Referral to radioisotope examination as a source of additional radiation exposure for staff

Background: Every exposure of human to ionizing radiation increases the likelihood of deterministic sequelae. At the same time, it is associated with the risk of stochastic effects. Consequently, this can lead to cancer, mainly of the hematopoietic system. Organs or tissues show a different affinity for gamma radiation. There are many technical and organizational measures which minimize the impact of this radiation on people and especially on the staff of the nuclear medicine laboratory. Materials and methods: The study was based on 208 referrals to the scintigraphic laboratory, which were executed between 26.09.2018 and 13.11.2018 in the Department of Nuclear Medicine of Military Medical Academy Memorial Teaching Hospital of the Medical University of Lodz – Central Veterans` Hospital. Referrals concerned scintigraphic tests of bones, salivary glands, parathyroid glands, myocardial perfusion, somatostatin receptor analogues, renoscintigraphic and lymphoscintigraphic tests. In case of each referral, radiation power was measured at a distance of approx. 10 cm with the use of a calibrated Geiger-Muller detector. Measurements were performed immediately after the end of the last examination each day. Daily measurement of the background radiation dose was also a standard procedure. For calculations, this value was averaged to 0.18µSv/h. Based on the above measurements, a statistical analysis of all data was performed. Obtained data was also analysed after it was ascribed to the person complexing radiopharmaceuticals on a given day. The annual dose for a radiopharmacist is 0.12 mSv, for a technician 0.35 mSv and for a doctor 0.45 mSv. Results: The average radiation dose received every working day by the staff was 11.49 µSv/h. After considering the average distance from the potential source of exposure (50 cm), this power decreased to 0.46µSv/h. In order to calculate the quarterly and annual radiation dose, it was assumed that the employee worked 250 days a year. Conclusions: Medical records may pose an additional personnel exposure to ionizing radiation. Physicians are the most vulnerable group of employees. The way of radiopharmacists work contributes to the contamination of medical records

Lung penetration, bronchopulmonary pharmacokinetic/pharmacodynamic profile and safety of 3 g of ceftolozane/tazobactam administered to ventilated, critically ill patients with pneumonia

Objectives: Ceftolozane/tazobactam is approved for hospital-acquired/ventilator-associated bacterial pneumonia at double the dose (i.e. 2 g/1 g) recommended for other indications. We evaluated the bronchopulmonary pharmacokinetic/pharmacodynamic profile of this 3 g ceftolozane/tazobactam regimen in ventilated pneumonia patients. Methods: This was an open-label, multicentre, Phase 1 trial (clinicaltrials.gov: NCT02387372). Mechanically ventilated patients with proven/suspected pneumonia received four to six doses of 3 g of ceftolozane/tazobactam (adjusted for renal function) q8h. Serial plasma samples were collected after the first and last doses. One bronchoalveolar lavage sample per patient was collected at 1, 2, 4, 6 or 8 h after the last dose and epithelial lining fluid (ELF) drug concentrations were determined. Pharmacokinetic parameters were estimated by noncompartmental analysis and pharmacodynamic analyses were conducted to graphically evaluate achievement of target exposures (plasma and ELF ceftolozane concentrations >4 mg/L and tazobactam concentrations >1 mg/L; target in plasma: similar to 30% and similar to 20% of the dosing interval, respectively). Results: Twenty-six patients received four to six doses of study drug; 22 were included in the ELF analyses. Ceftolozane and tazobactam T-max (6 and 2 h, respectively) were delayed in ELF compared with plasma (1h). Lung penetration, expressed as the ratio of mean drug exposure (AUC) in ELF to plasma, was 50% (ceftolozane) and 62% (tazobactam). Mean ceftolozane and tazobactam ELF concentrations remained >4 mg/L and >1mg/L, respectively, for 100% of the dosing interval. Therewere no deaths or adverse event-related study discontinuations. Conclusions: In ventilated pneumonia patients, 3 g of ceftolozane/tazobactam q8h yielded ELF exposures considered adequate to cover ceftolozane/tazobactam-susceptible respiratory pathogens

The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy

Background: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. Materials and methods: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. Results: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). Conclusions: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.  BACKGROUND: Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influ­ence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS: Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS: After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p &lt; 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS: In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

Multidirectional assessment of medical treatment influence on lower limb perfusion in patients suffering from obliterative atheromatosis

Wstęp. Przewlekłe niedokrwienie kończyn dolnych jest przedmiotem wielu badań, jednak w większości z nich nie dokonuje się porównania spoczynkowego i wysiłkowego przepływu naczyniowego. Medycyna nuklearna dysponuje metodami i programami pozwalającymi rozwiązać to zagadnienie. Celem pracy jest określenie za pomocą metod radioizotopowych zaburzeń perfuzji mięśni kończyn dolnych w spoczynku i po wysiłku u chorych z miażdżycą zarostową tętnic i porównanie wyników ze standardowymi metodami oceniającymi ukrwienie kończyn dolnych oraz ocena wpływu leczenia zachowawczego na analizowane parametry ukrwienia. Materiał i metody. Materiał stanowiło 35 pacjentów, leczonych zachowawczo z powodu niedokrwienia kończyn dolnych. Badaniem objęto chorych, którzy w momencie przyjęcia zgłaszali ziębniecie, drętwienie, chromanie przestankowe od 30-500 m. W celu kwalifikacji do grup u wszystkich chorych wykonano doplerowskie badanie USG kodowane kolorem. Do dalszych badań włączono chorych z drugim stopniem według klasyfikacji Foutaine&#8217;a (IIa i IIb), których dystans chromania wahał się w granicach 30÷500 m. Leczenie zachowawcze obejmowało modyfikację czynników i skojarzoną farmakoterapię oraz określenie wskaźników kostka-ramię, udo-goleń i udo-kostka. Radioizotopowe badania perfuzji mięśni kończyn dolnych w spoczynku i po wysiłku wykonywano za pomocą gamma-kamery według własnej metody i programu ALLP, określających wskaźniki perfuzji w badanych mięśniach. Wnioski. 1. Sześciomiesięczne leczenie zachowawcze, w tym skojarzone leczenie farmakologiczne, powoduje niewielką poprawę ukrwienia w zakresie krążenia w kończynach dolnych polegającą głównie na wzroście wartości wskaźnika kostka-ramię, obniżeniu wartości wskaźników udo-kostka i udo-goleń oraz poprawie prędkości przepływu we wszystkich badanych tętnicach. 2. Bardzo czułym i wartościowym badaniem określającym zmiany ukrwienia kończyn dolnych (goleni i ud) w spoczynku i po wysiłku, po zastosowaniu terapii zachowawczej, jest radioizotopowe badanie perfuzji mięśni. Uzyskane wskaźniki perfuzji precyzyjnie informują o wielkości zmian w mikrokrążeniu oraz pozwalają monitorować efekty leczenia zachowawczego. 3. Metoda radioizotopowa komplementarnie uzupełnia dotychczasową diagnostykę zaburzeń ukrwienia mięśni kończyn dolnych u chorych z miażdżycą zarostową tętnic.Background. Chronic lower-limb ischaemia has been the subject of several studies; however, most of them do not give a comparison between vascular flow at rest and vascular flow after exercise. Nuclear medicine is vested with methods and programmes allowing the solution of this matter. The aim of this study was to define, with the use of radioisotopic methods, the perfusion disturbances of lower limb muscles at rest and after exercise in patients with arterial obliterative atheromatosis, and to compare the results with the standard methods assessing lower limb perfusion, as well as to assess the influence of the medical treatment on the analyzed parameters of the perfusion. Material and methods. The material included 35 patients, medically treated because of lower limbs ischaemia. The study covered patients who, at the time of admission, reported feeling cold, numbness and intermittent claudication at 30 to 500 m For group classification, all the patients underwent USG-Doppler examination with a colour option. The patients with the second degree according to Foutaine (IIa, IIb), whose claudication distance ranged between 30 and 500 m, were included in the study. Medical treatment included modification of the factors and combined pharmacotherapy, and defining factors: ankle-brachial, femoral-tibial and femoral-ankle. Radioisotopic examinations of lower limb perfusion at rest and after exercise were performed with the use of a gamma camera according to our own method and an ALLP programme defining the perfusion indicators in the examined muscles. Conclusions. 1. A six-month period of medical treatment, including combined pharmacological treatment, causes a slight increase of lower limb perfusion, expressed mainly by an increase of the ankle-brachial index, decrease of the femoral-ankle and femoral-tibial indexes, and improvement of the speed of flow in all examined arteries. 2. Radioisotopic examination of muscle perfusion is a very precise and beneficial examination defining the changes in perfusion in the lower limbs (tibias and femora) at rest and after exercise. The obtained perfusion indexes give precise information about the scale of changes in microcirculation and allow the effects of the medical treatment to be monitored. 3. The radioisotopic method has completed previous diagnostics of lower limb perfusion disturbances in patients suffering from arterial obliterative atheromatosis

The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study

Introduction: While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations. Methods: A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status. Results: The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families. Conclusions: Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy

Are we close to the QGP? - Hadrochemical vs. microscopic analysis of particle production in ultrarelativistic heavy ion collisions

Ratios of hadronic abundances are analyzed for pp and nucleus-nucleus collisions at sqrt(s)=20 GeV using the microscopic transport model UrQMD. Secondary interactions significantly change the primordial hadronic cocktail of the system. A comparison to data shows a strong dependence on rapidity. Without assuming thermal and chemical equilibrium, predicted hadron yields and ratios agree with many of the data, the few observed discrepancies are discussed.Comment: 12 pages, 4 figure

CB1 Expression Is Attenuated in Fallopian Tube and Decidua of Women with Ectopic Pregnancy

BACKGROUND: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known. METHODS AND FINDINGS: Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p<0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant. CONCLUSIONS: CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool

Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies

Background: An increasing number of neo-adjuvant breast cancer studies are being conducted and a novel model for tumor biological studies, the "window-of-opportunity" model, has revealed several advantages. Change in tumor cell proliferation, estimated by Ki67-expression in pre-therapeutic core biopsies versus post-therapeutic surgical samples is often the primary end-point. The aim of the present study was to investigate potential differences in proliferation scores between core biopsies and surgical samples when patients have not received any intervening anti-cancer treatment. Also, a lack of consensus concerning Ki67 assessment may raise problems in the comparison of neo-adjuvant studies. Thus, the secondary aim was to present a novel model for Ki67 assessment. Methods: Fifty consecutive breast cancer cases with both a core biopsy and a surgical sample available, without intervening neo-adjuvant therapy, were collected and tumor proliferation (Ki67, MIB1 antibody) was assessed immunohistochemically. A theoretical model for the assessment of Ki67 was constructed based on sequential testing of the null hypothesis 20% Ki67-positive cells versus the two-sided alternative more or less than 20% positive cells.. Results: Assessment of Ki67 in 200 tumor cells showed an absolute average proliferation difference of 3.9% between core biopsies and surgical samples (p = 0.046, paired t-test) with the core biopsies being the more proliferative sample type. A corresponding analysis on the log-scale showed the average relative decrease from the biopsy to the surgical specimen to be 19% (p = 0.063, paired t-test on the log-scale). The difference was significant when using the more robust Wilcoxon matched-pairs signed-ranks test (p = 0.029). After dichotomization at 20%, 12 of the 50 sample pairs had discrepant proliferation status, 10 showed high Ki67 in the core biopsy compared to two in the surgical specimen (p = 0.039, McNemar's test). None of the corresponding results for 1000 tumor cells were significant - average absolute difference 2.2% and geometric mean of the ratios 0.85 (p = 0.19 and p = 0.18, respectively, paired t-tests, p = 0.057, Wilcoxon's test) and an equal number of discordant cases after dichotomization. Comparing proliferation values for the initial 200 versus the final 800 cancer cells showed significant absolute differences for both core biopsies and surgical samples 5.3% and 3.2%, respectively (p < 0.0001, paired t-test). Conclusions: A significant difference between core biopsy and surgical sample proliferation values was observed despite no intervening therapy. Future neo-adjuvant breast cancer studies may have to take this into consideration