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Biomedical subjects

A D Mason

Publications and source records attributed to A D Mason.

At least 109 records · Page 6Linked to original sources

Altered protein metabolism in diaphragms from thermally injured rats.

Thermal injury is known to cause increased muscle catabolism, but the mechanisms involved in this process are not clear. Diaphragms from thermally injured rats were removed and incubated in vitro on the third postburn day in order to determine the rates of protein synthesis and degradation using [14C]tyrosine uptake and release as an indicator of these processes. Diaphragms from rats that received 50% total body surface, full-thickness wounds and unburned sham-treated controls were examined. The rate of protein synthesis in the absence of insulin supplementation was found to decrease (26%) and the rate of protein degradation increased (81%) under these conditions. Insulin supplementation (0.1 U/ml) to the incubation media caused a significant increase (39%) in the rate of synthesis in the sham-controls but did not stimulate synthesis in the burned group. Degradation rates measured in the presence of insulin were increased in the burned group (64%), but were somewhat blunted in comparison to the insulin-deficient degradation rates (81%). These results indicate that diaphragm muscles from thermally injured rats show a decreased insulin stimulation of protein synthesis after injury, and insulin does not significantly alter the enhanced rate of protein degradation observed in these muscles after injury.

Animals↗

Mechanisms of in vitro sensitivity to sulfadiazine silver.

Sulfonamide-resistant organisms have been reported as a frequent consequence of the clinical use of sulfadiazine silver. At this burn center, sulfonamide resistance occurred in more than 80% of gram-negative isolates. We tested the requirement for the individual antimicrobial activities of sulfadiazine and silver for the vitro activity of sulfadiazine silver. The sulfadiazine component is not necessary for in vitro sensitivity. In vitro sensitivity to sulfadiazine silver does not consistently predict the presence of therapeutic activity in Pseudomonas aeruginosa-infected rats with burns. We describe an example of a transferable multiple-antibiotic resistance plasmid that contains selectable sulfonamide resistance. The use of sulfadiazine silver can, therefore, lead to the selection of organisms that are resistant not only to sulfonamides but to antibiotics of clinical consequence, and this possible risk must be considered in electing to use the agent.

Animals↗

Neutral proteinase activity in skeletal muscle from thermally injured rats.

Male Sprague-Dawley rats that received 60% total body surface, full-thickness, scald burns on the dorsum and abdomen were used in this study. Neutral proteinase and Ca2+-activated neutral proteinase activities were measured in gastrocnemius and soleus muscles at 3 and 21 days after the thermal injury. Neutral proteinase activity decreased significantly in the soleus (50%) and gastrocnemius (46%) muscles on the third postburn day. Ca2+-activated neutral proteinase was unchanged at this time. Neutral proteinase and Ca2+-activated neutral proteinase activities were unaltered at 21 days postinjury. These results may reflect a protein-sparing effect on the third postburn day which could be an early intracellular change prior to an increase in selected enzyme proteins during the hypermetabolic phase after thermal injury.

Animals↗

Inappropriate vasopressin secretion (SIADH) in burned patients.

To determine if concentration of plasma arginine vasopressin (AVP) is inappropriate for the plasma Na+ concentration in hyponatremic burned patients, we obtained 32 plasma samples from 20 patients with total burn size (TBS) 15 to 80% of body surface on or after postburn day (PBD) 4 in the morning following all-night recumbency. In the 25 samples (17 patients) with hyponatremia, AVP was elevated, 1.6 to 14.3 (normal less than 0.5) pg/ml. Most patients with normal serum Na+ had normal AVP values. Out of the total, nine patients (12 samples) without renal failure or sepsis, selected also for hyponatremia and urinary Na+ greater than or equal to 20 mEq/L, were considered separately. BUN of 11.7 +/- 1.8 mg/dl and plasma glucose of 130 +/- 5.6 mg/dl, Na+ of 130 +/- 1.1 mEq/L, calculated osmolality of 272 +/- 1.6 mosm/kg, and cortisol of 20.4 +/- 1.6 micrograms/dl were associated with a 24-hour fluid intake of 4.3 +/- 0.26 L and urinary output of 2.7 +/- 0.33 L, Na+ of 80 +/- 14 mEq/L, and osmolality of 520 +/- 73 mosm/kg (mean +/- SE). In all of the plasma samples, AVP was markedly elevated (6.9 +/- 1.1 pg/ml). In another study, four hyponatremic burned patients were given a standard water load. Excretion of the water was delayed, and further dilution of the initially hypotonic plasma resulted in a fall of urinary osmolality and plasma AVP. Cutaneous thermal injury can cause resetting of the mechanism linking plasma tonicity and AVP secretion resulting in dilutional hyponatremia. This syndrome occurs in the absence of gross physiologic perturbations such as volume depletion or adrenal insufficiency.

