Successful restoration of corneal surface integrity with a tissue-engineered allogeneic implant in severe keratitis patients.

OBJECTIVES: Corneal diseases are among the main causes of blindness, with approximately 4.6 and 23 million patients worldwide suffering from bilateral and unilateral corneal blindness, respectively. The standard treatment for severe corneal diseases is corneal transplantation. However, relevant disadvantages, particularly in high-risk conditions, have focused the attention on the search for alternatives. METHODS: We report interim findings of a phase I-II clinical study evaluating the safety and preliminary efficacy of a tissue-engineered corneal substitute composed of a nanostructured fibrin-agarose biocompatible scaffold combined with allogeneic corneal epithelial and stromal cells (NANOULCOR). 5 subjects (5 eyes) suffering from trophic corneal ulcers refractory to conventional treatments, who combined stromal degradation or fibrosis and limbal stem cell deficiency, were included and treated with this allogeneic anterior corneal substitute. RESULTS: The implant completely covered the corneal surface, and ocular surface inflammation decreased following surgery. Only four adverse reactions were registered, and none of them were severe. No detachment, ulcer relapse nor surgical re-interventions were registered after 2 years of follow-up. No signs of graft rejection, local infection or corneal neovascularization were observed either. Efficacy was measured as a significant postoperative improvement in terms of the eye complication grading scales. Anterior segment optical coherence tomography images revealed a more homogeneous and stable ocular surface, with complete scaffold degradation occurring within 3-12 weeks after surgery. CONCLUSIONS: Our findings suggest that the surgical application of this allogeneic anterior human corneal substitute is feasible and safe, showing partial efficacy in the restoration of the corneal surface.

Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the 'hygiene hypothesis'?

BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non-early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses. METHODS: Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein-Barr virus and human herpesvirus-6, as well as T-cell and natural killer (NK)-cell immunophenotypes. RESULTS: Cytomegalovirus seroprevalence in early MS was lower than in non-early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01-1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T-cells (CD27-CD28-, CD57+, LILRB1+) and NKG2C+ NK-cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age-related decline in serum anti-EBNA-1 antibodies (P < 0.01), but no CMV-related differences in anti-human herpesvirus-6 humoral responses. CONCLUSIONS: Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T-cell and NK-cell subsets and/or modulation of Epstein-Barr virus-specific immune responses at early stages of the disease.

Pairs of kidneys transplanted from the same donor: is there any difference?

OBJECTIVES: The aim of this study was to compare the evolution of the first kidney in relation to the second kidney transplanted from the same donor, focusing on the impact that a longer cold ischemia time may have as an independent variable. MATERIAL AND METHODS: The study included 44 pairs of kidneys transplanted from the same donor between February 2008 and October 2010, divided into Groups 1 and 2 according to the graft placement order. The variables analyzed were age, sex, comorbidities, number of transfusions, length of hospital stay, maximum peak PRA, immunologic incompatibility, ischemia time, delayed graft function (DGF), presence of rejection, creatinine clearance at first week, at 3 months and at 1 year, and vascular and tract complications in each group. RESULTS: The mean cold ischemia time was 15.6 hours in Group 1 and 20.1 hours in Group 2 (P < .001). The average recipient age was 52.79 years in Group 1 and 54.52 years in Group 2, with an equal sex ratio in the two groups; an average of 2.06 PRC were transfused prior to transplantation in Group 1 and 0.93 PRC in Group 2; the average length of stay was similar in the two groups. Major DR incompatibility was only found in Group 2 (P < .03). Creatinine clearance at first week, DGF and acute rejection showed worse results in Group 2, but these differences were not significant. Vascular complications were present in 4.5% and 2.3% of Groups 1 and 2, respectively, and tract complications were 6.8% and 11.4%. CONCLUSIONS: A greater tendency to DGF, early rejection and tract complications were found in the group with longer ischemia time, although the difference was not statistically significant. Larger series will be necessary to confirm our results.

Serum cholesterol levels and survival after rtPA treatment in acute stroke.

