Cleofé Romagosa

CD10 expression in epithelial tissues and tumors of the gynecologic tract: a useful marker in the diagnosis of mesonephric, trophoblastic, and clear cell tumors.

We tested 417 cases of formalin-fixed, paraffin-embedded normal or hyperplastic gynecologic tissues as well as neoplasms involving the gynecologic tract with a monoclonal antibody against CD10 (clone 56C6), with special emphasis on epithelial and epithelial-like structures and tumors. CD10 was always expressed in mesonephric remnants (mesonephric remnants of the uterine cervix, epoophoron, rete ovarii) and tumors (mesonephric adenocarcinoma of the uterine cervix, tumors of wolffian origin of the broad ligament and ovary). CD10 was also positive in the syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast of normal gestations, partial and complete moles, choriocarcinoma, and placental site trophoblastic tumors. Finally, CD10 was positive in several metastatic neoplasms to the gynecologic tract (100% in metastatic renal clear cell and intestinal carcinomas and melanomas). In contrast, CD10 was almost invariably negative in müllerian epithelia of the female genital tract and in their corresponding tumors, with the exception of focal expression found in squamous epithelia and tumors with squamous differentiation. Thus, the expression of CD10 may be useful in the establishing the diagnosis of mesonephric and trophoblastic tumors and in the differential diagnosis between gynecologic clear cell carcinoma (always negative) and metastatic clear cell carcinoma of renal origin.

A Randomized Placebo-Controlled Trial of Intermittent Preventive Treatment in Pregnant Women in the Context of Insecticide Treated Nets Delivered through the Antenatal Clinic

Background Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use. Methods 1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight. Findings Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITNs use was more than 90% in both groups. Conclusions Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa. Trial Registration ClinicalTrials.gov NCT00209781

An Autopsy Study of Maternal Mortality in Mozambique: The Contribution of Infectious Diseases

Background Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. Methods and Findings We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. Conclusions In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.

miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct targets ENPEP, CK2-α, CCNJ, and MEGF9.

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3’-UTRs of ENPEP, CK2-α, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-α, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40–56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-α was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-α, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-α, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer.

Clinical malaria in African pregnant women

BackgroundThere is a widespread notion, based on limited information, that in areas of stable malaria transmission most pregnant women with Plasmodium falciparum infection are asymptomatic. This study aim to characterize the clinical presentation of malaria in African pregnant women and to evaluate the adequacy of case management based on clinical complaints.MethodsA hospital-based descriptive study between August 2003 and November 2005 was conducted at the maternity clinic of a rural hospital in Mozambique. All women attending the maternity clinic were invited to participate. A total of 2,330 women made 3,437 eligible visits, 3129 were analysed, the remainder were excluded because diagnostic results were unavailable or they were repeat visits. Women gave a standardized clinical history and had a medical exam. Malaria parasitaemia and haematocrit in capillary blood was determined for all women with signs or symptoms compatible with malaria including: presence and history of fever, arthromyalgias, headache, history of convulsions and pallor. Outcome measure was association of malaria symptoms or signs with positive blood slide for malaria parasitaemia.ResultsIn 77.4% of visits pregnant women had symptoms suggestive of malaria; 23% (708/3129) were in the first trimester. Malaria parasitaemia was confirmed in 26.9% (842/3129) of visits. Headache, arthromyalgias and history of fever were the most common symptoms (86.5%, 74.8% and 65.4%) presented, but their positive predictive values for malaria parasitaemia were low [28% (27–30), 29% (28–31), and 33% (31–35), respectively].ConclusionSymptoms suggestive of malaria were very frequent among pregnant women attending a rural maternity clinic in an area of stable malaria transmission. However, less than a third of them were parasitaemic. In the absence of microscopy or rapid diagnostic tests, a large proportion of women, including those in the first trimester of gestation, would be unnecessarily receiving antimalarial drugs, often those with unknown safety profiles for pregnancy. Accessibility to malaria diagnostic tools needs to be improved for pregnant women and drugs with a safety profile in all gestational ages are urgently needed.

