Pretreatment Cancer-Related Cognitive Impairment in Hodgkin Lymphoma Patients.

BACKGROUND: Cancer-related cognitive impairment (CRCI) is one of the most serious side effects of cancer that negatively impacts the quality of life of cancer patients and survivors. There is evidence of CRCI in Hodgkin lymphoma patients (HL); however, there is a lack of studies examining the presence of cognitive deficits before starting any treatment in HL patients. METHODS: Forty adult patients (N = 40) newly diagnosed with HL (with no previous cancer diagnoses) and 40 healthy controls (N = 40) matched for age, sex, education, and premorbid intellect completed the neuropsychological battery and subjective and objective measures of affective distress and quality of life. RESULTS: The results showed impairment in three out of six cognitive domains: verbal memory and learning, speed of processing/psychomotor speed, and abstraction/executive functions in the HL patients before the initiation of any treatment. The speed of processing/psychomotor speed domain is negatively correlated with depression. CONCLUSION: Cognitive deterioration in verbal memory and learning and abstraction/executive functions domains in HL patients seems to occur before the initiation of treatment independently of anxiety, depression, or physical symptoms. This suggests that HL itself may cause cognitive deficits in these cognitive domains. However, the underlying causes of CRCI still remain unclear.

Several reasons why ketamine as a neuroplastic agent may have failed to prevent postoperative delirium: Implications for future protocols.

Ketamine exerts anti-inflammatory, neuroprotective and neuroplastic activity, therefore it may counteract the neurotoxic processes underlying postoperative delirium. However, the majority of studies in this field failed. We identified several pharmacological reasons why these studies may have failed, together with suggestions of how to remediate them. Among them, the interaction with intravenous general anesthetics exerting the opposite effect on GABA interneurons than ketamine may be of principal importance. We suggest biomarkers which may elucidate the influence of this interaction on the different steps of neuroplastic pathways. We hypothesize that administering ketamine before or after general anesthesia could both prevent the interactions and strengthen the effect of ketamine by timing surgery within the climax of ketamine-induced neuroplastic changes or by stabilizing AMPA receptors. It is vital to deal with these questions because the protocols of ongoing studies are based again on the administration of ketamine during general anesthesia (the major identified pitfall).

Cognitive impairment associated with Hodgkin's lymphoma and chemotherapy.

Chemotherapy-related cognitive impairment (CRCI) is a well-documented side effect of cancer treatment in various types of tumors including Hodgkin's lymphoma (HL). However, a longitudinal study evaluating the cognitive performance of HL patients has been completely lacking. The aim of the study was to determine the presence of CRCI in HL patients before, promptly after, and 6 months after treatment. Thirty-six patients newly diagnosed with HL and 45 healthy controls (HC) completed the neuropsychological battery and psychological measures of affective distress and quality of life. The results indicate that HL patients have impaired performance compared to HC which cannot be explained by emotional factors. Cognitive impairments prior to treatment were found in 3 of 6 cognitive domains, i.e., verbal memory and learning, speed of processing/psychomotor speed, and abstraction/executive function. Promptly after the chemotherapy, deficits were found in the domains of memory and learning, verbal memory, speed of processing/psychomotor speed, and abstraction/executive function. Weaker cognitive performance persist even 6 months after the end of chemotherapy, specifically in domains of verbal memory and learning, and abstraction/executive function. Our results indicate the presence of cognitive impairment in HL patients already prior to treatment and increased damages caused by chemotherapy, while some of them may last for up to 6 months after the treatment.

Molecular Mechanisms Underlying Flax (Linum usitatissimum L.) Tolerance to Cadmium: A Case Study of Proteome and Metabolome of Four Different Flax Genotypes.

Cadmium is one of the most toxic heavy metal pollutants, and its accumulation in the soil is harmful to agriculture. Plants have a higher cadmium tolerance than animals, and some species can be used for phytoremediation. Flax (Linum usitatissimum L.) can accumulate high amounts of cadmium, but the molecular mechanism behind its tolerance is unknown. Here, we employed four genotypes representing two fiber cultivars, an oilseed breeding line, and a transgenic line overexpressing the metallothionein domain for improved cadmium tolerance. We analyzed the proteome of suspensions and the proteome and metabolome of seedling roots in response to cadmium. We identified more than 1400 differentially abundant proteins representing putative mechanisms in cadmium tolerance, including metal-binding proteins and transporters, enzymes of flavonoid, jasmonate, polyamine, glutathione metabolism, and HSP70 proteins. Our data indicated the role of the phytohormone cytokinin in the observed responses. The metabolome profiling found that pipecolinic acid could be a part of the cadmium accumulation mechanism, and the observed accumulation of putrescine, coumaric acid, cinnamic acid, and coutaric acid confirmed the role of polyamines and flavonoids in tolerance to cadmium. In conclusion, our data provide new insight into cadmium tolerance and prospective targets for improving cadmium tolerance in other plants.

