Non-malignant silica-related diseases in a specialized outpatient clinic.

BACKGROUND: Uncontrolled occupational exposure to silica is still frequent in Brazil, with several recent records in the state of Minas Gerais. However, few national studies have addressed silica-related diseases other than silicosis. AIMS: To describe the occurrence of the main non-malignant silica-related diseases: silicosis, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), and autoimmune diseases in a specialized outpatient clinic. METHODS: Case series study of 1525 patients exposed to silica, seen between 1984 and 2021, with descriptive findings of clinical and occupational data from the first medical evaluation. RESULTS: Medians of age and exposure time were 47 and 15 years, respectively, and 97% of patients were male. The prevalence of silicosis was 44%, of which 27% had large opacities. The main occupational sectors were underground gold mining (28%), precious and semi-precious stone work (20%), and artisanal mining (9%). Spirometries were abnormal in 55%, with obstructive disorder being the most common finding. COPD (25%), active TB or sequelae (12%), and connective tissue diseases (6%) were diagnosed in patients with and without silicosis. CONCLUSIONS: The percentage of silicosis appears to be alarming, even considering the biases of selective referrals. The patients were relatively young and already had a functional impact, caused not only by silicosis but by one or more silica-related diseases. COPD, TB, and connective tissue diseases proved to be frequent, leading to the need for specifics protocols to investigate them in individuals exposed to silica. By adopting strategies to combat silicosis, the prevention of other silica-related diseases is concomitantly promoted.

Effect of chemotherapy with praziquantel on the production of cytokines and morbidity associated with schistosomiasis mansoni.

The objective of the present study was to test the hypothesis that treatment of schistosomiasis mansoni with praziquantel can alter significantly the immune response of patients and generate a reversal of the level of fibrosis. Peripheral blood mononuclear cell (PBMC) samples were collected from, and abdominal ultrasound examinations conducted on, volunteers infected with Schistosoma mansoni and living in an area where the disease is endemic, both prior to and one year after treatment with praziquantel. Subjects were classified into groups according to the level of pathology (i.e., absent, incipient, moderate, or severe fibrosis). PBMCs were stimulated with schistosome soluble egg antigens (SEA), and the levels of production of the cytokines gamma interferon (IFN-gamma), tumor necrosis factor alpha, transforming growth factor beta, and interleukin-4 (IL-4), IL-10, and IL-13 were determined. The chemotherapy was effective in reducing morbidity, particularly for individuals presenting with severe fibrosis. When levels of cytokine production in posttreatment PBMC cultures stimulated by SEA were categorized as low or high, significant differences in the distribution of IL-13 levels between groups presenting with or not presenting with fibrosis were established. Comparison of pre- and posttreatment SEA-induced cytokine levels in individuals who had experienced no change in the grade of fibrosis following chemotherapy revealed that the level of IFN-gamma decreased in subjects with fibrosis whereas that of IL-10 decreased in individuals with and without fibrosis. The data suggest that chemotherapy is effective in reducing the morbidity of the disease and that the level of IL-13 may be a useful indicator of the persistence of fibrosis following treatment.

The interaction of human serum with the surface membrane of schistosomula of Schistosoma mansoni.

After contact with human serum, a series of proteins become exposed on the surface membranes of schistosomula of Schistosoma mansoni as revealed by radioiodination of the intact parasites. Among the proteins, a doublet (Mr 45 000) is particularly prominent. These doublet proteins, which are believed to be parasite-derived, become apparent after a very short time of incubation with human serum (10 min or less) and are expressed on the surface membranes after contact with a high molecular weight component of human serum (Mr greater than 80 000). Pretreatment of the parasites with 1.25 mM colchicine or fixation with 2% glutaraldehyde does not prevent the serum-induced expression of the doublet proteins. Extraction of the parasites with chloroform:methanol 2:1 (v/v), however, blocks the human serum effect. Affinity chromatography using immobilized low density lipoproteins (LDL) from human serum shows a tight binding between the 125I-labelled 45 kDa doublet to the LDL. The possible role of the 45 kDa doublet as a receptor for LDL is discussed.

von Willebrand factor in plasma and urine of men with premature coronary artery disease.

