Clinical and biological differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome: results of a large multicentre study.

OBJECTIVES: To determine the clinical and laboratory differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome (pSS), in a large Italian multicentre cohort. METHOD: Patients were selected according to the following criteria: fulfilling the American-European classification criteria for pSS, serum cryoglobulin and gammaglobulin levels evaluated, and lack of hepatitis C virus (HCV) infection. Multinomial analyses were performed by distinguishing three groups of pSS: (i) purpura associated with cryoglobulinaemic vasculitis (CV), (ii) purpura associated with hypergammaglobulinaemic vasculitis (HGV), and (iii) pSS patients without purpura (pSS controls). Patients with purpura but without cryoglobulins or hypergammaglobulinaemia were excluded. RESULTS: A total of 652 patients were enrolled in this study. Group 1/CV comprised 23/652 patients (3.53%), group 2/HGV 40/652 patients (6.13%), and group 3/pSS controls 589/652 (90.34%). The three groups were found to be significantly different from each other (post-estimation test: group 1/CV vs. group 3/pSS controls: p < 0.0001; group 1/CV vs. group 2/HGV: p = 0.0001; group 2/HGV vs. group 3/pSS controls: p = 0.0003), thus confirming the different phenotypes of purpura in pSS.Multivariate analyses revealed that peripheral neuropathy (p < 0.001), low C4 (p < 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.02), and the presence of anti-SSB/La antibodies (p = 0.02) characterized CV whereas rheumatoid factor (p = 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.01), and anti-SSA/Ro antibodies (p = 0.049) were significantly associated with HGV. Lymphoma was associated only with CV. CONCLUSIONS: HGV is a cutaneous vasculitis, related to a benign B-cell proliferation, whereas CV is a systemic immune complex-mediated vasculitis with complement activation and a higher risk of lymphoma, thus confirming CV but not HGV as a prelymphomatous condition in pSS.

In vitro expansion of tumour cells derived from blood and tumour tissue is useful to redefine personalized treatment in non-small cell lung cancer patients.

The clinical development of locally and advanced non-small cell lung cancer (NSCLC) suffers from a lack of biomarkers as a guide in the selection of optimal prognostic prediction. Circulating Tumour Cells (CTCs) are correlated to prognosis and show efficacy in cancer monitoring in patients. However, their enumeration alone might be inadequate; it might also be critical to understand the viability, the apoptotic state and the kinetics of these cells. Here, we report what we believe to be a new and selective approach to visually detect tumour specific CTCs. Firstly, using labelled human lung cancer cells, we detected a specific density interval in which NSCL-CTCs were concentrated. Secondly, to better characterize CTCs in respect to their heterogeneous composition and tumour reference, blood and tumour biopsy were performed on specimens taken from the same patient. The approach consisted in comparing phenotype profile of CTCs, and their progenitor Tumour Stem Cells, (TSCs). Moreover, NSCL-CTCs were cultivated in short-time human cultures to provide response to drug sensitivity. Our bimodal approach allowed to reveal two items. Firstly, that one part of a tumour, proximal to the bronchial structure, displays a predominance of CD133+. Secondly, specific NSCL-CTCs Epithelial Cell Adhesion Molecule (EpCAM)+CD29+ can be used as a negative prognostic factor as well the high expression of CTCs EpCAM+. These data were confirmed by drug-sensitivity tests, in vitro, and by the survival curves, in vivo.

Synaptic defects associated with s-inclusion body myositis are prevented by copper.

