Usefulness of liver biopsy in chronic hepatitis C

Major requirements for performance of liver biopsy (LB) are the benefits for the patient and the impossibility of having the same information by less invasive procedures. In the last two decades physicians have faced the difficult task of convincing a patient positive for hepatitis C, with minimal clinical or laboratory alterations to be submitted to LB in order to evaluate the status of the disease for therapeutic management. The characteristics of the needle used for percutaneous LB interferes with the accuracy of diagnosis. In chronic hepatitis C (CHC), validity is achieved with liver fragments about 25mm in length containing more than 10 portal tracts. Morbidity due to LB is mainly related to bleeding but death is very rare. Severe complications are also uncommon, increasing with number of passes and decreasing with experience of operator and ultrasound guidance. Although CHC is a diffuse disease, the various areas of the liver may not be equally affected and sampling errors are possible. Another potential limitation of LB is the discordance between pathologists in its interpretation. To replace LB, many panels of surrogate markers have been described, aiming to identify extent of fibrosis and inflammation. All of them have used LB as their ""gold standard"". Liver biopsy continues to be the most reliable method to evaluate the possibility of therapy for CHC. Universal treatment of all patients with diagnosis of CHC would be ideal. But, there are mainly three drawbacks. Overall efficacy is as low as 50%, side effects are common and may be severe and treatment is prolonged and expensive. The acceptability of the biopsy by the patient is highly dependent on the physician`s conviction of its usefulness.

Use of AST platelet ratio index (APRI Score) as an alternative to liver biopsy for treatment indication in chronic hepatitis C

Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.

Multifocal Renal Allograft Biopsy: Impact on Therapeutic Decisions

Objective. There are no data to support the suggestion that samples removed from one segment of the transplanted kidney are representative of the whole graft. The aim of this study was to compare the histological differences between biopsies obtained from different portions of the renal allograft and their impact on treatment recommendations. Patients and Methods. Two hundred percutaneous biopsies were performed on kidney allografts and samples were collected from the upper and lower poles (100 kidneys). All samples were randomized and blindly reviewed. We obtained the discordance rates between the poles for the grading of acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression. We also checked if the differences found were sufficient to call for different clinical recommendations. These values were compared with the intrapathologist variation rates. Results. In 70 kidneys adequate sampling was obtained from both poles. The diagnosis of acute rejection were made in 1.7. The discordance rate between the upper and lower poles was 82.3% (kappa = 0.34), higher than the intrapathologist variation (P =.002). Nephrotoxicity was found in 14 kidneys. The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88), with no difference compared with the intrapathologist variation. In 14 of the 70 kidneys (25.7%), discordances between poles had impact on clinical recommendations, most of these cases due to different gradings of acute rejection (78%). This number was higher than the intrapathologist variation (P =.04). Conclusions. The histopathological changes in the kidney allograft are not always homogeneous. This heterogeneity may affect the therapeutic recommendations.

Model for Differential Nursing Diagnosis of Alterations in Urinary Elimination Based on Fuzzy Logic

Nursing diagnoses associated with alterations of urinary elimination require different interventions, Nurses, who are not specialists, require support to diagnose and manage patients with disturbances of urine elimination. The aim of this study was to present a model based on fuzzy logic for differential diagnosis of alterations in urinary elimination, considering nursing diagnosis approved by the North American Nursing Diagnosis Association, 2001-2002. Fuzzy relations and the maximum-minimum composition approach were used to develop the system. The model performance was evaluated with 195 cases from the database of a previous study, resulting in 79.0% of total concordance and 19.5% of partial concordance, when compared with the panel of experts. Total discordance was observed in only three cases (1.5%). The agreement between model and experts was excellent (kappa = 0.98, P < .0001) or substantial (kappa = 0.69, P < .0001) when considering the overestimative accordance (accordance was considered when at least one diagnosis was equal) and the underestimative discordance (discordance was considered when at least one diagnosis was different), respectively. The model herein presented showed good performance and a simple theoretical structure, therefore demanding few computational resources.

