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Biomedical subjects

D A McGrouther

Publications and source records attributed to D A McGrouther.

At least 19 recordsLinked to original sources

The cellular effect of a single interrupted suture on tendon.

The effects on cell and matrix morphology of a single interrupted suture are described in rabbit (vascular) and mouse (avascular) digital flexor tendons. This model of tendon injury is reproducible and suitable for quantitative histological analysis. Tendons analysed at day 1, 3, 5, 7 and 14 after wounding demonstrated a well-demarcated "acellular zone" around the suture within 24 hours and persisting over 14 days. The placement of an untied suture in tendon did not produce this effect but tying and releasing the tied knot did. The rapidity of onset suggests that cells move from the zone of injury into less mechanically strained tissue. The acellular zone was apparent in rabbit hind paw flexor tendon which is vascularised and the corresponding tendon in mouse which has no intrinsic blood vessels. This phenomenon highlights biological events that must be considered in parallel with the current trend for multistrand locking flexor tendon suture repairs.

Animals↗

The reinnervation pattern of wounds and scars may explain their sensory symptoms.

Anaesthesia, pruritus and pain are common in cutaneous scars. The reinnervation pattern of healing wounds and scars might help to explain these symptoms, as sensory neurotransmitters are known to be mediators of inflammation and healing. We quantified the regeneration patterns of blood vessels and nerves in excisional skin wounds as they matured into scars. Mice underwent 1cm(2) full thickness skin excisions. Wounds were harvested between five and 84 days. Sections underwent immunohistochemical staining for protein gene product 9.5 (PGP9.5) a pan-neuronal marker, and the sensory neuropeptides calcitonin gene related peptide (CGRP) and substance P (SP). The endothelial marker von Willebrand factor (VWF) was used to allow co-localisation and quantification of blood vessels. Nerve fibre density was quantified at multiple sites within wounds. There was no difference in the reinnervation/revascularisation pattern between peripheral and central sites. The density of PGP9.5, CGRP, SP and VWF peaked between 14 and 42 days, and levels of PGP9.5, CGRP and VWF all decreased to approximately those found in unwounded skin by 84 days (mature scar). SP levels, however, remained elevated at approximately twice the density found in unwounded skin. Increased densities of SP and CGRP in healing wounds could explain the unpleasant sensory symptoms of healing wounds.

Animals↗

The Patient Outcomes of Surgery-Head/Neck (POS-head/neck): a new patient-based outcome measure.

OBJECTIVES: To develop a new patient-based outcome measure in plastic surgery for head/neck skin lesions for use in audit, clinical trials and effectiveness studies. DESIGN AND SUBJECTS: Questionnaire development and validation study. Qualitative methods, including interviews with 27 patients, were carried out to develop a preliminary version of the questionnaire. The questionnaire was then field tested by postal survey of 141 pre- and 250 post-surgery patients to produce a shortened (item-reduced) questionnaire and to evaluate acceptability, reliability, validity and responsiveness. A second field test was carried out by postal survey in an independent sample of 67 pre-surgery patients to further evaluate the reliability and validity of the questionnaire. MAIN OUTCOME MEASURES: Psychometric properties of acceptability, reliability, validity, and responsiveness were assessed. RESULTS: We developed a new measure, the Patient Outcomes of Surgery-Head/Neck (POS-Head/Neck), which includes a six- and nine-item pre- and post-surgery questionnaire, respectively. Results confirmed the acceptability (missing data <10%, evenly distributed endorsement frequencies), reliability (Cronbach alphas >0.76, item-total correlations >0.22), validity (scale inter-correlations r=0.50, scaling assumptions, correlations with age and sex < -0.25) and responsiveness (effect size=0.63) of the questionnaire. CONCLUSIONS: The POS-Head/Neck is a new surgical outcome measure that can be used to evaluate outcomes in malignant and benign head/neck skin lesions before and after surgery is acceptable to patients and satisfies rigorous scientific criteria.

Adolescent↗

Management of Dupuytren's disease--clear advice for an elusive condition.

Dupuytren's disease is a progressive fibroproliferative disorder of an unknown origin affecting the hands causing permanent flexion contracture of the digits. Significant risk factors for development of Dupuytren's disease include old age, male sex, white northern European extraction, presence of positive family history of Dupuytren's disease, and diabetes mellitus. The disease also seems to deteriorate rapidly in those cases showing young age of onset and additional fibromatosis affecting the back of the hands, soles of the feet and the penis. Although there is no cure, patients with Dupuytren's disease of the hand may gain a significant functional benefit following surgical improvement or correction of the deformity. With realistic expectations, timely and appropriate surgical technique in a specialist centre, and attention to postoperative recovery and rehabilitation (occupational therapy and physiotherapy support), a beneficial outcome can be achieved in most cases.

Dupuytren Contracture↗

Keloid disease: clinical relevance of single versus multiple site scars.

