Rheumatoid Arthritis with Generalized Lymphadenopathy Mimicking Lymphoma on Positron Emission Tomography/Computed Tomography with 18F-Fluorodeoxyglucose.

A 42-year-old male presented with weight loss and progressively increasing pain and swelling in joints over the past 3 months. Contrast-enhanced computed tomography (CT) demonstrated pleuropulmonary opacities and supra/infradiaphragmatic lymph nodes enlargement. Positron emission tomography (PET/CT) with 18F-fluorodeoxyglucose showed intensely increased tracer uptake in joints, in pulmonary opacities, as well as in thoracic, iliac, and inguinal nodes. On suspicion of lymphoma with synovial involvement, he was submitted to lymph node and synovial biopsy, which revealed reactive follicular lymphadenopathy and synovium inflammatory changes, respectively. Rheumatoid factor resulted increased, and thus, diagnosis of rheumatoid arthritis with related lung and lymph node involvement was made.

Malignant Insulinoma with Multiple Liver Metastases and Hypercalcitoninemia in a Patient with Type 2 Diabetes Mellitus Presenting as Recurrent Episodes of Diaphoresis due to Severe Hypoglycemia.

Insulinoma is an insulin-producing pancreatic neuroendocrine tumor that can be malignant in about 10% of cases. Locoregional invasion, lymph node metastases, or remote metastases are the main criteria of malignant insulinoma. Its incidence in patients with pre-existing diabetes mellitus (DM) is exceptionally rare. In this report, we describe a 66-year-old man with long-standing type 2 DM who presented with recurrent episodes of diaphoresis due to severe hypoglycemia despite the withdrawal of insulin therapy, hypercalcitoninemia, and biochemical and radiological findings suggestive of metastatic malignant insulinoma. Unfortunately, after few days of diazoxide treatment, edema, hypotension, oliguria, and water retention were observed, patient's clinical status deteriorated rapidly, and he died in our department from acute renal failure.

Alpha- and gamma-tocopherol levels in human semen and their potential functional implications.

Vitamin E is a potent antioxidant that has been considered involved in fertility, but studies have mostly focused on α-tocopherol. Our study aimed at measuring, by an isotope dilution gas chromatography-mass spectrometry method, α- and γ-tocopherol concentration in human semen in a large and well-characterised population (134 men with different semen parameters and in varicocele patients), as well as their potential role in male fertility. We carried out freeze/thaw experiments in 15 samples with the two isomers in the cryoprotective medium. Moreover, our study included 10 subjects supplemented in vivo with α-tocopherol for 90 days. In seminal plasma, γ-tocopherol concentration was significantly lower in the varicocele group than in the normozoospermic group. We observed that γ-tocopherol, supplemented to cryopreservation medium, induced a higher post-thaw human sperm viability and motility than α-tocopherol. The results of in vivo α-tocopherol supplementation showed a decrease in γ-tocopherol concentration with increasing α-tocopherol level in blood. This is the first report related to γ-tocopherol distribution in human semen analysed by gas chromatography-mass spectrometry. γ-tocopherol would not seem to be related to semen parameters but to cellular oxidative condition. This tocopherol may contribute to human health in a yet unexplored way.

Adverse reactions of Amiodarone.

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in man. Older people are at elevated risk of adverse drug reactions-because of changes in pharmacodynamics, concurrent use of multiple medications and the related drug interactions. However, adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate drugs. Amiodarone is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older people. While amiodarone is an efficient drug for rhythm control, it's a carrier of different adverse reactions, and pro and cons must be carefully evaluated before its use especially in older people.

Combined Hepatocholangiocarcinoma Associated with Humoral Hypercalcemia of Malignancy and Chronic Inflammatory Demyelinating Polyneuropathy.

Paraneoplastic syndromes are often a diagnostic challenge to doctors and may have a heterogeneous presentation, including humoral hypercalcemia of malignancy (HHM), most commonly caused by squamous cell cancer and renal, ovarian, endometrial, and breast cancer. Chronic inflammatory demyelinating polyneuropathy (CIDP) has been described in patients affected by several types of cancer, especially hematologic malignancies, and a possible paraneoplastic pathogenesis of this neurological disease has been suggested. This report describes a 56-year-old man with a history of CIDP diagnosed 3 months earlier and persistently elevated aminotransferases for 18 months who was admitted to our internal medicine unit with abdominal pain, fatigue, and severe hypercalcemia with low serum intact parathyroid hormone. Parathyroid hormone-related protein (PTH-rP) was markedly high. Liver imaging showed a large hepatic mass in the right lobe, and percutaneous ultrasound-guided biopsy revealed histopathological findings consistent with a combined hepatocholangiocarcinoma (CHCC). We supposed that both HHM and CIDP could represent a paraneoplastic manifestation of CHCC.

Mass spectrometry profiling of oxysterols in human sperm identifies 25-hydroxycholesterol as a marker of sperm function.