Adolescent↗

A new open and closed respiration chamber.

A new, fully automated, open and closed respiration chamber has been constructed, which is large enough to accommodate man or comparable sized animals. Metabolic rate is calculated from measured changes in respiratory gas volumes while the system is hermetically sealed. When CO2 concentration reaches a prescribed level, large ports are opened and the chamber is ventilated. By repeating this process, a series of metabolic determinations can be conducted over an extended period. Temperature, humidity and air velocity are fixed, but chamber volume and pressure vary with changes in the respiratory exchange of the animal and/or barometric pressure. Small, rapid changes in gas volumes are monitored by a low-resistance spirometer and large changes accommodated in a second, high-volume, motorized spirometer. Chamber operations, data acquisition and metabolic calculations are performed by a small computer. System calibration with methanol combustion indicates that estimates of respiratory gas exchange are highly accurate over a temperature range from 10-40 degrees C.

Animals↗

Experimental Proteus mirabilis burn surface infection.

We established a human burn isolate of Proteus mirabilis as an experimental pathogen. Infliction of a nonfatal scald injury (30%) rendered rats highly susceptible to lethal surface infection with this isolate. Dose-response experiments indicated that the lethal inoculation dose (50%) was less than 10(3) organisms per square centimeter. Histopathologically, surface colonization was followed by progressive growth with subsequent invasion of viable tissue. The invasion was not characterized by the perivascular or perineural lesions observed in experimental Pseudomonas burn sepsis. Bacteriologic examinations showed moribund animals to be bacteremic with the test strain and to have wound biopsy counts exceeding 10(6) organisms per gram of tissue. The role of bacterial motility as a virulence factor in this surface infection was investigated. Substrains selected for loss of subsurface spreading in soft agar lost virulence. This model of burn infection with a member of the Enterobacteriaceae should be used to evaluate topical and parenteral antimicrobial agents needed for the control of wound infections caused by such agents.

Animals↗

Altered muscle metabolism in rats after thermal injury.

Burn injury is associated with an elevation in total body oxygen consumption, increased hepatic alanine uptake and conversion to glucose, and a negative nitrogen balance. The primary source of the alanine used for gluconeogenesis by the liver and of the nitrogen lost as urea is believed to be from skeletal muscle. Selected muscle regulatory enzymes and pyruvate and oleate oxidation rates were assayed for maximal activity during the postburn period. Male Sprague-Dawley rats that received 50% total body surface scald burns on the dorsum and abdomen were examined for citrate synthase (CS), phosphofructokinase (PFK), and glutamate-pyruvate transaminase (GPT) activity in uninjured muscle at 3, 7, 13, and 20 days postburn, and the ability of muscle to oxidize pyruvate and oleate was measured at 3 and 13 days after injury. Cs, PFK, and GPT activities increased significantly (p less than 0.05) by 13-20 days after injury in the soleus and diaphragm. The epitrochlearis showed no change in CS, but PFK and GPT were elevated within this time frame. The gastrocnemius muscle showed an elevated oleate oxidation rate at 13 days after injury, but no change at 3 days postburn. Pyruvate oxidation rates were unaltered. The results of this study indicate that during the postburn period several metabolic alterations occur in muscle. These adaptations include: (1) elevated CS activity which may be associated with increased oxidative capacity,, (2) increased PFK activity which implies that more substrate is being shuttled through the glycolytic pathway, (3) increased GPT activity which may reflect increased pyruvate conversion to alanine, and (4) increased oleate oxidation rates which demonstrate that muscle is utilizing more fatty acid substrates during the postburn period.

Adaptation, Physiological↗

Depressed reflex vasomotor control of the burn wound.

Total leg blood flow was measured by venous occlusion plethysmography in five normals and 14 burned patients before and after 30 min of external heating. Leg surface temperatures were held constant, but rectal temperatures increased on the average of 0.4 to 0.5 degrees C in all subjects following this heat load. Leg blood flow increased by 56.0% in the controls, 63.2% in five patients with essentially no leg burn (mean burn size = 1.5% leg surface), and 9.6% in nine patients with major leg injuries (mean burn size 55% leg surface). Failure of reflex vasodilatation in the burned leg was evident up to 107 days postinjury even when the wound was well-healed. All subjects sweated freely from the unburned skin. In two patients, where arm and leg blood flows were measured simultaneously, flow to the uninjured arm increased while that to the injured leg remained unchanged. This lack of reflex vasodilatation in the burned limbs suggests either that wound vessels are denervated or that they are so dilated in the basal state that further dilatation is limited. The bulk of this and other data would support the denervation concept. This physical or chemical denervation could occur at the time of injury, be localised to the area of the wound, and result in loss of both neurogenic vasoconstrictor tone and active reflex vasodilatation.

