Prostate Cancer in Deceased Organ Donors: Loss of Organ or Transplantation With Active Surveillance.

INTRODUCTION: Prostate cancer has become an important clinical issue within deceased organ donors. There is still a considerable number of undiagnosed cancers, especially in early stage, despite frozen section analysis. The aim of the study was to evaluate outcomes of orthotopic liver transplants (OLTx) with organs from donors with prostate cancer. MATERIAL AND METHODS: A retrospective analysis was performed in deceased liver donors whose prostate glands were harvested for histologic examinations because of prostate cancer suspicion. The study group consisted of 72 men reported as potential liver donors between 2011 and November 2017. Prostate glands were primarily assessed by frozen sections and afterward in routine examination. Generally cancer diagnosed in frozen specimen was not considered for OLTx. Recipients who received an organ from the donor with prostate cancer were actively surveilled. RESULTS: There were 19 cases (26.40%) of prostate cancer diagnosed among the study group. In 12 cases diagnosis was made by frozen section assessment, of which 11 organs were disqualified from OLTx and 1 was transplanted. In 7 cases prostate cancer was diagnosed after OLTx in final routine histologic examination. Finally, 8 recipients (5 men and 3 women) received a new organ. Only 1 died during the perioperative period. In the remaining 7 patients the perioperative period was uneventful and no disease transmission was observed during follow-up. CONCLUSIONS: Diagnosis of prostate cancer in donors should not be treated as a contraindication for OLTx because the risk of disease transmission is low. Potential recipients must be fully informed and kept under oncological surveillance.

CT Angiography of the Head in Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation is an artificial cardiopulmonary bypass technique used to support patients with severe pulmonary failure or both pulmonary and cardiac failure. The hemodynamic changes produced by extracorporeal membrane oxygenation affect the appearance of CTA of the head images, often confounding interpretation if the correct history and understanding of extracorporeal membrane oxygenation are not known. This technical report describes the principles of extracorporeal membrane oxygenation, techniques to optimize intracranial CTA imaging, and pitfalls.

Prostate Cancer in Deceased Liver Donors.

BACKGROUND: Prostate cancer is the second most common malignant tumor (13%) among male subjects in Poland. The aim of this study was to assess the prevalence of prostate cancer in a group of deceased liver donors. METHODS: A total of 784 liver procurement attempts from deceased donors were performed in the Department of General, Transplant and Liver Surgery, Medical University of Warsaw, from January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver transplant. A retrospective analysis was performed based on these data. Among male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the prostate performed before making the decision regarding liver graft utilization. RESULTS: In the group of 30 donors who underwent prostate examination, 3 (10%) were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other cases, fresh frozen section suggested prostate cancer; however, this fact was not confirmed in routine section. liver transplantation was not performed in these cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy specimens. The difference between groups of donors with prostate cancer and benign pathology of the prostate gland according to prostate-specific antigen serum concentration (P = .578) or age (P = .730) was not statistically significant. CONCLUSIONS: Increased prostate-specific antigen serum concentrations without a diagnosis of prostate cancer in histopathologic examinations should not be an independent contraindication for performing organ transplantation. Nevertheless, for recipient safety, even when prostate cancer is only suspected in the frozen biopsy sample, the procured organ should not be used for transplantation.

Orthotopic liver transplantation for cholestatic diseases.

