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The paper provides a review of prevalence and outcomes of cardiovascular comorbidities in patients with chronic obstructive pulmonary disease (COPD). From a clinical and patient-centered perspective, a COPD phenotype should be able to classify patients into distinct subgroups that provide prognostic information and allow to better determine appropriate therapy that alters clinically meaningful outcomes. It is hypothesized that both COPD and artherial hypertension (AH) have common pathway linking these comorbidities and explaining why they significantly complicate the management and influence the prognosis of patients with COPD and AH. Further studies will be required to explore this hypothesis and understand the relationship between COPD and AH.

The great prevalence of comorbidities, such as arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD), generates a need to study the impact of COPD on the pathogenesis, course, and clinical picture of associated cardiovascular diseases. The paper analyzes the data available in the literature on the pathogenesis and course of arterial hypertension in patients with COPD. The paper also gives the authors’ data on the clinicofunctional and pathophysiological features of AH in patients with COPD. The findings suggest that the study group has clinical vascular and organ dysfunction that may both play a role in the pathogenesis of AH in the presence of COPD and prevent a high cardiovascular risk. Key words: arterial hypertension, chronic obstructive pulmonary disease.

BACKGROUND: Non-pharmacological treatments are an integral part of the treatment of all patients with type 2 diabetes (T2D). However, due to many factors, doctors and patients themselves tend to underestimate or completely neglect such effective methods in managing the course of the disease. Despite the high level of evidence of the effectiveness of this type of treatment for T2D, every year scientists around the world continue to actively study the effect of various non-drug methods on the course of the disease.AIM: To study the effect of a 24-week structured non-pharmacological treatment program on glycated hemoglobin reduction and weight loss in middle-aged patients with compensated T2D taking metformin.MATERIALS AND METHODS: A two-group, randomized, parallel-group, blinded trial was designed. Patients with an established diagnosis of T2D in the stage of compensation (HbA1c ≤7%), aged 45–59 years, taking metformin, were randomized to receive either standard non-pharmacological treatment of diabetes according to clinical protocol of T2D treatment in Kazakhstan, or an intensive course of non-pharmacological treatment according to a structured program developed by researchers. The duration of the intervention was 24 weeks. Primary outcomes were glycated hemoglobin, body weight. Secondary outcomes: blood pressure, waist circumference, insulin resistance index (HOMA-IR), lipid profile: total cholesterol, high and low density lipoproteins, triglycerides. The outcomes of the participants in both groups were assessed at baseline, 12 and 24 weeks after randomization. The study is registered with ClinicalTrials.gov NCT04632823.RESULTS: The study included 200 patients, 67 patients completed the study: intervention group n=33, control group n=34. After 24 weeks of observation, patients in the intervention group showed a significant decrease in HbA1c from 6.34% to 6.22%, p

Purpose: to study the frequency and structure of undifferentiated connective tissue dysplasia (UCTD) in school-age children with myopia, their relationship to choroidal thickness and course of myopia.Patients and methods. The object of study was 120 children (240 eyes) aged 11–13 years with school axial myopia (axial length (AL) from 24.5 to 26.0 mm). Special ophthalmological examination included optical coherent tomography of macular zone (“RTVue 100” Optovue, USA) and “Cross Line” scan for measuring choroidal thickness in foveal area and 1000 μm from it in nasal and temporal regions.Results. According to studies, the phenotypic signs of UCTD were diagnosed in 56 children (46.7%) with school myopia, the largest group included phenotypic signs of locomotor syndrome; 14 children (25%) had a weak degree of UCTD, 34 children (60.7%) — moderate degree and 8 children (14.3%) — pronounced degree. Comparative characteristic of changes in choroidal thickness detected a high degree of interrelation between the severity of clinical manifestations of UCTD and the level of decrease in blood-flow in the choroid. In children of the main group with signs of UCTD, the annual growth of AL exceeded the same parameters in children of the control group by more than 2.5 times (p < 0.05); due of accumulation of phenotypic signs of UCTD, a more noticeable tendency to decrease of choroidal thickness and the increase of AL was observed (p < 0.05). The statistical analysis confirmed the presence of significant negative correlation between the decrease in average thickness index in segment of the macular map and the degree of increase of AL (p < 0.05).Conclusions. According to results of diagnostic screening, in 46.7% children with school myopia, we detected phenotypic signs of UCTD. The method of optical coherence tomography showed that with increasing severity of UCTD, indexes of choroidal thickness in the macular zone are significant decreased. In the catamnesis (duration 1 year), it was found that in children with myopia with moderate and pronounced degrees of UCTD, increase of AL is associated with degree of thinning choroidal thickness, which indicates violations of biomechanical status of sclera.

