[Comparison of 4 anesthetic techniques for in vitro fertilization]. / Comparación de cuatro técnicas anestésicas para fecundación in vitro.

UNLABELLED: Little is known of the effect on oocytes of anesthesia administered during retrieval. The main objective of this study was to compare the prolactin and stress hormone responses to surgical stimulus under 4 anesthetic techniques and to determine whether there is an effect of technique on the number and quality of oocytes retrieved. METHODS: We designed a clinical trial to determine the plasma and follicular levels of prolactin and cortisol in patients in an assisted reproduction program. The patients were randomized to 3 anesthetic groups: general anesthesia, spinal anesthesia, or sedation with alfentanil and midazolam plus paracervical block. Patients were consecutively assigned to the fourth group to receive sedation with remifentanil plus paracervical block. RESULTS: We studied 90 patients. The patients receiving general anesthesia had the greatest increase in prolactin by the end of the procedure. Follicular cortisol increased in the paracervical block group in which remifentanil was used for sedation. The only significant difference between groups was seen for the rate of gestation of 0% in the group receiving sedation with alfentanil and midazolam before a paracervical block. Adverse effects were few with all the techniques. All patients reported a high degree of satisfaction. CONCLUSIONS: Plasma increases in prolactin and hormonal responses to follicular puncture were fully attenuated by spinal anesthesia and partially attenuated by the techniques requiring sedation. None of the anesthetic techniques proved harmful to oocytes or embryos. Nor was the effectiveness of the in vitro fertilization technique affected by any of the anesthetic techniques studied.

Comparación de cuatro técnicas anestésicas para fecundación in vitro / Comparison of 4 anesthetic techniques for in vitro fertilization

El posible efecto de la anestesia administrada para la recuperación de ovocitos, en su funcionalidad, no es bien conocido. El objetivo principal de este trabajo es comparar los efectos sobre la respuesta de la prolactina y de las hormonas de estrés al estímulo quirúrgico de cuatro técnicas anestésicas diferentes y determinar si estas variaciones influyen en el número y calidad de ovocitos METODOLOGÍA: Diseñamos un ensayo clínico para determinar los niveles plasmáticos y foliculares de prolactina (PRL) y cortisol en pacientes programadas para técnicas de reproducción asistida (TRA). Distribución aleatoria en tres de ellos, y consecutiva en el grupo III. Grupo I: Anestesia general; Grupo II: Anestesia espinal; Grupo III: Sedación (remifentanilo)+bloqueo paracervical; Grupo IV: Sedación (alfentanilo+midazolam)+bloqueo paracervical. RESULTADOS: Se estudiaron 90 pacientes. La elevación de PRL es máxima en el grupo I al final del procedimiento. Aumenta el cortisol folicular en el grupo III. No hemos encontrado diferencias entre los grupos en las tasas salvo la tasa de gestación en el grupo IV 0%. Los efectos indeseables fueron escasos con todas las técnicas. Todas las pacientes tienen un elevado grado de satisfacción. CONCLUSIONES: El aumento de prolactina plasmática, respuesta hormonal de las pacientes a la punción folicular, queda totalmente atenuado por la anestesia espinal y parcialmente por la sedación. Ninguna técnica anestésica ha demostrado ser deletérea para los ovocitos ni para los embriones ni ha disminuido la eficacia del procedimiento de fecundación in vitro

Little is known of the effect on oocytes of anesthesia administered during retrieval. The main objective of this study was to compare the prolactin and stress hormone responses to surgical stimulus under 4 anesthetic techniques and to determine whether there is an effect of technique on the number and quality of oocytes retrieved. METHODS: We designed a clinical trial to determine the plasma and follicular levels of prolactin and cortisol in patients in an assisted reproduction program. The patients were randomized to 3 anesthetic groups: general anesthesia, spinal anesthesia, or sedation with alfentanil and midazolam plus paracervical block. Patients were consecutively assigned to the fourth group to receive sedation with remifentanil plus paracervical block. RESULTS: We studied 90 patients. The patients receiving general anesthesia had the greatest increase in prolactin by the end of the procedure. Follicular cortisol increased in the paracervical block group in which remifentanil was used for sedation. The only significant difference between groups was seen for the rate of gestation of 0% in the group receiving sedation with alfentanil and midazolam before a paracervical block. Adverse effects were few with all the techniques. All patients reported a high degree of satisfaction. CONCLUSIONS: Plasma increases in prolactin and hormonal responses to follicular puncture were fully attenuated by spinal anesthesia and partially attenuated by the techniques requiring sedation. None of the anesthetic techniques proved harmful to oocytes or embryos. Nor was the effectiveness of the in vitro fertilization technique affected by any of the anesthetic techniques studied

Probability of prostate cancer as a function of the percentage of free prostate-specific antigen in patients with a non-suspicious rectal examination and total prostate-specific antigen of 4-10 ng/ml.

