β-D-xylosides stimulate GAG synthesis in chondrocyte cultures due to elevation of the extracellular GAG domains, accompanied by the depletion of the intra-pericellular GAG pools, with alterations in the GAG profiles

The familial disease of hereditary multiple exostoses is characterized by abnormal skeletal deformities requiring extensive surgical procedures. In hereditary multiple exostoses patients there is a shortage in the pericellular glycosaminoglycan (GAG) of heparan sulfate (HS), related to defective activity of HS glycosyltransferases, mainly in the pericellular regions of chondrocytes. This study searched for a novel approach employing xylosides with different aglycone groups priming a variety of GAG chains, in attempting to alter the GAG compositional profile. Cell cultures of patients with osteochondroma responded to p-nitrophenyl β-D-xyloside by a significant increase in total GAG synthesis, expressed mainly in the extracellular domains, limited to chondroitin sulfate). The different β-D-xylosides, in addition to increasing the synthesis of extracellular GAGs, led to a significant depletion of the intracellular GAG domains. In mouse chondrocyte cultures, β-D-xylosides with different aglycones created a unique distribution of the GAG pools. Of special interest was the finding that the naphthalene methanol β-D-xyloside showed the highest absolute levels of HS-GAGs in both extracellular and intra-pericellular moieties compared with other β-D-xylosides and with controls without xyloside. In summary, β-D-xylosides can be utilized in chondrocyte cultures to modify the distribution of GAGs between the extracellular and intracellular compartments. In addition, xylosides may alter the profile of specific GAG chains in each moiety.     

A new subdivision,the marginal division,in the neostriatum of the human brain

<正> A new subetemtory was discovered byas at the caudal most edge of the neostriatum(St) and surrounding the rostral berder of the globus pallidus(GP) in the rat btain with neuroanato-my and immunohistochemistry methods.This area was named marginal division(MrD)based on its location.     

Evaluation of the therapeutic efficacy of amodiaquine versus chloroquine in the treatment of uncomplicated malaria in Abie, Côte-d'Ivoire

The WHO 14-days' test and an in vitro survey were carried out to study the efficacy of amodiaquine versus chloroquine in Abie, a hyperendemic village in the southern forest area of C?te-d'Ivoire. One hundred and nineteen children less than 15 years old suffering from uncomplicated malaria were randomised. Among these, 62 were given amodiaquine treatment and 57 chloroquine treatment. both 4-aminoquinoleines were administered at the same dose of 30 mg/kg spread over three days by 10 mg/kg/day. Before the drug was administered, parasites were taken from some patients of each group and were evaluated in vitro to both drugs. In vivo, the amodiaquine treatment shows 95% of clinical success, 2% of early clinical failures and 3% of late clinical failures. For the chloroquine treatment, the rates are respectively. 79%, 7% and 14%. However, some patients still had a level of parasitaemia for both treatments but were asymptomatic. These parasites were found to be resistant in vitro. The authors recommend that the treatment to be used in Abie must be firstly amodiaquine followed by sulfadoxine-pyrimethamine in cases where there is persistent asymptomatic parasitemia.     

Genotypic Analysis, Construction of the Expression System and Immunological Identification of the Recombinant Proteins of the LipL32 Gene in the Dominant Serogroups of Leptospira interrogans in China

Leptospirosisisoneofthemostimportantinfectiousdis easeinwaterloggingareasandpaddies[1 3].Thecur rentlyusedmultivalentvaccinesagainstleptospirosisare preparedfromdeadLeptospira[4 6].Sincethecross immuneprotectionamongdifferentserovarsofL.interro gansis…     

Study of the incidence of dialysis in São Paulo,the largest Brazilian city

OBJECTIVES:

Chronic kidney disease is a major public health problem worldwide. In Brazil, approximately 100,000 patients (January 2012) receive renal replacement therapy. Nevertheless, data on dialysis incidence in the Brazilian population are scarce. This study aims to analyze the incidence of patients starting dialysis therapy in São Paulo City, the largest Brazilian metropolis.

METHOD:

This cohort study analyzed data from 9,994 patients starting hemodialysis or peritoneal dialysis funded by the Brazilian Public Health System during a 5-year period (2007–2011). Patient data for this study (recorded as electronic files) were obtained from the São Paulo City''s Dialysis Regulatory Bureau, which regulates the allocation of patients requiring dialytic therapy.

