Impact of early diagnosis and control of chronic respiratory diseases on active and healthy ageing. A debate at the European Union Parliament.

A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc-Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy (PAPA). The third project is the GA(2)LEN sentinel network.

Hepatitis C virus-mixed cryoglobulinemia-lymphoma relationship.

HCV (hepatitis C virus) chronic hepatitis has become one the most expensive diseases for public health systems all over the world in the past 10-20 years, a real epidemic, the second most frequent, after hepatitis B virus infection. Due to the complex manifestations, one may consider HCV infection as a "systemic" disease. Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection, but cryoglobulinemic vasculitis (CV) is considered to be relatively sparse although prevalence studies are needed. Presence of serum cryoglobulins is essential for MC diagnosis, but serum levels do not correlate with the disease activity or prognosis. MC can be defined as a B lymphocyte proliferation disease being characterized by polyclonal activation and antibody synthesis. Evolution to lymphoma should be considered continuous but also other infectious, environmental or genetic factors could be involved. The t (14.18) translocation and Bcl-2 activation in B lymphocytes, B cell-activating factor (BAFF), E2-CD81 interaction, immunoregulatory T CD4+CD25(high) + lymphocytes and type III IFNs might play an important role in MC and lymphoma evolution in HCV patients.

Pathological evidence in support of total mesorectal excision in the management of rectal cancer.

BACKGROUND: Pelvic recurrence following conventional rectal resection for cancer is common. Preoperative iradiation has been shown in prospective randomized studies to halve this risk. AIM: This multiinstitutional study aimed to assess the necesity of total mesorectal excision in rectal cancer. PATIENTS AND METHOD: Pathological resections from 50 consecutive patients with adenocarcinoma of the rectum within 12 cm of the anal verge who underwent currative resection incorporating total mesorectal excision were examined. The resection specimen was examined by one of two pathologists. Some 50 total mesorectal excision specimens were examined following rectal excision for cancer. Some 38 had total mesorectal excision as a component of a low anterior resection and 12 with abdomino-perineal resection. "Cure" was defined as absence of metastatic disease and the excision of entire macroscopic tumor tissue with negative proximal and distal borders. TME was performed as described by Heald et al. The mesorectum was evaluated for lymph nodes and tumor deposists in three areas: deep to the tumor, in the proximal mesorectum and in the distal mesorectum. RESULTS: Six patients had Dukes A lesions. Of 21 patients with Dukes B tumors, five had discrete foci of adenocarcinoma in the mesorectum, with no evidence of lymph node metastasis. Dukes C lesions were more heterogeneous, but 12 out of 23 patients had distinct mesorectal deposists in addition to mesorectal node involvement. Circumferential margin involvement was rare, but mesorectal tumor deposits were present in 17 of 44 patients with pT3 tumors, and 23 of 44 had mesorectal nodal involvement. No patient with a pT2 tumor had mesorectal involvement. Failure to excise the mesorectum completely has the potential to leave gross or microscopic residual disease that may in theory predispose to local failure. CONCLUSION: Total mesorectal excision is necessary to avoid incomplete pathological evaluation of the mesorectum and understaging of rectal cancer.

[Difficult case of thoraco-abdominal injuries due to a motor vehicle accident]. / Caz dificil de plaga toraco-freno-abdominala prin accident rutier.

Recently, in our country we experience an increase incidence of motor vehicle accidents, which often leads to some severe cases brought to the A&E's departments, requiring prompt complex surgical treatment, with the surgeon facing out of ordinary situations. This is the case for the combined trauma of the chest and abdomen. The authors present the case of a 32 years old female patient, victim of a MVA, who had suffered a deep penetrating wound of her right chest and right upper quadrant, caused by a woden pole which penetrated the anterior V and VI intercostal spaces, went through the right inferior pulmonar lobe, the diaphragm and the 7th segment of the liver, resting on the posterior wall of the ribcage. This patient required emergency surgery, making un uneventful postoperative course.

Neuromyelitis optica--complication or comorbidity in primary Sjögren's syndrome?

