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Biomedical subjects

L Dumitriu

Publications and source records attributed to L Dumitriu.

At least 19 recordsLinked to original sources

Circadian rhythms of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), cortisol, and melatonin in women with breast cancer.

BACKGROUND: Circadian rhythms in plasma concentrations of many hormones and cytokines determine their effects on target cells. METHODS: Circadian variations were studied in cortisol, melatonin, cytokines (basic fibroblast growth factor IbFGF], EGF, insulin-like growth factor-1 [IGF-1]), and a cytokine receptor (insulin-like growth factor binding protein-3 [IGFBP-3]) in the plasma of 28 patients with metastatic breast cancer. All patients followed a diurnal activity pattern. Blood was drawn at 3h intervals during waking hours and once during the night, at 03:00. The plasma levels obtained by enzyme-linked immunoassay (ELISA) or radioimmunoassay (RIA) were evaluated by population mean cosinor (using local midnight as the phase reference) and by one-way analysis of variance (ANOVA). RESULTS: Cortisol and melatonin showed a high-amplitude circadian rhythm and a superimposed 12h frequency. bFGF showed a circadian rhythm with an acrophase around 13:00 with a peak-to-trough interval (double amplitude) of 18.2% and a superimposed 12h frequency. EGF showed a circadian rhythm with an acrophase around 14:20, a peak-to-trough interval of 25.8%, and a superimposed 12h frequency. IGF-1 showed a high value in the morning, which is statistically different (t test) from the low value at 10:00, but a regular circadian or ultradian rhythm was not recognizable as a group phenomenon. IGFBP-3 showed a low-amplitude (peak-to-trough difference 8.4%) circadian rhythm with the acrophase around 11:00 and low values during the night. CONCLUSIONS: (1) Circadian periodicity is maintained in hospitalized patients with metastatic breast cancer. (2) Ultradian (12h) variations were superimposed on the circadian rhythms of the hormones and several of the cytokines measured. (3) Studies of hormones and cytokines in cancer patients have to take their biologic rhythms into consideration. (4) The circadian periodicity of tumor growth stimulating or restraining factors raises questions about circadian and/or ultradian variations in the pathophysiology of breast cancer.

Analysis of Variance↗

The oculo-dento-digital syndrome: male-to-male transmission and variable expression in a family.

We report two siblings--a 5 1/2 year old female and her 4 1/2 year old brother, both presenting the classical clinical findings of oculo-dento-digital dysplasia (ODD). 1. Digital anomalies: bilateral complete cutaneous syndactyly of fingers IV-V (III-IV-V at the left hand of the boy) and camptodactyly IV. 2. Facial and ocular anomalies: microphtalamos-epicanthal folds, small midfacies, thin nose with hypoplastic alae nasi and small nares. 3. Dental anomalies with partial dental agenesis and enamel hypoplasia. Examination of the parents showed a bilateral cutaneous syndactyly IV-V in the father as the sole partial manifestation of ODD. The findings in the present family confirm the autosomal dominant inheritance of ODD with great variability in clinical expression. Moreover, the facial morphology (thin, hypoplastic nose) observed in several ODD patients suggests nosological overlap with the Hallerman-Streiff syndrome and could indicate that both syndromes are variable expressions of a contiguous gene deletion syndrome.

Abnormalities, Multiple↗

Stimulation of the secretion of dehydroepiandrosterone by melatonin in mouse adrenals in vitro.

Adrenals of young adult male mice kept on a LD 12:12 lighting regimen for three weeks prior to study and harvested at four different circadian stages were incubated for 2 hours with 0.4 IU synthetic ACTH in 2 ml Krebs-Ringer buffer (KR), or with 50, 150, and 450 microM of melatonin in KR containing 0.4 IU ACTH. The addition of melatonin to ACTH leads to a dose dependent stimulation of production and/or secretion of DHEA into the incubation medium irrespective of the circadian stage of harvesting of the adrenals. This relationship is of interest in view of the simultaneous decrease of dehydroepiandrosterone and melatonin in the course of aging, and the effects of these compounds upon aging related changes.

