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Biomedical subjects

A Foradori

Publications and source records attributed to A Foradori.

At least 19 recordsLinked to original sources

[Capacity to predict a recurrence of lupus erythematosus using double-stranded anti-DNA antibodies and Farr technique].

BACKGROUND: Patients with inactive systemic lupus erythematosus (SLE) and elevated high affinity double-stranded anti-DNA antibodies (anti-dsDNA), measured using Farr technique, would have a risk of relapse that fluctuates between 40 to 80% according to different series. AIM: To study the association between anti-dsDNA levels measured using Farr technique and disease activity and their predictive capacity for relapses. MATERIAL AND METHODS: Anti-dsDNA antibodies were measured according to Farr method in 60 healthy subjects, 69 patients with other connective tissue diseases and in 120 patients with SLE. Farr positive were considered those individuals with anti-dsDNA levels over 10.4 IU/ml. Disease activity, assessed using MEX-SLEDAI score was related with anti-dsDNA levels in 101 patients. Forty seven patients with inactive disease were followed for 17 +/- 14 months. RESULTS: Anti-dsDNA levels were 3 +/- 2.5 IU/ml (range 1-26) in subjects without LED, and 127 +/- 500 IU/ml (range 1-5280) in patients with LED. Sixty subjects had an active SLE and 43 (72%) were Farr positive; in 41 the disease was inactive and 13 (32%) were Farr positive (p < 0.001), OR 5.45. Twelve of the 47 followed patients had a relapse and 10 (83%) were Farr positive. Of those that did not have a relapse, 13 (37%) were Farr positive (p < 0.02, RR 5.22). Six of 15 patients that were followed for more than on year (40%), were Farr positive. CONCLUSIONS: Elevated anti-dsDNA antibodies measured using Farr technique in patients with inactive generalised lupus erythematosus, predicted the risk of relapse. However less than half of patients with inactive disease and elevated Farr relapsed in a period of one year. The need to treat patients with inactive SLE and positive Farr should therefore be considered debatable.

Adolescent

[Detection of thyroglobulin autoantibodies and potential interference with serum thyroglobulin measurement].

BACKGROUND: Thyroglobulin measurement is useful for the follow up of patients subjected to total thyroidectomy for differentiated thyroid carcinoma. Thyroglobulin autoantibodies may interfere with its determination. AIM: To measure thyroglobulin autoantibodies and their interference with thyroglobulin determination. MATERIAL AND METHODS: The presence of thyroglobulin autoantibodies was investigated in 801 serum samples sent to the laboratory for measurement of thyroglobulin levels. A serum was considered positive for these autoantibodies when radioactivity corresponding to 125I-thyroglobulin bound to thyroglobulin autoantibodies, precipitated with human gamma globulin, exceeded in 1.4 times that of a negative sera pool. In positive sera, thyroglobulin autoantibody concentration was measured and its interference with thyroglobulin radioimmunoassay was assessed through a recuperation test using exogenous thyroglobulin. RESULTS: Thyroglobulin autoantibodies were detected in 149 sera (18.6%). Of these, 65 had a recuperation that fluctuated between 1 and 80%. Thyroglobulin autoantibody concentration was negatively correlated with recuperation percentages (r = -0.64; p < 0.001) but not with thyroglobulin concentrations (r = 0.08). Thyroglobulin was higher in positive sera with a recuperation over 80% than in sera with a recuperation of less than 80% (12.7 +/- 1.7 and 5.9 +/- 0.6 ng/ml, respectively; p < 0.001). CONCLUSIONS: Thyroglobulin autoantibodies interfere with thyroglobulin measurement by radioimmunoassay, sequestering variable amounts of thyroglobulin. The presence of these autoantibodies must be investigated prior to thyroglobulin determination.

Autoantibodies

Salt-wasting congenital adrenal hyperplasia: detection of mutations in CYP21B gene in a Chilean population.

The steroid 21-hydroxylase deficiency (21OHD) is the most frequent cause of congenital adrenal hyperplasia. We have characterized the disease-causing mutations in the 21-hydroxylase genes of 63 patients with salt-wasting congenital adrenal hyperplasia from a Chilean population of Hispanic origin, a group that has been scarcely evaluated. Using allele-specific PCR, lesions were identified in 97 chromosomes out of 126 tested (77%). The most frequent findings were the gene deletion or large gene conversion (LGC) = 22.9%, I2 splice = 19%, R357W = 12.7%, and Q319X = 10.5%. We did not find alleles with the mutation F308insT and we found three alleles with the cluster E6. The frequency of the point mutation R357W was at least two times more frequent than the one found in Caucasians populations, but similar to that communicated in Asian populations; this finding may be explained by the Asian ancestry of our South-Amerindian population. The frequency of Q319X was also high, similar only to those patients studied in Italy and in a neighboring Argentinian population. In summary, this is a genetic characterization of 21OHD made in an almost pure Hispanic population in Latin America. The high frequency of deletion of CYP21B gene, I2 splice, R357W, and Q319X mutations probably reflects the European-Caucasian-Spanish influence of the conquerors, mixed with Amerindians of Asian ancestry and modulated by other European immigrations.

