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Biomedical subjects

N Lima

Publications and source records attributed to N Lima.

At least 37 records · Page 2Linked to original sources

The addition of dexfenfluramine to fluoxetine in the treatment of obesity: a randomized clinical trial.

Current evidence demonstrates that pharmacologic agents, alone or in combination produce short-term weight-loss and may remain effective for extended periods of time in obese patients. We have evaluated the weight loss of a selective inhibitor of serotonin uptake, fluoxetine, alone as compared with combined therapeutic trial with another serotoninergic drug, dexfenfluramine. Thirty-three patients were randomly assigned in a double-blind randomized clinical trial divided to two groups: Group I [Fluoxetine 40 mg and placebo (n = 13)] and Group II [Fluoxetine 40 mg plus dexfenfluramine 15 mg at night (n = 20)]. Both groups had a significant weight loss at the end of 8 months (Group I, mean +/- SEM 6.2 +/- 2.8 kg and Group II 13.4 +/- 6.3 kg, p < 0.05). Group II patients had a significantly greater weight loss as compared with Group I both in terms of mean weight loss in kg and BMI in kg/m2. However significance between Group I and II related to BMI mean values and weight mean values were only achieved after, respectively, 4 and 6 months of treatment. At laboratory level there was an elevation of HDL-cholesterol and lowering of serum lipids values (cholesterol and triglycerides) in both groups. Side effects were relatively minor and no altered clinical vital signs or abnormal laboratory values were observed. We concluded that the combination of fluoxetine (daytime) and dexfenfluramine (at night) may be more effective than fluoxetine alone in weight reduction although the small size of this study does not permit broad generalization.

Adult↗

The effect of oral administration of iodine to patients with goiter and hypothyroidism due to defective synthesis of thyroglobulin.

The effects of administration of iodine (1 mg/day orally, 64 days) were studied in three siblings with congenital goiter and hypothyroidism due to defective thyroglobulin (Tg) synthesis. The patients presented very large goiters, elevated RAI uptake, negative perchlorate discharge test, low serum T4, and elevated TSH concentrations. Immunoassayable Tg was low and failed to increase after stimulation with exogenous bovine TSH. Analysis of individual thyroid extracts by gel filtration failed to reveal a Tg component; the immunoassayable Tg antigens in these goitrous tissues were 0.12 and 0.21 mg/g tissue, respectively (normal 70-90 mg/g tissue). The histological pattern of their thyroids was compatible with defective Tg synthesis. The administration of iodine caused a rise in the mean serum T4, T3, and free T4 concentrations in all three siblings, but did not alter the serum Tg concentration. TSH concentrations rose in the terminal period of observation in the three subjects and this was considered to be due to a possible effect produced by the iodine load in the thyroperoxidase system (Wolff-Chaikoff effect). One patient showed an increase in goiter size during the period of observation. These results suggest that iodine administration enhanced the ability of the dyshormonogenetic gland to synthesize iodothyronines.

Adolescent↗

Introduction of flocculation into industrial yeast, Saccharomyces cerevisiae saké, by protoplast fusion.

Protoplast fusion was applied to obtain intraspecific fusion in yeast strains in order to overcome restrictions imposed by the natural mating system. Acriflavine was used to construct petite mutants from non-flocculent industrial Saccharomyces cerevisiae saké strain. UV radiation was used to construct ura- mutants from a respiratory competent and highly flocculent S. cerevisiae NCYC869 strain. Fusion products were selected by complementation on minimal medium. The frequency of appearance of prototrophic hybrids was five per 10(5) protoplasts. The stable hybrids showed not only the S. cerevisiae saké characteristics but also flocculation ability, thereby confirming the success of the fusion.

Cell Fusion↗

Is DL-fenfluramine a potentially helpful drug therapy in overweight adolescent subjects?

