Diagnosis of Multisystem Inflammatory Syndrome in Children by a Whole-Blood Transcriptional Signature.

BACKGROUND: To identify a diagnostic blood transcriptomic signature that distinguishes multisystem inflammatory syndrome in children (MIS-C) from Kawasaki disease (KD), bacterial infections, and viral infections. METHODS: Children presenting with MIS-C to participating hospitals in the United Kingdom and the European Union between April 2020 and April 2021 were prospectively recruited. Whole-blood RNA Sequencing was performed, contrasting the transcriptomes of children with MIS-C (n = 38) to those from children with KD (n = 136), definite bacterial (DB; n = 188) and viral infections (DV; n = 138). Genes significantly differentially expressed (SDE) between MIS-C and comparator groups were identified. Feature selection was used to identify genes that optimally distinguish MIS-C from other diseases, which were subsequently translated into RT-qPCR assays and evaluated in an independent validation set comprising MIS-C (n = 37), KD (n = 19), DB (n = 56), DV (n = 43), and COVID-19 (n = 39). RESULTS: In the discovery set, 5696 genes were SDE between MIS-C and combined comparator disease groups. Five genes were identified as potential MIS-C diagnostic biomarkers (HSPBAP1, VPS37C, TGFB1, MX2, and TRBV11-2), achieving an AUC of 96.8% (95% CI: 94.6%-98.9%) in the discovery set, and were translated into RT-qPCR assays. The RT-qPCR 5-gene signature achieved an AUC of 93.2% (95% CI: 88.3%-97.7%) in the independent validation set when distinguishing MIS-C from KD, DB, and DV. CONCLUSIONS: MIS-C can be distinguished from KD, DB, and DV groups using a 5-gene blood RNA expression signature. The small number of genes in the signature and good performance in both discovery and validation sets should enable the development of a diagnostic test for MIS-C.

Neonatal sepsis and transient immunodeficiency: Potential for novel immunoglobulin therapies?

Neonates, especially preterm neonates, have the highest risk of sepsis of all age groups. Transient immaturity of the neonatal immune system is an important risk factor. Neonates suffer from hypogammaglobulinemia as nor IgA nor IgM is transferred over the placenta and IgG is only transferred over the placenta late in gestation. In addition, neutrophil numbers and complement function are also decreased. This mini-review focuses on strategies to improve neonatal host-defense. Both clinical and preclinical studies have attempted to boost neonatal immunity to lower the incidence of sepsis and improve outcome. Recent advances in the development of (monoclonal) antibodies show promising results in preclinical studies but have yet to be tested in clinical trials. Strategies to increase complement activity seem efficient in vitro but potential disadvantages such as hyperinflammation have held back further clinical development. Increase of neutrophil numbers has been tested extensively in clinical trials but failed to show improvement in mortality. Future research should focus on clinical applicability of promising new prevention strategies for neonatal sepsis.

Monoclonal antibodies effectively potentiate complement activation and phagocytosis of Staphylococcus epidermidis in neonatal human plasma.

Central line associated bloodstream infections (CLABSI) with Staphylococcus epidermidis are a major cause of morbidity in neonates, who have an increased risk of infection because of their immature immune system. As especially preterm neonates suffer from antibody deficiency, clinical studies into preventive therapies have thus far focused on antibody supplementation with pooled intravenous immunoglobulins from healthy donors (IVIG) but with little success. Here we study the potential of monoclonal antibodies (mAbs) against S. epidermidis to induce phagocytic killing by human neutrophils. Nine different mAbs recognizing Staphylococcal surface components were cloned and expressed as human IgG1s. In binding assays, clones rF1, CR5133 and CR6453 showed the strongest binding to S. epidermidis ATCC14990 and CR5133 and CR6453 bound the majority of clinical isolates from neonatal sepsis (19 out of 20). To study the immune-activating potential of rF1, CR5133 and CR6453, bacteria were opsonized with mAbs in the presence or absence of complement. We observed that activation of the complement system is essential to induce efficient phagocytosis of S. epidermidis. Complement activation and phagocytic killing could be enhanced by Fc-mutations that improve IgG1 hexamerization on cellular surfaces. Finally, we studied the ability of the mAbs to activate complement in r-Hirudin neonatal plasma conditions. We show that classical pathway complement activity in plasma isolated from neonatal cord blood is comparable to adult levels. Furthermore, mAbs could greatly enhance phagocytosis of S. epidermidis in neonatal plasma. Altogether, our findings provide insights that are crucial for optimizing anti-S. epidermidis mAbs as prophylactic agents for neonatal CLABSI.

