[Fatal epidermal necrosis due to methotrexate use]. / Fatale epidermale necrose door methotrexaatgebruik.

A 53-year-old patient with known psoriasis presented with painful erosive plaques in existing psoriasis lesions, ulcerations in the mouth, and leukopenia. She used 10 mg of methotrexate daily without folic acid prophylaxis. During admission she developed pancytopenia, liver failure and acute kidney injury. She died after developing toxic shock syndrome. We aim to describe the use and toxic effects of methotrexate, how to recognise toxicity clinically and histologically, and treatment options.

Ghrelin, leptin and high-molecular-weight adiponectin in relation to depressive symptoms in older adults: Results from the Longitudinal Aging Study Amsterdam.

BACKGROUND: Ghrelin, leptin and high-molecular-weight (HMW) adiponectin have been linked to depression in middle-aged adults. Pathophysiological mechanisms of depression change as age progresses and it is unclear whether the same associations exist in older adults. METHODS: We analyzed the associations between ghrelin, leptin and HMW adiponectin and depressive symptoms (Center for Epidemiologic Studies Depression (CES-D) score ≥ 16) in a community-dwelling cohort of 898 participants in a multivariable logistic regression analysis at baseline and after three years of follow-up, were applicable stratified by sex, age and waist-hip-ratio (WHR). RESULTS: At baseline no significant associations were found. After three years of follow-up ghrelin was associated with higher odds for depressive symptoms (fully adjusted continuous analysis OR 2.27, 95% CI 1.42 - 3.61). There was effect modification for age and WHR, with significant associations in participants younger than 69.7 years (median) and with a WHR below 0.9554 (mean). In the sex-stratified analysis for leptin we found significant associations in men (fully adjusted continuous analysis OR 1.07, 95% CI 1.02 - 1.12). For HMW adiponectin there were no significant associations in the multivariable analysis. LIMITATIONS: As our cohort consisted of relatively healthy participants with intact cognitive function, selection bias may have contributed to lack of significant baseline associations. CONCLUSIONS: Our results show significant associations between ghrelin and - for men only - leptin and depressive symptoms after three years of follow up. This may provide a new therapeutic window for treatment of depressive symptoms in older adults, as both ghrelin and leptin are positively influenced by weight loss.

The Association Between High-Molecular-Weight Adiponectin, Ghrelin and Leptin and Age-Related Cognitive Decline: Results From Longitudinal Aging Study Amsterdam.

BACKGROUND: Age-related cognitive decline has large-scale functional and economic consequences and understanding its' pathophysiological mechanisms is therefore essential. Previous research has suggested associations between hormones adiponectin, ghrelin and leptin and neurodegenerative disease. However, their association with age-related cognitive decline has not been fully described. We examine the association between serum high-molecular-weight (HMW) adiponectin, ghrelin and leptin and age-related cognitive decline in older adults. METHODS: The associations between HMW adiponectin, ghrelin and leptin and the Mini-Mental-State-Examination, Coding task (Coding), 15 Words Test (15WT) and composite Z-score (general cognitive function) were analyzed by means of a sex-stratified multivariable linear regression analysis in a population-based cohort of 898 older adults at baseline and after 3 years of follow-up. RESULTS: In women, we found a positive association between HMW adiponectin and general cognitive function at baseline (fully adjusted model composite Z-score standardized regression co-efficient beta [ß] = .089, p = .025). After 3 years of follow-up, HMW adiponectin was associated with more decline in general cognitive function and information processing speed (fully adjusted model composite Z-score ß = -.123, p = .018; Coding ß = -.116, p = .027). Ghrelin and leptin were significantly associated with memory in a baseline subgroup analysis of older women. For men, we found no significant associations at baseline or follow-up. CONCLUSION: Our results show variable associations between hormones HMW adiponectin, ghrelin and leptin and age-related cognitive decline in women but not in men. As there was no clear trend, all our results should be interpreted with caution.

Adiponectin and Its Isoforms in Pathophysiology.

