Estimates of genetic parameters and genetic trend for growth traits and Kleiber ratio of Holstein-Friesian calves.

Growth traits of calves, which are quantitative characteristics determining cattle business profitability, vary according to genetic and environmental factors. In other words, growth traits depend on the genetics of the individual and vary with farm management. The aim of this study was to investigate the effective environmental factors, genetic parameters, and genetic trends for some growth traits and the Kleiber ratio (KR) in Holstein-Friesian calves. For this purpose, the records of 724 calves, progeny of 566 dams and 29 sires, reared between 2017 and 2019 on a private dairy farm in Türkiye, were used. MTDFREML software was utilized to estimate genetic parameters and genetic trends of growth traits and KR. In this study, regarding weight, the mean of birth weight (BW), 60-day weight (W60), and 90-day weight (W90) were 39.76 ± 6.15 kg, 69.23 ± 10.93 kg, and 95.76 ± 16.48 kg, respectively. Concerning weight gain, 1-60 daily weight gain (DWG1-60), 60-90 daily weight gain (DWG60-90), and 1-90 daily weight gain (DWG1-90) were 0.49 ± 0.16 kg, 0.91 ± 0.34 kg, and 0.63 ± 0.17 kg, respectively. With respect to KR, 1-60 daily KR (KR1-60), 60-90 daily KR (KR60-90), and 1-90 daily KR (KR1-90) were 2.03 ± 0.48, 2.93 ± 0.89, and 2.02 ± 0.34, respectively. As a result of the GLM analysis, only the effect of the birth season on all traits was significant (p < 0.05 or p < 0.01). In addition, it was detected that sex had a significant effect on BW and W60 (p < 0.05 or p < 0.01). For all traits, only the effect of parity on KR1-60 was not significant. In REML analysis, direct heritability differed between 0.26 ± 0.16 and 0.81 ± 0.27 obtained at DWG1-90 and DWG1-60, respectively. Also, the highest repeatability (0.100) was obtained in DWG1-60. It was detected that mass selection could be used in all traits for breeding program. In BLUP analysis, the current population had an increasing trend for BW and W90 and a decreasing trend for W60. However, there was no significant change in other weight gain traits and KR over the years. Calves with high breeding values for BW, W60, W90, DWG1-60, DWG60-90, and DWG1-90 should be chosen for selection programs. But for KR1-60, KR60-90, and KR1-90, calves with low breeding values should be selected for efficiency. Also, KR evaluated would contribute to the literature and other research should be studied regarding KR.

Lack of evidence for association between the leptin/Sau3AI gene and milk yield traits in Holstein Friesian dairy cattle.

This study aimed to investigate the effect of leptin gene polymorphism and some environmental factors on milk production traits. Blood samples from 212 Holstein Friesian dairy cattle reared on a private farm were used. The intron 2 region of the leptin gene was digested with Sau3AI restriction enzyme using the PCR-RFLP method. A and B alleles and AA, AB, and BB genotype frequencies for the Sau3AI polymorphism were determined as 0.8821 and 0.1179, and 0.764, 0.236 and 0.000, respectively. Chi-square analysis revealed that the leptin gene polymorphism followed the Hardy-Weinberg equilibrium, including the absence of animals with the BB genotype. The effect of leptin gene polymorphism on all milk production traits was insignificant. For milk production traits, direct heritability (ha2) varied between 0.03 ± 0.283 (for the dry period) and 0.50 ± 0.183 (for milk conductivity). Regarding the milking time (MT), the estimated breeding values (EBVs) of cattle with the AA genotype were higher than the AB genotype (P < 0.05). As a result of this study, in the selection program, allele or genotype could not be suggested as a marker for milk yield characteristics except for the possible exception of milking time and its relationship to mastitis incidence.

Can pretreatment hepatic artery perfusion scintigraphy in patients with liver malignancies predict the treatment response of the selective internal radiation therapy with 90Y resin microspheres?

