Evaluation of the physical and biological dosimetry methods in iodine-131-treated patients.

The aim of the study was to compare physical and biological dosimetry methods in iodine-131 (I-131)-receiving patients. The present study comprised of 47 patients (mean age: 47.9 ± 15.8 years), treated with I-131. Group I consisted of 17 patients with hyperthyroidism and mean administered activity of this group was 432.9 ± 111 MBq. There were 15 follow-up patients of differentiated thyroid cancer (DTC) in Group II with mean administered activity of 185 ± 22.2 MBq, who were administered scanning dose of I-131. Group III comprised of 15 patients with DTC, ablated with high-dose of I-131, and this group's mean administered activity was 4347.5 ± 695.6 MBq. The whole-body absorbed doses were calculated in all patients both with the Medical Internal Radiation Dosimetry (MIRD) method using MIRDOSE3 software and cytokinesis-block micronucleus (MN) assay-based MN analysis and were compared. The whole-body absorbed dose, calculated by MIRD method, showed very good correlation with the administered I-131 activity (r = 0.89, P < 0.001), but it was moderate in the MN method (r = 0.52, P < 0.01). Absorbed dose estimations with MIRD method were 49.2 ± 20.8 mGy in Group I, 6.5 ± 1.6 mGy in Group II, and 154.3 ± 47.8 mGy in Group III; the differences were statistically significant (P < 0.001), as expected. Pre- and posttreatment MN frequencies differed significantly in all groups (P < 0.05). The whole-body absorbed doses, based on MN method, were 68.2 ± 17.5, 46.0 ± 11.4, and 90.5 ± 26.9 mGy in Groups I-III, respectively. The difference was significant between Group II and Group III (P < 0.01). The mean absorbed dose was 74.6 ± 27.9 mGy with MN versus 68.0 ± 67.1 mGy in MIRD method (P = 0.087) in the entire study population and the correlation was moderate (r = 0.73, P < 0.001). The whole-body absorbed doses, estimated by MN method, showed moderate correlation with administered radioiodine activities in low radioiodine doses and had significantly different and fluctuating values as compared to MIRD method in patients treated with I-131.

Micronucleus frequencies in groups receiving external or internal radiation.

OBJECTIVE: In the current study, we aimed to explore whether there is alteration between pre- and post-treatment micronucleus (MN) frequencies induced by internal and external ionizing radiation. MATERIALS AND METHODS: The study enrolled a total of 67 patients including patients admitted to our hospital for treatment of hyperthyroidism (n = 17), scanning with low-dose I-131 (n = 15), and ablative therapy with high-dose I-131 (n = 15) at Department of Nuclear Medicine as well as patients with different diagnoses receiving external radiotherapy with various doses and durations at Department of Radiation Oncology (n = 20). Thirty-two patients who received radioactive iodine and returned for a follow-up visit at 1 month. RESULTS: Considering both pre- and post-treatment MN frequencies of each group, lowest MN frequencies were detected for patients undergoing screening with low-dose I-131, and highest MN frequencies were found in radiotherapy patients. Comparison of pre- and post-treatment MN frequencies among hyperthyroidism, when pre- and post-treatment MN frequencies compared among hyperthyroidism, I-131 whole body scanning, ablation, and radiotherapy patient groups differences between MN frequencies were significant for each group (P < 0.05). CONCLUSION: Our study showed that MN analysis might be of value in determining chromosome damage that could potentially occur in patients exposed to internal and external radiation.

Morphologic and Metabolic Comparison of Treatment Responsiveness with 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography According to Lung Cancer Type.

