Ultrastructural pathology of iron-loaded rat myocardial cells in culture.

The pathological changes induced by in-vitro iron-loading or cultured rat myocardial cells were studied. Cells were exposed to 59Fe-labelled ferric ammonium citrate for up to 24 h followed by 24-72 h chase experiment. After 24 h exposure 29% of the total cellular radioactivity was found in ferritin, 10% in non-ferritin heat supernatant and 61% in an insoluble heat-precipitable form. Mössbauer spectroscopy showed a gradual shift from intracellular iron particles less than 1.8 nm in diameter, through particles of intermediate size, to ferritin-like aggregates over 3.0 nm in diameter, reaching about 20% of total iron by 24 h. Ultrastructural studies showed premature damage such as mitochondrial abnormalities and excessive autophagocytosis. Small, 2.0-5.0 nm electron-dense cytosolic particles were noticed at 3 h of iron loading and reached maximal concentrations at 6 h. This was followed by accumulation of the small particles and of typical iron-rich ferritin cores within siderosomes. Because of the limited duration of iron loading and the high concentrations of non-transferrin inorganic iron employed, the present model is more relevant to acute than chronic iron overload. The efficient incorporation of large amounts of iron within ferritin molecules and its subsequent segregation, together with other smaller particles, within membrane-bound bodies, may represent a defence mechanism limiting iron toxicity in the face of advanced cytosiderosis.     

Microvillous inclusion disease: ultrastructural variability

Microvillous inclusion disease (MVID) is a congenital, usually neonatal, autosomal recessive condition manifested by severe, prolonged secretory diarrhea. Intestinal biopsies reveal extensive microvilli abnormalities, typical inclusions and vesicles mainly of the apical-luminal enterocytes and colonocytes. Although diagnosis can be suspected by special stains of the mucosa (PAS, CD10), the definitive diagnosis, recommended in view of potential intestinal transplantation, requires electron microscopy. In view of the marked variability of ultrastructural changes, extensive illustration is considered valuable for diagnosis. While the pathogenesis is still unknown, a number of images illustrate the suspected “arrested-trafficking” hypothesis of microvillous abnormalities. Others micrographs support the “engulfing” mechanism of inclusion formation. The electron micrographs should help ultrastructural diagnosis in this heterogeneous disease and can confirm diagnosis even in the absence of the typical inclusions.     

Favorable Changes in Arterial Elasticity,Left Ventricular Mass,and Diastolic Function After Significant Weight Loss Following Laparoscopic Sleeve Gastrectomy in Obese Individuals

Background

Obesity is accompanied by increased arterial stiffness, left ventricular (LV) hypertrophy, and diastolic dysfunction, all associated with a negative prognosis. The evolution of LV mass, function, and arterial elasticity after laparoscopic sleeve gastrectomy (LSG) was unknown, and this is what we have investigated.

Methods

Thirty-four consecutive obese subjects (mean age, 39?±?11 years; 35.2 % men), scheduled for LSG, were studied before, at 6 and 12 months after surgery.

Results

The body mass index (BMI) decreased from 43.6?±?11.9 to 32.1?±?7.4 and to 28.9?±?5.8 kg/m² at 6 and 12 months after surgery (all p?<?0.05). The baseline LV mass index was correlated with age, BMI, waist circumference, blood glucose level, systemic hypertension stage, and with aortic distensibility, strain, and stiffness index (all p?<?0.05). Aortic distensibility increased by 110 %, aortic strain by 58 %, and aortic stiffness index decreased by 88 % at 6 months after LSG (all p _{6 months–baseline}?<?0.05) and all the parameters had similar values at 12 months postoperatively (all p _{12–6 months}?=?NS). LV hypertrophy prevalence decreased from 61.8 to 47.1 % and to 32.3 % at 6 and 12 months after surgery (all p?<?0.05). The proportion of patients with LV diastolic dysfunction decreased from 52.9 to 23.5 % at 6 months (p _{6 months–baseline}?<?0.01) and to 20.6 % at 12 months postoperatively (p _{12?–6 months}?=?0.7).

Conclusions

Significant improvements of aortic elasticity and of LV diastolic function were recorded at 6 months, and they were maintained at 12 months after LSG. The LV hypertrophy showed also a favorable evolution: it has been slightly improved 6 months after surgery and further ameliorated 1 year postoperatively.     

Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy

Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called “chronic immune-mediated neuropathies”. Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.     

