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J I Tchervenkov

Publications and source records attributed to J I Tchervenkov.

52 records · Page 3Linked to original sources
PubMed1990

Effect of intraluminal antibiotics on translocation of Candida albicans in burned guinea-pigs.

Guinea-pigs were pretreated orally with various antibiotics and given 3 x 10(10) Candida albicans by gastric lavage followed by a 40 per cent TBSA full skin thickness burn. The mesenteric lymph nodes, liver and spleen were cultured for the presence of viable organisms. Caecal contents were quantitatively cultured for aerobic bacteria and C. albicans. Clindamycin and penicillin G were the greatest promoters of translocation followed by the combination streptomycin/bacitracin. The mechanism for antibiotic-induced translocation is multifactorial centering on intestinal flora, anaerobic spectrum of the antibiotic and host defense as well as microbe virulence. The systemic use of broad-spectrum antibiotics, particularly those with strong anaerobic activity, should not be taken too lightly. A severely immunocompromised patient on this type of therapy may be prone to a severe fungal infection. This study reaffirms the concept that translocation from the gastrointestinal barrier is a potential source of life-threatening nosocomial infection.

Animals↗
PubMed1989

The effect of donor-specific blood transfusion, cyclosporine, and dietary prostaglandin precursors on rat cardiac allograft survival. II. Effectiveness of a 24-hour induction period with DST and CsA in inducing long-term graft survival.

We investigated the effect of donor-specific transfusion given 24 hours pretransplant, a short course of low-dose cyclosporine, and dietary enrichment with the prostaglandin precursor linoleic acid (LA) to see which of the modalities could act synergistically on cardiac allograft survival in a stringent animal model. ACI male rats (RT1a) were used as blood and heart donors, and Lewis male rats (RT1l) were used as recipients. DST alone (1 ml) given 24 hr pretransplant or LA alone started 24 hr pretransplant and given daily p.o. until rejection prolonged cardiac allograft survival slightly but significantly, from 6 to 8 days. CsA alone started at the time of transplant at a dose of 5 mg/kg/day s.c. and given daily for 14 days prolonged cardiac survival to 11.8 days. However, when CsA was started 24 hr pretransplant and continued for two weeks, there was a significantly prolonged allograft survival to 55 days. CsA given together with DST 24 hr pretransplant and continued for two weeks posttransplant significantly prolonged cardiac allograft survival to 80 days and resulted in permanent tolerance in some animals. The addition of LA to a DST and CSA treatment regimen did not further improve allograft survival. CsA blood levels were determined in a separate group of Lewis rats. Three dosages of CsA were administered s.c. for 2 weeks: 2.5 mg/kg/day, 5 mg/kg/day, and 10 mg/kg/day. One injection of the three CsA doses did not achieve what are considered therapeutic levels in man. After 5 days, all three doses of CsA achieved significant blood levels. Significant blood levels were still present one week, but not 3 weeks after CsA was stopped. We conclude that DST given 24 hr before transplant and a 2-week course of low-dose CsA started one day pretransplant have strong synergism in inducing long-term graft survival in this rat model. Linoleic acid started 24 hr pretransplant, together with DST and CsA, did not contribute significantly to graft survival compared with the group given CsA and DST alone. Prolonged heart allograft survival was not due to persistently high CsA levels after the drug was discontinued.

Animals↗
PubMed1988

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions.

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries.

Animals↗
PubMed1988

Altered leukocyte delivery to specific and nonspecific inflammatory skin lesions following burn injury.

This study assessed the effect of burn trauma on the in vivo leukocyte cell delivery during the first 24 hr of the delayed type hypersensitivity (DTH) skin test reaction and a bacterial skin abscess. Inbred male Lewis rats sensitized to keyhole limpet hemocyanin (KLH) were given a 30% scald burn or sham burn. Three days later the animals were injected intradermally, at different sites, with 0.3 mg of KLH, 10(8) organisms of S. aureus 502A, and 0.1 cc of saline, at 2 to 24 hr. Leukocytes labelled with Indium111 oxine(leu111) were injected intravenously. In sham rats the peak leu111 influx in the DTH reaction occurred at 2-4 hr while in the abscess it was biphasic with peaks at 3 hr and 6-8 hr. In burn trauma rats there was a markedly increased leu111 peak at 2 hr in both the DTH and abscess reactions followed by a significantly lower than normal leu111 delivery in the late (6-24) hours. This marked early leukocyte influx in burned rats was paralleled by a reduced DTH skin test lesion (8.2 +/- 1.1 mm to 4.2 +/- 1.1 mm) and an increased bacterial abscess (5.1 +/- 1.1 mm to 8.1 +/- 0.9 mm) post burn. There was a direct correlation between leukocyte cell delivery to a DTH reaction and a bacterial abscess (r8 = 0.69, Spearman rank; p less than 0.001). We conclude that burn trauma results in altered leukocyte delivery to inflammatory lesions and the DTH response can be used to assess the ability of a burn trauma host to recruit leukocytes at a site of infection.