OBJECTIVE: The aim of the present study was to evaluate the response to treatment by histopathologic type in patients with lung cancer and under follow-up with 18F-fluoro-2deoxy-glucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging by using Response Evaluation Criteria in Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria that evaluate morphologic and metabolic parameters. METHODS: On two separate (pre- and post-treatment) 18F-FDG PET/CT images, the longest dimension of primary tumor as well as of secondary lesions were measured and sum of these two measurements was recorded as the total dimension in 40 patients. PET parameters such as standardized uptake value (SUVmax), metabolic volume and total lesion glycolysis (TLG) were also recorded for these target lesions on two separate 18F-FDG PET/CT images. The percent (%) change was calculated for all these parameters. Morphologic evaluation was based on RECIST 1.1 and the metabolic evaluation was based on EORTC. RESULTS: When evaluated before and after treatment, in spite of the statistically significant change (p<0.05) in SUVmax, the change was not significant in TLG, in the longest total size and in the longest size (p>0.05). In histopathologic typing, when we compare the post-treatment phase change with the treatment responses of RECIST 1.1 and EORTC criteria; for RECIST 1.1 in squamous cell lung cancer group, progression was observed in sixteen patients (57%), stability in seven patients (25%), partial response in five patients (18%); and for EORTC progression was detected in four patients (14%), stability in thirteen patients (47%), partial response in eleven patients (39%), in 12 of these patients an increase in stage (43%), in 4 of them a decrease in stage (14%), and in 12 of them stability in stage (43%) were determined. But in adenocancer patients (n=7), for RECIST 1.1, progression was determined in four patients (57%), stability in two patients (29%), partial response in one patient (14%); for EORTC, progression in one patient (14%), stability in four patients (57%), partial response in two patients (29%) were observed and in these patients, an increase in stage was detected in 3 of them (43%), while 4 of them remained stable. According to histopathologic diagnosis, between squamous cell cancer and adenocancer cases, no significant difference was determined in terms of SUVmax (p>0.05). Post-treatment SUVmax was significantly different in primary tumor but was not significantly different in nodal involvement and metastatic lesions for squamous cell carcinoma patients as compared to the pre-treatment SUVmax measurements. Similarly, there was no significant difference between primary tumor and nodal involvement for adenocarcinoma patients. CONCLUSION: Whether metabolic or morphologic changes are more accurate in evaluating treatment response in lung cancer remains unknown, and there is no gold standard diagnostic method on this issue yet. The most reliable results can only be achieved by survival curve parameters. However, we believe SUVmax seems to provide more easy and practical data for the evaluation of treatment response.

Sarcopenia in women with rheumatoid arthritis.

OBJECTIVE: To assess sarcopenia status in women with rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty female patients with RA and 30 female controls without RA were enrolled in this study. Sarcopenia status in patients with RA was evaluated by assessing body composition using dual X-ray absorptiometry (DXA). C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were measured, and body mass index (BMI) and Disease Activity Score (DAS28) were calculated. Because sarcopenia differs between men and women, the study groups comprised only females. RESULTS: It was found that skeletal muscle index (SMI) was lower in patients with RA (5.83±0.807) than in controls (7.30±1.640). Sarcopenia (in females with an SMI of ≤5.75 kg/m2) was more common in the RA group and the difference was statistically significant (p=0.004). Sarcopenia was more common in patients with RA who were normal or overweight than in those who were obese according to their BMI. There was no relationship between sarcopenia and DAS28 in the RA group (p=0.530), whereas CRP levels were significantly higher in patients with sarcopenia (p=0.230). No relationship was found between drug use and sarcopenia in the RA group. CONCLUSION: It was found that SMI was decreased and sarcopenia risk was elevated in patients with RA and the risk was higher in non-obese patients.

Potential impact of atelectasis and primary tumor glycolysis on F-18 FDG PET/CT on survival in lung cancer patients.

BACKGROUND: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. MATERIALS AND METHODS: The study consisted of patients with lung cancer with or without atelectasis who underwent (18)F-FDG PET/CT examination before receiving any treatment. (18)F-FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. RESULTS: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n=22) in the presence of atelectasis; the overall one-year survival rate was 65.7% (n=28) and median survival was 16 months (p=0.138) in the absence of atelectasis. With respect to PFS; the one-year survival rate of AT+ patients was 81.8% and median survival was 19 months; the one-year survival rate of AT- patients was 64.3% and median survival was 16 months (p=0.159). According to univariate analysis, MTV, TLG and tumor size were significant risk factors for PFS and OS (p<0.05). However, SUVmax was not a significant factor for PFS and OS (p>0.05). CONCLUSIONS: The present study suggested that total lesion glycolysis and metabolic tumor volume were important predictors of survival in lung cancer patients, in contrast to SUVmax. In addition, having a segmental lung atelectasis seems not to be a significant factor on survival.

p53 antibody: is it an indicator of dedifferentiated thyroid cancer?

AIM: Radioiodine is the most effective treatment modality in differentiated thyroid carcinoma, either in metastatic or residual thyroid tissue. However, sometimes dedifferentiation can develop and the effectiveness of radioactive I-131 decreases. The p53 is a tumor suppressor gene which plays an important role in controlling normal cell proliferation regulation. In the serum of healthy individuals, the presence of p53 autoantibodies is extremely rare. Mutations in this gene cause an accumulation of non-functional proteins and may lead to development of anti-p53 antibodies. The aim of the present study was to devise a simple blood test that could lead to early identification of patients with dedifferentiation. In this respect, we investigate whether the serum level of anti-p53 antibody is of diagnostic value in the follow-up of patients with high levels of thyroglobulin (Tg) and negative I-131 scan. MATERIALS AND METHODS: Patients who were diagnosed with thyroid cancer, treated with total or near total thyroidectomy and referred for I-131 therapy or low dose I-131 whole body scan were included in our study. Blood samples were taken before the administration of I-131 orally in the group of patients. Besides, 28 healthy subjects were included. We quantified the presence of p53 autoantibodies from serums. RESULTS: In the present study were enrolled 171 patients with a mean age of 47.7±13.5 years (range 16­80 years) and 28 healthy subjects with an age range of 18­52 years (mean 36.0±9.8 years). One hundred and forty-eight patients had papillary (86.5%), 7 (4.1%) follicular, 10 (5.8%) thyroid tumors of uncertain malignant potential, 2 (1.2%) Hürthle cell carcinoma, 3 (1.8%) poor differentiated, and 1 (0.6%) undifferentiated thyroid carcinoma. The p53 antibodies were positive in 16 (9.4%) patients and negative in 155 (90.6%). The p53 antibodies were positive in 3 (10.7%) healthy subjects, and negative in 25 (89.3%) healthy subjects. In five patients with high Tg level and negative radioiodine scan, who were accepted as dedifferentiated, p53 antibodies were also negative. CONCLUSION: The results of the present study suggested that the level of serum p53 antibody seems to be of limited value in the demonstration of dedifferentiation in thyroid cancer patients.

