Occupational exposure to ionizing radiation is associated with autoimmune thyroid disease

CONTEXT: The thyroid gland is a potential target organ for radiation-related damage. OBJECTIVE: The aim of the analysis was to investigate the association between occupational exposure to ionizing radiation and autoimmune thyroid disease (AITD). DESIGN: Our design was the cross-sectional Study of Health in Pomerania. SETTING: The setting was the general community. SUBJECTS: Analyses were performed in a population-based sample of 4299 subjects. Among them, 160 persons reported a history of occupational exposure to ionizing radiation. MAIN OUTCOME MEASURE: AITD was defined as the combined presence of hypoechogenicity in thyroid ultrasound and antithyroxiperoxidase antibodies greater than 200 IU/ml. RESULTS: Females with occupational exposure to ionizing radiation had more often AITD than nonexposed females (10.0 vs. 3.4%; P < 0.05). This association persisted after adjustment for relevant confounders (odds ratio, 3.46; 95% confidence interval, 1.16-10.31; P < 0.05). In males, there were too few subjects who fulfilled the criteria of AITD, but the association between the exposure to radiation and hypoechogenicity of the thyroid gland barely missed statistical significance (odds ratio, 2.20; 95% confidence interval, 0.92-5.26; P = 0.08). In both females and males, subjects who reported a length of exposure of more than 5 yr exhibited the highest risk of the endpoints. CONCLUSIONS: We conclude that occupational exposure to ionizing radiation is related to the risk of AITD. The usage of thyroid protection shields by radiation workers is strongly recommended.     

An analysis of the genetic factors involved in testicular descent in a cohort of 14 male patients with anorchia

Anorchia, or the "vanishing testis syndrome," is characterized by the absence of testis in a 46,XY individual with a male phenotype. The etiology is unknown; however, the familial occurrence of the disease and the association of this phenotype with 46,XY gonadal dysgenesis has led to the suggestion that genetic factors, which play a role in testicular determination, may be involved. Alternatively, exploratory laparoscopy has suggested that anorchia may be caused by a prenatal testicular vascular accident associated with torsion during testicular descent. We screened a cohort of 14 boys with bilateral anorchia for mutations in the Y chromosome-linked testis-determining gene SRY (sex-determining region, Y chromosome); in the gene necessary for correct testicular descent, INSL3; and in the gene of its receptor (LGR8). Mutations in the INSL3 gene and the LGR8 T222P mutation are known to cause cryptorchidism. We confirmed previous reports that mutations in the SRY gene are not associated with anorchia. Although a common polymorphism was identified in the INSL3 gene, no mutations were observed. The recurrent T222P mutation in the LGR8 gene was not found in any of the patients. These data show for the first time a lack of association between genetic factors necessary for correct testicular descent and anorchia.     

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily posttransplantation for determination of bile composition. Hepatic expression of bile transporters was studied before and after transplantation. Histopathological criteria as well as biliary concentrations of alkaline phosphatase (ALP) and gamma-glutamyltransferase (gamma-GT) were used to quantify bile duct injury. RESULTS: Early after transplantation, bile salt secretion increased more rapidly than phospholipid secretion, resulting in high biliary bile salt/phospholipid ratio (BA/PL). In parallel with this, mRNA levels of the bile salt transporters NTCP and BSEP increased significantly after transplantation, whereas phospholipid translocator MDR3 mRNA levels remained unchanged. Bile duct injury correlated significantly with bile salt secretion and was associated with a high biliary BA/PL ratio. CONCLUSIONS: Bile salt secretion after human liver transplantation recovers more rapidly than phospholipid secretion. This results in cytotoxic bile formation and correlates with bile duct injury. These findings suggest that endogenous bile salts have a role in the pathogenesis of bile duct injury after liver transplantation.     