PURPOSE We aimed to evaluate whether the perfusion pattern from pretreatment hepatic artery perfusion scintigraphy (HAPS) in patients with liver malignancies can predict response to selective internal radiation therapy (SIRT). METHODS This retrospective study analyzed 152 consecutive patients treated with yttrium-90 (90Y) resin microspheres between April 2015 and July 2017. HAPS using single-photon emission computed tomography/computed tomography (SPECT/CT) with 99mtechnetium macroaggregated albumin (99mTc-MAA) was performed before SIRT. Investigators visually classified perfusion patterns of tumors as heterogeneous or diffuse in HAPS. Between diffuse and heterogeneous pattern group, positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) were performed in third and sixth month after SIRT, and tumor response assessed and compared by using RECIST 1.1 or mRECIST. Overall survival (OS) and progression-free survival (PFS) were also compared with Kaplan-Meier/log-rank analyses. RESULTS Of 216 SIRT procedures, 172 were classified as heterogeneous and 44 as diffuse. Diffuse 99mTc- MAA uptake was associated with longer median OS than heterogeneous (22.2 vs. 14.4 months, respectively; P = .047). Subsegmental infusion was associated with longer OS than either lobar or segmental infusion (P = .090). Mean estimated OS was longer in patients with hepatocellular carcinoma (HCC) (34.2 months) than with colorectal carcinoma (CRC) (16.4 months) (P = .044). Patients with both diffuse and heterogeneous patterns were able to show complete response after SIRT. No statistically significant differences were observed between perfusion patterns and PFS or response rates to SIRT. CONCLUSION Although tumor perfusion patterns from preplanning HAPS analyses are useful for estimating tumor uptake of 90Y, they may not reliably predict hepatic treatment response, as patients with different perfusion patterns can show clinical response to SIRT.

The role and effect of FDG-PET/CT on patient management and restaging of bladder carcinoma.

OBJECTIVE: To compare the diagnostic role of Florine-18 2-fluoro-2-deoxy-D-glucose-Positron emission tomography/computed tomography (FDG-PET/CT) in the restaging of bladder cancer with other radiological methods and to determine its effect on the treatment management of patients with bladder cancer. MATERIAL AND METHODS: A total of 83 patients who showed suspicious lesions with radiologic methods and FDG-PET/CT images were enrolled in the study. Positive lesion sites were detected and compared in all imaging modalities. Positive lesions were confirmed by biopsy or serial radiological imaging. Furthermore, the rate of change of the management and treatment modalities of patients after FDG-PET/CT were noted. RESULTS: The most frequent metastasis was observed in lymphatic localizations in all imaging methods. Lymph node metastases was detected with FDG-PET/CT in 37/83 patients, with computed tomography in 28/80 patients, and with magnetic resonance imaging in 6/19 patients. Lymph node metastasis was detected most commonly in the pelvic region with all modalities. Following lymphatic localization in FDG-PET/CT and CT, metastases were found most frequently in the lung and bone regions. FDG-PET/CT also revealed 8 of the 12 local lesions that were detected by radiological methods and showed additional lesions in four patients that could not be demonstrated by radiological methods. FDG-PET/CT changed the treatment approaches in 34.9% (29/83) of patients. In 16 patients, it caused upstaging and commencement of advanced treatment methods. In 13 patients, malignancy was excluded in suspicious lesions and unnecessary advanced examination and treatment were avoided. FDG-PET/CT also caused three radical cystectomies, one partial cystectomy, and one urethrectomy in patients who had not undergone any operational procedure previously. CONCLUSION: Despite physiological urinary tract uptake, FDG-PET/CT is superior to other imaging modalities not only in distant localizations but also in evaluating pelvic lesions and lymph nodes. In addition, the use of FDG-PET/CT during the restaging process contributes to the management of maximum number of patients.

Correlation between 18F-FDG Positron-Emission Tomography 18F-FDG Uptake Levels at Diagnosis and Histopathologic and Immunohistochemical Factors in Patients with Breast Cancer.

