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Biomedical subjects

A O Grobbelaar

Publications and source records attributed to A O Grobbelaar.

At least 19 recordsLinked to original sources

Extensor tendon rehabilitation a prospective trial comparing three rehabilitation regimes.

Forty-two patients with 46 complete extensor tendon injuries were prospectively allocated to one of three rehabilitation regimes: static splintage; interphalangeal joint mobilization with metacarpophalangeal joint immobilization or; the "Norwich" regime. All 42 patients were operated on by one surgeon and assessed by one hand therapist. At 4 weeks the total active motion in the static splintage group was significantly reduced but by 12 weeks there was no difference between the regimes. There was no difference in total active motion between the repaired and uninjured hand at 12 weeks, with all patients achieving good or excellent results. However, grip strength at 12 weeks was significantly reduced compared to the uninjured hand after static splintage. There was no difference in hand therapy input between the regimes.

Adolescent↗

Ectopic nail formation in the hand.

This paper reports an unusual case of ectopic nail formation, reviews the literature and proposes a simple classification of this anomaly.

Female↗

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 relation between c-myc expression and interferon sensitivity in uveal melanoma.

BACKGROUND/AIM: Interferons (IFN) are currently being used to treat melanoma, including some patients with uveal melanoma. IFN is thought to inhibit tumour growth through downregulation of the c-myc oncogene; the overexpression of which has been shown to be associated with resistance in cell lines. The aim of this study was to investigate the relation between c-myc gene expression and IFN sensitivity in a series of uveal melanomas in a short term chemosensitivity assay. METHODS: Tumours from 45 patients with uveal melanoma who had undergone enucleation were studied. The ATP chemosensitivity assay was used to study sensitivity to IFN-alpha-2b in freshly isolated cells from each tumour. Flow cytometry was used to assess c-myc expression in formalin fixed material from the primary specimens. RESULTS: There was a wide range of IFN sensitivity between the specimens whereas c-myc expression was universal and present in 80% of the tumour cells in 80% of the specimens. Higher c-myc expression was associated with IFN-alpha resistance as measured by the maximum percentage of inhibition (p = 0.05) and there was a trend with the IFN sensitivity index (p = 0.07). CONCLUSIONS: These results demonstrate that tumours with high c-myc expression are also associated with IFN resistance. Future research is required to explore the potential of c-myc gene manipulation combined with IFN therapy.

Adult↗

The MD-medical doctorate or mandatory doctorate?

The introduction in the UK of the Calman Registrar training scheme envisaged seamless progression from Senior House Officer (SHO) grade through to Consultancy. Within this framework research was acknowledged to be a valuable (but optional) part of the training programme, as laid out by the 'Orange Guide' to Specialist Registrar (SpR) Training [A Guide to Specialist Registrar Training 1998; HM Press]. Time is provided for this activity within the SpR training scheme, but it is becoming increasingly evident that the majority of formal research (towards post graduate degrees) is being carried out by so-called 'gap' SHO's in order to gain entry into Higher Surgical Training (HST) programmes [Ann R Coll Surg Engng 81 (1999) 182], [Br J Plast Surg 55 (2002) 463-468]. With this in mind, a survey of all Plastic Surgery SHO's in the UK was undertaken to assess the extent of clinical research undertaken by individuals, and the perceived need for formal research for career progression.

Biomedical Research↗

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↗

Long-term results of facial rejuvenation by carbon dioxide laser resurfacing using a quantitative method of assessment.

Carbon dioxide laser resurfacing has been widely reported as an effective method for treating facial rhytides. Few published series, however, have assessed the long-term results of this procedure. We prospectively reviewed our long-term results of perioral CO(2) laser resurfacing using an accurate, reproducible and quantitative method of evaluation. Wrinkle depth was measured using a silicone elastomer to provide an exact negative-replica mask of the perioral region. Simple light microscopy was then used to measure the depth of rhytides. This was carried out preoperatively, 6 weeks postoperatively and 2 years postoperatively, and the results were compared for 31 patients. CO(2) laser resurfacing achieved a highly significant mean reduction in wrinkle depth at 6 weeks of 91% (paired t -test:P <0.00001), and this was well maintained at 2 years, when the mean reduction in wrinkle depth was 87% (paired t-test: P<0.00001). During the long follow-up, complications were few, with transient erythema being the most common; there were no cases of scarring. As in other series that have reported longer follow-up, we encountered three cases of minor hypopigmentation. We have used light microscopy on silicone moulds as an accurate method of assessing outcome after laser resurfacing of perioral rhytides. The early highly significant reduction in wrinkle depth was maintained at 2 years with minimal associated short-term or long-term morbidity.

