The impact of sputum quality on Xpert positivity in active case-finding for TB.

BACKGROUND: Studies evaluating sputum quality and Xpert® MTB/RIF positivity in the context of active case finding are scarce. We aimed to determine whether sputum quality is associated with Xpert positivity and whether the association differed according to demographic and clinical characteristics.METHODS: A cross-sectional analysis using data from a mass screening programme in Brazilian prisons was conducted from 2017 to 2021. We administered a standardised questionnaire, obtained a chest X-ray and collected a spot sputum sample for Xpert testing. Sputum quality was classified as 'salivary', 'mucoid/mucopurulent' or 'blood-stained'. We used log binomial regressions to estimate the relationship between sputum quality and Xpert positivity, assessing interactions with participant characteristics.RESULTS: Among 4,368 participants for whom sputum quality was assessed, 957 (21.9%) produced salivary specimens, 3,379 (77.4%) had mucoid/mucopurulent sputum and 32 (0.7%) had blood-stained sputum. Xpert positivity was higher among those with mucoid/mucopurulent sputum than among those with salivary samples (12.0% vs. 3.7%). Mucopurulent sputum independently predicted Xpert positivity among individuals with and without symptoms, current smoking and abnormal chest radiographs on CAD4TB.CONCLUSIONS: In our study, sputum appearance independently predicted Xpert positivity, and could be used together with chest X-ray and symptom screening to inform use of Xpert in individual or pooled testing.

Intrapulpal Concentration of Hydrogen Peroxide of Teeth Restored With Bulk Fill and Conventional Bioactive Composites.

This study evaluated intrapulpal concentration and hydrogen peroxide (HP) penetration at the interface of teeth restored with bioactive composites, using conventional or bulk-fill composites. Cylindrical cavities were prepared on the buccal surface of bovine incisor crowns (n=20) and restored with: resin modified glass-ionomer (RMGI, Riva Light Cure, SDI), non-bioactive bulk-fill composite (FB, Filtek Bulk, 3M Oral Care), non-bioactive conventional composite (FZ, Filtek Z350, 3M Oral Care), bioactive bulk-fill composite (AC, Activa BioActive, Pulpedent), and bioactive conventional composite (BII, Beautifil II, Shofu). After 5,000 thermal cycles, restorations (n=10) were exposed to high (35% HP [4 applications of 8 min/session-4 sessions]) or low (9.5% HP [30 min/day-14 days]) concentration bleaching protocols. After the last bleaching application, the HP intrapulpal concentration was determined. Additional teeth were restored, pigmented with rhodamine B solution, and HP penetration around the interface was observed under laser scanning confocal fluorescence microscopy (LSCFM, n=3). The presence of gaps at the interface was observed on replicas of the cross-sectioned samples under scanning electron microscopy (SEM, n=5). Data were submitted to one-way (gap analysis) and twoway analysis of variance (ANOVA; HP intrapulpal concentration) and Tukey test (α=0.05). The LSCFM images were qualitatively analyzed. The restored teeth submitted to 35% HP presented higher HP intrapulpal concentration than teeth submitted to 9.5% HP (p<0.05). No differences in HP intrapulpal concentration was observed among groups (p>0.05) when exposed to 9.5% HP. Lower HP intrapulpal concentration was observed for teeth restored with RMGI exposed to HP 35%, when compared with teeth restored with nonbioactive conventional (FZ; p=0.004) and bulk-fill composites (FB; p=0.01). No gap formation was observed at the outer enamel adhesive interface for all restorative materials. LSCFM images showed that 35% HP promoted greater degradation of rhodamine B at the enamel, except for RMGI. In this context, RMGI promoted lower HP intrapulpal concentration than non-bioactive conventional and bulk-fill composites.

Potential Effects of Future Climate Changes on Brazilian Cool-Adapted Stoneflies (Insecta: Plecoptera).

