Search PubMed⌕ Search

Biomedical subjects

J F Hansbrough

Publications and source records attributed to J F Hansbrough.

At least 91 records · Page 5Linked to original sources
PubMed1988

High dose intravenous immunoglobulin therapy in burn patients: pharmacokinetics and effects on microbial opsonization and phagocytosis.

Depressed serum immunoglobulin levels following severe burns may lead to subsequent infectious complications following such injuries. In a randomized study we administered multiple doses of Sandoglobulin (500 mg/kg) or albumin intravenously to patients with severe burn injuries and closely monitored serum IgG levels. Patients who received IgG therapy had earlier return of normal serum IgG levels compared to control patients; however, control patients attained normal IgG levels during the second postburn week. Serum half-lives of IgG following infusions were remarkably short (means, 47 hours for infusions within 3 days of injury and 154 hours for infusions in the third postburn week); Sandoglobulin has been reported to have approximately a 21-day half-life in normal individuals. We also measured the opsonic capacity of postburn serum, using fluorescein-labeled microbes and flow cytometry; we identified postburn opsonic defects with certain of the organisms as late as 15 days postinjury, even though serum IgG levels had normalized. These defects were corrected by the in vitro addition of Sandoglobulin to the incubation mixture.

Adolescent↗
PubMed1987

Immunomodulation following burn injury.

Severe burn injury is accompanied by suppression of almost all the components of immunity; such suppression undoubedly contributes to infectious complications in the burned patient. There has now been substantial experimental progress made in devising approaches to prevent or minimize these immune defects; however, clinical application is still limited.

Animals↗
PubMed1987

Biosynthetic skin substitute versus frozen human cadaver allograft for temporary coverage of excised burn wounds.

During the past 2 years a multicenter study was performed comparing Biobrane (Woodroof) and frozen cadaver allograft as temporary dressings on freshly excised full-thickness burns before the application of autograft. Each biologic dressing was evaluated with respect to the other on the same patient. Seventy-one patients were evaluated. The mean burn size was 35 +/- 20% with a mean full-thickness burn of 28 +/- 20%. Mean patient age was 34 +/- 21 years. Overall survival was 82%. The mean time of wound coverage was 10.2 +/- 6.7 days. There was no significant difference in the number of dressing changes, area changed, purulence, autograft take, and final results between allograft- and Biobrane-covered sites. There were no complications following use of either Biobrane or allograft. We conclude that Biobrane is as effective as frozen human cadaver allograft for the temporary coverage of freshly excised full-thickness burn wounds before autografting.

Adult↗
PubMed1986

Prevention of posttraumatic alterations in lymphocyte subpopulations in mice by immunomodulating drugs.

Infection is a major cause of morbidity and mortality in traumatized victims, as well as an unfortunate complication following surgical procedures. The incidence of such infections is probably related to immune suppression occurring after severe trauma and surgery. Cell-mediated immunity is an arm of immunity that is probably important in defense against bacterial as well as fungal and viral infections. The status of cell-mediated immunity appears to be reflected by the helper/inducer to suppressor/cytotoxic lymphocyte (Ly1+/Ly2+ in the mouse model) ratio. A depressed ratio has been shown to correlate with other measures of suppressed immunity. Using monoclonal antibodies and immunofluorescent analysis, splenic lymphocyte subpopulations were enumerated at different intervals after injury in mice receiving various injuries (laparotomy, 40% liver resection, burn injury covering 20% of total body surface area, and crush injury-amputation of hind limb). An immediate fall in the Ly1+/Ly2+ ratio was observed following the most severe injuries, namely, liver resection, burn, and crush injury-amputation, but not following laparotomy. Changes in the ratio were reflected by both decreases in helper populations (Ly1+) and increases in suppressor populations (Ly2+). Prostaglandins and histamines have been implicated as possible mediators in producing down-regulation of the immune system. Posttraumatic lymphocyte alterations were prevented in crush injury-amputation group mice when drugs (ibuprofen and cimetidine) to block such mediators were administered prior to trauma; changes were also prevented by administering cyclophosphamide, a drug which in low dose might inhibit proliferation of suppressor lymphocyte populations.

Animals↗
PubMed1986

Postburn serum drug binding and serum protein concentrations.