Aged↗

The c-myc oncogene: use of a biological prognostic marker as a potential target for gene therapy in melanoma.

The c-myc oncogene has been shown to be overexpressed in a number of malignancies, and may play an important role in the pathogenesis of malignant melanoma. Previous prognostic studies have demonstrated c-myc overexpression in a range of cutaneous melanomas, and levels of c-myc oncoprotein expression have been shown to correlate with clinical outcome in both primary and secondary disease. The purpose of this study was to investigate the in vitro manipulation of c-myc expression using antisense oligonucleotides. The human melanoma cell lines A375M, Be11 and WM115 were treated with c-myc antisense oligonucleotides, and the cellular growth was compared with controls. Antisense oligonucleotides reduced the growth rate of all three cell lines, and produced a reduction in c-myc gene expression as measured by flow cytometry. The growth inhibitions in the A375M, Be11 and WM115 cell lines at 72 h were 36.6%, 35.8% and 29.3%, respectively. Each of these was significantly different from control cultures (P<0.01). The c-myc antisense produced a mean 75% reduction in c-myc oncoprotein expression when compared with controls in the A375M cells (P<0.001), a 49% reduction in the Be11 cells (P<0.001) and a 28% reduction in the WM115 cells (P=0.005). This study demonstrates the importance of the c-myc oncogene in controlling melanoma growth. It suggests that blocking the expression of this gene, using an antisense approach, reduces melanoma cell growth, and may potentially provide a novel gene-therapy strategy for the treatment of advanced melanoma.

Cell Division↗

The role of human-derived fibrin sealant in the reduction of postoperative flexor tendon adhesion formation in rabbits.

This study assessed the role of a novel fibrin sealant (Vivostat in adhesion reduction after flexor tendon surgery. The deep flexor tendons of the 2nd and 4th digits of the left paw of 20 rabbits were exposed and a standard partial injury was performed on each. The rabbits were randomized to either immediate post-injury treatment with Vivostat or no treatment. In each case active movement of the 2nd digit was prevented while the 4th digit was allowed to move normally. The two groups were assessed at 14 days for adhesion formation with a tensiometer. The right paw acted as the unoperated control. Results showed that there was no significant difference in the force needed to remove the tendon from its sheath when comparing the two Vivostat((R))-treated groups to the unoperated controls. There was, however, a highly significant difference in this force between the non-Vivostat-treated groups and the unoperated controls. This suggests a beneficial effect of Vivostat in reducing post surgical tendon adhesion formation.

Animals↗

Silicone arthroplasty for trapeziometacarpal arthritis.

Twenty-three patients who had undergone trapeziectomy and Helal silicone rubber ball interposition for trapeziometacarpal arthritis were reviewed. The average age at operation was 63 (range 48-84) years and the mean follow-up was 59 (range 12-138) months. Of the 23 patients reviewed, two had pain at rest and four had some discomfort on exertion. Mean post-operative thumb extension was 37 degrees whilst mean palmar abduction was 40 degrees. Mean post-operative grip strength was 19 kg and thumb-pinch strength was 4.0 kg, 77% and 78% of the age- and sex-matched normal values. There were no cases of prosthetic dislocation, prosthetic fracture or silicone synovitis.

Aged↗

A prospective review of open central slip laceration repair and rehabilitation.

A prospective review was carried out to evaluate the outcome of surgically repaired open central slip (zone III) injuries which were treated with 3 weeks of proximal interphalangeal joint immobilization within a cylinder splint and then with 3 weeks of controlled mobilization within a Capener coil splint. Thirty-one fingers in 27 patients were assessed by the same independent therapist. All fingers achieved an excellent or good recovery with a mean proximal interphalangeal joint flexion of 94 degrees (range 70-110 degrees) and a mean distal interphalangeal joint flexion of 57 degrees (range 30-81 degrees). Extension deficits of the proximal interphalangeal joint were noted in five fingers (mean 6 degrees, range 3-15 degrees). The results show that a combination of immobilization and controlled mobilization is an effective rehabilitation regime for surgically repaired open central slip injuries.

Adolescent↗

Long-term results of digital arthrodesis with the Harrison-Nicolle peg.

This study determined the long-term success of digital arthrodesis with the Harrison-Nicolle peg. We reviewed 90 digital joints in 60 patients fused with the peg between 1986 and 1998 at a mean follow-up of 6 (range 2-11) years. The prime indication for surgery was rheumatoid arthritis. The early complication rate was 8%. At 1 month 89% of joints were pain-free and stable. In the long-term follow up, 96% of the joints were pain-free and stable, with the original angle of fusion. 85% achieved bony fusion, with no clinical difference between bony and fibrous fusion. Overall there was a significantly higher complication rate in the distal interphalangeal joint. We conclude that, with the exception of the distal interphalangeal joint, the Harrison-Nicolle peg is extremely effective for digital arthrodesis in the rheumatoid patient.

