Neoplasia trofoblástica gestacional após normalização espontânea da gonadotrofina coriônica humana em paciente com mola hidatiforme parcial

Neste relato, é apresentado um caso de neoplasia trofoblástica gestacional após normalização espontânea de gonadotrofina coriônica humana em paciente com mola hidatiforme parcial. Trata-se da segunda ocorrência publicada desse evento e a primeira em que há comprovação imuno-histoquímica. No bojo dessa apresentação, ademais de mostrar o tratamento para essa intercorrência da gravidez, discute-se a possibilidade de redução da duração do seguimento pós-molar, assim como estratégias para o precoce reconhecimento da neoplasia trofoblástica gestacional após a remissão espontânea da gravidez molar.

Prevalência da lesão HPV induzida em canal anal de mulheres com neoplasia intraepitelial cervical 2 e 3: um estudo de corte transversal

OBJETIVO: Determinar a prevalência da lesão anal induzida por HPV em mulheres com neoplasia intraepitelial cervical grau 2/3 (NIC2/3).MÉTODOS: Estudo transversal, realizado no período de dezembro de 2008 a junho de 2009, no Estado de Pernambuco, nordeste do Brasil. Foram incluídas no estudo apenas mulheres com diagnóstico de NIC2/3 confirmado por biópsia e excluídas aquelas que não realizaram exame na primeira visita. As amostras para identificação do DNA de HPV anal por PCR e citologia anal foram coletadas com escovinha endocervical. A biópsia anal foi realizada nos casos de citologia anal anormal ou alterações maiores na anuscopia de alta resolução (AAR).RESULTADOS: Das AARs, 32,1% (n=37/115) foram normais e 63,5% (n=73/115) exibiram epitélio acetobranco. Vinte e dois por cento das citologias anais (n=26/115) foram anormais. Dentre elas, 12,2% (14/26) corresponderam à lesão intraepitelial anal de baixo grau e 3,4% (n=4/26), a lesão intraepitelial anal de alto grau. Foram realizadas 22 biópsias, das quais 13,7% (n=3/22) tiveram diagnóstico de neoplasia intraepitelial anal (NIA2) e 9% (n=2/22), NIA 3. Identificou-se 72,1% (n=83/115) de DNA do HPV nas amostras.CONCLUSÃO: Mulheres com NIC2/3 apresentam elevada prevalência de infecção por HPV e lesão HPV induzida em canal anal.

Detection of Pneumocystis in lungs of bats from Brazil by PCR amplification

Pneumocystis has been isolated from a wide range of unrelated mammalian hosts, including humans, domestic and wild animals. It has been demonstrated that the genome of Pneumocystis of one host differs markedly from that of other hosts. Also, variation in the chromosome and DNA sequence of Pneumocystis within a single host species has been observed. Since information about the occurrence and nature of infections in wild animals is still limited, the objective of this work was to detect the presence of Pneumocystis sp. in lungs of bats from two states from Brazil by Nested-PCR amplification. The bats, captured in caves and in urban areas, were obtained from the Program of Rabies Control of two States in Brazil, Mato Grosso and Rio Grande do Sul, located in the Mid-Western and Southern regions of the country, respectively. DNAs were extracted from 102 lung tissues and screened for Pneumocystis by nested PCR at the mtLSU rRNA gene and small subunit of mitochondrial ribosomal RNA (mtSSU rRNA). Gene amplification was performed using the mtLSU rRNA, the primer set pAZ102H - pAZ102E and pAZ102X - pAZY, and the mtSSU rRNA primer set pAZ102 10FRI - pAZ102 10R-RI and pAZ102 13RI - pAZ102 14RI. The most frequent bats were Tadarida brasiliensis (25), Desmodus rotundus (20), and Nyctinomops laticaudatus (19). Pneumocystis was more prevalent in the species Nyctinomops laticaudatus (26.3% = 5/19), Tadarida brasiliensis (24% = 6/25), and Desmodus rotundus (20% = 4/20). Besides these species, Pneumocystis also was detected in lungs from Molossus molossus (1/11, 9.1%), Artibeus fimbriatus (1/1, 100%), Sturnira lilium (1/3, 33.3%), Myotis levis (2/3, 66.7%)and Diphylla ecaudata (1/2, 50%). PCR products which could indicate the presence of Pneumocystis (21.56%) were identified in DNA samples obtained from 8 out of 16 classified species from both states (5 bats were not identified). This is the first report of detection of Pneumocystis in bats from Brazil.

