The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

Sensing System Based on FBG for Corrosion Monitoring in Metallic Structures.

As corrosion has slow development, its detection at an early age could be an alternative for reducing costs of structural rehabilitation. Therefore, the employment of structural health monitoring (SHM) systems, sensing configurations collecting data over time allowing for observing changes in the properties of the materials and damage emergence, for monitoring corrosion can be a good strategy to measure the damage and to decide the better moment for intervention. Nonetheless, the current corrosion sensor technology and the high costs of the sensing system implementation are limiting this application in the field. In this work, an optical fiber Bragg grating (FBG)-based sensing system is proposed for monitoring the thickness loss of a 1020 carbon steel metal plate subjected to controlled corrosion. The natural frequency of the plate was collected as a function of the corrosion time over 3744 h. To validate the experimental results, ultrasound measures and electrochemical tests were also carried out under similar conditions. The experimental results show adequate reliability, indicating the suitable functionality of the proposed system for monitoring the thickness loss caused by corrosion in metallic structures, in comparison with traditional methods, as ultrasonic and electrochemical measures.

Endothelial progenitor dysfunction associates with a type I interferon signature in primary antiphospholipid syndrome.

OBJECTIVES: Patients with antiphospholipid syndrome (APS) are at risk for subclinical endothelial injury, as well as accelerated atherosclerosis. In the related disease systemic lupus erythematosus, there is a well-established defect in circulating endothelial progenitors, which leads to an accrual of endothelial damage over time. This defect has been at least partially attributed to exaggerated expression of type I interferons (IFNs). We sought to determine whether these pathways are important in APS. METHODS: We studied 68 patients with primary APS. Endothelial progenitors were assessed by flow cytometry and functional assay. Type I IFN activity was determined by a well-accepted bioassay, while peripheral blood mononuclear cells were scored for expression of IFN-responsive genes. RESULTS: Endothelial progenitors from patients with APS demonstrated a marked defect in the ability to differentiate into endothelial cells, a phenotype which could be mimicked by treating control progenitors with APS sera. Elevated type I IFN activity was detected in the circulation of patients with APS (a finding that was then replicated in an independent cohort). While IgG depletion from APS sera did not rescue endothelial progenitor function, the dysfunction was successfully reversed by a type I IFN receptor-neutralising antibody. CONCLUSIONS: We describe, for the first time to our knowledge, an IFN signature in primary APS and show that this promotes impaired endothelial progenitor function. This work opens the door to novel approaches that may mitigate vascular damage in APS, such as anti-IFN drugs.

Perioperative management of patients with antiphospholipid syndrome: a single-center experience.

The objective was to describe the management and risk factors for complications of antiphospholipid syndrome (APS) patients who underwent a surgical procedure in a single center. We reviewed medical records of all patients with primary or secondary APS who underwent an elective surgery during a 6-year period. Demographical data, management of anticoagulation and complications were recorded. We identified 43 patients, mean age 37.9 ± 8.9 years, who underwent a total of 48 elective surgeries. All patients had history of at least one thrombotic event and were under vitamin K antagonists. Before surgery, all patients received bridging therapy with intravenous infusion of heparin or low molecular weight heparin (LMWH). Among the LMWH group, 36 had a full anticoagulation regimen and nine prophylactic doses. In 62% of the surgeries, we identified an optimal management of periprocedural anticoagulation according to guidelines. Overall six patients had severe bleeding and three thrombotic complications (full anticoagulation regimen n = 2 and prophylactic dose group n = 1). Patients with optimal management of anticoagulation experienced less thrombotic and hemorrhagic complications (7 vs. 33%; OR 0.14, 95% CI 0.02-0.81; p = 0.040) and patients with INR ≤1.5 at surgery had fewer episodes of major bleeding (6 vs. 29%; OR 0.19, 95% CI 0.02-0.98; p = 0.050). All three thrombotic events occurred in patients with INR ≤1.5. Proper management of anticoagulation based on guidelines is associated with less complications in patients with APS. Notwithstanding the proper use of bridging therapy, some patients may develop thrombotic complications.

Thrombotic microangiopathy and poor renal outcome in lupus patients with or without antiphospholipid syndrome.

