Conformationally Restricted Glycoconjugates Derived from Arylsulfonamides and Coumarins: New Families of Tumour-Associated Carbonic Anhydrase Inhibitors.

The involvement of carbonic anhydrases (CAs) in a myriad of biological events makes the development of new inhibitors of these metalloenzymes a hot topic in current Medicinal Chemistry. In particular, CA IX and XII are membrane-bound enzymes, responsible for tumour survival and chemoresistance. Herein, a bicyclic carbohydrate-based hydrophilic tail (imidazolidine-2-thione) has been appended to a CA-targeting pharmacophore (arylsulfonamide, coumarin) with the aim of studying the influence of the conformational restriction of the tail on the CA inhibition. For this purpose, the coupling of sulfonamido- or coumarin-based isothiocyanates with reducing 2-aminosugars, followed by the sequential acid-promoted intramolecular cyclization of the corresponding thiourea and dehydration reactions, afforded the corresponding bicyclic imidazoline-2-thiones in good overall yield. The effects of the carbohydrate configuration, the position of the sulfonamido motif on the aryl fragment, and the tether length and substitution pattern on the coumarin were analysed in the in vitro inhibition of human CAs. Regarding sulfonamido-based inhibitors, the best template turned out to be a d-galacto-configured carbohydrate residue, meta-substitution on the aryl moiety (9b), with Ki against CA XII within the low nM range (5.1 nM), and remarkable selectivity indexes (1531 for CA I and 181.9 for CA II); this provided an enhanced profile in terms of potency and selectivity compared to more flexible linear thioureas 1-4 and the drug acetazolamide (AAZ), used herein as a reference compound. For coumarins, the strongest activities were found for substituents devoid of steric hindrance (Me, Cl), and short linkages; derivatives 24h and 24a were found to be the most potent inhibitors against CA IX and XII, respectively (Ki = 6.8, 10.1 nM), and also endowed with outstanding selectivity (Ki > 100 µM against CA I, II, as off-target enzymes). Docking simulations were conducted on 9b and 24h to gain more insight into the key inhibitor-enzyme interactions.

Comparing human to electronic observers to monitor hand hygiene compliance in an intensive care unit.

Objective: We sought to determine whether an electronic hand hygiene (HH) system could monitor HH compliance at similar rates to direct human observation. Methods: This 4-year proof-of-concept study was conducted in an intensive care unit (ICU) of a private tertiary-care hospital in São Paulo, Brazil, where electronic HH systems were installed in 2 rooms. HH compliance was reported respectively using direct observation and electronic counter devices with an infrared system for detecting HH opportunities. Results: In phase 1, HH compliance by human observers was 56.3% (564 of 1,001 opportunities), while HH compliance detected by the electronic observer was 51.0% (515 of 1,010 opportunities). In phase 2, human observers registered 484 HH opportunities with a HH compliance rate of 64.7% (313 of 484) versus 70.6% (346 of 490) simultaneously detected by the electronic system. In addition, an enhanced HH electronic system monitored activity 24 hours per day and HH compliance without the presence of a human observer was 40.3% (10,642 of 26,421 opportunities), providing evidence for the Hawthorne effect. Conclusions: The electronic HH monitoring system had good correlation with human HH observation, but compliance was remarkably lower when human observers were not present due to the Hawthorne effect (25%-30% absolute difference). Electronic monitoring systems can replace direct observation and can markedly reduce the Hawthorne effect.

Arthrotomy versus arthroscopy in the treatment of septic arthritis of the knee in adults: a randomized clinical trial.

PURPOSE: To evaluate the efficacy of treatment and functional recovery of patients diagnosed with septic arthritis of the knee submitted to two surgical techniques: conventional arthrotomy and arthroscopic approach for debridement. METHOD: In this prospective clinical study, all adult patients diagnosed with knee pyoarthritis in a 15-month period at a philanthropic hospital in Brazil were randomized into two groups: one group submitted to arthrotomy and the other to arthroscopy. The protocols of antibiotic therapy, physical therapy and postoperative assessment were standardized in both groups. Demographic, clinical, functional and laboratorial variables were compared between groups, with a minimum follow-up of 24 months. RESULTS: There was no difference in effectiveness of treatment in both groups, but 2 patients (18.2 %) of the arthrotomy group needed a new approach. The pain was higher in those undergoing treatment by arthrotomy, at 7 and 14 days postoperatively. The return to activities of daily living took an average of 5.7 days for both groups: 7.1 days for the arthrotomy group and 4.3 days for arthroscopy group. CONCLUSION: It was found that the treatment of knee septic arthritis by both techniques showed similar effectiveness in healing, but the arthroscopy procedure was better than arthrotomy because it has a lower reinfection rate and low initial inflammatory reaction. LEVEL OF EVIDENCE: Therapeutic studies, Level I.

