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Biomedical subjects

M Knobel

Publications and source records attributed to M Knobel.

At least 19 recordsLinked to original sources
PubMed2002

Prognostic value of serial serum thyroglobulin determinations after total thyroidectomy for differentiated thyroid cancer.

Serial weekly serum samples (for 3 weeks) were obtained from 42 patients with differentiated thyroid cancer (DTC, papillary no.=35, follicular no.=6, Hurthle cell no.=1) for serum thyroid hormone, TSH and TG before and after total thyroidectomy. Serum specimens were also obtained one month after radioiodine (131I) therapy followed by suppressive dose of L-thyroxine (L-T4, 2.5 microg/kg). The patients were subdivided into four groups: group I: the DTC was confined to a single solid nodule (no.=1 2); group II: thyroid malignancy invaded local cervical structures but there were no lymph node metastases (no.=8); group III: DTC with lymph node metastases (no.=6); and group IV: DTC with distant metastases (no.=16). In all group I patients serum TG remained undetectable in spite of elevated serum TSH levels at the 3rd week post-surgery (PS). Only one of group II patients had a detectable serum TG value of 5.2 ng/ml (3rd week PS). By contrast, 37.5% of group III patients had detectable serum TG levels, ranging from 3.4 to 16.8 ng/ml (3rd week PS). Lymph node metastases were detected in 5 of these patients by whole body scan (WBS) and removed surgically in 3. As expected, group IV patients had elevated serum TG values ranging 33.0-958.0 ng/ml and distant metastases were confirmed in all of them by WBS. From the calculations through univariate logistic regression comparing TG concentrations at the 3rd week PS from groups I and II vs groups III and IV, we obtained a cut-off value of 2.3 ng/ml with the following efficacy features: sensitivity=74.5%; specificity=95%; positive predictive value=92.3%; negative predictive value=65.5%; and accuracy=73.8%. After 131I and L-T4 suppressive therapy, only 5 out of 36 patients of groups I, II and III had detectable serum TG levels (3.1-7.0 ng/ml) whereas serum TG was detectable in all group IV patients (ranging 2.5-8.6 ng/ml). We concluded that serum TG concentrations above 2.3 ng/ml at the 3rd week PS could be suggestive of lymph node or distant metastases in patients with DTC. Patients with serum TG above this limit could be considered at risk for metastatic disease and higher doses of diagnostic iodine-131 (131I) may be indicated for actinic ablation.

Adenocarcinoma, Follicular↗
PubMed2001

Structural properties of Cu-Permalloy under annealing.

We have studied the structure of melt-spun copper-permalloy samples (Cu80Fe4Ni16), annealed at several temperatures up to 873 K by means of EXAFS spectroscopy. The results for iron first neighhor average distance showed a slow decrease for annealing temperatures higher than 673 K. The nickel first neighbor distance had almost no change in the whole temperature range. This behavior is discussed in the light of rich iron cluster formation, and is compared with magnetic measurement results.

Journal Article↗
PubMed2000

Decreased androgen levels in massively obese men may be associated with impaired function of the gonadostat.

