Endolumenal therapies for gastroesophageal reflux disease: are they dead?
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Fundoplication↗
Biomedical subjects
Jonathan P Pearl
Publications and source records attributed to Jonathan P Pearl.
The future of teaching surgical endoscopy.
Gastrointestinal surgery, with its emphasis on endoscopy, has renewed interest in teaching surgical endoscopy. The field is rapidly evolving, with innovative techniques emanating from the laboratory to the operating room and endoscopy suite. To ensure that surgeons spearhead the field of endoscopic surgery, a new strategy for teaching surgical endoscopy to residents and practicing surgeons must be developed.
Education, Medical, Graduate↗
Benign pneumoperitoneum after colonoscopy: a prospective pilot study.
Benign pneumoperitoneum is asymptomatic free intraabdominal air and is reported to occur occasionally with colonoscopy. Management of benign pneumoperitoneum after colonoscopy is controversial and may depend on incidence or etiology. No previous studies prospectively investigated the incidence or inciting factors of benign pneumoperitoneum resulting from colonoscopy. In this study, 100 patients underwent colonoscopy and then radiography of the chest and abdomen to detect free air. The average age was 58 +/- 6.2 years, and 48 of the colonoscopies were therapeutic. No cases of benign pneumoperitoneum were detected, estimating the incidence at 0% to 3% for diagnostic and therapeutic colonoscopy. These data indicate that benign pneumoperitoneum attributable to colonoscopy is rare and possibly nonexistent. Given the paucity of data favoring the occurrence of benign pneumoperitoneum after colonoscopy, we advocate treating all cases of free intraabdominal air after colonoscopy as perforations.
Colonoscopy↗
Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion.
T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naive T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant.
Alemtuzumab↗
IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates.
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.
Animals↗
Immune profiling: molecular monitoring in renal transplantation.
Molecular techniques have become a mainstay for most biomedical research. In particular, sensitive methods for gene transcript detection and advanced flow cytometry have been crucial in fostering our understanding of the basic mechanisms promoting allosensitization and adaptive immune regulation. These technologies have been validated in vitro, and in pre-clinical settings, and as such their clinical application is now clearly appropriate. It is becoming increasingly clear that these robust techniques hold much promise to better elucidate human transplant biology, and more importantly, guide clinical decision making with mechanistically-based information. This article will discuss our laboratory's use of several novel technologies, including gene polymorphism analysis, real-time polymerase chain reaction transcript quantification, and multi-color flow cytometry in clinical human renal transplantation. Specific technical methodology will be presented outlining keys for effective clinical application. Clinical correlations will be presented as examples of how these techniques may have clinical relevance. Suggestions for the adaptation of these methods for therapeutic intervention will be given. We propose that clinical transplantation should proceed in close step with modern molecular diagnostics.
Animals↗
Tolerance: is it achievable in pediatric solid organ transplantation?
Significant advances have been made in the understanding of allograft rejection. There is growing awareness that allograft acceptance, or tolerance, is also an active process rather than a passive absence of rejection. Mechanistic awareness of this process has spawned many preclinical strategies for the prevention of allograft rejection without the need for chronic immunosuppression. These therapies are currently entering clinical trials. This article reviews the prevailing therapies that hold promise for future clinical application. In particular, their application in children is discussed, as are biologic aspects of childhood immunity that may play a role in the success or failure of these strategies.
Animals↗
Femoral vessel injuries in modern warfare since Vietnam.
The incidence of lower extremity injuries is high in modern warfare; however the mortality rate from these injuries is low. Despite the overall low mortality of lower extremity injuries, many deaths in modern conflicts are due to femoral vessel injury. The modern warfare literature was reviewed. In Somalia, 1 of the 14 reported deaths was due to a laceration of the superficial femoral artery. In the Persian Gulf, three deaths were reported in an Army field hospital, one resulted from uncontrolled hemorrhage from a profunda femoris artery wound and two others resulted from traumatic amputations with consequent major arterial injury. Despite the advances in modern body armor, the groin is left unprotected. A strategy to help minimize U.S. casualties in modern warfare may be a method of field hemostasis specifically designed for femoral vessel injury.
Femoral Artery↗