The continuous pursuit of welfare and economic development through the exploitation of natural resources by human societies consequently resulted in the ongoing process of climate change. Changes in the distribution of species towards the planet's poles and mountain tops are some of the expected to biological consequences of this process. Here, we assessed the potential effects of future climate change on four cool-adapted Gripopterygidae (Insecta: Plecoptera) species [Gripopteryx garbei Navás 1936, G. cancellata (Pictet 1841), Tupiperla gracilis (Burmeister 1839), and T. tessellata (Brauer 1866)] from Southeastern Brazilian Atlantic forest. As species adapted to cold conditions, in the future scenarios of climate change, we expected these organisms to shrink/change their distributions ranges towards areas with suitable climatic conditions in Southern Brazilian regions, when compared with their predicted distributions in present climatic conditions. We used seven principal components derived from 19 environmental variables from Worldclim database for the present scenario and also seven principal components obtained from 17 different Atmosphere-Ocean Global Circulation Models (AOGCMs), considering the most severe emission scenario for green-house gases to predict the species' distributions. Depending on the climatic scenario considered, there were polewards distribution range changes of the species. Additionally, we also observed an important decrease in the amount of protected modeled range for the species in the future scenarios. Considering that this Brazilian region may become hotter in the future and have its precipitation regime changed, as observed in the severe 2013-2014 drought, we believe these species adapted to high altitudes will be severely threatened in the future.

Transcriptomic analysis of immunoglobulin novel antigen receptor (IgNAR) heavy chain constant domains of brownbanded bamboo shark (Chiloscyllium punctatum).

Cartilaginous fish are the evolutionarily oldest group of animals which possess antibodies, T cell receptors and major histocompatibility complex (MHC). The immunoglobulin novel antigen receptor (IgNAR) found in cartilaginous fish is a heavy chain homodimer which lacks light chain. The presence of non-canonical cysteine molecules and lack of CDR2 region make it more significant. To synthesize active binding domains based on variable region of IgNAR (VNAR), knowledge on the constant region dynamics play a significant role. The IgNAR exhibit species variations in its primary sequence features; hence, this study was conducted to determine the IgNAR heavy chain constant domain of the brownbanded bamboo shark (Chiloscyllium punctatum). Peripheral blood leukocytes (PBL) isolated from adult bamboo sharks were used to synthesize a cDNA library. A total of four billion residues of two million sequences (average length 218.41 bp) were obtained. Assembled sequences were aligned with published cartilaginous fish IgNAR constant region sequences. Transcriptome analysis revealed two distinct types of IgNAR in the brownbanded bamboo shark. Also, constant-1 domain sequences displayed 13 unique sequences which may reflect the least number of IgNAR gene clusters. The phylogenetic analysis revealed the closest relationship with the nurse shark (Ginglymostoma cirratum) followed by the wobbegong shark (Orectolobus maculatus) which belong to the same order Orectolobiformes. Analysis of the constant domains of the brownbanded bamboo shark IgNAR revealed an evolutionarily conserved nature and this knowledge can be used to design primers for VNAR cloning. Furthermore, knowledge on the structural features in IgNAR constant domains that increase the stability could be useful in the process of stabilizing human immunoglobulins.

Plasma butyrylcholinesterase activity: a possible biomarker for differential diagnosis between Alzheimer's disease and dementia with Lewy bodies?

Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for secondary hydrolysis of the acetylcholine. K and -116A BCHE variants were associated with decrease in plasma BChE activity, and their influence has been investigated in diseases with a cholinergic deficit such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE genetic variants on enzymatic activity, all patients and controls were genotyped for K and -116A variants. We found lower plasma BChE activity in DLB patients compared to elderly controls and to AD independent of the presence of K or -116A variants. Our results suggest that the reduction of total plasma BChE activity is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic marker for differential diagnosis between AD and DLB.

Contrasting Patterns in Solitary and Eusocial Bees While Responding to Landscape Features in the Brazilian Cerrado: a Multiscaled Perspective.

