Annexin A11 gene polymorphism (R230C variant) and sarcoidosis in a Portuguese population.

A recent genome-wide association study detected a protective effect for the annexin A11 rs1049550*T allele (R230Cvariant) in susceptibility to sarcoidosis. We evaluated the association between rs1049550 C/T and sarcoidosis susceptibility, distinct disease phenotypes and evolution in a Portuguese population. We performed a case-control study of 208 patients and 197 healthy controls. Samples were genotyped for rs1049550 C/T using real-time polymerase chain reaction. The frequency of the annexin A11 rs1049550*T allele was significantly lower in patients than in controls (33.2 vs 44.9%, P < 0.001). Odds ratio of 0.52 and 0.44 were obtained, respectively for carriers of one (CT) and two (TT) copies normalized to the CC wild-type genotype (P < 0.001). There were no significant differences in patients with and without Löfgren syndrome. A significant increase in the frequency of the T allele was observed in patients with bronchoalveolar lavage (BAL) fluid neutrophilia (P = 0.04). No significant associations were seen for lung function pattern, radiological stages or different forms of disease evolution. Our study confirms that rs1049550*T allele exerts a significant protective effect on sarcoidosis susceptibility. Given the role of annexin A11 in cell division, apoptosis and neutrophil function, this polymorphism may affect key elements of granulomatous and interstitial inflammation in sarcoidosis.

Identification of Latent Risk Clinical Attributes for Children Born Under IUGR Condition Using Machine Learning Techniques.

BACKGROUND AND OBJECTIVE: Intrauterine Growth Restriction (IUGR) is a condition in which a fetus does not grow to the expected weight during pregnancy. There are several well documented causes in the literature for this issue, such as maternal disorder, and genetic influences. Nevertheless, besides the risk during pregnancy and labour periods, in a long term perspective, the impact of IUGR condition during the child development is an area of research itself. The main objective of this work is to propose a machine learning solution to identify the most significant features of importance based on physiological, clinical or socioeconomic factors correlated with previous IUGR condition after 10 years of birth. METHODS: In this work, 41 IUGR (18 male) and 34 Non-IUGR (22 male) children were followed up 9 years after the birth, in average (9.1786 ± 0.6784 years old). A group of machine learning algorithms is proposed to classify children previously identified as born under IUGR condition based on 24-hours monitoring of ECG (Holter) and blood pressure (ABPM), and other clinical and socioeconomic attributes. In additional, an algorithm of relevance determination based on the classifier is also proposed, to determine the level of importance of the considered features. RESULTS: The proposed classification solution achieved accuracy up to 94.73%, and better performance than seven state-of-the-art machine learning algorithms. Also, relevant latent factors related to HRV and BP monitoring are proposed, such as: day-time heart rate (day-time HR), day-night systolic blood pressure (day-night SBP), 24-hour standard deviation (SD) of SBP, dropped, morning cortisol creatinine, 24-hour mean of SDs of all NN intervals for each 5 minutes segment (24-hour SDNNi), among others. CONCLUSION: With outstanding accuracy of our proposed solutions, the classification system and the indication of relevant attributes may support medical teams on the clinical monitoring of IUGR children during their childhood development.

[A new agent in the mechanisms underlying addiction and ingestion of alcohol: the nucleus incertus and the neuropeptide relaxin-3]. / Un nuevo agente en los mecanismos de la adiccion al alcohol y la ingesta: el nucleo incertus y el neuropeptido relaxina-3.

