Search

Norepimephrine (NE, .000001 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 to the -7 power - .00001 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 .000001 M) on melatonin accumulation in the medium of incubated hamster pineals taken after a short light exposure at night.

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 unsucessful. 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. (Reprints).

Oxygen consumption VO2 and colonic temperature T sub C measured in groups of rats before and after 30% total body surface, full thickness burns. Some wounds were seeded with Pseudomonas aeruginosa or Staphylococcus epidermidis, and some seeded wounds were treated with SULFAMYLON or SILVADENE. Three groups became bacteremic (B) during the 2-3 week period of observation. The metabolic cost of wound contamination appeared to vary with bacterial strain. The metabolic effects of infection appeared to vary with bacterial strain. The metabolic effects of infection appear to be a continuum, beginning with a modest rise in VO2 and progressing to greater increases in VO2 and T sub C with wound invasion and systemic infection.

(91-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 experimental model. Under general anesthesia with controlled mechanical ventilation with 100% oxygen, 32 sheep 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.

In humans, a reduction in the circulating concentrations of bioactive thyroid hormones is characteristic of nonthyroidal illness (NTI). In burned patients, similar to patients with other NTI, serum concentrations of 3,5,3' - triiodothyronine (T3) and often tetraiodothyronine (T4), as well as the indices of free hormonal concentrations, FT3I and often FT4I (index = total hormone concentrations, FT3I and often FT4I(index = total hormone concentration times T3 uptake), are suppressed. 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. Because of failure of the in vitro charcoal T3 uptake to account for this serum bindng abnormality, the results are most consistent with a burn-induced circulating inhibitor(s) for binding of T4 and T3, not only to transport proteins but also in vitro charcoal, perhaps similar to inhibitors previously described in the sera of patients with various nonthyroidal illnesses. The thermally traumatized rat appears to be a good model for thyroid changes in burns and other nonthyroidal illness.

The Syrian (golden) hamster has provided the most extensively studied model of pineal physiology, and in the species the pineal gland has a potent suppressive effect on the reproductive system and on serum free thyroxim (T4) concentration. The pineal's suppressive effect on the gonads and T4 is classically evoked by subjecting the hamsters to a short photoperiod (less than 12-h light/day) or to blinding by bilateral orbital enucleation. Additional pinealectomy prevents the regression of the reproductive system and the reduction of T4. Burn injury of humans results in depressed serum concentrations of free triiodothyroxine (T3) and T4, reduced serum binding of T4, and low testosterone concentrations. 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.

At the US Army Institute of Surgical Research, histologic diagnosis of infection using burn wound biopsies has proved superior to quantitative culture methods and is considered the most accurate method for distinguishing between microbial colonization and invasive infection of burn wounds. Although the frozen section technique is faster and is often useful, rapid section technique is the method of choice for histologic evaluation of burn wound biopsies. This technique takes about four hours to complete, yields permanent sections, and can be accomplished in any conventional histology laboratory. (Reprints).

Presented at the Annual Meeting of the American Burn Association (12th), San Antonio, TX, 27 Mar 80.

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 + or - SEM or range). 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., Published in Annals of Surgery, v192 n4 p491-504, Oct 1980. Presented at Annual Meeting of the American Surgical Association, Atlanta, GA, 23-25 Apr 1980.

The dose responsiveness of selected physiologic indices was studied in a sheep model of smoke inhalation injury. In this model, graded severity of injury was achieved by changing the contact time with smoke (defined by unit ), whereas other variables were kept constant. Blood gas and cardiopulmonary indices were measured in 70 sheep, including 12 controls, either 24 or 72 hours after exposure to 3, 6, 9, 12, 15, or 18 units of smoke. A 12-unit dose of smoke was fatal within 72 hours and an 18-unit dose was fatal within 24 hours. The best correlation between smoke dose and response was observed in arterial oxygen tension 24 hours after exposure. At 24 hours, most of the cardiopulmonary indices showed significant change only after a 12-unit exposure. Although the exact shape of the dose-response curve could not be defined, sigmoid or curved linear shape was suggested, reflecting the progressive deterioration.

The purpose of this study was to determine the extent to which quantitative cultures of burn-wound biopsy specimens are consistent with histologic diagnoses of invasive wound infection. Low levels of microbial growth in tissue were associated with negative histologic findings. Only four instances of invasive wound infection occurred in 102 specimens with microbial densities of less than 10,000 organisms per gram; two of these infections were fungal. The antinomy is that high levels of microbial growth were more often associated with negative histologic findings indicative of bacterial growth in nonviable tissue than with invasive wound infection. Thus, it appears that histologic and microbiologic diagnostic techniques yield equivalent information in clean wounds, but that there is no microbial density that, taken alone, permits the diagnosis of invasive wound infections.

