Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Elementos para una mirada crítica acerca de la efectiva aplicación de la ley nacional de salud mental / Critical elements for an effective implementation of the national mental health law

Con el propósito de avanzar en la producción de conocimiento rigurososobre las primeras repercusiones en el territorio de la Ley Nacional de SaludMental (LNSM), se planteó una hipótesis, a partir de la cual se considera quela persistencia del paradigma manicomial evidenciado en los tres momentosclave de la rutina institucional (admisión, tratamiento y externación) devieneen una barrera para la efectiva aplicación de la LNSM.ObjetivosIdentificar, describir y analizar los procedimientos y mecanismos institucionalesque promueven o limitan la aplicación de la LNSM en diferentes dispositivosde atención de salud mental y otras modalidades de internación previstas.MétodosSe utilizó un método cualitativo con un diseño de investigación flexible. No secontempló la medición de variables.ResultadosEl consentimiento informado es inválido porque no refleja la voluntad de lapersona. La persona cuenta con poca información respecto a sus derechos ylo inherente a su tratamiento. No se explicita una situación de riesgo ciertoe inminente que justifique la internación, ni las posibles alternativas al iniciode la medida. No hay tratamiento personalizado; aparece fragmentado, sedesarrolla en su totalidad dentro de la institución y es preponderantementepsicofarmacológico. Se tiende a la sobremedicación y a la polifarmacia.Hay poca participación de la persona en el tratamiento. No se observa confrecuencia la construcción de un plan de externación.ConclusionesPersiste el paradigma manicomial evidenciado en los tres momentos clave dela rutina institucional (admisión, tratamiento y externación), lo que constituyeuna barrera para la efectiva aplicación de la LNSM. Más allá de la nominaciónque se dé a estos dispositivos, a modo general se observan en forma recurrentedinámicas, actividades y acciones que refuerzan el estado de sometimiento ypasividad por parte de las personas internadas y reproducen la situación devulneración de derechos.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center.

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Paraovarian tumor of borderline malignancy--a case report.

A case of a 23-year-old woman with a paraovarian tumor is presented. The patient complained of pelvic pain and abdominal swelling. Cystectomy was the initial surgical treatment, but after the histological diagnosis, a staging surgery was carried out. The clinical aspects and subsequent management of related cases are discussed, and a literature review is made.

Carcinoma in situ and early breast carcinoma survey of the Portuguese Senology Society on treatment in Portugal and its evolution between 1985 and 2000.

By means of a questionnaire sent to Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the treatment of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed by the years 1985, 1990, 1995 and 2000. It was observed that, in terms of surgery, there was an increase in conservative surgery, which was over 40% in 2000, as well as an increase in the average of excised axillary lymph nodes. Progress in the surgical approach was similar both in cancer centres and in large and university hospitals, when compared with the other surveyed hospitals. Also, no differences between these two hospital groups in disease-free survival and overall survival were found. Postoperative radiotherapy was employed in more than 90% of the patients submitted to conservative surgery and adjuvant chemotherapy was used in 39% of all the patients, while tamoxifen as adjuvant treatment was used in 58% of the patients.

Carcinoma in situ and early breast carcinoma. Survey of the Portuguese Senology Society on the diagnostic tools used in Portugal and their evolution between 1985 and 2000.

By means of a questionnaire, sent to the Portuguese hospitals which diagnose and treat most female patients with breast cancer, it was intended to assess the situation regarding the diagnosis of carcinoma in situ and early breast cancer (T1 or T2, N0 or N1), as well as their evolution between 1985 and 2000. The hospital participation rate was 65% and a sample of 865 patients was collected, distributed in the years 1985, 1990, 1995 and 2000. It was found that the presentation form of breast cancer in 1985 was of palpable tumour in 87% of the cases, whereas in 2000 this situation only corresponded to 54% of the patients, being most of the remaining patients diagnosed by imaging without palpable tumour. In 94% of the patients, the first diagnostic investigation was mammography, associated or not to echography, and the second most frequent investigation was fine-needle aspiration biopsy. The time evolution of the tumour size showed an increasingly earlier diagnosis. Invasive tumours not more than 1 cm represented 13.2% in 1985 and 20.3% in 2000. On the other hand, breast cancers more than 2 cm and not more than 5 cm decreased from 67.2% in 1985 to 40% in 2000. When oncology centres and some large university hospitals (Group A) were compared to the other hospitals (Group B), there were no significant differences between the diagnostic methods, although the sequence of diagnostic methods was different in the hospitals in Group A versus those in Group B. It was observed that in more differentiated hospitals the diagnosis was achieved increasingly earlier along the studied periods, and this situation did not occur in the other hospitals.

