Phosphoinositide 3-kinase and Forkhead, a switch for cell division.

Cell cycle progression is a tightly controlled process. To initiate cell division, mitogens trigger a number of early signals that promote the G(0)-G(1) transition by inducing cell growth and the activation of G(1) cyclins. Activation of cyclin E/cdk2 (cyclin-dependent kinase 2) at the end of G(1) is then required to trigger DNA synthesis (S phase entry). Among the early signals induced by mitogens, activation of PI3K (phosphoinositide 3-kinase) appears essential to induce cell cycle entry, as it regulates cell growth signalling pathways, which in turn determine the rate of cell cycle progression. Another mechanisms by which PI3K and its downstream effector protein kinase B regulate cell cycle entry is by inactivation of the FOXO (Forkhead Box, subgroup O) transcription factors, which induce expression of quiescence genes such as those encoding p27(kip), p130 and cyclin G2. PI3K/FOXO then work as a complementary switch: when PI3K is active, FOXO transcription factors are inactive. The switch is turned on and off at different phases of the cell cycle, thus regulating cell cycle progression.

Hysteroscopy: an alternative to dilatation and curettage in the diagnosis of postmenopausal bleeding.

Data were collected prospectively on 100 women suffering from postmenopausal bleeding who were investigated by hysteroscopy in a 5-month period. Women using hormone replacement therapy were excluded. The most common hysteroscopic finding was atrophy (44%). Other findings were: endometrial cysts (13%), endometrial polyp (12%) and adenocarcinoma (6%). The sample was not representative in 41% of cases and the most frequent histopathological diagnosis was inactive endometrium (14%). Other diagnoses were: inactive endometrium (14%), adenocarcinoma (6%), hyperplasia (7%), endometrial polyp (3%), proliferation (5%) and atrophy (4%), Endometrial sampling was not performed in 13% of the cases. General anaesthesia was not needed and complications were minimal. We support hysteroscopy as a routine alternative to dilatation and curettage in the diagnosis of postmenopausal bleeding.

[Thickness variation of the dural sac]. / Variación del espesor del saco dural.

OBJECTIVE: To measure carefully the thickness of the dural sac and evaluate possible variation in recently removed human specimens that had not yet undergone postmortem change. The thickness of the dural membrane is of interest because of its function as a barrier during diffusion processes and during closure of spinal lesions. MATERIAL AND METHODS: After receiving the consent of our hospital's ethics committee and the family of the deceased, and immediately after extraction of organs for transplantation, we removed the dural sac and nerves contained therein from the cadaver of 56-year-old patient diagnosed of brain death. The membrane was dissected and 240 measurements of thickness were made over the entire surface of the sample. A micrometer was used, controlled through a surgical microscope. To analyze variations in thickness, the specimen was divided into 48 zones. RESULTS: The dural sac open on its anterior side was treated as a rectangular membrane measuring 130 x 54 mm. Mean thickness of the sample was 0.322 mm. Mean thickness of anterior zones was 0.353 mm, with no significant differences among them. Posterior zones measured a mean 0.295 mm with significant differences among them (p < 0.001). Up to the second lumbar root, anterior and posterior zone thicknesses presented no significant differences. However, after the space between the second and third lumbar roots, the posterior side was significantly thinner. Where the first, second and third lumbar roots emerged, we measured thicknesses of 0.315, 0.361 and 0.322 mm, with no significant differences among anterior, posterior and side zones on any level. At the fourth lumbar root and in the spaces of the dura mater between the emergence of the first and second, the second and third, the third and fourth and fourth and fifth lumbar roots, we observed significant differences. The measurements were 0.298 mm (p < 0.01); 0.348 mm (p < 0.01); 0.337 mm (p < 0.001), 0.306 mm (p < 0.01); 0.289 mm (p < 0.001), respectively. CONCLUSION: Possible inter- or intra-individual variation in dural sac thickness is an unpredictable variable affecting the management of dural lesions. The data we report on thickness allow for future objective assessment of the maximum sizes recommended for the lateral orifices of bevelled, pencil-point needles in order to avoid straddling the membrane when subarachnoid anesthesia is given. The data also contributes to the study of substance diffusion through this membrane.

[Microscopic characteristics of epidural filter pores]. / Características microscópicas de los poros de los filtros epidurales.