Adult↗

Hypermetabolic low triiodothyronine syndrome of burn injury.

The free tetraiodothyronine index (FT4I) and free triiodothyronine index (FT3I) in burn patients represented the serum levels of free (dialyzable) T4 and free T3, respectively. FT4I and FT3I were lower with greater burn size and were lower in nonsurvivors than expected for the burn size. there was no compensatory elevation of basal or releasing hormone-stimulated thyrotrophin (TSH) concentrations. Reverse T3 was higher with greater burn size. T3 treatment restored FT3I but did not affect mortality or resting metabolic rate (MR) measured in survivors, compared with placebo therapy. Whereas the hypermetabolic response to burn injury appeared t be independent of thyroid hormones, MR was correlated positively with burn size and with elevated plasma norepinephrine and epinephrine concentrations for several weeks after injury. Lack of augmented TSH concentrations, absence of low plasma reverse T3, and presence of hypermetabolism suggest that the reduced plasma free T3 does not indicate functional hypothyroidism, but may represent an adaptation to the assumption of metabolic control by the sympathetic nervous system.

Adolescent↗

Management of abdominal wounds in thermally injured patients.

Over a 10-year period, 103 burned patients (mean age, 25 years; mean burn size, 43% of the total body surface) required an intra-abdominal operation. Life-threatening complications dictated operative intervention, and the complications resulted in increased mortality. Abdominal incisions dehisced in 33 patients. In 75 patients whose 91 incisions were closed with retention sutures, 18 wounds (20%) separated postoperatively, including seven in which synthetic sutures disrupted. In 28 patients whose 35 abdominal incisions were closed without retention sutures, 15 wounds (43%) dehisced. Placement of the abdominal incision through the burn wound appeared not to affect the incidence of dehiscence. When an abdominal operation is required in burned patients, their wounds should be closed by stainless steel wire, usually as retention sutures, placed through all muscle and facial layers of the abdominal wall.

Abdominal Injuries↗

Cortisol and corticotrophin in burned patients.

In a study of 36 men burned in a fire, based on sequential early morning samples, plasma cortisol concentration was elevated in proportion to burn size. Plasma corticotrophin (ACTH) was not correlated with burn size, suggesting that factors other than ACTH contribute to the elevated cortisol. Cortisol levels did not fall on the days preceding death in nonsurvivors. During 24-hr sampling, burned patients exhibited a fitted cortisol curve mean that was elevated in proportion to burn size, a rhythm amplitude that was significantly less than that in uninjured controls, and a normal peak time. Metabolic rate, rectal temperature, and urinary catecholamine excretion were also elevated in proportion to burn size. Although plasma cortisol was positively correlated with metabolic rate and with temperature, this appeared to result from a common relationship of these variables with burn size. On the other hand, urinary catecholamine values significantly reduced the residual variance of metabolic rate and temperature after accounting for variance related to burn size. Cortisol appears to be less prominent than catecholamines as a possible mediator of the elevated thermogenesis.

Adolescent↗

Paradoxical effect of hyperoncotic albumin in acutely burned children.

Hyperoncotic albumin proved ineffective as a plasma volume expander in the resuscitation of four acutely burned children. Hypovolemia and pulmonary edema were apparently intensified by an obligatory fluid shift following tissue extravasation of protein. We conclude that, when used, hyperoncotic albumin should be suspended in a sufficient volume of saline to produce a solution isotonic and iso-oncotic relative to plasma.

Acute Kidney Injury↗

Burn wound infection.

Ninety-seven of 763 patients admitted to a burn center during a 3-year period had histologically confirmed bacterial or fungal burn wound invasion. Nine of these 97 patients survived and 88 died. Burn wound infection was the principal cause of death in 57 patients and was diagnosed perimortem in an additional 31 patients but was not judged to be the primary cause of death. Pseudomonas aeruginosa continues as the most frequent offending organism. The variety of mycotic and bacterial organisms identified, however, suggests that the compromise of the host is the critical factor, and not any particular microorganism. A variety of combinations of treatments are described: the selection of treatment depends upon the type and extent of infection.

Adolescent↗

A problem-oriented gynecology clinic for patients with sexually transmitted diseases.

