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Biomedical subjects

J Szabo

Publications and source records attributed to J Szabo.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

Adult↗
PubMed2000

Prevalence of iodine deficiency and goitre during pregnancy in east Hungary.

OBJECTIVE: To assess the iodine nutritional status and the prevalence of goitre during pregnancy in a region of Hungary that appeared to be iodine sufficient in previous studies. DESIGN: A cross-sectional voluntary screening study was organized in which 313 pregnant women participated. METHODS: Urine iodine concentration and the volume of the thyroid gland were measured in every woman. In the presence of low urinary iodine concentrations, goitre, or both, thyroid function tests were performed. RESULTS: Iodine deficiency was found in 57.1% of the pregnant women, and was severe in 15.6%. The volume of the thyroid gland was enlarged in 19.2% of individuals. Nodular goitre was found in 17 women (5.4%). The frequency of goitre and the mean thyroid volume were increased in the group of iodine-deficient women. In the 89 cases of iodine deficiency or goitre, thyrotrophin concentrations were in the normal range; however, the free triiodothyronine:free throxine ratio was increased in 97% of them, indicating that the thyroid gland was in a stimulated state in these individuals. CONCLUSIONS: Iodine deficiency with high prevalence of goitre was recognized among pregnant women in an area that previously appeared to be iodine sufficient. An unexpected mild iodine deficiency was also noted in the non-pregnant control group. Reassessment and continuous monitoring of iodine nutritional status is warranted even in populations that are apparently considered to be 'at no risk' of iodine deficiency, especially in pregnant women. Regular administration of iodine, starting at preconception or in early pregnancy and continuing during the period of nursing, is recommended in these regions.

Adult↗
PubMed2000

Influence of dietary protein and lipid on weight loss in obese ovariohysterectomized cats.

OBJECTIVE: To determine effects of dietary lipid and protein on development of hepatic lipidosis (HL) and on physical and biochemical indices following rapid weight loss in cats. ANIMALS: 24 ovariohysterectomized cats. PROCEDURE: Cats were fed a high energy diet until they gained 30% of their ideal body weight and then randomly assigned to receive 1 of 4 weight-reduction diets (6 cats/diet) at 25% of maintenance energy requirements per day. Diets contained a low or high quality protein source and a lipid source deficient or sufficient in long chain essential fatty acids (LCEFA). Serum and plasma samples and liver biopsy specimens were obtained for biochemical analyses and determination of hepatic lipid content before and after weight gain and during and after weight loss. RESULTS: Irrespective of weight-reduction diet fed, all cats lost weight at a comparable rate (4.51 to 5.00 g/d/kg of obese body weight). Three cats developed hepatic lipidosis. Significant changes in plasma insulin, cholesterol, triglyceride, and serum glucose concentrations were detected after weight gain and weight loss in all diet groups, but values for these variables did not differ among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cats can lose 25 to 30% of their obese body weight over 7 to 9 weeks without developing overt clinical signs of HL, provided that weight-reduction diets are highly palatable, contain a high quality protein, have a source of LCEFA, and are fortified with vitamins and microminerals. However, rapid weight loss may increase risk factors associated with development of diabetes mellitus.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Effect of dietary protein quality and fatty acid composition on plasma lipoprotein concentrations and hepatic triglyceride fatty acid synthesis in obese cats undergoing rapid weight loss.

OBJECTIVE: To determine effects of dietary lipid and protein on plasma lipoprotein and free fatty acid concentrations and hepatic fatty acid synthesis during weight gain and rapid weight loss in cats. ANIMALS: 24 ovariohysterectomized cats. PROCEDURE: Cats were fed a high energy diet until they gained 30% of their ideal body weight and then randomly assigned to receive 1 of 4 weight reduction diets (6 cats/diet) at 25% of maintenance energy requirements. Diets contained a low or high quality protein source and a lipid source deficient or sufficient in long chain essential fatty acids. Plasma samples and liver biopsy specimens were obtained before and after weight gain and during and after weight loss for determination of free fatty acid, triglyceride, and lipoprotein concentrations. Synthesis of these substances was measured by use of isotope enrichment. RESULTS: Plasma total cholesterol concentration and concentration of lipoprotein fractions increased after weight gain, compared with baseline values. Weight loss resulted in a significant decrease in concentrations of all lipoprotein fractions except high density lipoprotein. High density lipoprotein concentration was significantly greater in cats fed diets containing an oil blend, compared with cats fed diets containing corn oil. Fatty acid synthesis after weight loss was below the detection limit of the measurement technique. CONCLUSIONS AND CLINICAL RELEVANCE: In cats undergoing rapid weight loss there is neither increased triglyceride synthesis nor decreased transport of very low density lipoproteins from the liver, suggesting that their involvement in the development of hepatic lipidosis may be minimal.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Follow-up of prostate carcinoma patients treated with total androgen blockade by repeated map-biopsy.