Sporadic-inclusion body myositis (s-IBM) is the most common skeletal muscle disorder to afflict the elderly, and is clinically characterized by skeletal muscle degeneration. Its progressive course leads to muscle weakness and wasting, resulting in severe disability. The exact pathogenesis of this disease is unknown and no effective treatment has yet been found. An intriguing aspect of s-IBM is that it shares several molecular abnormalities with Alzheimer's disease, including the accumulation of amyloid-ß-peptide (Aß). Both disorders affect homeostasis of the cytotoxic fragment Aß(1-42) during aging, but they are clinically distinct diseases. The use of animals that mimic some characteristics of a disease has become important in the search to elucidate the molecular mechanisms underlying the pathogenesis. With the aim of analyzing Aß-induced pathology and evaluating the consequences of modulating Aß aggregation, we used Caenorhabditis elegans that express the Aß human peptide in muscle cells as a model of s-IBM. Previous studies indicate that copper treatment increases the number and size of amyloid deposits in muscle cells, and is able to ameliorate the motility impairments in Aß transgenic C. elegans. Our recent studies show that neuromuscular synaptic transmission is defective in animals that express the Aß-peptide and suggest a specific defect at the nicotine acetylcholine receptors level. Biochemical analyses show that copper treatment increases the number of amyloid deposits but decreases Aß-oligomers. Copper treatment improves motility, synaptic structure and function. Our results suggest that Aß-oligomers are the toxic Aß species that trigger neuromuscular junction dysfunction.

Comparison of physical and psychological status in younger and older overweight-obese women.

BACKGROUND AND AIM: Obesity prevalence is noticeably growing, even in the elderly. Most of the studies concerning the impact of obesity in the elderly evaluated physical co-morbidities, whilst very few data are available on psychological co-morbidities in people ≥ 60 years of age. The present study aimed to compare anthropometrical measures, physical co-morbidities and psychosocial factors correlated with overweight and obesity in younger and elderly people. METHODS AND RESULTS: In 456 women in the age range of 18-59 years and 128 women in the age range of 60-80 years with body mass index (BMI) ≥ 25/kg m², body weight, height and waist and hip circumferences were measured. The presence of co-morbidities such as osteoarthritis, hypertension, type 2 diabetes and hypercholesterolaemia was assessed. The Obesity Related Well Being 97 Questionnaire (ORWELL 97), Body Uneasiness Test (BUT), Symptom Check List 90 (SCL 90) and Binge Eating Scale (BES) tests were used to evaluate psychometric variables. BMI was not significantly different between younger overweight-obese subjects and older overweight-obese subjects, whereas waist circumference and waist-to-hip ratio (WHR) were significantly higher in the elderly. Osteoarthritis, hypertension and hypercholesterolaemia were significantly more frequent in the elderly. Older overweight-obese subjects had better scores in most of the psychometric questionnaires. CONCLUSIONS: Our results show that older overweight-obese subjects have generally more physical co-morbidities but a better psychological status than younger adults, despite similar BMI. These data may contribute to a better understanding of obesity consequences in the elderly and may help clinicians to differentiate obesity treatments in relation to patients' age.

[Diagnosis of thoracic outlet syndrome. Value of angiography in the sitting position]. / Diagnostic des syndromes du défilé cervico-thoraco-brachial: apport de l'artériographie réalisée en position assise.

PURPOSE: Thoracic outlet syndrome includes arterial, venous or neurological symptoms. Frequently difficult to diagnose clinically, confirmatory imaging studies are usually required. The purpose of this study is to review the diagnostic work-up during management of patients with thoracic outlet syndrome and demonstrate the value of angiography in the sitting position. MATERIALS AND METHODS: Retrospective study of 81 surgical procedures for thoracic outlet syndrome, between 1997 and 2005, in 56 patients aged 17-57 years. Surgery was bilateral in 26 cases, with bilateral surgery in a single setting for 1 patient. All patients presented clinical symptoms confirmed on US, angiography, venogram or EMG. Angiography, from a transfemoral approach, was initially performed in the supine position, without and with dynamic maneuver, and in the sitting position with dynamic maneuver when needed. RESULTS: In 48 patients, supine rest angiography showed stenosis in 6% of cases and supine dynamic angiography showed stenosis in 81% of cases, with severe stenosis in only 35% of cases (stenosis>80% or arterial occlusion). Angiography in the sitting position was performed in 33 patients, showing worsening of stenosis in 91% of cases, with severe stenosis in 87%. CONCLUSION: Angiography in the sitting position with dynamic maneuver improves the sensitivity for detection of thoraci coutlet syndrome. This procedure may be considered in addition to other imaging modalities routinely used including Doppler US, CT and MRI.

