Bilateral Transplantation Research Articles

Registry of the International Society for Heart and Lung Transplantation: Twenty-second Official Adult Lung and Heart-Lung Transplant Report—2005

Registry of the International Society for Heart and Lung Transplantation: Twenty-second Official Adult Lung and Heart-Lung Transplant Report—2005

Evolving Techniques and Perspectives in Lung Transplantation

Lung transplantation is currently a suitable option for patients with end-stage lung disease. Since the early 1980s the surgical technique and immunosuppressive protocols have been progressively modified to improve results and favor long-term survival. The original heart-lung transplantation under cardiopulmonary bypass is now rarely performed and single or bilateral lung transplantation is the procedure of choice. Bilateral transplantation is performed with two single lung transplants performed in sequence. Extracorporeal support is rarely employed and in most cases it is instituted through the femoral approach. Also, the surgical approach has been modified and the original clam shell incision has been replaced by two small anterior thoracotomies. The use of marginal donors has been increasingly proposed to enlarge the number of organs potentially available for transplantation. Immunosuppressive protocols have evolved to patient-specific regimens that can be quickly modified if required by the clinical status. Induction is now more aggressive and also rescue protocols for obliterative bronchiolitis can contribute to improved outcomes. Overall, lung transplantation is now performed with encouraging long-term results.

Evaluation of the oxygenation ratio in the definition of early graft dysfunction after lung transplantation

Despite the clinical importance of early graft dysfunction, no standardized definition is available. We hypothesized that the arterial blood gas oxygen tension/fraction of inspired oxygen ratio (PaO2 /FIO2) would prove to be a useful marker for predicting subsequent outcomes of early graft dysfunction. The aims of this study were to define the prevalence of various ranges of PaO2 /FIO2 over the first 48 hours after lung transplantation and to evaluate which measurement using the PaO2 /FIO2 best correlates with the duration of intubation, the length of stay in the intensive care unit, and 30-day mortality, which are important alternative indicators of early graft performance. A retrospective study was performed that included all 68 bilateral single-lung transplantations at The Alfred Hospital from January 2000 to December 2002. PaO2 /FIO2 at 6 and 12 hours after admission to the intensive care unit was significantly associated with the duration of intubation ( r = -0.44; P < .001 and r = -0.48; P < .001, respectively), and PaO2 /FIO2 at 6 and 24 hours was also significantly associated with the length of intensive care unit stay ( r = -0.38; P = .002 and r = -0.44; P = .001, respectively). Thirty-day mortality was significantly associated with a lower PaO2 /FIO2 at 6 hours (219 +/- 93 vs 306 +/- 101; P = .03). PaO2 /FIO2 taken between 6 and 12 hours after transplantation is a useful marker associated with lung transplantation outcomes. There is the potential for therapeutic interventions during this time that may be able to enhance PaO2 /FIO2 by 12 hours and improve subsequent outcomes.

Upper Lobe Fibrosis: A Novel Manifestation of Chronic Allograft Dysfunction in Lung Transplantation

Lung transplantation is an established treatment modality for a number of chronic lung diseases. Long-term survival after lung transplantation is limited by chronic allograft dysfunction, usually manifested by bronchiolitis obliterans syndrome. We describe a case series with upper lobe fibrosis, a novel presentation of chronic allograft dysfunction. We reviewed lung transplants at the Toronto General Hospital and Duke University Hospital from 1990 to 2002 and identified patients with upper lobe fibrosis. Thirteen of 686 patients (6 women) developed upper lobe fibrosis (Toronto, 9; Duke, 4); 12 of 13 had bilateral transplants. The median age at diagnosis was 42 years (range, 19-70). Primary diagnoses were cystic fibrosis, 6; emphysema, 4; sarcoidosis, 1; and pulmonary fibrosis, 2 patients. Radiographic diagnosis was made at a median of 700 days post-transplant (range, 150-2,920). Pulmonary function tests demonstrated predominantly a progressively worsening restrictive pattern. Open lung biopsy specimens revealed dense interstitial fibrosis, with occasional features of obliterative bronchitis, bronchiolitis obliterans obstructive pneumonia, and aspiration. Nine patients died at a median follow-up of 2,310 days (range, 266-3,740), 8 due to respiratory failure. Upper lobe fibrosis is a novel presentation of chronic allograft dysfunction in lung transplant recipients and is differentiated from bronchiolitis obliterans syndrome on the basis of physiologic and radiologic findings.