A prospective study was carried out on ten patients with prostate cancer. The TNM stage, Gleason's grade, general clinical status and, serum PSA level were all registered by the time of diagnosis. Total androgen blockade (TAB) was performed. Serum PSA control and general clinical examination re-biopsy was performed on average 107 days after the start of the therapy. The pre- and post treatment histology included HE and Tunel reaction to show apoptotic cells, as well as p53, bcl2 and Ki67 immunostaining. Clinical improvement of the disease, manifested by regression or by steady state was observed in all ten patients. An increase of apoptotic index, and a decrease of mitotic index was detected in most cases. The serum PSA level decreased in all patients. Ki67, bcl2 and mutant p53 were strongly expressed in tumor cells of patients in whom Gleason's grade was 7 or higher and decreased markedly in all cases upon therapy. Data obtained by repeated biopsy in the course of TAB therapy are indicators of the effectiveness of TAB, like changes in serum PSA, and may be considered as predictive factors.

Aged↗
PubMed1999

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the differential diagnosis of cold thyroid nodules.

Various diagnostic techniques have been successfully used in the clinical management of cold nodules; however, the decision on whether to employ surgery or a conservative treatment is not always easy. This study was designed to appraise the diagnostic value of technetium-99m methoxyisobutylisonitrile (MIBI) scintigraphy in the assessment of cold nodules detected using (99m)Tc-pertechnetate. Fifty-two patients were included in the study. All had already been selected for surgery, based on their clinical and laboratory findings, including fine-needle aspiration biopsy. The total number of cold nodules on (99m)Tc-pertechnetate scans was 59. The thyroid scan was performed 20-40 min after i.v. injection of 400 MBq of (99m)Tc-MIBI. Uptake of MIBI in thyroid nodules was compared with that in the surrounding normal thyroid tissue, and a score of between 0 and 3 was assigned to each nodule as follows: 0, cold; 1, decreased; 2, equal; 3, hot. Definitive histology revealed nodular goitre in 24 cases, adenoma in 19, thyroiditis in 1, differentiated cancer in 12, medullary cancer in 2, and anaplastic cancer in 1. None of the degenerative nodules were hot on MIBI scan, while the adenomas showed a variety of MIBI imaging patterns, most frequently the score 3 pattern. In the diagnosis of differentiated thyroid cancer the sensitivities of score 3 and score 2+3 MIBI uptake patterns were 83% (10/12) and 100%, respectively. The score 3 MIBI uptake pattern had a specificity of 100% and a positive predictive value of 100% with respect to thyroid (benign and malignant) neoplastic diseases, whereas a specificity of 72% and a positive predictive value of 43% were observed in the detection of differentiated cancer. After a cold nodule had been detected using (99m)Tc-pertechnetate, a second scan with high MIBI uptake increased by 7.8 times the probability that this nodule would be a differentiated cancer. In conclusion, (99m)Tc-MIBI scintigraphy is a useful method in the differential diagnosis of cold thyroid nodules if the primary aim is to differentiate degenerative from neoplastic diseases rather than to differentiate benign from malignant nodules. High MIBI uptake considerably increases the probability of a differentiated thyroid cancer and facilitates immediate surgical removal, while decreased uptake actually excludes it. We suggest a combination of fine-needle aspiration biopsy and MIBI scan as a routine diagnostic approach to cold thyroid nodules.

Biopsy, Needle↗
PubMed1999

Oxidative stress and antioxidant status in mouse kidney: effects of dietary lipid and vitamin E plus iron.

