Relationship between CDC cross-match in liver recipients and antibody screening by flow cytometry

Several authors have shown that anti-donor antibodies before liver transplantation are associated with decreased graft survival. The aim of this study was to investigate the relationship between anti-donor antibodies detected by the CDC technique or by FlowPRA, and acute or chronic rejection as well as graft survival. Furthermore, we sought to determine whether anti-donor antibodies, detected by the CDC technique, correlated with those discovered by cytometric screening. The acute rejection incidence among patients with complement-dependent cytotoxicity positive CDC cross-match was similar to that for patients with a negative cross-match. None of the patients with a positive cross-match developed chronic rejection. Allograft survival was significantly lower among recipients with a positive T-lymphocyte cross-match. Indeed, the majority of recipients with positive CDC cross-matches displayed graft failures before first posttransplant year. The results of a positive FlowPRA determination were concordant with a positive CDC cross-match in 85.71% of cases. Our data demonstrate that pretransplant FlowPRA correlates with the final CDC cross-match results. This finding suggests that in the future prospective pretransplant antibody screening with FlowPRA or CDC techniques may be useful to identify high-risk recipients.     

Multiparametric monitoring of ischemia-reperfusion in rat kidney: effect of ischemic preconditioning

BACKGROUND: Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could be appraised by real-time measurement of parameters representative of tissue hypoxia. METHODS: In a sample of pentobarbital-anesthetized and mechanically ventilated rats, we studied the effect of renal ischemic preconditioning (10-min ischemia and 10-min reflow interval) on subsequent ischemia-reperfusion (45 min and 60 min). Renal tissue electrical impedance, extracellular pH, and potassium concentration [K+] were measured continuously by implanted microelectrodes. RESULTS: Ischemia induced an early, rapid rise in extracellular potassium and impedance module, followed by a phase of slower increase, whereas pH decreased rapidly, reaching a plateau. Preconditioning treatment did not cause significant changes in interstitial pH and [K+] but increased ischemic tissue impedance. During reperfusion, the three variables recovered progressively; however, after a decline, electrical impedance showed a clear postischemic increase. This rise was suppressed by preconditioning. CONCLUSIONS: Real-time measurement of any of the three parameters showed capability for early detection of ischemia. In contrast with findings in myocardial tissue, preconditioning in the kidney did not increase potassium cell loss during ischemia or improve ischemic acidosis or tissue impedance. Electrical impedance increased for a second time during reperfusion, indicating the presence of a postischemic cellular edema; concealing this episode was the most noticeable effect of the preconditioning treatment.     

The mosaicplasty technique for osteochondral lesions of the talus

For years, OCD of the talus has been known as a symptomatic lesion that causes pain, recurrent synovitis, altered joint mechanism, and obstruction from loose bodies. It is a probable precursor of ankle osteoarthritis because of altered joint mechanics and recurrent synovitis. With the notable advance of diagnostic imaging and the advent of ankle arthroscopy, classification of the lesion has become standardized, which allowed for the comparison of treatment options. Arthroscopic procedures (eg, debridement, retrograde drilling, bone grafting, by nature of their minimally invasive approach, have a great advantage in treating small defects and stable OCD lesions compared with open methods. For larger osteochondral defects and unstable OCD lesions, the optimal treatment is the long-term replacement and integration of type-specific hyaline cartilage. In principle, mosaicplasty autogenous osteochondral transplantation fills these criteria. The early- and medium-term results are encouraging, complete with confirmatory radiographs and histology, and hold promise for this procedure to provide lasting relief of symptoms and the prevention of ankle arthrosis. Under the current dichotomy of nonoperative and operative treatments giving satisfactory results, and few comparative studies, there is a need for a randomized, prospective study in the treatment of talar OCD to define a reproducible treatment algorithm.     

Hydroxytyrosol increases norepinephrine transporter function in pheochromocytoma cells