BACKGROUND/AIMS: According to the data of the European Liver Transplant Registry (ELTR), liver transplantations (LTx) as a result of bile duct diseases were reported in 12.0% of cases. The aim of this study was to overview retrospective indications for operation and results of patients who underwent LTx for cholestatic diseases. METHODOLOGY: 725 LTx were performed between January 1989 to December 2008, including 173 (23.9%) patients with cholestatic diseases. 80 pts (46.2%) were operated because of PBC, 63 pts (36.4%) with PSC and 12 pts (6.9%) with SBC as a result of iatrogenic bile ducts injuries. In 6 pts (3.5%) Caroli's disease was the reason for transplantation and another 11 pts (6.4%) were operated because of infiltration of alveococcosis into the bile duct. Cholangiocarcinoma (CCC) developed in 6 pts with PSC (9.5%) undergoing LTx. The last patient (0.6%) of our group was operated because of mucoviscidosis. 24 pts (13.9%) underwent unsuccessful surgical treatment prior to the LTx. RESULTS: 142 pts (82.1%) presented good outcome, but complications in postoperative period were present in 31 pts (17.9%). 8 pts (4.6%) required re-laparotomy: 6 pts due to intraperitoneal bleeding and hematoma in the first postoperative week and 2 pts due to liver abscess, 1 month and 3 months after LTx respectivelly. 4 patients (2.3%) died in the first week after LTx (septic complications, acute rejection). 5 patients with CCC died in the period of 7 to 26 months after LTx. This was caused by the recurrence of the cancer. The overall mortality was 8.1% (14 pts). 4 pts (2.3%) underwent ReLTx due to various origins--one case due to hepatic artery thrombosis, another was ischemic type biliary lesion (ITBL) and two patients due to recurrence of PBC and PSC. Cumulative 1, 5 and 10 year recurrence-free survival rates after LTx were: 94.6% / 88.7% / 72.1% in PBC group, 95.3% / 86.5% / 70.2% in PSC group and 73.9% / 69.2% / 59.3% in SBC group of patients. CONCLUSION: There is no doubt that LTx is a good and effective option of treatment for patients with cholestatic diseases. Nevertheless the long-term benefits of LTx depend on precise indications and timing of the operation.

Correlation between selected prognostic factors and postoperative course in liver transplant recipients.

AIM: The objective was to identify the major prognostic factors influencing liver function after transplantation that predict the postoperative course and long-term survival among liver transplant recipients. We analyzed the results of biochemical, microbiological, serologic, and pathologic studies of the donor and recipient, as well as intraoperative data. MATERIALS AND METHODS: Of 542 liver transplant recipients, 215 (39.7%) were analyzed in the period from 1989 to 2006. Patients were divided according to the mechanism leading to the liver disease: group I, hepatitis C virus (HCV) infection (n = 80, 37.0%); group II, hepatitis B virus (HBV) infection (n = 33, 15.0%); group III, HBV and HCV infection (n = 13, 6.0%); group IV, alcoholic liver disease (ALD) (n = 66, 31.0%); and group V, autoimmune hepatitis (AIH) (n = 23, 11.0%). RESULTS: Prediction of patient survival based on clinical parameters showed a better prognostic value than that based only on liver function tests. Transplant urgency scores-Model for End-Stage Liver Disease (MELD), delta MELD and United Network for Organ Sharing (UNOS)-enabled us to predict early and long-term patient survival after liver transplantation. Update of these scores, reflecting the patient's condition, enabled us to evaluate pretransplant life-threatening factors and urgency level. Organ donation predictive factors were age, viral status, and degree of liver steatosis. Cold and warm ischemia times still were major prognostic factor. Routine biliary drainage resulted in worse long-term survival than non-drained patients. Liver transplantation for ALD showed the highest complication rate. Chronic liver rejection occurred more frequently in the AIH transplanted group. The most useful predictive factors for 1-year survival were urea/creatinine and liver function tests: aspartate and alanine aminotransferases, gamma-glutamyl transpeptidase the International normalized ratio, and Quick. CONCLUSION: The prognosis of patient outcomes after liver transplantation based on clinical parameters showed greater value than evaluation of the laboratory data.

Omega-3 polyunsaturated fatty acid enriched diet attenuates stress-induced lactacidemia in 10-day-old rats.

