Ali Gholamrezanezhad

In vivo tracking of 111In-oxine labeled mesenchymal stem cells following infusion in patients with advanced cirrhosis

BACKGROUND Several animal and few human studies suggest the beneficial role of bone marrow mesenchymal stem cells (MSCs) in liver cirrhosis. However, little is known about the fate of MSCs after infusion in cirrhotic patients. We evaluated stem cell biodistribution after peripheral infusion of MSCs in four cirrhotic patients. METHODS After three passages of MSCs, the patients received a total of 250-400×10(6) cells, of which only 50% of the cells were labeled. Specific activities of 0.21-0.67 MBq/10(6) cells were maintained for the injected labeled MSCs. Planar whole-body acquisitions (anterior/posterior projections) were acquired immediately following infusion as well as at 2 h, 4 h, 6 h, 24 h, 48 h, 7th and 10th days after cell infusion. RESULTS After intravenous infusion, the radioactivity was first observed to accumulate in the lungs. During the following hours to days, the radioactivity gradually increased in the liver and spleen, with spleen uptake exceeding that in the liver in all patients. Region-of-interest analysis showed that the percentage of cells homing to the liver (following decay and background corrections and geometric mean calculation) increased from 0.0%-2.8% at immediately post-infusion images to 13.0-17.4% in 10th-day post-infusion. Similarly, the residual activities in the spleen increased from 2.0%-10.2% at immediately post-infusion images to 30.1%-42.2% in 10th-day post-infusion. During the same period, the residual activities in the lungs decreased from 27.0-33.5% to 2.0-5.4%. CONCLUSION The infusion of MSCs labeled with (111)In-oxine through a peripheral vein is safe in cirrhosis. Cell labeling with (111)In-oxine is a suitable method for tracking MSC distribution after infusion.

Giardiasis and other intestinal parasitic infections in relation to anthropometric indicators of malnutrition: a large, population-based survey of schoolchildren in Tehran

Abstract The morbidity of intestinal parasitic infections is greatest among children of school age and may have an adverse effect on growth. In the present, cross-sectional study, the association between previously undiagnosed intestinal parasitic infections and growth was assessed in 19,209 children attending elementary schools in Tehran. The physical growth of these children was investigated by recording body weights, heights and weight-for-age Z scores. Faecal samples were collected and each checked for intestinal parasites using four methods (the microscopical examination of a smear stained with Lugols iodine, a smear prepared by formol–ether concentration, a wet smear in physiological normal saline, and a strip of adhesive tape that had been pressed against the subjects peri-anal region). The association between intestinal parasitic infection and growth was explored using multivariable models adjusted for the influence of age and polyparasitism. The prevalence of infection with any intestinal parasite was 18.4%. The prevalences of stunting (3.8% v. 2.8%), wasting (22.7% v. 20.4%) and the combination of stunting and wasting (3.7% v. 2.8%) were all significantly higher in the infected children than in the uninfected (P<0.01 for each). Although at least nine species of parasite were detected, only two, Giardia lamblia and Enterobius vermicularis, were each significantly associated with low height for age (stunting) and low weight for height (wasting). There were no such reductions with Ascaris lumbricodes, hookworm, Blastocystis hominis, Hymenolepis nana or Entamoeba coli infection. The data indicate fairly high prevalences of previously undiagnosed intestinal parasitic infections and highlight important interactions between nutrition and some of the parasites detected. School health programmes aimed at reducing the prevalences of parasitic infections (particularly giardiasis and enterobiasis) in schoolchildren, which may well have beneficial effects on growth and educational outcome, are clearly needed in Tehran.

Cytotoxicity of 111In-oxine on mesenchymal stem cells: a time-dependent adverse effect.