Avaliação ultrassonográfica de linfonodos na pesquisa de metástases de neoplasia mamária em cadelas

A avaliação de linfonodo, parte importante do estadiamento das neoplasias mamárias em cadelas, pode auxiliar no estabelecimento do prognóstico e na escolha da conduta terapêutica. A ultrassonografia em modo B possibilita avaliação de tamanho, contorno, borda, forma, arquitetura, ecotextura e ecogenicidade do parênquima dos linfonodos e, em modo Doppler, da quantidade e distribuição dos seus vasos internos. Este trabalho visou identificar as características ultrassonográficas mais importantes utilizadas para classificar os linfonodos em metastáticos e não-metastáticos, estabelecer elementos de confiabilidade do ultrassom como ferramenta para diferenciar linfonodos metastáticos de não-metastáticos e estabelecer procedimentos de reprodução deste exame. Foram examinados 67 linfonodos inguinais superficiais de 30 cadelas com tumor mamário e cada linfonodo foi classificado como metastático ou não-metastático. A impressão diagnóstica ultrassonográfica foi associada aos resultados do exame histopato lógico dos linfonodos obtendo-se taxa de concordância de 92,5%, índice de sensibilidade de 94,1%, índice de especificidade de 92%, valor preditivo positivo de 0,8 e valor preditivo negativo de 0,9787. Características ultrassonográficas que classificaram um linfonodo como metastático ou como não-metastático foram listadas. O exame ultrassonográfico dos linfonodos regionais constitui importante ferramenta na detecção de metástase e sugere-se incluí-lo como rotina do estadiamento de neoplasias mamárias em cadelas.

Human papillomavirus infection and p53 protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma

The etiopathogenesis of vulvar intraepithelial neoplasia (VIN III) and invasive squamous cell carcinoma are largely unknown. Since there are few studies on Brazilian patients, our purpose was to determine the frequency of human papillomavirus (HPV) infection and the expression of p53 in these lesions, and associate them with other factors such as age, morphological subtypes, multicentric and multifocal disease. Thirty-eight cases of VIN III, nine of superficially invasive carcinoma, and 55 of invasive vulvar carcinoma were retrospectively evaluated from 1983 to 1995 for the presence of HPV by immunohistochemistry and in situ hybridization, and for p53 protein expression by immunohistochemistry on paraffin sections. All cases for whom material (slides and paraffin blocks) and clinical data were available were included. HPV and p53 were detected in 57.9 and 21.1% of the VIN III lesions, 33.3 and 66.7% of superficially invasive carcinomas, and 7.3 and 58.2% of invasive squamous cell carcinomas, respectively. HPV infection was associated with younger age in the VIN III and invasive carcinoma groups. In the latter, HPV infection was associated with the basaloid variant. p53 expression rate was higher in superficially invasive and invasive lesions and was not related to HPV infection. Our findings are similar to others and support the hypothesis that there are two separate entities of the disease, one associated with HPV and the other unrelated, with p53 inactivation possibly being implicated in some of the cases.

Estrogen and progesterone receptors in human papilloma virus-related cervical neoplasia

Estrogen (ER) and progesterone (PR) receptors in the normal uterine cervix, cervical intraepithelial neoplasia and invasive carcinoma were studied in consecutive samples from Hospital do Câncer, São Paulo, between 1996 and 1997. Tissue was collected by removing a fragment of the tumoral area using a 5-mm diameter biopsy punch, followed by removal of a macroscopically normal area as close as possible from the tumor. Histopathological confirmation was obtained for all specimens analyzed. A total of 24 normal tissues, 17 cases of cervical intraepithelial neoplasia and 7 of invasive carcinomas were studied. The ER/PR ratio was determined by immunohistochemistry using monoclonal antibodies specific for each receptor. Adjacent tissue slides were submitted to generic PCR for human papillomavirus (HPV) DNA detection followed by typing by dot blot hybridization. About half (45.8%) of the tumors were HPV DNA positive while 29.1% of the patients were also HPV positive in their respective normal tissue. ER was negative in the tumoral epithelium of 11 HPV-positive patients (P = 0.04). There was a trend in the ER distribution in normal tissue that was opposite to that from lesions, but it was not statistically significant (P = 0.069). No difference in ER distribution in stromal tissues was observed between HPV-positive and HPV-negative tissues. PR staining was negative in the epithelium of all cases studied. The results obtained from this small number of cases cannot be considered to be conclusive but do suggest that factors related to viral infection affect the expression of these ER/PR cervix receptors.