Hair cortisol level as a molecular biomarker in retinitis pigmentosa patients.

PURPOSE: Retinitis pigmentosa (RP) patients commonly experience negative psychological states due to their progressive and unpredictable loss of vision and visual variations related to stress. The aim of this study was to examine hair cortisol concentrations (HCCs), which is usually associated with chronic stress, pretending to unveil possible associations between underlying psychological factors and disease severity in RP patients. METHODS: Seventy-eight RP patients and 148 healthy controls were included in this study. A complete ophthalmological exam was performed in all patients to grade into severity disease groups. Perceived stress and trait-anxiety were measured by the State-Trait Anxiety Inventory (STAI) questionnaire. RESULTS: Fifty-two (67%) patients had severe RP and 26 (33%) mild-moderate RP. Fifty-eight (58,9%) patients reported severely levels of stress and 18 (23.,1%) highly levels assessed by STAI questionnaire. RP patients exhibited higher HCCs (500.04 ± 120.99 pg/mg) than in controls (136.17 ± 60.51 pg/mg; p < 0.001). Severe RP patients had significant higher HCCs than mild-moderate patients differing in 274.27 pg/mg (p < 0.001). RP severity grade and perceived anxiety levels in the questionaries were not associated. Group differences were not affected by relevant covariates (age, grade of severity, stress status, and gender). CONCLUSIONS: HCC seems an effective biomarker associated with chronic stress in RP patients. This study shows that HCC in patients with RP are elevated compared to population-based controls, and association between HCC and RP severity was found. Future research is needed to characterize the effect of untreated negative psychological states on progression of the disease if any.

Suicidios en el Perú: Descripción epidemiológica a través del Sistema Informático Nacional de Defunciones (SINADEF) en el periodo 2017-2021 / Suicides in Perú: Epidemiological description through SINADEF in the period 2017-2021

RESUMEN Objetivo: Descripción de características epidemiológicas de suicidios ocurridos en el Perú durante el periodo 2017-2021. Material y Métodos: Estudio de tipo descriptivo-comparativo, basado en la revisión del Sistema Informático Nacional de Defunciones entre los años 2017-2021; la muestra final incluyó un total de 2579 suicidios. Resultados: El 69,5% de los suicidios ocurrieron en el género masculino, el promedio de edad fue 34,87 años, 79,5% solteros y 26,6% con instrucción secundaria completa. Los departamentos con mayor frecuencia de suicidio fueron Lima (20,3%), Arequipa (19,2%), Cusco (9,5%) y Junín (7,8%). Según CIE-10 la causa principal de muerte fue edema cerebral (20,06%) y el domicilio, el lugar más frecuente (63,4%). Las modalidades utilizadas fueron ahorcamiento (56,6%), envenenamiento (29,2%), arma de fuego (4,0%), precipitación (3,1%) y arma blanca (1,7%). Se pudo establecer diferencias significativas con un p < 0,05 entre tipo de suicidio y género, identificando un 74% de casos por ahorcamiento en el sexo masculino; entre tipo de suicidio y región natural: 60% de ahorcamientos en la costa; entre rango etario y tipo de suicidio: ahorcamiento 10-19 años (27,7%) y envenenamiento 20-29 años (26,5%), La mayoría (70,7%) cometió suicidio por ahorcamiento en su domicilio, seguida por envenenamiento en establecimientos de salud (56,9%) y por precipitación en la vía pública (16,8%). Conclusiones: El tipo más frecuente de suicidio fue por ahorcamiento, en personas jóvenes-adultas de sexo masculino y por envenenamiento en personas de sexo femenino.

SUMMARY Objectives: Description of epidemiological features of suicides in Peru between the years 2017-2021. Material and Methods: Descriptive-comparative study based on the review of the national computerized registry of SINADEF deaths between the years 2017-2021; the final sample included a total of 2579 suicides. Results: Male gender reached 69.5%, average age 34.87 years, 79.5% were single, and 26.6% had complete secondary education. The departments with highest frequency of suicides were Lima (20.3%), Arequipa (19.2%), Cusco (9.5%) and Junín (7.8%). According to ICD-10, the main cause of death was cerebral edema (22.71%), and place of death at home (63.4%). Suicide modalities included hanging (56.6%), poisoning (29.2%), firearm (4%), precipitation (3.1%), and knife (1.7%). It was possible to establish significant differences with a p<0.05 value in: type of suicide and gender, 74% of hangings among males; type of suicide and natural region: hanging in the coast (60%); type of suicide and age range: hanging 10-19 years (27.7%) and poisoning 20-29 years (26.5%). A majority (70.7%) died at home by hanging, followed by poisoning in health facilities (56.9%), and by precipitation (16.8%) on public roads. Conclusions: The most frequent type of suicide was by hanging in young-adult males, and poisoning among females.

