Increased capillary permeability in systemic sclerosis: help or hindrance?
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Biomedical subjects
Publications and source records attributed to W Grassi.
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Non-steroidal anti-inflammatory drugs (NSAIDs) give rise to a wide range of gastrointestinal side-effects. These are reviewed and it is stressed that some safety measures are possible only if the risk factors are considered. The relations between dyspeptic symptoms and gastrointestinal lesions are also debated. It is suggested that the ulcerogenic potential of various molecules must be carefully evaluated, especially in elderly patients.
OBJECTIVE: To characterize finger tendon involvement in patients with rheumatoid arthritis (RA). METHODS: The finger tendons of 20 RA patients were studied by ultrasonography using a high-frequency (13-MHz) transducer. RESULTS: Eighteen patients (90%) showed finger tendon abnormalities: widening of the flexor tendon sheath (80%), loss of the normal fibrillar echotexture (60%), irregularity of the extensor (30%) and flexor (50%) tendon margins, tendon tear (10%), synovial cyst (20%). CONCLUSION: High-frequency sonography is helpful in assessing even minimal finger tendon lesions in RA patients.
It has been demonstrated that the calcium antagonist nifedipine inhibits the reactive oxygen species (ROS) production by polymorphonuclear leucocytes (PMNLs) activated with phorbol myristate acetate (PMA), but the mechanism underlying this effect is still unknown. In the present study we investigated the influence of nifedipine on the PMNL plasma membrane using 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5,hexatriene (TMA-DPH) fluorescence polarization (P) and on PMA- and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced ROS production, measured by luminol-dependent chemiluminescence (CL). The plasma membrane fluidity of untreated PMNLs, expressed as P, was 0.371 +/- 0.008. After preincubation of 15 min, nifedipine induced a significant change in P values only at a concentration of 10(-4) M (P = 0.00018). After preincubation of 60 min significant changes in P values were also observed at concentrations of 10(-6) M (P = 0.023) and 10(-7) M (P = 0.023). PMA-induced ROS production by PMNLs was markedly inhibited by nifedipine. Nifedipine also determined a striking change in the FMLP-induced CL response, characterized by both an overall inhibition of PMNL activity and a modification of the kinetics of the oxidative burst (rapid increase in ROS production followed by a pronounced drop in the PMNL response). Such a pattern was found at concentrations of 10(-4) M (preincubation time: 15 min), 10(-6) M and 10(-7) M (preincubation time: 60 min). These findings indicate that nifedipine directly interacts with the PMNLs by inducing a marked decrease in plasma membrane fluidity and an inhibition of the oxidative burst.
OBJECTIVE: To determine the influence of cold exposure on microvascular permeability in systemic sclerosis (SSc). METHODS: Thirteen patients with SSc were studied by dynamic fluorescence videomicroscopy under basal conditions and after exposure to cold. RESULTS: Exposure to cold caused a significant reduction in the interstitial concentration of sodium fluorescein (P < 0.05 to 0.001). CONCLUSION: Our findings show that cold exposure has a striking effect on microvascular dynamics in SSc.