Adrenal Glands↗

Effects of radioiodine therapy in hyperthyroidism (thyroid function, thyroid volume, Graves' ophtalmopathy, thyrotoxic heart disease).

The study group consisted of 135 hyperthyroid patients--128 with Graves' disease and 7 with toxic multinodular goiter. A single dose of radioiodine was given in 110 cases (81.48%), two doses in 22 patients (16.3%) and three doses in 3 patients (2.22%); mean total dose was 6.8 mCi (range = 3-24 mCi). The main goal of radio iodine therapy is to achieve euthyroidism; after radioiodine treatment, 61 patients (45.2%) were euthyroid, 60 patients (44.4%) with permanent hypothyroidism and 14 (10.36%) with PERSISTING HYPERTHYROIDISM--the mean duration of follow-up being 4.2 years. After radioiodine therapy, goiter became absent in 30 patients (28%); in those patients, goiter was moderately enlarged or large before therapy. Around 63% (12 cases) of the patients with thyrotoxic atrial fibrillation reverted to sinus rhythm. During the last four years (1990-1994) the patients with Graves' ophthalmopathy from the study group were treated with Prednisone after radioiodine therapy; this corticotherapy contributes to the lower percentage (1.5%) of worsening Graves' ophthalmopathy after radioiodine therapy.

Adult↗

Chronobiology of pituitary-thyroid functions.

One hundred ninety four children, 11 +/- 1.5 years of age and 166 elderly men and women, 77 +/- 8 years of age were studied over one or (in the case of some of the elderly subjects) over several (up to 4) 24-hours spans. All subjects were diurnally active and rested at night and followed their regular three meal pattern. The subjects were studied in subgroups of 20-25 during all four seasons of the year. During each study, blood was collected at 4 hour intervals over one 24-hour span (6 samples). Circadian and circannual variations were found and described by cosinor analysis in the children as well as in the elderly subjects. The children with endemic goiter (134) as compared to those without endemic goiter (60) showed a slight circadian phase advance in plasma total and free T3, a lower circadian amplitude of total T4 concentrations and the absence of a detectable circadian rhythm in free T4. The children with goiter showed a phase delay in serum TBG. There was no difference between the children with and without goiter in the circadian MESOR of any thyroid parameter or of TSH. The children with endemic goiter in the region of Dimboviţa, Romania, are in clinical and biochemically euthyroid condition with some slight poral abnormalities of thyroid function. Seasonal variations in children and elderly patients showed the highest values of TSH during summer and fall, while the highest values in the plasma concentrations of thyroid hormones were found during the cold season of the years. Thyroglobulin in the children showed a circadian rhythm but no seasonal variation.

Aged↗

Circadian and circannual variations of thyroid function in children 11 +/- 1.5 years of age with and without endemic goiter.

A group of 194 children 11 +/- 1.5 years of age from Tirgoviste, Romania, an endemic goiter area, were studied over a 24-hr span (six blood samples at 4-hr intervals) during all four seasons. One hundred thirty-four of the children had some clinical evidence of endemic goiter, and 60 had none. Total and free T3 and T4, reverse T3, thyroglobulin, thyroxin-binding globulin (TBG; three seasons only), and TSH were studied. The circadian rhythms were analyzed by cosinor and the circannual variations by ANOVA. Children with and without endemic goiter showed circadian rhythms in all functions studied except free T4 for which no statistically significant rhythm was detected in the children with goiter. There were differences in the acrophase of total T3, free T3, and TBG, with phase advance in the children with goiter in total T3 and free T3 and a phase delay in TBG. Mesor and amplitude showed no differences except in total T4 for which the amplitude in the children with goiter was statistically significantly lower than in the children without goiter. Children with and without endemic goiter showed seasonal variations in total T4 and free T4 as well as total T3, free T3, and reverse T3, with the highest values in the fall; in thyroxin-binding globulin the highest values were in the winter; and in TSH the highest values were in the summer. There was no significant seasonal variation in thyroglobulin. There was no difference in the circannual variation between children with and without endemic goiter.

