Meltem Caglar

To use MIBI or not to use MIBI? That is the question when assessing tumour cells

Abstract99mTc-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.

A background infusion of morphine does not enhance postoperative analgesia after cardiac surgery

PurposeTo compare the effects of patient-controlled analgesia (PCA), with or without a background infusion of morphine on postoperative pain relief and stress response after cardiac anesthesia.MethodsWith University Ethics approval, 35 consenting adults undergoing elective open-heart surgery were randomly assigned preoperatively in a double-blind fashion to receive either morphine PCA alone (Group I, n = 15) or morphine PCA plus a continuous basal infusion (Group II, n = 14) for 44 hr postoperatively. Pain scores with visual analogue scale (VAS) at rest, deep inspiration and with cough, sedation scores, stress hormone levels [cortisol, adrenocorticotropin (ACTH) and growth hormone (GH)] and morphine consumption were assessed, and serum morphine levels were measured at four, 20, 28 and 44 hr after surgery. Adverse effects including nausea, vomiting, constipation, urinary retention and pruritus were noted. Total blood, fluid requirements, drainage and urinary output were recorded.ResultsPostoperative morphine consumption at 44 hr was less in Group I (29.43 ±12.57 mg) than in Group II (50.14 ±16.44mg), P = 0.0006. There was no significant difference between groups in VAS scores, GH levels, blood levels of morphine and adverse effects. While VAS scores, ACTH and GH levels decreased significantly in both groups, plasma cortisol levels increased significantly in Group I only at four hours. In Group II, ACTH and cortisol were higher at four and 44 hr respectively.ConclusionPCA with morphine effectively controlled postoperative pain after cardiac surgery. The addition of a background infusion of morphine did not enhance analgesia and increased morphine consumption.RésuméObjectifComparer les effets de l’analgésie autocontrôlée (AAC), avec ou sans une perfusion de morphine de base, sur l’analgésie postopératoire et la réaction de stress à la suite d’une anesthésle cardiaque.MéthodeNotre étude a été menée en double aveugle, avec l’accord du comité d’éthique de l’université, auprès de 35 adultes consentants devant subir une opération à cœur ouvert réglée. Les patients ont reçu, soit de la morphine en AAC seule (Groupe I, n = 15), soit de la morphine en AAC plus une perfusion de base continue (Groupe II, n = 14) pendant 44 h après l’opération. Nous avons évalué: la douleur, au repos, pendant l’inspiration profonde et la toux, selon une échelle visuelle analogique (EVA), la sédation, les niveaux d’hormones de stress [cortisol, les hormones adrénocortlcotropes (ACTH) et de croissance (GH)] et la consommation de morphine, ainsi que les niveaux sériques de morphine à quatre, 20, 28 et 44 h après l’opération. Les effets indésirables, incluant les nausées, les vomissements, la constipation, la rétention urinalre et le prurit ont été notés. Le sang total, les besoins liquidiens, le débit de drainage et la diurèse ont été enregistrés.RésultatsÀ 44 h, la consommation de morphine postopératoire était plus faible dans le Groupe I (29,43 ±12,57 mg) que dans le Groupe II (50,14 ±16,44 mg), P = 0,0006. Il n’y avait pas de différence Intergroupe significative des scores à I’EVA, des niveaux de GH, des niveaux sanguins de morphine et d’effets Indésirables. Les scores à I’EVA, les niveaux d’ACTH et de GH ont diminué slgnificativement dans les deux groupes, mais le cortisol plasmatique a augmenté de façon significative dans le Groupe I, à quatre heures seulement. Dans le Groupe II, l’ACTH et le cortisol étalent respectivement plus élevés à quatre et 44 h.ConclusionL’AAC avec de la morphine réduit efficacement la douleur postopératoire en cardiochirurgie, L’ajout d’une perfusion de base de morphine n’améliore pas l’analgésie, mais augmente la consommatlon de morphine.

Comparison of 800 and 3700 MBq iodine-131 for the postoperative ablation of thyroid remnant in patients with low-risk differentiated thyroid cancer.

