Effects of enteral nutrition on patients with pressure lesions: a single center, pilot study.

OBJECTIVE: Protein-energetic malnutrition (PEM) affects prognosis and mortality in elderly patients as an inadequate nutritional status is a risk factor for the development and worsening of pressure sores (PS). We aimed to evaluate the incidence of PEM in outpatients with PS and to study the impact of nutritional support on the stage of PS. PATIENTS AND METHODS: PS patients, divided in a group treated with artificial nutrition (group A) and those fed orally (group B) at home, were consecutively enrolled in the Integrated Home Care program of Ascoli Piceno between June and September 2015. At T0 the patients underwent medical history, nutritional, anthropometric/biochemical parameters assessment, and the staging of the PS. The same assessments and staging of the pressure lesions were performed three months later (T1). RESULTS: Group A (n=25) started from a better nutritional status vs. group B (n=25) at T0, according to MNA assessment. Group A showed a significant improvement of nutritional status correlating with detailed control of nutrients intake and improvement of PS stage (T0 vs. T1, p<0.05). On the other hand, group B showed a significant difference between nutrients intake and nutritional needs that correlated with both malnutrition state increase and worsening of the PS staging (T0 vs. T1, p<0.05). CONCLUSIONS: The present study shows that PEM has a significant prevalence in the elder, in general, and in older people with PS, in particular. A targeted nutritional intake can prevent and help the healing of PS.

Impact of patients nutritional status on major surgery outcome.

OBJECTIVE: Surgery is a major stress factor that activates several inflammatory and catabolic pathways in man. An appropriate nutritional status allows the body to react properly to this stressor and recover in a faster and more efficient manner. On the other hand, malnutrition is related to a worse surgery outcome and to a higher prevalence of comorbidities and mortality. The aims of this study were to evaluate the nutritional status of patients undergoing major surgery and investigate the potential correlation between malnutrition and surgical outcomes. PATIENTS AND METHODS: Mini Nutritional Assessment (MNA) and global clinical examination (including biochemical parameters and comorbidities existence) were undertaken in 50 consecutive patients undergoing major surgery. Patients' clinical conditions were re-evaluated at 3 and 6 days after surgery, recording biochemical parameters and systemic and/or wound-related complications. RESULTS: A compromised nutritional status was present in more than half (54%) of patients (malnutrition in 10% and risk of malnutrition in 44% of patients, respectively). Females were slightly more at risk of malnutrition (48% vs. 41%, p=NS, females vs. males) and clearly malnourished (14% vs. 7%, p<0.05, females vs. males). Age was an independent risk factor for malnutrition and within the elders' group (> 80 years old) 16.70% of patients was diagnosed with malnutrition and 58.3% was at risk of malnutrition. Systemic complications were registered in all patients both at 3 and 6 days after surgery. However, well-nourished and at-risk of malnutrition patients had earlier complications that only partially resolved within six days after the operation. Malnourished patients showed fewer complications at the 3rd post-surgery follow-up day but had a worse outcome six days after surgery. CONCLUSIONS: Older age and but not female sex are independent risk factors for malnutrition development in patients undergoing major surgery. More interestingly, more than half of patients with an impaired nutritional status presented a less appropriated stress response to surgery. These data suggest that nutritional status assessment may be important to recognize patients at potential risk of surgical complications and that early nutritional interventions must be promptly arranged.

Liver Graft Allocation by Means of a New, Regionally Shared "Mixed" Model: The Experience in Lazio.

