Successful ablation of ventricular tachycardia after correction of tetralogy of Fallot.

We present a case of a patient who, after correction of tetralogy of Fallot (TOF), experienced runs of ventricular tachycardia (VT). Mapping of the aortic root showed that the critical component of the reentry was located within the noncoronary cusp. The potential explanations of such an unusual isthmus location may be the presence of myocardial extensions in the aortic root or the close vicinity of the right ventricle (RV) to the noncoronary cusp, since in TOF the aorta overrides the RV. Our case highlights the advantage of using electroanatomic mapping systems together with intracardiac echocardiography in such complex cases.

New insights into mechanisms of atrial fibrillation.

Although atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, precise mechanisms that lead to the onset and persistence of AF have not completely been elucidated. Over the last decade, outstanding progress has been made in understanding the complex pathophysiology of AF. The key role of ectopic foci in pulmonary veins as a trigger of AF has been recognized. Furthermore, structural remodeling was identified as the main mechanism for AF persistence, confirming predominant role of atrial fibrosis. Systemic inflammatory state, oxidative stress injury, autonomic balance and neurohormonal activation were discerned as important modifiers that affect AF susceptibility. This new understanding of AF pathophysiology has led to the emergence of novel therapies. Ablative interventions, renin-angiotensin system blockade, modulation of oxidative stress and targeting tissue fibrosis represent new approaches in tackling AF. This review aims to provide a brief summary of novel insights into AF mechanisms and consequent therapeutic strategies.

Intracardiac echocardiography in electrophysiology.

Intracardiac echocardiography (ICE) broadens the spectrum of echocardiographic techniques. Modern 10F sector echocardiographic catheters introduced into the right atrium allow high quality imaging of all cardiac structures, including pulse and continuous wave Doppler and/or color Doppler. The main indication for ICE appears to be monitoring of catheter ablation of complex arrhythmic substrates such atrial fibrillation, postincisional tachycardias and ventricular tachycardias. The other important role of ICE is the early diagnosis and prevention of complications during ablation procedures. These include those occurring during transseptal catheterization, damage to cardiac structures, left atrial thrombus formation, pulmonary venous stenosis, esophageal injury and pericardial effusion.

Clinical outcome of salmon calcitonin nasal spray treatment in postmenopausal women after total hip arthroplasty.

OBJECTIVE: The increasing rate of hip fractures is giving rise to a number of socio-economic problems for the aging community. In addition to being unable to resume their previous living habits, many patients fail to achieve full functional recovery after the fractures. Total hip arthroplasty (THA) is a successful operation for the majority of patients with all forms of hip fractures, being performed increasingly often throughout the world. Revision rates for THA range up to 20% per year. Aseptic loosening is the reason for 75% of the revisions. An additional problem post-THA is the rate of heterotopic soft tissue calcification after THA, resulting in severely impaired function, pain, and a reduced range of hip movement. SUBJECTS: In an open study, 37 women who had undergone cementless THA after accidental hip fractures were treated twice daily with 200 IU of salmon calcitonin nasal spray for 12 months. Simultaneously the patients received one bag of 1,000 mg calcium plus 880 IU vitamin D daily throughout the treatment period of 1 year. A parallel group of 38 women with a similar clinical status in terms of hip fractures and cementless THA were treated with only one bag of 1,000 mg calcium plus 880 IU vitamin D daily through the treatment period. RESULTS: The results of this 12-month clinical trial show that 200 IU of salmon calcitonin nasal spray per day significantly improves the clinical outcome of postmenopausal elderly women following THA. Treatment with a salmon calcitonin nasal spray significantly reduces bone turnover, loss of bone density, and pain. The functional status of the patients was improved and the risk of falling reduced by rehabilitation during the observation period of 12 months. Additionally, calcitonin promoted the repair of hip fractures and was associated with a significantly lesser rate of refractures as well as periprosthetic ossifications. CONCLUSION: The increasing revision rate for THA during the first year and the patient's problem of resuming their previous living habits are the main foci of our study. Calcitonin nasal spray seems to cause few side effects. The additive treatment appears to improve the clinical outcome of THA in elderly postmenopausal women.

