine diphosphanilate (WP-973) in burn wound sepsis.

We studied the diphosphanilate salt of chlorhexidine (WP-973), as a 2% cream, for therapeutic activity in two rat models of fatal burn wound infection. Control treatments were infection and placebo cream; infection only; infection and 1% sulfadiazine silver; and burning only. Activity against Pseudomonas aeruginosa or Proteus mirabilis was tested in surface-inoculated rats with 20% scalds. Treatments were initiated 24 hours or four hours, respectively, after inoculation. Pseudomonas-infected rats were treated once a day for ten days. Proteus-infected rats were treated once a day for five days. In these experimental models, chlorhexidine diphosphanilate was equal to silver sulfadiazine, an established topical chemotherapeutic agent. In vitro activity was examined using bacteremia isolates from 65 burned patients. Using agar diffusion trench plates, chlorhexidine diphosphanilate was active against all strains. No evidence of cross-resistance between sulfonamide and chlorhexidine diphosphanilate or its components was observed.

Administration, Topical↗