Current status of prenatal diagnosis in Cuba: causes of low prevalence of Down syndrome.

OBJECTIVES: To analyze trends in cytogenetic prenatal diagnosis in Cuba and to analyze possible causes leading to a low Down syndrome prevalence in a country where the triple test is not available. METHODS: An analysis of the Cuban program in prenatal cytogenetic diagnosis from 1984 to 2012 was conducted. Results are described, with particular emphasis on indications, abnormal results, types of invasive procedures, and terminations of pregnancy. RESULTS: Cytogenetic prenatal diagnostic analyses (n = 75,095) were conducted; maternal age was the indication for 77.9% of the amniocenteses and chorionic villus samplings. The detection rate of chromosomally abnormal pregnancies was 2.3% for maternal age and increased to 8-9% for other indications. When a chromosomal abnormality was identified, 88.5% terminated the pregnancy. In 2002, the live birth prevalence of Down syndrome was 8.4 per 10,000 live births, and in 2012, 7 per 10,000. CONCLUSION: Prenatal diagnosis in Cuba has contributed to a significant reduction in chromosomal aberrations. The impact increased because of the demographic trends of the population, the high index of terminations of pregnancy, and the establishment of a network of cytogenetic laboratories throughout Cuba.

[Elbow dislocation]. / Luxación de codo.

Elbow dislocation is the most frequent dislocation in the upper limb after shoulder dislocation. Closed reduction is feasible in outpatient care when there is no associated fracture. A review is presented of the different reduction procedures.

Studies on the mode of action of somatostatin on insulin secretion.

The effect of somatostatin on insulin release by incubated slices of rat pancreas was studied. Somatostatin inhibited insulin release induced by arginine/glucose (A/G), glucagon, glibenclamide, pentoxifyllin, 3',5'-adenosine monophosphate (cAMP), phentolamine, and KCl. When A/G was used as a stimulus, the quantial inhibitory effect of somatostatin was not neutralized by progressively increasing glucose concentrations. The alpha adrenergic blocking agent phentolamine, the phosphodiesterase inhibitors theophylline (10 mM) or pentoxifyllin (10 mM), and KCl partially reversed the inhibitory effect of somatostatin on A/G stimulation. The maximal reversal of somatostatin inhibition was obtained when the slices of pancreas were stimulated with A/G in the presence of the calcium ioniphore A23187 plus ATP. These results suggest that the inhibitory effect of somatostatin on insulin secretion could result from calcium translocation in pancreatic beta cells.

A temporal study of somatostatin secretion and its inhibitory effect in genetically diabetic mice (C57BL/KsJ-db/db).

Somatostatin (SRIF) acts as a physiological regulator of insulin and glucagon secretion. This study explored whether alterations in SRIF secretion and activity in perifused pancreas from spontaneously diabetic mice (C57BL/KsJ-db/db) could be correlated with hypersecretion of insulin by the beta-cells. SRIF release upon stimulation with 27.5 mM glucose was biphasic in controls, whereas a first phase peak was absent in 30-to 90-day-old diabetic mice (db/db). Twelve- to 28-day-old db/db mice showed two distinct patterns compared to controls: biphasic hypersecretion in the 12- to 20-day-old group compared to normal secretion in the 22- to 28-day-old group. Basal SRIF secretion showed a tendency to be elevated above controls in some of the db/db age groups, but the difference was not statistically significant. Insulin release from control pancreases was biphasic, whereas in db/db mice, basal hypersecretion, absence of the first peak, and second phase hypersecretion were observed. beta-Cell sensitivity to the inhibitory effect of SRIF was diminished in db/db mice aged 12-90 days. Diazoxide, on the contrary, inhibited insulin secretion from the pancreas of diabetic and normal mice to the same extent. The results suggest that altered secretion of and response to SRIF in C57BL/KsJ-db/db mice might provide an explanation for the anomalies in insulin secretion in the first stages of this type of diabetic syndrome.

