Mahmut Yüksel

Results of a pilot study on the effects of propofol and dexmedetomidine on inflammatory responses and intraabdominal pressure in severe sepsis

STUDY OBJECTIVE To compare the effects of an intravenous infusion of propofol and the alpha-2 adrenoceptor, dexmedetomidine, on inflammatory responses and intraabdominal pressure (IAP) in severe sepsis after abdominal surgery, specifically, serum cytokine levels (interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) and IAP. DESIGN Prospective, single-center study. SETTING University hospital. PATIENTS 40 adult ICU patients who had undergone ileus surgery and who were expected to require postoperative sedation and ventilation. INTERVENTIONS Patients received either a loading dose infusion of propofol (Group P; n = 20) one mg/kg over 15 minutes followed by a maintenance dose of one to three mg/kg/hr (n = 20, Group P) or a loading dose of dexmedetomidine of one microg/kg over 10 minutes followed by a maintenance dose of 0.2-2.5 microg/kg/h (n = 20, Group D) at the 24th hour. MEASUREMENTS Biochemical and hemodynamic parameters, cytokine levels, and IAP were recorded before the start of the study and at the 24th and 48th hours. MAIN RESULTS TNF-alpha levels were significantly lower at the 24th hour (14.66 +/- 4.40 pg/mL vs. 21.21 +/- 11.37 pg/mL, respectively) and at the 48th hour (21.25 +/- 15.85 pg/mL vs. 46.55 +/- 35.99 pg/mL, respectively) in Group D. IL-1 levels were significantly lower at the 24th hour (5.03 +/- 0.15 pg/mL vs. 6.23 +/- 2.09 pg/mL, respectively) and the 48th hour (5.01 +/- 0.37 pg/mL vs. 6.42 +/- 2.76 pg/mL, respectively) in Group D. IL-6 levels were significantly lower at the 24th hour (253.1 +/- 303.6 pg/mL and 511.3 +/- 374.8 pg/mL, respectively) and at the 48th hour (343.5 +/- 393.4 pg/mL and 503.7 +/- 306.4 pg/mL, respectively) in Group D. Intraabdominal pressure also was significantly lower at the 24th hour (12.35 +/- 5.84 mmHg vs. 18.1 +/- 2.84 mmHg, respectively) and the 48th hour (13.9 +/- 6.15 mmHg vs. 18.7 +/- 3.46 mmHg, respectively) in Group D. CONCLUSION Dexmedetomidine infusion decreases TNF-a, IL-1, and IL-6 levels and IAP more than a propofol infusion.

99mTc-MIBI SPET in non-small cell lung cancer in relationship with Pgp and prognosis

Abstract Higher technetium-99m methoxyisobutylisonitrile (MIBI) uptake in non-small cell lung cancer (NSCLC) has been reported to be associated with a positive response to chemotherapy. It has previously been found that in tumour cells, P-glycoprotein (Pgp) expression is of importance for tracer uptake. However, some studies have indicated that Pgp expression does not play an important role in 99mTc-MIBI uptake in NSCLC; indeed, a negative correlation between 99mTc-MIBI uptake and Pgp expression has been reported. Against the background of conflicting results, our aim was to evaluate the relationship between 99mTc-MIBI uptake, prognosis and Pgp expression in NSCLC. A total of 37 patients with NSCLC underwent 99mTc-MIBI single-photon emission tomography (SPET) before chemotherapy. In 19 patients both Pgp and p53 expression, and in two patients only p53 expression (due to the limited biopsy material), were measured with immunohistochemical staining. 99mTc-MIBI uptake was significantly higher in responders than in non-responders: 3.09±1.14 vs 2.24±0.88 (P<0.03) and 3.09±1.08 vs 2.37±1.06 (P<0.05) for the early ratio (ER) and the delayed ratio (DR), respectively. The wash-out rate (WR) of responders was not significantly different from that of non-responders. We found no significant differences in ER, DR and WR among the groups positive or negative for Pgp and p53 status. There was a significant positive correlation between the survival rate and both ER and DR: r=0.49 (P=0.003) and r=0.40 (P=0.018), respectively. Patients with ER and DR values above 3 showed significantly longer survival than those with values below 3: 14.7±8.5 months vs 7.3±5.1 months (P<0.009) and 13.2±8.4 months vs 7.4±5.3 months (P<0.04) for ER and DR, respectively. However, interestingly, and in contrast to expectations, patients with a Pgp score of +2 showed significantly longer survival (12.9±6.7 months) than those with Pgp scores of +1 (4.4±3.0 months) or – (negative) (3.8±2.2 months) (P<0.009 and P<0.02, respectively). Our results suggest that in NSCLC, patients with higher 99mTc-MIBI uptake tend to show a positive response to chemotherapy, and patients with ER and DR values above 3 have a significantly better prognosis. We also found that Pgp expression seems to play only a minor role in 99mTc-MIBI uptake. Our finding that patients with ER and DR values above 3 have a better prognosis needs to be confirmed in larger series of patients.

