Local analysis of strains and rotations for macromolecular electron microscopy maps.

Macromolecular complexes perform their physiological functions by local rearrangements of their constituents and biochemically interacting with their reaction partners. These rearrangements may involve local rotations and the induction of local strains causing different mechanical efforts and stretches at the different areas of the protein. The analysis of these local deformations may reveal important insight into the way proteins perform their tasks. In this paper we introduce a method to perform this kind of local analysis using Electron Microscopy volumes in a fully objective and automatic manner. For doing so, we exploit the continuous nature of the result of an elastic image registration using B-splines as its basis functions. We show that the results obtained by the new automatic method are consistent with previous observations on these macromolecules.

[Therapeutic effect of mitomycin C in the immediate postoperative period in patients with intermediate-risk non-muscle-invasive bladder tumors]. / Efecto terapéutico de mitomicina C en el postoperatorio inmediato de pacientes con tumores vesicales no músculo invasores de riesgo intermedio.

INTRODUCTION: Approximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. PATIENTS AND METHODS: A prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. RESULTS: A total of 105 patients were included. Mean follow-up was 22, 70 +/- 8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34.0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53.8% had no recurrence and 44.2% had a non-muscle-invasive recurrence and only 1 patient had a muscle-invasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. DISCUSSION: In mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.

[Use of zoledromic acid on pain control in stages M1b of prostate cancer]. / Seguridad del ácido zoledrómico en el control del dolor en el estadio M1b del cáncer de próstata.

OBJECTIVES: To probe the use of Zoledromic acid in the control of the pain due to bone methastasis of a prostate cancer. MATERIAL AND METHOD: We included in our study 37 consecutive patients diagnosed of prostate cancer who developed bone methastasis during 2005 and 2006 to whom we gave a 4 mg dose of Zoledromic acid during a mean time of 10.24 months. RESULTS: We observed a complete control of the pain in 8 of the 20 patients, and partially in 6 of those patients. We did not evaluate any adverse reaction due to this treatment. CONCLUSIONS: We still yet to know whether the administration of this treatment in the early stages of the prostate cancer could prevent or retard the appearance of bone methastasis.

[Trombosis of the dorsal penis vein (of Mondor's phlebitis). Presentation of a new case]. / Trombosis de la vena dorsal del pene (Flebitis de Mondor). Aportación de un nuevo caso.

OBJECTIVE: We present a new case of trombosis of the superficial dorsal penis vein called Penile Mondor's disease. The characteristics of the disease are reviewed and the most usual diagnostic and therapeutic methods. METHODS: The case of a 41 year old man is reviewed who consulted for pain and induration on the proximal part of the penis. RESULTS: After phisical examination and Eco-doppler was made the diagnosis of Mondor's disease. He receibed treatment with non steroidal antiinflamatories and antibiotics. CONCLUSIONS: The dorsal vein thrombosis is a rare disease with pain an induration of the dorsal part of the penis. The ethiology can be traumatic, neoplasic, excesive sexual activity or abstinence. Is necesary the diferencial diagnosis with esclerosant linphangitis and the most important imaging is the Eco-doppler. The treatment is based in non steroidal antiinflamatories and antibiotics wit infection. The local aplication of heparine can be useful and the surgery with thrombectomy and resection is for persistent cases.

[Treatment of erectile dysfunction with penile prothesis. Our experience]. / Tratamiento de la disfunción eréctil mediante el implante de prótesis de pene. Análisis de nuestra serie.

INTRODUCTION AND OBJECTIVES: The aim of this study was to review the current situation of penile prosthesis in the treatment of erectile dysfunction and to analyze the indications, degree of acceptability and complications in our experience. MATERIAL AND METHODS: From 1984 to 2003, 48 implants were inserted in men suffering from impotence due to different etiologies. The mean age was 55 years. Vascular disease, Diabetes and pelvic surgery were the most common pathologies recorded. The type of prothesis inserted were malleable inactive in 7 cases (14.58%), Jonas6, Acu-form1. Inflable active with 3 components in 19 cases (39.58%), AMS 700 plus17, Alpha2. Inflable active integrated in 5 cases (10.41%) Hydroflex4, Dynaflex1. Inflable active with 2 components in 17 cases (35.4%), Ambicor2, Mark II15. RESULTS: Infection of the prosthesis was observed in 6.25% of the cases. This infectious complication required removal of the prosthesis. 4.16% of the cases complained of mechanical failure that required change of the prosthesis. 80% of the patients were satisfied with the results. CONCLUSIONS: Penile prostheses continue to be an effective and valid therapeutic alternative in impotent. Although the complication rate is low, adequate information must be provided to the patient.

