Biomedical subjects

A O Grobbelaar

Publications and source records attributed to A O Grobbelaar.

At least 19 recordsLinked to original sources

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

Can the carbon dioxide laser completely ablate basal cell carcinomas? A histological study.

Carbon dioxide laser ablation has been advocated as an alternative therapeutic modality for basal cell carcinoma. This study examined the limitations of carbon dioxide laser ablation for BCCs by the formal excision and histological examination of the tumour bed, following laser therapy. We evaluated the tumour type and ablation depth required to ablate the tumours completely. Fifty-one selected BCCs, ranging from 4 to 35 mm, were ablated with a carbon dioxide laser combined with a microprocessor controlled optomechanical flash scanner. Clinically there were 21 superficial, 28 nodular and 2 infiltrative types. Complete ablation at the deep margin was associated with ablation depth (P = 0.006) and with tumour type (P = 0.01). Overall, all tumours of superficial subtype (found most commonly on the trunk) could be completely ablated reliably, provided they were lasered to a depth of the middle dermis or deeper. In contrast, nodular tumours could not reliably be ablated by this method. A small subset of nodular tumours less than 10 mm diameter, however, were all completely ablated provided they were lasered to a depth of the lower dermis or deeper, however this may result in delayed healing and scarring. We conclude that this fast modality is useful for the treatment of some BCCs provided strict selection criteria are met. Laser ablation would be most beneficial for patients with multiple superficial BCCs.

Adult↗

PubMed2000

Chronic axillary hidradenitis--the efficacy of wide excision and flap coverage.

A number of different modalities of surgical treatment for axillary hidradenitis suppurativa have been suggested. This study compares three different methods of surgical excision. Fifty-nine patients (94 axillae) were treated over a 14-year period. There were 42 females and 17 males with an average age of 32 years (range 16-65 years). Twenty-six axillae had excision of only the diseased skin and recurrent disease occurred in seven. However, in 39 axillae that were treated by excision of all the hair bearing skin, only three developed recurrent disease, which is a significant reduction in the incidence of recurrent disease (P = 0.04, Fischer's exact test). Twenty-nine axillae were treated by wide local excision (2 cm beyond the hair bearing skin) and no recurrence occurred. However, there was no statistical difference (P = 0.18, Fischer's exact test) in disease recurrence between excision of all the hair bearing skin and wide local excision. This study suggests that excision of all the hair bearing skin is the preferred method of surgical treatment. Flap coverage was an effective method to achieve wound closure after adequate excision and can be achieved by random fasciocutaneous flaps for small or medium sized defects and parascapular flaps for large defects.

Adolescent↗

PubMed2000

Paralysis of the marginal mandibular branch of the facial nerve: treatment options.

Isolated paralysis of the marginal mandibular branch of the facial nerve results in an asymmetrical smile with elevation of the lower lip on the affected side. We discuss the surgical options for its correction and present a series of 26 patients who underwent either botulinum toxin injection, anterior belly of digastric transfer or free extensor digitorum brevis transfer as treatment. Botulinum toxin injection provided satisfactory results although these were temporary. Anterior belly of digastric transfer was the surgical procedure of choice. It yielded superior cosmetic results, less donor-site morbidity and required a shorter operating time. In more complex congenital facial hypoplastic syndromes, or following extensive surgery in the digastric triangle, the anterior belly of the digastric muscle may be absent or damaged. Extensor digitorum brevis transfer is the preferred option in these cases.

Adolescent↗

PubMed2000

Flexor tendon blood vessels.

The aim of this study was to assess rabbit long flexor tendon vascularity in a qualitative and quantitative manner using immunohistochemistry. The endothelial cell surface marker CD31 was targeted with a specific monoclonal mouse-anti-human antibody with good species cross-reactivity. Subsequent signal amplification and chromogen labelling allowed vessel visualization. Computer image analysis was performed. Values for vessel number and total vessel area per section, as well as the sections' cross-sectional tendon areas, were obtained. There was a consistent deep tendon avascular zone between the A2 and A4 pulley in the rabbit forepaw. This was not the case in the hindpaw, with dorsally orientated longitudinal vessels coursing the length of the intrasynovial tendon. The area of least vascularity in the hindpaw was around the metacarpophalangeal joint. We therefore recommend the use of hindpaw tendons when using the rabbit as a flexor tendon experimental model. This is because its vascular pattern is similar to that of the human flexor digitorum profundus.

Animals↗

PubMed2000

Reducing postoperative morbidity after the insertion of gold weights to treat lagophthalmos.

