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Biomedical subjects

A L Herrick

Publications and source records attributed to A L Herrick.

At least 19 recordsLinked to original sources
PubMed2002

Digital vascular response to topical glyceryl trinitrate, as measured by laser Doppler imaging, in primary Raynaud's phenomenon and systemic sclerosis.

OBJECTIVE: To investigate digital microvascular responses to topical glyceryl trinitrate (GTN) in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LCSSc) and healthy control subjects, using laser Doppler imaging. METHODS: Ten patients with PRP, 13 with LCSSc and 10 control subjects were studied. Baseline skin microvascular blood flow of the dorsum of the index, middle and ring fingers of the non-dominant hand was measured using scanning laser Doppler imaging. After the initial image, 2% GTN ointment was rubbed on the dorsum of one finger for 1 min; placebo ointment was rubbed on the dorsum of a second finger for 1 min, and the third finger remained untreated. Further laser Doppler scanning of these three fingers was conducted immediately, 10 and 20 min after ointment application. RESULTS: There was increased blood flow response to placebo compared with no treatment (P<0.001) and to GTN compared with placebo (P=0.004). The change in blood flow over time differed significantly between placebo and GTN (P<0.001), but not between placebo and no ointment application: blood flow increased with GTN and decreased with placebo/no treatment at 10 and 20 min. There were no differences in initial baseline blood flow or response between the subject groups. CONCLUSIONS: An exogenous supply of nitric oxide by topical GTN ointment causes local endothelial-independent vasodilatory responses in PRP, LCSSc patients and control subjects. As well as demonstrating the effectiveness of topical GTN in patients with PRP and LCSSc, this study illustrates the ability of laser Doppler imaging to quantify local vasodilatory effects.

Administration, Topical↗
PubMed2001

Ankle brachial pressure index in systemic sclerosis: influence of disease subtype and anticentromere antibody.

OBJECTIVE: To test the hypothesis that patients with limited cutaneous systemic sclerosis (SSc) have a higher incidence of lower limb large vessel disease than patients with diffuse cutaneous disease, and that anticentromere antibody is a risk factor for lower limb large vessel disease. METHODS: Clinical and laboratory data from 119 patients with SSc (91 patients with limited cutaneous disease, 28 patients with diffuse cutaneous disease) who had bilateral ankle brachial pressure indices (ABPI) measured between March 1997 and January 2000 were reviewed retrospectively. RESULTS: There was no evidence of reduced ABPI in limited cutaneous disease (P=0.65), average reduction 0.01 [95% confidence interval (CI) -0.04 to +0.07]. There was some suggestion of reduced ABPI in anticentromere-positive patients (P=0.12), average reduction 0.04 (95% CI -0.01 to +0.09). CONCLUSIONS: The severity of large vessel macrovascular disease, as assessed by ABPI, is not dependent on disease subtype. Anticentromere antibody may be weakly associated with a reduction in ABPI.

Adult↗
PubMed2001

Antibodies against oxidized low-density lipoproteins in systemic sclerosis.

OBJECTIVE: To investigate whether circulating concentrations of antibodies against oxidized low-density lipoproteins (LDL) are increased in patients with systemic sclerosis (SSc). METHODS: Oxidation of LDL and anti-oxidized LDL antibodies were measured in 26 patients with limited cutaneous SSc (LCSSc), in eight patients with diffuse cutaneous SSc (DCSSc) and in 24 healthy control subjects. Results were adjusted for age, sex and smoking. RESULTS: Binding to oxidized LDL was increased in patients with both limited and diffuse cutaneous disease (geometric mean 0.35 and 0.39 optical density units respectively) compared with controls (0.28) (P=0.03 and P=0.01 respectively). Circulating concentrations of anti-oxidized LDL were increased only in patients with diffuse SSc (geometric mean 0.22 optical density units) compared with controls (geometric mean 0.16, P=0.02). CONCLUSION: These preliminary findings lend further weight to the concept that oxidation of LDL contributes to the vascular pathology of SSc, particularly in patients with diffuse cutaneous disease. Prospective longitudinal studies are required to investigate whether anti-oxidized LDL antibodies may be a marker of vascular damage in SSC.