The purpose of this study was to determine the effects of dietary fat, vitamin E, and iron on oxidative damage and antioxidant status in kidneys of mice. Sixty 1-month-old male Swiss-Webster mice were fed a basal vitamin E-deficient diet that contained either 8% fish oil + 2% corn oil or 10% lard with or without 1 g all-rac-alpha-tocopherol acetate or 0.74 g ferric citrate per kilogram of diet for 4 weeks. Significantly (P < 0.05) higher levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), and conjugated dienes were found in the kidneys of mice fed with fish oil compared with mice fed lard irrespective of vitamin E status. Mice maintained on a vitamin E-deficient diet had significantly higher renal levels of TBAR, but not conjugated dienes, than the supplemented group. Fish oil fed mice receiving vitamin E supplementation had lower levels of alpha-tocopherol than did mice in the lard fed group. Significantly higher levels of ascorbic acid were also found in the kidneys of mice fed with fish oil than were found in mice fed lard. The levels of protein carbonyls and glutathione (GSH), and activities of catalase, superoxide dismutase, selenium (Se)-GSH peroxidase, and non-Se-GSH peroxidase were not significantly altered by dietary fat or vitamin E. Dietary iron had no significant effect on any of the oxidative stress and antioxidant indices measured. The results obtained provide experimental evidence for the pro-oxidant effect of high fish oil intake in mouse kidney and suggest that dietary lipids play a key role in determining cellular susceptibility to oxidative stress.

Journal Article↗
PubMed1999

A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene.

We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1). However, three of the four individuals developed extensive areas of acanthosis nigricans beginning in early childhood, suffer from severe neurological impairments, and have survived past infancy without prolonged life-support measures. The FGFR3 mutation (A1949T: Lys650Met) occurs at the nucleotide adjacent to the TD type II (TD2) mutation (A1948G: Lys650Glu) and results in a different amino acid substitution at a highly conserved codon in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs show that the Lys650Met mutation causes a dramatic increase in constitutive receptor kinase activity, approximately three times greater than that observed with the Lys650Glu mutation. We refer to the phenotype caused by the Lys650Met mutation as "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations.

Acanthosis Nigricans↗
PubMed1999

Calculation of the radioiodine dose for the treatment of Graves' hyperthyroidism: is more than seven-thousand rad target dose necessary?

Some authors recently suggested a significant increase in the target dose of radioiodine treatment in Graves' disease. The aim of the present study was to investigate the impact of thyroid gland mass on the success rate of radioiodine treatment. For this purpose, the thyroid function of 105 consecutive Graves' patients was assessed 6 and 12 months after a 131I treatment and correlated to the gland mass. The patients were categorized according to the gland mass into small (< or = 30 g; 19 patients), medium size (31-50 g; 40 patients), and large size (> 50 g; 46 patients) groups (S, M, L groups, respectively). None of the patients received more than a 10,000-rad (100-Gy) target dose. During the calculation of administered 131I activity, late uptake measurement has also been routinely used, in addition to the usual maximal uptake parameter. The established effective half-life of 131I was highly variable (5 +/- 1.2 days; range: 2-7.6 days) and could not be predicted based on other clinical data without measuring an extended radioiodine uptake curve of the given patient. However, the correlation between the administered activity calculated from the complete set of uptake values and that of only a single late one was excellent (r = 0.99). Six months after the 131I treatment, hyperthyroidism was cured in 81% of patients with small and medium size thyroid glands, with 62% euthyroid and 19% hypothyroid ratios respectively. In the early phase of study for large goiters, the same linear mass activity function was used during calculation as in smaller glands. In these 17 patients the nonhyperthyroid result was comparable to the results of treatment of the small and medium size gland groups only after 1 year (77%), but the 6-month success rate was significantly lower (53%; p < 0.05). After obtaining these results, the usual 7000-rad target dose was increased to 8000-10,000 rad (depending on the gland mass) in another group of 29 patients with large thyroid glands that result in an acceptable 6-month success rate of 72%. In conclusion, instead of the "mCi 131I/g gland mass/maximal uptake" dose calculation, we suggest a method in which (1) the late 131I uptake measurement is taken into account and (2) for large goiters there is an additional dose adjustment, ie, increase is needed over the usual linear, size driven calculation. No overall increase of target dose over 10,000 rad is necessary if no antithyroid medication is given shortly before 131I treatment.

Adult↗
PubMed1999

Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein.

Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis.

Cathepsin K↗