Características clínico epidemiológicas de la enfermedad de parkinson en un hospital nacional de la sierra peruana / Clinical epidemiological characteristics of parkinson's disease in a national hospital of the peruvian highlands

Objetivo: Determinar las principales características epidemiológicas y clínicas de la enfermedad de Parkinson en el Hospital Nacional "Ramiro Prialé Priale" de Huancayo. Métodos: Estudio observacional, descriptivo tipo retrospectivo de una serie de casos. Se estudió 84 pacientes entre los años 2015 y 2017, atendidos en la consulta externa u hospitalización de Neurología y Medicina interna, para ello se revisó sus historias clínicas, el muestreo fue no probabilístico de tipo censal seleccionados por juicio del investigador. Resultados: El promedio de edad fue 72,93 años, predominó el género masculino (58,3%), el grado de instrucción universitario (50%) y la procedencia de Huancayo (77,4%). La hipertensión arterial descompensada fue el motivo de hospitalización (19,1%), el tiempo de enfermedad tuvo un rango de 1-7 años (57,1%) y el temblor de reposo y bradicinesia fue el síntoma motor más frecuente (23,8%). En los síntomas no motores, 38,1% tuvieron alteraciones del sueño, 21,4% antecedentes familiares de enfermedad de Parkinson y las comorbilidades más asociadas fueron: depresión (48,8%) e insomnio (41,7%). Conclusión: La enfermedad de Parkinson es una patología frecuente en adultos mayores y en el sexo masculino; el síntoma motor que predomina es el temblor de reposo y bradicinesia, y las comorbilidades neuropsiquiátricas asociadas son la depresión e insomnio.

Objective: To determine the main epidemiological and clinical characteristics of Parkinson's disease at the National Hospital "Ramiro Prialé Priale" in Huancayo. Methods: Observational, descriptive retrospective study of a serie of cases. 84 patients were studied between 2015 and 2017, treated in the outpatient clinic or hospitalization of Neurology and Internal Medicine, for which their medical records were reviewed, the sampling was non-probabilistic of the census type selected by the investigator's judgment. Results: The average age was 72.93 years, the male gender prevailed (58.3%), the degree of university education (50%) and the origin of Huancayo (77.4%). Decompensated arterial hypertension was the reason for hospitalization (19.1%), disease time ranged between 1-7 years (57.1%) and tremor at rest and bradykinesia was the most frequent motor symptom (23.8%) In non-motor symptoms, 38.1% had sleep disorders, 21.4% family history of Parkinson's disease and the most associated comorbidities were: depression (48.8%) and insomnia (41.7%). Conclusion: Parkinson's disease is a frequent pathology in older adults and males; The predominant motor symptom is resting tremor and bradykinesia, and the associated neuropsychiatric comorbidities are depression and insomnia.

Effectiveness and safety of nutritional supplements in the treatment of hereditary retinal dystrophies: a systematic review.

The hereditary retinal dystrophies (HRDs) are a group of genetically determined disorders that result in loss of the visual function. There is a lack of standard pharmacological treatments or widely accepted nutritional recommendations. The objective of this review is to summarise the scientific evidence on the effectiveness and safety of nutritional supplements for the treatment of HRDs. We conducted a scientific literature search on Medline and PreMedline, EMBASE, SCI-EXPANDED, SSCI, and The Cochrane Library up to August 2014. Experimental, quasi-experimental and controlled observational studies were selected. Eight studies were ultimately included, seven on retinitis pigmentosa (RP) and one on Best disease. Vitamin A, vitamin E, docosahexaenoic acid (DHA), lutein and ß-carotene were assessed. A 15 000 IU daily dose of vitamin A was reported to have shown a small protective effect on the progression of RP, as was the use of the carotenoids lutein and ß-carotene. Different DHA doses has no effect on RP or Best disease. No supplement showed severe adverse effects in the selected studies although strong evidence of toxicity exists for high doses of vitamin A and ß-carotene in certain populations. The selected studies concluded that there may be a small beneficial effect of vitamin A, lutein and ß-carotene on the progression of RP. The limited evidence available indicates some well-designed additional studies on combined supplements strategies may achieve more robust conclusions. Moreover, the scarcity of evidence available on the treatment of HRD other than RP with nutritional supplements supports the need for further research efforts.

