Progresión en glaucoma. Guía de práctica clínica / Glaucoma progression. Clinical practice guide

Objetivo Ofrecer una serie de recomendaciones generales que sirvan de orientación en la evaluación y el manejo de la progresión glaucomatosa en la práctica clínica diaria a partir de la evidencia clínica de calidad existente. Métodos Tras la definición de los objetivos y del alcance de la guía se constituyó el grupo de trabajo que formuló las preguntas clínicas estructuradas siguiendo el formato PICO (Patient, Intervention, Comparison, Outcomes). Una vez evaluada toda la evidencia clínica existente con las herramientas AMSTAR2 (Assessment of Multiple systematic Rewiews) y Risk of bias de Cochrane de forma independiente por al menos dos revisores, se pasó a la formulación de recomendaciones siguiendo la metodología del Scottish Intercollegiate Guideline Network (SIGN). Resultados Se presentan recomendaciones con sus correspondientes niveles de evidencia que pueden ser de utilidad para la detección y el seguimiento de la progresión glaucomatosa con los distintos métodos disponibles y para el tratamiento de los pacientes. Conclusiones A pesar de que para muchas de las preguntas el nivel de evidencia científica disponible no es muy alto, esta guía de práctica clínica ofrece una revisión actualizada de los diferentes aspectos existentes relacionados con la evaluación y el manejo de la progresión glaucomatosa (AU)

Objective To provide general recommendations that serve as a guide for the evaluation and management of glaucomatous progression in daily clinical practice based on the existing quality of clinical evidence. Methods After defining the objectives and scope of the guide, the working group was formed and structured clinical questions were formulated following the PICO (Patient, Intervention, Comparison, Outcomes) format. Once all the existing clinical evidence had been independently evaluated with the AMSTAR2 (Assessment of Multiple Systematic Reviews) and Cochrane «Risk of bias» tools by at least two reviewers, recommendations were formulated following the Scottish Intercollegiate Guideline network (SIGN) methodology. Results Recommendations with their corresponding levels of evidence that may be useful in the interpretation and decision-making related to the different methods for the detection of glaucomatous progression are presented. Conclusions Despite the fact that for many of the questions the level of scientific evidence available is not very high, this clinical practice guideline offers an updated review of the different existing aspects related to the evaluation and management of glaucomatous progression (AU)

Glaucoma progression. Clinical practice guide.

OBJECTIVE: To provide general recommendations that serve as a guide for the evaluation and management of glaucomatous progression in daily clinical practice based on the existing quality of clinical evidence. METHODS: After defining the objectives and scope of the guide, the working group was formed and structured clinical questions were formulated following the PICO (Patient, Intervention, Comparison, Outcomes) format. Once all the existing clinical evidence had been independently evaluated with the AMSTAR 2 (Assessment of Multiple Systematic Reviews) and Cochrane "Risk of bias" tools by at least two reviewers, recommendations were formulated following the Scottish Intercollegiate Guideline network (SIGN) methodology. RESULTS: Recommendations with their corresponding levels of evidence that may be useful in the interpretation and decision-making related to the different methods for the detection of glaucomatous progression are presented. CONCLUSIONS: Despite the fact that for many of the questions the level of scientific evidence available is not very high, this clinical practice guideline offers an updated review of the different existing aspects related to the evaluation and management of glaucomatous progression.

Effects of systemic administration or intrabursal injection of serotonin on puberty, first ovulation and follicular development in rats.

To elucidate the role of serotonin in the onset of puberty, the effects of both systemic and in-ovarian bursa administration of serotonin on the neuroendocrine mechanism that modulates the onset of puberty, follicular development and first ovulation were evaluated. Two experiments were carried out. For the first, 25 or 37.5 mg kg⁻¹ of bodyweight of serotonin creatinine sulfate was administered by a subcutaneous route to 30-day-old female rats. In the second experiment, serotonin creatinine sulfate was administered directly into the ovarian bursa of 34-day-old female rats. Systemic administration of 25 or 37.5 mg kg⁻¹ of serotonin creatinine sulfate induced a delay in the ages of vaginal opening and first vaginal oestrus, a decrease in the number of ovulating animals, and serum concentrations of FSH, LH, oestradiol and progesterone. An increase in the number of Class 3 (>500 µm) and atretic follicles was observed in the ovaries of these animals. The administration of serotonin creatinine sulfate in the ovarian bursa did not modify the onset of puberty and ovulation, but a reduced serum concentration of oestradiol was observed. Our results suggest that serotonin acts on the components of the hypothalamus-hypophysis-ovary axis by modulating follicular development, ovarian functions and the onset of puberty.

