Resistance Exercise Program in Cognitively Normal Older Adults: CERT-Based Exercise Protocol of the AGUEDA Randomized Controlled Trial.

OBJECTIVES: To provide a comprehensive CERT (Consensus on Exercise Reporting Template)-based description of the resistance exercise program implemented in the AGUEDA (Active Gains in brain Using Exercise During Aging) study, a randomized controlled trial investigating the effects of a 24-week supervised resistance exercise program on executive function and related brain structure and function in cognitively normal older adults. DESIGN AND PARTICIPANTS: 90 cognitively normal older adults aged 65 to 80 were randomized (1:1) to a: 1) resistance exercise group; or a 2) wait-list control group. Participants in the exercise group (n = 46) performed 180 min/week of resistance exercise (3 supervised sessions per week, 60 min/session) for 24 weeks. INTERVENTION: The exercise program consisted of a combination of upper and lower limb exercises using elastic bands and the participant's own body weight as the main resistance. The load and intensity were based on the resistance of the elastic bands (7 resistances), number of repetitions (individualized), motor complexity of exercises (3 levels), sets and rest (3 sets/60 sec rest), execution time (40-60 sec) and velocity (as fast as possible). SETTINGS: The maximum prescribed-target intensity was 70-80% of the participants' maximum rate of perceived exertion (7-8 RPE). Heart rate, sleep quality and feeling scale were recorded during all exercise sessions. Those in the wait-list control group (n = 44) were asked to maintain their usual lifestyle. The feasibility of AGUEDA project was evaluated by retention, adherence, adverse events and cost estimation on the exercise program. RESULTS AND CONCLUSIONS: This study details the exercise program of the AGUEDA trial, including well-described multi-language manuals and videos, which can be used by public health professionals, or general public who wish to implement a feasible and low-cost resistance exercise program. The AGUEDA exercise program seems to be feasible by the high retention (95.6%) and attendance rate (85.7%), very low serious adverse event (1%) and low economic cost (144.23 € /participant/24 weeks). We predict that a 24-week resistance exercise program will have positive effects on brain health in cognitively normal older adults.

Physical fitness and white matter microstructure in children with overweight or obesity: the ActiveBrains project.

Recent studies investigated the association of cardiorespiratory fitness with white matter microstructure in children, yet little work has explored to what extent other components of physical fitness (i.e., muscular or motor fitness) are associated with white matter microstructure. Indeed, this association has not been previously explored in children with overweight/obesity who present a different white matter development. Therefore, we aimed to examine associations between physical fitness components and white matter microstructure in children with overweight/obesity. In total, 104 (10.04 ± 1.15 years old; 43 girls) children were included in this cross-sectional study. Physical fitness was assessed using the ALPHA-fitness test battery. Fractional anisotropy (FA) and mean diffusivity were derived from diffusion tensor imaging (DTI). No association was found between physical fitness and global DTI metrics (all P > 0.082). Within individual tracts, all associations became non-significant when analyses were adjusted for multiple comparisons. Using the voxel-wise approach, we identified a small cluster in the left lateral frontal lobe where children with greater upper-body muscular fitness showed higher FA (PFWE-corrected = 0.042). Although our results cannot conclude physical fitness is related to white matter microstructure in children with overweight/obesity; those findings indicate that the association of muscular fitness with white matter microstructure might be more focal on frontal areas of the brain, as opposed to global differences.

Concurrent Criterion Validity of a Test of Usual Gait Speed in Older Adults.

Usual gait speed has been shown to have very good reliability and convincing predictive validity for evaluating older adults' gait skills, but its criterion validity is unknown. We examined the criterion validity of the 8-feet (i.e., 2.44 meters) test in a laboratory environment to assess usual gait speed by comparing its results with the Intelligent Device for Energy Expenditure and Activity (IDEEA) monitor. Participants were 200 well-functioning community-dwelling adults aged 65 and older (113 women; 87 men; mean [M] age = 71.8, standard deviation [ SD] = 5.6 years). Participants wore the IDEEA monitor for 48 consecutive hours, and we used the participants' average usual gait speed for the analysis. The Spearman correlation of usual gait speed using both the 8-feet test and IDEEA monitor was moderate and statistically significant (ρ = .364, p < .001). The mean difference between both methods was 0.20 ( SD = 0.27) meters/second, and the corresponding limits of agreement were 0.73 and -0.33 meters/second. There was a small systematic bias when the difference between the two methods was correlated with usual gait speed as measured by the IDEEA (ρ = -.20, p = .011). The perfect agreement (weighted kappa) of both instruments for classifying usual gait speed into tertiles, quartiles, and quintiles was 48.3% ( k = 0.17), 30.9% ( k = 0.23), and 25.4% ( k = 0.29), respectively. Our results indicate that the 8-feet test showed moderate criterion-related validity for evaluating and assessing usual gait speed test in older adults.