Adult↗
PubMed2001

Foot problems in patients with systemic sclerosis.

OBJECTIVES: To assess the nature of the foot problems experienced in patients with systemic sclerosis (SSc) and patient awareness of such problems. METHODS: Fifty unselected patients (42 females, eight males) with SSc were assessed by means of examination by a senior podiatrist, completion of a questionnaire detailing past and present foot problems, determination of random plasma glucose, plain X-rays of the feet, and measurement of the ankle/brachial index and of digital pulses by Doppler ultrasound. RESULTS: Eighty-six per cent of patients reported colour changes in their feet in response to temperature changes, 82% reported pain usually related to cold, 26% had suffered foot ulceration and 8% had a history of foot surgery. Podiatry assessment confirmed the presence of significant abnormalities, including ulcerations in 10%, pre-ulcerative lesions in 34%, toenail changes in 62%, callus formation in 80% and calcinosis in 18%. Forty per cent of the patients had problems with the fitting of shoes, and 19% had been provided with footwear from the hospital. Plain films of the feet demonstrated the presence of erosions in 6%, soft-tissue calcification in 17%, osteopenia in 26% and degenerative changes in 60% of cases. Ten per cent of the patients had an abnormal ankle brachial index (less than 1.0). Only 21% of the 47 patients in whom digital pulses were examined had normal pulses in all toes, and in 26% all toe pulses were absent. CONCLUSION: Although problems with the hands are well recognized in SSc, foot problems also occur in the majority of patients, and can be a cause of major disability. Care of the feet is therefore an important part of the management of SSC.

Adult↗
PubMed2001

Development of agents for the treatment of systemic sclerosis.

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterised clinically by fibrosis and ischaemic atrophy. Internal organ involvement can be life-threatening. Although there are effective treatments for some of the organ-based manifestations of SSc, for example proton-pump inhibitors for upper gastrointestinal disease, no drug has so far been proven to modify the underlying disease process. Our increased understanding of the pathogenesis of SSc, which involves a complex interplay between excessive collagen production, vascular abnormalities and immune dysfunction, is directing development of drugs which hold promise as 'disease-modifying' agents. Some of the drugs under investigation for the treatment of SSc have already been used in other conditions which 'overlap' with SSc, for example primary pulmonary hypertension. Conversely, it is to be hoped that in the future, drugs shown to be effective in SSc might prove beneficial for other fibrotic diseases.

Humans↗
PubMed2000

Nailfold video capillaroscopy in psoriasis.

Changes in the microvasculature are considered to play an important part in the pathogenesis of psoriasis and its associated arthritis. The novel method of nailfold video capillaroscopy is an extension of the technique of widefield nailfold microscopy which has been of diagnostic and predictive use in the in vivo study of the microcirculation in systemic sclerosis and other connective tissue disorders. However, similar studies in patients with psoriasis and psoriatic arthritis and/or nail changes have produced conflicting results. We tested the hypothesis that any abnormalities in nailfold capillaries of either a quantitative or qualitative nature might be observed more readily in subjects with pathology adjacent to the nailfold, i.e. distal interphalangeal (DIP) joint changes and/or nail dystrophy, when using this technique. Forty-four patients with psoriasis were recruited (21 males, 23 females). Twelve patients had psoriasis alone, 13 had psoriasis and nail changes, six had DIP joint involvement with changes of psoriasis elsewhere, and 13 had psoriasis, DIP arthritis and nail changes. Capillary density and standard capillary dimensions were studied and compared with those of 44 age- and sex-matched control subjects. There was a significant (P < 0.05) decrease in capillary loop density in patients with either psoriasis plus nail disease (14.5 +/- 5.7 capillaries per 3 mm field) or psoriasis plus nail and DIP joint disease (14.3 +/- 5. 0) when compared with controls (19.2 +/- 3.8). In patients with psoriatic arthritis affecting the DIP joints, there was a statistically significant (P < 0.05) decrease in arterial and venous capillary limb diameters, and this was also seen in those with arthritis associated with nail changes. However, there was no difference in capillary dimensions between patients with psoriasis and/or nail changes when compared with normal controls. Morphological abnormalities previously described in the literature were not noted in any of our four patient groups. Our findings of diminution in both nailfold capillary bed density and dimensions of the arterial and venous capillary limbs suggest that vascular injury, previously noted in ultrastructural studies, may play a part in the pathogenesis of psoriatic arthritis. However, in contrast to previous studies, we found no specific pattern of a morphological nature of nailfold capillaries in patients with psoriasis with or without nail changes, when compared with normal controls.

