Recurrent mutations of BRCA1 and BRCA2 in Poland: an update.

Three founder alleles of BRCA1 (C61G, 4153delA, 5382insC) were reported in Poland in 2000, and these three mutations have comprised the standard testing panel used throughout the country. However, since 2000, other recurrent mutations of BRCA1 and BRCA2 have been reported. To establish if the inclusion of one or more of these mutations will increase the sensitivity of the standard test panel, we studied 1164 Polish women with unselected breast cancer diagnosed at age of 50 or below. All women were genotyped for 12 recurrent mutations of BRCA1 and BRCA2. We identified a mutation in 83 of 1164 patients (7.1%) including 61 women with one of the original three mutations (C61G, 4153delA, 5382insC) and 22 women with a different mutation (1.9%). Three new mutations (3819del5, 185delAG and 5370C>T) were seen in multiple families. By including these three mutations in the extended panel, the mutant frequency increased from 5.2 to 6.7%. Polish women with breast cancer diagnosed at age of 50 or below should be screened with a panel of six founder mutations of BRCA1 (C61G, 4153delA, 5382insC, 3819del5, 185delAG and 5370C>T).

The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues.

The properties of hyaluronic acid used for treatment of acute and chronic joint disease are known for many years and this compound is widely used both in humans and animals. To obtain a therapeutic effect of a certain drug, the appropriate concentration in the target organ or tissue is important. The application of labeled compounds is one of the frequently applied techniques to estimate drug penetration into the skin and other body tissues or organs. The aim of the study was to evaluate the penetration of hyaluronic acid labeled with I-131 through the skin and its distribution within the knee joint and other internal organs in rabbits after a topical application of an ointment containing hyaluronic acid. The experiment was performed on 22 albino rabbits divided into control and examined groups. Fifteen rabbits were exposed to the multicomponent ointment containing hyaluronic acid labeled with I-131. Time of exposure was 48 hours. Hyaluronate penetrated to a high degree into the examined tissues. No significant differences in terms of leg tissue activity were observed between a leg tissue exposed to labeled ointment and that unexposed, suggesting that after topical administration, the active component of the ointment is delivered to the joint via the blood stream. Hyaluronate applied topically penetrates through the skin into the rabbit tissues and organs and into the joint fluid of both legs (exposed and not exposed). This route of administration seems to be useful for this drug delivery and allows to avoid unnecessary side effects.

Thyroid Peroxidase Antibodies in Non-Autoimmune Hyperthyroidism Treated with Radioactive Iodine.

Introduction: Earlier studies suggest increased serum levels of thyroid peroxidase antibodies (TPOAb) in some cases with non-autoimmune hyperthyroidism. The aim of the study was to assess the incidence of hypothyroidism in patients with nodular toxic goitre and toxic adenoma at 12 months after radioactive iodine therapy in the relation to TPOAb levels. Patients & Measurements: The study comprised 100 patients (83 females; 17 males) treated with radioactive iodine therapy. Serum concentrations of thyrotropin, free thyroxin, TPOAb, and anti-TSH receptor antibodies were assessed at baseline and 12 months after radioactive iodine therapy. Results: High TPOAb level (>60.0 IU/mL) was found in 27% of patients at baseline and 32% at the follow-up. Baseline TPOAb values were higher in subjects with coexisting non-thyroid autoimmune disease (p=0.041). After radioactive iodine therapy, the mean TPOAb level increased in patients with normal baseline TPOAb (p=0.03) and the rates of euthyroidism and hypothyroidism were 61 and 34%, respectively. The rate of hypothyroidism after radioactive iodine therapy was not significantly different in groups with normal and high baseline TPOAb. Conclusions: 27% of patients with non-autoimmune hyperthyroidism were positive for TPOAb. However, baseline TPOAb level did not influence the rate of hypothyroidism at 12 months after radioactive iodine therapy. Our results suggest a more close surveillance after radioactive iodine therapy of patients harboring these antibodies.

A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a widespread functional disorder of the digestive tract. Its aetiology is unknown and therapeutic options are limited. Recent reports suggest that probiotics may have a role in regulating the motility of the digestive tract. AIM: To assess the efficacy of Lactobacillus plantarum 299V (LP299V) in patients with IBS. PATIENTS AND METHODS: Forty patients were randomized to receive either LP299V in liquid suspension (20 patients) or placebo (20 patients) over a period of 4 weeks. Clinical examination was performed at baseline and at the end of the study. Additionally, patients assessed their symptoms by applying a scoring system. RESULTS: All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group (P = 0.0012). There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo (P = 0.17). With regards to all IBS symptoms an improvement was noted in 95% of patients in the LP299V group vs 15% of patients in the placebo group (P < 0.0001). CONCLUSIONS: LP299V seems to have a beneficial effect in patients with IBS. Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS.