We report two cases of neuromyelitis optica (NMO) associated with primary Sjögren's syndrome (pSS), comparing the clinical and laboratory features of these predominant neurological patients and reporting their different outcome. NMO - a severe demyelinating disorder of the central nervous system - primarily affects the spinal cord and optic nerves, resulting in longitudinally extensive transverse myelitis and/or optic neuritis. Our patients had a late pSS diagnosis, due to the absence of sicca syndrome and specific Sjögren serology in the early stages of their diseases, when the neurological symptoms prevailed. Many NMO patients have an accompanying autoimmune disease, most commonly Sjögren syndrome and systemic lupus erythematosus or a related profile of non-organ-specific autoantibodies. Neurologic involvement occurs in approximately 20% of patients with pSS, usually preceding the diagnosis (in 75-80% of the cases) [1,2]. The frequency of both neurologic manifestations (revealing pSS) and negative autoimmune serology, especially in the event of CNS involvement, could explain why underlying pSS is misdiagnosed [3,4]. Screening for pSS should be systematically performed in cases of acute or chronic myelopathy and/or cranial nerve involvement, mainly because these patients have a severe outcome. The presence of the anti-aquaporin4 antibodies, besides anti-Ro and anti-La, in both reported cases, is intriguing and raises the question of whether we are facing two distinct diseases or the NMO is just complicating an unusually less expressive Sjögren's syndrome subtype.

Treatment of extrahepatic manifestations of chronic hepatitis C viral infection--a challenge.

Often, chronic hepatitis C infection is clinically manifested as extra hepatic disease. Therapy of the extra hepatic manifestations (EHM) is always difficult and based on the optimal and individual association of antiviral treatment, immunosuppressant and plasma cleaning techniques. We observed for 4 years 246 patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were diagnosed as chronic C hepatitis. 130 of those patients have had at least one EHM. In our experience, the presence of an EHM is significantly correlated with lack of early viral response and sustained viral response, as well. Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy associated to plasmapheresis. When present, peripheral neuropathy and cryocrit greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

Platelet histogram indices and cardiovascular disease in patients with rheumatoid arthritis.

UNLABELLED: BACKGROUND; Previous studies reported the increased prevalence of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general population. However, the predictors for the development of CVD in patients with RA were not clearly established, and the role of thrombosis mechanisms was inconsistently characterized in these patients. The aim of this study was to evaluate the platelet histogram indices, as markers of platelet activation, in patients with RA with or without CVD. MATERIAL AND METHODS: In 64 pts with RA (mean age: 58.0 +/- 12.7 yrs) we performed the standard clinical evaluation and biochemical workup with platelet histogram, including mean platelet volume (MPV) and platelet distribution width (PDW) as markers of platelet activation. We divided the study population into two groups: A - 41 patients with RA without CVD and B - 23 patients with RA and CVD (ischemic heart disease, peripheral artery disease or cerebrovascular disease). The values of MPV and PDW were also analyzed in an age- and sex-mached control group of 20 subjects without RA and CVD and in a group of 62 patients with CVD without RA (stable angina). RESULTS: The platelets number was similar in both groups, but the platelet histogram showed higher values for MPV (9.6 vs. 8.6 fL, p < 0.01) and PDW (16.1 vs. 14.0, p < 0.01) in patients with RA and CVD, reflecting greater platelet activation in these patients. MPV values were lower in patients with RA, but the values of PDW were higher in these patients comparing to control. Patients with RA with CVD have higher values of PDW than patients with CVD, but without RA, showing an increased platelet activation in RA. The PDW values correlate with fibrinogen (0.63; p = 0.003) but not with CRP or ESR, while the MPV was not correlated with the inflammatory markers in patients with RA. CONCLUSIONS: The pathogensis of CVD in patients with RA may be linked to an increased prothrombotic activity which might be evaluated by platelet histogram indices.

IL-17 in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression. MATERIAL AND METHODS: 89 subjects were recruited and divided in 5 groups-10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry. RESULTS: Immunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p<0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p<0.05). Serum IL-17A levels were similar in SCLE and negative controls (p>0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p<0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p>0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p<0.05). CONCLUSION: IL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.

T helper 17 cell population in lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) is an autoimmune inflammatory disease that involves many organs and systems. Immunological factors seem to play a key-role in LE pathogenesis. LE patients have T lymphocytes dysfunctions.Th17 is implicated in the pathogenesis of various autoimmune diseases like psoriasis, multiple sclerosis or rheumatoid arthritis. The purpose of this study was to evaluate the circulating Th17 cell population in LE patients. MATERIAL AND METHODS: A total of 15 LE patients were recruited and divided into three groups: systemic lupus erythematosus (SLE), discoid lupus (DLE) and subacute lupus (SCLE). Serum IL-17A, IL-17F and IL-23 were detected. Th17 circulating cells were evaluated by flow cytometry. RESULTS: Serum IL-17A and IL-17F levels were higher in SLE, DLE and SCLE patients compared to healthy controls. The number of Th17 cells were higher in SLE and DLE patients (p<0.05). the number of CD3+IL-17+ cells were higher in SLE, DLE and SCLE patients (p<0.05). CONCLUSION: Th17 lymphocytes are implicated in LE pathogenesis. Our findings suggest that IL-17 is implicated not only in SLE but also in DLE and SCLE immunopathogenesis.

