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Biomedical subjects

Moshe Kon

Publications and source records attributed to Moshe Kon.

At least 19 recordsLinked to original sources

Vascularized lymph node transplantation induces graft-versus-host disease in chimeric hosts.

BACKGROUND: The role of lymph nodes (LNs) in adaptive immune responses has been the subject of extensive research. In previous studies, the surgical removal of lymph nodes from rat hind limbs prevented the development of lethal graft-versus-host disease (GVHD) after allogeneic hind limb transplantation to chimeric recipient rats. The purpose of this study was to establish the role of the cellular fraction versus the microenvironment of LNs in the development of GVHD in this model. METHODS: A rat model for vascularized LN transplantation was developed and graft-versus-host responses were compared after: 1) naive ACI LN cells were infused into Wistar-Furth (WF) rats as chimeric recipients (e.g. [ACI-->WF]); 2) vascularized WF lymph nodes were transplanted to syngeneic WF recipients; 3) nonvascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients; 4) vascularized ACI lymph nodes were transplanted to [ACI-->WF] chimeric recipients. RESULTS: Transplantation of vascularized ACI lymph nodes to [ACI-->WF] chimeric recipient rats resulted in severe and sometimes lethal GVHD. In contrast, neither the infusion of purified ACI LN cells nor the transplantation of nonvascularized LNs led to GVHD in chimeric recipients. CONCLUSIONS: When introducing allogeneic cells into chimeric recipients, concomitant transplantation of the vascularized LN microenvironment makes a manifest difference between induction and absence of GVHD. This illustrates the important role of the LN microenvironment in adaptive immune responses.

Animals↗

Risk acceptance in composite-tissue allotransplantation reconstructive procedures.

Composite-tissue allotransplantation (CTA) is a new therapeutic modality to reconstruct major tissue defects of the face, larynx, and extremities. Unlike most life-saving organ-transplantation procedures, CTA is considered to improve quality of life. Therefore, the question arises, do the risks posed by the immunosuppression drugs that patients must take to prevent rejection justify the benefits of these procedures? The purpose of this study was to assess the relative risk that individuals are willing to accept in order to receive the benefits of CTA procedures. We used a psychometrically reliable and valid instrument to question two primary populations of individuals: those who live with the risks of immunosuppression, and healthy individuals. The level of risk acceptance for the seven transplant procedures tested (foot, single hand, double hand, larynx, kidney, hemiface, and full face) showed significant differences in research participants' risk acceptance for the different transplant procedures, but no significant differences between groups. Based on these findings, we conclude that certain CTA procedures convey benefits to recipients that are perceived by subjects, including individuals who live with the risks of immunosuppression, to warrant the risks of these procedures.

Adolescent↗

Neurological bypass for sensory innervation of the penis in patients with spina bifida.

PURPOSE: Most male patients with spina bifida have normal sexual desires. During puberty they begin to realize that they can achieve erection and sexual intercourse but without any sensation in the penis. We hypothesized that restored sensation in the penis would greatly contribute to their quality of life and sexual health. In this prospective study we investigated the outcome of a new operative neurological bypass procedure in patients with spina bifida. MATERIALS AND METHODS: In 3 patients who were 17, 18 and 21 years old with a spinal lesion at L5, L4 and L3-L4, respectively, the sensory ilioinguinal nerve (L1) was cut distal in the groin and joined by microneurorrhaphy to the divided ipsilateral dorsal nerve of the penis (S2-4) at the base of the penis. All patients underwent preoperative and postoperative neurological and psychological evaluations. RESULTS: By 15 months postoperatively all patients had achieved excellent sensation on the operated side of the glans penis. They were unequivocally positive about the results and the penis had become more integrated into the body image. In 2 patients masturbation became more meaningful and 1 became more sexually active with and without his partner. CONCLUSIONS: The newly designed neurological bypass procedure in patients with spina bifida resulted in excellent sensibility in the glans penis. The new sensation appeared to contribute to the quality of the patient sexuality and sexual functioning as well as to the feeling of being a more normal and complete individual who is more conscious of the penis. This new operation might become standard treatment in patients with spina bifida in the future.

Adolescent↗

Investigation of risk acceptance in facial transplantation.

