Maria José Cavaliere

Experimental mitochondrial myopathy induced by chronic intoxication by Senna occidentalis seeds.

Histochemical and electron microscopic studies of biceps femoris, pectoralis major and rectus femoris of chronically treated birds with seeds of the poisonous plant Senna occidentalis (0.2% external/internal tegment), were performed. The muscles had similar features of human mitochondrial myopathy as ragged-red fibers, cytochrome-oxidase negative fibers, and weak activity of the oxidative enzymes. Fibers with lipid storage were also present. Acid phosphatase activity in rare muscle fibers was also detected, and represents probably a secondary degenerative process. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. The present study presents a new experimental model of mitochondrial myopathy that may be useful for the best knowledge of this group of diseases and for experimental trials of drugs that could reverse the mitochondrial impairment in the mitochondrial myopathies.

Protective Effect of Pralidoxime on Muscle Fiber Necrosis Induced by Organophosphate Compounds

OBJECTIVE To determine the protective effect of pralidoxime on muscle fiber necrosis induced by organophosphate acute intoxication in rats. DESIGN Adult male Wistar rats were given oral organophosphate compounds dissolved in glycerol formal: dichlorvos, isofenphos, metamidophos, and diazinon. Half of the animals also received pralidoxime mesylate (20 mg/kg, intraperitoneal). Control animals received only the solvent. Twenty-four hours after treatment, the diaphragm muscle was collected for histological counts of necrotic muscle fibers in transverse sections. RESULTS Metamidophos- and isofenphos-treated animals showed the highest percentage of necrotic muscle fibers: 1.66 +/- 1.112 and 1.34 +/- 0.320, respectively. Diazinon-treated animals had a lower percentage of necrotic fibers: 0.40 +/- 0.032 (p < 0.05) compared to the first 2 products, and dichlorvos-treated animals showed the smallest: 0.05 +/- 0.021 (p < 0.05) when compared to the other 3 products. Pralidoxime reduced necrotic fibers about 20 times in metamidophos-treated animals, 10 times in isofenphos-treated animals and 6 times in diazinon-treated animals. Pralidoxime administration did not increase plasma cholinesterase activity in any group, although symptoms were reduced. CONCLUSIONS Oxime reduced diaphragmatic muscle necrosis in experimental organophosphate intoxication, despite little effect on plasma cholinesterase. Since respiratory insufficiency is an important cause of mortality and morbidity in organophosphate intoxications, early oxime administration may be particularly beneficial.

Estudo preliminar do SISCOLO-Qualidade na rede de saúde pública de São Paulo

The aim of the present work was to analyses critically the preliminary results of the computerized Quality System of gynecologycal cytology, implanted by the Public Health Ministry of Brazil - SISCOLO. Cervicovaginal smears stained by the Papanicolaou method were utilized. These smears were obtained through the diagnostic routine undertaken at the Oncocentro Foundation Pathology Laboratory of pathology, comprising cases of March 2000. Such cases were rescreened in a blind study, by the staff of the Pathology Division of the SP Adolpho Lutz Institutes Cytology Section. The SISCOLO-Quality Program selects, among all cases analyzed in the period, all such positive cases (ASCUS, AGUS, CIN and carcinomas) and to complete 10% of all cases it selects all non-satisfying and negative cases at random. From the 8,370 cases selected in March 2000, the SISCOLO-Quality program selected 837 samples. Among the selected samples, 23,4% showed squamo-columnar junction material, 5% were considered non-satisfactory for diagnosis and 71.1%, satisfactory although limited. The rescreening analysis showed concordance in 86.62% of the cases, one grade discordance was observed in 12.42% and two or more grades discordance in 0.96% of the cases. We concluded that the SISCOLO-Quality Program has applicability in the health public system as external monitoring method and meets the Health Ministrys expectations.

