C-Reactive Protein Levels and the Risk of Incident Cardiovascular and Cerebrovascular Events in Patients with Obstructive Sleep Apnea.

PURPOSE: Patients with obstructive sleep apnea (OSA) are at increased risk of cardiovascular and cerebrovascular disease (CVD) but it is unclear who are at greatest risk. We determined whether the inflammatory marker, C-reactive protein (CRP), could be a useful prognostic biomarker. METHODS: Adult patients referred for polysomnography (PSG) with OSA were studied. Serum CRP levels were measured using ELISA the morning after PSG. Validated CV events within 4 years of PSG were ascertained by linking to provincial research datasets. RESULTS: 155 patients with OSA (AHI ≥ 5/h) had CRP measured. Median age was 53 and median AHI was 21/h. 10 patients (7.1%) suffered at least one event, but rates varied substantially by CRP (0/35 patients in the lowest quartile, and 7/39 in the highest CRP quartile). In the unadjusted analysis, patients in the highest CRP quartile (≥ 2.38 mg/L) were significantly more likely to suffer an event (odds ratio = 9.72 (95% CI 2.43-38.84), p = 0.001). CRP continued to be a significant predictor after controlling for multiple confounders. OSA severity and desaturation were not significantly associated with prospective events. CONCLUSIONS: In this small preliminary study, OSA patients with an elevated CRP were significantly more likely to suffer a CVD event in the 4 years after PSG. Although these findings need to be confirmed in larger prospective cohorts, CRP may be useful in risk stratifying OSA patients to guide therapy or to identify patients that might be most appropriate for clinical trials of CVD prevention.

Neuropsychological features of dementia due to dural arteriovenous malformation.

We report two patients aged 65 and 61 years, who presented a subacute dementia with normal CT scan without contrast injection. Angiography showed a dural arteriovenous malformation. The patients improved dramatically with treatment of the malformation. Dementia was characterised by frontal dysfunction, emotional disorders, amnesic and praxic impairment. This neuropsychological pattern suggests a profile of global dementia in the field of vascular dementia.

Autochthonous acute Chagas' disease in São Paulo State, Brazil: epidemiological aspects.

Since the beginning of the seventies the natural transmission of Chagas' infection has been considered to be under control in the State of São Paulo and not even a case of American Trypanosomiasis, transmitted by triatomine bugs, has been detected by the epidemiological surveillance system. This situation justifies the report of a case of acute Chagas' disease that occurred in a forest area considered free of domiciliary triatomines along the Southern seacoast of São Paulo State. In May, 1995 the presence of trypomastigote forms of Trypanosoma cruzi had been diagnosed in a retired 57 year-old male patient, born and living in Santos (São Paulo State), complaining of fever, fatigue and malaise. The patient reported that 40 days before he had participated with 17 friends in a 7-day excursion in a forest area of the municipalities of Itanhaém and Peruíbe. During this period the group had been lodged in three houses located within the forest. Eight days after the end of the excursion the patient began to have fever, malaise and fatigue. During the next 31 days he had received medical care both as an inpatient and an outpatient, without any significant improvement. After the detection of T. cruzi trypomastigotes in his blood stream the patient began to be treated with benzonidazole in a hospital but died 8 days after the beginning of treatment. The epidemiological investigation carried out showed no signs of the presence of triatomine bugs in the three houses where the group had been lodged, or any indication of Chagas' infection in other excursionists.

Detection of Trypanosoma-decay accelerating factor antibodies in mice and humans infected with Trypanosoma cruzi.

Highly purified Trypanosoma-decay accelerating factor (T-DAF), a 87-93-kD glycoprotein present on the surface of metacyclic and trypomastigote forms of Trypanosoma cruzi, was used as antigen to evaluate the presence of specific serum antibodies in experimentally infected mice and patients with Chagas' disease by enzyme-linked immunosorbent assay (ELISA). Mouse T-DAF antibodies were first recorded on day 7 postinfection, reached maximal concentration on day 30, and maintained at positive titers thereafter. High immunogenicity was clearly demonstrated by the detection of T-DAF antibodies in 96% of the sera collected from chagasic patients in either the acute or the chronic phase of disease. Control sera from normal individuals and from patients with leishmaniasis or other chronic infections did not give positive results. Serologic evaluation using T-DAF as antigen did not discriminate between patients with the cardiac and the digestive forms of the disease. The performance of the T-DAF ELISA was compared with that of conventional screening tests for Chagas' disease (indirect immunofluorescence and hemagglutination). The T-DAF ELISA test showed a sensitivity of 96%, a specificity of 100%, an efficiency of 99%, a positive predicted value of 100%, a negative predicted value of 98%, and a kappa index of 0.96, thus indicating that it can be successfully used for the serodiagnosis of T. cruzi infection in humans.