BACKGROUND: Lactacidemia is often seen under stress conditions including septic shock in the newborn. Under stress conditions, plasma catecholamine concentrations are increased and play an important role in lactate metabolism. Our previous study shows that perinatal feeding of omega-3 polyunsaturated fatty acid enriched diet (omega-3PUFA) attenuates lactacidemia of endotoxic shock in 10-day-old rats. In the omega-6 fatty acids series, decosapentanoic acid, two series prostaglandins and four series leukotrienes are synthesized through linoleic acids. As plasma lactate concentration correlates with the outcome of septic shock in the newborn, it is important to understand the effects of omega-3PUFA on lactate metabolism. Thus, we tested the hypothesis that perinatal feeding of omega-3 polyunsaturated fatty acid enriched diet (omega-3PUFA) alters responses to catecholamines and attenuates the stress-induced lactacidemia in 10-day-old rats. METHODS: Ten-day-old rats which perinatally fed omega-3PUFA. Lactacidemia was induced by swimming for 5 min. Ten-day-old rats which perinatally fed omega-6PUFA were controls. Omega-6 fatty acids series are contained in animal fats and corn oil. Adrenergic blockers were used to assess roles of catecholamines in swimming-induced lactacidemia. RESULTS: Swimming increased plasma lactate concentration less (P<0.05) in rats fed omega-3PUFA than rats fed omega-6PUFA. Swimming increased plasma concentrations of glucose and glucagon, cyclic adenosine monophosphate (cAMP) concentration and phosphoenolypruvate carboxykinase mRNA in the liver, and cAMP concentration in the hindlimb muscle more (P<0.05) in rats fed omega-3PUFA than in rats fed omega-6PUFA. Phentolamine and propranolol enhanced swim-induced lactacidemia in the omega-3PUFA group, while they decreased the lactacidemia in the omega-6PUFA group. Propranolol enhanced swimming-induced hyperglycemia in the omega-6PUFA group more than in the omega-3PUFA group. CONCLUSIONS: Omega-3PUFA might increase beta-adrenergic response in the liver and increase gluconeogenesis in response to stress, resulting in decreased lactacidemia.

[Psychophysiological correlates of primary insomnia]. / Psychofizjologiczne wskazniki bezsennosci przewleklej.

Psychophysiological differences between 16 patients with primary insomnia, 7 men and 9 women, of mean age 40.8 years, and 16 controls, matched according to age, sex and education, were studied. Insomniacs differed from controls in the following results: their motor activity level was higher during night, sleep efficiency was lower and complexity in slow wave sleep was higher. The Hyperarousal Scale score was higher in insomniacs and it correlated with severity of insomnia in Athens Insomnia Scale. Sleep latency in MSLT was not shorter in patients group. Reaction time was shorter, moreover, the number of presentations necessary to memorize all items of Selective Reminding Test was greater in these patients. Degree of the learning disturbance correlated with the Athens Insomnia Scale score. No correlations were found between Selective Reminding Test and standard polysomnographic parameters. To sum up, the hypothesis on 24-hour hyperarousal in primary insomnia has been confirmed and learning impairment has been documented in the present study, independent of standard polysomnographic parameters.

Heterotopic expression of the Xl-Fli transcription factor during Xenopus embryogenesis: modification of cell adhesion and engagement in the apoptotic pathway.

In the Xenopus laevis embryo, the overexpression of the Xl-FLI protein, a transcription factor of the ETS family, provokes severe developmental anomalies, which affect anteroposterior and dorsoventral polarities, optic cup formation, head cartilage morphogenesis, and erythrocyte differentiation. It has been proposed that these effects could be correlated to modifications of cell adhesion properties and/or to an increased engagement of cells in the apoptotic pathway during early development (Remy et al., Int. J. Dev. Biol. 40, 577-589, 1996). To address these questions, we have first analyzed the behavior of cells overexpressing the protein in both aggregation and adhesion assays. We observe perturbations of cell-cell interactions as well as perturbations of cell adhesion and spreading on fibronectin and extracellular matrix (ECM). Second, we have analyzed apoptosis of cells overexpressing the Xl-FLI protein, by testing DNA fragmentation, caspase-3 activity and by performing TUNEL assay. We show that Xl-Fli overexpression results in the appearance of hallmarks of apoptosis, including exclusion of cells from the interior of the embryo, internucleosomal fragmentation of DNA and dose-dependent induction of caspase-3, resulting in the hydrolysis of poly(ADP-ribose) polymerase. In addition, a dominant-negative mutation of BMPs receptors decreases the effects of Xl-Fli overexpression, suggesting that a modification of the BMP signalling could be responsible for increased apoptosis. The latter appears to affect predominantly ventral and ventrolateral regions of the embryo.

