Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1 / The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients

Introducción y objetivos: El objetivo de este estudio fue analizar el impacto del grado histológico del tumor en la predicción de supervivencia de los tumores primarios T1 G2 y G3 OMS 1973, que han sido clasificados como HG (alto grado) en el sistema de clasificación OMS 2004. Materiales y métodos: Se revisaron retrospectivamente los datos de 481 pacientes con cáncer de vejiga T1HG primario, tratados entre 1986 y 2016 en 2 centros universitarios. Para comparar los grupos se realizaron pruebas de log-rank y análisis de regresión de Cox. Resultados: Noventa y cinco (19,8%) tumores fueron clasificados como G2 y 386 (80,2%) como G3. La mediana de seguimiento fue de 68 meses. Las tasas de recurrencia y progresión fueron 228 (47,5%) y 109 (22,7%) pacientes, respectivamente. Se realizó cistectomía radical en 114 pacientes (23,7%) y hubo 64 (13,3%) casos de muerte cáncer-específica. La tasa de supervivencia libre de recurrencia para G2, G3 y el total de los pacientes fue del 68,7, el 51,2 y el 56,3%, respectivamente, y la para tasa libre de progresión, se obtuvieron unos valores del 89,3, el 73,2 y el 78,1%. Durante todo el período de seguimiento, los pacientes con tumores G3 obtuvieron peores tasas de supervivencia libre de progresión y de recurrencia que los pacientes con tumores G2. En el análisis multivariante, después del ajuste de las características clínicas, el riesgo de recurrencia y progresión para los tumores G3 fue 1,65 y 2,42 veces mayor que para los tumores G2. Conclusiones: Se demostró que los tumores T1G3 se caracterizan por peores tasas de supervivencia libre de progresión y recurrencia en comparación con los cánceres G2

Introduction and objectives: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. Materials and methods: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2 university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. Results: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. Conclusions: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers

Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3 / Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder

Introducción y objetivos: Existen varios estudios con el objetivo de validar las tablas del Club Urológico Español de Tratamiento Oncológico (CUETO). Sin embargo, ninguno de estos estudios se ha centrado en el cáncer de vejiga de alto y muy alto riesgo. El objetivo del presente estudio fue validar externamente el modelo CUETO para predecir la recidiva y la progresión de la enfermedad en el grupo de tumores T1G3 tratados con bacilo Calmette-Guérin (BCG). Pacientes o materiales y métodos: Se analizaron los datos de 414 pacientes con cáncer de vejiga T1G3 primario. Para evaluar la discriminación del modelo se usaron modelos de riesgos proporcionales de Cox y se calcularon los índices de concordancia. Resultados: La mediana de seguimiento fue de 68 meses. Se observó recidiva en 212 (51,2%) y 64 pacientes (15,5%) experimentaron más de un episodio de recurrencia durante el periodo de seguimiento. La progresión del cáncer se observó en 106 pacientes (25,6%), 115 pacientes (27,8%) fueron tratados con cistectomía radical, y hubo 64 (15,5%) muertes por tumor. Para la probabilidad de recidiva y progresión, el índice de concordancia de los modelos CUETO fue de 0,633 y 0,697, respectivamente. Las tablas de CUETO subestimaron significativamente el riesgo de recidiva y marginalmente el riesgo de progresión en el primer año de observación. Durante los 5 años de observación, la tendencia de la recidiva fue mucho menos clara. Por el contrario, hubo una ligera sobreestimación en el riesgo de progresión. El estudio está limitado por su naturaleza retrospectiva. Conclusiones: Se demostró que las tablas de riesgo del grupo CUETO logran una discriminación correcta, tanto para la recidiva de la enfermedad como para la progresión, en pacientes con T1G3 tratados con BCG. El modelo de puntuación (CUETO) subestima el riesgo de recidiva del tumor, pero acierta al predecir el riesgo de progresión

Introduction and objectives: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. Patients or materials and methods: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. Results: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. Conclusions: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression

The 1973 WHO and 2004 WHO grading systems are not equal in prediction of survival among stage T1 bladder cancer patients. / Los sistemas de clasificación de la OMS de 1973 y 2004 difieren en la predicción de supervivencia entre los pacientes con cáncer de vejiga en estadio T1.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. MATERIALS AND METHODS: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. RESULTS: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. CONCLUSIONS: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder. / Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3.

INTRODUCTION AND OBJECTIVES: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. PATIENTS OR MATERIALS AND METHODS: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. RESULTS: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. CONCLUSIONS: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

Preoperative Computed Tomography Parameters and Deterioration of Remaining Kidney Function in Living Donors.

