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Alberto Artiles Medina, Rafael Rodríguez-Patrón Rodríguez, Mercedes Ruiz Hernández, Marina Mata Alcaraz, Silvia García Barreras, Guillermo Fernández Conejo, Agustín Fraile Poblador, Enrique Sanz Mayayo, Francisco Javier Burgos Revilla Department of Urology, Hospital Universitario Ramón y Cajal, University of Alcalá, Madrid, SpainCorrespondence: Alberto Artiles MedinaDepartment of Urology, Hospital Universitario Ramón y Cajal, M-607, km. 9, 100, Madrid, 28034, SpainTel +91.336.87.60Fax +91.336.87.59Email alberc.artiles@gmail.comPurpose: Prostatic multi-parametric magnetic resonance imaging (mpMRI) has markedly improved the assessment of men with suspected prostate cancer (PCa). Nevertheless, as mpMRI exhibits a high negative predictive value, a negative MRI may represent a diagnostic dilemma. The aim of this study was to evaluate the incidence of positive transperineal saturation biopsy in men who have negative mpMRI and to analyse the factors associated with positive biopsy in this scenario.Patients and Methods: A retrospective study of men with normal mpMRI and suspicion of PCa who underwent saturation biopsy (≥ 20 cores) was carried out. A total of 580 patients underwent transperineal MRI/transrectal ultrasound fusion targeted biopsies or saturation prostate biopsies from January 2017 to September 2020. Of them, 73 had a pre-biopsy negative mpMRI (with Prostate Imaging – Reporting and Data System, PI-RADS, ≤ 2) and were included in this study. Demographics, clinical characteristics, data regarding biopsy results and potential predictive factors of positive saturation biopsy were collected. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for MRI-invisible PCa.Results: The detection rate of PCa with saturation biopsy in patients with negative MRI was 34/73 (46.58%). Out of 34 MRI-invisible prostate cancers detected, 12 (35.29%) were clinically significant PCa (csPCa) forms. Regarding factors of positive biopsy, in univariate analysis, the use of 5-alpha reductase inhibitors and free:total prostate-specific antigen (PSA) ratio were associated with the result of the saturation biopsy. In multivariate analysis, only an unfavourable free:total PSA ratio remained a risk factor (OR 11.03, CI95% 1.93– 63.15, p=0.01). Furthermore, multivariate logistic analysis demonstrated that prostate volume > 50mL significantly predicts the absence of csPCa on saturation biopsy (OR 0.11, 95% CI 0.01– 0.94, p=0.04).Conclusion: A free:total PSA ratio < 20% is a risk factor for MRI-invisible PCa. Saturation biopsy could be considered in patients with suspected PCa, despite having a negative MRI.Keywords: clinically significant prostate cancer, multi-parametric magnetic resonance imaging, negative MRI, prostate cancer, saturation biopsy

David Parada D,1 Karla B Peña G,1 Margarida Vives,2 Alicia Molina,2 Emilio Mayayo,3 Frances Riu,1 Fàtima Sabench,2 Daniel Del Castillo2 1Pathology Service, University Hospital of Sant Joan. Faculty of Medicine, IISPV, “Rovira i Virgili” University, Reus, Tarragona, Spain; 2Surgery Service, University Hospital of Sant Joan, Faculty of Medicine, IISPV, “Rovira i Virgili” University, Reus, Tarragona, Spain; 3Pathology Service, University Hospital of Joan XXIII, Faculty of Medicine, IISPV, “Rovira i Virgili” University, Reus, Tarragona, SpainCorrespondence: Daniel Del CastilloHead Surgery Department, Hospital Universitari Sant Joan, Facultat de Medicina, U.R.V., Reus, SpainEmail fatima.sabench@urv.catPurpose: The cellular distribution of ghrelin positive cells is not well defined. The aim of the study is to quantify and determine the distribution of ghrelin cells in gastric mucosa in patients with morbid obesity and relate this finding to gender, comorbidities, gastritis, and plasmatic levels of acyl and desacylghrelin before and after laparoscopic sleeve gastrectomy.Patient and Methods: We performed a study on 61 patients with BMI≥ 50 kg/m2 operated by laparoscopic sleeve gastrectomy. Three gastric regions were analyzed by histopathology and immunohistology. Blood sample was taken before surgery, and at 6 and 12 months post-surgery, to study the plasma levels of ghrelin isoforms.Results: Ghrelin cells are present in all regions of the gastric mucosa, with a greater number in the body and the fundus. Difference was found in the antrum between male and female patients (p=0.018). Patients with arterial hypertension also showed a lower level of cells in antrum (p< 0.05). Acylghrelin levels after surgery were significantly lower (32.83+5.6 pg/mL to 10.09+11.8 pg/mL, p< 0.05). Values of desacylghrelin tended to decrease but no significant variation was observed (207.4+39.3 pg/mL to 188.84+52.3 pg/mL).Conclusion: Our patients show ghrelin cells in all areas of the stomach. Gender, comorbidities, and gastritis are determinant on gastric ghrelin-producing cells distribution.Keywords: ghrelin, cells, obesity, gastric, laparoscopic surgery