RESULTS:

The dialysis incidence rates were 178, 174, 170, 185 and 188 per million population for the years 2007, 2008, 2009, 2010 and 2011, respectively. The incidence rates increased with age. Hypertension and diabetes were the main etiologies diagnosed. Hemodialysis was the chosen dialysis modality in the majority of patients (92.6%), whereas the percentage of patients referred for peritoneal dialysis decreased from 10.1% to 5.5%.

CONCLUSION:

The incidence of patients starting renal replacement therapy from 2007–2011 in São Paulo was stable but higher than the projected incidence for the entire country. The authors emphasize the need for further studies of the incidence of dialysis in the Brazilian population and for the creation of a Brazilian registry of dialysis patients, which would be a valuable tool for developing healthcare policies and renal replacement therapy strategies.     

Changing attitudes towards the care of children in hospital: a new assessment of the influence of the work of Bowlby and Robertson in the UK, 1940–1970

It is generally believed that the work of Bowlby and Robertson was new and decisive in changing the hospital conditions for young children. The fact that parents in the UK and other European countries can now visit their sick child at any time they wish or even room-in is attributed to an acquaintance with Bowlby's findings and Robertson's well-known films about the potentially detrimental effects of hospital stays for young children. In this paper we shall argue that this picture is incomplete and that, historically, things were rather more intricate. Bowlby and Robertson were neither the first nor the only researchers who tried to change hospital policies. Moreover, the older hospital policies were not uniformly bad. Long before Bowlby and Robertson began their plea for reforms, several individuals and hospitals had already introduced conditions that we now still regard as exemplary. The whole change towards more liberal, flexible, and humane practices in children's wards took place over several decades and was fuelled by both worried medical doctors, pressure groups of parents, sympathetic editors of medical journals, and emerging new research findings such as those provided by Bowlby and Robertson. In that societal debate, the voices of Bowlby and Robertson were influential but not necessarily new or decisive.     

The spread of the wild Poliovirus in the rural environment, the case of the Adzopé health district, Côte d'Ivoire

Wild Poliovirus spreading in rural environment in Adzopé, C?te d'Ivoire In order to determine the level of wild Poliovirus spreading among rural children in an endemic poliomyelitis country 469 stools samples, from children aged between three weeks and twelve years old were processed according to WHO procedures for transportation, conservation, isolation and identification of Poliovirus. Intratypic differenciation was performed by an antigenic method using monoclonal antibodies and a genomic RFLP (Restriction Fragment Length Polymorphism). 50 Poliovirus strains (10.7%) were isolated and analyzed: 15 vaccine-like Poliovirus type 1 (30%), 30 vaccine-like Poliovirus type 2 (60%), 4 vaccine-like Poliovirus type 3 (8%) and one wild Poliovirus type 3 (2%). As expected, in the major cases the duration of post-vaccinal viral excretion did not exceed two months. However, in 14% of cases, it varied between 3 and 9 months after the third OPV dose. This long excretion could be due to an inefficient local intestinal immunity or no local immunity at all, in spite of the three OPV doses. These results argue in favor of an increase of the number of OPV doses in such endemic zones. Moreover, OPV strains are well-known to revert to pathogenicity in vaccinees, therefore, the long term excretion of pathogenic OPV derived strains by a certain amount of vaccinees needs to be considered quite seriously.     

Performance of the Genotype® MTBDRPlus assay in the diagnosis of tuberculosis and drug resistance in Samara, Russian Federation

Background

Russia is a high tuberculosis (TB) burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB). Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia.

Results

We performed an evaluation of the GenoType^® MTBDRplus assay (HAIN Lifescience GmbH, Germany) on a total of 168 sputum specimens from individual patients at a public health laboratory in Central Russia, as a model of a middle income site in a region with high levels of drug resistance. Phenotypic drug resistance tests (DST) were performed on cultures derived from the same sputum specimens using the BACTEC 960 liquid media system. Interpretable GenoType^® MTBDRplus results were obtained for 154(91.7%) specimens with readability rates significantly higher in sputum specimens graded 2+ and 3+ compared to 1+ (RR = 1.17 95%CI 1.04–1.32). The sensitivity and specificity of the assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance and MDR was 96.2%, 97.4%, 97.1% and 90.7%, 83.3%, 88.9% respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene dominated in RIF and INH resistant strains respectively. Disagreements between phenotypical and molecular tests results (12 samples) could be explained by the presence of rare mutations in strains circulating in Russia and simultaneous presence of resistant and sensitive bacilli in sputum specimens (heteroresistance).

Conclusion

High sensitivity, short turnaround times and the potential for screening large numbers of specimens rapidly, make the GenoType^® MTBDRplus assay suitable as a first-line screening assay for drug resistant TB.     