Effect of Lactic Fermentation and Cooking on Nutrient and Mineral Digestibility of Peas.

Peas are prospectively beneficial legumes in the human diet, and especially in a vegan and vegetarian diet, due to their high content of proteins and starch. Their frequent lack of appeal in human nutrition can be caused by their bloating effect and the content of some antinutritional compounds inhibiting the absorption of important nutrients. This study brings a comprehensive comparison of the nutrient content of pea flour after cooking and lactic fermentation before and after digestion in vitro. As a control sample, raw pea flour was used (sample 1). Raw pea flour was cooked for 10 min (sample 2) and 120 min (sample 3) at 100°C or it was fermented by Lactobacillus plantarum (sample 4) and cooked for 10 min at 100°C (sample 5). The samples were analyzed for protein and amino acids content, maltose, glucose, raffinose, total polyphenols, phytic acid, phytase, and mineral composition (P, Mg, Mn, Fe, Cu, Zn) before and after in vitro digestion. The results showed a significant (p < 0.05) increase in the protein digestibility of samples 3, 4 and 5. In the fermented samples were observed a higher concentration of Cys, Met, and Gln when compared to non-fermented samples. The fermentation of pea flour resulted in a significant (p < 0.05) decrease in glucose, maltose, and raffinose content. Cooking of pea flour for 10 and 120 min, but not fermenting, significantly (p < 0.05) decreased the polyphenols content. Cooking and fermentation together did not affect phytic acid concentration and phytase activity. Mg, Mn, Fe, Cu and, Zn concentration in pea flour was significantly (p < 0.05) decreased by cooking. On the other hand, fermentation significantly (p<0.05) improved the bioaccessibility of Mn and Fe. These findings suggest that lactic fermentation of pea flour is a promising culinary preparation that can improve the digestibility of peas.

Thyroid nodules and thyroid cancer in women with positive thyroid screening in pregnancy: a double-centric, retrospective, cohort study.

OBJECTIVE: Thyroid nodules are a common finding in the general population. The primary aim of the study was to determine the prevalence of thyroid nodules and cancer found by ultrasound (US) in women who underwent screening for thyroid dysfunction during pregnancy. DESIGN: A double-centric, retrospective, cohort study. PATIENTS AND METHODS: We searched through medical records, including thyroid ultrasonography, of pregnant women who were positively screened for thyroid disorders (using thyroid-stimulating hormone and thyroid antibodies) from an unselected population ('universal screening group', n = 690) and of women who underwent the testing based on the presence of clinical risk factors defined by American Thyroid Association ('case-finding group', n = 249). RESULTS: Prevalence of benign and malignant thyroid nodules was lower in the 'universal screening group' than in the 'case-finding group' (9.9% vs 17.7%, P= 0.002, and 0.9% vs 7.2%, P< 0.001, respectively). Consistently, the thyroid cancer rate was lower among the nodules in the 'universal screening group' than in the 'case-finding group' (8.1% vs 29.0%, P= 0.003). Ultrasound EU-TIRADS (European Thyroid Imaging and Reporting Data System) category ≥4 had a 95.8% sensitivity for thyroid cancer. In palpable nodules, the prevalence of cancer was significantly higher than in the non-palpable ones (44.0% vs 2.2%, P < 0.001). In a multivariate regression analysis, thyroid nodules were associated with a history of infertility and parity. CONCLUSIONS: Compared to the data from cancer registries, universal screening allowed detecting thyroid cancer in pregnancy three to five times more frequently, but the cancer rate among nodules (8.1%) did not differ from the common population. US had very good sensitivity for thyroid cancer in pregnancy.

Scintigraphic evaluation of salivary gland function in thyroid cancer patients after radioiodine remnant ablation.