Abscess↗
PubMed1988

The influence of long-term protein deprivation on in vivo phagocytic cell delivery to inflammatory lesions.

The effect of long-term protein deprivation and refeeding was assessed on the in vivo delivery of phagocytic leukocytes (PHAGS) to delayed-type hypersensitivity (DTH) reaction and a bacterial abscess. Male inbred Lewis rats sensitized to keyhole limpet hemocyanin (KLH) were fed either a normal diet or a 2% protein diet for 1, 6, and 10 weeks. Two additional groups were fed a 2% protein diet for 10 weeks but were refed with a normal diet for 1 or 4 weeks. At the end of each diet period rats were injected intradermally with KLH, Staphylococcus aureus 502A, and saline solution at different sites at from 1 to 24 hours. Technetium-99m-colloid labeled PHAGS (99PHAG) were injected intravenously and used to assess in vivo PHAG cell delivery. In normally fed rats the peak influx of 99PHAG was at 2 to 4 hours. After 1 week of protein-deficient diet there was a significant drop in early (2 to 4 hours) 99PHAG influx to both the DTH and bacterial reactions. After 10 weeks of protein deprivation (severe malnutrition) there was a further drop and a delay in the peak 99PHAG influx (from 2 to 4 hours, to 8 hours). A return to normal 99PHAG influx occurred only after 4 weeks of refeeding, and it coincided with a return to normal body weight and a normal DTH reaction. There was a direct correlation between total 99PHAG delivery to a DTH reaction and a bacterial abscess (rs = 0.87, Spearman rank; p less than 0.001). We conclude that both moderate and severe protein deprivation is associated with reduced in vivo phagocytic cell delivery to both a DTH reaction and a bacterial skin abscess, which can be restored with refeeding.

Abscess↗
PubMed1987

The effect of indomethacin on burn-induced immunosuppression.

Recent interest in the role of prostaglandin inhibitors as immunomodulators following major injury prompted us to study the effect of indomethacin on burn-induced immunosuppression in rats as measured by the delayed-type hypersensitivity (DTH) skin test response, ability to contain an intradermal bacterial challenge (10(8) Staphylococcus aureus 502A injected intradermally), and overall survival from spontaneous burn wound sepsis. Fifty male Sprague-Dawley rats sensitized to keyhole limpet hemocyanin (KLH) were subjected to a 30% full-thickness scald burn. Group 1 (n = 24) received indomethacin at 0.5 mg/kg intraperitoneally once daily with the first dose given immediately following the burn. Group 2 (n = 24) received vehicle only. Prostaglandin E2 measured by radioimmunoassay on day 17 was 2553 +/- 832 pcg/ml serum (+/- SEM) in the vehicle group and 1042 +/- 231 pcg/ml in the indomethacin group (P = 0.058, unpaired t test). Burn injury induced a decrease in the DTH response to KLH and an increase in the Staph lesion size (P less than 0.05) which was not corrected by indomethacin treatment. All animals developed spontaneous burn wound sepsis by day 14. Survival after 17 days in the indomethacin group was 100% compared to that of the vehicle group, 79%, P less than 0.05 (Fisher exact test). We conclude that despite unmeasurable corrections of the burn-induced suppression of the DTH response and local nonspecific bacterial defenses, low-dose indomethacin improves survival following burn sepsis.

Abscess↗
PubMed1986

Susceptibility to bacterial sepsis. Accurate measurement by the delayed-type hypersensitivity skin test score.

To test the hypothesis that any alteration in the delayed-type hypersensitivity (DTH) skin test response (not necessarily total anergy) reflects increased susceptibility to bacterial sepsis, male Sprague-Dawley rats presensitized to keyhole-limpet hemocyanin were subjected to a 30% full-thickness scald burn. Susceptibility to bacteria was assessed by the intradermal injection of Staphylococcus aureus 502A. The DTH response decreased following burn injury from 6.6 to 3.9 mm on days 2 and 8. Skin abscess size increased from 5.8 to 9.3 mm on day 2 and 8.9 mm on day 8. There was a significant inverse correlation between DTH skin test score and abscess size. Histologically there was no difference in the overall leukocyte accumulation in the abscess or the DTH reaction between the two groups, yet the overall size of the abscess was greater and the swelling of the dermis in the DTH response was less in the burned rats.

Abscess↗
PubMed1986

Malnutrition and humoral immunity: long-term protein deprivation.

The effect of long-term protein deprivation and refeeding on delayed-type hypersensitivity (DTH) and humoral immune function was investigated in rats. Animals previously sensitized to keyhole limpet hemocyanin (KLH) were placed on a 2% protein diet ad lib for 8 weeks, after which some groups of animals were refed for up to 4 weeks. Control rats received normal rat chow. Recall skin testing with KLH, and immunization with tetanus toxoid (TT) were used to assess DTH and humoral immune responses. Weight, DTH, and antibody responses declined progressively with protein deprivation. Refeeding restored skin test responses and humoral immunity. There was a direct correlation between degree of malnutrition as reflected by weight and antibody responses as well as between DTH and antibody responses. The data demonstrate that chronic protein deprivation modulates both DTH skin testing and humoral immune responses and show that under conditions of altered immune function, there is a correlation between DTH responses and humoral immune function.