The role of asynapsis in human spermatocyte failure.

The basic molecular mechanisms by which chromosomal rearrangements in heterozygous state produce spermatogenic disturbances are poorly understood. Testicular biopsies from five patients - one carrier of a Robertsonian translocation rob t(13;14), two carriers of two different Y-autosome translocations, a t(Y;6) and a t(Y;11), one carrier of a reciprocal translocation t(3;13) and one carrier of a heterochromatin duplication in chromosome 9 - were processed for histopathological analysis, electron microscopy and fluorescent immunolocalization of meiotic proteins. In all the patients, the asynaptic regions during pachytene are labelled by BRCA1 and retained RAD51 foci. The variant histone γ-H2AX is located on the chromatin domains of the asynaptic regions and the XY body. In contrast, these meiotic proteins are absent in those chromosomal segments that are non-homologously synapsed. The present observations on five new cases and a review of recent studies show that the common features shared by all these cases are the abnormal location of some meiotic proteins and the presence of transcriptionally silenced chromatin domains on asynaptic regions. The frequent association of these silenced regions with the XY body and the rescue of spermatocyte viability through non-homologous synapsis are also shared by all these carriers. A passive, random mechanism of clustering of asynaptic regions with the XY body is suggested.

Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy.

AIMS: Beradinelli-Seip congenital generalized lipodystrophy is a rare autosomal recessive disorder characterized by near-complete absence of adipose tissue, Herculean appearance, insulin resistance, hypoleptinaemia and diabetes mellitus. The aim of this study was to investigate the in vitro effects of pioglitazone on the expression of genes involved in adipogenesis in fibroblasts from a patient with this condition due to a seipin mutation. METHODS: Primary cultures of fibroblasts from the skin of the patient were obtained. Fibroblasts were treated with classic adipose differentiation medium, with and without pioglitazone. Several adipogenes were evaluated by real-time reverse transcriptase-polymerase chain reaction and western blotting. Intracellular localization of prelamin A was studied by immunofluorescence microscopy. RESULTS: The expression of the adipogenic genes PPARG, LPL, LEP and SLC2A4 was reduced in lipodystrophic fibroblasts, while treatment with pioglitazone increased the expression of these genes. Moreover, and unexpectedly, we found an accumulation of farnesylated prelamin A in lipodystrophic fibroblasts. CONCLUSIONS: The process of adipocyte differentiation is compromised in patients with Beradinelli-Seip congenital lipodystrophy owing to diminished expression of the regulatory genes involved, which pioglitazone treatment partially rescues. Prelamin A accumulation establishes a link with other types of familial lipodystrophies, as familial partial lipodystrophy.

Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients.

BACKGROUND: Klinefelter syndrome is the most frequent chromosome abnormality in human males. This paper aims to investigate the ploidy of meiotic and pre-meiotic germ cells found in spermatogenic foci, and furthermore, the sex chromosome constitution of Sertoli cells which surround these germ cells in non-mosaic Klinefelter patients. METHODS AND RESULTS: A survey of 11 adult patients diagnosed with classical, non-mosaic Klinefelter syndrome who underwent testicular biopsies, showed that six of them had spermatogenesis foci. The topographical study of the biopsies showed that tubuli with germ cells are a minor fraction (8-24%) of all tubuli, although the overwhelming majority is devoid of germ cells. Using fluorescence in situ hybridization (FISH) with probes for the X-centromere and immunolocalization of meiotic proteins, the present work shows that all the 92 meiotic spermatocytes analyzed with FISH were euploid, 46,XY, and thus can form normal, haploid gametes. On the other hand, Sertoli cells show two marks for the X chromosome, meaning that they are 47,XXY. CONCLUSIONS: These results provide a rationale for the high rate of success in the testicular sperm extraction plus ICSI procedures when applied to Klinefelter patients. It is also in agreement with previous studies in the XXY-mouse model. These spermatogenic foci most probably originate from clones of spermatogonia that have randomly lost one of the X chromosomes, probably during periods of life when high spermatogonial mitotic activity occurs.

