Reduction of cardiac TGFß-mediated profibrotic events by inhibition of Hsp90 with engineered protein.

Myocardial fibroblast activation coupled with extracellular matrix production is a pathological signature of myocardial fibrosis and is governed mainly by transforming growth factor TGFß-Smad2/3 signaling. Targeting the ubiquitous TGFß leads to cellular homeostasis deregulation with adverse consequences. We previously showed the anti-fibrotic effects upon downregulation of 90-kDa heat shock protein (Hsp90), a chaperone that associates to the TGFß signaling cascade. In the present study, we use a fluorescent-labeled Hsp90 protein inhibitor (CTPR390-488) with specific Hsp90 binding properties to reduce myocardial pro-fibrotic events in vitro and in vivo. The mechanism of action involves the disruption of TGFßRI-Hsp90 complex, resulting in a decrease in TGFß signaling and reduction in extracellular matrix collagen. In vivo, decreased myocardial collagen deposition was observed upon CTPR390-488 treatment in a pro-fibrotic mouse model. This is the first study demonstrating the ability of an engineered Hsp90 protein inhibitor to block collagen expression, reduce the motility of myocardial TGFß-activated fibroblasts and ameliorate angiotensin-II induced cardiac myocardial fibrosis in vivo.

Diagnostic reference levels and complexity indices in interventional radiology: a national programme.

OBJECTIVES: To propose national diagnostic reference levels (DRLs) for interventional radiology and to evaluate the impact of the procedural complexity on patient doses. METHODS: Eight interventional radiology units from Spanish hospitals were involved in this project. The participants agreed to undergo common quality control procedures for X-ray systems. Kerma area product (KAP) was collected from a sample of 1,649 procedures. A consensus document established the criteria to evaluate the complexity of seven types of procedures. DRLs were set as the 3rd quartile of KAP values. RESULTS: The KAP (3rd quartile) in Gy cm2 for the procedures included in the survey were: lower extremity arteriography (n = 784) 78; renal arteriography (n = 37) 107; transjugular hepatic biopsies (THB) (n = 30) 45; biliary drainage (BD) (n = 314) 30; uterine fibroid embolization (UFE) (n = 56) 214; colon endoprostheses (CE) (n = 31) 169; hepatic chemoembolization (HC) (n = 269) 303; femoropopliteal revascularization (FR) (n = 62) 119; and iliac stent (n = 66) 170. The complexity involved the increases in the following KAP factors from simple to complex procedures: THB x4; BD x13; UFE x3; CE x3; HC x5; FR x5 and IS x4. CONCLUSIONS: The evaluation of the procedure complexity in patient doses will allow the proper use of DRLs for the optimization of interventional radiology. KEY POINTS: • National DRLs for interventional procedures have been proposed given level of complexity • For clinical audits, the level of complexity should be taken into account. • An evaluation of the complexity levels of the procedure should be made.

Correlative 3D cryo X-ray imaging reveals intracellular location and effect of designed antifibrotic protein-nanomaterial hybrids.

Revealing the intracellular location of novel therapeutic agents is paramount for the understanding of their effect at the cell ultrastructure level. Here, we apply a novel correlative cryo 3D imaging approach to determine the intracellular fate of a designed protein-nanomaterial hybrid with antifibrotic properties that shows great promise in mitigating myocardial fibrosis. Cryo 3D structured illumination microscopy (cryo-3D-SIM) pinpoints the location and cryo soft X-ray tomography (cryo-SXT) reveals the ultrastructural environment and subcellular localization of this nanomaterial with spatial correlation accuracy down to 70 nm in whole cells. This novel high resolution 3D cryo correlative approach unambiguously locates the nanomaterial after overnight treatment within multivesicular bodies which have been associated with endosomal trafficking events by confocal microscopy. Moreover, this approach allows assessing the cellular response towards the treatment by evaluating the morphological changes induced. This is especially relevant for the future usage of nanoformulations in clinical practices. This correlative super-resolution and X-ray imaging strategy joins high specificity, by the use of fluorescence, with high spatial resolution at 30 nm (half pitch) provided by cryo-SXT in whole cells, without the need of staining or fixation, and can be of particular benefit to locate specific molecules in the native cellular environment in bio-nanomedicine.