OBJECTIVES: To assess the presence of acute thrombotic microangiopathy (aTMA) and chronic vascular lesions (cTMA) in lupus nephropathy, and to evaluate their association with extrarrenal lupus features, aPL positivity, antiphospholipid syndrome (APS) and renal survival. METHODS: We studied lupus patients with renal biopsy, ≥1 year of post-biopsy follow-up and at least two aCL (IgG-IgM), anti-ß2GP-I (IgG-IgM) and/or lupus anticoagulant (LAC) determinations. A blinded nephropathologist evaluated all biopsies. We retrospectively collected clinical, serological, treatment and renal survival data. We plotted survival curves and used Cox regression analysis. RESULTS: A total of 90 biopsies were included with a median disease duration 5.9 years and median follow-up 2.4 years. Eleven patients (12.2%) had cTMA and 3 (3%) aTMA. There was no difference in age, lupus duration, hypertension, drugs, APS, non-renal lupus features, low C3 or C4 aCL IgG, anti-ß2GP1-IgG or IgM and LAC between cTMA and non-cTMA groups. The cTMA group had aCL-IgM less frequently (27% vs. 66%, p=0.02), more class IV nephropathy (100% vs. 40%, p=0.01), higher activity index scores (7.5 vs. 2, p=0.03) and a tendency to need chronic dialysis (54.5% vs. 24% p=0.06). At four years of follow-up, 28% of the cTMA group and 62% of the non-cTMA group were free of dialysis (log rank p=0.03). cTMA was associated with chronic dialysis (RR 2.9, CI 95% 1.1-8.1, p=0.03). CONCLUSIONS: cTMA conferred a poor renal outcome. We found a low frequency of TMA that was not associated with with APL positivity or APS, suggesting that other factors hitherto not studied are involved in its pathogenesis.

The role of ß2-glycoprotein I (ß2GPI) carbohydrate chains in the reactivity of anti-ß2GPI antibodies from patients with primary antiphospholipid syndrome and in the activation and differentiation of U937 cells.

Several studies have shown that conformational changes of ß(2)-glycoprotein I (ß(2)GPI) when bound to negatively charged components expose cryptic epitopes and subsequent binding of anti-ß(2)GPI from patients with antiphospholipid syndrome (APS). However, the role of the carbohydrate chains of ß(2)GPI in this anti-ß(2)GPI reactivity is poorly understood. We therefore studied the reactivity and inhibition of anti-ß(2)GPI antibodies from APS patients with native, partially glycosylated ß(2)GPI (pdß(2)GPI; without sialic acid) and completely deglycosylated ß(2)GPI (cdß(2)GPI). To determine the potential biologic importance of these glycoforms and their interaction with anti-ß(2)GPI in vitro, stimulation assays were performed with the U937 cell line. Circular dichroism (CD) and fluorescence analysis of the three ß(2)GPI forms were also studied. We found an increased reactivity of anti-ß(2)GPI against pdß(2)GPI and cdß(2)GPI compared to native ß(2)GPI. Both deglycosylated ß(2)GPI isoforms showed higher inhibition of the anti-ß(2)GPI reactivity than the native protein in soluble-phase. Likewise, the antibody/ß(2)GPI/glycoform complexes increased the synthesis of IL-6, IFNγ and TNFα and the expression of HLA-DR, CD14 and CD11c in U937 cells. CD and fluorescence studies of the glycoforms yielded considerable changes in the fluorescence signals. Our work suggests that the partial or complete removal of the carbohydrate chains uncover cryptic epitopes present in ß(2)GPI. The differentiation and increased synthesis of pro-inflammatory cytokines by U937 cells in vitro may have pathogenetic implications.

Community health workers: to train or to restrain? A longitudinal survey to assess the impact of training community health workers in the Bolama Region, Guinea-Bissau.