Immunohistochemical aspects of apoptosis in subcutaneous lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) has a broad clinical spectrum from exclusively skin damage (chronic discoid lupus-DLE or subacute lupus erythematosus-SCLE) to systemic, multiorgan disease (involving skin, joints, kidney, central nervous system). LE is characterized by an autoimmune component. SCLE is characterized by erythemato-squamous lesions mainly in photoexposed areas. Apoptosis (programmed cellular death) is essential for normal embryogenesis and for normal tissue homeostasis and control. Inefficient apoptotic cell clearance has been correlated with inflammatory diseases and autoimmunity outburst. This study evaluates histological and immunohistochemical expression ofpro-apoptotic markers in patients with SCLE. MATERIALS AND METHODS: 20 patients with SCLE and 10 healthy controls were selected. Biopsies from skin lesions were performed. Biopsies were evaluated for immunohistochemical expression of caspase 3, CD25, CD35, CD21, CD36, CD68, CD31, IgM detection, T and B cell markers. RESULTS: In the inflammatory cells population we distinguished T lymphocytes, rare B lymphocytes, dendritic cells and macrophages. Within the lymphocyte population IL-2 receptor (CD25) expression was low but caspase 3 expression was intense in lymphocytes, epithelial cells and pericytes. Basal epithelial vacuolations were common. Phagocytic-cell and lymphocytic expression of CD35 (complement receptor 1-CR1) and CD21 (complement receptor 2-CR2) were lower when compared to healthy controls. CONCLUSIONS: In SCLE patients we observed lymphocytic, epithelial and pericytal cell apoptosis and CR1 and CR2 expression are lower in professional phagocytes, suggesting a delay in the uptake of apoptotic bodies.

Anti C1q antibodies in cutaneous lupus erythematosus.

UNLABELLED: Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Anti-C1q antibodies are strongly associated with lupus nephritis. Recent studies describe apoptosis as a key player in LE pathogenesis and C1q is an important opsonin, playing a central role in the uptake of apoptotic blebs. The aim of this study was to evaluate serum anti C1q antibodies, C1q with circulating immune complexes and correlation between serology and cutaneous apoptosis in patients with cutaneous lupus erythematosus. MATERIAL AND METHODS: 79 subjects were recruited and divided into 4 groups-13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum anti-C1q antibodies and C1q associated to the immune complexes concentrations were determined by ELISA. Cutaneous caspase-3 expression was evaluated by immunohistochemistry. RESULTS: SLE and SCLE patients had significantly higher levels of anti-C1q antibodies and serum C1q-CIC levels when compared to healthy controls (p < 0.05). Serum anti-C1q antibodies correlated with proteinuria in SLE patients (p < 0.05). Anti C1q antibodies levels also correlated with cutaneous caspase 3 expression in SLE and SCLE patients (both p < 0.05). CONCLUSIONS: Anti C1q antibodies might play a pathogenic role in SCLE pathogenesis and being positively associated with cutaneous apoptosis markers might be associated with a negative prognosis and secondary SLE development.

Endothelial dysfunction in inflammatory rheumatic diseases.

The importance of cardiovascular disease in inflammatory rheumatic diseases was recognized as one of the determinants of increased mortality in these patients. An increased cardiovascular disease was reported in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but also in other rheumatic diseases. Several hypotheses were elaborated, but the chronic inflammatory status seems to be a primordial factor. Therefore, the diagnostic and treatment of cardiovascular disease, even in subclinical status, should be one of most important goals in the global management of these patients. The endothelial dysfunction is now regarded as an important and early step in the processes that promote atherosclerosis. In patients with inflammatory rheumatic diseases, the presence of the endothelial dysfunction was reported and linked with several clinical or biological features of each disease. Moreover, the potential benefits on the endothelial dysfunction of several therapies were assessed especially in patients with RA or SLE. The aim of this article is to review the impact of the endothelial dysfunction and the methods to improve it in patients with these conditions.