Quantitative evaluation of three-phase bone scintigraphy before and after the treatment of post-traumatic reflex sympathetic dystrophy.

Three-phase bone scans performed in 65 patients with post-traumatic reflex sympathetic dystrophy (RSD) were reviewed to evaluate which changes in uptake of the tracer appear before and after treatment, whether the form of treatment affects the intensity of uptake, and to investigate the correlation between the results of treatment and the intensity of the uptake both at initial and final scintigraphic examination. Forty-nine patients were treated using three different methods; 16 patients were observed without treatment. Bone scintigraphy was performed twice in each patient: first before treatment or observation and then at the final assessment, from 6 to 18 months after the end of treatment. Clinical results were rated as follows: good, moderate and poor. Scintigrams were evaluated quantitatively after processing the data obtained from the selected regions of interest. A significant reduction in the initially increased uptake of the tracer was noted in each phase/region of interest 6-18 months after initial imaging. At final assessment, mean uptake ratios in treated and non-treated patients were similar. This suggests that treatment does not affect the rate of reduction of uptake. In patients with good and moderate response to treatment, mean uptake ratios at initial scanning were significantly higher than in patients with poor outcome. This indicates that three-phase bone scintigraphy has prognostic value in RSD: marked hyperfixation of the tracer indicates better final outcome. At final imaging, the mean uptake ratios of patients with good, moderate and poor response to treatment did not differ significantly. This suggests that three-phase bone scintigraphy has no value in monitoring the course of treatment of RSD.

Clinical outcomes of patients with suspected pulmonary embolism using 99Tcm-Technegas as a ventilatory agent for lung scanning.

Clinical outcome analysis was carried out in 175 of 206 consecutive patients referred for a lung scan with clinical suspicion of pulmonary embolism (PE). The follow-up time period ranged from 4 to 18 months. High-quality ventilation images corresponding to the six standard perfusion images were obtained using Technegas as a ventilatory agent. Lung scan reports showed that 22% of the patients had a high, 14% indeterminate, 18% low and 9% very low probability for PE and 37% were normal lung scans. These reports usually supported the referring clinicians' provisional diagnosis and were confirmed by the clinical outcome analysis of these patients giving an apparent sensitivity for the lung scan of 96% and specificity 93%. A strategy for lung scanning in PE is proposed.

Computer-generated attenuation correction does not improve the accuracy of myocardial perfusion scintigraphy.

A short study was performed to determine if it is possible to increase the accuracy of thallium-201 (201T1) single photon emission tomographic myocardial perfusion imaging using computer-generated ('Chang') attenuation correction. The stress and rest myocardial perfusion studies from 22 patients with suspected or known ischaemic heart disease were reconstructed with and without "Chang' attenuation correction. For all patients, the scintigraphy results were compared with those of coronary angiography. Attenuation correction improved the accuracy of 201T1 myocardial perfusion imaging for defining myocardial ischaemia or infarction in 8% of coronary artery territories (23% of patients), but it was worse in 5% of coronary artery territories (14% of patients). These changes were not significant (McNemar's test). Therefore, computer-generated 'Chang' attenuation correction does not appear to improve the accuracy of myocardial perfusion scintigraphy. It is important that all techniques suggested to improve the accuracy of clinical images should be tested on patients before being widely used.

A prospective study comparing SPET with MRI and CT as prognostic indicators following severe closed head injury.

Ten patients were studied prospectively afer severe closed head injury to determine the relationship between long-term clinical outcome and abnormalities detected by single photon emission tomography (99Tcm-HMPAO SPET), CT and MRI obtained within 60 days of injury. The ability of SPET to detect abnormalities not visualized by CT or MRI after cerebral trauma by the results of this study. Changes detected by SPET [global cerebral blood flow (gCBF) and number of regional cerebral blood flow (rCBF) deficits] soon after trauma were shown to be more closely correlated with long-term outcome than changes detected by MRI or CT. Templates were used to classify lesions by site and a multivariate analysis was undertaken to establish the importance of defect position in predicting clinical outcome. The results suggest that lesions in the temporal lobes, frontal lobes and basal ganglia are related to poor prognosis, and that SPET yields more useful prognostic data than the other methods.

Clinical efficacy of 'essential' phospholipids in patients chronically exposed to organic solvents.

A total of 45 workers, who had been chronically exposed to a potentially hepatotoxic xylene-toluene-benzene mixture in the atmosphere, were treated for 3 months with 'essential' phospholipids. Routine biochemical tests and radioisotope investigations to assess liver damage were carried out both at baseline and after treatment. The liver:spleen index was increased in 71% of subjects and the mean isotope transit time in the liver was reduced in 90% of the patients after treatment. The biochemical parameters remained within the normal range throughout the treatment period. The results suggest that 'essential' phospholipids may be of value in the treatment of liver damage that has arisen as a result of chronic exposure to organic solvents.