Our aim was to assess the usefulness of measuring the percentage of free prostate specific antigen (PSA) in serum in relation to reducing the number of prostate biopsies in men with benign prostate examinations and serum PSA levels between 4 and 10 ng/ml. The percentage of free PSA (Immulite) in serum was analyzed prospectively in 500 men, all of whom underwent ultrasound-guided sextant prostate biopsies. Cancer was detected in 21.4% (107/500) of the patients. Using a free PSA cutoff of < or = 23% as a criterion for performing prostate biopsy would have detected 94.4% of cancers, avoided 18.8% of benign biopsies and yielded a positive predictive value of 25.3%. The percentage of free PSA increased with prostate volume. Mean total PSA and mean free percent PSA values increased as patient age increased, influencing the calculation of cutoff values, sensitivity and specificity. PSA density had a sensitivity and specificity not significantly different than the percentage of free PSA. Measurement of the percentage of free serum PSA improves the specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations.

Determination of the percentage of free prostate-specific antigen helps to avoid unnecessary biopsies in men with normal rectal examinations and total prostate-specific antigen of 4-10 ng/ml.

OBJECTIVE: To assess the usefulness of measuring the percentage of free prostate-specific antigen (PSA) in serum to reduce the number of prostate biopsies in men with serum PSA levels between 4 and 10 ng/ml and benign prostate examinations. MATERIALS AND METHODS: The percentage of free PSA (Immulite((R))) in serum was analyzed prospectively in 180 men with benign digital rectal examinations and total PSA serum levels of between 4 and 10 ng/ml. All patients underwent ultrasound-guided sextant prostatic biopsies. Sensitivity, specificity and positive and negative predictive values were calculated as well as the percent of patients in which biopsies could have been avoided for various cutoff values of the percentage of free PSA as an indicator for biopsy. Influence of age in the determination of cut points was evaluated. RESULTS: Cancer was detected in 22.2% (40/180) of the patients. Mean percentage of free PSA was 13.4% in patients with cancer and 18.9% in patients with benign prostatic hyperplasia (p = 0.001). Using a percentage of free PSA cutoff of 22% or less as a criterion for performing prostatic biopsy would have detected 95% of cancers, avoided 25% of benign biopsies and yielded a positive predictive value of 29% in patients who underwent biopsy. Mean percent of free PSA values increased as mean subject age increased, influencing the calculation of cut points, sensitivity and specificity. Leaving the cut point constant across all age groups will oblige older patients to undergo an increased number of unnecessary biopsies, although allowing for higher sensitivity in younger men. CONCLUSIONS: Measurement of the percentage of free serum PSA improves specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations. Subject age seemed to influence the determination of optimal cut points.

Protective effect of enriched diet plus growth hormone administration on radiation-induced intestinal injury and on its evolutionary pattern in the rat.

Adequate nutritional support can enhance the protective action of growth hormone in radiation-induced mucositis. Our aim is to address the evolutionary pattern of radiation injury to the small intestine of rats fed a high-protein diet and treated with growth hormone before irradiation. Male Wistar rats were fed a high-protein diet and killed two, four or seven days after irradiation. Animals were given either growth hormone or saline. The combination of growth hormone and high-protein diet reduced mortality, increased mucosal height and crypt proliferation, and reduced apoptosis from day 2 to day 7 after irradiation. Bacterial translocation was increased in rats fed the high-protein formula. Insulin-like growth factor was reduced by radiation and further reduced by the high-protein diet. The combination of growth hormone and high-protein diet protects from the damage caused by radiation to the bowel and accelerates its recovery. This effect does not seem to be mediated through insulin-like growth factor levels.

[Gly380Arg and Asn540Lys mutations of fibroblast growth factor receptor 3 in achondroplasia and hypochndroplasia in the Spanish population]. / Análisis de las mutaciones Gly380Arg y Asn540Lys del receptor 3 del factor de crecimiento de fibroblastos en la acondroplasia y la hipocondroplasia en la población española.

