The role of vanilloid receptor type 1 (TRPV1) in hyperalgesia related to bovine digital dermatitis.

Bovine digital dermatitis is a contagious and chronic disease affecting the digits of dairy cattle worldwide. Tissue degradation may alter ionic channels and further activate vanilloid channels, more specifically the vanilloid receptor type 1 (TRPV1) that can generate and modulate hyperalgesia in cows affected with bovine digital dermatitis. The aim of this pilot study was to identify and quantify TRPV1 channels in dairy cows presenting with different stages of bovine digital dermatitis and compare these data according to the disease evolution and degree of hyperalgesia described in previous studies. Biopsies were taken from 15 lactating Holstein cows (23 lesions), and immunochemistry was performed to identify the number of TRPV1 fibers in the 4 M-stages of digital dermatitis and the control group. This pilot study had 5 experimental groups, M1 (5 samples), M2 (5 samples), M3 (4 samples), M4 (4 samples), and the control group (5 samples), with inclusion criteria was the presence of a bovine digital dermatitis lesion in at least one digit. The pilot results demonstrate an increase in expression of TRPV1 receptors in group M4 in comparison with the other groups. Bovine digital dermatitis may cause an increase in expression of TRPV1 receptors in the chronic stages of the disease, possibly contributing to the hyperalgesia described in affected animals; nevertheless, further research is needed to define this relation.

Autoadjusting-CPAP effect on serum leptin concentrations in obstructive sleep apnoea patients.

BACKGROUND: Leptin is an hormone that regulates body weight. Studies have shown increasing leptin concentrations according to body mass index (BMI) and intermittent hypoxia. Our aim is to evaluate the basal leptin levels in OSA patients and its possible relation to OSA severity, independently of confounders and investigate the Autoadjusting-CPAP effect on leptin values. METHODS: In ninety eight male patients with moderate to severe OSA leptin serum levels were evaluated before therapy, 9 days and 6 months after therapy. RESULTS: In this group mean age was 55.3 years, mean BMI was 33.2 Kg/m2 and mean Apnoea- Hypopnea Index (AHI) was 51.7/h. Mean basal serum leptin value was 12.1 ug/L. Univariate analysis showed a significant correlation between serum leptin values and BMI (R = 0.68; p < 0.001), waist-hip ratio (R = 0.283; p = 0.004) and AHI (R = 0.198; p = 0.048); in stepwise multiple regression analysis only BMI (p < 0.001) was a predictor of serum leptin values. One week after therapy, mean leptin serum level decreased to 11.0 ug/L and 6 months after it was 11.4 ug/L. (p = 0.56 and p = 0.387, respectively) CONCLUSION: Baseline leptin serum levels positively correlate with BMI, fat distributio and OSA severity. BMI is the only predictor of basal leptin levels.Treatment with Autoadjusting-CPAP has a small effect on leptin levels.

Pap test in a high-risk population comparison of conventional and liquid-base cytology.

Liquid-based cytology (LBC) is believed to have better sensitivity than conventional smears (CSs) and offers the possibility to perform molecular assay. The goal of this work was to study the performance of CS and LBC in a high-risk population and to compare the results with the hybrid capture (HC) II for high-risk human papillomavirus (HPV). Samples were collected from selected women with clinical suspicions of low genital tract lesion at Pérola Biygnton Hospital (São Paulo, Brazil). After CS preparation, the brush was introduced in the endocervix and a new sample was collected and rinsed in the preservative medium of the system. The residual material was used to HC2. From 925 cases, LBC was unsatisfactory in 4 (1.51%) cases and CS was unsatisfactory in 100 cases (10.81%); among theses cases HC2(+) reactions was observed in 54 (54%) CSs and 3 (21.4%) LBCs. Considering cases with atypia of undetermined significance (squamous and glandular), 85 (77.27%) cases from LBC and 44 (86.4%) from CS were positive for HC2 assay for high-risk DNA-HPV. The difference among the methods was not significant (P < 0.38). The diagnosis improvement of LBC in comparison with CS was 86% in satisfactory samples, 92.76% in undetermined atypical lesions (including glandular), 83% in positive low-grade squamous intraepithelial lesions (LSIL(+)), and 86.84% in high-grade SIL(+) (HSIL(+)). HC2(+) reactions were observed in 144 CS cases and 266 LBC cases with abnormalities. Our results have showed that LBC was superior to CS in a high-risk population to detect lesions with high concordance with HC2(+) reactions; CSs also exhibit a high concordance with HC2 assay but with inferior performance to detect lesions.