OBJECTIVE: In this study, we aimed to determine the correlation between pretreatment-staging 18F-FDG total body positron-emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUVmax) levels and histopathologic and immunohistochemical predictive and prognostic factors in patients with breast cancer. MATERIALS AND METHODS: One hundred thirty-nine women with breast cancer who were treated between 2009 and 2015 at our hospital and who had pretreatment-staging PET/CT were included in the study. SUVmax levels and histopathologic and immunohistochemical results were compared. RESULTS: The median age was 48 years (range, 29-79 years). The mean tumor diameter was 33.4 mm (range, 7-120 mm). The histology was invasive ductal carcinoma in 80.6% of the patients. In the univariate analysis, SUVmax levels were significantly higher in patients with invasive ductal carcinoma; in patients with a maximum tumor diameter more than 2 cm; patients who were estrogen, progesterone, and combined hormone receptor-negative, triple-negative patients, and in tumors with higher grades (p<0.05). In HER2-positive patients, SUVmax levels were higher even if it was not statistically significant. There was no correlation between lymph node metastases and pathologic stage. In multivariate analysis, tumor diameter was an independent factor. CONCLUSION: SUVmax levels are correlated with known histopathologic and immunohistochemical prognostic factors. PET/CT could be useful in preoperative evaluation of patients with breast cancer to predict biologic characteristics of tumors and prognosis.

Staging with PET-CT in patients with locally advanced non small cell lung cancer is superior to conventional staging methods in terms of survival.

BACKGROUND: Of patients with non small cell lung cancer (NSCLC), around one third are locally advanced at the time of diagnosis. Because only a proprotion of stage III patients can be cured by surgery, in order to improve the outcomes, sequential or concurrent chemoradiation, or concurrent chemoradiation with induction or consolidation is offered to the patients with locally advanced NSCLC. Today, PET combined with computerized tomography (PET-CT) is accepted as the most sensitive technique for detecting mediastinal lymph node and extracranial metastases from NSCLC. We aimed to compare PET-CT and conventional staging procedures for decisions regarding curative treatment of locally advanced NSCLC. MATERIALS AND METHODS: A total of 168 consecutive patients were included from Acibadem Kayseri Hospital, Acibadem Adana Hospital and Kayseri Research and Training Hospital in this study. RESULTS: While the median PFS was 13.0 ± 1.9 months in the PET-CT group, it was only 6.0 ± 0.9 in the others (p<0.001). The median OS values were 20.5 ± 15.6 and 11.5 ± 1.5 months, respectively (p<0.001). DISCUSSION: As a result, we found that staging with PET CT has better results in terms of survival staging. This superiority leads to survival advantage in patients with locally advanced NSCLC.

False Positive 18F-FDG Uptake in Mediastinal Lymph Nodes Detected with Positron Emission Tomography in Breast Cancer: A Case Report.

Breast cancer is the most frequently diagnosed cancer among females. It is accepted that lymph node involvement with metastatic tumor and the presence of distant metastasis are the most important prognostic factors. Accurate staging is important in determining prognosis and appropriate treatment. Positron emission tomography with computed tomography detects malignancies using 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG PET CT) with high accuracy and they contribute to decisions regarding diagnosis, staging, recurrence, and treatment response. Here, we report a case of false positive metastatic mediastinal lymph nodes that were diagnosed by 18F-FDG PET CT in a 40-year-old breast cancer patient who had undergone preoperative evaluation. Right paratracheal, prevascular, aorticopulmonary, precarinal, subcarinal, hilar, and subhilar multiple conglomerated mediastinal lymph nodes were revealed in addition to left breast mass and axillary lymph nodes. Mediastinoscopy was performed with biopsy and pathology was reported as granulomatous lymphadenitis. In conclusion, any abnormal FDG accumulation in unusual lymph nodes must be evaluated carefully and confirmed histopathologically.

Sunlight may increase the FDG uptake value in primary tumors of patients with non-small cell lung cancer.