Lung Transplantation for Non-Cystic Fibrosis Bronchiectasis: Analysis of a 13-Year Experience

Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis. Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months. One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4). Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.

The International Registry on Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This inaugural report provides a review of all hand transplants performed to date. Between September 1998 and September 2004, 18 male patients underwent 24 hand/forearm/digit transplantations (11 monolateral and 4 bilateral hand transplantations, 2 bilateral forearm transplantations, and 1 thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. The average age of the patient was 32 years. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 17 to 70 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date were caused by severe inflammation and progressive rejection in a noncompliant patient. Acute rejection episodes occurred in 12 patients within the first year. Rejection was reversible in all compliant patients. Side effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. All patients had achieved protective sensation, and 17 patients also achieved discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities. Despite the enormous antigen load associated with composite tissue allograft, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.

Outcome Following Single vs Bilateral Lung Transplantation in Recipients 60 Years of Age and Older

Aims The significant shortage of donor organs in lung transplantation necessitates a careful selection of lung transplant recipients. The outcome of lung transplant recipients aged 60 years and older has not been analyzed systematically. Methods We retrospectively reviewed our experience with older recipients. Between January 1999 and July 2003, 248 patients underwent lung transplantation at our institution, of which 18 were aged 60 years and older (7.3%, range 60–66, mean 62 ± 1.1). Results Eleven (61%) of the recipients 60 years and older received a single (SLTx) and seven (39%), a bilateral lung transplant. Donor age in the single transplant cohort was 30 ± 4 years. It was 33 ± 3 years in bilateral patients. Posttransplant ventilation time was significantly different among groups, with 282 ± 32 hours after bilateral and 56 ± 13 hours after transplant ( P < .05). Also significantly longer was the length of the ICU stay in the bilateral group. First PaO 2 in the ICU was not different among the two groups. The 1-year survival in the single transplant group was significantly better compared to the bilateral group with 73% versus 43%, respectively. Conclusions The 1-year survival following lung transplantation in patients older than 60 years is markedly reduced compared to recipients under 60 years of age. If a lung transplant is considered in a recipient above the age of 60 years, a single transplant should be favoured. If that is not indicated, patients over 60 should be very carefully selected for bilateral transplant.

Lung transplantation for emphysema. Lung hyperinflation: incidence and outcome

Lung transplantation, single or bilateral sequential, is the final option for patients with emphysema. This study analyzed the outcome of lung transplants for emphysema (single or double), and evaluates the incidence, predictive factors and prognosis of lung hyperinflation (LHI) in unilateral transplants. We prospectively studied patients undergoing lung transplantation for emphysema. On admission to the Intensive Care Unit (ICU) and at 12, 24, 48 and 72 h we tested the patients' respiratory function, oxygen arterial pressure (PaO2) and mean pulmonary arterial pressure (MPAP) before transplantation. LHI incidence, duration of mechanical ventilation and hypoxemia, ICU stay and mortality was also analyzed. We studied 34 consecutive patients undergoing lung transplantation for emphysema, 14 single and 20 bilateral. Single-lung transplantation had a higher mortality (50%) than double-lung transplantation (11%), with an odds ratio of 9.0 (1.3-48.7). Of the 14 patients who received a single graft, 9 patients (64%) developed LHI. No predictive factors for LHI could be established. Duration of mechanical ventilation (22 vs 3 days) and ICU stay (36 vs 6 days) was much longer in patients with LHI; however, only ICU stay reached statistical significance (P = 0.011). Mortality in patients with LHI was higher, 67% vs 20% (NS). We conclude that single-lung transplant in emphysema patients has a worse prognosis than bilateral transplant, with a 9-fold higher mortality rate. LHI is a common event in single-lung transplant for emphysema and is associated in our patients with a longer stay at the ICU.