Persistence of specific antibody response in different experimental infections of mice with Toxocara canis larvae.

Anti-Toxocara antibody production and persistence were studied in experimental infections of BALB/c mice, according to three different schedules: Group I (GI)-25 mice infected with 200 T. canis eggs in a single dose; Group II (GII) 25 mice infected with 150 T. canis eggs given in three occasions, 50 in the 1st, 50 in the 5th and 50 in the 8th days; Group III (GIII)-25 mice also infected with 150 T. canis eggs, in three 50 eggs portions given in the 1st, 14th and 28th days. A 15 mice control group (GIV) was maintained without infection. In the 30th, 50th, 60th, 75th, 105th and 180th post-infection days three mice of the GI, GII and GIII groups and two mice of the control group had been sacrificed and exsanguinated for sera obtention. In the 360th day the remainder mice of the four groups were, in the same way, killed and processed. The obtained sera were searched for the presence of anti-Toxocara antibodies by an ELISA technique, using T. canis larvae excretion-secretion antigen. In the GI and GII, but not in the GIII, anti-Toxocara antibodies had been found, at least, up to the 180th post-infection day. The GIII only showed anti-Toxocara antibodies, at significant level, in the 30th post-infection day.

Clinical and laboratorial features of visceral toxocariasis in infancy.

Forty children with a diagnosis of Visceral Toxocariasis were evaluated prospectively from February 1982 to June 1989. Diagnosis was established by clinical, laboratory and serological (ELISA - ES Toxocara canis antigen) evaluations. A great clinical polymorphism was found in our patients, ranging from unspecific or absent manifestations to an exuberant symptomatology. The laboratory findings were: leukocytosis, eosinophilia and elevation of serum gammaglobulin and isohemagglutinin levels. No significant relationship between clinical findings and laboratory parameters was found. Serology (ELISA) was a method of great diagnostic support but did not show a correlation with clinical and laboratory findings in this study. There was a significant relationship between pulmonary manifestations and the presence of signs and/or symptoms, when the patients were sent to us. Our findings, especially the high incidence of pulmonary manifestations, suggest that Visceral Toxocariasis has to be included in the differential diagnostic of children with pulmonary manifestations, characteristic epidemiological data and associated eosinophilia.

Possible oral transmission of acute Chagas' disease in Brazil.

In October 1986, 7 to 22 days after a meeting at a farm in Paraíba state, 26 individuals presented with a febrile illness associated with bilateral eyelid and lower limb edema, mild hepatosplenomegaly, lymphadenopathy and, occasionally a skin rash. A 11-year-old boy exhibited atrial premature complexes and a 74-year-old patient developed acute heart failure. In two patients hospitalized in São Paulo city, acute Chagas' disease was diagnosed by the demonstration of circulating Trypanosoma cruzi. At autopsy in a fatal case, acute Chagas' cardiomyopathy was demonstrated. Xenodiagnosis were positive in 9 out of 14 tested patients. A specific IgG immune response was found in all patients and specific IgM antibodies were identified in 20 out of 22 tested patients. A epidemiological survey showed the existence of Triatoma brasiliensis in the outbuildings of this farm, but none in the house where most of the guests stayed. A high rate of infection with Trypanosoma cruzi was found in opossums. These observations together with those related to the food consumed by the patients, lead the authors to suggest that the human infections resulted from oral contamination probably originating from naturally infected marsupials in the area or crushed infected bugs.

Effects of passive tactile and auditory stimuli on left visual neglect.

