Restoration of delayed hypersensitivity in mice receiving immunosuppressive drugs by cimetidine.
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Animals↗
Biomedical subjects
J F Hansbrough
Publications and source records attributed to J F Hansbrough.
Restoration of suppressed immunity in burned mice with cimetidine.
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Animals↗
Postburn immunosuppression in an animal model. III. Maintenance of normal splenic helper and suppressor lymphocyte subpopulations by immunomodulating drugs.
Delineation of lymphocyte subpopulations by labeling cells with specific monoclonal antibody now appears to be a reliable means of measuring cellular immunity in various disease states. We determined splenic helper/inducer and suppressor/cytotoxic lymphocyte populations in mice given a 20% to 25% body surface area steam burn injury. The lymphocyte helper: suppressor ratio fell from 3.13 +/- 0.06 in control mice to 1.77 +/- 0.04 in burned animals (p less than 0.0005) 14 days after burn. Immediate postburn eschar removal resulted in improvement in the ratio 14 days later (2.66 +/- 0.14) although not in restoration to normal levels. Postburn treatment of burned mice with intraperitoneal cimetidine, ibuprofen, indomethacin, cyclophosphamide, and topically applied cerium nitrate resulted in substantial restoration of the lymphocyte ratio toward normal values; in animals treated with cimetidine and ibuprofen the resultant lymphocyte ratio was not statistically different from that in control (unburned) mice. These drugs probably inhibit suppressor cell populations or suppress the immunosuppressive effect of toxic materials in the burn wound. Specific pharmacologic therapy improves immune function in burned mice and may result in increased resistance to infection.
Animals↗
Topical cerium nitrate prevents postburn immunosuppression.
Suppression of cell-mediated immunity (CMI) follows a major thermal injury and is associated with an increased incidence of serious infections. Adult female CF-1 mice received a 20% full-thickness steam burn and were then treated with various topical antimicrobial creams in an attempt to alter the course of postburn immunosuppression. Topical agents included cerium nitrate (CE), silver sulfadiazine (SSD), mafenide (SML), silver nitrate (AG), and a mixture of CE and SSD (CE-SSD). CMI was determined in vivo by measuring ear swelling in response to 2,4-dinitrofluorobenzene (DNFB) challenge in previously sensitized mice. The usual nadir in CMI (ear swelling) when mice were sensitized at day 14 postburn did not occur in burned mice treated with CE or CE-SSD, AG was only modestly effective, and SML or SSD failed to restore CMI. These studies suggest that topical CE may have potential as an immunomodulator in the treatment of burns.
Animals↗
Administration of intravenous alcohol for prevention of withdrawal in alcoholic burn patients.
We studied the effects of intravenous alcohol infusions on 22 alcoholic burn patients admitted to our burn center. The relationship of infusion rates to blood alcohol levels was studied over a 3 to 8 day period of administration, and daily blood test results in liver function were followed. No patients had signs of withdrawal either during the infusion period or after the discontinuation of alcohol therapy. Our data suggest that the intravenous infusion of ethanol at rates of 0.02 to 0.06 g/kg per hour provides low but measurable blood alcohol levels (2 to 8 mg/100 ml), avoids sedation and toxic effects, and prevents the appearance of withdrawal symptoms in severely alcoholic burn patients.
Adolescent↗
Altered helper and suppressor lymphocyte populations in surgical patients. A measure of postoperative immunosuppression.
Although a wealth of evidence has suggested that cell-mediated immunity is suppressed after simple surgical trauma, there have been contradictory results using stimulation assays of lymphocyte function. We quantitated T-lymphocyte subsets in 11 patients undergoing routine cholecystectomy by immunofluorescence microscopy using specific monoclonal antibodies. T-helper to T-suppressor cell ratios were calculated on the preoperative day and the first postoperative day in all patients, and on the third or fourth postoperative day in five patients. Helper to suppressor ratios decreased in all patients on the first postoperative day (p greater than 0.01), but returned to within normal limits on subsequent days. Changes were due more to decreases in helper cells than to increases in suppressor cells, although changes in both populations were statistically significant. The measurement of T-cell subsets by antibody-specific labeling and immunofluorescence microscopy may prove to be a more sensitive, quantifiable, and reproducible assay of immune function in surgical or traumatized patients than use of stimulation assays. Measurements of specific helper and suppressor lymphocyte populations may prove useful in predicting morbidity and mortality, and may also help in studying the effect of immunomodulating agents on the immune response.
Adolescent↗
Characterization of the immunosuppressive effect of burned tissue in an animal model.