Multiple suppurative cystic lesions of the lips and buccal mucosa: A case of suppurative stomatitis glandularis

Cheilitis glandularis (CG) is a rare inflammatory salivary gland disease that usually affects the lips. Although the etiology of CG is still unknown, it is believed to be a hereditary disease with an autosomal dominant pattern of inheritance. Three clinical presentations of CG are described in the literature: simple, superficial suppurative, and deep suppurative. A case of deep suppurative CG that extended to the buccal mucosa has been previously reported as suppurative stomatitis glandularis (SSG). Here we report a case of SSG in a 64-year-old white female with a history of bilateral renal transplants for adult polycystic kidney disease, who presented with painful swollen lips and bilateral buccal mucosal lesions. The diagnosis and management of the case is discussed. To the best of our knowledge, this is the second report of SSG, a rare condition affecting the minor salivary glands in the oral cavity.

Plasticity in central olfactory processing and pheromone blend discrimination following interspecies antennal imaginal disc transplantation

The antennal imaginal disc was transplanted between premetamorphic male larvae of two different Lepidopteran moth species. Following adult eclosion, electrophysiological recordings were made from 33 central olfactory neurons in the antennal lobes of both Helicoverpa zea donor to Heliothis virescens recipient (Z-V) and reciprocal (V-Z) transplants. Under the influence of sensory neuron input derived from the transplanted antennal imaginal disc, most antennal lobe projection neurons (29/33) were classified as belonging to physiological categories encountered previously in donor species males. Furthermore, when stained many of these neurons had dendritic arbors restricted to donor-induced glomerular locations predicted by their physiology. However, some neurons with unexpected physiological profiles were also identified (4/33), but only in V-Z transplants. These profiles help to explain why some V-Z bilateral transplants were able to respond to both pheromone blends in flight tunnel bioassays, an unforeseen result counter to the assumption that a donor antenna develops a normal donor antennal olfactory receptor neuron complement. Stainings of several neurons in V-Z transplant males also revealed unusual morphological features including multiglomerular dendritic arbors and "incorrect" glomerular locations. These results indicate a developmental plasticity in the final dendritic arborization pattern of central olfactory neurons, including an ability to colonize and integrate inputs across topographically novel donor glomeruli, different from those found in the normal recipient antennal lobe.

Genistein inhibits invasive potential of human hepatocellular carcinoma by altering cell cycle, apoptosis, and angiogenesis

To study the in vitro and in vivo inhibitory effects of genistein on invasive potential of Bel 7402 hepatocellular carcinoma (HCC) cells and to explore the underlying mechanism. Bel 7402 HCC cells were exposed to genistein. The invasive activity of tumor cells was assayed in transwell cell culture chamber. p125FAK expression and cell cycle were evaluated by a functional assay. Cell apoptosis analysis was performed with TUNEL method. In addition, bilateral subrenal capsule xenograft transplantation of HCC was performed in 10 nude mice. Genistein was injected and the invasion of HCC into the renal parenchyma was observed. Microvessels with immunohistochemical staining were detected. Genistein significantly inhibited the growth of Bel 7402 cells, the inhibitory rate of tumor cells was 26-42%. The invasive potential of Bel 7402 cells in vitro was significantly inhibited, the inhibitory rate was 11-28%. Genistein caused G2/M cell cycle arrest, S phase decreased significantly. The occurrence of apoptosis in genistein group increased significantly. The expression of p125FAK in 5 microg/mL genistein group (15.26+/-0.16%) and 10 microg/mL genistein group (12.89+/-0.36%) was significantly lower than that in the control group (19.75+/-1.12%, P<0.05). Tumor growth in genistein-treated nude mice was significantly retarded in comparison to control mice, the inhibitory rate of tumor growth was about 20%. Genistein also significantly inhibited the invasion of Bel 7402 cells into the renal parenchyma of nude mice with xenograft transplant. The positive unit value of microvessels in genistein-treated group (10.422+/-0.807) was significantly lower than that in control group (22.330+/-5.696, P<0.01). Genistein can effectively inhibit the invasive potential of Bel 7402 HCC cells by altering cell cycle, apoptosis and angiogenesis, inhibition of focal adhesion kinase may play a significant role in this process.