El linfoma testicular primario es un tumor testicular infrecuente, suponiendo no más del 9% de los tumores testiculares en las series con mayor incidencia; a su vez el linfoma testicular como tumor hematopoyético es infrecuente, con una incidencia del 1% de los linfomas, pero debido a su histopatología en la mayoría de los casos de alta malignidad, les hace ser de los tumores testiculares más agresivos. La edad de aparición es por encima de los 60 años, convirtiéndose en el tumor más frecuente para este grupo de edad. La falta de series amplias, hace que no exista un protocolo establecido para el tratamiento de esta patología. Presentamos un nuevo caso, realizando revisión de la bibliografía presentando las tendencias terapéuticas actuales para este tipo de patología.

10.1016/j.diagmicrobio.2013.05.011

10.1111/myc.12064 We have evaluated the virulence of two clinically relevant species of Curvularia; Curvularia spicifera and C. hawaiiensis, using an experimental model of disseminated infection in immunocompromised mice. Several inocula were tested over a range 1 × 103-1 × 106 colony-forming units/animal. Both species had a similar behaviour, producing a high mortality. Tissue burden and histopathology studies demonstrated that lung was the organ most affected.

A controlled study in the rabbit eye was performed to clarify the suitability of collagen shields in accelerating the wound healing process in damaged cornea. After a standardized bilateral keratectomy, the spontaneous evolution of the healing process in the right eye (control eye) was compared with the evolution in the left eye, treated with a collagen shield (a shield of the 12- or 24-h type). The healing area was measured by planimetry after fluorescein staining at 0, 24, 48, and 72 h after keratectomy. Histological and immunohistochemical analysis of the healing process was also performed. Reepithelization of the damaged cornea was almost complete at 72 h, and there were no differences in the time course of the healing process between control and treated eyes. There was an important polymorphonuclear infiltration in treated eyes, mainly composed of eosinophiles, which was not present in control eyes. This indicates a subacute inflammatory immunological reaction. It is concluded that the usefulness of collagen shields should be reappraised, especially in injured corneas.

OBJECTIVES The aim of the study is to analyze the utility of ultrasound in the evaluation and treatment selection of patients with benign prostatic hyperplasia (BPH). METHODS A total of 5000 patients older than 50 years and with prostatic symptoms were evaluated with abdominal ultrasound and in selected cases with transrectal ultrasound. RESULTS The first ultrasonographic sign of BPH is the increase of anteroposterior and longitudinal diameters. Prostatic volume is measured with a safety of 80%, post-void volume and indirect signs of bladder obstruction are also determined by ultrasound. Upper urinary tract pathological conditions can be also detected. CONCLUSIONS Ultrasound associated with PSA and urinary flow are adequate to evaluate and select treatment in patients with BPH.