Alcohol intake is facilitated by its relationship with eating behavior and both processes are highly influenced by situations of stress and anxiety. The dysregulation of these processes can reach pathological situations such as anorexia, bulimia or obesity. The neurobiological elements which underlie this control are not completely clarified. The nucleus incertus (NI) in the pontine tegmentum is a common element in the food intake and alcoholism. NI is characterized by using the neuropeptide relaxin-3 (RLN3) as transmitter and its receptor RXFP3. In the present review, we will analyze the participation of the NI-RLN3-RXFP3 system in these behaviors under conditions of anxiety or stress in animal models. The activation of NI has a positive effect on intake (orexigenic) and generates a wide response in the amygdala modulating anxiety states. The activity of RLN3-RXFP3 in the amygdala could affect alcohol addiction since the application of the RXFP3 antagonist in extended amygdala attenuates the relapse to alcohol induced by stress. The neuroanatomical data indicate that the NI-RLN3-RXFP3 system acts on the feeding behavior and alcohol intake by means of projections parallel to the canonical mesolimbic pathways. Thus, data in animal models indicate that the NI-RLN3-RXFP3 system should be taken into account as a target in the future treatment of disorders of eating and alcohol addictive behaviors.

TITLE: Un nuevo agente en los mecanismos de la adiccion al alcohol y la ingesta: el nucleo incertus y el neuropeptido relaxina-3.La ingesta de alcohol esta facilitada por la relacion con la conducta alimentaria, y ambas conductas estan altamente influidas por situaciones de estres y ansiedad. La desregulacion de estos procesos puede llegar a situaciones patologicas, como la anorexia, la bulimia o la obesidad. Los elementos neurobiologicos que subyacen a este control no estan completamente esclarecidos. El nucleo incertus (NI) en el tegmento pontino constituye un elemento comun a la ingesta y a la adiccion al alcohol. Las neuronas del NI utilizan como señalizacion el neuropeptido relaxina-3 (RLN3) y su receptor RXFP3. En esta revision se analiza la participacion del sistema NI-RLN3-RXFP3 en estas conductas bajo condiciones de ansiedad o estres en modelos animales. La activacion del NI tiene un efecto positivo sobre la ingesta (orexigeno) y desarrolla una respuesta amplia en la amigdala, donde se modulan los estados de ansiedad. La actividad de RLN3-RXFP3 en la amigdala podria afectar a la adiccion al alcohol, ya que la aplicacion del antagonista de RXFP3 en la amigdala extendida atenua la recaida al alcohol inducida por el estres. Los datos neuroanatomicos indican que el sistema NI-RLN3-RXFP3 actua sobre la conducta de ingesta y adiccion al alcohol mediante proyecciones paralelas a las vias canonicas mesolimbicas. Con ello, los datos en modelos animales indican que el sistema NI-RLN3-RXFP3 deberia tenerse en cuenta como diana en el tratamiento futuro de trastornos de las conductas alimentarias y adictivas.

A barbourin-albumin fusion protein that is slowly cleared in vivo retains the ability to inhibit platelet aggregation in vitro.

Barbourin is a 73 amino acid venom protein that inhibits platelet aggregation. Recombinant barbourin (BARH6), rabbit serum albumin (RSAH6), and a barbourin-RSA fusion protein (barbourin-linker-albumin; BLAH6) were secreted from Pichia pastoris yeast, and purified by nickel-chelate affinity chromatography via their C-terminal hexahistidine (H6) tags. BARH6 and BLAH6 did not differ in their IC50s for inhibition of platelet aggregation using either human platelets stimulated with thrombin or ADP, or rabbit platelets stimulated with ADP. BARH6 and BLAH6 were also effective in inhibiting platelet aggregation in whole blood, and formed complexes with platelet integrin alphaIIbbeta3. The terminal catabolic half-life of BLAH6 approached that of RSAH6 [3.4 +/- 0.2 versus 4.0 +/- 0.1 days (n = 4 +/- SD)], but was substantially increased relative to that of BARH6 [0.15 +/- 0.03 days (n = 3 +/- SD)]. Our results suggest that fusion to albumin slows the clearance of barbourin in vivo, while preserving its ability to inhibit platelet aggregation.

Acute effects of inhaled and i.v. cocaine on airway dynamics.

