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.

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.

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.

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.

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.

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.

SDZ PRI 053, an orally bioavailable human immunodeficiency virus type 1 proteinase inhibitor containing the 2-aminobenzylstatine moiety.

A series of inhibitors of human immunodeficiency virus type 1 (HIV-1) proteinase containing the 2-aralkyl-amino-substituted statine moiety as a novel transition-state analog was synthesized, with the aim to obtain compounds which combine anti-HIV potency with oral bioavailability. The reduced-size 2-aminobenzylstatine derivative SDZ PRI 053, which contains 2-(S)-amino-3-(R)-hydroxyindane in place of an amino acid amide, is a potent and orally bioavailable inhibitor of HIV-1 replication. The antiviral activity of SDZ PRI 053 was demonstrated in various cell lines, in primary lymphocytes, and in primary monocytes, against laboratory strains as well as clinical HIV-1 isolates (50% effective dose = 0.028 to 0.15 microM). Cell proliferation was impaired only at 100- to 300-fold-higher concentrations. The mechanism of antiviral action of the proteinase inhibitor SDZ PRI 0.53 was demonstrated to be inhibition of gag precursor protein processing. The finding that the inhibitory potency of SDZ PRI 053 in chronic virus infection, determined by p24 release, was considerably lower than that in de novo infection may be explained by the fact that the virus particles produced in the presence of SDZ PRI 053 are about 50-fold less infectious than those from untreated cultures. Upon intravenous administration, half-lives in blood of 100 and 32 min in mice and rats, respectively, were measured. Oral bioavailability of SDZ PRI 053 in rodents was 20 to 60%, depending on the dose. In mice, rats, and dogs, the inhibitor levels after oral administration remained far above the concentrations needed to efficiently block HIV replication in vitro for a prolonged period. This compound is thus a promising candidate for clinical use in HIV disease.

Mode of action of SDZ NIM 811, a nonimmunosuppressive cyclosporin A analog with activity against human immunodeficiency virus (HIV) type 1: interference with HIV protein-cyclophilin A interactions.

Cyclosporins, in particular the nonimmunosuppressive derivative SDZ NIM 811, exhibit potent anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. SDZ NIM 811 interferes at two stages of the viral replication cycle: (i) translocation of the preintegration complex to the nucleus and (ii) production of infectious virus particles. Immunosuppressive activity is not correlated with anti-HIV-1 activity of cyclosporins. However, binding to cyclophilin A, the major cellular receptor protein of cyclosporins, is a prerequisite for HIV inhibition: all structural changes of the cyclosporin A molecule leading to loss of affinity to cyclophilin abolished the antiviral effect. Cyclosporin derivatives did not interact directly with HIV-1 proteins; cyclophilin was the only detectable receptor protein for antivirally active cyclosporins. There is no evidence that inhibition of HIV occurs via a gain of function of cyclophilin in the presence of cyclosporins: the complex of cyclophilin A with SDZ NIM 811 does not bind to calcineurin or to any other viral or cellular proteins under conditions in which calcineurin binding to the cyclophilin A-cyclosporin A complex is easily detectable. Thus, the loss of function caused by binding of cyclosporins to cyclophilin seems to be sufficient for the anti-HIV effect. Cyclophilin A was demonstrated to bind to HIV-1 p24gag, and the formation of complexes was blocked by cyclosporins with 50% inhibitory concentrations of about 0.7 microM. HIV-2 and simian immunodeficiency virus are only weakly or not at all inhibited by cyclosporins. For gag-encoded proteins derived from HIV-1, HIV-2, or simian immunodeficiency virus particles, cyclophilin-binding capacity correlated with sensitivity of the viruses to inhibition by cyclosporins. Cyclophilin A also binds to HIV-1 proteins other than gag-encoded proteins, namely, p17gag, Nef, Vif, and gp120env; the biological significance of these interactions is questionable. We conclude that HIV-1 Gag-cyclophilin A interaction may be essential in HIV-1 replication, and interference with this interaction may be the molecular basis for the antiviral activity of cyclosporins.

CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines.

