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Biomedical subjects

M Knobel

Publications and source records attributed to M Knobel.

At least 37 records · Page 2Linked to original sources

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↗

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↗

Qualitative and quantitative defects of thyroglobulin resulting in congenital goiter. Absence of gross gene deletion of coding sequences in the TG gene structure.

Seven subjects belonging to three families (ME, MA, MO), with congenital goiter and various degrees of thyroid hypofunction, were investigated from the standpoints of clinical, biochemical, and molecular biology. In two of these families (ME, MA), 6 individuals had low serum levels of Tg-related antigens with a minor increase after bovine TSH (bTSH) stimulation. A large proportion of the tracer was incorporated into serum albumin, and Tg antigens in the thyroid extracts were barely detectable by RIA. (0.19 mg/g tissue; normal, 70-90 mg/g). Gel filtration (CL6B Sepharose gel) showed absence of a normal Tg peak, and SDS agarose gel electrophoresis indicated complete absence of Tg dimer and monomer. Immunoelectrophoresis confirmed the absence of Tg-related antigens. Thus, in these patients a quantitative defect of Tg gene expression was characterized. By contrast, in the MO family a high basal serum concentration of immunoreactive Tg was present, with an exaggerated response to bTSH. Thyroid extracts revealed elevated TPO activity and normal levels of Tg-related antigens. Tg was also eluted in the gel filtration columns with the same mobility as standard 19S Tg. Immunoelectrophoresis against rabbit and human Tg was abnormal, with two precipitin arcs being detected. The Tg molecule after hydrolysis yielded only DIT and MIT, with poor formation of iodothyronines. Microscopic studies revealed a pronounced lack of colloid in the follicular lumina, and overdistended endoplasmic reticulum cisternae.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Low levels of thyroglobulin messenger ribonucleic acid in congenital goitrous hypothyroidism with defective thyroglobulin synthesis.

We characterized the virtual absence of immunoassayable thyroglobulin (Tg) in the serum and thyroid gland of two siblings (MA, JNA) and one nephew (RSS) from a family without inbreeding or familial goiter. Diagnosis of defective Tg gene expression was based on findings of normal PBI and low serum T4, low or normal serum T3, negative perchlorate discharge test, and virtual absence of the serum Tg response to challenge by bovine TSH. This conclusion was confirmed by analysis of proteins in the goiter extracts. Only minute amounts of immunoassayable Tg were detected by RIA (MA, 0.11; JNA, 0.19 mg/g tissue; compared to 70-90 mg/g in normal thyroid tissue). Gel filtration in Sephacryl S300 showed the absence of a normal Tg peak at 280 nm and concentration of label mostly on albumin. A minor intermediate peak of radioactivity was also detected, with the size of, approximately, normal Tg. Sodium dodecyl sulfate-agarose gel electrophoresis indicated the absence of Tg dimer and monomer, and Western blotting and immunoelectrophoresis confirmed this finding. Dot blot quantification of Tg and thyroid peroxidase mRNA indicated decreased hybridization of the patients' mRNA (MA, 44%; JNA, 63%) with phTgM2 (Tg probe) and increased hybridization (MA, 191%; JNA, 182%) with the pM5 (thyroid peroxidase probe) compared with control thyroid tissue. Dot blot analysis of Tg mRNA from the two siblings weakly hybridized with 3' and 5' Tg probes. RNA analysis by means of Northern transfer showed a clear signal of hybridization with Tg probe (phTgM1) in the 8- to 9-kilobase range, corresponding to the normal size Tg mRNA. No major polymorphisms were noted in Southern blotting, using seven restriction endonucleases. We conclude that no gross alteration of the 5' region of Tg gene was present in these patients. Ultrastructural examination of the thyroid tissue indicated that the rough endoplasmic reticulum was not augmented, nor were the cisternae of rough endoplasmic reticulum dilated. The defect observed in these goiters is diminished tissue concentration of Tg mRNA with defective translation. However, small amounts of functionally active Tg could be synthesized, iodinated, and immediately hydrolized, yielding mostly T3, owing to the intense tissue stimulation by TSH.

Adult↗

Effect of thyroid hormone therapy on plasma insulin-like growth factor I levels in normal subjects, hypothyroid patients and endemic cretins.