Weight loss and quality of life improvement in obese subjects treated with sibutramine: a double-blind randomized multicenter study.

BACKGROUND AND AIM: Obesity affects cardiovascular risk and also quality of life (QoL). The aim of this study was to test weight loss and impact on QoL after sibutramine treatment in obese subjects. METHODS: Double-blind randomized trial on 309 outpatients (51 males, 258 females; age 41.8 +/- 10.9 years, BMI 35.0 +/- 3.1 kg/m(2)) randomized to sibutramine (n = 154) or to placebo (n = 155) treatment. A combination of sibutramine 10 mg or matching placebo and a balanced hypocaloric diet was given for 6 months with monthly evaluations. The main outcome measures were weight loss, the impact of weight on QoL, BMI, and waist circumference. RESULTS: The mean weight reduction was 8.2 kg in the sibutramine group and 3.9 in the placebo group at 6 months (p < 0.01). 40% of the sibutramine subjects and 14% of the control subjects lost > or =10% of their body weight (p < 0.01). The improvement in the impact of weight on QoL was statistically significant only in the sibutramine group at 6 months (mean -12.5 vs. -4.5 points; p < 0.01). In the sibutramine group the reduction in BMI (-3.1 vs. -1.4 kg/m(2)) and waist circumference (7.7 vs. 3.5 cm) was significantly greater (p < 0.001). The incidence of adverse events was low and similar to the placebo. CONCLUSIONS: This study confirmed that sibutramine significantly enhances the effect of diet on weight loss, BMI and waist circumference reduction, and showed a significant improvement of QoL.

Individual versus group therapy for obesity: comparison of dropout rate and treatment outcome.

AIMS: To compare outcome and dropout rates of an individual nutritional counselling (IT) and a cognitive behavioural group therapy (GT) after 6 months of treatment. METHODS: One hundred and twenty-nine women (72 in the IT and 57 in the GT group) aged 18-65 years, with body mass index (BMI) > or =25 kg/m(2). Body weight, height and waist circumference were measured. Obesity Related Well Being 97 questionnaire (ORWELL 97), Body Uneasiness Test (BUT), Symptom Check List 90 (SCL 90) and Binge Eating Scale (BES) tests were used to evaluate psychometrical variables. RESULTS: After 6 months, 37.2% (54.2% of initial IT sample and 15.8% of initial GT sample) of subjects abandoned the treatment programme. Completers were older (p<0.03) and had a worse BUTa General Severity Index score (p<0.04) than non-completers. IT had a higher dropout rate than GT. After 6 months of treatment completers lost 6.39% of initial weight and obtained improvements in all studied variables, except scores of SCL 90 and BUTb Positive Symptom Distress Index questionnaires. IT and GT groups did not differ significantly. CONCLUSIONS: Outcomes of IT and GT were comparable in all studied variables, whereas dropout rate of IT was higher than that of GT, suggesting that some characteristics of GT can contribute to the reduction of attrition. Younger age and better body image (measured by BUT) were associated to dropout. After weight loss we observed improvements in almost all variables in both groups without differences.

Genetic and molecular analysis of spe-27, a gene required for spermiogenesis in Caenorhabditis elegans hermaphrodites.