Serum 25-hydroxyvitamin D levels in restless legs syndrome patients.

OBJECTIVE: Restless legs syndrome is characterised by discomfort during rest and an urge to move the limbs that is accompanied by abnormal sensations. Studies on disease pathophysiology have focused on dopaminergic dysfunction. Vitamin D may play an important role in dopamine function, but the role of vitamin D in restless legs syndrome has not been examined. We compared the serum vitamin D levels of RLS patients and matched controls and explored the correlation of plasma vitamin D levels with disease severity. PATIENTS/METHODS: We measured serum 25-hydroxyvitamin D levels in 36 patients with restless legs syndrome and compared them to 38 healthy control subjects. RESULTS: The mean serum 25-hydroxyvitamin D levels were 7.31±4.63 ng/mL in female patients with restless legs syndrome and 12.31±5.27 ng/mL in female control subjects (p=0.001). We found a significant inverse correlation between vitamin D levels and disease severity in females (p=0.01, r=-0.47). CONCLUSION: The mean serum vitamin D levels were lower in female patients with restless legs syndrome. Low vitamin D levels may cause dopaminergic dysfunction in restless legs syndrome patients. Further studies are required to confirm these results.

Increased T-allele frequency of 677 C>T polymorphism in the methylenetetrahydrofolate reductase gene in differentiated thyroid carcinoma.

BACKGROUND: Epigenetic alterations in the global DNA methylation status may be associated with an increased risk of some cancer types in humans. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in folic acid metabolism and plays an essential role in inherited DNA methylation profiles. The common 677 C>T and 1298 A>C polymorphisms in the MTHFR gene cause the production of a thermolabile enzyme with reduced function and, eventually, genomic DNA hypomethylation. The current preliminary study was designed to determine the association between germ-line polymorphism in the MTHFR gene and differentiated thyroid carcinoma (DTC). METHODS: In the current case-control study of 60 thyroid carcinomas (TC); 45 papillary TC, 9 follicular TC, and 6 DTC of an uncertain malignant potential were examined. Genomic DNA was extracted from peripheral blood with EDTA, genotyped by a multiplex real-time polymerase chain reaction. RESULTS: An elevated 2.33-fold risk was observed for DTC in individuals with the 677TT genotype when compared with the control group (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.03-3.58). Current DTC patients showed similar results as a control group for the 1298 A>C allele. No significant risk was detected for the homozygous 1298CC genotype (CC vs. AA or AC) (OR: 1.30, 95% CI: 0.73-2.29). CONCLUSION: The current results are supportive of the hypothesis that the homozygous MTHFR 677TT genotype increases the risk factor of developing thyroid cancer, and further large-scale studies are needed to validate this association.

Contrast-induced nephropathy: controlled study by differential GFR measurement in hospitalized patients.

BACKGROUND: Without appropriate control measures, contrast-induced nephropathy (CIN) incidence has been claimed to be overestimated. PURPOSE: To evaluate the relationship and the difference between differential serum creatinine (DsCr), which is currently surrogating as a marker of CIN, and measured differential GFR values as a control measure (DGFR) in hospitalized patients. MATERIAL AND METHODS: GFR was measured two times by Tc-99m DTPA, before and 48 h after contrast media (CM), along with sCr and BUN in 35 inpatients (22 men, 13 women, mean age ± SD = 61 ± 14) with no known chronic kidney disease. RESULTS: Relationship was moderate between GFR and sCr (R = 0.50, P < 0.01) in the study population. Pre-CM vs. post-CM values of GFR, sCr and BUN were not statistically different as (mean ± SD); 78 ± 36 vs. 73 ± 35 mL/min/1.73m(2), 0.95 ± 0.26 vs. 0.94 ± 0.26 mg/dl and 21 ± 16 vs. 19 ± 13 mg/dl, respectively, in the study group. According to basal GFR values, 14 patients (40%) seemed carrying risk of CIN (GFR < 60 mL/min/1.73m(2)) in whom only two had sCr >1.5 mg/dl. Twenty-five patients (71%) had discordant results in relation to DsCr and DGFR and two of them had CIN according to classical definition of DsCr, although having basal sCr <1.1 mg/dl. Yet, both had low, but stable GFR values. None of patient from the study group underwent hemodialysis. CONCLUSION: Significant discordance was observed between differential serum creatinine and measured differential GFR in hospitalized patients, suggesting that CIN incidence calculations only based on hospital registry may carry risk of error.

