Erythropoietin, GDF15, IL6, hepcidin and testosterone levels in a large cohort of elderly individuals with anaemia of known and unknown cause

Epidemiologic studies have documented an increasing frequency of anaemia in individuals 65 yrs and older. Elderly individuals with anaemia have been categorised into the following: those with chronic disease, those with iron, B12 or folate deficiency and those with anaemia of unknown aetiology (AUE). There is considerable interest and debate as to whether AUE has an inflammatory component, is caused by cytokine dysregulation affecting production or response to erythropoietin (EPO) or iron availability or represents a novel pathologic process. Here, we compare a large cohort of AUE cases with a matched, non-anaemic control group and with individuals who have anaemia of defined cause. IL-6, hepcidin, GDF15, EPO and testosterone levels were compared. IL6 and hepcidin levels did not differ significantly between AUE and control groups, indicating that inflammation or iron restriction is not central feature of anaemia in this group. GDF15 levels were significantly elevated when comparing AUE with controls and were markedly elevated in patients with renal disease. Testosterone levels were lower in men from the AUE group compared with non-anaemic controls. EPO levels in the AUE group were increased relative to controls but were inappropriately low for the degree of anaemia. Our data indicate that an impaired EPO response, in the absence of evidence for iron restriction or inflammation, is characteristic of AUE.     

Innate immunity and systemic lupus erythematosus

Innate immunity is the first‐line host defence against pathogens and damaged host cells, and the major cellular components are phagocytes such as monocytes/macrophages, polymorphonuclear cells and dendritic cells. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the loss of tolerance to self‐antigens, the source of which has been suggested to be apoptotic cells. In this article, we will review studies on apoptosis in SLE and discuss the contribution of innate immunity abnormalities in the development of this condition.     

Placental pathology and neurological morbidity in preterm infants during the first two weeks after birth

Background

The placenta plays a crucial role during pregnancy and dysfunction causes long-term neurological problems. Identifying placenta-related risks for neurological problems shortly after birth may provide clues for early interventions aiming to improve neurological outcome.

Objective

To determine the association between placental pathology and neurological morbidity in preterm infants during the first two weeks after birth.

Study design

Placentas of 52 singleton, preterm infants (GA: 25–31 weeks, BW: 560–2250 grammes) were examined for histopathology. The infants' neurological condition shortly after birth was determined by assessing the quality of their general movements (GMs): normal, abnormal, or hypokinetic, on days 5, 8, and 15. A motor optimality score (MOS) was also assigned.

Results

Examination of the placentas revealed maternal vascular underperfusion (n = 29), ascending intrauterine infection (AIUI) (n = 19), villitis of unknown aetiology (n = 6), chronic deciduitis (n = 11), foetal thrombotic vasculopathy (FTV) (n = 9), and elevated nucleated red blood cells (NRBCs) as a marker for foetal hypoxia (n = 7). None of the placental lesions were significantly associated with the quality of GMs or MOS.

Conclusions

This study indicated that placental lesions were not associated with infants' neurological condition as measured by the quality of their general movements during the first two weeks after birth.     

Epiglottitis in Sydney before and after the introduction of vaccination against Haemophilus influenzae type b disease

BACKGROUND: Acute epiglottitis due to infection with Haemophilus influenzae type b (Hib) is much less common in children following the introduction of Hib vaccination; however, adult epiglottitis cases have not decreased. In addition, epiglottitis hospitalizations are consistently more numerous than notifications and the reason for this is not clear. AIMS: To more accurately describe the clinical, aetiological and epidemiological features of epiglottitis and to ascertain the accuracy of hospitalization data in an era of widespread Hib vaccination. METHODS: Medical records in 11 public hospitals in three area health services in New South Wales with a principal or stay diagnosis (International Classification of Diseases (ICD)-9-CM or ICD-10-AM code) of acute epiglottitis between July 1990 and June 1992 (prior to Hib vaccination = pre-vaccine era) and July 1998 and June 2000 (widespread Hib vaccination = vaccine era) were reviewed. Case definitions of epiglottitis were applied. RESULTS: One hundred and forty-two records were identified (114 pre-vaccine era and 28 vaccine era). Incorrect coding was more common in vaccine era records (32 vs 7%). Of correctly coded records, adults over 20 years old comprised the majority in the vaccine era (84 vs 17%). Hib bacteraemia was identified in 62% of cases in the pre-vaccine era compared to no cases in the vaccine era, despite equivalent blood cultures being taken between the two eras (84 vs 74%). Streptococcus pneumoniae was the only other organism isolated. Three deaths were recorded (1 child, 2 adults), all in the pre-vaccine era. CONCLUSIONS: Acute epiglottitis hospitalizations in the current Hib vaccine era are predominantly in adults, and rarely are Hib or other causative organisms identified, although microbiological data are often incomplete. The discrepancy between hospitalization and notification data appears to be due to misclassification of hospitalization records.     

