Protecting workers in the temporary staffing industry.

BACKGROUND: Workers hired through temporary staffing companies have a high rate of severe and fatal injuries despite the legally mandated, shared responsibility of the temporary staffing company and the host company to assure safe work. AIMS: The aim of this study was to elucidate the perspective of temporary staffing personnel on approaches to mitigating injury risk among the workers they hire. METHODS: Based on a conceptual model representing the interplay between work and health, we conducted a 'brainstorm' of temporary staffing personnel regarding perceived barriers to protecting temporary workers. A content/context analysis used standard qualitative methods, and the findings were triangulated with notes taken during the discussion. RESULTS: Temporary staffing employers describe loss of control of the working conditions once workers are placed at host/client companies. Further, they describe a contentious relationship between temporary staffing and host companies, where it is difficult to hold host companies to account. Other barriers to providing temporary workers with a safe work environment include the temp companies' lack of knowledge of site-specific hazards, the poor quality of onsite Occupational Safety and Health training, and ignoring Occupational Safety and Health Administration (OSHA) requirements. CONCLUSIONS: The perspective of temporary staffing companies should be considered to address the lack of cooperation and shifted responsibility described in this study. Policy and practice changes could include requiring contract language, implementing communication about safety, either sharing workers' compensation purchase or removing exclusive remedy protections from hosts, and prescribing safety training, such as an OSHA 10-h programme. Suggested interventions need further study.

Thermally enhanced polyolefin composites: fundamentals, progress, challenges, and prospects.

The low thermal conductivity of polymers is a barrier to their use in applications requiring high thermal conductivity such as electronic packaging, heat exchangers, and thermal management devices. Polyolefins represent about 55% of global thermoplastic production, and therefore improving their thermal conductivity is essential for many applications. This review analyzes the advances in enhancing the thermal conductivity of polyolefin composites. First, the mechanisms of thermal transport in polyolefin composites and the key parameters that govern conductive heat transfer through the interface between the matrix and the filler are discussed. Then, the advantage and limitations of the current methods for measuring thermal conductivity are analyzed. Moreover, the progress in predicting the thermal conductivity of polymer composites using modeling and simulation is discussed. Furthermore, polyolefin composites and nanocomposites with different thermally conductive fillers are reviewed and analyzed. Finally, the key challenges and future directions for developing thermally enhanced polyolefin composites are outlined.

A bibliometric study of the top 100 most-cited randomized controlled trials, systematic reviews and meta-analyses published in endodontic journals.

AIM: To identify and analyse the main features of the top 100 most-cited randomized controlled trials, systematic reviews and meta-analyses published in endodontic journals from 1961 to 2018. METHODOLOGY: The Clarivate Analytics' Web of Science 'All Databases' was used to search and analyse the 100 most frequently cited randomized controlled trials, systematic reviews and meta-analyses having 'randomized', 'randomised', 'randomized controlled', 'randomised controlled', 'randomized controlled trial', 'randomized controlled trials', 'clinical trial', 'systematic', 'systematic review', 'meta-analysis', and 'meta-analyses' in the title section. The 'International Endodontic Journal', 'Journal of Endodontics', 'Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology', 'Australian Endodontic Journal', 'Endodontics & Dental Traumatology', 'Endo-Endodontic Practice Today' and 'European Endodontic Journal' were included in the publication name section. After ranking the articles in a descending order based on their citation counts, each article was cross-matched with the citation counts in Elsevier's Scopus and Google Scholar. The articles were analysed, and information on citation counts, citation density, year of publication, contributing authors, institutions and countries, journal of publication, study design, topic of the article and keywords was extracted. RESULTS: The citation counts of the 100 most-cited articles varied from 235 to 20 (Web of Science), 276 to 17 (Scopus) and 696 to 1 (Google Scholar). The year in which the top 100 articles were published was 2010 (n = 13). Among 373 authors, the greatest number of articles was associated with three individuals namely Reader A (n = 5), Beck M (n = 5) and Kvist T (n = 5). Most of the articles originated from the United States (n = 24) with the greatest contribution from Ohio State University (USA) (n = 5). Randomized controlled trials were the most frequent study design (n = 45) followed by systematic reviews (n = 30) with outcome studies of root canal treatment being the major topic (n = 35). The Journal of Endodontics published the largest number of included articles (n = 70) followed by the International Endodontic Journal (n = 27). Among 259 unique keywords, meta-analysis (n = 23) and systematic review (n = 23) were the most frequently used. CONCLUSION: This study has revealed that year of publication had no obvious impact on citation count. The bibliometric analysis highlighted the quantity and quality of research, and the evolution of scientific advancements made in the field of Endodontology over time. Articles before 1996, that is prior to the CONSORT statement that encouraged authors to include specific terms in the title and keywords, may not have been included in this electronic search.

