Cardiac abnormalities in the acquired immunodeficiency syndrome. A prospective study with a clinical-pathological correlation in twenty-one adult patients

OBJECTIVE - To evaluate the cardiac abnormalities and their evolution during the course of the acquired immunodeficiency syndrome, as well as to correlate clinical and pathological data. METHODS - Twenty-one patients, admitted to the hospital with the diagnosis of acquired immunodeficiency syndrome, were prospectively studied and followed until their death. Age ranged from 19 to 42 years (17 males). ECG and echocardiogram were also obtained every six months. After death, macro- and microscopic examinations were also performed. RESULTS - The most frequent causes of referral to the hospital were: diarrhea or repeated pneumonias, tuberculosis, toxoplasmosis or Kaposi sarcoma. The most frequent findings were acute or chronic pericarditis (42%) and dilated cardiomyopathy (19%). Four patients died of cardiac problems: infective endocarditis, pericarditis with pericardial effusion, bacterial myocarditis and infection by Toxoplasma gondii. CONCLUSION - Severe cardiac abnormalities were the cause of death in some patients. In the majority of the patients, a good correlation existed between clinical and anatomical-pathological data. Cardiac evaluation was important to detect early manifestations and treat them accordingly, even in asymptomatic patients.

Echocardiographic Abnormalities and Antiphospholipid Antibodies in Patients with Systemic Lupus Erythematosus

OBJECTIVE: Lupus anticoagulant and anticardiolipin antibodies (aCL) have been associated with thrombosis, recurrent abortion, and thrombocytopenia in patients with systemic lupus erythematosus (SLE), but their relationship with cardiac disease is less clear. The purpose of this study was to evaluate the association between antiphospholipid antibodies (aPL) and echocardiographic abnormalities in patients with SLE. METHODS: A total of 70 consecutive patients and 42 control subjects underwent M-mode, 2-dimensional and Doppler echocardiography and tests for lupus anticoagulant, aCL IgG, IgM, and IgA. Lupus anticoagulant was assayed with the dilute Russell viper venom time, and aCL IgG, IgM, and IgA were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Lupus anticoagulant showed a prevalence of 10%. As a whole, aCL had a prevalence of 44.3% and aPL had a prevalence of 50%. Patients with echocardiographic abnormalities had a prevalence of 54.3% and showed a trend towards an association with aCL IgG (P=0.06). The presence of pulmonary hypertension (PH) was significantly associated with aCL IgG (p=0.02). CONCLUSION: aCL IgG was significantly associated with PH and showed a strong trend towards an association with echocardiographic abnormalities taken together. These findings suggest a role for aCL IgG in the development of lupus cardiovascular disease.

Electrocardiographic abnormalities in neurological diseases

OBJECTIVE: To evaluate electrocardiographic abnormalities in patients with neurologic diseases. METHODS: We studied 161 patients with neurologic disorders by analyzing the 12-lead electrocardiogram during the pathological process. An expert who did not know anything about the patients evaluated the traces. RESULTS: Neurological process included brain tumor (41%), stroke (27.3%), cerebral aneurysm (15.5%), subarachnoid hemorrhage (6.8%), subdural hemorrhage (5%), and head injury (4.4%). Electrocardiograms were normal in 61% of cases, and the most frequent abnormality was ventricular repolarization (23.7%). The presence of T waves (4.6%) and prolonged QT intervals (8.8%) was the most characteristic of brain injuries. CONCLUSION: We observed a lower incidence of electrocardiographic abnormalities than that described in the literature.

Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization

OBJECTIVE: To evaluate the cardiovascular findings and clinical follow-up of patients with Williams-Beuren syndrome. METHODS: We studied 20 patients (11 males, mean age at diagnosis: 5.9 years old), assessed for cardiovascular abnormalities with electrocardiography and Doppler echocardiography. Fluorescence in situ hybridization (FISH) was used to confirm the diagnosis of the syndrome. RESULTS: Elastin gene locus microdeletion was detected in 17 patients (85%) (positive FISH), and in 3 patients deletion was not detected (negative FISH). Sixteen patients with a positive FISH (94%) had congenital cardiovascular disease (mean age at diagnosis: 2,3 years old). We observed isolated (2/16) supravalvular aortic stenosis and supravalvular aortic stenosis associated (11/16) with pulmonary artery stenosis (4/11); mitral valve prolapse (3/11); bicuspid aortic valve (3/11); aortic coarctation (2/11), thickened pulmonary valve (2/11); pulmonary valvular stenosis (1/11); supravalvular pulmonary stenosis (1/11); valvular aortic stenosis (1/11); fixed subaortic stenosis (1/11); pulmonary artery stenosis (2/16) associated with pulmonary valvar stenosis (1/2) and with mitral valve prolapse (1/2); and isolated mitral valve prolapse (1/16). Four patients with severe supravalvular aortic stenosis underwent surgery (mean age: 5.7 years old), and 2 patients had normal pressure gradients (mean follow-up: 8.4 years). CONCLUSION: A detailed cardiac evaluation must be performed in all patients with Williams-Beuren syndrome due to the high frequency of cardiovascular abnormalities.

Cytogenetic study in natural hybrids of Callithrix (Callitrichidae: Primates) in the Atlantic forest of the state of Rio de Janeiro, Brazil

In the Atlantic forest of Rio de Janeiro, Callithrix aurita (É. Geoffroy in Humboldt, 1812) is a native species vulnerable to extinction and C. jacchus (Linnaeus, 1758) and C. penicillata (É. Geoffroy, 1812) are invasive species. The major threats to the native species are habitat degradation and hybridization, although there are currently no genetic data about natural hybrids available. Previous studies have revealed that species of the Callithrix genus are extremely homogeneous in their karyotypes with the exceptions of the morphology and size of the Y chromosome and its nucleolar organizer region (NOR) banding pattern. Three male marmosets captured in the wild in Guapimirim municipality, Rio de Janeiro, Brazil, considered as possible hybrids between C. aurita and C. jacchus or C. penicillata on the basis of pelage pattern, were cytogenetically studied. Metaphase chromosomes were obtained by using short-term lymphocyte cultures and Ag-NOR staining was performed. The hybrids karyotypes were 2n=46, 14 uni- and 30 bi-armed autosomes, a median size submetacentric X and NOR bearing autosomes, being compatible with that observed for the genus. In the three individuals studied, Y chromosomes were similar to those found for C. aurita, without NORs. The data obtained suggest the involvement of C. aurita in natural hybridization with one of the invasive species. We discuss the possible consequences of this hybridization.

Immunological abnormalities of acquired immunodeficiency syndrome and related disorders in patients from Rio de Janeiro, Brazil

The immunoloical profile of acquired immunodeficiency syndrome (AIDS) and chronic lymphadenopathy syndrome (CLAS) in 15 and 11 Brazilian patients, respectively, was studied. The AIDS patients showed reduced percentage of total T (CD3) and T-helper-inducer (CD4) lymphocytes, relative increase in numbers of T-suppressor-cytotoxic (CD8) cells and a marked inversion of T-helper-inducer/suppressor-cytotoxic (CD4/CD8) ratio. Lymphoproliferative responses to PHA, ConA, PPD and PWM were diminished. Hypergamaglobulinemia and high levels of circulating immune complexes were also found. The CLAS patients also showed important immunological alterations, but not so intense as those with AIDS. These data seems to be similar to those observed in other parts of the world.

Human chronic chagasic cardiopathy: participation of parasite antigens, subsets of lymphocytes, cytokines and microvascular abnormalities

This article tries to demonstrate by new pathological findings (with the use of immunohistochemical technique and confocal laser microscopy) that chronic chagasic cardiomyopathy is a result of multiple factors involving myocarditis, immunodepression, severe fibrosis and microvessels dilatation and that all of these alterations are probably directly related with the presence of Trypanosoma cruzi parasites in the host associated with inadequate immunological response of the host.