We have studied the therapeutic effects of two different doses (30 mg and 60 mg, twice daily) of DL-fenfluramine (DL-F) in, respectively, prepuberal (11-13 years old) and adolescent subjects (14-17 years old). Sixty-eight obese subjects were recruited for this study (22 boys, 36 girls, aged 10-17 years old) with body mass index ranging from 24.5 to 44.0 kg/m2, absolute weight ranging from 37.0 to 119.5 kg and % over IBW ranging from 122% to 260%. Results were compared to a placebo treated group of obese adolescent patients (n = 17), 6 boys and 11 girls, aged 10-17 years old, BMI ranging from 26-44 kg/m2, absolute weight 53.1 to 96.5 kg, and with 129% to 253% over IBW. In the DL-F-treated subjects most patients (n = 41) had a continuous weight loss during 12 months but 27 individuals were unable to lose any additional weight after the initial 6 months of the trial. Taken together 65% of all patients lost weight during DL-F treatment (12 months) whereas only 17.4% of the placebo group lost a significant (> 10% BMI) amount of excess weight. Also the placebo group had a higher withdrawal rate (57%) as compared with the DL-F-treated group (24%). There was a significant (p < 0.05) decrease of the mean +/- SD of the BMI (at 6 and 12 months of therapy). No significant change of the BMI was observed for control group. Minor adverse side effects consisted of a brief period of drowsiness and dry mouth. Our findings indicated that the continuous administration of DL-Fenfluramine might help obese adolescent subjects adhere to a diet and to maintain the weight loss achieved without major or harmful adverse effects.

Adolescent↗

The effect of hypocaloric diet with and without D-fenfluramine treatment on growth hormone release after growth hormone-releasing factor stimulation in patients with android obesity.

Basal and stimulated growth hormone (GH) secretions are impaired in obesity, and partial restoration of the GH response to various stimuli is observed after weight loss. The aim of the present study was to investigate whether D-fenfluramine, a serotoninergic agent, would increase the GH response to growth hormone-releasing factor (GRF) as compared with placebo in obese android patients. The subjects were 17 patients with android obesity (four men and 13 women) aged 21 to 58 years with a body mass index (BMI) ranging from 32.0 to 52.2 kg/m2 and an abdominal-gluteal ratio greater than 1.0. The following four GRF (1-44) tests were performed: T-30 (control), T0 (after 30 days of a hypocaloric diet), T1 (after 30 days of either placebo or D-fenfluramine 15 mg twice daily), and T2 (after 30 additional days of placebo or D-fenfluramine). The hypocaloric diet was maintained during the T1 and T2 periods. At each test, the serum GH response to GRF was measured at frequent intervals, and the peak GH response and the GH area under the curve were calculated. Serum insulin concentrations were also assayed before GRF stimulation, and the insulin to GH ratio was obtained. The D-fenfluramine-treated group had a mean +/- SEM GH peak level after GRF significantly higher at T1 (43.3 +/- 8.2 micrograms/L) and T2 (50.9 +/- 9.2 micrograms/L) compared with the placebo group. Likewise, the mean integrated areas of GH response were significantly higher for the D-fenfluramine-treated group as compared with the placebo group at both T1 and T2 of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Treatment of Graves' disease: effects of the administration of L-thyroxine associated with methimazole as a single daily dose.

OBJECTIVES: To reduce the number of tablets to be administered daily during antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the effectiveness of adding thyroxine after the patients had become euthyroid during methimazole therapy. PATIENTS AND METHODS: All patients were given gelatin capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken once a day for 18-24 months. Thirty patients with Graves' disease without previous treatment for hyperthyroidism were included. Two were lost to follow-up and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed for 18 to 24 months with methimazole and thyroxine medication plus an additional 2 years after the treatment was suspended. After completion of the study the patients were, retrospectively, divided in two groups: group 1 (G1, n = 20) patients considered to be in remission, and group 2 (G2, n = 8) with persistent active Graves' disease. RESULTS: All patients in group 1 had a significant reduction in the glandular mass, as estimated by ultrasonographic studies (mean +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g). Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin concentrations did not decrease significantly after therapy (58 +/- 20 micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/- 5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after treatment withdrawal, indicating a remission rate of 67.8%. CONCLUSION: The administration of L-thyroxine during anti-thyroid drug treatment, with subsequent inhibition of thyroid-stimulating hormone secretion, may be an important factor in glandular mass reduction, decreasing both the production of antibodies to thyroid-stimulating hormone receptors and the frequency of recurrence of hyperthyroidism.

Adolescent↗

Immunologically mediated cytotoxicity against human eye muscle and thyroid cells in euthyroid and thyrotoxic Graves' ophthalmopathy.