INTRODUCTION: Since 2013, the regional network of transplantation centers "LAZIO TRANSPLANT" have adopted a new, mixed system for the allocation of liver grafts. METHODS: The organs from donors aged <65 are assigned to patients with higher Model for End-stage Liver Disease (MELD) scores on a common regional waiting list, whereas those from donors aged >65 are allocated to patients with higher MELD scores on a specific local waiting list (LWL) at each center, on a rotational basis. RESULTS: The new mixed allocation model grants a more rational allocation of the "standard" organs to the patients with the actual worst MELD score in the entire region, avoiding the possibility that a patient in relatively better clinical condition might be transplanted before a more severely ill patient on another center's waiting list. Nonstandard organs, presenting slightly increased transplant risks, are still allocated on a rotational basis among the different transplant centers, ensuring them the possibility to select, on the basis of a global clinical risk evaluation, those patients in their LWL whose MELD score would not grant any possibility to compete for the "standard" organ allocation. CONCLUSIONS: The application of the new model had no negative impact on the overall number of transplants performed or on the global list-satisfaction percentages, but has slightly improved the cumulative mortality of the patients in the waiting list, granting to the clinically worst patients a prompt graft allocation, independent of the local center belonging.

Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism.

Recent evidence indicates a greater frequency of primary aldosteronism (PA) among patients with hypertension than the previously accepted prevalence. PA was once considered a relatively benign form of hypertension associated with low incidence of organ complications. Recent views, however, suggest that long-term exposure to increased aldosterone levels might result in cardiovascular, renal, and metabolic sequelae that occur independently of the blood pressure level. Cross-sectional comparisons with patients with essential hypertension have demonstrated that patients with PA are at higher risk of cardiovascular events, have more frequent left ventricular hypertrophy and diastolic dysfunction, have greater urinary albumin losses as a marker of a hemodynamic intrarenal adaptation, and are insulin resistant. Some of these findings have been corroborated by the results of short-term, follow-up studies where it was shown that unilateral adrenalectomy or treatment with mineralocorticoid receptor (MR) antagonists are effective in correcting hypertension and hypokalemia. Normalization of blood pressure and correction of hypokalemia, however, are not the only goals in managing PA and effective prevention of organ complications is mandatory in these patients. The relative efficacy of adrenalectomy and MR antagonists, in the long-term, on the cardiovascular, renal, and metabolic outcomes still needs evaluation, being the aldosterone-induced tissue damage the main factor that could justify the cost of increasing efforts in screening of disease and differentiation of subtypes. In this narrative review, we summarize the results obtained with either surgical or medical treatment of PA and outline the findings of long-term, prospective studies on the effects of treatment on cardiovascular and renal outcomes and on insulin sensitivity.

The inner jet of an active galactic nucleus as revealed by a radio-to-gamma-ray outburst.

Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV gamma-ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images.

Hypercholesterolaemia alters the responses of the plasma lipid profile and inflammatory markers to supplementation of the diet with n-3 polyunsaturated fatty acids from fish oil.

BACKGROUND: The influence of supplementing the diet with long-chain n-3 polyunsaturated fatty acids (PUFA) from fish oil on plasma lipids and lipid peroxides and the production of pro-inflammatory mediators in normolipidaemic and hypercholesterolaemic rats were studied. MATERIALS AND METHODS: Rats were divided into four groups and fed one of the following diets: a control diet (containing 4% corn oil); an n-3 PUFA diet [containing 4% eicospentaenoic (EPA) + docosahexaenoic (DHA)]; a hypercholesterolaemic diet (HCH); or a HCH + n-3 PUFA diet over a 4-week period. Plasma lipids, lipid peroxides, cytokines [tumour necrosis factor (TNF)alpha, interleukin (IL)-6, interferon (IFN)gamma] and mRNA for hepatic nuclear factor-4alpha (HNF4alpha) were determined. RESULTS: Plasma triglyceride (TG), but not cholesterol, levels were decreased by the n-3 PUFA as compared with the control diet (P < 0.001), but the addition of n-3 PUFA to the HCH diet decreased both the TG (P < 0.01) and cholesterol (P < 0.05) concentrations. Plasma lipid peroxides and expression HNF4alpha mRNA were increased by n-3 PUFA in the normolipidaemic (P < 0.05), but not in the hyperlipidaemic rats. Compared with the control diet group, plasma concentrations of TNFalpha and IL-6 were increased in the n-3 PUFA (P < 0.05) and HCH diet (P < 0.05, P < 0.01, respectively) groups, but not in animals given the HCH + n-3 PUFA diet, whereas IFNgamma levels were increased in hypercholesterolaemia (P < 0.05), but were unaffected by n-3 PUFA. CONCLUSION: These results demonstrate that the major effect of fish oil n-3 PUFA is to lower the TG levels in both normo- and hyperlipidaemia. Furthermore, in the hypercholesterolaemic state, fish oil n-3 PUFA induces additional beneficial changes in the immune and peroxidation responses.