Serotoninergic system blockage in the prepubertal rat inhibits spermatogenesis development.

The stimulatory and inhibitory role of serotonin in gonadotropin secretion and in the onset of puberty in the male rat has been previously described, but its role in the establishment of spermatogenesis is not known. The aim of this study was to investigate the effects of serotoninergic inhibition by p-chloroamphetamine (pCA) on the prepubertal-to-adult stage of the rat reproductive system. Hypothalamic serotonin, gonadotropins and sex steroid hormone concentrations were measured, and a histopathological analysis of seminiferous epithelium was carried out on animals treated with pCA from day 30 and killed at 45 or 65 days of age. The pCA treatment significantly reduced the hypothalamic levels of serotonin and its metabolite (5-hydroxyindole-3-acetic acid). This inhibition did not affect the sex steroid hormone or LH concentrations, but rather it induced an increase in FSH concentration in animals of both ages. Spermatogenesis was impaired by pCA treatment. Disruption of seminiferous epithelium and the death of numerous germ cells were observed. Sperm produced by pCA-treated animals was of poor quality and appeared in small quantities. Apparently, serotonin depletion did not affect communication between the hypothalamus and the pituitary, but the FSH increase could have been related to alterations in the seminiferous epithelium effects. The seminiferous epithelium cycle was altered in rats killed at both 45 and 65 days of age, because at each age of killing the distribution of spermatogenesis stages was different. Germ cell apoptosis did not appear to be related to changes in the FSH concentrations, but other factors produced during spermatogenesis could have been involved in this induction. This study showed that serotonin was necessary for the development of normal spermatogenesis in prepubertal rats.

Vanadium induced ultrastructural changes and apoptosis in male germ cells.

Vanadium is a transition metal that is emitted to the atmosphere during combustion of fossil fuels. In the environment, vanadium occurs in the (V) oxidized form, but in the body it is found exclusively in the (IV) oxidized form. Vanadium tetraoxide is an inorganic chemical species in the (IV) oxidized form that has been shown to induce toxic effects in vitro and in vivo. The reproductive toxicity of vanadium in males was studied through monitoring germ cell apoptosis during spermatogenesis. We analyzed ultrastructural damage, and testosterone and progesterone concentrations following vanadium tetraoxide administered to male mice for 60 days. Spermatogenesis stages I-III and X-XII frequently showed apoptotic germ cells in control and treated animals; vanadium tetraoxide treatment induced an increase in the number of germ cell apoptosis in stages I-III and XII at 9.4 and 18.8 mg/kg, respectively. Although spermatogenesis is regulated by testosterone, in our study this hormone level was not modified by vanadium administration; thus, germ cell death was not related with testosterone concentration. At the ultrastructural level, we observed inclusion structures that varied as to location and content in the Sertoli and germ cells.

Nefritis bacteriana aguda difusa en riñón de herradura / Acute diffuse bacterial nephritis in a horseshoe kidney

El riñón en herradura es una malformación congénita que predispone al desarrollo de infecciones urinarias altas, por la ectasia piélica inherente a la malrotación de las unidades renales.La nefritis bacteriana aguda es un estadio evolutivo de la infección renal aguda situado entre la pielonefritis aguda y el absceso renal. El diagnóstico diferencial entre estas entidades sólo es posible mediante el apoyo de alguna técnica de imagen, ya que desde el punto de vista clínico son indistinguibles. El TAC con contraste es la técnica de mayor sensibilidad y especificidad en el diagnóstico de nefritis bacteriana aguda, y se considera la prueba de elección. Los hallazgos característicos del TAC son áreas corticales redondeadas o cuneiformes que adquieren una apariencia estriada tras la administración de contraste. El tratamiento está basado en antibioterapia de amplio espectro, que debe mantenerse durante un período de 3-6 semanas.Presentamos un caso de nefritis bacteriana aguda difusa, en un paciente pediátrico con riñón en herradura, que se resolvió satisfactoriamente con tratamiento antibiótico prolongado (AU)

Anuria obstructiva secundaria a prolapso uterino / Obstructive anuria secondary to uterine prolapse