Locally advanced/inflammatory breast cancers treated with intensive epirubicin-based neoadjuvant chemotherapy: are there molecular markers in the primary tumour that predict for 5-year clinical outcome?

BACKGROUND: Locally advanced and/or inflammatory breast cancer (LABC) is a heterogeneous disease. Molecular markers may help to understand this heterogeneity. This paper reports the results of a study assessing the potential prognostic or predictive value of HER-2, p53, cyclinD1, MIB1, ER and PgR expression by immunohistochemistry from patients included in an EORTC-NCIC-SAKK trial. PATIENTS AND METHODS: A total of 448 patients with a cytological or histological diagnosis of LABC were randomised into a trial comparing two anthracycline-based neoadjuvant regimens. Chemotherapy was followed by standard locoregional therapy. Survival was comparable in both arms. We collected and analysed centrally paraffin-embedded tumour specimens from 187 (72.5%) of 258 patients that had a histological diagnosis. RESULTS: Of the patients included in this molecular marker study 114 relapsed and 91 died. In the multivariate analysis p53 positivity was associated with a shorter progression-free survival [hazard ratio (HR) = 1.96; 95% CI 1.33-2.91; P = 0.0008) and a shorter overall survival (HR = 1.98; 95% CI 1.28-3.06; P = 0.002). PgR positivity predicted for a longer overall survival (HR = 0.54; 95% CI 0.35-0.83; P = 0.0045). CONCLUSIONS: p53 was an independent factor predicting for survival. In order to clarify whether p53 is a pure prognostic and/or a predictive factor, a phase III trial is being conducted (EORTC 10994/BIG 00-01 study) using functional assay in yeast from frozen tumour samples.

Sclerosis of gross cysts of the breast: a three-year study.

Breast cysts can be separated into two types: Type I cyst with a lining epithelium which shows apocrine metaplasia, and Type II cyst with an epithelium which is markedly attenuated or absent. The risk of subsequent breast cancer among patients with Type I cysts can be up to 4. The standard treatment is fine needle aspiration, but 20% of the cysts recur. Pharmacological treatment has been tried, which reduces size and volume, but has side-effects and a high recurrence rate post-treatment occurs. The objectives of this prospective study were to sclerose the cyst, induce its regression and prevent or reduce recurrence rate, with the administration of a sclerosing solution (Sclerovein) within the cyst post-aspiration. Fifty-seven patients were followed in the study, 37 with Type I cysts and 20 with Type II cysts. At the end of six months all patients with Type II cysts had no detectable cyst. On the other hand, two patients still had a residual Type I cyst. At the end of three years our recurrence rate appears to be less than 2%, with one patient with a possible recurrence. No significant side-effects were observed. The use of Sclerovein is a simple and safe alternative in the treatment of recurring cysts.

[Prognosis value of p53, C-erB-2 and Ki67 proteins in ovarian carcinoma]. / Valor prognóstico das proteínas p53, C-erB-2 E Ki67 no carcinoma do ovário.

The prognosis in ovarian carcinoma remains poor. We need to identify patients who are less likely to respond to treatment. In order to evaluate the prognostic value of C-erb-B2, p53 and Ki 67 expression and correlate these markers with classic prognostic factors, we studied paraffin-embedded tumor tissue from 81 patients with epithelial ovarian cancer and made a quantitative evaluation of C-erb-B2, p53 and Ki 67 expression by immunohistochemistry. The results were: age 5.4 +/- 15(22-88); 66% with normal physical activity; 48.2% with residual disease < 2 cm; initial stage--42% and advanced stage--58%. Age, performance status, residual disease and stage were correlated with 2 and 5 years survival. Positive immunostaining: p53--87%, C-erb B-2--51% and Ki67--100%. P53 and C-erb B-2 were associated with residual disease and stage; patients with no C-erbB-2 staining had a significantly better survival. A direct and significant correlation was found between p53 and Ki67 and between C-erb B-2 and p53. We conclude that these markers have a high expression in ovarian carcinoma and p53 and C-er B-2 correlate with stage and residual disease. Although C-erb B-2 was associated with better survival, it was not found to be an independent prognostic factor.

[Wertheim-Meigs procedure. 10-year results]. / Operação de Wertheim-Meigs. Resultados de 10 anos.