Physical fitness and psychological health in overweight/obese children: A cross-sectional study from the ActiveBrains project.

OBJECTIVES: To examine the associations of physical fitness (i.e. cardiorespiratory fitness, muscular strength, and speed/agility) with psychological distress and psychological well-being in overweight/obese pre-adolescent children. DESIGN: 110 overweight/obese children (10.0±1.1years old, 61 boys) from the ActiveBrains project (http://profith.ugr.es/activebrains) participated in this cross-sectional study. METHODS: Physical fitness was evaluated by the ALPHA battery test. Cardiorespiratory fitness was additionally evaluated by a maximal incremental treadmill. Stress was assessed by the Children's Daily Stress Inventory, anxiety by the State-Trait Anxiety Inventory, depression by the Children Depression Inventory, positive affect and negative affect by the Positive and Negative Affect Scale for Children, happiness by the Subjective Happiness Scale, optimism by the Life Orientation Test, and self-esteem by the Rosenberg Self-Esteem questionnaire. Linear regression adjusted for sex and peak height velocity was used to examine associations. RESULTS: Absolute upper-body muscular strength was negatively associated with stress and negative affect (ß=-0.246, p=0.047; ß=-0.329, p=0.010, respectively). Furthermore, absolute lower-body muscular strength was negatively associated with negative affect (ß=-0.301, p=0.029). Cardiorespiratory fitness, expressed by the last completed lap, and relative upper-body muscular strength were positively associated with optimism (ß=0.220, p=0.042; ß=0.240, p=0.017, respectively). Finally, absolute upper-body muscular strength was positively associated with self-esteem (ß=0.362, p=0.003) independently of sex and weight status (p for interactions >0.3), and absolute lower-body muscular strength was also positively associated with self-esteem (ß=0.352, p=0.008). CONCLUSIONS: Muscular strength was associated with psychological distress (i.e. stress and negative affect) and psychological well-being (i.e. optimism and self-esteem) as well as cardiorespiratory fitness was associated with optimism. Therefore, increased levels of physical fitness, specifically muscular strength, could have significant benefits for overweight/obese children psychological health.

Changes in objectively measured physical activity in adolescents with Down syndrome: the UP&DOWN longitudinal study.

BACKGROUND: It is a priority to understand that physical activity behaviour over time is a priority in Down syndrome population in order to design and promote succesfull interventions to maintain or increase levels of physical activity. We aimed to study 1 and 2-year changes in objectively measured physical activity among a relatively large sample of adolescents with Down syndrome. METHODS: This study comprised a total of 99 adolescents with Down syndrome (38 girls) aged from 11 to 20 years old at baseline. Participants with valid accelerometer data at baseline and at least one of the follow-up visits were included in the analysis. RESULTS: Overall, levels of physical activity observed in adolescents with Down syndrome declined from baseline to follow-ups, but these changes were not significant (all P > 0.05). Moderate-to-moderately high tracking of physical activity was observed in adolescents with Down syndrome (all P < 0.001). Youths who met physical activity guidelines at baseline demonstrated a greater decline in physical activity in 1 and 2-year changes (P < 0.05), although they were also more likely to meet physical activity guidelines at 1 and 2-year follow-ups (P < 0.05). CONCLUSIONS: Adolescents with Down syndrome do not change their levels of physical activity at 2-year follow-ups, but those who met physical activity guidelines presented stronger declines in physical activity over time.

Physical fitness as a mediator between objectively measured physical activity and clustered metabolic syndrome in children and adolescents: The UP&DOWN study.

