Serial determinations of asymmetric dimethylarginine and homocysteine during pregnancy to predict pre-eclampsia: a longitudinal study.

OBJECTIVE: To evaluate the usefulness of serial determinations of asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations during pregnancy to predict pre-eclampsia, taking into account maternal obesity and B vitamin status. DESIGN: Longitudinal study. SETTING: Two obstetric referral hospitals. SAMPLE: Two hundred and fifty-two of 411 women invited to participate in the study. METHODS: The women made monthly visits from ≤20 weeks of gestation until delivery for measurements of plasma ADMA, Hcy, and vitamins B6 , B12, and folic acid, and for the recording of clinical information. MAIN OUTCOME MEASURE: Early elevations in plasma ADMA and Hcy related to the development of pre-eclampsia. RESULTS: Of the 252 women who completed the study, 179 had no complications, 49 developed pre-eclampsia, and 24 presented with complications other than pre-eclampsia. ADMA and Hcy increased gradually throughout pregnancy in the pre-eclampsia group, independent of maternal B-vitamin status and obesity, but remained constant in women with no complications. Relative to the preceding month, ADMA and Hcy levels increased 1 month prior to the onset of pre-eclampsia: 124 ± 27 nmol (P < 0.001) and 1177 ± 278 nmol (P = 0.001), respectively, in the pre-eclampsia group. The group of women with no complications did not show any significant changes. Increases of 80 nmol ADMA and 1000 nmol Hcy at 1 month prior to the onset of pre-eclampsia demonstrated the best potential for prediction. CONCLUSIONS: Increased ADMA and Hcy levels precede clinical manifestations of pre-eclampsia. Therefore, serial determinations of their concentrations may be helpful in identifying women at risk. TWEETABLE ABSTRACT: Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk.

Cell density influences the effect of celecoxib in two carcinoma cell lines.

It has been reported that when ovarian carcinoma cell lines are exposed to various concentrations of celecoxib, a COX-2 inhibitor, cell growth is decreased in a dose dependant manner. To examine further the effect of celecoxib, different cell densities of two carcinoma cell lines were exposed to various concentrations of celecoxib. LNCAP prostate and CAOV3 ovarian carcinoma cells were obtained from the American Type Culture Collection and maintained in Rosewell Park Memorial Institute 1640 and Dulbeceo's modified Eagle's medium, respectively. Each cell line was supplemented with 10% fetal bovine serum, 2 mM L-glutamine, and antibiotic-antimycotic solution, and placed in a humidified atmosphere containing 5% CO2 at 37 degrees C. After each cell line reached a confluency of 70-80%, 1,000, 2,000, 3,000, 5,000, 7,000 and 10,000 cells/well were seeded in 96 well plates in 100 microl medium/per well for 24 h. Each cell line was exposed to the same concentrations of celecoxib (10-100 microM) at each cell density for 72 h. Cell growth was assessed using a tetrazolium conversion assay. A significant decrease compared to controls was observed in cell growth at each cell density of LNCAP and CAOV3 cells plated with >or=30 microM and >or=50 microM celecoxib, respectively. When the cell growth curves were compared for each cell density at the same concentration of celecoxib, a significant decrease in cell growth was observed when LNCAP cells were plated at 10,000 cells/well and exposed to 10-100 microM celecoxib. At a cell density >or= 5,000 LNCAP cells/well, the inhibitory effect of celecoxib was less. Similarly, a significant decrease in cell growth was observed in CAOV3 cells plated at 1,000 cells/well compared to other cell numbers plated at the same drug concentrations. At a cell density of > 5,000 CAOV3 cells/well, the inhibitory effect of celecoxib was significantly less compared to other cell densities at the same concentration. We observed a more sensitive decrease in cell growth in both carcinoma lines studied at a cell density of 1,000 cells/well with exposure to 10-100 microM celecoxib. Both carcinoma cell lines were less sensitive at a cell density of 5,000 cells/well. Our results suggest that the inhibitory effect of celecoxib may be affected by cell density. Therefore, careful attention must be paid to determining the appropriate cell density for cytotoxicity studies.