Split lung transplantation with intraoperative extracorporeal membrane oxygenation (ECMO) support

Pulmonary bipartitioning or split lung transplantation, which was first described in 1997, presently represents the most efficient use of donor lungs. With this technique, a left donor lung can be separated into an upper and lower lobe and used for bilateral transplantation in a smaller recipient. The right donor lung remains for use as a single lung graft in another patient. In 2001, a similar technique for splitting a right lung was described. The technique of harvesting and procurement of the donor organ for split lung transplantation is identical to the standard lung transplantation technique. The final separation of the donor lung is performed at the level of the interlobar fissure immediately prior to implantation. The lower lobe is implanted in the left recipient hemithorax, whereas the upper lobe, after closing of the central end of the left main pulmonary artery, and a 180° rotation along the vertical axis, is grafted into the right hilus. The use of extracorporeal membrane oxygenation (ECMO) provides intraoperative hemodynamic stability and protects the first implanted lobe from overflow and resulting reperfusion injury. This report discusses the technique developed at the department of cardiothoracic surgery of the Medical University of Vienna.

RECURRENT LOWER GASTROINTESTINAL (GI) BLEED IN AN ADOLESCENT WITH END-STAGE RENAL DISEASE (ESRD)

GI bleeding is an uncommon occurrence in infants and children. Unlike adults, the incidence of upper and lower GI bleeding in children is comparable. Causes include bleeding from an ulcer, esophageal varices, Meckel's diverticulum, vascular ectasia in the small or large bowel, and colitis. Occasionally, the cause is not identified. We present a case of an adolescent with ESRD and recurrent lower GI bleeding. The patient is a 13 year-old male with nephrotic syndrome diagnosed at age 7 years. He developed ESRD and underwent bilateral nephrectomy and renal transplant. Due to transplant failure he is on peritoneal dialysis (PD). He presented to the emergency department with one-day history of painless hematochezia. He had a similar episode 2 weeks prior to admission that resolved. On exam he was pale, awake and alert, well nourished and well developed. Vital signs were stable. His abdomen had multiple healed surgical scars and a PD catheter. Lab data: Hemoglobin 6.4 g/dl, hematocrit 19.5%, and MCV 87 fl. Platelets, PT, PTT, liver panel, and metabolic panel were unremarkable except for a creatinine of 11.9 mg/dl. Stool culture was negative for salmonella, shigella, campylobacter, Escherichia coli O157 and acid-fast bacilli. Stool for ova and parasites, cryptosporidium, and yeast was negative. Upper endoscopy and colonoscopy revealed mild gastric erythema, and unremarkable duodenum and colon. No site of active bleeding was seen. Bleeding resolved and he was discharged. For two months following the initial admission the patient had 5 episodes of rectal bleeding with drop in hemoglobin to 6 gm/dl, requiring multiple blood transfusions. Further workup included two nuclear radiology tagged RBC scans that were negative and a negative Meckel's scan. Three separate arteriograms with cannulation of the celiac axis, the superior, and inferior mesenteric arteries were performed during active bleeding. They revealed hyperemia at the rectosigmoid colon with no extravasation of blood and no arteriovenous malformations. Repeat colonoscopy showed non-fresh blood in the colon, but no site of active bleeding was identified. Wireless Capsule Endoscopy did not disclose a site of bleeding in the small bowel. He was taken to the operating room for exploratory laparotomy and was found to have a fistula between the jejunum and the transplant renal artery stump in the retroperitoneum. The fistula was resected and the patient has not had recurrence of bleeding for 3 months following surgery.

A donor history of smoking affects early but not late outcome in lung transplantation.