Landscape structure is an important determinant of biological fluxes and species composition, but species do not respond equally to landscape features or spatial extents. Evaluating "multi-scale" responses of species to landscape structure is an important framework to be considered, allowing insights about habitat requirements for different groups. We evaluated the response of Brazilian Cerrado's bees (eusocial vs. solitary ones) to both the amount and isolation of remnant vegetation in eight nested multiple-local scales. Response variables included abundance, observed, and estimated species richness, and beta diversity (split into nestedness and turnover resultant dissimilarities). Eusocial species' abundance responded to landscape structure at narrow scales of fragment isolation (250 m of radius from sampling sites), while solitary species' abundance responded to broader scales to fragment area (2000 m). Eusocial species nestedness also responded to landscape features in broader scales (1500 m), especially to increasing fragment isolation. However, all the remaining response variables did not respond to any other landscape variables in any spatial scale considered. Such contrasting responses of the abundances of eusocial vs. solitary species are related to the inherent life-history traits of each group. Important attributes in this context are different requirements on food resources, population features, and flight abilities. Species-specific dispersal abilities may be the main determinants of the nested patterns found for eusocial species at 1500 m. Considering these results, we suggest that different bee groups are considered separately in further landscape analyses, especially in other Brazilian biomes, for a better understanding of landscape effects on these organisms.

The Size But not the Symmetry of the Wings of Eulaema nigrita Lepeletier (Apidae: Euglossini) is Affected by Human-Disturbed Landscapes in the Brazilian Cerrado Savanna.

Among other human-related activities, habitat loss and fragmentation are currently ranked as the most important environmental features affecting the persistence of animal and plant populations in landscapes, as well as the maintenance of ecological processes and services. Since these processes are also capable of affecting the ontogenetic development of species inhabiting those landscapes, here we measured the wing veins of male Eulaema nigrita Lepeletier (Apidae: Euglossini) bees in order to evaluate whether the bees sampled in agriculture (AG) areas suffer higher fluctuating asymmetry (FA) than those sampled in Cerrado (CE) areas in the Brazilian state of Goiás. We believe that individuals sampled in CE areas would be less asymmetric than those sampled in AG areas, given a potential higher exposure of these specimens to environmental stresses (mostly pesticides). However, we did not observe a significant trend in the FA measures we obtained, although three wing measures were bigger for bees from CE areas. The lack of significant effects of FA may be related to inherent bionomic features of E. nigrita. For instance, given their high individual dispersal abilities, the individuals we analyzed may have developed in different areas than those where they were sampled. Their generalist feeding behavior may also have given them a higher resistance to environmental perturbations, buffering the normal development of immatures even in areas with local high environmental stress. Nonetheless, higher death rates of individuals from anthropic areas may also have killed the developing immatures of E. nigrita before they reached adulthood consequently equalizing our sampled estimates.

Características das carcaças e carne de tourinhos Nelore alimentados com níveis de concentrado e farelo do mesocarpo de babaçu / Carcass and meat characteristics of cattle fed concentrate levels and babassu mesocarp bran

Avaliaram-se as características da carcaça e da carne de tourinhos Nelore alimentados com diferentes níveis de concentrado e farelo do mesocarpo do babaçu na dieta. Foram utilizados 28 tourinhos da raça Nelore, com idade inicial de 21 meses e 356,66±19,25kg de peso corporal inicial, distribuídos inteiramente ao acaso em dietas com dois níveis de concentrado (65 e 71%), associadas ou não à inclusão de 35% de farelo do mesocarpo do babaçu no concentrado. A elevação da fração concentrada na dieta de 65 para 71%, bem como a inclusão de 35% de farelo do mesocarpo do babaçu no concentrado, não alterou a quantidade de músculo, gordura e osso da carcaça, com valores médios de 63,91; 19,46 e 16,63% do peso de carcaça fria, respectivamente. O rendimento dos cortes comerciais secundários do traseiro especial não foi alterado pela inclusão de 35% de farelo do mesocarpo do babaçu no concentrado nem pelo teor de concentrado da dieta. A força ao cisalhamento das fibras musculares, a perda de líquido por descongelamento e cozimento não foram alteradas pelos fatores estudados, apresentando valores médios de 6,57kgf/cm3, 16,08% e 22,20%, respectivamente. O marmoreio aumentou (5,78 para 9,79 pontos) pelo avanço do nível de concentrado na dieta, mas não foi alterado pela inclusão do farelo do mesocarpo do babaçu. O farelo do mesocarpo do babaçu apresenta características nutricionais que possibilitam substituir parcialmente o milho em dietas com elevada proporção de concentrado, não alterando a composição física da carcaça e a qualidade da carne de tourinhos Nelore confinados.