Mesenchymal tumors of the gastrointestinal tract: a paradise for acronyms (STUMP, GIST, GANT, and now GIPACT), implication of c-kit in genesis, and yet another of the many emerging roles of the interstitial cell of Cajal in the pathogenesis of gastrointestinal diseases?

This commentary addresses the nature of interstitial cells of Cajal (which can now be conveniently demonstrated by immunostaining for c-kit) and their possible role in the genesis of various motility disorders of the gastrointestinal tract. The evolution of the concept on the nature of gastrointestinal stromal tumors is discussed, with emphasis on the recent finding of a very high frequency of c-kit immunoreactivity in these tumors, suggesting that they might exhibit differentiation toward interstitial cells of Cajal. The practical immunohistochemical applications of antibodies to c-kit in diagnostic pathology are also discussed.     

BamH1 polymorphism in the Chinese,Malays, and Indians in Singapore and its application in the prenatal diagnosis of β-thalassemia

Summary The distribution of restriction fragment length polymorphism (RFLP) at theBamH1 site of the -globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 -thalassemia carriers in which 13 were couples with at least one -major child. The results from this study indicate thatBamH1 polymorphism will be informative in 22% of pregnancies at risk for -thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis usingBamH1 polymorphism for one -major affected family, the fetus was diagnosed to be normal or -carrier. The validity ofBamH1 polymorphism in the exclusion of -thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.     

Effectiveness of the PPARγ agonist, GW570, in liver fibrosis

Introduction  

The peroxisome proliferator-activated receptors (PPARs) are well established to be important in modulating the fibrogenic response to liver injury. PPARγ plays a role in hepatic fibrosis, presumably by virtue of its expression in hepatic stellate cells, which are key effectors of fibrosis. In this study, we evaluated whether the potent nonthiozolidinedione PPARγ agonist, GW570, had effects on isolated stellate cells and hepatic fibrosis in vivo.     

Expression of E-cadherin, α-catenin, and β-catenin in tubulolobular carcinoma of the breast

Tubulolobular carcinoma (TLC) of the breast is a rare subtype of breast carcinoma categorized by Fisher et al. (Hum Pathol 8:679–683, 1977) as a tubular variant of lobular carcinoma. E-cadherin is a transmembrane glycoprotein, and complete loss of E-cadherin expression has been observed in invasive lobular carcinoma. Ductal carcinoma retains at least some expression of E-cadherin. Moreover, the adhesive function of E-cadherin is dependent on the integrity of the catenin components, which link E-cadherin to the actin filaments. In order to achieve improved categorization of TLC, we decided to investigate both E-cadherin and the catenins in TLCs and invasive lobular carcinomas. We reviewed all 1,430 cases of primary breast carcinoma that were surgically resected at Saitama Medical Center, Saitama Medical School, and at Saitama Red Cross Hospital between 1990 and 2005. Among these, 16 cases of TLC were reported retrospectively. The results were compared with those of 20 cases of invasive lobular carcinomas that were included as controls. Tumor tissue was immunostained for E-cadherin, α-catenin, and β-catenin. The presence of immunoreactivity in the TLC was seen in 12 (75%) cases for E-cadherin, in 8 (50%) cases for α-catenin, and in 10 (62.5%) cases for β-catenin. However, plasma-membrane-associated staining for E-cadherin, α-catenin, and β-catenin was completely absent in invasive lobular carcinomas. These results suggest the possibility that TLCs are not a variant of lobular carcinoma, but rather ductal carcinomas with a lobular growth pattern.     

Prevalence of infection by Toxocara in schoolchildren in the community of El Moján, Zulia state, Venezuela

The systemic Toxocariasis or migrant larva is a helminto-zoonosis caused by the migration of nematode larvae through human tissues mainly, of the canine helminth Toxocara canis, which can infect humans, especially children. The aim of this study was to determine the prevalence of anti-T. canis antibodies in an infantile population. Serum samples of 73 children of either sex with ages between 4 and 6 years were examined. The determination of anti-Toxocara antibodies was carried out through an ELISA test (using excretory/secretory antigen from the Toxocara larvae). The statistical analysis was carried out through the Chi square test, the Fisher exact test and the correlation of Spearman. The overall prevalence of infection was 9.72%, the highest percentage (50%) was observed in 4 year-old children (3/6), there were significant differences among the ages. No differences were observed with regard to sex. An inverse correlation was observed between the age and ELISA positivity. These results suggest that the toxocariasis is frequent in children from this community.     