In total, 40 patients with various stages of arterial hypertension (AH) were examined. All patients received nifedipine GITS as monotherapy or in combination with hydrochlorothiazide for 6 months. Nifedipine GITS demonstrated not only good antihypertensive activity, but also substantial organo-protective effects. Cardioprotection manifested in the reduction of left ventricular (LV) hypertrophy and LV diastolic dysfunction, as well as in correction of pathological LV geometry types. Vasoprotection was manifested in the correction of pathological microcirculation types. In addition, retinal functional status was improved.

Aim. To investigate endothelium-regulating and antioxidant effects of trandolapril and verapamil SR combination (Tarka) in patients with arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD).Material and methods. In total, 42 COPD and AH patients, aged 48-70 years, were examined. All participants received continuous basis COPD treatment and 16-week Tarka therapy. At baseline and at the end of the study, lung function, systemic inflammation, oxidative stress and antioxidant potential parameters were measured.Results. All patients achieved office-measured target blood pressure (BP) levels. Bronchial conductivity increase was explained by therapy-associated improvement in pulmonary hemodynamics. The medication was safe and well-tolerated by patients with COPD and AH. Decrease in C-reactive protein levels, possibly explaining antiinflammatory medication effect, pointed to the suppression of endothelium-damaging influences. The treatment was also associated with decreased lipid peroxidation, reduced serum levels of acylhydroperoxides, and increased concentration and activity of antioxidant enzymes.Conclusion. AH and COPD therapy should include antihypertensive agents with pleiotropic effects, specifi- cally, suppressing systemic inflammation, correcting endothelial function, and enhancing antioxidant potential. These characteristics could act as additional criteria of AH treatment effectiveness in patients with combined cardiovascular and respiratory pathology.

The association of autoimmune cytopenia (AIC) and inflammatory bowel disease (IBD) has been reported in small series, but the incidence of and risk factors for IBD in children with AIC are not known. One thousand six hundred nine children with chronic immune thrombocytopenic purpura, autoimmune haemolytic anaemia or Evans syndrome from the prospective OBS'CEREVANCE cohort are included in this study. Overall, 15 children were diagnosed with IBD, including 14 who developed IBD after AIC diagnosis (median delay: 21 months). The only risk factor for IBD development is age at AIC over 10 years. Out of 10 children genetically tested, germline variants associated with autoimmune disorders were identified in three (CTLA4: two, DOCK11: one). In children and adolescents monitored for AIC or past history of AIC, especially children over 10 years, gastro-intestinal (GI) symptoms (recurrent abdominal pains, GI bleeding, chronic diarrhoea, weight loss) should suggest IBD and deserve specific work-up and genetic studies. Identification of a causal germline variant will allow targeted therapy., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Cell-free protein expression systems are here combined with 3D-printed structures to study the challenges and opportunities as biofabrication enters the spaces of architecture and design. Harnessing large-scale additive manufacturing of biological materials, we examined the addition of cell-free protein expression systems ("TXTL" i.e., biological transcription-translation machinery without the use of living cells) to printed structures. This allowed us to consider programmable, living-like, responsive systems for product design and indoor architectural applications. This emergent, pluripotent technology offers exciting potential in support of health, resource optimization, and reduction of energy use in the built environment, setting a new path to interactivity with mechanical, optical, and (bio) chemical properties throughout structures. We propose a roadmap towards creating healthier, functional and more durable systems by deploying a multiscale platform containing biologically-active components encapsulated within biopolymer lattices operating at three design scales: (i) supporting cell-free protein expression in a biopolymer matrix (microscale), (ii) varying material properties of porosity and strength within two-dimensional lattices to support biological and structural functions (mesoscale), and (iii) obtaining folded indoor surfaces that are structurally sound at the meter scale and biologically active (we label that regime macroscale). We embedded commercially available cell-free protein expression systems within silk fibroin and sodium alginate biopolymer matrices and used green fluorescent protein as the reporter to confirm their compatibility. We demonstrate mechanical attachment of freeze-dried bioactive pellets into printed foldable fibrous biopolymer lattices showing the first steps towards modular multiscale fabrication of large structures with biologically active zones. Our results discuss challenges to experimental setup affecting expression levels and show the potential of robust cell-free protein-expressing biosites within custom-printed structures at scales relevant to everyday consumer products and human habitats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ho, Kubušová, Irabien, Li, Weinstein, Chawla, Yeung, Mershin, Zolotovsky and Mogas-Soldevila.)