Fibrinogen polymorphisms are not associated with the risk of myocardial infarction

In the Study of Myocardial Infarctions Leiden, we investigated the prevalence of three polymorphisms in the alpha- and beta-fibrinogen genes among 560 patients with a myocardial infarction and 646 control subjects. Secondly, we studied the relationships between these polymorphisms and fibrinogen activity and antigen levels. The TaqI, HaeIII and BclI polymorphisms in the fibrinogen gene were not associated with myocardial infarction. As we found an association of the rare B2 allele with fibrinogen levels and a similar, but weak, effect for the rare H2 allele, we conclude that a genetic propensity to high fibrinogen levels does not affect the risk of myocardial infarction. This is evidence against a causal role for fibrinogen levels in the aetiology of myocardial infarction.     

Understanding the pathogenesis of type 2 diabetes: can we get off the metabolic merry-go-rounds?

The aetiology of non-insulin-dependent diabetes mellitus (NIDDM) is not known. The concordance of NIDDM in identical twins and differences in the prevalence rate of NIDDM between different racial groups suggest a genetic cause. Hyperglycaemia in established diabetes is caused by a combination of hepatic insulin resistance, impaired peripheral (muscle and fat) glucose uptake and a defect in glucose-mediated insulin secretion. However, it is not known if these defects are all inherited or if one can cause the others. This uncertainty is due to the fact that hyperglycaemia per se can cause defects in insulin action and insulin secretion that resemble those found in NIDDM. Furthermore the elevated free fatty acid (FFA) levels found when NIDDM is associated with obesity are known to cause both peripheral and hepatic insulin resistance. Recently we have demonstrated the mechanism by which elevated FFA levels can cause hepatic insulin resistance. However, we also have evidence that the converse holds in that genetically engineered hepatic insulin resistance in a transgenic rat model leads to obesity. Thus an understanding of the pathogenesis of NIDDM is complicated by the fact that hyperglycaemia and obesity can be both causes and consequences of insulin resistance. To overcome these difficulties, studies in young, euglycaemic diabetes-prone subjects have been conducted. Results suggest that there may be different causes for NIDDM in different racial groups.     

Discovery of rotavirus: Implications for Child health

For centuries, acute diarrhea has been a major worldwide cause of death in young children, and until 1973, no infectious agents could be identified in about 80% of patients admitted to hospital with severe dehydrating diarrhea. In 1973 Ruth Bishop, Geoffrey Davidson, Ian Holmes, and Brian Ruck identified abundant particles of a 'new' virus (rotavirus) in the cytoplasm of mature epithelial cells lining duodenal villi and in feces, from such children admitted to the Royal Children's Hospital, Melbourne. Rotaviruses have now been shown to cause 40–50% of severe acute diarrhea in young children worldwide in both developing and developed countries, and > 600 000 young children die annually from rotavirus disease, predominantly in South-East Asia and sub-Saharan Africa. Longitudinal surveillance studies following primary infection in young children have shown that rotavirus reinfections are common. However the immune response that develops after primary infection is protective against severe symptoms on reinfection. This observation became the basis for development of live oral rotavirus vaccines. Two safe and effective vaccines are now licensed in 100 countries and in use in 17 countries (including Australia). Rotarix (GSK) is a single attenuated human rotavirus, representative of the most common serotype identified worldwide (G1P[8]). RotaTeq (Merck) is a pentavalent mixture of naturally attenuated bovine/human rotavirus reassortants representing G1, G2, G3, G4, and P(8) serotypes. Preliminary surveillance of the numbers of children requiring hospitalization for severe diarrhea, in USA, Brazil, and Australia, after introduction of these vaccines, encourages the hope that rotavirus infection need no longer be a threat to young children worldwide.     