BACKGROUND: Wheezing has been reported by 32% of habitual smokers of crack cocaine, and several cases of crack-related acute exacerbations of asthma have been reported. STUDY OBJECTIVE: To compare the acute effects of physiologically active doses of smoked cocaine base and, i.v. cocaine hydrochloride (HCl), a subphysiologic dose of cocaine base (smoked "placebo"), and i.v. saline solution placebo on bronchomotor tone, subjective level of intoxication, and cardiovascular responses in healthy habitual crack users. DESIGN: A single-blind crossover study in which the order of route of administration (inhaled vs i.v.) was random but placebo always preceded the active drug. SUBJECTS: Fourteen healthy, nonasthmatic current crack-smoking subjects, 34 to 48 years of age, with a history of previous i.v. cocaine use (1 to 12 times per lifetime). METHODS: Heart rate, BP, self-rated level of intoxication (scale of 0 to 10), and measurements of airway resistance (Raw) and specific airway conductance (SGaw) were recorded during separate sessions before and 3 to 5, 10, 15, and 30 min after administration of smoked cocaine base (38.5 +/- 2.3 [SEM] mg), smoked placebo (2.3 +/- 0.9 mg cocaine base), i.v. cocaine HCl (30.0 +/- 2.0 mg), and i.v placebo (saline solution). RESULTS: Both smoked active cocaine and i.v. cocaine HCl caused comparable, significant (p < 0.05) peak levels of acute intoxication (6.7 +/- 0.7 and 7.3 +/- 0.8, respectively) and increases in heart rate from baseline (29.6 +/- 2.9% and 21.4 +/- 3.7%, respectively, at 5 min). However, only smoked active cocaine caused significant decreases from baseline in SGaw (25.4 +/- 6.3% at 5 min), in contrast to nonsignificant changes after i.v. cocaine HCl (5.6 +/- 7.0% increase) and smoked placebo (10.2 +/- 6.0% decrease). CONCLUSIONS: Smoked cocaine base, but not systemically administered cocaine HCl, causes acute bronchoconstriction that is probably mediated by local airway irritation and could account for reports of crack-induced wheezing and asthma attacks in nonasthmatic and asthmatic individuals, respectively.

Modulation of clearance of recombinant serum albumin by either glycosylation or truncation.

Albumin is an abundant non-glycosylated plasma protein with a slow clearance profile. It has been employed as a fusion partner in efforts to slow the clearance of small antithrombotic proteins like hirudin. In the present study, the in vivo clearance of recombinant rabbit serum albumin (rRSA), of mutant rRSAs containing consensus sequences for N-linked glycosylation (D494N and V14T variants), and of mutant mini-proteins truncated at albumin domain boundaries (rRSAs 1-185, 1-377, or 378-584) was examined. Mean terminal catabolic half-lives (t(0.5)cat) in rabbits for plasma-derived RSA, rRSA, and the V14T variant did not differ significantly (range 4. 32-4.76 days). In contrast, mean t(0.5)cat was reduced to 2.87 days for the D494N variant and to less than 0.071 days for all mini-proteins. The mini-proteins were found in the urine in tissue distribution experiments, suggesting a renal route of clearance. Our results suggest that all three internally repeated albumin domains are required to maintain the slow in vivo clearance profile of albumin, and that albumin glycosylation can be associated with an acceleration of clearance. This information could be used to design fusion proteins, including those with antithrombotic properties, with predictably altered in vivo half-lives less than that of serum albumin.

Suberosis and bird fancier's disease: a comparative study of radiological, functional and bronchoalveolar lavage profiles.

Hypersensitivity Pneumonitis (HP) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles have been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of HP seen in our practice: Suberosis (an HP related to moldy cork dust exposure) and bird fancier's disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8 +/- 11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3 +/- 11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of HP had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 10(5) ml-l cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-l cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in bird fancier's disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p < 0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are HP with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Gastroduodenal resistance and neural mechanisms involved in saline flow decrease elicited by acute blood volume expansion in anesthetized rats.