Squamous intraepithelial lesions in cervical smears of human immunodeficiency virus-seropositive adolescents

Various authors have reported a high rate of human papillomavirus (HPV) infection and HPV‐related neoplasias in human immunodeficiency virus (HIV)‐seropositive women. On the other hand, young women are most susceptible to cervical infection because of immaturity of the cervix, as it appears that HPV has more access to the basal cells of the differentiating epithelium. The purpose of the present work was to study cervical smears of 82 adolescent HIV‐seropositive women (13–21 years of age) to search for cytological evidence of cervical intraepithelial neoplasias. Twenty‐one cases showed characteristic features of HPV infection and squamous intraepithelial lesions (SIL; 25.6%). Sixteen cases aged from 17 to 21 years (mean age 19.5 years) had low‐grade SIL (LSIL; 19.5%) and five cases aged from 18 to 21 years (mean age 20.2 years) had high‐grade SIL (HSIL; 6.1%). There was no significant difference between the mean age of patients with LSIL and HSIL. Two cases had atypical squamous cells of undetermined significance (ASCUS). In the present work it was found that HIV‐seropositive adolescents have a high risk for preneoplastic lesions of the cervix (25.6%) as well as a high incidence of more aggressive lesions (6.1% of HSIL) when compared to the general population of adolescents. As it can be assumed that, if the age of acquisition of the infection in both groups (in the general population and HIV‐seropositive women) is the same, it is probable that HIV infection in adolescents not only increases the frequency of HPV infections but also facilitates the evolution to more aggressive preneoplastic lesions of the cervix due to HPV. Diagn. Cytopathol. 1998;18:91–92.

Expression of Ki-67 can assist in predicting recurrences of low-grade anal intraepithelial neoplasia in AIDS

PURPOSE: The incidence of anogenital squamous-cell carcinoma was observed to have increased since the beginning of the human immunodeficiency virus infection epidemic among male homosexuals, both with acquired immunodeficiency syndrome and without acquired immunodeficiency syndrome. It seems that immunosuppression is the most important risk factor for the progression of anogenital lesions, recurrences of anal condyloma, and development of anal carcinoma, in particular in acquired immunodeficiency syndrome. High-grade anal intraepithelial neoplasia was predominantly observed in the human immunodeficiency virus-positive men. We have also observed a high rate of recurrences of anal lesions in cases of high-grade anal intraepithelial neoplasia. However, there are many cases of recurrences of low-grade anal intraepithelial neoplasia that cannot be predicted by routine histologic studies. By using immunohistochemical methods, we studied the expression of Ki-67 in epithelial cells of low-grade anal intraepithelial neoplasia of patients with acquired immunodeficiency syndrome to try to predict recurrence of these lesions. METHODS: Anal biopsies of 38 patients were studied retrospectively. Of these patients, 14 had no recurrences (Group 1), and 24 patients had recurrence of the anal lesions before one year of follow-up (Group 2). RESULTS: The median percentage of Ki-67-positive cells in Group 1 was 6.3±7.03 and in Group 2 was 24.1±16,72. The difference between Groups 1 and 2 was statistically significant (P<0.001). CONCLUSIONS: Our results showed a high correlation between the percentage of Ki-67-positive cells and recurrences. We concluded that Ki-67 counting in low-grade anal intraepithelial neoplasia can aid in predicting recurrences and therefore aid in the follow-up of these patients.

Progression of cervical lesions in HIV-seropositive women : A cytological study

It has been reported that cervical intraepithelial lesions have a more aggressive course in HIV‐seropositive than in HIV‐seronegative women. In the present investigation, the progression of these cervical lesions was studied in a group of HIV‐seropositive women. Of 1,587 patients, 200 (12.6%) had a cytological diagnosis of squamous intraepithelial lesion (SIL) or invasive carcinoma. In 409 patients, more than one cytological smear was collected in 3½ years. Progression occurred in 39 cases. In 24 (61.5%), the first diagnosis was benign cellular changes (BCC) and the second was low‐grade SIL (LSIL) (1‐yr interval in 21 cases); in 11 (28.2%), the first was BCC, and the second, high‐grade SIL (HSIL) (1‐yr interval in 9 cases); in 2 (5.0%), the first diagnosis was LSIL. and the second, HSIL (1‐yr interval); in 2 (5.0%), the first was HSIL, and the second, invasive carcinoma (2‐yr interval). These results point to the importance of cervical cytologic surveillance in HIV‐seropositive patients. Diagn. Cytopathol. 24:117–119, 2001.

Cervical intraepithelial neoplasia in adolescents: study of cytological findings between 1987 and 1995 in São Paulo State-Brazil.