Sister chromatid exchanges in lymphocytes of nuclear medicine physicians

OBJECTIVE The aim of this study was to assess whether occupational exposure to chronic, low doses of Iodine 131 (I-131) and Technetium 99m (Tc-99m) may lead to genotoxicity. Medical personnel occupied in nuclear medicine departments are occupationally exposed to low doses of I-131 and Tc-99m. The determination of the frequency of sister chromatid exchanges (SCEs) and of cells with a high frequency of SCEs (HFC) is considered to be a sensitive indicator for detecting genotoxic potential of mutagenic and carcinogenic agents. Therefore, we examined peripheral lymphocytes from nuclear medicine physicians for the presence of both SCE and HFC. METHODS Sixteen exposed nuclear medicine physicians (non-smokers) were compared to 16 physicians (non-smokers) who had not been exposed to chemical or physical mutagens in their usual working environment at the same hospital. RESULTS A statistically significant difference was found between SCE frequencies and HFC percentages measured in lymphocytes from the exposed and control groups. CONCLUSIONS The present observation on the effect of chronic low doses of I-131 and Tc-99m indicates the possibility of genotoxic implications of this type of occupational exposure. Hence, the personnel who work in nuclear medicine departments should carefully apply the radiation protection procedures and should minimize, as low as possible, radiation exposure to avoid possible genotoxic effects.

Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy

OBJECTIVE To compare serum cytokine levels in patients with hyperemesis gravidarum with levels in healthy pregnant and nonpregnant women. DESIGN Case-control study. SETTING Clinical and academic research center. PATIENT(S) Thirty women with hyperemesis gravidarum, 30 healthy women in the first trimester of pregnancy, and 30 healthy nonpregnant women. MAIN OUTCOME MEASURE(S) Serum levels of interleukin-1beta, interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor (TNF)-alpha. RESULT(S) Median serum levels of interleukin-2 receptor and interleukin-8 did not differ significantly among the three groups. Serum levels of interleukin-1beta and interleukin-6 were significantly higher in healthy pregnant women than in healthy nonpregnant women. Median TNF-alpha levels were significantly higher in women with hyperemesis (25.8 pg/mL [range, 4.9-140 pg/mL]) than in healthy pregnant and nonpregnant women (10.85 pg/mL [range, 4.1-35.8 pg/mL] and 12 pg/mL [4.3-68.2 pg/mL], respectively). CONCLUSION(S) Levels of TNF-alpha were significantly higher in patients with hyperemesis gravidarum than in healthy pregnant and nonpregnant women. Thus, TNF-alpha may be involved in the etiology of hyperemesis gravidarum.

Maternal serum levels of tumor necrosis factor-α and interleukin-2 receptor in threatened abortion: a comparison with normal and pathologic pregnancies

OBJECTIVE We evaluated tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) receptor levels in patients with threatened abortion and compared the levels with normal and pathologic pregnancies. DESIGN A prospective, nonrandomized, case-control study. SETTING Academic research setting. PATIENT(S) Twenty-two patients with threatened abortion, 18 patients with pathologic pregnancies, 20 healthy pregnant women, and 20 nonpregnant women. INTERVENTION(S) Maternal serum TNF-alpha and IL-2 receptor levels were measured with a solid-phase, two-site chemiluminescent enzyme immunometric assay method. MAIN OUTCOME MEASURE(S) TNF-alpha and IL-2 receptor levels. RESULT(S) The mean +/- SEM maternal serum IL-2 receptor level for patients with threatened abortion was 481.3 +/- 35.7 U/mL, compared with 426.5 +/- 22.4 U/mL in the normal pregnant group. There was no statistically significant difference in the mean +/- SEM serum TNF-alpha level between the patients with threatened abortion and those with normal pregnancies (16.1 +/- 2.7 pg/mL vs. 10.9 +/- 0.8 pg/mL). The mean +/- SEM maternal serum IL-2 receptor level was significantly higher in patients with pathologic pregnancies than in those with normal pregnancies (506.2 +/- 27.6 U/mL vs. 426.5 +/- 22.4 U/mL). The mean +/- SEM maternal serum TNF-alpha level was significantly higher in patients with pathologic pregnancies than in those with threatened abortion (39.2 +/- 9.5 pg/mL vs. 16.1 +/- 2.7 pg/mL) and normal pregnancies (39.2 +/- 9.5 pg/mL vs. 10.9 +/- 0.8 pg/mL). CONCLUSION(S) In comparison with normal pregnancies, maternal serum IL-2 receptor and TNF-alpha levels were not significantly increased in patients with threatened abortion with good outcome.