Autoantibodies associated with rheumatic diseases.

The identification of circulating autoantibodies contributes to the correct diagnosis as well as to the follow-up of rheumatic diseases. Some autoantibodies are even included in diagnostic and classification criteria for these types of autoimmune diseases. There are several relatively specific screening and identification methods for the measurement of autoantibodies available. The type of assay crucially influences the diagnostic value of the parameters. In general, routine laboratories should prefer enzyme immunoassays (ELISA) using well characterized antigens, although ELISA tests tend to produce more false-positive and true weakly positive results, which reduce their positive predictive value. Therefore one should be aware that laboratory results can only be properly interpreted when there is a correlation with the clinical situation and when the limitations of the technologies used for autoantibody identification have been taken into consideration. A diagnostic algorithm consisting of screening and identification steps should be established by each laboratory in order to create a rational, evidence-based and cost-effective basis for the diagnosis of rheumatic diseases.

Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers.

In this study we evaluated the routine practice and clinical application of serum crosslaps to urinary-crosslaps, -N-telopeptide-related fraction of type 1 collagen, -deoxpyridinoline, -totalpyridinoline and serum osteocalcin. The utility of both the serum and urine immunoassays for bone formation and resorption marker were tested in a cohort of 593 female and male patients from our outpatient clinic for osteology and rheumatology and compared to important osteoporosis risk factors like age, gender, E2 deficiency, bone density and chronic renal failure. The biochemical maker of bone formation, serum osteocalcin exhibit significant correlations to all five tested serum and urinary markers of bone resorption (p < 0.0001) crosswise to all different groups of patients. The group of chronic renal failure patients showed no significant correlation between the tested bone turnover parameters and the serum creatinine level except a significant increase and correlation for serum crosslaps and for the ratio of serum and urinary crosslaps. Associations between the age of the patients and the markers of bone turnover were rather poor. We found a significant, negative association between serum and urinary bone turnover markers and bone density and were interested, whether in patients with bone density < 2.5 SD an enhanced bone turnover could be detected in the same way as for E2 deficiency. Applying a discriminant analysis it was possible to discriminate between the patient with BD < 2.5 SD and those with BD > 1.0 SD with a sensitivity of 70% and a specificity of 65% using serum crosslaps. In case of urinary crosslaps the discriminatory power was slightly lower (sensitivity: 65.6%, specificity: 67.5%) and for serum osteocalcin the discriminatory power was negligible higher (sensitivity: 79%, specificity: 56%). The highly significant correlation between the urinary and serum crosslinked peptides by ELISA and serum osteocalcin supports the concept that these respective indices of bone formation and resorption both in urine and serum reflect a coupled process in vivo with sensitivity and specificity to pathological bone density, estrogen deficiency and chronic renal failure.

Serum osteocalcin and urinary crosslaps are suitable markers of bone turnover in response to short-term hormone replacement therapy.

In this study we evaluated the effect of short-term hormone replacement therapy (HRT) on bone formation (serum osteocalcin) and resorption markers (urinary type I collagen peptides (crosslaps), urinary total free pyridinoline (TPYRI) and urinary free deoxypyridinoline (DPYRI)) as well as female sex hormones (serum estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH)) in a group of early postmenopausal women with severe estrogen deficiency. The 46 healthy postmenopausal women with serum estradiol levels < 10 ng/l were subsequently divided into two groups, according to their compliance with HRT. In the group taking HRT significant changes from baseline values could be observed in estradiol, FSH, urinary crosslaps and serum osteocalcin levels after 6 months, whereas no changes could be observed in LH, TPYRI and DPYRI from baseline values. In the group which refused HRT all values were increased relative to baseline values, indicating increased bone turnover. Serum osteocalcin and urinary crosslaps were significantly decreased in women taking HRT in comparison to the group refusing HRT. After 6 months the treated patients showed a decrease in urinary crosslaps of 42% (SD 12%) and in serum osteocalcin of 24% (SD 6%) in comparison with baseline values. In patients who refused HRT, urinary crosslaps were increased by 43% (SD 20%) and serum osteocalcin levels decreased by 2% (SD 9%) compared to baseline values. In postmenopausal women suffering from severe estrogen deficiency (estradiol < 10 ng/l) serum osteocalcin and urinary crosslaps are significantly increased, indicating a clear correlation between estrogen deficiency and an increase in bone resorption as well as bone formation. The recommended HRT dose was sufficient to reduce the rate of bone turnover to premenopausal values. Serum osteocalcin and urinary crosslaps are suitable candidates not only for the assessment of a high postmenopausal bone turnover, but also for monitoring the response to and for verifying the actual intake of HRT or other antiresorptive treatment.