[The critical period in natural fertility]. / El periodo crítico de la fertilidad natural.

In order to learn the natural expectancy period of first pregnancy as well as the influences of some biosocial variables, a clinical-retrospective study was performed within 1120 gravida I women. All of them attended the major institutes of health care in Mexico City (IMSS, ISSSTE, SS and DDF). Data were obtained by means of predetermined questions from subjects after the first postpartum hours. None of them had previously used any contraceptive method. Results showed age at the first pregnancy: 21.6 +/- 3.8 (years); gestational interval 22.1 +/- 19.9 (months) and a 67% achievement rate the following twelve months of sexual activity. Eutocia was seen in 54% of these population and significant linear correlation was attained between age of the patient and the gestational interval. It seems that this is the first information regarding the fertility critical period within our society.

PIP: The interval between first intercourse and pregnancy and the influence on it of various biosocial variables were studied in 1120 women who gave birth in maternity centers in Mexico City belonging to the Mexican Institute of Social Security (IMSS), the Institute of Social Security Services for State Workers (ISSSTE), the Secretariat of Health (SS), and the Medical Services of the Department of the Federal District (DDF). Women who had used contraceptives or who had a history of infertility or of endocrine or metabolic diseases were excluded. Data were obtained by means of questionnaires administered postpartum. The average age of the women was 22 + or - 4 years. 60% were married and 40% single. 41% were housewives and 59% were employed. 2% were illiterate, 22% had primary educations, 48% had secondary educations, and 8% were professionals. The average age at menarche varied from 12 to 13 years. Average age at first intercourse was 20 + or - 4 for the IMSS, 22 + or - 4 for the ISSSTE, 18 + or - 3 for the SS, and 17 + or - 2 for the DDF subsamples. The average age at first pregnancy was 21.6 + or - 2.8 years, and the average gestational interval was 22.1 + or - 19.9 months. But 67.5% of the total sample became pregnant in the 12 months following first intercourse, as did 82.9% of the SS and 86.3% of the DDF subsamples. The interval between first intercourse and first pregnancy was 8 years or more for 1-2% of the sample in each institution. 36% of women in the IMSS group, 73% in the SS and DDF groups, and 77% in the ISSSTE group had normal vaginal deliveries. 18% in the ISSSTE, 21% in the SS and DDF, and 51% in the IMSS groups had Cesarean deliveries.

[Evolution of breast cancer. A 5-year clinical experience at a city hospital]. / Evolución del cáncer Mamario. Experiencia Clínica de cinco años en un Hospital Urbano.

In order to clarify the role that some epidemiologic factor might have on the clinical evolution of breast cancer, a retrospective study was conducted. Seventy six women diagnosed with breast cancer were selected from the population of the Hospital de Ginecobstetricia 3 del Centro Medico Nacional "La Raza" del Instituto Mexicano del Seguro Social, from 1985 to 1990. Age, medical and family history, clinical onset, diagnosis, treatment, evolution and clinical status at present were analyzed. Survival analysis and Pearson's correlation were carried out. Thirty one percent of the women were 41 to 50 years old, and thirty percent had family history of breast cancer. Other systemic condition was present in 42% of the patients and multiparity in 12%. The mean age of menopause onset was 47 +/- years. Eighty-three percent of the patients looked for medical attention due to a mammary tumor mainly in the left breast (75% of the cases). Fifty-one percent of the cases were diagnosed in advanced stages. The commonest histologic variety found was the invasive ductal carcinoma (94%). Sixty six patients underwent surgical therapy. Sixteen percent of the sample had already metastases when diagnosed; mainly at lung, bone liver or brain, in that order. Systemic therapy was administered in 63% of the cases and radiotherapy in 22 patients. About 48% of the whole sample presented recurrency and 24% progression. The overall survival at five years was 82%. Sixteen percent of these patients had tumor activity clinically apparent. In general, mortality was present in advanced stages. Survival analysis demonstrated that age and tumor persistency directly influenced survival rate in this population. Other variables' role could not be evaluated. Nevertheless variables analyzed are very helpful in actions implementation to the breast cancer management.