Early neonatal morbidity and mortality in growth-discordant twins

Objective. To evaluate early neonatal morbidity and mortality in twin pregnancies with growth discordance. Design. Retrospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. A total of 151 twin pregnancies managed and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital between 1998 and 2004. Methods. Comparison between twin pregnancies with weight discordance 20% and pregnancies concordant for fetal weight. Cases with fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks or in another hospital were excluded. Outcome measures. Early neonatal morbidity (Apgar at 5 minutes 7, respiratory or neurological complications, infection, necrotizing enterocolitis, length of hospital stay) and mortality. Results. Forty (26.5%) pregnancies presented discordance 20% and 111 (73.5%) were concordant. In the discordant group, 75% of pregnancies had at least one growth restricted fetus (10th centile). In concordant twin pregnancies, monochorionic cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs. 3.0) compared to dichorionic concordant twins. No differences between monochorionic and dichorionic subgroups were observed in discordant twins. Pregnancies in which at least one baby was born with a birthweight below the 10th centile showed that discordant pregnancies had a lower gestational age at delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4 weeks) compared to concordant cases. Neonatal mortality was similar in discordant (3.7%) and concordant (4.5%) twins. Conclusion. Early perinatal morbidity is increased in twin pregnancies with birthweight discordance 20% only when associated with fetal growth restriction and low birthweight.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

Accuracy and cost- and time-effectiveness of digital clip versus videotape interpretation of echocardiograms in patients with valvular disease

Background. Although digital and videotaped images are known to be comparable for the evaluation of left ventricular function, their relative accuracy for assessment of more complex anatomy is unclear. We sought to compare reading time, storage costs, and concordance of video and digital interpretations across multiple observers and sites. Methods. One hundred one patients with valvular (90 mitral, 48 aortic, 80 tricuspid) disease were selected prospectively, and studies were stored according to video and standardized digital protocols. The same reviewer interpreted video and digital images independently and at different times with the use of a standard report form to evaluate 40 items (eg, severity of stenosis or regurgitation, leaflet thickening, and calcification) as normal or mildly, moderately, or severely abnormal Concordance between modalities was expressed at kappa Major discordance (difference of >1 level of severity) was ascribed to the modality that gave the lesser severity. CD-ROM was used to store digital data (20:1 lossy compression), and super-VHS video-tape was used to store video data The reading time and storage costs for each modality were compared Results. Measured parameters were highly concordant (ejection fraction was 52% +/- 13% by both). Major discordance was rare, and lesser values were reported with digital rather than video interpretation in the categories of aortic and mitral valve thicken ing (1% to 2%) and severity of mitral regurgitation (2%). Digital reading time was 6.8 +/- 2.4 minutes, 38% shorter than with video (11.0 +/- 3.0, range 8 to 22 minutes, P < .001). Compressed digital studies had an average size of 60 <plus/minus> 14 megabytes (range 26 to 96 megabytes). Storage cost for video was A$0.62 per patient (18 studies per tape, total cost A$11.20), compared with A$0.31 per patient for digital storage (8 studies per CD-ROM, total cost A$2.50). Conclusion. Digital and video interpretation were highly concordant; in the few cases of major discordance, the digital scores were lower, perhaps reflecting undersampling. Use of additional views and longer clips may be indicated to minimize discordance with video in patients with complex problems. Digital interpretation offers a significant reduction in reading times and the cost of archiving.

Effect of tissue Doppler on the accuracy of novice and expert interpreters of Dobutamine echocardiography

The subjective interpretation of dobutamine echocardiography (DBE) makes the accuracy of this technique dependent on the experience of the observer, and also poses problems of concordance between observers. Myocardial tissue Doppler velocity (MDV) may offer a quantitative technique for identification of coronary artery disease, but it is unclear whether this parameter could improve the results of less expert readers and in segments with low interobserver concordance. The aim of this study was to find whether MDV improved the accuracy of wall motion scoring in novice readers, experienced echocardiographers, and experts in stress echocardiography, and to identify the optimal means of integrating these tissue Doppler data in 77 patients who underwent DBE and angiography. New or worsening abnormalities were identified as ischemia and abnormalities seen at rest as scarring. Segmental MDV was measured independently and previously derived cutoffs were applied to categorize segments as normal or ab normal. Five strategies were used to combine MDV and wall motion score, and the results of each reader using each strategy were compared with quantitative coronary angiography. The accuracy of wall motion scoring by novice (68 +/- 3%) and experienced echocardiographers (71 +/- 3%) was less than experts in stress echocardiography (88 +/- 3%, p < 0.001). Various strategies for integration with MDV significantly improved the accuracy of wall motion scoring by novices from 75 +/- 2% to 77 +/- 5% (p < 0.01). Among the experienced group, accuracy improved from 74 +/- 2% to 77 +/- 5% (p < 0.05), but in the experts, no improvement was seen from their baseline accuracy. Integration with MDV also improved discordance related to the basal segments. Thus, use of MDV in all segments or MDV in all segments with wall motion scoring in the apex offers an improvement in sensitivity and accuracy with minimal compromise in specificity. (C) 2001 by Excerpta Medica, Inc.

