Von Willebrand factor: a possible biomarker for disease activity in vasculitis.

OBJECTIVE: Inflammation markers, e.g. C- reactive protein (CRP) and sedimentation rate, can be normal despite active vasculitis. Von Willebrand factor (vWF) is secreted from endothelial cells in response to vascular damage. Some reports suggest increased vWF levels in vasculitis. This study aimed to evaluate vWF serum concentration in vasculitis patients as a possible biomarker of disease activity and to review the current literature. METHOD: Adult patients with systemic vasculitis were prospectively enrolled. Disease activity was recorded using the Birmingham Vasculitis Activity Score (BVAS) version 3. Blood group-adjusted vWF antigen serum level was evaluated at diagnosis and, when available, after treatment. RESULTS: Twenty-five vasculitis patients were compared to 15 healthy controls. The mean age of patients was 56 ± 17 years and 56% were women. Forty percent had anti-neutrophil cytoplasmic autoantibody-associated vasculitis, 20% giant cell arteritis, 16% polyarteritis nodosa, 8% Takayasu arteritis, and the rest had other vasculitides. The mean disease duration was 3.4 ± 4.8 years. Mean vWF was higher in patients with active vasculitis than in healthy controls (212 ± 81% vs 106 ± 26%, p < 0.001). vWF levels directly correlated with BVAS. In 13 patients with active vasculitis who reached remission or low disease activity after treatment, vWF level at follow-up decreased significantly. In three out of five patients who were treated with interleukin-6 inhibitors, vWF was elevated despite normal CRP levels, while vasculitis was clinically active. CONCLUSION: vWF antigen serum level is increased in active vasculitis and could potentially serve as a biomarker for active disease.

Burden of early, advanced and metastatic breast cancer in The Netherlands.

BACKGROUND: The aim of this study was to estimate the total economic and health related burden of breast cancer in the Netherlands. METHODS: Data on incidence, prevalence, mortality and survival were extracted from the Dutch National Cancer Registry and were used to calculate the economic and health related burden of breast cancer for overall, DCIS (stage 0), early- (stage I), locally advanced- (stage II-III) and metastatic- (stage IV) breast cancer by age groups and by year (if applicable). RESULTS: The overall incidence of breast cancer increased from 103.4 up to 153.2 per 100,000 women between 1990 and 2014. The increase was driven by DCIS and early breast cancer as the incidence of locally advanced and metastatic breast cancer remained stable. Between 1990 and 2014, ten-year overall survival rates increased from 87% to 93% for early breast cancer, 41% to 62% for locally advanced- and from 6% to 9% for metastatic disease. Annually, breast cancer in the Netherlands is responsible for approximately 3100 deaths, 26,000 life years lost, 65,000 Disability Adjusted Life Years (DALYs) and an economic burden of €1.27 billion. CONCLUSIONS: This study provides a comprehensive assessment of the burden of breast cancer and subsequent trends over time in the Netherlands.

The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis.

The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.

Endoscopic implantation of autologous myoblasts for stress urinary incontinence and evaluation of its efficacy in sphincterotomized rabbits.