Open fractures and the incidence of infection in the surgical debridement 6 hours after trauma.

OBJECTIVES: To determine whether a time delay greater than 6h from injury to surgical debridement influences the infection rate in open fractures. METHODS: During a period of 18 months, from October 2010 to March 2012, 151 open fractures were available for study in 142 patients in our hospital. The data were collected prospectively and the patients were followed up for 6 weeks. The patients were divided into two groups regarding the time delay from injury to surgical debridement (more or less than 6 hours). RESULTS: Surgical debridement was carried out in less than 6h from injury in 90 (59.6%) fractures and after 6 hours from injury in 61 (40.4%) fractures. Infection rates were 12.22% and 13.24%, respectively. The global infection rate was 13.24%. CONCLUSION: A significantly increased infection rate was not observed in patients whose surgical debridement occurred more than 6h after injury. However, in the fractures of high-energy trauma, a statistically significant increase of the rate of infection was observed in those operated 6 hours after trauma. Level of Evidence II, Study Type Comparative and Prospective.

Open fractures and the incidence of infection in the surgical debridement 6 hours after trauma

Objectives: To determine whether a time delay greater than 6h from injury to surgical debridement influences the infection rate in open fractures. Methods: During a period of 18 months, from October 2010 to March 2012, 151 open fractures were available for study in 142 patients in our hospital. The data were collected prospectively and the patients were followed up for 6 weeks. The patients were divided into two groups regarding the time delay from injury to surgical debridement (more or less than 6 hours). Results: Surgical debridement was carried out in less than 6h from injury in 90 (59.6%) fractures and after 6 hours from injury in 61 (40.4%) fractures. Infection rates were 12.22% and 13.24%, respectively. The global infection rate was 13.24%. Conclusion: A significantly increased infection rate was not observed in patients whose surgical debridement occurred more than 6h after injury. However, in the fractures of high-energy trauma, a statistically significant increase of the rate of infection was observed in those operated 6 hours after trauma. Level of Evidence II, Study Type Comparative and Prospective.

Fraturas expostas: estudo epidemiológico e prospectivo / Open fractures: prospective and epidemiological study

OBJETIVO: Traçar o perfil epidemiológico dos pacientes atendidos em uma unidade de urgência com diagnóstico de fratura exposta. MATERIAIS E MÉTODOS: O trabalho é do tipo epidemiológico, prospectivo, descritivo, observacional, das fraturas expostas atendidas por amostra de conveniência na instituição, no período de 1 setembro de 2005 a 31 de março de 2007. A coleta dos dados foi através de questionário com diversas variáveis. RESULTADOS: Obtivemos 342 pacientes portadores de 346 fraturas, sendo a maioria do sexo masculino (86,84 por cento), com idade média de 30,41 anos e tempo médio de internação de 6,87 dias. As profissões encontradas foram os estudantes (21,92 por cento), seguido dos "motoboys" (11,40 por cento). Os acidentes ocorreram em vias públicas (57,30 por cento), acometendo os ossos da perna (37,86 por cento) e classificadas como grau III (45,36 por cento). Lesões associadas ocorreram em 27,19 por cento, apresentando 11,11 por cento de complicações. Houve consumo de bebida alcoólica (12,86 por cento) e drogas (1,46 por cento) nas 6 horas que antecederam o trauma. CONCLUSÃO: Houve o predomínio do paciente jovem do sexo masculino, com ensino fundamental incompleto, acidentes de trânsito, no período das 19hs às 0hs, acometendo os ossos da perna e classificadas como grau III. As lesões associadas e complicações precoces estão mais relacionadas às lesões de maior gravidade.

OBJECTIVE: to delineate the epidemiological profile of patients attended by an emergency unit, diagnosed with open fractures. MATERIALS AND METHODS: This is an epidemiological, prospective, descriptive, observational study of open fractures attended at the institution, selected by convenience sampling, in the period September 1, 2005 to March 31, 2007. The data were collected from patients using a questionnaire with multiple variables. RESULTS: we obtained 342 patients with 346 open fractures. The majority of the patients were male (86.84 percent), with an average age of 30.41 years and average hospitalization time of 6.87 days. The main professions were students (21.92 percent), followed by motorcycle couriers (11.40 percent). The accidents occurred on public roads (57.30 percent), affecting mainly the leg bones (37.86 percent) and classified as level III (45.36 percent). Associated injuries occurred in 27.19 percent, with 11.11 percent complications. There was evidence of alcohol consumption (12.86 percent) and drug use (1.46 percent) in the six hours prior to the trauma. CONCLUSION: The patients were mainly young, male, with incomplete school education. The main cause of the traumas was road accidents, occurring at night (between 7 pm and midnight), with leg bone injuries classified as level III. The associated injuries and early complications were predominantly related to injuries of greater severity.