[Training and clinical activity of Spanish retinologists: a preliminary approach. Retina 2 project. Descriptive analysis]. / Formación y actividad clínica de los retinólogos en España: un primer acercamiento. Proyecto retina 2. Análisis descriptivo.

PURPOSE: To create a database of Spanish ophthalmologists mainly dedicated to retinal pathology care, describing their training period characteristics and their daily activity (clinical and surgical). METHODS: A postal questionnaire was sent to 504 possible retinologists identified through the information supplied by the Spanish Ophthalmological Society and the Spanish Vitreous-Retina Society, with a minimum of 3 retinologists per Autonomous Region. RESULTS: 267 (52.9% of the sample population) responses were collected and processed. Most of the respondents had started their residency after 1980 (82.4%). Ninety-four percent had received specific training in retinal pathology, mostly during the residency period (82.1%) and from more experienced colleagues (62.9%). Official fellowships were held in a minority of cases (around 12%). Twelve percent of retinologists performed retinal surgery only, 14.6% performed anterior segment surgery, and 60.7% performed both types of surgery. CONCLUSIONS: Despite not having taken into consideration non-response bias, this study provides the first reported data on the professional profile of Spanish retinologists.

Formación y actividad clínica de los retinólogos en España: un primer acercamiento. Proyecto Retina 2. Análisis descriptivo / Training and clinical activity of spanish retinologists: A preliminary approach. Retina 2 project. Descriptive analysis

Objetivo: Obtener un listado de oftalmólogos españolesdedicados a la patología retiniana y describiralgunas características de su formación específica yde su actividad clínica cotidiana.Método: Se ha enviado una encuesta por correopostal a 504 probables retinólogos identificados apartir de la información proporcionada por lasSociedades Española de Oftalmología y de Retina yVítreo y un conjunto mínimo de tres retinólogos decada Comunidad Autónoma.Resultados: Se han obtenido 267 respuestas(52,9% de la población). El 83% obtuvo su especialidaddespués de 1980. El 94% ha recibido formaciónespecífica, sobre todo durante la residencia(82,1%) y de compañeros más expertos (67,7%). La realización de masteres oficiales es muy minoritaria (solo un 16,7% tienen al menos un master).El 12% se dedica en exclusiva a la patología quirúrgica,el 24,7% a la médica y el 62,9% combinanambas actividades. Un 22,5% opera patología retiniana,un 14,6% realiza cirugía del segmento anteriory un 60,7% combina ambas.Conclusiones: A pesar de no haberse tenido encuenta el sesgo de la no repuesta, se dispone de losprimeros datos sobre el perfil y la actividad de losdenominados retinólogos, en España(AU)

Purpose: To create a database of Spanish ophthalmologistsmainly dedicated to retinal pathologycare, describing their training period characteristicsand their daily activity (clinical and surgical).Methods: A postal questionnaire was sent to 504possible retinologists identified through the informationsupplied by the Spanish OphthalmologicalSociety and the Spanish Vitreous-Retina Society,with a minimum of 3 retinologists per AutonomousRegion.Results: 267 (52.9% of the sample population) responseswere collected and processed. Most of therespondents had started their residency after 1980(82.4%). Ninety-four percent had received specifictraining in retinal pathology, mostly during the residency period (82.1%) and from more experiencedcolleagues (62.9%). Official fellowships were heldin a minority of cases (around 12%). Twelve percentof retinologists performed retinal surgery only,14.6% performed anterior segment surgery, and60.7% performed both types of surgery.Conclusions: Despite not having taken into considerationnon-response bias, this study provides thefirst reported data on the professional profile ofSpanish retinologists(AU)

Surgical outcomes for primary rhegmatogenous retinal detachments in phakic and pseudophakic patients: the Retina 1 Project--report 2.