INTRODUCTION: Stress urinary incontinence (SUI) is one of the health problems with more impact on patients' lives. The aim of the present work was to develop a therapy for SUI using tissue engineering by isolation and culture of autologous myoblasts (CAM) followed by endoscopic implantation. We also evaluated the efficacy of this therapy in a rabbit model of incontinence after sphincterotomy. MATERIALS AND METHODS: We used healthy male New Zealand rabbits. The animals were first bled to obtain platelet-poor plasma (PPP) and biopsied for myoblast isolation. Post-sphincterotomy, they were divided into two groups: the treatment group (including animals that received CAM resuspended in PPP) and the control group (including animals receiving only PPP). The leak-point pressure (LPP) was used to measure continence in both groups at different time points. The results were evaluated with hierarchical linear regression models. Histological evaluation of the rabbits' sphincters was also performed at the end of follow-up. RESULTS: No statistically significant differences were observed between the baseline LPP values of each group. The post-sphincterotomy values of both groups were below 50% of the baseline value, which was a mandatory condition for incontinence. The post-implantation values of the treatment group were higher than 50% of the baseline value, which led us to assume continence recovery. A statistically significant difference was observed in the LPP values between the two treatment groups (p=0.003). Histological study revealed interconnected islands formed by muscle fibers in the treatment group, and connective tissue surrounding the urethral lumen and inflammatory infiltrate in the control group. DISCUSSION AND CONCLUSIONS: The implantation of CAM significantly improved LPP values in the treatment group, and the improvement remained throughout the evaluation period. It may be associated with the consistency of the implant and its stability at the injection site. Longer follow-up studies and human clinical investigations are required to consider CAM implantation as an alternative treatment for stress urinary incontinence.

Modelling the impact of extended vaccination strategies on the epidemiology of pertussis.

The aim of this study was to investigate the optimal pertussis booster vaccination strategy for The Netherlands. A realistic age-structured deterministic model was designed. Assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996-2000. Several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infection, underreporting factors, and transmission probabilities). The optimal age of an additional booster dose is in the range of 10-15 years, and implementation of this booster dose will reduce both symptomatic and asymptomatic infections, although the incidence of symptomatic infections in older age groups will increase. The impact of the different assumptions used in the model was in general limited. We conclude that over a wide range of assumptions, an additional booster dose can reduce the incidence of pertussis in the population.

[Intellectual activity and longevity (to memory of academician Vladimir Frol'kis)].

The article presents results of studies. These results show dependence of life expectancy from the social status and intellectual activity. Quality of life of scientists of advanced age in comparison with other pensioners has been analyzed. Continuation of scientific activity became guarantee of their health and longevity.

Cost-effectiveness estimates for antenatal HIV testing in the Netherlands.

This paper provides an estimation of the lifetime health-care cost of HIV-infected children and an update of the cost-effectiveness of universal HIV-screening of pregnant women in Amsterdam (The Netherlands). During 2003-2005, we collected data concerning the prevalence of newly diagnosed HIV-infected pregnant women in Amsterdam. Also, data on resource utilization and HAART regimen for HIV-infected children was gathered from a national registry. Using Kaplan-Meier survival analysis, we estimated the life-expectancy of a vertically HIV-infected child at 19 years, with the corresponding lifetime health-care costs of 179,974 Euros. HIV-screening of pregnant women could prevent 2.4 HIV transmissions annually in Amsterdam, based on an estimated prevalence of nine yet undiagnosed HIV-positive pregnant women per 10,000 pregnancies. We show that universal HIV screening during pregnancy generates significant net cost savings and health benefits in most situations. Universal antenatal HIV screening is justified in Amsterdam from a health-economic point of view.

[A complex psychological assessment of health care quality of medical personnel and quality of life of four generation of Ukrainians].

The article presents experience of the assessment of labour quality and professionalism of medical personnel (physicians and nurses) after the study conducted in 20 medical institutions in Kiev and 20 in Moscow. Expert-points method of assessment was used, correlation analysis of finalized qualifying assessment and social status of staff in each department was the mechanism of check of obtained results. Quality of life of population depends a lot on professionalism of specialists (physicians, teachers, scientists and others). The article presents results of four year (2003-2006) study of quality of life of four generations of Ukrainians aged from 11 to 85 years. Regularity was revealed in different sides of life of four group of responders, including personal, behavioral and psychological aspects.

Aortic involvement in rheumatic diseases.

