Expression of CD47 antigen in Reed-Sternberg cells as a new potential biomarker for classical Hodgkin lymphoma.

INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis. RESULTS: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.

Brentuximab vedotin and ESHAP is highly effective as second-line therapy for Hodgkin lymphoma patients (long-term results of a trial by the Spanish GELTAMO Group).

BACKGROUND: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). PATIENTS AND METHODS: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. RESULTS: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3-4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). CONCLUSION: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.

Late Onset of Cholesterol Embolism Leading to Graft Failure After Renal Transplantation: Report of Two Cases.

Cholesterol-crystal embolization (CE) usually presents as an acute or subacute multisystemic disease. When affecting native kidneys prognosis is poor, often leading to chronic kidney disease. Presentation in renal allografts is a rare condition although probably underdiagnosed. If renal CE originates from the recipient, allograft survival is usually good, whereas if the donor is the origin, graft dysfunction and subsequent graft loss are common. Associated risk factors are common to native and transplanted kidneys. We report 2 renal graft recipients of different cadaveric donors, both male and 68 years old, diagnosed with CE in renal grafts at 19 and 72 months after transplantation, respectively. They presented previous risk factors for CE, including severe atherosclerosis. They presented insidious and asymptomatic impairment of renal function initially. Renal graft biopsy specimens showed CE in the interlobular arteries. Potential triggers for CE were suspended and high doses of steroids were started. However, progressive decline in renal function and requirement of chronic dialysis occurred within the first year after diagnosis in both cases. Herein we discuss the causal or incidental role of CE in the graft failure of these cases, highlighting the serious outcome despite the recipient origin of the CE and the initiation of treatment.

Nodular Arteriolar Hyalinosis as Histopathologic Hallmark of Calcineurin Inhibitor Nephrotoxicity: Does It Always Have the Same Meaning?

INTRODUCTION: Nodular arteriolar hyalinosis (NAH) is a typical, although not specific, histological finding of calcineurin inhibitor toxicity (CNIT). The objective of our study was to assess the reason why some patients showing strong NAH in renal graft biopsies who underwent calcineurin inhibitor (CNI) withdrawal presented very poor outcome whereas others improved graft function. MATERIAL AND METHODS: We performed 207 renal graft biopsies between January 2011 and May 2014 due to clinical criteria. In 13 patients CNI withdrawal was performed, and the major histopathological finding was severe NAH. The results after this action were analyzed. RESULTS: We selected 2 groups: good outcome and poor outcome. Eight patients showed good results including stabilization or improvement of graft function. Five patients presented poor results requiring chronic hemodialysis. C4d staining was negative in all biopsy specimens, and peritubular capillaritis was not observed. To identify potential prognostic markers we retrospectively reviewed biopsy samples looking for minor or nonspecific features, especially inflammation scores both global and on fibrotic areas as per Banff classification. Mean serum creatinine level at time of biopsy and mean arteriolar hyalinosis score did not show significant differences between both groups. In contrast, the poor results group presented a higher mean global inflammation score compared with the good results patients. CONCLUSIONS: NAH is not a risk factor for poor renal graft outcome by itself. Other histopathologic findings, usually considered as secondary markers, like the inflammation score, should be considered before deciding CNI withdrawal.

Short-term hybridisation activates Tnt1 and Tto1 Copia retrotransposons in wild tuber-bearing Solanum species.

Interspecific hybridisation in tuber-bearing species of Solanum is a common phenomenon and represents an important source of variability, crucial for adaptation and speciation of potato species. In this regard, the effects of interspecific hybridisation on retrotransposon families present in the genomes, and their consequent effects on generation of genetic variability in wild tuber-bearing Solanum species, are poorly characterised. The aim of this study was to analyse the activity of retrotransposons in inter- and intraspecific hybrids between S. kurtzianum and S. microdontum, obtained by controlled crosses, and the effects on morphological, genetic and epigenetic variability. For genetic and epigenetic analysis, S-SAP (sequence-specific amplification polymorphism) and TMD (transposon methylation display) techniques were used, respectively, with specific primers for Tnt1 and Tto1 retrotransposon families (Order LTR, Superfamily Copia). The results indicate that at morphological level, interspecific hybrid genotypes differ from their parental species, whereas derived intraspecific hybrids do not. In both cases, we observed significant reductions in pollen grain viability, and a negative correlation with Tnt1 mobility. Both retrotransposons, Tto1 and Tnt1, were mobilised in the genotypes analysed, with mobility ranging from 0 to 7.8%. Furthermore, at the epigenetic level, demethylation was detected in the vicinity of Tnt1 and Tto1 in the hybrids compared with the parental genotypes. These patterns were positively correlated with the activity of the retrotransposons. The results suggest a possible mechanism through which hybridisation events generate genetic variability in tuber-bearing species of Solanum through retrotranposon activation.