Objectives: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth., Design: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC)., Results: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables., Conclusion: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation., Competing Interests: Conflict of interest AC has provided consulting services to SkopeMR, Inc., SubtleMedical, Chondrometrics GmbH, Image Analysis Group, ICM, Culvert Engineering, and Edge Analysis; is a stockholder of Subtle Medical, LVIS Corp., and Brain Key; is on the advisory board for Chondrometrics GmbH and Brain Key; has received royalties from LVIS Corp.; and reports grant support from NIH (R01AR063643, R01AR077604, R01EB002524, R01EB026136, K24AR062068, and P41EB015891). CD reports grant support from NIHNIAMS (R01AR074453). ED is a stockholder of Biomediq A/S. MN reports honoraria for lectures from General Electric. SBZ reports personal fees from Infirst Healthcare, Pfizer, and Osteoarthritis Research Society International and grants from The Netherlands Organisation for Health Research and Development, Dutch Research Council, European Union, Foreum, and Dutch Arthritis Association outside the submitted work. None of the mentioned organizations were involved in the design, execution, data analysis, or the reporting of this study., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely., Aim: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures., Methods: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS)., Findings: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (C T ) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed., Conclusion: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Perspective taking, or "theory of mind," involves reasoning about the mental states of others (e.g., their intentions, desires, knowledge, beliefs) and is called upon in virtually every aspect of human interaction. Our goals in writing this chapter were to provide an overview of (a) the research questions developmental psychologists ask to shed light on how children think about the inner workings of the mind, and (b) why such research is invaluable in understanding human nature and our ability to interact with, and learn from, one another. We begin with a brief review of early research in this field that culminated in the so-called litmus test for a theory of mind (i.e., false-belief tasks). Next, we describe research with infants and young children that created a puzzle for many researchers, and briefly mention an intriguing approach researchers have used to attempt to "solve" this puzzle. We then turn to research examining children's understanding of a much broader range of mental states (beyond false beliefs). We briefly discuss the value of studying individual differences by highlighting their important implications for social well-being and ways to improve perspective taking. Next, we review work illustrating the value of capitalizing on children's proclivity for selective social learning to reveal their understanding of others' mental states. We close by highlighting one line of research that we believe will be an especially fruitful avenue for future research and serves to emphasize the complex interplay between our perspective-taking abilities and other cognitive processes., (© 2017 Elsevier Inc. All rights reserved.)

Patients with methicillin-resistant Staphylococcus aureus (MRSA) clones, which were traditionally seen in the community setting (USA400/CMRSA7 and USA300/CMRSA10), are often identified as hospital-acquired (HA) infections using Infection Prevention and Control (IPC) surveillance definitions. This study examined the demographics and healthcare risk factors of patients with HA-MRSA to help understand if community MRSA clones are from a source internal or external to the hospital setting. Despite USA300/CMRSA10 being the predominant clone in Alberta, hospital clones (USA100/CMRSA2) still dominated in the acute care setting. In the Alberta hospitalized population, patients with USA400/CMRSA7 and USA300/CMRSA10 clones were significantly younger, had fewer comorbidities, and a greater proportion had none or ambulatory care-only healthcare exposure. These findings suggest that there are two distinct populations of HA-MRSA patients, and the patients with USA400/CMRSA7 and USA300/CMRSA10 clones identified in hospital more greatly resemble patients affected by those clones in the community. It is possible that epidemiological assessment overidentifies HA acquisition of MRSA in patients unscreened for MRSA on admission to acute care.