Radioiodine (131 I, RAI) has traditionally been used in thyroid cancer treatment but its benefit should be balanced against possible risks. Among them, salivary gland dysfunction has often been discussed, although the reported data have been inconsistent. The aim of our prospective study was to evaluate salivary gland function in 31 thyroidectomised patients (6 men, 25 women; median age 52 yr) before and 4-6 months after RAI remnant ablation (RRA), using activity of 3.7 GBq 131 I-NaI. Salivary gland uptake and excretion fractions were quantitatively assessed with 99m Tc - pertechnetate salivary gland scintigraphy. Pre- and post-treatment values were compared using Wilcoxon signed rank test. No statistically significant difference in the pre- and post-treatment values was observed in parotid or submandibular glands uptake, or in the parotid or submandibular excretion fractions. The calculated power for minimum relevant difference of 25% with the sample size of 31 ranged between 86% and 96% for the individual variables, making our negative results reasonably reliable. The results suggest that RRA with the most commonly used activity of 3.7 GBq has no important impact on salivary gland function. Therefore, the concerns about putative salivary gland functional deterioration following RRA are probably unjustified.

Salivary gland function in thyroid cancer patients with radioiodine administration history.

AIM: Radioiodine (RAI) improves survival in patients with locally advanced or metastatic differentiated thyroid carcinoma (DTC). Although there has been an ongoing debate on RAI-induced salivary gland damage, published data have been inconsistent. Therefore, the purpose of our study was to compare salivary gland function in intermediate and high risk DTC patients after single or repeated RAI treatment with their age- and sex-matched RAI-naive counterparts. METHODS: Uptake and excretion of parotid and submandibular glands were quantitatively evaluated using 99mTc-pertechnetate salivary gland scintigraphy in 23 patients previously treated with RAI. Patients (median 9.25 GBq 131I-NaI; Q1-Q3: 5.55-16.65; range: 5.55-27.5) were divided into subgroups according to previously administered 131I-NaI activity using cut-off values 5.55 GBq and 9.25 GBq. Their salivary gland scintigraphy results were compared with RAI-naive patients using Mann-Whitney test. RESULTS: Compared to RAI-naive patients, parotid glands pertechnetate uptake was significantly lower in those treated with > 9.25 GBq (P=0.034) and parotid glands excretion fraction was already decreased with RAI activities > 5.55 GBq (P=0.031). In submandibular glands, no statistically significant difference in either function was observed even with RAI activity > 9.25 GBq. CONCLUSION: Our data suggest that RAI therapy using activities ≤ 5.55 GBq does not substantially decrease saliva production. Activities > 5.55 GBq may lead to significant decrease in parotid excretion, and activities > 9.25 GBq also diminish parotid uptake. Surprisingly, submandibular glands, providing majority of seromucinous saliva under basal condition, seem to be unaffected even by RAI activities above 9.25 GBq.

The effect of gabapentin and pregabalin on bone turnover and bone strength: A prospective study in Wistar rats.

BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

Cannabis-induced altered states of consciousness are associated with specific dynamic brain connectivity states.

BACKGROUND: Cannabis, and specifically one of its active compounds delta-9-tetrahydrocannabinol in recreational doses, has a variety of effects on cognitive processes. Most studies employ resting state functional magnetic resonance imaging techniques to assess the stationary effects of cannabis and to-date one report addressed the impact of delta-9-tetrahydrocannabinol on the dynamics of whole-brain functional connectivity. METHODS: Using a repeated-measures, within-subjects design, 19 healthy occasional cannabis users (smoking cannabis ⩽2 per week) underwent resting state functional magnetic resonance imaging scans. Each subject underwent two scans: in the intoxicated condition, shortly after smoking a cannabis cigarette, and in the non-intoxicated condition, with the subject being free from cannabinoids for at least one week before. All sessions were randomized and performed in a four-week interval. Data were analysed employing a standard independent component analysis approach with subsequent tracking of the functional connectivity dynamics, which allowed six connectivity clusters (states) to be individuated. RESULTS: Using standard independent component analysis in resting state functional connectivity, a group effect was found in the precuneus connectivity. With a dynamic independent component analysis approach, we identified one transient connectivity state, characterized by high connectivity within and between auditory and somato-motor cortices and anti-correlation with subcortical structures and the cerebellum that was only found during the intoxicated condition. Behavioural measures of the subjective experiences of changed perceptions and tetrahydrocannabinol plasma levels during intoxication were associated with this state. CONCLUSIONS: With the help of the dynamic connectivity approach we could elucidate neural correlates of the transitory perceptual changes induced by delta-9-tetrahydrocannabinol in cannabis users, and possibly identify a biomarker of cannabis intoxication.

Dual Tracer 99mTc-Pertechnetate/99mTc-MIBI Dual-Time-Point SPECT/CT Parathyroid Gland Assessment Regarding to Parathyroid Gland Size and Biochemical Parameters - Two Years Single Imaging Centre Experience.