The free fractions of diazepam, imipramine, lidocaine, meperidine, phenytoin, propranolol, and salicylic acid were determined in the serum of seven burn patients (25% to 80% of their skin surface burned) about one week after the burn and in three of the patients at about four weeks following the injury. Serum protein fractions were measured by electrophoresis, and alpha-1 acid glycoprotein levels were determined. For the drugs that bind predominantly to albumin, the serum free fractions were greater in patients one week after the burn incident than in control subjects (diazepam, 0.055 vs. 0.017; phenytoin, 0.24 vs. 0.16; and salicylic acid, 0.69 vs. 0.32). The increase in free fraction for these drugs was attributed to the postburn decrease in serum albumin levels (2.2 vs. 4.4 g/dL, control). Imipramine, lidocaine, meperidine, and propranolol bind primarily to alpha-1 acid glycoprotein. The free fractions for these drugs decreased one week following the burn (imipramine, 0.074 vs. 0.095; lidocaine, 0.17 vs. 0.35; meperidine, 0.37 vs. 0.48; and propranolol, 0.045 vs. 0.107), presumably in response to the increased alpha-1 acid glycoprotein concentration (222 vs. 83 mg/dL, control). Diazepam, lidocaine, propranolol, and salicylic acid free fractions were still different from control values at four weeks after the accident.

Adult↗
PubMed1986

Prevention of alterations in postoperative lymphocyte subpopulations by cimetidine and ibuprofen.

Surgical procedures probably result in a temporary state of immunosuppression. Identification of functional lymphocyte subclasses using appropriate monoclonal antibodies appears to serve as a sensitive, accurate, and reproducible measure of immune status in patients in many disease states. Using monoclonal antibodies specific for lymphocyte surface markers and immunofluorescent assay, we quantitated lymphocyte subpopulations in patients undergoing surgical procedures. Cholecystectomy, colon surgery, and coronary bypass procedures all resulted in postoperative decreases in helper and inducer populations and increases in cytotoxic suppressor populations, with resultant depressions in the helper to suppressor lymphocyte ratio. Studies in an additional group of patients who underwent cholecystectomy demonstrated that these changes could be prevented by perioperative administration of ibuprofen and cimetidine. These results suggest that prostaglandins and histamines are involved in immunoregulatory events after major operation. The ability of specific pharmacologic therapy to prevent alterations in lymphocyte populations suggest that postoperative immunity may be preserved, hopefully leading to greater host resistance against infection and tumor dissemination.

Adult↗
PubMed1986

Immunomodulating drugs increase resistance against sepsis in traumatized mice.

Immune suppression occurs frequently after major injury and undoubtedly contributes to infection and mortality in trauma patients. Prevention of such suppression may lead to decreased infection and improved survival in trauma patients surviving the immediate insult of injury. Suppressor-cell activation appears to play a key role in immune suppression after major injury. For several years we have studied the effects on immune functions after injury of various drugs which have been shown in the immunologic literature to have inhibitory effects on suppressor cell populations. H2-antagonists may inhibit suppressor cell activation by blocking surface H2-receptors, which are present in higher numbers on suppressor cells than on helper cells. Prostaglandin inhibitors may block the multiple immune suppressive effects of prostaglandins, particularly PGE2. Immunological studies suggest that low-dose cyclophosphamide selectively inhibits the proliferation of suppressor T cells. Our previous work suggested that such drugs preserve cell-mediated immune functions after injury. In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP). Nontraumatized (control) mice had a 36.2% mortality after CLP; when crush injury/amputation was followed by CLP in 24 hrs the mortality rose to 63.8% (p less than 0.0035). When mice were given 24 hrs before crush/amputation: cimetidine, an H2-antagonist (10 mg/kg/day); ibuprofen, a prostaglandin blocker (5 mg/kg/day); or cyclophosphamide (2.5 mg/kg/day), and a second dose on the day of trauma, with CLP 24 hrs later, subsequent mortality was not different from the mortality in nontraumatized, control mice (p less than 0.0035).(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1986

Postburn immunosuppression in an animal model. IV. Improved resistance to septic challenge with immunomodulating drugs.

We have previously demonstrated that certain pharmacologic agents administered to burned mice will restore cell-mediated immunity, as evidenced by measurement of delayed hypersensitivity responses and determination of splenic helper/suppressor lymphocyte ratios. These drugs are systemic cimetidine, ibuprofen, cyclophosphamide, and topical cerium nitrate. In the studies reported here we performed cecal ligation and puncture (CLP) in burned mice as a measure of resistance to infectious challenge. Survival after CLP with a 23-gauge needle used for puncture was markedly decreased when performed on the tenth postburn day (normal 63.7%, 10 days postburn 20.0%; p less than 0.001), but survival was not decreased when CLP was performed on the fifth (60.0%; p not significant) or twenty-first postburn day (65.3%; p not significant). Animals were then treated with the four agents in carefully defined dosage regimens, and survival was again determined on the tenth postburn day. Survival figures with p values compared to burned, untreated animals: burn plus cimetidine 62.2%, p less than 0.0005; burn plus: ibuprofen 64.7% p less than 0.0003; burn plus cyclophosphamide 68.2%, p less than 0.0001; burn plus cerium nitrate 54.1%, p less than 0.004. Specific pharmacologic therapy in burned mice in dosage regimens that have been shown to improve cell-mediated immunity is also able to significantly improve resistance to subsequent infectious challenge.

