Central systolic blood pressure (cSBP) to brachial systolic blood pressure (brachSBP) ratio reproducibility during antihypertensive therapy.

OBJECTIVES: Higher CSBP than brachial SBP in individual patient increases cardiovascular (CV) risk. For follow-up it is important to assess the reproducibility of such measurements. The aim of this study was to assess the reproducibility of these differences, expressed as a CSBP/BrachSBP ratios. SUBJECTS AND METHODS: Eighty-three patients on antihypertensive therapy were analysed for the reproducibility of such ratios after time interval of several month up to several years. For CSBP estimation, we used the Arteriograph (Tensiomed Ltd.), based on blood pressure measurements by cuff on oscillometric principle, using pulse wave analysis (PWA) for assessment of CSBP. RESULTS: The proportion of patients retained the same characteristics (either higher central or higher peripheral SBP) between the first and second measurement was 71.1 %. The association between 1st and 2nd measurement, was statistically significant, p < 0.001. CONCLUSION: In our study, a high proportion (60 %) of treated hypertensive patients had CSBP higher than brachial SBP, which may adversely influence their prognosis. This characteristic is highly reproducible. Taking into the account these differences may increase the exactness of CV risk estimation and may contribute to explanation of residual risk of individual patient (Tab. 3, Fig. 1, Ref. 28).

Testosterone replacement therapy (TRT) and its effect on bone marrow. How serious is it and is there a true polyglobulia?

INTRODUCTION: TRT in men with testosterone deficiency syndrome (TDS) had multiple positive effects and restore a quality of life of affected men. Polyglobulia is the most common dose-limiting adverse effect of TRT, but the mechanisms of TRT-mediated erythropoesis remain unclear. In this study, we evaluated long term haematological side effects of TRT: polyglobulia, elevated hemoglobin (Hb) and haematocrit (Ht). METHODS: In a cross-sectional descriptive study, the authors treated 69 men with TDS and the average age 59 years and the follow-up period 81.32 months. The men were treated with three-month i.m. injections of 1000 mg testosterone undecanoate. The elevated values were: Hb above 176 g/l, Ht above 0.52 and erythrocytes (Ery) above 6.0 mil/mcl. RESULTS: 21 out of 69 patients (30.43 %) had an increased Hb, Ht or Ery during treatment. The interesting fact was that only five men (7.24 %) had increased the number of Ery (true polyglobulia). No men with elevated level of Hb, Ht or Ery had other side effects (like thrombosis). CONCLUSION: It is still not clear, why in some men on TRT the feedback does not work and bone marrow production of red blood cells continues even if the upper limit is reached. Authors expect that only 7% of men had true polyglobulia, other men had elevated Hb or Ht. Based on our own experience we recommend a regular check of men on TRT on order to avoid possible serious side-effects (Tab. 1, Fig. 2, Ref. 25).

[Gastroenteropatic neuroendocrine tumors: multidisciplinary approach in therapy]. / Multidiscipliniárny prístup k liecbe gastroenteropankreatických neuroendokrinných tumorov.

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are classified on the basis of hormonal activity of tumor cells to functional and non-functional tumors. Therapy of well differentiated NETs includes surgical procedures, debulking of tumor mass, biotherapy and peptid receptor radionuclid therapy. AIM OF THE STUDY: Analysis of therapeutic modalities in group of patients with well differentiated GEP-NETs. RESULTS: In time period from 1. 1. 2005 to 1. 1. 2010 we followed up 50 pts (19 men/31 women) with well differentiated GEP neuroendocrine tumors. Primary localisation was: stomach--6 times, pancreas--9 times, duodenum--1 times, jejunum-- 4 times, appendix--3 times, ileum--23 times, rectum--4 times. Metastatic disease was affirmed in time of diagnosis in 36 patients. Carcinoid syndroma had 20 pts, 4 pts with pancreatic tumor had functional tumors (2 times overproduction of calcitonine, 1 times of gastrin, 1 times of insuline). Surgical treatment was performed in 40 pts--resection of primary tumor and debulking of metastases, in 5 pts with pancreatic tumor resection was not possible due to invasion to sorrounding tissue and vessels. Biological treatment with long acting somatostatin analogues was indicated in 20 pts with carcinoid syndroma and in 4 pts with functional pancreatic tumors. In 5 pts with non resectable neuroendocrine carcinoma of pancreas peptid radionuclide receptor therapy (PRRT) was indicated: in 4 of them with 90Ytrium-DOTA-octreotid and in 1 patient with MIBG. In all pts a reduction of tumor volume was noticed. Biotherapy with somatostatin analogues reduced symptoms of hormonal activities and brought on stabilisation of disease in most of patients. In period of follow up 5 patients died. CONCLUSION: Complex therapy in patients with well differentiated neuroendocrine tumors markedly contributes to prolongation of survival of patients and also to enhancement quality of their life.