Lipid peroxidation and total radical-trapping potential of the lungs of rats submitted to chronic and sub-chronic stress

Exposure to stress induces a cluster of physiological and behavioral changes in an effort to maintain the homeostasis of the organism. Long-term exposure to stress, however, has detrimental effects on several cell functions such as the impairment of antioxidant defenses leading to oxidative damage. Oxidative stress is a central feature of many diseases. The lungs are particularly susceptible to lesions by free radicals and pulmonary antioxidant defenses are extensively distributed and include both enzymatic and non-enzymatic systems. The aim of the present study was to determine lipid peroxidation and total radical-trapping potential (TRAP) changes in lungs of rats submitted to different models of chronic stress. Adult male Wistar rats weighing 180-230 g were submitted to different stressors (variable stress, N = 7) or repeated restraint stress for 15 (N = 10) or 40 days (N = 6) and compared to control groups (N = 10 each). Lipid peroxidation levels were assessed by thiobarbituric acid reactive substances (TBARS), and TRAP was measured by the decrease in luminescence using the 2-2'-azo-bis(2-amidinopropane)-luminol system. Chronic variable stress induced a 51% increase in oxidative stress in lungs (control group: 0.037 ± 0.002; variable stress: 0.056 ± 0.007, P < 0.01). No difference in TBARS was observed after chronic restraint stress, but a significant 57% increase in TRAP was presented by the group repeatedly restrained for 15 days (control group: 2.48 ± 0.42; stressed: 3.65 ± 0.16, P < 0.05). We conclude that different stressors induce different effects on the oxidative status of the organism.

Toxicity of a cyanobacterial extract containing microcystins to mouse lungs

Toxic cyanobacteria in drinking water supplies can cause serious public health problems. In the present study we analyzed the time course of changes in lung histology in young and adult male Swiss mice injected intraperitoneally (ip) with a cyanobacterial extract containing the hepatotoxic microcystins. Microcystins are cyclical heptapeptides quantified by ELISA method. Ninety mice were divided into two groups. Group C received an injection of saline (300 µl, ip) and group Ci received a sublethal dose of microcystins (48.2 µg/kg, ip). Mice of the Ci group were further divided into young (4 weeks old) and adult (12 weeks old) animals. At 2 and 8 h and at 1, 2, 3, and 4 days after the injection of the toxic cyanobacterial extract, the mice were anesthetized and the trachea was occluded at end-expiration. The lungs were removed en bloc, fixed, sectioned, and stained with hematoxylin-eosin. The percentage of the area of alveolar collapse and the number of polymorphonuclear (PMN) and mononuclear cell infiltrations were determined by point counting. Alveolar collapse increased from C to all Ci groups (123 to 262%) independently of time, reaching a maximum value earlier in young than in adult animals. The amount of PMN cells increased with time of the lesion (52 to 161%). The inflammatory response also reached the highest level earlier in young than in adult mice. After 2 days, PMN levels remained unchanged in adult mice, while in young mice the maximum number was observed at day 1 and was similar at days 2, 3, and 4. We conclude that the toxins and/or other cyanobacterial compounds probably exert these effects by reaching the lung through the blood stream after ip injection.

L1 sequence of a new human papillomavirus type-58 variant associated with cervical intraepithelial neoplasia

The present study on molecular characterization of a human papillomavirus (HPV) isolated in Central Brazil describes the L1 gene sequence from a new variant of HPV-58, the isolate Bsb-02. The sample was from a smear obtained from a woman with cervical intraepithelial neoplasia grade II. The whole L1 gene from isolate Bsb-02 was sequenced automatically, showing 99.1% nucleotide identity with the gene from the HPV-58 reference. The clustering between Bsb-02 and HPV-58 reference sequence was also supported by phylogenetic analysis. Fourteen nucleotide substitutions were observed: eight were synonymous and six were associated with amino acid substitutions. A10V and V144I have not been previously described. At GenBank, the only complete L1 sequence from HPV-58 in addition to the HPV-58 reference one is that of Bsb-02. These data provide information that may be relevant to HPV diagnosis and to rational vaccine strategies. HPV variants may also be associated with host immune responses and with the risk of cervical neoplasia.

