Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

A study of 15 cases of primary mediastinal lymphoma of B-cell type.

Fifteen cases of pure supradiapragmatic lymphoma with initial prominent antero-superior mediastinal involvement displaying a B-cell pattern of reactivity were studied. These cases occurred in six men and nine women with a median age of 33 years at diagnosis (range, 23 to 75 years). Supradiapragmatic peripheral lymphadenopathies were present in three cases, and intrathoracic extension to the lung, pericardium, or pleura was possible. In five cases a thymic origin was obvious. All cases exhibited a B-cell pattern of differentiation, with a great variety of histopathologic aspects associated with a high frequency of fibrosis and/or necrosis. Hodgkin's disease was initially misdiagnosed in four cases. The evolution was purely local, with extrathoracic extension in five cases, at the ultimate phase of the disease. The prognosis appeared to be poor with only five patients still alive at a median survival time of 16 months. A complete chemoresistance and radio-resistance was observed in seven cases; only two complete remissions were achieved with aggressive chemotherapy. Prolonged remission could be achieved after surgical reduction of the mass. Primary B-cell mediastinal lymphoma appears to be a distinct clinical entity with local evolution and resistance to therapy. A new therapeutic regimen, which could include surgery in some cases, should be found for this disease.     

Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

Heart rate variability,exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate cystic fibrosis

Background:Autonomic nervous system balance is altered in cystic fibrosis (CF), although its influence on physical fitness has been poorly explored.Objective:This study aimed to evaluate the association of heart rate variability (HRV) with exercise capacity and levels of daily physical activity in children and adolescents with mild-to-moderate CF.Methods:A cross-sectional study including individuals with CF aged 6–18 years, not under CFTR modulator therapy, was performed. Sociodemographic (age, sex) and clinical information (airway colonization, pancreatic insufficiency, and genotyping) were collected. In addition, exercise capacity (modified shuttle test — MST), lung function (spirometry), body composition (bioimpedance), levels of daily physical activity (5-day accelerometer), and HRV (both at rest and during the MST) were evaluated.Results:30 individuals (20 females) aged 11.2±3.7 years, mean FEV162.8±27.6%, were included. A sympathovagal balance (LF/HF) increase (p<0.001) during the MST was shown, indicating a predominance of sympathetic modulation. The standard deviation of all RR intervals (SDNN) and the high frequency (HF) index during exercise correlated significantly with FEV₁ (r=0.45, p=0.01 and r=0.46, p=0.01; respectively). MST distance also correlated positively and significantly with SDNN (r=0.43, p=0.01), square root of the mean of the sums of squares of frequencies between RR intervals greater than 50 ms — RMSSD (r=0.53, p<0.01), low frequency — LF (r=0.48, p<0.01), HF (r=0.64, p<0.01), dispersion of points perpendicular to the short-term identity line — SD1 (r=0.40, p=0.02) and negatively with LF/HF (r=−0.57, p<0.01). Regarding daily physical activity, SDNN at rest (r=0.37, p=0.04) and exercise (r=0.41, p=0.02) showed positive correlations with time in moderate-to-vigorous activities. When normalizing the SDNN and classifying individuals as normal or altered, those presenting altered SDNN showed poorest FEV₁ (p=0.001) and lower exercise capacity (p=0.027).Conclusion:HRV correlates with lung function, exercise capacity and levels of daily physical activity in children and adolescents with CF. The study highlights the influence of CF on autonomic function and suggests HRV measurement as an easy tool to be used in clinical settings as an alternative marker to monitor CF individuals.     