Currently, positron emission tomography with computerized tomography (PET-CT) is the most sensitive technique for detecting extracranial metastases in non-small cell lung cancer (NSCLC). It has been reported that there is a correlation between the maximal standardized uptake value (SUV(max)) of primary tumors and prognosis in patients with NSCLC. The effect of sunlight exposure on PET-CT SUV(max) value is not known. Therefore, we aimed to evaluate the effect of sunlight exposure on PET-CT SUV(max) value in patients with NSCLC. A total of 290 patients with NSCLC from two different regions of Turkey (Kayseri, n=168 and Adana, n=122) that have different climate and sunlight exposure intensity, were included in the study. Age, gender, histology of cancer, cancer stage, smoking status, comorbidity and SUV(max) of the primary tumor area at the time of staging were evaluated as prognostic factors. In the multivariate analysis, we detected that the region was the only independent factor affecting SUV(max) (P=0.019). We identified that warmer climate and more sunlight exposure significantly increases the SUV(max) value of the primary tumor area in patients with NSCLC. Further studies are warranted to clarify the issue.

Does sunlight exposure improve survival in patients with non-small cell lung cancer?

BACKGROUND: Some epidemiological studies reported that sunlight exposure and highvitamin D levels may decrease the morbidity and mortality related to cancer. We aimed to evaluate whether sunlight exposure has an impact on survival in patients with non small cell lung cancer. MATERIALS AND METHODS: A total of 546 patients with NSCLC from two different regions (Kayseri and Adana) differing according to sunlight exposure were analysed retrospectively. RESULTS: The median overall survival (OS) rates were 11. 6 (CI: 9.50-13.6) and 15.6 months (CI: 12.4-18.8) for Kayseri and Adana, respectively, in all patients (p=0.880). CONCLUSIONS: There were no differences between groups in terms of OS. While there is strong evidence regarding inverse relationship between cancer incidence and sunlight exposure, it is still controversial whether sunlight exposure is a good prognostic factor for survival in patients with lung cancer.

Effects of selective Cox-2 inhibitor, rofecoxib, alone or combination with furosemide on renal functions and renal Cox-2 expression in rats.

BACKGROUND: Nonsteroidal anti-inflammatory drugs act by inhibiting the rate-limiting enzymes cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2), which are important in prostanoid formation. The aim of this experimental study was to examine the effects of selective Cox-2 inhibitor, rofecoxib, with or without furosemide, on urine and serum electrolytes, creatinine clearance, plasma renin activity (PRA), and Cox-2 expression in the renal cortex. METHODS: Forty male Wistar albino rats were randomized into four groups, group 1, group 2, group 3, and group 4, and were treated with placebo, furosemide (20 mg/kg), rofecoxib (10 mg/kg) plus furosemide (12 mg/kg), and rofecoxib (10 mg/kg), respectively, and followed for 7 days. Body weights were measured daily. Urine osmolality and volume, and serum and urinary creatinine, sodium (Na(+)), and potassium (K(+)) were measured. Renal cortical Cox-2 protein expression was examined by immunohistochemical method. RESULTS: Compared with groups 1 and 3, body weights were significantly reduced in groups 2 and 4 (16.2 and 19.8 g, respectively; P < 0.05 for all). Urine volume in group 2 increased significantly compared with groups 1, 3, and 4 (P < 0.001, P < 0.008, and P < 0.004, respectively). Urine osmolality in group 2 decreased significantly compared with groups 1 and 3 (P < 0.05 for all). Blood urea nitrogen, serum creatinine and sodium, creatinine clearance, and 24-h urine Na(+) and K(+) levels were similar in all groups. Serum K(+) level was lowest in group 2, and there was a statistically significant difference between groups 2 and 4 (P < 0.05). Plasma renin activity was similar in all groups (P > 0.05). Renal cortical Cox-2 protein expression was lowest in group 1 and was significantly different from the other groups (P < 0.01 for all). The relationship between Cox-2 expression and plasma renin activity was not significant in any group (P > 0.05, r(2):0.05). CONCLUSIONS: Rofecoxib neutralized the diuretic effect of furosemide in rats treated with a combination of furosemide and rofecoxib. Renal cortical Cox-2 protein expressions due to furosemide and rofecoxib with or without furosemide were similar and significantly increased compared with controls. Renal failure due to rofecoxib did not developed in any rat, but selective Cox-2 inhibitor, rofecoxib, might have similar renal effects as nonselective nonsteroidal drugs for blunting the diuretic effect of furosemide.