IntroductionThe initial treatment of differentiated thyroid cancer is thyroidectomy, followed by remnant ablation with iodine-131 (I-131) in some patients. However, controversy exists concerning the appropriate radioiodine dose. The aim of the study is to compare the success rate of low and high activities of I-131 for postoperative remnant ablation. Patients and methodsA total of 108 nonmetastatic low-risk patients (mean age: 46, 85% women) with papillary and follicular carcinoma had I-131 ablation for the postoperative thyroid remnant. Fifty-three patients received a low dose (L) (800 MBq) and 55 patients received a high dose (H) (3700 MBq) of I-131. After total thyroidectomy, thyroid bed I-131 uptake (RAIU) and neck ultrasonography (USG) were performed to determine the remnant volume and the iodine avidity, which were used to calculate the dose delivered to the remnant tissue. The success rate of I-131 ablation was assessed with four different criteria based on serum thyroglobulin (Tg) and USG with and without the utilization of I-131 diagnostic whole-body scintigraphy (DxWBS). Ablation was considered to be successful if patients fulfilled all of the following criteria. (a) Strict criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or up to 0.2% RAIU, and (iii) Tg<0.2 ng/ml; (b) lax criteria based on three tests: (i) USG negative, (ii) no tracer uptake or less than twice the background activity in the thyroid bed on DxWBS and/or ⩽0.2% RAIU, and (iii) Tg<2 ng/ml; (c) strict criteria based on two tests: (i) USG negative and (ii) Tg <0.2 ng/ml; (d) lax criteria based on two test: (i) USG negative and (ii) Tg <2 ng/ml. ResultsWhen three tests were used to define successful ablation, in group L, 32 out of 53 (60%) and 43 out of 53 (81%) patients were successfully treated versus 35 out of 55 (64%) and 42 out of 55 (76%) for group H on the basis of strict and lax criteria, respectively (P=NS). The differences were not statistically significant between the two groups when only two tests were used to define ablation success (62 vs. 69% with strict and 89 vs. 87% with lax criteria, respectively). ConclusionOur findings suggest that remnant thyroid tissue in patients with low-risk, well-differentiated thyroid cancer after total thyroidectomy can be ablated with 800 MBq of I-131. The success rate is not different from that obtained with 3700 MBq I-131.

Differential renal function estimation by dynamic renal scintigraphy: influence of background definition and radiopharmaceutical.

ObjectivesDifferential renal function (DRF) calculation with Tc-diethylenetriamine-pentaacetic acid (DTPA) or mercaptoacetyltriglycine (MAG3) is gaining clinical importance in the evaluation of patients with ureteropelvic junction obstruction with hydronephrosis (HN). Although many decisions regarding surgery are based on the functional changes detected by serial diuretic renography, the reliability of DRF estimation has been questioned. Factors such as the correction of nonrenal activity included in the renal region of interest (background subtraction) and immature function resulting in poor renal extraction may cause unusual elevation in the differential function. The aim of this study is to evaluate the impact of the radiopharmaceutical and positioning of the background on the DRF. Patients and methodsA prospective study was undertaken in 83 patients (48 male, 35 female, median age 5 years) with unilateral or bilateral ureteropelvic junction obstruction with or without HN. Forty-five and 38 renograms were performed with 99mTc-DTPA and 99mTc-MAG3, respectively. DRF was calculated using two different regions of interest (subrenal and perirenal) for background subtraction. Of the 83 patients, 37 also had dimercaptosuccinic acid scans. The difference between DRF based on background selection, age, radiopharmaceutical, and correlation with dimercaptosuccinic acid uptake was analyzed. The difference in DRF between two background (BG) drawings (sebrenal and perirenal) and 95% confidence intervals were calculated. ResultsFor 83 renograms, the mean difference was 4.82 (range −7 to +25, SD 5.26). The 95% confidence intervals were −3.67 to 5.97. Analysis of the data revealed that greater spread of DRF between the techniques was seen in patients with right HN (mean 7.96, P<0.001). In patients with right HN, when lower pole background activity was used, the right renal function was overestimated by an average of 4.67%. When MAG3 was used, all patients had statistically significant DRF for the different BG subtraction techniques, whereas the DRF values were only statistically different in those with right HN when DTPA was used. DiscussionThe current study supports the existence of BG-related variation in the DRF calculations. We found that the average counts in the perirenal BG more precisely represent nonrenal activity and recommend the use of semilunar-perirenal background region of interest to reduce the overlapping hepatic activity.