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.

Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.

Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.

Large interindividual variability has been observed in the metabolism of CYP2C19 substrates in vivo. The study aimed to evaluate sources of this variability in CYP2C19 activity, focusing on CYP2C19 diplotypes and the cytochrome P450 oxidoreductase (POR). CYP2C19 gene analysis was carried out on 347 human liver samples. CYP2C19 activity assayed using human liver microsomes confirmed a significant a priori predicted rank order for (S)-mephenytoin hydroxylase activity of CYP2C19*17/*17 > *1B/*17 > *1B/*1B > *2A/*17 > *1B/*2A > *2A/*2A diplotypes. In a multivariate analysis, the CYP2C19*2A allele and POR protein content were associated with CYP2C19 activity. Further analysis indicated a strong effect of the CYP2C19*2A, but not the *17, allele on both metabolic steps in the conversion of clopidogrel to its active metabolite. The present study demonstrates that interindividual variability in CYP2C19 activity is due to differences in both CYP2C19 protein content associated with gene diplotypes and the POR concentration.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.58.

Effects of Varying Levels of Fungal (Arachniotus sp.) Treated Wheat Straw as an Ingredient of Total Mixed Ration on Growth Performance and Nutrient Digestibility in Nili Ravi Buffalo Calves.

The study was carried out to explore the effects of replacing wheat straw with fungal treated wheat straw as an ingredient of total mixed ration (TMR) on the growth performance and nutrient digestibility in Nili Ravi buffalo male calves. Fungal treated wheat straw was prepared using Arachniotus sp. Four TMRs were formulated where wheat straw was replaced with 0 (TMR1), 33 (TMR2), 67 (TMR3), and 100% (TMR4) fungal treated wheat straw in TMR. All TMRs were iso-caloric and iso-nitrogenous. The experimental TMRs were randomly assigned to four groups of male calves (n = 6) according to completely randomized design and the experiment continued for four months. The calves fed TMR2 exhibited a significant improve in dry matter intake, average daily weight gain, feed conversion ratio and feed economics compared to other groups. The same group also showed higher digestibility of dry matter, crude protein, neutral-, and acid detergent fibers than those fed on other TMRs. It is concluded that TMR with 33% fungal-treated wheat straw replacement has a potential to give an enhanced growth performance and nutrient digestibility in male Nili Ravi buffalo calves.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 3.

Detailed, country-specific epidemiological data are needed to characterize the burden of chronic hepatitis C virus (HCV) infection around the world. With new treatment options available, policy makers and public health officials must reconsider national strategies for infection control. In this study of 15 countries, published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates were gathered from the literature and validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Iran and Lebanon to 4.2% in Pakistan. The largest viraemic populations were in Pakistan (7 001 000 cases) and Indonesia (3 187 000 cases). Injection drug use (IDU) and a historically unsafe blood supply were major risk factors in most countries. Diagnosis, treatment and liver transplant rates varied widely between countries. However, comparison across countries was difficult as the number of cases changes over time. Access to reliable data on measures such as these is critical for the development of future strategies to manage the disease burden.

Phenotypic spectrum associated with PTCHD1 deletions and truncating mutations includes intellectual disability and autism spectrum disorder.

Studies of genomic copy number variants (CNVs) have identified genes associated with autism spectrum disorder (ASD) and intellectual disability (ID) such as NRXN1, SHANK2, SHANK3 and PTCHD1. Deletions have been reported in PTCHD1 however there has been little information available regarding the clinical presentation of these individuals. Herein we present 23 individuals with PTCHD1 deletions or truncating mutations with detailed phenotypic descriptions. The results suggest that individuals with disruption of the PTCHD1 coding region may have subtle dysmorphic features including a long face, prominent forehead, puffy eyelids and a thin upper lip. They do not have a consistent pattern of associated congenital anomalies or growth abnormalities. They have mild to moderate global developmental delay, variable degrees of ID, and many have prominent behavioral issues. Over 40% of subjects have ASD or ASD-like behaviors. The only consistent neurological findings in our cohort are orofacial hypotonia and mild motor incoordination. Our findings suggest that hemizygous PTCHD1 loss of function causes an X-linked neurodevelopmental disorder with a strong propensity to autistic behaviors. Detailed neuropsychological studies are required to better define the cognitive and behavioral phenotype.