AIMS: To investigate: (1) whether Helicobacter pylori directly induces interleukin-8 (IL-8) message expression and protein secretion in established gastric epithelial cell lines; and (2) if CagA/cytotoxin positive and negative strains of H pylori differ in their ability to induce epithelial IL-8. METHODS: Gastric epithelial cell lines were co-cultured with H pylori NCTC 11637 and 10 clinical isolates (four cytotoxic, six non-cytotoxic) and secreted IL-8 was measured by enzyme linked immunosorbent assay (ELISA). Specific induction of gastric epithelial IL-8 mRNA was examined by reverse transcription and polymerase chain reaction (RT-PCR) amplification. RESULTS: H pylori (NCTC 11637) induced IL-8 secretion from three gastric epithelial cell lines (KATO-3, ST42, AGS) but not from MKN 45 (gastric) or intestinal (SW480, HT29) cell lines. H mustelae did not stimulate IL-8 secretion from KATO-3, ST42, and AGS cells. H pylori induced IL-8 secretion was reduced by heat killing, sonication, freeze thawing or formalin fixation of the bacteria. CagA/cytotoxin positive strains of H pylori induced significantly higher IL-8 secretion than CagA/cytotoxin negative strains in the three positive gastric epithelial cell lines (KATO-3, ST42: p < 0.01; AGS: p < 0.02). A significant increase (p < 0.01) in the expression of IL-8 mRNA relative to G3PDH mRNA was observed in KATO-3 cells after three hours of co-culture with CagA/cytotoxin positive strains. CONCLUSIONS: H pylori directly increases gastric epithelial IL-8 mRNA expression and IL-8 protein secretion in a strain specific manner. Induction of epithelial IL-8 by CagA/cytotoxin positive strains is likely to result in neutrophil chemotaxis and activation and thus mucosal damage. These observations on epithelial IL-8 may explain the association between CagA/cytotoxin positive strains and gastroduodenal disease.

In vitro activity of inhibitors of late stages of the replication of HIV in chronically infected macrophages.

Because of the importance of macrophages in the pathogenesis of the disease caused by HIV, we investigated the efficacy of various anti-HIV drugs in human primary macrophages acutely or chronically infected by this virus. The results obtained for acutely infected macrophages show that dideoxynucleosides (AZT, ddI, and ddC), interferon-alpha and -gamma, mismatched double-stranded RNA, Tat inhibitor, phosphorothioate antisense, and inhibitors of HIV protease, all significantly inhibit virus replication at concentrations far below those toxic for the cells. However, in macrophages in which proviral DNA is already integrated (chronically infected macrophages), only the three inhibitors of HIV protease induced significant virus inhibition at concentrations 100 or more times higher than those effective in acutely infected macrophages. Treatment of macrophages with macrophage colony-stimulating factor does not affect the anti-HIV efficacy of protease inhibitors. These results suggest that therapeutic strategies with activity for macrophages, including inhibitors of HIV protease, are worth pursuing in patients with HIV infection.

Interleukin-8 expression in Helicobacter pylori infected, normal, and neoplastic gastroduodenal mucosa.

AIMS: To investigate the expression of interleukin-8 (IL-8) in Helicobacter pylori infected normal and neoplastic gastroduodenal mucosa, and in established gastric cancer cell lines. METHODS: Immunofluorescence techniques were used to localise IL-8 in cryosections of gastric (n = 25) and duodenal (n = 17) endoscopic biopsy specimens an in resected gastric tumour tissue samples from 16 patients. Two gastric cancer cell lines (Kato 3 and MKN 45) were examined for IL-8 protein expression by immunofluorescence and for the presence of IL-8 mRNA by reverse transcription followed by the polymerase chain reaction (RT-PCR). RESULTS: IL-8 was localised to the epithelium in histologically normal gastric mucosa, with particularly strong expression in the surface cells. IL-8 expression was also a feature of surface epithelium in the duodenal bulb, but was much reduced in the second part of the duodenum. In chronic H pylori-associated gastritis gastritis gastric epithelial IL-8 expression was increased and expression of IL-8 within the lamina propria was evident. By contrast, large areas of IL-8 negative epithelium were observed in the body mucosa of a subject with Ménétrier's disease. In gastric carcinoma the tumour cells were positive for IL-8. IL-8 was also detected by immunofluorescence in unstimulated Kato 3 and MKN 45 cells, and constitutive IL-8 gene expression in these cell lines was confirmed by detection of IL-8 mRNA by RT-PCR. CONCLUSIONS: Immunoreactive IL-8, a potent neutrophil chemotactic and activating factor, is present in the epithelium of both normal and inflamed gastric mucosa with increased expression in the latter. There is site dependent variation in epithelial IL-8 expression within the gastroduodenal mucosa. The expression of the pro-inflammatory cytokine IL-8 in gastric carcinoma cells may influence peritumoural cellular infiltrates.