BACKGROUND: According to the reverse epidemiology hypothesis, high cholesterol levels might be protective and associated with greater survival rates under certain conditions. In stroke patients, a clear correlation between lipid levels and mortality after ischaemic and hemorrhagic strokes has been demonstrated. The aim of this study was to analyze the impact of lipid levels on 3-month mortality in patients with ischaemic stroke (IS) homogeneously treated with intravenous rtPA and admitted to a monitored acute stroke unit. METHODS: Retrospective analysis of a prospective cohort of 220 patients with an IS treated with rtPA within the first 4.5 h in a single tertiary hospital from January 2005 to August 2010. RESULTS: Mortality at 3 months was 15.0%. Univariate analysis showed that age, NIHSS at admission, heart failure, and atrial fibrillation were directly related to 3-month mortality; cholesterol, triglycerides, and low density lipoprotein were inversely associated. The death rate by cholesterol level was 5.5% for the highest tertile (>192 mg/dl), 13.7% for the middle (192-155 mg/dl), and 25.7% for the lowest (<155 mg/dl), P = 0.003. Multivariate analysis showed that amongst the lipid determinations, only cholesterol [OR: 0.985 (95% CI: 0.972-0.998), P = 0.021] was inversely associated with 3-month mortality. The 'protective' effect of cholesterol was independent of stroke severity and remained significant in non-lacunar strokes. CONCLUSIONS: Survival of stroke patients receiving current, most effective medical treatment is related to blood cholesterol levels, with an inverse relationship between cholesterol and mortality. The mechanism of this apparently paradoxical situation remains unexplained but merits further research.

Natural killer cell phenotype and clinical response to interferon-beta therapy in multiple sclerosis.

CD56(bright) NK cells, which may play a role in immunoregulation, are expanded in multiple sclerosis (MS) patients treated with immunomodulatory therapies such as daclizumab and interferon-beta (IFNß). Yet, whether this NK cell subset is directly involved in the therapeutic effect is unknown. As NK receptor (NKR) expression by subsets of NK cells and CD8+ T lymphocytes is related to MS clinical course, we addressed whether CD56(bright) NK cells and NKR in IFNß-treated MS patients differ according to the clinical response. IFNß was associated to lower LILRB1+ and KIR+NK cells, and higher NKG2A+NK cell proportions, an immunophenotypic pattern mainly found in responders. After IFNß treatment, a CD56(bright) NK cell expansion was significantly related to a positive clinical response. Our results reveal that IFNß may promote in responders changes in the NK cell immunophenotype, corresponding to the profile found at early maturation stages of this lymphocyte lineage.

El citoesqueleto celular en la glándula mamaria y su aplicación diagnóstica / The cellular cytoskeleton in the mammary gland and its diagnostic application

Objetivos: Valorar la importancia de las modificaciones que aparecen en el citoesqueleto celular (en particular a nivel de unos filamentos intermedios denominados queratinas) a lo largo de los cambios que sufre la glándula mamaria, con especial referencia a la lactación. Su expresión será diferente y servirá como método de contraste. Diseño: 40 ratones distribuidos en cinco grupos según la etapa de estudio. El esquema experimental es común para todos ellos. Material y métodos: Análisis inmunohistoquímico de las muestras procedentes de las glándulas mamarias para evidenciar modificaciones a nivel de las citoqueratinas y comparación con otros estudios en diferentes modelos animales. Resultados: Cada citoqueratina presenta una expresión diferente según sea la estirpe celular y el periodo de lactación. Se diferencian mediante el uso de anticuerpos específicos marcados. Conclusiones: La expresión citoqueratínica varía de manera fisiológica y en células tumorales. La detección inmunohistoquímica de citoqueratinas puede servir como método de diagnóstico complementario (AU)

Objectives: To assess the importance of the changes that appear into the cytoskeleton (especially referred to some specific intermediate filaments called keratins) through different stages the mammary gland bears, focusing on the lactation. Their expression will be different in pathological conditions and this will be useful for contrasting other procedures. Design: 40 mice distributed into five groups according to the tage of study. The experimental project is the same for everyone. Material and methods: Immunohistochemical analysis from samples obtained from mammary glands in order to show changes into cytokeratin expression and comparison with other researches in different animal models. Results: The expression of every cytokeratin is different according to the cell lineage and the lactation period. Specific antibodies can reveal it. Conclusions: The cytokeratinic pattern changes in a physiological sense and also in malignant processes. Immunohistochemical detection of cytokeratins may be useful as complementary diagnosis (AU)

Natural killer receptors distribution in multiple sclerosis: Relation to clinical course and interferon-beta therapy.