Extended lipid profile in Romanian ischemic stroke patients in relation to stroke severity and outcome: a path analysis model

IntroductionOur aim was to evaluate the extended lipid profile in ischemic stroke patients and the relationship with stroke type, severity and outcome.Material and methodsWe prospectively enrolled 124 ischemic stroke patients and 40 healthy controls; baseline plasma and erythrocyte membrane fatty acids concentrations and common lipid profile were analysed. Stroke severity was evaluated by NIHSS on admission, while the functional outcome was defined by mRS at discharge and after 3 months.ResultsTotal cholesterol, triglycerides, HDL-cholesterol, DHA, adrenic, stearic and lauric acid were all lower in patients, taking into account that 87.7% of patients did not receive statins before admission. There was a different pattern in plasma and erythrocyte membrane of fatty acids between patients and controls, also omega-3 index was significantly lower in patients. Patients with poor outcome without statins had significantly lower triglyceride (p = 0.028), while the total cholesterol levels were significantly lower in patients with poor outcome (p = 0.03) but with treatment initiated after admission. Bivariate analysis revealed that patients with poor outcome had significantly lower triglyceride levels regardless the statins use, while the total cholesterol and HDL-cholesterol levels were significantly lower in patients with poor outcome under statin treatment. The long-term outcome were positively influenced by age ($\widehat{\beta }$ = 0.22, p = 0.001), and NIHSS score at admission ($\widehat{\beta }$ = 0.55, p < 0.001), and negatively by cholesterol levels ($\widehat{\beta }$ = –0.17, p = 0.031).ConclusionsDHA, adrenic, stearic and lauric acid were lower in stroke patients; plasma adrenic acid was consumed during the acute phase. The most important predictors for long-term outcome was NIHSS at admission followed by age and total cholesterol.     

Upper digestive hemorrhage appearing after cephalic duodeno-pancreatectomy

The frequency of upper gastrointestinal hemorrhage as a postoperative complication of cephalic duodenopancreatectomy remained constant for decades despite the overall decrease in the incidence of mortality occuring after cephalic duodeno-pancreatomy. It is the second most common complication after anastomotic fistulas, but more frequently fatal, especially when the pancreas is anastomosed with the stomach. The case presented here is of a patient of 55 years age, diagnosed in our clinic with vaterian ampuloma for which was performed cephalic duodenopancreatectomy and gastrointestinal and hepatobiliary continuity was restored by performing terminolateral pancreato-gastric anastomosis, termino-lateral hepato-jejunal anatomosis and termino-lateral gastro-jejunal anastomosis on a jejunal loop ascended transmezocolic. Postoperative evolution of the patient was marked by appearance of two episodes of upper gastrointestinal hemorrhage, the first being solved by relaparotomy and the second benefiting from the contribution of an endoscopic intervention. From this case, we analyze risk factors for upper gastrointestinal hemorrhage appearing after cephalic duodeno-pancreatectomy and its therapeutic modalities, starting from the fact that currently there is no consensus among experts on this matter.     

A steroid-independent regimen of bortezomib, liposomal doxorubicin and thalidomide demonstrate high response rates in newly diagnosed multiple myeloma patients

Novel agents have provided a new foundation for multiple myeloma therapies. When combined with other anti-myeloma agents, these compounds significantly enhance clinical efficacy. High-dose steroids are frequently used in anti-myeloma combination regimens; however, the doses employed are often poorly tolerated, especially in patients with concurrent comorbid conditions. We hypothesized that a steroid-independent combination regimen could be developed without significant compromise of efficacy. The availability of such a regimen will be important for patients whose concurrent ailments make them poor candidates for steroid containing anti-myeloma regimens. A phase II single institute, non-randomized clinical trial was conducted to investigate a novel steroid-free three-drug combination of bortezomib (V), pegylated liposomal doxorubicin (D), and thalidomide (T), the VDT regimen. Forty-three newly diagnosed multiple myeloma patients requiring treatment were enrolled on this study. The overall response rate and complete response (CR) + near complete response (nCR) rate was 78% and 35%, respectively. Median time to progression was 29·5 months. Fatigue, rash, neuropathy, constipation and infections were the most common side effects. We concluded that VDT is a tolerable and an effective regimen capable of inducing high response rates and can be employed in patients considered to be poor candidates for steroid-based treatment regimens.     

Exposure to antidepressant medications and suicide attempts in adult depressed inpatients

The effects of antidepressant medication on suicide risk remain unclear. This study explores any association between antidepressant medication and suicide attempts leading to hospitalization in adult depressed patients.The medical records of 103 patients admitted after a suicide attempt were examined and compared with those of a matched control group of depressed patients (n = 103) admitted without suicide attempts as well as a patient group with and without suicide attempts on separate hospitalizations (n = 25). No significant difference in antidepressant medication exposure before hospitalization was found between groups. Selective serotonin reuptake inhibitor exposure was higher in patients with suicide attempts, albeit nonsignificant, but was identical in patients admitted on two occasions with and without suicide attempts. The most common method for suicide attempt was drug overdose (52.4%). Patients in the group with suicide attempts had significantly more past suicide attempts. Study results do not confirm any relationship between antidepressants and suicide attempts. Close monitoring of depressed patients is advised especially in early treatment.