Value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) gated SPECT for the detection of silent myocardial ischemia in hemodialysis patients: clinical variables associated with abnormal test results.

BackgroundAlthough coronary artery disease is a major cause of mortality and morbidity in patients undergoing hemodialysis, there is no accurate diagnostic strategy for these patients. AimTo assess the value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) gated single-photon emission computed tomography for the detection of silent myocardial ischemia in patients undergoing hemodialysis and to evaluate the clinical variables associated with abnormal test results. MethodsThirty-one asymptomatic patients undergoing hemodialysis (20 men, 11 women), with a mean age of 45 years (range, 25–75 years), were included in the study. Serum electrolytes, creatinine, homocysteine and adhesion molecules were measured prior to dialysis. Ambulatory blood pressure, carotid intima–media thickness measurements, echocardiography and stress 99mTc-MIBI imaging were performed in all patients, whereas coronary angiography was performed only in patients with abnormal myocardial perfusion scintigraphy and/or echocardiography. ResultsGated myocardial perfusion scintigraphy results were abnormal in nine patients (29%) and coronary angiography was abnormal in six patients. After a median follow-up of 20 months (range, 14–28 months), nine patients experienced a cardiac event. Seven of the nine patients (78%) with abnormal myocardial perfusion scintigraphy suffered a cardiac event, compared with only two of 22 patients (9%) with normal myocardial perfusion scintigraphy (P<0.0001). Patients with abnormal perfusion scintigraphy had higher serum C-reactive protein, homocysteine and adhesion molecule levels and the duration of hemodialysis was significantly longer. ConclusionIn asymptomatic hemodialysis patients, gated myocardial perfusion scintigraphy is a safe and non-invasive screening technique for the detection of coronary artery disease and for predicting future cardiac events. The presence of ischemia correlates significantly with markers of inflammation. The discordant results (abnormal myocardial perfusion scintigraphy/normal coronary angiography) can be attributed to angiographically unrecognized occult atherosclerotic changes and abnormal vasodilatation capacity of the coronary circulation.

Association between activated renin angiotensin system and bone formation in hemodialysis patients: is the bone mass genetically determined by ACE gene polymorphism?

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty‐eight end‐stage renal disease patients (28 male, 20 female mean age 42 ± 13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than − 1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92 ± 0.17 g/cm2 and − 1.36 ± 1.50, respectively. Twenty‐one patients (43,7%) were osteopenic (T score worse than − 1.5) and mean T score of osteopenic patients was − 2.72 ± 0.72. T score of nonosteopenic group was − 0.29 ± 0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre‐ and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p < 0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R = 0.48 p < 0.05). Serum ACE activity was positively correlated with serum iPTH (R = 0.29, p = 0.02), serum OC (R = 0.35, p = 0.01), serum bAP (R = 0.34, p = 0.01), serum PCIP (R = 0.36, p = 0.01). T score (− 0.7 ± 1.5, vs − 1.7 ± 1.3 p < 0.05) was higher in DD group (n = 19) compared to II + ID group (n = 29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.

Primary sternal osteomyelitis in a healthy child due to community-acquired methicillin-resistant Staphylococcus aureus and literature review

Primary sternal osteomyelitis is a rare condition. Most of the recent cases have been reported in intravenous drug abusers. A 4-y-old male case of primary sternal osteomyelitis due to community-acquired methicillin-resistant Staphylococcus aureus with no apparent risk factors is reported. The diagnosis should be suspected in a young patient presenting with acute inflammatory swelling over the sternum. While bacteriological culture results are pending, antibiotic therapy with Staphylococcus aureus coverage should be initiated empirically and the possibility of community-acquired methicillin-resistant S. aureus must be borne in mind. In this report we also review the literature of paediatric primary sternal osteomyelitis.

