Cardiopulmonary exercise testing for personalized job reintegration after acute cardiovascular attacks: a pilot cross-sectional study

Background:Cardiovascular diseases (CVD), particularly the ischemic heart disease, are a growing public health issue. In addition, the return to work after an acute cardiovascular attack represents a complex challenge.Objectives:To evaluate utility and safety of cardiopulmonary exercise testing (CPET), particularly performed “on site”, to promote a return to work in line with the residual working capacity.Methods:Fifty-nine workers affected by a major cardiovascular event, aged 18-63 years, have been enrolled between 2015 and 2018. All the patients underwent a CPET in outpatient clinic. Eleven workers also underwent the “on site” CPET, recorded during their working activities.Results:Outpatient clinic CPET outcomes (i.e. normal, mild impairment or moderate/severe impairment of cardiopulmonary function) were associated with the subjective perception of workers’ health status after returning to work. The “on site” CPET was found to be safe and reliable to promote a personalized return to work of patients. In 7 out of 11 patients, the values of O₂ consumption (VO₂) during the working activity were higher than 40% of VO₂ max as obtained from laboratory CPET.Conclusions:This study provides evidence for safety and usefulness of “on site” CPET for a personalized statement of fitness for work. This may facilitate the job retention of patients characterized by a high risk of unnecessary job loss. The use of CPET represents a first step of energy expenditure evaluation associated with specific working tasks.Key words: Acute coronary syndrome, cardiopulmonary exercise testing, return to work     

Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for chronic hepatitis C: ribavirin is not always the culprit.

A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D1 (SCH 23390) or D2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D1 receptor blockade and completely abolished by D2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.     

Enzymuria in carboplatin nephrotoxicity

Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is an early marker of nephrotoxicity. NAG activity was assayed by the fluorimetric method of Leaback and Walker in 17 patients treated (22 courses) with carboplatin (CBDCA, 220-550 mg/m2) before infusion and 24, 48, 72 and 96 h after. Increased excretion of NAG, a sensitive index of renal tubular damage, was observed following 10 of the 22 courses. A transient increase in plasma creatinine and/or abnormal proteinuria was observed in 6 cases. Impaired renal function prior to therapy seems to be a predisposing factor to the nephrotoxicity.     

Endovascular repair for concomitant multilevel aortic disease.

OBJECTIVE: Patients with multilevel aortic disease represent a small subgroup with the need for extensive surgical treatment at considerable risk. We present our experience of endovascular exclusion for simultaneous thoracic and abdominal aortic disease in four patients. METHODS: Between January 2002 and January 2005, four patients underwent endovascular repair for simultaneous thoracic and abdominal aortic disease. Mean age was 69+/-10 years (range, 60-81). Thoracic lesions included penetrating aortic ulcer (n=2, ruptured=1), atherosclerotic aneurysm (n=1), and chronic type B dissection (n=1). Abdominal aortic disease included atherosclerotic infrarenal (n=3) and juxtarenal (n=1) aortic aneurysms. Thoracic aortic stent-grafts had been the following: Excluder/TAG (n=3) or Talent (n=1) straight tube devices. Abdominal aortic stent-grafts used were as following: Excluder (n=3) or Zenith (n=1). All patients were followed-up with CT-angiography and chest X-rays 1, 4, 12 months after the procedure, and once per year thereafter. RESULTS: Stent-graft deployment was technically successful in all cases. Intraoperative mortality was not observed. Mean procedure time was 94+/-34 min (range, 70-145). Early postoperative complications occurred in one patient that developed acute renal failure but dialysis was not required. Mean hospitalisation was 8+/-5 days (range, 4-15). Late death occurred in one patient for an undetected ruptured thoracic type 1 endoleak. All three survivors are currently well 16.5 months (range, 3-36) after surgery. No neurological complications developed. CONCLUSION: Simultaneous abdominal and thoracic endovascular repair for multilevel aortic disease is feasible and could be a viable alternative in high-risk patients, who otherwise may not be suitable candidates for conventional repair.