Wertheim-Meigs hysterectomy is used in the treatment of cervical cancer, but since 1988 we have also used it to stage and treat endometrial carcinoma. To evaluate the morbidity of Wertheim Meigs hysterectomy as well as node invasion incidence and its correlation with other prognostic factors, the authors made a retrospective study of 112 patients, from October 1986 to March 1996. Among the 112 cases evaluated, 52% had cervical carcinoma and 48% had endometrial carcinoma; mean ages were 45 +/- 10 and 60 +/- 8 years (p < 0.005). FIGO stage distribution was: I-94.8 and 33.3%; II-5.2 and 51.9%; III-0 and 13%; IV-0 and 1.8%, for cervical and endometrial carcinoma. Hemorrhagic and traumatic accidents happened in 24.3% and 1.7% respectively. We had 15.5% early post operative complications and 1.7% late post operative ones. The mean duration of surgery and hospitalization was 163 +/- 29 minutes and 10 +/- 5 days. Pelvic lymphadenectomy was performed in 70% of patients and para-aortic nodes were also excised in the other 30%. The mean number of lymphatic nodes excised were 17 +/- 9. Pelvic node invasion was found in 9% and in 3.7% of para-aortic ones. When we studied endometrial cancer, we found a positive correlation between external myometrium invasion and lymphovascular invasion and positive node (p < 0.05). From the data available we may conclude that the complication rate of Wertheim Meigs is quite important, even though all but one complication were transitory. It may be possible to make a better selection of patients who need this surgical procedure by correct evaluation of risk factors.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine)

The first edition of the W.A.A.V.P. anthelmintic guidelines for ruminants was published in 1982. Since then improved parasitological procedures have been developed, new therapeutic and prophylactic products have appeared requiring different test methods, and registration authorities are requesting more detailed record keeping and data validation. This second edition addresses these developments and fulfills the original goal of publishing guidelines for high quality, scientifically valid testing standards for trials that would be accepted as proof of efficacy by registration authorities regardless of country of origin. This second edition includes updated guidance on standard parasitological procedures, dose titration, dose confirmation and clinical trials, and provides guidelines for evaluating products for efficacy against anthelmintic resistant parasites, persistence of activity and prophylactic activity. Tests for efficacy against nematodes, trematodes and cestodes are included.

[Anthropometric profile of children aged 0 to 5 years in the city of Niterói, Rio de Janeiro, Brazil]. / Perfil antropométrico de crian as de 0 a 5 anos do Município de Niterói, Rio de Janeiro, Brasil.

The Niterói-based Nutritional and Food Surveillance System (SISVAN Niteroi, RJ, Brazil) performed an anthropometric survey which included 2,248 children from zero to 60 months of age in September 1992, during a mass vaccination day program. The purpose was to determine the nutritional status of children from that city. The indexes used were Weight for Age (WA), Weight for Height (WH), and Height for Age (HA), and the reference population was that of the NCHS (National Center for Health Statistics, USA), adopted and recommended by the WHO. The indexes were analyzed using the classifications by Gomez and Z-Scores. Prevalence of undernutrition was calculated on the basis of the proportion of children with Z-scores under -2.00, using HAZ to stabilish chronic forms and WHZ for acute ones. A data base was built using Epi Info, version 5.0 1b, and a special program from CDC (Centers for Disease Control) was used to calculate anthropometric indexes. The results showed as much as 20.1 % of undernutrition, including all forms from the Gomez classification. In the city as a whole, 6.8% had HAZ under -2.00. The results indicated a serious situation of chronic undernutrition that demands continuous nutritional surveillance in Niteroi, and especially in the city's Eastern District.

Effect of selection for lean tissue growth on body composition and physiological state of the pig at birth.