Adult↗
PubMed2000

Quantitation of microcirculatory abnormalities in patients with primary Raynaud's phenomenon and systemic sclerosis by video capillaroscopy.

OBJECTIVE: : To assess nailfold capillary density and dimensions in patients with primary Raynaud's phenomenon (PRP), limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous SSc (DSSc), and healthy control subjects. METHODS: : Using the technique of nailfold video capillaroscopy, capillary density and dimensions were averaged from all visible capillaries in a 3 mm length of the nailfold from right and left ring fingers of each subject. Twenty healthy control subjects, 15 patients with PRP, 13 patients with DSSc and 21 patients with LSSc were examined. Intra-observer and inter-observer variability were calculated in 18 and 23 patients, respectively. RESULTS: : There were significant trends for capillary density to fall and for all dimensions to rise across the four groups (P < 0. 0001 for density and all dimensions, order healthy controls, PRP, DSSc and LSSc). Intra- and inter-observer reproducibility studies showed that although there was good correlation between and within observers, the limits of agreement were between +/-25-50% indicating lack of reproducibility. CONCLUSIONS: : Microcirculatory abnormalities can be quantified using the technique of video capillaroscopy and were most marked in patients with LSSc.

Adult↗
PubMed2000

Vascular function in systemic sclerosis.

Raynaud phenomenon is often the earliest manifestation of systemic sclerosis. This fact highlights the role of vascular dysfunction early on in the disease process. Although this review deals primarily with digital vasculature, recent research confirms that vascular dysfunction is widespread, and affects large as well as small vessels. Abnormalities of vascular function and structure are interdependent, and together result in the ischemic atrophy so characteristic of SSc. Key areas of research include the pathophysiology of the imbalance between vasodilation and vasoconstriction, with particular interest in understanding the relative contributions of endothelial-dependent and endothelial-independent vasodilation, and the development of new methodologies by which to quantify vascular function.

Endothelium, Vascular↗
PubMed2000

The influence of age on nailfold capillary dimensions in childhood.

OBJECTIVE: To identify the influence of age on nailfold capillary dimensions in children between 6 and 15 years. METHODS: Capillary density (the number of capillaries in a 3 mm length of the distal row) and capillary dimensions were measured in 110 healthy children using the technique of nailfold video microscopy. The age groups studied were as follows: 6 to 7 years (17 children), 8 to 9 years (15 children), 10 to 11 years (34 children), 12 to 13 years (24 children), and 14 to 15 years (20 children). RESULTS: There was a significant trend for the arterial and venous diameters to rise with age. However, this trend was not present for apical or loop diameters, nor for the capillary density. Results did not differ between males and females. CONCLUSION: In studies incorporating capillary dimensions in children, results should ideally be age adjusted, and dimensions should not be categorized as normal or abnormal without taking the child's age into account.

Adolescent↗
PubMed1999

Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis skin.