Improvements in population-based survival of patients presenting with metastatic rectal cancer in the south of the Netherlands, 1992–2008

We analysed population-based treatment and survival data of patients who presented with metastatic rectal cancer. All patients diagnosed with primary synchronous metastatic rectal cancer between 1992 and 2008 in the Eindhoven Cancer Registry area were included. Date of diagnosis was divided into three periods (1992–1999, 2000–2004, 2005–2008) according to the availability of chemotherapy type. We assessed treatment patterns and overall survival according to period of diagnosis. The proportion of patients diagnosed with stage IV disease increased from 16% in 1992–1999 to 20% in 2005–2008 (P < 0.0001). Chemotherapy use increased from 5% in 1992 to 61% in 2008 (P < 0.0001). Resection rates of the primary tumour decreased from 65% in 1992 to 27% in 2008 (P < 0.0001), while metastasectomy rates remained constant since 1999 (9%). Median survival increased from 38 weeks (95% confidence interval (CI) 32–44) in 1992–1999 to 53 weeks (95% CI 48–61) in 2005–2008. Among patients not receiving chemotherapy median survival remained approximately 30 weeks. Multivariable analysis confirmed the lower risk of death among patients diagnosed in more recent years. Increased use of chemotherapy went together with improved median survival among patients with metastatic rectal cancer in the last two decades. Stage migration as an effect of more effective imaging procedures is likely to be partly responsible for this improved survival.     

Effect of the Arginine-Containing μ,δ-Opiate Receptor Agonist Sedatin on DNA Synthesis in the Epithelium of the Gastric Fundus in Albino Rats

We studied the effect of arginine-containing mu,delta-opiate receptor agonist sedatin on DNA synthesis in the epithelium of the gastric fundus in albino rats. Fivefold intraperitoneal injection of sedatin in various doses increased the index of labeled nuclei. Similar changes were observed after intranasal and intraperitoneal treatment with sedatin in a dose of 10 microg/kg for 21 days. Administration of sedatin for 21 days prevented the decrease in weight gain induced by experimental stress. Our results suggest that arginine entering the composition of sedatin plays a role in its biological effects.     

Assessment of airborne mycoflora in critical areas of the Principal Hospital of Cumaná, state of Sucre, Venezuela

The study of the nosocomial infections of fungic origin has attained importance in the last years, due to the rise in the number of patients that are inmunocompromised and susceptible to suffer this kind of infection. The objective of the present study was to evaluate the frequency of filamentous fungi and yeast, present in the environment of the Intensive Care Unit, operating and newborn children rooms of the Hospital Universitario "Antonio Patricio de Alcalá" (HUAPA) from the city of Cumaná. Suere State, Venezuela. The recount of colony forming units/plate (UCF/plate) of the filamentous fungi and yeast was done in Petri plates with Sabouraud dextrose agar, which were exposed in the different studied areas. Eventually, the fungus colonies found were isolated and identified. The area that presented the highest average of UCF/plate was the Intensive Care Unit (9 UCF/plate). The isolated genus of filamentous fungus in higher proportion were Aspergillus (46.80%), Penicillium (19.19%) and Fusarium (11.06%). The isolated species with more frequency were Aspergillus niger (24.80%), Aspergillus flavus (10.54%) and Fusarium solani (9.52%). Rhodotorula glutinis was the isolated yeast with most frequency and different species of the genus Candida and the genus Criptococcus were isolated as well.     

What Is the Evidence for Rest,Ice, Compression,and Elevation Therapy in the Treatment of Ankle Sprains in Adults?

Context:

Ankle sprains are common problems in acute medical care. The variation in treatment observed for the acutely injured lateral ankle ligament complex in the first week after the injury suggests a lack of evidence-based management strategies for this problem.

Objective:

To analyze the effectiveness of applying rest, ice, compression, and elevation (RICE) therapy begun within 72 hours after trauma for patients in the initial period after ankle sprain.

Study Selection:

Eligible studies were published original randomized or quasi-randomized controlled trials concerning at least 1 of the 4 subtreatments of RICE therapy in the treatment of acute ankle sprains in adults.

Data Sources:

MEDLINE, Cochrane Clinical Trial Register, CINAHL, and EMBASE. The lists of references of retrieved publications also were checked manually.

Data Extraction:

We extracted relevant data on treatment outcome (pain, swelling, ankle mobility or range of motion, return to sports, return to work, complications, and patient satisfaction) and assessed the quality of included studies. If feasible, the results of comparable studies were pooled using fixed- or random-effects models.