Much of our current understanding of keloid disease (KD) is based on anecdote rather than objective observation and statistical analysis. To elucidate further the aetiology of KD, we compared the profiles of patients with single versus multiple anatomical site keloid scars. We studied the clinical characteristics of 211 cases of keloid scarring, 137 (65%) females and 74 (35%) males. There were 122 cases with scars in single anatomical site and 89 cases with 369 scars in multiple anatomical sites entered into the study. Patients were of Afrocaribbean origin that presented to the department of Plastic and Reconstructive Surgery at the University of West Indies in Kingston, Jamaica. A total number of 491 keloid scars (single and multiple sites) were evaluated in the study. Data were collected on multiple parameters. The association of age of onset, anatomical area, cause of scarring, sex of the patient, presence or absence of family and medical history in patients with single as opposed to multiple site keloid scars were examined in detail and statistically evaluated. The formation of keloid scars in multiple anatomical sites was found to be statistically significant in that it was more common in younger age groups (p < 0.001) and in females (p < 0.001). Previous medical history, including other fibrotic disorders, was not statistically associated with development of keloid scars in multiple anatomical sites (p > 0.05). More than 50% (111) of all keloid cases had a positive family history of keloid scarring, and family history was strongly associated with the formation of keloid scars in multiple sites as opposed to a single anatomical site (p < 0.002). We conclude that in this particular study group female sex, younger age at presentation and the presence of a positive family history were associated with the development of keloid scars in multiple anatomical sites in Afrocaribbean individuals. This knowledge further emphasizes the need for genetic studies in KD, which may lead to better diagnostic and therapeutic regimes.

Adolescent↗

A prospective randomised clinical trial of the intra-operative use of 5-fluorouracil on the outcome of dupuytren's disease.

5-Fluorouracil reduces proliferation rates of fibroblasts, myofibroblast differentiation and contractility of ocular fibroblasts in vitro. This double-blind randomized clinical trial assesses whether intra-operative topical treatment with 5-fluorouracil reduces the recurrence rate after limited excision of Dupuytren's tissue. Patients with two-digit disease were randomized to having 5-fluorouracil (25mg/ml) treatment for 5 minutes on one digit and placebo on the other. Fifteen patients were enrolled with 18 months follow-up. There were no peri-operative complications. Wound healing was not delayed and there was no deterioration in the flexion deformity of the 5-fluorouracil treated digits. Patients were subsequently assessed by joint angle measurement at 3, 6, 12 and 18 months. There was no significant difference between control and 5-fluorouracil treated digits.

Antimetabolites↗

The Patient Outcomes of Surgery-Hand/Arm (POS-Hand/Arm): a new patient-based outcome measure.

The purpose of this study was to develop and validate a new patient-based outcome measure for hand/arm disorders for use in audit, clinical trials and effectiveness studies. There were three stages. First, we carried out interviews with 40 patients with hand/arm disorders to develop and pilot questionnaire content. Second, in a postal survey with 165 pre- and 181 post-surgery patients, we reduced the number of items and identified scales. Third, in a postal survey with 132 pre- and 204 post-surgery patients we evaluated the psychometric properties of the measure. Findings confirmed the acceptability, reliability, validity and responsiveness to clinical change of the questionnaire. The Patient Outcomes of Surgery-Hand/Arm (POS-Hand/Arm) is a new surgical outcome measure that can be used before and after surgery (29 and 33 items, respectively) to evaluate and compare new techniques, surgical teams and units.

Activities of Daily Living↗

Skin scarring.

Explore the source record for details and available documents.

Cicatrix↗

Manoeuvring a-head in plastic surgery.

Surgical training has undergone a rapid transformation over the last decade. One outcome of these changes is the interest that has been generated in the possibility of training surgical skills outside the operating theatre. We describe a cost-effective tool that may be used to improve surgical handling and improve surgical concepts in facial plastic surgery.

Costs and Cost Analysis↗

The different characteristics of Dupuytren's disease fibroblasts derived from either nodule or cord: expression of alpha-smooth muscle actin and the response to stimulation by TGF-beta1.

Mechanisms behind the onset and progression of Dupuytren's disease are poorly understood. Both myofibroblasts and transforming growth factor beta 1 (TGF-beta(1)) have been implicated. We studied fibroblast cultures derived from nodules or cords of Dupuytren's contracture tissue to determine the proportion of myofibroblasts present in comparison with flexor retinaculum fibroblast cultures. We identified myofibroblasts by immunohistochemical staining for alpha-SMA. We then investigated the effects of TGF-beta(1) stimulation on these fibroblasts. Basal myofibroblast/fibroblast proportions were 9.7% in nodule cell cultures, 2.7% in cord cell cultures and only 1.3% in flexor retinaculum cell cultures. Nodule and cord myofibroblast proportions increased to 25.4% and 24.2%, respectively, in response to TGF-beta(1) treatment. Flexor retinaculum cell cultures showed no response to TGF-beta(1) stimulation. Fibroblasts cultured from specific regions of Dupuytren's tissue retain myofibroblast features in culture. TGF-beta(1) stimulation causes an increased myofibroblast phenotype to similar levels in both nodule and cord, suggesting that previously quiescent cord fibroblasts can be reactivated to become myofibroblasts by TGF-beta(1). This could be an underlying reason for high recurrence rates seen after surgery or progression following injury.