Urachal adenocarcinoma with late brain metastases.

OBJECTIVE: To describe a case of urachal adenocarcinoma with late brain metastases in a sixty one year old man who presented abdominal discomfort and hematuria during six months. METHODS: The clinical suspicion was bladder tumor and diagnostic studies were performed (urinary cytology, cystoscopy, abdominal ultrasound and abdominopelvic CT scan). Surgical treatment was performed. RESULTS: Negative urinary cytology. Cystoscopy showed a lesion with infiltration of the bladder dome. Ultrasound and CT scan showed a five centimeter rounded lesion, with intermediate density, internal echoes and calcifications on the anterior supravesical middle line, that infiltrated the bladder. The extension study had not findings. Partial cystectomy and lymphadenectomy were performed. The histopathologic diagnosis was mucin-secreting urachal adenocarcinoma. After five years without disease the patient suffered lung and brain metastases. CONCLUSIONS: Urachal adenocarcinoma is a tumor which must be distinguished of primary bladder adeno-carcinoma. The mucing-secreting adenocarcinoma can be associated with calcifications that can be demostrated on imaging studies. Late metastases without signs of local recurrence (after five years without disease) are an infrequent clinical-pathologic finding.

[Obstructive uropathy secondary to vesico-ureteral endometriosis: clinical, radiologic and pathologic features]. / Uropatía obstructiva secundaria a endometriosis vésico-ureteral: características clinico-radiológicas y anatomopatológicas.

OBJECTIVES: To report the case of a 37 year-old woman suffering from endometriosis of the urinary tract, that presented with lumbar and pelvic pain associated to cyclic recurrent haematuria. METHODS: Following history, physical examination, abdomino-pelvic ultrasound (USS), CT scan and cystoscopy with biopsies, surgical treatment was indicated RESULTS: Imaging (USS-CT ) revealed a protrusion of the left bladder hemi-trigone with a nodular, irregular thickening and ipsilateral grade II-III/IV uretero-hydronefrosis. Cistoscopy confirmed a swollen and oedematous lesion in left hemi-trigone that seemed extrinsic in origin. With the clinical diagnosis of a possible neoplasia of gynaecological origin, the patient underwent surgical treatment consisting in radical hysterectomy with bilateral oophorectomy, partial cystectomy and left ureteroneocystostomy. CONCLUSIONS: The frequency of endometriosis in the urinary tract is relatively low and therefore, endometriosis presenting with ureteral obstruction (uretero-hydronephrosis) has been rarely reported in the literature and should be part of the differential diagnosis in young women, especially if symptoms are cyclic. The treatment is surgery and the final diagnosis by pathology report.

[Comparison of diferents suburethral slings for the treatment of stress urinary incontinence]. / Estudio comparativo de diferentes procedimientos de sling suburetral para el tratamiento de la incontinencia urinaria de esfuerzo.

OBJECTIVES: To compare the results of the different procedures of sling suburetral used in our service (TVT, Sparc, IVS, Obtape and Monarc) for the treatment of the female urinary incontinence. MATERIAL AND METHODS: 96 patients retrospective analysis affects of female urinary incontinence and subjected to different procedures of sling suburethral without tension. The half age: 56.1 +/- 10.7 years. 75 patients were intervened by means of procedures retropubics (48 TVT, 17 Sparc, 10 IVS) and 21 with obturators (10 Obtape, 11 Monarc). The half time of pursuit: 26.3 +/- 12.7 months (29.4 months for the methods retropubics and 11.7 for the obturators). The analyzed variables were: age, obesity, grade of previous incontinence, type of used procedure, time of pursuit, and previous surgical procedures. We compare the complications and the results obtained with the different ones technical. RESULTS: the cure percentage was of 95.7%. 7 patients presented complications: one intestinal perforation, two bladders perforations, one erosion of vaginal wall, three incontinences of novo urgency. In 6 cases the stress incontinence persists. When analyzing the association between the diverse variables and the success, we appreciate that the variables with value presage were the age and the obesity (P < 0.05) not observing relationship with the technique employeed. CONCLUSIONS: The existence of multiple surgical approachs and a varied auxiliary materials allow each surgeon to choose that with the one that is more familiarized and comfortable without, seemingly, influence it in the results.