BackgroundRadioactive labeling with 111indium (111In) tracers has been among the most widely used methods for tracking stem cells. As the first experiment on human stem cells, we designed a study to continuously follow the influence of 111In labeling on stem cell viability during the 2-week period of postlabeling. MethodsAfter culturing mesenchymal stem cells (MSCs), we divided the cells into six samples, each of which contained 1×106 MSCs. The first sample was considered as the control. The remaining five samples (samples 2–6) were labeled with the following doses of 111In-oxine, respectively: 0.76, 1.64, 3.48, 5.33, and 7.16 MBq/106 MSCs. To evaluate the effects of 111In-oxine labeling on cellular viability and count, all samples were examined immediately after labeling (2 h) as well as 24, 48 h, and 5, 7, and 14 days postlabeling. ResultsNo statistically significant relationship was found between labeling efficiency and administered dose. Associations between the specific activity and radiotracer dosage was significant (P=0.001, r=0.9). In addition, a negative correlation was noted between radiotracer dosage and viability during the 2-week period of follow-up. ConclusionCytotoxic effects of 111In on human stem cells is a time-dependent phenomenon and hence, assessment of the stem cell viability immediately after labeling (which is frequently made in clinical trials) is unable to detect adverse effects of this radiopharmaceutical on the integrity of stem cells. Even low doses of 111In-oxine are accompanied by significant cell loss in a 2-week period. Although it has been confirmed that nuclear medicine techniques are the most sensitive methods for stem cell tracking, we recommend that the application of this tracking technique should be treated with great reserve, and if necessary, as little of 111In-oxine as possible should be added to the cells (or only a limited portion of the cells should be labeled) to minimize cell death.

Evaluation of the profile of alopecia areata and the prevalence of thyroid function test abnormalities and serum autoantibodies in Iranian patients

BackgroundThe study aimed at evaluating the prevalence of thyroid function abnormalities in patients with alopecia areata (AA) and its association with other autoimmune diseases and various autoimmune antibodies.MethodWe retrospectively analyzed medical records of 123 patients with AA. The main site of involvement, pattern, and extent of alopecia as well as presence of the similar disease in first-degree family members and serologic status of patients were recorded.ResultsParticipating in the study were 57 males and 66 females (6 to 59 years old). In the majority of patients (69.9%) the disease was manifested in the first two decades of life. Patients with family members having alopecia were recorded in 24.4%. Thyroid function abnormalities were found in 8.9% of patients. Positive autoimmune antibodies were associated with AA in 51.4% of patients with no significant association between the severity and duration of disease and presence of these antibodies.ConclusionThe incidence of positive auto-immune antibodies in Iranian patients is higher than previous reports. Concerning the female:male ratio, thyroid function tests and the prevalence of alopecia in first-degree relatives, our results are compatible with previous data obtained from different ethnic populations. Previous reports documented that a greater severity and longer duration of AA were seen in the early onset forms; however our result are relatively different which could be explained by differences in genetic factors.

Predictors of bone metastasis in pre-treatment staging of asymptomatic treatment-naïve patients with prostate cancer

BACKGROUND There is no general consensus on the optimal criteria for the application of bone scintigraphy in screening of bone metastasis in patients with prostate cancer. Our study was conducted to assess the value of bone scan for pre-treatment staging of asymptomatic treatment-naïve patients with prostate cancer. METHODS A total of 203 consecutive asymptomatic and treatment-naïve patients with prostate cancer (age: 67.6±6.4 years) who were referred to our department for whole body bone scintigraphy were enrolled in the study. Three hours after intravenous injection of 20mCi (99m)Tc-MDP, all patients underwent whole body bone scanning using a single head gamma camera. The planar images were supplemented with SPECT as needed for questionable abnormalities or those having uncertain location on planar images. RESULTS The mean serum PSA levels, serum alkaline phosphatase (ALP) and Gleason score (GS) were 42.41±37.1ng/ml, 223.9±129.9IU/L and 6.7±1.1, respectively. A total of 55 cases (27.1%) out of 203 patients had bone metastases. The univariate analysis showed that serum PSA levels, GS and ALP were all significant predictors of bone metastases. However, only serum PSA and ALP levels were found to be independent predictors of bone metastasis in the multivariate logistic regression analysis. The combination of PSA and ALP (in which patients with either elevated PSA [>20ng/ml] or elevated ALP were considered as positive) had the best screening value, with 98.2% sensitivity and 48.6% specificity. CONCLUSION Serum ALP screening can be employed as a tool to detect the subgroup of patients who are at high risk of bone metastases, while having a PSA of <20ng/ml. The combination of PSA and ALP can be used to improve predictability of bone metastasis in newly diagnosed patients with prostate cancer, without affecting staging accuracy.

