Evaluation of the thyroid function of healthy pregnant women by five different hormone assays.

A normal function of the thyroid gland during pregnancy is essential. Any change can affect both the pregnant woman and the fetus. Thyroid hormones play a crucial role in the brain development of the fetus, thus proper maternal free thyroid hormone levels are important especially during the first trimester. We compared the free thyroid hormone levels FT3 and FT4 in forty pregnant women with no thyroidal disease by five different assays available on the market. The blood samples were collected between the 8th and 22nd weeks of pregnancy. The correlation coefficient "r" between different assays was 0.908-0.975 for TSH, 0.676-0.892 for FT4 and 0.480-0.789 for FT3. These data show that the inter-assay results varied widely in the studied population. One reasonable explanation may be that during pregnancy the serum levels of the thyroid hormone binding proteins are altered and "free" hormone measurements by immunoassays are influenced by these alterations. Thus, the results may show higher or lower thyroid hormone values depending upon the assay used. Therefore, it is strongly suggested that every laboratory should establish its own pregnant reference ranges for the tests used for the evaluation of thyroid function, based on values of the population served.

Graves' ophthalmopathy: eye muscle involvement in patients with diplopia.

BACKGROUND: Diplopia identifies patients with eye muscle involvement in Graves' ophthalmopathy (GO). OBJECTIVE: To identify clinical parameters that could eliminate the need for magnetic resonance imaging (MRI) to assess the activity of inflammation in the eye muscles of GO patients with diplopia. METHODS: In 43 patients with GO with recently developed diplopia, orbital ultrasound and MRI were performed. Muscle diameters and MRI T2 relaxation times were measured, and the amount of orbital connective tissue was calculated from MRI scans and compared with ultrasound readings, diplopia grades, degree of protrusion, ocular pressure, tear production, antibody levels and hormonal parameters of thyroid function. RESULTS: No correlation was found between diameters of 233 extraocular muscles measured by MRI and by ultrasound. For each of the four muscles, there was a diameter above which ultrasound was always unreliable. MRI data were used in further analysis. Of the muscles examined, the inferior rectuses were the most frequently enlarged - at least one, in 93% of cases. Medial, lateral and superior rectuses were enlarged in 59%, 37% and 34% of the orbits respectively. The pattern of muscle involvement of the two orbits tended to be symmetric (r=0.49, P=0.003), particularly for the medial rectuses (r=0.90, P=0.000). Proptosis correlated with the sum of the muscle diameters for a given eye (right eye: r=0.54, P=0.003; left eye: r=0.57, P=0.001), but it failed to correlate with the amount of orbital connective tissue. In 53% of the patients, normal T2 relaxation times were found in all eight muscles. There was only a weak correlation between muscle thickness and T2 relaxation time (r=0.49, P=0.003), indicating that muscle enlargement alone is not a sign of disease activity. The severity of diplopia was independent of T2 relaxation time. The amount of orbital connective tissue showed a negative correlation with the greatest T2 relaxation time for a given eye (r= -0.52, P=0.004); this suggests that disease types exist that have predominant muscle involvement and predominant connective tissue expansion. No correlation between connective tissue expansion and proptosis, diplopia grade, muscle thickness or disease duration was found - that is, connective tissue expansion is not a major factor in diplopia. Both muscle and connective tissue findings were independent of thyroid function. CONCLUSION: Ultrasound and MRI eye muscle diameter readings do not correlate, because of the inherent inaccuracy of orbital ultrasound. Muscle enlargement alone does not mean oedematous swelling and active disease. Neither ultrasound, nor any combination of 11 clinical and laboratory parameters provided the degree of information on muscles and connective tissue that was obtainable by MRI. In unclear cases of recently developed diplopia, before orbital decompression surgery, in the case of treatment failure or if, for any other reason, imaging is needed in GO, MRI is the method of choice.

The role of different tumor markers in the early diagnosis and prognosis of pancreatic carcinoma and chronic pancreatitis.

The examination of tumor markers in the diagnosis and in the evaluation of progression of tumors has got an increasing significance. The serum level changements of three tumor markers (CEA, CA 19-9, CA 125) were examined before and after the operation in 94 patients operated for pancreatic carcinoma (PC) and chronic pancreatitis (CP) between March 1994 and December 1996 at the 2nd Dept. of Surgery of Debrecen Medical University. From the patients 62 were operated for carcinoma, in 19 cases the tumor was resectable, 43 patients had palliative operation. In 32 patients ductal decompression was performed because of CP. The authors evaluate the serum level changements of the three tumor markers examined in three groups of patients before and after the operation. In conclusion CA 19-9 is the most sensitive marker of PC, the sensitivity was 77.4%, the specificity was 87.5%. CEA and CA 125 are not as sensitive markers of PC as CA 19-9, while CEA and CA 125 serum levels are both increased in half of the patients with chronic pancreatitis.

Tracheostomy can make a difference in recurrent respiratory failure secondary to olivopontocerebellar atrophy.