Plasma and urine samples from 17 men who had suffered a myocardial infarction before the age of 45 years were quantitatively and qualitatively analyzed for von Willebrand factor antigen (vWF), and compared with samples obtained from controls. The levels of vWF in plasma and its characteristic multimeric composition in the patient samples were not different from those of the controls. However, when analyzed for lower molecular weight components, plasma samples from some patients contained more degraded material than those of the controls as indicated by the presence of an extra protein band of vWF related material having a molecular weight of about 200 kDa. The levels in urine of vWF and the molecular weight of the fragments excreted did not differ between patients and controls. A relative increase in excretion of lower molecular fragments was, however, observed in the patient group. In a second group of 97 consecutive post-infarction patients under the age of 45 years the extra 200 kDa vWF band was found in 46% of the patients, whereas it was not detected in control plasmas. Taken together these findings suggest that degraded forms of vWF occur in normal plasma and that a more extensive degradation may occur in patients with coronary atherosclerosis, which could account for the relative increase in the excretion of lower molecular weight fragments observed in these patients.

Factors affecting high and low human IgE responses to schistosome worm antigens in an area of Brazil endemic for Schistosoma mansoni and hookworm.

We have previously examined the antibody isotype responses to schistosome worm and egg antigens in human populations living in areas of Kenya and the Philippines endemic for Schistosoma mansoni and S. japonicum, respectively. Here, we have analyzed antibody isotype responses to S. mansoni adult worm (AW) antigen and soluble egg antigen (SEA) in more than 500 Brazilian individuals, and found similar relationships with age and sex as in the Kenyan and Filipino populations. Isotype responses to AW antigen broadly increased with age whereas isotype responses to SEA decreased, and a higher proportion of males than females had detectable IgE against AW antigen. Most isotype responses to AW antigen and SEA correlated positively with intensity of infection with S. mansoni except AW antigen-specific IgG2, which correlated negatively. The overall prevalence of infection with S. mansoni in this area was relatively low at only 39.5%; hookworm prevalence was higher at 57.4%. The majority of those infected with S. mansoni were also infected with hookworm (76%). Those individuals with high IgE responses to AW antigen were matched for sex, age, and total IgG to AW antigen as closely as possible with individuals with low levels of AW antigen-specific IgE. The two groups were compared for factors potentially influential in IgE production. No difference was found between the high and low IgE responders for 1) intensity or prevalence of infection with S. mansoni, 2) relative exposure to S. mansoni, 3) number of previous treatments for schistosomiasis, or 4) prevalence of infection with hookworm, but differences were found in other isotype responses to S. mansoni. The high IgE responders had higher IgA and IgG4 against both AW antigen and SEA but lower IgG3 responses to AW antigen than the low IgE responders. The IgE responses to three S. mansoni antigens (paramyosin, Sm22.6, and a 12-kD AW antigen band) were detected in individuals with IgE against AW antigen only.

Structural characterization of urinary von Willebrand factor by using monoclonal antibodies.

The presence of von Willebrand factor (vWF) related antigens has been previously described in urine. By gel filtration, three immunoreactive peaks have been demonstrated having Mr about 350 kDa, 60 kDa and 20 kDa. In this report, a structural characterization of the urinary fragments of vWF was studied by using monoclonal antibodies having known specificities towards the plasma sub-unit. The biggest urinary fragments contain the C-terminal portion and the central portion of the sub-unit. The other two urinary fragments come from the central part of the sub-unit. Antibodies to the N-terminus of the sub-unit do not react with any of the urinary fragments. These results led to a picture for degradation of vWF that is complex and may involve sequential degradation by several proteases. Patients with different types of vWD show qualitatively the same vWF degraded material in their urines, suggesting that whatever the mechanisms for degradation of vWF they are intact in these patients. Quantitatively, it seems that in patients receiving factor VIII-vWF concentrates there is an increased tendency to vWF excretion, which may be due to the presence of denatured material in the concentrates infused to these patients.

Application of an enzyme-linked immunosorbent assay (ELISA) to von Willebrand factor (vWF) and its derivatives.