Objetivo: Revisar la incidencia de Neoplasia Intraepitelial Prostática (PIN) y Atípia Glandular Focal (AGF) en primera biopsia, el riesgo de estos pacientes de padecer cáncer en biopsias sucesivas y qué importancia se concede a estos hallazgos analizando con qué frecuencia son rebiopsiados estos pacientes y cuánto tiempo después del hallazgo inicial. Método: Estudio retrospectivo sobre 6.000 pacientes biopsiados entre 1994 y 2002. No se han incluido pacientes con diagnóstico previo de cáncer. De los 6.000 pacientes 861 se han rebiopsiado en alguna ocasión sumando en conjunto 7.127 biopsias. Se ha realizado un estudio descriptivo que incluye los porcentajes y percentiles para variables cualitativas y medidas de tendencia central para las variables cuantitativas continuas. Resultados: La incidencia de cáncer en la primera biopsia fué del 39,1%. Las cifras de PIN o AGF se mantienen estables o aumentan progresivamente desde un 2 y 2,1% respectivamente en la primera biopsia hasta más del 6% en la cuarta y quinta biopsia. La media de tiempo entre biopsias en el caso de encontrar AGF o PIN en el diagnóstico inicial es de 180± 221,6 y 264±213,8 días respectivamente. Sólo el 42 y el 40% de pacientes con diagnóstico inicial de PIN o AGF se rebiopsian, encontrando finalmente un 45 y un 40% de tumores en las posteriores biopsias respectivamente. Conclusión: La presencia de PIN o AGF implica un mayor riesgo de cáncer en biopsias posteriores; a pesar de ello menos de la mitad vuelven a biopsiarse. La realización de dos biopsias posteriores o una biopsia ampliada localiza la mayoría de los tumores asociados. Objective: To review the incidence of PIN and Atypical Small Acinar Proliferation (ASAP) on first biopsy, the risk to find cancer on following biopsies and what is the importance given to this findings, analizing how frequently and how long after the initial finding this patients are rebiopsied. Method: We selected 6000 patients who underwent TRUS biopsy between 1994 and 2002. Patients with prior cancer diagnosis were not included. 861 of them underwent more than one biopsy, adding up to a total of 7127 biopsies. A descriptive study has been done including percentages and percentiles for qualitative variables, mean and median for continuous variables. Results: Incidence of cancer on the first biopsy was 39,1% .PIN and ASAP are stable or slightly increase from 2 and 2,1% respectively on the first biopsy to more than 6% on the fourth and fifth ones. Mean time between biopsies when ASAP or PIN are the initial findings is 180± 221,6 and 264±213,8 days respectively. Just 42 and 40% of patients with prior PIN or ASAP diagnose are rebiopsied. On subsequent biopsies 45 and 40% of cancers were respectively found. Conclusions: Presence of PIN or ASAP implies a higher cancer risk on subsequent biopsies; in spite of that, less than half of them are biopsied again. Performing two more biopsies or an amplified biopsy can find most of the tumors associated.

El tumor de células renales supone el 1% de los tumores del adulto, mientras que el carcinoma transicional tiene una incidencia del 7%. La aparición simultánea de un carcinoma de células renales, y un tumor transicional de pelvis en el mismo riñón, suponen un hecho excepcional no existiendo más de 30 casos publicados en el mundo, presentando una incidencia aproximada del 0,14% de la patología tumoral renal. Presentamos un nuevo caso de esta inusual asociación que supone el 4 caso referenciado en la literatura en español. The renal cell tumour supposes 1% of the adult’s tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish.

La incidencia de neoplasias retroperitoneales primitivos varía del 0,3 al 3%. Los sarcomas suponen el grupo mas frecuente de neoplasias retroperitoneales, siendo el Schwannoma un tumor inusual con una incidencia del 1% al 5% del los tumores retroperitoneales primarios. El schwannoma también denominado neurinoma o neurolenoma, es un tumor derivada de las células de Schwann de los nervios periféricos. Se caracteriza por su inespecificidad clínica y radiológica, siendo el diagnostico patológico, con intensa positividad inmunohistoquímico a la proteína S-100. El tratamiento de elección es la exéresis quirúrgica, con márgenes amplios; no estando descrito casos de malignización ni de metástasis a distancia, pero si la existencia de recurrencia a nivel local probablemente secundaria a resección incompleta. The incidence of retroperitoneal primitive tumour varies from the 0,3 to 3%. The sarcomas suppose the group but it frequents of retroperitoneal tumour, being the Schwannoma an unusual tumour with an incidence from 1% to 5% of the retroperitoneal primary tumours. The schwannoma also denominated neurinoma or neurolenoma, it is a derived tumour of the cells of Schwann of the outlying nerves. It is characterized by their clinical and radiological inespecify, being the diagnose pathological, with intense positive inmunohistoquimics to the protein S-100. The election treatment is the surgical remove, with wide margins; not being described cases of malignización neither of metastasis at distance, but if the recurrence existence at probably secondary local level to incomplete resection.