Adoções, esperas, desejos, realidades... o que dizem os números: levantamento para pesquisa

O artigo apresenta levantamento de dados sobre adoção, adotantes, adotados, crianças ou adolescentes no aguardo de adoção, e pretendentes, relativo a período de quatro meses em uma das Varas da Infância e da Juventude de São Paulo. A população estudada constituiu-se de 133 crianças e adolescentes, 44 adotantes e 190 pretendentes. Conclui-se que, embora a preferência seja por meninas, os meninos foram maioria nas adoções e na espera. No tocante à cor, houve maior número de crianças pardas adotadas porque são maioria em nossa população e não porque preferidas. Apesar de o pedido ser por criança saudável, constatou-se proporção significativa de adotados com problemas de saúde, bastante próxima da proporção geral existente. Com relação à idade, a realidade das crianças e adolescentes é inversamente proporcional ao desejo dos pretendentes e, por essa razão, crianças e adolescentes juridicamente adotáveis e pessoas cadastradas esperam tanto. Para 95 porcento das preferências por crianças menores de três anos, tem-se 5 porcento apenas de crianças aguardando por adoção (AU)

[Atherogenic lipid profile in children with subclinical hypothyroidism]. / Perfil lipídico aterogénico en niños con hipotiroidismo subclínico.

OBJECTIVE: To evaluate lipid profile in children with subclinical hypothyroidism. PATIENTS AND METHODS: Forty-six children of both sexes aged between 2 and 9 years old, 17 with subclinical hypothyroidism (study group) and 23 healthy children (control group), were studied. Subclinical hypothyroidism was diagnosed when levels of thyroid-stimulating hormone (TSH) were greater than 4.65 .U/mL and those of free thyroxin (fT4) were normal. Children with subclinical hypothyroidism were observed for 4 months with no interventions and TSH and fT4 were again determined to confirm the diagnosis. A complete medical history was taken and a blood sample was extracted for lipid determinations including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Anti-thyroglobulin antibodies (ATGA) and antithyroid peroxidase (anti-TPO) antibodies were also determined. RESULTS: Of the 17 children who initially presented elevated serum TSH levels, seven (41.2 %) had normal levels at 4 months and were consequently excluded. No significant differences were found in age, weight, height or body mass index between the study and the control groups. No differences were found between the two groups in levels of anti-TPO antibodies and ATGA. The mean plasma HDL-C level was significantly lower in children with subclinical hypothyroidism than in controls (p < 0.05) and a statistically significant association (p < 0.013) was found between the presence of subclinical hypothyroidism and a greater frequency of low HDL-C levels. CONCLUSION: Subclinical hypothyroidism may be transitory in a considerable percentage of children. Children with subclinical hypothyroidism had significantly lower HDL-C levels, suggesting an atherogenic lipid profile in this entity.

Perfil lipídico aterogénico en niños con hipotiroidismo subclínico / Atherogenic lipid profile in children with subclinical hypothyroidism