The Evaluation of Microcarcinoma in Differentiated Thyroid Cancers According to Old and New TNM Classification.

OBJECTIVE: In this study, we aimed to evaluate the tumor size for proximal and distant metastases when the new and old TNM classification is taken into account in differentiated thyroid cancers. MATERIAL AND METHODS: Two hundred sixty eight patients diagnosed with thyroid carcinoma, undergoing bilateral total or subtotal thyroidectomy treated with high doses of I-131 were examined retrospectively. The data of these patients were compared after classification, according to tumor size <1 cm and <2 cm, lymph node metastases thyroid and tumor capsule invasion at the time of diagnosis, and accumulation of abnormal activity in post I-131 treatment whole-body scan. I-131 uptakes besides physiological and thyroid bed were considered as abnormal activity uptakes. RESULTS: A total of 268 patients with average age of 19-82 yrs (mean: 47.0±13.8 yrs) were included in the study. At postoperative histopathological evaluation, 228 (85.1%) of patients were reported as papillary, 13 (4.9%) as follicular, 23 (8.6%) as well differentiated tumor of unknown malignant potential, 2 (0.7%) as insular and 2 (0.7%) as Hürthle-cell carcinoma. In patients with known tumor size, 96 of 207 (46.4%) patients' tumor size was <1 cm and in 111 (53.6%) >1 cm. In the same group, according to the revised TNM classification, in 149 of 207 patients (72%) the tumor size was <2 cm, whereas in 58 (28%) >2 cm. Of 187 patients with negative lymph nodes, 15 (8%) showed abnormal activity accumulation in the first post I-131 treatment whole-body scan and 10 (40% of 25 patients) positive lymph node (p<0.05) involvement. CONCLUSION: Since the treatment of patients with microcarcinoma is controversial, tumor size should not be the only factor considered in patients with differentiated thyroid cancer Tissue tumor invasion, age, gender and multifocality should also be taken into account. CONFLICT OF INTEREST: None declared.

Evaluation of myocardial viability with thallium-201 infusion MPSPECT after oral glucose application in patients with chronic coronary artery disease.

AIM: The aim of this study was to evaluate the myocardial viability in nondiabetic patients with chronic coronary artery disease (CCAD) or past myocardial infarction (MI), using thallium-201 infusion myocardial perfusion single-photon emission computed tomography (MPSPECT) imaging after oral glucose application (Glu+Tl-infusion). MATERIALS AND METHODS: In this study, 33 nondiabetic patients (three female, 30 male, mean age: 55.24+/-11 years, range: 33-77 years) with MI history or known CCAD were included. Rest/redistribution/24 h-late-MPSPECT imaging was performed for all patients. In all patients in whom fixed perfusion defect was observed on any wall of the left ventriculi, after 24 h-late-MPSPECT imaging, 75 g oral glucose was given. Thirty minutes later, 1 mCi thallium-201 in 100 ml of physiological saline solution was applied in a period of 20 min by slow infusion. After infusion at the 10th minute, MPSPECT imaging was performed. Perfusion was evaluated visually for a total of 3432 segments with the 26-segment 5-point scoring technique. Scoring measured perfusion as 0 = no perfusion defect, 1 = mildly reduced, 2 = moderately reduced, 3 = severely reduced, and 4 = absent uptake. Scores '0 and 1' were considered normal and scores '2-4' were considered abnormal. RESULTS: For serum insulin levels measured after glucose application, a significant increase was determined, according to the period before glucose application (P<0.001). When compared with rest MPSPECT images, segmental perfusion improvement both in redistribution and in the 24 h-late-MPSPECT images were 16.3 and 18.3%, respectively. This ratio was found to be 27.2% for Glu+Tl-infusion images. The ratios of segments in which perfusion was worsening were calculated to be 9.4, 14.5, and 7.3%, respectively, for redistribution, 24 h-late-MPSPECT, and Glu+Tl-infusion images. When this evaluation was made for all three vessel areas, again the highest perfusion improvement and the lowest perfusion worsening were detected for Glu+Tl-infusion images. In addition, when this evaluation was made for the three vessel areas according to the coronary narrowing degree, again the highest perfusion improvement was detected for Glu+Tl-infusion images, in segments in the left anterior descending artery, and right coronary artery areas with >/=90% narrowing. In rest images, in segments with segmental scores of 3 and 4, when the total reversibility ratio was evaluated, this ratio was calculated to be 0.7% for redistribution images and 4.5% for 24 h-late-MPSPECT. The highest total reversibility ratio in these segments was detected with Glu+Tl-infusion images to be 10.3%. When we evaluated the patients with respect to the MI history time, the highest segmental perfusion improvement was detected in patients with 0-3 months of MI history. CONCLUSION: We conclude that in nondiabetic patients who are known to have CCAD or past MI history, Glu+Tl-infusion is an easily applicable method that gives better results for the evaluation of myocardial viability.