AIMS: To compare anatomical and functional outcomes for 546 phakic and pseudophakic primary rhegmatogenous retinal detachments (RDs) treated by pars plana vitrectomy or scleral buckling. METHODS: Prospective, non-randomised, interventional study in 15 centres in Spain and Portugal, with data from RDs consecutively treated from January 2005 to May 2007. Cases with preoperative proliferative vitreoretinopathy grade C-1 or higher and perforating trauma were excluded. Minimum follow-up was 3 months. Twenty-seven pre-, intra- and post-surgical variables for each patient were analysed. Multivariate analysis was carried out by logistic regression analysis with stepwise selection of variables. RESULTS: Data from 546 patients were analysed. Global anatomical success was 94.7%. Logistic regression analysis showed that only the development of postoperative proliferative vitreoretinopathy was associated with a poor anatomical outcome. The poorest functional results were associated with macular involvement, extension of RD, previous RD surgery, time of evolution of RD, and age of patient. Hierarchical log-linear analysis showed no effect of the lens status (phakic versus pseudophakic) on the functional results. However, pars plana vitrectomy was most often performed in pseudophakic eyes and resulted in a worse final visual acuity (p<0.001). CONCLUSIONS: No differences in anatomical success between phakic and pseudophakic eyes were found in this series. Pars plana vitrectomy was most often performed in pseudophakic eyes and had a greater probability of a worse final visual acuity than scleral buckling.

Non-complicated retinal detachment management: variations in 4 years. Retina 1 project; report 1.

AIMS: To assess variations in the characteristics and management of two series of non-complicated rhegmatogenous retinal detachments (RD) carried out 4 years apart in Spain. METHODS: Prospective, multicentric, non-randomised comparative study. 339 consecutive cases of RD treated in five hospitals were included. Group 1 (G1) (n = 186) included cases operated on from 1999 to 2001; group 2 (G2) (n = 153) included cases from 2004 to 2006. 83 variables related to preoperative characteristics of RD, surgical management and postoperative evolution were recorded. Surgeons were allowed to treat patients following their personal criteria. Differences in preoperative characteristics, rate of vitrectomy and anatomical outcome were studied. Quantitative variables were compared by Mann-Whitney U test and qualitative variables by standard contingency tables. Multivariate analysis was carried out by logistic regression analysis. RESULTS: G1 showed a significantly longer delay in performing surgery, since the first symptoms appeared (G1: 29 (SD 50) days; G2: 22 (55); p<0.001) and more RD without visible retinal break than G2 (G1: 17.4%; G2: 9.2%; p = 0.028). In G2, cases with multiple retinal breaks (G1: 31.6%; G2: 44.6%) were more frequent (p = 0.022). No significant differences in other preoperative variables were observed. Vitrectomy was performed in 30.1% in G1 and in 78.4% in G2 as a primary surgical approach (p<0.001). Regardless of the characteristics of the RD, the rate of vitrectomy was higher in G2. The reattachment rate was over 94% in both groups (p = 0.833). Pseudophakic RD showed better anatomical outcomes in G2 (G1: 83.9%; G2: 96.4%; p = 0.028). CONCLUSION: There is an increasing tendency to treat RD with primary vitrectomy, which is related to neither a higher complexity of cases nor better anatomical results.

A constitutional complex chromosome rearrangement involving meiotic arrest in an azoospermic male: case report.

Complex chromosome rearrangements are rare aberrations that frequently lead to reproductive failure and that may hinder assisted reproduction. A 25-year-old azoospermic male was studied cytogenetically with synaptonemal complex analysis of spermatocytes from a testicular biopsy and fluorescence in situ hybridization (FISH) of lymphocytes. The spermatocytes showed a pentavalent plus a univalent chromosome. Cell death occurred mainly at advanced pachytene stages. The sex chromosomes were involved in the multiple, as shown by their typical axial excrescences. Two autosomal pairs, including an acrocentric chromosome (15), were also involved in the multiple. FISH allowed the definite identification of all the involved chromosomes. An inverted chromosome 12 is translocated with most of one long arm of chromosome 15, while the centromeric piece of this chromosome 15 is translocated with Yqh, forming a small marker chromosome t(15;Y). The euchromatic part of the Y chromosome is joined to the remaining piece of chromosome 12, forming a neo-Y chromosome. The patient shows azoospermia and a normal phenotype. The disruption of spermatogenesis is hypothetically due to the extent of asynaptic segments and to sex-body association during pachytene. This CCR occurred 'de novo' during paternal spermatogenesis. Meiotic analysis and FISH are valuable diagnostic tools in these cases.

[Retinal shortening: the most severe form of proliferative vitreoretinopathy (PVR)]. / Acortamiento retiniano: la forma más grave de la vitreorretinopatía proliferante (VRP).