La prevalencia de uropatía obstructiva asociada al prolapso uterino varía según las series entre un 4 per cent y un 80 per cent, probablemente debido a la diferente severidad de los prolapsos considerados. El desarrollo de insuficiencia renal o anuria es una complicación poco frecuente. Se han postulado diversas teorías etiopatogénicas sobre la uropatía obstructiva producida por el prolapso: compresión ureteral por los vasos uterinos, angulación uretral extrema, compresión ureteral sobre la musculatura elevadora del ano y elongación y estrechamiento del uréter distal. La exploración radiológica princeps en el estudio del tracto urinario de estas pacientes es la urografía intravenosa en bipedestación. El tratamiento de urgencia de la anuria obstructiva secundaria a prolapso uterino consiste en la reducción manual del prolapso. La cirugía se considera como el tratamiento definitivo de elección, aunque en pacientes con elevado riesgo anestésico-quirúrgico, la colocación de un pesario de forma permanente puede ofrecer un resultado satisfactorio. Presentamos un caso de anuria obstructiva secundaria a prolapso uterino, que resolvió satisfactoriamente mediante la colocación de un pesario (AU)

[Acute diffuse bacterial nephritis in horse shoe kidney]. / Nefritis bacteriana aguda difusa en riñón en herradura.

Horseshoe kidney is a congenital malformation which predisposes the patient to severe urinary tract infections, due to pelvic ectasia which is inherent in the malrotation of the renal units. Acute bacterial nephritis is an evolutionary stage of the acute renal infection situated between acute pyelonephritis and renal abscess. It is only possible to carry out a differential diagnosis of these two bodies through the application of some imaging technique, as it is impossible to differentiate them from a clinical point of view. A CT contrast scan is the most sensitive and specific means of diagnosing acute bacterial nephritis, and is considered to be the most appropriate test method. The CT scan usually reveals circular or wedge-shaped cortical areas which become striated after contrast administration. Treatment is based on broad-spectrum antibiotherapy, which must be continued for a period of 3 to 6 weeks. We present a case of diffuse acute bacterial nephritis, occurring in a paediatric patient with a horseshoe kidney, which was successfully treated by means of a prolonged course of antibiotics.

[Obstructive anuria secondary to uterine prolapse]. / Anuria obstructiva secundaria a prolapso uterino.

The prevalence of obstructive uropathy linked to uterine prolapse ranges between 4% and 80%, depending on the series, probably due to the varying degree of severity of the prolapses under consideration. Renal failure or anuria is an unusual complication. Several etiopathogenic theories regarding obstructive uropathy secondary to prolapse have been put forward: ureteral compression by the uterine vessels, severe urethral angulation, ureteral compression against levator ani muscles and the elongation and narrowing of the distal ureter. The major radiological exploration used in studying the urinary tract of these patients is intravenous urography in bipedestation. Emergency treatment for obstructive anuria resulting from a uterine prolapse consists of manually replacement of the prolapse. Surgery is considered to be the definitive ideal treatment, although in the case of surgical or anaesthetic high risk patients, inserting a permanent pessary may constitute a satisfactory solution. We present a case of obstructive anuria resulting from uterine prolapse, which was successfully treated with the insertion of a ring pessary.

[Inflammatory pseudomotor of the bladder. A diagnostic and therapeutic dilemma]. / Pseudotumore infiammatorio vescicale. Un dilemma diagnostico e terapeutico.

Inflammatory pseudotumor is a reactive benign lesion which can be very difficult to distinguish from some malignant bladder tumors like sarcomas or sarcomatoid carcinoma. The aim of this study was to present a new case of inflammatory pseudotumor and to review the present diagnostic and therapeutic criteria for this lesion. A 72-year-old female was admitted to the emergency room due to important hematuria. Transurethral resection of a bladder tumor located in the left lateral wall was performed. Pathologic studies were suggestive of inflammatory pseudotumor, but a mixoid leiomyosarcoma couldn t be completely discarded and a partial cystectomy with ipsilateral lymphadenectomy were carried out. Immunohistochemical studies were positive for vimentin, desmin, smooth muscle actin and cytoqueratins while epithelial membrane antigen and S-100 protein were negative. The patient is disease free after a year follow-up. When diagnosis is certain, complete transurethral resection is the treatment of choice. However, if there is no total pathologic confirmation, if it is a very wide lesion or if it is recurring after endoscopic resection, a partial cystectomy is suggested.

Changes in monoaminergic activity in the anterior, medium and posterior hypothalamus, gonadotropins levels and ovarian hormones during puberty of the female rat.