A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays

OBJECTIVE Because there is discordance between different immunoassay values for serum hGH, and because clinical state may not correlate with immunoreactive hGH, we have developed an assay to accurately measure serum hGH somatogenic bioactivity. The results of this assay were compared with the Elegance two-site ELISA assay across 135 patient samples in a variety of clinical states. DESIGN The somatogenic assay was based on stable expression of hGH receptor in the murine BaF line, allowing these cells to proliferate in response to hGH. To eliminate interference by other growth factors in serum, we created a specific antagonist of the hGH receptor (similar to Trovert or Pegvisomant) which allowed us to obtain a true measure of hGH somatogenic activity by subtraction of the activity in the presence of the antagonist. The assay was carried out in microtiter plates over 24 h, with oxidation of a chromogenic tetrazolium salt (MTT) as the endpoint. PATIENTS These encompassed a number of different clinical conditions related to short stature, including idiopathic short stature, neurosecretory dysfunction and renal failure, as well as obese patients on dietary restriction and normal volunteers. MEASUREMENTS In addition to the colourimetric (MTT) response to hGH, we measured free hGH by stripping out GHBP-bound hGH using beads coupled to a monoclonal antibody to the GHBP (GH binding protein). All samples were measured in both bioassay and ELISA assay. RESULTS This bioassay was sensitive (5 mU/l or 2 mug/l) and precise, and not subject to interference by the GHBP. There was a good correlation (r = 0.95) between bioactivity and immunoactivity across clinical states. There was, however, an increased bioactivity during secretory peaks (over 25 mU/l), which has been reported previously for the Nb2 bioassay. Free hGH did not correlate with clinical state. CONCLUSIONS Because the results of the Elegance ELISA and the bioassay correlate well, even though there is greater bioactivity at higher hormone concentrations, it is evident that an appropriate immunoassay is able to act as a reliable indicator for clinical assessment. In those rare cases where bio-inactive GH exists, our bioassay should provide an appropriate means to demonstrate this.

Avaliação do teste Quantiferon TB Gold in tube no diagnóstico de infecção latente pelo Mycobacterium tuberculosis em profissionais de saúde da atenção básica

Introdução: Os ensaios de liberação do interferon- γ (ELIG) surgiram como uma alternativa para o diagnóstico de infecção latente pelo Mycobacterium tuberculosis (ILTB). Neste estudo, nós comparamos o desempenho de um dos ELIG, teste Quantiferon TB Gold in tube – QFT, com a prova tuberculínica (PT) em dois pontos de corte (≥ 5 mm e ≥ 10 mm), em profissionais de saúde da atenção básica à saúde (ABS). Métodos: Estudo transversal realizado em profissionais de saúde da ABS de quatro capitais nacionais com alta incidência de TB. O resultado do teste QFT foi comparado com o resultado da PT nos pontos de corte ≥ 5mm e ≥ 10 mm. Resultados: Foram incluídos 632 profissionais de saúde. Ao considerar o ponto de corte ≥ 10 mm para a PT, a concordância entre QFT e a PT foi de 69% (k = 0,31) e para o ponto de corte ≥ 5 mm, a concordância entre os testes foi de 57% (k = 0,22). Devido a baixa concordância entre a PT e o QFT, nós avaliamos os possíveis fatores associados com a discordância entre eles. Ao comparar o grupo PT- / QFT- com o grupo PT+ / QFT-, no ponto de corte ≥ 5 mm, a idade entre 41-45 [OR = 2,70, IC 95%: 1,32-5,51] e 46-64 [OR = 2,04, IC 95%: 1,05-3,93], presença de cicatriz vacinal do BCG [OR = 2,72, IC 95%: 1,40-5,25] e trabalhar apenas na ABS [OR = 2,30, IC 95 %: 1,09-4,86] apresentaram associação estatística significativa. Para o ponto de corte ≥ 10 mm, a presença de cicatriz vacinal do BCG [OR = 2,26, IC 95%: 1,03-4,91], ter tido contato domiciliar com paciente portador de tuberculose ativa [OR = 1,72, IC 95%: 1,01-2,92] e ter feito a PT anteriormente [OR = 1,66, IC 95%: 1,05-2,62] revelaram associação estatística significativa. Curiosamente, a discordância observada no grupo PT- / QFT + não apresentou associação estatistica com nenhuma das variáveis consideradas, independentemente do ponto de corte da PT. Conclusões: Apesar de termos identificado que a vacina BCG contribuiu para a discordância entre os testes, as recomendações brasileiras para o início do tratamento da ILTB não devem ser alteradas devido as limitações do QFT.