BACKGROUND AND AIMS: The extent to which physical fitness (PF) attenuates or modifies the association between physical activity (PA) and clustered metabolic syndrome risk factors (CMetSRF) is controversial. We aimed: i) To examine the independent and combined association of objectively measured PA and PF with CMetSRF in children and adolescents; ii) To test the mediating effect of PF in the association of PA with CMetSRF. METHODS AND RESULTS: A total of 226 children and 256 adolescents participated. Levels of PA (light, moderate, vigorous and moderate-to-vigorous [MVPA]) and PF were measured by accelerometry and ALPHA battery, respectively. Cardiorespiratory and muscular fitness values were combined in a global PF variable. A CMetSRF was computed by assessing the following variables: waist circumference, systolic blood pressure, high-density lipoprotein cholesterol, triglycerides and glucose. In children, the highest vigorous PA (ß = -0.193; P = 0.003) and MVPA (ß = -0.149; P = 0.025) were individually associated with lower CMetSRF, but these associations were not independent of global PF. In adolescents, the association of moderate (ß = -0.123; P = 0.046) and MVPA (ß = -0.147; P = 0.024) with CMetSRF was independent of PF. Among unfit adolescents, the higher time they spent in MVPA the lower CMetSRF levels were found (P = 0.032). CONCLUSIONS: The results are suggestive of a full mediation of global PF in the association of MVPA and vigorous PA with CMetSRF in children. In adolescents, the association of higher moderate and MVPA with lower CMetSRF was independent of levels of PF, and mediation analyses suggest only a partial mediation of global PF in the association of MVPA with CMetSRF.

Cognition and the risk of eating disorders in Spanish adolescents: the AVENA and AFINOS studies.

UNLABELLED: Eating disorders (ED) can arise from a combination of biological and psychological factors. Some studies suggest that intellectual factors might be important in the development of ED, although the evidence is still scarce. The aim of this study was to examine the association between cognition measurements (cognitive performance and academic achievement) and the risk of developing ED in adolescents considering their weight status. The sample consisted of 3,307 adolescents (1,756 girls), aged 13-18.5 years, who participated in the AVENA (n = 1,430; 783 girls) and AFINOS (n = 1,877; 973 girls) studies. Cognitive performance was measured by the TEA test in the AVENA study, and academic achievement was self-reported in the AFINOS study. ED risk was evaluated in both studies by using the SCOFF questionnaire. Body mass index was calculated to classify adolescents as non-overweight or overweight (including obesity). Overweight adolescents showed a higher risk of developing ED than non-overweight ones in both studies. In the AVENA study, overweight boys with low performance in reasoning ability showed increased risk of ED (p = 0.05). In the AFINOS study, overweight boys with low academic performance in physical education and non-overweight girls with low academic achievement in all the areas analyzed showed higher risk of ED than their peers (all p < 0.05). CONCLUSION: No association between cognitive performance and ED risk was found in adolescents, while academic achievement was associated with ED risk, especially in non-overweight girls. The non-cognitive traits that accompany academic achievement could influence the likelihood of developing ED in these girls.

Independent and combined influence of neonatal and current body composition on academic performance in youth: The UP & DOWN Study.

BACKGROUNDS: Unhealthy body composition is a cause for concern across the lifespan. OBJECTIVE: The objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth. METHODS: This cross-sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self-reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records. RESULTS: Birth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P < 0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082-0.989) than boys in the group of both adverse effects (P < 0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029). CONCLUSIONS: Neonatal and current body composition, both independently and combined, may influence academic performance in youth.

Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era.

HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.

Cloning, cellular distribution and functional expression of small intestinal epithelium guinea pig ClC-5 chloride channel.

We report the cloning of a guinea pig ClC-5 chloride channel (gpClC-5) from distal small intestinal epithelial cells by RT-PCR and RACE. The transcript is shown to be present in duodenum, jejunum and ileum epithelium by RT-PCR and Northern analysis. This is confirmed by in situ hybridisation which also shows the transcript to be homogeneously distributed in the crypt and villus regions. Expression of gpClC-5 in HEK-293 cells generated markedly outwardly rectified chloride currents with a perm-selectivity sequence of NO(3)(-)>Cl(-)>Br(-)>I(-)>F(-)>gluconate(-). The possible role of gpClC-5 in this epithelial location is discussed.