Bartonella henselae infection-associated vasculitis and crescentic glomerulonephritis leading to renal allograft loss.

Bartonella henselae (BH) is the main cause of cat scratch disease (CSD), which more typically presents as a self-limited localized suppurative lymphadenopathy in immunocompetent individuals. In contrast, immunocompromised patients commonly have systemic disease with life-threatening complications. In addition to the angioproliferative lesions, such as bacillary angiomatosis, an increasing number of immune post-infectious complications are being recognized with BH infections, including glomerulonephritis, vasculitis, hemophagocytic syndrome, and neurological problems. We report the case of a renal transplant recipient who developed CSD in the second year post transplantation. In addition to prolonged fever and generalized lymphadenopathy and splenomegaly requiring differentiation from a post-transplant lymphoproliferative disorder, the course was complicated by the development of dermal leukocytoclastic vasculitis and pauci-immune necrotizing and crescentic glomerulonephritis, which led to failure of the renal graft. Glomerulonephritis as a complication of CSD has never been described in a kidney allograft, to our knowledge. Awareness of the diverse clinical symptoms associated with BH, including granulomatous/suppurative lesions and other less common complications can lead to more rapid and accurate diagnosis. Also, as recommended by the current guidelines, a thorough history of pet ownership should be part of the clinical evaluation before and after transplantation for all transplant recipients.

Isolated right pulmonary artery agenesis with agenesis of right upper lobe and bronchiectasis of right lower lobe with anomalous arterial supply from celiac axis with normal venous drainage.

Isolated unilateral absence of pulmonary artery (UAPA) is a rare congenital anomaly. When detected in infancy, the condition is commonly associated with cardiovascular defects which are more frequently associated with left pulmonary artery agenesis. Patients with isolated right pulmonary artery agenesis survive into adulthood with minimal or no symptoms and are diagnosed incidentally on the chest radiographs. We report a case of a 19-year-old female patient who presented to us with recurrent haemoptysis. She was symptomatic since the age of four years. We report the rare occurrence of UAPA on right side, agenesis of right upper lobe and bronchiectasis of right lower lobe with anomalous arterial supply of right lung from coeliac axis in this patient.

Long-term renal function following radical cystectomy and ileal conduit creation.

BACKGROUND: Treatment for bladder cancer includes radical cystectomy (RC) and urinary diversion; RC is associated with long-term morbidity, kidney impairment and mortality. AIM: To identify risk factors associated with postoperative long-term kidney function and mortality. METHODS: Retrospective study of patients with RC and urinary diversion in Beaumont Hospital from 1996 to 2016. We included patients who had follow-up at least 2 years post-procedure. We assessed estimated glomerular filtration rate (eGFR) preoperatively and yearly post-procedure, dialysis commencement and mortality. Cox and Fine-Gray regression analyses were applied; p-value < 0.05 was considered significant. RESULTS: We included 264 patients, median age 68.3 years, 73.7% males. The most common diagnosis was bladder cancer 93.3%, TNM stages T ≥ 2 75.9%, N ≥ 1 47.6% and M1 28%. The median eGFR preoperative was 65.8 ml/min/1.73m2 and after 2 years 58.2 ml/min/1.73m2 (p: 0.009); 5.3% required chronic dialysis and 32.8% had a decrease > 10 ml/min/1.73m2. Risk factors associated with ESKD and start dialysis included younger age (HR: 0.90, CI 95% 0.87-0.94) and lower pre-operative eGFR (HR: 0.97, CI 95% 0.94-1.00). Overall mortality was 43.2% and 54.1% at 5 and 10 years, respectively; risk factors were older age (HR: 1.04, CI 95% 1.02-1.06), tumour stage T ≥ 2 (HR: 2.22, CI 95% 1.39-3.54) and no chemotherapy (HR: 1.72, CI 95% 1.18-2.51). Limitations include retrospective design, absence of control group and single centre experience. CONCLUSIONS: Patients with RC are at risk of progressive kidney function deterioration and elevated mortality and the main risk factors associated were age and preoperative eGFR. Regular monitoring of kidney function will permit early diagnosis and treatment.

