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Biomedical subjects

Pedro Acién

Publications and source records attributed to Pedro Acién.

13 recordsLinked to original sources
PubMed2007

The effect of intraperitoneal interleukin-2 on surgically induced endometriosis in rats.

OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) on an experimental model of endometriosis. STUDY DESIGN: Double blind and randomized experimental prospective placebo-controlled study. Experimental endometriosis was induced in 66 three-month-old female Wistar rats, by auto-transplanting fragments of endometrium to the peritoneum. After four weeks, the size of each implant was measured in millimeters by laparotomy (L2), and animals were randomly distributed for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks later, the implants were measured (L3) and a second dose was given. After four weeks, endometriosis size was evaluated again (L4). RESULTS: We found a reduction of experimental endometriosis at L3 that was only significant in IL-2 treated groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p<0.001 with respect to L2 size), versus a non-significant reduction of 9.0% found in placebo group, but the differences were not statistically significant between groups. The decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2, rat-IL-2 and placebo, respectively (p<0.001 in IL-2 groups versus L2 and L3, and p<0.05 in both groups versus placebo at L4). CONCLUSION: Intraperitoneal administration of IL-2 reduces experimental endometriosis, and this effect is similar using rat-IL-2 or human IL-2 (non specie-specific effect).

Animals↗
PubMed2007

Intraperitoneal recombinant interleukin-2 activates leukocytes in rat endometriosis.

The aim of this double-blinded study was to determine changes in leukocyte populations in blood, peritoneal lavage fluid, eutopic and ectopic endometrium after treatment with recombinant rat interleukin-2 (IL-2) using an in vivo experimental model of rat endometriosis. The in vivo model involved transplanting four square fragments of autologous endometrium onto the inner surface of the abdominal wall in 20 Wistar rats. The control group was constituted by 20 sham-operated rats. Both groups were randomly treated (1-month interval treatment) with 2 intraperitoneal doses of glucose solution (5%) that did or did not contain recombinant IL-2, and animals were sacrificed 4 weeks after the last dose of treatment. Blood and peritoneal lavage were obtained during the initial and final laparotomy, whereas eutopic and ectopic endometrium were collected at the end of the experiment. Endometriotic implants were measured in each laparotomy to determine any change in size. Leukocyte populations were analyzed by flow cytometry and immunofluorescence microscopy. Cytometric results were similar in blood and peritoneal lavage. CD25+ and natural killer (NK) cell levels in peripheral blood were lower in rats with endometriosis treated with IL-2, whereas NK cells increased in lavage compared to placebo group. The percentage of macrophages and dendritic cells in blood were higher in all rats treated with IL-2, as well as peritoneal dendritic cells. Implant size of these rats decreased significantly, showing a greater number of activated lymphocytes, macrophages, NK and dendritic cells inside them. In conclusion, recombinant IL-2 induced recruitment of activated leukocytes into endometriotic-like foci, and this was related to a reduction of the implant size, suggesting potential effectiveness of IL-2 as an immunomodulatory agent in this pathology.

Animals↗
PubMed2005

Treatment of endometriosis with transvaginal ultrasound-guided drainage under GnRH analogues and recombinant interleukin-2 left in the cysts.

BACKGROUND: To analyze the therapeutic results of one dose of 3 million IU of recombinant interleukin-2 (rIL-2) left intracyst (group I) versus two doses with a 1-month interval (group II) after transvaginal ultrasound (US)-guided drainage of endometriomas under the effect of GnRH analogues. METHODS: Prospective and randomized clinical trial (helped by a random number table) at a University Hospital. Twenty-four consecutive patients with endometriomas initially sent to us for laparotomy and conservative surgery for endometriosis were included. INTERVENTIONS: Treatment with GnRH analogues every 28 days, 3 doses. Under their effect, one or two transvaginal US-guided punctures were performed in order to aspirate the endometriomas, and 3 million IU of rIL-2 were left in the aspirated cysts each time. MAIN OUTCOME MEASURES CLINICAL RESULTS: two menstruations after GnRH analogues. Other secondary outcome measures were: the time until recurrence of cysts, symptoms and CA-125 >35 U/ml, and the need for further medical or surgical treatment. RESULTS: They were moderate or good in >50% of cases with one drainage and one dose of 3 million IU of rIL-2 intracyst, but were better with a second drainage and two doses of rIL-2 (25 vs. 58.3% 'good results'). There were fewer recurrences and the interval before recurrence was longer after two doses but differences were not significant. Six patients from group I (50%) and 3 from group II (25%) needed laparotomy and conservative surgery at 17.5 +/- 8.7 months (total time of follow-up = 33 +/- 8.8 months). CONCLUSIONS: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts under endometrial suppressive therapy with GnRH analogues has beneficial effects, improving clinical manifestations and avoiding some surgical therapies. The use of a higher dose of rIL-2 does not produce better results, whereas drainage + rIL-2 twice does.