Validity of the CA125 level in the differential diagnosis of pulmonary tuberculosis.

The aim of the current study was to determine the possible crucial role of cancer antigen 125 (CA125) in the diagnosis of pulmonary tuberculosis (PTB). The CA125 levels of study and control groups were statistically compared. In a total of 146 patients that were included in the current study, 30 had active PTB, 37 inactive PTB, 28 community-acquired pneumonia (CAP), 25 pleural or pulmonary malignancies, and 13 patients exacerbation of chronic obstructive pulmonary disease. The mean CA125 levels in PTB, inactive PTB, CAP, and pleural-pulmonary malignancies were 118.46 +/- 248.41, 40.80 +/- 50.95, 47.76 +/- 60.76, and 57.77 +/- 65.59, respectively. For active-inactive discrimination of PTB, with a cut-off level of >35 U/ml, the sensitivity, specificity, positive predictive value, and negative predictive value of CA125 were 63, 59, 56, and 67%, respectively. Increased CA125 levels were detected in active PTB in the current results. The current results also show that high level CA125 should be reconsidered in the prediagnosis and/or discrimination of active and inactive PTB patients.

Evaluation of the cell death pathway and apoptosis-stunning effect relationship after low- and high-dose I-131 administrations in rat thyroid tissue.

OBJECTIVES: This study had two aims; (1) to describe the cell death pathway (apoptosis or necrosis) induced by a low and high dose of radioiodine (I-131) in rat thyroid tissue in in vivo conditions and (2) to determine the role of apoptosis in the development of "stunning effect" in the thyroid tissue with low and high doses of I-131 application. DESIGN: The experimental group consisted of 18 rats; low and high I- 131 doses with a 1-week interval were administered to this group. At first, low doses were injected intraperitoneally (i.p.) (net injected dose was 51.54 +/- 8.6 microCi). After 1 week of the low-dose injection, high doses were also injected (net injected dose was 934.9 +/- 211.8 microCi). Thyroidal I-131 uptakes for both low- and high-dose applications were calculated by using a gamma camera after 24 hours of injections. Immediately after the uptake calculation, thyroid tissues were resected. A control group of 10 rats was also included in the study; in this group, I-131 was not administered. Thyroid tissues of this group rats were also resected. DNA was extracted from thyroid tissues, and damage was examined with the "DNA ladder by agaroz gel electrophoresis." RESULTS: Thyroidal I-131 uptakes were calculated as 11.3% +/- 3.6% and 9.8% +/- 5.3% at the 24th hour after low- and high-dose I-131 applications, respectively. When the low- and high-dose uptake values were compared for each rat; a significant relationship was not found between thyroidal uptakes and injected low and high doses of I-131. When the chromosome images were examined, there was healthy DNA appearance in 1 rat; in 4 rats, only necrotic hyperfragmentations were observed; in 9 rats, both apoptotic specific fragmentations and necrotic hyperfragmentations were observed; and in 4 rats, apoptosis, necrosis, and healthy DNA appearances were seen together. In none of the rats, specific fragmentations concordant only with apoptosis was found. When the thyroidal uptake alterations were taken into consideration, significant difference was not found between first and second uptake calculations (p = 0.28). No significant relationship was also observed between thyroidal uptake alterations and apoptosis-necrosis-healthy DNA findings. Additionally, when we take into consideration the DNA results of only 13 of the rats that had reduced thyroidal uptake, a significant relationship could also not be observed between reduced uptake and apoptotic, necrotic, or healthy tissue findings. Interestingly, apoptotic and necrotic tissue or only necrotic, tissue findings were observed in the other 5 rats which had increased thyroidal uptake. CONCLUSIONS: Following I-131 administration, two types of cell death--both apoptosis and necrosis findings--have been observed in most of the rats. We think that the decreased uptake values are because of the probable stunning effect in thyroid tissue. We also investigated whether the stunning effect is related to apoptosis. According to our results, it can be concluded that the stunning effect is not related to tissue damage, cell decrease, or cell death. Alternatively, we think that this can be related to a radiation-induced reduction of iodine uptake/metabolism or a modified iodine transport mechanism. For further in vivo studies, this experimental model using normal rat thyroid tissue may be useful in investigating the cell death pathways induced by I-131 and its probable roles in the development of the stunning phenomenon.

