Management of the recalcitrant postpneumonectomy bronchopleural fistula: the transsternal transpericardial approach.

The authors review the management of postpneumonectomy bronchopleural fistulae and describe the place of the transsternal transpericardial approach, especially in the management of recalcitrant postpneumonectomy bronchopleural fistulae. The technique is described in detail, and the results of the published series are analyzed. The authors do recommend the use of this approach in the recalcitrant fistula that has failed standard approaches.

Safety and efficacy of an improved antiseptic catheter impregnated intraluminally with chlorhexidine.

The safety and efficacy of a second-generation improved antiseptic catheter impregnated with silver sulfadiazine and increased levels of chlorhexidine on its outer surface and chlorhexidine alone on its luminal surfaces was compared in vitro and in vivo to standard antiseptic catheters impregnated with these antimicrobials on their outer surfaces only. In rat and pig intravenous models, the improved antiseptic catheter was significantly more effective in resisting both outer surface and luminal colonization compared with the standard antiseptic or control catheters. There was no evidence of tissue toxicity in any group.

Regulatory T cells maintain peripheral tolerance to islet allografts induced by intrathymic injection of MHC class I allopeptides.

Although transplantation remains the treatment of choice for diabetes mellitus, immunological rejection of allografts continues to be a major problem. The search for strategies to prevent graft rejection led us to examine if the fate of developing T cells may be influenced by the presence of allo MHC class I peptides in the thymus because T cell receptor-MHC class I/self-peptide interaction regulates thymocyte development. We studied the effects of intrathymic (IT) injection of a short segment of a synthetic immunogenic MHC class I peptide (peptide 2, residues 67-85) of the hypervariable domain of RT1.A derived from WAG rat (RT1U) on islet graft survival in the WF(RT1U)-to-ACI combination. Adult diabetic male recipients were treated with IT injection of a single WAG-derived MHC class I peptide 7 days before intraportal islet transplantation. Long-term unresponsive islet recipients were examined for the development of alloantigen (Ag)-specific regulatory cells. The results showed that while IT injection of 150 microg peptide 2 on day -7 did not prolong graft survival in naive recipients [median survival time (MST) of 14.0 days vs. 9.6 in controls], IT injection of 300 or 600 microg peptide 2 led to normoglycemia and permanent islet survival (> 200 days) in 4/6 and 3/5 STZ-induced diabetic ACI recipients, respectively. IT injection of 150, 300, or 600 microg peptide 2 combined with 0.5 antilymphocyte serum (ALS) immunosuppression on day -7 led to 100% permanent islet allograft survival (> 200 days) compared to MST of 15.0 +/- 2.3 days in ALS alone-treated controls. Similarly prepared animals rejected third-party Brown Norway (BN) islets in an acute fashion, thus demonstrating donor specificity. Intravenous injection of 300 microg peptide 2 combined with 0.5 ml ALS did not prolong islet allograft survival. The long-term unresponsive islet allograft recipients challenged with second set grafts accepted permanently 100% donor-type cardiac allografts while rejecting third-party (BN) hearts without rejecting the primary Wistar Furth (WF) islets. In analyzing the underlying mechanisms of acquired systemic tolerance, we found no suppressor/regulatory cells in adoptive transfer studies in tolerant animals at 30 days after IT injection of allopeptides. In contrast, adoptive transfer of 5 x 10(7) unseparated spleen cells from tolerant animals at 60 and 100 days after islet transplantation into lightly irradiated [200 rad total body irradiation (TBI)] ACI recipients led to donor-specific permanent islet graft survival in 2/3 and 4/5 secondary recipients, respectively, compared to an MST of 13.8 days in lightly irradiated ACI given unmodified syngeneic spleen cells. In addition, adoptive transfer of 2 x 10(7) purified T cells obtained from long-term functioning islet recipients led to permanent donor-specific islet survival in secondary recipients. The finding that IT injection of a short segment of a synthetic immunodominant MHC class I peptide derived from WAG that shares the RT1.A(U) domain with the graft donor is capable of inducing acquired systemic tolerance to WF islets suggests that linked recognition or epitope suppression may be involved in the induction of unresponsiveness. Generation of peripheral Ag-specific regulatory cells that suppress Ag-specific alloreactive T cells is, in part, responsible for the maintenance of tolerance in this model.

Comparative studies of specific acquired systemic tolerance induced by intrathymic inoculation of a single synthetic Wistar-Furth (RT1U) allo-MHC class I (RT1.AU) peptide or WAG (RT1U)-derived class I peptide.