The effect of thyroid hormone therapy (L-T4 or L-T3) on plasma immunoreactive insulin-like growth factor I (somatomedin C, Sm-C) concentrations was studied in 8 normal controls, 14 primary hypothyroid subjects and in 7 patients with endemic cretinism. In normals basal levels of Sm-C (1.56 +/- 0.77 U/ml) increased to (2.46 +/- 1.0 U/ml; L-T4) and to (2.9 +/- 0.95 U/ml; L-T3). Plasma Sm-C basal levels were significantly lower in primary hypothyroid subjects (0.81 +/- 0.48 U/ml) and increased to 2.54 +/- 1.43 U/ml (L-T4) and to 2.16 +/- 0.83 U/ml (L-T3). A significant and positive correlation (r = 0.56) was found between Sm-C and serum T4 and T3 concentrations. Plasma Sm-C concentrations in endemic cretinism were initially normal in 4 patients, but low in the remaining 3 (mean +/- SD: 1.18 +/- 0.63 U/ml) and did not increase after 12 months (1.34 +/- 0.61 U/ml) or 18 months (1.01 +/- 0.43 U/ml) of L-T4 and L-T3 therapy. Plasma T4 levels and free T4 increased considerably in EC after therapy with a significant decrease in the previously elevated plasma TSH concentrations. The subnormal response of plasma Sm-C during effective thyroid thyroid hormone therapy could be an additional factor involved in growth failure of endemic cretins.

Adolescent↗

Iodized oil treatment for endemic goiter does not induce the surge of positive serum concentrations of anti-thyroglobulin or anti-microsomal autoantibodies.

Forty-three goitrous patients (grade II and III, WHO classification), living in areas of chronic iodine deficiency, were treated with an injection of iodized oil (470 mg iodine). Serial measurements of serum thyroid hormone levels after the therapy revealed increasing concentrations of both hormones, with a significantly lower serum T3/T4 ratio, and progressively significantly lower serum TSH mean values. Serum Tg mean value, initially elevated (58 +/- 9 ng/ml), decreased after 6 months and returned to the normal range at 36 months of therapy. In none of the examined patients (except for one subject with positive autoantibodies before therapy), it was observed the surge of positive anti-thyroglobulin or anti-microsomal autoantibodies after the iodized oil. We conclude that iodized oil therapy does not induce an abnormal autoimmune reaction in endemic goiter patients.

Adolescent↗

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↗

[The relationship between the physician and the psychotherapist in the treatment of somatic diseases].

Different points of view in regard to psychosomatic approaches to illness are still a deem and questionable matter. Even though recognizing the psychogenic component of certain diseases, it appears that the therapeutic approach to the patient is, as yet, a debatable question, where both physician and psychotherapist, are disputing primacy. The old question of psychogenesis and somatogenesis was displaced to who is the main responsible for the patient's treatment. The psychosomatic old dichotomy became nowadays a physician-psychotherapist divergence. Again, the patient ignored as a person and exercising a therapeutic "power" becomes paramount. It becomes again evident the lack of psychological knowledge on the physician's side, as well as rejection of a somatic reality on the psychotherapist's side. The patient finds, in this "external" conflict, an easy way to project his own anxieties in a very self damaging confusing manner, into those who are supposed to be the helpers. It looks like a new, bizarre and distorted edition of the Oedipical conflict, which shall remain unsolved, perpetuating disease. Both professionals reject themselves in several levels. Rivalry, jealousy, envy, and even psychotic aggression come into the picture in disputing the triumph over the sick body. The concept of "bodyness" should be restudied from a psychological and a somatic perspective, in order to allow for an understanding of a real therapeutic endeavour. Relationship physician-psychotherapist will rally be therapeutic when both will be able to diminish fantasies of omnipotence, possessiveness of the patient, and also when both will realize that the patient is also an active participant of the therapeutic process as human being, integrating the dynamic process structuring his/her own personality in a dialectic action with those who can assist and help professionally.

Body Image↗

Serum thyroglobulin (Tg) stimulation with bovine TSH: a useful test for diagnosis of congenital goitrous hypothyroidism due to defective Tg synthesis.