We have studied the role of eye muscle and thyroid autoimmunity in patients with Graves' hyperthyroidism with or without ophthalmopathy in an area of relatively low iodine intake. Antibody dependent cell mediated cytotoxicity (ADCC) and complement mediated antibody dependent cytotoxicity (CMAC) against thyroid and eye muscle cells, and levels of antibodies against TSH receptor antigen and the thyroid microsomal antigen (thyroid peroxidase) were determined in three groups of patients: (1) thyrotoxic with exophthalmos (TX, n = 28), (2) thyrotoxic without ophthalmopathy (GR, n = 10), and (3) euthyroid ophthalmopathy (EU, n = 12). The thyroid glandular mass of the EU group was significantly less (P less than 0.01) compared with TX or GR. Mean (+/- SD) TSH receptor antibody (TRAb) level was 27 +/- 14% in EU which was significantly lower compared with TX (52.4 +/- 20%) and GR (59 +/- 18%). The prevalence of microsomal antibodies were similar and not significantly different in the three groups. On the other hand the prevalence of positive ADCC and CMAC tests was significantly greater, and at higher levels, in EU (ADCC THY CELLS 10.9 +/- 8.9% SL, ADCC Eye muscle = 25.9 +/- 20% SL, CMAC = 70.2 +/- 43% SL) and TX (ADCC THY CELLS = 9.3 +/- 9.2% SL, ADCC Eye muscle = 20.1 +/- 19% SL, CMAC = 62.4 +/- 30% SL) compared to GR (ADCC THY CELLS = 4.4 +/- 9.5% SL, ADCC Eye muscle = 7.7 +/- 6.7% SL, CMAC = 24.7 +/- 23% SL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thyroid atrophy in myxedematous endemic cretinism: possible role for growth-blocking immunoglobulins.

We have examined the ability of IgGs obtained from 8 endemic cretins to inhibit TSH-stimulated thyroid cell growth in culture. Clinical and laboratory evidence for hypothyroidism was present in six subjects; the two remaining patients had borderline low serum T4, normal T3 and exaggerated TSH response to TRH. In six patients 2 mg IgG exhibited an inhibitory effect in the cellular growth expressed by a diminished incorporation of 3H-thymidine into the DNA of TSH-stimulated FRTL-5 cells (range: 26-87% inhibition). Seven patients presented clinically with thyroid atrophy of relatively small thyroid enlargements for the degree of chronic iodine deficiency that was present in the area. The remaining subject had a large multinodular goiter and IgG purified from this patient had no inhibitory effect in the FRTL-5 cellular growth. A direct relationship was noted between the degree of thyroid growth inhibition (%) and the basal serum TSH concentration. We conclude that the presence of thyroid growth inhibiting immunoglobulin may be related to the absence of thyroid growth or even thyroid atrophy in endemic cretins.

Adolescent↗

Natural course of iodine-induced thyrotoxicosis (Jodbasedow) in endemic goiter area: a 5 year follow-up.

In the Balsas region of North Brazil (85% prevalence of goiter), 1876 goitrous subjects (1663 with goiter grade I and II and 103 with grade III multinodular goiter) were treated with 1 ml of iodized oil im (l-oil). From the population with grade III goiter we were able to follow-up for 5 yr 13 euthyroid goitrous patients (group 1) and 8 goitrous individuals (group 2) who developed iodine-induced thyrotoxicosis (IIT, 0.42% of the total population or 7.76% of the multinodular goiter subjects). The two groups were matched for age and goiter size, and had no significant differences in the baseline levels of thyroid hormone concentration, T3/T4 ratio or mean serum TSH. However, group 2 had a higher concentration of serum Tg, and 48 h after challenge with 10 U of bovine TSH (bTSH) had a significantly higher absolute release of T3 and Tg than group 1. In 4 patients IIT was transitory and resolved by 12 months. Four other subjects, however, maintained a mild clinical form of IIT that only normalized at 50 months. Only one patient needed treatment with methylmercaptoimidazol. There was no evidence of autoantibodies (TSH-receptor inhibiting antibody, anti-Tg or anti-microsomal antibodies) against thyroid antigens in group 2 patients. All subjects, including those with thyrotoxicosis, showed a remarkable shrinkage of the goiter by 60 months which was reflected by a significantly lower absolute response of T3 and Tg after bTSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Brazil↗

Long-term effect of iodized oil on serum thyroglobulin levels in endemic goitre patients.