NK cell receptors (NKR) are expressed in subsets of NK and CD8+ T cells, lymphocytes involved in multiple sclerosis (MS) pathogenesis. Clinical implications of NKR expression in MS are unknown. Here, we show that the proportions of CD8+ T cells displaying LILRB1, an inhibitory NKR expressed at late stages of T cell differentiation, were directly related with age and MS duration, and inversely with the immunomodulatory therapy-dependent increase of CD56(bright) NK cells. Similar associations were found for KIR+ and CD56+ CD8+ T cells, whereas no age-related NKR distribution was perceived in controls. Moreover, active MS had lower LILRB1+ NK cells, and IFN-ß-treated patients exhibited a phenotypic profile related to shorter disease evolution. Progressive accumulation of terminally differentiated T lymphocytes and experienced NK cells in MS, presumably stimulated in response to a persistent challenge and modulated by IFN-ß therapy, may support the analysis of NKR distribution as new biomarkers.

Ganglio centinela en cáncer de mama: biopsia selectiva comparada con linfadenectomía axilar. Seguimiento a largo plazo / Sentinel ganglion in breast cancer: selective biopsy compared with axillary lymphadectomy

Fundamento. La biopsia selectiva del ganglio centinela(BSGC) ha reemplazado a la linfadenectomía axilar (LA),como procedimiento de elección, en el estadiaje del cáncerde mama en estadios iniciales y axila clínicamente negativa.El objetivo de este trabajo es comparar la supervivenciaglobal y libre de eventos de aquellas pacientes a lasque se realizó, en el periodo de validación de la técnica,BSGC seguida de LA respecto a las que se practicó BSGCy LA si el ganglio centinela (GC) presentaba metástasis.Material y métodos. Se han incluido 148 pacientes, 81pertenecientes al periodo de validación y 67 al grupo deaplicación clínica. El radiocoloide se administró intraperitumoralmente,obteniéndose imágenes hasta la visualizacióndel GC, posteriormente en la intervenciónquirúrgica se procedió a su identificación y extirpación.Resultados. En el grupo de validación, la eficacia de latécnica ha sido del 92,5%, la sensibilidad del 95,6% y latasa de falsos negativos del 4%. De las 81 pacientes, 75se encuentran libres de enfermedad (92,6%). De las 67pacientes pertenecientes al grupo de aplicación clínica,63 (94%) viven libres de enfermedad. Ninguna pacienteha presentado recurrencia ganglionar axilar.Conclusiones. En la validación de la técnica hemos obtenidounos valores que se hallan dentro de las exigenciasde calidad generalmente aceptadas. Con una mediade seguimiento de 6 años no hemos observado recurrenciaaxilar en ninguno de los dos grupos. No existediferencia estadísticamente significativa en la supervivenciaglobal y libre de eventos entre ambos grupos(AU)

Background. Selective biopsy of the sentinel ganglion(SBSG) has replaced axillary lymphadectomy (AL) asthe procedure of choice in staging breast cancer in itsinitial stages and in clinically negative axilla. The aimof this study is to compare global event-free survival ofthose patients subjected to SBSG followed by AL, duringthe period of validation of the technique, with respectto those subjected to SBSG and AL if the sentinelganglion (SG) showed metastasis.Methods. One hundred and forty-eight patients wereincluded, 81 belonging to the period of validation and67 to the clinical application group. Radiocoloid wasadministered intraperitumorally, obtaining images upuntil the visualisation of the SG; its identification andextirpation were carried out subsequently in the surgicalintervention.Results. The efficacy of the technique in the validationgroup was 92.5%, sensitivity was 95.6% and the rate offalse negatives was 4%. Of the 81 patients, 75 are freeof disease (92.6%). Of the 67 patients belonging to theclinical application group, 63 (94%) are free of disease.No patient has presented axillary ganglion recurrence.Conclusion. In the validation of the technique we obtainedvalues that fall within the demands of generallyaccepted quality. With an average follow up of 6 yearswe did not observe axillary ganglion recurrence in anyof the two groups. There is no statistically significantdifference in global and event free survival between thetwo groups(AU)

Multiple sclerosis associates with LILRA3 deletion in Spanish patients.

The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1(*)1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only approximately 400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.

[Sentinel ganglion in breast cancer: selective biopsy compared with axillary lymphadectomy]. / Ganglio centinela en cáncer de mama: biopsia selectiva comparada con linfadenectomía axilar. Seguimiento a largo plazo.