Calcium-channel blockers are widely used in the treatment of systemic sclerosis (SSc), but their in vivo influence on microcirculation is not fully elucidated. We evaluated the acute effect of nifedipine on the cold-induced changes of microvascular dynamics in SSc. Eleven SSc patients and seven healthy volunteers were studied. Dynamic aspects of the nailfold microcirculation (appearance time at the nailfold, transcapillary diffusion, interstitial distribution and interstitial clearance of sodium fluorescein given i.v.) were quantitatively assessed by a computer-aided fluorescence videomicroscope. Fluorescent light intensities (FLIs) at predefinite pericapillary and interstitial sites were measured under three experimental conditions: (1) baseline; (2) after cold test; (3) after single oral administration of 10 mg of nifedipine 5 min before cold exposure. The interval between the intravenous injection of sodium fluorescein and the first appearance of the dye at the nailfold significantly increased after cold exposure in the SSc patients (224.1 +/- 182.3 s vs 27.5 +/- 25.1 s at baseline) (P = 0.0026), but not in the controls (28.0 +/- 13.3 s vs 29.6 +/- 12.4 s at baseline). The effect of cold exposure on the appearance of the dye was not significantly antagonized by nifedipine (112.7 +/- 91.8 s) in the SSc patients (P = 0.07). Cold exposure significantly decreased transcapillary diffusion and interstitial distribution of sodium fluorescein in the SSc patients (P < 0.016), but not in the controls. The cold-induced changes of FLI values were antagonized by nifedipine in the SSc patients (P < 0.016), but not in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
The prevalence of Raynaud's phenomenon in RA was retrospectively reviewed in 411 consecutive RA patients and in a control group of 919 consecutive outpatients with OA. Raynaud's phenomenon was found in 19 (4.6%) of 411 RA patients and in 52 (5.6%) of 919 patients with OA: its prevalence was 4.3% (13 cases) in RA inpatients and 5.4% (six cases) in RA outpatients. Among the RA patients, the prevalence of Raynaud's phenomenon was 7.5% in men (7% of inpatients, 8.8% of outpatients) and 3.2% in women (3% of inpatients, 3.9% of outpatients) (P = N.S.). Conversely, the prevalence of Raynaud's phenomenon in patients with OA was higher in women (6.5%) than in men (2.9%) (P = 0.045). Our study indicates that the reported association between Raynaud's phenomenon and RA cannot be confirmed on the basis of a retrospective assessment of its prevalence.
OBJECTIVE: To examine capillary permeability in fibromyalgia (FMS) we studied the nailfold capillaries of 13 unselected patients with FMS and 9 healthy controls using dynamic fluorescence videomicroscopy. METHODS: The transcapillary permeability of a 20% solution of sodium fluorescein injected into an antecubital vein was assessed by videodensitometric analysis. The pericapillary and interstitial fluorescent light intensities (FLI) were calculated at different sites on a transverse axis crossing the selected capillary. RESULTS: Fluorescence videomicroscopy revealed no abnormalities in the pattern of dye distribution around the nailfold capillaries in the patient group. Videodensitometric analysis showed a trend to an increased early transcapillary diffusion in patients with FMS, but the difference was only significant at 3 s from the first appearance of the dye (p < 0.05). From 10 s to 1 min after the dye's appearance, the mean FLI in the patients equalled that of the controls. The patients with FMS showed an earlier but lower FLI peak. Moreover, the FLI were significantly lower in the patients than in the controls from 5 to 30 min after the dye appearance in all of the sites of the densitometric analysis (p < 0.05). Thirty min after the first appearance of the dye, the FLI was reduced by more than 50% in the patient group compared to the controls. CONCLUSION: Our results indicate that transcapillary permeability and the interstitial persistence of the tracer in FMS are significantly reduced compared to controls. This difference may be caused by the abnormal microvascular dynamics induced by low capillary flow and/or capillary bed hypotension.