OBJECTIVE: To review the prevalence, mechanisms, presentations and clinical significance of aortic involvement in rheumatic inflammatory diseases. METHODS: The medical literature, available through a PUBMED search was reviewed and the relevant information was summarized. In addition, selected articles related to aortic involvement in rheumatic diseases were included in this review. RESULTS: Rheumatic disorders may be categorized by their propensity to involve the aorta: conditions with a prevalence of 10% and more (Takayasu's arteritis, temporal arteritis, long-standing ankylosing spondylitis, Cogan's syndrome and relapsing polychondritis), disorders with uncommon but well documented aortic involvement and rheumatic conditions with rare case reports of such involvement. Clinical presentation of aortic disease is dependent on the part of aorta involved and may manifest by aortic pain and/or other symptoms caused by aortic dilatation, narrowing or aneurysm. The histopathology of inflammatory aortitis is characterized by lymphoplasmacytic infiltration with or without giant cells or granulomas. On the other hand, non-inflammatory aortic damage in rheumatic diseases may include Marfan-like cystic disintegration of the aortic media as well as accelerated atherosclerosis. Awareness of rheumatic conditions with a high potential for clinically significant aortic involvement may promote referral of such patients for aortic imaging and sometimes surgery before fatal complications intervene. CONCLUSION: Early diagnosis of aortic involvement can be advanced by informed consideration of such a complication in a rheumatic patient.

The emergency room in systemic rheumatic diseases.

Complications of systemic rheumatic diseases frequently have protean manifestations and may present a diagnostic problem. Patients with connective tissue diseases and vasculitides may have dangerous or life threatening conditions, which must be recognised and treated promptly to prevent rapidly evolving morbidity and mortality. Knowledge of possible emergencies in the context of a defined rheumatic disease may aid in promoting a high index of suspicion and contribute significantly to the timely diagnosis of many potentially dangerous conditions. This review is written for the emergency room physician and discusses the early recognition of selected emergencies in the context of a defined rheumatic disease.

[Quality of life of Ukrainians in the beginning of 21st century].

Study carried out in the period of three years (2003-2005) allowed comparing ukrainian residents' life quality in three generations via subjective assessment of responders, which revealed different sides of their life depending on age, including individul, behavioral and psychological features.

Increased spontaneous apoptosis of CD4+CD25+ T cells in patients with active rheumatoid arthritis is reduced by infliximab.

Increased secretion of tumor necrosis factor-alpha (TNF-alpha), along with interleukin-1 (IL-1) and interleukin-6 (IL-6), is important in the pathogenesis of rheumatoid arthritis (RA). T regulatory CD4(+)CD25(+) cells play a role in maintaining self-tolerance by downregulating Th1-induced proinflammation. This function has been found to be altered in active RA, whereas anti-TNF-alpha therapy has been found to improve the suppressive abilities of these cells. Our objectives were to investigate whether T regulatory cells in patients with active RA display a higher sensitivity to spontaneous apoptosis than in normals, and to look into the potential of infliximab (anti-TNF-alpha therapy) to reduce the sensitivity of these cells to spontaneous apoptosis. Seventeen patients suffering from active RA, having failed multiple disease-modifying antirheumatic drug (DMARD) therapies, were treated with infliximab. Spontaneous apoptosis (as detected by annexin V binding) was determined in all patients and compared with a group of normal individuals at baseline and after three months on infliximab treatment. Peripheral blood mononuclear cells were incubated in 24-well plates at 1 x 10(6) cells/mL for 48 hours. Annexin V binding on CD4(+)CD25(+) was assessed using three-color assay by flow cytometry. Prior to infliximab initiation, spontaneous apoptosis of T regulatory cells from active RA patients was found to be increased in comparison with controls (26 +/- 4.2% vs. 19.8 +/- 4.8%, respectively; P = 0.01). Three months later (while still on infliximab) spontaneous apoptosis was comparable in the two groups (20.7 +/- 5.2% vs. 20.9 +/- 3.4%; P 5 0.8). The absolute number of CD4(+)CD25(+) cells/mL in the peripheral blood at baseline was reduced in 11 out of 17 active RA patients when compared with that of the control group (24 +/- 7 vs. 32 +/- 11, respectively; P = 0.02). Following anti-TNF-alpha therapy, CD4(+)CD25(+) cell counts of patients were equivalent to those of normals. The alteration and reversal in both spontaneous apoptosis and cell count of T regulatory cells was found to correlate with RA disease activity. CD4(+)CD25(+) T regulatory cells display increased proclivity to undergo spontaneous apoptosis in active RA. Alterations in CD4(+)CD25(+) cell apoptosis and cell count were found to correlate with RA disease activity. Reversal of these deviations from normal was documented in association with the beneficial outcome of infliximab therapy.