Adult↗

The prognostic importance of c-myc oncogene expression in head and neck melanoma.

Melanomas of the head and neck have a poorer prognosis than melanomas arising at other cutaneous sites. To study the biology of this disease, the expression of the c-myc oncogene was studied in tumors from 97 patients with head and neck melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene expression provided a prognostic marker with shorter overall survival in tumors with high nuclear c-myc oncoprotein positivity (log-rank test, chi2 = 8.77, p < 0.005). Multifactorial analysis using Cox's proportional hazards model revealed nuclear c-myc oncoprotein to be an independent prognostic marker (log-rank test, chi2 = 8.82, p = 0.005). These results support the authors' previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical importance in identifying high-risk patients.

Adolescent↗

The effect of 5-fluorouracil on Dupuytren fibroblast proliferation and differentiation.

INTRODUCTION: Dupuytren's disease is a proliferative disease with contractile properties, prone to recur after surgery. Intra-operatively applied 5-fluorouracil has been used to avoid scar problems in the eye after glaucoma filtration surgery and was therefore investigated as a means to inhibit proliferation and myofibroblast differentiation in Dupuytren fibroblasts in vitro. METHOD: Primary cell lines were obtained by explants from Dupuytren's tissue (n = 6), non-diseased palmar fascia from patients with Dupuytren's disease (n = 3) and carpal ligament from patients undergoing carpal tunnel release (n = 3). The effect of 5-fluorouracil on proliferation was assessed by cell counting. Myofibroblast differentiation, an intergral part of Dupuytren's contracture, was investigated by staining for alpha smooth muscle actin, a marker for contractile cells, using immunohisto-chemical methods. RESULTS: A single exposure to 5-fluorouracil caused a sustained inhibition of proliferation in Dupuytren's and non-diseased fascia cultures, whilst the effect on carpal ligament cultures was transient. Untreated Dupuytren's fibroblasts exhibited the highest myofibroblast differentiation, whilst differentiation in non-diseased fascia cultures was shown to be proportional to cell density and virtually non-existent in carpal ligament cultures. After 5-fluorouracil exposure, the differentiation was significantly reduced in Dupuytren's fibroblasts cultures, reduced at high cell densities in non-diseased fascia and unchanged in carpal ligament cell cultures. DISCUSSION: 5-fluorouracil inhibits both proliferation and myofibroblast differentiation in Dupuytren's cell cultures and may have a potential use as an adjuvant treatment to Dupuytren surgery in order to reduce the rate of recurrence and contracture.

Aged↗

The Merkel cell carcinoma: survival and oncogene markers.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and malignant tumour. Survival data and prognostic factors are scarce. AIM: To investigate the usefulness of biological markers to predict the prognosis for these aggressive tumours. METHODS: C-myc oncoprotein and proliferation was analysed in specimens from 13 patients with MCC, treated between 1983 and 1997. The average age at presentation was 68.3 years. Overall follow-up ranged from 14 to 158 months, with a mean of 68.2 months. Specimens were analysed by immunohistochemistry for proliferation (mib-1) and flow cytometry for oncogene activity (c-myc). RESULTS: The median positivity was 52% for the c-myc oncogene and 50% for proliferation, but these did not correlate to survival as analysed by the Kaplan-Meier method. Other parameters such as median age at presentation, sex, site of tumour and adjuvant radiotherapy were also analysed, but none were found to be significant. CONCLUSIONS: This study showed that neither c-myc oncogene activity or mitotic index in MCC can be related to patient survival.

Aged↗

An analysis of p16 tumour suppressor gene expression in acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive melanocytic lesion but, due to its comparative rarity, biological investigations into the behaviour of this subtype of melanoma are lacking. The activity of the recently described p16 tumour suppressor gene, thought to be the 'familial melanoma gene', was studied in 24 patients with subungual melanoma and 44 patients with plantar melanoma. Lower levels of p16 oncoprotein were demonstrated than that found in other histogenetic types of melanoma. Stratification of patients of all disease stages revealed a poorer survival in patients with low p16 expression (log rank test, chi(2)= 3.9, P = 0. 05). These data suggest that p16 inactivation may play an important role in the development and progression of acral lentiginous melanomas. However, the level of p16 expression was not prognostic since survival analysis on stratification of stage I patients according to p16 level did not reach statistical significance for both survival and disease free interval.

Aged↗