The immunosuppressive effect of burned tissue was studied using a mouse burn model. To evaluate the immunologic status an in vivo measure of cell-mediated immunity (CMI) involving contact sensitization of mice by painting the skin with dinitrofluorobenzene was used; mice were challenged 5 days later by painting the ear with the same antigen. Ear swelling in response to antigenic challenge was used as a quantitative measure of CMI; diminution in ear swelling in treatment mice compared to sensitized, unburned control mice indicated the degree of immunosuppression. A full-thickness steam burn covering 20% body surface ares (BSA) was profoundly immunosuppressive as reflected by ear swelling of 45 to 60% of that found in normal mice; partial thickness burns and burns of 10% BSA extent were not significantly immunosuppressive. Transfer into unburned mice of burned skin equivalent in size to a 20% BSA burn eschar resulted in marked immunosuppression, but transfer of smaller amounts of burned skin, or of larger amounts of unburned skin and normal and burned liver tissue, did not produce immunosuppression. Mice receiving a very high-temperature (300 degrees C), dry burn were only slightly more suppressed than mice receiving a standard steam burn. Normal immunity was preserved in burned mice which received daily application of cerium nitrate to the wound for 7 days, but application of other topical agents commonly used in burn treatment did not preserve immunity. Postburn immunosuppression thus appears related quantitatively to toxic factors in burned skin, and these toxic factors can be abrogated in burned mice by the topical application of cerium nitrate.
Animals↗
Clinical experience with Biobrane biosynthetic dressing in the treatment of partial thickness burns.
Biobrane, a synthetic, bicomposite wound dressing, has been used to treat 17 patients with partial thickness burn wounds covering 0.5-12.5 per cent of the total body surface area (mean 4.4 per cent). In 16 patients we found complete healing of the wound after removal of the dressing, 6-15 days after the injury. In one patient, the wounds were determined on the third day post-injury to be deeper than initially suspected, and she was taken to the operating room for surgical debridement and grafting. Biobrane is an effective wound covering for clean, superficial partial thickness burns of limited extent; the simultaneous use of topical antimicrobial agents for such wounds is not necessary.
Adult↗
Assessment of the proficiency of the surgeon in providing basic and advanced cardiac life support.
The results of this study demonstrate a need for further improvement in the ability of selected surgeons to manage competently a cardiac arrest according to current AHA guidelines. The importance of formal training is demonstrated by the fact that prior BCLS or ACLS certification increased the likelihood that proper resuscitative measures will be used by the surgeon. In particular, greater emphasis should be placed upon standard dysrhythmia treatment protocols since we have shown that the level of the expertise of the surgeon in this area is lowest. Improvement in resuscitation skills should enhance the ability of the surgeon to treat effectively patients who are critically ill.
Arrhythmias, Cardiac↗
Spontaneous bacterial peritonitis and pneumoperitoneum. A false surgical emergency.
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Abdomen, Acute↗
Arteriovenous fistulas following central venous catheterization.
We report three patients in whom arteriovenous fistulas probably occurred following placement of central venous catheters. Two fistulas apparently followed internal jugular vein catheterization (or attempts), and one was demonstrated angiographically following subclavian vein cannulation. One fistula was repaired operatively, and in this case two separate fistulas in the same anatomical region were found. One patient refused surgery but remained asymptomatic after 6 months of follow-up. In the third patient the fistula probably spontaneously disappeared within one week of its appearance. We discuss two methods of central vein cannulation which should decrease the occurrence of complications following the procedure.
Adult↗
Placement of 10-gauge catheter by cutdown for rapid fluid replacement.
The establishment of immediate venous access and rapid fluid administration remains of paramount importance in the treatment of hypovolemic shock. We describe a technique for placement of a recently available 10-gauge catheter via venous cutdown. This technique is simpler and quicker than placing intravenous tubing directly into the vein, and we show that flow rates through the catheter with both saline and blood are equivalent to rates obtained through intravenous extension tubing. In addition, our studies show that the use of wide-bore intravenous tubing (urology irrigating tubing) instead of standard intravenous tubing allows for much higher infusion rates through the 10-gauge catheter. With the wide-bore tubing and pressure infusion, it is possible to administer 1,200 cc of blood per minute through this catheter.
Catheterization↗
Postburn immunosuppression in an animal model: monocyte dysfunction induced by burned tissue.
We studied cell-mediated immunity (CMI) in burned mice using an assay that involves the induction of contact sensitivity to dinitrofluorobenzene (DNFB). Subsequent painting of the ears with DNFB and measurement of ear swelling with calipers is a sensitive and quantifiable assay for CMI. Results may be expressed as mean ear swelling (MS) in units of 10(-4) inches +/- 2 standard errors of the mean. CMI was severely depressed in burned mice over a 2-week period following burn (control MS 48.3 +/- 1.0, 14 days after burn 29.0 +/- 1.0, P less than 0.01). Immediate postburn eschar removal resulted in avoidance of immunosuppression (MS 41.5 +/- 1.0, P less than 0.01) while transfer of burned tissue subcutaneously into unburned mice resulted in severe immunosuppression (MS 33.2 +/- 2.6, P less than 0.01). CMI was restored by intravenous infusion of peritoneal macrophages from unburned mice (MS 41.4 +/- 2.2), but not by infusion of lymphocytes or of macrophages taken from burned mice. This model should prove useful for further study of burn injury-induced immunosuppression.