[Treatment of males with post-prostatectomy stress urinary incontinence by a mesh anchored to the ischio-pubic bones]. / Tratamiento de la incontinencia urinaria de esfuerzo post-prostatectomía radical mediante malla anclada a ramas isquiopubianas.

We presented the results of an alternative in the treatment of the stress urinary incontinence of male radical postprostatectomy. Is a technique of renewed interest in the last years, cradle in the procedure of Stamey, consisting of placing an on guard suburetral polypropylene mesh, anchored by means of screws to the isquiopubian branches. We have applied the procedure in 4 patients and with stress urinary incontinence of long evolution. After an average pursuit of 12.5 months, two patients present total continence, one has improved significantly and in the other the incontinence persists. There have been no postoperating complications nor rejection of the mesh. From these preliminary results and the reviewed bibliography, we thought that this technique can constitute an alternative to the artificial urinary sphincter, dices its clinical results, its facility of execution, the good tolerance and his low cost.

[Urological attendance in the Integral Health Center "Alto Palancia": model of primary-specialized integration and unique consultation]. / La asistencia urológica en el Centro Sanitario Integral "Alto Palancia": modelo de integración primaria-especializada y consulta única.

INTRODUCTION AND OBJECTIVE: The progressive increase in the demand of urological attendance demands to establish new welfare models that avoid the saturation of consultations and improve the quality in the attention to the user. The objective of this work is to analyze the improvement of the welfare activity developed in Integral the Sanitary Center Alto Palancia, after the restoration of new welfare models based on integration between Attention Primary and Specialized and the putting in practice of the denominated Unique Consultation. MATERIAL AND METHODS: We analyzed the characteristics of the Center, functions and activity of the specialty developed during year 2002. We described to the application of the model of Unique Consultation and the elements of integration with Primary Attention. We analyzed the improvement of the activity through indicators, that we compared with preceding years. In order to determine the degree of satisfaction of the users we made a survey of opinion of patients and/or taken care of relatives in the Center under the new welfare models. Finally we analyzed the advantages that the applied process presents for the patient and the own sanitary institution. RESULTS: 42% of patients have been taken care of by means of the model of Unique Consultation, being the predominant pathology the HBP in the man and the ITUs in the woman. The time of delay for first visit has been reduced from 49 days in single December 2001 to 3 in December 2002. Single 7.7% of patients discharged from the hospital for pursuit by Primary Attention have been sent again to the specialist. The time that the urólogo dedicates to consultations has reduced in a 29%, being this time dedicated to the accomplishment smaller surgery and final reconnaissances (echography, urodynamic studies and others). The opinion survey has shown a satisfaction of the user very elevated. CONCLUSION: The model of Integral Attention Primary-Specialized and the putting in practice of Unique Consultation applicable to the specialty of Urology, increasing the quality perceived by the user and with evident advantages for the Sanitary Organization.

[Rupture of aneurysm of anomalous hepatic artery (right unfolding)]. / Ruptura de un aneurisma de arteria hepática anómala (desdoblamiento derecho).

Un uncommon case of aneurysm located in an aberrant hepatic artery is described. It was the cause of massive hemoperitoneum. It was treated by ligation and excision without post-operative complications. In spite of the complex vascular malformation, there was no hepatic insufficiency. We have not been able to find a similar case in the literature.