The effects of selection for lean tissue growth on the metabolic and physiological state (i.e., level of maturity) of the pig at birth have been examined on newborns from three breeds that markedly differ with respect to birth weight and postnatal muscle growth potential: a primitive Chinese breed (Meishan, MS), a European breed (Large White, LW), and a composite line (CL) highly selected for high rate of gain. Within each breed, 40 pigs from eight litters were used for whole carcass and tissue sampling, blood sampling, and for a fat tolerance test at 2 h of age. The CL pigs were heavier (P < .001) than the LW and MS pigs at birth but exhibited lower percentages of carcass protein, fat, mobilizable fat, and ash than the MS pigs (P < .05). In addition, MS pigs had larger adipose tissue adipocytes than pigs from the two other breeds (P < .001). Despite their 31% higher RNA capacity in longissimus muscle (higher RNA:protein ratio, P < .05), CL pigs exhibited a lower percentage of muscle protein (P < .05) than did MS pigs. Relative liver weight was higher for LW than for CL pigs (P < .05), which had the lowest percentage of liver phospholipids (P < .01). The CL pigs exhibited lower hematocrit (P < .01), glucose (P < .01), albumin (P < .01), cortisol (P < .01), and thyroxine (P < .05) levels than the MS pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ecological aspects of American cutaneous leishmaniasis. 9. Prevalence/incidence of the human infection in the municipality of Pedro de Toledo and Miracatu, São Paulo, Brazil]. / Aspectos ecológicos da leishmaniose tegumentar americana 9. Prevalência/incidência da infecção humana nos municípios de Pedro de Toledo e Miracatu, São Paulo, Brasil.

The epidemiologic study was conducted during the 1973-1984 period. The clinical prospective exam and Montenegro skin, immunofluorescent and passive hemagglutination tests have been carried out in three small localities between Pedro de Toledo e Miracatu municipalities, São Paulo, Brazil. The retrospective study of human-cases involved 108 and 65 cases registered in Pedro de Toledo e Miracatu, respectively. In the three communities studied, 273 people were examined clinically and serologically. Twenty two individuals had had signals of cutaneous leishmaniasis; 10.2 and 12.8% were seropositive to IF and HA. Leishmanin skin testing of a sample of 154 people residents in Pedra do Largo showed prevalence of Leishmania infection in 25.5%. This result involved individual of all ages and sex. However, 5.8% of them were from 0 to 9 years old. The data confirmed that active parasite transmission didn't occur every year, either. The human infection seems not to depend on man contact with a forest. The incidence relatively low suggests low endemic area for cutaneous leishmaniasis and an explosive behavior of the cases. The temporal distribution of disease was irregular and the epidemiological pattern seen was different from the other endemic area of South America.

Topically applied ivermectin: efficacy against torsalo (Diptera: Cuterebridae).

To determine the systemic efficacy and persistence of a 0.5% ivermectin topical formulation against natural infestation of torsalo, Dermatobia hominis (L., Jr.), larvae in cattle, two trials in Colombia and two trials in Brazil were done. Of 56 infested cattle used in these trials, 28 were treated and 28 served as untreated controls. The formulation was poured along the back of each animal at a rate of 0.5 mg (AI)/kg body weight. Significantly fewer larvae were counted in the treated animals than on controls on days 9 and 10; greater than 99% control resulted. The first reinfesting larvae were observed in a few animals on days 30 and 31.

Efficacy of topically applied ivermectin against Boophilus microplus (Canestrini, 1887) in cattle.

Systemic efficacy of ivermectin applied topically was evaluated against the cattle tick, Boophilus microplus. Twenty cattle with induced infestations were randomly allocated to five groups of equal size based on the numbers of engorged female ticks which fell through the slatted floor of individual pens during the 3 days prior to treatments. Control cattle were non-medicated. Cattle in three groups were given ivermectin at 200, 500 or 1000 mcg kg-1 in a topical formulation applied along the backline from the withers to the rump; cattle in the fifth group were given ivermectin in an injectable formulation subcutaneously at 200 mcg kg-1. Individual 24-h tick collections were made three times weekly for 5 weeks after treatment. Engorged female B. microplus were incubated to determine effects on reproduction. Based on the numbers of engorged female B. microplus collected following treatments, overall efficacy of ivermectin applied topically at 200, 500 and 1000 mcg kg-1 was 50, 85 and 91%, respectively, whereas ivermectin given at 200 mcg kg-1 subcutaneously was 80% effective. The index of reproduction for ivermectin given topically was reduced by 84, 94 and 95%, respectively, and that for ivermectin subcutaneously was 94%. No significant differences (P greater than 0.05) were found for these variables between ivermectin given topically at 500 or 1000 mcg kg-1 versus 200 mcg kg-1 given subcutaneously.

Percutaneous transluminal angioplasty of the hepatic veins for treatment of Budd-Chiari syndrome.

The authors report a case of Budd-Chiari syndrome caused by occlusion of all of the hepatic veins which was treated by percutaneous transluminal angioplasty. There were two recurrences requiring redilatation. Two years later, the patient was asymptomatic and off medication.