We have previously demonstrated that blood volume (BV) expansion decreases saline flow through the gastroduodenal (GD) segment in anesthetized rats (Xavier-Neto J, dos Santos AA & Rola FH (1990) Gut, 31: 1006-1010). The present study attempts to identify the site(s) of resistance and neural mechanisms involved in this phenomenon. Male Wistar rats (N = 97, 200-300 g) were surgically manipulated to create four gut circuits: GD, gastric, pyloric and duodenal. These circuits were perfused under barostatically controlled pressure (4 cmH2O). Steady-state changes in flow were taken to reflect modifications in circuit resistances during three periods of time: normovolemic control (20 min), expansion (10-15 min), and expanded (30 min). Perfusion flow rates did not change in normovolemic control animals over a period of 60 min. BV expansion (Ringer bicarbonate, 1 ml/min up to 5% body weight) significantly (P < 0.05) reduced perfusion flow in the GD (10.3 +/- 0.5 to 7.6 +/- 0.6 ml/min), pyloric (9.0 +/- 0.6 to 5.6 +/- 1.2 ml/min) and duodenal (10.8 +/- 0.4 to 9.0 +/- 0.6 ml/min) circuits, but not in the gastric circuit (11.9 +/- 0.4 to 10.4 +/- 0.6 ml/min). Prazosin (1 mg/kg) and yohimbine (3 mg/kg) prevented the expansion effect on the duodenal but not on the pyloric circuit. Bilateral cervical vagotomy prevented the expansion effect on the pylorus during the expansion but not during the expanded period and had no effect on the duodenum. Atropine (0.5 mg/kg), hexamethonium (10 mg/kg) and propranolol (2 mg/kg) were ineffective on both circuits. These results indicate that 1) BV expansion increases the GD resistance to liquid flow, 2) pylorus and duodenum are important sites of resistance, and, 3) yohimbine and prazosin prevented the increase in duodenal resistance and vagotomy prevented it partially in the pylorus.

Congenital inclusion cysts of the anterior fontanelle.

BACKGROUND: Congenital inclusion cysts of the anterior fontanelle are rare lesions. Both dermoid and epidermoid cysts are located in the midline of the scalp and occupy the subgaleal space. METHODS: We report 7 cases, 4 boys (57.1%), and 3 girls (42.9%), with ages ranging from 3 months to 16 years (mean 40.85 +/- 68.56 months; median 10 months). Four patients (57.1%) were white and 3 (42.9%) were Afro-Brazilian. RESULTS: The cysts had manifested soon after birth in all patients. They gradually enlarged, with no intracranial extensions. Four patients had dermoid cysts and the others had epidermoid cysts. All of them underwent surgery with complete excision of the cyst and no capsular rupture. There were no complications and no deaths. CONCLUSIONS: Congenital inclusion cysts of the anterior fontanelle are rare lesions that usually manifest at birth. The diagnosis is usually easy and surgery is mandatory, with a good prognosis. Recurrence is rare.

Effect of grazing system on fetal development in Nellore cattle.

Intensive grazing systems for beef females, based on abundant availability of high quality forages and supplementary concentrates, may affect fetal development. The objective of this study was to determine the effect of grazing system on length of gestation, fetal development, and characteristics of the calf at birth. Twenty-four pregnant (bred to Nellore bulls) Nellore females were allocated into two groups. The control group (G1) grazed Brachiaria decumbens (signal grass) in a traditional (extensive) grazing system and the second group (G2) were managed on Panicum maximumcv. Tanzania 1 (Tanzania grass) in an intensive grazing system. Fetal development was evaluated by ultrasonography on days 31, 45, 59, 94, 122, 220, and 255 of gestation. The diameter of the amniotic and allantoic cavities, crown-rump length, circumference, and diameter of the head and ocular orbit were determined. At birth, calves were weighed and height, length, thoracic circumference, and ocular orbit and bi-parietal diameters were measured. There were no differences (P > 0.05) in fetal development. The G1 cows had a longer gestation period (4.5 days; P<0.05) and their calves had greater (P<0.05) weight, height, length, and thoracic circumference at birth. In conclusion, Nellore females raised under intensive pasture management conditions, had significantly shorter gestation and smaller calves at birth than those raised under extensive pasture management conditions. Therefore, adoption of new management practices (e.g. intensive pasture management), should take into consideration animal behavior and productivity.

[Lipoma of the cerebellopontine angle: case report]. / Lipoma do ângulo pontocerebelar: relato de caso.