Pseudopodagra: A presenting manifestation of infective endocarditis.

Podagra is a term used to describe acute monoarthritis of the first metatarsophalangeal (1st MTP) joint. The most common diagnoses of arthritis in this joint are: crystal-induced synovitis, septic arthritis, traumatic conditions and reactive arthritis. When etiologies other than gout are involved this is frequently referred to as pseudopodagra. We report the case of a patient who presented with pain and swelling of the 1st MTP The absence of intraarticular crystals and hyperuricemia encouraged further evaluation of the patient. A cardiac murmur was investigated by echocardiography, which revealed valvular vegetations and the diagnosis of infective endocarditis (IE) was established. This is the first reported case of a podagra-like presentation of IE. As in this case, the diagnosis of gout should rest on findings beyond the presence at 1st MTP arthritis, with evaluation of all extraarticular signs in order to rule out other possible diagnoses.

Behçet's disease, myelodysplastic syndrome, trisomy 8, gastroenterological involvement--an association.

Only a limited number of cases of Behçet's disease and hematological malignancies have been reported in the literature. We report the case of a 45 year old female patient with Behçet's disease who developed myelodysplastic syndrome, refractory anemia with excess blasts in transformation subtype, with complex chromosomal abnormalities, including excess of chromosome 8, following several years of treatment with chlorambucil for Behçet's disease. As has been described in most such cases, gastrointestinal involvement was most prominent. This case is described and the occurrence of myelodysplastic syndrome in Behçet's disease reviewed.

[Psychological assessment of the quality of life of elderly people born in America and immigrants].

Comparative study of different aspects of the quality of life of two groups of the former Soviet Union elderly immigrants and native Americans was carried out by means of sociometric technique using expert estimation expressed in numbers. Considerable discrepancy in assessment of individual, behavioral, social and psychological features of the two groups of the responders has been detected and explained.

Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF).

Familial Mediterranean Fever is one of the most frequent recessive disease in non-Ashkenazi Jews. The gene responsible for the disease (MEFV) has very recently been identified. The M694V ('MED') mutation was found in about 80% of the FMF Jewish (Iraqi and North African) chromosomes. To see if the presence of this mutation could be correlated with particular traits of the disease, we examined a number of clinical features in a panel of 109 Jewish FMF patients with 0, 1 or 2 MED mutations. We showed that homozygosity for this mutation was significantly associated with a more severe form of the disease. In homozygous patients, the disease started earlier (mean age 6.4 +/- 5 vs 13.6 +/- 8.9) and both arthritis and pleuritis were twice as frequent as in patients with one or no M694V mutation. Moreover, 3/3 patients with amyloidosis displayed two MED mutations. No association was found with fever, peritonitis, response to colchicine and erysipeloid eruption. The present result strongly suggests the potential prognostic value of the presence of this mutation.

Scintigraphy of posterior tibial tendinitis.