Sandwich ELISA systems were developed to measure human von Willebrand factor (vWF). In one system the microtitre plates were coated with goat F(ab')2 to vWF. The F(ab')2 different molecular forms in the soluble phase. VWF antigen bound by the F(ab')2 antibody was subsequently determined by using horse-radish peroxidase labeled goat Fab' to vWF. In plasma 3 X 10(-4) units of vWF per ml could be detected with this system. In a different approach the antigen bound by the F(ab')2 antibody was probed by monoclonal antibodies to multimeric as well as to the reduced and carboxymethylated (RCM) form of vWF. Using these monoclonals and RCM-as well as native plasma as antigen, the total antigen and the relative proportion of multimeric forms in the sample were estimated.

von Willebrand factor antigen in urine.

Human urine was analyzed using a sensitive enzyme linked immunosorbent assay (ELISA) for von Willebrand factor (VWF) antigen. Urine of healthy persons contained VWF immunoreactivity. In the urine of a patient with severe von Willebrand disease, the VWF antigen was not detectable before but after intravenous infusion of von Willebrand factor-Factor VIII (VWF-FVIII) concentrate. The VWF antigen in normal urine was analyzed by gel permeation high performance liquid chromatography (HPLC). Three immunoreactive components of Mr 350 KDa, 60 KDa, and 20 KDa, respectively, were observed. Chromatography on concanavalin A-Sepharose revealed heterogeneity of the major 60 KDa component since only part of the material had affinity for the matrix. The 350 KDa material displayed affinity for Con A-Sepharose but not the 20 KDa. Gel electrophoresis combined with immunoblotting of normal urine gave similar results to those obtained by HPLC analysis. Immunoreactive components with apparent molecular weights similar to the largest urinary antigens were also observed in normal plasma but they were, nevertheless, not identical to the urinary antigens.

Fibrinogenemia Tampere--a dysfibrinogenemia with defective gelation and thromboembolic disease.

Fibrinogen Tampere was found in a woman with severe thromboembolic disease. The thrombin induced clotting time of her plasma and purified fibrinogen was slightly prolonged. The activation of fibrinogen Tampere appeared to be normal but subsequent gelation was defective. We studied fibrin gels formed at different ionic strengths and at different fibrinogen and calcium concentrations by liquid permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS-gel electrophoresis. The gels formed from fibrinogen Tampere were at ionic strength above 0.2 much tighter and had lower fiber mass-length ratios than normal gels as judged by permeability and turbidity data. At ionic strength 0.15 and at different calcium concentrations analysis by permeability showed the same results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic strength 0.15 suggested swelling of the fibers at low calcium concentrations. 3D microscopy revealed perturbed clot architecture under all conditions. In fibrin gels from fibrinogen Tampere, the gamma-chain crosslinking was normal but the crosslinking of alpha-chains was delayed at ionic strength 0.2 and also at lower ionic strengths on lowering the calcium concentration. The abnormal gelation may be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin gels and/or insufficient crosslinked fibrin matrix may be pathogenetic in this thrombotic disease.

Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni.

Analysis of the proliferation in vitro of peripheral blood mononuclear cells and the production of interferon-gamma (IFN-gamma) in individuals infected with Schistosoma mansoni and showing different clinical forms of the disease, as well as normal putatively immune individuals from an endemic area, was undertaken using total and fractionated soluble adult worm antigens (SWAP). A higher frequency of detectable response to fractionated antigens in T cell Western blot assays was observed in individuals with the more severe forms of the disease. Analysis of variance showed that, in the Western blot assays, there was a statistically significant difference in the level of cellular proliferation to antigens with low molecular weight (less than 21 kDa) between hepatosplenic patients and those with intestinal and hepatointestinal forms of the disease. No correlation between cellular proliferation and IFN-gamma production was observed. Most of the normal individuals from an endemic area failed to show significant proliferative responses to SWAP T cell Western blot assays or to antigen immobilized on nitrocellulose; they did show significant proliferative responses to whole soluble SWAP with positive IFN-gamma production. The results are consistent with the hypothesis that variations in the cellular immune responses to SWAP influence both the development of pathology and resistance to infection in schistosomiasis mansoni.

von Willebrand factor antigen in plasma and urine in patients with type I (insulin-dependent) diabetes mellitus with and without nephropathy.