Liberalization of tobacco exposure history as an exclusion to lung donation has recently occurred to increase donor organ availability. This study investigated the effect of donor smoking status and current and cumulative cigarette dose on early and late outcomes in lung transplantation. From 1995 to 2002, 173 heart-lung and bilateral single-lung transplant recipients were retrospectively reviewed. Seventy-seven (45%) of 173 donors were ever-smokers and 64 of those 77 were current smokers. These were divided into subgroups by current number of cigarettes smoked to investigate acute dose effects and by pack-year to investigate cumulative dose effects. Risks of smoking were assessed by univariate and multivariate hazard regression models. Univariate analysis revealed that there were significant differences between current and cumulative dose subgroups in early postoperative variables, including Pao2/Fio2 ratio, ventilation time, and intensive care unit stay. Additionally, these variables were dose dependent. There was no significant difference in 3-year survival between never-smokers and ever-smokers (73% versus 64%, P = 0.27), and a rate of decline of survival was similar. There was a trend for the percentage of patients dying of bronchiolitis obliterans syndrome to be lower in the ever-smokers group compared with the never-smokers group (6% versus 11%, respectively). Multivariate analysis revealed current and cumulative smoking as a risk factor for early but not late outcomes. Donor smoking history had a significant effect on early outcomes in lung transplantation in a current and cumulative dose-dependent fashion. However, no significant effect on late outcomes, including bronchiolitis obliterans syndrome, was seen.

Medium-term results of extracorporeal membrane oxygenation for severe acute lung injury after lung transplantation

Background Extracorporeal membrane oxygenation (ECMO) has been used successfully for early, severe reperfusion injury after lung transplantation. The purposes of this study are to: (1) document the medium-term survival of patients treated with ECMO; and (2) assess the extent of recovery of their pulmonary function. Methods We retrospectively reviewed charts of 172 patients having lung transplants at our institution from 1997 through 2002. The group included 16 patients (9% of total; 10 bilateral, 5 single, 1 living lobar) treated with ECMO for primary allograft failure after single or bilateral single-lung transplantation. Survival and bronchiolitis obliterans syndrome (BOS)-free survival rates were calculated. Pulmonary function was assessed at 2 months, 1 year and 2 years post-transplant. Results Median hospital stay was 48 days for the ECMO group and 16 days for the overall group ( p < 0.05). The 90-day survival was 60% in the ECMO group, and 90% in the overall group. The 2-year survival was 46% in the ECMO group, and 69% in the overall group. Mean forced expiratory volume in 1 second (FEV 1) in the ECMO group at 1 year was 59 ± 13% of predicted, and at 2 years 60 ± 15% of predicted; it was not significantly different for the overall group. Conclusions Patients treated with ECMO for primary allograft failure after lung transplantation showed acceptable medium-term survival and pulmonary function.

Steroid- and ATG-Resistant Rejection After Double Forearm Transplantation Responds to Campath-1H

We herein report on immunological and histological observations in the first bilateral forearm transplant recipient. The last of three rejection episodes occurring on day 95 after transplantation was resistant to steroid and antithymocyte globulin (ATG) treatment. Histology demonstrated lymphocytic infiltrates, apoptotic and necrotic keratinocytes and focal desquamation of the epidermis. Therapy with Campath-1H, however, resulted in complete restitution of normal skin. This is the first report on a successful rescue therapy with Campath-1H in a severe, steroid- and ATG-resistant rejection. Hence, Campath-1H treatment might be a novel and powerful therapeutic option for multiresistant allograft rejection.