OBJECTIVE: The increased use of the epidural route for administering opioids to treat chronic pain and the need to reduce complications as much as possible, has led some authors to recommend using micro filters to reduce catheter contamination. This study was motivated by the lack of technical information documenting epidural filters used routinely, as well as by the scarcity of literature describing their characteristics. Our aim was to investigate the true nature of the membrane pores, their characteristics and dimensions. MATERIAL AND METHOD: Samples from 30 epidural filters labelled "Porosity: 0.2 microns" from three different manufacturers were studied. Filters from Vygon, Braun and Abbot were labelled A, B and C, respectively. The samples were placed in six groups of five filters each, and 15 random studies were made of each sample. Three of the six groups were used to study prefiltration surfaces and the others to study postfiltration surfaces. Each sample was metalized with gold and its center was then studied by scanning electron microscope. Given that the pores were anfractuous, they were measured by taking the diameter of the largest circle fitting inside that could predict the size of the smallest spherical non elastic body that might be retained. The samples for measuring thickness were cryofractured for determining the number of filtration planes in the 15 filters. RESULTS: Prefiltration surface: Pore diameters were 0.70 (0.66 to 0.74), 0.45 (0.41 to 0.49), and 2.077 (2.01 to 2.15) microns on the filtration surfaces of manufacturers A, B and C, respectively. The differences were significant (p < 0.01) and the pore shapes were also different. Postfiltration surface: The function pores of filters from manufacturers A and B measured 0.26 (0.25 to 0.28) and 0.26 (0.24 to 0.28) microns, and the differences were not significant. The pores of filters from company C were significantly larger (p < 0.01), measuring 0.46 (0.43 to 0.49) microns. There were significant differences (p < 0.001) in pore size on the pre- and postfiltration surfaces from all three manufacturers. Gauge: The five A, B and C filters averaged 130, 118 and 165 microns thick, respectively, with an average number of 140, 220 and 210 filtration planes, respectively. CONCLUSION: The pores of filters for epidural use labelled "0.2 microns" actually had much larger pores on their prefiltration surfaces and throughout the membrane thickness. On the postfiltration surface, however, the diameters of pores on filters manufactured by Vygon and Braun approached 0.2 microns. Pores on filters manufactured by Abbot, however, were approximately 0.46 microns. We believe that in the future manufacturers should include more information in the documentation accompanying their filters.

[Pseudosarcomatous tumor of the bladder]. / Tumor seudosarcomatoso de vejiga.

Pseudosarcomatous tumour of the bladder is a benign neoforming process of uncommon occurrence, consisting in a fibroblastic proliferation originated in the vesical wall and the perivesical fat, with unknown etiology, that given its cellular pleomorphism and the infiltrative nature of the injury can be incorrectly diagnosed as a sarcoma. This paper presents one case of pseudosarcomatous tumour of the bladder in a 9 year-old child, with no history of local traumatism or previous surgery, consisting in a tumoration affecting the vesical wall associated with a significant perivesical fibrosis with extension towards the area of the iliac veasels. Microscopically, the injury shows proliferation of spindle cells, arranged in a myxoid stroma with a prominent vascular net. No cytologic atypia is demonstrated or increase in the number of mitosis. The immunohistochemical study shows features of myofibroblasts in the proliferant cell. A review of the literature is made on 40 cases of inflammatory pseudosarcoma, evaluating the clinical characteristics, morphologic findings and treatment involved, as well as the postoperative evolution of the patient.

[Transitional carcinomas of the urinary tract: synchronous and metachronous lesions]. / Carcinomas transicionales del tracto urinario: lesiones sincrónicas y metacrónicas.