Animals↗
Concentrations of cefoxitin in gallbladder bile of cholecystectomy patients.
Cefoxitin was administered in a dose of 2 g intravenously to 17 patients scheduled for cholecystectomy. The concentrations of this agent in serum and gallbladder bile were measured simultaneously upon opening of the abdominal cavity. Concentrations of cefoxitin in excess of 10 microgram/ml were present in the gallbladder bile of 12 of the 13 patients from samples obtained between 35 and 165 min after cefoxitin infusion. Cystic or common duct obstruction did not preclude entry of the drug into gallbladder bile.
Adult↗
Cardiac perforation and tamponade from a malpositioned subclavian dialysis catheter.
We report a case in which the tip of a malpositioned subclavian dialysis catheter perforated the right atrium and caused a hemopericardium and cardiac arrest. This complication must be immediately recognized and treated, probably by thoracotomy, to ensure survival. Needle aspiration of the pericardium will not remove clotted blood and is unlikely to be of value.
Adolescent↗
Cardiopulmonary resuscitation by medical and surgical house-officers.
In teaching hospitals the responsibility for cardiopulmonary resuscitation usually rests with the house-staff, yet most house-officers receive no formal training in life support. The life-support skills of 45 medical and surgical house-officers in a university teaching hospital were tested by means of simulated cardiac arrests. House-officers were graded on the basis of a performance checklist derived from the standards of the American Heart Association. No house-officer received a pass score in basic life support (BLS). Only 29% could properly compress and ventilate the mannequin. In advanced cardiac life support (ACLS) only one-third could intubate in 35 s or less; only 31%, 40%, and 33% could manage ventricular fibrillation, asystole, and complete heart block, respectively. Some house-officers were unable to operate the defibrillator or assemble resuscitation equipment. Many house-officers displayed helplessness and anxiety during the simulations; fourteen (40%) were prompted to register for additional advanced life-support courses. The performance of medical and surgical house-officers was equal. House-officers who had received prior life-support training performed better in BLS (p less than 0.001) but not in ACLS. It was concluded that (a) most medical and surgical house-officers are not reasonably proficient in BLS and ACLS, and (b) cardiac arrest simulation is a motivating exercise which permits analysis of each house-officer's life-support skills. House-officers should have more training and practice in life support, or they should not have primary responsibility for cardiopulmonary resuscitations.
Clinical Competence↗
Concentrations of kanamycin and amikacin in human gallbladder bile and wall.
The concentrations of amikacin and kanamycin were determined in the serum, gallbladder bile, and gallbladder wall of 20 patients undergoing elective cholecystectomy. Of 20 patients, 14 received 500 mg of amikacin intramuscularly and 6 received 500 mg of kanamycin intramuscularly at various times before surgery. In patients receiving kanamycin, detectable levels appeared in bile within 90 min after drug administration, and in five of six patients concentrations ranged from 1.9 to 23 micrograms/ml. Levels of kanamycin in gallbladder wall ranged from 8.0 to 14 micrograms/g. In patients receiving amikacin, detectable levels appeared in bile within 48 min after drug administration and ranged from 1.3 to 7.5 micrograms/ml in 12 of 14 patients. Levels of amikacin in gallbladder wall ranged from 4.7 to 34 micrograms/g. The presence of an obstructed cystic duct did not preclude the entry of either antibiotic into gallbladder bile, and this may reflect passage of antibiotic through the gallbladder wall rather than accumulation via bile secretion.
Adolescent↗
Immunosuppression by hyperbaric oxygen.
Reports from several laboratories have indicated that hyperbaric oxygen might be immunosuppressive in animals. We examined the effect of hyperbaric oxygen on a well-studied model of cell-mediated immunity in the mouse, contact sensitivity to dinitrofluorobenzene (DNFB). Using this model, we showed that daily 5-hour exposure of mice to 2.5 ATA hyperbaric oxygen was markedly immunosuppressive. Immunosuppression occurred when mice were exposed to hyperbaric oxygen (HBOX) for 4 days daily before DNFB sensitization or for 5 days daily after sensitization. The immunosuppression was reversed by intravenous administration of 2 x 10(7) peritoneal exudate cells from syngeneic mice, but was not reversed by 5 x 10(7) lymph node cells intravenously. We showed that daily HBOX exposure resulted in a dramatic decrease in circulating total leukocytes and lymphocytes in spleen weight, and in DNA synthesis in draining lymph nodes of sensitized mice. Serum cortisol levels were only marginally elevated in HBOX-treated mice.
Animals↗