Hermaphrodites with mutations in the spe-27 gene are self-sterile, laying only unfertilized eggs; mutant males are fertile. Hermaphrodites make spermatids that fail to activate to crawling spermatozoa so passing oocytes sweep them out of the spermatheca. These spermatids do activate and produce self-progeny if young mutant hermaphrodites are mated by fertile (or sterile) males. Spermatids isolated from either mutant males or hermaphrodites initiate activation in vitro when treated with proteases, but then arrest with spiky membrane projections that resemble those of a normal intermediate in pseudopod formation. These phenotypes are identical to spe-8 and spe-12 mutants. They can be explained if males and hermaphrodites have distinct pathways for spermatid activation, and these three genes are necessary only for the hermaphrodite pathway. Consistent with this model, when spe-27 mutant male spermatids without seminal fluid are artificially inseminated into hermaphrodites, they fail to activate. The spe-27 gene has been isolated, sequenced and its regulatory regions identified. The sequence predicts a 131 amino acid polypeptide that has no striking structural motifs and no resemblance to known proteins. Two of the mutations in spe-27 alter mRNA splicing; a third mutation is a temperature-sensitive missense mutation.

The Caenorhabditis elegans spe-6 gene is required for major sperm protein assembly and shows second site non-complementation with an unlinked deficiency.

Caenorhabditis elegans spermatozoa move by crawling. Their motility requires thin cytoskeletal filaments assembled from a unique cytoskeletal protein, the major sperm protein (MSP). During normal sperm development the MSP is segregated to developing sperm by assembly into filaments that form a paracrystalline array in a transient organelle, the fibrous body-membranous organelle. Mutations in the spe-6 gene cause sterility because they lead to defective primary spermatocytes that do not form spermatids. In these mutant spermatocytes the MSP fails to assemble into fibrous body filaments. Instead, the unassembled MSP distributes throughout the cytoplasm and nucleus. Thus, the spe-6 gene product is necessary for normal MSP localization and assembly during sperm development. In addition to their MSP assembly defect, spe-6 mutant spermatocytes arrest meiosis at diakinesis although their spindle pole bodies still replicate and separate. This results in spermatocytes with four half-spindles surrounding condensed, but unsegregated, chromosomes. All four spe-6 alleles, as well as a chromosome III deficiency that deletes the spe-6 gene, fail to complement two small overlapping chromosome IV deficiencies, eDf18 and eDf19. This non-allele-specific second site non-complementation suggests a concentration-dependent interaction between the spe-6 gene product and products of the gene(s) under eDf18 and eDf19, which include a cluster of sperm-specific genes. Since MSP filament assembly is highly concentration-dependent in vitro, the non-complementation might be expected if the sperm-specific gene products under eDf18 and eDf19 were needed together with the spe-6 gene product to promote MSP assembly.

spe-12 encodes a sperm cell surface protein that promotes spermiogenesis in Caenorhabditis elegans.

During spermiogenesis, Caenorhabditis elegans spermatids activate and mature into crawling spermatozoa without synthesizing new proteins. Mutations in the spe-12 gene block spermatid activation, rendering normally self-fertile hermaphrodites sterile. Mutant males, however, are fertile. Surprisingly, when mutant hermaphrodites mate with a male, their self-spermatids activate and form functional spermatozoa, presumably due to contact with male seminal fluid. Here we show that, in addition to its essential role in normal activation of hermaphrodite-derived spermatids, SPE-12 also plays a supplementary but nonessential role in mating-induced activation. We have identified the spe-12 gene, which encodes a novel protein containing a single transmembrane domain. spe-12 mRNA is expressed in the sperm-producing germ line and the protein localizes to the spermatid cell surface. We propose that SPE-12 functions downstream of both hermaphrodite- and male-derived activation signals in a spermatid signaling pathway that initiates spermiogenesis.

Liposarcoma of the pleural cavity. An exceptional tumour.

Primitive liposarcomas of the pleura are exceptional tumours. We report a new case of primitive liposarcoma of the pleura revealed by chest pains in a 50 year old man. Computed tomography showed a large fat density mass in the left pleural cavity. Surgical resection was performed, completed with adjuvant radiotherapy. Few reports are available in the literary world. We present our case, review previously reported cases and discuss treatment.

Personality, attrition and weight loss in treatment seeking women with obesity.