Objetivo: Evaluar el perfil lipídico en niños con hipotiroidismo subclínico. Pacientes y métodos: Se estudiaron 46 niños de ambos sexos, en edades comprendidas entre 2 y 9 años, 17 con hipotiroidismo subclínico (grupo de estudio) y 23 niños sanos (grupo control). El hipotiroidismo subclínico se diagnosticó cuando los niveles de tirotropina (TSH) fueron mayores de 4,65 mU/ml y los de tiroxina libre (T4L) fueron normales. Los niños con hipotiroidismo subclínico se observaron por 4 meses sin intervención alguna y se les tomó nueva muestra para TSH y T4L con el objeto de corroborar el diagnóstico. Se les realizó una historia clínica completa y se les tomó muestra de sangre para lipidograma, que incluyó triglicéridos, colesterol total (CT), colesterol unido a las lipoproteínas de alta densidad (c-HDL) y el cálculo del colesterol unido a las lipoproteínas de baja densidad (c-LDL); además se determinaron los anticuerpos antitiroglobulina (anti-TG) y antiperoxidasa (anti-TPO). Resultados: De los 17 niños que presentaron niveles séricos elevados de TSH al inicio, 7 (41,2 %) los normalizaron a los 4 meses, por lo que fueron excluidos. No se apreciaron diferencias significativas en cuanto a la edad, peso, talla e índice de masa corporal entre el grupo de estudio y el control. Los niveles de anticuerpos anti-TPO y anti-TG no fueron diferentes entre los grupos. El nivel plasmático promedio de c-HDL fue significativamente más bajo en los niños con hipotiroidismo subclínico que en los controles (p < 0,05) y se observó una asociación estadística significativa (p < 0,013) entre la presencia de este proceso y la mayor frecuencia de niveles bajos de c-HDL. Conclusión: El hipotiroidismo subclínico puede ser una condición transitoria en un porcentaje importante de niños. Los niños con hipotiroidismo subclínico presentan una disminución significativa en los niveles de c-HDL, lo cual sugiere un patrón lipídico aterogénico en esta entidad

Objective: To evaluate lipid profile in children with subclinical hypothyroidism. Patients and methods: Forty-six children of both sexes aged between 2 and 9 years old, 17 with subclinical hypothyroidism (study group) and 23 healthy children (control group), were studied. Subclinical hypothyroidism was diagnosed when levels of thyroid-stimulating hormone (TSH) were greater than 4.65 mU/mL and those of free thyroxin (fT4) were normal. Children with subclinical hypothyroidism were observed for 4 months with no interventions and TSH and fT4 were again determined to confirm the diagnosis. A complete medical history was taken and a blood sample was extracted for lipid determinations including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Anti-thyroglobulin antibodies (ATGA) and antithyroid peroxidase (anti-TPO) antibodies were also determined. Results: Of the 17 children who initially presented elevated serum TSH levels, seven (41.2 %) had normal levels at 4 months and were consequently excluded. No significant differences were found in age, weight, height or body mass index between the study and the control groups. No differences were found between the two groups in levels of anti-TPO antibodies and ATGA. The mean plasma HDL-C level was significantly lower in children with subclinical hypothyroidism than in controls (p < 0.05) and a statistically significant association (p < 0.013) was found between the presence of subclinical hypothyroidism and a greater frequency of low HDL-C levels. Conclusion: Subclinical hypothyroidism may be transitory in a considerable percentage of children. Children with subclinical hypothyroidism had significantly lower HDL-C levels, suggesting an atherogenic lipid profile in this entity

Frecuencia de obesidad y sobrepeso en escolares de la zona urbana de Mérida-Venezuela

Objetivos. Determinar la frecuencia de alteraciones en el peso en escolares de 3 planteles públicos, ubicados en la zona urbana de la ciudad de Mérida-Venezuela. Métodos. Estudio observacional, transversal, en el cual se incluyeron 349 escolares, con edades entre 6 y 13 años, 189 de sexo femenino y 160 de sexo masculino, provenientes de 3 planteles públicos, ubicados en la Urb. J.J. Osuna Rodríguez y la Parroquia, de la Ciudad de Mérida; 127 niños del plantel A (Los Curos), 111 del B (Bicentenario) y 111 del C (10 de Diciembre). A los niños se les determinó el peso y la talla y se calculó el índice de masa corporal (IMC) y el indicador talla edad (T/E). Según el IMC, se ubicó cada niño en el percentil correspondiente para sexo y edad; se clasificaron en: obesos: IMC > percentil 97th, sobrepeso: IMC <97th y > 90th, normopeso: IMC< 90th y >10th y bajo peso: IMC < 10th. El diagnostico nutricional antropométrico se hizo por combinación de los indicadores IMC y T/E. Resultados. El 35% del total de niños presentó alteraciones del IMC para su edad; el sobrepeso representó el 11%, la obesidad el 14% y el bajo peso el 10% del total. En cada plantel no se observó la misma distribución. La frecuencia de alteraciones en el IMC fue significativamente menor (p<0,01) en las niñas (26%) que en los varones (42%). Esta diferencia se correspondió con un aumento significativo en la frecuencia de obesidad y sobrepeso en los varones. En el 26,4% hubo alteraciones en la talla-edad, siendo mas frecuentes en los varones que en las niñas. Los niños con obesidad y sobrepeso presentaron una mayor frecuencia de talla alta (p<0,05) que los normales. En base al diagnostico nutricional antropométrico el 8,8% de los niños presentaron peso y talla bajos. Conclusiones. Las cifras obtenidas documentan un importante aumento en la frecuencia de obesidad y sobrepeso en nuestros escolares. Las potenciales consecuencias en términos de morbilidad y mortalidad nos obligan a mejorar las estrategias en prevención primaria y secundaria, no solo promoviendo el ejercicio y optimizando la alimentación de nuestros niños, sino además, identificando a los grupos de riesgo.