Gait assessment in Parkinson's disease patients through a network of wearable accelerometers in unsupervised environments.

Parkinson's disease (PD) predominantly alters the motor performance of the affected individuals. In particular, the loss of dopaminergic neurons compromises the speed, the automaticity and fluidity of movements. As the disease evolves, PD patient's motion becomes slower and tremoric and the response to medication fluctuates along the day. In addition, the presence of involuntary movements deteriorates voluntary movement in advanced state of the disease. These changes in the motion can be detected by studying the variation of the signals recorded by accelerometers attached in the limbs and belt of the patients. The analysis of the most significant changes in these signals make possible to build an individualized motor profile of the disease, allowing doctors to personalize the medication intakes and consequently improving the response of the patient to the treatment. Several works have been done in a laboratory and supervised environments providing solid results; this work focused on the design of unsupervised method for the assessment of gait in PD patients. The development of a reliable quantitative tool for long-term monitoring of PD symptoms would allow the accurate detection of the clinical status during the different PD stages and the evaluation of motor complications. Besides, it would be very useful both for routine clinical care as well as for novel therapies testing.

Increased risk for major depression associated with the short allele of the serotonin transporter promoter region (5-HTTLPR-S) and the CYP2C9*3 allele.

In the present study, we aimed to analyze the potential relevance of the polymorphism in the promoter region of the serotonin transporter (SERT or 5-HTT) gene (5-HTTLPR) and the risk of suffering major depression (MDD) in a population of patients previously genotyped for CYP2C9. Seventy white European psychiatric outpatients suffering from MDD and a group of 142 healthy volunteers (HVs) were studied. The frequency of subjects carrying the 5-HTTLPR-S allele was higher (P < 0.05) among MDD than in HV. The odds ratio associated with 5-HTTLPR-S allele was 2.03 for the MDD patients in comparison with the HV group. Previously, we found in this population that the CYP2C9*3 allele frequency was higher among this population of MDD patients than in HV. The frequency of subjects with the combination 5-HTTLPR-S and CYP2C9*3 alleles was higher (P < 0.01, odds ratio 3.47) in MDD than in HV. The present findings provide preliminary evidence about the greater risk of suffering MDD for individuals carrying both 5-HTTLPR-S and CYP2C9*3 alleles.

Relación entre la disfunción temporomandibular y las alteraciones del oído medio. Primeros resultados del tratamiento rehabilitador / Relationship between temporomandibular dysfunction and middle ear disorders. First results of rehabilitation treatment

Introducción. La disfunción tubárica suele determinar una hipoacusia de transmisión o barotraumas por cambios de presión no compensada por la trompa obstruida. Objetivo. Revisar la relación entre la disfunción temporomandibular y las alteraciones del oído medio. Realizar una primera valoración de la eficacia del tratamiento primario de la disfunción temporomandibular y de ejercicios específicos en pacientes con disfunción tubárica. Material y métodos. Estudio prospectivo sobre 14 pacientes bajo el criterio de inclusión de padecer una mala adaptación a los cambios de presión o una hipoacusia de conducción secundaria a una disfunción tubárica. Se estableció un protocolo de tratamiento dirigido no sólo a la disfunción temporomandibular sino también al oído medio y la trompa de Eustaquio. Resultados. Se incluyeron 14 pacientes, 10 mujeres y 4 hombres con una edad media de 37,14 años (R: 13-74). El 92,85 % presentaba un síndrome de disfunción temporomandibular, el 85,71 % hipoacusia de transmisión y el 64,28 % mala adaptación a los cambios de presión. Casi todos los pacientes empezaron el tratamiento con un timpanograma y una audiometría previos, y tras dicho tratamiento se repitieron estas pruebas, mejorando el 71,42 % de los timpanogramas y el 85,75 % de las audiometrías. Subjetivamente se encontraba mejor el 92,85 % de los pacientes. Conclusiones. La mayoría de los pacientes respondió muy bien a los ejercicios específicos, con casos espectaculares desde las primeras sesiones. Mejoraron síntomas como la hipoacusia y la mala adaptación a los cambios de presión. La rehabilitación de la disfunción tubárica es eficaz, sencilla y no necesita de gran aparataje, pero sí de una gran colaboración terapeuta-paciente