The use of evidence has become a foundational part of health promotion practice. Although there is a general consensus that adopting an evidence-based approach is necessary for practice, disagreement remains about what types of evidence practitioners should use to guide their work. An empirical understanding of how practitioners conceptualize and use evidence has been lacking in the literature. In this article, we explore (i) practitioners' purposes for using evidence, (ii) types of evidence they valued, and (iii) qualities that made evidence useful for practice. 58 semi-structured interviews and 250 h of participant and non-participant observation were conducted with 54 health promotion practitioners working across New South Wales, Australia. Interviews were recorded and transcribed, and field notes were written during the observations; these were analysed using Grounded Theory methods. Practitioners used evidence for practical and strategic purposes, and valued four different types of evidence according to their relevance and usefulness for these purposes. Practitioners' ideal evidence was generated within their practice settings, and met both substantive and procedural evaluation criteria. We argue that due to the complex nature of their work, practitioners rely on a diverse range of evidence and require organizational structures that will support them in doing so., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background:  The development of an inhibitor is the major complication facing patients with hemophilia A treated by administration of factor (F) VIII concentrates. Restoration of tolerance to FVIII can be achieved by prolonged administration of FVIII (immune tolerance induction, ITI). Although ITI has been used for more than 30years in patients with hemophilia A and inhibitor, its mechanism of action is still poorly understood., Objectives:  As administration of high doses of antigen can induce the apoptosis of the T cells recognizing the antigen, a potential mechanism of action of ITI may be the deletion of FVIII-specific T cells., Patients/methods:  We studied the CD4+ T-cell response to FVIII in five (one mild, one moderate and three severe) patients successfully desensitized by administration of FVIII and in control subjects., Results:  Following repeated stimulation with autologous dendritic cells loaded with FVIII, FVIII-specific T oligoclonal cell lines were expanded from the blood of one of the successfully desensitized patients. The FVIII-specific T cells produced IL-5, IL-13 and IL-2. By contrast, FVIII-specific T-cell lines could not be derived from three patients with mild hemophilia A without inhibitor or from four normal control subjects., Conclusions:  These data represent the first analysis of the cellular mechanisms regulating the induction of tolerance to FVIII. They demonstrate that successful tolerance induction may occur without deletion of FVIII-specific T cells., (© 2011 International Society on Thrombosis and Haemostasis.)

Unlabelled: Discovering chronic illnesses in children initially shatters the family balance and triggers emotional reactions., Patients and Methods: We retrospectively report parents' experiences and emotional reactions to learning the diagnosis of hemophilia in their children. Twenty-six parents (18 mothers, 8 fathers) of 24 hemophiliac A or B children (major n=8, moderate n=6, mild n=10), aged from 0 to 18 years, were individually asked to answer a separate questionnaire for each child during a systematic consultation. We obtained 29 completed questionnaires., Results: The diagnostic circumstances were a major bleeding episode (n=8), frequent hematomas (n=4), preoperative blood sample (n=4), and familial screening (n=8). In 9 cases, both parents were informed of the diagnosis at the same time and in 13 cases, the mother was alone. The most frequent feelings were future apprehension (n=20), initial shock reaction (n=18), anxiety (n=12), and guilt (n=10) expressed by mothers only. Parents' emotional states were neither correlated with the severity of the disease nor with the diagnostic circumstances. All parents questioned reported being satisfied with the quality of the initial information., Conclusion: The crisis generated by learning the diagnosis of a chronic disease in their children warrants delivering initial information to both parents at the same time, especially in hemophilia since mothers tend to be more concerned., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Life expectancy after transplantation has improved, and cancer may soon be the leading cause of late death after transplantation. The guidelines of the American and European societies of nephrology and urology have not yet established the optimal frequency for screening for renal cell carcinoma (RCC) of native kidneys in patients who have undergone renal transplantation., Objective: To evaluate the prevalence, prognosis, and risk factors of RCC in a series of patients followed up for 16 years in our transplantation unit., Materials and Methods: Our study is a follow-up observational cohort study conducted in 694 consecutive renal transplant recipients admitted to our institution from July 1991 through July 2007. At our institution, ultrasound studies of the native kidneys were performed every 6 months after renal transplantation., Results: In the patient cohort studied, 10 patients developed a renal tumor (1.6% incidence). Three patients died of causes other than recurrence of RCC. Seven patients are alive with no evidence of RCC recurrence or metastatic disease after a mean (range) follow-up of 41 (12-96) months. Acquired cystic kidney disease and dialysis duration were positively associated with development of RCC., Conclusions: The incidence of RCC in the literature varies between 0.3% and 4.8%. The variability depends on the timing of follow-up, with a higher incidence in prospective studies with strict follow-up. We advise ultrasound studies performed by specialized physicians every 6 months after transplantation. More detailed guidelines designed by the major international transplantation societies are necessary.

Dyspepsia is an extrarenal symptom frequently found in hemodialysed patients; it is due to chronic renal failure, and uremic gastritis is a specific associated condition in chronic renal failure (CRF). On the other hand, in the general population, Helicobacter pylori infection is an important dyspepsia-related risk factor; its close connections with gastro-duodenal pathology are already known, above all the peptic disease in a really exclusive way. By observation of a dyalitic group of patients, opportunely matched with a no CRF group, we evaluated CRF-associated uremia and Helicobacter pylori infection which could eventually interact causing symptoms and lesions. A statistical analysis of obtained data allowed us to conclude that, although there is not, from an epidemiological view-point, a larger diffusion of Helicobacter pylori among dyalitic patients compared to general population, moreover the infection is uremia-synergic in causing gastro-duodenal symptoms and lesions. These findings, therefore, suggest systematically investigation a possible Helicobacter pylori infection in CRF patients and its relation to gastritis grading, and searching for probable active peptic lesions.