[Renoscintigraphy applied with etylenedicysteine labeled with technetium 99m and SPECT technique as a method of examining kidneys in children with vesicoureteric reflux]. / Renoscyntygrafia z zastosowaniem etylenodicysteiny znakowanej technetem 99m oraz technika SPECT jako metody badania nerek u dzieci z rozpoznanymi wstecznymi odplywami pechorzowo-moczowodowymi.

Vesicoureteric reflux (VUR) can lead to renal parenchymal damage. Renal scarring is an important cause of chronic renal failure and hypertension in children. The significance of possible effects determines the necessity of early diagnosis of urinary tract pathology. The aim of the paper was to evaluate the morphology and function of kidneys with VUR using selected radioisotope techniques, and to compare the sensitivity of planar technique and single-photon emission computed tomography (SPECT) technique in detection of renal scarring. In 45 children with VUR the following test were performed: ultrasonography, renoscintigraphy with technetium-99m-ethylenedicysteine (EC-Tc-99m) and technetium-99m-dimercaptosuccinic acid (DMSA-Tc-99m) scintigraphy with planar and SPECT mode. Stage of VUR correlates with stage of cortical lesions estimated as a value of effective renal plasma flow (ERPF) in kidney, as well as scarring intensity in static scintigraphy. The use of SPECT increases sensitivity of examination for detection small, single scars. It seems that SPECT should be used more frequently in children in the group of scarring risk. That would allow for earlier diagnosis of renal scarring, enabling efficient treatment. Due to the correlation between ERPF and parameters obtained in DMSA scintigraphy, renoscintigraphy with EC-Tc-99m may be applied to monitor the progress of renal scarring.

Quantitative SPECT/CT reconstruction for ¹77Lu and ¹77Lu/9°Y targeted radionuclide therapies.

We investigated the quantitative accuracy of SPECT/CT imaging studies as would be performed before and after targeted radionuclide therapy (TRT) using phantom experiments with (i) (99m)Tc, (ii) ¹77Lu and (iii) 9°Y/¹77Lu. While the experiment with (99m)Tc imitated a diagnostic scan, the experiments with ¹77Lu and 9°Y/¹77Lu modeled post-therapy acquisitions. At the next stage, we reconstructed images from pre- and post-therapy patient studies. The data were first reconstructed using two methods with limited corrections for the physics effects. Then, to generate quantitatively accurate absolute activity distributions, we applied a hybrid (model-based and window-based) reconstruction strategy where some of the physics effects were accurately modeled while corrections for other effects were empirical and based on information obtained from the projection data. The accuracies of absolute activity recovered by the hybrid method from the six phantom experiments were very similar to each other and acceptable for potential use in TRT. When measured in identical regions of interest, the (99m)Tc 9°activity was reconstructed with errors ranging between -3.3% and 2.9%, while the ¹77Lu activity was reconstructed from experiments with ¹77Lu and Y/¹77Lu with errors ranging between -1.6% and 1.6%. The reconstruction algorithms with limited corrections led to larger and case-specific errors as might have been expected. From a clinical prospective, our results showed that physics-based reconstructions improved resolution of images corresponding to both diagnostic scans with (99m)Tc and post-therapy scans with ¹77Lu. Our analysis of patient study demonstrated that lack of corrections led to overestimation of activities in organs and tumor by 29-39% for the diagnostic scan with (99m)Tc and by 105-218% for post-therapy scan with ¹77Lu.

Long-term monitoring of radiation exposure of employees in the department of nuclear medicine (Szczecin, Poland) in the years 1991-2007.

Occupational radiation exposure is a hazard that should be avoided or at least minimised. This study aimed to evaluate the radiation exposure of nuclear medicine department employees monitored during the 1991-2007 period, and to investigate the relationship between the annual effective doses of the personnel and the number of radioisotope procedures performed. Overall, 2014 quarterly effective whole-body doses, categorised into six occupational groups, monitored with personal dosemeters, were analysed statistically. There was a wide variation in the average annual doses among the different occupational groups. During the 17 years covered by this study, there was no incidence of a dose exceeding the annual dose limit of 20 mSv. There was a weak correlation between the average annual dose for monitored employees and the number of nuclear medicine procedures performed. Apart from exposure, personal skill in dealing with radioactive substances, compliance with radiation protection rules is an important factor to minimise the effective dose.

[Scintigraphic bone scans in evaluation of aseptic and septic hip prosthesis loosening]. / Badanie scyntygraficzne koscca w ocenie aseptycznego i septycznego obluzowania endoprotez stawu biodrowego.

The results of clinical examination, three-phase bone scintigraphy and intraoperative findings were compared in 29 patients. Scintigraphic criteria of infection or aseptic loosening have been presented. The method proved to be highly useful with sensitivity, specificity and accuracy being 100, 73 and 90 per cent respectively.