Animals↗
PubMed1985

Malnutrition and humoral immunity: short-term acute nutritional deprivation.

The effects of short-term acute nutritional deprivation and refeeding on immune function was investigated in rats. Animals previously sensitized to keyhole-limpet hemocyanin were starved for 72 hours and refed for 7 days. Recall skin testing with keyhole-limpet hemocyanin and immunization with tetanus toxoid (TT) were used to assess delayed-type hypersensitivity (DTH) and humoral immune responses. DTH was maximally depressed late, after refeeding had begun. Anti-TT responses were depressed early during starvation. Neither DTH nor anti-TT responses had returned to normal after a period of refeeding sufficient to restore weight. The data indicate that short-term acute nutritional deprivation may contribute to acquired immunodeficiency in patients undergoing surgery.

Animals↗
PubMed1985

Effect of cyclosporine on host defence.

To discover whether cyclosporine administered daily in therapeutic equivalent doses for 3 consecutive weeks suppressed host defence, the authors measured the delayed-type hypersensitivity (DTH) skin response to keyhole-limpet hemocyanin (KLH) in rats. Twenty, male, Sprague-Dawley rats were sensitized to KLH and reactivity was confirmed 14 days later. Following sensitization, cyclosporine (20 mg/kg orally) was administered daily for 21 days to 10 rats. The other 10 (control group) received equivalent volumes of diluent (polysorbate 80 and ethanol). There was no difference in the DTH response between the cyclosporine and control groups for 5 weeks following treatment. Larger doses of cyclosporine (100 mg/kg) given intraperitoneally 30 minutes before and 6 hours after skin testing, suppressed the DTH response (7.2 mm to 2.4 mm) but resulted in a high mortality (eight of nine rats) at 48 hours. Delayed-type hypersensitivity was also suppressed in the control group but to a lesser extent and with no deaths (6.4 to 3.9 mm, p less than 0.05). Cyclosporine, in therapeutic equivalent doses, does not suppress the nonspecific immune component of host defence as reflected by the DTH skin response in previously sensitized animals. This may partially explain the lower frequency of septic morbidity and mortality in cyclosporine-treated transplant patients, compared with those receiving conventional therapy.

Animals↗
PubMedDate not supplied

The impact of thymoglobulin on renal function and calcineurin inhibitor initiation in recipients of orthotopic liver transplant: a retrospective analysis of 298 consecutive patients.

BACKGROUND: Renal dysfunction remains the Achilles' heel of calcineurin inhibitor (CI)use. The purpose of this study was to assess our institutional, renal-sparing strategy using thymoglobulin (TMG) in recipients of orthotopic liver transplants. METHODS: We performed a retrospective analysis of data from 298 adult recipients who were transplanted between 1991 and 2002. The patients were divided into two groups: those induced with TMG (group 1) and those that were not treated with this agent (group 2). A subgroup analysis was performed of patients with baseline serum creatinine values above 1.5 mg/dL (group 1A received TMG; group 2A did not). All patients received tacrolimus or cyclosporine (CyA) maintenance immunosuppression. RESULTS: Indications and demographics were similar between the two groups. Although there was no difference in patient and graft survivals, there was a statistically significant benefit in the rejection-free graft survival at 1 year for group 1 (51% vs 39%; P =.02). Furthermore, serum creatinine at 6 months was lower for group 1, despite a similar baseline creatinine. Subgroup analysis for patients with baseline abnormal serum creatinines showed that group 1A displayed an improved rejection-free graft survival at 1 month but not at 1 year. CONCLUSIONS: Thymoglobulin induction therapy may allow a delay in the initiation of CI therapy without compromising patient and graft survival, while preventing early rejection, even among patients with baseline renal dysfunction.

Adult↗
PubMedDate not supplied

Leukoreduction and acute rejection in liver transplantation: an interim analysis.

BACKGROUND: Little is known about the effect of blood transfusions and leukoreduction on acute rejection in liver transplantation. The purpose of this study was to assess the impact of leukoreduction on the occurrence of early rejection episodes in liver transplantation. METHODS: In 1999, mandatory leukoreduction was implemented in our program. Data from 339 consecutive liver transplant recipients were analyzed with attention to the time period as a proxy for leukoreduction, the number of transfusions, the wait list status, the hepatitis B or C status, the recipient age, and the type of immunosuppression. RESULTS: Using an early (6-month) rejection-free graft survival model, we observed that introduction of leukoreduction was independently associated with fewer rejection episodes (P =.001). Despite the lower rejection rate, due to a regimen of tacrolimus and antithymocyte globulin, the effect of implementation of leukoreduction remained significant (P =.021). CONCLUSION: The use of leukoreduction is associated with fewer early rejections, irrespective of the type of immunosuppression. These data support an exploration of the immunomodulatory effect of leukoreduction.

Disease-Free Survival↗