Gastric interleukin-8 and IgA IL-8 autoantibodies in Helicobacter pylori infection.

Gastric infection with Helicobacter pylori is frequently characterized by neutrophil infiltration. The production of the neutrophil-activating peptide (NAP-1/IL-8) and mucosal IgA autoantibodies to IL-8 by human antral biopsies have been examined during short-term in vitro culture. Detectable IL-8 was secreted by 84% of H. pylori-negative patients with normal antral mucosa (range < 0.07-61.5 ng/mg biopsy protein, n = 19). Concentrations in 4 patients with reactive gastritis and 10 with inactive gastritis were not significantly different from subjects with normal mucosa. In H. pylori-positive patients with active gastritis and neutrophil infiltration into the epithelium (n = 17) IL-8 secretion was significantly increased relative to subjects with normal mucosa (P < 0.0001), inactive gastritis (P < 0.001) and reactive gastritis (P < 0.01). IL-8 concentrations in active gastritis were significantly correlated with the extent of epithelial surface degeneration (r = 0.64). IgA autoantibodies were present in 19 patients (13 active, 4 inactive gastritis) and concentrations were significantly correlated with IL-8 production (P < 0.001). Gastric synthesis of IL-8 is likely to be an important factor in regulating mucosal neutrophil infiltration and activation in patients with H. pylori infection. The local production of IgA antibodies to IL-8 may represent a down-regulatory response of the host to limit mucosal damage associated with a chronic bacterial infection.

Presence of NAP-1/IL-8 in synovial fluids indicates a possible pathogenic role in rheumatoid arthritis.

The synovial fluid in affected joints of rheumatoid arthritis (RA) patients contains many cells, in numbers strongly correlated with the severity of disease. As the disease worsens and the cell count increases, the polymorphonuclear leucocyte becomes the predominant cell type. Although the inflammatory cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) have no direct neutrophil-attractant activity, they are both potent inducers of interleukin 8 (IL-8) in a variety of cell types. Chemotactic attraction of neutrophils is a major activity of IL-8. Examination of a number of synovial fluids showed that significant levels of IL-8 are present in a high proportion of RA cases (10 out of 17), at concentrations directly related to the number of cells in the joint, and to circulating C-reactive protein (CRP) levels. The cytokine is present only at background levels in other diseases accompanied by arthritic manifestations, including systemic lupus erythematosus (SLE) and induced arthritis. The progressive joint destruction seen in all cases where high IL-8 levels were measured, coupled with the neutrophil-rich cell count and the strong correlation between concentration of IL-8 and both serum CRP and cellular influx into the joint, is strongly suggestive of a pathogenic role for IL-8 in RA.

Selective binding of rheumatoid factors to antigen structures of cytomegalovirus (CMV).

In rheumatoid arthritis patients with malignant progress, short remissions and unimprovement response of activity to therapy Ab with both properties (antiviral and anti IgG) are compared. The selective binding of RF to antigen structures of CMV were tested by 180 patients in a new established ELISA with antiidiotypic goat antibodies of CMV neutralizing human monoclonal Ab and against virus antigen directly. Displacement reactions on the idiotypic binding side as well as comparative ELISA proved the special RF activity. 24.2% of patient suffering from RA with IgM RF showed selective bindings to antigen structures of CMV and anti IgG activity. The evidence of the specific binding capacity of RF to virus antigen in chronical CMV infection as well as their defined binding capacity to the Fc Fragment of IgG suggest CMV specific RF as pathogenetic factor of malignant forms of inflammatory rheumatism.