Adrenal Hyperplasia, Congenital

[Measurement of low levels of plasma renin activity. A methodological improvement].

BACKGROUND: The present method to measure plasma renin activity is cumbersome and imprecise, factors that limit its clinical application. AIM: To assess the importance of blood sampling conditions and the usefulness of increasing incubation time to measure plasma renin activity at low levels. PATIENTS AND METHODS: Twenty hypertensive patients, 14 female, aged 14 to 76 years old, were studied. Two blood samples were obtained after a 10 min rest in the sitting position and after a 30 min rest in supine position. One blood sample of each condition was sent to the laboratory at room temperature and the other sample was sent refrigerated. Angiotensin I concentration was determined after 3 h of enzymatic incubation at 37 degrees C and, in subjects with an activity of less than 1 ng/ml/h, after 18 h of incubation. RESULTS: No significant differences in plasma renin activity were observed between the samples obtained with different rest times or different transportation methods. In people with low plasma renin activity, the 18 h enzymatic incubation reduced the lower detection from 0.3 to 0.014 ng/ml/h and the coefficient of variation from 14.4 to 3.2%. CONCLUSIONS: A simplified blood sampling method does not change plasma renin activity values, and the longer enzymatic incubation in people with low plasma renin activity improves both the sensitivity and accuracy of the determination.

Adolescent

[Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population].

BACKGROUND: The most frequent cause of congenital adrenal hyperplasia, manifested as virilization and salt wasting, is the deficit of 21-hydroxylase. This disease is originated by mutations of the gene CYP21 that codifies this enzyme, mostly recombination between this gene and its inactive pseudogene called CYP21P. AIM: To study the molecular origin of this enzyme deficiency in Chilean patients. PATIENTS AND METHODS: Twenty five patients with salt wasting congenital adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. In all patients, a polymerase chain reaction (PCR) with selective primers was done with extracted genomic DNA, to amplify the active gene and specific primers for normal or mutated alleles (Allele-specific PCR). RESULTS: The affected allele was identified in 39 (78%) of the 50 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26% of cases, followed by mutations Arg357Trp in 22% of cases and Gln319Stop in 12% and deletion in 12%. The identification of two affected alleles in a same patient was achieved in 17 cases (68%). The most frequent genotypes were homozygosity for ASIn2 (16%), homozygosity for Arg357Trp (12%) and the homozygote deletion of the gene in 12%. CONCLUSION: The most frequent mechanisms of genetic damage in this population of patients with salt wasting congenital adrenal hyperplasia due to deficiency of 21-hydroxylase were the mutations ASIn2 and Arg357Trp. This type of studies allows prenatal diagnosis and genetic counseling.

Adrenal Hyperplasia, Congenital

An alternative ELISA for T4 determination based on idiotype anti-idiotype interaction and a latex method for anti-idiotype monoclonal antibody selection.

This paper is the first report on the use of an idiotype-anti-idiotype monoclonal antibody reaction to develop an enzyme immunoassay for thyroxine (T4). We have developed a monoclonal antibody against T4, named 1F10 of IgG1 subclass and KA 5.21 x 10(8) M-1 which was used to obtain anti-idiotypic monoclonal antibodies. Anti-idiotypic antibodies were selected by a novel method, a passive agglutination assay with the idiotype monoclonal 1F10 absorbed on latex particles and subsequently characterized by RIA. One of these anti-idiotype antibodies, named 5B3--type beta antibody--of IgG1 subclass, was used to develop an enzyme-linked T4 idiotype-anti-idiotype immunosorbent assay. The T4 calibration curve, using the 1F10 idiotypic antibody adsorbed to solid phase and the 5B3 anti-idiotypic antibody conjugated to alkaline phosphatase (ALP), shows adequate performance in the range between 0.7-25 micrograms% of the analyte. The reliability of the proposed method is demonstrated by the correlation coefficient r = 0.74, found between T4 measured by RIA and our assay, with a panel of sera from euthyroid, hypothyroid and hyperthyroid individuals. The correlation coefficient was r = 0.93 within assays and r = 0.88 between assays. These results provide the basis for a new non isotopic assay for the study and diagnosis of T4-related human disease and provides a model to develop immunoassays for other haptens and small molecules of clinical interest.

Animals

[Breast cancer: comparison between biochemical and immunohistochemical determination of estrogen receptors].

