Advance in phlebology in Japan

Vascular surgery has recently been witnessing remarkable progress in Japan, supported in part by an increase in the number of researchers. Although the actual researchers specializing in the field of phlebology are much fewer in Japan as opposed to the West because of a seemingly lesser number of patients suffering from venous diseases particularly those which are fatal, the participants in the annual meetings of the Japanese Society of Phlebology have shown a gradual increase since 1980. Notably, the 9th World Congress of Phlebology was held in late September 1986 in Kyoto with a great many global authorities giving lectures, presenting papers and discussing a wide range of topics with the 600 participants attending. This event markedly stimulated our phlebologists and will undoubtedly contribute to enhancing the level of phlebology in Japan. This positive environment was also given an earlier boost in 1985 by the Japanese Ministry of Health and Welfare establishing a study group for angiology including phlebology and lymphology. The activity of this group may be a important foundation for the most significant advances in phlebology in Japan.     

Rabies in wildlife in Latvia

In the Baltic States, lyssaviruses are often detected in wildlife and presumed to constitute an important public health hazard. In order to decrease rabies incidence and eradicate wildlife reservoirs, a national rabies eradication program has been in place. Since 1970 a vaccination program in dogs and cats has been executed, and in 1991 oral vaccination of foxes was started. However, due to an insufficient budget, the latter was not done regularly and nationwide before 2000. Now, the program in force consists of compulsory vaccination of all dogs and cats, and a tetracycline marker vaccine oral vaccination program of foxes in the whole country. In 2001, 151 of 285 (53%) fox jaws were tested positive for tetracycline. All animals showing rabies-like symptoms were killed and tested for rabies. In this way, 250-400 cases of rabies per year were diagnosed in wildlife. To molecularly characterize the prevalent lyssaviruses in wildlife, lyssavirus RNA of 25 recent rabies positive samples, collected in the year 1999, was amplified by RT-PCR. Direct sequencing of the RT-PCR-amplified products of the virus' nucleoprotein encoding region and subsequent sequence analyses resulted in a 99.3-100% homology between isolates and a 99.0-100% similarity with a 1995 genotype I, classical rabies virus (RABV) raccoon dog isolate from Estonia. These results confirmed that RABV is endemic in wildlife in Latvia and should be considered a serious public health threat. To successfully eradicate the wildlife reservoirs, the national rabies eradication program must be continued, and it may need to be intensified.     

Changes in xylosyltransferase activity and in proteoglycan deposition in bleomycin-induced lung injury in rat.

Several lines of evidence support the hypothesis of the involvement of altered proteoglycan deposition in the development of lung diseases. UDP-D-xylose: core protein beta-D-xylosyltransferase (UDP-xylosyltransferase; EC 2.4.2.26) is a key enzyme for the glycosylation of proteoglycan core proteins. This study examined the catalytic activity of UDP-xylosyltransferase in lung tissue and in isolated fibroblasts, as well as the deposition of the proteoglycans versican, biglycan and decorin in rat lung tissue during bleomycin-induced lung injury. Rats were given, endotracheally, a single dose of bleomycin. Deposition of proteoglycans in lung tissue was assessed by immunohistochemistry and the catalytic activity of xylosyltransferase was determined with an acceptor peptide of the sequence Q-E-E-E-G-S-G-G-G-Q-G-G as a substrate. The results show coincidence of increasing xylosyltransferase activities in lung tissue with accumulation of versican at alveolar entrance rings and in fibrotic regions in close proximity to alpha-smooth muscle actin-positive cells. In contrast, no changes in biglycan and decorin deposition in fibrotic lungs were observed, except for decorin in alveolar type II pneumocytes and alveolar macrophages. Bleomycin treatment of isolated rat lung fibroblasts resulted in a concentration-dependent increase of xylosyltransferase activity up to 2 mU bleomycin x mL(-1). The data suggest a participation of myofibroblasts with increased xylosyltransferase activities in accumulation of versican in fibrotic foci of injured lung tissue at the early stages of development of lung fibrosis.     

Pulmonary sporotrichosis in Oklahoma in susceptibilities in vitro

Six cases of pulmonary sporotichosis were observed in 2 institutions in Oklahoma City, Okla. Three of the patients were treated with iodides with or without surgery. Although one patient required a second course of iodides, the patients have remained well after at least 34 months of follow-up. Three patients treated with amphotericin B, single course as well as multiple courses, and other antifungal agents (hydroxystilbamidine and miconazole) have all relapsed. These cases and a reviewed of more than 40 cases of pulmonary sporotrichosis susceptibilities of Sporothrix schenckii that we observed in vitro suggest that amphotericin B is not an effective agent for the treatment of pulmonary sporotrichosis. It is our opinion that the treatment of choice for pulmonary sporotrichosis is a supersaturated solution of potassium iodide. If the patient is allergic to the medication or fails to respond, then a combination of amphotericin B plus flucytosine may be tried.     