INTRODUCTION: After living kidney donation, a decrease of kidney function (described as estimated glomerular filtration rate [eGFR]) is observed in majority of donors. However, the loss is more significant in some patients without an explicable reason. The aim of this study was to identify quantitative parameters in computed tomography (CT) of the abdomen that would predict greater eGFR reduction after kidney removal. MATERIAL AND METHODS: One hundred and ten preoperative multiphase CT examinations of the abdomen of kidney donors were analyzed for the following renal parameters: cortex, parenchyma and pyramids volume, scarring thickness (low grade: <1 cm, high grade: >1 cm), cortical gaps, vascularisation, and cortex-to-aorta enhancement index (CAEI). The radiologic and biometric (eg, donor weight) parameters were correlated with eGFR (CKD-EPI formula) change between baseline and at discharge. RESULTS: Donor weight was correlated with a loss of eGFR (P < .001). Kidney volumetric parameters including renal cortex and parenchyma volume, as well as renal artery cross-section area were associated with donor weight (r = 0.50 P < .001 and r = 0.39 P < .001). CAEI was correlated with a loss of eGFR (P = .003) and was related to the donor's sex in favor of men. Forty-one (37%) donors had an additional renal artery, which did not influence kidney function. No influence of cortical gaps or scarring on eGFR was observed. CONCLUSIONS: CAEI may be a helpful tool in predicting greater short-term kidney function decrease after living kidney donation. Male sex is the strongest risk factor of greater eGFR loss after kidney donation.

Diabetes and Cancer: a Review of Current Knowledge.

Diabetes mellitus (DM), one of the most common life-threatening illnesses worldwide, is a group of metabolic diseases, characterized by sustained hyperglycemia. The global prevalence of diabetes mellitus among adults reached 387 millions in 2014 and is still rising. It is suggested there is a strong association between diabetes mellitus (especially type 2 diabetes mellitus) and carcinogenesis. The possible biological links between diabetes mellitus and cancer comprise hyperinsulinemia, hyperglycemia and fat-induced chronic inflammation. Although, the strongest association refers to pancreas and liver, there are many other organs involved in carcinogenesis in diabetic patients including breast, endometrium, bladder and kidney.Recent studies suggest that there is also association between cancer incidence and anti-diabetic medications. It was observed that some medications decrease the risk of carcinogenesis and some increase that risk. The majority of studies concern metformin, a drug of choice in type 2 diabetes mellitus, and its anti-neoplastic and tumor-suppressing activity. The positive effect of metformin was found in numerous researches investigating breast, pancreas, liver, colon, ovaries and prostate tumors.Because a variety of studies have suggested that diabetes mellitus and cancer are frequently coexisting diseases, recently published studies try to explain the influence of diabetes mellitus and anti-diabetic medications on carcinogenesis in different organs.We present the review of the latest studies investigating the association between both diabetes mellitus and anti-diabetic medications and cancer incidence and prognosis.Particularly we highlight the problem of concomitant head and neck cancers in diabetics, rarely analysed and often omitted in studies.

Activation of the lectin pathway of complement by cardiopulmonary bypass contributes to the development of systemic inflammatory response syndrome after paediatric cardiac surgery.

The systemic inflammatory response is a challenge in the management of paediatric patients undergoing cardiac surgery. Although multi-factorial, a contribution by the lectin pathway of complement activation has been postulated. We therefore investigated the changes in serum levels of mannose binding lectin (MBL) and activities of MBL-MBL-associated serine protease (MASP)-1 and MBL-MASP-2 complexes immediately before and during surgery, throughout the first postoperative day and at discharge from the hospital. These changes were analysed in relation to postoperative complications. Blood samples were obtained from 185 children with congenital heart disease undergoing surgical correction with the use of cardiopulmonary bypass: preoperatively (MBL-1), 15 min after initiation of cardiopulmonary bypass (CPB) (MBL-E), 30 min (MBL-2), 4 h (MBL-3), 12 h (MBL-4) and 24 h (MBL-5) post-CPB and at discharge from hospital (MBL-K). Alterations in serum MBL levels were calculated as a ratio of its serum level at subsequent time-points (MBL-2, -3, -4, -5) to the preoperative (MBL-1) value. Decreases in MBL and MBL-MASP complexes were observed in all samples, correlating with a decrease in C4 and increase in C4a, confirming activation of the lectin pathway. Changes in MBL levels between children with an uncomplicated postoperative course and those suffering from infection or low cardiac output syndrome did not differ significantly, but significant differences were observed between the SIRS and non-SIRS groups. Paediatric cardiac surgery with the use of cardiopulmonary bypass activates the complement system via the lectin pathway and the latter contributes to the development of the post-bypass systemic inflammatory response.