The aim of present study is the analysis of monoamines concentrations changes in the anterior, medium and posterior hypothalamus, as well as changes in serum gonadotropins levels, ovarian steroids and follicular growth during the prepubertal development of the female rat. Noradrenergic activity in the anterior, medium and posterior hypothalamus reached highest level at day 13 after birth, followed by a subsequent decrease from day 15 to 19 and an increase on days 22 and 27 postnatal. At day 1, neural activity in the medium hypothalamus was higher than the activity in the anterior and posterior hypothalamus. Serotoninergic activity in three portions of the hypothalamus was higher throughout the prepubertal development. Follicle-stimulating hormone and luteinizing hormone serum levels increased between days 11 and 17 and decreased from day 19 to 36. The concentration of 17beta-estradiol was consistently low throughout the prepubertal development and increased at day 39 after birth. These results indicate that during the prepubertal development of the rat, the three regions of the hypothalamus show significant changes in the monoaminergic neural activity. There is an inverse relationship between the noradrenergic activity on the anterior and medium hypothalamus and serotoninergic activity in the posterior hypothalamus with ovarian steroids during sexual maturation. These changes may be linked to the development of the neuroendocrine processes that modulate gonadotropin secretion and ovarian function.

Postnatal androgenization induces premature aging of rat ovaries.

In the present paper, we report that ovaries of adult rats treated with testosterone propionate (TP) on a critical postnatal Day 5 exhibit histologic and immunohistochemical findings which resemble those of the anovulatory ovaries in middle-aged female rats. The sterile rat model has been long known whereas ovarian failure seems to be a reason for anovulation with normal hypothalamo-pituitary-gonadotropin background. Appropriate function of ovarian steroidogenic cells is also regulated by mesenchymal cells. To characterize the ovarian failure, we studied the histology, luteinizing hormone receptor (LHR) expression, and characterized changes of vascular pericytes, T cells, and dendritic cells in ovarian steroidogenic compartments consisting of interstitial cells (ISC) of ovarian interstitial glands, and granulosa and theca interna cells of ovarian follicles. Normal adult ovaries contained 63% of mature interstitial glands. The mature ISC exhibited moderate cytoplasmic and strong surface LHR expression and fine (<5 micrometer) cytoplasmic vacuoles (ISC of 'luteal type'). They originated from young ISC of 'thecal type,' which exhibited strong cytoplasmic LHR expression. Remaining 37% were aged interstitial glands, which consisted of aged ISC (increased cytoplasmic vacuolization, nuclear pyknosis, and reduced surface LHR expression) and regressing ISC (weak cytoplasmic and no surface LHR expression). However, no mature ISC of 'luteal type' were detected in anovulatory ovaries of adult rats (45- and 60-day-old) injected with TP (100 or 500 microgram) on postnatal Day 5 (TP rats). Their ovaries contained 96% of aged interstitial glands with aged and regressing ISC. Remaining 4% were abnormal interstitial glands with direct transition of young ISC of 'thecal type' into aged ISC (young/aged glands). Lack of mature ISC, and similar amount of aged (96%) and young/aged interstitial glands (4%) was also detected in anovulatory ovaries of untreated persistently estrous middle-aged (10-month-old) females (aging PE rats). The aging process in TP and aging PE rats was accompanied by regression of vascular pericytes, T cells, and dendritic cells within the interstitial glands. In addition, anovulatory ovaries of TP rats and aging PE females contained mature follicles exhibiting LHR overexpression by granulosa cells, and aged (cystic) follicles with reduced layers of granulosa cells lacking LHR expression. In contrast, when the rats were injected with 500 microgram of TP later, on postnatal Day 10, the adult females exhibited estrous cycles and normal ovaries with corpora lutea. These results show that injection of TP during the critical postnatal period causes a lack of mature and preponderance of aged ISC in adult ovaries, accompanied by degeneration of mesenchymal cells. We suggest that mesenchymal cells regulate qualitative aspects of tissue-specific cells, and this function of mesenchymal cells is programmed during the critical period of development.

Effects of a lesion in the dorsal raphe nuclei performed during the juvenile period of the female rat, on puberty.

The present study examined the effect of thermic lesions on the dorsal raphe nuclei (DRN) of the female rat, performed at various ages during the prepubertal period (21, 24, or 27 days), on puberty, and at first ovulation. In comparison with sham-operated animals, the age of vaginal opening and first vaginal oestrus was delayed in rats with a DRN lesion performed at the end of the infantile period (day 21) (45.6+/-0.94 vs. 89.9+/-1.03, p < 0.05), whereas differences were not observed in animals with lesions performed during the juvenile period (day 24 or 27). The number of ova shed by ovulating animals was greater in those rats with lesions performed on day 24 or 27 (9.7+/-0.4 vs. 7.4+/-0.4; 9.5+/-0.5 vs. 7.7+/-0.4, p < 0.05). Ovarian follicular atresia in these animals was significantly lower than in control and sham-operated ones. On the day of first vaginal oestrus and 48 h after the lesion, the serotonin-hypothalamic concentration decreased in all lesioned animals. Present results support the idea of the participation of the serotoninergic system, arising from the DRN, in the neuroendocrine mechanisms regulating the onset of puberty and the first ovulation, with variations depending on animal maturity.