Evaluation of the p53 tumor suppressor gene mutation in normal rat salivary gland tissue after radioiodine application: an experimental study.

In this experimental study, investigators explored p53 tumor suppressor gene mutation induced by low and high doses of iodine-131 sodium iodide (I-131) in salivary gland tissue in rats. Group 1 consisted of 10 rats; low and high I-131 doses were applied at a 1-wk interval. First,low doses of I-131 were injected. (The net injected dose was 47.5-/+9.2 microCi.) After 1 wk, high doses of I-131 were also injected. (The net injected dose was 1007.2-/+53 microCi.) Group 2 consisted of 5 rats, and only a low I-131 dose was applied. (The net injected dose was 52.7-/+5.5 microCi.) The Control Group consisted of 5 rats that did not receive I-131. Thyroidal I-131 uptakes were calculated for Groups 1 and 2 with the use of a gamma camera after 24 h of injections. Immediately after uptake was calculated, salivary glands were resected in all groups and DNA was extracted for genotyping. Genomic DNA of the p53 gene exon 5 was examined by polymerase chain reaction single-strand conformational polymorphism. In Group 1, thyroidal I-131 uptakes were calculated as 12.45%-/+4.14% and 9.66%-/+6.73% after low-dose and high-dose I-131 applications, respectively. In Group 2, thyroidal I-131 uptake was calculated as 13.12%-/+3.04%. In Group 1, p53 gene abnormality was seen in the salivary gland of only 1 of the rats. Double- and single-strand gene profiles showed that both alleles of this rat have a mutated single-strand conformational polymorphism profile of point mutation in the p53 gene exon 5. This rat received the highest low dose and the second highest total dose of I-131; its thyroidal uptakes were the second highest. In the other rats in Group 1, and in Group 2 and the Control Group, p53 gene abnormalities were not observed. In Groups 1 and 2, a significant relationship could not be discerned between thyroidal uptake of I-131 and p53 gene mutation in the salivary gland. No significant relationship was observed between thyroidal uptake alterations and p53 gene mutations in salivary glands in Group 1. A point mutation in the p53 gene exon 5 that was seen in only 1 of the rats in Group 1 seems related to the high-dose application of I-131, although coincidental occurrences could not be excluded. We believe that this topic is open to additional in vivo studies.

Comparison of effects of formoterol and BRL 37344 on isolated term-pregnant rat myometrial strips in vitro.

This study was designed to compare the effects of beta-adrenoceptor agonists formoterol and BRL 37344 on spontaneous contractions and the levels of cAMP and cGMP of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from term-pregnant Wistar albino rats (n=12), mounted in organ baths and tested for changes in isometric tension in response to formoterol and BRL 37344. We evaluated the effect of increasing concentrations of formoterol and BRL 37344 on oxytocin-induced myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (beta1, beta2, beta3-adrenoceptor antagonist, respectively, 10(-6) M). Effects of formoterol and BRL 37344 on cAMP and cGMP levels in isolated myometrial strips (n=6) were evaluated by radioimmunoassay kits. Formoterol (10(-12)-10(-8) M) and BRL 37344 (10(-11)-10(-5) M) concentration-dependently decreased the amplitude of oxytocin-induced contractions. E(max) value (100%) of formoterol was increased significantly more than E(max) value (70.6%) of BRL 37344 (P<0.05), with no change in pD(2) value (9.54+/-0.12 and 9.12+/-0.12, respectively). The inhibition of the amplitude of oxytocin-induced contractions by formoterol was antagonized with ICI 118.551 (10(-6) M), but they were not changed by metoprolol (10(-6) M) or SR 59230A (10(-6) M). The inhibition of the amplitude of oxytocin-induced contractions by BRL 37344 were antagonized with SR 59230A (10(-6) M), but they were not changed by metoprolol (10(-6) M) or ICI 118.551 (10(-6) M). Formoterol and BRL 37344 increased cAMP levels. BRL 37344 increased cGMP levels in BRL 37344 group more than control group, but this increase is less significant than cAMP levels (P>0.05). Formoterol and BRL 37344 decreased amplitude of myometrial contractions with similar potency, but efficacy of formoterol was better than BRL 37344.

Evaluation of tumor markers CA-125 and CEA in acute myocardial infarction.