[Primary renal lymphoma in a patient with IgM monoclonal gammapathy]. / Linfoma renal primario en paciente con gammapatía monoclonal IgM.

Reports on primary renal lymphoma are scarce in the urological literature, the most part of them are secondary on a lymphomatous infiltration of the kidneys. We report the case of a 77 year old man with an incidental mass on the kidney. After radiological studies (CT), we practise nephrectomy with a pathological result of a non-Hodgking B primary lymphoma. The patient present a IgM monoclonal gammapathy who need complementary treatment with chemotherapy. A literature review on currently recommended diagnostic and treatment practices in presented.

Analysis of the interaction between the eukaryotic chaperonin CCT and its substrates actin and tubulin.

Two mechanisms have thus far been characterized for the assistance by chaperonins of the folding of other proteins. The first and best described is that of the prokaryotic chaperonin GroEL, which interacts with a large spectrum of proteins. GroEL uses a nonspecific mechanism by which any conformation of practically any unfolded polypeptide interacts with it through exposed, hydrophobic residues. ATP binding liberates the substrate in the GroEL cavity where it is given a chance to fold. A second mechanism has been described for the eukaryotic chaperonin CCT, which interacts mainly with the cytoskeletal proteins actin and tubulin. Cryoelectron microscopy and biochemical studies have revealed that both of these proteins interact with CCT in quasi-native, defined conformations. Here we have performed a detailed study of the docking of the actin and tubulin molecules extracted from their corresponding CCT:substrate complexes obtained from cryoelectron microscopy and image processing to localize certain regions in actin and tubulin that are involved in the interaction with CCT. These regions of actin and tubulin, which are not present in their prokaryotic counterparts FtsA and FtsZ, are involved in the polymerization of the two cytoskeletal proteins. These findings suggest coevolution of CCT with actin and tubulin in order to counteract the folding problems associated with the generation in these two cytoskeletal protein families of new domains involved in their polymerization.

The 'sequential allosteric ring' mechanism in the eukaryotic chaperonin-assisted folding of actin and tubulin.

Folding to completion of actin and tubulin in the eukaryotic cytosol requires their interaction with cytosolic chaperonin CCT [chaperonin containing tailless complex polypeptide 1 (TCP-1)]. Three-dimensional reconstructions of nucleotide-free CCT complexed to either actin or tubulin show that CCT stabilizes both cytoskeletal proteins in open and quasi-folded conformations mediated through interactions that are both subunit specific and geometry dependent. Here we find that upon ATP binding, mimicked by the non-hydrolysable analog AMP-PNP (5'-adenylyl-imido-diphosphate), to both CCT-alpha-actin and CCT- beta-tubulin complexes, the chaperonin component undergoes concerted movements of the apical domains, resulting in the cavity being closed off by the helical protrusions of the eight apical domains. However, in contrast to the GroE system, generation of this closed state does not induce the release of the substrate into the chaperonin cavity, and both cytoskeletal proteins remain bound to the chaperonin apical domains. Docking of the AMP-PNP-CCT-bound conformations of alpha-actin and beta-tubulin to their respective native atomic structures suggests that both proteins have progressed towards their native states.

Eukaryotic chaperonin CCT stabilizes actin and tubulin folding intermediates in open quasi-native conformations.

Three-dimensional reconstruction from cryoelectron micrographs of the eukaryotic cytosolic chaperonin CCT complexed to tubulin shows that CCT interacts with tubulin (both the alpha and beta isoforms) using five specific CCT subunits. The CCT-tubulin interaction has a different geometry to the CCT-actin interaction, and a mixture of shared and unique CCT subunits is used in binding the two substrates. Docking of the atomic structures of both actin and tubulin to their CCT-bound conformation suggests a common mode of chaperonin-substrate interaction. CCT stabilizes quasi-native structures in both proteins that are open through their domain-connecting hinge regions, suggesting a novel mechanism and function of CCT in assisted protein folding.

[Determination of NMP-22 as recurrence marker in bladder cancer. Preliminary study]. / Determinación de NMP-22 como marcador de recidivas en el cáncer vesical. Estudio preliminar.