OBJECTIVE: The urothelium is a pseudostratified cylindrical epithelium that lines the calices, renal pelvis, urethers, bladder, part of the urethra and part of the prostate ducts. Transitional cell carcinoma (TCC) is a malignant neoplasia that can appear in any site where urothelium is present, being the bladder the most frequently affected organ. We performed an analysis of our experience and conducted a literature-based metanalysis to evaluate the coexistence of tumoral lesions at different locations in the urinary tract. MATERIAL AND METHODS: Between 1983 and 1993, 397 patients with TCC lesions involving the upper urinary tract (UUT), bladder, urethra or prostate, were diagnosed and treated. Coexistence, either synchronic or metachronic, of several lesions in different sites of the urinary tract was considered as a multiple tumor. RESULTS: Overall, 440 tumors were diagnosed in 397 patients. A single lesion appeared in 360 patients, while 37 presented multiple locations with a total of 79 tumors. The lesions were located at the following levels: 17 renal, 21 uretheral, 372 vesical, 13 in the urethra and 17 in the prostate ducts. According to the location, the frequency of single lesions was: UUT 58%, bladder 91%, urethra 8% and prostate ducts 35%. Synchronic UUT and intravesical tract tumors develops in 1% and 4% of patients with bladder TCC, respectively. Two percent of vesical tumors showed metachronic relationship with UUT tumors and the same rate was seen for intravesical lesions. CONCLUSIONS: Urothelial UUT tumors have a typical nosologic entity with specific features. Their coexistence with vesical tumors is frequent. When tumors of the bladder occur after a UUT tumor the interval of highest incidence between diagnoses is 2-3 years, and there are no histological risk factors among them for prognosis. Transitional cell prostatic urethral tumors are most often secondary to histologically similar, poor prognosis, bladder tumors, and usually synchronic.

[Descriptive epidemiology of bladder cancer in the health area 8 in Madrid. Retrospective study on 315 patients]. / Epidemiología descriptiva del cáncer vesical en el area sanitaria 8 de Madrid. Estudio retrospectivo sobre 315 pacientes.

The Madrid Health Care District No. 8 includes 19 town councils located in the South and West of the Autonomous Community. The actual population is 381,052 inhabitants with a floating population of 50,000 people. Currently, Mostoles Hospital is the Referral Health Centre of this district. Between 1983 and 1992, 315 patients received treatment for vesical cancer. Of them, 77% were primarily superficial and 23% infiltrant. 98% were transitional carcinomas. Patient's mean age was 65.9 years, with 83.5% men and 15.5% women. Incidence obtained was 14 x 10(5) inhabitants (23.5 men and 4.6 women). Smoking was the only risk factor statistically significant. Prevalence was 39.3 x 10(5). Actual mortality rate obtained for vesical cancer was 1.3 x 10(5). Comparison of our overall data with national and international statistics show extended consistence except for the mortality rate which was lower than the data consulted.

Intravesical BCG therapy of superficial bladder cancer: study of adverse effects.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) has proved to be more effective than most chemotherapeutic agents in the prophylaxis and treatment of superficial bladder tumours. Side-effects, both local and systemic, are the main limitations against its use. With the aim of lowering the incidence and severity of side-effects, we started to use two vials of BCG, Connaught type, per instillation, instead of three vials, as recommended by the manufacturer. We prospectively reviewed adverse effects of BCG treatment at the lower dosage in 92 patients. Compared with other series, we found a similar incidence of adverse effects except for some local effects as haematuria which showed a higher incidence, but we also found a lower rate of tumour relapse. Four primary tumours were recorded during the study period. In our open study, a lower BCG intravesical dosage is not followed by a reduction in side-effects.

[Flow index: a substitute for uroflow nomograms?]. / Indice de flujo: sustituye a los nomogramas de uroflujo?

One hundred and twenty-nine flowmetries from an equal number of male patients with urinary obstructive symptoms have been analyzed, and the data provided by Siroky's nomogram compared to the flow ratios. Flow ratio was considered compatible with obstruction if below 0.80, which in turn correlated to -2 DE in Siroky's nomogram. Agreement between both parameters was noted in 95% cases (p < 0.05). The use of a flow ratio as a substitute for Siroky's nomogram to evaluate urinary obstructive disease would be justified by the easiness of interpretation, since it avoids translation of maximum flow and mean flow data to a plot. Flowmetry should only be considered determinant with clearly obstructive values.

[Extracorporeal lithotripsy for urolithiasis: retrospective study of 227 patients]. / Litotricia extracorpórea por urolitiasis: estudio retrospectivo de 227 pacientes.