A problem-oriented clinic designed to provide continuity of care for female patients with sexually transmitted diseases (STDs) is described. The primary goal of the clinic is to ensure adequate follow-up care for individuals diagnosed as having pelvic inflammatory disease. Functions of the clinic also include follow-up care for patients with positive gonorrhea cultures and consultation for individuals with other STDs. From the time of initiation of the clinic in January, 1976, until November 15, 1979, 4,305 patients were seen. A stratified random sample of 190 of these patients revealed the reasons for attending the clinic to be: (1) follow-up for PID, 85 patients (44.7%), (2) positive gonorrhea culture, 63 (36.3%), (3) unsatisfactory gonorrhea culture, 14 (7.4%), (4) gonorrhea contact, 10 (5.3%), and (5) other, 12 (6.3%). Complete follow-up has been obtained on 3,935 (91.4%) of the patients. Of the 370 patients who did not return for follow-up visits, 336 were reported to the local health department for retrieval. There were 34 patients in whom the follow-up status could not be determined. The establishment, operation, advantages, and disadvantages of the clinic are discussed.

Ambulatory Care Facilities↗

Plasma norepinephrine, epinephrine, and thyroid hormone interactions in severely burned patients.

In this prospective study of thyroid catecholamine interactions, 15 severely burned patients were divided into two groups. Nine patients receiving 200 micrograms/day of triiodothyronine constituted the T3-treated group. Eight additional patients constituted the untreated group. Mean serum concentrations of T3 were significantly lower in the untreated group than in the treated group. Mean serum thyroxine (T4) concentrations were significantly higher in the untreated group than in the treated group. The mean plasma norepinephrine concentration in the untreated group was significantly greater than that of the treated group. In the untreated group, log plasma norepinephrine correlated inversely with serum T3. Similarly, in the untreated group, log plasma epinephrine correlated inversely with serum T3. Metabolic rates were not different between groups. These data suggest that a reciprocal relationship exists between plasma concentration of T3 and both norepinephrine and epinephrine in untreated burn patients and that treatment with the metabolically active hormone, triiodothyronine, does not alter the level of hypermetabolism accompanying thermal injury.

Adult↗

Effect of injury and infection on visceral metabolism and circulation.

To characterize the role of the liver and kidney in the metabolic response to injury and infection, selective catheterization of the hepatic (42 veins) and renal veins (21 veins) was performed in 31 burn patients (mean burn size: 51% TBS), studied 4-129 days postinjury. Blood flow was determined by standard clearance techniques (ICG and PAH), and simultaneous arterial and hepatic and/or renal vein blood was obtained for oxygen, glucose, lactate, pyruvate, and amino acids. Patients studied in the first to third weeks postinjury were classified as noninfected (8 studies), bacteremic (8 studies), or bacteremic with complications (5 studies). There was no difference in age, weight, mean burn size, pulse rate, blood pressure, rectal temperature, total body oxygen consumption, or cardiac index among these groups. Estimated hepatic blood flow (EHBF) and hepatic substrate balance of these patients were compared with postabsorptive normal subjects in the literature (mean +/- SEM or range). :Formula: (See Text) Thermal injury alone resulted in marked increases in EHBF, hepatic oxygen uptake, and glucogenesis. The added insult of bacteremia significantly increased hepatic glucose output; as clinical sepsis progressed, glucose output decreased sharply. The kidney consistently demonstrated a net uptake of glucose in all studies. The changes in hepatic glucose output in bacteremic patients occurred without significant differences in EHBF, oxygen utilization or lactate uptake, but were associated with marked alterations in amino acid uptake.

Adult↗

Free T4, free T3, and reverse T3 in critically ill, thermally injured patients.

A prospective study of thyroid function was performed in 25 thermally injured patients. These patients are divided into two groups. The first group contains five patients with greater than 50% burn size studied longitudinally during the first 15 days following thermal injury. Significant suppression of serum concentrations of 3,5,3'-triiodothyronine (T3) and elevation of serum concentrations of 3,3',5'-triiodothyronine (rT3) were seen. The free thyroxine index and serum TSH concentrations remained within the normal range. To assess the clinical significance of these alterations in peripheral thyroid hormone concentrations, a second group of 20 patients was studied. We measured the free serum levels of T4 (FT4) and T3 (FT3) in ten patients, mean age 34 years, mean burn size 56%, studied during a period of clinical deterioration, and in ten patients of comparable age and burn size who were clinically stable. Both FT4 and T3 values were significantly lower in the unstable patients (p < 0.01). All FT3 values for the unstable patients (M +/- SE), 193 +/- 14 pg/dl, were below the normal range for FT3 of 230 to 669 pg/dl, and significantly lower than those observed in the stable patients (M +/- SE), 430 +/- 59 pg/dl (p < 0.001). This correlation of biochemical hypothyrodisim with clinical deterioration may have functional significance for the critically ill trauma patient.

Adolescent↗