The value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in carcinoma of an unknown primary: diagnosis and follow-up.

BACKGROUND: The management of the patients with carcinoma of an unknown primary represents a difficult challenge in oncology. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has provided new insights in the diagnosis, staging, and follow-up of oncological patients. AIM: This study aimed to investigate the value of FDG PET/CT in clarifying the primary site in our patients with histologically proven tumor metastasis (HPM) or with a high clinical suspicion of malignancy, and the clinical impact of this technique on the management of these patients. METHODS: In total 94 patients from two centers underwent FDG PET/CT imaging; 78 patients with HPM and 16 patients with a clinical suspicion of malignancy. The histology and/or follow-up data were used as the gold standard. Hypermetabolic findings at the site of the pathological CT changes or at physiological FDG uptake sites were the criteria for malignancy. PET/CT findings were analyzed for the identification of the primary tumor site, for the relationship with survival, and also for the effect in chemotherapy monitoring. RESULTS: Primary malignancy was discovered in 53 of 90 patients (59%) histologically and 37 (41%) patients' primary tumor sites were not found during the study period. Amongst 90 patients, five (6%) were normal on FDG PET/CT. Of 85 patients (94%) with pathological findings on FDG PET/CT, 27 patients (32%) had solitary and 58 (68%) patients had multiple organs affected. Regarding the whole study population, a sensitivity of 74% and a specificity of 78% were calculated for FDG PET/CT imaging. Regarding the patients with HPM, the sensitivity and specificity values were 84 and 81%, respectively. The mean survival time of the patients with disseminated disease was significantly shorter than those of the patients with single or no lesion (13.44+/-1.61, 20.98+/-2.0 and 26.67+/-2.73 months, respectively, P=0.014). In seven of eight patients, follow-up FDG PET/CT scans effectively monitored the patients' therapies. CONCLUSION: Whole-body FDG PET/CT has to be considered a useful method, especially in an early phase of the diagnostic workup of patients with carcinoma of an unknown primary syndrome, to optimize the management.

The effects of the nonsteroidal anti-inflammatory drug diclofenac sodium on the rat kidney, and alteration by furosemide.

INTRODUCTION: Renal physiology is a partially cyclooxygenase (COX)-dependent system. Kidneys express both COX-1 and COX-2 enzymes. In this study, we tried to investigate the effects of diclofenac sodium (D), with or without furosemide (F), on plasma renin activity (PRA), serum and urine electrolytes, creatinine clearance, and COX-1 and COX-2 expression in the renal cortex. METHOD: Forty-two Wistar-albino rats were divided into four groups (G). G1, G2, G3, and G4 were treated with placebo, F (20 mg/kg), F (20 mg/kg) plus D (2.5 mg/kg), and D (2.5 mg/kg), respectively, and followed for seven days. Urinary osmolality and volume, and levels of serum and urinary creatinine, sodium, and potassium were measured. Renal COX-1 and COX-2 expression were examined by the immunohistochemical method. RESULTS: Compared with G1, body weights were significantly reduced in G3 and G4 (P < 0.05 for all). Serum sodium in G2 decreased significantly compared with G1, G3, and G4. Serum potassium in G2 decreased significantly compared with G1 and G3. Urine volume in G2 increased significantly compared with G1, G3, and G4. Urine osmolality in G2 and G4 decreased significantly compared with G1 and G3. Urine Na in G2 increased significantly compared with G4. Although urine K was lowest in G4, there were no statistically significant differences between the groups. Creatinine clearance decreased in G4 compared with the other groups. PRA was similar in all groups. Renal cortical COX-2 expression was lowest in G1. COX-1 expression in cortical collecting tubules was significantly reduced in G3 and G4 compared with G1 and G2 (P < 0.05 for all). Although creatinine clearance in G4 was significantly lower than in G3, COX-1 and COX-2 expression were no different in G3 and G4. DISCUSSION: Acute renal failure was caused by D. F prevented development of renal failure in rats treated with a combination of D and F. The diuretic effect of F was neutralized by D. Whereas COX-1 expression was reduced by D and by the combination of D and F in G3 and G4, renal COX-2 immunoreactivity was increased by F and D and the combination of both. Although creatinine clearance was lower in rats that were given D alone compared with the combination of F and D, COX-1 and COX-2 expression were similar in these groups.

