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Dynamic capillaroscopy: a minimally invasive technique for assessing photodynamic effects in vivo.

A noninvasive method for visualizing the microvasculature in the mouse tail is described, consisting of a custom-built microscope with through-lens illumination. The microscope is fitted with a television camera and images can be recorded on videotape and displayed on a television monitor. Blood vessels are imaged as columns of red blood cells, in which flow is clearly observed. Administration of photosensitizers and illumination with the standard light source produces no observable photodynamic effect on blood flow. The combination of photosensitizer and a more intense light source (either broadband light from a filtered mercury arc or red light from a laser) causes photodynamic cessation of flow within a few minutes. The magnitude of the effect is dependent on the dose and nature of the photosensitizer, the delay after photosensitization and the match between the laser light and the absorption spectra of the photosensitizers in the red region. We conclude that the technique yields results consistent with the known photodynamic effects of the photosensitizers in tumors and propose its use as an initial screening method in vivo, as a means of conducting pharmacokinetic experiments and as an assay of prolonged cutaneous photosensitivity.

Angioscopy↗

Increased circulating levels of tissue kallikrein in systemic sclerosis correlate with microvascular involvement.

BACKGROUND: In systemic sclerosis (SSc) the lack of an angiogenic response to hypoxia may be due to inappropriate synthesis of angiogenic and angiostatic factors. Tissue kallikrein (t-kallikrein), regulating the kallikrein-kinin system and acting on the microcirculation, is a potent angiogenic agent, and kallistatin is its natural inhibitor. OBJECTIVE: To evaluate, in patients with SSc, t-kallikrein and kallistatin levels and their correlation with clinical features and measures of microvascular involvement. PATIENTS AND METHODS: Serum levels of t-kallikrein and kallistatin (ELISA) and t-kallikrein skin expression (immunohistochemistry) were studied in patients with SSc, and evaluated for subset (dSSc or lSSc), clinical and immunological features, and microvascular involvement (ulcers, telangiectasias, nailfold videocapillaroscopy). RESULTS: Circulating levels of t-kallikrein were higher in SSc than in controls (p<0.001). T-kallikrein did not differ between lSSc and dSSc, although it was higher in lSSc than in controls (p<0.001).T-kallikrein levels were higher in patients with early and active capillaroscopic pattern than in those with late pattern (p = 0.019 and 0.023). Patients with giant capillaries and capillary microhaemorrhages had higher t-kallikrein concentrations than patients with architectural derangement (p = 0.04). No differences in kallistatin levels were detected between patients with SSc and controls, or between lSSc and dSSc. In early SSc skin, the presence of t-kallikrein was found in endothelial and in perivascular inflammatory cells, while no staining in skin of advanced SSc was detected. CONCLUSION: T-kallikrein levels are increased in patients with SSc, particularly in lSSc, and are associated with early and active capillaroscopic patterns. T-kallikrein may play a part in SSc microvascular changes.

Adult↗

Intravital microscopy and capillaroscopically guided nail fold biopsy in scleroderma.

OBJECTIVES: To describe the frequency, extent, and nature of microvascular lesions in patients with scleroderma by means of capillaroscopy and capillaroscopically guided nail fold biopsy, and to determine the diagnostic value of the two methods and the pathophysiological significance of the lesions described. METHODS: A cohort study was made of 24 consecutive patients with scleroderma and 10 healthy controls, using standardised clinical, serological, capillaroscopic, and histological (nail fold biopsy) techniques. RESULTS: All patients with scleroderma had distinct lesions of the microvascular system. Capillaroscopy revealed more than 90% of the patients to have the typical scleroderma pattern. Histologically, these changes most frequently consisted of splitting of the basal lamina, broadening of the perivascular connective tissue, perivascular round cell infiltrations, and immunoglobulin deposits (each in 60-75% of the patients). Electron microscopy was the most sensitive method of histological examination, detecting abnormalities in 87.5% of patients; with light microscopy and immunohistochemical techniques, abnormalities were revealed less frequently (83.3% and 75%, respectively). In contrast, normal findings were observed in most of the healthy controls: capillaroscopy = 90%; histology = 80%. CONCLUSIONS: Microvascular lesions are a predominant feature in scleroderma and seem to have a central pathogenetic role in the disease. Capillaroscopy is able to identify this microangiopathy noninvasively, and capillaroscopically guided nail fold biopsy can detect the frequency and nature of the underlying ultrastructural changes. This may therefore be a useful tool in describing the pathogenetic role of the microvascular system in scleroderma.