Effect of melatonin on the basal and stimulated gonadotropin levels in normal men and postmenopausal women.

The effect of melatonin on LH and FSH secretion in basal conditions and after stimulation with synthetic LHRH was studied in 3 volunteer normal men and 3 women two to five years after menopause. During the first three days of study, blood samples were obtained at 8 AM. On the second day, an iv injection of 50 mug LHRH was performed; on the third day, 2 ml of 0.9% saline were injected. In both cases, blood samples were obtained 30 and 60 minutes after the injection. On the fourth day, the subjects began melatonin (10 mg daily im for 13 days). Blood samples at 8 AM were obtained after 5, 11, and 13 days of administration of the drug. On days 5 and 11 of the treatment, iv injections of 50 mug LHRH were performed and on day 13 an iv injection of saline 0.9% was given. Blood samples were obtained 30 and 60 minutes after each injection. In each sample LH and FSH levels were determined by radioimmunoassay. Melatonin treatment did not cause any significant change in basal or post-stimulation LH and FSH levels either in men or in post-menopausal women. These results do not support previous findings of an insults do not support previous findings of an inhibitory effect of melatonin on gonadotropin secretion, even with the same dose as the one used in this study. Further studies with higher doses of melatonin are needed to clarify the action of this drug on gonadotropin secretion.

Pituitary-gonadal response to acute I.M. stimulation with clomiphene citrate in normal men.

In order to asses the effect of acute i.m. injection of clomiphene citrate (CC) on LH, FSH, and testosterone (T) secretion, five normal, fertile men received 5 mg of the drug dissolved in 2 ml 0.9% saline, while a further five were injected 10 mg of the same preparation. All tests were performed at 8 a.m. Blood samples were drawn at 0, 30, 60, 120 and 180 minutes of the injection. Serum LH, FSH, and T values were determined by the double antibody radioimmunoassay technique. A significant rise of the LH, FSH, and T levels was obtained in both groups. Peak LH values were obtained at 30 minutes (average), whereas FSH and T peaks occurred at 60 minutes. The 180-minute values were similar to basal. The results seem to indicate that intramsucularly administered CC could be useful, as a rapid test, in evaluating the function of the hypothalamic-pituitary-gonadal axis.

Effect of sulpiride on serum prolactin levels in humans.

The effect of acute and chronic administration of sulpiride sulphate on serum prolactin levels in humans was studied. Six normal women and four normal men received an i.m. injection of 100 mg sulpiride at 0800 h. A control group received saline solution 0.9%. Blood samples were taken before and 30, 60 and 120 minutes after the injection. Serum prolactin was determined by a double antibody radioimmunoassay technique. Sulpiride induced in all subjects a quick and marked increment of serum prolactin levels with peak values at 30 minutes. At 120 minutes the levels remained high. In another experiment six post menopausal women received 150 mg of sulpiride orally during 10 days. Five of them had marked increments of circulating levels of prolactin at the end of treatment. It is suggested that sulpiride could be used in the dynamic functional exploration of hypothalamic-pitutiary system.

Daily variations of FSH, LH and testosterone response to intravenous luteinizing hormone-releasing factor (LRF) in normal men.

The responses of FSH, LH and testosterone to acute stimulation with synthetic LRF were studied in 6 healthy, fertile men aged 33.4 plus or minus 1.6 yr (X plus or minus SE). Fifty mug of LRF were given, iv at 0600 h, 1200 h, 1800 h and 0000 h, at 1-week intervals, to all 6 volunteers simultaneously. Blood samples were collected by venipuncture before (-5 and 0 min) and 8, 16, 32, 64 and 128 min after LRF injection. Plasma levels of FSH, LH and testosterone were determined by double antibody radioimmunoassay techniques. The responses of FSH and LH to LRF injection showed a clear difference at the times studied. Maximal values were obtained at 0600 h and 1800 h while the response at noon was not significant for LH and absent for FSH. Testosterone secretion showed a clear-cut response to LRF in all the subjects. At three of the four studied times (0600 h, 1800 h, 000 h) plasma testosterone was already increased at 8 min reaching its maximum at 16 min and persisted high until the end of the study. The noon response reached its maximum at the end of the test period. The daily variations of FSH and LH responses to acute LRF stimulation should be taken into consideration in clinical practive and the increment in testosterone secretion makes this test a useful indicator for androgenic testicular reserve.