BACKGROUND: Selective biopsy of the sentinel ganglion (SBSG) has replaced axillary lymphadectomy (AL) as the procedure of choice in staging breast cancer in its initial stages and in clinically negative axilla. The aim of this study is to compare global event-free survival of those patients subjected to SBSG followed by AL, during the period of validation of the technique, with respect to those subjected to SBSG and AL if the sentinel ganglion (SG) showed metastasis. METHODS: One hundred and forty-eight patients were included, 81 belonging to the period of validation and 67 to the clinical application group. Radiocoloid was administered intraperitumorally, obtaining images up until the visualisation of the SG; its identification and extirpation were carried out subsequently in the surgical intervention. RESULTS: The efficacy of the technique in the validation group was 92.5%, sensitivity was 95.6% and the rate of false negatives was 4%. Of the 81 patients, 75 are free of disease (92.6%). Of the 67 patients belonging to the clinical application group, 63 (94%) are free of disease. No patient has presented axillary ganglion recurrence. CONCLUSION: In the validation of the technique we obtained values that fall within the demands of generally accepted quality. With an average follow up of 6 years we did not observe axillary ganglion recurrence in any of the two groups. There is no statistically significant difference in global and event free survival between the two groups.

Clustering of vascular risk factors and in-hospital death after acute ischemic stroke.

OBJECTIVE: to evaluate the influence of clustering of vascular risk factors (VRF) on in-hospital mortality in patients with acute ischemic stroke (AIS) developing a risk score for mortality prediction. METHODS: clinical data from 1527 patients admitted to hospital with a first-ever AIS were prospectively evaluated from 1997 to 2005 assessing the presence of six VRF: diabetes, hypertension, hyperlipidemia, ischemic heart disease, atrial fibrillation and peripheral arterial disease. A composite vascular risk score (VRS) was created using five risk factors. Hyperlipidemia was excluded from the score due to its protective impact on mortality. Two modified VRS models were created and assessed for their accuracy as predictors for in-hospital mortality based on the odds ratio for each VRF obtained in the univariate analysis. RESULTS: 197 patients (12.9 %) died during the acute hospitalization period. Stroke severity increased with each additional VRF (p = 0.002). Cox proportional hazards model adjusted for confounders showed an association between the composite VRS and in-hospital mortality (p = 0.045). According to the clustering of VRS, the risk for in-hospital death increased from 1.951 (95 % CI 1.041-3.665) for patients having one VRS to 2.343 (95% CI 1.081-5.076) for those having a VRS > or = 4. ROC curves showed that the modified VRS model based on a given value of one for each accumulated VRF, including the absence of hyperlipidemia, had the highest predictive capability for in-hospital mortality (p < 0.0001). CONCLUSIONS: the presence of multiple VRF in patients with acute ischemic stroke increases the stroke severity and the risk of in-hospital death.

Prevalence of autoimmune thyroid disorders in a Spanish multiple sclerosis cohort.

The aim of the study was to determine the prevalence of thyroid autoimmune disorders in a cohort of untreated multiple sclerosis (MS) patients and compare it with a stratified sample of an adult population. We prospectively studied 93 untreated MS patients. The control group included 401 healthy subjects selected by stratified sampling in a non-iodine-deficient area. Antithyroid antibodies (ATA) (antibodies against peroxidase and thyroglobulin) were considered positive at titres > or =149 IU/ml. Antibodies were positive in 11 MS patients (11.8%; 95% CI 5.3-18.4%). This prevalence was five times higher (P = 0.0001) when compared with that in the control population. We found six cases with subclinical hypothyroidism (6.45%; 95% CI 11.4-1.5) in contrast to 2.24% in the control group. Comparing MS with positive and negative ATA, there was a non-significant, slightly higher frequency of low Expanded Disability Status Scale (EDSS) score in the ATA-positive group (81% vs. 73.2%). One year after start of interferon (IFN) treatment, only one patient developed subclinical thyroid dysfunction. MS patients have a higher prevalence of ATA compared with the general population. An initial ATA and thyroid-stimulating hormone (TSH) determination is recommended in all MS patients. A periodic assessment of thyroid function during IFN treatment only seems to be justified in those cases where positive ATA or dysfunction is present before treatment.

Cladribine in aggressive forms of multiple sclerosis.