Reproductive system abnormalities in Schistosoma mansoni adult worms isolated from Nectomys squamipes (Muridae: Sigmodontinae): brightfield and confocal laser scanning microscopy analysis

Schistosoma mansoni adult worms with genital anomalies isolated from Nectomys squamipes (Muridae: Sigmodontinae) were studied by confocal laser scanning microscopy under the reflected mode. One male without testicular lobes (testicular agenesia/anorchism) and two females, one with an atrophied ovary and another with 17 uterine eggs, were identified. The absence of testicular lobes occurred in a worm presenting otherwise normal male adult characteristics: tegument, tubercles and a gynaecophoric canal with spines. In both female specimens the digestive tube showed a vacuolated appearance, and the specimen with supernumerary uterine eggs exhibited a developing miracidium and an egg with a formed shell. The area of the ventral sucker was similar in both specimens however the tegument thickness, ovary and vitelline glands of the specimen with the atrophied ovary were smaller than those of the one with supernumerary eggs. These reported anomalies in the reproductive system call attention to the need to improve our understanding of genetic regulation and the possible role of environmental influences upon trematode development.

Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study

This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.

Cytogenetic and molecular analysis of the Pantaneiro cattle breed

The objective of this work was to characterize Pantaneiro cattle genetically through its paternal ancestry by the morphology of the Y chromosome, whether submetacentric or acrocentric, as well as to identify the maternal ancestry through mitochondrial DNA. The karyotype and mitochondrial DNA of 12 bulls of Pantaneiro breed were analyzed. The Y chromosome was analyzed in lymphocyte metaphases and the mitochondrial DNA by diagnosing its haplotype (Bos taurus and Bos indicus). Among Pantaneiro animals analyzed three had a taurine (submetacentric) Y and nine had a zebuine (acrocentric) Y chromosome, suggesting breed contamination by Zebu cattle, once Pantaneiro is considered to be of European origin. The mitochondrial DNA was exclusively of taurine origin, indicating that the participation of zebuines in the formation of the breed occurred entirely through the paternal line.

Chromosomal abnormalities in couples with recurrent first trimester abortions

PURPOSE: To investigate the prevalence of chromosomal abnormalities in couples with two or more recurrent first trimester miscarriages of unknown cause. METHODS: The study was conducted on 151 women and 94 partners who had an obstetrical history of two or more consecutive first trimester abortions (1-12 weeks of gestation). The controls were 100 healthy women without a history of pregnancy loss. Chromosomal analysis was performed on peripheral blood lymphocytes cultured for 72 hours, using Trypsin-Giemsa (GTG) banding. In all cases, at least 30 metaphases were analyzed and 2 karyotypes were prepared, using light microscopy. The statistical analysis was performed using the Student t-test for normally distributed data and the Mann-Whitney test for non-parametric data. The Kruskal-Wallis test or Analysis of Variance was used to compare the mean values between three or more groups. The software used was Statistical Package for the Social Sciences (SPSS), version 17.0. RESULTS: The frequency of chromosomal abnormalities in women with recurrent miscarriages was 7.3%, including 4.7% with X-chromosome mosaicism, 2% with reciprocal translocations and 0.6% with Robertsonian translocations. A total of 2.1% of the partners of women with recurrent miscarriages had chromosomal abnormalities, including 1% with X-chromosome mosaicism and 1% with inversions. Among the controls, 1% had mosaicism. CONCLUSION: An association between chromosomal abnormalities and recurrent miscarriage in the first trimester of pregnancy (OR=7.7; 95%CI 1.2--170.5) was observed in the present study. Etiologic identification of genetic factors represents important clinical information for genetic counseling and orientation of the couple about the risk for future pregnancies and decreases the number of investigations needed to elucidate the possible causes of miscarriages.