Effect of a new benzodiazepine derivate, clobazam, in anxious patients with gastrointestinal disorders.

Thirty-four anxious patients with gastrointestinal disorders were studied in order to evaluate the effectiveness of a new 1,5-benzodiazepine antianxiety agent (HR 376). The disorders were classified as organic or functional according to the presence or absence of radiologic signs of ulcer. Dietetic measures, gastric antacids, anticholinergic agents, and antianxiety treatment were applied for six weeks. Anxiolytic treatment consisted of 30 mg/day clobazam (HR 376) or 15 mg/day diazepam, given in a randomized, double-blind manner. Clinical follow-up was performed with the PEN Personality Inventory (PEN), Taylor Manifest Anxiety Scale (TMAS), Hamilton Anxiety Scale (HAS), and Wittenborn Psychiatric Rating Scales (WPRS). The score of the psychoticism dimension of the PEN inventory was significantly higher in organic than in functional patients. Significant differences occurred in the reduction of the rating scores of HAS and WPRS before/after treatment in the clobazam and diazepam groups. This would express a modification of state anxiety. The TMAS, which evaluates trait anxiety, disclosed statistically significant improvement in the clobazam group. This group showed an early reduction of the HAS and TMAS scores, which would suggest an early onset of action.

Effect of two phosphodiesterase inhibitors, cyclic adenosine 3':5'-monophosphate, and a beta-blocking agent on human sperm motility.

Mann-fructose fluid (MF), and MF plus caffeine, MF plus pentoxifylline, MF (dibutyryl cAMP), MF plus propranolol, and MF plus propranolol plus dibutyryl cAMP were individually added to aliquots of semen samples obtained from 18 normal men. These drugs were added to a final concentration of 0.6 mM. One aliquot with no addition served as control. Samples were incubated at 37 degrees C and observed by light microscopy at 30 minutes and at 1,2, and 4 hours after obtained the material. At each observation time, semen quality was evaluated by determinating the percentages of forwardly progresssive spermatozoa, slowly progressive spermatozoa, "in situ" motile spermatozoa, live and nonmotile spermatozoa, and dead spermatozoa. Mann-fructose fluid resulted in a decrease in motility and the duration of activity of spermatozoa, Caffeine seemed to neutralize the deleterus effect on the buffer, whereas pentoxifylline and cAMP seemed to increase the duration of activity of spermatozoa. Propranolol resulted in a dramatic decrease in motility, an effect that could not be neutralized by the simultaneous addition of cAMP.

PIP: Mann-fructose fluid (MF), MF plus caffeine, MF plus pentoxifylline, MF plus dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP), MF plus propranolol, and MF plus propranolol plus dibutyryl cAMP were individually added to aliquots of semen samples obtained from 18 normal men to a final concentration of .6 mM to determine whether these drugs affected percentage, quality, and duration of activity of ejaculated human spermatozoa. At each observation time (30 minutes, 1, 2, and 4 hours), semen quality was evaluated by determining percentages of forwardly progressive, slowly progressive, in situ motile, live and nonmotile, and dead sperm. MF resulted in a decrease in motility and duration of activity compared with controls (P .001). Caffeine seemed to neutralize the deleterious effect, whereas pentoxifylline and cAMP seemed to increase duration of activity. Propranolol resulted in a dramatic decrease in motility, an effect that could not be neutralized by adding cAMP. The effects of adding cAMP seem to confirm that an increase of the intracellular content of this compound could determine a longer-lasting activity of ejaculated human spermatozoa.