Traditional and nontraditional risk factors for atherosclerosis in patients with systemic lupus erythematosus.

Premature atherosclerosis (ATS) in SLE patients is an important clinical problem. It is explained not only by excess of traditional risk factors, but also by specific factors linked to disease activity and therapy. Such specific factors include the following: antioxLDL and anti CRP antibodies, immune complexes, mannose-binding lectin, disturbances of metabolism of annexin A5, antiphospholipid syndrome, immunologically determined dyslipidemia, influence of medication. As a conclusion,atherosclerosis in SLE patients results from an interplay between traditional and nontraditional risk factors. Therapeutic influences suggest antiatherogenic effects for hydroxychloroquine and immunosuppressants and a doubtful proatherogenic influence of cortisone.

[Fever of unknown origin in Romania. II. Diagnostic Procedures. Prospective multicenter study of 164 patients]. / Febra de origine necunoscuta: II. Mijloace diagnostice. Un studiu prospectiv multicentric pe 164 de pacienti.

BACKGROUND: The Diagnostic workup of patients with fever of unknown origin is a challenge, due to the great number of possible etiologies. After we studied the etiologic spectrum of fever of unknown origin in Romania, we tried to evaluate the diagnostic procedures used and their efficiency. METHODS: A multicenter cohort study of two years, with another two years of follow-up was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. We used a standardised diagnostic protocol. MAIN OUTCOME MEASURED: The role of every diagnostic procedure in establishing the final diagnosis. RESULTS: The diagnosis was made by microbiology and serology in 41 cases (25%), by histopathology in 22 cases (18%), with the help of imaging techniques in 30 cases (1.3%), based on the clinical evolution and response to treatment in 54 cases (33%) and by other methods in 12 cases (7.3%). The abdomino-pelvic ultrasonography had a sensitivity of 60%, a specificity of 70%, a positive likelihood ratio of 2.02 and a negative likelihood ratio of 0.57, while the scanner had a sensitivity of 81%, a specificity of 64%, a positive likelihood ratio of 2.23 and a negative likelihood ratio of 0.29. CONCLUSIONS: Of all the diagnostic procedures used, none had a good sensitivity/specificity. The clinical evolution and the treatment response had an important role in the diagnostic workup.

[Fever of unknown origin: 1. Etiology. A prospective multicenter study of 164 patients]. / Febra de origine necunoscuta. I. Etiologie. Studiu prospectiv multicentric pe 164 de pacienti.

BACKGROUND: The spectrum of fever of unknown origin seems to be determined by geographic and economic factors, and it appears to change in time. Excepting a small retrospective study, no other study on fever of unknown origin has been performed in Central or Eastern Europe. METHODS: A multicenter cohort study was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. The study lasted 2 years (1997-1998) and included a follow-up period of another 2 years. MAIN OUTCOME MEASURED: The final diagnosis at the end of follow-up. RESULTS: 74 (45%) patients had infections (tuberculosis: 27 patients, 16%), 41 patients (25%) had neoplasms, 30 (18%) had non-infectious inflammatory diseases, three (2%) drug fever, and four (2%) other causes. The etiology remained obscure for 12 patients (7%). CONCLUSIONS: Infections represent the most important etiology, among them predominating tuberculosis.

Chronic hepatitis C virus infection mimicking rheumatoid arthritis.

We present the case of a young female patient diagnosed two years ago with rheumatoid arthritis (AR) for which she is taking methotrexate (MTX), who develops cutaneous lesions highly suggestive of porphyria cutanea tarda, diagnosis confirmed by biochemical means. It is noteworthy that she was regularly taking oral contraceptives until the moment of appearance of the skin lesions. The association of those two illnesses, particularly in the case of MTX treatment can raise some problems regarding the potential direct causality relationship. This is why we tried a new diagnostic hypothesis: is chronic hepatitis C virus infection, hypothesis that we verified by means of the presence of anti-VHC and of RNA-VHC. It is well known now the association between chronic viral C infection, rheumatoid syndrome and porphyria cutanea tarda (PCT). The latter are extrahepatic manifestations of that viral infection, thus representing a major indication for antiviral treatment. Our patient received that treatment and she had a very good outcome of the skin lesions. We suggest that the differential diagnosis of any arthritis should always comprise chronic hepatitis C viral infection.

Kikuchi's disease associated with systemic lupus erythematosus and autoimmune-like hepatitis.