Integrins: regulators of embryogenesis.

Integrins are heterodimeric transmembrane glycoproteins involved in cell-cell and cell-extracellular matrix adhesion. They also participate in cytoskeletal rearrangements, co-regulation of growth factor activities and activation of signal transductions. This review describes experimental approaches that have given new insights into the integrin functions during embryogenesis. Using anti-functional antibodies, peptide inhibitors of integrin-ligand interactions and genetic ablation of integrins results, this review will show that integrins are key molecules during early development of both invertebrates and vertebrates.

Therapeutic drug monitoring in depression.

The difference between Therapeutic Drug Monitoring (TDM) and uncontrolled therapy consists in the fact that in TDM we can predict a certain scheme of treatment according to clinical and laboratory results. It is a method which serves to increase the efficacy and safety of pharmacotherapy in an individual patient. This paper presents the results of the treatment with tricyclic antidepressants based on the monitoring of serum drug level in 32 patients with indications for using pharmacogenetic as well as pharmacoelectroencephalographic tests. Clinical status of the patients was evaluated according to: Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Clinical Global Impression Scale (CGIS), and TCA concentration in serum was determined using Fluorescence Polarization Immunoassay (FPIA). Hydroxylation phenotype was determined using debrisoquine as a model drug. EEG was recorded in four leads: F3-C3, F4-C4, P3-O1, P4-O2. In the present study, we did not found any significant correlation between clinical status and serum TCAs concentrations measured by FPIA method. Efficacy of antidepressant treatment and stabilization of serum TCA concentrations depended largely upon the time course of the treatment. Debrisoquine phenotyping revealed the presence of one poor metabolizer (MR = 15) in the examined group of patients. A significant improvement in the clinical status of the patients, the stabilization of therapeutic drug concentrations, the appearance of antidepressive profiles in the pharmaco-EEG profile after 14 days of therapy, as well as the starting value determined by SERS were shown to be prognostic factors for the further antidepressant therapy.

A key function for alphav containing integrins in mesodermal cell migration during Pleurodeles waltl gastrulation.

During cleavage of Pleurodeles waltl amphibian embryos, inner cells of the blastocoel roof (presumptive ectodermal and mesodermal cells) organize a fibrillar extracellular matrix (ECM) containing fibronectin on their basal surface by a beta1-integrin-dependent process. This matrix is used as a migratory substrate by mesodermal cells during gastrulation. While alpha5beta1 integrin is expressed on both ectodermal and mesodermal cell surface, we have shown previously that alphav containing integrins are essentially restricted to the surface of mesodermal cells (Alfandari, D., Whittaker, C. A., DeSimone, D. W., and Darribère, T., Dev. Biol. 170, 249-261, 1995). To investigate the function of alphav integrins during gastrulation, we have generated a function blocking antibody directed against the extracellular domain of the Pleurodeles integrin alphav subunit. The antibody did not prevent fibronectin fibril formation, whereas an antibody against the alpha5beta1 integrin did. When injected into the blastocoel, the antibody against integrin alphav subunit perturbed gastrulation and further development in a stage-dependent manner. Developmental defects were correlated to an abnormal positioning of the mesoderm layer. In vitro, the antibody blocked spreading of mesodermal cell to fibronectin or blastocoel roof ECM but not their attachment. In contrast, the antibody directed against the alpha5beta1 integrin inhibited both cell attachment and spreading to the same substrates. We propose that the alpha5beta1 integrin is required for fibronectin assembly into fibrils and mesodermal cell attachment to the blastocoel roof ECM, while the alphav containing integrins are necessary for cell spreading, and possibly migration, on this complex network.

Assessment of diazepam loading dose therapy of delirium tremens.