Changes in hemostasis in malignant diseases

Tumourous diseases are associated with haemorrhagic as well as thrombotic complications. The most frequent cause of haemorrhagic states in tumourous diseases is thrombocytopenic haemorrhage, consumption coagulopathy and activated fibrinolysis. Trousseau described in 1865 a mutual association between tumourous diseases and venous thromboembolism. As many as 15-20% patients with venous thromboembolism have an undetected malignity which is a prevalence of 2-3% in the population. From this ensues the relative risk of a newly diagnosed malignity which is higher during the first year after venous thromboembolism. The prevalence varies between 2% and 6%. Migrating thrombophlebitiis (saltans and migrans) are a relatively specific sign in tumours, in particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases in particular the following factors play a part: elevated coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical operations in the case-history, chemotherapy, hormonal therapy and central venous catheters. The authors present a brief review of changes of haemostasis in tumourous diseases, their possible diagnosis and possible pharmacological prevention and treatment of thromboembolisms.     

Postural changes in cardiac volumes in men in relation to adult age

Cardiac volumes by equilibrium gated cardiac blood pool scans and heart rate were measured in the supine and sitting positions in 64 male volunteer subjects (age 25-80 yrs) who had been rigorously screened to exclude cardiovascular disease. After the upright position was assumed, the average cardiac output of all subjects was unchanged but heart rate increased and stroke volume decreased due to a decrease in end diastolic volume. Neither the supine or sitting cardiac output nor the average postural change in cardiac output, cardiac volumes or heart rate was age-related. While the average cardiac output among the subjects was unaltered with a change in posture, in some individuals it increased slightly while in others it decreased. The postural change in cardiac output among the individuals correlated by linear regression analysis with a change in heart rate only in younger subjects and with a change in stroke volume in all age groups, but the slope of this relationship was greater in older than in younger subjects. The postural change in stroke volume was strongly correlated with a change in end diastolic volume and this relationship did not vary with age. Thus, although the average postural change in cardiac output among healthy subjects is not age-related, a given change in cardiac output with posture in an older individual depends more on a change in stroke volume and less on a heart rate change than in a younger one. This result, like the response to vigorous upright exercise previously demonstrated to occur with aging, indicates a greater reliance in the elderly on the Frank-Starling mechanism than on heart rate for a given change in cardiac output in response to perturbations from the basal supine state.     

Morbidity in cardiovascular diseases in immigrants in Sweden

INTRODUCTION: Although immigration to Sweden has increased in the last few decades, the incidence rates of cardiovascular disease and coronary heart disease in immigrants are unknown. The aim of the present study is to estimate whether place of birth affects the incidence rates of cardiovascular disease and coronary heart disease. MATERIAL AND METHODS: The study was designed as a follow-up study on morbidity in cardiovascular disease and coronary heart disease between 1 January 1997 and 31 December 1998, including three and a half million persons with age range 35-64 years, of whom 550 000 were born abroad, from the database MigMed consisting of the whole Swedish population. Incidence rates and relative risks were estimated by indirect standardization and a proportional hazard model. RESULTS: The age-adjusted risk of coronary heart disease was higher in most foreign-born groups than in Swedes. For example, in nine of 12 male groups, the relative risks varied between 1.1 and 2.2, and in seven of 12 female groups, the relative risks varied between 1.4 and 2.5. When also adjusting for level of education and employment status, the risks were still high, but on a lower level. CONCLUSIONS: Foreign-born people possess an over-risk of cardiovascular or coronary heart disease(CVD/CHD) compared with Swedish-born persons, also when level of education and employment status are taken into account.     