Serum thyroglobulin (Tg) response to bovine TSH (bTSH) was evaluated in 44 goitrous patients (grades III and IV) living in conditions of chronic iodine (I) deficiency (iodine urinary excretion less than 40 micrograms I/g) and in 26 normal subjects. After the initial clinical evaluation and laboratory tests (bTSH test, T4, T3, anti-Tg and anti-microsomal antibodies) all goitrous patients received 1 ml i.m. of iodized oil (I-oil) and were followed up for 30 months. The bTSH test was repeated at 6, 12, 20 and 30 months after I-oil in 21 subjects. A marked reduction in goitre size was observed in 85% of the patients with a concomitant significant increase in the mean serum T4 and T3 concentrations, a significant fall in the mean serum TSH level and a significant decrease in the T3/T4 ratio. Goitrous patients had elevated serum basal Tg levels (55 +/- 8 SEM micrograms/l) and a significantly mean higher peak Tg value after bTSH (200 +/- 65 micrograms/l) as compared with normal subjects (respectively, 11 +/- 1.4 and 32 +/- 3.4 micrograms/l). Larger goitres (grade IV) had a significantly higher mean peak Tg response as compared with grade III goitres. Treatment with I-oil significantly reduced the mean peak Tg response to bTSH after 6 months (59 +/- 10 micrograms/l) but at 12 and 20 months the peak Tg response after the injection rose, respectively, to 110 +/- 19 micrograms/l and 92 +/- 14 micrograms/l (P less than 0.02 as compared with 6 months), returning to the normal range only at 30 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thyroid growth immunoglobulins in large multinodular endemic goiters: effect of iodized oil.

Iodized oil (IO) was administered to 10 goitrous patients recently emigrated to São Paulo (SP) from iodine deficiency areas and to 42 goitrous patients from 2 Brazilian chronic iodine deficiency regions, Loreto and Luziania (L). Thyroid growth-promoting immunoglobulin G (IgG) thyroid-stimulating antibody, serum thyroglobulin (Tg), TSH, and thyroid hormones were measured before and 1 yr after IO administration. In all patients there was a remarkable reduction of gland mass associated with a significant decrease (P less than 0.01) in both basal serum Tg and peak Tg levels after bovine TSH administration. The mean percent Tg increase after bovine TSH treatment was reduced to 82% above basal levels compared with 224% before IO. Mean serum TSH levels, elevated only in the L group [7.3 +/- 11 (+/- SD) microU/ml] decreased to the normal range after IO (2.5 +/- 2.1 microU/ml). Serum T3 and T4 concentrations did not change greatly. Tests for microsomal antibodies were negative before and after IO. IgG concentrates of serum obtained before and after IO were tested for their ability to stimulate incorporation of [3H]thymidine into DNA or to increase intracellular generation of cAMP in FRTL-5 cells. Thymidine incorporation activity was found in 8 of 10 patients from SP [316 +/- 37% (+/- SEM); range, 140-480%] and 25 of 42 patients in the L group (mean, 206 +/- 14; range, 120-500%) before IO. Stimulation of thymidine incorporation reflected true growth-promoting activity, as confirmed by experiments measuring cell number, was not accounted for by TSH in the preparation, and reflected IgG action because it was abolished by absorption with antihuman IgG. IgG from only 1 patient in group SP and 4 patients in group L stimulated intracellular production of cAMP in FRTL-5 cells. All patients except 1 in both groups had no IgG stimulation (less than 120%) of growth-promoting activity 1 yr after IO treatment. There was a significant positive correlation between thyroid growth-promoting activity and serum Tg concentrations (r = 0.58; P less than 0.001), but no significant correlation was found with other parameters (TSH, T4, and T3). We conclude that growth-promoting IgGs lacking ability to stimulate cAMP production may play a role in the large multinodular goiters due to chronic iodine deficiency.

Adenylyl Cyclases↗

Transient thyrotoxicosis in endemic goitre patients following exposure to a normal iodine intake.

Twenty-three endemic goitrous subjects (goitre grade: III and IV) that were living in a chronic iodine-deficient area (iodine intake: less than 40 micrograms I/d) were submitted to clinical and laboratory evaluation within 3-8 weeks of arrival at the metropolitan area of São Paulo, where daily iodine intake is estimated to be 150-200 micrograms I/d. Eight patients developed a mild thyrotoxic state (T4 = 14.7 +/- 2.3 micrograms/dl, T3 = 279 +/- 55 ng/dl, no TSH response to TRH). Five additional subjects, although euthyroid, had a blunted TSH-response to TRH, and the remaining ten patients were euthyroid and had a normal TSH response to TRH. Thyrotoxicosis was associated with larger goitres (mean thyroid weight: 133 +/- 46 g), with high thyroid uptake of RAI (mean 24 h 131I uptake: 40 +/- 15%) but not with increased urinary iodine excretion. Serum Tg levels were more elevated in the first two groups of patients (respectively, geometric means 68 and 72 ng/ml), than in the euthyroid, TRH-responsive group (52 ng/ml). Thyrotoxicosis resolved spontaneously after three to six months without the need for any specific medication. It was concluded that a relatively small and normal iodide intake due to regular consumption of iodized salt and industrialized foods may induce a transient form of thyrotoxicosis in endemic goitre patients arriving into urban areas.

Adult↗