The association of p16(INK4A) and fragile histidine triad gene expression and cervical lesions.

OBJECTIVE: This cross-sectional study was intended to assess the association between immunohistochemical analysis of p16 and fragile histidine triad (FHIT) and the presence of precancerous cervical lesions. MATERIALS AND METHODS: Women seen at Pérola Byington Hospital, São Paulo, Brazil, with histologically confirmed cervicitis (n = 31), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2,3 (n = 30), and cervical cancer (n = 7) had also cervical material collected for liquid-based cytology, human papillomavirus Hybrid Capture 2 (HC2) test, and p16 and FHIT immunohistochemical reactions. RESULTS: p16 and FHIT reactions were scored as the following: <1%, 1% to 5%, >5% to 25%, and >25%. Receiver operating curve analysis was used to select p16 and FHIT score cutoffs for further categorical analyses. All but one of the 37 CIN 2,3/cancer cases had a p16 score of greater than 1% to 5%. Among the 61 cervicitis/CIN 1 cases, 46 (75%) had a p16 score lower than 1% to 5%. In contrast, no association of FHIT expression and severity of cervical lesions could be demonstrated in this data set. Receiver operating curve analyses suggested the score of 1% to 5% for p16 as the cutoff that best discriminates CIN 2,3/cancer from cervicitis/CIN 1. No cutoff for FHIT scores could be suggested with data set. CONCLUSIONS: p16, but not FHIT expression, has the potential to be used as complementary diagnostic tool to investigate human papillomavirus-induced cervical lesions, if these results are confirmed in larger studies.

Screening for cervical cancer in high-risk populations: DNA pap test or Hybrid Capture II test alone?

This study was designed to evaluate whether Hybrid Capture II (HC2) test alone refer women to colposcopy as appropriately as DNA Papanicolaou (Pap) test, in the context of a high-risk group of women using the recently validated DNACitoliq LBC system. Women with suspected cervical disease were included in this cross-sectional study at a tertiary center in São Paulo, Brazil, for further workup. All women had cervical material collected for LBC and HC2 for high-risk human papillomavirus (hrHPV)-DNA test. Irrespective of cytology and HC2 results, colposcopy, and cervical biopsy when applicable, was systematically performed. All tests were performed blindly. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both methods were computed in relation to histology. A total of 1,080 women were included: 36.4% (393/1080) had ACUS+, 10.2% (110/1080) were high-grade squamous intraepithelial lesions (HSIL) or cancer. Mean age was 33.5 years. All women underwent colposcopy, and cervical biopsies were performed in 38.4% (415/1080): 33% (137/415) of the biopsies were negative, 14.4% (155/415) were low-grade squamous intraepithelial lesions (LSIL), 10.7% (116/415) were HSIL, and 0.6% (7/415) were cancer. HC2 sensitivity to diagnose biopsy-proven HSIL was 100%. Because all HSIL cases had a positive HC2 test, sensitivity could not be improved by adding LBC. Specificity and positive and negative predictive values of DNA Pap were not significantly different from HC2 test alone when considering LSIL+ histology as "gold standard" and HSIL+ histology. As a screening strategy for women with high-risk for cervical cancer, DNA Pap test does not seem to add substantially to HC2 alone in terms of appropriately referring to colposcopy.

DCS liquid-based system is more effective than conventional smears to diagnosis of cervical lesions: study in high-risk population with biopsy-based confirmation.

OBJECTIVE: To compare the performances of Papanicolaou test (PapTest) and of a new liquid-based cytology method, DNA-Citoliq System (DCS), in a high-risk population, with histology confirmation. METHODS: Paired specimens of exfoliated cervical cells were collected under split-sample protocol. All patients were submitted to colposcopy and a biopsy taken when any atypical transformation zone was seen. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of both conventional and DCS methods were computed in relation to histology. RESULTS: A total of 1095 patients were analyzed by two cytology methods and, in 425 (38.8%), histologically. There were significantly more adequate samples with DCS (98.63%) than with conventional (89.6%) smears (P < 0.001). ASCUS was diagnosed significantly more with DCS than with conventional Pap (P < 0.001). Conventional Pap misclassified as normal 55.4% (158/285) of cases with either LSIL or HSIL or cancer at histology, whereas DCS misclassified 31.2% (89/285) of cases (P < 0.001). DCS had a significantly higher sensitivity (70% and 91.3%) than the conventional Pap (49.8% and 72.8%) to detect both LSIL+ and HSIL+ at histology, respectively. On the other hand, specificity of conventional smear (88.2% and 85.2%) was significantly higher than DCS (75.4% and 70.9%) considering both LSIL+ and HSIL+ at histology, respectively. CONCLUSIONS: This study confirms the superiority of the liquid-based cytology system DCS to detect cervical lesions. The rate of adequate DSC slides was significantly higher than with conventional cytology.

Heated humidification during nasal continuous positive airway pressure for obstructive sleep apnea syndrome: objective evaluation of efficacy with nasal peak inspiratory flow measurements.

BACKGROUND: Nasal obstruction is one of the most frequent and sometimes troublesome side effects of nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnea syndrome (OSAS). METHODS: We describe a 60-year-old man with allergic seasonal rhinitis and OSAS, with worsening nasal symptoms 1 week after beginning home nCPAP, making nCPAP use difficult (nasal peak inspiratory flow [nPIF], 80 L/minute [57% of his best]). RESULTS: No significant improvement was obtained with topical steroids or cold humidification. Heated humidification was then considered, achieving an improvement in mean nPIF and symptom scores. An acceptable compliance with CPAP could be obtained during the heated humidification period (3.9 hours of mean daily use). CONCLUSION: In this patient with moderately severe OSAS and allergic rhinitis, monitoring nasal symptoms and nasal PIF objectively showed the benefit of heated humidification to overcome nasal intolerance and increase compliance to nCPAP treatment.

Cigarette smoking behavior and respiratory alterations during sleep in a healthy population.

BACKGROUND AND STUDY OBJECTIVE: The importance of tobacco smoking in the origin of sleep ventilatory abnormalities is disputed. The purpose of our study was to evaluate the influence of cigarette smoking behavior on the sleep respiratory alterations in a healthy population. DESIGN AND METHODS: We studied 38 healthy volunteers (21 M, 17 F; age 42 +/- 12 years; BMI 23.7 +/- 3.6 kg/m(2)) who were divided into two matched groups: current tobacco smokers (n = 18; over 10 pack-years) and nonsmokers (n = 20). All individuals underwent a single nocturnal domiciliary polygraphic study (Polygraphics CNS, Minneapolis, Minnesota). Apnea (AI), apnea-hypopnea (AHI), and desaturation (DI) indexes were defined according to conventional criteria. A nocturnal hypoxia index (NHI) was calculated as an index of the magnitude and duration of oxyhemoglobin desaturation during sleep. The mean transcutaneous oxygen saturation (SpO(2)) of the first 60 seconds of oxymetric registration (subject supine and awake) was considered basal SpO(2). Venous carboxyhemoglobin (COHb) levels were measured (CO-Oximeter AVL-912, Basel, Switzerland) in all individuals before (22:00 h) and after (10:00 h) sleep. A correction factor of 0.9 x COHb was applied to the basal SpO(2) values to calculate the corrected basal SpO(2) (SpO(2 corr)). RESULTS: AI, AHI, and DI were not significantly different between smokers and nonsmokers. The smokers have significantly higher NHI than nonsmokers [median (25th percentile-75th percentile): 5.3 (0-39.7) vs. 0.5 (0-1.7); p = 0.017]. There were significant correlations (P < 0.05) in smokers between NHI and pack-years index, between NHI and COHb levels, and between current smoking intensity and COHb levels. As expected, smokers had higher COHb levels at 10:00 as well as at 22:00 hours. The SpO(2 corr) was significantly lower (p < 0.001) among smokers than nonsmokers (88.9 +/- 3.3% vs. 94.7 +/- 1.3%). In multiple regression analyses, AHI and DI showed a significant correlation (p = 0.02 and p = 0.05, respectively) with habitual snoring, and NHI with pack-years and BMI (p = 0.02 and p = 0.04, respectively). CONCLUSIONS: Cigarette smoking does not seem to be associated with increased apneic activity during sleep. However, it is associated with a decrease in nocturnal oxygen saturation.

Estudo de mecanismos e fatores relacionados com o abuso sexual em crianças e adolescentes do sexo feminino / Study of mechanisms and factors related to sexual abuse in female children and dolescents

Objetivo:estudar mecanismos e fatores relacionados com o abuso sexual, comparando suas freqüências entre vítimas crianças e adolescentes. Métodos: estudo retrospectivo de 617 vítimas de abuso sexual atendidas entre julho de 1994 e agosto de 1999 pelo Centro de Referência da Saúde da Mulher: 71 crianças (idade<10 anos) e 546 adolescentes (10 a 20 anos). As variáveis de estudo foram crime sexual; constrangimento; presunção de violência; tipificação do agressor; número de agressores; situação da vítima no momento do crime; e ocorrência de traumas físicos. Os dados foram informatizados em programa Epi Info 6 e os resultados analisados pelo teste de X2. Resultados: o estupro ocorreu em 90,8 por cento das adolescentes e o atentado violento ao pudor em 46,5 por cento das crianças. A violência presumida (VP) foi mais freqüente nas crianças (63,4 por cento) e a grave ameaça nas adolescentes (63,2 por cento). A inocencia consilli foi VP exclusivas entre crianças, atingindo 59,5 por cento das dolescentes. Entre crianças, 84,5 por cento foram abusadas por agressores identificáveis, geralmente do núcleo familiar, enquanto desconhecidos violentaram 72,3 por cento das adolescentes. Nas crianças, o abuso ocorreu em 42,3 por cento em suas residências e em 28,2 por cento na do agressor. Adolescentes foram vitimadas durante atividades cotidianas (34,8 por cento) e no percurso do trabalho ou escola (28,4 por cento). A maioria das pacientes não apresentou traumas físicos genitais ou extragenitais. Conclusões: crianças foram submetidas, principalmente, ao atentado violento ao pudor, perpetrado por agressor conhecido, por meio de violência presumida e em ambientes privados. Nas adolescentes predominou o estupro por agressores desconhecidos, sob grave ameaça, em ambientes não domésticos

O impacto do diagnóstico citológico de atipias indeterminadas no sistema público de saúde / The impact of cytological diagnosis of undetermined atypias in public health system

Introdução: as alterações citológicas, de significado indeterminado representam uma importante limitação diagnóstica nos programas de escrutíneo de lesões cérvico-vaginais. A introdução de métodos biomoleculares, como o sistema de captura híbrida para detecção de HPV de alto risco contribui para a otimização da conduta clínica dessas pacientes, indicando colposcopia com precisão. Objetivo: avaliar o significado de lesões de significado indeterminado com relação à infecção pelo HPV, com o uso do teste de DNA para HPV com o método da captura de híbridos II. Métodos: foram estudadas amostras de 236 casos consecutivos examinados no laboratório da DIGENE-BRASIL, de pacientes com diagnóstico citológico prévio de ASCUS. As amostras foram submetidas ao teste de captura híbrida para identificação de DNA-HPV dc alto e baixo riscos. Resultados: dos 236 casos analisados, 183 (77,5 por cento) foram negativos para o teste de captura híbrida, seis (2,6 por cento) foram positivos para HPV de baixo risco e 47 (19,9 por cento) foram positivos para HPV de alto risco. Conclusão: as amostras positivas para HPV de baixo risco representam uma pequena e não-considerável minoria de casos, provavelmente, transientes. Cerca de 20 por cento dos casos foram positivos para HPV de alto risco e deverão ser encaminhados à colposcopia e biópsia, se necessário. Esses casos representam um grande potencial de progressão para lesões cervicais

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