Presentation of a retrospective study in 227 lithiasic patients with indication for extracorporeal lithotrity (ESWL) as first line of therapy or as adjuvant treatment, referred to three lithotripter units over the last five years. There was a high percentage of personal history of lithiasis (55.5%), colic pain being the most frequent symptom (78%). Lithiasis largely affected one single renal unit, most often the left one (54.7%) and was solitary in 54.6% of cases. Calyceal and pyelic sites were the most common ones, the size of the stones ranging between 10-19 mm in 44.5% of cases. Overall results reflect a 78.5% success rate, with statistically significant lower occurrence of residual fragments in the right renal unit. There was greater success rates in ureteral calculi followed by calyceal ones and also in the smaller ones compared to those greater than 20 mm. Double-J ureteral catheterism was performed in 27% patients, with evidence of statistical significance between them and those uninstrumented in relation to occurrence of lithiasic trail. An 11% rate of significant complications requiring endourological handling due to obstruction in 7.5%, and open surgery in 3.5% due to complication or lack of resolution was detected.

[Flurbiprofen: therapeutic alternative in nephritic colic]. / Flurbiprofen: alternativa terapéutica en el dolor del cólico nefrítico.

A double blind randomized study was conducted in 52 patients with renoureteric colic to compare the therapeutic efficacy of two analgesics given in a single intramuscular dose. Following the administration of 2 gm dipirone plus 20 mg hyoscine N-butylbromide (n = 26) or 150 mg flurbiprofen (n-26), the patients were assessed for pain intensity, relief and pain status for a period of one hour. Both treatments afforded a similar analgesic effect, with pain remitting in 76.9% of the cases. No significant differences were observed for the latency periods or degree of pain at 5, 10, 30 and 60 minutes following treatment. Additional analgesic therapy was required in 34.6% of the patients who received dipirone and 26.9% of the flurbiprofen group, the difference not being statistically significant. Overall both drugs were well tolerated and only local adverse effects were observed, pain being the most frequent.

[Scrotal suspension with hypogastric suture. Hemostatic technique in intrascrotal surgery]. / Suspensión del escroto con sutura a hipogastrio. Técnica hemostática en la cirugía intraescrotal.

Appearance of haemorrhages and bruises after surgery of scrotal bags contents is one of the most frequent complications in Urology. Presentation of results obtained in a prospective study carried out on 86 patients who had underwent surgery due to intrascrotal disease. In all of them and regardless of the approach used (inguinal or scrotal), suspension of bags to hypogastrium using suture traction was performed by Oesterling technique in combination to Joseph and O'Boyle's technique. Drainage was not used in any case. The article explains the characteristics of undergoing pathologies' surgical indications, describing both the technique used and the results obtained. It concludes by stating this is a useful method to prevent routine complications in scrotal surgery.

[Renal fungal infection: presentation forms and therapeutic advances]. / Infeccion fúngica renal: formas de presentación y avances terapéuticos.

Fluconazole is a broad spectrum anti-fungal agent which combines good tolerance, efficacy and low toxicity, and offers useful advantages in the treatment of certain forms of mycosis. Three cases of renal fungal disease treated with surgery (nephrectomy in two cases and pyelolitectomy plus partial nephrectomy in the third one) and fluconazole or amphotericin B are presented. In all three cases there was at least one predisposing factor (diabetes, urolithiasis, urinary catheter, previous therapy with antibiotics, or AIDS), and the causing pathogens were Candida and Mucor. Administration of fluconazole 100 mg b.i.d. for 4 weeks in the two candida infected patients accomplished a complete cure of the disease. Incidence, etiopathology, presentation forms and diagnostic techniques of urinary mycosis are analyzed together with the current therapeutical options, making special reference to fluconazole.

[Diagnosis and treatment with ureterorenoscopy of ureteral obstruction caused by papillary necrosis]. / Diagnóstico y tratamiento mediante ureterorrenoscopia de la obstrucción ureteral por papila necrosada.

Increasing use of endourological procedures to establish a diagnosis of pyeloureteral lesions detected as a repletion deficiency during urographic study, which when they are obstructive, affect the upper urinary tract. The present report describes the use of ureterorenoscopy as a diagnostic and therapeutic procedure for the ureteral obstruction occurring in a patient with papillary necrosis secondary to analgesics abuse. The papilla was indwelt in the right distal ureter causing obstruction and symptoms of renal colic and septicemia.

[Orchiectomy and buserelin in combination with flutamide: comparative results in metastatic prostatic carcinoma]. / Orquiectomía y buserelin asociados a flutamida: resultados comparativos en el carcinoma prostático metastásico.