Aged↗

Differences in morphology, cytoskeletal architecture and protease production between zone II tendon and synovial fibroblasts in vitro.

Fibroblast migration is an integral component of the processes resulting in the formation of restrictive adhesions in the injured tendon, especially in Zone II. Pre-requisites for cell migration are an intact cytoskeleton and an ability to biochemically degrade the extra-cellular matrix. The relative characteristics of fibroblasts from the fibro-osseus sheath (SC), the tissue surrounding the tendon in Zone II, and the endotenon (TC) with respect to morphology, cytoskeletal structure and ability to produce matrix metalloproteinases (MMPs) 2 and 9 were compared in vitro. It was found that SCs were larger in size and demonstrated greater amounts of intra-cellular alpha-smooth muscle actin (alpha-SMA) and intra-membranous vinculin. Filamentous actin (F-actin) fibres in SCs were more densely packed and concentrated, resulting in stress fibres. The SCs also produce greater amounts of MMP-2 and MMP-9 compared to TCs. These observations imply that SCs play an active role in adhesion formation and should be specifically targeted to inhibit or treat tendon adhesions.

Actins↗

Burn depth and its histological measurement.

This paper describes a new technique for burn depth measurement, based on the histological assessment of dermal microvascular occlusion in burn biopsies. The technique was validated in a preliminary study of acute progressive microvascular damage in five adults with partial thickness burns. Burn depth was calculated at three time points post burn from the mean histological measurement of the most superficial patent and the deepest blocked vessels in five separate sections from each biopsy. The results were expressed as a percentage of the total dermal thickness and correlated well with the laser Doppler measurement of dermal blood flow and clinical estimation of burn depth. The reproducibility of the technique was tested by the repeated blind analysis of five randomly chosen biopsies on a separate occasion. Altman-Bland plot analysis demonstrated a median variation of 0.1% (95% confidence interval -1 to 2%). A second independent observer (MPHT), who carried out a blind analysis of the same randomly chosen biopsies, tested the precision of the technique. The median variation was 2% (95% confidence interval -5 to 8.5%).

Adult↗

Dermal cellular inflammation in burns. an insight into the function of dermal microvascular anatomy.

The damage caused by thermal trauma is augmented by the subsequent inflammatory response in a similar fashion to reperfusion injury. Animal studies have demonstrated a significant role for neutrophils in this delayed damage, but little is known about the numbers of neutrophils or other leucocytes that enter human skin following burns. We have longitudinally examined profiles of leucocyte migration into five cases of human partial thickness burns in relation to continued dermal microvascular destruction during the acute post-burn period. All burn wounds had a rapid influx of neutrophils that was followed by a delayed influx of macrophages. Compared to the controls, the two superficial burns also had rapid and sustained influx of CD4 and CD8 lymphocytes via patent post capillary venules in the dermal superficial vascular plexus, whilst in the three deeper burns, in which this superficial vascular plexus was occluded, the number of lymphocytes decreased. These results suggest that the patterns of leucocyte extravasation were dependent on the initial level of vascular occlusion, indicating that the dermal microvascular anatomy plays a pivotal role in determining the composition of the extravascular inflammatory cell infiltrates. The potential importance of this finding is highlighted by the differences in wound behaviour associated with the different leucocyte profiles.

Adult↗

Reduction in matrix metalloproteinase production by tendon and synovial fibroblasts after a single exposure to 5-fluorouracil.

This study investigated the effect of treatment with 5min exposures to 5-fluorouracil (5-FU) on the production of matrix metalloproteinases (MMPs) by endotenon and synovial fibroblasts. Fibroblasts were grown from the flexor tendons of New Zealand White rabbits and were then exposed to varying concentrations (ranging from 0.25 mg x ml(-1)to 25 mg x ml(-1)of 5-FU for 5 min. The treated fibroblasts were suspended in a three-dimensional collagen lattice. The conditioned media from these collagen lattices were then analysed for MMP production using gelatin zymography on days 1, 3 and 7 after treatment. In the majority of cases this treatment produced a dose- and time-dependent reduction in total MMP production by both cell lines, specifically in the production of MMPs 2 and 9. This reduction was significant for most concentrations (P< or =0.01-P< or =0.05) when compared to phosphate-buffered-saline-treated controls. We conclude that 5-FU may reduce adhesions by limiting the migratory capacity of synovial fibroblasts (extrinsic healing).

Animals↗