Cholesterol is a main lipid component of sperm cell that is essential for sperm membrane fluidity, capacitation, and acrosomal reaction. Recent data obtained in bovine sperm showed that sperm capacitation is associated to the formation of oxysterols, oxidized products of cholesterol. The aim of this study was to profile oxysterol content in human semen, and to investigate their potential role in sperm pathophysiology. Among the 12 oxysterols analyzed, 25-hydroxycholesterol (25-HC) resulted the most represented in normozoospermic samples, and its concentration positively correlated with spermatozoa number. We detected Cholesterol 25-hydroxylase, the enzyme responsible for 25-HC production, in human spermatozoa at the level of the neck and the post acrosomal area. Upon incubation with spermatozoa, 25-HC induced calcium and cholesterol transients in connection with the acrosomal reaction. Our results support a role for 25-HC in sperm function.

Effects of dietary fatty acids and cholesterol excess on liver injury: A lipidomic approach.

Lipid accumulation is the hallmark of Non-alcoholic Fatty Liver Disease (NAFLD) and has been suggested to play a role in promoting fatty liver inflammation. Previous findings indicate that during oxidative stress conditions excess cholesterol autoxidizes to oxysterols. To date, the role of oxysterols and their potential interaction with fatty acids accumulation in NASH pathogenesis remains little investigated. We used the nutritional model of high fatty acids (HFA), high cholesterol (HCh) or high fat and high cholesterol (HFA+FCh) diets and explored by a lipidomic approach, the blood and liver distribution of fatty acids and oxysterols in response to dietary manipulation. We observed that HFA or HCh diets induced fatty liver without inflammation, which was otherwise observed only after supplementation of HFA+HCh. Very interestingly, the combination model was associated with a specific oxysterol fingerprint. The present work provides a complete analysis of the change in lipids and oxysterols profile induced by different lipid dietary model and their association with histological alteration of the liver. This study allows the generation of interesting hypotheses on the role of interaction of lipid and cholesterol metabolites in the liver injury during NAFLD development and progression. Moreover, the changes in the concentration and quality of oxysterols induced by a combination diet suggest a novel potential pathogenic mechanism in the progression from simple steatosis to steatohepatitis.

IL-6-Producing, Noncatecholamines Secreting Pheochromocytoma Presenting as Fever of Unknown Origin.

Fever of unknown origin (FUO) can be an unusual first clinical manifestation of pheochromocytoma. Pheochromocytomas are tumors that may produce a variety of substances in addition to catecholamines. To date, several cases of IL-6-producing pheochromocytomas have been reported. This report describes a 45-year-old woman with pheochromocytoma who was admitted with FUO, normal blood pressure levels, microcytic and hypochromic anemia, thrombocytosis, hyperfibrinogenemia, hypoalbuminemia, and normal levels of urine and plasma metanephrines. After adrenalectomy, fever and all inflammatory findings disappeared.

Dipyridamole: a drug with unrecognized antioxidant activity.

Dipyridamole was introduced on the market as coronary vasodilator drug more than half a century ago and is still used as antithrombotic and vasodilator. Among cellular targets, it inhibits phosphodiesterases and raises extracellular levels of adenosine through inhibition of adenosine reuptake by red blood cells. As a consequence, endocellular levels of cyclic nucleotides are upregulated. The rise of cGMP in vascular smooth muscle cells and of cAMP in platelets provide the mechanism of vasodilation and antithrombosis, which are further potentiated by the release of PGI2 consequent on the increase in endothelial cell cAMP. These effects support the use of dipyridamole in cardiovascular diseases in which the drug is approved for the secondary prevention of cerebrovascular events. On the other hand, dipyridamole has been shown to possess a potent, little perceived, antioxidant activity of potential use in the several fields where pathophysiological pathways are dependent on oxidative stress, including those occurring in atherosclerosis, thrombosis, CNS-related diseases, and cancer.

Plasma fatty acid lipidomics in amnestic mild cognitive impairment and Alzheimer's disease.

Polyunsaturated fatty acids (PUFA) of the n-3 series have been linked to brain physiology and cognitive decline, but little is known about the other components of the complex fatty acids category. Here, we compared 30 molecular species pertaining to saturated, monounsaturated, polyunsaturated, and trans fatty acids, measured in plasma by gas chromatography, in 14 patients with a diagnosis of amnestic single domain mild cognitive impairment (aMCI), 30 patients with mild Alzheimer's disease (AD), and 30 healthy controls (HC). As no participants showed neuroimaging evidence of cerebrovascular disease, patients could be considered as purely neurodegenerative. We found differences in specific components of almost all fatty acid classes except n-3-polyunsaturated fatty acids. Compared with HC, aMCI and AD patients had higher levels of arachidic (C20:0), erucic (C22:1, n-9), and vaccenic acid (C18:1, n-9) and lower levels of cerotic (C26:0) and linoleic acid (C18:2, n-6). In particular, level of linoleic acid decreased and level of mead acid increased progressively from HC to aMCI to AD patients, and they were also inversely correlated in AD and aMCI patients. In conclusion, we found a previously unrecognized linoleic acid deficiency in the early phase of neurodegeneration that was strongly supported by an increased, compensatory mead acid level. These findings suggest the importance of creating new dietary manipulation strategies to counteract disease progression.