Unlabelled: Neonates with Down's syndrome have an increased risk for congenital leukaemia, particularly acute megakaryoblastic leukaemia (FAB, M7) which most often resolves spontaneously and is called transient leukaemia. It can be observed in non-constitutional trisomy 21 infants then presenting trisomy 21 on blasts cells., Observation: We report a transient leukaemia with an isolated pericardial effusion in a phenotypically normal neonate. Trisomy 21 was found on blasts cells. Complete remission remains after 32 months., Discussion: Congenital leukaemias, with trisomy 21 on blasts cells have a good prognosis that justifies observation before using chemotherapy.

Unlabelled: No data are available on incisional hernia in renal transplant recipients using a midline incision. This study evaluated the incidence of abdominal wall incisional hernia, comparing two surgical approaches: midline and J-shaped incisions., Methods: Between 1991 and 2005, 415 consecutive patients underwent renal transplantation: between 1991 and 1997, 139 patients through a lateral incision; between 1997 and 2005, 137 of 276 renal transplant patients via a midline incision, and 139 via a J-shaped incision. We evaluated the incidence of incisional herniae in these patients. Analyzed factor risks included: age, sex, body mass index, diabetes, reoperation, lymphocele, dialysis time, underlying renal disease, and immunosuppressive therapy., Results: During follow-up, 15 patients of 415 transplantations were dead or lost to follow-up. Incisional herniae were identified in 12 cases of 132 (9%) between 1991 and 1997. Between 1997 and 2005 we identified 3 of 133 (2.2%) patients who underwent a midline incision and 15 of 135 (11.1%) who received a J-shaped incision (P=.005). Comparing midline and J-shaped incisions before and after 1997, the incidence reduction was significant (P=.01). Comparing the incidence among patients treated with J-shaped incision before versus after 1997, the increased incidence was insignificant (P=.6). Multivariate analysis found the most important risk factor was obesity followed by polycystic kidney disease, reoperation, wound infection, and mycophenolate mofetil therapy., Conclusions: Our data showed an advantage of a midline incision. Strategies to prevent surgical complications, such as abdominal wall relaxation and poor cosmetic results, are needed; the midline incision may be a possible alternative to address this complication.

In spite of our present improved knowledge of the epidemiology and pathways of contamination of the hepatitis C virus (HCV), infection still remains a public health problem. One category of patients who have suffered greatly from the consequences of HCV infection is certainly that of hemodialysis patients. In the past, in fact, their need for transfusions exposed these patients to infection and, as a result, subjects on dialysis for over 15 years are today paying the price for those inevitable transfusions, as the virus and its pathways of contagion were unknown then. However, still today, albeit at a much lower prevalence, even subjects with a shorter dialysis age present a higher prevalence of anti-HCV than the general population, suggesting that other factors of contamination than the classical ones contribute to keeping this prevalence high. Its clinical course is generally asymptomatic and the biological and virological progression of the disease is quite particular and apparently benign. The mortality rate of infected patients is higher than in noninfected subjects and this is not only due to the liver disease itself but also to cardiovascular disorders. Even anti-viral therapy, after its first timid steps, is now routinely used in patients with a certain degree of liver damage and kidney transplant candidates. The appropriate use of pegylated interferons is expected to improve the percentage of eradication and limit side effects, in parallel with what has been observed in non-dialysis patients. Ribavirin, however, is at present contraindicated due to its toxic effects on red blood cells as hemoglobin content could be dangerously reduced in these patients.