Global aphasia due to left thalamic hemorrhage.

Global aphasia is an acquired language disorder characterized by severe impairments in all modalities of language. The specific sites of injury commonly include Wernike's and Broca's areas and result from large strokes--particularly those involving the internal carotid or middle cerebral arteries. Rarely, deep subcortical lesions may cause global aphasia. We present three cases with global aphasia due to a more rare cause: left thalamic hemorrhage. Their common feature was the large size of the hemorrhage and its extension to the third ventricule. HMPAO-SPECT in one of the cases revealed ipsilateral subcortical, frontotemporal cortical and right frontal cortical hypoperfusion. Left thalamic hemorrhage should be considered in the differential diagnosis of global aphasia.

Tc-99m MIBI uptake in traumatic vertebral fractures and metastatic vertebral lesions: comparison with Tc-99m MDP.

This study compared technetium-99m-hexakis-2-methoxyisobutyl-isonitrile (Tc-99m MIBI) with technetium-99m methylene iphosphonate (Tc-99m MDP) to determine whether Tc-99m MIBI could distinguish vertebral metastases from traumatic vertebral fractures. Twenty patients with traumatic vertebral fracture (and no malignant disease) and 14 patients with metastatic vertebral lesions were evaluated. Three to 4 hours after intravenous injection of Tc-99m MDP, images of the vertebrae in all patients were obtained. Corresponding Tc-99m MIBI images were acquired within 4 days after the Tc-99m MDP bone images were obtained. Computed tomography and magnetic resonance imaging demonstrated 24 vertebral traumatic fractures and 44 vertebral metastases. On conventional bone scans, Tc-99m MDP activity was increased in 92% of vertebral fractures and in 100% of vertebral metastases. However, on MIBI scans, no abnormal findings were observed in the vertebrae with fracture, although increased activity was seen in 73% of vertebral metastases. In this study, traumatic vertebral fractures tended to display no pathologic increases in Tc-99m MIBI uptake, whereas bone metastases usually appeared with high uptake. In light of the excellent specificity of Tc-99m MIBI scans compared with Tc-99m MDP bone scans, imaging studies that use Tc-99m MIBI scans may play an important complementary role in differentiating vertebral metastases from traumatic vertebral fractures.

Thyroid hemiagenesis: a report of three cases and review of the literature.

Thyroid hemiagenesis resulting from the failure of embryologic development of one thyroidal lobe is a very rare anomaly. It is usually incidentally discovered during the investigation of accompanying thyroid disorders. Here we report three cases with right lobe agenesis in two patients and left lobe agenesis in one patient. Two of them were hyperthyroid, while the other euthyroid patient had a thyroid mass.

Washout rates of Tc-99m tetrofosmin in asymmetric septal hypertrophy.