The incidence of recurrence and hypothyroidism after radioiodine treatment in patients with hyperthyroidism in Trakya, a mild iodine deficiency area, during the period 1991–2003

ObjectiveThe purpose of this retrospective study was to evaluate the incidence of recurrence and the success of radioiodine treatment (RIT) in the Trakya region of Turkey, an area with mild iodine deficiency, and to compare the effect of dose regimen selection (fixed (FD) or calculated dose (CD)) on treatment success.Material and MethodsThe study sample included 148 patients (40 male, median age 50) treated with radioiodine between the years 1991-2003. Patients were categorized into three diagnostic groups: Graves’ disease (GD) (n = 65), solitary toxic adenoma (TA) (n = 29), and toxic multinodular hyperthyroidism (TMH) (n = 54), and each divided into two subgroups according to treatment method; the first group was treated with a FD of 370 MBq (10 mCi), and the second with CD.ResultsThe largest group was GD (44%), followed by TMH (36%). Median duration of follow-up was 28 months (range 6-147). FD was given to 52.7% of all patients and CD was given to 47.3%. There was a partial difference in the dose regimen between all groups, but did not reach statistically significant levels (FD vs. CD: 65%–35%; 38%–62%; 46%–54%; GD, TA, TMH respectively, p > 0.05). Total cure rate in FD and CD was 46 (59%) and 37 (52.9%), respectively. The rates of hypothyroidism for GD, TA, and TMH groups were 28 (43.1%), 6 (20.7%) and 16 (29.6%), respectively. The incidence of hypothyroidism did not vary significantly between any groups (p > 0.05). At the end of the follow-up period, a total of 104 patients (70.3%) were treated successfully. There was no significant difference in the cure rate between any groups (p > 0.05).ConclusionsThe treatment success in all groups and subgroups did not differ significantly between FD and CD. Our lower cure rate than in previous studies may be related to iodine deficiency. Higher doses of radioiodine may be required to increase final treatment success in endemic goiter areas. If this true, dosimetry and calculated dose regimen would be required in all groups of patients instead of an FD concept. However, our findings should be verified in larger series of patients, with longer follow-up period, and urinary iodine concentration measurements.

111In-pentetreotide scintigraphy in medulloblastoma: a comparison with magnetic resonance imaging.

Medulloblastoma (MB) is a primitive neuroectodermal tumour constituting a grade IV brain malignancy. Early and correct detection of recurrence or metastasis is desirable for follow-up of patients in this entity. Frequent expression of somatostatin receptors by MB lesions facilitates functional tumour imaging by somatostatin receptor scintigraphy (SRS). To investigate the value of SRS in the follow-up of MB, the results of ten consecutive patients (seven children and three adults) undergoing additional imaging with 111In-pentetreotide were reviewed. Four, 24 and 48 h p.i. planar and whole body images as well as a SPECT study at 4 h p.i. were acquired after intravenous injection of 109±35 MBq 111In-pentetreotide (Octreoscan®). SRS yielded 11 positive and ten negative imaging results, compared to 17 positive and four negative in magnetic resonance imaging (MRI). The lesion-by-lesion analysis with a total of 44 lesions revealed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 42%, 83%, 94%, 18% for SRS and 89.5%, 50%, 92%, 43% for MRI. Based on a per-patient analysis, considering the patient as to be either tumour-free or tumour-positive by one imaging modality, the following values for sensitivity, specificity, PPV and NPV were obtained: 61%, 100%, 100%, 30% for SRS and 94%, 67%, 94%, 67% for MRI. MRI remains the first step imaging technique in medulloblastoma patients before and after surgery and during the follow-up providing the highest sensitivity. However, to improve specificity and contribute to correct diagnosis in MB 111In-pentetreotide scintigraphy should be considered as a confirmatory second step imaging tool, especially in case of equivocal MRI results. Moreover, a positive SRS scan might serve as a reference before and after somatostatin receptor targeted radiotherapy.