Detection of antibodies to Chlamydophila pneumoniae by immunoblotting in patients with cardiovascular diseases.

Chlamydophila pneumoniae, one of the most prevalent human pathogens worldwide, is not only a significant cause of pneumonia, but may also be associated with cardiovascular diseases (CVD) as suggested by multiple studies. A total of 228 sera from CVD patients with hypertension, ischemic heart disease or previous reconstructive vascular surgery were screened for the presence of anti-C. pneumoniae IgG and IgA antibodies by ELISA. Out of 150 positive serum samples, 80 with similar IgG and IgA levels were investigated by immunoblot (IB). IgG antibodies were directed predominantly against the 35 kDa and 39 kDa proteins as well as 50-54 and 56-60 kDa proteins of C. pneumoniae. IgA antibodies reacted most frequently with the 50-54 and 56-60 kDa proteins.

General changes in hemostasis in gastric cancer.

Disorders of haemostasis and haemocoagulation are often seen in patients with cancer as a part of paraneoplastic syndrome. Thrombotic and/or haemorrhagic complications are the second most common cause of mortality in patients with cancer. The evaluation of the haemostatic parameters of 67 patients with gastric cancer have indicated tendency to thrombophilia and activation of intravascular coagulation, of which 31.3% showed tendency to hypercoagulation and 47.8% disseminated intravascular coagulation (DIC). Only 7.5% of subjects have yielded normal laboratory findings while 5.9% of patients had DIC with remarkable hypocoagulation. Thrombocytosis, platelet hyperaggregability and elevation of beta-thromboglobulin are the indicators of changes in primary haemostasis and elevation of thrombomodulin indicates vascular wall damage. Lower antithrombin III levels, C-protein and S-protein in plasma have indicated lower antithrombotic potential in patients with gastric cancer. It can be concluded that patients suffering from gastric cancer are at higher risk of thromboembolism as for haemorrhagic diathesis (20.1% thromboembolism, 11.94% fatal thromboembolic events vs 5.9 % haemorrhagic diathesis) (Tab. 5, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

Local changes in hemostasis in patients with gastric cancer.

Disorders of haemostasis and haemocoagulation are often seen in cancer patients as a part of the paraneoplastic syndrome. This study describes a novel compound that activates coagulation and also inhibits fibrinolytic system and fibrin degradation products in the gastric juice of 33 patients with gastric cancer. Similar, but less pronounced changes have been found in gastric juice of patients with gastric precancerosis. Procoagulant activity, induced by pathologically changed cells or monocytes, macrophages from tumor stroma, indicates the activation of local coagulation with the production of fibrin. It can be concluded that the local changes of coagulation and fibrinolysis may precede coagulopathies in cancer patients (Tab. 2, Ref. 15). Full Text (Free, PDF) www.bmj.sk.

[Symmetrical phlebothrombosis of lower extremities resulting from congenital malformation of vena cava inferior]. / Obojstranná flebotrombóza dolných koncatín zaprícinená vrodenou malformáciou dolnej dutej zily.

Agenesis/atresia ofvena cava inferior is a rare congenital anomaly, caused by an aberrance of embryonal venous system development. This is in most cases asymptomatic, because of well developed collateral venous circulation. However, in some cases, it can be manifested with occurence of deep thrombosis in area of pelvis and lower limbs. In this case report, we repon a 21 year old male with painful swelling of both lower limbs. Ultrasonographic examination revealed a bilateral thrombosis in deep venous system of lower limbs and pelvis. Subsequent CT angiography showed atresia ofinfrarenal segment ofvena cava inferior. According to the CT image thrombotic proces affected also collateral venous system, that joined mostly to vena azygos and hemiazygos. Examination of coagulation system didn't reveal a procuring cause ofthrombotic occurrence. We realized a systemic trombolysis with streptokinase during 5 days. Starting from the fifth day we administered a low molecular weight heparin in anticoagulant dose. This treatment showed a good clinical effect. Pacient was discharged with a long-term oral warfarin therapy in combination with acetylsalicylic acid. In next four months of taking recommended therapy no relapse of thrombotic process nor evolvement of bleeding complication was observed.

Hemosuccus pancreaticus.