LONG-TERM RESULTS OF TWO CASES OF BILATERAL HAND TRANSPLANTATION: LYON EXPERIENCE

O130 Aims: To report our experience about bilateral hand allotransplantation. Methods: The first bilateral hand transplantation was performed in January 2000 and the second case on April 30, 2003. The first recipient was a 33-year old man with bilateral amputation at midforearm level from four years and the second recipient was a 22-year old man with amputation at proximal forearm level on the right side and at wrist level on the left side from two years. The immunosuppressive protocol included tacrolimus, mycophenolate mofetil, prednisone and, for induction, antithymocyte globulins. An intensive rehabilitation program started 12 hours after surgery and included physiotherapy, electrostimulation and occupational therapy. Results: An arterial thrombosis, which was quickly reversed, occurred at day 1 post-transplantation in the second recipient. Side-effects included transient hyperglycemia during the first month post-transplantation in the first recipient and an ostheomyelitis at day 152 in the second patient with complete resolution after 6 months of antibiotics. During the follow-up period no malignancies occurred and no signs of graft-versus-host disease were shown in either patient. Only two episodes of acute skin rejection (asymptomatic maculopapular lesions) occurred on days 52 and 82 and on days 55 and 86 in the first and in the second recipient respectively. In all cases the episodes resolved by increasing oral steroid dose within 10-15 days. Nerve regeneration has been demonstrated by histological studies, electromyography and sensitive tests as well as cortical reorganization by functional magnetic resonance imaging in both patients. In the first bilateral hand transplantation there is a normal sensitivity to pain and thermal stimuli and a good sensitivity to dynamic and static pressure with some errors in discrimination of the localisation. Intrinsic musculature recovery started at 9 months and at present he can dissociate each single finger movement. His grip and pinch strength is 3 Kg and 1.5 Kg respectively. The patient is able to perform the same daily activities that were possible with the myoelectric prostheses before the transplantation. In addition, several activities such as holding a pen or a glass or a pair of scissors, shaving, taking care of his personal hygiene that were impossible before are at present easily performed by the patient. In the second bilateral hand transplantation there is a normal sensitivity to pain and thermal stimuli, a discrete tactile sensation and a discriminative sensation ranging between 8 and 15 mm. Intrinsic musculature recovery started at 6 months on the left side and at 9 months on the right side. His grip strength is 8 kg on the right and 10 Kg on the left side while his pinch strength is more than 1 kg on both sides. He is already able to take care of his personal hygiene and to hold several objects, such as a glass. Conclusions: Although these results are very encouraging, other cases are required.

THE INTERNATIONAL REGISTRY ON HAND AND COMPOSITE TISSUE ALLOGRAFT

O132 Aims: Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This inaugural report provides a comprehensive review of all hand transplants performed to date. Methods: From September 1998 to March 2004 nineteen male patients underwent 25 hand/forearm/digit transplantations (12 monolateral and 4 bilateral hand transplantations, 2 bilateral forearm transplantations, 1 thumb transplantation). Recipients were all males aged between 19 and 52 (average 32 years). Time since amputation ranged from two months to 22 years (mean 5.4 yrs). Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Results: Acute rejection episodes occurred in 75 % of the patients. In most cases treatment of the first rejection episode included high-dose intravenous steroids; in cases where no steroids were administered intravenously, oral steroid treatment was increased. Tacrolimus, corticosteroid or flumix ointment (alone or in combination between them) was applied in all cases of rejection. Treatment of a second, third or fourth rejection episode varied considerably, but it was completely reversible in all compliant patients. In one case, following the patient’s non-compliance with immunosuppressive therapy, cutaneous lichenoid-like lesions occurred. Side-effects included opportunistic infections, such as CMV infections, and metabolic complications, such as transient hyperglycemia, and increase in creatinine values. No life-threatening complications or malignancies were reported. All transplants were technically successful, and only minor surgical complications were observed. There was one case of early perioperative arterial thrombosis which was quickly reversed. Patient as well as graft survival was 100 % at 2 years. Two cases of graft failure at a later date were caused by severe inflammation and progressive rejection in a non-compliant patient Nerve regeneration was particularly good in all patients, showing a satisfactory degree of protective sensation recovery (i.e. the ability to detect pain, thermal stimuli and gross tactile sensation). A certain degree of discriminative sensation was also reported, although this was not to the same degree at all parts of the graft. At two years post-transplantation 12 hands showed different degrees of discriminative sensation recovery. Motor recovery began with extrinsic muscle function, allowing the patients to perform grasp and pinch activities. Function of intrinsic muscles was only observed at a later stage, starting at 12 months post-transplantation in the majority of patients. Patients showed the ability to perform the majority of daily activities. Conclusions: Despite the enormous antigen load associated with CTA, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.