Frequency of glutamic acid decarboxylase autoantibodies in Mexican diabetic children.

OBJECTIVE: Use radio binding assay (RBA) to quantify the frequency of autoantibodies to glutamic acid decarboxylase in Mexican children with type 1 diabetes mellitus (DM 1). RESEARCH DESIGN AND METHODS: GAD antibodies were measured in 140 mestizo children with DM 1, 66 female (47.14%) and 74 male (52.8%); age 11.7 +/- 3.55 years, and range 1.10 to 18.5 years. Most patients were treated with intermediate acting insulin, and some with the former combined with regular insulin. Mean disease duration was 3.11 +/- 2.94 years, and range 1 month to 14.5 years. Once the signed written consent was obtained, a 5.0-mL blood sample was drawn, immediately centrifuged, and the serum was kept frozen to -20 degrees C until RBA evaluation was performed with a commercial kit. RESULTS: The anti-GAD was positive in 76 DM 1 patients (54.28%) with values from 1.11 to 156.73 U/mL, and negative in 64 (45.71%). In 19 positive anti-GAD patients, the test was repeated and levels were found between 1.38 and 156.62 U/mL. An initial control group consisting of 25 healthy non-related volunteers matched by sex and age, showed negative anti-GAD for all. CONCLUSIONS: The frequency of anti-GAD in these patients was lower than that of the DM 1 European patients, but similar to that of Asians. This supports the heterogeneity of the etiopathogenic factors of DM 1 in different ethnic groups.

[Androgen-producing steroid cell ovarian tumor. Report of a case]. / Tumor ovárico de células esteroideas productor de andrógenos. Informe de caso.

UNLABELLED: Ovarian Tumors with Endocrine Repercussion make-up 5% of neoplasms in this gland, occupying the first place are the estrogen-producing tumors, in the second place are the androgen-producing tumors, progesterone, corticosteroids and renin are exceptional. In these tumors' nomenclature has existed a kind of synonyms that create confusion about their histogenesis and their difficult use in the literature. CASE REPORT: A 23 yr-old woman with opsomenorrhea of several years evolution, secondary amenorrhea, deep voice and progressive hirsutism. Weight: 98.500 kg. Height: 1.74 m. Body Mass Index (BMI): 32.61 (kg/m2). Vellus hair in the face (beard and moustache), android distribution in abdomen, forearms, thighs and legs (Ferriman score of 20), acne and bilateral breast involution. All paraclinic exams were negative. Human chorionic gonadotropin quantification in urine of 24 hours was negative. X-Ray: Right ovarian tumor was demonstrated with pelvic ultrasound and computerized axial tomography of abdomen. Cytogenetic study expressed 46 XX chromosomes. Presurgery endocrinologic studies were: total and free testosterone: 3.55 ng/mL and 14.30 pg/mL, respectively. Insulin: 43.3 microU/mL and C peptide: 5.7 ng/mL. The glucose tolerance test demonstrate intolerance to carbohydrates. During operation, the hormone levels in the right ovarian vein were: total and free testosterone of 2.70 ng/mL and 12.70 pg/mL respectively, which normalized after 12 hours of surgery. Other steroid hormones were normal. After six months of surgery the patient had Ferriman score of 10 and eumenorrhea. Weight: 98.100 kg, glucose tolerance test and basal hormone levels were normal. Electron Microscopy showed characteristic data of a steroid producing tumor without crystalloids of Reinke.

Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix.