Objective. To assess the frequency of weight problems in school-children from educational centers of Mérida-Venezuela. Methods. An observational and transversal study was performed. Three hundred forty nine school-children, 6 to 12 years old, 160 boys and 189 girls, were studied. They belong to three educational centers from Mérida; 127 children from the school A (Los Curos), 111 from the school B (Bicentenario), and 111 from the school C (10 de Diciembre). The weight and stature were measured in all children. Body mass index-for age (BMI/A) and stature-for age (S/A) were established: obese (BMI ³ 97thpercentile), overweight (BMI <97th and > 90th), normal weight (BMI £ 90th and ³10th), and low weight (BMI< 10th). The nutritional evaluation was done by the combination of 2 indexes: BMI-for age (BMI/A) and stature-for age (S/A). Results. BMI-for age abnormal values were obtained in 35% of the 349 school-children; overweight was diagnosed in 11% of them, 14% were obese and low weight was found in 10% of the sample. There was a significative difference in the BMI/A related to the sex: alterations were observed in the 26% of girls and 42% of boys (p<0,01). The difference was attributed to a higher frequency of obesity and overweight in boys. The overall frequency of alterations in the S/A index was 26.4%, and it was more frequent in boys than in girls. The school-children with obesity and overweight showed a higher frequency of high stature compared to normal weight subjects (p<0,05). According to the nutrition evaluation, 8.8% of these school-children showed low weight and height. Conclusion. Our results reveal a substantial increase in frequency of obesity and overweight in children from educational centers in Mérida city-Venezuela. The potential consequences in terms of morbidity and mortality, should be taking in consideration in order to develop secure and preventive strategies. Individuals at risk should be identified. Promoting regular physical activities in childhood and improving the quality of nutrition, are priorities to overcome these problems.

Living donor transplant: wider selection criteria.

The availability of cadaveric donor organs is insufficient for actual needs. The organ demand increases by 20% per year. Living donor transplant (LDT) may be a valid therapeutical alternative provided one uses proper criteria. LDT provides many advantages, like improved patient and organ survival, short waiting time, and the possibility to carefully plan the procedure. Potential risks include perioperative mortality and renal dysfunction in the kidney donor. At present, kidney LDTs in Italy represent 8% of the total, with an organ survival rate of 97% after 1 year (vs 93% for cadaveric transplants) and donors mortality rate of almost null. Most LDTs are performed from kinsmen. Presently, law no. 458, 26 June 1967, is in force in Italy for kidney LDT and law no. 453, 16 December 1999, for liver LDT. The foundations of LDT are, of course, the recipient's condition, the donor's motivation, and the altruism of the donation. It is desirable that in the future an increasing number of LDT be performed, supported by a careful, widespread health education regarding organ donation from living subjects and by the possibility to obtain insurance for the donor, which has been considered but never provided by actual laws.

Sirolimus in kidney transplantation from marginal donors.