The authors present a case of Kikuchi's disease associated with systemic lupus erythematosus (SLE) and autoimmune-like hepatitis. Kikuchi's disease, or histiocytic necrotizing lymphadenitis is occasionally associated with SLE and mildly elevated aminotransferases. A 17-year old woman presented with fever, arthritis and bilateral cervical adenopathy. Histopathological and immunohistochemical examinations of an excised lymph node showed evidence of Kikuchi disease. An elevation of hepatocytic enzymes (aminotransferases and gamma-glutamyl transpeptidase) associated with smooth muscle antibodies in a titer of 1/320 was present. Clinical symptoms and laboratory tests improved after "pulse" corticotherapy. The association described has not been described in the literature, but is considered possible due to the immune pathogenicity of the 3 simultaneous diseases. Kikuchi-Fujimoto's disease, or histiocytic necrotizing lymphadenitis (HNL), is a rare condition first described in 1972 independently by Kikuchi and Fujimoto. HNL is rarely associated with systemic lupus erythematosus (SLE). It is a benign illness characterized by fever and cervical adenopathy and has a self-limiting course.

Chronic viral hepatitis, the treatment with spiruline for one month has no effect on the aminotransferases.

CONTEXT: Spirulina platensis is extracted from an alga and theoretically has many good effects on the majority of the organs. There is not any published clinical trial on humans. OBJECTIVE: The evaluation of the efficacy of spiruline in chronic viral liver disease. DESIGN: Double blind, randomised clinical trial. SETTING: Secondary care university hospital. PATIENTS: 24 patients with chronic viral liver disease, treated with spiruline or placebo for one month. OUTCOME MEASUREMENT: Aminotransferases diminution and the modification of a general state score self-evaluated by the patient on an analogic visual scale. RESULTS: A modification of the aminotransferases level in the detriment of the spiruline treated group has been found (p = 0.036 for ALAT, p = 0.017 for ASAT), and not at the level of the general state score (p = 0.30). CONCLUSION: Despite the little number of patients, significant results not favouring spiruline have been found.

Biliary cystadenocarcinoma with two types of tumour cells.

We report a rare case of biliary cystadenocarcinoma that occurred in the left hepatic lobe of a 62-year-old man and measured 20 cm in its greatest dimension. The neoplastic epithelium consisted of two types of cells: (1) cells with clear cytoplasm containing abundant mucin, and (2) cells with eosinophilic cytoplasm, which in some areas formed nodules with hepatocytoid features (polygonal cell shape, large nuclei with prominent nucleoli, and pseudoglandular structures). Histochemical stains revealed the presence of cytoplasmic mucin in the hepatocytoid areas, whereas immunohistochemical stains clearly showed a biliary phenotype (diffuse positive staining for "biliary type" cytokeratins, rare foci of positive staining with antibody to human hepatocytes (HEP-PAR1), absence of staining for alpha-fetoprotein, and no evidence of canalicular pattern of staining with polyclonal antibody to carcinoembryonic antigen). These findings indicate that areas reminiscent of hepatocellular carcinoma may occur in biliary cystadenocarcinomas. Histochemical and immunohistochemical stains are useful in reaching a definitive diagnosis in such cases.

Comparison of two microemulsion of cyclosporine A in healthy volunteers.

This study evaluated the bioequivalence of a new Cyclosporine A microemulsion formulation in comparison to the reference market standard. Twenty-four adult healthy volunteers were randomised to receive the two Cyclosporin A microemulsion formulations, at a dose of 2.5 mg/kg, according to a cross-over design. Blood samples were taken before drug administration and at 12 points within 24 hours. Cyclosporine A whole blood concentrations were determined by HPLC. The pharmacokinetic parameters AUC0-t and AUC0-infinity were calculated by the trapezoidal rule, Cmax and Tmax were obtained directly from blood data. AUCs and Cmax were tested for bioequivalence after log transformation of data, differences for Tmax were evaluated by the rank test of Wilcoxon for paired data. The 90% confidence interval ratio between tested/reference drug was 0.98 for AUC0-t, 0.96 for AUC0-infinity and 1.01 for Cmax. All of them were within the range of bioequivalence. Tmax was 1.60 +/- 0.44 hours after test drug and 1.67 +/- 0.48 after reference drug (p = 0.27, Wilcoxon test). According to these results the two Cyclosporine A microemulsion formulations can be considered bioequivalent.