Immunohistochemical (IH) assessment of nuclear estrogen receptor has been considered an alternative method to conventional biochemical assay. The present work intends to compare specificity and sensitivity of IH and biochemical technique to assess nuclear estrogen receptor in formalin-fixed and paraffin-embedded mammary carcinoma samples. IH positive reaction was defined as 14% or more nuclear staining in 100 cells counted under high magnification (400x). Biochemical assay was considered positive over 10 fmol/mg of protein. 66 cases were collected with a mean age of 55.6 years and a mean tumor size of 25.2 mm. Histologically, 62 cases were ductal carcinomas, 2 lobular carcinomas, and 2 medullary carcinomas. Biochemical assay for estrogen receptor was positive in 35 cases (63%) and IH in 40 cases (71%). The present results show that IH assessment of estrogen receptor is highly specific and sensitive. Estrogen receptor present in non-tumor cells and blood vessels walls may disclose false positive biochemical results and false negative result if the tumor mass is small or there are isolated tumor cells. IH assessment of estrogen receptor can be performed in small samples, including in situ lesions. The method of fast, reliable, and of lower cost, IH may be considered the method of choice in cases with insufficient sample for biochemical assay and/or in tumors containing scant cells.

Adolescent

[Effect of a 17 beta estradiol gel preparation on hormone levels in menopausal women].

Different delivery forms of supplemental estrogens may differ in their hormonal effects. The aim of this study was to assess the effects of a daily dose of 2.5 g of 17 beta estradiol transdermal gel, given during four weeks, on hormone levels of six postmenopausal women. At the fourth week we observed a significant increase in estradiol and a decrease in FSH levels. Estrone levels also increased but the estradiol/estrone ratio was maintained in values over 1. No changes in SHBG or IGF1 levels were observed. Two patients that used the gel in the abdominal skin achieved lower estradiol levels (below 60 pg/ml). We conclude that the gel increased serum estradiol levels over 60 pg/ml in four of six women, that there is a big individual variability and the application zone could influence the serum estradiol levels achieved.

Administration, Cutaneous

[Cardiovascular response to exercise at high altitude in workers chronically exposed to intermittent hypobaric hypoxia].

The isotonic work performance was assessed in 34 workers aged 35 +/- 5.8 years old that had working shifts of four days at 4500 m over the sea level and resting periods of other four days at the sea level during at least two years. Subjects were assessed in one occasion at the sea level, and at the first and fourth day of the working shift at 4500 m over the sea level. Resting arterial oxygen saturation in these three periods was 97 +/- 1.1, 88 +/- 18 and 91 +/- 1.1% respectively (p < 0.01), and markedly decreased during maximal and submaximal exercise at 4500 m over the sea level. Exercise duration in the three periods was 931 +/- 210, 775 +/- 105 and 778 +/- 105 seg respectively (p < 0.001). Heart rate in the resting period was at least 10% higher and maximal and submaximal rates were lower at high altitude. No differences in blood pressure or packed red cell volume were observed. Exercise duration correlated inversely with age (r = -0.49 p = 0.03) and directly with maximal heart rate (r = 0.44 p = 0.009) at the sea level. No correlation between aerobic capacity and other measured parameters was observed. These results show no differences in the cardiovascular response to exercise between the first and fourth day of stay at high altitude in workers chronically exposed to intermittent hypobaric hypoxia.

Adult

Uterine kallikrein in the early pregnant rat.

Uterine homogenates of cycling and early pregnant Sprague Dawley rats and purified rat urinary kallikrein showed similar curves of displacement of 125I-kallikrein binding to a polyclonal antibody. Uterine kallikrein concentration measured by RIA was 8.7 +/- 2 SEM ng/g wet weight during the cycle (n = 6 in diestrus and metestrus) and 20.8 +/- 2 SEM (n = 7) ng/g wet weight on Day 7 of pregnancy (P7) (p < 0.001). On P7, kallikrein concentration was increased 12.4-fold in the implantation nodes, as compared to the interimplantation segments. Uterine homogenates of rats on P7, submitted to DEAE-cellulose chromatography and Sephadex gel filtration, yielded two fractions containing kallikrein immunoreactivity and kininogenase activity, with molecular masses that ranged from 120-125 kDa and 39-43 kDa, respectively. In the RIA, both fractions displayed parallelism with purified kallikrein. Enzymatic activity was expressed after activation by trypsin. It was inhibited by aprotinin, PMSF, p-amino-benzamidine, and leupeptin, but not by soybean or ovomucoid trypsin inhibitors. Kallikrein mRNA was demonstrated by reverse transcriptase/polymerase chain reaction in uteri of nonpregnant and P7 rats. These results show that rat uterus synthesizes one or more serine proteases that are immunologically and enzymatically related to tissue kallikrein in the implantation node on P7--determined both by an increment of whole uterus kallikrein content and a depletion of the interimplantation segments--suggests that kallikrein may play a role in the vasoactive changes of implantation.