This article describes the case of a 55-year-old white male with olivopontocerebellar atrophy who was admitted to the ICU at Ohio Valley Medical Center because of recurrent respiratory failure. He had to remain in the ICU for 21 days on a ventilator even though he was hemodynamically stable with no evidence of pneumonia. A tracheostomy was then performed and within five days he was able to be weaned from the ventilator and transferred to a long-term care facility. This case suggests that early tracheostomy may play an important role in acute and long-term management in patients with olivopontocerebellar atrophy.

Induction of renin release from isolated glomeruli by inorganic mercury(II).

Mercury(II) ions are known to accumulate in the kidney and their effect upon the renin-angiotensin system has also been described. The question, however, whether mercury(II) also exerts direct effect on the juxtaglomerular cells (JGC) to induce renin release remained to be answered. Suspension of isolated glomeruli was used to measure the mercury(II)-induced renin release in vitro. The glomeruli were isolated from female BALBc mice. HgCl2 was found to be capable of inducing renin release directly from JGC. The effect is concentration-dependent (P < 0.05, r = 0.914 and P < 0.01, r = 0.982, with and without Neutral Red vital staining) and becomes apparent already at a mercury(II) ion concentration as low as 1 microM. The renin-releasing effect of the mercury ion is to be inhibited by dithiothreitol (DTT) (renin activity 20.37 vs. 2.60 ng/ml.h in supernatant) as well as the elevated osmotic concentration of the incubating bath medium (20.37 vs. 6.84 ng/ml.h). This suggests that certain membrane sulfhydryl groups are implicated in the process on the one hand, and it is also in accordance with the known sensitivity of the renin granules to osmotic pressure on the other hand. Light and electron micrographs also demonstrate the direct, effective role of Hg(II) in the renin release process. Therefore, it is assumed that apart from its influence on tubulo-glomerular feedback a direct way of action of mercury(II) on renin release must also be taken into account.

[Value of thyroglobulin determination in the follow up treatment of patients with thyroid cancer]. / Thyreoglobulin meghatározások értéke differenciált pajzsmirigycarcinomában szenvedö betegek utókezelésében.

Tg measurements were performed regularly in 96 thyroid carcinomas in order to evaluate metastases and local recurrencies. Elevated Tg level was detected in 11 patient. 7 of them were operated on because of local recurrencies and lymph node metastases. All patients that needed reoperation had elevated Tg level. During the follow up period no patient needed reoperation who had elevated Tg level or metastases detected by other diagnostic procedures. Summarising the results they found the Tg level measurements valuable in the follow up of patients with differentiated thyroid cancer. The Tg level measurements can supplement or sometimes replace 131J thyroid scanning.

A non-isotopic screening test for antibodies to TSH receptor: dot immunobinding assay.

A dot immunobinding assay (DIBA) for thyrotropin (TSH) receptor antibodies is described. The method depends on the detection of antibody binding to highly purified thyroid plasma membrane attached to nitrocellulose solid support by horse-radish peroxidase - conjugated anti-human IgG. The method can detect down to 0.75 mU LATS standard and 1/1000 dilution of Graves' serum or immunoglobulin fraction. The interaction is inhibited dose-dependently by bTSH but not by insulin or human chorionic gonadotropin. The DIBA results show close correlation to those of TRAK (TBII) but not to cyclic AMP generation assay. DIBA is reproducible when tested monthly for 4 months. Sera and immunoglobulins gave virtually the same results. The method has a sensitivity of 90%, validity of 90% and specificity of 80% for both. We have, thus developed a sensitive and reliable method for screening for TSH receptor antibodies which can be performed in routine clinical laboratories.

Hormonal changes in haemodialysed and in kidney-transplanted patients.

A total of 48 haemodialysed patients were studied by radioimmunoassay for the serum concentrations of parathormone, calcitonin, gastrin, insulin, prolactin, T3, T4, rT3, TSH and cortisol. Residual urines were measured for cAMP and ultrafiltrates for iPTH and gastrin. The duration of the dialysis programme, the number of haemodialysis sessions per week, sex distribution, the dialysis alternatives (including haemofiltration, haemoperfusion) and successful kidney transplantations were correlated with the serum hormone levels. Significant increases in PTH, gastrin and prolactin values were demonstrated in the dialysed patients. However, their calcitonin and insulin concentrations decreased, parallel with the time elapsed since the start of the haemodialysis programme (HDP). The number of dialysis sessions per week was found to affect the hormone concentrations diversely. In the course of haemofiltration and haemoperfusion some of the hormone levels (e.g. PTH, gastrin) decreased significantly. The patients were in general euthyroid. One of them, on HDP for several years, developed clinical and laboratory signs indicative of hyperthyroidism. In a considerable proportion of the cases the results of the hormone studies (increased PTH, CT, cAMP) were consistent with secondary hyperparathyroidism. Kidney transplantation was followed by a decline of the serum prolactin, parathormone, calcitonin and aldosterone levels.

Clinical correlates of circulating immune complex levels in advanced lung cancer. A discrimination analysis.