Animals↗
PubMed1985

Comparison of Biobrane and Scarlet Red dressings for treatment of donor site wounds.

Two methods of autograft donor site management were tested in 31 patients with burn injuries. Two donor sites of equivalent size were respectively covered with Biobrane and Scarlet Red, two commercial dressing materials available for donor wound coverage. Pain, the amount and type of exudate developing underneath the dressing, adherence, and cellulitis were evaluated on a daily basis, and healing time was determined. Biobrane proved superior to Scarlet Red with respect to control of pain, accumulation of exudate, and healing time; the materials were equal with regard to adherence to the wound, the character of exudate, and the appearance of cellulitis.

Adolescent↗
PubMed1985

Prevention of suppressed cell-mediated immunity in burned mice with histamine-2 receptor antagonist drugs.

Thermal injury has been shown to suppress many aspects of both specific and nonspecific immune responses. We investigated the effect of two histamine H-2 antagonist drugs on cell-mediated immunity in burned mice, utilizing a method of quantitating the degree of contact sensitivity elicited to the antigen. 2,4-dinitrofluorobenzene (DNFB). Following sensitization by painting the abdomen with DNFB, animals were challenged 5 days later by painting the ears; subsequent ear swelling is a sensitive and reproducible measure of cell-mediated immunity. We have previously demonstrated that burned mice are maximally immunosuppressed 10 to 14 days following burn injury. In the present study we found that daily intraperitoneal administration of appropriate doses of the H-2 antagonists cimetidine (2 and 10 mg/kg/day) and ranitidine (2 and 10 mg/kg/day) resulted in maintenance of normal cell-mediated immunity in burned animals. Neither a lower dose of ranitidine (0.2 mg/kg/day) nor higher doses of cimetidine (20 and 50 mg/kg/day) restored immunity, and diphenhydramine, an H-1 antagonist, had no effect. There was no augmentation of contact sensitivity in unburned mice treated with cimetidine. The immunorestorative effect is probably secondary to antagonism of histamine H-2 receptors on suppressor T lymphocytes, and may reflect increased suppressor cell activity in burned mice; however, other mechanisms may be involved.

Animals↗
PubMed1985

The effect of histamine receptor antagonists on specific and nonspecific suppression of experimental contact sensitivity.

We studied the effects of H1 and H2 histamine receptor antagonists on down regulation of contact sensitivity (CS) to dinitrofluorobenzene (DNFB). Two H2 receptor antagonists, cimetidine and ranitidine, reversed the nonspecific immunosuppression of CS induced by burns. On the other hand, these two drugs did not affect the antigen-specific suppressor T cell-mediated tolerance to DNFB induced by dinitrobenzene sulfonic acid. Two H1 antagonists did not affect the down regulation of CS induced by either tolerance or burning. The differential sensitivities to histamine 2-receptor antagonists indicate that the mechanisms for nonspecific burn-induced immunosuppression are different from those for hapten-specific tolerance to DNFB.

Animals↗
PubMed1985

Identification and antibiotic susceptibility of bacterial isolates from burned patients.

We retrieved bacterial blood isolates from 397 adult burned patients admitted over a 7-year period. Sixty-two patients (15.6 per cent) developed true-positive bacterial blood cultures (judged non-contaminants), and of these 30 (48.4 per cent) expired. Pseudomonas aeruginosa (24 isolates), Staphylococcus aureus (19) and Klebsiella pneumoniae (19) were the most frequent isolates. In vitro susceptibilities of 149 isolates were determined to 12 antibiotics (gentamicin, amikacin, ticarcillin, piperacillin, mezlocillin, azlocillin, cefazolin, cefotaxime, ceftazidime, cefoperazone, thienamycin and ticarcillin-clavulinic acid) using agar diffusion assay. Thienamycin proved the most active agent (97 per cent of isolates susceptible). Cefoperazone was the most active cephalosporin (95 per cent susceptible). Twenty-eight organisms demonstrated multiple drug resistance; patients with such organisms had a 71 per cent mortality. Thienamycin was the most active agent against such isolates (27/28 susceptible). Susceptibilities of all 149 isolates to combinations of antibiotics were calculated, assuming no synergism or antagonism; some combinations of third-generation cephalosporins with the newer penicillins may prove to be as effective as combinations including aminoglycosides.

