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Biomedical subjects

Eric A Elster

Publications and source records attributed to Eric A Elster.

12 recordsLinked to original sources

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↗

Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin.

BACKGROUND: Perioperative lymphocyte depletion induces allograft tolerance in some animal models, but in humans has only been shown to reduce immunosuppressive requirements. Without maintenance immunosuppression, depleted human renal allograft recipients experience rejection characterized by infiltration of the allograft with monocytes and macrophages. T-cell depletion combined with a brief course of deoxyspergualin (DSG), a drug with inhibitory effects on monocytes and macrophages, induces tolerance in nonhuman primates. We therefore performed a trial to determine if lymphocyte depletion with alemtuzumab combined with DSG would induce tolerance in humans. METHODS: Five recipients of live donor kidneys were treated perioperatively with alemtuzumab and DSG and followed postoperatively without maintenance immunosuppression. Patients were evaluated clinically, by flow cytometry, and by protocol biopsies analyzed immunohistochemically and with real-time polymerase chain reaction. Results were compared to previously studied patients receiving alemtuzumab alone or standard immunosuppression. RESULTS: Despite profound T-cell depletion and therapeutic DSG dosing, all alemtuzumab/DSG patients developed reversible rejection that was similar in timing, histology, and transcriptional profile to that seen in patients treated with alemtuzumab alone. Chemokine expression was marked prior to and during rejections. CONCLUSIONS: We conclude that treatment with alemtuzumab and DSG does not induce tolerance in humans. Chemokine production may not be adequately suppressed using this approach.

Adult↗

Steroid-free immunosuppression in organ transplantation.

Although steroids have been the cornerstone of immunosuppressive regimens to treat and prevent rejection in organ transplantation, the past decade has seen many successful attempts to minimize or eliminate steroid use. This has been undertaken to decrease the diverse side effects seen with chronic steroid treatment. These efforts have focused on both steroid avoidance and complete elimination, and have been successful across broad patient groups. The key to these efforts has been the adoption of induction protocols with either lymphocyte-depleting agents or anti-interleukin-2 strategies, coupled with the use of the newer maintenance immunosuppressants. In this review, we address the feasibility and benefits of steroid-free and steroid avoidance protocols in kidney, pancreas, liver, and heart transplantation.

Graft Rejection↗

Surgical transplant physical examination: correlation of renal resistance index and biopsy-proven chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) remains the leading cause of late renal allograft loss that is minimally responsive to therapy once graft dysfunction is clinically evident. A screening test capable of identifying individuals at high risk for CAN would be a valuable adjunct to patient care, but to be cost effective, should be administered during routine evaluations by transplantation clinicians. STUDY DESIGN: We have compared the resistive index (RI) as measured by Doppler ultrasonography with subsequent biopsy findings on 91 renal allograft recipients who had a subsequent protocol-directed biopsy at least 3 months after renal transplant. All ultrasonography was performed by the transplantation surgical staff without involving the radiology department or a separate appointment time. RESULTS: Twenty-one patients had RI >/= 80 (average 621 days posttransplantation). Among these individuals, the subsequent incidence of CAN was 38%. Length of time between initial assessment of increased RI and biopsy-proved CAN averaged 233 days. The remaining 70 patients with RI < 80 had an incidence of CAN of 11.4% (p = 0.018). There were minimal complications from these biopsies. Sensitivity and specificity of an elevated RI in predicting CAN were 50% and 83%, respectively. The negative predicted value of an elevated RI in determination of CAN was 89%. CONCLUSIONS: These results suggest that elevated RI is an early predictor of histologically relevant CAN, possibly a result of burgeoning vasculopathy. The technical expertise required to make this appraisal is well within the capabilities of transplantation surgeons and trainees. Early evidence of CAN may allow for a targeted change in therapy before clinically significant injury. Ultrasonography should become a routine part of a transplantation clinic evaluation.

Adolescent↗

Rare mesenteric location of Meckel's diverticulum, a forgotten entity: a case study aboard USS Kitty Hawk.

The traditional understanding of Meckel's diverticulum has always emphasized its antimesenteric location, ever since its original description in 1809. We report the finding of an acutely inflamed mass located on the mesenteric aspect of distal ileum, which was discovered during a celiotomy performed aboard a U.S. Navy aircraft carrier. Pathological features of this unusual mass, including focal submucosal abscess formation, proximity to the ileocecal valve, and heterotopic gastric tissue are all characteristic of inflammatory Meckel's diverticulum. The atypical intraoperative finding of a desmoplastic reaction associated with this lesion is discussed within the context of a pertinent differential diagnosis. In addition, both the pathological characteristics and the unusual location of this mass are the basis for a discussion that revisits a 50-year-old surgical controversy regarding Meckel's diverticulum.

Adult↗

Effects of combined treatment with CD25- and CD154-specific monoclonal antibodies in non-human primate allotransplantation.

The CD154-specific monoclonal antibody (Mab) hu5c8 greatly prolongs allograft survival in primates. The CD25-specific Mab daclizumab has not, to date, been paired with hu5c8. We evaluated the effects of hu5c8 in vitro, alone and in combination with daclizumab on rhesus-mixed lymphocyte reactions (MLRs). We then evaluated therapy with hu5c8 and daclizumab in four monkey renal allograft recipients compared with monkeys untreated or contemporaneously treated with hu5c8 alone. Lymphocyte proliferation in MLR was reduced by both daclizumab and hu5c8, and their combined effects were additive. Rejection-free allograft survival in monkeys treated with both hu5c8 and daclizumab (74-479 days) was not significantly better than animals treated with hu5c8 alone (257-587 days), and one combined therapy animal rejected while still on hu5c8 therapy, a condition not typically seen with hu5c8 monotherapy. Although daclizumab and hu5c8 are additively effective in MLR, they do not appear to be synergistic in vivo in rhesus monkeys.