von Willebrand factor (vWF) antigens were quantitatively and qualitatively analyzed in plasma and urine in 41 patients with type I (insulin-dependent) diabetes. The patients were divided into three groups according to their albumin excretion: group N (n = 24) without any excretion (less than 20 micrograms/min), group M (n = 8) with microalbuminuria (20-200 micrograms/min), and group P (n = 9) with persistent albuminuria (greater than 200 micrograms/min). Healthy subjects served as controls (n = 28). The plasma concentration of vWF was higher (p less than 0.05) in the patients with diabetes mellitus than in the controls. Differences between the groups of patients were not statistically significant. The typical multimeric structure described for vWF in normal plasma was observed in all patients. In urine, significantly higher excretion of vWF fragments was observed in the three diabetic study groups as compared with the controls. In group P the patients' urinary vWF/creatinine levels tended to be higher than in groups N and M. Qualitative analysis of urinary vWF fragments demonstrated a similar distribution pattern of fragments, with three distinctive peaks, in the patients of groups N and M and in the controls. The distribution pattern of vWF fragments in group P, however, differed clearly from that in the controls and showed a great variation within the group. The urinary fragments tended to be of a higher molecular weight and several less distinct fragments with the whole spectrum of molecular weight were observed. Because in these patients with proteinuria no qualitative changes appeared in plasma, it is suggested that abnormal degradation of vWF occurred in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection.

The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-gamma may be associated with resistance to infection.

Facial growth during adolescence in early, average and late maturers.

The relative stage of maturity of a child may be determined by comparing the child's hand-wrist radiograph to known standards of skeletal development. Hand-wrist radiographs of 70 adolescents were used to categorize the individuals by skeletal maturation into early, average and late maturation groups using the Fishman SMA method of assessment. The rates of mandibular and maxillary growth relative to the last stages of the pubertal growth spurt were measured. Statistical evaluation of the data was performed using an analysis of variance. The magnitude of change in growth increments of the mandible was greater in the late maturers than in the early or average maturers. Incremental differences in growth between the maxilla and mandible during the last stages of puberty were noted, with the mandible growing significantly more than the maxilla.

Longitudinal predictability of AF-BF value in Angle Class I patients.

AF-BF is a linear cephalometric measure of the anteroposterior jaw relationship in the sagittal plane. A retrospective, longitudinal study was made to determine the mean Caucasian American AF-BF values at ages 8 and 18 years for 30 male and 32 female participants of the Bolton Growth Study. Mean AF-BF values (+/- s.d.) for males were 7.3 +/- 2.7 mm at 8 years and 6.5 +/- 4.2 mm at 18 years. Mean AF-BF values (+/- s.d.) for females were 6.7 +/- 2.1 mm at 8 years and 5.2 +/- 2.9 mm at 18 years. No significant difference was found between the mean AF-BF values for males and females at either age group (P < 0.05). The decrease in AF-BF mean values with increasing age both for males and females was statistically significant. The correlation (r) for the AF-BF values was 0.49 (P < 0.05) for females and 0.86 (P < 0.05) for males. With increasing age, the mean difference between ANB values for females was 1.40 +/- 1.60 and 1.10 +/- 1.40 for males. The correlation of ANB angle and AF-BF provides a clinically useful tool for the cephalometric assessment of anteroposterior sagittal discrepancies of maxillary and mandibular denture bases.

A meta-analysis of mandibular intercanine width in treatment and postretention.

The meta-analysis technique of literature review was applied to a total of 26 previous studies to assess the longitudinal stability of postretention mandibular intercanine width. Weighted averages and standard deviations for the means of 1,233 subjects were compared for linear changes in intercanine transverse dimensions during treatment (T1), immediately after treatment (T2), and after removal of all retention (T3). Net change was defined as the difference between means at T3 and T1. Dimensional changes were also evaluated on the basis of patient pretreatment Angle classification, extraction, and nonextraction treatment modalities of each group. Paired two-tail t-tests were performed between T3 and T1 means on all groups at the a priori level of significance set at a < or = 0.05. Statistically significant differences were observed for the following groups: all patients; nonextraction; extraction; Class I; Class I extraction; Class II extraction; and, Class I Division 1 nonextraction. The findings of this study indicate that regardless of patient diagnostic and treatment modalities, mandibular intercanine width tends to expand during treatment on the order of one to two millimeters, and to contract postretention to approximately the original dimension. While statistically significant differences could be demonstrated within various groups, the magnitudes of the differences were not considered clinically important.