Paralysis of the orbicularis oculi muscle leads to an unopposed action of the levator of the upper eyelid (lagophthalmos) in facial nerve palsy. The resultant exposure of the cornea may lead to keratitis, corneal ulceration, and eventual blindness. Although many surgical options exist in the treatment of lagophthalmos, upper lid loading with a gold weight implant has become one of the preferred methods to reduce the complications that may follow. The problems encountered after gold lid loading and methods to reduce postoperative morbidity are not well documented. The objective of this study was to determine the range of morbidity seen after gold weight insertion and to evaluate the effect of supratarsal fixation on subsequent morbidity. After retrospective reviews by questionnaire and case note analysis, supratarsal fixation was found to noticeably reduce the rate of implant ulceration and extrusion. This study demonstrates upper lid loading to be an effective method for the treatment of lagophthalmos, and it supports fixation of gold weights in reducing surgical morbidity.

Adolescent↗

PubMed2000

The abnormal nucleus as a cause of congenital facial palsy.

BACKGROUND: Congenital facial palsy (CFP) is clinically defined as facial palsy present at birth. It is associated with considerable disfigurement and causes functional and emotional problems for the affected child. The aetiology of the majority of cases however, remains elusive. AIMS: To investigate the role of a neuroanatomical abnormality as a cause of unilateral CFP. METHODS: Magnetic resonance imaging (MRI) scans were performed on 21 patients with unilateral CFP. Fifteen patients had unilateral CFP only; six suffered from syndromes which can include unilateral CFP. RESULTS: Of the 15 patients with unilateral CFP only, four (27%) had an abnormal nucleus or an abnormal weighting of this area on the MRI scan, compared to one (17%) of the remaining six patients. CONCLUSION: Developmental abnormalities of the facial nucleus itself constitute an important, and previously ignored, cause of monosymptomatic unilateral CFP.

Adolescent↗

PubMed1999

Ruby laser-assisted hair removal reduces the coarseness of regrowing hairs: fallacy or fact?

There have been anecdotal reports that hairs that regrow after ruby laser-assisted hair removal are finer in appearance. If true, this phenomenon adds to the improved aesthetic effect of laser treatment of unwanted hair. It is the aim of this study to determine whether this phenomenon indeed occurs, and if so, assess its permanence and its mode of action. In this prospective clinical study, 71 patients with 94 treatment sites were treated with the Chromos 694 Depilation Ruby Laser. Hair diameter was measured pre-treatment, and at 3 and 7 months post-treatment. In addition, ex vivo scalp skin was used to assess if the ruby laser selectively damaged coarser hairs. Laser-treated and matched untreated skin samples were histologically assessed and the diameters of hair shafts (normal or obviously damaged) were measured. Results of this study were analysed using Kruskal-Wallis one-way analysis. There was no statistically significant difference between the hair diameter of non-lasered specimens and the hair diameter of the normal hair in lasered specimens. However, a statistically significant difference was seen between the hair diameter of non-lasered specimens and diameters of damaged hair in lasered specimens (P < 0.05). There was a statistically significant difference (P < 0.05) between pre-treatment and 3 month hair diameters, but no statistically significant difference was found between pre-treatment and 7 month hair diameters. In conclusion, ruby laser-assisted hair removal results in a temporary reduction in hair diameter of regrowing hair. This is not due to the selective targeting of larger hair follicles.

Adolescent↗

PubMed1999

Measurement of c-myc oncogene expression provides an accurate prognostic marker for acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive tumour with a worse prognosis than other varieties of primary cutaneous melanoma. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 45 patients using flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis with stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (Log-Rank test, chi 2 = 16.7, P < 0.0001) and overall survival (Log-Rank test, chi 2 = 8.9, P = 0.002) in tumours with high oncoprotein levels. Multivariate analysis revealed c-myc oncogene expression to be more accurate in predicting clinical outcome than all existing clinicopathological parameters including the Breslow depth (Cox's proportional hazards model, P = 0.0011). This study provides biological evidence to explain the aggressive behaviour of acral melanoma and supports the application of oncogene measurement as an accurate prognostic marker.

Adult↗

PubMed1999

The removal of unwanted hair using a ruby laser.

A ruby laser has been developed to remove unwanted hair. Melanin within the hair is used as a natural chromophore. It is postulated that photothermal damage destroys the hair itself and also key cells surrounding the hair follicle to prevent regrowth. A prospective study of laser depilation in 116 patients or 175 sites was performed over a period of 18 months. All the patients had tried other methods of hair removal and found them to be unsatisfactory. Hair counts (follicles/cm2) were used to judge the outcome. The mean follow-up time was 23.25 weeks (range 12-76 weeks). After a mean number of treatments of 1.92 (range 1-20) there was a 56.4% reduction in hair density. Comparing pre- and post-treatment hair density, there was a highly significant reduction (paired t-test: P < 0.00001). Laser removal of hair is now a realistic treatment option.

Adolescent↗

PubMed1999

Ruby laser-assisted hair removal: an ultrastructural evaluation of cutaneous damage.