[Anterograde insertion of ureteral catheter]. / Inserción anterógrada de catéter ureteral.

We report twenty-four patients with urinary obstruction, in which twenty-seven antegrade ureteral stent (double J) insertions were attempted (in six patients the obstruction was bilateral and in three other patients we failed). In all of them access to the urinary tract was through a nephrostomy catheter, in seventeen cases we proceeded to insert the antegrade catheter immediately after percutaneous nephrostomy and in ten remaining cases we achieved in a second try after carrying nephrostomy and failing a conventional retrograde approach to ureteral stent insertion. We got a 90-per cent success rate. A case of perirrenal hematoma occurred after applying a nephrostomy. It was the only relevant complication. In conclusion we consider that the antegrade ureteral stent insertion is a good alternative when, under several circumstances, the conventional retrograde insertion fails.

[Tuberous angioma of the glans penis: treatment with laser and local anesthesia]. / Angioma tuberoso del glande del pene: tratamiento con láser y anestesia local.

A case of angioma tuberous of the glans penis treated with Neodymiun:Yag laser under local anesthesia in a eleven-years-old outpatient is reported. These lesions are extremely rare. Local excision of this tumor was accepted treatment, but we think that laser treatment (Neodymiun:Yag) is far superior to surgical excision and we think this treatment of choice. The particularity of the case we report, is aside the rarity, the possibility of treatment in an outpatient child, with local anesthesia and excellent tolerance.

[Retroperitoneal germ cell tumor]. / Tumor de células germinales retroperitoneal.

We report a case of retroperitoneal extragonadal germ-cell tumor in an 17 years old patient who presented with aedema and pain in left inferior extremity asociated with hemopthysis caused by pulmonar metastasis, who was treated with chemotherapy and resection of residual mass and pulmonary nodes. Dyagnosis was stableshed by fine neadle aspiration biopsy of the wass. We comment on the difficult of stableshing differential dyagnosis between retroperitoneal extragonadal germ-cell tumor and metastasis of a testicular tumor. Dyagnosis is stableshed by the finding of a histologically malignant germ-cell tumor with normal testis. We considered physical examination and ecographyc exploration enough for a correct dyagnosis.

[Unusual bladder tumors: primary epidermoid carcinoma, adenocarcinoma, and sarcoma. Clinical behavior. Our experience]. / Tumores vesicales inusuales: carcinoma epidermoide, adenocarcinoma y sarcoma primarios. Comportamiento clínico. Nuestra experiencia.

INTRODUCTION AND OBJECTIVES: Non-transitional cell tumours of the bladder are both a diagnostic challenge for the pathologist and a therapeutic challenge for the urologist, because although uncommon (less than 5% of all malignancies of the bladder) they show different biological behaviours each requiring a unique approach. The most significant pathoanatomical types are: primary epidermoid carcinoma, primary adenocarcinoma and primary sarcoma. This paper presents an analysis of our experience in these types of tumours. MATERIAL AND METHODS: A retrospective study of unusual cases of cancer of the bladder seen in our hospital between 1988-2001. Their biological behaviour and the therapies applied are analysed. The extravesical origin of the tumour was ruled out in all cases. RESULTS: We found 21 cases of the following pathoanatomical varieties: 13 epidermoid carcinomas, 7 adenocarcinomas (3 urachal) and 1 sarcoma. Mean age was very different between epidermoid carcinomas (69.2 +/- 9.1 years) and adenocarcinomas (50.3 +/- 8.1). Tumour behaviour was very aggressive in all three histological varieties. At the time of diagnosis 19 patients had locally advanced stages (> or = T2). Although elective therapy was cystectomy, this was only feasible in 10 cases. Systemic chemotherapy (most frequently M-VAC) and/or local radiotherapy was used in 7 cases. 14 patients have died after a mean survival of 15.7 +/- 11.6 months. CONCLUSIONS: Late diagnosis of these tumours and their aggressive biological behaviour involve a gloomy prognosis. Only early diagnosis and radical therapy could improve the prognosis.