BACKGROUND: Achondroplasia, the most common type of genetic dwarfism characterised by disproportionate short stature and other skeletal anomalies, results from a defect in the maturation of the chondrocytes in the growth plate cartilage. Hypochondroplasia, considered allelic to achondroplasia is clinically and genetically heterogeneous. Recent studies have mapped the gene on chromosome 4p16.3, and frequent mutations in the fibroblast growth factor 3 (FGFR3) have been described in these diseases in other populations. PATIENTS AND METHODS: Analysis of the FGFR3 gene mutations Gly380Arg and Asn540Lys in 20 Spanish patients (10 achondroplasic, 6 hypochondroplasic and 4 with skeletal dysplasias with some phenotypic and radiological characteristics of hypochondroplasia) by PCR and restriction analysis. RESULTS: All the achondroplasic patients have shown the same mutation (Gly380Arg) in the transmembrane domain of the receptor. Five hypochondroplasic patients presented the mutation Asn540Lys in the proximal thirosine kinase domain. CONCLUSIONS: Achondroplasia in this sample from Spanish patients is also homogeneous in its molecular basis. Genetic heterogeneity has been found in hypochondroplasia corresponding with the phenotypic diversity in this disease. Molecular analysis of FGFR3 may be an additional diagnostic tool and facilitates genetic counselling in these chondrodysplasias.

Peritoneal kinetics of cancer antigen 125 in peritoneal dialysis patients: the relationship with peritoneal outcome.

Cancer antigen 125 (CA125) is a mesothelial product that has been directly related with mesothelial bulk in peritoneal dialysis (PD) patients. Here, we evaluate CA125 levels in peritoneal effluent over time on PD, and relate them to changes in peritoneal function. We analyzed 27 peritoneal kinetic studies in 20 stable PD patients. Three patients dropped out of PD for peritoneal membrane failure after the last kinetic study, and six patients required a peritoneal rest period as treatment for membrane failure type I. We recorded the standardized daily ultrafiltration capacity, net ultrafiltration during the kinetic study, peritoneal mass transfer coefficients, time from onset of PD, and incidence of peritonitis prior to the study. A linear increase in CA125 levels over time was observed, and a strong correlation appears among the levels at different dwell times (r: 0.85-0.98, p < 0.05). At 180 minutes, the mean CA125 concentration was 48.5 +/- 39.7 U/mL. We observed significant differences in CA125 levels in effluent between the group of patients who later required a peritoneal rest period and the group of stable patients (27.7 +/- 26.3 U/mL vs 55.7 +/- 41.5 U/mL respectively, p < 0.05). Patients who left PD showed lower CA125 levels in effluent (31.4 +/- 30.6 U/mL vs 52.3 +/- 41.1 U/mL, p < 0.1). No correlation was seen between CA125 levels in effluent and time on PD, episodes of peritonitis, accumulated days of peritoneal inflammation, ultrafiltration capacity, or urea and creatinine mass transfer coefficients (MTCs). In conclusion, we believe that serial determinations of peritoneal effluent CA125 levels may help in the early identification of patients who show abnormal responses to peritoneal dialysis or its complications.

Dehydroepiandrosterone sulphate, body fat distribution and insulin in obese men.

Sex steroid hormones may be involved in determining body fat distribution in men. Recent evidence suggests that insulin may be an important regulator of sex hormones metabolism in men. Few data, however, are available on the relationship of dehydroepiandrosterone sulphate (DHEA-SO4), a major secretory product of the adrenal gland, to regional distribution of body fat or to insulin levels in men. We therefore examined the association of DHEA-SO4, total testosterone and free testosterone to waist-to-hip ratio (WHR) and to subscapular-to-triceps ratio (STR) in 34 obese, otherwise healthy men. In addition, we examined the relation between these sex steroid hormones and insulin response to an oral glucose tolerance test. DHEA-SO4 was significantly positively related to STR and significantly negatively related to insulin area. These associations remained significant after adjustment for age and obesity. Using multiple linear regression, DHEA-SO4 was independently related to both STR and insulin area. Without claiming any causality in the observed associations, we conclude that, in obese men, high DHEA-SO4 levels are related to centralized adiposity, while low DHEA-SO4 levels are related to hyperinsulinemia.

Sex hormones in chronic systemic lupus erythematosus. Correlation with clinical and biological parameters.