Health, safety and environmental protection in a biological research laboratory.

This manuscript summarizes the mandatory regulations for Health, safety and environmental protection (HSE) at the Novartis Forschungsinstitut-Vienna to ensure the safe and contained biological laboratory work especially with class II agents in the specialized biosafety level 2 (BL2) facilities available at this institute. These regulations apply to work practices conducted within these facilities; to special safe-containment features of these BL2 facilities; to containment and decontamination of biohazardous or potentially biohazardous materials of risk class II; and to the procedures in place to guarantee that these regulations are strictly carried out, and that only individuals with the appropriate training and approval have access to these facilities. The regulations governing BL2 facilities summarized here have been taken directly from CDC and NIH public documents; any special adaptations or additions to these regulations have been stated as such, in order to make these guidelines as transparent and nonredundant as possible.

Cranioventral Subluxation of the Odontoid Process With Accompanying Neo(pseudo)arthrosis in Rheumatoid Arthritis.

Cervical spine involvement is a common feature in the course of long existing rheumatoid arthritis (RA).We describe a rare type of vertical subluxation with pronounced cranioventral disposition of the odontoid process and neo(pseudo)arthrosis between the skull and the tip of the odontoid processus. This 74-year-old women with RA for 40 years had progressive neck symptoms over the previous 5 years. She no longer had signs of active synovitis. Plain roentgenographs performed in a neutral position and full flexion and extension gave information about neither the osseous integrity nor the subluxation of the dens axis. Computed tomography and MR imaging techniques established the nature of the atlantoaxial and atlantooccipital joint involvement. During 2 years, this rare cranio-ventral subluxation with neo(pseudo)arthrosis seems to be rather solid, and follow up CT-images demonstrate no signs of progressive migration or suggestion of immediate fracture risk. Pronounced reduction of cervical spine mobility by long standing destructive cases of RA should always raise suspicions for cervical subluxation at the atlantoaxial level, irrespective of serological and clinical signs of rheumatoid arthritis. Vertical subluxation as seen in this patient may be missed on routine x-rays.

Gastric mucosal interleukin-8 and IL-8 antibody concentrations related to prevailing Helicobacter pylori infections. A Danish-Albanian study.

OBJECTIVES: Helicobacter pylori (H. pylori) appears to initiate an inflammatory cascade. Thus, phagocytes are accumulated in the gastric mucosa, in inflammatory conditions. Further, a potent chemotactic mediator, interleukin 8 (IL-8) is synthesized at such sites. The recently described IL-8 autoantibodies may, however, counteract the pro-inflammatory actions of IL-8. The aim was to study the correlation between H. pylori infection and IL-8, together with IL-8 autoantibodies in two different populations from a developed and a developing country. METHODS: Two different endoscopically characterized populations (65 Danes and 89 Albanians) were examined. IL-8 and IL-8 autoantibodies were detected by ELISA techniques, and H. pylori was identified by histological examinations. RESULTS: Significantly more Albanian controls and dyspeptic patients (80 out of 89 persons) were H. pylori positive as compared to 24 of 65 Danes (p < 0.001). The median IL-8 level among Albanian controls 349 pg/mg protein was significantly higher than among Danes < 61 pg/mg protein (p < 0.001), and was at the same level as found in Danish peptic ulcer patients (p > 0.05). Further, H. pylori positive patients from both countries had significantly higher levels of IL-8 as compared to H. pylori negative patients (p < 0.001). However, significantly higher levels of IL-8 autoantibodies were found in the Albanian sub-population (median 138 O.D. units versus 52 O.D. units among Danes) (p < 0.001). CONCLUSIONS: In H. pylori related disorders, a high mucosal IL-8 production has been found. However, this investigation further demonstrates higher levels of IL-8 autoantibodies among dyspeptic patients from a developing country, which might possibly counteract the pro-inflammatory actions of IL-8 by binding the molecule. The physiological significance of an altered immune response as described here needs to be elucidated in future studies.