PURPOSE: To identify the clinical characteristics of patients developing retinal shortening due to intraretinal PVR. METHODS: Observational and retrospective cohort study on 110 PVR patients operated on between 2000 and 2001. During surgery, after removing epiretinal membranes and ruling out the presence of subretinal membranes, a perfluorocarbon liquid was injected. Those cases in which retinal flattening was not accomplished, were considered intraretinal PVR (group 1). Those in which retinal flattening allowed endolaser application, were taken as the control group (group 2). Clinical features of both groups were compared by chi-square test. RESULTS: 60 cases (54.5%, CI 95%: 40.5-68.5) showed retinal shortening (group 1). In 24 cases (21.8%, CI 95%: 12.9-30.7) complete retinal flattening was accomplished (group 2). In 26 cases (23.6%), evaluation was inconclusive. In 9 out of the 60 cases of group 1 (15%) a retinectomy was necessary to reattach the retina. Differences between both groups were not statistically significant for any of the clinical variables. However, the number of retinal detachments of more than 60 days of evolution was significantly higher in retinectomized eyes (20.7%) than in group 1 (3.7%) (p=0.04). CONCLUSIONS: Retinal shortening is a relatively frequent phenomenon in PVR. Further studies are necessary to characterize this clinical presentation of PVR and its pathogenesis.

Acortamiento retiniano: la forma más grave de la vitreorretinopatía proliferante (VRP) / Retinal shortening: the most severe form of proliferative vitreoretinopathy (PVR)

Objetivo: Identificar las características clínicas de los pacientes que presentan una VRP con acortamiento retiniano no producido por membranas perirretinianas. Método: Estudio observacional, retrospectivo, de una cohorte de 110 pacientes intervenidos por VRP en 2000 y 2001. Durante la cirugía, tras eliminar las membranas epirretinianas y comprobar que no existían subretinianas, se inyectó un perfluorocarbono líquido. Los ojos en los que no se consiguió la reaplicación retiniana se catalogaron como VRP intrarretiniana (grupo 1). Los casos en los que se consiguió una reaplicación que permitió la aplicación de endoláser sin realizar otras maniobras, constituyeron el grupo control (grupo 2). Se han comparado las características clínicas preoperatorias de ambos grupos mediante el test de la chi- cuadrado. Resultados: 60 casos (54,5 por ciento, IC 95 por ciento: 40,5-68,5) se incluyeron en el grupo 1 y 24 casos (21,8 por ciento, IC 95 por ciento: 12,9-30,7) en el grupo 2. En los casos restantes, 26 (23,6 por ciento), la evaluación presentó dudas. En 9 (15 por ciento) de los 60 casos del grupo 1 fue necesario realizar una retinectomía. No hubo diferencias estadísticamente significativas en ninguna de las variables preoperatorias comparadas entre ambos grupos. Únicamente se observó un mayor número de casos con larga evolución (más de 2 meses) entre los pacientes del grupo 1 que requirieron una retinectomía (20,7 por ciento), que en los que no fue necesaria (3,7 por ciento) (p=0,04). Conclusión: La aparición de fenómenos de acortamiento retiniano es frecuente en la VRP. Son necesarios más estudios para caracterizar mejor esta presentación clínica de la VRP y para conocer los mecanismos patogénicos que la provocan (AU)

Pharmacokinetics of 0.5 mg of a single and a multiple dose of intravitreal vancomycin in infected rabbit eyes.

The purpose of this study was to determine the pharmacokinetics governing distribution and elimination of 0.5 mg of intravitreal vancomycin in a single dose and in a multiple therapeutic regime in infected rabbit eyes. A total of 96 rabbits was injected with approximately 200 CFU of S. aureus intravitreally. Four days later, a single dose of 0.5 mg of vancomycin was administered to Group I (n=36). Group II (n=60) was injected with a maximum of 4 doses of 0.5 mg every 36 hr. Four animals were sacrificed at different time points in each group. Samples of vitreous, aqueous and blood were taken from each animal for analyses by HPLC. These results were evaluated using the RSTRIP program. High vancomycin concentrations were demonstrated in the vitreous of Group I, with a calculated half-life of 12 hr. In Group II, vancomycin levels were within the therapeutic range during the entire experiment. There was minimal accumulation of the drug, and the half-life did not seem to be longer with multiple doses. In conclusion, the pharmacokinetics do not change significantly when a multidose regime is used compared with a single dose. Therapeutic intravitreal concentrations of vancomycin can be achieved by using repeated doses of 0.5 mg of vancomycin.