OBJETIVO: La neuromodulacion de raíces sacras es una técnica eficaz para el tratamiento de la Disfunción Miccional Crónica (DMC), refractaria a tratamientos convencionales. En la actualidad están surgiendo nuevas indicaciones en el ámbito urológico, como el dolor pélvico crónico y la cistitis intersticial. Diversos grupos de cirujanos digestivos están optando por esta técnica para el tratamiento de patología rectal (estreñimiento, disfunción esfinteriana). Este trabajo aporta nuestra experiencia en el tratamiento de pacientes con DMC y los resultados comparativos al año del implante de todos los pacientes. MATERIAL Y MÉTODOS: Desde diciembre de 1998 a julio del 2003 hemos realizados 18 implantes definitivos de neuromodulacion. La indicación principal fue la DMC, en un 62,5% de los pacientes. El seguimiento de los pacientes lo realizamos al mes, tres meses, y posteriormente cada seis meses. Este se realiza mediante diario miccional y cuestionario de calidad de vida. El implante del electrodo en los 16 primeros pacientes se ha realizado mediante cirugía abierta, mientras que los 2 siguientes se ha colocado el electrodo mediante técnica percutánea, utilizando el kit "Tined Lead". RESULTADOS: Comparamos resultados al año del implante en todos los pacientes. Se han realizado 18 implantes de neuromodulación de los cuales 14 (77,7%) han sido en mujeres y 4 (22,3%) en varones. La edad media es de 52,56 años. La indicación del implante en un 72,2% de los pacientes fue por DMC, un 22,1% por incontinencia mixta (urinaria y fecal), y un 5,5% fue por cistopatía intersticial. La mejoría de los síntomas al año del implante, medidos por el calendario miccional y el cuestionario de calidad de vida fue de 76,4%. La mejoría clínica fue mayor en los pacientes con síntomas de urgencia, que los pacientes con predominio de la sintomatología de vaciado. OBJECTIVE: Sacral root neuromodulation is an effective technique for the treatment of Chronic Micturition Dysfunction (CMD) refractory to conventional therapy. New indications such as chronic pelvic pain and interstitial cystitis are currently making their way within the urologic setting. Several groups of gastric surgeons are now choosing this technique for the management of rectal diseases (constipation, sphincter dysfunction). This paper contributes our experience in the treatment of patients with CMD and the comparative results at one year from implant in all patients. MATERIAL AND METHODS: From December 1998 through July 2003, 18 neuromodulation definite implants were performed. The main indication was CMD in 62.5% patients. Follow up of patients was done at one month and three months, and every six months thereafter. Follow up is conducted through a micturition diary and QoL questionnaire. Electrode implant in the first 16 patients was achieved by open surgery. The next 2 patients had the electrode placed by a percutaneous technique using the "Tined Lead" kit. RESULTS: Results at one year after implant were compared in all patients. The total number of neuromodulation implants placed was 18, 14 (77.7%) of which were women and 4 (22.3%) men. Mean age was 52.56 years. Implant indication was CMD in 72.2% patients, mixed incontinence (urinary and faecal) in 22.1%, and interstitial cystic disease in 5.5%. Symptoms improvement at one year from implant, as determined by a micturition diary and QoL questionnaire was 76.4%. Clinical improvement was greater in patients with urgency symptoms than in patients with predominance of voiding symptoms.

La enfermedad renal quística adquirida (E.R.Q.A), es un factor de riesgo para el desarrollo de carcinoma renal en los riñones propios, tras el trasplante renal (T.R.). El desarrollo de un tumor primitivo del injerto renal es infrecuente. De otro lado, la incidencia de tumor primitivo en el injerto renal es infrecuente, pero la presencia de metástasis en el de un tumor epitelial es excepcional, siendo este el segundo caso de literatura de metástasis de tumor epitelial en injerto renal; y el primer caso descrito de metástasis de carcinoma de células renales (C.C.R.), sobre injerto renal. El caso de un paciente con TR normofuncionante y ERQA que desarrolla CCR en riñón propio, con metástasis sobre el injerto renal. Acquired cystic renal disease (A.C.R.D.) is a risk factor for the development of renal carcinoma in the patient’s own kidney after renal transplant (R.T.). development of a primitive tumor in the renal graft is infrequent, but the presence of metastasis of an epithelial tumor is very rare. This is the second case reported in the literature of metastasis of an epithelial tumor in the renal graft and the first case described of renal cell carcinoma metastasis (R.C.C.) in the renal graft. This paper describes the case of a patient with a normally functioning renal transplant and A.C.R.D. who develops RCC in his own kidney, with metastasis in the renal graft.

The possible impact of IUGR on the intellectual outcome of children born with IUGR gives special relevance to this condition. In order to determine the psychomotor and intellectual development of such children, we analyzed the evolution of 60 children through appropriate tests, along the years, and the possible influence of two factors, the socio-economic status of the family, and whether or not there was catch-up growth. Our results show a negative impact of IUGR on the intellectual outcome of these children, independent of catch-up growth, although those with catch-up growth showed better evolution. The socio-economic status plays a limited role only at older age. Those children followed longitudinally for 1 year did not show any amelioration of their IQ.