Reduced Tc-99m DMSA uptake in a patient with renal tubular acidosis: effect of acid-base imbalance.

Tc-99m dimercaptosuccinic acid (DMSA) is used as a renal cortical imaging agent to detect parenchymal abnormalities especially in children. Kidney uptake of DMSA provides an index for evaluation of a functional tubular mass, which depends on the renal blood flow and proximal tubular cell membrane transport function. We here report a boy with renal tubular acidosis, which has noticeably reduced uptake on his Tc-99m DMSA scintigraphy, despite a totally normal Tc-99m MAG-3 study. The case reported here clearly demonstrates a situation in which renal uptake of DMSA may be dissociated from a functional renal mass and the importance of acid-base balance which alters Tc-99m DMSA uptake.

Multiple brown tumors simulating bone metastases: a case of parathyroid adenoma coexisting with papillary carcinoma of the thyroid.

A 55-year-old man with multiple brown tumors who initially was thought to have multiple bone metastases is described. He had elevated parathyroid hormone levels and was referred to the nuclear medicine department, where a parathyroid adenoma was diagnosed. At surgery, abnormal lymph nodes were seen, which were found to contain metastatic thyroid papillary carcinoma cells. On further exploration, the patient’s bone scintigraph revealed multiple sites of increased uptake but no bone abnormalities on whole-body iodine and Tc-99m MIBI scans.

Tc-99m DTPA acetylsalicylic acid (aspirin) renography in the detection of renovascular hypertension.

Purpose Prostaglandins play important roles in renal physiology and in the development of renovascular hypertension. In a recent study, inhibition of renal prostaglandin synthesis was found to be useful for detecting renovascular hypertension using renal scintigraphy. In the current study, the authors evaluated the role of aspirin (an inhibitor of prostaglandin synthesis) and compared it with Tc-99m DTPA captopril renal scintigraphy (CS). Materials and Methods Twenty-five patients were examined with Tc-99m DTPA in a three-step manner: a baseline study, CS, and aspirin scintigraphy (AS). Each scintigraphic study was interpreted visually and according to the renogram curve patterns. Semiquantitative parameters (Tmax, renal indices [%], 20-minute/max count ratio, glomerular filtration rate) were also calculated. Plasma renin activity was determined for each study. The blood pressures of all patients were measured during AS. All patients had a contrast-enhanced angiogram that was used as the reference test. Results Three groups of patients were observed based on the scintigraphic and angiographic results. In each group, no difference was observed in blood pressure after aspirin administration. In group 1, seven patients had normal angiographic and scintigraphic results. In group 2, eight patients had angiographically confirmed renal artery stenosis (RAS). In 6 patients (mean, 47% RAS), both AS and CS were negative for RVH. In the remaining two patients with RAS (mean, 83% stenosis), the kidneys were atrophic on the stenotic side, and thus the kidneys did not respond to the interventions. No difference was observed in plasma renin activity in groups 1 and 2. Group 3 included 10 patients who had angiographically confirmed RAS (mean, 86%). In 9 patients, both CS and AS were positive for RVH. In the remaining one patient, scintigraphic results were falsely negative. Statistical analyses performed for semiquantitative parameters did not reveal any significant difference in this group, although there was a tendency toward prolonged Tmax values after captopril and aspirin administration. In four cases, unexpected elevation of plasma renin activity was observed in group 3. Conclusions These data indicate that AS with Tc-99m DTPA is an alternative for CS. It has the advantage of having no effect on blood pressure and does not require that angiotensin-converting enzyme inhibitors be discontinued. Although in this study 9 of 10 patients had correct diagnoses of RAS, further studies, especially using tubular agents with the calculation of parenchymal transit time, might provide valuable information in this patient group. An ongoing study is being performed in the authors’ institute.