Introduction. Tubal dysfunction generally determines transmission hypoacusis or barotraumas due to uncompensated pressure changes by obstructed tube. Objective. Review the relationship between temporomandibular dysfunction and middle ear disorders. Perform a first assessment of primary treatment efficacy of the temporomandibular dysfunction and of specific exercises in patients with tubal dysfunction. Material and methods. Prospective study on 14 patients with the enrollment criterion of suffering poor adaptation to pressure changes or transmission hypoacusis secondary to tubal dysfunction. A treatment protocol aimed not only at temporomandibular dysfunction but also at the middle ear and Eustachian tube was also established. Results. Fourteen patients, 10 women and 4 men with a mean age of 37.14 years (R: 13-74) were enrolled. A total of 92.85 % had temporomandibular dysfunction syndrome, 85.71 % transmission hypoacusis and 64.28 % poor adaptation to pressure changes. Almost all the patients began treatment with a previous tympanogram and audiometry and the tests were repeated after this treatment, 71.42 % of the tympanograms and 85.75 % of the audiometries improving. A total of 92.85 % of the patients felt better subjectively. Conclusions. Most of the patients responded very well to specific exercises, with spectacular cases from the first sessions. Symptoms such as hypoacusis, poor adaptation to pressure changes, etc. improved. Rehabilitation of tubal dysfunction is effective, simple and does not need much equipment but does need great therapist-patient collaboration

Liquen plano vulvar en la infancia / Childhood vuvar lichen planus in children

El liquen plano (LP) es una dermatosis inflamatoria, no infecciosa, que puede afectar a piel, mucosas y anejos. Es infrecuente en niños, sobre todo en las formas de afectación de mucosas. Mientras que la historia natural del liquen plano cutáneo tiende a la remisión espontánea, las lesiones orogenitales y, en particular, la forma erosiva, suelen ser persistentes. La clínica del liquen plano vulvar puede comprender desde casos asintomáticos, hasta pacientes con prurito, gran dolor y quemazón vulvar. Puede autorresolverse, responder al tratamiento o bien progresar hacia una alteración de la estructura genital externa, con formación de sinequias e incluso estenosis vaginal. El tratamiento clásico consiste en la aplicación de corticoides tópicos de elevada potencia, requiriendo los casos complicados tratamientos más agresivos. Recientemente, se ha utilizado el tacrolimus como terapéutica del liquen plano y se han obtenido buenos resultados. Se presenta el caso de una niña prepuberal con liquen plano vulvar

Lichen planus is an noninfectious, inflammatory dermatosis that usually affects the skin, mucosa, hair and nails. It is uncommon in children, in whom mucosal involvement is especially rare. While cutaneous lichen planus eventually resolves spontaneously, the oral and genital lesions, in particular in the erosive form, are usually persistent. Vulvar lichen planus can be asymptomatic or can be accompanied by symptoms ranging from itching to intense pain and burning sensation of the vulvar region. It can resolve without any treatment or respond well to treatment, or its progression may lead to changes in the structure of the external genitalia, with synechia that may cause vaginal narrowing or closure. Highly potent topical corticosteroids are very useful. although complicated cases may require more aggressive treatments. Tacrolimus has recently been used with very good results

Curvature elasticity of mixed amphiphilic bilayers.

Elastic bending constants of mixed amphiphilic bilayers are calculated using a molecular approach. The free energy is expanded up to quadratic order in curvatures and compositions, choosing a flat symmetrical bilayer as the reference state. Bending constants are then calculated from the derivatives of the free energy evaluated at this reference state. Two-component bilayers are considered. As a novelty, the local compositions are allowed to fully relax upon bending so that the 2 monolayers are at chemical equilibrium with each other at every curvature. The compositional degree of freedom is shown to affect the bending constant k, but not the saddle-splay constant k. The influence on the membrane elastic properties of various chain structural features, such as length, volume, and stiffness, is investigated. This may prove useful to model mixed bilayers composed of hydrocarbon/hydrocarbon and hydrocarbon/fluorocarbon chains.