Clinico-Pathological Discrepancies in the Diagnosis of Causes of Maternal Death in Sub-Saharan Africa: Retrospective Analysis

Background Maternal mortality is a major public-health problem in developing countries. Extreme differences in maternal mortality rates between developed and developing countries indicate that most of these deaths are preventable. Most information on the causes of maternal death in these areas is based on clinical records and verbal autopsies. Clinical diagnostic errors may play a significant role in this problem and might also have major implications for the evaluation of current estimations of causes of maternal death. Methods and Findings A retrospective analysis of clinico-pathologic correlation was carried out, using necropsy as the gold standard for diagnosis. All maternal autopsies (n = 139) during the period from October 2002 to December 2004 at the Maputo Central Hospital, Mozambique were included and major diagnostic discrepancies were analyzed (i.e., those involving the cause of death). Major diagnostic errors were detected in 56 (40.3%) maternal deaths. A high rate of false negative diagnoses was observed for infectious diseases, which showed sensitivities under 50%: HIV/AIDS-related conditions (33.3%), pyogenic bronchopneumonia (35.3%), pyogenic meningitis (40.0%), and puerperal septicemia (50.0%). Eclampsia, was the main source of false positive diagnoses, showing a low predictive positive value (42.9%). Conclusions Clinico-pathological discrepancies may have a significant impact on maternal mortality in sub-Saharan Africa and question the validity of reports based on clinical data or verbal autopsies. Increasing clinical awareness of the impact of obstetric and nonobstetric infections with their inclusion in the differential diagnosis, together with a thorough evaluation of cases clinically thought to be eclampsia, could have a significant impact on the reduction of maternal mortality.

Mother-to-child transmission of HIV-1: association with malaria prevention, anaemia and placental malaria*

Malaria infection may impact on mother‐to‐child transmission (MTCT) of HIV‐1. Prevention of malaria in pregnancy could thus potentially affect MTCT of HIV. We studied the impact of intermittent preventive treatment during pregnancy (IPTp) on HIV‐1 MTCT in southern Mozambique.

Seasonal variations in maternal mortality in Maputo, Mozambique: the role of malaria

Objective  To evaluate the impact of malaria on maternal death through the analysis of the seasonal variations of crude and malaria‐specific maternal mortality rates.

Contribución de la detección del virus del papiloma humano de alto riesgo al estudio de las lesiones premalignas y malignas del cérvix uterino

Fundamento y objetivo: La casi constante relacion entre infeccion por el virus del papiloma humano de alto riesgo (VPH-AR) y carcinomas y lesiones premalignas del cervix uterino plantea la posibilidad de utilizar tecnicas moleculares de deteccion del virus para mejorar los resultados de las estrategias convencionales utilizadas en el diagnostico de estas lesiones. En el presente estudio se valora la utilidad de la deteccion del VPH-AR en una unidad de patologia cervical de un centro terciario. Pacientes y metodo: A 1.005 mujeres (edad media [DE], 38,4 [12,3] anos; limites, 16-83) referidas por haber presentado en los 6 meses previos al menos una citologia con el diagnostico de atipias de significado incierto (ASCUS), lesion escamosa intraepitelial (SIL) o carcinoma, se les realizaron colposcopia, citologia cervicovaginal y/o biopsia, y deteccion del VPH-AR utilizando el test Hybrid Capture II. Resultados: Se detecto VPH en el 96% de los SIL de alto grado, en el 86% de los carcinomas de cervix, en el 86% de los SIL de bajo grado y solo en el 25% de las mujeres sin lesion y en el 0% de los carcinomas metastasicos al cervix (p < 0,001). La sensibilidad del test para la deteccion de SIL de alto grado o carcinoma fue del 90,2% y el valor predictivo negativo del 96,5% (odds ratio = 18,9; intervalo de confianza del 95%, 10,9-33,1). En los casos de ASCUS la negatividad para el VPH-AR practicamente excluyo la existencia de lesion cervical (valor predictivo negativo del 98,2%). Conclusiones: La deteccion del VPH-AR mediante el test Hybrid Capture II es util en el estudio de las enfermedades del cervix uterino, dada su alta sensibilidad para la deteccion de lesiones intraepiteliales de alto grado y carcinomas de origen cervical, asi como su utilidad en la evaluacion de las ASCUS.

Carcinoma of the fallopian tube presenting as acute pelvic inflammatory disease

BACKGROUND Primary carcinomas of the fallopian tube are rare and their preoperative diagnosis is difficult due to the lack of specific symptoms. CASES We present two tumors diagnosed in women 74 and 77 years old. On examination both patients presented as acute pelvic peritonitis with abdominal pain and tenderness with guarding and rebound, as well as fever and leukocytosis. At surgery, a left tubal carcinoma was found in each patient. Marked inflammatory and purulent reaction involving the uterus, the adnexa, and the pelvic peritoneum, and no abnormalities in the digestive tract were identified. A total hysterectomy with bilateral salpingo-oophorectomy was performed in both patients. CONCLUSION Carcinoma of the fallopian tube should be considered in the differential diagnosis of pelvic peritonitis, a previously poorly reported clinical presentation.