OBJECTIVES: To investigate whether in vivo capillary microscopy of the lower lip mucosa can be used to assess microvascular disease in systemic sclerosis. METHODS: Thirteen patients with systemic sclerosis and 11 healthy control subjects were studied by conventional nailfold capillary microscopy and labial capillaroscopy. The following parameters were analysed: loop length; loop width (maximum distance between the arteriolar and venular limbs); loop density (number of capillaries/mm2); venular plexus visibility; megacapillaries; and the architectural arrangement of the capillary network. RESULTS: A typical 'scleroderma pattern' at the nailfold was observed in 12 of 13 (92%) patients with systemic sclerosis. Labial capillaroscopy showed a different morphological pattern of microangiopathy. A diffuse architectural derangement of the capillary network was the most striking abnormality in 12 (92%) patients. Labial capillaries in the patients with systemic sclerosis were shorter (mean (SD) loop length 133 (32.2) microns) than in healthy controls (211 (48.4) microns) and showed an increased loop width (41.7 (13.1) v 27.6 (5.5) microns in controls. The loop density was 10.5 (4.6) capillaries/mm2 in patients with systemic sclerosis and 9 (1.7) capillaries/mm2 in controls. Labial capillaroscopy in patients with systemic sclerosis did not provide definite evidence of enlarged capillaries or avascular areas, or both, even where such abnormalities were clearly evident at the nailfold. CONCLUSIONS: This study shows that labial capillary microscopy is a simple, non-invasive technique which allows a careful morphological assessment of the mucosal microcirculation. Labial capillaroscopy in patients with systemic sclerosis showed significant microvascular changes with respect to the controls. The results of labial and nailfold capillaroscopy are not superimposable, even if some common findings, such as architectural derangement, are present.
To evaluate the ability of ultrasonography with high frequency transducer (13-MHz) in detecting metacarpophalangeal (MCP) joint abnormalities, 20 patients with rheumatoid arthritis (RA) and a symptomatic involvement of MCP joints were studied. Twenty healthy subjects served as controls. In all RA patients, ultrasonography clearly demonstrated one or more soft tissue and/or bone abnormalities. Sixteen patients (80%) had joint cavity widening because of effusion (1 case), synovial thickening (7 cases), and joint effusion with synovial thickening (8 cases). Loss of definition of the metacarpal articular cartilage was observed in 17 cases (85%). Sixteen (80%) had bone erosions and 9 (45%) showed a definite widening of the flexor tendons sheath. Margin irregularities of the extensor and flexor tendons were respectively visualized in 7 (35%) and in 8 (40%) cases. An extensor tendon rupture was observed in 2 cases (10%). Ultrasound examination by 13-MHz transducer appears to increase the accuracy of MCP joints evaluation in RA with respect to conventional radiography. It can be recommended as the first investigation in the assessment of soft tissue involvement in RA patients.
This study is the first report of the permeability status of nailfold capillaries in psoriatic arthritis (PA). "Traditional" nailfold capillary microscopy and intravital fluorescence videomicroscopy were carried out at the nailfold of 13 patients with PA. Twenty five healthy subjects served as controls for nailfold capillary microscopy, and 15 out of these for fluorescence videomicroscopy. The following parameters were assessed: capillary length, apex width, maximum loop width, maximum limb width, loop density, visibility of subpapillary venular plexus, loop tortuosity, transcapillary diffusion, and interstitial concentration at different sites and times of Na-fluorescein given in intravenous bolus. Morphometric analysis of capillaroscopic findings showed a significant increase of loop length (mean +/- SD: 290.1 +/- 73.5 microns) when compared to healthy controls (223.3 +/- 51.9 microns) (P < 0.02). Transcapillary passage of Na-fluorescein was homogeneous and symmetric both in PA patients and in controls. Mean transcapillary and interstitial diffusion was not significantly enhanced at the nailfold in PA patients. Our data support the view that PA is not characterized by a specific capillaroscopic pattern and/or significant abnormalities of microvascular dynamics at the nailfold.
The association between hidradenitis suppurativa and joint involvement is well recognized. We describe a 63-year-old man with a severe HLA-B27 negative ankylosing spondylitis associated with hidradenitis suppurativa. We are not aware of any reports of such an association in the literature.
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Until now, little or no attention has been paid to the monitoring of therapy with nonsteroidal antiinflammatory drugs (NSAIDs). The authors discuss reasons for that situation. They emphasize that lack of monitoring of unwanted side-effects of the widely used NSAIDs is no doubt due to the overuse of these drugs. The expedience and a protocol concerning the efficacy and toxicity monitoring of such drugs are critically discussed. The authors stress that toxicity monitoring should be performed in selected patient groups that to only in those patients at risk.
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