Sex hormones may play a major role in the pathogenesis and course of systemic lupus erythematosus (SLE). OBJECTIVE--To evaluate the immunoregulatory effect of gonadal steroids in SLE and their mechanisms of action, and to establish a correlation with the clinical and biological activity. DESIGN--Cross-sectional study of a cohort with SLE. SETTING--Outpatient SLE clinic. PATIENTS--27 patients with chronic SLE, 14 were fertile women, 8 postmenopausal women and 5 men. MEASUREMENT--Serum gonadotropins (FSH, LH), prolactin (PRL), progesterone (PG), testosterone (T), estradiol (E2) and total urinary estrogens (UE) were studied in SLE patients and in 35 healthy controls of similar age and sex. Blood and urine samples of several days of the study cycle were obtained for hormonal assay. RESULTS--An increased LH activity was observed in all groups of patients. There were no changes in serum T levels, but absence of steroid therapy increased their levels in fertile women. A decrease in E2 values in the fertile women was observed, but total UE was similar to those in controls. This suggests an alteration in intermediate estrogen metabolism. Men with SLE showed a higher levels in PG and UE than controls. Also, in both groups of women on steroid treatment, a decrease of PRL was observed compared to the controls. In the fertile women in luteal phase, there was a decrease in PG. In the fertile women with higher clinical activity in the midcycle phase, and those with higher biological activity in the luteal phase, a decrease in serum E2 was seen. CONCLUSIONS--Our results support the hypothesis that there is an alteration of intermediate metabolism of the estrogens and of the testosterone. As well, a lower production of PRL during steroid treatment, and a lower production of PG may be important contributing factors in immunomodulation of SLE. Mechanism for this action should be mediated through a stimulation of the gonadotropins as LH.

Protein intake during aggressive calorie restriction in obesity determines growth hormone response to growth hormone-releasing hormone after weight loss.

OBJECTIVE: We evaluated the influence of two types of calorie restriction, total fast or very low calorie diet, on GH responsiveness to GHRH in severely obese patients. DESIGN: Twenty patients with massive obesity underwent one of two types of calorie restriction, total fast (10 patients) or very low calorie diet (10 patients). MEASUREMENTS: Fasting GH, IGF-I, glucose, insulin and GH secretion after GHRH (100 ug i.v.) were assessed in all patients before and after diet therapy. RESULTS: Both types of diet produced similar weight reduction (total fast, 5.6 +/- 1.6 kg/m2 vs very low calorie diet, 5.6 +/- 1.5 kg/m2 mean +/- SD). A significant increase in the integrated GH secretion was observed after weight loss with very low calorie diet (17 +/- 9 vs 27 +/- 12 mU/l min; P < 0.05). However, no change was found in GH response after weight loss with total fast (13 +/- 5 vs 15 +/- 7 mU/l min). Glucose, insulin and IGF-I levels showed a significant decrease with weight reduction which was similar for both groups. CONCLUSION: These findings suggest that the type of dietary manipulation during calorie restriction in obese patients may influence the changes in GH response to GHRH after weight loss.

Inadequate production of progesterone in women with systemic lupus erythematosus.

We have performed a longitudinal study of the hypothalamic-pituitary-ovary axis and adrenal function during the menstrual cycle in 26 women with inactive or quiescent systemic lupus erythematosus (SLE) and in 21 healthy women as controls. In all women studied, the menstrual cycle was proved to be ovulatory by ultrasound imaging and detection of an appropriately elevated value of peak serum progesterone. Blood samples were obtained for hormonal assay on several days of the menstrual cycle studied. Patients with SLE had lower peak and day-7 postovulation serum progesterone concentrations which were both significantly lower than those found in controls, whereas no major differences were observed for any of the other hormones analysed. Although the significance of the inadequate production of progesterone we have observed in SLE women with inactive disease is not clear, our data seem to indicate that a relative deficiency of progesterone might be considered among the potential predisposing factors for development of SLE in women.

[The hormonal changes in postmenopausal women with rheumatoid arthritis]. / Alteraciones hormonales en mujeres postmenopáusicas con artritis reumatoide.

We have studied the levels of sexual hormones in 45 female patients suffering seropositive rheumatoid arthritis (RA). Patients were classified in two groups. Group 1 (premenopausal), was formed by 26 women and group 11 (postmenopausal) by 19 women. They were compared to 40 control women (20 premenopausal and 20 postmenopausal). Age and body surface as similar in both groups. Mean estradiol, progesterone and androgen plasma levels in group 1 were similar to the premenopausal control group. On the contrary, group 11 patients presented a statistically significant increase in plasma androgen levels when compared to the postmenopausal control group. This seems to indicate that postmenopausal women suffering rheumatoid arthritis present a hyperandrogenic situation, which could have a beneficial effect on the clinical expression of the disease.

