Hepatic iron overload in blacks and whites: a comparative autopsy study

OBJECTIVE: Genetic susceptibility to iron loading is an important factor in the development of iron overload in Africans. This suggests that persons of African descent may be at risk to develop iron overload with its attendant complications, but relatively little is known about hepatic iron overload among blacks. The aim of this study was to compare the prevalence, histological features, and clinical correlates of hepatic iron overload in a group of autopsied black and white veterans. METHODS: Hepatic iron concentrations (HIC) were determined on liver tissue from autopsies performed at the John Cochran Veterans Affairs Medical Center during the period 1993 to 1996. Clinical information was obtained from autopsy protocols. Sections from livers in which the HIC exceeded the upper limit of normal were examined histologically. RESULTS: Of 256 specimens, 99 were from blacks (39%), whereas 157 were from whites (61%). Thirty-one blacks (31%) had an elevated HIC versus 44 whites (28%) (ns). In the majority of these cases (18 blacks, 30 whites), the HIC was less than twice the upper limit of normal. Nine of 15 subjects with an HIC greater than twice the upper limit of normal and no evident cause of secondary iron overload were black. CONCLUSIONS: The prevalence of mild-to-moderate hepatic iron overload was similar in this group of black and white veterans. Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population.     

Effects of gender and age on esophageal biomechanical properties and sensation

OBJECTIVES: The effects of gender and age on human esophageal function is poorly defined. Our aim was to investigate the sensory perception and the biomechanical properties of the esophagus both at the smooth muscle and the striated muscle segments in age- and gender-matched healthy subjects. Eleven older individuals (five men and six women, aged 55-82 yr) and 11 younger healthy individuals (five male and six female, aged 22-45 yr) participated in this study. METHODS: Graded balloon distentions were performed at the striated muscle and the smooth muscle segments of the esophagus in a random order using impedance planimetry. Impedance planimetry facilitated simultaneous assessments of the biomechanical properties and sensory perception. RESULTS: We found that both at the striated and smooth muscle segments, the cross-sectional area, circumferential wall tension-strain relationship and the sensory thresholds were similar between men and women. In contrast, at both of these segments, the cross-sectional area was larger (p < 0.05), the circumferential wall tension-strain association had shifted significantly (p < 0.05) to the left (i.e., the wall was stiffer), and the median thresholds for discomfort and pain were higher (p < 0.05) in older subjects. The biomechanical properties and thresholds for sensory perception also varied between the two esophageal segments. CONCLUSIONS: Aging was associated with a larger lumen and a stiffer but less sensitive esophageal wall. Thus, aging but not gender may influence esophageal function.     

Issues in cross‐cultural validity: Example from the adaptation,reliability, and validity testing of a Turkish version of the Stanford Health Assessment Questionnaire

Objective

Guidelines have been established for cross‐cultural adaptation of outcome measures. However, invariance across cultures must also be demonstrated through analysis of Differential Item Functioning (DIF). This is tested in the context of a Turkish adaptation of the Health Assessment Questionnaire (HAQ).

Methods

Internal construct validity of the adapted HAQ is assessed by Rasch analysis; reliability, by internal consistency and the intraclass correlation coefficient; external construct validity, by association with impairments and American College of Rheumatology functional stages. Cross‐cultural validity is tested through DIF by comparison with data from the UK version of the HAQ.

Results

The adapted version of the HAQ demonstrated good internal construct validity through fit of the data to the Rasch model (mean item fit 0.205; SD 0.998). Reliability was excellent (α = 0.97) and external construct validity was confirmed by expected associations. DIF for culture was found in only 1 item.

Conclusions

Cross‐cultural validity was found to be sufficient for use in international studies between the UK and Turkey. Future adaptation of instruments should include analysis of DIF at the field testing stage in the adaptation process.

     

Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function

OBJECTIVE: To document the effectiveness, including the longterm effect, of a course of intravenous (IV) pulses of methylprednisolone (MP) and cyclophosphamide (CYC) in patients with scleroderma (SSc) who had evidence of lung inflammation on high resolution computer tomographic (HRCT) scan of the chest. METHODS: Fourteen consecutive patients with SSc and lung involvement were treated with 6 pulses of IV MP (10 mg/kg) and IV CYC (15 mg/kg) given at 3-4 weekly intervals. HRCT scans and lung function tests were performed at baseline and after the 6th pulse. Further lung function tests were repeated at 12 months and annually thereafter. RESULTS: Modified Rodnan skin scores improved significantly by 35% from a median baseline score of 17 (IQR 14-26.5) to a posttreatment score of 13 (IQR 10.5-18.5; p = 0.0058). HRCT scan scores improved significantly (p = 0.04). Twelve of 13 patients experienced either improvement or stabilization of the HRCT score. Median DLCO and lung volumes remained stable during the first 12 months. After a median followup of 26 months (IQR 19-43), 67% of patients experienced deterioration in DLCO. Median deterioration was 23% (IQR 44-0.6), with the median rate of deterioration of the predicted value of the DLCO/month being 0.87% (IQR 1.24-0.02). The treatment was safe and well tolerated. CONCLUSION: This IV regimen stabilized lung disease in patients with SSc. When treatment was stopped, or reduced in intensity, a deterioration in lung function occurred in the majority of patients. Rate of deterioration of DLCO may be a useful marker for determining the intensity of treatment. These findings have implications for treating lung disease and designing clinical trials in patients with SSc.     