The efficacy of the diazepam loading dose method of treatment of delirium tremens was assessed in comparison with the traditional therapy. The experimental group and the control group comprised 51 and 45 patients respectively. The clinical institute withdrawal assessment for alcohol (CIWA-A) scale was applied to assess the intensity of the symptoms. Diazepam doses in the experimental group oscillated from 40 to 210 mg (mean 86.9 +/- 47.2 mg). The control group was receiving diazepam and other psychotropic drugs in divided doses. In the experimental group deliric symptoms were present from 2 to 24 h (mean 6.9 +/- 4.8 h), and in the control group from 2 to 123 h (mean 33.8 +/- 25.7 h). The results show a large efficacy of the loading dose method corresponding to substantial reduction of the psychosis duration (fivefold in comparison to the control group). The method proved to be safe, with no significant complications.

Analysis of complexity of EEG during sleep.

New multichannel descriptors of EEG activity: complexity (omega), total power (zeta) and generalized frequency (phi) were applied to whole night sleep analysis in 11 healthy subjects. The values of omega and phi decreased systematically from waking to slow wave sleep, and increased systematically in consecutive NREM-REM sleep cycles. The changes of zeta were opposite to omega and phi. These descriptors may be an alternative approach to the EEG sleep analysis.

Interhemispheric differences of sleep EEG complexity.

Complexity of EEG (omega), a global measure reflecting degree of spatial synchronization, was computed for whole night recordings of sleep EEG of 10 healthy volunteers, 9 males and 1 female (age 21-53) and 6 depressive patients, 5 males and 1 female (age 23-64). Sleep was scored visually in 20 s epochs, omega was calculated in 2.5 s segments and the median from 8 segments (20 s) was calculated. omega was calculated for the whole field of 21 electrodes and for the left and right hemisphere separately (2 x 8 electrodes). Measure of global power (sigma) and generalized frequency (phi) were also computed for the same data. In healthy subjects the complexity was higher over the right hemisphere during waking, and the difference shifted to higher complexity over the left hemisphere in slow wave sleep (F = 5.15, df1 = 4, df2 = 6856, P < 0.0005). The opposite trend was found in depressives (F = 10.51, df1 = 4, df2 = 3960, P < 0.0001).

[Treatment of delirium tremens with quick administration of diazepam]. / Terapia majaczenia alkoholowego metoda szybkiego nasycania diazepamem.

In this efficacy the study of diazepam loading-dose treatment of delirium tremens was evaluated in comparison with traditional therapeutic methods. Experimental and control groups consisted of 42 and 40 patients respectively. The severity of the withdrawal symptoms was evaluated from clinical status, in the experimental group CIWA-A score was also employed. Study results suggest high efficacy of the loading-dose method, which was characterized by significant shortening of psychosis duration (five times shorter in experimental vs. control group). The method turned out to be safe, no complications were observed during and after the treatment.

Principles, main goals and methods of the nationwide program: "investigations on iodine deficiency and model of iodine prophylaxis in Poland".

The main reasons to start investigations on IDD in Poland as a nationwide project of the Ministry of Health and Welfare sponsored by the State Committee For Scientific Research and Foundation for Polish Science were: cessation of iodizing of kitchen salt in Poland in 1980, increase of the incidence of goitre in the population and hyperthyrotropinemia in newborns, results of the survey undertaken after Chernobyl disaster indicating an increase of goiter incidence (Nauman et al.) and results of the pilot study (Gutekunst, Gembicki, Kinalska and Rybakowa) indicating an increase of thyroid volume and diminishing of iodine excretion in urine of children in Kraków, Bialystok ad Poznan regions. Therefore the main goals of the project were as follows: to evaluate IDD in Poland on the population basis, to map goiter incidence and iodine deficiency in geographic areas, to evaluate a voluntary model of iodine prophylaxis in Poland (20 mg of KI/kg of salt). The investigations were carried out in 19330 children (48.7% of boys and 51.3% for girls) in age group 6-13 years, attending 111 coeducational randomly selected schools from all the country. This number represents 0.35% of children subpopulation in the above age-groups. For practical purposes local coordinating centers at the relevant Departments of Endocrinology and Board of Coordinators were set up. The programme of survey included: filling the questionnaire by children's parents, thyroid palpation and classification according to WHO and ICCIDD criteria, thyroid volume determination by means of ultrasonograph Kontron Sigma 1 L with linear transducer 7.5 MHz, determination of iodine in casual morning urine sample using Sandell and Kalthoff method. Determination of iodine concentration in urine was performed in each case of goiter and in the same number of children without goiter. The results were segregated according to coordinating centers and according to 6 geographical areas of the country. The results were calculated according to the descriptive statistics using Student's test, Chi-square test F-test and Leven's test. The results segregated according to geographic areas were tested by means of analysis of variance using the linear model. The final results of the programme are presented in the next papers.