Data Synthesis:

After deduction of the overlaps among the different databases, evaluation of the abstracts, and contact with some authors, 24 potentially eligible trials remained. The full texts of these articles were retrieved and thoroughly assessed as described. This resulted in the inclusion of 11 trials involving 868 patients. The main reason for exclusion was that the authors did not describe a well-defined control group without the intervention of interest.

Conclusions:

Insufficient evidence is available from randomized controlled trials to determine the relative effectiveness of RICE therapy for acute ankle sprains in adults. Treatment decisions must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines.Key Words: ankle ligament injury, cryotherapy, bandages

Key Points

• Randomized controlled trials provide insufficient evidence to determine the effectiveness of rest, ice, compression, and elevation (RICE) therapy for acute ankle sprains in adults.
• Treatment decisions must be made on an individual basis, carefully weighing the relative risks and benefits of each option, and must be based on expert opinions and guidelines.
• Sufficiently powered, high-quality, and appropriately reported randomized trials of the different elements of RICE therapy for acute ankle sprains are needed.

Ankle sprains are one of the most prevalent injuries of the musculoskeletal system. Researchers have estimated that 1 ankle sprain occurs per 10 000 people each day.¹ The most common mechanism of injury is inversion of the plantar-flexed foot. Inversion injuries involve about 25% of all injuries of the musculoskeletal system, which affect more than 20 000 patients in the United States each day.^2,3 About 50% of these injuries are sport related^4,5; some sports (basketball, soccer, and volleyball) have a particularly high incidence of ankle injuries.^6,7 If not treated properly, inversion injuries of the ankle can result in persistent problems in 30% to 40% of patients.^4,8The treatment of inversion ankle injuries is provided by emergency and primary health care physicians, athletic trainers, physiotherapists, and orthopaedic and trauma surgeons. Each year, approximately 1 million patients with acute lateral ankle ligament injuries are examined by primary care physicians in the United States.⁹ The annual cost to society for ankle injuries has been estimated to be approximately €40 million (US $30.4 million) per 1 million people.¹⁰ Most authors use the term sprain to describe a morphologic condition representing a diversity of pathologic conditions, ranging from overstretching of the ligament to complete rupture with gross instability of the joint.¹¹The ankle ligaments are the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL), and together they form the lateral ligament complex of the ankle.¹² The ATFL is the first or only ligament to sustain injury in 97% of the cases.^13,14 Broström⁵ found that combined ruptures of the ATFL and the CFL occurred in 20% of the cases and that isolated rupture of the CFL occurred in only 3%. The PTFL usually is not injured unless a true dislocation of the ankle occurs.⁵ Rest, ice, compression, and elevation (RICE) are generally accepted methods for treating inflammation after trauma, such as acute ankle sprain.^15,16 Inflammation causes pain, edema, hyperalgesia, and erythema, all of which can limit the patient''s ability to perform the rehabilitation required for proper healing.¹⁷ Gentle tension and stretching at the joint promote proper ligament fiber growth into tight, parallel strands. Accumulation of fluid and edema around an injury site also increases tissue damage, delays healing, and can result in some degree of chronic disability.¹⁸According to the Dutch Quality Institute for Healthcare CBO consensus guidelines,¹⁹ RICE therapy is the preferred treatment for the first 4 to 5 days. After this period, the physical examination provides a high-quality assessment.^19–21 The inconsistent outcome of physical examination within 48 hours of trauma is caused by the diffuse character of the pain, the swelling that gives no information about whether it is due to hematoma or edema formation, and the unreliability of the anterior drawer test due to pain and swelling.^19–21Rest, ice, compression, and elevation therapy is an accessible and popular modality in the treatment of acute ankle sprains. Therefore, the objective of our study was to analyze the effectiveness of applying RICE therapy begun within 72 hours after trauma for patients in the initial period of ankle sprain. The specific null hypotheses included the following: (1) No differences existed in outcome measurements between using rest, immobilization, or no movement or mobilization and using early mobilization or movement for acute treatment of ankle sprains; (2) No differences existed in outcome measurements between using ice, cold, cold therapy, cryotherapy, or cooling and using no ice, no cold, or heat for acute treatment of ankle sprains; (3) No differences existed in outcome measurements between using compression and using no compression for acute treatment of ankle sprains; and (4) No differences existed in outcome measurements between using elevation and using no elevation for acute treatment of ankle sprains. In addition to other reviews concerning the treatment of acute lateral ankle sprains^22–28 (also G.M.M.J.K., unpublished data, January 2011), our systematic review will be helpful in the further development of evidence-based treatment recommendations and protocols.