Introduction: The incidence of urological complications after kidney transplantation varies from 3% to 14%, with a probable loss of the graft in 10% to 15% of cases and a mortality rate of up to 15%, despite improvements in prevention, diagnosis, and treatment as well as the use of new immunosuppressive therapies. Urinous fistulae, which are considered early complications of transplantation, are due to ischemic damage or necrosis generally occurring in the distal third of the ureter. Preservation of accessory arteries to the lower portion of the kidney is important, as they may constitute the blood supply of this segment of the collecting system or ureter. Their ligation may lead to necrosis and urinary fistulae. Ureteral stenosis, as late complication, is related to a pathology of the ureter itself, to infections, to abscesses, to fibrosis, and to ischemia. An early endoscopic approach permits resolution in 70% of cases. The aim of this retrospective study was to determine incidence and treatment of these complications., Materials and Methods: From 1991 to 2004 we performed 453 kidney transplantations both from cadaveric and living donors. In 199 patients we performed a transvesical ureteroneocystostomy (UNCS), and in 260, an extravesical UNCS., Results: The nine patients who showed fistulae (1.9%) underwent surgical treatment. In eight we used a direct ureteral reimplantation, and in one, a Boari flap technique. Nephrectomy was necessary in four patients, including two who died of septic complications. In all 26 cases of ureteral stenosis (5.6%), we used an endourological approach (anterograde or retrograde), with surgical treatment afterward in 11 patients (42%) nine direct reimplants, one anastomosis to the native ureter (transplantation from a living donor), and in one case a Boari flap technique four patients who underwent surgical treatment showed progressive damage to graft function., Conclusions: In all patients who showed fistulae we suggest surgical review: for patients with ureteral stenosis, we suggest first an endourological approach and only when it is not successful do we consider surgical treatment.

Study Design: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients., Objectives: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg., Setting: Neurourology Section, Careggi Hospital, Florence, Italy., Methods: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3., Results: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks. Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner., Conclusion: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients., Sponsorship: This study was not sponsored.

Objectives: To identify patient-related risk factors of infection and ways of transmission of extended-spectrum betalactamase (ESBL) producing Serratia marcescens in the paediatric intensive care unit (PICU) of Amiens university hospital (France) between June and July 2002., Methods: Five cases (four pulmonary infected and one stool contaminated symptom-free neonates) and 35 controls, admitted in the PICU, are included. S. marcescens ESBL analysed are isolated from respiratory tract and faecal samples for cases and urine and pus samples from two non-paediatric other patients. Univariate and multivariate analysis are performed on EPI INFO 6.04 dFr and SPSS 11.0.1., Results: S. marcescens ESBL infections or colonisations rate is 12.5% [4.7-27.6]. The incidence is 8.8 [6.7-11.6] per 1000 hospital-stay days. By univariate analysis, cases and controls don't differ with respect of age, sex, and weight at admission or preterm delivery. Cases don't have more often invasive nursing care than controls. But, they were intubated (P <0.03) and hospitalised (P <0.03) for a longer time than controls. Linear regression analysis showed that duration of intubation was independent predictor of acquisition of S. marcescens ESBL (P <0.008). S. marcescens ESBL strains implicated in pulmonary infections, showed the same pattern of multidrug resistant and ERIC-PCR profile. This clone differs from others isolated from stool or other samples from other hospital wards., Conclusion: As S. marcescens cross-colonization appears to be due to lake of hand hygiene and asepsis during invasive nursing care, reinforcing hygiene measures permit to contain the outbreak.

Objective: This study assesses 2,5-hexanedione (2,5-HD) in the urine of subjects exposed to n-hexane solvent between 1991 and 1998, from details obtained from the Registry of Biological Monitoring (BM) at the Florence Local Health Unit, and its development over time., Methods: The Registry contains 15,925 samples from 6,650 subjects occupationally exposed to n-hexane, especially in leather (9,099 samples; 3,607 subjects) and shoe (3,865 samples; 1,938 subjects) production., Results: Over the time span studied there was a total reduction of 31.9% in urinary 2,5-HD level. The yearly decrease over the entire period was 5.4%. Dividing the 8 years into three periods: before the introduction of the new legislation for health protection in the workplace (1991-1993), during its transition (1994-1996) and after its complete enforcement (1997-1998), respectively, we observed a marked decrease in the last period. Women and young people (under 30 years) experienced significantly higher absorption levels (respectively, 7.1% and 24.4%)., Conclusion: The data suggest that monitoring was more frequent in subjects with higher starting values, and the greatest decrease was reported in this group. Reduction may be due to less n-hexane in the products used, better structural conditions in the factories, and the effectiveness of inspections carried out by the authority for hygiene and safety in the workplace. The results confirm the usefulness of the reporting of risk levels of exposure to industrial toxicants by routine biological monitoring.

This article reviews the standard techniques of cerebrospinal fluid (CSF) shunt procedures and comments on advantages and disadvantages between various techniques. Complications of these procedures also are discussed.