Patients with left-sided visual neglect fail to copy the left part of drawings or the drawings on the left side of a sheet of paper. Our aim was to study the variations in copying drawings induced by passive stimulation in patients with left-sided visual neglect. No stimulation at all, tactile unilateral and bilateral, binaural auditory verbal, and nonverbal stimuli were randomly applied to 14 patients with right-hemisphere strokes. Only nonverbal stimuli decreased the neglect. As nonverbal stimuli mainly activate the right hemisphere, the decrease in neglect suggests right-hemispheric hypoactivity at rest in these patients. The absence of modification of neglect during verbal stimulation suggests a bilateral hemispheric activation and the persistence of interhemispheric imbalance. Our results showed that auditory pathways take part in the network involved with neglect. Passive nonverbal auditory stimuli may be of interest in the rehabilitation of patients with left visual neglect.

Chagas'disease: IgA, IgM and IgG antibodies to T. cruzi amastigote, trypomastigote and epimastigote antigens in acute and in different chronic forms of the disease.

In an attempt to find a better T. cruzi antigen and possible immunological markers for the diagnosis of different clinical forms of Chagas'disease, amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with T. cruzi (Y strain) were assessed in comparison with conventional epimastigote antigens. A total of 506 serum samples from patients with acute and with chronic (indeterminate, cardiac and digestive) forms, from nonchagasic infections, and from healthy individuals were assayed in immunofluorescence (IF) tests, to search for IgG, IgM and IgA antibodies. Amastigote proved to be the most convenient antigen for our purposes, providing higher relative efficiency indexes of 0.946, 0.871 and 0.914 for IgG, IgM and IgA IF tests, respectively. Anti-amastigote antibodies presented higher geometric mean titers (GMT) than anti-trypomastigote and anti-epimastigote. Anti-amastigote IgG antibodies were found in all forms of Chagas'disease, and predominantly IgA antibodies, in chronic digestive and in acute forms, as well as IgM antibodies, in latter forms. Thus, tests with amastigote antigen could be helpful for screening chagasic infections in blood banks. Practical and economical aspects in obtaining amastigotes as here described speak in favour of its use in developing countries, since those from other sources require more complex system of substruction, specialized personnel or equipment.

Immunoglobulin A antibodies to Trypanosoma cruzi antigens in digestive forms of Chagas' disease.

In an attempt to find a serological marker for the diagnosis of chronic digestive forms of Chagas' disease, we compared amastigote and trypomastigote antigens obtained from immunosuppressed mice infected with Trypanosoma cruzi (Y strain) with conventional epimastigote antigens to search for immunoglobulin A (IgA) antibodies. A total of 255 serum samples from patients with acute and chronic (indeterminate, digestive, and cardiac) forms of Chagas' disease and with nonchagasic diseases and from healthy individuals were studied. Amastigote antigens proved to be the most adequate for our purpose, since IgA antibodies could be detected in 23 of 25 serum samples from patients with digestive forms, with relative indices of sensitivity, specificity, and efficiency of 0.920, 0.911, and 0.912, respectively. These antigens also showed high reactivity with IgA antibodies, with a geometric mean titer of 16,635 (12.7 log2). IgA antibodies were detected in 16 of 28 serum samples from patients with the acute form as well, but this clinical form is easily distinguished from the chronic form by the demonstration of IgM antibodies. Poor results were seen with trypomastigote and epimastigote antigens. The finding of IgA antibodies in about 20% of indeterminate forms and 20% of cardiac forms, although in low titers, requires further investigation to ascertain their role as an early signal of gastrointestinal lesions. In addition, the amastigote antigens described here seem more convenient for use in endemic areas than those obtained from cell cultures because of their lower cost.

Larva migrans visceral por "Toxocara canis". Estudo das caracteristicas clinicas e laboratoriais de 7 casos humanos. / Visceral larva migrans due to Toxocara canis. Study of the clinical and laboratorial characteristics of 7 human cases