The role of fish oil/omega-3 fatty acids in the treatment of IgA nephropathy

Beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported in recent epidemiologic studies and randomized clinical trials in a variety of cardiovascular and autoimmune diseases. Fish and marine oils are the most abundant and convenient sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major n-3 fatty acids that serve as substrates for cyclooxygenase and lipoxygenase pathways leading to less potent inflammatory mediators than those produced through the n-6 PUFA substrate, arachidonic acid. N-3 PUFA can also suppress inflammatory and/or immunologic responses through eicosanoid-independent mechanisms. Although the pathophysiology of IgA nephropathy is incompletely understood, it is likely that n-3 PUFA prevents renal disease progression by interfering with a number of effector pathways triggered by mesangial immune-complex deposition. In addition, potential targets of n-3 PUFA relevant to renal disease progression could be similar to those involved in preventing the development and progression of cardiovascular disease by lowering blood pressure, reducing serum lipid levels, decreasing vascular resistance, or preventing thrombosis. In IgA nephropathy, efficacy of n-3 PUFA contained in fish oil supplements has been tested with varying results. The largest randomized clinical trial performed by our collaborative group provided strong evidence that treatment for 2 years with a daily dose of 1.8 g of EPA and 1.2 g of DHA slowed the progression of renal disease in high-risk patients. These benefits persisted after 6.4 years of follow up. With safety, composition, and dosing convenience in mind, we can recommend two products that are available as pharmaceutical-grade fish-oil concentrates, Omacor (Pronova Biocare, Oslo, Norway) and Coromega (European Reference Botanical Laboratories, Carlsbad, CA).     

Role of paravertebral block anaesthesia during percutaneous transhepatic thermoablation

Purpose

This paper discusses the technique and preliminary results of right thoracic paravertebral block (TPVB) for percutaneous thermal ablation of liver tumours.

Materials and methods

Between October 2011 and August 2012 we treated 36 lesions (25 hepatocellular carcinoma and 11 metastases) in 30 patients aged 47–85 years (mean 67.5). Patients received ultrasound (US)-guided injection of 7 ml of naropin 0.75 % in T7, T9 and T11 levels, below the costo-vertebral ligament, until we observed an anterior displacement of the parietal pleura. For the subcapsular lesions, a cervical right phrenic nerve block was associated. The level of analgesia was evaluated during and after the percutaneous procedures with the Numerical Rating Scale. Finally, we investigated statistical correlations between pain and lesions (histological type, site, dimensions), and ablation time and technique (microwave or radiofrequency ablation).

Results

Technical success was achieved in all patients. Despite the correct anaesthetic diffusion during the ablation, 10 patients (33.3 %) reported medium/severe pain and intravenous sedation was required. Pain was not found to correlate with any variable. No complications were observed.

Conclusions

In most cases, TPVB is a safe and effective technique for conscious anaesthesia during percutaneous thermal ablation of liver tumours. Failures probably derive from left sympathetic and parasympathetic fibre stimulation. We recommend performing a TPVB in the presence of the anaesthetist.     

Organ Donation and Transplantation in Migrants: Piedmont Reality From 2004 To 2011

Background

Over the last 20 years, an increasing number of people have immigrated into Italy. On January 1, 2011, there were 4,570,317 foreign residents in Italy, including 398,910 in the Piedmont region (Italian National Statistics Institute data). The Romanian community was the largest, followed by the Moroccan and Albanian ones. The numbers are even layer if we consider illegal immigrants. As a result, the number of foreign people with brain death has increased, as well as the number of foreign people needing organ transplantations.

Methods

The Piedmont Regional Coordination Agency of Tissue and Organ Procurement has analyzed our 1781 brain death situations between January 2004 and December 2011, including 126 (7%) in people not born in Italy (migrants).

Results

Non-refusal for donation occurred in 79 cases (62.7%). The agency also analyzed each community looking at number of brain deaths and non-refusals of donation. We utilized 61 donors, for 174 transplantations. Migrants in Italy are not only potential tissue and organ donors, but also potential tissue and organ recipients. Between 2004 and 2011, 222 patients who had not been born in Italy had been transplanted with: a liver (n = 66), a kidney (n = 130), a heart (n = 21) or a lung (n = 5).