Avaliação endócrina e morfológica de transplante ovariano homógeno

INTRODUÇÃO: A insuficiência ovariana decorre de ooforectomia bilateral em diversas afecções do ovário, como neoplasia e sepse, além de quimioterapia, radiação pélvica e fatores relacionados à idade. Suas complicações sistêmicas, como insuficiências hormonais, podem ser de difícil controle. OBJETIVOS: Avaliar aspectos endócrinos e histológicos ovarianos após seu transplante ortotópico, sem anastomose vascular e submetidos à imunossupressão pela ciclosporina. MATERIAL E MÉTODO: Foram utilizadas 12 coelhas da raça Nova Zelândia Branca (n = 6) e Califórnia (n = 6), divididas em dois grupos: grupo 1 (n = 4), de controle, submetido apenas a laparotomia, sem outro procedimento cirúrgico; e grupo 2 (n = 8), submetido a ooforectomia bilateral e transplante ortotópico dos ovários, que foram trocados entre as duas raças de animais. De um lado, foi transplantado o ovário íntegro e, do outro, o ovário fatiado. Não houve anastomose vascular. As coelhas foram imunossuprimidas com ciclosporina (10mg/kg ao dia). No final do período de acompanhamento de seis meses, foram feitas dosagens de estradiol, progesterona, hormônio foliculoestimulante (FSH) e hormônio luteinizante (LH), além de estudo histológico de ovários, tuba uterina e útero. RESULTADOS: Os ovários transplantados estavam rodeados por tecido conjuntivo, bem vascularizados, mostrando folículos em diferentes estádios de desenvolvimento. A histologia tubária e uterina também foi preservada em ambos os grupos. A dosagem hormonal foi normal em todas as coelhas, indicando que, do ponto de vista endócrino, o ovário transplantado estava funcionando. O transplante ovariano homógeno ortotópico, sem pedículo vascular e submetido à imunossupressão pela ciclosporina, foi eficaz para a manutenção de hormônios ovarianos em níveis normais.

Effects on erectile function of transplanted major pelvic ganglion into the corpus cavernosum of adult rats with bilateral cavernous nerve injury

To investigate the effects on erectile function of transplanted major pelvic ganglion into the corpus cavernosum of adult male rats undergoing transection of bilateral cavernous nerves. Twenty-six male Sprague-Dawley rats (3 - 4 month-old and 300 - 400 g/each) were divided into 2 groups: experimental group (transection of bilateral cavernous nerves and transplantation of left ganglion into left crus of penis, n = 16) and control group (transection of bilateral cavernous nerves only, n = 10). Erectile function was measured by injecting APO, and intracavernous pressure was measured 1 and 3 months afterwards by electric-stimulating the right major pelvic ganglion or the left crus. Half animals in each group were sacrificed 1 and 3 months afterwards for detecting nNOS-containing nerve fibers of corpus cavernosum. Electron microscopy of the implanted area was performed to assess neuronal survival. Both of the two groups have no erectile response to APO injection. Electrostimulation on the right major pelvic ganglion and left crus failed to produce erection in experimental group. The mean pressure changes in the two groups, measured by stimulating the left crus, were (9.41 +/- 3.20) and (4.16 +/- 2.58) cmH(2)O 1 month afterwards, and (13.67 +/- 4.18) and (5.09 +/- 2.74) cmH(2)O 3 months afterwards, respectively (P < 0.05). An increased number of nNOS-containing nerve fibers in left crus was detected in experimental group 1 and 3 months later, compared with control one (218.7 +/- 24.5, 18.0 +/- 3.7; 183.2 +/- 19.7, 19.0 +/- 3.8; P < 0.05). Ultrastructure examination by transmission electron microscope confirmed the survival of the implanted ganglion. Major pelvic ganglion can survive in the corpus cavernosum, and it has significant effects on the number of nNOS-containing nerve fibers and the alteration of intracavernous pressure.