RadioVisioGraphy of the temporomandibular joint: comparisons with transcranial radiography.

RadioVisioGraphy (RVG), a new digital imaging technique, is compared to conventional transcranial radiographic imaging of the temporomandibular joint. The results of this study using fixed human cadaver specimens revealed an excellent correlation between the recorded images and the actual anatomic specimens. Dosimetry, using a beryllium-windowed ionization chamber, showed a 64% dose reduction with charge-coupled device (CCD) when compared to standard film-screen combination.

Three-dimensional CT scan of hemimandibular hyperplasia: case report.

Three-dimensional images of craniofacial structures are reconstructed from conventional CT scans with the use of special computer software. These reconstructed images do not exhibit magnification nor superimposition of CT scans of structures. Quantitative measurements of three-dimensional craniofacial structures can be very precise. This technique has broad applications in the field of special patient care and is demonstrated in a case report of hemimandibular hyperplasia.

[Use of cyclodextrins in the formulation of polyalkylcyanoacrylate nanoparticles charged with different active ingredients]. / Emploi des cyclodextrines dans la formulation de nanoparticules de poly(cyanoacrylate d'alkyle) chargées en divers principes actifs.

Cyclodextrins were used to improve the loading capacity of biodegradable pol(yisobutyl cyanoacrylat)e nanoparticles, which were obtained by anionic polymerization in aqueous medium. We investigated the feasibility of blank nanoparticles in the presence of a series of cyclodextrins (5 mg/ml) and poloxamer 188 (1%). The smaller particles (87 +/- 3 to 103 +/- 6 nm) were obtained in the presence of hydroxypropyl beta- or gamma-cyclodextrin. The nanoparticle loading capacity investigated in the presence of hydroxypropyl beta-cyclodextrin, in the previous conditions, on a series of steroids revealed an increase varying from 5.5 times (megestrol acetate) to 130 times (prednisolone). Differential scanning calorimetry study of the active ingredient (progesterone) in the nanoparticles, revealed an amorphous or molecular state. The in vitro release of the active ingredient occurred very rapidly but reached a plateau depending on the nanoparticle size and the dissolution medium nature. All the active ingredient was released in the presence of esterases. The addition of a preformed hydroxypropyl beta-cyclodextrin/saquinavir inclusion compound to the preparation medium of poly(isobutyl [or] isohexyl cyanoacrylate) nanoparticles, resulted in a 20-fold increase in the encapsulation yield. Presently, poly(isobutyl cyanoacrylate) hydroxypropyl beta-cyclodextrin combined nanoparticles loaded with doxorubicin are in phase II clinical trials.

Metal and physico-chemical variations at a hydroelectric reservoir analyzed by Multivariate Analyses and Artificial Neural Networks: environmental management and policy/decision-making tools.

This paper compared and evaluated seasonal variations in physico-chemical parameters and metals at a hydroelectric power station reservoir by applying Multivariate Analyses and Artificial Neural Networks (ANN) statistical techniques. A Factor Analysis was used to reduce the number of variables: the first factor was composed of elements Ca, K, Mg and Na, and the second by Chemical Oxygen Demand. The ANN showed 100% correct classifications in training and validation samples. Physico-chemical analyses showed that water pH values were not statistically different between the dry and rainy seasons, while temperature, conductivity, alkalinity, ammonia and DO were higher in the dry period. TSS, hardness and COD, on the other hand, were higher during the rainy season. The statistical analyses showed that Ca, K, Mg and Na are directly connected to the Chemical Oxygen Demand, which indicates a possibility of their input into the reservoir system by domestic sewage and agricultural run-offs. These statistical applications, thus, are also relevant in cases of environmental management and policy decision-making processes, to identify which factors should be further studied and/or modified to recover degraded or contaminated water bodies.