El linfoma testicular primario es un tumor testicular infrecuente, suponiendo no más del 9% de los tumores testiculares en las series con mayor incidencia; a su vez el linfoma testicular como tumor hematopoyético es infrecuente, con una incidencia del 1% de los linfomas, pero debido a su histopatología en la mayoría de los casos de alta malignidad, les hace ser de los tumores testiculares más agresivos. La edad de aparición es por encima de los 60 años, convirtiéndose en el tumor más frecuente para este grupo de edad. La falta de series amplias, hace que no exista un protocolo establecido para el tratamiento de esta patología. Presentamos un nuevo caso, realizando revisión de la bibliografía presentando las tendencias terapéuticas actuales para este tipo de patología. Primary testicular lymphoma is an uncommon testicular tumour that accounts for no more than 9% of all testicular tumours in those series with higher incidence; testicular lymphoma as haematopoietic tumours are also rare accounting for just 1% of all lymphomas; but due to their highly malignant histopathology they may become highly aggressive tumours. Patient age at presentation is over 60 years old which makes it the most frequent tumour for this age group. There is no standard protocol to treat this malignancy due to lack of extensive series. We contribute one case and make a literature review discussing the current therapeutic trends for this disease.

OBJETIVO: Presentar un caso de recidiva de carcinoma epidermoide de pene a los 21 años de la cirugía. MÉTODO: Se trata de un paciente de 85 años con antecedentes de penectomía parcial por carcinoma epidermoide, que presenta lesión excrecente a nivel de glande de 1 mes de evolución. Se biopsia siendo el resultado carcinoma epidermoide por lo que se realiza penectomía total con uretrostomía cutánea. RESULTADO: El estudio histopatológico de la pieza confirmó un carcinoma epidermoide bien diferenciado. OBJETIVE: We report a recidive of pennis carcinoma after 21 years of surgery. METHODS: This is the case of a male of 85 years old, with parcial penectomy; by epidermoid carcinoma. In phisics exploration, that it displays excrecente lesion at level of glande of 1 month of evolution. Biopsy being the result of epidermoid carcinoma reason why is made. Total penectomy, a with cutaneus uretrostomy. RESULTS: The histopathological study of the piece, confirm a epidermoid carcinoma well differentiated.

Se presenta un nuevo caso de carcinoma renal sarcomatoide, en un varón de 67 años con recidiva locorregional a los 4 meses de la cirugía, con dos episodios de hemorragia retroperironeal tras la segunda intervención. El objetivo de este trabajo es aportar un nuevo caso y hacer una revisión de la bibliografía. We report a new case of sarcomatoid renal cell carcinoma, in a male of 67 years old, with locoregional recidive four months after first surgery, with two episodes of retroperitoneal hemorrhage after second surgery. The objective of this work is to contribute a new case and of doing one revision.

La torsión testicular en el adulto, es una nosología infrecuente aunque debe de entrar dentro del diagnostico diferencial de cualquier adulto de mas de treinta años, con cuadro de escroto agudo. El retraso e incorrecto diagnóstico, aumenta la frecuencia de orquiectomías por procesos vasculares en el adulto frente al niño. Presentamos el caso de varón de 74 años con escroto agudo, y revisión de la literatura. Testicular torsion in adult, is an uncomunly etiology, but we should make diferencial diagnostic in every person over thirty years old, with accurate escrotum. The wrong diagnostic gives up the incidence orchiectomy in adults for vascular etiology. We report a male of 74 years old with acurate escrotum andreview ofthe literature

OBJETIVO: Presentar el caso de una metástasis renal solitaria secundaria a hepatocarcinoma. MÉTODO: Describimos el caso de un paciente de 51 años que en ecografía abdominal se descubre incidentalmente una masa renal izquierda y una masa hepática. En el TAC se objetivó la masa renal izquierda de 17 cm de diámetro con posible afectación de vena renal izquierda y una masa hepática en lóbulo derecho. La PAAF guiada por TAC de ambas masas demostró en hígado celularidad maligna compatible con hepatocarcinoma, y en riñón celularidad maligna compatible con carcinoma renal o suprarrenal. Se indicó tratamiento quirúrgico con nefrectomía radical izquierda más hepatectomía derecha. RESULTADO: El análisis histopatológico de la pieza mostró hepatocarcinoma trabecular moderadamente diferenciado con metástasis ganglionar y renal izquierda. OBJECTIVE: To report the case of a solitary renal metastasis secondary to hepatocellular carcinoma. METHODS: We report the case of a 51 year old patient who on abdominal ultrasonography was revealed a left renal tumour and a hepatic mass incidentally. A TAC showed the left renal tumor measuring 17 cm in size, possible involvement of left renal vein and a tumour mass in the right lobe of the liver. A TAC guided fine needle punction aspiration biopsy demonstrated a malignant hepatic lesion compatible with hepatocarcinoma, and malignant renal cells compatible with renal or adrenal carcinoma. Left radical nephrectomy and right hepatectomy was performed. RESULTS: Histopathologic study confirmed the diagnosis of moderately differentiated trabecular hepatocarcinoma with lymph node and left renal metastasis.

Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a reversible cholinesterase inhibitor, was effective in the treatment of Alzheimer's disease (AD). In turn, desferrioxamine (DFO), a chelating agent with ability to chelate iron and aluminum (Al), produced a 50% decrease in the rate of cognitive decline in patients with AD. Since combined therapy with tacrine and DFO might be more effective than individual administration of these drugs for the treatment of AD patients, this study evaluated the toxic effects of concomitant administration of tacrine and DFO to rats. Three groups of 8 rats each received the following treatments for 8 w: 80 mg DFO/kg/d i.m., 7.5 mg tacrine/kg/d po, or 80 mg DFO/kg/d i.m. +7.5 mg tacrine/kg/d po. A control group received distilled water by gavage daily and a 0.9% saline injection i.m. The administration of DFO + tacrine for 8 w did not increase most of the side effects caused by the individual DFO or tacrine administrations. These results open the possibility of considering the effectiveness of simultaneous administration of DFO and tacrine as a palliative treatment for AD patients.

The corneal wound-healing properties of fibronectin (FN) and a fibronectin hydrolysate (FNH) have been evaluated in comparison with commonly used drugs. Nonpenetrating bilateral surgical keratectomy was performed in male albino rabbits. The left eye was treated with the active product, whereas the right eye served as a control (vehicle). The healing area was measured by planimetry after fluorescein staining at 0, 24, 48, and 72 h after keratectomy. Histological and immunohistochemical analysis of the healing process was also performed. Results were as follows: (a) Nandrolone (p < 0.005) and asiaticoside (p < 0.001), both at 10 mg/ml, in eyedrops delayed the healing process. (b) An ointment containing vitamin A and amino acids also delayed the process but at the limit of statistical significance (p = 0.055). (c) FNH (20-80 mg prot/ml) significantly improved the quality and shortened the time of the healing process at 60 mg prot/ml and above. (d) Human FN (100-800 micrograms/ml) did not affect the healing process. Immunohistochemical analysis demonstrated that FNH accelerated the appearance of endogenous FN in the damaged cornea earlier than in the control eyes. It is concluded that FNH may be useful in the management of corneal wounds, whereas the effectiveness of FN is doubtful.

Forty-eight girls with Turner's syndrome were assigned to one of three treatments; recombinant human growth hormone (rhGH) alone, rhGH plus oxandrolone, and rhGH plus ethinyloestradiol. Treatment with rhGH alone or in combination with oxandrolone induced catch-up growth. Older girls treated with rhGH plus ethinyloestradiol showed less marked improvement. The gain in height was associated with a gain in bone diameter and cortical thickness (reflecting increased bone mass). There was a rapid loss of subcutaneous fat. These effects of growth hormone are similar to those observed in patients with growth hormone deficiency.

In this paper, we review the etiological, clinical and evolutive aspects of patients with fever of unknown origin (FUO) whose hepatic biopsy showed the presence of granulomas (GH). This is retrospective study covering a period of 10 years (1982-1991). The clinical records of all the patients hospitalized due to FUO (n = 71) and of all those in whose hepatic biopsy the presence of GH (n = 70) was documentated, were reviewed. Thirty patients fulfilled both criteria: FUO + GH. In our environment, Q Fever is the most frequent cause of FUO and GH in patients without infection by the HIV. On the contrary, in patients infected by HIV, the most frequent etiology is tuberculosis.

Background: Androgen receptor (AR) gene mutations are the most frequent cause of 46, XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). Objective: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46, XY DSD in a series of Spanish patients. Setting: We studied a series of 133 index patients with 46, XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. Methods: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. Results: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. Conclusions: AR gene mutation is the most frequent cause of 46, XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel. (J Clin Endocrinol Metab 95: 1876-1888, 2010)