Although a multisystem disease, systemic sclerosis (SSc) most commonly affects the skin. The skin lesion is characterized by progressive changes, chief amongst which are vascular abnormalities, including endothelial cell (EC) injury and death, and dermal fibrosis. The pathogenesis of the vascular changes, and their relationship to dermal fibrosis, is poorly understood. The purpose of this study was to examine the potential role of nitric oxide (NO)-related free radical production, as part of an assessment of mechanisms leading to endothelial damage. Histologically graded skin biopsies from 33 patients with SSc (ten grade 0, ten grade 1, eight grade 2, and five grade 3) and eight healthy controls were reacted with antibodies against constitutive (eNOS) and inducible (iNOS) forms of nitric oxide synthase and nitrotyrosine. The degree of staining was assessed using a semi-quantitative system and a staining score was developed for the ECs of different vessel types in different areas of dermis at all grades. In biopsies from patients with SSc, superficial microvessel ECs showed a peak of eNOS expression in grade 1 skin which fell as the grade increased. By contrast, iNOS staining increased with the grade of skin lesion, a pattern paralleled by endothelial nitrotyrosine expression. From these findings, it is concluded that a metabolic switch occurs in dermal ECs from endothelial to cytokine inducible forms of NOS during the progression of the skin lesion of SSc. iNOS is a potent inducer of NO production which, in turn, can mediate NO free radical production. At a time of development of the SSc skin lesion when previous studies report evidence of EC damage, the cells express immunodetectable nitrotyrosine, a marker of NO-mediated free radical injury. The data suggest a role for iNOS-induced NO production in EC damage in SSc.

Endothelium, Vascular↗
PubMed1999

Laser doppler imaging--a new technique for quantifying microcirculatory flow in patients with primary Raynaud's phenomenon and systemic sclerosis.

This was a pilot study to investigate the new technique of laser Doppler imaging (scanning laser Doppler) as a tool to quantify microvascular blood flow in the digits of patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and to determine in the first instance whether the flux patterns obtained differ between patients with SSc, patients with PRP, and healthy control subjects. Laser Doppler images of the dorsum of the hand and fingers were acquired at 23 and 30 degrees C in 17 healthy control subjects, 7 patients with PRP, 9 patients with the diffuse cutaneous variant of SSc, and 24 patients with the limited cutaneous variant of SSc. Different flux parameters were compared between groups. Analysis of variance found significant differences between groups in two tests: maximum difference in flux between fingertips of the same hand at 23 degrees C (P = 0.001) and maximum gradient in flux along a finger ("distal-dorsal" flux difference) at 30 degrees C (P = 0. 019). Post hoc tests highlighted the differences between controls and patients with limited cutaneous SSc. This pilot study suggests that laser Doppler imaging may allow objective measurement of microvascular flow in patients with PRP and SSc. This new technique may overcome many of the problems inherent in single-channel laser Doppler equipment.

Adult↗
PubMed1998

TGF beta--a role in systemic sclerosis?

Systemic sclerosis (SSc) is a multisystem connective tissue disorder in which there is progressive fibrosis. Transforming growth factor beta (TGF beta) has wide-ranging cellular actions. It is a potent chemoattractant for human dermal fibroblasts, from which it may induce synthesis of collagen, which suggests that it may have a central role to play in the pathogenesis of SSc. This is supported to some extent by in vitro studies. SSc fibroblasts produce more collagens and fibronectin than normal fibroblasts and elevated TIMP levels have been observed, all of which could be explained on the basis of TGF beta stimulation of fibroblasts. Some studies have suggested that fibroblasts are the source of TGF beta. However, the serum of patients with SSc is cytotoxic to endothelial cells, which could culminate in TGF beta synthesis by them, with secondary fibroblast stimulation. The role of TGF beta remains elusive, although it would seem an ideal candidate as a mediator of fibrosis in systemic sclerosis.

Cell Culture Techniques↗