The efficacy of the luteinizing hormone-releasing hormone antagonist Cetrorelix (SB-75) in the medical management of uterine leiomyomas (fibromas) was evaluated. Cetrorelix was administered to 18 pre-menopausal women with myomas with a mean age of 33.3 years, who had been candidates for hysterectomy. The initial dose of Cetrorelix was 5 mg twice daily s.c. for the first 2 days and thereafter 0.8 mg was given twice daily s.c. for at least 3 months. The mean duration of the treatment was 4.4 months. Before the therapy with Cetrorelix, the mean uterine volume, measured by ultrasonography, was 395.4 +/- 69.2 ml (range 89-1166). Sixteen patients showed a progressive reduction in uterine volume from 410.4 +/- 77.1 to a mean of 230.8 +/- 52.6 ml at 3 months. All patients became amenorrhoeic and had hot flushes. After treatment with Cetrorelix, a surgical myomectomy was performed in 12 women. One of the patients subjected to myomectomy after therapy with Cetrorelix became pregnant. These patients have been followed for up to 25 months and only in one case has the uterine volume increased after therapy. Three patients had good responses to therapy with Cetrorelix and it was decided to follow them only by observation. One patient became pregnant 2 months later. In the other patient, the uterine volume remained unchanged for the duration of the follow-up of 2 years and the third patient showed an increase after 21 months. In three patients, it was necessary to perform total hysterectomy. In 14 patients, serum concentrations of luteinizing hormone, follicle stimulating hormone and oestradiol decreased after the administration of the first dose of Cetrorelix and continued at subnormal values throughout therapy. In 15 patients who were not subjected to total hysterectomy, menstrual function returned at 1 month after cessation of treatment. Overall results support the use of Cetrorelix for the management of uterine leiomyomas.

[Efficacy and tolerability of the captopril and hydrochlorothiazide combination in the treatment of mild to moderate hypertension. Multicenter study]. / Eficácia e tolerabilidade da associação captopril + hidroclorotiazida no tratamento da hipertensão arterial leve a moderada. Estudo multicêntrico.

PURPOSE: To evaluate the antihypertensive efficacy and tolerability of captopril 50 mg + hydrochlorothiazide 25 mg daily in mild to moderate primary hypertension. METHODS: Out-patients (n = 471) with mild to moderate hypertension, diastolic blood pressure (DBP) 95-115 mmHg, with 15 days of washout, were included to the treatment initially with half tablet of the association of captopril 50 mg + hydrochlorothiazide 25 mg once daily, for 30 days. After this period, patients with DBP > 90 mmHg had the dosage duplicated, while the others had the same dosage for 60 days more. Evaluation was performed 15 days before and then every month during active drug. RESULTS: Twenty six patients were withdrawn, 13 (2.7%) by adverse effects and 13 by protocol violation. At the end of the wash-out period, the blood pressure (BP), 162 +/- 16/103 +/- 6 mmHg decreased significantly at the 30th day to 146 +/- 14/92 +/- 8 mmHg (p < 0.001 vs 0th day); 139 +/- 12/86 +/- 7 mmHg at the 60th day, (p < 0.001 vs 30th day), and further to 136 +/- 11/84 +/- 5 mmHg, (p < 0.001 vs day 0) till the end of the 90th day. Antihypertensive efficacy (DBP < or = 90 mmHg and decreased of the DBP > or = 10 mmHg) was obtained in 82% of the patients. There was no difference in BP control considering race, hypertension level, previous antihypertensive treatment and obesity. Cough (4%) was the main adverse event. CONCLUSION: Captopril + hydrochlorothiazide was effective and safe in the treatment of mild to moderate hypertension. The favorable response was observed in 82% of the patients independently of race, hypertensive level, previous antihypertensive treatment and obesity. Low incidence of side effects was reported, with no difference from others reported in the literature.

[Arterial hypertension in obese patients with heart hypertrophy. Effects of captopril on insulin sensitivity and growth hormone]. / Hipertensão arterial em pacientes obesos com hipertrofia cardíaca. Efeitos do captopril sobre a sensibilidade à insulina e hormônio de crescimento.