BACKGROUND: The shortage in human resources for health affects most dramatically developing countries which frequently use community health workers (CHW) as the basis for health programmes and services. The traditional definition refers CHWs as members of the community who are recruited and trained in health prevention and promotion to provide services within their community. In Guinea-Bissau, CHWs play a fundamental role in the diagnosis and treatment of childhood diarrheal diseases - one of the main health problems in the country. METHODS: This study is based on 22 CHW, 79% of the total number of CHW in the Sanitary Region of Bolama. The main goal was to assess how training CHW on diarrheal diseases impacted the accuracy of the diagnosis and treatment of these diseases in children under the age of 5 years. Three evaluations were made throughout time - one evaluation before the training and two follow-up evaluations.An observation grid was developed to evaluate the identified signs, symptoms, diagnosis and treatments prescribed by the CHW in consultations to children with a suspicion of diarrhoeal disease. A similar grid was filled by a medical doctor who took the role of the external validation standard.Friedman's variance analysis and Cochran's Q test were performed to compare the accuracy depicted by CHWs in identifying items throughout time. A logistic regression model was also used to check the possible influence of socio-demographic characteristics of CHWs on the accuracy of the diagnosis and treatment prescribed by the CHW. RESULTS: The results show that CHWs improve significantly their performance in identifying the correct diagnosis in the first follow-up moment after the training (P = 0.001, n = 22) but, 3 months later, the effectiveness decreases. No statistical evidence was found for the logistic regression models applied. This progressive loss of performance after training may occur because CHWs fail to apply treatment algorithms and guidelines over time. A limited set of socio-demographic characteristics of the CHWs can influence their performance and should not be disregarded when selecting CHW candidates. CONCLUSION: The selection, supervision, support and continuous training of CHW are as important as the training provided.

Difference of endothelial function during pregnancies as a method to predict preeclampsia.

BACKGROUND: Systemic endothelial dysfunction has been identified as one of the main events in preeclampsia (PE). A nonhealthy vascular endothelium can be pointed out as the pathophysiological explanation of the clinical manifestations and complications of PE. Once normal pregnancy is characterized by a constant increase in endothelial function, a follow-up of this physiological event could be used as an early marker or a prediction tool to predict PE. OBJECTIVES: To perform a longitudinal assessment of endothelial function, using an ultrasound study of brachial artery flow Flow-mediated dilation (FMD), in normotensive and preeclamptic pregnancies, to evaluate the difference of FMD values along the second trimester of pregnancy to predict PE. PATIENTS AND METHODS: In a prospective cohort study, 91 pregnant women with a high risk of developing PE were subjected to FMD of the brachial artery. The difference in the FMD values, between 16(+0) and 19(+6) and 24(+0) and 27(+6) weeks of gestation were compared, taking PE development into consideration. Receiver operator characteristics (ROC) curves were created to determine the sensibility and specificity of FMD difference to predict PE. RESULTS: A total of 19 patients developed PE and the other 72 women remained normotensive until 1 week after delivery. When considering a cut off of +2.50 %, FMD difference, between the two evaluations, sensitivity for PE prediction was 87.5 % for early onset PE and 95.5 % for late PE. CONCLUSION: The difference of FMD values between the second trimester of pregnancy can be used for PE prediction for both, early and late forms of PE.

Assessment of endothelial function in pregnant women with preeclampsia and gestational diabetes mellitus by flow-mediated dilation of brachial artery.

PURPOSE: To compare endothelial function, as assessed by flow-mediated dilation (FMD) in pregnant women with preeclampsia (PE), gestational diabetes mellitus (GDM) and healthy pregnant women. METHODS: We conducted a cross-sectional study of eighty women who were selected and divided into three groups: Group A comprising 42 pregnant women with PE, Group B (control) consisting of 19 normotensive pregnant women with no comorbidities and Group C consisting of 19 pregnant women with GDM. The women underwent FMD and the results were compared between groups. The data were obtained from the Center for Fetal Medicine, Hospital das Clínicas, Federal University of Minas Gerais, Brazil (CEMEFE-HC-UFMG) after approval by the Ethics and Research Committee on June 4, 2008 under no CAAE-0280.0.203.000-08. RESULTS: Nonparametric variance analysis showed no statistically significant difference between the characteristics of the three groups. The comparison between the results of the mean values of brachial artery FMD groups of pregnant women with preeclampsia (FMD = 5.36 ± 4.61 %), gestational diabetes (FMD = 9,18 ± 5.98 %) and pregnant women in the control group (FMD = 17.55 ± 8.35 %) showed that a statistically significant difference was found between groups using the Dunn test. The comparison between groups PE × GDM was not statistically significant. The group consisting of pregnant women with GDM associated with those with PE had significantly lower results for FMD (6.55 ± 5.33 %) than the control group (17.55 ± 8.35 %, p = 0.00). CONCLUSIONS: The group consisting of pregnant women with GDM or PE showed results for FMD significantly lower than the control group, suggesting possible endothelial injury in these patients.

A Challenging Case of Recurrent Fever.