INTRODUCTION: Preoperative parathyroid imaging is inevitable part of focused parathyroid surgery. The aim of our study was assessment of parathyroid scintigraphy diagnostic accuracy regarding to size and metabolic parameters of hyperfunctioning parathyroid tissue. MATERIAL AND METHODS: Parathyroid scintigraphy for suspected primary hyperparathyroidism was performed in 95 patients during years 2015 and 2016. Of them, 75 patients with known clinical outcome (40 underwent surgery, 35 had documented laboratory follow-up) were further retrospectively evaluated. The performance of dual tracer 99mTc-pertechnetate and 99mTc-MIBI subtraction and dual-time-point 99mTc-MIBI imaging with SPECT/CT was analysed. Serum parathyroid hormone (PTH), calcaemia, ionized calcaemia and phosphataemia and ultrasound detected adenoma volume and largest diameter in false negative and true positive findings were compared using Mann-Whitney test. RESULTS: Sensitivity and specificity of parathyroid scintigraphy was 74.5% and 95.8%, respectively. NPV was 63.8% and PPV 97.4%. Hyperfunctioning parathyroid tissue detectability was almost significantly associated with hypophosphataemia and PTH levels. CONCLUSION: Parathyroid scintigraphy provides high sensitivity and superior specificity in parathyroid adenoma location, nevertheless the diagnostic accuracy tends to decline in smaller adenomas and in less metabolically active parathyroid tissue causing only subtle biochemical changes. 18F-Fluorocholine PET/CT or 3D SPECT/CT subtraction should be a reasonable option for those cases.

Effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on MK-801-induced schizophrenia models.

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

Parathyroidectomy in Hyperparathyroidism-Associated Calciphylaxis in End-Stage Renal Disease Should be Prompt and Radical - a Case Report with Two Original Therapeutic Modifications and Successful Outcome.

We present a case of severe calciphylaxis in both thighs and calves in a patient with end-stage renal disease and advanced secondary hyperparathyroidism with successful outcome after modified therapeutic approach. The cause of calciphylaxis is multifactorial. In our case, not only severe hyperparathyroidism and mediocalcinosis, but also medication (warfarin, calcium and active vitamin D) was involved. Because the initial conservative therapy was not successful, we indicated parathyroidectomy. However, we were not able to localize parathyroid glands and we contraindicated bilateral neck exploration due to the patient's critical status. Therefore, we decided for total thyroidectomy with total parathyroidectomy. Surgery was uncomplicated and histology confirmed that all four parathyroid glands were removed. The expected post-operative hypocalcaemia was asymptomatic and we did not use any calcium supplementation or vitamin D. Thyroid hormone replacement was easy. After surgery, the large and multiple subcutaneous defects started to heal. We achieved complete healing within several months of continuing dedicated care. There is no recurrence after three years. Prompt and radical surgical parathyroidectomy was extremely useful in our patient.

Is radioiodine administration in patients with papillary thyroid multifocal microcarcinoma unnecessary?

UNLABELLED: Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient's upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria. LEARNING POINTS: (131)I is a combined beta-gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging.RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging.RAI should be considered also in "low-risk" patients, especially when the lymph node involvement is not reliably documented.Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.

ISPD gene homozygous deletion identified by SNP array confirms prenatal manifestation of Walker-Warburg syndrome.

Walker-Warburg syndrome (WWS) is a rare form of autosomal recessive, congenital muscular dystrophy that is associated with brain and eye anomalies. Several genes encoding proteins involved in abnormal α-dystroglycan glycosylation have been implicated in the aetiology of WWS, most recently the ISPD gene. Typical WWS brain anomalies, such as cobblestone lissencephaly, hydrocephalus and cerebellar malformations, can be prenatally detected through routine ultrasound examinations. Here, we report two karyotypically normal foetuses with multiple brain anomalies that corresponded to WWS symptoms. Using a SNP-array examination on the amniotic fluid DNA, a homozygous microdeletion was identified at 7p21.2p21.1 within the ISPD gene. Published data and our findings led us to the conclusion that a homozygous segmental intragenic deletion of the ISPD gene causes the most severe phenotype of Walker-Warburg syndrome. Our results also clearly supports the use of chromosomal microarray analysis as a first-line diagnostic test in patients with a foetus with one or more major structural abnormalities identified on ultrasonographic examination.