Carcass characteristics and meat of young bulls fed different levels of concentrate and babassu mesocarp bran in the diet were evaluated. A total of 28 Nellore young bulls, initial age of 21 months and 356.66±19.25kg of initial body weight were randomized in diets containing two levels of concentrate (65% and 71) associated or not to the inclusion of 35% of babassu mesocarp bran in the concentrate. The elevation of the concentrate fraction of the diet from 65 to 71%, and the inclusion of 35% of babassu mesocarp bran in the concentrate did not alter the amount of muscle, fat and bone of the carcass, with average values of 63.91, 19.46 and 16.63% of cold carcass weight, respectively. The yields of retail cuts from the pistol cut were not altered by the concentrate level of the diet or by the inclusion of 35% babassu mesocarp bran in the concentrate. The shear force of muscle fibers and the losses of liquid during thawing and cooking were not altered by the factors studied, with average values of 6.57kgf/cm3, 16.06% and 22.20%, respectively. Marbling increased (5.78 to 9.79 points) to advance the level of concentrate in the diet, but was not altered by the inclusion of babassu mesocarp bran. Babassu mesocarp bran has nutritional characteristics that allow partial replacement of corn in diets with high concentrate, not changing physical carcass composition and meat quality of confined young Nellore bulls.

Butyrylcholinesterase: K variant, plasma activity, molecular forms and rivastigmine treatment in Alzheimer's disease in a Southern Brazilian population.

Alzheimer's disease (AD) is a neurodegenerative disorder in which there is a decline of cholinergic function. The symptomatic AD treatment involves the use of ChEIs (cholinesterase inhibitors) as rivastigimine, a dual inhibitor. The human butyrylcholinesterase (BChE) is an enzyme that has specific roles in cholinergic neurotransmission and it has been associated with AD. In the serum, BChE is found in four main molecular forms: G1 (monomer); G1-ALB (monomer linked to albumin); G2 (dimer); and G4 (tetramer). The interaction between the products of BCHE gene and CHE2 locus results in CHE2 C5+ and CHE2 C5- phenotypes. CHE2 C5+ phenotype and BChE-K are factors that influence on BChE activity. This work aimed to verify the proportions of BChE molecular forms, total and relative activity in 139 AD patients and 139 elderly controls, taking into account K variant, CHE2 locus, rivastigmine treatment and clinical dementia rating (CDR) of AD patients. Phenotypic frequencies of CHE2 C5+ and frequency of the carriers of the K allele were similar between groups. Total BChE activity in plasma was significantly lower in AD patients than in elderly controls. Furthermore, we found that reduction on plasma BChE activity is associated directly with AD progression in AD patients and that rivastigmine treatment has a stronger effect on BChE activity within the CDR2 group. The reduction in BChE activity did not occur proportionally in all molecular forms. Multiple regression analysis results confirmed that AD acts as the main factor in plasma BChE activity reduction and that severe stages are related with an even greater reduction. These findings suggest that the reduction of total plasma BChE and relative BChE molecular forms activity in AD patients is probably associated with a feedback mechanism and provides a future perspective of using this enzyme as a possible plasmatic secondary marker for AD.

No Evidence of Habitat Loss Affecting the Orchid Bees Eulaema nigrita Lepeletier and Eufriesea auriceps Friese (Apidae: Euglossini) in the Brazilian Cerrado Savanna.