Can ficolin-2 (L-ficolin) insufficiency be established by a single serum protein measurement?

Serum ficolin-2 was measured in multiple (2-27) samples from 68 paediatric sepsis patients. Fourteen individuals (21%) gave values that included a change in status from 'normal' to 'insufficient' or vice versa. Therefore, if possible, ficolin-2 concentration should be determined in samples obtained when a disease is inactive.

Comparison of the chemical and thermal denaturation of proteins by a two-state transition model.

The conformational stabilities of eight proteins in terms of the free energy differences between the native "folded" state of the protein and its "unfolded" state were determined at 298 K by two methods: chemical denaturation at 298 K and extrapolation to 298 K of the thermal denaturation results at high temperature. The proteins were expressed in Escherichia coli from the Haemophilus influenzae and E. coli genes at different levels of expression, covered a molecular mass range from 13 to 37 kg mol(-1) per monomeric unit (some exhibiting unique structural features), and were oligomeric up to four subunits. The free energy differences were determined by application of a two-state transition model to the chemical and thermal denaturation results, ranged from 9.4 to 148 kJ mol(-1) at 298 K, and were found to be within the experimental uncertainties of both methods for all of the proteins. Any contributions from intermediate states detectable from chemical and thermal denaturation differences in the unfolding free energy differences in these proteins are within the experimental uncertainties of both methods.

Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide.

BACKGROUND: Previous studies demonstrated inactivation of vitamin B12 by nitrous oxide (N(2)O). The intraoperative exposure to N(2)O was shown to induce megaloblastic anaemia and myelopathy in subjects with subclinical vitamin B12 deficiency. In contrast, no data concerning the influence of occupational exposure to N(2)O on vitamin B12 metabolic status are available to date. In the present study, the vitamin B12 status in operating theatre personnel was assessed in relation to the extent of exposure. METHODS: Ninety-five operating theatre nurses with the history of exposure to N(2)O and 90 unexposed counterparts were examined. Vitamin B12 and folic acid were measured by immunoassay. Total homocysteine (tHcy), an indicator of impaired vitamin B12 metabolism, was determined by high performance liquid chromatography. N(2)O concentration was monitored by adsorption gas chromatography and mass spectrometry. RESULTS: No significant differences were found between both groups with respect to haematological parameters and folic acid. However, subjects exposed to N(2)O presented with lower vitamin B12 [372.8 (12.1) vs 436.8 (13.2) pmol litre(-1), P<0.001] and higher tHcy [11.2 (0.5) vs 8.9 (0.5) micromol litre(-1), P=0.006]. The changes in vitamin B12 status were aggravated in subjects exposed to N(2)O in concentrations substantially exceeding occupational exposure limit (180 mg m(-3)) [vitamin B12: 341.9 (17.7) vs 436.8 (13.2) pmol litre(-1), P=0.006; tHcy: 12.9 (0.7) vs 8.9 (0.5) micromol litre(-1), P=0.047]. CONCLUSIONS: Exposure to N(2)O in healthcare workers is associated with alterations of vitamin B12 metabolic status, the extent of which depends on the level of exposure.

Increased incidence of micronuclei assessed with the micronucleus assay and the fluorescence in situ hybridization (FISH) technique in peripheral blood lymphocytes of nurses exposed to nitrous oxide.

It has been postulated that exposure to nitrous oxide and halogenated anaesthetics is associated with various adverse health effects such as neurological and reproductive abnormalities or impairment of hepatic functions. In spite of the quite well known genotoxic effects of exposure to nitrous oxide in vivo, the mechanisms of these effects are still not clear. The aim of this study was to assess the frequency of micronuclei and to identify the type of chromosomal damage (clastogenic or aneugenic) in peripheral blood lymphocytes of operating-room nurses exposed to nitrous oxide. The study group comprised 46 women working at departments where the concentration of nitrous oxide ranged from 14 to 2308 mg/m3. The control population was composed of 28 women employed in the same hospitals but in non-surgical departments. The clastogenic/aneugenic effect of nitrous oxide was evaluated in lymphocytes using the standard micronucleus (MN) assay in combination with the fluorescence in situ hybridization (FISH) technique with pancentromeric probes. The results show a significant increase of the MN frequency in lymphocytes of exposed nurses compared with the control group (4.36+/-2.23 versus 9.02+/-4.67). The multiple regression analysis revealed a statistically significant relationship (p=0.0009) between MN frequency and exposure status, indicating that the level of exposure was the main factor affecting chromosomal damage. As assessed by FISH analysis, the overall frequencies of centromere-positive MN in the control and exposed groups were 43 and 49%, respectively. The increase observed in the exposed group may suggest a slight, statistically insignificant pro-aneugenic effect of exposure to nitrous oxide.