BACKGROUND: The surgical techniques necessary to transplant a human face are well established, and the early success of human hand transplants suggests that the immunological hurdles of transplanting human facial tissues have largely been overcome. Therefore, it is the ethical barriers that pose the greatest challenge to performing facial transplantation. At the center of the ethical debate is the question, "Do the risks posed by the life-long immunosuppression that a recipient would have to take justify the benefits of receiving a face transplant?" In this study, the authors answer this question by assessing the degree of risk individuals would be willing to accept to receive a face transplant. METHODS: To quantitatively assess risks versus benefits in facial transplantation, the authors developed the Louisville Instrument for Transplantation, or LIFT, which contains 237 standardized questions. Respondents in three study populations (healthy individuals, n = 150; organ transplant recipients, n = 42; and individuals with facial disfigurement, n = 34) were questioned about the extent to which they would trade off specific numbers of life-years, or sustain other costs, in exchange for receiving seven different transplant procedures. RESULTS: The authors found that the three populations would accept differing degrees of risk for the seven transplant procedures. Organ transplant recipients were the most risk-tolerant group, while facially disfigured individuals were the least risk tolerant. All groups questioned would accept the highest degree of risk to receive a face transplant compared with the six other procedures. CONCLUSIONS: This study presents an empirical basis for assessing risk versus benefit in facial transplantation. In doing so, it provides a more solid foundation upon which to introduce this exciting new reconstructive modality into the clinical arena.

Decision Making↗

The segmental pectoralis major free flap: anatomical features of its vascular pedicle.

BACKGROUND: The pectoralis major muscle may be suited for free transplantation of a segment of the muscle. We investigated the length and diameter of its vascular pedicle to determine its feasibility. METHODS: The length of the pedicle, its arterial diameter, and its entry point into the muscle were determined in 17 cadaveric flaps. RESULTS: The pedicle length up to the medial border of the pectoralis minor muscle averaged 6.6 cm. The mean external arterial diameter was 1.8 mm, and the venous diameter was consistently larger. The vascular pedicle consistently entered the muscle lateral to the midpoint of, and a mean of, 8.8 cm caudal to the clavicular line. CONCLUSION: The vascular length and diameter are sufficient for microvascular anastomosis. Although an anatomic landmark for the cranial border of the flap could not be defined, the sternocostal part of the pectoralis major muscle may potentially be used as a segmental free flap.

Anastomosis, Surgical↗

Bone quality in swine composite tissue allografts: effects of combination immunotherapy.

BACKGROUND: Tacrolimus (FK506)/mycophenolate mofetil (MMF)/prednisone combination immunosuppression therapy has been found to effectively prevent composite tissue allograft (CTA) rejection with minimal toxicity in a preclinical porcine model. These findings have been reproduced in 24 human hands transplanted in 18 patients. In CTAs containing bone, adequate bone quality and healing are essential for long-term functional success. The purpose of this study was to determine the effect FK506/MMF/prednisone immunotherapy has on bone quality and healing. METHODS: Forelimb CTA-flaps were transplanted in nine pigs. Recipient animals received FK506/MMF/prednisone therapy for 3 months. Bone quality was studied pre- and posttransplant by measuring acoustic velocity and density and by calculating elastic coefficients. Additional bone quality analyses were performed on unoperated limbs, and in bone grafts from two pigs that had autograft procedures performed. Bone healing was assessed using radiographic analysis. RESULTS: Three animals were lost to immunosuppression-related complications before the endpoint of the study. The bone component of all six CTA-flaps showed normal healing. Although results of the bone density measurements were not significantly different when comparing pre- to posttransplant values, acoustic velocity and elastic coefficient measurements showed a significant decrease posttransplant indicating a decrease in bone quality. CONCLUSIONS: FK506/MMF/prednisone combination therapy prevented rejection, did not adversely affect bone quality, and showed normal bone healing. The transplant procedure itself decreased bone quality more than the immunosuppression regimen did over the observation period in this study. Based on these findings, we conclude to prevent CTA failure it is important to monitor bone quality posttransplant.

Animals↗

Do preservation solutions protect rat cremaster microcirculation during ischemia and reperfusion?