In this study, authors describe a rare case of a 40-year old patient with a history of chronic pancreatitis due to ethanol abuse, repeatedly hospitalized for intermittent bleeding into gastrointestinal tract (GIT). The sources of bleeding were pseudoaneurysms of the peripancreatic arteries (gastroduodenal artery, right hepatic artery) bleeding into GIT via pancreatic duct. This type of bleeding is referred as hemosuccus pancreaticus and belongs to a rare form of bleeding into upper GIT. Development of each pseudoaneurysm was monitored with a 6 month time interval. The diagnosis was established using endoscope, Doppler ultrasound and CT angiography. During the therapeutic process, while stopping bleeding, two different radiological interventions were used. In pseudoaneurysm of gastroduodenal artery, hemostasis was achieved using selective transcatheter arterial embolization (TAE) with steel coils. In the second intervention, a stent was inserted into vascular lesion. In the discussion, authors review the problems of hemosuccus pancreaticus, epidemiology, symptoms, diagnostic and possible therapeutic approaches (Fig. 3, Ref. 31). Full Text (Free, PDF) www.bmj.sk.

Identification and characterization of Coxiella burnetii strains and isolates using monoclonal antibodies.

We evaluated 6 monoclonal antibodies (MAbs) for their usefulness in identifying and characterizing recognized laboratory strains as well as field isolates of Coxiella burnetii. Five had been generated in response to strain Nine Mile (3 IgM class, 1 IgG class, 1 light chain producers only) and were polypeptide-specific, and 1 was anti-Priscilla (IgG class) and was lipopolysaccharide (LPS)-specific. Initially, the MAbs were used in conjunction with a dot blot assay with which we could differentiate C. burnetii from rickettsiae or chlamydiae. Confirmation of the specificity of these MAbs was provided by demonstrating that only C. burnetii antigens were recognized by certain combinations of antibodies used for immunoblotting proteins of various C. burnetii strains. Subsequently, we characterized antigens of 11 C. burnetii field isolates and 3 reference strains by Western blotting with individual MAbs. MAb 921 and 922 (IgG class), MAb 241, 242, 384, 386, 614 (IgM class), and 7A5, 7A1 (light chain) consistently recognized a protein. Staining intensity differed, depending on the strain tested, and there was variability in the size of the antigen immunoreactive with MAb 14H (IgG class, LPS-specific). The most reactive region was at about 249 kD. Variability of reactivities with field isolates was seen in both the distribution of individual bands and their intensities. We conclude that an extensive immunoblotting technique may be useful for C. burnetii strain differentiation and routine identification of C. burnetii can be accomplished using this MAb-based dot blot assay.

Monitoring of humans and animals for the presence of various Rickettsiae and Coxiella burnetii by serological methods.

Serological examination of humans in Slovakia suspected of having rickettsial infections revealed the presence of antibodies to spotted fever group rickettsiae (R. conorii, R. slovaca, and R. typhi). Of interest is the finding of serological positivity to the newly recognized "IRS" agent. Antibodies to these rickettsiae and to C. burnetii were demonstrated also in domestic and hunting dogs and pet animals. These results confirm the occurrence and possible circulation of these rickettsiae and C. burnetii in the Slovak Republic.

Induction of tumor necrosis factor alpha in murine macrophages with various strains of Coxiella burnetii and their lipopolysaccharides.

The ability of various strains of Coxiella burnetii (C.b.) and their phase I and II lipopolysaccharides (LPSs) to induce tumor necrosis factor alpha (TNF-alpha) in peritoneal Balb/c mouse macrophages in vitro was investigated. Considerable differences in the induction ability were observed in dependence on the strain applied. In a TNF-alpha bioassay, the most effective inducers were both corpuscles and LPSs of the strains Priscilla and Scurry, followed by Nine Mile, Luga, and Henzerling I. In contrast, in ELISA, the most effective inducers were LPSs of the strains Luga and Henzerling, followed by Nine Mile, Priscilla, and Scurry. The role of toll-like receptor 4 (TLR4) in the induction was confirmed by the use of C3H/HeJ mouse macrophages. Thus, the induction of TNF-alpha was much higher in Balb/c mouse macrophages than that in TLR4-deficient C3H/HeJ mouse macrophages. Differences in the results of the bioassay and those of ELISA suggest a role of another secreted factor(s) induced with C.b. in murine macrophages that could act synergically with TNF-alpha in L929 cells in the bioassay. The observed differences in TNF-alpha induction might play a role in the pathobiology of Q fever.