OBJECTIVES: The present study was conducted to determine the efficacy of NMP-22 as a diagnostic test for recurrence of bladder tumors and to compare its efficacy with urine cytology. METHODS: 30 patients (25 male, 5 female), aged 41-87 years (mean 73.4), with bladder tumor were evaluated by cytology, cystoscopy and determination of NMP-22 at 3 and 6 months post-TUR of the bladder. A positive test was defined as NMP-22 greater than 10 U/ml. RESULTS: 80.7% were T1, 15.3% T2-T3, 76.8% were grade I and II, and 23.2% were grade III. NMP-22 showed a sensitivity of 69%, a specificity of 64%, a positive predictive value of 52% and a negative predictive value of 78%, using tumor recurrence at 3 and 6 months as the unit of analysis, for a recurrence rate of 36%. Cytology showed a sensitivity of 44%, a specificity of 92%, a positive predictive value of 77% and a negative predictive value of 74%. When both tests were used, we obtained a sensitivity of 87.5%, a specificity of 64.2%, a positive predictive value of 58.3% and a negative predictive value of 90%. In grade I tumors, determination of NMP-22 had a sensitivity of 100%, a specificity of 77.7%, a positive predictive value of 60% and a negative predictive value of 69%. CONCLUSIONS: NMP-22 showed an acceptable sensitivity but a low positive predictive value, therefore control cystoscopic evaluation cannot be avoided. The sensitivity and negative predictive values increased when NMP-22 and cytology are used in combination. We found NMP-22 to be a very useful marker for recurrence of low grade tumors.

[Quantification of bladder tumor antigen (BTA trak) and its correlation with bladder cancer grade and stage]. / Cuantificación del antígeno tumoral vesical (BTA trak) y su correlación con el grado y estadio del cáncer vesical.

OBJECTIVE: To analyze the efficacy of the BTA Trak test as a diagnostic marker for bladder cancer, determine its correlation with tumor grade and stage, compare its sensitivity with urinary cytology and its utility in urological conditions other than bladder cancer. METHODS: 77 patients comprised the study; 33 with bladder cancer and 44 without. A urine sample was obtained from all patients for the BTA Trak test and another three samples for urinary cytology from each of the 33 patients with bladder cancer. Of the 44 patients without bladder cancer, 36 had conditions involving the urinary tract and 8 presented conditions without urothelial involvement. The BTA Trak test was repeated three months after treatment in 11 of the patients with bladder cancer and three months after the first test in 13 patients without bladder cancer. RESULTS: Using BTA Trak threshold values of 14 U/ml as first reference and 50 U/ml as the value indicating clinical warning, these were found to be higher in 24 of 33 patients with bladder tumor (sensitivity 72.7%). By tumor stage, BTA Trak was positive in 12 of 21 pT1 (sensitivity 57%) and in 11 of 11 pT2 (sensitivity 100%). Concerning tumor grade, values were higher than threshold in 13 of 22 GI-II (sensitivity 59.9%) and 10 of 10 GIII (sensitivity 100%). Urinary cytology was positive in only 8 cases (sensitivity 24.4%). In the patients without bladder cancer, values are higher than threshold in 3 of 8 patients with urological conditions without urinary tract involvement and 14 of 36 with a probable urothelial involvement without tumor, accounting for an overall sensitivity of BTA Trak of 61.4%. The BTA Trak test three months after treatment showed lower value in 7 of 8 patients with bladder tumor and pretreatment values higher than threshold. CONCLUSIONS: The BTA Trak test is a simple quantitative method with a high sensitivity for the diagnosis of bladder tumors, especially those in the advanced stages and grades. It is superior to cytology, although it has a lower specificity, particularly in conditions with urinary tract involvement.

[Tumor bladder antigen (TBA). A new method for the diagnosis and detection of recurrence of bladder cancer]. / Antígeno vesical tumoral (BTA). Nuevo método para el diagnóstico y detección de recidiva del cáncer vesical.

OBJECTIVE: To compare the usefulness and accuracy of the BTA test versus urinary cytology. METHODS: The BTA test was performed in 45 patients distributed into three groups: group I comprised patients with hematuria of unknown origin; group II had a diagnosis of bladder cancer; and group III comprised patients who had undergone TUR for a bladder tumor and were undergoing endoscopic control evaluation. The sensitivity and specificity of each diagnostic method were determined for each group of patients. RESULTS: The BTA test showed a higher sensitivity than urinary cytology in all groups, the difference being significant for groups II and III. Its specificity, however, was lower than that of cytology in groups I and III, and similar in group II. CONCLUSION: The BTA test is a simple and useful method for the diagnosis and follow-up of bladder cancer. It has a higher sensitivity than urinary cytology, although its specificity is lower due to the higher number of false positives observed in patients with inflammatory bladder conditions. Randomized studies are warranted to determine if the accuracy of urinary cytology can be enhanced with the combined use of the BTA test which has been demonstrated to have a higher specificity.

[Squamous cell carcinoma of the prostate. Presentation of a case and review of the literature]. / Carcinoma de próstata de células escamosas. Presentación de un caso y revision de la literatura.

Presentation of one case report of squamous cells prostate carcinoma. This type of prostate tumour accounts for 0.5-1% of all prostate neoplasias and presents clinical and evolutive aspects that are different from those of prostate adenocarcinoma with a poor response to any therapy and a very poor prognosis relative to adenocarcinoma. A literature review is included.