[Ovarian apoptosis]. / Apoptosis ovárica.

Apoptosis, or programmed cell-dead is one of the main mechanisms in the process of tissular loss. This is an active process of cellular depletion that participates in a direct manner in tissular homeostasis during the life span. This apoptotic process is a key event on the pathology of tumors development. The nature of apoptosis is genetic, but it is triggered by external factors. The caspases are been mentioned as responsible of the specific cellular lost, which is the final outcome. The equilibrium between proliferation and cellular death is determined by a balance of survival factors and death promoters such as genic regulators, hormones, cytokines and growth factors among others. In the ovary, apoptosis regulates follicular proliferation and differentiation. During embryogenesis the magnitude of the population of oogonias is mediated by apoptosis. During the ovarian cycle, apoptosis participates also in the follicular atresia process. It is probable that apoptosis is participating also directly in the accelerated follicular atresia. This mechanism has been hypothesized to be involved in the pathophysiology of premature ovarian failure. The role of apoptosis is some reproductive pathological events such as chronic anovulation, low ovarian reserve and early ovarian dysfunction is still not known. The knowledge of the role of apoptosis in such pathological conditions will contribute to the understanding of the ovarian physiology and will permit to intervene early during the natural history of the disease.

[Clomiphene acetate and prednisone: alternative approach for the management of patients with chronic anovulation and clomiphene treatment failure]. / Citrato de clomifeno y prednisona: un esquema alternativo de manejo en pacientes con anovulación crónica y falla terapéutica al clomifeno.

Chronic anovulation is a common neuroendocrine cause of infertility. Pharmacological management of such condition includes the use of clomiphen citrate (CC), which is the most utilized of the ovulation inductors. Clinical efficacy of CC provides ovulation rates of around 70%. Those patients who did not respond are candidates to receive gonadothrophin treatment, which will increase costs and the risk of ovarian hyperstimulation and multiple pregnancies. Because of that, new alternative treatments have been assayed, such as the concomitant use of dexametasone. This alternative has improved the response, but its use has been limited because the side effects of this treatment overcome their benefits. Another alternative is the use of prednisone throughout the menstrual cycle together with CC administered in pre-established days. This treatment is expected to improve the response without adding side effects. However, its clinical efficacy and clínical tolerance have not been studied. In this study we used CC and prednisone in a sample of patients diagnosed with infertility and chronic anovulation, and with previous failure to the treatment with CC. Patients were compared to a group of women with similar characteristics but who received additional cycles of CC. The group that received prednisone and CC increased their ovulation rates in 38%, compared to 8% in women that received only CC. Similarly, pregnancy rates increased 20% in the CC plus prednisone group while the group that received CC alone remained in 0 pregnancies. In the total sample, tolerance to treatment was adequate. There were no side effects associated to the use of prednisone. We conclude that the treatment with CC plus prednisone is an alternative treatment for patients in which the classical treatment with CC has failed.

[Primary sterility and cervical pregnancy. A case report]. / Esterilidad primaria y embarazo cervical. A propósito de un caso.

Fortunately cervical pregnancy, an ectopic gestation that frequently represents obstetric urgency, is a rare entity. We present here the case of a woman who developed cervical pregnancy despite no risk factor associated with ectopic pregnancy was identified. The patient came to the office because of primary sterility of 4 years of evolution. Among her background she reported previous cervical surgery due to benign pathology. She reached pregnancy after medical and surgical treatment. In the week eleven of gestation, the patient presented to the hospital with clinical symptoms of abortion. An ultrasound revealed abdominal pregnancy. Laparotomy was "white", cervix was found enlarged with the external orifice closed, suggesting cervical pregnancy. Conservative treatment consisted in cervical evacuation, endometrial curettage and vaginal tampon. She evolved satisfactorily. We do not know about any previous report of cervical-pregnancy associated with cervical surgery and sterility. We also recognize the need to increase the number of similar cases to generalize results. Thus, it is important to highlight in this case the absence of known risk factors for cervical pregnancy and the background of cervical surgery and sterility. Therefore, we recommend to search for antecedents of cervical surgery and sterility when cervical pregnancy is suspected.

[Insulin-glucose ratio and body fat composition in patients with chronic anovulation and sterility]. / Relación insulina-glucosa y composición corporal grasa en pacientes con anovulación crónica y esterilidad.

A clinical, descriptive, and transversal study was conducted in a group of patients with chronic anovulation and sterility, to correlate insulin resistance, determined by the fasting glucose/insulin ratio, with body fat composition using anthropometrics parameters and the interaction of light near infrared region method, we studied 41 young patients with chronic anovulation and sterility. Based on their body mass index, all patients had obesity or overweight. Similarly, most of them presented with a percentage of body fat over the recommended limits. Forty percent of all studied patients had a fasting glucose/insulin ratio below 4.5, which corresponds to insulin resistance. The correlation between the percentage of body fat and fasting glucose/insulin ratio was significant, as was the correlation between body mass index and the percentage of body fat. We found overweight or obesity in the majority of our patients, and insulin resistance in almost half of them. Such disturbances were positively associated with the percentage of body fat and android distribution. Therefore, we recommend a routinely anthropometrics evaluation in these patients as well as fasting glucose/insulin ratio determination in order to act in an early stage over the natural history of metabolic syndrome, whose common denominator is insulin resistance.

[Flexible vaginal cast covered with oxidated cellulose. Surgical option in neovagina for patients with Rokitansky-Kuster-Hauser syndrome]. / Molde vaginal flexible recubierto de celulosa oxidada. Una opción quirúrgica en neovagina en pacientes con síndrome de Rokitansky-Kuster-Hauser.

The alterations in differentiation of the mullerian derivatives and urogenital sinus are a frequent cause of demanding attention in the gynecologist office. Vaginal agenesis and hypoplasia are the representative events of alterations of human sexual differentiation. Handling such conditions is in direct relationship to the magnitude of the anatomical damage and the biopsychosocial consequences of such pathologies. From historical perspective, several surgical techniques of neovagina to correct such alterations have been described. We are presenting our experience in surgical treatment of vaginal agenesis, as well as the aesthetic-functional outcomes obtained from a highly specialized hospital of the Health Sector in Mexico City. Our patients attended the gynecologist office mainly because of primary amenorrhea, anatomical alterations and sexual dysfunction. Tbe age range varied between 19 and 28 years. Basic laboratory tests were conducted. Urography, genetic studies, and a laparoscopic procedure were included. All the women received psychological support. The diagnosis in all the cases was Rokitansky Kuster-Hauser Syndrome with agenesis of the 2 proximal thirds of vagina. A neovagina assisted by laparoscopy using a technique previously modified was conducted. In such technique we use a flexible vaginal mould and oxide cellulose to prevent fibrosis and surgical retraction. Cosmetic outcome was satisfactory and dysfunction sexual was all improved. We conclude that our procedure that includes the neovagina assisted by laparoscopy and the use of a vaginal mould and oxide cellulose is a surgical option in those patients presenting with vaginal agenesis and hypoplasia. This procedure improves the aesthetic and sexual performances that are profoundly altered in such patients.

[Plasma concentration of biochemical markers in pre-eclampsia-eclampsia and its association with the severity of the disease]. / Concentración plasmática de indicadores bioquímicos en la preeclampsia-eclampsia y su asociación con la severidad de la patología.

UNLABELLED: It has been demonstrated that the concentrations of molecules related to endothelial cell dysfunction, coagulation and vasoconstriction are altered in preeclamptic patients, but they have not been evaluated in their relationship with the severity of preeclampsia. OBJECTIVE: To determine the relationship between the plasmatic concentrations of fibronectin ED1+, antithrombin III, prostacyclin and thromboxane, and the severity of preeclampsia. METHODS: Peripheral blood was collected from 215 women in the third trimester of pregnancy, admitted to the Luis Castelazo Ayala Gynecology and Obstetrics Hospital with mild preeclampsia (n = 103), severe preeclampsia (n = 71), HELLP syndrome (n = 25) or eclampsia (n = 16). Plasma aliquots were stored at -70 degrees C until analysis. Fibronectin ED1+ was measured by ELISA; antithrombin III activity was determined using an automated amidolytic technique, and the concentrations of the stable metabolites 6-keto-prostagiandin F1a and thromboxane B2 were measured by RIA. Statistical analysis included ANOVA and logistic regression. RESULTS: Maternal age was similar in all participants. Prematurity and low birth weight were present in the patients with severe preeclampsia, HELLP and eclampsia. The values for fibronectin were similar among the 4 groups of patients. Antithrombin III activity was significantly lower in the patients with HELLP. In patients with severe preeclampsia and HELLP syndrome, prostacyclin (Pc) and thromboxane (Tbx) concentrations were significantly higher, and the Pc/Tbx ratio was lower than in patients with mild preeclampsia. Those patients who had the highest thromboxane levels and the lowest Pc/Tbx ratio had a higher chance to develop severe preeclampsia or HELLP (5 times), as well as to have premature babies (12 times) than patients with mild preeclampsia. CONCLUSIONS: Our study demonstrates relationships among antithrombin III activity, prostacyclin and thromboxane concentrations, and the severity of preeclampsia. These compounds were significantly more altered in patients with HELLP syndrome, probably due to a higher organic and vascular dysfunction. Plasma determination of these compounds may be valuable as a tool in the screening of preeclampsia, and as an indicator of severity of the disease.

[Heterotopic pregnancy following ovulation induction by clomiphene citrate and prednisone. Report of a case]. / Embarazo heterotópico, después de inducción de ovulación con citrato de clomifeno y prednisona. Informe de un caso.

Heterotopic pregnancy (HP) is a very rare pathologic event. The incidence of ectopic pregnancy has increased as the consequence of assisted reproduction and the wider use of ovulation induction agents. The diagnosis of HP is frequently done not as earlier as it should be, and it has serious repercussions. The concept of screening, to find relevant rise factors and the correct diagnosis of HP should be pursued as early as possible. In this report we describe an unusual case of a female patient with therapeutic failure to clomiphene citrate. She was treated with two cycles of combined clomiphene citrate and prednisone, and ovulation induction assent. The after she developed HP. Overall, we conclude that the possible association observed could be an accident. The land of investigation is open, to fill cover. The holes on understanding that we still have.

Differential expression of functionality markers in mid-secretory endometrium of infertile women under treatment with ovulation-inducing agents.

OBJECTIVES: To analyze the expression of protein markers related to cell proliferation and death, as well as oestrogen and progesterone receptors in the endometrium of infertile women with hypothalamic-pituitary dysfunction treated with clomiphene citrate (CC) or recombinant follicle-stimulating hormone (rFSH), and compare them with ovulatory women. STUDY DESIGN: The study included 12 control ovulatory women and 29 anovulatory women, 19 of whom underwent ovulation induction with CC (n = 12) or rFSH (n = 5). Endometrial biopsies were obtained by Pipelle during the mid-secretory phase. Samples were stained with haematoxylin and eosin. Immunohistochemistry of proteins related to cell proliferation and cell death, as well as steroid receptors, was undertaken, and apoptosis was determined using TUNEL analysis. RESULTS: Immunohistochemical analysis of Ki67 expression showed significantly higher expression in the glandular epithelium of ovulatory women compared with the other groups. Glandular oestrogen receptor α expression was significantly lower in rFSH-treated women compared with ovulatory women. The number of apoptotic cells, Bax expression and progesterone receptor expression were similar in all groups. In contrast, Bcl-2 expression was significantly lower in the glandular epithelium of rFSH-treated women. CONCLUSIONS: In infertile women with hypothalamic-pituitary dysfunction, treatment with ovulation-inducing agents modifies the expression of proteins involved in cell proliferation and death, as well as the expression of steroid hormone receptors in the endometrium. These differences may help to explain, at the molecular level, the functionality of the endometrium during the implantation window, and may help to optimize pregnancy rates obtained with these treatments.

Selective COX-2 inhibitor (celecoxib) decreases cellular growth in prostate cancer cell lines independent of p53.

Celecoxib is a clinically available COX-2 inhibitor that has been reported to have antineoplastic activity. It has been proposed as a preventative agent for several types of early neoplastic lesions. Earlier studies have shown that sensitivity of prostatic carcinoma (PCa) to celecoxib is associated with apoptosis; however, these studies have not demonstrated adequately whether this effect is dependent on p53 status. We studied the relation between sensitivity to celecoxib and the phenotypic p53 status of PCa cells lines, LNCaP (wild type p53), PC3 (null p53) and DU145 (mutated p53). Cellular growth was assessed at 24, 48, 72 and 96 h after celecoxib treatment at concentrations of 0, 10, 30, 50, 70 and 100 µM using an MTT assay. Cellular proliferation (Ki-67 expression) was determined by immunocytochemistry. Phenotypic expression of p53 was analyzed by western blotting. The effects of celecoxib on cellular growth and its association with p53 were assessed after down-regulation of p53 using synthetic interfering RNAs (siRNA) in LNCaP cells. Expression of p53 and COX-2 at mRNA levels was assessed by quantitative real time polymerase reaction (qRT-PCR). We found that celecoxib inhibited cellular growth and proliferation in a dose-dependent manner in all three cell lines; LNCaP cells with a native p53 were the most sensitive to celecoxib. We observed a down- regulation effect on p53 in LNCaP cells exposed to ≥ 30 µM celecoxib for 72 h, but found no significant changes in the p53 levels of DU145 cells, which have a mutated p53. Reduced COX-2 expression was found with decreased p53 in LNCaP and PC-3 cells that were exposed to ≥ 20 µM of celecoxib for 72 h, but COX-2 expression was increased in DU145 cells. All three cell lines demonstrated pan-cytotoxicity when exposed to 100 µM celecoxib. When p53 expression was inhibited using siRNA in LNCaP cells, the inhibitory effects on cellular growth usually exerted by celecoxib were not changed significantly. Celecoxib reduces the growth of prostate cancer cell lines in part by decreasing proliferation, which suggests that the inhibition of growth of LNCaP cells by celecoxib is independent of normal levels of native p53.

Biosocial trends at first pregnancy in Mexican women not exposed to contraceptive methods.

PIP: Infertility is a problem for many couples who wish to conceive and bear children. This paper investigates the relationships of educational status, age, onset of menarche, first sexual intercourse, menstrual cycle, gestational interval, and coital frequency to infertility in 509 Mexican women who were not exposed to any contraceptive method. This study was conducted to gain insight into when infertility studies should commence during the course of a woman's sexual life. Two thirds of the women were married. On average, menarche took place at age 13 years, first intercourse at age 20, and they had sexual intercourse 9 times/month. 68% of women became pregnant within the first 12 months of sexual activity; earliest pregnancy was at age 14 and the latest was at age 44. A significant linear correlation was observed between chronological age and gestational interval with the achievement of first pregnancy significantly related to age and coital frequency. Overall, first pregnancy was achieved in almost 90% of monthly menstruating women. Significant estimated risk of sterility exists for older women and when periods of expectancy for pregnancy are longer than 1 year.^ieng