Nephrotoxicity caused by calcineurin inhibitors can lead to either delayed graft function or long-term decline of renal function after kidney transplantation. Therefore, recipients of renal transplants from marginal donors require non-nephrotoxic immunosuppression. Eighteen patients received kidney transplants from marginal donors, with a calcineurin inhibitor-free immunosuppressive regimen, based on basiliximab, mycophenolate mofetil, steroids, and sirolimus. Renal graft biopsy was performed in all cases before surgery. Mean follow-up was 11.8 months. We report immediate renal function in 9 patients, delayed graft function in 5 and acute tubular necrosis in 4 patients. One patient was successfully treated for biopsy-proven acute rejection. Hypercholesterolemia and hypertriglyceridemia were the most common adverse effects (n = 13) associated with arthralgia (n = 2) and thrombocytopenia (n = 2). Five patients underwent a switch to tacrolimus, due to sirolimus-induced side effects. Immunosuppression without the use of calcineurin inhibitors is a safe and effective regimen in kidney transplantation, although sirolimus-related side effects still represent a morbidity factor in these patients.

Topological textures in a ferromagnet-superconductor bilayer.

The homogeneous state of a ferromagnet-superconductor bilayer (FSB) with the magnetization perpendicular to the layer can be unstable with respect to the formation of vortices in the superconducting layer. The developing topological instability in the FSB leads to formation of domains in which the direction of the magnetization in the magnetic film and the direction of vorticity in the superconducting film alternate together. This is a new, combined topological structure, which does not appear in isolated layers. Equilibrium domains can appear in the FSB even if the single magnetic film is in a monodomain state.

A monoclonal antibody, MIN/3/60, that recognizes the sulpho-Lewis(x) and sulpho-Lewis(a) sequences detects a sub-population of epithelial glycans in the crypts of human colonic epithelium.

Monoclonal antibodies (MAbs) directed to Lewis(x) (Le(x)) and related carbohydrate sequences have been invaluable in anticipating biological roles for these oligosaccharides by detecting the remarkable changes that occur in their expression from the earliest stages of embryogenesis, through development and sequential stages of cell differentiation and maturation. A notable impact has been in the molecular dissection of ligand-receptor interactions in key cell adhesion events at the initial stages of leukocyte recruitment in inflammation, and almost certainly in the metastasis of epithelial tumours. Antibodies that recognise Le(x) and the 3'-sialyl forms were observed to identify leukocyte subsets; these were subsequently found to match those recognized by the leukocyte-endothelium adhesion molecules, the E- and P-selectins. We now describe a MAb (rat hybridoma MIN/3/60) raised to 3'-sulpho-Le(x), a carbohydrate sequence which, in vitro, is bound not only by the E-, L-, and P-selectins, but also by the cysteine-rich domain of the macrophage endocytosis receptor. We observe that MIN/3/60 is bispecific, however; it binds 3'-sulpho-Le(a) as well as 3'-sulpho-Le(x). Nevertheless, our exploratory studies reveal that it may be a useful histochemical reagent when used in conjunction with a monospecific antibody to 3'-sulpho-Le(a). The MIN/3/60 antibody reveals a sub-population of epithelial glycans in the crypts of Lieberkühn in normal human colon.

Impact of donor-specific antibodies on chronic rejection occurrence and graft loss in renal transplantation: posttransplant analysis using flow cytometric techniques.