PURPOSE: To evaluate the effects of captopril (Cpt).on carbohydrate metabolism and growth hormone (GH) in adults hypertensive obese patients with normal (NGT) or impaired (IGT) glucose tolerance and left ventricular hypertrophy. METHODS: Ten patients (53 +/- 8 years), 8 women and 2 men, white, body mass index (BMI) > or = 26kg/m2, left ventricular mass index (LVMI) > 135g/m2 in man and > 110g/m2 in woman, with diastolic blood pressure (DBP) 95-115mmHg after 3 weeks of placebo, were identified by oral glucose tolerance test (OGTT-75g) as either with NGT or IGT, and treated with Cpt 25mg t.i.d. for 8 weeks. At the 8 weeks, dosage was increased to 50mg b.i.d. if DBP > 90mmHg or the decrease of the DBP < 10%, during the next 8 weeks. OGTT and clonidine tests (0,04mg/kg) with determinations, every 30 minutes of glucose, insulin, and GH during 2 hours, were performed. RESULTS: Cpt lowered SBP and DBP in the NGT group and IGT group. The LVMI and the left ventricular mass (LVM) decreased in the IGT group with no significant change in the NGT group. Cpt promoted in the IGT group decrease in the area under the curve (AUC) of glucose, and AUC of insulin, with increase of the AUC of the percent of the beta cell function, AUC of HC, and insulin sensitivity index with no significantly change in the NGT group. CONCLUSION: Adults hypertensive obese patients with IGT had decreased significantly in mean fasting level of GH concentrations compared to age, race, and BMI matched hypertensive patients with NGT. Treatment with Cpt induced a significant increased of the GH, with improvement of the metabolism in patients with IGT.

Luteinizing hormone-releasing hormone antagonist cetrorelix as primary single therapy in patients with advanced prostatic cancer and paraplegia due to metastatic invasion of spinal cord.

OBJECTIVES: To assess the clinical response to luteinizing hormone-releasing hormone (LH-RH) antagonist cetrorelix (SB-75) in patients with advanced carcinoma of the prostate and paraplegia due to metastatic invasion of spinal cord. METHODS: Cetrorelix was given at two different dose regimens to 5 patients with prostatic cancer Stage D2 and paraplegia. Urologic and neurologic examinations, laboratory studies, radiography (myelography), and prostate ultrasonography were carried out. Prostate-specific antigen (PSA) and free testosterone were also measured. RESULTS: In all patients, the neurologic symptoms regressed. The recovery of the thermic and vibratory sensation and motility of the toes was observed. The neurologic improvement continued during the treatment and at 3 months all the patients were able to walk with the aid of a cane. In 1 patient, the myelography showed that the spinal cord compression had disappeared and prostate volume assessed by ultrasonography showed a significant decrease. The bladder function greatly improved in all 5 patients during the treatment with cetrorelix. Baseline levels of luteinizing hormone fell from 9.28 to 1.0 IU/L and those of follicle-stimulating hormone (FSH) fell from 18.28 to 12 IU/L (P < 0.05) after the first day of therapy with cetrorelix. Mean levels of free testosterone were reduced from 52.4 to 14.7 pmol/L (P < 0.005) at 12 hours and to 13.1 pmol/L (P < 0.005) 3 days after the first injection of cetrorelix. A persistent inhibition of gonadotropins and testosterone was maintained during the subsequent 3 months of therapy. The high levels of PSA gradually decreased. CONCLUSIONS: Our results show that LH-RH antagonist cetrorelix causes an immediate lowering of the serum testosterone levels in patients with prostate cancer and metastases in the spinal cord, in whom the LH-RH agonists cannot be used as single drugs because of the possibility of flare-up and appears to be appropriate for long-term therapy.

Inhibition of luteinizing hormone, follicle-stimulating hormone and sex-steroid levels in men and women with a potent antagonist analog of luteinizing hormone-releasing hormone, Cetrorelix (SB-75).

Cetrorelix (SB-75; [Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] luteinizing hormone-releasing hormone (LHRH)) is a new highly potent antagonist analog of LHRH containing the D-ureidoalkyl amino acid D-citrulline at position 6 and is free of allergenic effects. This study shows the inhibition of LH and follicle-stimulating hormone (FSH) release in normal men, postmenopausal women and patients with gonadal dysgenesis, using different doses and i.m., s.c. and i.v. routes of administration of SB-75. The mean serum levels of LH and FSH in normal men who received one single dose of 300 micrograms of SB-75 sc started to decline rapidly 1 h after its administration; the LH suppression was sustained for 14 h and that of FSH up to 24 h or longer as the samples were obtained only up to this time. The nadir for LH was reached at 14 h and that for FSH at 24 h or later after administration of the antagonist (p < 0.05). Serum levels of total and free testosterone decreased after the first hour and this inhibition was maintained for up to 14 h. The nadir for total testosterone was at 6 h and that for free testosterone was at 8 h (p < 0.001), corresponding to 56% and 60% of inhibition, respectively. In postmenopausal women, inhibition of the elevated basal serum LH and FSH levels occurred after a single injection of the antagonist analog SB-75 in doses of 75, 150, 300, 600 and 1200 micrograms using im, sc and iv routes of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of mild and moderate hypertension with fosinopril. Comparison of adverse effects with other antihypertensive agents]. / Tratamento da hipertensão arterial leve e moderada com fosinopril. Comparação de efeitos adversos com outros anti-hipertensivos.