Animals↗

Combination induction therapy with monoclonal antibodies specific for CD80, CD86, and CD154 in nonhuman primate renal transplantation.

BACKGROUND: Antibodies and fusion proteins specific for CD80, CD86, and CD154 have shown promise as agents capable of inducing donor-specific tolerance in rodents. These agents have also been shown to be synergistic with one another in many settings of counter-adaptive immunity. In the nonhuman primate, monoclonal antibodies specific for CD80 and CD86 have prolonged the time to rejection of renal allografts but have not resulted in tolerance. A monoclonal antibody specific for CD154 has resulted in markedly prolonged survival of kidney, islet, cardiac, and skin allografts, but again most animals have eventually developed rejection after prolonged periods of rejection-free survival off therapy. METHODS: A combination of monoclonal antibodies specific for CD80, CD86, and CD154 were used in a mismatched nonhuman primate renal-allograft model. Doses used were based on optimized treatment protocols for each agent individually. RESULTS: Treatment of four rhesus macaques with this combination yielded a mean rejection-free survival of 565 days (311-911 days), significantly greater than untreated controls (mean survival=7.0 days, P=0.001) and animals treated with only a combination of anti-CD80 and CD86 (mean survival=191 days, P=0.01). The survival of animals treated with this combination of monoclonal antibodies was not significantly greater than those treated with anti-CD154 alone, but the production of alloantibody was delayed compared with monotherapy anti-CD154. CONCLUSION: These data suggest that a synergy exists between these agents, particularly with regard to T-dependent B-cell responses, but that they fail to induce durable tolerance in nonhuman primates.

Animals↗

Humanized anti-CD154 antibody therapy for the treatment of allograft rejection in nonhuman primates.

The anti-CD154 antibody hu5C8 prevents acute allograft rejection and prolongs allograft survival after withdrawal of therapy in nonhuman primates. This study describes the use of hu5C8 as a rescue agent for rejection developing after the withdrawal of hu5C8. Twelve rhesus monkeys that had received renal allografts under hu5C8 induction and subsequently rejected were studied. Rescue with hu5C8 was analyzed based on the histological character of the rejection (acute versus chronic) and whether conventional therapy was received at the time of rescue or induction. The diagnosis of rejection and response to therapy was based on allograft function and histology. Four monkeys that had acute rejection associated with conventional immunosuppression and hu5C8 were not reversed by hu5C8 rescue. Four animals with isolated chronic rejection following prolonged rejection-free survival after the withdrawal of hu5C8 did not respond to hu5C8 rescue therapy. Hu5C8 rescue therapy effectively reversed acute rejection occurring in two monkeys after hu5C8 withdrawal. One of two animals with combined acute on chronic rejection responded to hu5C8 rescue therapy. Hu5C8 effectively reverses acute but not chronic allograft rejection and appears to have no synergistic effect with conventional rescue agents.

Acute Disease↗

Adventitial cystic disease of the axillary artery.

Adventitial cystic disease (ACD) is an extremely rare cause of arterial and venous insufficiency, with only 317 reported cases in the world literature. These lesions have been previously described in the popliteal fossa, external iliac artery, and distal brachial, radial, and ulnar arteries as well as in the proximal saphenous vein at the ankle. We describe here the first reported case of this disease in a proximal vessel, the axillary artery. A 33-year-old man was evaluated for upper extremity arterial insufficiency and was diagnosed with ACD on the basis of physical examination and radiographic findings, which was confirmed by pathological assessment. The patient was treated by excision of the lesion and interposition vein bypass. As this represents the first case of ACD in the proximal vasculature, it demonstrates that these lesions can occur in axial blood vessels.

Adult↗

Primary acinic cell carcinoma of the breast.

Acinic cell carcinoma (ACC) is an uncommon neoplasm of the salivary glands with low malignant potential. Even rarer is the occurrence of primary ACC of the breast, there is only one previously documented case. We now describe the second case of a primary carcinoma of the breast with morphological, ultrastructural, and immunohistochemical features consistent with an ACC. In contrast to the previous case report we report the lack of encapsulation of the tumor and a spectrum of cell types within the tumor including cells resembling well-differentiated infiltrating ductal carcinoma. Additionally we did not observe the abundant nuclear abnormalities noted in the previously published case. We report for the first time the mucicarmine-staining pattern of this tumor as well as immunohistochemistry directed against cytokeratin 7, the estrogen receptor, and the progesterone receptor.

Breast Neoplasms↗

The road to tolerance: renal transplant tolerance induction in nonhuman primate studies and clinical trials.

Organ transplantation has become a standard life-saving therapy for many causes of end stage organ failure. Although valuable, it remains hampered by the requirement for, and complications of, immunosuppression to prevent immune rejection of the transplanted organ. It is now clear that rejection can be avoided in some experimental systems without a requirement of immunosuppressive medication, and these experimental concepts are now making their way into the clinic in the form of early transplantation tolerance trials. This manuscript will discuss the most promising techniques for tolerance induction, namely, costimulation blockade, lymphocyte depletion, and mixed chimerism. Seminal preclinical studies will be cited and the results of initial clinical trials will be reviewed. The data to date indicate that while tolerance remains elusive, immunosuppression minimization is a feasible near-term alternative.

Animals↗