Response of luteinizing hormone and follicle-stimulating hormone to different doses of synthetic luteinizing hormone-releasing hormone by intramuscular administration in normal and oligospermic men: preliminary report.

The response of LH and FSH levels to intramuscularly administered synthetic LH-RH was studied in two healthy volunteers and three oligospermic patients. Four tests with 50, 100, 250, and 500 mug of LH-RH, respectively, were carried out on each subject at 8 am; the interval between tests was one week. The serum levels of LH and FSH were determined by radioimmunoassay (double-antibody method) before each injection, and 60, 120, 180, and 240 minutes after each injection. No differences in the basal values of either hormone were observed. In both oligospermic and normal men, maximal responses were obtained with doses between 100 and 250 mug. With 500 mug, levels decreased rather than increased. Maximal peaks occurred between 60 and 180 minutes after injection. In the two normal subjects, the responses of LH and FSH were similar. Two of the three oligospermic patients showed discordant responses. From the results, we can assume that LH-RH doses between 100 and 250 mug should be used as a basis for chronic treatment.

Release of prolactin during pregnancy: effect of sulpiride.

The aim of this trial was to study the prolactin-releasing capacity of the pituitary during pregnancy by means of an acute stimulation with sulpiride. Thirty women with normal pregnancies were included in the study (first trimester, nine women; second trimester, eleven women thir trimester, ten women). Each woman received an intramusclar injection of 100 mg of sulpiride sulfate between 8 and 9 A.M. Three similar groups received injections of a saline solution. Blood samples were obtained before and 30 and 60 minutes after the injection. In each sample the prolactin concentration was determined by radioimmunoassay. Basal prolactin levels increased during pregnancy. Significant responses to sulpiride were observed during the three stages of pregnancy, and the levels in the second and third trimesters were higher than those in the firsttrimester. The prolactin-releasing capacity of the pituitary, as judged by the response to sulpiride, seems to be maintained during pregnancy.

Effect of D-leucine-6-luteinizing hormone-releasing hormone ethylamide in patients with hypogonadotropic hypogonadism with anosmia.

Four men with hypogonadotropic hypogonadism and anosmia were tested with acute intravenous injections of luteinizing hormone-releasing hormone (LH-RH) and D-leucine-6-LH-RH-ethylamide (D-L eu-6-LH-RH-EA) with a 1-week interval. Each patient was then treated with this drug for 60 days and tested again after this period with an intravenous injection of D-L eu-6-LH-RH-EA. The administration of LH-RH resulted in a significant increase in the LH level in only one patient and in follicle-stimulating hormone (FSH) and testosterone increases in none. The analog D-Leu-6-LH-RH-EA resulted in significant increases in LH levels in two patients, in FSH levels in three, and in testosterone levels in one. Results obtained after treatment were closely similar to those observed before treatment. Clinical improvement in terms of increased libido, erection, pubic hair growth, and testicular size was observed. D-Leu-6-LH-RH-EA could be useful in the treatment of patients with hypogonadotropic hypogonadism, a possibility deserving further studies.

D-leucine-6-luteinizing hormone-releasing hormone ethylamide in the treatment of normogonadotropic oligoasthenospermia.

The effectiveness of D-leucine-6-luteinizing hormone-releasing hormone ethylamide (D-Leu-6-LH-RH-EA) in the treatment of idiopathic normogonadotropic oligoasthenospermia was assessed in 17 patients selected on the basis of at least three previous sperm counts; a history of long-standing infertility; normal serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone; and lack of any evidence of other pathologic involvement. On testicular biopsy all patients showed hypospermatogenesis or arrest at the spermatid stage with the exception of two with more severe disorders. D-Leu-6-LH-RH-EA- was administered intramuscularly for 90 days at a daily dose of 5 microgram (four patients), 10 microgram (four patients), 20 microgram (five patients), and 200 microgram (four patients). The results showed no significant improvement in the parameters considered (number of spermatozoa per milliliter, percentage of live and motile spermatozoa, and percentage of forwardly progressive spermatozoa). D-Leu-6-LH-RH-EA does not seem promising for the treatment of oligoasthenospermic patients.