Rituximab for ANCA-associated vasculitis in the setting of severe infection.

OBJECTIVES: The combination of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and severe infection presents a challenge because current therapies with high-dose glucocorticoids and cyclophosphamide (CYC) are immunosuppressive and increase the risk of infection. Thus, coincident infection delays and complicates the introduction of treatment. Rituximab (RTX) is an alternative to CYC in AAV and may be preferable in the setting of severe infection. METHOD: From 2005 to July 2011, 100 patients with AAV were treated with RTX at our institution and those who received RTX instead of CYC because of concomitant infection were studied. RESULTS: Eight patients were identified. The mean follow-up was 12 months (range 6-30 months). All patients achieved remission by 6 months that was sustained to the end of follow-up. There were no deaths or further severe infections. CONCLUSIONS: RTX can be considered for patients with generalized AAV and concomitant severe infection.

Core needle biopsy causing a pseudoaneurysm in the breast.

Core needle biopsy (CNB) is the first-choice method of sampling suspicious, focal breast lesions for histological analysis. Here we present the case of a 65-year-old woman who was recalled for evaluation of the left breast following a screening mammogram. An ultrasound-guided biopsy was performed using a disposable core biopsy needle and 3 weeks later a magnetic resonance imaging scan showed a distended vessel with adjacent sac measuring 17 × 15mm2. A Doppler ultrasound scan confirmed pseudoaneurysm. A review of the literature was made on breast pseudoaneurysm following CNB, and over the past 20 years there were few other reports. Pseudoaneurysms in the breast are a rare but serious complication of CNBs. They may spontaneously thrombose, but often require intervention, so it is essential that clinicians are aware of the risk.

Effects of Protein Source, Whole Wheat and Butyric Acid on Live Performance, Gut Health and Amino Acid Digestibility in Broiler Chickens.

A total of 896 1-day-old straight-run (Ross-308) broilers were used to investigate the interactive effects of protein source (PS), diet structure (DS) and butyric acid (BA) on live performance and carcass characteristics, gut development and its morphology and apparent ileal digestibility (AID) of protein and amino acids (AA). Eight experimental diets comprising 8 replicates with 14 birds each were tested in a 2 × 2 × 2 factorial arrangement with complete randomized design by two levels of BA (0 and 0.1%), two forms of DS (whole vs. ground wheat) and two PS, i.e., soybean meal and canola meal (SBM vs. CM). Throughout the entire experimental period (0 to 35 d), broilers fed SBM-based diets exhibited better (p < 0.05) growth performance (feed intake (FI), body weight gain (BWG) and feed conversion ratio (FCR)), carcass parameters (p < 0.05), gut health (p < 0.05), and nutrient digestibility (p < 0.05) than CM-fed broilers. Dietary whole wheat (WW) positively affected FI (p = 0.001), BWG (p = 0.004) and FCR (p = 0.035) during the overall experimental period. Broilers fed WW had 6, 5, 8, 11 and 10% lower empty relative weights of crop, proventriculus, jejunum, ileum and colon and 25 and 15% heavier gizzard and pancreas, respectively, with longer villus height (p < 0.001), reduced crypt depth (p = 0.031) and longer villus height-to-crypt depth ratio (p < 0.001) than those fed ground-wheat-based diets. Broilers fed WW had greater (p < 0.05) AID of CP and most of the AA. Butyric acid supplementation resulted in improved (p < 0.05) growth performance and digestibility of threonine, valine, leucine, isoleucine, phenylalanine, serine and aspartate. The broilers consuming SBM had 28% lower abdominal fat than those fed CM-based diets. In conclusion, harmful consequences of a less digestible PS can partially be compensated by the inclusion of WW, and supplementation of BA further reduces these detrimental effects.

Using mixed silages of sweet sorghum and alfalfa in total mixed rations to improve growth performance, nutrient digestibility, carcass traits and meat quality of sheep.

