How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

Paediatric referrals in rural Tanzania: the Kilombero District Study – a case series

BACKGROUND: Referral is a critical part of appropriate primary care and of the Integrated Management of Childhood Illness (IMCI) strategy. We set out to study referrals from the aspect both of primary level facilities and the referral hospital in Kilombero District, southern Tanzania. Through record review and a separate prospective study we estimate referral rates, report on delays in reaching referral care and summarise the appropriateness of pediatric referral cases in terms of admission to the pediatric ward at a district hospital METHODS: A sample of patient records from primary level government health facilities throughout 1993 were summarised by age, diagnosis, whether a new case or a reattendance, and whether or not they were referred. From August 1994 to July 1995, mothers or carers of all sick children less than five years old attending the Maternal and Child Health (MCH) clinic or outpatient department (OPD) of SFDDH were interviewed using a standard questionnaire recording age, sex, diagnosis, place of residence, whether the child was admitted to the paediatric ward, and whether the child was referred. RESULTS: From record review, only 0.6% of children from primary level government facilities were referred to a higher level of care. At the referral hospital, 7.8 cases per thousand under five catchment population had been referred annually. The hospital MCH clinic and OPD were generally used by children who lived nearby: 91% (n = 7,166) of sick children and 75% (n = 607) of admissions came from within 10 km. Of 235 referred children, the majority (62%) had come from dispensaries. Almost half of the referrals (48%) took 2 or more days to arrive at the hospital. Severe malaria and anaemia were the leading diagnoses in referred children, together accounting for a total of 70% of all the referrals. Most referred children (167/235, 71%) were admitted to the hospital paediatric ward. CONCLUSIONS: The high admission rate among referrals suggests that the decision to refer is generally appropriate, but the low referral rate suggests that too few children are referred. Our findings suggest that the IMCI strategy may need to be adapted in sparsely-populated areas with limited transport, so that more children may be managed at peripheral level and fewer children need referral

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Young women's use of a microbicide surrogate: The complex influence of relationship characteristics and perceived male partners' evaluations

This is the post-print version of the article. The official published version can be found at the link below.Currently in clinical trials, vaginal microbicides are proposed as a female-initiated method of sexually transmitted infection prevention. Much of microbicide acceptability research has been conducted outside of the United States and frequently without consideration of the social interaction between sex partners, ignoring the complex gender and power structures often inherent in young women’s (heterosexual) relationships. Accordingly, the purpose of this study was to build on existing microbicide research by exploring the role of male partners and relationship characteristics on young women’s use of a microbicide surrogate, an inert vaginal moisturizer (VM), in a large city in the United States. Individual semi-structured interviews were conducted with 40 young women (18–23 years old; 85% African American; 47.5% mothers) following use of the VM during coital events for a 4 week period. Overall, the results indicated that relationship dynamics and perceptions of male partners influenced VM evaluation. These two factors suggest that relationship context will need to be considered in the promotion of vaginal microbicides. The findings offer insights into how future acceptability and use of microbicides will be influenced by gendered power dynamics. The results also underscore the importance of incorporating men into microbicide promotion efforts while encouraging a dialogue that focuses attention on power inequities that can exist in heterosexual relationships. Detailed understanding of these issues is essential for successful microbicide acceptability, social marketing, education, and use.This study was funded by a grant from National Institutes of Health (NIHU19AI 31494) as well as research awards to the first author: Friends of the Kinsey Institute Research Grant Award, Indiana University’s School of HPER Graduate Student Grant-in-Aid of Research Award, William L. Yarber Sexual Health Fellowship, and the Indiana University Graduate and Professional Student Organization Research Grant

Exclusive neuronal expression of SUCLA2 in the human brain

SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort

BACKGROUND: Estimates of the incidence and prevalence of chronic diseases can be made using established cohort studies but these estimates may have lower reliability if based purely on self-reported diagnosis. METHODS: The MRC Cognitive Function & Ageing Study (MRC CFAS) has collected longitudinal data from a population-based random sample of 13004 individuals over the age of 65 years from 5 centres within the UK. Participants were asked at baseline and after a two-year follow-up whether they had received a diagnosis of Parkinson's disease. Our aim was to make estimates of the incidence and prevalence of PD using self-reporting, and then investigate the validity of self-reported diagnosis using other data sources where available, namely death certification and neuropathological examination. RESULTS: The self-reported prevalence of Parkinson's disease (PD) amongst these individuals increases with age from 0.7% (95%CI 0.5–0.9) for 65–75, 1.4% (95%CI 1.0–1.7) for 75–85, and 1.6% (95%CI 1.0–2.3) for 85+ age groups respectively. The overall incidence of self reported PD in this cohort was 200/100,000 per year (95%CI 144–278). Only 40% of the deceased individuals reporting prevalent PD and 35% of those reporting incident PD had diagnoses of PD recorded on their death certificates. Neuropathological examination of individuals reporting PD also showed typical PD changes in only 40%, with the remainder showing basal ganglia pathologies causing parkinsonism rather than true PD pathology. CONCLUSION: Self-reporting of PD status may be used as a screening tool to identify patients for epidemiological study, but inevitably identifies a heterogeneous group of movement disorders patients. Within this group, age, male sex, a family history of PD and reduced cigarette smoking appear to act as independent risk factors for self-reported PD

Back pain reporting in young girls appears to be puberty-related

BACKGROUND: There is a large increase in back pain reporting in the early teens. In no previous study has the prevalence of low back pain been investigated in relation to the onset of puberty. The objective of this study was to establish whether the onset of puberty is associated with back pain reporting in young girls. METHODS: A subsample of 254 girls aged 8–10 years and 165 girls aged 14–16 years from a cross-sectional survey of 481 children aged 8–10 years and 325 adolescents aged 14–16 years of both sexes. Main outcome measures were back pain defined as low back pain, mid back pain, and/or neck pain in the past month. Other variables of interest were Puberty (five different stages), age, body mass index, and smoking. Independent information on onset of puberty was obtained through a physical examination and on back pain through an individual structured interview. The association was studied between onset of puberty and the outcome variable (the one month period prevalence of back pain), controlling for overweight, and smoking. Odds ratios with 95% confidence intervals were used to describe bivariate associations, logistic regression with robust standard errors was used for multivariate analyses. RESULTS: There is a highly significant trend for increased back pain reporting with increasing level of puberty until maturity is reached. The biggest leap appears between the second level (beginning of puberty) and the third level (mid puberty) and the findings remain after controlling for the covariates. These results emanate from the low back, whereas pain in the mid back and neck do not seem to be linked with pubertal stage. CONCLUSION: In girls, the reporting of low back pain increases in frequency during puberty until maturity, regardless of age. Why some girls are susceptible to back pain in the early stage of puberty is unknown