In a prospective, non-randomized study in 44 patients with metastatic prostate carcinoma (D2), without previous hormone therapy, two alternative therapeutic courses to achieve complete androgenic blockade were compared. A first group (n = 29) was assigned to received Flutamide plus Buserelin, whereas the second group (n = 15) underwent orchidectomy, also in association to Flutamide. Both regimes were sustained without interruption, except when progression was evident, and both achieved castration levels of testosterone plasma titres. Mean follow-up duration was 13 months and 7 days, ranging between 2 and 36 months. There were no significant differences between both groups with regard to therapy objective responses and survival. Whereas the responses (CR + PR + E) were 93% in the LHRH analogues group and 86% in the orchidectomy group, overall survival was 66% and 67%, respectively. There were no secondary complications related to the surgical procedure nor adverse effects to drug therapy which required its cessation.

[Alkaline encrusted cystitis: factors affecting prognosis]. / Cistitis incrustada alcalina: factores condicionantes del pronóstico.

Alkaline encrusted cystitis is characterized by the formation of calcareous plaques in the bladder mucosa and submucosa in the presence of several factors: infection by urolithic organisms, earlier pathology of the vesical wall and precipitation of calcium phosphate salts. Treatment includes: urine acidification, correction of the urinary infection and use of acetohydroxamic acid. This paper presents three patients where the response to medical treatment was conditioned by the evolution of the existing vesical impairment. The conclusions state that in the alkaline encrusted cystitis, the concurrent pathology is a major predictor of the disease's future evolution.

[Conservative treatment of bladder and prostatic rhabdomyosarcoma in childhood: possibilities for non-radical surgery]. / Tratamiento conservador del rabdomiosarcoma vesical y prostático en pediatría: posibilidades de la cirugía no radical.

Treatment of rhabdomyosarcoma (RMS) of the bladder and prostate has always been difficult. Despite the significant advancements that have permitted cure, there is no agreement in the choice and order of the different therapeutic options. We reviewed the available literature evaluating the role of non-radical surgery and attempts at bladder preservation especially in children. Partial resection with sufficient margin of safety is only possible in 20% of the primary bladder tumors and the 3-year survival rate is 80%, similar to the overall survival rate for tumors localized to this site. The excellent results achieved in the case described herein underscores the possibilities of a conservative treatment modality in well-selected cases. The patient, who was submitted to partial cystectomy and received VAC polychemotherapy for a period of one year, is alive, tumor free and has preserved bladder function 50 months post-operatively.

[Obstructive uropathy in genital prolapse]. / Las uropatías obstructivas en los prolapsos genitales.

Two cases of genitourinary prolapse are presented, with a severe high obstructive uropathy complicated with lithiasis and infectious picture. Both cases were elderly patients and had had this problem for many years. They had received no urological or gynaecological examination that could have prevented later complications. As presentation frequency of this pathology is scarce, which undoubtedly is an index of health care, we have reviewed the existing literature to confirm the few descriptions currently reported. Incidence, different etiopathogenic theories explaining this picture, distinctive radiological data and treatment are analyzed.

[Retroperitoneal hematoma secondary to traumatic rupture of the psoas muscle]. / Hematoma retroperitoneal secundario a rotura traumática del músculo psoas.

Rupturing of the psoas muscle by closed injury as a result of the formation of a retroperitoneal hematoma is a very uncommon pathological entity, which may rise problems of differential diagnosis with kidney lesions. Supplementary explorations do not always clear up diagnostic doubts, and it is surgery, if indicated, that confirms the picture. We present a case of retroperitoneal hematoma of traumatic origin in a one-kidney ipsilateral patient, in whom the abdominal CAT revealed affection of the renal capsule associated with rupture of teh psoas. In the surgery carried out due to formation of an abscess in the hematoma we verified that the kidney was undamaged.

[Transverse testicular ectopy with common deferent duct]. / Ectopia testicular transversa con conducto deferente común.

Transverse testicular ectopia is a malfunction of which there are 65 cases described in the Western literature. The pathogeny is unknown, although in the cases in which it is associated with persistence of Mullerian residue, it is attributed to a defect in the secretion of MIF (Mullerian inhibiting factor). In the other cases the fundamental cause is considered to stem from alterations in the vascularization of the genital crest, which determines the type of testicular ectopia. We present a case of crossed testicular ectopia with common deferent duct in a three-year-old male, treated by means of descent and transposition via the interscrotal septum with modified Ombrédanne's technique.