OBJECTIVE: In obese men, sex hormone-binding globulin (SHBG) as well as total testosterone (TT) levels are decreased. Data concerning serum free testosterone (FT) levels in obese men are discordant. FT levels are decreased in only some morbidly obese men, consistent with an impairment of the feedback regulatory mechanism. In this study we aimed to verify serum levels of TT and FT in two groups of obese men (BMI < 35.0 kg/m2 and BMI > 35.1 kg/m2) before and after weight loss. DESIGN: Two groups of obese men (group 1: BMI < or = 35 kg/m2; and group 2: BMI > or =35.1 kg/m2) were studied before and after 6 months of a low energy diet (1200 kcal/day). Every patient received a therapeutic prescription of dexfenfluramine (15 mg b.i.d.) that was maintained for 6 months. SUBJECTS: Thirty-seven obese men and 20 normal weight men. MEASUREMENTS: Serum sex hormones (TT and FT), serum luteinizing hormone (LH) and insulin were analyzed by RIA assays. Plasma insulin levels, serum TT, FT and LH concentrations were obtained before and after weight loss. RESULTS: Moderately obese men (BMI = 32.3+/- 1.9 kg/m2) presented significantly decreased TT levels (390+/-120ng/dl) as well as FT (mean+/-s.d.:16.0+/-4.8pg/ml) as compared with normal controls. FT serum levels had a significant and negative correlation with body mass index (BMI), whereas for TT concentrations this correlation was not significant. Serum LH concentrations (4.5+/-2.9mlU/ml) were normal. Insulin levels were elevated in all patients (46.3+/-30.1 microU/ml). After weight loss there was a significant (P< 0.01) increase in TT, FT and LH levels, whereas insulin concentrations significantly decreased. In massively obese men (BMI = 43.0 6.7 kg/m2), TT (320+/-110ng/dl), FT (11.0+/-2.1 pg/ml) and LH (3.1+/-1.3mlU/ml) were decreased and significantly lower as compared with the previous group and normal controls. As expected, after weight loss TT, FT and LH levels increased significantly while insulin concentrations decreased. CONCLUSIONS: We concluded that FT levels are dependent on the degree of obesity, massively obese men (BMI > or =35.1 kg/m2) being considered as candidates for consistently low FT levels. A functional decrease of LH pulse amplitude and serum LH levels as well as a possible negative action of excess of circulating leptin on the steroidogenesis may be related to the decreased androgens levels in massively obese men.

Adult↗
PubMed2000

Prevalence and characteristics of postpartum thyroid dysfunction in São Paulo, Brazil.

OBJECTIVE: Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder characterized by the development of transient hyperthyroidism and, more frequently, hypothyroidism (or both) during the first six months of the puerperal period. A variable incidence has been reported in part because of differences in the number of women studied, the frequency of thyroid assessment postpartum, diagnostic criteria and methodology. The aim of this study was to evaluate thyroid function, ultrasound images and titre of autoantibodies against thyroid antigens in a cohort of pregnant women who met the criteria of 'normal' thyroid gland structure on clinical examination and imaging and normal thyroid function tests without a significantly positive anti-thyroid peroxidase (TPO) antibody titre (i.e. < 100 U/ml) in the first trimester. DESIGN AND PATIENTS: Eight hundred nulliparous or multiparous (one to seven previous pregnancies) pregnant women (age 26.1 +/- 4.8 years, mean +/- SD), were submitted to clinical, laboratory and ultrasonographic examination in the first trimester of pregnancy. Among these forty-six patients were excluded because of thyroid dysfunction, ultrasound structural abnormalities or a positive anti-TPO antibody titre (> 100 U/ml). A total number of 754 women were available for further studies in the postpartum period. A relatively large number of these patients (386) were lost for follow-up either before or after delivery. MEASUREMENTS: A cohort of 368 puerperal women was followed up regularly at 3, 6, 12 and 24 months after delivery, with periodic thyroid function tests, random urine iodine measurements, assays for serum autoantibodies against thyroid antigens and imaging by ultrasound. RESULTS: The provisional diagnosis of PPTD was established in 78 out of 368 who had positive anti-TPO levels and ultrasonographic thyroid structural changes. Twenty-nine of these patients had a transient rise of anti-TPO autoantibodies characterizing an autoimmune reaction. These autoantibodies levels progressively declined or became negative. Moreover none of these patients had evidence for altered thyroid function during the 18-24 months of follow-up. The remaining 49 patients (13.3%) progressively developed thyroid function abnormalities (mainly hypothyroidism) indicating the presence of thyroid gland changes due to PPTD. Further follow-up studies indicated that at 18-24 months, 42 patients had serum levels of anti-TPO-Ab that were more elevated, as compared with the first year values. Predictive factors found during pregnancy for developing PPTD were: (1) relatively low levels of anti-TPO, between 60 and 100 U/ml (odds ratio 3.1 : 1), and (2) ultrasonographic thyroid structural changes in the first trimester (odds ratio 6.4 : 1). CONCLUSIONS: We conclude that the prevalence of postpartum thyroid dysfunction in our geographical area ranges from 6.7% to 13.3%, considering, respectively, all pregnant women that were examined (n = 754) or only the number of puerperal women actually followed-up (n = 368). A transient form of thyroid autoimmune reaction characterized by elevated serum levels of anti-TPO that progressively declined or disappeared was observed in 29 puerperal women. Sonographic structural and echogenicity changes in the thyroid gland and borderline positive anti-TPO levels (between 60 and 100 U/ml) during pregnancy were considered to be of predictive value for development of postpartum thyroid dysfunction.