Studies on mosquitoes (Diptera: Culicidae) and anthropic environment: 1- Parity of blood seeking Anopheles (Kerteszia) in South-Eastern Brazil

Populations of Anopheles (Kerteszia) were sampled fortnightly over a one-year period (August 1991 to July 1992) at Ribeira Valley, S. Paulo State, Brazil. Indoor and outdoor collections were made on human bait at evening crepuscular period. The Polovodova technique for age grading was applied to 3,501 females of Anopheles cruzii and to 416 females of An. bellator. That sample represented 34.4% of the total number of mosquitoes collected. The most abundant species found was An. cruzii. However, An. bellator showed an endophagy that was almost three times greater than that of An. cruzii. The overall parous rate was 25.4% and uniparity was practically dominant one. A proportion of 26.9% of An. cruzii and 12.0% of An. bellator were found to be uniparous. Only three outdoor females of the former species (0.1%) showed biparity. Parity of An. cruzii was higher in females caught outdoors than in those caught indoors. Nevertheless, 497 nulliparous females examined (417 cruzii and 80 bellator) had ovaries that had advanced to Christophers and Mer stages III to V. These results imply that these females had already practised hematophagy. Relating these results to those from the parous females, a high statistical significance was found, leading to the conclusion that gonothophic discordance is a common pattern among these anophelines. Further, these results obtained with human bait catches strongly suggest that nearly 38.0% of these host-seeking females had already taken at least one previous blood-meal. So it is possible that enough time could thus be available for the plasmodian development in the vectors.

Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker of replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV - related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.

Determination du niveau d'anticorps antitetaniques en donneurs de sang au moyen du test ELISA-TÉTANOS (São Paulo, SP, Bresil)

Le test ELISA-TÉTANOS (Biosys, France) a été utilisé pour le titrage des anti-corps tétaniques (sensibilité = 0,0025 UI/ml) en sérums humains de donneurs de sang, 566 hommes et 108 femmes, âges de 18 à 58 ans, moyenne de 29 ans, provenant de São Paulo, SP, Brésil. L'OMS, acceptant seulement la séroneutralisation sur souris (NT), la méthode de référence, pour les études sur la protection contre le tétanos, préconise le titre de 0,01 UI/ml comme minimum protecteur. BOURLEAUD & HUET ont proposé la limite de 0,06 UI/ml quand s'emploie le test ELISA, en attendant à une certaine discordance inévitable entre les méthodes. Parmi les 674 sérums étudiés, 178 (26,41%) n'ont pas présenté d'anticorps (< 0,0025 UI/ml); 413 (61,28%) ont présenté des résultats égaux ou supérieurs à 0,01 UI/ml et en 232 (34,42%) les titres ont été égaux ou supérieurs à 0,06 UI/ml. Le pourcentage d'individus protégés a été inversement proportionnel à 1'âge: environ 50% dans le groupe le plus jeune (hommes de 18 à 35 ans et femmes de 18 à 23 ans) contre environ 10% dans le groupe de plus de 42 ans ont présenté des titres sûrement protecteurs (> 0,06 UI/ml).

O tratamento contabilístico do goodwill nas empresas do PSI- 20

Dissertação de Mestrado apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Contabilidade e Finanças, sob orientação de Drª Mónica D’Orey

Entamoeba histolytica: detection of coproantigens by purified antibody in the capture sandwich ELISA

A sensitive and specific Capture Sandwich ELISA (CSE) was developed using polyclonal purified rabbit antibodies against three different axenic strains of Entamoeba histolytica: CSP from Brazil and HM1 - IMSS from Mexico, for the detection of coproantigens in fecal samples. Immunoglobulin G (IgG) againstis E. histolytica was isolated from rabbits immunized with throphozoites whole extract in two stages: affinity chromatography in a column containing E. histolytica antigens bound to Sepharose 4B was followed by another chromatography in Sepharose antibodies 4B-Protein A. A Capture Sandwich ELISA using purified antibodies was able to detect 70ng of amebae protein, showing a sensitivity of 93% and specificity of 94%. The combination of microscopic examination and CSE gave a concordance and discordance of 93.25% and 6.75%, respectively. It was concluded that CSE is highly specific for the detection of coproantigens of E. histolytica in feces of infected patients, is quicker to perform, easier and more sensitive than microscopic examination.