Lipoma of the cerebellopontine angle is a very rare tumor. We report the case of a 14-years-old female, with left side deafness during three years, associated with headache. CT scan showed an hypodense mass, without enhancement at the cerebellopontine angle. The patient was treated surgically by left retrosigmoid approach. The lesion involved the eighth and seventh cranial nerves and only a partial removal was performed. The postoperative course was uneventful. She had no more headache; the deafness of the left side remained unchanged. Asymptomatic lipoma of the cerebellopontine angle can be treated conservatively, although those with progressive symptoms should be treated surgically, with total or partial remove based on their neurovascular involvement.

[Cavernoma of the lateral ventricle: case report]. / Cavernoma do ventrículo lateral: relato de caso.

UNLABELLED: Cavernous malformations are uncommon lesions that are usually present in the cerebral hemispheres. They occur rarely in the ventricular system, and even more rarely in the lateral ventricle. Only 28 cases have been previously reported in the literature. CASE: We present one case of lateral ventricle cavernoma in a 15-years-old female patient, who suffered of mild chronic headache for 8 months, followed by two episodes of sudden intensive headache and stupor with complete recovery after 48 hours. CT scan was performed and revealed a voluminous size, hiperdense mass in the frontal horn of the lateral ventricle. The surgical access to site was through transcallosal interhemisphere approach. The patient had a good recovery without complications. CONCLUSION: Although lateral ventricle cavernomas are rare they should be considered in the differential diagnosis of intraventricular tumors. A wrong preoperative diagnosis has sometimes induced a wrong therapy, such as radiotherapy, for these surgically curable benign lesions.

[Carotid body tumors: review of 8 cases and surgical approach]. / Tumores do corpo carotídeo: revisão de oito casos e abordagem cirúrgica.

Carotid body tumors are rather uncommon. Even though there is a great amount of literature on the subject, the controversy regarding its biological behavior and therapeutics and mainly, the surgical management still remains. We present eight patients with carotid body tumors (total of 9 tumors, one bilateral) surgically treated at the Neurosurgery Department of Santa Casa in Belo Horizonte, from 1989 to 1999. The age ranged from 11 to 66-years-old (35,6+/-17.7). Four patients were women and four were men. We had satisfactory postoperative results with low morbidity and no deaths. Based on our experience and on the review of the literature, some aspects of this disease are discussed. We conclude that carotid body tumors are uncommon and should be treat with carefully surgery techniques to obtain low morbi-mortality rates.

Inhibition of hematopoiesis by a plasma factor in a case of aplastic anemia associated with systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) may be associated with inhibition of hematopoiesis mediated by antibodies, T-cells or both. A 41-year-old woman with a five-year history of SLE treated with prednisone was admitted to Cabrini Medical Center in New York. The patient complained of fever, chills, arthralgias, general malaise, weakness and dyspnea on exertion, and showed malar rash, pallor, and a systolic ejection murmur along the left sternal border. Admission work up included a CBC with evidence of moderate pancytopenia, a normal EKG, and a normal chest X-ray. The patient's anemia was symptomatic and required a transfusion of packed red blood cells (PRBC's). Bone marrow biopsy and aspiration revealed an aplastic marrow with few hypoplastic islands of hematopoietic elements. The patient was treated with plasmapheresis, achieving immediate progress towards recovery. Bone marrow culture studies (erythroid BFU-E, and myeloid CFU-GM) were done by incubating various titers of the patient's acute phase plasma with normal bone marrow cells. This was done to determine if the patient's plasma contained any hematopoietic inhibitory activity, as has been reported in other cases. Our experiments demonstrated marked inhibition of erymathropoiesis and myelopoiesis in vitro, when various titers of the patient's plasma were included in the culture media. Control plasma produced no inhibition. These studies support the hypothesis that a circulating antibody which inhibits hematopoiesis may be produced in SLE patients with aplastic anemia, and be responsible for it.

[Obstructive sleep apnoea and cardiovascular disease--a retrospective study]. / Síndroma de apneia obstrutiva do sono e doença cardiovascular--estudo retrospectivo.