BACKGROUND: Because T cell receptor-MHC class I/self-peptide interactions regulate T-cell development, the presence of MHC allopeptides in the thymus may influence T-cell tolerance to alloantigens. This hypothesis is supported by our most recent finding that intrathymic (IT) inoculation of nonimmunogenic synthetic peptides derived from "WAG" RT1.A induces tolerance to cardiac allografts in the Wistar-Furth (WF)-to-ACI model. To evaluate whether in vivo immunogenicity of MHC peptides is relevant to tolerance induction and to examine the effect of peptide specificity, we compared the effects on graft survival of well-defined, strain-specific immunogenic WF MHC class I peptides (RT1.AU) with closely related but non-strain-specific class I peptides derived from WAG (RT1U). METHODS: In vivo immunization of seven MHC class I peptides synthesized from RT1.AU sequences showed that two (u-5 and u-7) were immunogenic, whereas five others were not immunogenic in ACI recipients. We then examined the effects on cardiac allograft survival in the WF-to-ACI model of the two immunogenic RT1.AU peptides (u-5 and u-7) and three immunogenic WAG-derived peptides (peptides 1, 2, and 5). RESULTS: A combination of equal amounts (150 microg or 300 microg) of u-5 or u-7 each with 0.5 ml of antilymphocyte serum (ALS) on day -7 led to 60% and 100% permanent graft survival (>150 days), respectively. IT injection of the individual peptides on day -7 showed that only 300 microg of u-5 significantly prolonged graft survival to a median survival time of 17.3 days from 10.5 days in naive recipients. IT injection of 150, 300, and 600 microg of u-5 combined with 0.5 ml of ALS on day -7 led to permanent graft survival (> 150 days) in four of six, nine of nine, and six of six ACI recipients, respectively, compared with a median survival time of 15.4 days in ALS alone-treated controls. In contrast, similar treatments with peptide u-7 with or without 0.5 ml of ALS did not prolong graft survival, thus demonstrating that peptide u-5 alone mediates the observed effects on graft prolongation. A total of 300 microg of u-5 injected IT combined with ALS led to acute rejection of third-party (Lewis) grafts. Intravenous injection of 300 microg of u-5 with ALS also did not prolong WF graft survival in ACI recipients. The long-term unresponsive ACI recipients accepted permanently donor-type (WF) but not third-party (Lewis) second-set cardiac and islet allografts. Similarly, we showed that although IT injection of 600 and 1200 microg of a mixture of immunogenic WAG-derived peptides 1, 2, and 5 combined with 0.5 ml of ALS on day -7 led to permanent WF graft survival in ACI, only IT injection of 300 microg of peptide 2 combined with ALS led to permanent graft survival (>150 days) in four of five animals. To define the underlying mechanisms of tolerance, we examined in vitro the mixed lymphocyte reaction (MLR), cell-mediated lymphocytotoxicity, and cytokine profile of unresponsive recipients. Although the results showed nonspecific T-cell suppression in the MLR at 25 days after transplantation, which correlated with the persistence of ALS immunosuppression, long-term unresponsive animals showed normal MLR to donor and third-party antigens. In contrast, the donor-specific reactive cytotoxic T lymphocytes remained suppressed in short-term and long-term unresponsive rats. CONCLUSION: Of interest is our finding that IT injection of a short segment of WAG-derived MHC class I peptide induces active acquired tolerance similar to results obtained with the use of pure WF-derived peptide u-5 in the WF-to-ACI rat combination. It is noteworthy that we could not confirm the T helper (Th)1/Th2 paradigm in this model by initial cytokine analysis. Whether induction of tolerance by IT injection of allo-MHC peptides will have clinical usefulness must await results of similar studies in large animals. However, of major interest is the finding that a short segment of RT1.AU represents the tolerogenic

[Simultaneous repair of type IV rectovaginal fistula (cloaca) and "ectopic anus" deformity. Presentation of a case and review of the literature]. / Reparación simultánea de fístula rectovaginal tipo IV (cloaca) y deformación de tipo "ano ectópico". Presentación de un caso y revisión de literatura.

A 40-year-old woman presented with a 7-year-old type IV rectovaginal fistula (cloaca) and an associated "ectopic anus" deformity. The initial step of the operation was the creation of two v-shaped full-thickness skin flaps. Subsequently, a longitudinal repair was performed. The initial elevation of the flaps facilitates the identification of muscular structures needing repair. The overlap of the flaps as a final step of the operation corrects the "ectopic anus" deformity. Critical steps of the operation are described in detail and illustrated.

Acute urinary retention secondary to urethral inflammation from a vaginal contraceptive suppository in a 17-year-old boy.

We report the case of a 17-year-old boy who developed acute urinary retention following unprotected intercourse. His partner employed for the first time a nonoxynol-9-based commercial vaginal contraceptive insert. During intercourse the patient felt severe burning pain in the urethra. He was subsequently unable to void. Flexible cystourethroscopy revealed gross mucosal erythema and inflammation in the distal urethra and navicular fossa. We discuss the clinical management and review relevant literature.

PIP: Reported is the case of a 17-year-old US boy who developed acute urinary retention due to severe urethral inflammation, secondary to absorbance of a nonoxynol-9-based contraceptive. He had a recent history of unprotected intercourse with his regular sex partner until she used, for the first time, a vaginal suppository containing nonoxynol-9. During intercourse on this occasion, the adolescent experienced severe burning pain in the urethra and was subsequently unable to void. He denied any prior history of urinary tract infection, sexually transmitted diseases, or urethral discharge prior to this episode. The only significant clinical findings at examination were an inflamed meatal mucosa and severe tenderness to palpation 2 cm proximal to the glans. Flexible cystourethroscopy revealed gross mucosal erythema and inflammation in the distal urethra and navicular fossa. A French Foley catheter was easily inserted into the bladder and 1000 cm of clear urine were drained. An indwelling catheter was kept in place for 48 hours until the patient voided successfully. This is the first reported case of severe urethritis and obstruction in a young male. In this case, urethral absorption of nonoxynol-9 caused a severe inflammatory reaction sufficient to obstruct the distal urethra. When evaluating young men with acute urinary retention, clinicians should inquire about recent use of contraceptive inserts.