Increase of axial and appendicular trabecular and cortical bone density in established osteoporosis with intermittent nasal salmon calcitonin therapy.

The aim of this study was to examine the effect of intranasal administration of salmon calcitonin to a group of 24 postmenopausal women with severe, established osteoporosis (t score < -2.5 SD) and more than one vertebral fracture. The patients were treated with 200 IU of nasal salmon calcitonin daily for 2 months with a subsequent pause of 2 months (3 cycles) and 500 mg calcium daily over a total of 12 months in an open randomized study. The patients were compared with an age matched control group of 18 women of a similar clinical status who were treated with calcium and vitamin D only. In the nasal calcitonin treatment group an increase in the trabecular axial bone density of 2.8% was achieved, as well as increase in trabecular appendicular (forearm) bone density of 1.6%, together with a cortical bone density increase of 1.8% axial and 1% appendicular. Initially, elevated values of urinary deoxypyridinoline were found in 12 women in the nasal calcitonin treatment group; these levels returned to normal under salmon calcitonin nasal therapy and documented the inhibition of increased osteoclastic activity. Cyclic intermittent calcitonin nasal therapy led to a general increase in trabecular and cortical axial and appendicular bone density, marked alleviation of the subjective sensation of pain, and a reduction in the daily dose of accompanying nonsteroidal anti-inflammatory drugs by 50%.

[Hypersensitivity vasculitis causing an acute abdomen]. / Hypersensitivitätsvaskulitis als Ursache eines akuten Abdomens.

The members of a family of four persons suffered acute gastroenteritis after eating a meal consisting of chicken. While three of them recovered rapidly, the 18-year old son developed an acute abdomen which had to be treated surgically and led to a complicated stay at the intensive care unit. Intraoperatively, a mild insignificantly inflamed appendix and an obscure segmental inflammatory process of the small bowel with local peritonitis were seen; this required an appendectomy and a peritoneal lavage. The development of bacterial peritonitis with multiple organ dysfunction required several surgical revisions with an open abdominal toilet treatment. Histological examination of the resected appendix specimen showed a severe primary fibrinoid necrotizing vasculitis with epitheloid-granulomatous reaction. Diseases such as Panenteritis nodosa, Wegener's disease and Churg-Strauss's syndrome were excluded by negative serology. By a process of exclusion, a hypersensitivity vasculitis was diagnosed and treated successfully with a high-dose cortisone regime.

Anti-IL-8 autoantibodies and complexes in rheumatoid arthritis: polyclonal activation in chronic synovial tissue inflammation.