Viral and bacterial aetiology of community‐acquired pneumonia in adults

Please cite this paper as: Huijskens et al. (2012) Viral and bacterial aetiology of community‐acquired pneumonia in adults. Influenza and Other Respiratory Viruses 7(4), 567–573. Background Modern molecular techniques reveal new information on the role of respiratory viruses in community‐acquired pneumonia. In this study, we tried to determine the prevalence of respiratory viruses and bacteria in patients with community‐acquired pneumonia who were admitted to the hospital. Methods Between April 2008 and April 2009, 408 adult patients (aged between 20 and 94 years) with community‐acquired pneumonia were tested for the presence of respiratory pathogens using bacterial cultures, real‐time PCR for viruses and bacteria, urinary antigen testing for Legionella and Pneumococci and serology for the presence of viral and bacterial pathogens. Results Pathogens were identified in 263 (64·5%) of the 408 patients. The most common single organisms in these 263 patients were Streptococcus pneumoniae (22·8%), Coxiella burnetii (6·8%) and influenza A virus (3·8%). Of the 263 patients detected with pathogens, 117 (44·5%) patients were positive for one or more viral pathogens. Of these 117 patients, 52 (44·4%) had no bacterial pathogen. Multiple virus infections (≥2) were found in 16 patients. Conclusion In conclusion, respiratory viruses are frequently found in patients with CAP and may therefore play an important role in the aetiology of this disease.     

Spectrum of congenital heart disease in Malta. An excess of lesions causing right ventricular outflow tract obstruction in a population-base study

Aims To quantify birth prevalence and spectrum of congenital heartdisease in the Island population of Malta, and compare theserates with previous studies. Methods All patients diagnosed as having congenital heart disease byechocardiography, cardiac catheteriz-ation, surgery or post-mortemby 1 year of age between 1990–1994 were included. Therewere 231 cases of live born congenital heart disease with abirth prevalence of 8·8/1000 live births. The commonestlesions were ven-tricular septal defect, pulmonary stenosisand tetralogy of Fallot. The rates of individual lesions werecompared with two recent epidemiological studies with similarmethodologies. Results Although the overall birth prevalence of congenital heart diseasewas similar in three studies, significantly higher rates ofpulmonary stenosis, tetralogy of Fallot and double outlet rightventricle were found in Malta, all of which predispose to rightventricular outflow tract obstruction. In contrast, there werelower rates of lesions causing left ventricular outflow tractobstruction. A higher rate of ventricular septal defect wasalso found. The Maltese gene pool may contain an inherent predispositiontowards lesions causing right ventricular outflow tract obstruction.     

Cytomegalovirus, Epstein-Barr virus and risk of breast cancer before age 40 years: a case-control study

We investigated whether there is an association between cytomegalovirus (CMV) and Epstein-Barr virus (EBV) IgG levels and risk of breast cancer before age 40 years. CMV and EBV IgG levels were measured in stored plasma from 208 women with breast cancer and 169 controls who participated in the Australian Breast Cancer Family Study (ABCFS), a population-based case-control study. CMV and EBV IgG values were measured in units of optical density (OD). Cases and controls did not differ in seropositivity for CMV (59 and 57% respectively; P=0.8) or EBV (97 and 96% respectively; P=0.7). In seropositive women, mean IgG values were higher in cases than controls for CMV (1.20 vs 0.98 OD, P=0.005) but not for EBV (2.65 vs 2.57 OD, P=0.5). The adjusted odds ratios per OD unit were 1.46 (95% CI 1.06-2.03) for CMV IgG and 1.11 (0.93-1.33) for EBV IgG. The higher mean CMV IgG levels found in women with breast cancer could be the result of a more recent infection with CMV, and may mean that late exposure to CMV is a risk factor for breast cancer.