BACKGROUND: Our aim was to investigate the potential of the preservation solution Celsior to protect rat cremaster muscle microcirculation during ischemia and reperfusion, and to compare its effects with those of HTK (histidine-tryptophan-ketoglutarate-Bretschneider solution). Because of its anti-oxidant contents, we expected Celsior to be more protective than HTK. MATERIALS AND METHODS: Capillary perfusion and leukocyte-endothelium interactions were examined in rat cremaster muscle using intravital microscopy. After perfusion with Celsior or HTK (4 degrees C), the cremaster was subjected to 4 or 6 h of warm (33-34 degrees C) ischemia and 2 h of reperfusion. Measurements were performed prior to perfusion and/or ischemia, and 0, 1, and 2 h after restoration of flow. RESULTS: Without Celsior or HTK, capillary perfusion transiently decreased to 50% of baseline after 4 h of ischemia; it remained low (45%) after 6 h of ischemia. Whereas HTK had no significant influence, Celsior deteriorated capillary perfusion: it remained low after 4 h of ischemia (39-48%) and decreased even further after 6 h of ischemia (18-8%). Both preservation solutions similarly reduced the increase in leukocyte-endothelium interactions after ischemia. CONCLUSIONS: Preischemic tissue perfusion with Celsior had an adverse effect on capillary perfusion in rat cremaster muscle after 4 and 6 h of ischemia, whereas HTK did not significantly influence this parameter. Both preservation solutions similarly prevented the increase in leukocyte-endothelium interactions after ischemia. These data suggest that HTK is more suited as a preservation solution for muscular tissue than Celsior, especially when the known protective effects of HTK on muscle function are taken into account.

Animals↗

Effect of HTK on the microcirculation in the rat cremaster muscle during warm ischemia and reperfusion.

Histidine-tryptophan-ketoglutarate (HTK) preserves rat muscle function during cold storage. We examined the effect of HTK perfusion on preservation of microvascular function during 4 h of warm ischemia and subsequent reperfusion (I/R) in the rat cremaster muscle. Leukocyte-endothelium interactions, capillary perfusion, and arteriole diameters were quantified prior to HTK-perfusion and/or ischemia, and at 0, 1, and 2 h after restoration of blood flow. In all groups, the number of rolling leukocytes increased with time, whereas I/R induced a slight increase in leukocyte adhesion. After ischemia, capillary perfusion rapidly recovered to about 50% and returned to near normal (90%) after 2 h. HTK at 22 degrees C did not affect the assessed microcirculation variables, whereas HTK at 4 degrees C reduced leukocyte rolling, but not adhesion. Therefore, microvascular function of HTK-perfused muscles was not better preserved during warm I/R than that of nonperfused muscles. Contrary to other preservation solutions, HTK perfusion in itself was not detrimental to the microcirculation.

Animals↗

Effect of hypothermia and HTK on the microcirculation in the rat cremaster muscle after ischaemia.

Hypothermia is an important preservation method for tissues and solid organs. The aim of the present study was to assess in rat cremaster muscle the effect of hypothermia, without or with pre-ischaemic HTK (histidine-tryptophan-ketoglutarate-Bretschneider solution) perfusion, on microvascular consequences of 4 or 6 h ischaemia and 2 h of reperfusion. Intravital microscopy was applied to examine capillary perfusion and leucocyte-endothelium interactions. The cremaster muscle was subjected to 4 or 6 h of cold (4 degrees C) or warm (33-34 degrees C) ischaemia and 2 h of reperfusion. Measurements were performed at baseline, prior to HTK perfusion and ischaemia, and at 0, 1 and 2 h after blood flow restoration. Hypothermia completely prevented the 50% reduction in capillary perfusion that was observed previously at start of reperfusion after 4 h warm ischaemia. After 6 h of warm ischaemia, perfusion resumed in only 45% of capillaries and remained at this low level during reperfusion. In contrast, only a slight decrease (< 10%) in capillary perfusion was observed after 6 h of cold ischaemia. Pre-ischaemic HTK perfusion had no beneficial effect on tissue perfusion. Both hypothermia and HTK attenuated the significant increase in venular leucocyte-vessel wall interactions, which was observed after 4 h of warm ischaemia in a previous study. Combined application of both interventions had no additional effects. After 6 h of warm ischaemia, no increase in leucocyte-vessel wall interactions was observed, possibly due to venular flow reduction. In conclusion, hypothermia preserves capillary perfusion and prevents an increase in leucocyte-vessel wall interactions during reperfusion after muscle tissue ischaemia. Preischaemic perfusion of the vasculature with HTK does not improve the effects of cold storage on tissue perfusion, but attenuates the inflammatory response independently of temperature effect.

Animals↗

Bone quality and healing in a swine vascularized bone allotransplantation model using cyclosporine-based immunosuppression therapy.