PURPOSE: To evaluate the adverse reactions of fosinopril with other antihypertensives used as monotherapy. METHODS: Out-patients (n = 2,568) with diagnostic of mild to moderate hypertension, diastolic blood pressure (DBP) 95-115mmHg, with no antihypertensive treatment for 15 days, were included to treatment initially with fosinopril (F) 10mg, once daily, for six weeks. After this period, patients with DBP > 95mmHg had the dosage, once daily, increased to 20mg, while the others were maintained with the same dosage for six more weeks. Adverse reactions of 822 patients treated as monotherapy were grouped as absent, musculoskeletal, cardiovascular, cough, gastrointestinal, neurological, genital-urinary dysfunctions and dermatological and compared with 1,568 with F. Monotherapy consist in alpha-methyldopa (100 patients); beta-blocker (129); calcium blocker (106); diuretic (394); and another ACE inhibitors (93). RESULTS: At the end of the period without treatment, the blood pressure (BP), 165 +/- 16/105 +/- 7mmHg decreased significantly at 6th week to 144 +/- 15/91 +/- 9mmHg (p < 0.05 vs week 0) with further lowering to 139 +/- 13/86 +/- 7mmHg till the end of 12th week. BP response (DBP < or = 90mmHg) was obtained in 89% of the patients with F. Absence of adverse reactions were > or = 70% in patients with F compared to other drugs. CONCLUSION: Fosinopril has demonstrated therapeutic efficacy and less adverse reactions compared to antihypertensives used previously as monotherapy.

[Comparative and double-blind study of the efficacy and safety of cilazapril compared to nifedipine retard in the treatment of mild and moderate arterial hypertension]. / Estudo comparativo duplo-cego da eficácia e segurança do cilazapril comparadas à nifedipina "retard" no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. METHODS: forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmHg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. RESULTS: The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 +/- 14/103 +/- 5 - nifedipine 157 +/- 17/108 +/- 7mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 +/- 9 - nifedipine 96 +/- 11mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no difference inter groups. BP normalization was obtained in 58% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. CONCLUSION: Cilazapril 2.5 to 25mg normalized BP in 58% of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects.

Responses to the antagonistic analog of LH-RH (SB-75, Cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer.

Among new highly potent antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), containing neutral hydrophilic D-ureidoalkyl amino acids such as D-Cit and D-Hci at position 6 and free of edematogenic and anaphylactoid reactions, Ac-D-Nal(2)1, D-Ph(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10 (LH-RH) (SB-75; Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 micrograms SB-75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6 prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of SB-75 administration. This improvement continued during the course of treatment. Before therapy with SB-75, the serum levels of prostate-specific antigen (PSA) (6.73 +/- 1.46 ng/ml), acid phosphatases, total (12.67 +/- 1.15 U/l), and prostatic (2.27 +/- 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 +/- 0.59 ng/ml; P < 0.01), (7.68 +/- 0.89 U/l; P < 0.01), and (1.39 +/- 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 +/- 8.86 to 37.92 +/- 8.52 cm3; P < 0.01, which represents a reduction of 44%. In patients with prostate cancer, after the first week of therapy with SB-75, we observed a significant decrease in bone pain, relief in urinary outflow obstruction, and reversal of the signs of prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed analgesics. PSA, acid, and alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum testosterone levels in BPH and prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog SB-75, fell to castration values. A major fall in free testosterone levels was observed after the first dose; the maximal inhibition was seen after 6-12 hr, with a simultaneous decrease in levels of both gonadotropins. Our results show that antagonist SB-75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of prostatism obtained with antagonistic analog SB-75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a therapeutic alternative in men who are considered poor surgical risks.(ABSTRACT TRUNCATED AT 400 WORDS)