Identification of clonally rearranged T-cell receptor beta chain genes in HTLV-I carriers as a potential instrument for early detection of neoplasia

We analyzed the genetic recombination pattern of the T-cell receptor beta-chain gene (TCR-beta) in order to identify clonal expansion of T-lymphocytes in 17 human T-lymphotropic virus type I (HTLV-I)-positive healthy carriers, 7 of them with abnormal features in the peripheral blood lymphocytes. Monoclonal or oligoclonal expansion of T-cells was detected in 5 of 7 HTLV-I-positive patients with abnormal lymphocytes and unconfirmed diagnosis by using PCR amplification of segments of TCR-beta gene, in a set of reactions that target 102 different variable (V) segments, covering all members of the 24 V families available in the gene bank, including the more recently identified segments of the Vbeta-5 and Vbeta-8 family and the two diversity beta segments. Southern blots, the gold standard method to detect T-lymphocyte clonality, were negative for all of these 7 patients, what highlights the low sensitivity of this method that requires a large amount of very high quality DNA. To evaluate the performance of PCR in the detection of clonality we also analyzed 18 leukemia patients, all of whom tested positive. Clonal expansion was not detected in any of the negative controls or healthy carriers without abnormal lymphocytes. In conclusion, PCR amplification of segments of rearranged TCR-beta is reliable and highly suitable for the detection of small populations of clonal T-cells in asymptomatic HTLV-I carriers who present abnormal peripheral blood lymphocytes providing an additional instrument for following up these patients with potentially higher risk of leukemia.

Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia

Epidemiological studies show that human papillomaviruses (HPV) are strongly related to cervical cancer and cervical intraepithelial neoplasias (CIN). Unlike the case for women, there are no consistent data on the natural history of HPV in the male population even though these viruses are prevalent in males. We carried out a prospective study to assess the prevalence of HPV in males as well as the factors that determine such infections in 99 male sexual partners of women with CIN. The genitalia of the males were physically examined and subjected to peniscopy for the collection of scrapings which were subjected to the polymerase chain reaction and restriction fragment length polymorphism to detect HPV. Of the 99 males sampled, 54 (54.5%) were positive for HPV DNA, 24% of whom presented normal peniscopy, 28% presented evident clinical lesions and 48% isolated lesions consistent with subclinical infection. In the HPV-negative group, 53% showed normal peniscopy, 4% presented evident clinical lesions and 42% isolated lesions consistent with subclinical infection. The study detected a statistically significant association (P < 0.02, Pearson chi-square test) between HPV infection and both the mean number of sexual partners which a male had during his life and the mean number of sexual partners in the year prior to testing. Viral types 6 and 11 were most frequently encountered. The study shows that infection with HPV was frequent in male sexual partners of women with CIN.

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs

Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor α and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.

Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation.

Laringectomia frontal anterior: técnica de Tucker. Estudo retrospectivo

O carcinoma epidermóide da laringe é a sexta neoplasia mais comum, sendo uma das neoplasias malignas mais freqüentes na cabeça e pescoço, ocupando o segundo lugar imediatamente após o câncer da cavidade oral. FORMA DE ESTUDO: Estudo clínico retrospectivo. MATERIAL E MÉTODO: Entre os anos de 1991 e 2003, 24 pacientes portadores de lesões glóticas envolvendo a comissura anterior foram submetidos a laringectomia frontal anterior com epiglotoplastia descrita por Tucker e colaboradores no ano de 1979. RESULTADO: Nossos resultados confirmam aqueles encontrados em outras publicações. Não ocorreram mortes no pós-operatório e o seguimento foi relativamente simples. Todos os pacientes foram decanulizados e recuperaram um efetivo trato digestivo e aéreo. CONCLUSÃO: Nossos achados mostram que a laringectomia pela técnica de Tucker é uma cirurgia efetiva para o tratamento dos carcinomas glóticos que acometem a comissura anterior e a porção membranosa das cordas vocais com a motilidade preservada, pois tais lesões não devem ser tratadas pela ressecção endoscópica trans-oral ou por uma laringectomia fronto lateral.

Paralisia facial periférica bilateral na leucemia linfóide aguda: relato de caso

A mímica facial é fundamental para a expressão e comunicação humana, que são possíveis apenas através da integridade do nervo facial. Sendo assim, a paralisia facial periférica (PFP) pode deixar seqüelas estéticas, funcionais e psicológicas. A causa mais comum é a paralisia de Bell (50 a 80%), onde a maioria dos pacientes apresenta manifestação unilateral. O acometimento bilateral simultâneo é raro, sendo a leucemia a neoplasia que com maior freqüência pode resultar nesse tipo de manifestação. A seguir, relatamos o caso de um paciente de dezoito anos de idade apresentando leucemia linfóide aguda (LLA) e PFP simultânea, ambas refratárias ao tratamento quimioterápico, culminando com o óbito cinco meses após o início da PFP. Realizou-se considerações importantes sobre a fisiopatologia da PFP na LLA, além de uma revisão da literatura.