Although vascularized bone and joint allotransplantation is a promising new treatment option for reconstructing large bone defects, the need for immunosuppressive agents to prevent rejection in these procedures poses a major problem. This problem stems from the fact that several of these agents can cause harmful side effects, such as alterations in bone quality and healing. Therefore, the purpose of this study was to determine what effect the commonly used immunosuppressant regimen cyclosporine A-based combination therapy has on bone quality and healing. In 10 pigs, vascularized bone allografts with skin and muscle components (osteomyocutaneous free flaps) were transplanted from size-matched donor animals. Recipient animals received oral cyclosporine A/mycophenolate mofetil/prednisone therapy for 90 days. Bone quality was studied before and after transplantation by measuring the bone's acoustic velocity and density and calculating the bone's elastic coefficient. Bone healing was assessed using radiographic analysis. Four animals were lost as a result of graft rejection or immunosuppression-related complications before the 90-day endpoint of the study. Although bone specimens taken from the six animals that completed the 90-day protocol had histological signs of rejection, they all seemed to have normal bone healing. Posttransplant bone density values were significantly decreased (p < 0.05) (1544.7 +/- 47.5 kg/m3) as compared with pretransplant values (1722.7 +/- 44.1 kg/m3). Results of the acoustic velocity and elastic coefficients measurements showed a significant decrease (p < 0.05) in posttransplant values (from 3503.0 +/- 165.1 meters/sec to 2963.0 +/- 54.6 meters/sec and from 21.6 +/- 2.2 GPa to 13.6 +/- 0.5 GPa, respectively), indicating diminished bone quality. The findings indicate that cyclosporine A/mycophenolate mofetil/prednisone combination therapy is ineffective in preventing bone rejection, that it decreases bone quality, and that it is associated with systemic toxicity, suggesting that this immunosuppressive regimen at the doses used in this study is not ideal for vascularized bone allotransplantation procedures.

Animals↗

Who benefits from peer review? An analysis of the outcome of 100 requests for review by Plastic and Reconstructive Surgery.

BACKGROUND: Little is known of what is done with the comments on submitted manuscripts provided by peer reviewers or to what extent these comments benefit the editor in deciding to accept or reject the manuscript, the author(s) in revising their manuscript, or the readership at large. Furthermore, nothing is known of any possible benefits of the process to the peer reviewer. Finally, the peer-review process may even be maleficent because of its implicit delay of publication and a possible bias against manuscripts originating from non-Anglo-American countries. METHODS: The authors evaluated the benefits of the peer-review process to authors, editor, readers, and reviewers by a bibliometric analysis of the outcome of 100 requests for review made by the editor of Plastic and Reconstructive Surgery from 1992 through 2003. The publication delay and potential geographical bias were evaluated as potential disadvantages. RESULTS: The authors' reviewer advised acceptance of 56 percent of the manuscripts, and the editor mostly agreed with his advice. This suggests that the editor benefited from the review. The authors addressed 48 to 81 percent of the reviewer's constructive suggestions, and this suggests that they and the readers benefited also. Readers of Plastic and Reconstructive Surgery may further benefit because manuscripts rejected by Plastic and Reconstructive Surgery end up in less prestigious journals. The implicit delay of publication is limited, and the authors found no bias against non-Anglo-American submissions. The cost-effectiveness of the process for the peer reviewer remains unclear. CONCLUSIONS: The peer-review system of Plastic and Reconstructive Surgery, in general, is beneficial.

Bibliometrics↗

Repair of damaged organs in vitro.

Treatments that can be performed ex vivo following ischemia to accelerate cellular recovery and ameliorate reperfusion injury could have major impact. An acellular, near-normothermic perfusion was employed to deliver growth factors to ischemically damaged kidneys. During the treatment oxidative metabolism was sufficiently restored to support up-regulation of cellular processes with the potential to modulate both injury and repair proteins in damaged kidneys. The results suggest that growth factor administration, without concomitant inflammation, triggers pathways for new synthesis leading to cellular recovery rather than cell death.

Animals↗

Ruby laser treatment of congenital melanocytic nevi: a review of the literature and report of our own experience.

The authors describe the possibilities and advantages of ruby laser treatment of large congenital nevi as an alternative to surgical excision. The literature (from 1980 to 2002) is reviewed and a case report is presented. Literature and the authors' experience show good cosmetic results after ruby laser treatment. Skin texture is improved and there is a considerable reduction in pigmentation and unsightly hair growth. Ruby laser treatment does not result in scarring, mutilation, or functional impairments, in contrast to surgical treatment. Only short outpatient sessions are required, recovery periods are extremely short, and no rehabilitation period is needed. No malignant changes have been reported after treatment with the ruby laser, even after 8 years of follow-up. The results imply that ruby laser treatment could be a valuable new treatment modality for large congenital nevi. It should be considered when patients refuse to undergo surgery, or when surgery would cause severe morbidity. More research should be initiated to assess possible risks and long-term results.

Child↗

Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts.

In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI-->Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized. Rejection, GVHD and donor chimerism was assessed. Chimeric hosts rejected none of their limbs. However, hosts of non-irradiated hind limbs succumbed to GVHD 22.4+/-0.8 days after transplantation. In contrast, chimeras that received irradiated or lymphadenectomized ACI hind limbs showed no clinical or histological signs of GVHD at 5 months. We conclude that mixed chimeric hosts are susceptible to GVHD due to the immunocompetent cell load provided by the LNs, not the BM, of hind limb allografts.

Animals↗

Pisotriquetral instability causing an unusual flexor tendon rupture.

We present a case of a closed rupture of the flexor digitorum profundus tendon of the small finger. It is our hypothesis that because of pisotriquetral instability as a result of a lesion of the pisotriquetral ligaments the flexor digitorum profundus tendon was entrapped repeatedly between the pisiform and triquetrum. This resulted in an attritional lesion of the tendon. The pisotriquetral joint showed no bone abnormalities.

Female↗

On the ethics of facial transplantation research.

Transplantation continues to push the frontiers of medicine into domains that summon forth troublesome ethical questions. Looming on the frontier today is human facial transplantation. We develop criteria that, we maintain, must be satisfied in order to ethically undertake this as-yet-untried transplant procedure. We draw on the criteria advanced by Dr. Francis Moore in the late 1980s for introducing innovative procedures in transplant surgery. In addition to these we also insist that human face transplantation must meet all the ethical requirements usually applied to health care research. We summarize the achievements of transplant surgery to date, focusing in particular on the safety and efficacy of immunosuppressive medications. We also emphasize the importance of risk/benefit assessments that take into account the physical, aesthetic, psychological, and social dimensions of facial disfiguration, reconstruction, and transplantation. Finally, we maintain that the time has come to move facial transplantation research into the clinical phase.

Body Image↗

Validity of a structured method of selecting abstracts for a plastic surgical scientific meeting.

In 1999, the European Association of Plastic Surgeons accepted a structured method to assess and select the abstracts that are submitted for its yearly scientific meeting. The two criteria used to evaluate whether such a selection method is accurate were reliability and validity. The authors previously established this method to be reliable on the basis of a prospective evaluation of the selection process used for the 2000 meeting of the European Association of Plastic Surgeons. It is more difficult to assess the validity of this method because there is no objective standard of quality of a scientific abstract against which the accuracy of selection can be assessed. This study statistically evaluated the accuracy of the meeting participants' assessment of presentations made during the meeting as the criterion standard for abstract selection on the basis of data obtained from the 2002 selection process. The authors evaluated the interobserver repeatability among five meeting participants of selecting the best presentations, the validity of the method of abstract selection after this criterion standard had been established, and the validity of reviewers' rating of abstracts as indicators of the scientific value of the actual presentations. The authors conclude that the assessment of platform presentations at a plastic surgical meeting is reliable. Accepting this assessment as the criterion standard, however, they could not prove the validity of their selection method or the validity of the reviewers' rating of abstracts as an indicator of the scientific value of the actual presentations.

Abstracting and Indexing↗

Full publication of papers presented at the 1995 through 1999 European Association of Plastic Surgeons annual scientific meetings: a systemic bibliometric analysis.

From the multitude of oral presentations at major medical meetings, the most informative and highest-quality studies make it to full publication in peer-reviewed journals. The rate of publication may be regarded as an indicator of the scientific level of the meeting. Study of the publication rates of consecutive annual meetings allows for the evaluation of the consistency of the scientific level of these meetings and for comparison with publication rates of other meetings in the same field of interest. To grade how useful any publication is to other authors, one can furthermore measure how frequently they cite it in their own publications. Finally, the time lag between oral presentation and full publication is of importance to both its authors and the audience at the meeting. The main objectives of this study were to determine the publication rate of papers of various fields of interest as presented at five consecutive annual meetings of the European Association of Plastic Surgeons (EURAPS) and the time lag between these presentations and their publication. The authors compared their overall findings to those reported for other surgical specialties. Moreover, they identified and classified the journals in which the full publications appeared as an indicator of the scientific value of the meeting. They conclude that a greater than average number of papers presented at the 1995 through 1999 annual EURAPS meetings went on to full publication in peer-reviewed journals. Among these journals, Plastic and Reconstructive Surgery was the best source for information presented at the meetings. Although approximately 90 percent of the publications appeared before 3 years had passed after a meeting, additional publications may be expected to appear even more than 6 years after the meeting. Given the high publication rate and the high average normalized impact factor of the journals in which the presentations appeared, the five studied EURAPS meetings overall had high scientific value.

Bibliometrics↗