Neste trabalho sao apresentados sete casos com caracteristicas clinicas e laboratoriais de larva migrans visceral por Toxocara canis. O estudo foi realizado em 7 criancas com manifestacoes sugestivas da sindrome, atendidas de marco de 1982 a agosto de 1983 no Instituto da Crianca do Hospital das Clinicas da FMUSP. Todas as criancas foram submetidas a exames clinicos, oftalmologicos e laboratoriais: hemograma, eletroforese de proteinas, dosagem de imunoglobulinas sericas, iso-hemaglutininas, sorologia para Toxocara canis pelo teste ELISA e RX do torax. A idade variou de 1 ano e 5 meses a 8 anos e 6 meses e o achado clinico mais frequente foi febre (presente em 6 dos 7 casos). Manifestacoes pulmonares estavam presentes em 2 dos 7 casos. A contagem de leucocitos variou de 20.600/mm3 a 73.000/mm3, com eosinofilia de 36% a 72%. Os titulos de iso-hemaglutininas foram superiores a 512 em 5 dos 7 casos. Para o diagnostico sorologico, os soros foram submetidos ao teste de ELISA com dois antigenos de larvas de Toxocara canis. Os niveis de anticorpos variaram de 1.280 a 10.240 com os dois antigenos. Todas as criancas foram tratadas com tiabendazol e continuam em seguimento ambulatorial para avaliacao

The significance of atypical mitoses in malignant meningiomas.

A group of 5 selected malignant meningiomas was studied in relation to the incidence and morphology of the mitoses. Beside a high mitotic rate many structural chromosomal abnormalities were observed. In agreement with other malignant onco-types previously studied, the authors suggest that atypical mitoses together with a tissue and cytological undifferentiation may be assumed to be an important prognostic criterium for meningiomas. The problem of malignancy in meningiomas has not been, so far, satisfactorily resolved, so that, in our opinion, the definition of even minimal details may be of some interest. For example, as it clearly appears from reviewing the literature on this sugject, no particular attention has been paid to the mitotic features. Referring to previous studies on the mitotic abnormalities in different malignant cerebral onco-types, the authors aimed to examine the various mitotic aspects in a limited group of tumors selected on the basis of clinical and histological malignancy.

The microglia in brain granulomatoses. Histo-enzymological study.

The microglial participation in the different granulomatous processes was studied by silver impregnation techniques and histoenzymological methods. In florid granulomatous areas two types of metallophilic cells were detected, corresponding to the common macrophages and perhaps to the ameboid modification of the microglia. Hydrolytic enzyme preparations showed a pattern of distribution and intensity similar to that of the impregnated cells. Only in the adjacent nervous parenchyma the different methods evidenced the presence of hyperplastic ramified microglia associated with reactive astrocytes.

Cerebral cryptococcosis. Report of an unusual case.

A case of cerebral cryptococcosis associated with pulmonary and bone lesions is described. While discussing some general data of the literature, the authors outline the rarity of granulomatous CNS Cryptococcosis. From a clinical standpoint the similarity with tuberculous processes is emphasized. The methods of histopathologic diagnosis both intraoperatively and in permanent sections are discussed.

Granulomatous mycoses of the central nervous system.

A clinical and pathological description of five cases of granulomatous mycoses of the C.N.S. is reported. Four had an intracranial and one a spinal localization. In all patients the clinical pattern was of tumoral type, while the disease evolution was favourable only in one case. From a histipatholic point of view the preliminary diagnosis was of granulomatous process. The fungi organisms were identified only by means of combined stain methods. Beside the pathogenetic problems the Authors outline some histological methods useful for diagnostic purposes when a culture procedure for fungi is lacking.

[Rosenthal fibres and vascular anomalies in cerebral gangliocytomas (author's transl)]. / Fibre di Rosenthal e anomalie vasali in gangliocitomi cerebrali

The Authors describe three cases of gangliogliomas histologically studied among 3100 neoplasias of the CNS. In one case the study was supported by the cytological observations on the in vitro cultures as performed with the roll technique. The tumors differed in location and clinical behaviour, but showed the same histological characteristics of mixed neoplasias. In fact in all cases a component of mature ganglion cells together with glial proliferation of spongioblastic type was identified. Particular attention was given to the vascular stroma and to the morphological aspects of the glial proliferation. All tumors presented a large amount of anomalous vessels frequently of angiomatous type. Beside neuronal cells, a neoplastic glial cell proliferation was identified as of spongioblastic nature by means of in vitro culture and on the basis of particular degenerative changes typical of the spongioblastic elements, such as Rosenthal fibres. According to the Authors these data support the hamarto-blastomatous origin of the oncotype.