Subcapsular Orchiectomy in the Primary Therapy of Patients with Bone Metastasis in Advanced Prostate Cancer: An Anachronistic Intervention?

Background. The therapeutic impact of palliative androgen deprivation in metastatic prostate cancer is indisputable. Bilateral orchiectomy represents the traditional method of AD but was reduced during the last years in favor for treatment with LHRH analogues. Due to limited economic resources of the health care system, the economically priced definite surgical castration might experience a renaissance. Methods. In this single-center retrospective study, 83 consecutive patients with osseous metastasized prostate cancer were evaluated, who had primarily been treated by subcapsular bilateral orchiectomy. Response to therapy, time until therapy failure, overall survival time, psychological disorders due to loss of organ, and disease-associated and postoperative surgical complications were recorded. The median followup was 35 months (IQR: 26–46). Results. Patients' mean age at surgery was 72.1 (54–91) years. Six patients (7.2%) displayed immediate tumor progression after orchiectomy. Median time of tumor remission and overall survival time were 29 and 36 months, respectively. 14% of the study group showed minor postoperative complications. No psychological problems occurred following bilateral orchiectomy. Conclusion. Due to an effective and persistent oncological effectiveness, less morbidity, and absence of psychological implications, bilateral subcapsular orchiectomy seems to be a practicable and advisable alternative in the first-line therapy of metastasized PCa

Back to basics: A mediation analysis approach to addressing the fundamental questions of integrated care evaluations.

Health systems around the world are aiming to improve the integration of health and social care services to deliver better care for patients. Existing evaluations have focused exclusively on the impact of care integration on health outcomes and found little effect. That suggests the need to take a step back and ask whether integrated care programmes actually lead to greater clinical integration of care and indeed whether greater integration is associated with improved health outcomes. We propose a mediation analysis approach to address these two fundamental questions when evaluating integrated care programmes. We illustrate our approach by re-examining the impact of an English integrated care program on clinical integration and assessing whether greater integration is causally associated with fewer admissions for ambulatory care sensitive conditions. We measure clinical integration using a concentration index of outpatient referrals at the general practice level. While we find that the scheme increased integration of primary and secondary care, clinical integration did not mediate a decrease in unplanned hospital admissions. Our analysis emphasizes the need to better understand the hypothesized causal impact of integration on health outcomes and demonstrates how mediation analysis can inform future evaluations and program design

Establishment of diuretic activity indicators for (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols and their derivatives

Diuretic drugs are drugs that, by blocking the transport systems of the renal tubules, promote the removal of excess electrolytes and water from the body, normalization of the internal environment. They eliminate edema, reduce the fluid content in the body cavity. Diuretic drugs differ in their chemical structure, the mechanism of action on the urinary tract function of the kidneys and on the mechanisms of regulation of this function. It should be noted that the use of the above mentioned agents can lead to undesirable side effects, such as nausea, vomiting, unpleasant sensations in the stomach, headache, facial hyperemia. To date, there is evidence that 5-R-1,2,4-triazole derivatives have diuretic activity. The advantage of synthetic triazole derivatives is that, along with the expressed pharmacological action of the compound, there are relatively low rates of acute and chronic toxicity, but almost no side effects. Therefore, it is important to create new low-toxic substances of derivatives (3-thio-4-R-4-H-1,2,4-triazole-3-yl)(phenyl)methanols and study their diuretic properties. The purpose of the work is the purposeful search for new low-toxic and highly effective diuretic compounds among the derivatives of (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols. Materials and methods. To establish the influence of compounds, which have been synthesized at the Physical and Chemical Chemistry Department of ZSMU, the method of E. B. Berchin was used on the excretory function of kidneys. Experiments on diuretic activity were conducted at the Department of Clinical Pharmacy, Pharmacotherapy and MFE of FPE, Zaporizhzhia State Medical University. Results. The diuretic activity of derivatives (3-thio-4-R-4H-1,2,4-triazole-5-yl)(phenyl)methanols was investigated. The study and analysis of the obtained experimental data were compared with the reference diuretic hypothiazide. Regularities "structure – activity" were established. The studies indicate that (3-thio-4-R-4H-1,2,4-triazoles-3-yl)(phenyl)methanol are not able to exceed hypothiazide diuretic effect, but 4-(5-hydroxy(phenyl)methyl-4-phenyl-4H-1,2,4-triazolе-3-ylthiomethyl)benzonitrile showed the results closer to the reference drug. Conclusion. By the method of E.B. Berchin the diuretic activity of derivatives (3-thio-4-R-4H-1,2,4-triazol-5-yl)(phenyl)methanols was investigated. Derivatives (3-thio-4-R-4H-1,2,4-triazole-3-yl)(phenyl)methanols do not excee the diuretic action of hypothiazide. Patterns "structure – action" were established. The most active compound was 4-(5-hydroxy(phenyl)methyl-4-phenyl-4H-1,2,4-triazolе-3-ylthiomethyl)benzonitrile

Hepatoprotective activity of 1,2,4-triazole-3-thione derivatives, which contains on c5-atomic carbon hydroxy(phenyl)methyl dependent