Cladribine (2-chlorodeoxyadenosine) is an immunosuppressant drug previously evaluated in multiple sclerosis (MS) with variable results. We report six patients with aggressive relapsing MS who despite a poor response to other therapies had a favourable clinical evolution after cladribine. Four women and two men with a rapid increase in the number and severity of relapses leading to increasing disability [mean Expanded Disability Status Scale (EDSS) 6.42, standard deviation +/- 0.58, mean relapse rate per year in the 2 years prior to study entry 2.67 +/- 0.75] were retrospectively evaluated. Brain magnetic resonance imaging (MRI) performed in five patients showed active disease with gadolinium-enhancing lesions. Cladribine was given at 0.07 mg/kg/day for five consecutive days once monthly with a total of 2- to 4-monthly courses. After 6 months, mean EDSS decreased to 3.75 +/- 1.64 and MRIs showed a decrease or suppression in the number of gadolinium-enhancing lesions. After 1 year from first dose, cladribine dosage was repeated in four patients because of recurrence of relapses with subsequent similar positive clinical results. In the follow-up period (49.33 +/- 39.66 months), the mean relapse rate decreased to 0.71 +/- 0.55 and no unexpected or serious adverse events were observed.

Periodic hyperthermia and abnormal circadian temperature rhythm in a patient with multiple sclerosis.

Disturbances of the central thermoregulation in patients with multiple sclerosis (MS) are not often reported. We describe a 45-year old patient with a 13-year history of MS, who developed a clinical picture of recurrent hyperthermia. MRI showed a bilateral involvement of the hypothalamus in the setting of diffuse white matter disease. Serial body temperature measurement for five consecutive months disclosed an inversion of the circadian temperature rhythm. The clinical presentation and MRI findings suggested abnormalities of the central thermal control in relation to MS widespread involvement of the central nervous system (CNS).

No association of the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) to multiple sclerosis.

Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by neurons and immune cells, promotes neuronal survival and repair during development and after CNS injury. The BDNF-Val66Met polymorphism is functional and induces abnormal intracellular trafficking and decreased BDNF release. Therefore, we investigated the impact of the BDNF-Val66Met polymorphism on the susceptibility and clinical course in a case-control study of 224 multiple sclerosis (MS) Spanish patients and 177 healthy controls. We found no evidence for association to susceptibility or severity of the disease in our population. Moreover, we did not observe, in a subgroup of 12 MS patients, that the methionine substitution at position 66 in the prodomain had negative impact in the capacity to produce BDNF by peripheral blood mononuclear cells (PBMC).

Narcolepsia e hipersomnia idiopática / No disponible

La narcolepsia es una enfermedad crónica relacionada con una hipofunción del sistema hipocretina (orexina) que se cree es secundaria a una pérdida de las neuronas hipotalámicas que la sintetizan. Clínicamente se manifiesta como somnolencia excesiva diurna, síntomasde disregulación del sueño REM (cataplejía, parálisis de sueño y alucinaciones hipnagógicas) y sueño nocturno fragmentado. La asociación de hipersomnia con cataplejía es altamente sugestiva de narcolepsia pero no ocurre en todos los pacientes, al igual que la presencia de tres o más inicios de sueño en REM en el Test de latenciasmúltiples de sueño (MSLT). Unos niveles bajos de hipocretina en el líquido cefaloraquídeo tienen una especificidad y sensibilidad elevadas y pueden ser de ayuda en el diagnóstico. El tratamiento es sintomático:la hipersomnolencia con estimulantes y la cataplejía conantidepresivos. Es posible que en los próximos años dispongamos de agonistas que permitan restaurar la función hipocre tinérgica de una manera práctica.La hipersomnia idiopática es una entidad de causa desconocida caracterizada por la presencia de somnolencia excesiva sin otros síntomas acompañantes y cuyo diagnóstico se realiza por exclusión de otras enfermedades que produzcan somnolencia. Su tratamientoes sintomático, con estimulantes

Narcolepsy is a chronic disease produced by a dysfunction of the hypocretine (orexin) system usually secondary to a loss of the hypothalamic hypocretinergic neurons. Clinically, patients show diurnal hypersomnia together with symptoms of REM sleep dysregulation (cataplexy, sleep paralysis and hypnagogic hallucinations) and fragmentation of nocturnal sleep. The association of hypersomnia with cataplexy is highly suggestive of narcolepsy, but it does not occur in every patient, similarly to what happens with the presence of three ormore sleep onset REM periods in the multiple sleep latency test (MSLT). Low levels of hypocretin in the cerebrospinal fluid have a high sensitivity and specificity for narcolepsy and can be helpful in the diagnosis. The treatment is symptomatic: hypersomnolence with stimulants and cataplexy with antidepressants. It is possible that in the near future hypocretine agonists will be available to treat the disease. Idiopathic hypersomnia is a disorder of unknown cause characterizedby hypersomnolence in the absence of other symptoms. It is diagnosed only after excluding other possible causes of hypersomnia. Treatment is also symptomatic, with stimulants