The chemokine interleukin-8 (IL-8) is frequently associated with inflammatory diseases, and autoantibodies against IL-8 are present in the periphery at elevated levels in such conditions as rheumatoid arthritis (RA). Circulating free anti-IL-8 IgG autoantibodies correlate with inflammatory parameters and disease severity in RA. In this study, correlations were sought between these disease parameters and other antibody subclasses. We assayed IgM, IgA and IgG anti-IL-8 antibodies and IL-8 immunoglobulin immune complexes in the serum of 29 healthy controls and 56 patients with defined RA, and compared the results with clinical and humoral disease parameters. IgG and IgM antibodies directed against IL-8 were present in all samples. In the disease groups, all isotypes of free anti-IL-8 antibodies correlated with increasing humoral disease parameters like CRP and CIC and their related anti-IL-8 immune complexes. Samples which contained high titers of anti-IL-8 antibody subclasses and complexes were RF subclass-positive, while IgM RF-negative sera showed low levels of anti-IL-8 and complexes. Detectable levels of IgG and IgA RF were found in all sera. Patients with extra-articular organ manifestation showed significantly increased free IgA and IgA/IL-8 complexes, with no correlation to the IgA RF titer or IgA hypergamma-globulinemia. The highest titers were seen in two RA cases with vasculitis and in one patient with colitis. Polyclonal activation of the humoral antibody system, which normally precedes the resolution of an inflammatory response, can itself lead to secondary stimulation of inflammatory processes via immune complex formation. In the immune pathology of RA, it degenerates into a persistent chronic inflammation accompanied by progressive joint destruction. The presence of elevated IgA subclass anti-IL-8 autoantibodies in RA patients with extra-articular manifestations suggests these autoantibodies as a clinically useful marker of disease severity and extra-articular manifestations.

Association between female sex hormones and biochemical markers of bone turnover in peri- and postmenopausal women.

In an epidemiological study, markers of bone formation (serum osteocalcin and C-terminal propeptide of type I collagen) and bone resorption [urinary type I collagen peptides (Crosslaps), urinary total pyridinoline (TPYRI), urinary deoxypyridinoline (DPYRI) as well as female sex hormones (serum estradiol)], follicle-stimulating hormone (FSH) and luteinizing hormone were measured in 237 women. This cohort aged 44-66 years, came for their first medical examination since menopause to the outpatient menopause clinic at the Kaiser-Franz-Josef-Hospital, Vienna. The women were all 0.5-5.0 years since cessation of menses and were not taking medications other than hormone replacement therapy [52 cases, 21.9%)] and had no diseases known to affect bone and mineral metabolism. The best correlation was found between urinary DPYRI and urinary TPYRI (r = 0. 63, P = 0.0001), followed by urinary Crosslaps and urinary DPYRI (r = 0.47, p = 0.0001). Only weak but significant correlations between E2 and urinary Crosslaps (r = -0.21, P < 0.0001) as well as serum E2 and serum osteocalcin (r = -0.16, P = 0.0007), were observed. Of the 237 women 53% suffered from a severe E2 deficiency (E2 < 10.0 ng/liter). In these patients, urinary Crosslaps (+48%) and serum osteocalcin (+22%) were significantly higher (P < 0.0001) compared with those patients with E2 levels > 10 ng/liter. Women with E2 levels >10 ng/liter were further subdivided into those with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these groups. We could clearly demonstrate that in postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/liter), urinary Crosslaps and serum osteocalcin are significantly increased, indicating in principle a clear correlation between E2 deficiency and these markers of bone turnover.

[Alprostadil (PGE 1) and cyclosporin A in treatment of vasculitis in rheumatoid arthritis]. / Alprostadil (PGE 1) und Cyclosporin A zur Behandlung der Vaskulitis bei rheumatoider Arthritis.

A 56-year old female patient with rheumatoid arthritis and histologically verifiable vasculitis with necrosis around the nail bed and distal phalanx gangrene on both hands as well as skin ulcers on both thighs was treated over 16 weeks with Cyclosporin A, glucocorticoids and Alprostadil. This immunosuppressive therapy resulted in a clinically relevant improvement of acral microperfusion with complete remission of nail bed necrosis and of gangrenous distal phalanxes. Due to improved tissue perfusion the deep ulcers on both thighs could granulate and were closed by proliferative connective tissue, and the high-positive immunological parameters CIC, CRP and the number of activated T-cells normalized.

Presence of cyclophilin A in synovial fluids of patients with rheumatoid arthritis.