The relationship between bacteremia and mortality was studied in 5882 burn patients consecutively admitted to one burn center between 1959 and 1983. Among 5877 patients with adequate data, 1481 had one or more positive blood cultures; 1529 patients died. A predictor of mortality was developed, based on data from the 4396 patients without positive blood cultures, and used to assign a discrete probability of death in the absence of bacteremia to all the patients with bacteremia due to (1) enteric organisms, (20 Pseudomona species, (3) gram- positive organisms, or (4) yeastlike organisms, or without bacteremia. These comparisons indicate significantly increased mortality in patients with gram- negative bacteremia, an equivocal increase in patients with blood cultures positive for yeastlike organisms, and no increase attributable to gram -positive bacteremia. Reprints., Presented at the Annual Meeting of the Surgical Infection Society (5th), New Orleans, LA, 29 Apr 85.

Increased infection rates in burned patients may result from a disproportionate increase in the suppressor subpopulations. Measurement of lymphocyte subpopulations is difficult in burned patients because gradient- purified cells are contaminated by nonlymphoid cells. The accuracy of flow cytometric subpopulation analysis was improved by restricting (gating) the analysis to cells with light scatter intensity typical of lymphocytes. Blood was obtained 48 hours after burn from rats receiving no burns, 30% scald burns, or burns seeded with Pseudomonas aeruginosa to induce infection. Subpopulations were identified by monoclonal antibodies to T-lymphocyte antigens. Gating increased the values obtained for most subpopulations, but the relative differences between groups were unchanged. Burned and infected animals, but not animals burned only, had a decreased ratio of helper to suppressor lymphocytes (HSR) relative to control. A decreased HSR relative to control. A decreased HSR correlated with sepsis, but not with infection susceptibility. This suggests that a decrease in HSR may be a result of infection rather than a cause of susceptibility to infection.

The relationship between the number of red blood cell transfusions and major infections complications was evaluated in 594 thermal injury patients admitted between 1982 and 1986 who had burns over 10% or more of total body surface area and survived more than 10 days. The mean age of this group was 32.9 years, with a mean burn size of 36% of total body surface area; 83% were male. Of the 594 patients, 23.7% died and 38.7% had documented inhalation injury. The mean number of red blood cell transfusion received was 19.7, with a range of 0 to 201. Two hundred fourteen patients (36%) had major infectious complication, defined as pneumonia or invasive burn wound infection. A cross-tabulation of predicted mortality, number of transfusions, and infectious complications revealed a significant positive correlation between transfusion number and infectious complications in patients with predicted mortalities between 10 and 70%. (JS), Pub. in The Jnl. of Trauma, v29 n7 p948-954 1989.

The in vitro response of melatonin synthesis was assessed by incubation of individual whole pineal glands for 4 hr without or with different concentrations of isoproterenol in the medium. Pineals were taken either at the end of the 14-hr light phase (day), or at 6.5 hr into the 10-hr dark phase (night) after a 30-min exposure of the animals to light just before sacrifice at night. The response was greater in pineals taken at night than in those taken at the end of the light phase in rats, but was absent at end of the light phase in Syrian hamsters. Hamster pineals taken at night responded, though higher isoproterenol concentrations were required than in the rats. Unresponsiveness of hamster pineals during the day may explain previous failure of isoproterenol administration to stimulate pineal MEL content in this species., Pub. in Comparative Biochemistry and Physiology, v87C n1 p71-74 1987.

Rats with a cutaneous burn exhibited a burn-size-related depression of serum thyroid hormones 2 weeks after injury. Thyroidectomized rats had a marked rise in brain in vitro T4 deiodination to T3 and in serum TSH concentration compared to controls. These normal responses to depressed thyroid hormones were not seen in burned rats. The depression of serum thyronines and thyrotrophin suggests that the burned rat may be a model for human burn injury and other nonthyroidal illness. In this model it appears that the brain and pituitary do not respond as in thyroidectomy, suggesting lack of true hypothyroidism in burn injury.

In order to assess the specific effects of inhalation injury and pneumonia on mortality in burn patients, the records of 1058 patients treated at a single institution over a five-year period, 1980-1984, were reviewed. Of these patients, 373 (35%) had inhalation injury diagnosed by bronchoscopy and/or ventilation perfusion lung scan. Of the 373 patients, 141 (38%) had subsequent pneumonia. Among the patients without inhalation injury, pneumonia occurred in 60 of 685 (8.8%). A multiple logistic equation was developed to estimate expected mortality at any age and burn size for patients without either inhalation injury or pneumonia, with either alone, or with both. Subtraction of the expected mortality without either inhalation injury or pneumonia from the expected mortality in the presence of either or both permitted the estimation of additional mortality attributable to these complications. Inhalation injury alone increased mortality by a maximum of 20% and pneumonia by a maximum of 40%, with a maximum increase of approximately 60% when both were present. The influence on mortality was maximal in the midrange of expected mortality without these complications for any age group. These data indicate that inhalation injury and pneumonia have significant, independent, additive effects on burn mortality and that these effects vary with age and burn size in a predictable manner. Reprints.