Asthma control in adults in Asia-Pacific

OBJECTIVE: The Asthma Insights and Reality in Asia-Pacific (AIRIAP) survey collected detailed information on asthma severity and management in the urban centres of eight areas of the Asia-Pacific region. This study compared asthma morbidity and management practices in these areas. METHODOLOGY: Following recruitment, face-to-face interviews were completed with 2323 adults with diagnosed asthma, who had current symptoms or were using asthma medication. Comparisons between areas were made for asthma severity, asthma burden and management practices. RESULTS Asthma severity varied significantly between areas (P < 0.01), with Vietnam and mainland China reporting the most cases with severe, persistent symptoms. Severity of asthma was significantly associated with advancing age and a lower level of education in a multivariate analysis (P < 0.001). The total use of acute healthcare for asthma was significantly associated with increased asthma severity. Work absence due to asthma was highest in the Philippines (46.6%) and lowest in South Korea (7.5%). The use of inhaled corticosteroids was associated with age in a non-linear manner. There was significant variation among countries in usage of inhaled corticosteroids, from 1.3% in South Korea to 29.0% in Taiwan (P < 0.00001). A peak flow meter was owned by a total of 7.7% of respondents, and overall, 17.9% of adults had a written action plan for asthma management. CONCLUSIONS: Within the Asia-Pacific region, asthma in adults differs significantly in disease severity, management and treatment according to area of residence. International recommendations on the management of asthma are generally not being followed.     

Lymphogranuloma venereum in the UK in 2003

Lymphogranuloma venereum in the United Kingdom was detected in 2004, following the introduction of enhanced surveillance. This report describes a previously undiagnosed case, detected retrospectively in a sample obtained in 2003 from a male patient with high-risk behaviour, indicating that this previously rare disease in Europe, was present in the UK in 2003.     

Defects in hemostasis in P-selectin-deficient mice

Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et at, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin--deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman- like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin--deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin--deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P- selectin plays a role in hemostasis as suggested by its support of platelet rolling.     

Hyperglycaemia in pregnancy in Mediterranean women

New diagnostic criteria have recently been proposed that will result in a higher proportion of individuals being diagnosed as suffering from gestational diabetes mellitus (GDM) than previously. The present circum-Mediterranean study sets out to identify the relevance of the new criteria in this population. The study was a prospective, non-interventional, multicentre study in the Mediterranean region. A convenient sample of 1,368 pregnant women was recruited. All participants underwent a 75?g oGTT subdivided into five different glycaemic categories. The women??s anthropomorphic and biological data, together with obstetric and infant outcomes, were collected. There was a threefold increase in diagnosis using the new criteria. Most of the biological characteristics generally associated with GDM showed high specificity and low sensitivity values. The biological characteristics, including maternal age, BMI and FBG, showed a progressive increase as a function of maternal glycaemia with moderate sensitivity and specificity values. Using these latter characteristics in combination ensures that 72.3?% of the GDM population would be correctly identified, while an oGTT would only be required in 18.7?% of the population. The progressive relationship of increasing glycaemia to adverse characteristics suggests that the new IADPSG criteria are reasonable provided that dietary advice is given to all pregnant women. In situations of economic restraints, it appears possible to screen Mediterranean women for GDM risk using a composite model using FBG >5.0?mmol/l combined with the performance of an oGTT in women with a low FBG but who are overweight and aged >30?years.     

Immune-endocrine relations in obesity in children

A total of 196 children aged 5 to 14 (156 of them with obesity, 40 healthy children) were investigated. The immune status of children with various clinicogenetic types of obesity was characterized by the reduction of the number of T-lymphocytes and their function, change in the ratio of T-lymphocyte subpopulations, an increase in the level of 0-lymphocytes, dysimmunoglobulinemia resulting from an increase in IgA concentration and a decrease in the IgG level, an increase in CIC concentration. Hyperinsulinemia and a rise of the blood level of C-peptide were revealed. Insulin inhibited rosette formation with sheep erythrocytes. A study of the effect of insulin on LBTR permitted a conclusion of insulin stimulation of immature lymphocytes and lymphocyte sensitization of obese children to insulin. Immune deviations were most probably determined by direct or metabolic-associated effects of insulin. The investigation opens up opportunities for the development of appropriate effective therapy.     

Dynamics of estrogen receptor turnover in uterine cells in vitro and in uteri in vivo

The rate at which the estrogen receptor (ER) is synthesized and degraded (turns over) in target cells is a major factor regulating the levels of ER and cell sensitivity to estrogen. We have used the ability of tamoxifen aziridine [(TAZ)(Z)-1-[4-(2-[N-aziridinyl]ethoxy)phenyl]1,2-diphenyl-1-buten e] to affinity label the ER in intact cells to study the dynamics of ER turnover in uterine cells in vitro and in intact rat uteri in vivo. In primary cultures of rat uterine cells (from 21-day-old rats), ER is degraded with a half-life of 3-4 h, as determined by pulse-chase experiments in which ER in cells are covalently labeled with [3H]TAZ (20 nM) and then exposed to a chase of 10(-6) M estradiol. Density shift experiments, in which uterine cells are exposed for different time periods to medium containing dense (15N,13C,2H) amino acids and the shift of receptor from a normal density to a more dense species is analyzed on sucrose gradients, also confirm this rapid turnover for the uterine ER. A similar half-life is obtained for ER in rat uteri in vivo, after intralumenal installation of [3H]TAZ to label effectively ER covalently. Analysis of nuclear ER on sodium dodecyl sulfate-polyacrylamide gels during the chase period reveals the loss of the 65,000 mol wt [3H]TAZ-labeled receptor species; no lower mol wt [3H]TAZ-labeled fragments are observed. Likewise, immunoblot analyses of receptor with the ER monoclonal antibody H222Sp gamma reveal only the 65,000 mol wt receptor species, with no evidence of any smaller receptor forms in cells. Interestingly, incubation of uterine cells with 10(-5) M cycloheximide (which inhibits 98% of protein synthesis) completely arrests ER turnover, suggesting that ER turnover, which is rapid, is probably dependent upon the synthesis of other rapidly turning over proteins. Hence, we conclude that ER turnover is rapid in uterine cells, that turnover of uterine ER occurs at a rate similar to that previously reported for ER turnover in MCF-7 human breast cancer cells, and that ER turnover is similar in uterine cells under in vitro and in vivo conditions. These findings indicate that the receptor is a dynamic and rapidly turning over protein whose level could be adjusted quickly by alterations in the rate of synthesis and/or degradation.     

Estrogen prevents glucocorticoid-induced apoptosis in osteoblasts in vivo and in vitro.

The ability of estrogen to prevent glucocorticoid-induced apoptosis in osteoblasts was studied both in vitro and in vivo. Glucocorticoid treatment for 72 h produced a dose-dependent increase in the number of apoptotic cells, determined by acridine orange/ethidium bromide staining, with a maximal response of 31+/-2% and 26+/-3% with 100 nM corticosterone in primary rat and mouse osteoblasts, respectively. Simultaneous administration of varying concentrations of 17beta-estradiol and 100 nM corticosterone decreased apoptotic osteoblasts in a dose-dependent manner, with a maximal decrease of 70% with 0.01 nM 17beta-estradiol. Terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling also demonstrated glucocorticoid-induced DNA fragmentation that was inhibited by estrogen. Estrogen was shown to inhibit apoptosis induced by lipopolysaccharide treatment. As early as 6 h, Western blots demonstrated a dose-dependent decrease in the Bcl-2/Bax ratio, which reached a minimum of 0.18 in osteoblasts treated with 1000 nM corticosterone for 72 h. This reduction in Bcl-2/Bax was abolished by treating osteoblasts simultaneously with 17beta-estradiol, but not with 17alpha-estradiol. In 7-day-old mice, administration of varying concentrations of dexamethasone for 72 h resulted in a dose-dependent increase in the number of apoptotic osteoblasts as demonstrated by in situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling staining of calvaria. A maximum of 22+/-1% apoptotic osteoblasts on the bone surface was found with 1 mg/kg BW dexamethasone compared with 2+/-1% in vehicle-treated mice. Injection of varying concentrations of 17beta-estradiol (0.5-5 mg/kg BW), but not 17alpha-estradiol, with 1 mg/kg dexamethasone produced a dose-dependent decrease in the number of apoptotic osteoblasts to 5+/-1% with 5 mg/kg 17beta-estradiol. Thus, glucocorticoid-induced apoptosis of osteoblasts may be prevented at least in part by 17beta-estradiol.     

alpha-Melanotropin-induced changes in protein phosphorylation in melanophores

To investigate a possible role of protein phosphorylation in the mechanism of action of alpha-MSH, excised tail-fins of Xenopus tadpoles were incubated with or without alpha-MSH. After homogenization, in vitro endogenous protein phosphorylation was assayed using [gamma-32P]ATP. alpha-MSH treatment of intact tail-fins, producing full pigment dispersion, resulted in a 5-fold increase in 32P-incorporation into a 53 kDa protein band. This increase in 53 kDa phosphorylation was completely reversible. The increase was not found in homogenates from the melanophore-free part of the alpha-MSH-treated tail-fins. Phosphorylation of the 53 kDa protein could be detected in homogenates of alpha-MSH-treated primary cultured melanophores. Incubation of tail-fins with ACTH1-24, an alpha-MSH-like peptide producing full pigment dispersion, also induced an increase in 53 kDa phosphorylation. A structurally related peptide (ACTH15-24) and an unrelated peptide (LH-RH), neither of which induced pigment dispersion, were ineffective in stimulating 53 kDa phosphorylation. Injection of white adapted tadpoles with 1 micrograms of alpha-MSH or adaptation of tadpoles to a black background also resulted in a significant increase in 53 kDa phosphorylation. alpha-MSH added to the homogenates did not affect 53 kDa phosphorylation, indicating that alpha-MSH acts through a receptor-mediated mechanism. The increase in 53 kDa phosphorylation measured in vitro (post hoc), most likely reflects an alpha-MSH-induced decrease in 53 kDa phosphorylation in vivo. Our results strongly suggest that a decrease in 53 kDa phosphorylation is involved in the mechanism of action of alpha-MSH on melanophores.     

Promise and problems in relating cellular senescence in vitro to aging in vivo

According to the 'Hayflick limit', human fetal fibroblasts have a uniform, limited replicative lifespan of about 50 population doublings in cell culture. This concept was extrapolated to diverse cells in the body. It seemed to decrease with the age of the cell donor and, as a form of cell senescence, was thought to underlie the aging process. More discriminating analysis, however, showed that the fibroblasts decayed in a stochastic manner from the time of their explantation, at a rate that increased with the number of population doublings in culture. There was no consistent relation to the age of the donor. Despite the contradictory evidence, the original version of the Hayflick limit retained its general acceptance. Cell senescence was attributed to the absence of telomerase in the fibroblasts, which resulted in shortening of telomeres at each division until they fell below a critical length needed for further division. However, it is well established that stem cells in renewing tissues undergo many more than 50 divisions in a lifetime, without apparent senescence. Contrary to early findings of no telomerase in most tissues, their stem cells retain telomerase and presumably telomere length despite many divisions in vivo. Massive accumulation of lipofuscin granules occurs under stress in long term crowded cultures, but the granules dissipate on subculture or neoplastic transformation. The overall results indicate a critical disjunction between cell senescence in vitro and aging in vivo. By contrast, cell culture has been useful in showing a need for telomere capping in maintaining cell stability and viability. It may also provide information about the biochemical mechanism of lipofuscin production.     

Alterations in body composition in acromegaly

Acromegaly is a condition characterized by growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion, and is associated with boney overgrowth, and soft tissue abnormalities due to anabolic, lipolytic, and sodium retaining actions of GH. GH and IGF-1 excess is associated with alterations in body composition, including an increase in body water and lean body mass, and a reduction in body fat. Achievement of biochemical control of the disease results in a reduction in body water and fat-free mass, and an increase in body fat. BMD is generally increased in acromegaly, though the anabolic effect of GH excess on bone is reduced, if not negated, by the presence of hypogonadism, particularly with regard to the trabecular compartment. Further studies are necessary to determine the effect of long-term biochemical control on bone density in subjects with acromegaly.     

Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology

The article summarizes published data regarding the prophylaxis of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology. In surgical patients with low risk, no specific thromboprophylaxis is needed. Patients with moderate risk levels are the candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3 400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression (IPC). At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration (LDUH) over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people with a history of heparin induced thrombocytopenia over the past three months. The sole use of acetylsalycilic acid is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC is indicated only in those patients who undergo laparoscopic surgeries and who moreover display the additional thrombosis factors. Patients with additional risk thrombosis factors undergoing major venous reconstructions require prophylaxis with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low risk urologic surgery require no specific thromboprophylaxis. If they undergo a major intervention and/or they display additional risk thrombosis factors, they require the administration of LMWH or LDUH. Elastic panty-hose and/or intermittent pneumatic compression have the same indication as in abdominal surgeries.     

Specialist training in rheumatology in Europe

Rheumatology is a broad discipline managing a spectrum of different conditions and there are divergences in what is routinely treated by rheumatologists both within and between countries. The free movement of doctors throughout the European Community has lead to moves to harmonize specialist training to ensure common standards of care. The Union Européene des Médecins Spécialistes (UEMS) has developed recommendations for the specialist training of rheumatologists in Europe that recognizes the broad definition of the discipline and the diversity of clinical practice in Europe. The core curriculum aims to provide a common standard around which to develop locally applicable national curricula. The provision of high quality care requires some assessment of training and competency as well as continuing professional development and ways of ensuring the provision of this throughout the European Community to a mutually high standard are being developed. The future may see more overlap in the training of all the disciplines concerned with the management of those with musculoskeletal conditions to their benefit.