Abstract. The purpose of the present study was to ascertain the frequency of Pap smears abnormalities (SIL/carcinoma) in two populations in the State of S. Paulo (Brazil) who were screened for cervical cancer during the last nine years: adolescents (up to the age of 21) and adults (over 21). Statistical analysis showed a tendency to linear increase in frequency of abnormal Pap smears in both groups (adolescent: slope = 0.118±0.56; adult: slope = 0.079±0.021), being greater in the adolescent group (slope 0.039±0.038) than in the adult group. Between 1987 and 1995 the prevalence of abnormal smears tripled in the adult group (from 0.37 to 1.18) and almost quadruplicated in the adolescent group (from 0.64 to 2.10). Low grade squamous intraepithelial lesions (SIL) were the most frequent findings in cervical cytology in both groups: 92.3% in the adolescent group and 69.8% in the adult group. Few cases of high grade squamous intrapeithelial lesions (HSIL) (7.7%) and no cases of carcinoma were found in adolescent population. We suggested that sexually active adolescents should be included in cervical screening programs.

Miotoxicidade por organofosforados

Organophosphates comprise a group of chemical compounds extensively used in farming as insecticides, which cause accidental poisoning in animals and men and are also used in suicide attempts. The toxicity of these compounds is due especially to the cardiac and respiratory impairment in consequence of autonomic nervous system disorders. However, it is known that some of these products induce a myopathy in experimental animals and humans. This myopathy is characterized by muscle cell degeneration, involving above all the respiratory muscles. Based on the fact that this involvement certainly enhances the respiratory impairment, this study offers an experimental method for routine evaluation of organophosphate myotoxicity, using a minimal and sufficient battery of stains and histochemical reactions, for muscle necrosis quantification. For this purpose, albino rats (Wistar) treated with the organophosphate paraoxon, were used both with and without antidotes (atropine or pralidoxime). Muscle fiber necrosis in the diaphragm of the rats treated with paraoxon or paraoxon and atropine, that affected about 15% of the fibers in some areas, was detected. In the group treated with paraoxon and pralidoxime, a minimal necrosis was seen, revealing a protective role of this later antidote during the development of myopathy.

Papillomavirus in cervicovaginal smears of women infected with human immunodefficiency virus

It has been described that women infected with the human immunodeficiency virus (HIV) present more frequent cytological abnormalities in cervicovaginal smears, generally related to infection by human papillomavirus (HPV). The present work is a study of cervicovaginal smears of 147 HIV-seropositive women submitted to routine gynecological examinations. The smears were stained by the Papanicolaou method. Cytopathic effects of HPV were found in 38 (25.8%) cases. Nuclear atypias of cervical intraepithelial neoplasia (CIN) were evident in 36 (24.5%) of these cases: 27 (18.4%), CIN I; 6 (4.0%), CIN II and 3 (2.0%) CIN III. Also 2 (1.4%) invasive carcinomas and one (0.7%) endocervical dysplasia were found. Other agents observed were: Candida sp, 19 (12.9%) cases, Gardnerella vaginalis, 19 (12.9%), Trichomonas vaginalis, 13 (8.4%), Chlamydia trachomatis 5 (3.4%), Mobiluncus sp 2 (1.4%) and Herpes simplex virus 1 (0.7%). This study emphasizes the high frequency of HPV/CIN cervicovaginal abnormalities in HIV-seropositive in our population. It is possible that immunological factors and sexual promiscuity are involved in this phenomenon.

Morphometric evaluation of nucleolar organizer regions in cervical intraepithelial neoplasia.

The objective of this study was to determine whether some morphometric parameters and two different methods of counting AgNOR dots were correlated with the grade of cervical intraepithelial neoplasia. Thirty uterine cervix biopsies (8 cases of cervicitis, 9 CIN I, CIN II and 6 CIN III) were studied. Two methods were used to count AgNOR dots. The first one consisted of counting the number of epithelial cells with 1, 2, 3, 4, or more dots. The second method, based on a computer analysis system, consisted of counting the total number of dots in 100 cells, without considering the number of dots per cell. Using the same computer analysis system, the following parameters were measured: area, diameter, perimeter, roundness and length of each dot. The following parameters were found to be correlated with the grade of intraepithelial neoplasia: 1) number of cells with 1 dot, which decreased with increasing grade of cervical intraepithelial neoplasia; 2) number of cells with 4 dots or more, which increased with increasing grade of cervical intraepithelial neoplasia; 3) total number of dots per 100 cells, which progressively increased with increasing grade of intraepithelial neoplasia. We conclude that counting cells with 4 or more dots is the more trustworthy parameter for distinguishing the grade of cervical intraepithelial neoplasia.