Cathepsin D in breast cancer tissue.

The cathepsin D concentration in 18 women with benign breast pathology has a cut-off value of 43 pmol/mg of protein. High values have been detected in two cases of chronic mastitis. These high values of cathepsin D were found in a study of 62 patients suffering from breast cancer and are independent of the hormone dependent state of the tumour. The cathepsin D concentration may have a prognostic function in breast cancer determination, as high concentrations are found in combination with other prognostic factors such as clinical stage, size of the tumour, state of the axillary lymph nodes and in the histological differentiation grade, where from a statistical point of view, the combination is important.

[Increase in plasma androgens in menopausal women with rheumatoid polyarthritis]. / Elévation des androgènes plasmatiques chez les femmes ménopausées atteintes de polyarthrite rhumatoïde.

The concentrations of sex hormones were studied in 45 women with rheumatoid arthritis (RA). The patients were classified into two groups. Group I (premenopausal) consisted of 26 women and group II (postmenopausal) included 19 women. The two groups were compared with 40 control women (20 premenopausal and 20 postmenopausal). Age and weight were comparable in the 2 groups (controls and patients). The average plasma concentrations of oestradiol, progesterone and androgens were comparable in group I (patients with RA) and the control group (premenopausal women). On the other hand, the plasma concentration of androgens was statistically significantly higher in patients in group II by comparison with the postmenopausal controls. It thus seems that a hyperandrogenic situation may occur in menopausal women with RA, and this might have a beneficial clinical effect on the disease.

Mechanism of action of high-load copper IUDs.

A comparative study was made of four intrauterine contraceptive devices: the Nova-T, MLCu250 Short, MLCu375, and the Gyne T. An endometrial biopsy was performed on the 25th day of the menstrual cycle. The tissue obtained was analyzed to determine estrogen and progesterone receptor concentration. After two years of IUD use, both estrogen and progesterone receptors decreased proportionally to the increased amount of copper in the IUD.

The effect of copper ions in vivo on specific hormonal endometrial receptors.

A comparative randomized study was made of three intrauterine contraceptive devices: the Nova-T, MLCu250 Short and MLCu375. An endometrial biopsy was performed on the 25th day of the menstrual cycle before and after IUD insertion. The tissue obtained was analyzed to determine estrogen and progesterone receptor concentration and endometrial morphology patterns in IUD users. Both estrogen and progesterone receptors decreased proportionally to the increased amount of copper in the IUD. The histologic study showed changes in endometria relative to the amount of copper, but these changes were transitory and disappeared after a year of IUD use.

The functional value of collateral testicular vascularisation. An experimental study.

The functional value of the collateral testicular vascularisation has been studied in the rat. In some cases the spermatic artery was sectioned at different levels and in others the vasal artery was sectioned. Hormonal, pathological and anatomical parameters were investigated. The results support the concept that the vasal artery is the most important collateral artery and that the cremasteric artery plays little, if any, part. They also support the view that following proximal section of the testicular artery, the collateral testicular blood supply is variable and the effects of this division are unpredictable and inconsistent.

Transection of the spermatic vessels (Bevan's technique): an experimental study.

Intracanalicular or intra-abdominal undescended testicles often present a difficult surgical problem, due to a vascular pedicle shortening that prohibits scrotal placement with a 1 stage orchiopexy. The division of spermatic vessels to properly place the testis in the scrotum solves the problem of the shortening of the vessels, but raises the question of whether the endocrine function and the potential for fertility are preserved. In the present study transection of spermatic vessels before arterial branch-off was done intra-abdominally in rats. Angiographic, patho-anatomic and hormonal evaluations have been made. Revascularization of the testicular artery through the vasal artery has occurred in all cases. The anastomotic circuit, however, does not always have the same functional value. The spermatogenic alterations suggest that fertility can be impaired in a significant percentage of cases. Spermatogenesis was quantified taking into account the mean tubular diameter and the situation of seminiferous epithelium, expressed as the percentage of tubules containing well-developed spermatogenesis. Plasma testosterone levels are in a low range. However, Leydig cell functional response to human chorionic gonadotropin stimulation is maintained in every case and so are plasma and pituitary luteinizing hormone levels, suggesting that plasma testosterone levels are high enough to maintain an adequate hormonal activity.