While cranial birth injuries in term infants are well recognized, to date, only small case series have been described. In an attempt to further define the spectrum of cranial birth injuries, we analyzed 41 consecutive cranial birth injuries at our institution over the period 1991-1998. The most common clinical presentations were apnea (39%) and seizures (37%). Average Apgar scores were 5.7 at 1 min and 7.3 at 5 min; 54% of infants had abnormally low Apgar scores at 1 min and 31% had abnormally low scores at 5 min. The most common intracranial lesion was subdural hemorrhage, present in 73% of infants; most had either a tentorial (57%) and/or interhemispheric (50%) location. Operative treatment was required in 5 infants (12%). Two of the 41 infants (4.8%) died. The study group was compared with a control group of 63 randomly selected births without cranial injury. Using a stepwise logistic regression model, independently significant variables included neonatal birth weight, Apgar scores at 1 and 5 min and mode of delivery. Compared with the controls, the study group had a significantly higher incidence of forceps and/or vacuum deliveries. Combining vacuum, forceps and urgent cesarean section deliveries together as 'urgent' and elective cesarean and spontaneous vaginal deliveries as 'nonurgent', we could find no significant differences between these two groups. Our data conflict with those of Towner et al. [N Engl J Med 1999;341:1709-1714], and suggest that the method of assisted delivery, rather than the urgency of the delivery or dysfunctional labor per se, is a more important variable in cranial birth injuries., (Copyright 2001 S. Karger AG, Basel)

Commercially available anterior cervical internal fixation devices are designed for placement in adults and older children. Use of these systems in preschool-aged children is precluded due to the small size of their cervical vertebral bodies (VBs). The authors describe a 2-year-old boy who suffered a C3-4 injury, resulting in complete ligamentous disruption. Because of the gross cervical instability, they elected to perform surgery via posterior and anterior approaches, supplemented with internal fixation, during the same operation. The purpose of the anterior internal fixation device is to deliver compressive forces onto the interbody graft and keep it in place, thus optimizing the potential for a successful fusion. Because of the discrepancy in size between the VBs and the plate and screws, however, the authors were unable to use any of the standard anterior cervical fixation devices. Instead, they implanted a craniofacial miniplate, and the patient was required to wear an external halo brace. The miniplate provided enough stability to allow for a solid fusion. The authors believe that this technique is a reasonable option in young children who require anterior cervical fixation.

Studies performed to date on the prevalence of biliary lithiasis (BL) in chronic renal failure patients on hemodialysis (HD) have given contradictory results. The aims of the present study were to evaluate the prevalence of BL and its main associated risk factors in a population of hemodialysis patients, and to compare the results with those we had obtained previously in an overt population of the same zone. The study included 171 patients (83 M, 88 F), mean age 62.5 years and mean duration of dialysis 66.7 months. The screening protocol also included body mass index (BMI), a number of biochemical parameters and an ultrasound scan of the gallbladder and biliary tract. The general prevalence of BL was 33.3% (30.1% in men and 36.4% in women), and this figure was significantly higher than that found in our previous study. Prevalence increased with age in both sexes (Mantel-Haenszel Chi-squared = 5.4, p < 0.03), but not with duration of dialysis. The main risk factors, evaluated with multiple logisstic regression, were the presence of diabetes mellitus and high serum phosphorus levels. Specific symptoms were also significantly associated in BL patients. No association was found with parity, BMI or serum lipid alterations. In conclusion, the prevalence of BL in a Sicilian population of HD patients was higher than that found in an overt population of the same area and the associated main risk factors were not coincident. Further studies are needed to establish the role played by the phase of end-stage renal disease before HD and to correct the metabolic disturbances to limit a high percentage of morbidity in a disease already in itself sufficiently disabling.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a diverse range of chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). Although no endogenous physiological ligand for the AhR has yet been described, numerous studies support the existence of such a ligand(s). Here we have examined the ability of prostaglandins and related chemicals to activate the AhR signaling system. Using two AhR-based bioassay systems we report that relatively high concentrations of several prostaglandins (namely, PGB3, PGD3, PGF3alpha, PGG2, PGH1, and PGH2) can not only stimulate AhR transformation and DNA binding in vitro, but also induce AhR-dependent reporter gene expression in mouse hepatoma cells in culture. PGG2 also induced AhR-dependent reporter gene expression to a level three-to four fold greater than that observed with a maximal inducing dose of TCDD. Sucrose gradient ligand binding analysis revealed that PGG2 could competitively displace [3H]TCDD from the AhR. Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway., (Copyright 2001 John Wiley & Sons, Inc.)

Ketamine, an NMDA antagonist, has been used in pain treatment for a number of years. Recent reports have suggested its utility in a variety of pain states including post-herpetic neuralgia [1], cancer [2], and postoperative pain [5]. While a variety of neuropsychologic side effects are observed with parenteral ketamine, in oral use these side effects have been less pronounced [2,3]. We report a patient with severe hepatic disease who developed hallucinations following a 75-mg oral dose of ketamine for treatment of severe cancer pain unresponsive to morphine.