Sera from 53 patients with unresectable lung cancer were tested for the presence of immune complexes by 12 assays. 5 assays (EA rosette inhibition, ADCC inhibition, platelet aggregation, IgG and C3 concentrations in PEG precipitates) could discriminate cancer patients from healthy subjects with over 80% reliability. On the basis of 3 assays (EA-I, ADCC-I and PEG-C3) a function allowing a 100% correct classification could be formulated:--(EA-I)--0.5 (ADCC-I) + 2.4 (PEG-C3) greater than 69.3, i.e., results higher than 69.3 are characteristic for cancer patients and lower than 69.3 for normal subjects. The relationship between the immune complex levels and the average survival time was not altered by sex, age, histology and treatment. None of the immune complex assays or their combination were useful for the estimation of individual life expectation.

Evaluation of different methods for detecting circulating immune complexes. Studies in patients with lung cancer.

In a collaborative study involving 7 laboratories, sera from 53 patients with lung cancer, 37 primary and 16 secondary tumours, and sera of 40 healthy blood donors were tested by 19 different assays or assay modifications used for detecting immune complexes. In 12 out of 19 assays, significantly higher immune complex levels were found in the cancer patients than in the healthy subjects. Assays based on interactions between immune complexes and Fc receptors of different cells (lymphocytes, macrophages of platelets) discriminated between cancer patients and health subjects and a high percentage (47-87%) of positivity was observed in such assays in patients with lung cancer. In contrast, none of the tests based on immune complex-complement interactions discriminated between cancer patients and health subjects. Immunochemical analyses of the PEG precipitates obtained from the sera tested revealed that the concentrations of IgG, IgA and C3 were significantly higher in the precipitates obtained from patients sera than from control sera, but no significant differences were seen in IgM and C1q concentrations. A 100% correct classification of individuals tested was obtained on discriminant analysis of results with 3 assays: EA rosette inhibition, ADCC inhibition and C3 concentration in PEG precipitates. Correlation between results obtained with individual sera by the different assays was very poor: significant correlation coefficients were found in only 13% of all possible paired comparisons. Our results suggest that Fc receptor-dependent assays are more suitable for detection and measurement of circulating immune complexes in lung cancer than tests based on interactions with complement.

Evaluation of different methods for detecting circulating immune complexes. An inter-laboratory study.

Forty serum samples of healthy blood donors and 60 sera of SLE patients were tested in parallel by 7 different assays for detecting immune complexes. Significantly higher titres and significant higher incidence of positive results were observed in the patient group than in the control group in 6 tests. No test discriminated between patients in an active stage of the disease and those whose disease was inactive. Significantly higher immune complex levels were found in lupus nephritis than in the non-nephritic patients by the complement consumption test. Significant positive correlation was obtained between the results of the macrophage aggregated IgG uptake inhibition and PEG-precipitation tests and between two tests based on the interaction of the complexes with the complement system. A characteristic 'profile' of the immune complex assay was observed in the course of the repeated testings of the same patients. The results indicate that the different methods detect different types of immune complexes present in the blood of the patients.

Circulating immune complexes and phagocytic activity of polymorphonuclear cells in patients with glomerulopathies.

Out of 92 renal patients with various types of glomerulonephritis diagnosed by renal biopsy 49 (52 per cent) proved to be immune complex positive by the platelet aggregation test. The highest frequency of circulating immune complexes was found in Henoch-Schoenlein (5 out of 5) and IgA (4 out of 5) nephropathies. The occurrence of circulating immune complexes correlated well with the clinical activity of the renal disease. The phagocytic activity of the polymorphonuclear cells was investigated in 46 patients and depressed activity was detected in all but one of the patients. There was no relationship between the titer of circulating immune complexes in serum and the extent of phagocytic activity.

Experimental studies on factors causing acute serum sickness glomerulonephritis of immune complex origin. I. The role of immune complexes and the immunological status of the host.

In acute serum sickness glomerulonephritis induced in rabbits by large doses of BSA, the relationship of the host's immunological status and the severity of renal histological changes was studied. It was found that good antibody producers developed more severe renal lesions. The higher avidity of antibodies enhances the inflammatory effect of immune complexes. Kidney is favoured for deposition of immune complexes especially in the case of chronic immune complex formation in the presence of antigen excess. Diminished phagocytic function of leukocytes (probably decreased immune complex saturating capacity) may also contribute to the severity of renal histological alterations.

Experimental studies on factors causing acute serum sickness glomerulonephritis of immune complex origin. II. Pathomorphological analysis.

Seventeen rabbits were given a single, large dose of bovine serum albumin (BSA) intravenously. Percutaneous kidney biopsy was carried out on the 14th and 31st days after BSA administration. Proteinuria was measured and the glomerular changes were analysed in order to find a correlation between the degree of proteinuria and glomerular alterations, i.e. number of electron-dense deposits (EDD), polymorphonuclear leukocytes (PMNL), and mononuclear marcophages (MNM). The results speak in favour of the decisive role of mononuclear macrophages in enhancement of glomerular permeability.