[Indoleamine 2,3-dioxygenase in oncology and psychiatry]. / Indolamin 2,3-dioxygenáza v onkologii a psychiatrii.

In the last years an attention has been paid to the indoleamine 2,3-dioxygenase (IDO), an enzyme catabolising L-tryptophan to kynurenine. Growing evidence has been accumulated that kynurenine and other metabolites of tryptophan play an important role in the pathogenesis of malignant tumours and some neurological and psychiatric disorders. The gradual recognition of mechanisms operative in their development may help to identify etiological factors involved and becomes prerequisite for the progress in their diagnostics and therapy. In oncology, great effort is directed to the development and testing of substances inhibiting IDO activity. It is expected that some of them will be utilized in the immunotherapy of cancer. In the field of psychiatric disorders, namely in schizophrenia and depression, the role of IDO is linked to immune dysregulation. In those diseases, IDO represents a potential mediator between immunological reactivity and alterations of the brain function. Changes in the IDO activity may also mediate interaction between the genetic predisposition and environmental factors.

Prothrombotic changes due to an increase in thyroid hormone levels.

OBJECTIVE: With increasing free thyroxine levels, a gradually rising risk of venous thromboembolism has been described in case-control studies. However, reports on the influence of thyroid hormones on haemostasis, while suggesting a hypercoagulable state in thyrotoxicosis, have often been inconclusive. This study evaluates multiple markers of haemostasis and fibrinolysis in a paired design, making it more sensitive to changes in thyroid hormone levels. DESIGN: We analysed multiple variables in patients who shifted from severe hypothyroidism to mild hyperthyroidism during thyroid cancer treatment. Those with possible residual disease were excluded. METHODS: Ninety patients following total thyroidectomy were tested on two occasions: i) before radioiodine remnant ablation and ii) 6 weeks later, on levothyroxine (lT4) suppression treatment, and the results were compared using the Wilcoxon's test for paired data. RESULTS: During lT4 treatment, significant increases (all P<0.001) in fibrinogen (from median 3.4 to 3.8 g/l), von Willebrand factor (from 85 to 127%), factor VIII (from 111 to 148%) and plasminogen activator inhibitor 1 (from 6.5 to 13.9 µg/l) were observed. In addition, the activation times of platelet adhesion and aggregation stimulated with collagen and epinephrine (EPI)/ADP, i.e. closure times in platelet function analyser (PFA-100), were significantly shortened (P<0.001): for EPI from median 148 to 117 s and for ADP from 95 to 80 s. Changes in other tests were less prominent or insignificant. CONCLUSIONS: An increase in thyroid hormone levels shifts the haemostatic balance towards a hypercoagulable, hypofibrinolytic state. This may contribute to the increased cardiovascular morbidity and mortality observed even in mild thyrotoxicosis.

The effect of lacosamide on bone tissue in orchidectomised male albino Wistar rats.

AIMS: While most antiepileptic drugs (AEDs) have been associated with various adverse effects on bone health, for the recently introduced lacosamide (LCM) no corresponding data have been published. The present study evaluates the effect of LCM on bone mineral density, bone turnover markers, and bone mechanical strength in a rat model. METHODS: 16 orchidectomized Wistar rats were divided into control and experimental groups, 8 rats each. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). As bone metabolism markers, the concentrations of bone markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. RESULTS: Compared to the control group, we found lower BMD in the experimental group in the area of the left (8%) as well as the right femur (12%), all differences being statistically significant. In both femur diaphyses, but not in lumbar vertebrae, BMD was lower in the LCM group, suggesting a preferential effect on cortical bone. However, neither the thickness of the diaphyseal cortical bone nor the fragility in biomechanical testing was different between the groups. Of the bone metabolism markers, the significant decline was in procollagen type I N-terminal peptide (PINP) levels (37.4%), suggesting a decrease in osteoid synthesis. CONCLUSION: We assume then that long-lasting exposure to LCM can represent a certain risk to the health of bone in the setting of gonadal insufficiency. Further studies will be needed to confirm these findings and to determine how high the risk will be in comparison to the other AEDs.

[The occurrence of agranulocytosis due to antithyroid drugs in a cohort of patients with Graves disease treated with radioactive iodine 131I during 14 years]. / Výskyt agranulocytózy po tyreostaticích v kohorte pacientu s Gravesovou nemocí lécených radioaktivním jodem 131I v prubehu 14 let.

INTRODUCTION: Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit. PATIENTS AND METHODS: We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU). RESULTS: Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8). CONCLUSION: Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.