Response of luteinizing hormone and follicle-stimulating hormone to different doses of D-leucine-6-LH-RH ethylamide in oligospermic patients.

The rise in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels after intramuscular administration of D-leucine-6-LH-RH ethylamide was studied in seven patients with idiopathic normogonadotropic oligospermia. Four tests with 2.5, 5.0, 10.0, and 20.0 mug of the analog, respectively, were carried out at 8 A.M. on each subject. The interval between tests was 1 week. Serum levels of LH and FSH were determined by radioimmunoassay before (-15 And 0 minutes) and 2, 4, 6, 12, and 14 hours after each injection. No differences in the basal values for either hormone were observed. D-Leucine-6-LH-RH ethylamide produced significant increases in LH and FSH levels for 6 to 12 hours after the injection. Peak values were obtained between 4 and 6 hours. A dose-response relationship for both gonadotropins was observed. The highest average levels of LH and FSH were obtained after injection of 20.0 mug of the drug. A great individual variation in magnitude of response was observed which seemed to be related to the functional reserve of the pituitary. It is suggested that doses of 10.0 to 20.0 mug of D-leucine-6-LH-RH ethlamide/day could be used for chronic treatment in male infertility.

Treatment of idiopathic normogonadotropic oligoasthenospermia with synthetic luteinizing hormone-releasing hormone.

An assessment of the effectiveness of synthetic luteinizing hormone-releasing hormone (LH-RH) in the treatment of idiopathic normogonadotropic oligoasthenospermia was made in 21 subjects selected on the basis of at least three previous sperm counts; a history of long-standing infertility; normal urinary gonadotropin excretion; normal serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone; and lack of any evidence of other clinical, endocrine, vascular, infectious, and/or urologic involvement. On testicular biopsy, 14 patients showed hypospermatogenesis or arrest up to the spermatid stage (group 1), while the remaining 7 had more severe spermatogenetic disorders (group 2). Libido and/or potency were previously unaltered in all subjects. Five patients in group 1 and five patients in group 2 received intramuscular injection of 100 to 500 mug of LH-RH daily for no less than 60 days (long-term treatment); the remainder received the drug for 30-day periods, with 30-day intervals (short-term treatment). Qualitative and quantitative assessment of the results during and after treatment showed frank improvement in spermatozoal concentration, vitality, and motility in group 1 patients, particularly in those undergoing long-term treatment (three of five patients under these conditions were able to impregnate their wives). The long-term regimen also resulted in predomantly qualitative improvements in group 2 (one of five patients impregnated his wife). The short-term regimen was less effective. Improvements under either regimen usually occurred at the end of, or after, treatment. Six of seven patients in group 1 who were followed for a long period retained values above preliminary values for 90 to 150 days after the drug was discontinued. Increased libido and potency were spontaneously reported by 15 patients, 20 to 30 days after the start of administration of synthetic LH-RH.

Use of synthetic luteinizing hormone-releasing hormone in treatment of oligospermic men: a preliminary report.

Synthetic luteinizing hormone-releasing hormone (LH-RH) was administered to four normogonadotropic, oligospermic men (24 to 39 years of age) who had no endocrinologic, urologic, or associated vascular disease, to assess its possible therapeutic value in male infertility. Previous testicular biopsies of these subjects indicated alteration of spermiogenesis only. LH-RH (mean dose, 500 mug/day) was administered intramuscularly for 100 to 135 days. Each patient had at least two sperm count before starting therapy and had one every 20 to 30 days during and for two to five months after treatment. The sperm count, semen volume, sperm motility and morphology, and seminal plasma concentrations of fructose and citric acid were studied in each semen sample. In three of the four patients, urinary LH and FSH excretion and plasma testosterone levels were also measured. The sperm count increased clearly in two subjects 30 to 80 days after therapy started; the response was small in the third subject and negative in the fourth. The remaining parameters followed variable courses. Libido increased in all subjects. In the post-treatment period, the two patients who had shown the best response during treatment experienced a new and abrupt increase in the sperm count which remained well above initial values at the end of follow-up. LH-RH appears to be of value in the treatment of certain types of oligospermia, but several issues remain unsettled.