Serum carbohydrate antigen (CA-125) and carcinoembryonic antigen (CEA) have always been of clinical importance in the diagnosis and follow-up of various tumors. This study was devised to investigate the relationship between these tumor markers and acute myocardial infarction (MI). Seventy consecutive cases (59 male patients with a diagnosis of acute ST segment elevation MI and 11 male patients with a diagnosis of non-ST segment elevation MI; mean age, 57+/-8.2 y) were admitted to the University Medical Center and were included in this study as "the patient group." All patients in the patient group underwent transthoracic echocardiographic examination on the third day of hospitalization. On the basis of echocardiographic findings, these 70 patients were grouped according to left ventricular ejection fraction (EF) values; EF <55% (group 1) (n=40) and EF >or=55% (group 2) (n=30). Other parameters, including systolic pulmonary artery pressure (sPAP) and mean pulmonary artery pressure (mPAP), were also measured on transthoracic echocardiography. Serial blood samples (for follow-up of myocardial enzymes (eg, creatine kinase MB [CKMB], troponin I [TnI], troponin T, and other routine parameters) were drawn from each patient. Serum concentrations of CEA and CA-125 measured at the 72nd hour of hospitalization and peak serum concentrations of CKMB and TnI in the patient group were collected for comparison between subgroups (groups 1 and 2) and with "the control group," which included 30 subjects (mean age, 54+/-7.6 y) with no history or evidence of overt cardiac disease and with normal echocardiographic findings. The presence of any condition characterized by potential elevations in CA-125, CEA, and myocardial enzymes (CKMB, TnI) was considered an exclusion criterion. Patients included in patient groups 1 and 2 differed significantly in terms of mean EF, mean sPAP, mean mPAP, and mean CA-125 values (P<.001 for CA-125; P<.05 for the other values). EF was found to be negatively correlated with sPAP (r=-0.692, P=.000) and mPAP (r=-0.393, P=.001). EF was also negatively correlated with CA-125 (r=-0.557, P=.000). A positive correlation was noted between CA-125 and sPAP (r=0.396, P=.001) and between CA-125 and mPAP (r=0.754, P=.000). A statistically significant difference was identified between the patient and control groups with regard to values for EF, PAP, CA-125, and myocardial enzymes (CKMB and TnI) (P<.05 for mPAP; P<.001 for the other values). The serum concentration of CA-125, but not of CEA, may be elevated in those with acute MI compared with normal subjects. Regardless of the presence of pulmonary hypertension, elevations in CA-125 during myocardial infarction were significantly correlated with the severity of left ventricular systolic dysfunction on transthoracic echocardiography.

Preoperative localization of parathyroid adenomas with technetium-99m methoxyisobutylisonitrile imaging: relationship with P-glycoprotein expression, oxyphilic cell content, and tumoral tissue volume.

UNLABELLED: In addition to tumor size, it has been suggested that P-glycoprotein (P-gp) expression and/or oxyphilic cell content in parathyroid adenomas has an important influence on the results of technetium 99m methoxyisobutylisonitrile (Tc-99m MIBI) parathyroid imaging. AIM: In this study, we compared the results of MIBI parathyroid imaging and immunohistochemical analysis (IHA) of P-gp expression, oxyphilic cell content, and tumoral tissue volume in parathyroid adenomas. We also evaluated the relationship between MIBI and ultrasound (US) results, operation findings, serum biochemical values. MATERIALS AND METHODS: Forty (40) patients (36 female and 4 male; mean age, 53.2 +/- 8.16 years) with hyperparathyroidism who had undergone surgery were included in this study. Preoperatively, "double phase" parathyroid scintigraphy with Tc-99m MIBI (including imaging of the neck and mediastinum) was performed in all patients. Thirty-two (32) of the patients had also neck US. Serum parathormon (PTH), calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured preoperatively. In resected parathyroid tissues, P-gp expression and percentage of oxyphilic cell content were analyzed with IHA in 34 patients. RESULTS: Three (3) of the resected parathyroid tissues were hyperplastic parathyroid tissue, whereas 31 of the tissues were parathyroid adenoma (mean volume, 1.99 +/- 1.93 mL). In Tc-99m MIBI parathyroid scintigraphy, 70% of the parathyroid adenoma/hyperplastic parathyroid tissue was detected in correct localization; at US, this rate was 46.8%. According to the resected parathyroid tissue localization at surgery, sensitivity, accuracy, positive predictive value, and prevalence in scintigraphy were 82.3%, 70%, 82.3%, and 85%, respectively. Those were 60%, 46.8%, 68.2%, and 78.1% for US, respectively. No significant correlation and no concordance was found between MIBI and US results (kappa, -0.103, r = -0.11; p: 0.53). Interestingly, significant correlation was found between tumoral volume and ALP level (r = 0.42; p = 0.010) and between PTH and ALP levels (r = 0.72; p < 0.001). Significant correlation was also found between patient age and tumoral volume (r =-0.37; p = 0.02) and between PTH and serum Ca levels (r = 0.32; p = 0.04). In 23 of 34 patients in whom histopathological examination was done MIBI was positive and in 13 of these patients (56.5%), P-gp expression was positive. When the histopathological results and MIBI results were compared, there was no significant correlation and concordance between P-gp expression (kappa = 0.09, r = 0.10; p = 0.54), oxyphilic cell content (r = -0.17; p = 0.33), and tumoral tissue volume (r = -0.14; p = 0.38). In 12 of 19 patients (63%) who had parathyroid tissue < 1 mL and in 15 of 24 patients (62.5%) who had oxyphilic cell content < 10%, lesions were also detected correctly with MIBI scintigraphy. CONCLUSIONS: Present study results suggest that MIBI scintigraphy was clearly superior to US as a diagnostic tool. However, P-gp expression, oxyphilic cell content, and tumoral volume may have not a main effect on MIBI parathyroid scintigraphy results in parathyroid adenoma.