Habitat loss, landscape fragmentation, and agriculture intensification constitute the main threats to bees. As the organisms responsible for almost one third of the food produced worldwide, there are growing concerns on bees' response to human-related disturbances. Among all bee groups, orchid bees (Apidae: Euglossini) compose an interesting group to test landscape-related hypotheses. In here, we tested the effect of landscape features (amount of anthropic areas and isolation) on the probability of occurrence and the abundances of both Eulaema nigrita Lepeletier and Eufriesea auriceps Friese in the Cerrado savanna. In general, we did not observe any effect of landscape features on the probability of occurrence and abundances of both species in our sampling sites. Given their potential high dispersal abilities, these bee species may be less sensitive to fragmented landscapes or even positively affected by the increase of anthropic habitats. Since we sampled many E. nigrita specimens in highly preserved Cerrado savanna areas, we believe that at least for this biome, this species may not be a good indicator of landscape disturbance.

An outbreak of respiratory syncytial virus infection in hematopoietic stem cell transplantation outpatients: good outcome without specific antiviral treatment.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of seasonal respiratory viral infection in hematopoietic stem cell transplantations (HSCT) patients. The efficacy of treatment, however, remains controversial. We describe an outbreak of 31 cases of RSV that occurred in an HSCT outpatient care unit in the fall season from March through May 2010, with a good outcome without any specific antiviral treatment. METHODS: During these 3 months, 222 nasal wash samples were tested and, of these, 31 outpatients were positive for RSV. In 2009, 99 samples had been tested and only 10 outpatients were positive for RSV in the same period. RESULTS: Seven (22.5%) patients had severe neutropenia (<500 cells/µL); severe lymphopenia (<200 cells/µL) was present in 13 (41.9%) patients, and 14 (45%) had received intravenous broad-spectrum antibiotics. Hospitalization was necessary only for 8 patients (25.8%); 20 had lower respiratory tract infection (64.5%). Only 1 patient died as a result of proven invasive aspergillosis. CONCLUSION: This report suggests that HSCT outpatients with no risk factors may not always require specific treatment for RSV.

Patterns of in vitro cell-death, metaloproteinase-9 and pro-inflammatory cytokines in human monocytes induced by the BCG vaccine, Moreau strain.

Mononuclear cells have been implicated in the primary inflammatory response against mycobacteria. Yet, little is known about the interaction of Mycobacterium bovis bacillus Calmette-Guerin (BCG) with human monocytes. Here, we investigated the potential of BCG Moreau strain to induce in vitro specific cell-death utilizing a flow cytometry approach that revealed an increase in apoptosis events in BCG-stimulated monocytes from healthy adults. We also detected a concomitant release of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), but not metalloproteinase (MMP)-9. In addition, annexin V-propidium iodide double staining demonstrated an enhancement of monocytes necrosis, but not apoptosis, following BCG Moreau strain stimulation of umbilical vein cells from naïve, neonate. This pattern was paralleled by different pro-inflammatory cytokine levels, as well as MMP-9 induction when compared to the adults. Our findings support the hypothesis that BCG induces distinct cell-death patterns during the maturation of the immune system and that this pattern might set the stage for a subsequent antimycobacterial immune response that might have profound effects during vaccination.

Estrogen receptor, progesterone receptor, and bcl-2 are markers with prognostic significance in CIN III.

There are no known biological markers or technologies to predict the natural history of an individual CIN III. The probability of progression is considered greater with the persistence of high-risk human papillomavirus (HPV) infection and age. p53 polymorphism has been associated with cervical carcinogenesis. Hormone-induced cervical cancer is mediated by estrogen receptor (ER) and progesterone receptor (PR). In cervical cancer, increased bcl-2 and Bax immunoreactivity is generally associated with a better prognosis. The purpose of this study was to evaluate the value of HPV 16 and HPV 18 typing and p53 codon polymorphism genotyping by polymerase chain reaction and ER, PR, bcl-2, and Bax expression by immunohistochemistry in predicting the CIN III clinical behavior of CIN III lesions. We studied the expression of these prognostic factors in the CIN III adjacent to squamous cell microinvasive carcinomas of the cervix (MIC) from 29 patients with FIGO stage IA1 cervical cancer and in 25 patients with CIN III and no documented focus of invasion. In the MIC group, only the CIN III was considered at least 2 mm away from the microinvasive complex. The ER, PR, bcl-2, and Bax immunoreactivity was scored as positive (>10% staining cells) and negative (<10% staining cells). No significant difference was observed between MIC and CIN III group concerning HPV infection and p53 polymorphism. The ER, PR, bcl-2, and Bax immunohistochemical expression was stronger and more frequent in the CIN III group. After multivariable analysis, coexpression of ER, PR, and bcl-2 was the only independent factor in defining low risk of progression for CIN III. Our study suggests that coexpression of ER, PR, and bcl-2 may be a useful tool in identifying the CIN III lesions with low risk of progression to cervical cancer.