Effects of unilateral or bilateral superior ovarian nerve section in prepubertal rats on the ovulatory response to gonadotrophin administration.

The modulating effects of ovarian innervation reaching the ovary through the suspensory ovarian nerve on the reactivity of the ovaries to gonadotrophins were analysed. Juvenile rats (32 days old), with or without unilateral or bilateral section of the superior ovarian nerve, were injected with 8 iu of pregnant mare serum gonadotrophin (PMSG), 10 iu of human chorionic gonadotrophin (hCG) or with 8 iu of PMSG followed 56 h later with 10 iu of hCG. Treatments were given immediately after surgery or 4 days later, and the rats were killed on the day of first vaginal oestrus. In rats with unilateral section, treatment with PMSG did not induce full ovulatory response by the denervated ovary whether the treatment was applied immediately or 4 days after surgery (0/11 rats treated immediately ovulated vs 5/5 (sham) and 11/12 (control, P < 0.05 Fisher's exact probability test), and 4/19 did when treatment was done 4 days after surgery vs 8/10 (sham) and 11/12 (control, P < 0.05). The rats with bilateral section receiving the same hormonal treatment, PMSG administration, ovulated. The number of ova shed by the left ovary was similar to those of the control, while the right ovary released fewer ova. Stimulation with hCG immediately after unilateral section did not induce ovulation in normal or denervated ovary. When the treatment was applied 4 days after surgery, ovulation was observed only in the innervated ovary. In the rats with bilateral section, hCG injection induced ovulation in both ovaries. In those rats with unilateral section of the superior ovarian nerve, the treatment with PMSG + hCG given immediately after surgery resulted in a compensatory ovulation by the innervated ovary (the number of ova shed/ovulating animal was significantly higher than those released by control or sham-operated animals: left section, number of ova shed by the right ovary 7.6 +/- 0.3 vs 5.5 +/- 0.8 and 4.9 +/- 1 respectively, P < 0.05; right section, number of ova shed by the left ovary 10.2 +/- 0.6 vs 4.4 +/- 1.1 and 7.0 +/- 0.9, P < 0.05), while the denervated one showed a lower ovulation rate as well as a smaller number of ova shed than those by the control animals. When the hormonal replacement was given 4 days after surgery, such compensatory ovulation was observed in the left ovary of those rats with a section of the right nerve (14.3 +/- 2.6 vs 4.4 +/- 1.1 and 6.5 +/- 1.1, P < 0.05). When the PMSG + hCG treatment was applied to animals with bilateral section of the superior ovarian nerve, the ovulation rate by the right ovary was significantly lower than in control and sham-operated treated animals (2/10 vs 11/11 and 6/7, P < 0.05). Because the ovaries receive innervation through the superior ovarian nerve, the ovarian plexus and the vagus nerve, the results obtained in unilateral denervated animals suggest that the innervation of the ovary via the superior ovarian nerve regulates in a stimulatory way the effects of gonadotrophin resulting in ovulation. The ovulation induced by hormonal treatment of rats with bilateral section of the superior ovarian nerve suggests that the effects of bilateral section on ovulation are not the addition of the effects of left and right denervation, implying the existence of a modulatory effect in gonadotrophin action on ovulation via other neural pathways.

Different effects of unilateral and bilateral lesions of the dorsal raphe nucleus on puberty and first ovulation.

The effects of unilateral and bilateral electrolytic lesions of the dorsal raphe nuclei (DRN) of 30-day-old rats, on the spontaneous and induced ovulation, were analyzed. The bilateral lesion and the lesion on the right side of the DRN delayed the age of first vaginal estrous. None of the animals with bilateral lesion on the DRN ovulated on the day of first estrous (0/8 vs. 12/15, p < 0.05). The ovulation rate in animals with unilateral lesion on the DRN was similar to sham-operated animals, but the number of ova shed by ovulating animals increased in the ovary ipsilateral to the lesion (lesion on right DRN, right ovary: 6.5 +/- 0.5 vs. 4.5 +/- 0.4; lesion on left DRN, left ovary: 6.4 +/- 0.3 vs. 4.2 +/- 0.4, p < 0.05). By the injection of human chorionic gonadotropin, ovulation was restored in rats with a bilateral lesion on the DRN (3/5 vs. 0/8, p < 0.05). The present results suggest that serotoninergic input to the hypothalamus, arising from the DRN, exerts a facilitatory influences on the control of luteinizing hormone release. To explain the increase in the number of ova shed by the left and right ovary, observed in rats with an ipsilateral lesion, we suggest the existence of a neural connection between the DRN and the ovary.