Child↗

[Craniofacial dysostosis with diaphyseal hyperplasia].

The only family known so far to have developed cranio-facial dysostose, has been the object of a new study. Since 1962, 3 new infants affected by this disease were born and another 3 died. The syndrome is characterized by an important growth deficit, small cranium with thin skull bone, a peculiar facies with marked hypoplasia of the middle portion and mandible, multiple and various teeth anomalies. The long bones are short and bent; thickening of the cortex occurred during puberty or in the post-puberal period and seems to increase with age. The mean life-span seems normal. The syndrome is transmitted in an autosomal dominant way with great penetrating force.

Adult↗

Quantitative study of extrathyroid enzymatic conversion of T4 to T3 in man.

The authors present a quantitative study of the extrathyroid conversion process of T4 to T3 in 3 athyroid patients, on the basis of an original biochemical model and a rigorous mathematical treatment, utilizing the kinetic isotope method. The values of thor the constant of the reaction rate of conversion of T4 to T3 and of the T4 fraction that undergoes this process--serum concentrations of T4 and T2--were determined in two completely different ways: 1) the radiochromatographic method, and 2) radioimmunoassay of T3 and competitive protein binding of T4. The results thus obtained supported each other and revealed that more than 1/3 of the body total thyroxine is turned into triiodothyronine by the extrathyroid conversion process. The maximum concentration of the triiodothyronine thus formed is reached after 5-6 days, if the reference level of this hormone is zero. However, the higher the T3 reference concentration in the body, up to the normal physiologic level, the shorter the time interval for reaching the T3 maximum concentration following a single moderate dose of T4.

Humans↗

Radioiodine treatment in recurrences of subacute thyroiditis.

The three cases of subacute thyroiditis treated by radioiodine were refractory to systemic corticoid therapy (2-3 recurrences in a mean duration of 7.6 mos) and to external antiinflammatory radiotherapy (relapses after 2 and 4 mos, respectively). No relapse after radioiodine administration has appeared (mean follow-up period: 3 yrs) and post-iodine hypothyroidism was mild.

Adult↗

A 22-year old female with the 9p deletion syndrome.

A 22-year old female patient with psycho-motor retardation, statural hypotrophy and clinical picture characteristic of the 9p deletion syndrome, i.e., trigonocephalia (corrected surgically), epicanthus, hypertelorism, long filtrum, micrognathia, low inserted and malformed ears, filiform fingers, is presented.

Abnormalities, Multiple↗

Thyroglobulin autoantibodies in endocrine diseases.

A simple, rapid haemagglutination laboratory kit was developed for the measurement of the thyroglobulin autoantibodies (Tgl-AAb). The Tgl-AAb kit was applied to the measurement of the AAbs titres in the sera collected from 2861 endocrine patients either hospitalized in the Institute of Endocrinology (about 75%) or endocrine outpatients--the great part of patients (over 90%) being however diagnosed as thyroid disorders. The sex classification showed the F/M ratio 6.61/1 for the whole group and 7.4/1 for the positive cases. The prevalence of the Tgl-AAbs positive sera at low titre (under 1:200) is 11.6% about twofold higher than in a population of 700 blood donors (6.4%), previously reported. Among the significant Tgl-AAbs titres, chosen more or less arbitrarily over 1:200, 30.47% of the patients have titres in the range 1:200-1:5000. The Tgl-AAbs positive and negative sera are classified and analysed according to the endocrine pathology but especially thyroid disorders and the positive thyroid disease are grouped by low, high and very high Tgl-AAbs titres and by Tgl-precipitin positive. Our results are rather similar to those reported for endocrine collectivities in other countries. The technical and methodological sources of some discrepancies between the laboratory Tgl-AAbs results and the clinical symptoms and/or anatomo-pathologic results are commented as well as some of the future perspectives of the laboratory investigation of the thyroid autoimmune diseases. Concluding, a strategy schema for a possible immunogram is presented.

Autoantibodies↗