Fraturas vertebrais em grandes animais: estudo retrospectivo de 39 casos (1987-2002) / Vertebral fractures in large animals: retrospective study of 39 cases (1987-2002)

Realizou-se estudo retrospectivo (1987-2002) dos aspectos clínicos das fraturas vertebrais em eqüinos, bovinos, ovinos, caprinos e suínos atendidos no hospital veterinário da FMVZ-Unesp de Botucatu. Todos os casos tiveram confirmaçäo radiográfica ou post-mortem. Segundo a espécie, a ordem de acometimento foi: bovina, eqüina, ovina, caprina e suína. As lesöes ocorreram desde os 12 dias de idade até os 10 anos, com maior freqüência até os 12 meses. O segmento torácico foi o mais comprometido seguido dos segmentos lombar, cervical e sacral. As fraturas vertebrais devem fazer parte da lista de diagnósticos diferenciais de animais em decúbito, independente da espécie, sexo ou idade

Overexpression of glucose-6-phosphate dehydrogenase in genetically modified Saccharomyces cerevisiae.

Glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) is an abundant enzyme in Saccharomyces cerevisiae. This enzyme is of great interest as an analytical reagent because it is used in a large number of quantitative assays. A strain of S. cerevisiae was genetically modified to improve G6PD production during aerobic culture. The modifications are based on cloning the G6PD sequence under the control of promoters that are upregulated by the carbon source used for yeast growth. The results showed that S. cerevisiae acquired from a commercial source and the same strain produced by aerobic cultivation under controlled conditions provided very similar G6PD. However, G6PD production by genetically modified S. cerevisiae produced very high enzyme activity and showed to be the most effective procedure to obtain glucose-6-phosphate dehydrogenase. As a consequence, the cost of producing G6PD can be significantly reduced by using strains that contain levels of G6PD up to 14-fold higher than the level of G6PD found in commercially available strains.

Effect of agitation and aeration on production of hexokinase by Saccharomyces cerevisiae.

A batch culture of Saccharomyces cerevisiae for the production of hexokinase was carried out in a 5-L fermentor containing 3 L of culture medium, which was inoculated with cell suspension (about 0.7 g/L), and left fermenting at 35 degrees C and pH 4.0. The aeration and agitation were adjusted to attain k(L)a values of 15, 60, 135, and 230 h(-1). The highest hexokinase productivity (754.6 U/[L x h]) and substrate-cell conversion yield (0.21 g/g) occurred for a k(L)a of 60 h(-1). Moreover, the formation of hexokinase and cell growth are coupled events, which is in accordance with the constitutive character of this enzyme. Hexokinase formation for kLa > 60 h(-1) was not enhanced probably owing to saturation of the respiratory pathway by oxygen.

Vulvar squamous cell carcinoma. Prognostic factors for local recurrence after primary en bloc radical vulvectomy and bilateral groin dissection.