Adiponectin circulates in blood in multiple isoforms. High molecular weight (HMW) adiponectin is thought to be most biologically active and promotes glucose uptake, insulin sensitivity, and fatty acid oxidation. In obesity, adiponectin isoform formation is disrupted, leading to an inverse association between metabolic disease and HMW and total adiponectin. Adiponectin isoforms also function as acute-phase reactants influencing inflammation in acute and chronic disease. Interestingly, adiponectin and mortality have a U-shaped association. Unfortunately, data concerning adiponectin and its pathophysiologic function conflict. This is predominantly due to difficulties in adequate measurement of adiponectin isoforms and lack of a gold standard. In this review we provide a general overview of the formation and function of adiponectin and its isoforms under physiologic conditions. We highlight the ways adiponectin isoform formation is disrupted in obesity and its ensuing pathologic conditions. Furthermore, we will elaborate on the role of adiponectin isoforms as inflammatory proteins with respect to cardiac and kidney disease and discuss the association of adiponectin with mortality. Finally, we will provide a historical perspective on the measurement of adiponectin isoforms, current limitations, and future challenges.

More, less or both?

A 67-year-old Caucasian woman with no prior medical history was admitted to our hospital with complaints of generalised weakness, nausea, diarrhoea and weight loss. The patient suffered from tachycardia and hypotension. Blood tests revealed Graves' thyrotoxicosis and the patient was treated accordingly. However, patient's health continued to decline rapidly and further tests revealed a concomitant Addisonian crisis. Additional treatment with corticosteroids led to a full recovery. It is well known that autoimmune endocrine disorders tend to cluster. However, the presentation is usually sequential in time. This case reports the highly rare simultaneous presentation of Addison's disease and Graves' thyrotoxicosis. It also provides several suggestions to help establish the diagnoses.

A method comparison of total and HMW adiponectin: HMW/total adiponectin ratio varies versus total adiponectin, independent of clinical condition.

BACKGROUND: Total and high-molecular-weight (HMW) adiponectin have been associated with endocrine and cardiovascular pathology. As no gold standard is available, the discussion about biological relevance of isoforms is complicated. In our study we perform a method comparison between two commercially available assays measuring HMW and total adiponectin, in various patient groups, thus contributing further to this discussion. METHODS: We determined levels of HMW and total adiponectin using assays by Lumipulse® and Millipore® respectively, in 126 patients with different clinical characteristics (n=29 healthy volunteers, n=22 dialysis patients, n=25 elderly with body mass index (BMI) <21kg/m2, n=25 elderly with BMI 30-35kg/m2, n=26 children). RESULTS: The Passing & Bablock regression analysis resulted in HMW adiponectinLUMIPULSE∗0.5-0.9=total adiponectinMILLIPORE, albeit with significant deviation from linearity (p<0.001). Pearson's correlation was R=0.987 (p=0.000). No significant differences between patient groups were observed (p=0.190). CONCLUSIONS: The HMW/total adiponectin ratio varies with total adiponectin concentration independent of clinical conditions studied. Our results imply that total and HMW adiponectin have similar utility when assessing adiponectin levels in blood, as the ratio is independent of clinical condition.

[Periaortitis following endovascular aortic repair]. / Periaortitis na endovasculaire aortareparatie.

BACKGROUND: Infection is the most obvious cause of fever following implantation of an endovascular prosthesis; however, fever and inflammation around the arterial wall can also be caused by a sterile inflammatory reaction: periaortitis. CASE STUDY: An 81-year-old man was referred because of fever and back pain. He had undergone an endovascular aortic repair (EVAR) 1 year earlier; an endovascular prosthesis had been placed during this procedure, to repair an abdominal aortic aneurysm. A positive emission tomography (PET)-CT scan revealed uptake of 18F-fluorodeoxyglucose around the endovascular prosthesis, consistent with infection; however, intensive microbiological investigation, including biopsy from the site of the endovascular prosthesis, revealed no micro-organisms. Empirical administration of antibiotics had no effect. Decreased renal function occurred approximately 4 weeks later, and a CT scan revealed spread of the inflammatory process accompanied by hydronephrosis, consistent with periaortitis. Following treatment with glucocorticoids, renal function returned to normal and the symptoms disappeared. CONCLUSION: Periaortitis is a rare, late complication of an EVAR. Clinical presentation can closely resemble an infection, while distinguishing infection from (sterile) periaortitis is important for the choice of treatment.