Surgical management strategies in patients with primary hyperparathyroidism: which technique in which patients?

OBJECTIVE: This study was planned to investigate the efficacy of either 99mTc-sestamibi scan or ultrasonography in predicting the operative treatment in patients with primary hyperparathyroidism (PHPT). SUBJECTS AND METHOD: Thirty patients (25 female, 5 male; mean age: 53 years) being operated for symptomatic primary PHPT were included in this study. Ultrasonography was used in 29 patients while 99mTc-sestamibi scintigraphy was done in 28 patients to localize the hyperfunctioning gland(s). Standard bilateral neck exploration was done in 6 patients. Although unilateral intervention had been planned for 24 patients, bilateral intervention was performed in 9 of them. RESULTS: Sensitivity of 99mTc-sestamibi was 81%, while that of ultrasonography was 42%. 99mTc-sestamibi localization method led to misleading results in 10/28 (35.7%) patients. False-positive localization and accompanying thyroid pathologies played an important role in determining transition from unilateral to bilateral intervention. CONCLUSION: Our findings indicate that bilateral intervention remains a successful management option without prior localization in patients with PHPT especially in an endemic goiter region.

Usefulness of measuring the gastric emptying time in a case of brittle diabetes.

Gastric emptying time measurement by radionuclide study, although quite informative, is rarely remembered in clinical practice. We presented a patient with brittle diabetes who had multiple emergency admissions due to hypoglycemia under routinely prescribed insulin therapy. She had severe gastroparesis, which was determined by scintigraphic gastric emptying study (gastric half-emptying time = 260 min for a mixed meal). She had not presented to the emergency service for two years because of only a slight change the timing of her insulin administration time (after meal instead of before meal) in the light of gastric-emptying study.

Iodine-131 treatment and chromosomal damage: in vivo dose-effect relationship.

Although it is well known that radiation induces chromosomal aberrations, there is a lack of information on the in vivo dose-effect relationship in patients receiving iodine-131 treatment, and the results of previous studies are controversial. In this study, the sister chromatid exchange (SCE) method was employed to investigate acute and late chromosomal damage (CD) in the peripheral lymphocytes of 15 patients who received various doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX) or for ablation treatment in differentiated thyroid cancer (DTC). The SCE frequencies in cultured peripheral lymphocytes were determined before treatment (to assess basal SCE frequencies), on the 3rd day (to assess acute SCE frequencies) and 6 months later (to assess late SCE frequencies). The basal, acute and late SCE frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and 5.75+/-2.06, respectively, in the whole group, and these values differed significantly from each other ( P<0.001). In order to perform a quantitative evaluation of the present data and a comparative analysis with the results of previous studies reported in the literature, we defined acute and late effects using a "damage ratio" (DR) and a "recovery ratio" (RR), based on the basal, acute and late data for individual patients. No statistically significant difference was found in the DR between DTC and TTX patients (76.4%+/-11.5% vs 67.6%+/-9.0%), while the mean RR was higher in TTX patients than in the DTC group (75.2%+/-24.4% vs 36.8%+/-13.7%). The DR on the 3rd day was not related to the administered (131)I dose in the whole group, but a negative correlation was found between the (131)I dose and the RR at the 6th month (r=-0.60, P=0.04). The best fit for this relationship was obtained by a linear-quadratic model, as y=104.89x-28.4x(2)+38.1 ( R(2)=0.51, P=0.04). On the other hand, comparative analysis with the results of previous studies with comparable sampling times revealed that the best fit for the relationships between the administered dose of (131)I and DR and RR were obtained with a linear-quadratic model (Y=alpha D+beta D(2)) rather than a linear one. However, there was an interesting difference in comparison with in vitro studies, in that we found the coefficient beta to have a negative value, suggesting the disappearance of damaged lymphocytes from the peripheral circulation in a dose-dependent manner following (131)I treatment. Further studies are therefore needed to clarify the effect of the negative beta value on the biological dosimetry approach in continuous internal low LET radiation, as in the case of (131)I treatment.