Adult↗

Differentiation between primary and secondary Raynaud's phenomenon: a prospective study comparing nailfold capillaroscopy using an ophthalmoscope or stereomicroscope.

BACKGROUND: Nailfold capillary microscopy is a routine procedure in the investigation of patients with Raynaud's phenomenon (RP). As a standard method, nailfold capillary morphology is inspected with a stereomicroscope to look for capillary abnormalities such as giant loops, avascular areas, and bushy capillaries, which have all been found to be associated with certain connective tissue diseases. AIM: To investigate prospectively whether nailfold capillary inspection using an ophthalmoscope is of equivalent diagnostic value to standard nailfold capillary microscopy. METHOD: All the fingers of 26 patients with RP were examined in a blinded fashion and compared with the final diagnosis one month later. RESULTS: All giant loops, large avascular areas, and bushy capillaries were identified by both methods. The correlation for moderate avascular areas and crossed capillaries was 0.93 and 0.955 respectively. The correlation for minor abnormalities that do not contribute to the differentiation between primary and secondary RP was 0.837 and 0.861 respectively. All patients were classified identically by the two methods. CONCLUSION: For the evaluation of patients with RP, nailfold capillary morphology can reliably be assessed with an ophthalmoscope.

Female↗

Nailfold capillary microscopy in healthy children and in childhood rheumatic diseases: a prospective single blind observational study.

OBJECTIVES: To develop an objective method of nailfold capillaroscopy (NFC), applicable to a wide age range of paediatric patients. To compare the morphological characteristics of the nailfold capillaries in different rheumatology patient groups and controls. METHODS: A colour digital video camera attached to a stereomicroscope was used to capture nailfold capillary images. Computerised image processing was used to analyse and store data. Subsequent quantitative and qualitative morphological analysis was performed in the following paediatric patient and control groups: 18 children with connective tissue diseases (CTD: juvenile dermatomyositis, systemic sclerosis, and undifferentiated connective tissue disease), eight with systemic lupus erythematosus, nine with primary Raynaud's disease, three with primary vasculitis, 15 with juvenile idiopathic arthritis, 17 healthy children and 20 healthy adults. Images were analysed by a single assessor who was unaware of the patient details. RESULTS: The NFC technique was simple to perform and gave reproducible results, although some intra- and intersubject variation was noted. Capillary density and width was age related, with younger children having fewer and wider capillaries than older children and adults. Linear capillary density was significantly higher in healthy adults (mean (SD) 8.6 (1.6) capillaries/mm) compared with healthy children (HC 6.9 (0.9) capillaries/mm). The group with CTD had the most abnormal findings, with lower linear density (4.9 (1.7) capillaries/mm) and increased capillary loop width (10.7 (7.3) mm) compared with HC (3.5 (1.7) mm). In addition, 11/18 (61%) patients in the CTD group had more than two definitely abnormal capillaries in at least two nailfolds, an abnormality not seen in other subjects. Two qualitative measures, the degree of avascularity and general disarrangement of capillary pattern, were more commonly observed in the CTD group than in HC. The proportion of tortuous capillaries did not differ significantly between study groups. CONCLUSIONS: This study is unique in measuring objective quantitative and qualitative parameters of the nailfold vasculature across a wide spectrum of age and disease. Differences in capillary morphology and frequency in children with CTD compared with other paediatric diseases and healthy controls were demonstrated. In the clinical situation, an assessment of the general degree of disarrangement may offer a fast tool for assessment of the nailfold vasculature which correlates well with NFC data.

Adolescent↗

Neck-bridge device for endovascular treatment of wide-neck bifurcation aneurysms: initial experience.