Sixteen patients with congenital goitre were submitted to a bovine TSH stimulation test (bTSH), and serum thyroid hormones (T3, T4), TSH and thyroglobulin (Tg) were measured before and after bTSH injection. In 9 patients with an organification defect basal levels of Tg were normal (19.4 +/- 3.1 micrograms/l) rising after bTSH to a mean level +/- SEM of 37.3 +/- 4.1 micrograms/l. Six patients with defective Tg synthesis or release had a mean basal level of serum Tg of 8.7 +/- 1.9 microgram/l (mean +/- SEM) and failed to raise serum Tg concentrations after bTSH (mean +/- SEM: 10.4 +/- 2.1 micrograms/l). In both groups a modest although significant (P less than 0.05) change in serum thyroid hormones after bTSH was noted. We conclude that the bTSH test may be used to distinguish the group with defective Tg synthesis or release from other types of congenital goitre.

Adolescent↗

Hereditary congenital goitre with thyroglobulin deficiency causing hypothyroidism.

The thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21-year-old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12.9-20.0 micrograms/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80-220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3 + T4 and MIT + DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg-like proteins (RIA) in the thyroid soluble protein extract was only 16-122 micrograms/g (normal: 50-70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18-20S) thyroglobulin. Only one peak (3.6-4.1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.

Adolescent↗

Thyroid function and chronic hepatosplenic schistosomiasis: peripheral conversion of thyroxine to 3,5,3'-triiodothyronine and pituitary-thyroid relationship.

The relationship between chronic hepatosplenic schistosomiaisis (CHES) and circulating thyroid hormones as well as the TSH response to TRH were investigated in 41 hospitalized CHES patients and compared to those in 11 patients with non-CHES cirrhosis with severe hepatic failure. CHES patients were subdivided into 3 groups depending on the severity of parenchymal dysfunction, based upon a composite clinical and laboratory index. Angiographic and hemodynamic studies of CHES patients revealed altered hepatic arteriograms, suggesting a decreased arterial blood flow associated with an increased venous blood flow from the portal system. A significantly reduced serum concentration of total T4 (but not free T4) was only found in the cirrhotic patients. Compared to CHES groups I and II, CHES group III patients and the non-CHES cirrhotics had significantly lower mean serum T3 levels of 80 +/- 12 and 52 +/- 8 ng/dl, respectively. The serum rT3 concentration was elevated (69 +/- 6.2 ng/dl) only in the cirrhotic patients. Both basal and peak TSH levels after TRH were within the normal range for all 4 groups of patients. The basal (40.7 +/- 8.3 ng/ml) and peak (85.5 +/- 13.7 ng/ml) serum PRL levels T4-binding globulin after TRH administration were only elevated in the cirrhotic group. Although the mean T4-binding globulin values were lower in CHES group III (17.5 +/- 3.2 micrograms/ml) and in the non-CHES cirrhotic group (18.3 +/- 2.1 micrograms/ml) compared to those in groups I (21.8 +/- 2.2 micrograms/ml) and II (20.4 +/- 2.3 micrograms/ml), the differences between groups were not statistically significant. It was concluded that hemodynamic changes without parenchymal failure have little, if any, effect on the hepatic T4 5'-monodeiodination to T3, and that the low T3 and high rT3 state does not modify the pituitary secretion of TSH, presumably by a local (at the thyrotroph level) normal conversion of T4 to T3, even at very low peripheral T3 concentrations.

Chronic Disease↗

Triac (3,5,3'-triiodothyroacetic acid) partially inhibits the thyrotropin response to synthetic thyrotropin-releasing hormone in normal and thyroidectomized hypothyroid patients.

The effects of a daily oral dose (1.4 mg) of 3,5,3'-Triiodothyroacetic acid (Triac) on thyroid hormone levels (T4, T3 and rT3) and on the TSH and PRL responses to TRH were studied in 15 normal subjects and 5 hypothyroid patients. There were no significant changes in weight, heart rate, reflex time, or serum concentration of either cholesterol or triglycerides after 6 weeks of Triac administration. However, T4 was significantly reduced to a lower mean level (mean +/- SEM, 7.3 +/- 0.7 to 4.3 +/- 0.6 microgram/dl) in the control group. T3 and rT3 concentrations increased, possibly due to a cross-reaction with Triac in their respective RIAs. The peak TSH response to TRH in the normal subjects was 17.6 +/- 3.4 muU/ml and fell significantly to 2.0 +/- 0.8 muU/ml after Triac administration. In the hypothyroid subjects the mean serum TSH level was significantly reduced from 136 +/- 66 to 12.6, 10.5, and 11.6 muU/ml in the weeks after Triac administration. The mean peak response of both TSH and PRL after TRH (206 muU and 44.8 ng/ml, respectively) declined significantly to 63.4 muU/ml and 24 ng/ml. It was concluded that this dose of Triac partially inhibits the synthesis and secretion of TSH and PRL without any major peripheral metabolic effects.