Relevance of pharmaceuticals with high efficiency and low cost for the prevention and treatment of diseases of the digestive system is unquestionable. It would be appropriate to mention that we carried out an analysis of a number of studies in which hepatoprotective effects of 1,2,4-triazole derivatives were carried out, and showed high hepatoprotective effects. Therefore, the search for hepatoprotectors in the series of 1,2,4-triazole derivatives has not only theoretical but also practical significance. The aim of our work was to study the first synthesized derivatives of 1,2,4-triazole-3-thione, which was containing substituents on C5 by carbon atom in conditions of tetrachormethane hepatitis. To model toxic hepatitis, a hepatotoxic xenobiotic, carbon tetrachloride, was used. The study of biochemical indicators of liver status was carried out 24 hours after the last injection of carbon tetrachloride. The ability of the test compounds to restore the integrity of hepatocyte membranes was determined by the anti-cytolytic effect (decrease in the activity of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)). According to the results of the study, it was found that among 43 test compounds, 5 are able to prevent survival at 85.71%. Thus, among the substances studied, compound 2c, which contributed 85.71% of the survival of the experimental animals and decrease 33.43% in ALT and 34.33% in AST. In this case, a very weak inverse dependence of the above indices was observed (r = -0.31). Some regularities of the chemical structure of the hepatoprotective action of 1,2,4-triazole derivatives have been established, so the survival of the experimental animals decreased with the introduction of a phenyl substituent of the starting thiones with N4

Гепатопротекторна активність похідних 1,2,4-тріазол-3-тіону, які містять за с5 атомом вуглецю гідрокси(феніл)метильний замісник

Topicality. Actually it is very important to create highly effective but relatively inexpensive medications for the prevention and treatment the digestive system diseases. It would be appropriate to mention that we carried out an analysis of studies and examined hepatoprotective effects of 1,2,4-triazole derivatives, high rates of hepatoprotective effects were detected. Therefore, the search for hepatoprotectors in the series of 1,2,4-triazole derivatives has not only theoretical but also practical significance.Aim. To study the first synthesized derivatives of 1,2,4-triazole-3-thione, containing substituents on C5 by carbon atom in conditions of tetrachormethane hepatitis.Materials and methods. To model toxic hepatitis, a hepatotoxic xenobiotic, carbon tetrachloride, was used. The study of liver biochemical indicators was carried out in 24 hours later after the last injection of carbon tetrachloride. The ability of test compounds to restore the integrity of hepatocyte membranes was determined by anti-cytolytic effect (Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) activity decrease). According to the results of the study, it was found that among 43 test compounds, 5 are able to prevent survival at 85.71 %.Results and discussion. Thus, among the substances studied, compound 2c, which contributed 85.71 % of the survival of the experimental animals and decrease 33.43 % in ALT and 34.33 % in AST. In this case a very weak inverse dependence of the above was observed (r = -0.31).Conclusions. As a result, some chemical structure patterns of the hepatoprotective action of 1,2,4-triazole derivatives were established, so the survival of the experimental animals decreased with the introduction of a phenyl substituent of the starting thiones with N4.Актуальность. Актуальность создания лекарственных средств с высокой эффективностью и низкой стоимостью для профилактики и лечения заболеваний пищеварительной системы является бесспорной. Нами проведен анализ ряда работ, в которых проводились исследования гепатопротекторного действия производных 1,2,4-триазола, и поэтому поиск гепатопротекторов в ряду производных 1,2,4-триазола имеет не только теоретическую, но и практическую значимость.Цель работы. Целью нашей работы было исследование впервые синтезированных производных 1,2,4-триазол-3-тиона, содержащих по С5 атому углерода заместители в условиях тетрахлорметанового гепатита.Материалы и методы. Для моделирования токсического гепатита был использован гепатотоксический ксенобиотик – тетрахлорметан. Изучение биохимических показателей состояния печени проводили через 24 ч после последнего введения тетрахлорметана. Способность исследуемых соединений к восстановлению целостности мембран гепатоцитов определяли по антицитолитическому действию (снижение активности аланинаминотрансферазы (АлАТ), аспартатаминотрансферазы (АсАТ)).Результаты и их обсуждение. По результатам исследования было установлено, что среди 43 исследуемых соединений 5 способны содействовать выживанию на уровне 85,71 %. Таким образом, среди исследуемых веществ эффективным следует считать соединение 2c, которое способствовало 85,71 % выживаемости подопытных животных и снижению уровня АлАТ на 33,33 % и АсАТ на 34,33 % соответственно. При этом наблюдалась очень слабая обратная зависимость вышеуказанных показателей (r = -0,31).Выводы. В ходе исследования установлены некоторые закономерности химического строения, зависящие от гепатопротекторного действия производных 1,2,4-триазола; так выживаемость подопытных животных снижалась при введении с N4 атомом азота фенильного заместителя исходных тионов.Актуальність створення лікарських засобів з високою ефективністю і низькою вартістю для профілактики і лікування захворювань травневої системи є безперечною. Нами проведено аналіз ряду робіт, в яких проводилися дослідження гепатопротекторної дії похідних 1,2,4-тріазолу, і проявляли високі показники гепатозахисної дії. Тому пошук гепатопротекторів в ряду похідних 1,2,4-тріазолу має не тільки теоретичну, а й практичну значимість.Метою нашої роботи було дослідження вперше синтезованих похідних 1,2,4-тріазол-3-тіонів, що містять по С5 атому вуглецю замісники в умовах тетрахорметанового гепатиту.Для моделювання токсичного гепатиту був використаний гепатотоксичний ксенобіотик – Тетрахлорметан. Вивчення біохімічних показників стану печінки проводили через 24 години після останнього введення тетрахлорметана. Здатність досліджуваних сполук до відновлення цілісності мембран гепатоцитів визначали по антіцітолітічному дії (зниження активності аланінамінотрансферази (АлАТ), аспартатмінотрансферази (АСТ)).За результатами дослідження було встановлено, що серед 43 досліджуваних сполуки 5 здатні попереджати виживання на рівні 85,71%.Таким чином серед досліджуваних речовин ефективною слід вважати сполуку 2c, яка сприяло 85,71% виживання піддослідних тварин і зниження рівня АлАТ на 33,33% і АсАТ на 34,33% відповідно. При цьому спостерігалася дуже слабка зворотня залежність вищевказаних показників (r = – 0.31).В ході дослідження встановлено деякі закономірності хімічної будови від гепатопротекторної дії похідних 1,2,4-тріазолу, так виживаність піддослідних тварин знижувалася при введенні з N4 атомому азоту фенильного замісника вихідних тіонів