[Cystic lymphangioma of the adrenal gland in adults. Review of the literature and report of a new case]. / Linfangioma quístico de la glándula suprarrenal del adulto. Revisión de la literatura y aportación de un nuevo caso.

Presentation of one case of cystic lymphangioma of the suprarenal gland in a 34-year-old female patient with a background of lower urinary tract infections, presenting with continuous and aggravating pain in left lumbar area and with no other associated symptomatology, diagnosed with ultrasound, IVU and CAT. A review of the literature is made. The present study pretends to give an overall view of a rare and benign disease, commenting upon the difficulties found in its diagnosis and the different therapeutical options.

[Severe hematuria caused by radiation cystitis. Selective percutaneous embolization as an alternative therapy]. / Hematuria grave debida a cistitis rádica. Embolización percutánea selectiva como alternative terapéutica.

Post-radiotherapy cystitis is a high morbidity entity that involves difficult-to-treat haematurias and sometimes results in death. Percutaneous arterial embolization is an accepted approach for haemorrhages of pelvic origin. Selective, percutaneous embolization of both vesical arteries could be an alternative treatment to control severe haematurias caused by radiation. Presentation of our experience in two cases and proposal of this approach as a valid option in post-radiotherapy haemorrhagic cystitis.

[Malignant mesothelioma of the tunica vaginalis of the testis]. / Mesotelioma maligno de la túnica vaginal del testículo.

We report a case of malign mesothelioma of the tunica vaginalis of testis in a 84 years-old male. Clinical presentation was hydrocele. Special attention is given to differential diagnosis and therapeuticals possibilities.

Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study.

BACKGROUND: Dietary supplement use is increasing, but there are few comparable data on supplement intakes and how they affect the nutrition and health of European consumers. The aim of this study was to describe the use of dietary supplements in subsamples of the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Specific questions on dietary supplement use were asked as a part of single 24-h recalls performed on 36,034 men and women aged 35-74 years from 1995 to 2000. RESULTS: Between countries, the mean percentage of dietary supplement use varied almost 10-fold among women and even more among men. There was a clear north-south gradient in use, with a higher consumption in northern countries. The lowest crude mean percentage of use was found in Greece (2.0% among men, 6.7% among women), and the highest was in Denmark (51.0% among men, 65.8% among women). Use was higher in women than in men. Vitamins, minerals or combinations of them were the predominant types of supplements reported, but there were striking differences between countries. CONCLUSIONS: This study indicates that there are wide variations in supplement use in Europe, which may affect individual and population nutrient intakes. The results underline the need to monitor consumption of dietary supplements in Europe, as well as to evaluate the risks and benefits.

Common bile duct stones after laparoscopic cholecystectomy and its treatment. The role of ultrasound and intravenous and intraoperative cholangiography.

In the present work we recount our experience in handling common bile duct stones (CBDS) in our first 100 cases of laparoscopic cholecystectomy. In the first 50 cases our diagnostic procedures involved the use of ultrasound exploration and intravenous cholangiotomography 48 h before laparoscopic surgery. We found three cases of residual CBDS. One of the cases was treated by means of ERCP. The other two cases were resolved by carrying out a transparietohepatic cholangiography after the ERCP procedure failed. After this experience, we changed our strategy, introducing the intraoperative cholangiography in the cases with an unclear diagnosis. With this new approach, no residual CBDS occurred in the following 50 cases. These findings demonstrate the following: (1) In our hands, intravenous cholangiography is not more effective than ultrasound exploration in resolving dubious cases. (2) These dubious cases are more effectively diagnosed by means of selective intraoperative cholangiography. (3) When CBDS is treated by transparietohepatic cholangiography it proves to be less uncomfortable for the patient than ERCP and, as we found, even more efficient in removing the stones, although our experience is based on only two cases.