INTRODUCTION: Obstructive Sleep Apnea (OSA) is associated with adverse effects in cardiovascular physiology. Some studies have connected this pathology with Cardiovascular Disease (CVD). AIM: Determine the prevalence of CVD in patients with OSA of different severity and verify the association between CVD and OSA. MATERIAL AND METHODS: Retrospective study based on data from 155 consecutive patients with OSA referred to a Sleep Disordered Breathing Clinic in an University Hospital during the year of 2001. RESULTS: The majority of patients were male (83,2%), the mean age was 53,6 +/- 11,9 years. Severe OSA was observed in 52,9% patients, moderate in 20% and mild in 27,1% patients (mean Apnea Hypopnea Index of 35,2 +/- 23,8/hour). Among the studied individuals 52,3% showed CVD, being Arterial Hypertension (AH) the most common disease (45,8%). Acute Myocardial Infarction appeared in 6,5% and Angina in 3,9% cases. The majority of the patients (67,1%) were obese (Body Mass Index - BMI>30). The mean BMI was 33,1 +/- 6,34. A significant (31%) number of patients reported Lipid Disorders and 11% reported Diabetes mellitus. The majority (51,3%) of patients referred smoking habits. Severity of OSA (evaluated by AHI) was significantly higher in women with AH (p= 0,033) and significantly lower in patients who developed Cerebrovascular Disease (CeVD) (p = 0,036). CONCLUSIONS: The studied population presented a high prevalence of CVD, being the severity of OSA significantly higher in women with AH. The increased prevalence of CVD in patients with OSA has been documented in recent epidemiologic studies. The physiopathologic mechanisms underlying this association, certainly, deserve further investigation.

[Prevalence of asthma in the city of Porto]. / Prevalência da asma na cidade do Porto.

It is possible that asthma epidemiology will contribute to the definition of asthma precipitant factors. This work is enrolled in an international study co-ordinated by COMAC-EPI. In Oporto, among 137.000 residents in the same town region, a standardised sample of 4.047 male and female individuals aged from 20 to 44 years was defined. A screening questionnaire was sent with a stamped envelope. Four months later the same questionnaire was sent to the individuals who did not answer it and finally those who do not answer the second letter were visited in their own residence. We got 2075 answers. Among the responders about half were women: 1075, 25.39% belonging (273) to the 20-29 years age group; 42.69% (459) 30-39 years; 31.90% (343) 40-44 years. In men the percentage of distribution by age groups was similar. Question nQ 5 was answered affirmatively by 60 individuals, corresponding to the prevalence of 2.89%. Seventy-one (3.42%) said they had been under asthma treatment during the last year. Among the symptoms that usually define the attack of asthma, those inquired in the group of question 1 show a prevalence close to that of the asthma diagnosis: 6.45%. The prevalence of being awakened by tightness in the chest, shortness of breath and coughing, with values of 16.17%, 10.69% and 25.68% is quite superior than in question nQ 5. The prevalence obtained with the Hay Fever question was 18.84%. Data obtained is similar to the data of other centers.

[Inter- and intra-observer variation in silicosis radiology]. / Variação inter e intra-observador na radiologia da silicose.

The radiologic criteria are important for the diagnosis of silicosis and must be objective. Initial radiologic changes are nonspecific and sometimes misinterpreted. We asked six Pulmonologists with distinct training in pulmonary disease to interpret 112 chest films according to a simple established protocol. No further information was given. One year later, all the observers analysed the same films over again. Then, we compared the results among the observers and between the two analysis made by the same individual. In 34 cases (30%) there was unanimity in asserting or denying the presence of micronodules and in 74 cases (66%) there was an agreement among the three more experienced observers. The intraobserver variability ranged from 8% to 40% and it was more important in the least trained observers. We concluded that when interpreting early radiologic changes in silicosis inter and intraobserver variability was elevated, more objectivity was achieved by the observers with more experience in epidemiologic studies and that we must be careful in interpreting results of epidemiologic studies concerning this matter.