Adolescent↗
PubMed1985

Alterations in splenic lymphocyte subpopulations and increased mortality from sepsis following anesthesia in mice.

The authors evaluated the potential of a variety of anesthetics in mice to produce subsequent alterations in host defenses. Specific monoclonal antibodies and immunofluorescent microscopy were used to enumerate splenic helper/inducer: suppressor/cytotoxic lymphocyte ratios (HSR), and resistance to bacterial challenge was evaluated by a cecal ligation and puncture (CLP) model. Two hours of anesthesia with the intravenous agents ketamine and pentobarbital and with the inhalational agents isoflurane, enflurane, halothane, and halothane-nitrous oxide, were utilized. All anesthetics produced marked depression in the HSR, measured 24 h postanesthesia (P less than 0.05); with all agents, helper T-cell populations were decreased and suppressor populations increased. The HSR remained depressed 72 h postanesthetic, following both ketamine and halothane anesthesia (P less than 0.05). A dose-response curve was determined with enflurane; increasing the anesthetic time from 1 to 6 h resulted in progressively greater depression of the HSR 24 h later. Changes in lymphocyte subtypes of similar magnitude were found in mice after burn injury or hind limb crush injury and amputation, whereas simple laparotomy did not produce such changes. Serum corticosterone levels were not elevated 24 h post-anesthetic with enflurane, suggesting that the alterations were not nonspecific stress reactions. Resistance to sepsis was determined by measuring survival for 96 h after CLP. With CLP performed 24 h following 2 h anesthesia, mortality was increased from normal: control mortality 36.3%; ketamine 65.0% (P less than 0.023); isoflurane 69.5% (P less than 0.006); enflurane 84.2% (P less than 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

Amputation, Surgical↗
PubMed1985

Restoration of immunity in burned mice by cimetidine.

We have previously described a mouse model of postburn suppression of cell-mediated immunity (CMI). Ear swelling (ES) in response to contact antigen challenge is depressed maximally 14 days following a 25% steam burn and recovers to control levels 3 weeks postburn. Splenic lymphocyte proliferation in response to Concanavalin A (Con A) is also depressed 14 days postburn. Splenic T-lymphocyte subset analysis with monoclonal antibodies for helper cells (Lyt 1.2) and suppressor cells (Lyt 2.2) reveals that T-helper cells reach a minimal level and T suppressor cells reach a maximum level 14 days postburn. The helper: suppressor ratio (HSR) reaches its nadir at day 14. Treatment of burned mice with low-dose cimetidine (2 or 10 mg/kg/day), but not high-dose (50 mg/kg/day), for 14 days restores CMI. Low-dose cimetidine also normalizes the HSR but does not effect postburn depression of mitogen responsiveness. Low-dose cimetidine probably restores CMI by inhibiting suppressor cells, whereas high doses provide more global inhibition. Recovery of mitogen responsiveness may require continued cimetidine presence in culture.

Animals↗
PubMed1985

Hydrocarbon contact injuries.

Cutaneous injury caused by exposure to gasoline and other hydrocarbons is a clinical entity with potentially life-threatening effects. We report four cases of such injury. One patient developed full-thickness skin loss following gasoline immersion, and another developed severe systemic complications following contact with a carburetor cleaning solvent. Initial therapy should consist of removal of solvent-containing clothing and extensive lavage or soaking with water, followed by wound care that is generally similar to that used in the treatment of partial-thickness burns. In most cases this includes debridement, topical antimicrobial agents, and dressing changes. Severe pulmonary, cardiovascular, neurologic, renal, and hepatic complications may accompany hydrocarbon absorption, particularly in cases involving gasolines containing lead additives. Therefore immediate surgical debridement should be considered if there is suspicion of continued absorption of toxic compounds from the wound.

Absorption↗
PubMed1985

Granulocyte stem cells are decreased in humans with fatal burns.

The number of granulocytic stem cells (CFU-C) was measured in the peripheral blood of surviving and nonsurviving burned humans. It has been shown that the number of CFU-C in the peripheral blood of survivors increases over time and is elevated compared to the number found in normal humans. The number found in nonsurvivors, however, falls significantly in the later stages of burn injury, suggesting perhaps a defect in stem cell production and/or differentiation in patients with severe thermal injuries. The mechanism is unclear but its delineation may have an important bearing on understanding the nature of infectious complications following thermal injury.

Adult↗