The aim of this study was to evaluate the washout rate of Tc-99m tetrofosmin in asymmetric septal hypertrophy (ASH). As Tc-99m tetrofosmin accumulation and retention depend on sarcolemmal and/or mitochondrial function, the presence or absence of abnormalities in the washout rate of Tc-99m tetrofosmin could provide information about sarcolemmal and/or mitochondrial damage noninvasively. The study group consisted of 18 patients with ASH and 10 healthy subjects. After intravenous injection of 1110 MBq (30 mCi) Tc-99m tetrofosmin, tomographic images were obtained 1 hour later (early image) and again 4 hours later (delayed image). Using tomographic images, the distribution and washout of tetrofosmin in the left ventricle was examined quantitatively. Short-axis SPECT images were divided into 5 segments (anterior, septal, lateral, inferior wall and apex) in early and delayed images, and the mean radioactivity counts were measured in each segment by drawing regions of interest. Washout rates of apex, anterior, septal, lateral and inferior walls were 0.34 +/- 0.06, 0.37 +/- 0.07, 0.36 +/- 0.07, 0.33 -/+ 0.08, 0.33 +/- 0.07 in ASH and 0.20 +/- 0.05, 0.23 +/- 0.05, 0.22 +/- 0.03, 0.21 +/- 0.03, 0.22 +/- 0.03 in the normal group, respectively. In ASH, the washout rates of all myocardial segments were significantly increased as compared to those of the normal controls (p < 0.05). The findings of the present study suggest that there could be dysfunction of sarcolemma and/or mitochondria in the entire left ventricle which would be important in the pathophysiology of this disease. Also our study revealed that Tc-99m tetrofosmin washout was higher in NYHA II-III patients compared to NYHA I patients and the degree of Tc-99m tetrofosmin washout corresponded well with the thickness of the interventricular septum and posterior walls.

99mTc tetrofosmin scintigraphy in acute leukaemia: the relationship between marrow uptake of tetrofosmin and P-glycoprotein and chemotherapy response.

BACKGROUND: The non-invasive detection of P-glycoprotein (Pgp) and multidrug resistance related proteins in vivo, will represent the greatest challenge in overcoming multidrug resistance. Although 99mTc tetrofosmin has been used previously as a myocardial perfusion agent, it is now also being used in the imaging of various tumours. In the current study, Tc tetrofosmin was used in the investigation of acute leukaemia. AIM: To show the uptake pattern of 99mTc tetrofosmin in the bone marrow of patients with acute leukaemia, and to ascertain the relationship between 99mTc tetrofosmin uptake and the level of Pgp expression and their relation to the response to chemotherapy. In addition, CD95, which is an indicator of apoptosis (programmed cell death), has also been assessed. MATERIALS AND METHODS: Pgp and CD95 were detected by using flow cytometry. Of the 27 acute leukaemia patients assessed, nine had previously received chemotherapy, and 18 had had an initial diagnosis. All patients had undergone 99mTc tetrofosmin scintigraphy, and their Pgp and CD95 levels had been determined. The same parameters were studied again for 14 patients. The responses to chemotherapy were assessed by patients' clinicians. A control group of 37 patients without bone marrow pathology was also studied in order to provide comparisons for the scintigraphy results. The control images were assessed only qualitatively. RESULTS: In leukaemia patients the uptake of 99mTc tetrofosmin into bone marrow was found to be considerably higher than in control patients (P=0.000). An analysis of the relationship between Pgp, CD95, and the qualitative and quantitative tetrofosmin uptake ratios (URs) showed that there was an inverse correlation only between Pgp and the quantitative uptake ratio (P=0.016, r=-0.461). When the patients were grouped as 'good' and 'poor', as related to the chemotherapy response, there were no meaningful differences between these two groups regarding Pgp, CD95 and tetrofosmin URs (P>0.05). By evaluating the scintigraphic findings of the 'repeated' 14 patients, we showed that if the 99mTc tetrofosmin UR in the second imaging test was reduced by >0.08, the response to chemotherapy tended to be good. This method, based on follow-up scanning with tetrofosmin, showed a sensitivity of 83% and a specificity of 62% in the prediction of a 'good' response, if a decrease of 0.08 was taken into consideration. CONCLUSION: In this study, patients with acute leukaemia showed significant uptake of tetrofosmin into the bone marrow. The addition of basal and repeated 99mTc tetrofosmin scintigraphy to the management protocol for leukaemia could lead to the preferential determination of responses to chemotherapy, by evaluating whole bone marrow non-invasively. This method seems promising, but it needs further support from various similar investigations comprising more patients in order to confirm our results.

Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder.