Age at first drink and the first incidence of adult-onset DSM-IV alcohol use disorders

Background: Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. Methods: This study examined associations between AFD (ages <15 and 15–17 vs. 18+ years) and first incidence of DSM‐IV alcohol dependence, abuse, and specific AUD criteria over a 3‐year follow‐up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors. Results: After adjusting for all risk factors, the incidence of dependence was increased for AFD < 15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD <15 and 15 to 17 years (OR = 1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages <18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy‐volume drinkers. In a population of low‐risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (<18) and the incidence of dependence (OR = 3.79) and continued drinking despite physical/psychological problems (OR = 2.71), but no association with incidence of abuse. Conclusions: There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision‐making and/or reward‐processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low‐risk adolescents.     

MicroRNAs in laser-induced choroidal neovascularization in mice and rats: their expression and potential therapeutic targets

Choroidal neovascularization characterizes wet age-related macular degeneration. Choroidal neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis. A primary cause of choroidal neovascularization pathogenesis is alterations in pro-and anti-angiogenic factors derived from the retinal pigment epithelium, with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal neovascularization. MicroRNAs(miRNAs) which are short, non-coding, endogenous RNA molecules have a major role in regulating various pathological processes, including inflammation and angiogenesis. A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular degeneration. Upregulation of miR-505(days 1 and 3 post-laser), miR-155(day 14) occurred in retina; miR-342-5 p(days 3 and 7), miR-126-3 p(day 14) in choroid; miR-23 a, miR-24, miR-27 a(day 7) in retina/choroid; miR-505(days 1 and 3) in retinal pigment epithelium/choroid; downregulation of miR-155(days 1 and 3), miR-29 a, miR-29 b, miR-29 c(day 5), miR-93(day 14), miR-126(day 14) occurred in retinal pigment epithelium/choroid. Therapies using miRNA mimics or inhibitors were found to decrease choroidal neovascularization lesions. Choroidal neovascularization development was reduced by overexpression of miR-155, miR-188-5 p, miR-(5,B,7), miR-126-3 p, miR-342-5 p, miR-93, miR-126, miR-195 a-3 p, miR-24, miR-21, miR-31, miR-150, and miR-184, or suppression of miR-505, miR-126-3 p, miR-155, and miR-23/27. Further studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported findings. Important experimental variables need to be standardized; these include the strain and age of animals, gender, number and position of laser burns to the eye, laser parameters to induce choroidal neovascularization lesions including wavelength, power, spot size, and duration.     

How do people with knee pain from osteoarthritis respond to a brief video delivering empowering education about the condition and its management?

ObjectiveTo evaluate responses by people with knee osteoarthritis to a brief educational video about their condition that aimed to empower and motivate effective self-management. The video content addressed psychosocial contributors to pain and barriers to behaviour change.MethodsA mixed methods design, including a survey and semi-structured interviews, was used to collect data from 118 people (46–83 years, 78% female) with knee osteoarthritis.ResultsQuantitative data analysis showed the video was rated positively on 0–6 scales for enjoyability (mean 5.0), helpfulness (4.9), relevance (5.0) and believability (5.4). The majority would recommend the video (89%), learned new information (78%) and/or reported intentions to change behaviour (78%). A minority disliked aspects of the video (23%). The thematic analyses identified three main themes: Reactions to the video, including emotions; Learning from the video, including new knowledge and empowerment, but also unmet information needs or disagreement; and Intentions, including behaviour changes, cognitive changes and help seeking.ConclusionEducation about knee osteoarthritis with a focus on empowerment is well received by people with the condition, although some discordant views emerged.Practice implicationsThe educational video about knee osteoarthritis can be recommended to promote effective self-management and counteract potential drawbacks associated with biomedical-based education.     

The epidemiology of milk allergy in US children

BackgroundMilk is one of the most common food allergies in US children, yet little is known about its distribution and diagnosis.ObjectiveTo better understand current pediatric milk allergy distribution and diagnosis trends in the United States.MethodsA randomized, cross-sectional survey was administered to parents belonging to a representative sample of US households with children from June 2009 to February 2010. Data from 38,480 parents regarding demographic characteristics, allergic symptoms associated with food ingestion, and methods used to diagnose food allergy were collected and analyzed as weighted proportions. Adjusted models were estimated to examine association of these aspects with odds of milk allergy.ResultsOf the 3,218 children identified with food allergy, 657 (19.9%) were reported to have milk allergy. Asian (odds ratio [OR], 0.5) and black (OR, 0.4) children were half as likely as white children to develop milk allergy. The highest percentage of milk-allergic children (23.8%) were aged 6 to 10 years, and the lowest percentage of milk-allergic children (15.0%) were aged 11 to 15 years. Nearly one-third (31.4%) of children with milk allergy had a history of severe reactions. Compared with children with other food allergies, children with milk allergy had a higher odds of having physician-diagnosed allergy (OR, 1.7) and were twice as likely (OR, 2.1) to outgrow their milk allergy.ConclusionChildhood milk allergy, which accounts for one-fifth of US food allergies, is less prevalent among Asian and black children than white children. Although less than half of children with milk allergy received confirmatory testing, it is the most commonly diagnosed food allergy.