111In-pentetreotide and123I-MIBG for detection and resection of lymph node metastases of a carcinoid not visualized by CT, MRI or FDG-PET

A patient with a history of a jejunal carcinoid and resection of liver metastases underwent CT, MRI and FDG-PET as well as somatostatin receptor scintigraphy using111In-pentetreotide during follow-up. Octreoscan demonstrated one extrahepatic abdominal lesion with pathologic uptake, while the other imaging modalities failed to show a corresponding abnormality. For verification of this finding123I-MIBG scintigraphy was performed. The MIBG scan confirmed the octreotide positive lesion and showed an additional abdominal lesion in the SPECT study. According to the scintigraphic results, radioguided surgery (RGS) was implemented using123I-MIBG. This resulted in the intra-operative detection of two para- and pre-aortic lymph node metastases by the gamma probe and successful resection. An additional preaortal lymph node, suspicious by palpation, was also removed. Histopathology revealed metastases of a carcinoid tumor in all three specimens. In conclusion, the use of RGS facilitates successful removal of carcinoid metastatic lesions despite negative conventional imaging results. Secondly,123I-MIBG scintigraphy may provide advantages over octreoscan for preoperative localization as well as radio-guided surgery of neuroendocrine metastatic lesions, if the involved site is located in proximity to highly octreotide-avid organs such as the kidneys or spleen.

Incidence of Antiheparin−Platelet Factor 4 Antibodies and Heparin-Induced Thrombocytopenia in Turkish Patients Undergoing Cardiac Surgery

The frequency of antiheparin−platelet factor 4 antibodies by means of antigenic and functional assays (14 C-serotonin release assay and citrated plasma platelet aggregation) was determined in 115 Turkish patients undergoing cardiac surgery. Blood samples were taken immediately before surgery and on days 5 and 10 ± 2. Platelet counts were recorded and thrombotic events were determined by clinical methods. Antibody generation measured by enzyme-linked immunosorbent assay before surgery (n = 44) and on days 5 (n = 44) and 10 (n = 115) was 15.9%, 34.1%, and 65.2%, respectively. Positive samples from functional assays were 4.4% on day 0 and 7.0% on day 10. All positive samples had been negative on day 0. A high frequency of antiheparin−platelet factor 4 antibody generation and a low frequency of clinical heparin-induced thrombocytopenia were determined in these patients. These results obtained for Turkish patients are similar to those of other studies of heparin-induced thrombocytopenia.

Thallium-201 SPECT in advanced non-small cell lung cancer: In relation with chemotherapeutic response, survival, distant metastasis and p53 status

Purpose: The aim of this study was to evaluate the relationship between201Tl tumor uptake, chemotherapeutic response, metastasis, p53 status and survival in non-small cell lung cancer (NSCLC).Methods: A total of 23 patients underwent201Tl SPECT. In 9 patients, 2nd201Tl SPECT study were performed 1 week after the 3rd cycle of chemotherapy (ChT), and early (ER) and delayed (DR) tumor/normal lung ratios and retention indices (RI) were obtained. In 15 patients p53 status was assayed with immuno-histochemical staining. The patients were divided into subgroups after the 3rd cycle of ChT; responders [R(+) (n=10)] and non-responders [R(−) (n=13)], distant metastasis [(M1) n=11] and [(M0) n=12], and mutant p53 status [p(+) n=7, p53(−) n=8].Results: The differences for ER, DR and RI values between all of the subgroups were not statistically significant. ER and DR of responders decreased significantly after ChT; from to 2.46 to 1.36 (p=0.04) and 2.29 to 1.53 (p=0.04), respectively. In the non-responder group, both ER and DR slightly increased after ChT (p>0.05).Conclusion: Our results suggest that in NSCLC, there was a weak correlation between higher201Tl ratios and positive response to chemotherapy, absence of distant metastasis, and p53(−) status. Significant201Tl uptake decrease after chemotherapy indicates that delayed201Tl uptake can be used in evaluating the chemotherapeutic response.