UNLABELLED: Our goal was to describe the typical scintigraphic pattern of posterior tibial tendinitis. METHODS: Bone scintigraphs were reviewed to study the scintigraphic characteristics of posterior tibial tendinitis in nine patients with posterior tibial tendinitis related to generalized rheumatic disease and in eight patients with isolated posterior tibial tendinitis. RESULTS: The scintigraphic pattern of posterior tibial tendinitis is elongated increased uptake in the blood flow and blood-pool phase along the anatomical course of the tibialis posterior tendon at the medial aspect of the ankle (malleolus region). Static images demonstrate increased focal abnormal uptake at the medial malleolus and in the navicular bone. CONCLUSION: Bone scintigraphy depicts a characteristic pattern of posterior tibial tendinitis. It is useful for the early diagnosis of idiopathic- or rheumatic-related posterior tibial tendinitis.

Cancer-associated rheumatic disorders: clues to occult neoplasia.

Interest in the rheumatologic manifestations of cancer is related in part to practical considerations, ie, earlier cancer diagnosis is possible through enhanced awareness of cancer-associated rheumatic syndromes. The spectrum of rheumatic disorders associated with cancer includes over 30 conditions, including hypertrophic osteoarthropathy, polymyalgia rheumatica, palmar fasciitis with polyarthritis, most autoimmune connective tissue diseases, and the more recently described antiphospholipid syndrome. It is generally held that extensive search for occult malignancy in most rheumatologic disorders is not cost efficient and not recommended unless accompanied by specific findings suggestive of malignancy. The present article discusses the supplementary findings that may justify malignancy evaluation.

Rheumatic syndromes: clues to occult neoplasia.

OBJECTIVES: Rheumatic disorders associated with cancer include a variety of conditions, most of which have no features distinguishing them from idiopathic rheumatic disorders. It is generally held that an extensive search for occult malignancy in most rheumatic syndromes is not recommended unless accompanied by specific findings suggestive of malignancy. The objective of this review are to identify rheumatic syndromes associated with cancer, to call attention to features that may suggest the presence of a hidden cancer, and to examine the role to additional clinical and laboratory data as clues to the possible neoplastic cause of those syndromes. METHODS: A MEDLINE search of the literature dealing with cancer-associated rheumatic syndromes was conducted. RESULTS: Review of the literature identified significant progress in this area. First, the association of malignancy with certain rheumatic syndromes was convincingly established, such as asymmetric polyarthritis presenting in the elderly with an explosive onset, rheumatoid arthritis with monoclonal gammopathy, Sjögren's syndrome with monoclonality, hypertrophic osteoarthropathy, dermatomyositis, polymyalgia rheumatica with atypical features, Lambert-Eaton myasthenic syndrome, palmar fasciitis and arthritis, eosinophilic fasciitis poorly responsive to corticosteroid therapy, erythema nodosum lasting more than 6 months, and onset of Raynaud's phenomenon or cutaneous leukocytoclastic vasculitis after age 50 years. Second, the list of cancer-associated rheumatic syndromes was extended by including additional entities such as benign edematous polysynovitis, sacroiliitis, adult-onset Still's disease, dermatomyositis sine myositis, systemic sclerosis, Sweet's syndrome, osteomalacia, skeletal hyperostosis, antiphospholipid syndrome, and essential mixed cryoglobulinemia. Third, evidence was provided substantiating that certain long-standing rheumatic syndromes, in particular rheumatoid arthritis, Felty's syndrome, Sjögren's syndrome, dermatomyositis, systemic sclerosis, systemic lupus erythematosus, and temporal arteritis behave like "premalignant conditions." Fourth, it was shown that the recognized tumor markers alpha-fetoprotein, prostate-specific antigen, CA-125, CA 19-9, and CA-3 have low sensitivity and specificity in screening for occult cancer in a population of rheumatic patients, whereas the presence of a monoclonal gammopathy in rheumatoid arthritis and the monoclonal antibody 17-109 in Sjögren's syndrome are reliable signs of malignant transformation. CONCLUSIONS: The presence of specific rheumatic syndromes and certain clinical and laboratory findings may justify a workup for hidden cancer. Studies of the epidemiology of the cancer-associated rheumatic syndromes and evaluation of the validity of aforementioned clues in prospective studies are goals for future investigations.