First Observation of the Doubly Charmed Baryon Xi_cc^+

We observe a signal for the doubly charmed baryon Xi_cc^+ in the charged decay mode Xi_cc^+ --> Lambda_c^+ K- pi+ in data from SELEX, the charm hadro-production experiment at Fermilab. We observe an excess of 15.9 events over an expected background of 6.1 +/- 0.5 events, a statistical significance of 6.3sigma. The observed mass of this state is (3519 +/- 1) MeV/c^2. The Gaussian mass width of this state is 3MeV/c^2, consistent with resolution; its lifetime is less than 33fsec at 90% confidence.Comment: 5 pages, 3 figures, accepted for publication in Physical Review Letter

Observation of the Cabibbo-suppressed decay Xi_c+ -> p K- pi+

We report the first observation of the Cabibbo-suppressed charm baryon decay Xi_c+ -> p K- pi+. We observe 150 +- 22 events for the signal. The data were accumulated using the SELEX spectrometer during the 1996-1997 fixed target run at Fermilab, chiefly from a 600 GeV/c Sigma- beam. The branching fractions of the decay relative to the Cabibbo-favored Xi_c+ -> Sigma+ K- pi+ and Xi_c+ -> X- pi+ pi+ are measured to be B(Xi_c+ -> p K- pi+)/B(Xi_c+ -> Sigma+ K- pi+) = 0.22 +- 0.06 +- 0.03 and B(Xi_c+ -> p K- pi+)/B(Xi_c+ -> X- pi+ pi+) = 0.20 +- 0.04 +- 0.02, respectively.Comment: 5 pages, RevTeX, 3 figures (postscript), Submitted to Phys. Rev. Let

First observation of a narrow charm-strange meson DsJ(2632) -> Ds eta and D0 K+

We report the first observation of a charm-strange meson DsJ(2632) at a mass of 2632.6+/-1.6 MeV/c^2 in data from SELEX, the charm hadro-production experiment E781 at Fermilab. This state is seen in two decay modes, Ds eta and D0 K+. In the Ds eta decay mode we observe an excess of 49.3 events with a significance of 7.2sigma at a mass of 2635.9+/-2.9 MeV/c^2. There is a corresponding peak of 14 events with a significance of 5.3sigma at 2631.5+/-1.9 MeV/c^2 in the decay mode D0 K+. The decay width of this state is <17 MeV/c^2 at 90% confidence level. The relative branching ratio Gamma(D0K+)/Gamma(Dseta) is 0.16+/-0.06. The mechanism which keeps this state narrow is unclear. Its decay pattern is also unusual, being dominated by the Ds eta decay mode.Comment: 5 pages, 3 included eps figures. v2 as accepted for publication by PR

First Measurement of pi e -> pi e gamma Pion Virtual Compton Scattering

Pion Virtual Compton Scattering (VCS) via the reaction pi e --> pi e gamma was observed in the Fermilab E781 SELEX experiment. SELEX used a 600 GeV/c pi- beam incident on target atomic electrons, detecting the incident pi- and the final state pi-, electron and gamma. Theoretical predictions based on chiral perturbation theory are incorporated into a Monte Carlo simulation of the experiment and are compared to the data. The number of reconstructed events (9) and their distribution with respect to the kinematic variables (for the kinematic region studied) are in reasonable accord with the predictions. The corresponding pi- VCS experimental cross section is sigma=38.8+-13 nb, in agreement with the theoretical expectation sigma=34.7 nb.Comment: 10 pages, 12 figures, 4 tables, 25 references, SELEX home page is http://fn781a.fnal.gov/, revised July 21, 2002 in response to journal referee Comment