Adolescent↗
PubMed1999

Elevated anti-galactosyl antibody titers in endemic goiter.

Anti-Gal is a human polyclonal antibody that constitutes approximately 1% of the circulating immunoglobulin G (IgG), interacts specifically with the mammalian carbohydrate alpha-galactosyl epitope. Furthermore, it was found to mimic in vitro thyrotropin (TSH) effects regarding stimulation for cyclic adenosine monophosphate (cAMP) synthesis, 125I uptake, and cellular proliferation on cultured porcine thyrocytes and on Graves' disease thyrocytes, but not on normal human thyrocytes. As immune activation in sporadic and endemic goiters might play a secondary role in regulating thyrocyte proliferation and function, we evaluated anti-Gal titers in endemic goiter. Serum was obtained from 109 Chagas'-negative patients living in an endemic goiter area of Brazil (Grao Mogol, MG) and 160 controls. The patients were divided into 3 groups, according to their goiter size (World Health Organization [WHO] classification): grade 0 (group 1, n = 24), grade I-II (group 2, n = 41), and grade III-IV (group 3, n = 44). Anti-Gal was assessed by a radioimmunological procedure (results expressed as the percentage of bound radioactivity/total activity [%B/T]). The antibody titer was significantly more elevated in group 1 (mean +/- SEM: 9.27%+/-0.80%), in group 2 (mean +/- SEM: 16.17%+/-0.97%), and in group 3 (20.97%+/-1.30%) than in normal controls (6.46%+/-0.33%). Analysis of the male and female data separately for anti-Gal titer did not substantially alter these results. We concluded that the anti-Gal titer is higher in patients with endemic goiter and presented a possible relationship with the size of goiter. Whether these antibodies contribute to the pathogenesis of the disease needs further clarification.

Adult↗
PubMed1997

Hypothyroidism in a Brazilian kindred due to iodide trapping defect caused by a homozygous mutation in the sodium/iodide symporter gene.

A 36 year old man with a large goiter was suspected of having iodide (I-) transport defect based on low thyroidal and salivary gland radioiodide uptake. Thyroid surgery was performed, because thyroid cytology could not exclude a malignancy. Sequencing of the entire Na+/I- symporter (NIS) cDNA derived from thyroidal mRNA revealed a homozygous substitution of the normal cytosine in nucleotide (nt) 1163 with an adenine, resulting in a stop (TGA) at codon 272. This nonsense mutation produces a truncated NIS with undetectable I- transport activity when expressed into COS-7 cells. Genotyping confirmed that the propositus was homozygous for the mutation whereas his unaffected mother, son, and paternal aunt were heterozygous. This nt substitution was not detected in any of 50 normal individuals, ruling out a polymorphism. While the homozygous mutant NIS-272X causes congenital hypothyroidism, expression of one normal allele in the heterozygote (C272X) is sufficient to maintain active thyroidal I- uptake and function.

Adult↗
PubMed1997

Levothyroxine suppressive therapy is partially effective in treating patients with benign, solid thyroid nodules and multinodular goiters.