Syndrome of undifferentiated recurrent fever (SURF) includes heterogeneous episodes of systemic inflammation without documented infection, without response to antibiotherapy, and characterized by a paucity of specific clinical or molecular criteria. Colchicine is an effective treatment with an impact on morbimortality. We describe a case of a previously healthy one-year-old male, with consanguineous ancestry, admitted four times due to recurrent fever, associated with nonspecific symptoms and an increase of inflammatory markers in a sepsis-like pattern. No consistent infection was documented, and there was no response to broad-spectrum antibiotics. The evolution revealed corticosteroid dependency. The autoinflammatory syndrome-targeted next-generation sequencing (NGS) gene panel didn't detect relevant pathogenic variants. SURF was postulated as a diagnosis of exclusion, and the effectiveness of colchicine supports an autoinflammatory etiology. We aimed to draw attention to recurrent fevers associated with autoinflammatory disorders due to their challenging diagnosis. Improved understanding of immune pathways and advances in genetic testing will enable greater accuracy in the approach.

Strikes of physicians and other health care workers in sub-Saharan African countries: a systematic review.

Introduction: Strikes in the health sector have been of growing concern, given their disruptive nature, negatively impacting the provision of health care and jeopardizing the well-being of patients. This study aims to identify the main actors, the reasons behind industrial actions protests, strikes and lockouts (IAPSL) in sub-Saharan African countries and their impact on health care workers (specifically doctors) and health services, as well as to identify the main strategies adopted to reduce their impact on healthcare services. Methods: Studies published between January 2000 and December 2021 and archived in MEDLINE, Google Scholar, Scopus, ProQuest, and Science Direct were included. Quantitative, observational (i.e., cohort, case-control, cross-sectional, and ecological) and experimental studies, as well as mixed methods, quasi-experimental, and qualitative studies were eligible. Results: A total of 5521 studies were identified and after eliminating duplicates, applying the inclusion criteria, and assessing the risk of bias, a total of 11 studies were included in the review. Nurses and doctors are the actors most commonly involved in strikes. The main causes of strikes were salary claims and poor working conditions. The main strategies adopted to mitigate the strike consequences were to restrict services and prioritize emergency and chronic care, greater cooperation with the private sector and rearrange tasks of the available staff. The strikes led to a reduction in hospitalizations and in the number of women giving birth in health units, an increase in maternal and child morbidities and delays in the immunization process. Increased mortality was only reported in faith-based hospitals. Discussion: This evidence can assist decision-makers in developing strategies and interventions to address IAPSL by health care workers, contributing to strengthen the health system. Strikes in the health sector disrupt healthcare services provision and compromise the well-being of patients, especially the most disadvantaged, with consequences that may be difficult to overcome ever. The potential health impacts of strikes highlights the importance of their prevention or timely resolution through regulation and negotiations to balance the rights of health care workers and the rights of patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=334173, identifier CRD42022334173.

The role of lupus anticoagulant and triple marker positivity as risk factors for rethrombosis in patients with primary antiphospholipid syndrome.

OBJECTIVES: To ascertain rethrombotic risk factors in patients with primary antiphospholipid syndrome (PAPS). METHODS: We retrospectively evaluated 95 patients according to their rethrombotic status. We registered anticoagulation (OA) status, comorbidities, traditional thrombotic factors, prevalence of aCL (IgG-IgM), anti-ß2GP-I (IgG-IgM), LA and triple marker positivity (LA, aCL and anti-ß2GP-I). RESULTS: Forty-two patients had rethrombosis and 53 were rethrombosis-free. The median follow-up was 4.5 (0.3-26) years. There were no differences in comorbidities and traditional thrombotic factors. Patients with rethrombosis had more frequently LA (62% vs. 40%, p=0.04), were younger (41 vs. 47 years, p=0.01) and received less frequently OA (23% vs. 54%, p=0.002). A logistic regression analysis showed that the OA status (OR 0.17, 95% CI 0.05-0.57, p=0.004) and age (OR 0.94, 95% CI 0.90-0.98, p=0.01) remained significant. Patients who discontinued OA and developed rethrombosis (Group 1, n=32) vs. patients who discontinued OA, but remained rethrombosis-free (Group 2, n=24) were also analysed. We found a higher prevalence of LA and triple marker positivity in Group 1 (67% vs. 31%; OR= 4.5, 95% CI 1.3-14.9, p= 0.01 and 57% vs. 27%; OR 3.6, 95% CI 1.7-12; p=0.03), respectively. Both variables remained associated with rethrombosis when compared with the overall rethrombosis group vs. Group 2 (LA 62% vs. 31%, OR= 3.6 95% CI 1.1-11.2, p=0.03; triple marker 54% vs. 27%; OR 32 95% CI 1.01-10.2, p=0.05). CONCLUSIONS: LA positivity and triple aPL positivity confer a more severe risk of rethrombosis in PAPS patients, irrespective of their anticoagulation status and known conventional risk factors.