Reproductive biology and cytology of Hypericum brasiliense Choisy (Hypericaceae)

This is the first study of reproductive biology and cytology carried out with Hypericum brasiliense, a species with medicinal properties and potential agronomic interest. Three populations of H. brasiliense collected at Southeastern Brazil were studied. The results indicate that H. brasiliense is preferentially allogamous, self-compatible, facultative apomitic and anemophilous. Male sterility was observed in about 50% of individuals from the three populations. Anatomical studies evidenced structural abnormalities in anthers of male sterile flowers, showing enlarged tapetal cells and thick secretion deposits on the tapetal cell surfaces that may cause nutritional deficit for pollen mother cells. In cytogenetic studies several haploid chromosome numbers were observed like n = 4, 8, 9, 11, 16 and 17, including the presence of multivalents and micronuclei in tetrads, indicating the occurrence of abnormalities in the meiotic process of H. brasiliense. Despite these meiotic abnormalities the pollen viability and in vitro pollen germination rate observed in fertile flowers may be considered high. The diploid chromosome number 2n = 16 was observed, and the chromosomes in metaphase were small and similar. Fluorochrome staining techniques using DAPI and CMA3 were applied, with no positive bands observed.

Cytogenetic study of the genus Saguinus (Callithrichidae, Primates)

Eight subspecies from the genus Saguinus (S. fuscicollis fuscicollis, S. fuscicollis weddelli, S. bicolor bicolor, S. bicolor martinsi, S. mystax mystax, S. imperator imperator, S. midas midas, and S. midas niger) were studied. Five of them (S. f. fuscicollis, S. f. weddelli, S. b. martinsi, S. m. mystax and S. i. imperator) had their karyotypes described for the first time. Conventional coloration, banding patterns G, C and NOR, and G/C sequential banding tecniques were used. All samples showed the same diploid number (2n = 46). The patterns of the G, C and NOR bands were very similar with little differences in the quantity and constitutive heterochromatin distribution of the autosomes. Constitutive heterochromatin was observed only in telomeric regions of some chromosomes of S. f. fuscicollis and S. f. weddelli. The X chromosome was the same in all subspecies, but chromosome Y differed in size and morphology. XX/XY chimerism was verified in all subspecies

Experience with molecular and cytogenetic diagnosis of fragile X syndrome in Brazilian families

We report on the cytogenetic and DNA analysis of 55 families with the fragile X (FMR-1 locus) mutation (318 individuals and 15 chorionic villi samples). A total of 129 males were investigated, 54 mentally normal and 75 presenting mental retardation. Among the 54 normal males, 11 had the premutation, and none expressed the fragile site. The full mutation was detected in 73 retarded males, and 14 (18%) presented a premutation along with the full mutation (mosaics). All of them manifested the fragile site. The frequencies of fragile site expression correlated positively with the sizes of the expansion of the CGG repeats (D). Among 153 normal females, 85 were found to be heterozygous for the premutation and 15 had the full mutation. In the premutated females the fragile site was not observed or it occurred at frequencies that did not differ from those observed in 53 noncarriers. Cytogenetic analysis was thus ineffective for the diagnosis of premutated males or females. Among the 51 heterozygotes for the full mutation, 36 (70%) had some degree of mental impairment. As in males, a positive correlation was detected between the frequencies of fragile site manifestation and the size of the expansion. However, the cytogenetic test was less effective for the detection of fully mutated females, than in the case of males, since 14% false negative results were found among females. Segregation analysis confirmed that the risk of mental retardation in the offspring of heterozygotes increases with the length of D. The average observed frequency of mental retardation in the offspring of all heterozygotes was 30%. There was no indication of meiotic drive occurring in female carriers, since the number of individuals who inherited the mutation did not differ from the number of those inheriting the normal allele. No new mutations were detected in the 55 genealogies studied here.

Apolipoprotein and lipid abnormalities in chronic liver failure

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P<0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P<0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver