Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue

To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05), systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2; P<0.05) and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2; P<0.05) from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05). Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05) after 60 min. The PaO2/FiO2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05) after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/l, mean ± SD (P<0.05) after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock and, particularly, if it has an effect on pulmonary function.

Risk factors for the increasing trend in low birth weight among live births born by vaginal delivery, Brazil

OBJECTIVE: To identify risk factors for low birth weight (LBW) among live births by vaginal delivery and to determine if the disappearance of the association between LBW and socioeconomic factors was due to confounding by cesarean section. METHODS: Data were obtained from two population-based cohorts of singleton live births in Ribeirão Preto, Southeastern Brazil. The first one comprised 4,698 newborns from June 1978 to May 1979 and the second included 1,399 infants born from May to August 1994. The risks for LBW were tested in a logistic model, including the interaction of the year of survey and all independent variables under analysis. RESULTS: The incidence of LBW among vaginal deliveries increased from 7.8% in 1978--79 to 10% in 1994. The risk was higher for: female or preterm infants; newborns of non-cohabiting mothers; newborns whose mothers had fewer prenatal visits or few years of education; first-born infants; and those who had smoking mothers. The interaction of the year of survey with gestational age indicated that the risk of LBW among preterm infants fell from 17.75 to 8.71 in 15 years. The mean birth weight decreased more significantly among newborns from qualified families, who also had the highest increase in preterm birth and non-cohabitation. CONCLUSIONS: LBW among vaginal deliveries increased mainly due to a rise in the proportion of preterm births and non-cohabiting mothers. The association between cesarean section and LBW tended to cover up socioeconomic differences in the likelihood of LBW. When vaginal deliveries were analyzed independently, these socioeconomic differences come up again.

Trends in the modes of delivery and their impact on perinatal mortality rates

OBJECTIVE: To determine changes in the incidence of vaginal deliveries, cesarean sections, and forceps deliveries and their potential association with fetal, early neonatal, and perinatal mortality rates over time. METHODS: A retrospective study was carried out and the occurrence of deliveries supervised by university services between January 1991 and December 2000 was determined. Data regarding fetal, early neonatal, and perinatal deaths were assessed using obstetric and pediatric records and autopsy reports. RESULTS: Of a total of 33,360 deliveries, the incidence of vaginal deliveries, cesarean sections, and forceps deliveries was relatively steady (around 60, 30, and 10%, respectively) while, at the same time, there was a marked reduction in fetal mortality (from 33.3 to 13.0‰), early neonatal mortality (from 30.6 to 9.0‰), and perinatal mortality (from 56.4 to 19.3‰). CONCLUSIONS: The marked reduction in perinatal mortality rates seen during the study period without an increase in cesarean sections indicates that the decrease in perinatal mortality was not impacted by cesarean section rates. The plausible hypothesis seems to be that the reduction in perinatal mortality of deliveries performed under the supervision of university services was more likely to be associated with better neonatal care rather than the mode of delivery.

Obesity and gestational weight gain: cesarean delivery and labor complications

OBJECTIVE: To assess the association between pre-gestational obesity and weight gain with cesarean delivery and labor complications. METHODS: A total of 4,486 women 20-28 weeks pregnant attending general prenatal care clinics of the national health system in Brazil from 1991 to 1995 were enrolled and followed up through birth. Body mass index categories based on prepregnancy weight and total weight gain were calculated. Associations between body mass index categories and labor complications were adjusted through logistic regression analysis. RESULTS: Obesity was present in 308 (6.9%) patients. Cesarean delivery was performed in 164 (53.2%) obese, 407 (43.1%) pre-obese, 1,045 (35.1%) normal weight and 64 (24.5%) underweight women. The relative risk for cesarean delivery in obese women was 1.8 (95% CI: 1.5-2.0) compared to normal weight women. Greater weight gain was particularly associated with cesarean among the obese (RR 4th vs 2nd weight gain quartile 2.2; 95% CI: 1.4-3.2). Increased weight at the beginning of pregnancy was associated with a significantly higher adjusted risk of meconium with vaginal delivery and perinatal death and infection in women submitted to cesarean section. Similarly, greater weight gain during pregnancy increased the risk for meconium and hemorrhage in women submitted to vaginal delivery and for prematurity with cesarean. CONCLUSIONS: Pre-gestational obesity and greater weight gain independently increase the risk of cesarean delivery, as well as of several adverse outcomes with vaginal delivery. These findings provide further evidence of the negative effects of prepregnancy obesity and greater gestational weight gain on pregnancy outcomes.

Incremental yield of bronchial washing for diagnosing smear-negative pulmonary tuberculosis

OBJECTIVE To assess the increased diagnostic yield for pulmonary tuberculosis using bronchial washing cultures compared with sputum cultures. METHODS Study conducted with 61 adults in Lima, Peru, from January 2006 to December 2007. The yield of sputum cultures was compared with the yield of acid-fast bacilli smears and cultures of bronchial washing for diagnosing pulmonary tuberculosis in suspected cases of clinical tuberculosis with negative acid fast bacilli sputum smears. RESULTS Twenty seven (95%CI 32;58) of the cases were eventually diagnosed with smear-negative pulmonary tuberculosis. Bronchial washing samples detected 23 (95%CI 72;99) of the smear-negative pulmonary tuberculosis cases compared with 15 (95%CI 37;74) for sputum cultures (p = 0.02). The incremental diagnostic yield of acid fast bacilli smear and culture of bronchial washing specimens over sputum culture was 44% (95%CI 25;65). CONCLUSIONS In function of the epidemiological context and the resources available, bronchoscopy should be deployed as part of a comprehensive work up that optimizes smear-negative pulmonary tuberculosis diagnosis and minimizes risk and costs.

Schistosoma mansoni: importance of skin and pulmonary phases to concomitant immunity in albino mice

Fourteen-day-old schistosomula obtained from mice previously infected were surgically transferred to the portal vein of receptor mice. Another group of mice was infected with cercariae by transcutaneous route. After 90 days, those groups were challenged with 100 cercariae, transcutaneously, as well as a control group. Two weeks later the animals were perfused and mature and immature worms counted separately. Statistically significant differences were observed in the recovery of immature worms, when the control group was compared with those twice infected. No statistical difference was detected between the group infected transcutaneously, and that infected by worm inoculation in portal vein. Results demonstrated that suppression of skin and lung migration of the parasite does not interfere with the development of the so called concomitant immunity.

Acute pulmonary histoplasmosis and first isolation of Histoplasma capsulatum from soil of Rio Grande do Sul, Brazil

A case of acute pulmonary histoplasmosis, where the clinical histoiy and epidemiological data led to the identification of H. capsulatum natural source, is described. Specimens of spleen and liver, obtained after intraperitonial inoculation in mice, grew H. capsulatum in culture from the soil of rural area of General Câmara, by the first time in Rio Grande do Sul.

Mediastinal and pulmonary entomophthoromycosis with superior vena cava syndrome: case report

The first case of mediastinal and pulmonary entomophthoromycosis with supe rior vena cava syndrome is reported. The patient presented with a history of edema of the face, neck and upper limbs as well as collateral circulation in the anterior wall of the chest. Histological examination of tissue from mediastinum revealed a granulomatous reaction with microabscesses surrounded by eosinophilic amorphous material and with broad hyphae in the center. Culture was not performed because a preliminary diagnosis of nonHodgkin's malignant lymphoma was made. Surgical correction of the obstructed area was performed and the patient was sucessfully treated with potassium iodide. The authors propose that mediastinal entomoph thoromycosis must be considered in the differential diagnosis of diseases causing superior vena cava syndrome in tropical and sub-tropical regions. This case enlarges the spectrum of clinical manifestations of the zigomycosis caused by Entomoph-thoraceae.

Pulmonary cavities colonized by actinomycetes: report of six cases

Six cases of a cavitary pulmonary ball formed by Actinomycetes are reported. They were observed in the state of Bahia, Brazil. All patients complained of cough and hemoptysis and the pathological study showed bronchiectasis and small cavities in the lungs. The lesions contained micro-colonies of Actinomyces, identified by morphology, staining properties and culture in two cases (thioglycolate media). In the six patients the disease was limited to the lungs. In one patient grains were found, within micro-abscesses in the surrounding parenchyma. Probably the invasion occurred due to ulceration of bronchial mucosa that was covered by granulation tissue. The author suggests that as in nocardiosis actinomycosys may have an invasive form, a saprophytic one may and colonize pulmonary cavities.

Kinectics of the pulmonary phase of Schistosoma mansoni in mice treated with dexamethasone

In the experimental schistosomiasis mansoni glucocorticoids cause a reduction in the worm burden when administered in the week of infection or, the longest, at the next week. In order to determinate the probable(s) site(s) of reduction of the worm burden, mice were infected with cercariae of LE strain of S. mansoni and dexamethasone was administered daily (50 mg/kg, subcutaneously) starting 1 hour before infection until the eighth day. Mice were sacrificed daily starting on the third day after infection until the ninth day, and schistosomula from lungs were collected. Six weeks after infection, the remaining mice were sacrificed and perfused for adult worm recovery. Analysis of the results showed that the non-treated mice presented larger numbers of lung larvae than the treated ones, and this difference was also found later in the worm burden in the portal system. This difference may reflect the early death of larvae in treated animals, before or after reaching the lungs.

Schistosoma mansoni: acquired immunity in mice after the use of oxamniquine at the evolutive skin and pulmonary phases

Mice infected with 350 cercariae of Schistosoma mansoni (LE strain) were treated with oxamniquine, at the dose of 400 mg/kg, 24, 48, 72, and 96 h after infection. Forty days after the treatment, the animals were submitted to a challenge infection with 80 cercariae, through the abdominal and ear skins. The number of immature worms in the animal groups treated 24 and 96 h after the first infection was found to be lower than that in the control group, thus showing that the death of schisto-somes by chemotherapy, at the skin and pulmonary phases, causes an acquired resistance state.

Herpes simplex virus type 2 infection in pregnancy: asymptomatic viral excretion at delivery and seroepidemiologic survey of two socioeconomically distinct populations in São Paulo, Brazil

The objective of the present study was to estimate the prevalence of herpes simplex virus type 2 (HSV 2) antibodies in child bearing women of 2 Brazilian populations with different socioeconomic status and to determine the risk of neonatal HSV exposure by means of maternal cultures at the onset of labor. The study was conducted at 2 hospitals: A, serving very low income patients and B, serving middle socioeconomic class. 173 participants from group A and 127 from B answered a questionnaire which showed that the patients had similar ages (27.7 and 26.8 years, respectively) but differed with regard to socioeconomic status, age at first intercourse (18.6 vs 20.6 years), number of sex partners (1.5 vs 1.2) and previous sexually transmitted diseases (15% vs. 1.5%). History of genital herpes was given by 11% of group A participants and by a similar number, 7%, of patients from group B. In addition, 200 serum samples from population A and 455 from B were tested by ELISA for and HSV antibodies and 92% and 86%, respectively, were found to be positive. Sixty seropositive samples from group A and 90 from B were further analyzed by Western blot, which showed the presence of type 2 specific antibodies in 46% and 36%, respectively, suggesting an overall HSV 2 prevalence of 42% in group A and 31% in B. Cervical specimens were obtained for culture from 299 asymptomatic patients of population A and 313 of B. HSV was isolated from one specimen in each group, indicating a 0.3% incidence of asymptomatic viral excretion in both populations. In conclusion, the prevalence of type 2 antibodies in childbearing women was very high, but it did not differ with the socioeconomic status. The risk of HSV perinatal transmission was also similar in the 2 study populations and it was comparable with the data from developed countries. Our findings do not indicate the need of special screening programs for asymptomatic HSV excretion in Brazilian pregnant women.

Experimental pulmonary schistosomiasis: lack of morphological evidence of modulation in schistosomal pulmonary granulomas

Numerous pulmonary schistosome egg granulomas were present in mice submitted to partial portal vein ligation (Warren's model). The granulomas were characterized by cellular aggregations formed within alveolar tissue. Main cellular types were macrophages (epithelioid cells), eosinophils, plasma cells and lymphocytes. These cells were supported by scanty fibrous stroma and exhibited close membrane contact points amongst themselves, but without forming specialized adhesion apparatus. When granulomas involved arterial structures, proliferation of cndothelial and smooth muscle cells occurred and fibrosis associated with angiogenesis became more evident. Granulomas formed around mature eggs in the pulmonary alveolar tissue presented approximately the same size and morphology regardless of the time of infection, the latter being 10, 18 and 25 weeks after cercarial exposure. This persistence of morphological appearance suggests that pulmonary granulomas do not undergo immunological modulation, as is the case with the granulomas in the liver and, to a lesser extent, in the intestines. Probably, besides general immunological factors, local (stromal) factors play an important role in schistosomal granuloma modulation.

Pulmonary manifestations in the initial phase of schistosomiasis mansoni

The clinical and radiological pulmonary manifestations in the initial phase of schistosomiasis mansoni were studied in thirty previously healthy individuals who were simultaneously infected. The findings were compared with those concerning a control group and related to possible pathogenetic factors. The respiratory manifestations were of light or of moderate intensity, the dry cough being the most common symptom. The significant radiological alterations were: thickening of bronchial walls and beaded micronodulation, predominantly localized in the lower pulmonary fields. It was observed significant association between wheezing and IgE levels, estimated by the area of immediate intradermal reaction, as well as between the number of blood eosinophils and the occurrence of radiological changes. Moreover, there was correlation between the worm burden and the presence of wheezing, thoracic pain and beaded micronodulation. Thus, the clinical and radiological pulmonary manifestations described are significant part of the initial phase of schistosomiasis mansoni and present the worm burden, eosinophilia and levels of IgE as probable pathogenetic factors.

Human pulmonary dirofilariasis: a review

The authors presented a detailed summary of the geographical distribution, clinical and pathological aspects of human pulmonary dirofilariasis. Although benign, this zoonosis, of which Dirofilaria immitis is the major etiological agent, represents a medical problem since it produces symptoms which may be confused with neoplasia and thus may subject patients to unnecessary thoracic surgery. Of 229 cases cited in the literature, only 17 were reported in Brazil, despite the existence of highly favorable conditions for the transmission of this infection in man. Thus it may well be that this parasitic infection remains underdiagnosed. Finally, the importance of a differential diagnosis between dirofilariasis and pulmonary neoplasia is emphasized in cases where there is a solitary subpleural nodule ("coin lesion") present. In addition, the development and improvement of modern immunological diagnostic techniques are essential to distinguish this benign disease from other pathological conditions and thus avoid unneccessary surgery. These techniques may reveal the true prevalence of this parasitic infection in our environment.