Adult↗

Congenital goitre and hypothyroidism with impaired iodide organification and high thyroid peroxidase concentration.

A sibship of thirteen subjects whose parents were first cousins was studied for a defect in thyroid hormone synthesis. Five sibs were goitrous and had congenital hypothyroidism. All but one showed a positive perchlorate discharge test (PDT). Three other subjects were goitrous and euthyroid (one with a positive PDT), and the remaining five sibs were euthyroid with a presumably normal thyroid. However, an abnormally exaggerated TSH response to TRH was observed not only in the hypothyroid patients but also in six of the other subjects, indicating a decreased thyroid feedback at the pituitary level in the presence of a normal serum concentration of thyroid hormones. In two hypothyroid patients a normal serum T3, low serum T4 and a low reverse T3 were observed. Microscopic studies of thyroid tissue from three of the sibs disclosed marked cellular hyperplasia with no lymphocytic infiltration anywhere in the tissue. Peroxidase activity was determined on tissue from three sibs by three different assay procedures. It was within the normal range in one patient and was significantly elevated in the other two. There was no evidence for a qualitatively defective peroxidase. The defect in thyroid function in this family does not appear to involve a peroxidase deficiency. Thyroglobulin isolated from the thyroid glands of two of the goitrous, hypothyroid subjects was poorly iodinated but was judged to be normal by immunoreactive and ultracentrifugation procedures. Although the nature of the thyroid metabolic defect in this family was not elucidated, the evidence suggests a genetic defect, probably involving a recessive gene.

Adolescent↗

Hebiatric psychosomatic medicine.

Adolescent disease should not be considered as something similar to infantile pathology or adult sicknesses. Special consideration must be given to the adolescent as such, taking into account the characteristics of adolescents as described in the 'Normal Adolescence Syndrome'. Symptom formation follows the same pattern as described elsewhere for children, adolescents and adults, but with very special differences in this stage of human development. Hysterical, hypochondriacal and psychotic types of psychosomatic illnesses can be described with the qualification of 'adolescent type'. Hebiatric medicine must be the specialized approach to illnesses in this developmental stage and must define its study object: the adolescent. Interviewing, clinical examination, diagnosis treatment and prognosis are of a specialized kind and the psychosomatic approach is also different. There are some more typical hebiatric pathologies that must be considered properly.

Adolescent↗

Imparied cyclic-AMP response to thyrotrophin in congenital hypothyroidism with thyroglobulin deficiency.

A 19 year old man had congenital hypothyroidism and severely retarded development. His thyroid gland was not enlarged and laboratory findings included low serum concentration of T4 (2.8 microgram/100 ml) and T3 (16 ng/100 ml) with a high level of TSH (52 microU/ml) that rose to 192 microU/ml after TRH. 131I uptake by the thyroid was normal (41.5% at 24 h) and did not show a normal increase after exogenous TSH administration (49.5% at 24 h). The perchlorate discharge test was negative and no antibodies against thyroid antigens were found. Studies on the biopsy specimen revealed low iodide trapping by the thyroid slices and no formation of cyclic AMP after TSH was added to the medium. The endogenous TSH of the patient was biologically active increasing cyclic adenosine monophosphate c-AMP concentration in normal thyroid slices. No thyroglobulin was found in the thyroid tissue either by immunological or ultracentrifugational methods. An increased proportion of iodoalbumin was present in the serum. We postulate that the fundamental defect in this gland is an impaired generation of c-AMP by the defective thyroid cell and deficiency of thyroglobulin formation resulting in inadequate thyroxine and triiodothyronine synthesis.

Adult↗