Methicillin-resistant Staphylococcus aureus (MRSA) strains, principally resistant to penicillinase-resistant penicillins and aminoglycosides, are increasingly common hospital isolates. We have examined the significance of MRSA colonization and infection in 1100 consecutively admitted, seriously burned patients in whom vancomycin was used to treat all staphylococcal infections. Colonization with S ureus (SA) was identified i 658 patients, in 319 of whom MRSA colonization was identified. Two hundred fifty- three SA infections occurred in 58 of the SA-infected patients. A severity index, based on multiple-regression analysis of mortality as a function of burn size and age in the study population, was used to estimate expected mortality. We demonstrated no measurable increase in mortality attributable to MRSA in this population of burned, SA-infected patients. (js), Pub. in Archives of Surgery, v134 p1456-1459 Dec 89.

Infection remains the most common cause of morbidity and mortality is severely burned patients. Such an infection is a manifestation of injury related immunosuppression and failure of treatment often resulting from the development of microbial resistance. Opportunistic organisms causing infections in burned patients are frequently hospital acquired and may be resistant to multiple antibiotics. The combination of host susceptibility and the possible presence of resistant organisms make the infected burn patient a chemotherapeutic challenge. The continuing accumulation of antibiotic resistant organisms in the clinical environment mandates evaluation of the effectiveness and a safety of newly developed antibiotics. We have examined the effectiveness of imipenem/ cilastatin, a novel thienamycin antibiotic, in a group of patients with burns and serious infections. This antibiotic, the first representative of a new class of beta-lactam antibiotics, the carbapenems, has a wide range of activity against most clinically important gram-positive and gram-negative human pathogens. Imipenem/cilastatin appears to be an antimicrobial of low toxicity that is clinically effective in the treatment of infections in seriously burned patients. Keywords: Pseudomonas aeruginosa; Haemophilus parainfluenzae; therapy; Resistance(Biology); Reprints.

Water soluble hydrogels of alkali metal alginate and glycerin containing 0.01% to 1% cupric (copper) sulfate pentahydrate or silver salts such as silver acetate, silver lactate monohydrate and silver nitrate have been found to be excellent wound dressing treatment composition for white phosphorus burns. Cupric sulfate pentahydrate of silver salts such as silver acetate, silver lactate monohydrate and silver nitrate in the gel reacts with the particles of white phosphorus to form a coating around said particles thus rendering them unable to cause further burn injury to the skin. The gels dry to an adherent, non-toxic pliable protective film which can be removed by water-washing when desired. The gels are also compatible with other medicaments and hence can serve as vehicles or carries for medicaments application to wounds as well as a protective cover., Supersedes PAT-APPL-316 575-81.

Water soluble hydrogels of alkali metal alginate and glycerine have been found to be excellent wound dressings. The gels dry to an adherent, non-toxic pliable protective film which can be removed by water-washing when desired. The gels are also compatible with medicaments and hence can serve as vehicles or carriers for medicament application to wounds as well as a protective cover., Supersedes PAT-APPL-316 574-81.

Presented at the Annual Session of the American Association for the Surgery of Trauma, Phoenix, AZ 18-20 Sep 80.

Read before the First Annual Meeting of the Surgical Infection Society, 25 Apr 81, Chicago.

Combat injuries to the hand often result in massive destruction of skin and soft tissue, bones, nerves, and tendons, necessitating many reconstructive procedures and a long convalescence. One of the most disabling injuries is destruction of the flexor tendons of the fingers, not amenable to conventional tendon surgery such as primary suture or delayed tendon grafting. The purpose of this study was to design artificial tendons for use in these injuries and to test their acceptance by the host., Prepared in cooperation with Fort Detrick, Frederick, Md.

Hypermetabolism characterizes the metabolic response to thermal injury, and the magnitude of this post-traumatic physiologic alteration is closely related to the extent of injury. Negative nitrogen balance, loss of other intracellular constituents, and a rapid decrease in body weight are consequences of the increase in metabolic activity, and extensive loss of protoplasmic mass may result in severe erosion of energy and protein stores essential to optimal body function. Similarities between the thermally injured and individuals with thyrotoxicosis prompted early metabolic and endocrine studies, but the increased oxygen consumption has not been related to abnormal thyroid function. The purpose of this study was to define the relationship between surface cooling and hypermetabolism and to determine the mediator of the profound hypercatabolic response following thermal injury.