[Leydig cell tumor in the adult]. / Tumor de células de Leydig del adulto.

Presentation of 3 cases of Leydig's cells tumour in the adult seen in our hospital over the last 10 years. They account for 3% of all testicular tumours, 20 to 25% of them appearing during the pre-puberty period. Although an isolated testicular nodule is the most frequent symptom, gynaecomastia can be found in about 30% of adult patients, as it happened in 2 of our patients. Even though no malignant case has been described in children, up to 10% of cases in adults have metastasis, this being the only demonstration of malignant behaviour in these tumours, so radical orchiectomy is the choice therapy. Certain histological and hormonal parameters may be suggestive of the aggressive behaviour of this neoplasia which, however, we have not found in our series of all whom presented a good evolution after surgery. The most common diagnostic and therapeutic approaches, based on the different characteristic of the tumour, are reviewed.

[Testicular infarction as a cause of benign intrascrotal tumor]. / Infarto testicular como causa de tumoración benigna intraescrotal.

OBJECTIVES: We report on a patient with an increase in testicular size that had been initially diagnosed as neoplasm. METHODS: The ultrasound and histological findings, the atypical clinical features and possible causes are analyzed. RESULTS: Segmental infarction with diffuse testicular atrophy. CONCLUSION: Infarction of testis may atypically present as a testicular mass that may lead us to suspect a testicular neoplasm since the age of presentation of both types of lesions are similar.

[Our experience with renal adenocarcinoma (II): clinical course, diagnosis, and prognostic factors before surgical treatment]. / Nuestra experiencia en adenocarcinomas renales (II): Clínica, diagnóstico y factores pronósticos antes del tratamiento quirúrgico.

OBJECTIVES: We evaluated the form of presentation, clinical features and analytical values and their relationship with survival in renal cell carcinoma patients and analyzed the efficiency of different diagnostic and staging procedures. METHODS: We reviewed the form of presentation, clinical features, staging procedures and analytical values of 229 consecutive renal cell carcinomas diagnosed at our hospital between 1975 and 1991. RESULTS: Malaise and weight loss or symptoms different from those of the classical triad (hematuria, pain and a flank mass) are factors of poor prognosis and lower survival. The time of presentation of symptoms does not influence prognosis. Computerized tomography was found to be the best imaging technique, with a low sensitivity and a high specificity in our experience. We have found a correlation between hypercalcemia and lower survival, but not for the more advanced tumoral stage. There was a correlation between the levels of hemoglobin and alkaline phosphatase and survival: patients with hemoglobin levels less than 14 g/dl or alkaline phosphatase levels greater than 85 U/l had a lower survival rate and a more advanced tumoral stage. CONCLUSIONS: Computerized tomography was found to be the best imaging technique. Symptoms different from those of the classical triad, malaise and weight loss, hypercalcemia, low levels of hemoglobin or high levels of alkaline phosphatase are factors of poor prognosis.

[Our experience with renal adenocarcinoma (I): epidemiologic data]. / Nuestra experiencia en adenocarcinomas renales (I): Datos epidemiológicos.

OBJECTIVES: The present study was conducted to review the epidemiological factors of patients with renal cell carcinoma. METHODS: We reviewed the familial, social, cultural, toxic, occupational and pathological factors of 229 patients who were diagnosed as having renal cell carcinoma between 1975 and 1992 at our hospital. RESULTS: As in other series, we found a greater predisposition in male patients around the seventh decade. However, unlike other studies, we observed a greater predisposition in the lower social and cultural levels and rural population. Of the epidemiological factors related to adenocarcinoma of the kidney, smoking was the most common in this series (41.8%), followed by high blood pressure (15.7%) and toxic-occupational factors (8.2%). We found no correlation between these factors and tumor stage or survival. CONCLUSIONS: Our data show a greater predisposition for renal cell carcinoma in male patients, around the seventh decade, in the lower social and cultural levels and rural population. Smoking, high blood pressure and occupational exposure to toxic agents were the most common epidemiological factors.

[Iatrogenic lesions of the urinary tract. I: ureter]. / Lesiones yatrógenas del apartado urinario. I: Uréter.

Ureteral iatrogenic lesions occur with variable frequency in the different types of surgery, mainly in uncomplicated abdominal hysterectomy. This paper contributes 29 patients (2 male and 27 female) with several types of lesions, secondary to gynaecological, intestinal and vascular surgery. The series produced 16 cases of clamping, 6 ureterovaginal fistulae, 6 ureteral sections (5 total and 1 partial) and 1 ureterouterine fistula. The terminal ureter was the most frequently damaged. The diagnostic and therapeutical methods used in this type of lesions are analyzed.