Bromocriptine in the treatment of hyperolactinemic amenorrhea.

Thirty women with secondary amenorrhea and hyperprolactinemia were studied; galactorrhea was present in 25 of them, and 18 were infertile. Serum prolactin (PRL) levels were high in all cases, between 26 and 120 ng/ml. All women were treated with bromocriptine in increasing doses from 2.5 to 5.0 or 7.5 mg daily, according to the response obtained, for 4 months. In 27 patients a PRL determination was performed during treatment; values returned to normal (up to 20 ng/ml) in 23 women and remained high in 4. Galactorrhea disappeared in 21 of 25 women. Ovulatory menses were re-established in 17 patients (56.6%). Seven women became pregnant (38.8%), one of them after bromocriptine and clomiphene were given simultaneously in the same cycle. According to our results and a literature review the following conclusions may be drawn: (1) bromocriptine is a useful therapeutic tool for re-establishing menstruation and inducing ovulation in patients with the hyperprolactinemic-amenorrhea syndrome; (2) the association of bromocriptine and clomiphene could be the next step in the treatment of patients who fail to ovulate with bromocriptine alone.

Correlation between leuteinizing hormone responses to luteinizing hormone-releasing hormone (LH-RH) and to D-leu-6-LH-RH-ethylamide in patients with hypothalamo-pituitary disease.

Seventeen patients (eleven females and six males) with organic hypothalamo-pituitary disease were subjected to a test consisting of a rapid intravenous injection of 50 mug of luteinizing hormone-releasing hormone (LH-RH) at 8:00 A.M., with blood sampling before and 30 and 60 minutes afterward. Two to four weeks later, a rapid intravenous injection of 50 mug of D-Leu-6-des-Gly-10-LH-RH-ethylamide (D-Leu-6-LH-RH-EA) was given under similar conditions, with blood sampling before and 30, 60, and 90 minutes afterward. Serum LH levels were determined by radioimmunoassay. D-Leu-6-LH-RH-EA caused a greater and more sustained rise in serum LH levels than did an equal dose of LH-RH. However, functional classifications of patients were similar with either preparation. This finding suggests that acute administration of D-Leu-6-LH-RH-EA does not cause a higher number of relevant responses as compared with LH-RH, but only a greater stimulation of LH releases in responsive patients.

Luteinizing hormone-releasing hormone in the treatment of anovultory infertility.

Fifteen infertile, anovulatory women, ages 20 to 37, were treated with synthetic luteinizing hormone-releasing hormone (LH-RH) to stimulate follicular maturation and/or ovulation. Thirteen of the patients had been treated unsuccessfully with other therapeutic regimens. To obtain follicular maturation, LH-RH was given intramuscularly in daily doses of 25 mu-g for 7 days and 50 mu-g for the next 7 days, or 100 mu-g for 3 days and 150 mu-g for the next 3 days. Both regimens were begun on the 4th day of a spontaneous or induced cycle. Follicular maturation (evaluated by the cervical mucus scale) occurred in three of seven cycles treated withe the first regimen and three of five treated with the second regimen. To induce ovulation, LH-RH was given in intravenous infusion (50 to 500 mu-g), intramuscularly (100 mu-g), or in a combination of both methods. The drug was administered after follicular maturation with LH-RH, clomiphene citrate, or human menopausal gonadotropin had been achieved; it was also given during four cycles in which spontaneous follicular maturation had occurred. Ovulation occurred in 10 of 25 treated cycles. Five pregnancies resulted, three in the first post-treatment cycle.