Translation of clinical prediction rules for febrile children to primary care practice: an observational cohort study

BackgroundClinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice.AimTo evaluate the diagnostic value of published CPRs for febrile children in primary care.MethodAlarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. ‘Referral to emergency department (ED)’ was used as a proxy outcome measure for ‘serious infection’. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area).ResultsA total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0–4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were ‘ill appearance’, ‘inconsolable’, and ‘abnormal circulatory or respiratory signs’. The height of the CPR’s predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months.ConclusionPublished CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice.     

Predicting prolonged duration of fever in children: a cohort study in primary care

Background

Fever in children in primary care is commonly caused by benign infections, but often worries parents. Information about the duration of fever and its predictors may help in reassuring parents, leading to diminished consultation of health care.

Aim

To determine which signs and symptoms predict a prolonged duration of fever in febrile children in primary care and evaluate whether C-reactive protein (CRP) measurement has an additive predictive value for these symptoms.

Design and setting

A prospective cohort study at a GPs’ cooperative (GPC) out-of-hours service.

Method

Children (aged 3 months to 6 years) presenting with fever as stated by the parents were included. Exclusion criteria were no communication in Dutch possible, previous enrolment in the study within 2 weeks, referral to the hospital directly after visiting the GPC, or no informed consent. The main outcome measure was prolonged duration of fever (>3 days) after initial contact.

Results

Four-hundred and eighty children were analysed, and the overall risk of prolonged duration was 13% (63/480). Multivariate analysis combined model of patient history and physical examination showed that ‘sore throat’ (OR 2.8; 95% CI = 1.30 to 6.01) and ‘lymph nodes palpable’ (OR 1.87; 95% CI = 1.01 to 3.49) are predictive for prolonged duration of fever. The discriminative value of the model was low (AUC 0.64). CRP had no additive value in the prediction of prolonged duration of fever (OR 1.00; 95% CI = 0.99 to 1.01).

Conclusion

The derived prediction model indicates that only a few signs and symptoms are related to prolonged duration of fever. CRP has no additional value in this model. Overall, because the discriminative value of the model was low, the duration of fever cannot be accurately predicted.     

The clinimetric properties of the World Health Organization Disability Assessment Schedule II in early inflammatory arthritis

OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.     

Diagnostic approaches to suspected deep vein thrombosis and pulmonary embolism

The present paper aims at reviewing our present knowledge on the diagnosis of deep vein thrombosis and pulmonary embolism with a particular emphasis on clinically suspected outpatients. The various contemporary diagnostic tools (including clinical probability assessment, fibrin D-Dimer measurement, venous compression ultrasonography, ventilation/perfusion lung scintigraphy, helical CT scan, and echocardiography) are presented and rational sequential strategies are discussed in their various aspects, including validation in outcome studies, and cost-effectiveness analyses.     

Corneal epithelial stem cells for corneal injury

Introduction: Ocular surface diseases with limbal insufficiency represent a therapeutic challenge for restoring vision. This corneal deficiency includes both classical ocular diseases (as chemical burns) and rare ocular diseases (as congenital aniridia and ocular cicatricial pemphigoid).

Areas covered: Our understanding of limbal epithelial stem cells (LESCs) has increased the potential for treatment options. Pharmacological treatment strategies (as regenerating agent ophthalmic solutions) and especially surgical treatment strategies are available. Isolated LESCs can be produced by limbal primary cultures obtained from explants or cell suspensions. We review the latest cornea surgery techniques.

Expert opinion: The adjunction of human limbal mesenchymal cells as a support for limbal stem cell primary cultures appears to be of great interest. Recently, human-induced pluripotent stem cells have allowed the generation of minicorneal organoids. This potential means of creating a three-dimensional cornea with in vitro maturation opens up important research areas for corneal regeneration therapy.     

Hydrogen sulfide: physiological properties and therapeutic potential in ischaemia

Hydrogen sulfide (H₂S) has become a molecule of high interest in recent years, and it is now recognized as the third gasotransmitter in addition to nitric oxide and carbon monoxide. In this review, we discuss the recent literature on the physiology of endogenous and exogenous H₂S, focusing upon the protective effects of hydrogen sulfide in models of hypoxia and ischaemia.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6