Cyclophilins have been suggested to act as leukocyte chemotactic factors produced in the course of inflammation. Therefore we looked for the presence of cyclophilins in the synovial fluids (SF) from patients with rheumatoid arthritis (RA). Peptidyl prolyl cis-trans isomerase activity (PPIase) was measured in SF from knee punctures of 26 patients with RA and five patients with knee osteoarthritis (OA). PPIase was detected in SF from RA patients, but not in samples from OA patients. Enzyme activity was sensitive to inhibition by cyclosporin A (IC50 = 28-50 nM). Estimated concentrations of the SF-derived cyclophilin based on the enzyme activity were in the range of 11 to 705 nM. The presence of cyclophilin in the SF showed disease correlation; its concentration correlated with the number of cells in the SF (r = 0.91, P < 0.0001) and with the percentage of neutrophils in the cellular infiltrate and was higher in more acute cases of joint swelling. In immunoblots of partially purified preparations of SF from RA patients, an approximately 18-kD protein band reacted with polyclonal antibodies that recognize cyclophilin A and B, but not with antibodies specific for cyclophilin B. Sequencing of this protein revealed identity of the NH2-terminal amino acids with those of human cyclophilin A. The finding is unexpected since cyclophilin B rather than A is generally regarded as the secreted isoform, the presence of cyclophilin A being confined to the cytoplasm. Our data support the hypothesis that cyclophilins may contribute to the pathogenesis of inflammatory diseases, possibly by acting as cytokines. This may offer a possible explanation of the effectiveness of cyclosporin A in RA, in addition to the known immunosuppressive effects of the drug.

Biochemical markers in menopausal women.

Markers of bone formation (osteocalcin and C-Terminal Propeptide of Type I Collagen [CICP]) and of resorption (Crosslaps, total pyridinoline [Pyd] and deoxypyridinoline [Dpd]) as well as female sex hormones (estradiol [E2], follicle stimulating hormone [FSH] and luteinizing hormone [LH]) were measured in 237 women aged 44-66 years coming for the first medical examination to the outpatient clinic of menopause at the Kaiser-Franz-Josef-Hospital, Vienna. All women (0.5-5.0 years since cessation of menses) selected were not taking medications other than hormone replacement therapy in 52 cases (21.9%) and did not have diseases known to affect bone and mineral metabolism. The best correlation was found between Dpd and Pyd (r = 0.63, p = 0.0001), followed by Crosslaps and Dpd (r = 0.47, p = 0.0001). Only weak but significant correlations between E2 and Crosslaps (r = 0.21, p < 0.0001) as well as E2 and osteocalcin (r = 0.16, p = 0.0007) were observed, 53% of the 237 women suffered from a severe E2 deficiency (E2 < 10.0 ng/L). In these patients Crosslaps (approx. +48%) and osteocalcin (+22%) were significantly higher (p < 0.0001) compared to those with E2 concentrations > 10 ng/L. Women with E2 concentrations > 10 ng/L were further subdivided into women with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these both groups. In conclusion, we could clearly demonstrate that in postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/L) Crosslaps and osteocalcin are significantly increased, indicating in principle a clear correlation between E2 deficiency and these markers of bone turnover.

[Epidemiology, incidence and sex specific differences in primary gout]. / Epidemiologie, Häufigkeit und geschlechts-spezifische Unterschiede in der primären Gicht.

Gout is common disease with a worldwide distribution. The major risk factor for the development of gout is sustained asymptomatic hyperuricemia. Primary prevention of gout can be achieved through lifestyle changes including weight loss, restricting protein and calorie intake, limiting alcohol consumption and optimal treatment of hypertension.

[Uric acid crystals and chemotactic cytokines--pathogenesis of an acute gout attack]. / Harnsäurekristalle und chemotaktische Zytokine--Die Pathogenese des akuten Gichtanfalls.

The identification of monosodium urate crystals in synovial fluid is essential for the definite diagnosis of gout. Neutrophils interact with urate crystals to produce inflammatory reactions associated with acute arthritis. Crystals activate monocyte-macrophages and synoviocytes to produce high levels of proinflammatory cytokines, like TNF alpha und interleukin-1 and different chemokines. High levels of interleukin-8, a powerful neutrophil attractant with activating properties, were demonstrated in the synovial fluid of patients with acute gout arthritis.