Displasia renal multiquística unilateral y megacaliosis contralateral. Una asociación inusual / Unilateral multicystic dysplastic kidney and contralateral megacalycosis. An unusual association

La dilatación de vías urinarias no siempre es sinónimo de obstrucción. Es conocido que existen malformaciones con aparente hidronefrosis en las que el flujo de la orina no está interrumpido. Por otra parte, con cierta frecuencia, se observa que en un mismo paciente pueden coexistir dos o más malformaciones distintas de vías urinarias. Se presenta un caso clínico en el que coexistían una displasia renal multiquística unilateral y una megacaliosis contralateral, asociada a un megauréter segmentario distal ipsolateral. Esta asociación es inusual en la literatura médica. A pesar de ello, la función glomerular renal es normal y existe, únicamente, un ligero defecto de la capacidad de concentración renal (AU)

[Unilateral multicystic dysplastic kidney and contralateral megacalycosis. An unusual association]. / Displasia renal multiquística unilateral y megacaliosis contralateral. Una asociación inusual.

Dilation of the genitourinary tract is not always synonymous with obstruction. It is well known that malformations with apparent hydronephrosis and normal urinary flow can exist. In addition, two or more distinct malformations of the genitourinary tract can coexist in the same patient. We present a case of coexistence of a unilateral multicystic dysplastic kidney and contralateral megacalycosis associated with ipsilateral distal segmental megaureter. This association is unusual in the literature. Glomerular renal function was normal, with only a slight defect of renal concentration capacity.

Los pies del niño, motivo de consulta en rehabilitación / Foot problems in a children's rehabilitation service

Uno de los motivos más frecuentes de consulta en Rehabilitación infantil es la enfermedad podológica. Las consultas sobre posibles alteraciones de los pies tienen su importancia por el alto número de éstas, por tratarse de niños con padres preocupados, y porque, en ocasiones, son alteraciones secundarias a afecciones neurológicas, infecciosas y traumáticas, entre otras. En la mayoría de los casos, sólo es necesario recomendar un calzado adecuado, sencillas normas posturales y realizar un seguimiento del paciente, por lo que consideramos fundamental el conocimiento del desarrollo evolutivo normal del pie infantil. En menos casos, será precisa la indicación de ejercicios, estiramientos, estimulación, calzados correctores y adaptaciones ortopédicas. Las indicaciones quirúrgicas quedan reducidas a un porcentaje mínimo de los pacientes. En esta revisión intentaremos familiarizarnos con el crecimiento y el desarrollo del pie normal y distinguir las alteraciones más frecuentes observadas en Rehabilitación; por último, se tratarán algunos aspectos del tratamiento de estas alteraciones (AU)

CYP2C9 gene and susceptibility to major depressive disorder.

Alteration of monoaminergic neurotransmission has been implicated in the pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to be modulated by serotonin in vitro. The present study was aimed at analysing the frequency of CYP2C9 alleles (*1, *2, *3) among patients suffering from major depressive disorder. In all, 70 such suffering psychiatric outpatients were studied. The CYP2C9 genotypes were determined by allele-specific PCR. The CYP2C9*3 allele frequency was higher (P<0.01) among the patients suffering from major depression than in a population of 89 schizophrenic patients (odds ratio=3.3) and 138 healthy volunteers (odds ratio=2.8). The results suggest that CYP2C9 genetic polymorphism may be related to a major depressive disorder due to an alteration in endogenous metabolism, although a linkage between CYP2C9 and some other gene related to depression cannot be ruled out.

Enfermedad de Duchenne: tratamiento rehabilitador / Rehabilitation in Duchenne muscular dystrophy: a review

Mediante el presente trabajo realizamos una revisión actualizada de la enfermedad de Duchenne, dando especial relevancia al tratamiento rehabilitador. La enfermedad de Duchenne es la distrofia muscular más frecuente, con una incidencia del orden de 10 a 30 casos/100.000 habitantes. Se transmite de forma recesiva ligada al cromosoma X, y afecta a los hombres, pero es transmitida por las mujeres. La patogénesis no está clara y la sintomatología se inicia generalmente antes de los 2-3 años. Las manifestaciones clínicas más frecuentes son: la seudohipertrofia de pantorrillas, “marcha de pato” o en Trendelenburg, la dificultad para levantarse del suelo o de una silla, la hiperlordosis y el abdomen prominente, la cifoscoliosis, el desequilibrio entre grupos musculares agonistas y antagonistas, la deficiencia mental leve y las fracturas fáciles. Suele existir un retraso en el control del tronco en la bipedestación y la deambulación. Cuando el paciente logra la deambulación, lo hace con dificultad y caídas frecuentes; pierde la capacidad de deambulación a los 10-15 años, por lo que debe utilizar una silla de ruedas. Generalmente, estos pacientes fallecen antes de los 25 años por insuficiencia cardiorrespiratoria. El diagnóstico se establece después de la sospecha clínica mediante analítica, electromiografía y biopsia. El tratamiento rehabilitador es la única alternativa terapeútica para el “paciente Duchenne”, y se basa en una cinesiterapia general y específica respiratoria, balneoterapia, tratamiento ortopédico, terapia ocupacional e integración escolar (AU)