PURPOSE: To report the authors' initial experience in treating patients with wide-neck aneurysms with assistance from a recently developed neck-bridge device (TriSpan; Target Therapeutics/Boston Scientific, Fremont, Calif). MATERIALS AND METHODS: Twenty-five patients were examined. Aneurysms were most frequently at the basilar bifurcation (n = 19). Sixteen aneurysms were treated electively: six aneurysms that recurred after coil-only embolization and 10 nontreated aneurysms (including four that had failed coil-only embolization). Nine aneurysms were treated acutely following subarachnoid hemorrhage. All lesions except one had a wide neck. A dual-catheter technique was used in 23 patients. Immediate angiographic results, technical incidents, and complications were recorded. Follow-up angiography was performed in 16 patients. Clinical follow-up ranged from 1 to 12 months. RESULTS: Neck-bridge device-assisted coil packing was successfully performed in 23 lesions, with complete obliteration in three, residual necks in 13, and a minimal residual sac in seven patients. Parent vessel protection failed, with coil protrusion and arterial occlusion, in one of these patients. Other complications that were not directly related to use of the neck-bridge device included retroperitoneal hematoma, rebleeding, coil perforation, and transient embolic arterial occlusion. One patient died of vasospasm and heart failure. Follow-up angiography revealed complete obliteration in four, a residual neck in one, a persistent residual sac in four, and recurrent aneurysm in seven patients. One patient had a small occipital infarction 5 weeks after treatment. CONCLUSION: The described neck-bridge device is useful for assisting coil embolization of wide-neck bifurcation aneurysms.

Adult↗

Human peripheral arteries: feasibility of transvenous intravascular MR imaging of the arterial wall.

Feasibility of in vivo transvenous intravascular magnetic resonance (MR) imaging of the human arterial wall was determined. All subjects provided written informed consent, and institutional review board approved the study. Six arteries in six patients were imaged with a guidewire placed in the iliac vein (n = 5) or left renal vein (n = 1). Pre- and postcontrast T1-weighted and T2-weighted transvenous MR imaging were performed. An atherosclerotic plaque with a fibrous cap was identified on 27 (42%) of 64 images of veins without stents; intimal hyperplasia in a renal artery with a stent was identified on 12 images. Contrast-to-noise ratios (CNRs) on arterial wall postcontrast T1-weighted images were superior to those on images obtained with other sequences (P < .001), and the postcontrast images demonstrated the greatest number of plaques with a low-signal intensity core and fibrous cap. Preliminary results show that transvenous MR imaging is feasible for high-spatial-resolution imaging of the arterial wall and atherosclerotic plaque. Postcontrast T1-weighted imaging affords greatest CNR for the arterial wall.

Aged↗

Human aorta: preliminary results with virtual endoscopy based on three-dimensional MR imaging data sets.

PURPOSE: To determine the feasibility of use of magnetic resonance (MR) imaging data sets to perform virtual intraarterial endoscopy (VIE). MATERIALS AND METHODS: Seven female and 14 male patients (aged 9-86 years [mean, 42 years]) with various pathologic aortic conditions underwent three-dimensional gadolinium-enhanced spoiled gradient-echo MR imaging. With prototype software, VIE postprocessing algorithms (based on ray casting) were applied to the imaging data sets. Findings at conventional angiography were used as the standards of reference. RESULTS: The vessel wall was seen from the inside in each case, and the following pathologic conditions were depicted clearly: the two lumina in a congenial double aortic arch and the single lumen after correction, vessel narrowing in coarctations, characteristics of Leriche syndrome, stenoses, occlusions, and the true and false lumina of dissections. CONCLUSIONS: Limitations of VIE include the image quality of the original data set, the threshold chosen to minimize intraluminal artifacts, and the inherent smoothing of vessel walls.

Adult↗

Dermoscopic features of plaque psoriasis and lichen planus: new observations.