Studies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre-treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m(-2)) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12-month observation period, 32.3% of cases were lost to follow-up. After adjustment for demographic confounders and the severity of eating disorders, no TCI personality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss ≥ 10% (odds ratio, 0.983; 95% confidence interval, 0.975-0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight.

Electrophysiological evidence of a perceptual precedence of global vs. local visual information.

Aim of the present study was to investigate the mechanisms of attentional selection of hierarchically organized visual patterns (compound letter stimuli), while subjects were engaged in target selection at either the global or local level. Event-related brain potentials (ERPs) were recorded using a high density electrode montage. Reaction times (RTs) to target stimuli were also recorded. RT data indicated the interference effect of global incongruent information with the local one. ERP data were consistent with behavioral data. In fact, the early sensory N115 component recorded at the primary visual areas exhibited smaller responses to locally attended elements when the global configuration was incongruent rather than congruent, suggesting an interference effect of the global with the local level. Conversely, no interference effect was found for globally attended configurations. These results strongly support the view of a perceptual advantage of globally conveyed information, very likely mediated by low spatial frequency channels. At later processing levels, N1 and P3 components were faster and larger when attention was paid to the global configuration. The difference between target and nontarget responses, indexing the attentional target selection, yielded a broad occipital-temporal negativity focused onto the left hemisphere in the attend-local, and over the right hemisphere in the attend-global condition. The present findings indicate a hemispheric asymmetry in cerebral activation during local/global processing. In addition, they provide robust evidence of a sensory precedence of global information.

Esophageal perforation: life threatening complication of endotracheal intubation.

OBJECTIVE: To raise awareness of this complication of tracheal intubation, to emphasize the gravity due to delayed diagnosis, and to advocate a surgical treatment. METHODS: Between April 1980 and January 2000, 97 patients were treated for esophageal perforation in our department. We reviewed the cases of perforation occurring after attempted tracheal intubation. Each case is presented. Discussion is focused on diagnosis and treatment. RESULTS: Esophageal perforation occurred after attempted endotracheal intubation in five cases among 58 iatrogenic perforations. There were four women and one man (mean age 72 years). In all cases, it was for a planned operation. Intubation was performed by a single lumen tube in three cases and a double lumen tube in two cases. Presenting symptoms were acute in one case and insidious in four cases. Free interval before diagnosis and treatment was long in all but one case, with an average of 179 h (range 5--432). Two patients suffered from septic shock when they were transferred. All patients were operated on. Two patients died. CONCLUSION: Post intubation esophageal perforation is one of the most life threatening esophageal perforation. Delayed diagnosis is the first cause of gravity. Prevention of this complication begins with recognition of a potentially difficult intubation. Good outcome follows from rapid diagnosis and early surgical treatment.

[Mortality from iatrogenic esophageal perforations is high: experience of 54 treated cases]. / La mortalité des perforations instrumentales de l'oesophage est élevée: expérience de 54 cas traités.

OBJECTIVE: To underline the severity of instrumental esophageal perforations and to discuss their management. PATIENTS AND METHODS: Data from patients treated for instrumental esophageal perforation were collected retrospectively from 1980 to 1995 then prospectively since 1995 to 2000. RESULTS: Fifty-four patients were treated for instrumental perforations. Perforation occurred after exploratory endoscopy (n = 24), endoscopic dilation (n = 13), attempted tracheal intubation (n = 5), foreign body extraction (n = 5), treatment of esophageal varices (n = 4), trans-esophageal echocardiography (n = 2), and duodenal prosthesis implantation (n = 1). Clinical manifestations were immediate in 18 cases and delayed in all others, with an interval before treatment ranging from 2 hours to 45 days (mean = 70 hours). All patients were operated after large spectrum antibiotherapy and intensive care, except 3 who were treated medically due to their poor general condition. Fourteen (26%) patients died, including the 3 non-operated ones. CONCLUSION: Instrumental esophageal perforations are associated with a high mortality, probably due to the poor general condition of the patients. Diagnosis of these perforations is often delayed. A good experience of endoscopic maneuveurs and adequate post-endoscopic monitoring could allow earlier surgical treatment with lower mortality.