Analysis of specificity of interaction between synthetic key saccharide components of lipopolysaccharides and monoclonal antibodies to Coxiella burnetii.

Two monoclonal antibodies (MAbs) against the lipopolysaccharides (LPSs) of Coxiella burnetii (C.b.) strains Priscilla and Nine Mile were prepared characterized by their interaction with synthetic glycoconjugates representing parts of LPSs of C.b. in virulent phase. Both MAbs were directed against immunodominant epitopes comprising core constituent of LPSs, Kdo (3-deoxy-alpha-D-manno-2-octulo-pyranosylonic acid). ELISA showed that the anti-Nine Mile MAb 4/11 bound preferably to disaccharides (alpha-Kdo (2 --> 4) alpha-Kdo and alpha-Kdo (2 --> 4) alpha-(5d) Kdo), while the anti-Priscilla MAb 1/4/H bound to all conjugates, though with various intensity. On the other hand, immunoelectron microscopy revealed a positive binding of only one glycoconjugate, namely the trisaccharide alpha-Kdo (2 --> 4) alpha-Kdo (2 --> 4) alpha-Kdo-BSA, to both MAbs. In competitive ELISA (cELISA), the anti-Priscilla MAb 1/4/H distinguished the strains Nine Mile and Priscilla, while the anti Nine Mile MAb 4/11 did not.

Behcet's syndrome.

Behcet's syndrome is a systemic illness of unknown etiology characterized by necrotising vasculitis originally described in Turkey. Typical manifestations include urogenital ulcerations, eye inflammation and migratory thrombophlebitis. An unusual course of this disease is described. A 56 year-old man was admitted to the hospital with fever, milk-glass opacities on chest x-ray, mucosal defects on the tongue and penis, hematuria and proteinuria with functional disorder of kidney. Chlamydia pneumoniae, CIK positivity and C 3 complement decrease were found. Antibiotics and antimycotic drugs have shown only slight improvement of pulmonary lesions. An excellent effect in all pathological findings was achieved after prednison administered in dosis of 1 mg/kg and later cyclophosphamide administration (Fig. 7, Ref. 12).

Chlamydia pneumoniae antibodies and markers of inflammation in patients with cardiovascular diseases.

BACKGROUND: Chlamydia pneumoniae is suggested to be associated with cardiovascular diseases. OBJECTIVES: To study the presence of IgG, IgA anti-C. pneumoniae antibodies, interleukin-6 (IL-6), and C-reactive protein (CRP) as markers of previous C. pneumoniae infection and inflammation, in sera of patients with acute myocardial infarction (AIM), hypertension (HT), and coronary heart disease (CHD). METHODS: Determination of these markers by ELISA method. RESULTS: Proportion of samples containing both IgG and IgA antibodies as well as IL-6 was significantly higher in all groups of patients than in a control group. The CRP was significantly higher in patients with AIM and HT, however, in other patients, the proportion of positive samples depended on the chosen cut-off value. CONCLUSIONS: The results obtained indicate the feasibility of following chlamydial antibodies on higher number of serum samples extended to direct detection of C. pneumoniae in blood and vascular tissue (Tab. 2, Ref. 24).

Q fever is absent from New Zealand.

To investigate the presence of Coxiella burnetii in sheep and cattle, the two major ruminant populations of New Zealand, its seroprevalence was determined in aborting cattle and sheepdogs. These groups of animals were chosen because of their accessibility and the fact that they would be good indicators for the presence of the organism. A total of 2181 bovine and 12,556 canine samples were all seronegative. On the basis of these results and previous reports it is argued that New Zealand is free of coxiellosis or Q fever.

Rickettsial diseases and their serological diagnosis.

Rickettsial diseases (typhus and spotted fever group rickettsioses, scrub typhus and Q fever) may pose a serious public health problem, namely when they are non-diagnosed or misdiagnosed. Although rickettsiae can be isolated from or detected in clinical specimens, serological tests still remain an indispensable tool in the diagnosis of rickettsial diseases. The complement fixation test widely used in the past is being replaced by other tests which make differentiation of immunoglobulin classes possible. Of these tests microimmunofluorescence is considered the test of choice followed by the latex agglutination, indirect hemagglutination, immunoperoxidase assay, and enzyme-linked immunosorbent assay. The last one is also suitable for seroepidemiological studies. Immunoblot analysis can be used to confirm the results of other tests. The use of the low-specific and low-sensitive Weil-Felix test should be reserved only for situations in which other serologic tests are not available.

Rickettsiae belonging to the spotted fever group from ticks in the Tribec Mountains.