Aneurisma calcificado de la arteria renal en paciente monorrena, una patología inusual / Renal artery calcified aneurysm in a solytary kidney woman patient, rare pathology

Los aneurismas de la arteria renal son infrecuentes. La prevalencia real de los mismos en la población general es desconocida, aunque se estima que es inferior al 0,4%. Con el uso cada vez mayor de la Angiografía y la Tomografía Computerizada (TC), así como por la mejora en las técnicas de imagen, cada vez se diagnostican con más frecuencia. Las causas más comunes son la displasia fibromuscular y la oclusión arteriosclerótica de la arteria renal. Generalmente no hay una clínica patognomónica de los aneurismas renales, produciendo síntomas inespecíficos como dolor en el costado, hematuria, hipertensión e hipotensión (sospecha de rotura). Presentamos el caso de una paciente monorrena con aneurisma calcificado en la arteria renal

Renal artery aneurysm are uncommon. The true prevalence of renal aneurysms in the general population is unknown (less than 0.4%). Because of more widespread use of Angiography and CT as well as improved imaging techniques, they are diagnosed more frecuently. Fibromuscular dysplasia and arteriosclerotic occlusion of the renal artery are believed to be the most frecuent causes. In general, there are no pathognomonic signs and symptoms of renal aneurysm. Nonspecific complaints include flank pain, hematuria, hypertension and hypotension (suspect rupture of aneurysm). We report a case of a woman with a renal artery calcified aneurysm in a solitary kidney

[Renal artery calcified aneurysm in a female patient with solitary kidney, rare pathology]. / Aneurisma calcificado de la arteria renal en paciente monorrena, una patología inusual.

Renal artery aneurysm are uncommon. The true prevalence of renal aneurysms in the general population is unknown (less than 0.4%). Because of more widespread use of Angiography and CT as well as improved imaging techniques, they are diagnosed more frecuently. Fibromuscular dysplasia and arteriosclerotic occlusion of the renal artery are believed to be the most frecuent causes. In general, there are no pathognomonic signs and symptoms of renal aneurysm. Nonspecific complaints include flank pain, hematuria, hypertension and hypotension (suspect rupture of aneurysm). We report a case of a woman with a renal artery calcified aneurysm in a solitary kidney.

Valor pronóstico de los factores clinicopatológicos Ki67, ciclina D1, ciclina D3 y CDK4 en el carcinoma gástrico / Pronostic value of clinicopathologic factors Ki67, cyclin D1, cyclin D3 and CDK4 in gastric carcinoma

- Propósito: Conocer el valor pronóstico de la ciclina Dl, ciclina D3, cdk4 y Ki67, estudiados por métodos inmunohistoquímicos, junto con las características clinicopatológicos de los carcinomas gástricos.- Métodos y resultados: Realizamos estudio inmunohistoquimicos de material incluido en parafina para ciclina D1, ciclina D3, cdk4 y Ki67 en 74 pacientes con carcinoma gástrico. Las inmunotinciones para ciclinas D1, D3 y cdk4 así el índice de proliferación de Ki67, el grado histológico y el tipo histológico (según la clasificación de Lauren) se compararon con la supervivencia. El 97 por ciento de los casos eran Ki67 positivos, el 29 por ciento para ciclina D1, el 23 por ciento para ciclina D3 y el 35 por ciento para cdk4. El análisis multivariante sólo mostró correlación entre el Ki67 (PI) (p<0,01) y la supervivencia. En el análisis univariante el grado histológico también se correlaciona con la supervivencia (p<0,03). La expresión de ciclina D3 se relaciona con cdk4 (p<0,001) y Ki67 (PI) (p<0,02) y la expresión de ciclina D1 con el grado histológico (p<0,03).- Conclusiones: Nuestros resultados sugieren que un índice de proliferación elevado de Ki67 y el grado histológico son marcadores de mal pronóstico. La sobreexpresión de la ciclina D1 podría tener un importante papel en la proliferación celular. La relación entre ciclina D3, cdk4 y Ki67 podrían explicarse por su papel a lo largo del ciclo celular. (AU)