BACKGROUND: Improvements in immunosuppressive therapy have greatly reduced acute rejection (ARj) episodes, ensuring better short-term graft outcome, but have not modified long-term survival in renal transplantation. It is now well accepted that chronic rejection (CRj) can be determined by both immune and/or nonimmune mechanisms. The aim of this study was to evaluate the importance of the posttransplant humoral immune response towards mismatched HLA graft antigens in CRj occurrence and graft outcome. METHODS: Serum samples from 120 nonpresensitized renal transplant recipients were prospectively screened for 1 year after surgery by means of flow cytometry cross-match (FCXM) and FlowPRA beads (microbeads coated with purified HLA class I and class II antigens) assays. All transplants were followed-up for 2 years or until graft removal. RESULTS: FCXM monitoring identified donor-specific antibodies (DS-Abs) in 29 (24.2%) of 120 transplanted patients. Correlation with clinical data highlighted a higher incidence of ARj in DS-Abs-positive patients compared to negative patients (62% vs. 13%, P<0.00001). Furthermore, graft failure occurred more frequently among FCXM-positive patients than among negative patients (34% vs. 1%, P<0.00001). The deleterious effect of DS-Abs on graft function was confirmed by serum creatinine levels 2 years after transplantation. These were in fact higher in subjects producing DS-Abs than in subjects with only ARj (mean creatinine: 2.5+/-1.3 mg/dL vs.1.7+/-0.5 mg/dL, P=0.04). FlowPRA analysis of DS-Ab HLA specificity highlighted the presence of anti-HLA class I antibodies in 85% of FCXM-positive patients, who also presented with a higher incidence of HLA-B mismatches than FCXM-negative patients (1.23+/-0.66 vs. 0.92+/-0.59, P=0.02). CONCLUSIONS: Flow cytometric techniques are precious tools for investigating the activation of the humoral response against HLA antigens of the graft in renal transplantation. DS-Abs production has a worse impact on organ function and survival than ARj episodes. These findings represent further proof of the threat posed by DS-Abs on long-term graft function and draw attention to the need for a specific immunosuppressive therapy aimed at counteracting the different kinds of immune activation toward graft.

PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks.

In a search for molecular markers of progression in prostate cancer by means of differential display, we have identified a new gene, which we have designated PTOV1. Semiquantitative RT-PCR has established that nine out of 11 tumors overexpress PTOV1 at levels significantly higher than benign prostatic hyperplasia or normal prostate tissue. The human PTOV1 protein consists almost entirely of two repeated blocks of homology of 151 and 147 amino acids, joined by a short linker peptide, and is encoded by a 12-exon gene localized in chromosome 19q13.3. A Drosophila melanogaster PTOV1 homolog also contains two tandemly arranged PTOV blocks. A second gene, PTOV2, was identified in humans and Drosophila, coding for proteins with a single PTOV homology block and unrelated amino- and carboxyl-terminal extensions. A 1.8-Kb PTOV1 transcript was detected abundantly in normal human brain, heart, skeletal muscle, kidney and liver, and at low levels in normal prostate. Immunocytochemical analysis and expression of chimeric GFP-PTOV1 proteins in cultured cells showed a predominantly perinuclear localization of PTOV1. In normal prostate tissue and in prostate adenomas, PTOV1 was undetectable or expressed at low levels, whereas nine out of 11 prostate adenocarcinomas showed a strong immunoreactivity, with a focal distribution in areas of carcinoma and prostatic intraepithelial neoplasia. Therefore, PTOV1 is a previously unknown gene, overexpressed in early and late stages of prostate cancer. The PTOV homology block represents a new class of conserved sequence blocks present in human, rodent and fly proteins.

Posttransplant donor-specific antibody characterization and kidney graft survival.

This study was designed to investigate the clinical relevance of donor-specific antibodies (DS-Abs) and their influence on graft survival. Among 106 patients who underwent cadaveric kidney donor transplantation and were monitored by flow cytometry crossmatch (FCXM) during the 1st posttransplantation year, 25 (23.6%) resulted positive for DS-Ab production. During a 2-year follow up only 12 of the 81 FCXM-negative patients (14.8%) suffered rejection vs 17 of 25 FCXM-positive patients (68%; P = 0.00001). Correlating graft loss to DS-Ab production, 9 FCXM-positive patients lost the graft vs only 1 among the FCXM-negative patients. A worse graft function was evidenced in FCXM-positive subjects who had also suffered rejection episodes than in those which had acute rejection but did not produce DS-Abs. A high incidence of HLA-AB mismatches was found in FCXM-positive subjects which produced anti-class I antibodies. FCXM appears useful in estimating posttransplant alloimmune response. Moreover our findings confirm the harmful effects of anti-class I DS-Abs on long-term graft survival.