We prospectively evaluated the effect of thyrotropin (TSH)-suppressive therapy with levothyroxine (LT4) on the size of a benign, solitary, solid nodule and multinodular goiter in a relatively low iodine intake area. In this study, 101 euthyroid subjects with a benign, solitary, predominantly solid nodule (n = 54) confirmed by biopsy or multinodular goiter (n = 47) received 200 microg of levothyroxine daily as a single morning tablet for 12 months. Thirty-five receiving no therapy were considered as controls (solitary nodules, n = 20, multinodular, n = 15). Patients were admitted to the study after evaluation of thyroid biochemical parameters (thyroxine [T4], free thyroxine [FT4], triiodothyronine [T3], thyrotropin [TSH], and thyroglobulin [Tg]), thyroid scanning, ultrasound examination, and fine-needle aspiration biopsy. Every 3 months, thyroid function tests and every 6 months ultrasound examinations were repeated. Twelve months later 20 of 54 (37.1%) patients with single, solid nodules had 50% or more regression of the nodular volume (responders). Eleven of 54 (20.3%) patients had more than 20%, but less than 49.9% reduction of nodular volume (partial responders). Nonresponders were 23 of 54 (42.5%). One-third of subjects with multinodular goiter had 50% or more regression of the glandular volume, whereas 46.8% were considered as nonresponsive. The mean serum Tg levels decreased significantly only in responders with solitary nodular disease or multinodular goiter. In the control group only 1 patient (5% of total) with a solitary nodule had a 50% reduction in the nodular volume. Five others had a partial response (<49%, >20% reduction). None of the patients with multinodular goiter had a significant reduction (>50%) of the combined nodular volumes. We concluded that LT4 may be effective, among other factors, in arresting the growth or in reducing the volume of relatively small, benign, solitary, solid thyroid nodules or the combined nodular volume of multinodular goiter.

Adult↗
PubMed1996

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↗
PubMed1995

Prevalence of incidental thyroid disease in a relatively low iodine intake area.

An ultrasonographic survey of thyroid abnormalities was conducted in 547 consecutive apparently normal overweight subjects (380 females and 167 males), aged 27-58 years in an urban area with relatively low iodine intake (mean daily urinary iodine excretion: 10.6 micrograms/dL). Individuals with any previous thyroid disease or familial thyroid pathology were excluded. In 240 subjects (44%) high resolution ultrasonography of the thyroid was considered normal. In 307 individuals (56%) abnormalities of the echo structure (39%) or thyroid nodular disease (17%) were detected by ultrasonography. Marked heterogeneity of the echo structure that was considered suggestive of chronic autoimmune thyroiditis was present in 81 subjects (15%). In 72 of these patients the serum anti-TPO levels were positive by a sensitive RIA. Thyroid nodules either solid or predominantly cystic were present in 90 subjects (17%). Eighteen patients had a relatively large nodule (diameter 15-18 mm). Eleven of these nodules were missed at clinical examination. Fine needle aspiration cytology was performed in 14 patients and 7 individuals underwent thyroid surgery. In 6 subjects the pathologic diagnosis was benign adenomatous goiter and one patient had a follicular carcinoma. Thyroid function studies confirmed subclinical hypothyroidism in 27 patients (4.9%), all of them with elevated serum anti-TPO autoantibodies levels. It was concluded that the overall occurrence of thyroid disease is more common than suspected by clinical examination.

Adolescent↗
PubMed1994

Prevalence of anti-thyroid peroxidase antibodies in autoimmune and nonautoimmune thyroid disorders in a relatively low-iodine environment.

We evaluated the prevalence of antithyroid peroxidase antibodies (anti-TP0 Ab) in 402 patients with thyroid disease and 30 healthy controls by a commercial radioimmunoassay (RIA) and compared the results with the passive hemagglutination (HA) method. The patients in the study had autoimmune thyroid disorders (AITD) such as Graves' disease and Hashimoto's disease or had nonautoimmune thyroid diseases (NAITD) such as thyroid cancer, congenital goiter, endemic goiter, and nodular goiter. Subjects were recruited from a population with a mild iodine deficiency (Sao Paulo, Brazil). The effect of specific therapy (for either thyrotoxicosis or chronic thyroiditis) on the circulating anti-TPO levels was also investigated. Positive anti-TPO Ab was detected in 89.9% of the patients with AITD as compared with a prevalence of positive tests of only 4.8% in patients with NAITD. Positive microsomal antibody (M Ab) was found in 68.4% of the patients with AITD and in 6.4% of the patients with NAITD. A positive and significant correlation was obtained between M Ab and anti-TPO Ab. A positive anti-TPO test with negative anti-M was found in 14.1% of the patients with AITD but in only 4.3% of the patients with NAITD and normal controls. These results suggest that anti-TPO Ab by RIA is more sensitive and specific than M Ab by HA. In patients with AITD, anti-TPO Ab levels usually decreased after treatment, suggesting that this parameter could be used in the follow-up of these thyroid disorders.

Antibody Specificity↗
PubMed1993

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↗
PubMed1991

Genetic linkage studies of thyroid peroxidase (TPO) gene in families with TPO deficiency.

We have conducted biochemical and genetic studies in five unrelated families (denoted A, C, R, P, and G), which included nine goitrous subjects (five borderline euthyroid and four hypothyroid) with complete (n = 6) or partial (n = 3) thyroid peroxidase (TPO) deficiency. Thyroid tissue was obtained from four subjects, respectively, in families A, C, and R. No iodide organification or iodide incorporation into protein was present in families A and C. The two affected siblings in family R had a low normal tissue thyroperoxidase activity. Using a 0.8-kilobase (kb) cDNA clone (pM5) encoding 30% of the cDNA of human TPO gene down-stream from basepair 730 and four restriction enzymes (TaqI, PstI, BglI, and BglII), we were unable to find any polymorphisms in family A. In another family (C) blood samples were obtained from only two family members, and consequently, it was not possible to determine linkage. DNA from families G, P, and C showed biallelic polymorphisms when digested with BglII, at 8.7 and 8.5 kb. In family R we detected two biallelic polymorphisms at 9.0 and 8.5 kb, and the 9.0-kb bands were clearly larger than 8.7-kb bands found in the other subjects. Also, there was an absence of a 4.0- to 3.9-kb band that may represent a partial gene deletion. With PstI-restricted DNA a possible deletion of 5.5-kb band was also present in affected siblings of family R. The logarithm of odds (Lod) score analyzed from the family with inbreeding (R) was compatible with linkage of disease and the TPO gene (Lod = 2.08). When this method was used with families G and P, the Lod score was inconsistent with linkage between disease and the TPO gene. These data suggest that the cause of TPO deficiency in these families is heterogeneous. However, the restriction fragment length polymorphism pattern of BglII-restricted DNA in the R family strongly suggests that a partial TPO gene deletion has occurred in this family.

Bacterial Proteins↗
PubMed1990

Dyshormonogenetic goiter: presence of an inhibitor of normal human thyroid peroxidase.

A dialyzable, thermostable inhibitor of normal thyroid peroxidase (TPO), with UV absorption maximum at 250-260 nm, was found in the digitonized, washed particulate fraction of two dyshormonogenetic goiters. No intrinsic TPO iodide-oxidation activity was detectable in either of these goiters, and their TPO iodination activity was below the method sensitivity threshold, even after dialysis. These findings could be explained by an absent or abnormal TPO associated with the synthesis of a TPO-inhibitor, or by the irreversible inhibition of a normal enzyme by the inhibitor.

Dialysis↗
PubMed1990

Significance and importance of the psychotherapist's personality and experience.

The psychotherapist's personality demands an open dynamic organization of the psychophysical systems that determine characteristic behavior and thought. A therapist must think and act coherently with his social ideals. Freedom, creativity and affection shall help to achieve a true 'therapeutic disposition' where knowledge and empathy are paramount and constantly available. A real experience develops from authentic self-correcting practice. 'Countertransferential narcissism' must be studied in order to free the therapist from internal conflictive compromises. Thus, epistemophilic feelings--basic for psychotherapy--can increasingly be developed within a therapist's personality.

Clinical Competence↗
PubMed1990

Training in short-term psychotherapy.

A new approach to short-term psychotherapy, based on psychoanalytic theory is presented as 'Therapy of limited time and objectives'. Personal experience, psychoanalytic knowledge and flexibility for accepting technical modifications allows for familiarity with concepts such as 'available setting', 'operational time' and 'adequate therapeutic time', which together with supervision and deep psychoanalytic learning, emphasizing counter-transferential knowledge, shall help to achieve a true epistemophilic sentiment, essential for empathic observation and listening, basic for training in short-term psychotherapy.

Curriculum↗