Administration, Topical↗
PubMed2005

Changes in cytokine levels of patients with ovarian endometriosis after treatment with gonadotropin-releasing hormone analogue, ultrasound-guided drainage, and intracystic recombinant interleukin-2.

OBJECTIVE: To determine the changes in cytokine levels from women with endometriomas who are treated with recombinant interleukin-2 after ultrasound-guided cyst aspiration, and to relate these changes to the clinical results observed in these patients. DESIGN: A double-blind randomized controlled trial. SETTING: University hospital. PATIENT(S): Twenty-four women with endometriosis-related symptoms and endometriomas. INTERVENTION(S): Endometriomas in women receiving GnRH analogues and undergoing transvaginal ultrasound-guided cyst aspiration were injected with dextrose that did or did not contain recombinant interleukin-2 (IL-2). Serum samples were collected before and after treatment. MAIN OUTCOME MEASURE(S): Serum samples were analyzed by enzyme immunoassay to determine the levels of IL-1beta, IL-2, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17. RESULT(S): The cytokine levels after treatment with GnRH analogues and recombinant IL-2 were similar to the initial levels. The patients receiving GnRH analogues without IL-2 had higher IL-1, IL-2, IL-8, and IL-13 levels. Good clinical results were observed in 90% of the patients in the first group but in only 30% of the second one. CONCLUSION(S): Administration of recombinant IL-2 intracystically decreases cytokine production in women with endometriomas. These results have important implications for the design of future therapies based on immunomodulation, such as using higher or repeated doses of recombinant IL-2 in the cysts.

Adult↗
PubMed2004

Complex genital malformation: ectopic ureter ending in a supposed mesonephric duct in a woman with renal agenesis and ipsilateral blind hemivagina.

We present a clinical case of a patient with left renal agenesis and ipsilateral blind hemivagina who also had one or more atretic ectopic ureters opening into supposed mesonephric duct, which in turn opened into, or joined onto, the ipsilateral hemicervix, continuing with the blind hemivagina. The diagram of this complex genitourinary malformation would strongly support our hypothesis of the embryology of the human vagina as deriving from the Wolffian ducts and the Mullerian tubercle.

Abnormalities, Multiple↗
PubMed2004

Complex malformations of the female genital tract. New types and revision of classification.

BACKGROUND: Complex malformations of the female genital tract are often incorrectly identified, treated and reported, probably due to not considering the malformation as a cause of the clinical symptoms and neither the embryological origin of the different elements of the genitourinary tract. METHODS: Complex malformations are studied and classified, and new types are presented. The new types of complex malformations presented are: (i) Cases of unilateral vaginal or cervico-vaginal atresia with renal agenesis and uterine duplication, with or without communication between hemiuteri; (ii) the unilateral Rokitansky syndrome; and (iii) the combination in the same patient of unilateral Rokitansky syndrome (Müllerian defect) on one side and blind vagina and ipsilateral renal agenesis syndrome (Wolffian defect) on the other side. RESULTS: A revised version of the clinical and embryological classification of genital malformations is presented and an associated diagram points out the origin of these malformations. CONCLUSIONS: These genital malformative anomalies reaffirm our hypothesis about the embryology of the human vagina as deriving from the Wolffian ducts and the Müllerian tubercle; and they show that gynecologists should be aware of the related symptoms and the embryology of the female genital tract in order to achieve a better comprehension of the malformations for their right correction or therapeutic approach.

Abnormalities, Multiple↗
PubMed2003

GnRH analogues, transvaginal ultrasound-guided drainage and intracystic injection of recombinant interleukin-2 in the treatment of endometriosis.