Goiter incidence and urinary iodine excretion in children of age group 6-13 years living in south-eastern Poland (Kraków coordinating center).

The study included 4103 school children attending randomly selected schools localized in towns and villages of 3 geographically distinct regions: mountainous, (Carpathian endemia), upland, lowland. The children were divided into four age-related groups. The incidence of goiter as detected by palpation was 38.1% in all the children studied, the value being similar in all three regions (38.1, 37.3 and 38.6%, respectively). Goiter incidence differs slightly among urban and rural children, amounting to 40.5 and 34.5%, respectively, in the two groups. In about 60% of children urinary iodine excretion was lower than 50 micrograms/l, while in about 30% it was normal. In about 10% of children studied urinary iodine excretion was lower than 20 micrograms/l. The results obtained indicate the occurrence among children of the studied region of goiter endemy of moderate degree. It was found that the percentage of children excreting more than 50 micrograms/l of urinary iodine was higher among those consuming iodized salt as compared to those consuming non-iodized salt. The first effects of resumption of common salt fortification with iodide in southern Poland can already be noted. There is, however, a need for optimization and steady control over this prophylactic action.

[Results of epidemiologic studies performed after the disaster in Czernobyl among the adult part of the population in the region of Krakow]. / Wyniki badan epidemiologicznych podjetych po awarii w Czarnobylu wsród doroslej czesci populacji regionu krakowskiego.

Epidemiologic studies following the Czernobyl accident were performed in region Kraków, including Kraków, Nowy Sacz and Kielce district. 1426 males and 2495 females were selected according to the random sample on the whole population of Kraków and Nowy Sacz, as well as in some selected areas in Swietokrzyski Mountains, and in Kielcecity. The aim of the study was to assess the results of the prophylaxis with Kalium iodine after the radiation and the incidence of the goiter in the population. It was stated, that 19.2% of the population in Kraków district, 16.9% in Nowy Sacz and 20% in Kielce received the prophylactic dosis of K.J. 80% took mainly the Lugol solution, between May, the 1st and 5th, 1986. Among 18 of person showing side effects like gastrointestinal disturbances, 16 were of female sex. Goiter incidence according to WHO classification was 50.7%, 67.3% and 49.9% in Kraków, Nowy Sacz and Kielce respectively. The difference between the incidence of goiter in males and females was 1:3. In women it was rather Ist and IInd degree of goiter, in men OB and Ist. Nodules of thyroid gland in the rural region of Kraków, Nowy Sacz and Kielce were seen in women in 10.8%, 1.7%, add 12.3% consecutively. Hormonal studies i.e T3, T4, TSH serum concentration showed normal results in all groups studied. TSH concentration was the highest in the group OB. The microsomal and antithyroglobulin antibodies level was the same independently on the prophylactic dosis of Lugol solution. The high incidence of thyroid diseases not related to the accident was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmaco-EEG analysis by means of FFT and FAD.

The EEG effects of a single oral dose of diazepam, amitriptyline and pernazine were studied in 26 healthy volunteers. The EEG analysis was performed by means of FFT and a new parametric method FAD. The results indicate that the FAD method reveals drug changes significantly more often than does the FFT analysis and that the medication effects are more clearly defined by the FAD. The method can be useful in the assessment of the subtle effects of the psychotropic drugs.