BACKGROUND: Dermoscopic features of common inflammatory dermatoses are not well studied and previous reports on this topic are limited to the search of vascular features (capillaroscopy). OBJECTIVE: Dermoscopic features of psoriasis and lichen planus (LP) are investigated to determine both vascular and nonvascular features of these two dermatoses. PATIENTS AND METHODS: Dermoscopic images of 25 patients with LP and 20 patients with plaque psoriasis (PP) were evaluated. Findings were statistically analyzed including the reproducibility of scoring (Cohen's kappa statistics). RESULTS: Our observations clearly showed that the evaluation of both vascular and nonvascular findings improved the surface microscopy of these diseases. A vascular feature (homogeneous red globules) was the most significant dermoscopic finding in the PP dermoscopic pattern (20/20, 100%; p < 0.001). A nonvascular feature (whitish striae) was the most significant dermoscopic feature in the LP pattern (23/25, 92%; p < 0.001). Dermoscopic features of LP also included gray-blue dots, comedo, milium-like cysts, and vascular structures (red lines). The intraobserver and interobserver reproducibility of scoring was very high (k value, 0.9). CONCLUSION: Our study shows for the first time that the efficacy of surface microscopy of common inflammatory dermatoses may be improved by investigating both vascular and nonvascular findings and its practicability in daily practice by using the dermoscope. Although dermoscopy does not provide clear additional help in the clinical differentiation between typical PP and LP, it could be helpful in patients with darker skin and for teaching settings.

Adult↗

Age-related changes of the cutaneous microcirculation in vivo.

BACKGROUND: The architectural frameworks of the skin microcirculation are rather complex and change continuously with aging. But these changes are yet poorly documented in vivo. OBJECTIVES: Using non-invasive methods belonging to the field of biometrology, the study aimed to investigate quantitatively the changes of the cutaneous microvasculature in different anatomic sites with age. METHODS: Measurements were performed on crow's feet, forehead, volar forearm and dorsum of hand in 50 women (aged 20-74 years who consisted of 10 probands in each live decades). The superficial vascular plexus was scanned by videocapillaroscopy and assessed with the software Capilab Toolbox. The subpapillary vascular plexus was explored with laser Doppler flowmetry. The skin color a* was analyzed by chromametry. RESULTS: A marked site and age effect on the skin microcirculation has been demonstrated. The density of capillary loops in the eldest group decreased by about 40-70% compared with the youngest group whereas the vascular length increased by 35-156%. The capillary density in the back of the hand was 4 times higher than in the crow's feet. The vascular length in the crow's feet was 3 times longer than in the back of the hand. Both blood flow and skin redness (a*) increased also with age. CONCLUSION: Both morphology and quantification of the cutaneous microvasculature showed changes with site and age. Videocapillaroscopy associated to an image processing and laser Doppler flowmetry revealed different vascular layers. So the combination of both instruments offers an easy way to observe the architectural frameworks in vivo.

Adult↗

Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp.

BACKGROUND: Videocapillaroscopy (VCP) can be used to explore microcirculatory modifications in skin diseases. Psoriasis shows specific capillary alterations reflecting typical histopathological changes. OBJECTIVE: To compare capillary morphology, distribution and density in psoriasis and seborrheic dermatitis of the scalp for differential diagnosis. METHODS: VCP was performed on histology-confirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 age- and sex-matched patients with seborrheic dermatitis and 30 healthy subjects. The morphology, mean density per mm(2) and mean diameter of capillary loops was measured. RESULTS: Scalp psoriasis exhibited homogeneously tortuous and dilated capillaries (bushy pattern), with a 73 +/- 17 mum (mean +/- standard deviation) diameter of capillary bushes. In contrast, scalp seborrheic dermatitis presented a multiform pattern, with mildly tortuous capillary loops and isolated dilated capillaries, but a substantial preservation of local microangioarchitecture. Mean diameter of capillary bush was significantly lower (27 +/- 4 microm; p < 0.001) and similar to that of the scalp of healthy subjects (21 +/- 5 microm). Capillary loop density was similar in patients with psoriasis (23 +/- 5/mm(2)) seborrheic dermatitis (24 +/- 2/mm(2)) and healthy scalp skin (24 +/- 3/mm(2)). CONCLUSION: VCP could be a useful noninvasive approach for differentiating between psoriasis and seborrheic dermatitis, especially when the scalp is the only affected site.