Anatomical and physiological changes in the venous system of lower limbs in pregnant women and findings associated with the symptomatology.

PURPOSE: Quantify the volume and diameter of veins in the lower limbs of primigravidae and associate the presence of venous signs and symptoms with the vascular measurements. METHODS: A cross-sectional study assessed 64 lower limbs of 32 healthy women of whom 16 were primigravidae between 22 and 36 weeks pregnant, and 16 nulligravidae. The women were submitted to physical assessment, air plethysmography and vascular ultrasound. The volumes and diameters of the main veins in the lower limbs were compared between pregnant and non-pregnant women. In the group of pregnant women, the attempt was also made to associate such measurements to the presence of vascular signs and symptoms. RESULTS: The average venous volume of the lower limbs (110.1 ± 30.2 and 94.7 ± 27.3 mL; p = 0.036), as well as the diameters of the common femoral (12.72 ± 2.27 and 10.14 ± 1.24 mm; p < 0.0001), saphenous (4.81 ± 1.15 and 3.55 ± 0.98 mm; p < 0.0001) and popliteal (6.87 ± 1.68 and 5.36 ± 1.07 mm; p < 0.0001) veins were, respectively, greater in the pregnant women compared with the control group. In pregnant women with venous stasis symptoms, a venous diameter of the saphenous vein compared to those without no symptoms (5.05 ± 1.19 and 4.09 ± 0.70 mm; p = 0.011) was noted. CONCLUSIONS: Anatomical and functional changes in the venous system during pregnancy were detected by the air plethysmography and the vascular ultrasound in primigravidae. In pregnant women, the presence of venous stasis symptoms found an anatomical and functional substrate detected in the differences in diameter of the saphenous vein.

Comparison of vitrification and slow cooling for umbilical tissues.

The tissue cryopreservation maintains the cellular metabolism in a quiescence state and makes the conservation possible for an indefinite period of time. The choice of an appropriate cryopreservation protocol is essential for maintenance of cryopreserved tissue banks. This study evaluated 10 samples of umbilical cord, from which small fragments of tissue (Wharton's jelly and cord lining membrane) were subjected to two protocols of cryopreservation: slow cooling and vitrification. The samples were frozen for a period of time ranging from 5 to 78 days. The efficiency of cryopreservation was evaluated by testing cell viability, histological analysis, cell culture, cytogenetic analysis and comparison with the results of the fresh samples. The results showed that the slow cooling protocol was more efficient than the vitrification for cryopreservation of umbilical cord tissue, because it has caused fewer changes in the structure of tissue (edema and degeneration of the epithelium) and, despite the significant decrease cell viability compared to fresh samples, the ability of cell proliferation in vitro was preserved in most samples. In conclusion, this study showed that it is possible to cryopreserve small fragments of tissue from the umbilical cord and, to obtain viable cells capable of proliferation in vitro after thawing, contributing to the creation of a frozen tissue bank.

Prenatal diagnosis of congenital syngnathia by 3D ultrasound and pathological correlation.

Congenital syngnathia is a maxillomandibular fusion, and it can vary in severity from single mucosal bands (synechiae) to complete bony fusion (synostosis). Cases of combinations of bony or soft tissue adhesions between the mandible and maxilla with cleft of the lip or palate, aglossia, popliteal pterygium, and van der Woude syndrome have been reported. It is a very rare condition, with only one case report of prenatal diagnosis using two-dimensional ultrasound in the literature. We present the first case of prenatal diagnosis of congenital syngnathia by three-dimensional ultrasound and the postnatal pathology correlation.

Peripheral Neuropathy Potentially Associated to Poly (ADP-Ribose) Polymerase Inhibitors: An Analysis of the Eudravigilance Database.