Combining sweet sorghum (SS) with alfalfa for ensiling has the potential to make a high-quality silage with relatively a better nutrient balance. However, the existing data are insufficient about how changes in ratios of SS to alfalfa in different silage mixtures affect animal performance and meat quality. Therefore, the objective of this study was to determine the effect of feeding total mixed rations containing mixed silages of SS and alfalfa on growth performance, nutrient digestibility, carcass traits and meat quality of Karakul sheep. Five total mixed rations were formulated with different SS proportions at 100%, 80%, 60%, 40%, and 20% on a fresh weight basis. Thirty 4-month old male Karakul sheep with 25.5 ± 1.4 kg BW were randomly allocated into five treatment groups, each with six lambs for this experiment. The results indicated that the Karakul sheep consuming total mixed rations containing SS-Alfalfa (SS-AF) silage mixtures with a lower proportion of SS tended to increase nutrient digestibility, growth performance, carcass traits, and meat quality. Feeding diets with SS at 40% and 20% inclusion rate showed a significant linear increase in the apparent digestibility of DM, CP and NDF, as well as subcutaneous fat thickness and water holding capacity (P < 0.5). Moreover, reduction in SS inclusion rate in these diets caused significant (P < 0.05) linear and quadratic increases in DM intake, final BW, average daily gain, carcass weight, and the amino acid contents of meat (P < 0.05). Conversely, feeding diet with lower SS inclusion rate led to decrease in feed conversion ratio and shear force significantly (P < 0.05) for these sheep. It appears that 40% inclusion of SS was the optimal rate in making the SS-AF silage mixture for lambs to achieve a superior production performance and high-quality meat products in Karakul sheep. However, further research is needed to investigate the effect of feeding SS-AF silage mixtures alongside contrasting ingredients on rumen function, ruminal microorganisms and digestive enzyme activity of sheep and other ruminant animals.

Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats.

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia (C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably (p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

Hazardous drinking is associated with an elevated aspartate aminotransferase to platelet ratio index in an urban HIV-infected clinical cohort.

OBJECTIVES: The aim of the study was to determine the relationship between alcohol consumption and liver fibrosis as assessed by aspartate aminotransferase to platelet ratio index (APRI) in HIV-infected adults and to explore the relative contributions of alcohol and hepatitis C virus (HCV) to APRI among HIV/HCV-coinfected adults. METHODS: We performed a cross-sectional analysis of data from an observational clinical cohort. Alcohol consumption was categorized according to National Institute on Alcohol Abuse and Alcoholism guidelines. We defined significant liver disease as APRI>1.5, and used multinomial logistic regression to identify correlates of increased APRI. RESULTS: Among 1358 participants, 10.4% reported hazardous drinking. It was found that 11.6% had APRI>1.5, indicating liver fibrosis. Hazardous drinking was associated with increased APRI [adjusted relative risk ratio (RRR) 2.30; 95% confidence interval (CI) 1.26-4.17]. Other factors associated with increased APRI were male gender, viral hepatitis, and HIV transmission category of injecting drug use. Among coinfected individuals, 18.3% had APRI>1.5, and hazardous drinking was not associated with APRI. Among non-HCV-infected individuals, 5.3% had APRI>1.5 and hazardous drinking was associated with increased APRI (adjusted RRR 3.72; 95% CI 1.40-9.87). CONCLUSIONS: Hazardous drinking is an important modifiable risk factor for liver fibrosis, particularly among non-HCV-infected patients. Clinicians and researchers must address alcohol use as the burden of liver disease increases among HIV-positive individuals.

Severe insulin resistance due to anti-insulin antibodies: response to plasma exchange and immunosuppressive therapy.

Anti-insulin antibodies have been described in two contexts: in insulin-naive individuals (so-called 'insulin autoimmune syndrome') and in patients with insulin-treated diabetes, in whom antibodies are rarely of clinical significance. We report the case of an 68-year-old woman who exhibited a local allergic reaction to subcutaneous insulin followed by severe insulin resistance, evidenced by poor glycaemic control despite treatment with > 3.5 U/kg of insulin per day. She was found to have circulating polyclonal anti-insulin antibodies of the IgG subtype and responded clinically to a course of plasma exchange and immunosuppression with mycophenolate mofetil and, subsequently, intravenous immunoglobulin. Falling titres of antibodies on this regimen correlated with improved glycaemic control. This case suggests that clinicians should be alert to the possibility of insulin resistance due to anti-insulin antibodies and that immunosuppression in this situation may be a valuable therapeutic option.