Quantitative Assessment of Dacryoscintigraphic Images in the Evaluation of Epiphora

Background: At the present time, only visual analysis is implemented on dacryoscintigraphic images and quantitative assessments are not routinely obtained. The authors have designed a novel, simple, quantitative method for the diagnosis of sac and post-sac obstructions based on the dacryoscintigraphic images. Method: Fifty-nine patients with severe unilateral epiphora were included and the contralateral asymptomatic eyes were used as controls. After ocular instillation of 0.1 cc isotonic saline containing 4 MBq 99mTcO4, dynamic images were obtained for 20 minutes. Visual interpretation was done by two blinded specialists in nuclear medicine. A Time-Activity Curve (TAC) was generated for each eye and its pattern was divided to plateau type, shallow-down sloping and deep-down sloping. The excretion ratio (expressed as the percentage of drained activity) in the 2nd, 3rd, 5th, 7th, 10th, 15th and 20th minute of the study was calculated based on the following formula: (the total count in the region of interest (ROI) in the 1st minute – the total ROI count in the 2nd, 3rd, 5th, 7th, 10th, 15th or 20th minute/the total ROI count in the 1st minute) × 100. The results of the quantitative analysis were compared with the clinical symptoms, visual analysis and TAC pattern. Results: At the optimal cut-off points for the 2nd, 3rd, 5th and 7th minute, the sensitivity of the prediction of obstruction was 76%, 72%, 71% and 69%, respectively. The correlation between visual interpretation and the TAC pattern was statistically significant. Conclusion: The quantitative evaluation of dacryoscintigraphic images would contribute greatly to achieving an easier and more objective interpretation of the scintigraphic results and also provides a reliable tool for inter-individual comparison and the follow-up of patients. As it is the first time that this innovative method has been examined clinically, it will be necessary to investigate its clinical utility in a larger series of patients.

The prevalence and significance of increased gastric wall radiotracer uptake in sestamibi myocardial perfusion SPECT

Background: Limited available data indicate that a specific pattern of increased gastric wall radiotracer uptake is associated with dyspepsia. Our purpose was to evaluate the frequency of this finding and its relation with dyspeptic evidences. Method: 1056 consecutive outpatients referred for myocardial perfusion SPECT were interviewed concerning the dyspeptic symptoms, current gastric medications and previous gastroduodenal interventions. The intensity of gastric wall activity was graded qualitatively as G1 or hyperactive gastric wall (equivalent to the patient’s heart activity) and G2 (less than heart activity). Results: The pattern of gastric wall hyperactivity was identified in 1.9% of patients. Dyspeptic symptoms were present in 80 and 18.6% of G1 and G2 patients, respectively (p<0.001). The dyspeptic symptoms were classified as ulcer-like in 37.5%, dysmotility-like in 43.75% and GERD-like in 18.75% of the dyspeptic G1 patients. Considering the classification of dyspepsia, there was no significant difference between the dyspeptic patients of groups. The history of previous gastroduodenal interventions and current use of gastric medications was significantly higher among G1 patients. Conclusion: The infrequent pattern of gastric wall hyperactivity could be clinically important and can identify a category of patients, who require additional diagnostic gastrointestinal investigation to specify another possible noncardiac origin of complaints.

Radio-iodine therapy and Helicobacter pylori infection

BackgroundHelicobacter pylori is the most important cause of gastritis and related morbidities. Following consumption, radioactive iodine accumulates considerably in the stomach. On the basis of this observation, we decided to determine whether the high radiation induced by radio-iodine in the stomach is effective in the eradication of this infection.MethodsAll consecutive patients with differentiated thyroid carcinoma, who were referred for radio-iodine therapy [dose 117.1 ± 24.4 mCi (4.3 ± 0.9 GBq), range 100–200 mCi (3.7–7.4 GBq)], were enrolled. To detect H. pylori infection, the urease breath test (UBT) was performed 1-2 h before radio-iodine consumption and the test was repeated 2 months later.ResultsOf 88 patients, 71 had pre-treatment positive UBT. Of these, 23 patients had negative post-treatment result, which means a significant reduction (26.1%, 95% CI 16.8–35.5%) in the number of positive UBT results in our treated population (32.4% of UBT-positive cases became UBT-negative).ConclusionsConsidering the high prevalence of reinfection in developing countries, the therapeutic benefit would have been more considerable if the second UBT had been done with a lag time of less than 2 months. Although radio-iodine therapy is not a logical method for the treatment of patients suffering from H. pylori, our finding provides indirect evidence about the radiosensitivity of bacteria, the future clinical applications of which need to be further evaluated. Also this finding can be useful for the food industry, where radiation is used widely to sterilize food. Regarding the possibility of H. pylori suppression, we recommend not using UBT for screening for the infection for at least within 2 months following radio-iodine therapy.