While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data on children exist. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls. Eighteen drug-free obsessive compulsive children, aged 11 to 15, without comorbid states except for anxiety disorders--participated in this study. The control group consisted of 12 children, aged 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting pre- and post-treatment CBF values for the control group and study group. The right and left caudates, right and left dorsolateral prefrontals, and cingulate had significantly higher rCBF in children with obsessive compulsive disorder than in the control group. These areas, in addition to the right anteromedial temporal, showed significant rCBF reduction after treatment with paroxetine. The mean percentage of change in obsession scores during the treatment correlated significantly with the baseline and post- treatment rCBF level of the right caudate, post-treatment left caudate, and baseline left caudate. Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD.

Comparison of direct radionuclide cystography and voiding direct cystography in the detection of vesicoureteral reflux.

PURPOSE: The aim of this study is to compare the results of direct radionuclide cystography (DRNC) and voiding cystourethrography (VCUG) in a group of children with a high suspicion of vesicoureteral reflux (VUR). METHODS: For this purpose, 25 children were studied with both VCUG and DRNC. Among 50 ureter units able to be compared 39 ureter units did not show any VUR on either study. Eleven ureter units (10 children) had VUR either on one study or on both (VCUG and DRNC). In the children who had VUR on either study, a dimercaptosuccinic acid scintigraphy (DMSA) was performed to determine their cortical function. RESULTS: We identified the following four patterns: 1) Five ureter units (five children) read positive on DRNC who were negative on VCUG and four of these children had positive findings on DMSA; 2) Four ureter units (four children) read positive on VCUG who were negative on DRNC, and two of them had positive findings on DMSA; 3) Two ureters (one child) read positive in both studies and also had abnormal DMSA findings; 4) Thirty-nine ureter units read as negative on both studies. CONCLUSION: Although the results of these two methods did not show a significant difference, DRNC offers a high sensitivity in the younger age group whereas VCUG seems to be more sensitive in the older age group. DRNC also offers continuous recording during the study, ease of assessment and lower radiation dose to the gonads, which makes it a preferable method for the initial diagnosis and follow-up of VUR.

The value of Tc-99m-tetrofosmin scintigraphy in the assessment of P-glycoprotein in patients with malignant bone and soft-tissue tumors.

UNLABELLED: P-glycoprotein (Pgp) overexpression has been shown to be correlated with resistance to chemotherapy in patients with malignant bone and soft-tissue tumors. The aim of our study was to investigate the role of 99mTc-tetrofosmin as a functional imaging agent reflecting Pgp expression in these tumors. METHODS: Twenty eight patients with various malignant bone and soft-tissue tumors were studied. Radionuclide angiography with 99mTc-tetrofosmin was done first and planar images were acquired at 15 min and 90 min postinjection. Vascular phase was evaluated visually on dynamic images, metabolic state was evaluated both visually and quantitatively on planar images. Quantitative analysis was performed by the calculation of tetrofosmin uptake in the lesion against background and percent washout rate (WR%) of the tracer. Immunohistochemical analysis of Pgp was performed on biopsy specimens and the degree of expression was graded from 0 to 3. RESULTS: There was a positive correlation between the Pgp score and the washout rate of tetrofosmin (r = 0.73, p = 0.000). The mean washout rate of tetrofosmin from the lesions with Pgp expression (31.81 +/- 6.72) was found to be significantly higher than those of without Pgp expression (21 +/- 3.49) (p = 0.000). No statistically significant correlation was found between 15 min and 90 min uptake ratios (UR) of tetrofosmin and Pgp score (r = -0.10, p = 0.6 and r = -0.21, p = 0.2, respectively). When the cut-off value of 24.5 (according to ROC-analysis) for the washout rate was used to discriminate the lesions with and without Pgp expression, the test yielded a sensitivity value of 87.5% with a specificity of 100%. CONCLUSIONS: In malignant bone and soft-tissue tumors, 99mTc-tetrofosmin uptake were not related to Pgp overexpression. Pgp overexpression was found to be correlated with the washout rate of the tracer. 99mTc-tetrofosmin scintigraphy with washout analysis may not only be a useful method for evaluating Pgp overexpression but also its function.