Adult↗

Reocclusion following successful thrombolysis. Emerging concepts.

Thrombolytic therapy, through the restoration of coronary arterial blood flow and myocardial perfusion significantly improves outcome among patients with acute myocardial infarction. Despite its widely appreciated benefits, however, thrombolysis removes only a small portion of existing thrombus at the site of atheromatous plaque rupture. Further, thrombogenic substrate is frequently exposed and may even be generated to the extent that rethrombosis occurs, causing recurrent ischemia, reinfarction, and coronary reocclusion. The mechanisms underlying this important event are discussed.

Angioscopy↗

A new technique for controlling the finger skin temperature in microcirculatory research demonstrated in a local cold stress test in healthy controls and patients with Raynaud's phenomenon.

Changes in skin temperature cause great changes in blood flow and capillary blood pressure. The new technique presented here makes it possible to control the temperature of the finger during nailfold capillaroscopy. Automatic temperature control, both for warming and cooling, is made possible with the aid of a temperature-controlled finger holder. The temperature of the finger holder can be automatically matched to the spontaneous skin temperature of the examined finger, or the finger holder temperature and temperature change velocity can be set digitally to a desired value. We used this new technique in a local cold stress test on 9 healthy controls (3 men, 6 women) and 9 patients (3 men, 6 women) with Raynaud's phenomenon due to systemic sclerosis. We simultaneously measured capillary red blood cell velocity (CBV) and laser Doppler flux (LDF) in adjacent areas of the finger nailfold with three different cooling procedures (8, 10, 12 degrees C for 5 min). CBV and LDF values showed the most pronounced differences between patients and controls at 12 degrees C. This new technique supplements capillaroscopy with full temperature control and defined temperature changes. It can also be combined with measurements of LDF and capillary blood pressure. In view of the disadvantages of other cooling methods we recommend this new and easy-to-handle technique for clinical practice and research.

Adult↗

Repeatability of intravital capillaroscopic measurement of capillary density.

The reliability of intravital capillaroscopy for determining capillary density (CD) of skin has been questioned because it depends upon the variability of the measuring process and subjective interpretation of data as well as the intrinsic heterogeneity of capillary spacing. The aim of this study was to assess the repeatability of a standardised method for measuring CD of the skin of the dorsum of foot. In each of 30 subjects (10 controls and 20 patients with peripheral vascular disease), the foot was systematically mapped by examining 20 sites on the dorsum of foot and 2 sites on each toe, using white light (native) videomicroscopy at 40 x magnification. Off-line analysis of videoprints was then undertaken to determine CD at each site, by counting capillaries within areas of acceptable photographic quality only, having first defined the criteria for counting capillaries. The mean values were then calculated and taken to represent the CD of the foot or toes. Repeatability of the measuring equipment was first assessed by noting the presence or absence of each corresponding capillary in 2 prints, taken at intervals of hours or days (in 10 subjects) or months (in 2 patients), of an identical area of skin which was marked by a microtattoo on the first occasion. On average, 95% of corresponding capillaries were identified in both prints (from controls and patients), thus implying little intrinsic temporal variation of capillary anatomy as well as excellent repeatability of the measuring equipment. Repeatability of data analysis was assessed by the same observer reading the same 20 prints in a blinded manner on three separate occasions (intraobserver repeatability), and 2 observers reading the same 24 prints (interobserver repeatability). The mean coefficient of intraobserver variation of CD estimate was 5.6% and the interobserver correlation coefficient was 0.94. Finally, overall repeatability of the method was assessed by repeating the procedure on a subsequent occasion (mean time interval of 5 days) in 10 subjects. The rate of agreement in mean CD between the two procedures [defined as 100- (difference between the two measurements/mean of the two measurements) x 100]% ranged from 86.4 to 97.1% (mean 93.5%). Thus using the above methodological technique, native capillaroscopy can be reliably used to determine CD of the dorsum of foot in comparing patient subgroups, as well as in longitudinal studies.

Aged↗