OBJECTIVE: To evaluate clinical prognostic factors for local recurrence of vulvar squamous cell carcinoma after primary surgical treatment. STUDY DESIGN: Of 104 patients treated for squamous cell carcinoma of the vulva in an 11-year period (1987-1997) at the Portuguese Cancer Institute, we selected for study 56 patients who meet the following criteria: (1) International Federation of Gynecology and Obstetrics (FIGO) stage Ib-IVa, (2) primary treatment of en bloc radical vulvectomy and bilateral groin dissection, and (3) follow-up reports. Files were retrieved for retrospective analysis. Fifteen patients (26.8%) had local recurrence at the fifth year. At the 24th month, 11 patients had local recurrence, and 31 were in follow-up, without recurrence. We evaluated age at initial diagnosis, date of surgical treatment, tumor size, results of tumor macroscopy, histologic differentiation, groin lymph node status, FIGO stage, resection limits, adjuvant radiotherapy, duration of stay, associated vulvar skin disease, date of detection of recurrence, site/sites of recurrence and follow-up status at the 24th month after surgical treatment between the 11 patients with local recurrence and 31 in follow-up without recurrence. RESULTS: The 11 patients with local recurrence had a significant initial FIGO stage, IVa (P = .049) and a significant association with the number of groin lymph nodes containing metastasis in comparison to the 31 patients without local recurrence. No other statistically compared data were significant. CONCLUSION: These results suggest that vulvar squamous cell carcinoma local recurrence after a primary surgical procedure is related to poor tumor prognostic factors (number of groin nodes containing tumor metastasis and FIGO stage IVa). On multivariate analysis, the presence of metastasis in two or more groin nodes was a powerful factor related to local recurrence. Postoperative radiotherapy to the vulva for such patients with a high risk of local recurrence is advisable.

[Screening for cancer of the cervix. Program of the Central Region of Portugal]. / Rastreio do cancro do colo. Programa da Região Centro de Portugal.

Cervical cancer screening is clearly efficient, as can be proved by a simple comparison of the incidence and mortality rates for this neoplasia before and after the implementation of screening programmes in various countries and regions. The Screening Programme of the Central Region of Portugal is done by the G.P., who collects cytological smears in the Health Centres and sends them to the Cytopathology Laboratory of the Coimbra Cancer Institute (IPO). The IPO not only does the cytological test but also coordinates the programme and is responsible for quality control. To date, 83,173 women have been screened. Although the average participation rate is low (34.5%) some Health Centres have a very high rate, above 90%. The detection rate of pre-malignant lesions by cytology is 4.5%, which falls within the parameters provided by the WHO. The study of these cases confirms the high degree of sensitivity of cytology. For women who were tested a second time, the number of pre-malignant lesions revealed was not significant, so this procedure is more for quality control. When the programme began, only 0.4% of carcinomas were pre-invasive, compared to 42.1% now! Before the programme, only 18.6% of patients were able to be treated surgically, whilst now, 74.4% are able to benefit this way. The main problem continues to be the lack of definitions of the role of the Health Centres in the screening programme.

Creatine kinase brain isoenzyme (BB-CK) presence in serum distinguishes osteopetroses among the sclerosing bone disorders.

Creatine kinase (CK) isoenzyme BB-CK is predominantly found in brain and is not normally detected in the blood. A few recent reports, however, have described BB-CK in serum from several patients with osteopetrosis (OP). To evaluate the presence and specificity of BB-CK in serum in the osteopetroses among disorders that increase skeletal mass, we quantitated total CK activity and CK isoenzymes in 15 patients representing the five major clinical forms of OP (2 infantile, 3 intermediate, 7 adult [2 type I, 5 type II], and 3 carbonic anhydrase II [CA II] deficiency cases) and in 22 patients representing 14 other types of sclerosing bone disease. All OP patients (except the two adult type I subjects) had BB-CK readily detected in their serum. Conversely, only 1 of the 22 patients with other sclerosing bone disorders had detectable BB-CK in serum (1 of 3 patients with fibrodysplasia [myositis] ossificans progressiva who had barely measurable activity). In three OP patients (one of two with the infantile form and two of five with adult, type II disease), BB-CK values were sufficiently high that serum total CK activity was elevated. In a newborn with malignant OP, both cord blood plasma and peripheral blood serum had substantial amounts of BB-CK. In three subjects (with adult type II OP), who were restudied 2-6 years later, BB-CK was still elevated in their blood. BB-CK in serum appears to distinguish the osteopetroses among the sclerosing bone disorders. Absence of serum BB-CK in adult type I disease suggests that this condition may not be a genuine form of OP. Assay of BB-CK in fetal blood could be studied as a means for prenatal diagnosis of malignant OP. Why the osteoclast failure that characterizes all true forms of OP is associated with BB-CK in the circulation is a new question for skeletal biologists.