[Yersinia enterocolitica in fresh and packaged meats]. / Ricerca di Yersinia enterocolitica in carni fresche ed insaccate.

In these last years it was observed an increased frequency of human infections by Y. enterocolitica supported mostly in Europe by serotype 0:3 and 0:9, and by serotype 0:8 in U.S.A. As far as it is concerned the transmission form to man, in addition to the possible infection between men, the one from animal to man and the one consequent on water use, most important suspicions are about foods derived from infected animals or however contaminated by man (fresh or preserved or processed meat, milk and its products; the produce of sea). Y. enterocolitica was isolated from all the animals for slaughter (especially from the swine's pharynx and excrement, where pathogenic serotypes for man were isolated), this ascertainment has led the Authors to research the microorganism in foods of animal kind. It is a facultative anaerobe and this characteristic allows it to survive and multiply also in packed products kept in the refrigerator. For this reason the A.A. carry out a research of Y. enterocolitica on 484 samples of fresh meats and sausages as follows: beef (150 samples), superficial scratching of ox's skeleton (150 samples), minced meat (20 samples), sausages (164 samples). Sausages and beef were bought in some butcher's shops, the other samples were drawn from slaughter-houses of Messina province. The results have pointed out that none of the analysed samples is found contaminated by these microorganisms.

[Solitary fibrous thoracic tumor: a rare tumor with unpredictable course]. / Tumeur fibreuse solitaire de la plèvre.

A 68-year-old woman presented chest pain and exercise-induced dypnea for one year. Diagnosis was a thoracic solitary fibrous tumor. These tumors are very rare. Clinical outcome is generally good except in 13% of the cases with a malignant component. Complete surgical resection is required.

[Our experience with Van Cleefs clips. Analysis of middle-term results]. / Nostra esperienza delle clip endovenose di Van Cleef. Risultati a medio termine.

The purpose of this study is to evaluate the effects of Van Cleef's intervention, performed in operating theater with a road mapping X-ray to document the procedure. Between January 1999 and April 2001, 35 patients and 38 legs were treated with our surgical technique. Mean follow-up was 42.6 months. The feasibility was excellent and the material well supported. The Authors conclude that the procedure, in selected subjects, may be an alternative to other surgical methods in the treatment of superficial venous disease.

[A case of extraskeletal Ewing's sarcoma of the thoracic wall]. / A proposito di un caso di sarcoma extraosseo di Ewing della parete toracica.

The Authors report a case of extraskeletal Ewing's sarcoma of thoracic wall in a 15-year-old sport-man, who complained about pain in the left upper extremity. The diagnosis was performed by radiology (ultrasound study, TC, RM) and pre-operative needle-aspiration biopsy. The patient was treated by neoadjuvant chemotherapy, wide surgical resection and, then, radiotherapy. Neither local recurrence nor metastases have developed for 8 months.

[Thymectomy in myasthenia gravis. A series of 68 patients]. / Timectomia per miastenia gravis. Una serie di 68 pazienti.

Since January 1988 to December 1998, by the Department of Thoracic Surgery, Haut-Lévêque Hospital, University of Bordeaux, 68 consecutive patients were operated for myasthenia gravis. The aim of our study was to evaluate the results obtained in a group of patients who underwent a thymectomy for myasthenia gravis, in order to contribute for the determination of the prognostic factors which can influence the post-operative course. This series consists on 68 patients. Females were predominant, 41 patients (60.2%) versus 27 males (39.7%). The age extended between 15 and 80 years, average of 45.2 years. The follow-up concerned 52 patients (76.4%); out of there, 8 are in complete remission (15.3%), 31 (59.6%) are in a phase of clinical improvement, 11 patients did not benefit from thymectomy (21.1%), 1 patient died immediately after the surgical operation, I patient died some years after the surgical operation for another reason. In conclusion the thymectomy is a beneficial procedure for myasthenia gravis patients.