Effect of organic matter and liming on the reduction of cadmium uptake from soil by triticale and spring oilseed rape.

The aim of the study conducted on triticale and spring oilseed rape was to determine the role of liming, brown coal and compost medium in reducing the effect of cadmium contamination (at the rates of 0, 7.5, 15 and 22.5 mg Cd kg(-1) of soil) on yield and chemical composition of the crop. In the series of experiments without liming, a considerable decline in the yield of spring triticale grain, straw, root weight and green mass yield of rape was observed in response to the soil contamination with cadmium. Brown coal and especially compost medium added to soil neutralised the negative effect of cadmium on the grain yield and reduced a decrease in the yield of straw and roots of triticale. Soil liming proved to reduce the yield drop in oilseed rape caused by the contamination of soil with cadmium. The content of cadmium in roots and grain of spring triticale far exceeded that determined in triticale straw. The pollution of soil with cadmium caused a 26-fold increase in the content of this metal in grain, a 10-fold increase in roots of triticale and a twofold in oil-seed rape. Application of compost medium, brown coal and, to a smaller extent, liming reduced the level of cadmium in the parts of triticale brought to investigation. The soil contamination with cadmium caused certain modifications in the content of nitrogen, potassium, magnesium, calcium and sodium in spring triticale and in the content of N-total, potassium and magnesium in spring oilseed rape.

Histone hyperacetylation facilitates chromatin remodelling in a Drosophila embryo cell-free system.

We found that Drosophila embryo extract contains a protein activity (or activities) that can destabilize nucleosomes, resulting in increased sensitivity to DNase I, release of nucleosomal supercoiling, high levels of conformational flexibility of DNA and more diffuse micrococcal nuclease digestion patterns. Incorporation of histone H1 did not significantly affect this nucleosome remodelling. Remodelling occurs more efficiently in hyperacetylated chromatin. It was shown previously that hyperacetylated chromatin, reconstituted in a Drosophila embryo cell-free system, exhibits increased DNase I sensitivity and a high degree of conformational flexibility of DNA. The present data suggest that the more diffuse structure of acetylated chromatin is a result of chromatin remodelling by protein activities in the Drosophila embryo extract.

Chromatin structural transitions in Drosophila embryo cell-free extract result in a high conformational flexibility of nucleosomal DNA.

DNA within chromatin has considerably more restricted flexibility in comparison with naked DNA. This raises the main question of how the functioning multi-enzyme complexes overcome the nucleosomal level of DNA packaging. We studied the DNA conformational flexibility of reconstituted chromatin in a cell-free system derived from Drosophila embryo extracts. Using this system, we have found evidence for a energy-independent chromatin remodelling process that efficiently destabilizes the nucleosome structure resulting in a high conformational flexibility of nucleosomal DNA. The described chromatin remodelling process may lay on the basis of defined molecular principles governing the molecular heterogeneity of chromatin structures in vivo.

Effect of in vivo histone hyperacetylation on the state of chromatin fibers.

We evaluated the contribution of in vivo histone acetylation to the folding of chromatin into its higher-order structures. We have compared high-order folding patterns of hyperacetylated vs. unmodified chromatin in living green monkey kidney cells (CV1 line) using intercalator chloroquine diphospate to induce alterations in the twist of internucleosomal linker DNA. We have shown that histone hyperacetylation induced by antibiotic Trichostatin A significantly alters intercalator-mediated chromatin folding pattern.

Reiter's syndrome among Asian shipboard immigrants: the case of The Golden Venture.

OBJECTIVE: To assess the incidence of Reiter's syndrome aboard The Golden Venture, a ship carrying illegal immigrants from China to the United States. METHODS: After identification of an index case, we conducted telephone interviews with medical staff at immigrant detention centers in Pennsylvania, New York, and Virginia. When a potential case was identified at one facility, we performed a site inspection, reviewing the medical records of all detainees and performing histories and physicals on all those with joint and/or ocular complaints. RESULTS: We identified two patients, both HLA B27 positive, with Reiter's syndrome. The observed incidence (0.87%) approximated the predicted incidence but may have underestimated the actual incidence. We review the history of shipboard Reiter's syndrome, and discuss the pathogenic roles of HLA B27 and particular infectious agents. CONCLUSION: Continued transportation of illegal immigrants from China and other parts of the world is likely to result in occasional clusters of Reiter's syndrome. Physicians treating immigrant populations should remain aware of the possibility of reactive arthritis.