Poly (ADP-Ribose) polymerase inhibitors (PARPi) have emerged as a targeted therapy in cancer treatment with promising results in various types of cancer. This work aims to investigate the profile of adverse drug reactions (ADRs) associated with PARPi through the reports provided by the Eudravigilance (EV) database. We also intend to analyze the potential association of peripheral neuropathy to PARPi. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. A total of 12,762 ICSRs were collected from the EV database. Serious cases of nervous system disorders were analyzed providing strong evidence that peripheral neuropathy was reported in a higher frequency in patients treated with niraparib. Most cases reported a not recovered/not resolved outcome and involved drug withdrawal. However, several studies suggest that PARPi attenuate chemotherapy-induced painful neuropathy. Unexpected ADRs such as peripheral neuropathy may also occur, mostly in patients taking niraparib. Further pharmacovigilance studies should be conducted in this area to clarify with more precision the toxicity profile of these drugs.

Antiphospholipid-associated thrombocytopenia or autoimmune hemolytic anemia in patients with or without definite primary antiphospholipid syndrome according to the Sapporo revised classification criteria: a 6-year follow-up study.

The updated Sapporo classification criteria for antiphospholipid syndrome (APS) only include thrombosis or pregnancy morbidity as clinical criteria. To test this notion, we studied 55 patients (80% women) with hematologic manifestations. All fulfilled the laboratory criteria for primary APS. Thirty-five patients (64%) had thrombocytopenia, 14 (25%) had autoimmune hemolytic anemia, and 6 (11%) had both. Twenty-five patients (22 women, 88%) also fulfilled one clinical criterion for APS after a median follow-up of 13.2 years (range, 1.45-37 years), whereas the remaining 30 patients (22 women, 73%) have not had any thrombotic event nor pregnancy morbidity after a median follow-up of 5.4 years (range, 0.12-24 years). No patient developed systemic lupus erythematosus during follow-up. The hematologic manifestation was asynchronous with the APS onset in 84% of patients. The response to treatment was similar regardless of the APS status. Patients with definite APS were more frequently positive for the lupus anticoagulant (63%) than lupus anticoagulant-positive patients without APS (30%; odds ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .02). Anticardiolipin or anti-ß(2)-glycoprotein-I antibodies were highly prevalent among the study groups. Our study suggests that, depending upon their antiphospholipid profile, patients with hemocytopenias appear to comprise a peculiar subset of patients with APS; some develop thrombotic and/or obstetric APS whereas others continue with hematologic APS.

Variation in ovarian follicle density during human fetal development.

PURPOSE: To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. METHODS: Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 µm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. RESULTS: The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. CONCLUSION: Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

Ultrasound evaluation of the fetal nasal bone: what is the most appropriate first-trimester cut-off point for aneuploidy screening?

PURPOSE: To establish fetal nasal bone length cut-off points for first trimester aneuploidy screening based on a normal curve of a Brazilian population. METHODS: The following tests were proposed: presence or absence of the nasal bone (NB); 2.5 and 5.0 NB percentiles relative to the normal curve; and 0.70, 0.75 and 0.80 multiples of the median (MoM) values defined in the receiver operating characteristic (ROC) curve. Nasal Bone tests were based on positive and negative likelihood ratio value detection rates (LR); the confidence interval was 95% in all tests. Cases in which ultrasonographic images of the NB were absent were not taken into account when evaluating the 2.5 and 5.0 percentiles and the 0.70, 0.75 and 0.80 MoM. RESULTS: The sample consisted of 571 fetuses (10-14 weeks). After exclusions (11) and loss of follow-up (53), the study sample was reduced to 507 patients. There were 23 Down syndrome patients among 41 aneuploid fetuses. The sensitivity of the qualitative NB test (absent vs. present) was 34.1%, and the specificity was 99.1% (+LR 37.89, -LR 0.66). An image of the nasal bone was absent in 52.2% of fetuses with the Down syndrome (+LR 58.00, -LR 0.48). CONCLUSIONS: The best tool for aneuploidy screening was the qualitative NB test (absent vs. present). Ultrasonography of the NB is a component of aneuploidy screening, and should not be used alone.

Acute obstructive apnea produces natriuresis in spontaneously hypertensive rats (SHR) by a renal nerve-dependent.

The role of renal nerve in excretion was investigated during acute obstructive apnea (OA) episodes in SHR. The animals (SHR and control, C) were presented for renal denervation (D; CD; SHRD) or undenervation (U; CU; SHRU). Tracheal catheterization was performed to induce OA via its total occlusion. Urine samples were collected every 2 min after 20 s of OA. Obstructive apnea resulted in bradycardia, hypotension, and induced elevations in the urinary measurements in SHRU, but not in CU. Conversely, the denervation increased in CD, but not in the SHRD. Urinary excretion was dependent of renal nerve in SHR during OA.