Animals

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.

Animals

Effect of maternal administration of thyrotropin releasing hormone on the preterm fetal pituitary-thyroid axis.

We evaluated the response of preterm fetuses to maternal intravenous injection of 400 micrograms of thyrotropin releasing hormone (TRH) between 30 minutes and 5 hours before delivery (n = 12). An additional seven mothers received saline solution and served as control subjects. There were no statistically significant differences in gestational age, birth weight, or Apgar scores between groups. At delivery, concentrations of maternal thyrotropin were elevated in the TRH group compared with the control group (12.0 +/- 1.6 vs 5.6 +/- 0.5 mU/L; p less than 0.005); however, maternal triiodothyronine (T3) values remained unchanged. Significant elevations of fetal thyrotropin and T3 were observed after maternal administration of TRH compared with control subjects (45.8 +/- 7.7 vs 8.4 +/- 0.9 mU/L (p less than 0.002) and 1.3 +/- 0.07 vs 0.7 +/- 0.04 nmol/L or 87 +/- 5 vs 49 +/- 3 ng/dl (p less than 0.001), respectively). Fetal thyroxine (T4) and prolactin values were also elevated after exposure to TRH (135 +/- 5 vs 86 +/- 10 nmol/L or 10.5 +/- 0.4 vs 6.7 +/- 0.8 micrograms/dl (p less than 0.001) and 212 +/- 31 vs 105 +/- 28 micrograms/L (p less than 0.05), respectively). Two hours after birth, a significant increase in T3 but not T4 levels was observed in both groups of infants. These data indicate that fetal exposure to a single dose of TRH via maternal administration of this hormone results in marked stimulation of the preterm fetal pituitary-thyroid axis, as in the fetus at term, and that this treatment does not inhibit the early postnatal surge of T3.

Female

A prepubertal surge of thyrotropin precedes an increase in thyroxine and 3,5,3'-triiodothyronine in normal children.

The variations in plasma levels of TSH, T4, T3, and rT3, during the pubertal period, were studied in 647 school students from the urban area of Santiago in Chile (47% males and 53% females) with ages ranging between 7.5 and 15 yr. The subjects were grouped by age in consecutive intervals of 6 months each, and pubertal development was determined in every subject. TSH showed a significant increase, reaching a peak in the 9- to 9.5-yr interval. The same was found for T3 and T4, which reached a peak by 10 and 11 yr. The T4/T3 ratio did not show any significant variation with age. After 9.5 yr, a decrease in rT3 and increase in the T4/rT3 ratio was found. The TSH peak preceded the onset of clinical pubertal development, while the T3 and T4 peaks coincided with this onset. The variations in rT3 suggest an increase of peripheral conversion of T4 to T3. These transient events, not described until now, could be termed thyroidarche and could have a significant effect on pubertal growth and development.

Adolescent

[The effect of anti-insulin antibodies and of peptide C residual secretion on the metabolic control of diabetes type 1].

In 20 type I diabetic patients treated with conventional insulin preparations, we measured insulin antibodies and peptide C secretion. Peptide C levels 90 and 120 min after a standard breakfast correlated well with glucosylated Hb levels (r = -0.48 and -0.52, respectively). No correlation with free insulin levels was observed, in spite of a good correlation of the latter with blood glucose levels (r = -0.50 and -0.73, respectively). There was no relation between insulin antibody levels and peptide C or free insulin. Metabolic control was not affected by insulin antibodies. Insulin dose decreased in relation to the duration of the disease and reduction of body weight index and was not correlated to glycosylated Hb levels.

Adult

[Clinical use of CA-125 in gynecology. Preliminary experience].

CA-125 levels were measured in 27 normal women, 11 with benign gynecologic pathology and 13 with ovarian cancer in different stages of evolution. The analysis of data was made retrospectively. Considering a level of 65 U/ml as normal, no false positives were found. Patients with benign gynecologic pathology behave as the normal ones with no significative differences in their levels. Levels higher that 65 U/ml were always found in women with ovarian cancer. There were 4 patients with negative levels and clinically or surgically verified disease. Positive levels correlated with histologic type and with surgical staging. In patients with serial levels, decrease in tumoral volume was correlated with decrease in levels. These data suggest that the behaviour of CA-125 in our local population is the same as reported in the literature. It is useful, when is positive, in follow-up, management and prognosis of patients with ovarian cancer. Its negativity is not guarantee of cure and positive levels make evident the presence of the disease. It is a poor diagnostic method because of its low sensitivity.

Antibodies, Monoclonal