INTRODUCTION: The norepinephrine transporter is responsible for the intracellular uptake of (131)I- iodometaiodobenzylguanidine ((131)I-MIBG), which is used for the diagnostic localization and treatment of pheochromocytomas as well as other tumors such as neuroblastomas and carcinoids. This agent is variably delivered into tumor cells by the norepinephrine transporter, but few studies have shown treatments that work to increase norepinephrine transporter activity. The objective of the present study was to test the possible beneficial effects of hydroxytyrosol in enhancing norepinephrine transporter function, which may have implications for its combined use with (131)I-MIBG in the diagnosis and treatment of pheochromocytomas. METHODS: Rat pheochromocytoma PC12 cells were labeled with [(3)H]-norepinephrine in the presence or absence of different concentrations of hydroxytyrosol, a naturally occurring compound with strong antioxidant properties, followed by measurements of uptake and release of radiolabeled norepinephrine. RESULTS: Hydroxytyrosol pronouncedly increased norepinephrine transporter activity, with the rapid onset excluding effects on norepinephrine transporter expression levels. Concomitant with increased norepinephrine transporter activity, hydroxytyrosol caused a decrease of both spontaneous and evoked norepinephrine release, indicating that it affects pre-existing plasma membrane-associated norepinephrine transporter, rather than the incorporation of novel norepinephrine transporter molecules into the plasma membrane. CONCLUSION: Hydroxytyrosol potently enhances norepinephrine transporter activity in pheochromocytoma PC12 cells, suggesting that combinatorial therapy employing hydroxytyrosol may improve the effectiveness of (131)I-MIBG as a diagnosis and treatment modality.     

<Superscript>99m</Superscript>Tc-HYNIC octreotide in neuroblastoma

Disease status assessment of neuroblastoma patients requires computed tomography (or magnetic resonance imaging), bone scan, metaiodobenzylguanidine (MIBG) scan, bone marrow tests, and urine catecholamine measurements. There is no clinical experience concerning the evaluation of these patients by means of technetium-99m (^99mTc)-somatostatin analog scintigraphy. Furthermore, these radiopharmaceuticals are promising imaging agents owing to their lower cost, availability, dosimetry, and ease of preparation. An 8-year-old boy already diagnosed with stage-IV neuroblastoma received chemotherapy. In the follow-up, after obtaining the parents’ informed consent, iodin 131 (¹³¹I)-MIBG and ^99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-octreotide scans were done on separate days to evaluate tumor extension. Even as the ¹³¹I-IBG scan showed mild diffuse uptake in the projection of both lung hili, the ^99mTc-HYNIC-octreotide scan showed multiple axial and appendicular bone uptakes and paravertebral, abdominal, mediastinal, and supraclavicular ganglionar uptakes. The ^99mTc-HYNIC-octreotide showed much more lesion extension than the ¹³¹I-MIBG. Therefore, ^99mTc-HYNIC-octreotide may be a promising radiopharmaceutical for the evaluation of neuroblastoma patients. This finding justifies the pre liminary evaluation of this tracer in the context of a clinical trial.     

The effect of vertebral fracture as a risk factor for osteoporotic fracture and mortality in a Spanish population

There is little data concerning the morbidity, mortality, and epidemiology of vertebral fracture. The aim of this study was to evaluate the effect of prevalent and incident vertebral fractures as risk factors for further osteoporotic fractures and mortality. The study was performed on a cohort of 316 women and 308 men older than 50 belonging to the EVOS study, randomly selected from our city register. At the beginning of the study and 4 years later, lateral dorsal and lumbar X-rays were performed. In addition, evaluation of the incidence of osteoporotic nonvertebral fractures was performed throughout 8 years. The incidence of all osteoporotic fractures was higher in women than in men (two-fold increase in vertebral fracture incidence and five-fold increase in Colles' and femur incidence). Vertebral fracture was a strong risk factor for a new vertebral fracture [RR=4.7 (1.8-11.9)], hip fracture [RR=6.7 (2.0-22.7)] and Colles' fracture [RR=3.0 (1.1-7.8)]. Prevalent and incident vertebral fractures were associated with a higher risk of having a hip fracture [RR=10.0 (2.0-50.2)] and Colles' fracture [RR=5.5 (1.3-23.4)]. In addition, in women, the vertebral fracture was associated with a higher mortality. By contrast, no association was found in men. These results demonstrate the association between a previous vertebral fracture with increments in the incidence of osteoporotic fractures of any type. In addition, we found a significantly higher mortality rate in women having vertebral fractures. These findings support the necessity of preventing the occurrence of vertebral fractures to limit their strong negative impact on mortality.     

Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer

OBJECTIVE: To confirm the very high male:female ratios previously observed among Spanish bladder cancer patients and to assess gender differences in tumoral characteristics, diagnostic procedures, and treatment in a large series of consecutive bladder cancer patients. PATIENTS AND METHODS: All newly diagnosed bladder cancer patients (n=615) in 17 Spanish hospitals, between 1997-2000, were included. Information was collected both through personal interviews to patients and from medical records using a structured form. RESULTS: Seventy-six percent of tumours were superficial. The male:female ratio was 6.7 and it was similar for superficial and infiltrating tumours. Women were older than men at the diagnosis of bladder cancer (68.2+/-9.4 years versus 65.7+/-9.7 years, p=0.01). Ten percent of superficial tumours in women, versus 3% in men, were classified as "other histological types" (p=0.008). T1GIII tumours were more frequent among men (17% versus 7%, p=0.047). On the other hand, women were more likely to present with 0a-stage tumours (48.6% versus 35.5%, p=0.04), multiple tumours (50% versus 29%, trend test: 0.005), multi-centric tumours (54% versus 38%, p=0.019), and larger infiltrating masses (5.2 cm versus 3.8 cm, p=0.03) than men. Among 0a-stage tumours, only 23% of women compared to 54% of men received transurethral resection (TUR) alone (p=0.002). Women were almost five-fold more likely to receive additional therapies to TUR (p=0.004) after adjusting for age, geographical area, stage, tumoral size, nuclear grade, and multiplicity. CONCLUSION: The study confirms the very high male:female ratio of bladder cancer in Spain. We found substantial differences in the pathological characteristics of tumours from men and women. There was a tendency for women to receive more frequently non-standard, more aggressive, therapy than men.     

Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study

Background/purpose

Endoscopic variceal ligation (EVL) is effective in controlling rebleeding from esophageal varices in children, but there is no data on the use of EVL to prevent initial bleeding. The objective of this study was to prospectively evaluate the efficacy of EVL in preventing the first hemorrhage from esophageal varices in children.

Methods

Thirty-seven children with portal hypertension (22 liver cirrhosis, 15 portal vein thrombosis), aged 4 to 17 years (M = 9.5 ± 4.4 years) were included in the study. The criteria for inclusion were (1) no previous variceal bleeding; (2) the presence of esophageal varices classified grade II or more, and (3) their enlargement by at least I grade after 6 months of observation without endoscopic treatment or appearance of endoscopic signs of high bleeding risk. A Multi-Band Ligator was used, and 2 to 6 bands were fixed under general anesthesia during one procedure depending on the number and size of varices. Follow-up examinations were performed every 3 months, repeating the procedure if necessary. In total, 75 procedures of EVL were performed, from one to 5 in each patient

Results

Four patients underwent liver transplantation before eradication of varices. Two others were excluded from the observation because of lack of compliance to the protocol. Of the remaining 31 patients, eradication of varices was achieved in 28 children (90.3%) after 2.0 EVL sessions performed at 3-month intervals. The average time of follow-up after cessation of treatment is 16 months. No bleeding from varices occurred in any child during or after treatment. There were no differences in results between children with liver cirrhosis and portal vein thrombosis. Development of hypertensive gastropathy was observed in 2 children with one episode of bleeding. Recurrence of varices without bleeding occurred in 3 children after 12, 13, and 28 months from eradication.

Conclusions

The study results confirmed that endoscopic variceal ligation is a safe and highly effective procedure in children with portal hypertension, regardless of its etiology. Eradication of esophageal varices was followed by 16 months free of bleeding. Prolonged observation is mandatory to conclude if preventive EVL influences the natural history of disease and diminishes the risk of first bleeding onset.     

First orthotopic liver transplantation in patient with biliary atresia and situs inversus in spain

Biliary atresia is the most common indication for liver transplantation in the pediatric age group. The Kasai portoenterostomy has become established as the primary treatment for biliary atresia. If portoenterostomy fails, death before 2 years of age is likely without liver transplantation. The most common multiple malformation syndrome associated with biliary atresia is polysplenia syndrome, which forms a constellation of defects of body symmetry, splenic development and vascular anomalies, including situs inversus, polysplenia and others. The situs inversus was formerly considered an absolute contraindication for liver transplantation. Recently however, several case reports have been published suggesting that neither situs inversus nor this particular subset of vascular abnormalities should be considered contraindications to liver transplantation. We present one case of liver transplantation performed in patient with biliary atresia, situs inversus and polysplenia. This is the first report described in Spain for a liver transplant in a child with biliary atresia plus situs inversus.     

Valoration of the FAS in the contralateral testis after unilateral testicular torsion. Experimental study in rats

The role the FAS and BCL-2 in the apoptosis of testicular cells in the contralateral testis after unilateral testicular torsion, was investigated. We compared with control group. These experiments were performed in male Wistar rats prepuberal old. FAS and BCL-2 determination is realized in cells cultures of contralateral testis. Flow cytometry and immunohistochemistry studies, using a FAS and BCL-2 specific monoclonal antibody, were utilized to value FAS y BCL-2 expression on testiculaires cells following unilateral testicular torsion. We observed an increase of expression of FAS and decrease of BCL-2 in the contralateral testis in comparison with control group. The present results may indicate that the expression of this molecules is implicated in cellular apoptosis.