Rickettsiae of the spotted (SF) group were found in a selected locality of the Tribec Mountains in southern Slovakia in 1974. The rickettsiae were found in 10.8% of females and 6.1% of males of Haemaphysalis inermis and 7.3% of females and 4.8% of males of Ixodes ricinus. No significant differences in the incidence were observed during the year. Coxiella burneti was found in 1 male and 4 females of H. inermis and 1 male of I. ricinus in ad adjacent locality. Antibodies against rickettsiae of the SF group were detected in 22.5% and against C. burneti in 1.9% of small mammals in other adjacent localities. Trypanosomes and Nosema slovaca were recovered from I. ricinus ticks; both records are the first for Europe.

Comparison of virulence of Coxiella burnetii isolates from bovine milk and from ticks.

Laboratory animals (mice and guinea pigs) were infected with the isolates of Coxiella burnetii (Derrick, 1939) obtained from bovine milk (M18 and M35) and the ticks Ixodes ricinus (Linnaeus, 1758) and Dermacentor marginatus (Sulzer, 1776) (Kl3 and Kl6, respectively), and with the reference strain Nine Mile. Neither mortality nor lethality occurred with the mice. Antibody response in mice infected with isolates from milk was lower (1:16-512) than that from ticks (1:32-4096). Onset of seropositivity also occurred later - on the 10th day post-infection (p.i.) for M18 and M35 in comparison with the 7th day for Kl3 and Kl6. In guinea pigs, infection manifested by fever. The fever was less evident in guinea pigs infected with isolates from milk (39.5-40.1 degrees C) than in guinea pigs infected with isolates from ticks (39.5-40.6 degrees C). Partially engorged females of Dermacentor reticulatus (Fabricius, 1794) were inoculated with isolates M18 and Kl3. No differences in the multiplication of C. burnetii in haemocytes between these two isolates were ascertained.

Q fever--still a query and underestimated infectious disease.

Coxiella burnetii (C.b.) is a strictly intracellular, Gram-negative bacterium. It causes Q fever in humans and animals worldwide. The animal Q fever is sometimes designated "coxiellosis". This infection has many different reservoirs including arthropods, birds and mammals. Domestic animals and pets, are the most frequent source of human infections. Q fever may appear basically in two forms, acute and chronic (persistent). The latter form of Q fever in animals is characteristic by shedding C.b. into the environment during parturition or abortion. Human Q fever results usually from inhalation of contaminated aerosols originating mostly from tissue and body fluids of infected animals. Q fever may appear in humans either in an acute form accompanied mainly by fever (pneumonia, flu-like disease, hepatitis) or in a chronic form (mainly endocarditis). Diagnosis of Q fever is based on isolation of the agent in cell culture, its direct detection, namely by PCR, and serology. Detection of high phase II antibodies titers 1-3 weeks after the onset of symptoms and identification of IgM antibodies are indicative to acute infection. High phase I IgG antibody titers >800 as revealed by microimmunofluorescence offer evidence of chronic C.b. infection. For acute Q fever, a two-weeks-treatment with doxycycline is recommended as the first-line therapy. In the case of Q fever endocarditis a long-term combined antibiotic therapy is necessary to prevent relapses. Application of Q fever vaccines containing or prepared from phase I C.b. corpuscles should be considered at least for professionally exposed groups of the population. Infections caused by C.b. are spread worldwide and may pose serious and often underestimated health problems in human but also in veterinary medicine. Though during the last decades substantial progress in investigation of C.b. has been achieved and many data concerning this pathogen has been accumulated, some questions, namely those related to the pathogenesis of the disease, remain open.

Failure of Q fever phase I corpuscular vaccine to influence the persistence and reactivation of Coxiella burnetii infection in mouse and guinea pig tissues.

In mice and guinea pigs infected with Coxiella burnetii, accumulation of large numbers of rickettsiae in the spleen and liver occurring at the early stages of infection was followed by clearing of these organs from the infectious agent but by its persistence in kidneys and reproductive tract at later intervals. The persistence of C. burnetii was not affected when one to six months-infected mice or guinea pigs were immunized with 100 or 500 micrograms of Q fever phase I corpuscular vaccine. Administration of the vaccine also did not substantially influence the reactivation of C. burnetii infection elicited in mice by parturition or developing in mice and guinea pigs upon treatment with cortisone or cyclophosphamide (CPA). Some differences observed between groups of immunized or non-immunized animals were only quantitative in nature. The possibility to disbalance the steady state of persisting C. burnetii in the host tissues by inhibition or stimulation of the immune response is discussed.