The osteoblast-like MC3T3-E1 cell line provides an excellent in vitro model of bone development. This system undergoes three orderly time-dependent phases characterized by proliferating preosteoblasts, matrix accumulation by postmitotic differentiating osteoblasts, and mineralization of the matrix, which results in the formation of multilayered bone nodules. The Ets family transcription factors regulate genetic programs that affect the proliferation and differentiation of osteoblasts. Of the eight Ets family transcription factors examined by our laboratory, only Etsl and Ets2 were found to be expressed at significant levels in this osteogenic system. Etsl is expressed in proliferating preosteoblastic cells, whereas Ets2, silent during this phase, is expressed by differentiating and mature osteoblasts. In addition, the expression of Etsl can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development and bone turnover and induce specific cellular responses in bone cells. Thus, the multiple functions of RA in bone cells are likely to be mediated in part by Etsl. We show that the expression of Ets2 precedes and then parallels osteopontin expression and that the OPN promoter contains Ets binding sites and is a transcriptional target of Ets2. In order to identify other potential Ets target genes, we analyzed promoter regions of genes revealed by serial analysis of gene expression as present in the differentiation stage. The functional analysis of these genes has the potential to provide much needed information as to their function in osteogenesis and mineralization of the extracellular matrix and in bone-related diseases.

The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates many of the biologic and toxicologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) and related chemicals. Here we utilized two AhR-dependent bioassay systems as screening tools to identify novel AhR agonists and to detect the presence of AhR agonists in sample extracts. These assays measure the ability of a chemical to activate AhR DNA binding in vitro (GRAB bioassay) or AhR-dependent (luciferase) gene expression in cultured cells (CALUX bioassay). Known AhR agonists (halogenated and nonhalogenated aromatic hydrocarbons) were positive in both assays, whereas the AhR antagonist alpha-naphthoflavone exhibited agonist activity only in the GRAB assay. In vitro GRAB analysis has identified several imidazoline receptor ligands and beta-carbolines as AhR agonists and also revealed the presence of AhR agonist activity in crude DMSO extracts of commercial newspapers. In contrast to their positive activity in the GRAB assay, the majority of these chemicals/extracts were only weakly active or inactive in the cell-based CALUX assay. Our results not only reveal that the ability of a chemical to activate the AhR in vitro does not necessarily correlate with its ability to induce gene expression in intact cells, but the high level of false positives obtained with the GRAB assay clearly demonstrates its inability to accurately identify AhR agonists or agonist activity. Screening of unknown chemicals, chemical classes, and samples for AhR agonist activity will require the use of intact cell bioassays.

The v-ets oncoprotein and its progenitor Ets1 belong to a family of transcription factors that are related by an 85 amino acid conserved DNA binding domain, the ets domain. Ets1 plays important role(s) in control of cell proliferation, differentiation and apoptosis. Abnormal expression of Ets1 could lead to disruption of these processes and contribute to development of malignancy. Retinoic acid (RA) inhibits proliferation, induces differentiation and regulates apoptosis in many different cell types. Here, we demonstrate that RA treatment increases the expression of Ets1 mRNA, but not that of Ets2, Elk1 or Fli1 in MC3T3-E1 cells. Ets1 induction is detectable after 4 h, can be maintained for at least 14 days, and is inhibited by Actinomycin D, which suggests that RA regulation of Ets1 occurs at the transcriptional level. The promoter region of Ets1 contains four retinoic acid response element (RARE) half sites located at -94, -152, -1765 and -2252 from the translation start site. We show that RARbeta is expressed by MC3T3-E1 cells in the presence of RA and demonstrate that it binds to the -94 RARE half site. Furthermore, RA induces transcription of Ets1 promoter-reporter constructs containing this RARE half site.

The care of patients with shunted hydrocephalus is one of the most common clinical problems facing a pediatric neurosurgeon. Despite the prevalence of this clinical entity, it is our impression that the management strategies for these patients vary significantly amongst pediatric neurosurgeons. In an effort to better understand how varied these practices are, we surveyed 261 neurosurgeons with an expressed interest in pediatric neurosurgery, of whom 149 (57%) responded. The survey contained questions pertaining to preoperative and intraoperative management, choice of shunt valve, treatment philosophies with respect to shunt revision, evaluation process for potential shunt malfunction, treatment strategies for shunt infections and routine follow-up care. The answers to the questions confirmed our expectations that there are a variety of ways to manage these patients.