We performed a double-blind, randomised controlled trial to evaluate the results of ultrasound-guided aspiration of endometriomas under the effect of GnRH analogues and a possible additional beneficial effect by leaving 600000 IU of recombinant interleukin-2 (rIL-2) in the cysts. Twenty-four women with endometriosis-related symptoms, increased values of CA-125 and transvaginal ultrasonography showing endometriomas >3 cm who were initially sent to us for laparotomy and conservative surgery for endometriosis were included. Main outcome measures were severity of symptoms, size and percentage of echographical reduction of endometriomas and CA-125 levels after 2 menses post-GnRH analogues. Secondary outcome measures were the time until recurrence of abnormal parameters and the need for surgery after treatment. We found moderate clinical results after treatment with drainage plus GnRH analogues and significantly improved results in women having received rIL-2 intracystically. There were no side effects. Two out of 3 previously infertile patients became pregnant after therapy. Though the rates of recurrence of endometriomas >or=3 cm were similar in both groups, the period until recurrence was significantly greater when rIL-2 was used, and the rates of recurrence of symptoms and increased CA-125 values were also significantly lower in patients who received rIL-2. Surgery was finally performed on 10 patients (4 with and 6 without previous rIL-2 treatment) during follow-up (30 +/- 12.7 months). These findings led to the conclusion that transvaginal ultrasound-guided puncture and aspiration of endometriomas under endometrial suppressive therapy with GnRH analogues have some value for endometriosis treatment, improving the clinical manifestations and avoiding some surgical therapies, and that rIL-2 left in the cyst increases these beneficial effects significantly.

Adult↗
PubMed2002

Use of intraperitoneal interferon alpha-2b therapy after conservative surgery for endometriosis and postoperative medical treatment with depot gonadotropin-releasing hormone analog: a randomized clinical trial.

OBJECTIVE: To evaluate the possible therapeutic effects of interferon alpha-2b left in the peritoneum after surgery, followed by or not followed by treatment with GnRH analogs. DESIGN: A prospective, randomized clinical trial. SETTING: University hospital. PATIENT(S): Fifty-two infertile patients with moderate or severe endometriosis. INTERVENTION(S): Laparotomic conservative surgery and either interferon alpha-2b or saline alone left in the pouch of Douglas followed by administration of either GnRH analogs depot or oral indomethacin with transvaginal echography and analysis of CA-125, immunoglobulins, and lymphocyte populations. MAIN OUTCOME MEASURE(S): Recurrence of endometriosis was considered clinically, echographically, and laparoscopically. RESULT(S): Recurrence of endometriosis in four cases without interferon (15.4%) versus 11 patients (42.3%) with interferon alpha-2b. Life table analysis showed significant differences between the groups with and without interferon 21 months after conservative surgery. There were no differences in the recurrence between the groups with or without GnRH analogs. Likewise, there were no significant changes in immunoglobulins and lymphocyte populations among patients with and without recurrence of endometriosis. The patients that received GnRH analogs depot showed a decrease in the number of CD16 and an increase of CD11b cells after treatment. CONCLUSION(S): The use of interferon alpha-2b within the peritoneal cavity after conservative surgery may be inappropriate because it increased later recurrence of endometriosis. The postoperative treatment with GnRH analogs did not significantly reduce the recurrence rate. Immunoglobulins and lymphocyte populations did not change in relation to the recurrence of endometriosis.

Adult↗
PubMed2002

Embryotoxicity of peritoneal fluid in women with endometriosis. Its relation with cytokines and lymphocyte populations.

BACKGROUND: The goals of the present work were to study the embryotoxic effects of peritoneal fluid (PF) in women with or without endometriosis, and to relate any embryotoxicity to the severity of endometriosis, infertility or achievement of pregnancy, cytokine concentrations and lymphocyte populations. METHODS: Sixty-six consecutive women of reproductive age, 54 with endometriosis (21 infertile) and 12 infertile without endometriosis, and another 12 fertile women as control group, were included in this study. They all underwent laparoscopy or laparotomy in the second half of the cycle, and PF was collected from the pouch of Douglas. The embryotoxicity of the PF was assessed by means of a mouse embryo assay, and expressed as the number of embryos that did not reach blastocyst stage. Cytokines and lymphocyte populations present in PF were also studied and correlated with embryotoxicity. RESULTS: PF embryotoxicity was increased in women with endometriosis, but there was little correlation with the severity of the disease. However, although a clear relationship to the presence of infertility was not found, embryotoxicity appeared to be lower in those infertile patients with endometriosis who later became pregnant. We found a significant increase in embryotoxicity in the presence of high cytokine concentrations, especially with interleukin-6, and less so with interleukin-8 (P < 0.05). No good correlation was observed with lymphocyte populations, but CD56 (NK) cells were significantly increased in the PF of women with endometriosis. In general, the correlations for embryotoxicity were better when PF was diluted at 20% (91.4 +/- 17 versus 68.1 +/- 31, P < 0.01). CONCLUSIONS: These results suggest that alteration in the production of cytokines in the PF, especially IL-6, besides contributing to the endometriosis and its evolution, probably increases embryotoxicity. However, no correlation was found between the latter and associated infertility.

Adult↗