Increased hair shedding may be associated with the presence of Pityrosporum ovale.

AbstractBackground and objective: Although the available data show that hair loss is an important cosmetic problem worldwide, the pathogenesis of common hair shedding is not fully understood. The aim of this study was to evaluate the association between hair shedding and cutaneous Malassezia infection. Malassezia fungi have been the suspected cause of dandruff for more than a century. Previously referred to as Pityrosporum ovale or P. orbiculare, these fungi are now known to consist of at least seven species. Methods: Over a 4-year period, we obtained 300 hair samples from medical students. Based on the clinical history and a hair-pull test, the participants were divided into two groups: normal subjects and subjects with hair shedding. The students’ scalp skin was gently scraped, smeared on a slide, colored by methylene blue, and observed under 10× magnification. Results: All participants who had positive smears with ≥3 P. ovale organisms per low-power microscopic field (10×) were defined as ‘ecarriers.’ Seventy-six percent of students were Malassezia carriers. The prevalence of positive smears was significantly higher among subjects with hair shedding than among normal subjects (89.92% vs 9.52%, p < 0.001). Furthermore, participants with positive smears had a significantly higher frequency of hair loss complaints and positive hair-pull tests. Conclusion: The proportion of subjects who were carriers of Malassezia yeasts was significantly higher in the group with hair shedding, and our results therefore raise the possibility of a relationship between this unicellular organism and hair loss. Our study findings should be explored in a larger series of patients.

An important but easily forgettable review: extracardiac activity in myocardial perfusion scans

articles concerning extracardiac activity in the myocardial perfusion scans, we would find numerous reports regarding the fact which extracardiac activities have been observed in the myocardial scintigraphy [1–8]. Most of the authors in such reports have recommended to review of cinematic projections in order to finding extracardiac activities [2, 6–8]. Perhaps the reason for such repeated emphasis is that nuclear medicine specialists in their daily practices forget to review cinematic projections. Maybe this negligence is due to the high amount of heavy load works that devolves on to their shoulders. Since using myocardial perfusion scans by cardiologists have considerably increased the last two decades, the amount of work of nuclear medicine physicians have considerably increased, too. As a consequence although most specialists in the research purposes reviewing the cinematic projections, they ignore such important factor in their daily practices, usually. With presence of new modalities such as CT angiography, demands for myocardial perfusion scintigraphy will be decreasing gradually in the years to come. So there is no any justifiable excuse for ignoring the important part of interpreting of myocardial perfusion scans. In view of numerous reports in recent years it seems that extracardiac activities can be an indirect but important guidance for a lot of noncardiac diseases. These noncardiac diseases occasionally mimic the cardiac symptoms. Some of such diseases include gastric disease [6, 7], liver and gallbladder disease [1], spleen disorders [1], vertebral pathologies [1] and pulmonary pathologies [8]. Regarding this fact that thallium and sestamibi are tumoral avid agents, it is not surprising that several tumors in old people (it implies that the age at which the prevalence of cardiac diseases increase, the demand for myocardial perfusion scintigraphy increase proportionally) discovered incidentally. However, with respect to the nonspecific nature of these radiotracers, the interpretations should be performed with caution. Using such a delicate point in interpreting and devoting time in reviewing myocardial perfusion images, can add additional advantages over other imaging modalities. As there is the opportunity to reveal other pathologic conditions, the interpretation of myocardial perfusion imaging should not be limited to the heart A. Gholamrezanezhad (&) Æ S. Mirpour Research Institute for Nuclear Medicine, Tehran University of Medical Sciences, Shariati Hospital, Northern Kargar St., 14114 Tehran, Iran e-mail: gholamrezanejhad@razi.tums.ac.ir