We present an update on Duchenne muscular dystrophy, focusing especially on rehabilitación therapy. This disease is the most common type of muscular dystrophy, with an incidence ranging from 10 to 30 cases per 100,000 population. It is an X-linked recessive disorder that is transmitted to male children by their mothers. The pathogenesis is unclear and the symptoms generally appear between the ages of 2 and 3 years. The most common clinical signs are calf pseudohypertrophy, duck gait or Trendelemburg, difficulty in rising from the floor or chair, hyperlordosis and prominent abdomen, kyphoscoliosis, imbalance between agonist and antagonist muscle groups, mild mental retardation and easy fractures. There is usually delayed trunk control on standing and walking. Walking, when achieved, is difficult and falls are frequent; the ability to walk is lost between the ages of 10 and 15 years, after which the child requires a wheelchair. These patients usually die before the age of 25 years due to cardiorespiratory failure. When clinically suspected, the diagnosis is established on the basis of laboratory analyses, electromyography and biopsy. Rehabilitation, the only therapeutic alternative for Duchenne patients, involves general kinesiotherapy, respiratory therapy, hydrotherapy, orthopedic treatment, occupational therapy and integration into school life (AU)

Carolina rinse attenuates postischemic microvascular injury in rat small bowel isografts.

BACKGROUND: Apart from rejection-related events, the manifestation of ischemia/reperfusion (I/R) injury remains a major problem, hampering success in human small bowel transplantation (SBTx). Therefore the aim of this study was to determine the potential of Carolina rinse (CR) to attenuate microvascular reperfusion injury in rat intestinal isografts. METHODS: After 18 hours of cold preservation in 4 degrees C University of Wisconsin solution (UW), rat SBTx was performed. Immediately before reperfusion the intestine was flushed with 4 degrees C or 37 degrees C Ringer's lactate (RL, groups 1 and 2) or CR (groups 3 and 4), respectively. In vivo fluorescence microscopy was used to analyze the grafts' microcirculation. RESULTS: In group 1 severe microvascular I/R injury was observed in mucosa and muscle layers. Microcirculatory deterioration was paralleled by enhanced leukocyte accumulation in submucosal venules and by impaired subserosal lymphatic capillary drainage (FCLD). Rinsing the grafts with 37 degrees C RL attenuated leukocyte-endothelial cell interaction and improved subserosal FCLD; however, it did not affect mucosal microvascular reperfusion damage. In contrast, 4 degrees C CR dramatically improved nutritive perfusion within muscle and mucosa (p < 0.05) and attenuated leukocyte adherence within submucosal venules (p < 0.05). Additional prewarming of CR almost completely prevented mucosal I/R injury (p < 0.05 versus group 3) and caused a fourfold increase of FCLD. CONCLUSIONS. With this study we demonstrate that CR in combination with rewarming of the graft before reperfusion is an effective regimen to prevent leukocyte accumulation and to counteract microvascular injury after SBTx.

In vivo assessment of the influence of cold preservation time on microvascular reperfusion injury after experimental small bowel transplantation.

BACKGROUND: This study describes the impact of prolonged cold storage on microvascular reperfusion injury of transplanted rat small bowel isografts. METHODS: In vivo fluorescence microscopy was used to assess intestinal microcirculation after 6, 12, 18 and 24 h of cold (4 degrees C) ischaemia in University of Wisconsin solution and 20-90 min of reperfusion. Sham-operated animals served as controls. RESULTS: Whereas 6 and 12 h of ischaemia did not affect functional capillary density of the intestinal graft mucosa, villous perfusion was significantly impaired after 18 and 24 h of cold preservation. Similarly, microvascular perfusion of circular and longitudinal muscle was not affected after 6 h, but deteriorated following prolonged cold ischaemia. Leucocyte-endothelial cell interaction in submucosal venules was significantly enhanced after 6 h of ischaemia with peak values after 12 and 18 h. A progressive reduction of lymphatic capillary drainage indicated an ischaemia time-related deterioration in graft function. CONCLUSION: The results provide evidence that leucocyte-endothelial cell interaction in submucosal venules of the transplanted intestine is a primary step in the manifestation of reperfusion injury following short periods of cold ischaemia.