Effect of malaria on soluble transferrin receptor levels in Tanzanian infants

The diagnosis of iron deficiency anemia in malaria endemic areas is complicated by the influence of the infection on the laboratory tests conventionally used to assess iron status. Determination of soluble transferrin receptor (sTfR) levels has been shown to be a sensitive indicator of iron deficiency in adults and is not affected by a range of infectious and inflammatory conditions. The utility of sTfR levels in the diagnosis of iron deficiency in malaria endemic areas remains unresolved. Three hundred and fourteen infants in a rural area of southern Tanzania living under conditions of intense and perennial malaria transmission were studied to determine the utility of sTfR plasma levels in the assessment of iron deficiency anemia. Independent of the presence of anemia, malaria parasitemia was associated with a significant increase in sTfR plasma levels that were even higher than those found in iron deficiency anemia. We conclude that the measurement of sTfR levels does not have a role in the diagnosis of iron deficiency anemia in young children exposed to malaria infection.     

Solitary rectal ulcer syndrome

A retrospective study of 20 cases of biopsy-proven solitary rectal ulcer syndrome seen at a large oncology hospital which highlight the clinicopathologic features is presented. Thirty five percent of patients were in their sixth decade and there was a male preponderance of 2.3∶1. All patients presented with anorectal symptoms. Eighty five percent had normal abdominal findings and seventy five percent had positive findings on rectal examinations. Fifty four percent had a diagnosis of carcinoma of the rectum on barium enema studies. On sigmoidoscopy, a solitary ulcer was found in 80 percent; 50 percent had lesions between 6 and 10 cm from the anal verge, and 40 percent had the lesion on the anterior rectal wall. All patients were treated conservatively and 35 percent were disease free at the end of five years, while 30 percent had persisting symptoms.     

Repositioning chloroquine and metformin to eliminate cancer stem cell traits in pre-malignant lesions

Ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium-originated carcinomas at their non-invasive, pre-malignant stages. Such ideal molecules, which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells (CSCs) to by-pass tumour suppressor barriers, might already exist. We here illustrate how system biology strategies for repositioning existing FDA-approved drugs may accelerate our therapeutic capacity to eliminate CSC traits in pre-invasive intraepithelial neoplasias. First, we describe a signalling network signature that overrides bioenergetics stress- and oncogene-induced senescence (OIS) phenomena in CSCs residing at pre-invasive lesions. Second, we functionally map the anti-malarial chloroquine and the anti-diabetic metformin (“old drugs”) to their recently recognized CSC targets (“new uses”) within the network. By discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self-renewal of CSCs we finally underscore the expected translational impact of the “old drugs–new uses” repurposing strategy to open a new CSC-targeted chemoprevention era.     

Maternal Infection in Pregnancy and Risk of Asthma in Offspring

This study estimates the effect of maternal infections during pregnancy on childhood asthma. One-thousand four-hundred and twenty-eight pregnant women were prospectively followed using structured interviews and chart review until their child’s 6th year of life. Infections were identified from outpatient and hospital visits. Childhood asthma was defined as physician diagnosis with symptoms at age six. Adjusted odds ratios were calculated from multivariable logistic regression models. Six-hundred and thirty-five women experienced an infection during pregnancy. Among antepartum infections, maternal urinary tract infections were significantly associated with childhood asthma (aOR 1.60, 95 % CI 1.12–2.29). Chorioamnionitis and maternal group beta streptococcus colonization were not significantly associated with an increased risk in childhood asthma. This study found an increased risk of asthma in children of women diagnosed with urinary tract infections during pregnancy, while other maternal infections did not increase the risk.     

Measurement of placental alpha-microglobulin-1 in cervicovaginal discharge to diagnose rupture of membranes

OBJECTIVE: To compare the accuracy of an immunoassay to measure levels of placental alpha-microglobulin-1 in cervicovaginal secretions with that of conventional clinical assessment for the diagnosis of rupture of membranes. METHODS: A prospective observational study was performed in consecutive patients with signs or symptoms of rupture of membranes at Seoul National University Hospital from March 2005 to February 2006. Initial evaluation included both the standard clinical evaluation for rupture of membranes and placental alpha-microglobulin-1 immunoassay. Rupture of membranes was diagnosed if fluid was seen leaking from the cervical os or if two of the following three conditions were present: pooling of fluid, positive nitrazine test, or ferning. Rupture of membranes was diagnosed definitively on review of the medical records after delivery. RESULTS: Of 184 patients (11-42 weeks of gestation), rupture of membranes was diagnosed at initial presentation in 76% (139 of 184) using conventional clinical assessment and 88% (161 of 184) using placental alpha-microglobulin-1 immunoassay. Follow-up confirmed that a total of 159 of 183 patients (87%) had rupture of membranes at their initial presentations. Using this longitudinal assessment as the clinical gold standard, placental alpha-microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 98.7% (157 of 159), specificity of 87.5% (21 of 24), positive predictive value of 98.1% (157 of 160), and negative predictive value of 91.3% (21 of 23). Placental alpha-microglobulin-1 immunoassay was better than both the conventional clinical assessment and the nitrazine test alone in confirming the diagnosis of rupture of membranes. CONCLUSION: Measurement of placental alpha-microglobulin-1 in cervicovaginal secretions is superior to conventional clinical assessment in the diagnosis of rupture of membranes. LEVEL OF EVIDENCE: II.