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Biomedical subjects

R H Harries

Publications and source records attributed to R H Harries.

6 recordsLinked to original sources

Effect of healing on the expression of transforming growth factor beta(s) and their receptors in chronic venous leg ulcers.

The transforming growth factor betas are of major importance in the wound repair process; however, no studies to date have investigated the role of the transforming growth factor beta receptors in chronic venous leg ulcers or what effect healing has on these proteins. To determine whether the transforming growth factor beta peptides and their receptors are expressed in chronic venous wounds, we used immunofluorescent analysis and quantitative competitive reverse transcription polymerase chain reaction to identify the protein and mRNA expression, respectively. Biopsy samples from wounds and normal skin were collected from 12 patients with chronic venous leg ulcers and three patients undergoing reconstructive surgery, respectively. Additionally four of the chronic venous leg ulcer patients were re-biopsied between 2 and 8 wk after the first biopsy when the wounds had entered the healing phase. The tissue excised from the ulcers included the surrounding intact skin, the ulcer edge, and the ulcer base. Immunofluorescent staining for transforming growth factors beta1, beta2, and beta3 was observed within the epidermis of the skin surrounding the chronic venous ulcers and in fibroblasts and inflammatory cells of the dermis, although this staining was not as strong as that seen in normal unwounded skin. Very little staining could be seen within the ulcers for any of the ligands, however. In contrast the transforming growth factor beta type I receptor was observed throughout the ulcers and the normal unwounded skin biopsies, particularly in the basal epidermal cells. No immunofluorescence for the type II transforming growth factor beta receptor was observed in any of the ulcer biopsies investigated, although it was observed throughout the epidermis and in fibroblasts and inflammatory cells in the surrounding skin. Quantitative, competitive reverse transcription polymerase chain reaction was used to analyze mRNA expression for transforming growth factor beta1 and the type II receptor in the nonhealing ulcers and normal unwounded skin biopsies. These studies revealed that transforming growth factor beta1 and transforming growth factor beta receptor II mRNA was expressed in all the chronic nonhealing ulcers albeit at very low levels for the type II receptor. In marked contrast to the staining observed in nonhealing chronic ulcers, positive immunostaining was observed for the transforming growth factor betas and both the type I and type II receptors in healing ulcers. These results suggest that the absence of a viable receptor complex for the transforming growth factor betas in nonhealing chronic venous ulcers may contribute to wound chronicity.

Aged↗

An in vivo model for epithelialization kinetics in human skin.

Epithelialization of wounds has been difficult to measure objectively due to the lack of an adequate model. This paper presents a model for the investigation of epithelialization kinetics in human skin using athymic (nude) rats as an in vivo vehicle. Nude rats are T-cell depleted and as such tolerate xenografts. This technique allows an epithelialization rate for a graft to be calculated by plotting the percentage of its designated analysis area to be closed by neoepithelium over time. This model provides a tool whereby the effect of various agents on the epithelialization kinetics of human skin can be objectively and reproducibly examined. This information may be usefully applied to the clinical management of wounds.

Animals↗

Laparoscopic versus open appendicectomy for suspected appendicitis: a prospective study.

Despite recent advances in minimally invasive surgery, laparoscopic appendicectomy has been questioned as a feasible method of treating patients with suspected appendicitis because open appendicectomy carries few risks and complications. Between February 1992 and January 1993 a non-randomized prospective study comparing open and laparoscopic appendicectomy was designed to assess differences in postoperative morbidity, pain, inpatient hospital stay and a return to normal lifestyle. One hundred and sixty-seven patients with suspected clinical appendicitis were assigned to open (n = 74) or laparoscopic (n = 93) appendicectomy. Six patients were excluded due to the presence of other significant pathology such that the appendix was not removed. Eighty-seven patients underwent attempted laparoscopic appendicectomy, of which 81 were completed. The diagnosis of appendicitis was confirmed histologically in 63.5% of patients undergoing open appendicectomy and 63% of patients undergoing laparoscopic appendicectomy. There were no significant differences in anaesthetic times, postoperative morbidity and analgesic requirements. There was a significant reduction in both postoperative inpatient stay (P < 0.0001) and time taken to return to work or normal activities (P < 0.0001) for the laparoscopic group. The use of laparoscopy for patients with suspected appendicitis aids definitive diagnosis and should reduce the negative appendicectomy rate to an acceptable figure. The results suggest that laparoscopic appendicectomy is safe and offers advantages over open appendicectomy in the management of patients with suspected appendicitis.

Adolescent↗

Frequency of low molecular weight IgM in human cord blood.

Thirty cord blood sera from healthy neonates and five sera from still-born infants (two with suspected infections and high IgM) were assessed for the presence of low molecular weight (LMW) IgM using two independent sensitive techniques, viz. filtration chromatography and immunoblotting. The first technique revealed this LMW moiety in 4 of 22 sera, all from healthy full-term infants, and it constituted 4-25% of the total IgM. LMW IgM was not found in any of the 30 sera using the immunoblotting technique or in 15 healthy adult sera, but was found consistently in rheumatoid sera used as positive controls.

Adult↗

In vivo characterization of interleukin-4 as a potential wound healing agent.

Interleukin-4 increases the synthesis of extracellular matrix proteins, including types I and III collagen and fibronectin, by both human and rat fibroblasts. Because fibroblasts are the final common effector cells of most phases of tissue repair, this study set out to investigate the effects of interleukin-4 on the healing of three different types of wounds. Acute excisional and chronic granulating wounds inoculated with Escherichia coli and incisional wounds in streptozotocin-induced diabetic Sprague-Dawley rats were used. Recombinant murine or human interleukin-4 was applied topically to the open wounds at doses of 0.1, 1.0, or 10.0 microg/cm(2)/wound for 5 or 10 days. Incisional wounds received the same doses once-at the time of wounding. The time taken to achieve wound closure or wound breaking strength measurements of wounds was recorded and compared with relevant untreated control groups. Wound contraction was impaired in the presence of bacteria, and this was reversed by all doses of recombinant murine interleukin-4. Recombinant murine interleukin-4 had no effect on the wound closure of noncontaminated wounds; it reduced wound breaking strength in acute excisional wounds, except in a contaminated setting when wounds were treated with 1.0 pg/cm(2)/wound. Recombinant interleukin-4 (1.0 microg) improved breaking strength of both diabetic and normal incisional wounds. The apparent pleiotropic effect of interleukin-4 on wound breaking strength under different wound conditions may be related not only to the activity of the fibroblast but also the ratio of cross-linked collagen/total collagen content of wounds. This study suggests that interleukin-4 may be a useful agent for accelerating closure of wounds, particularly where healing is impaired.

Journal Article↗