Ruby laser-assisted hair removal is thought to act via selective photothermolysis of melanin in the hair follicles. Although initial clinical trials of permanent hair removal using ruby lasers are promising, the exact mechanisms of hair destruction and the potential damage to other structures of skin are not known. The aim of this study was to evaluate the cutaneous ultrastructural changes following ruby laser hair removal. Nineteen healthy Caucasian patients with dark (brown/black) hair were treated with the ruby laser and biopsies taken after 0, 2, 3, 5, 7, 14 and 21 days. Specimens were examined by light and electron microscopy. Laser-treated specimens showed widespread coagulation and charring of subcutaneous hair shafts. These obviously damaged follicles were randomly dispersed amongst intact follicles within the same treatment sites. Microscopic changes were also seen in the basal epidermis where melanin was concentrated, irrespective of any obvious macroscopic damage. A low level of inflammatory response seen up to 2 weeks after treatment always followed laser treatment. Suprabasal epidermal necrosis was only seen in patients with blister formation after treatment. Ruby laser irradiation results in selective damage to the hair follicles, with microscopic changes to the basal epidermis. The damage is probably compounded by the inflammatory response to the damaged hair. The normal appearance and distribution of collagen in the dermal layer supported the clinical evidence that laser-assisted hair removal, if performed correctly, does not lead to scar formation.

Biopsy↗

PubMed1999

Is Dupuytren's disease caused by an imbalance between proliferation and cell death?

Dupuytren's contracture shares certain properties with malignant tumours, characterized by proliferation and lack of apoptosis, which may be induced by the c-myc oncogene. Because of these similarities, the relationship between the c-myc oncogene expression, bcl-2 oncogene (anti-apoptotic gene) and proliferation was investigated in Dupuytren's disease. Proliferation was assessed by immunohistochemical staining of the mib-1 antibody. Results were compared with those from fibrosarcoma specimens, representing a related malignant tumour. Non-diseased fascia from Dupuytren patients and flexor retinaculum from patients undergoing carpal tunnel release without Dupuytren's disease were used as controls. Expression of c-myc was elevated in primary Dupuytren's disease and fibrosarcoma specimens, whilst recurrent Dupuytren's disease, non-diseased Dupuytren fascia and flexor retinaculum exhibited significantly lower levels. Neither bcl-2 nor mib-1 were detected in Dupuytren's disease, non-diseased fascia or flexor retinaculum, in contrast to fibrosarcoma. The imbalance between proliferation and apoptosis, producing malignant growth was thus confirmed for fibrosarcoma, but not for Dupuytren's disease.

Adult↗

PubMed1999

The effect of ruby laser light on ex vivo hair follicles: clinical implications.

Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that regrowth of hair after treatment is common. One of the reasons for the regrowth of hair is the incomplete destruction of germinative hair cells due to the insufficient penetration of the ruby laser in the skin. It was the aim of this study to estimate the extent of damage to the hair follicles after one ruby laser treatment and to determine whether the ruby laser destroyed the bulbs and the bulge regions of hair follicles. The extent of laser damage in hair shafts was determined by serial examination of six specimens of ex vivo scalp skin lasered with the Chromos 694 Depilation Ruby Laser at 14 J per square centimeter and 20 J per square centimeter. Another nine specimens of ex vivo scalp skin were similarly lasered, and monoclonal antibody LP2K was used to identify the bulge regions of the hair follicles using the immunoperoxidase technique. Damage to the bulge region was assessed from consecutive specimens, which were stained with hematoxylin-eosin stain. The mean depth of laser damage sustained by hair follicles was 1.34 mm (14 J per square centimeter) and 1.49 mm (20 J per square centimeter) underneath the skin surface. Most of the laser damage involved the bulge regions but fell short of the hair bulbs. The laser damage did not seem to extend far enough down the hair shafts to result in permanent hair destruction. The clinical implications of this finding are discussed.

Hair Follicle↗

PubMed1999

Ruby laser-assisted hair removal: a preliminary report of the correlation between efficacy of treatment and melanin content of hair and the growth phases of hair at a specific site.

An unpredictable response, even in patients with dark hair, often undermines successful ruby laser hair removal. A prospective clinical study was carried out to evaluate the roles of melanin content and growth phases of hair in treatment efficacy. Thirty-six volunteers with white skin and dark hair were recruited for the study, and were all treated using the Chromos 694 Depilation Ruby Laser. The overall efficacy of treatment was assessed at the end of 3 months. The efficacy of laser treatment is not due solely to the proportion of hair in the growing or static phase of the hair cycle. There is a lack of correlation between the melanin content and the overall efficacy of laser hair removal in those treated once, but patients with darker hair responded better after repeated treatments. The proportion of hair in the growth phase and the melanin content of hair do not contribute solely to the efficacy of ruby laser hair removal.

Hair↗

PubMed1999

The effect of ruby laser light on cellular proliferation of epidermal cells.

In ruby laser-assisted hair removal, microscopic damage is often seen in the basal epidermal cells, where melanosomes are concentrated. It is not known whether this treatment leads to cellular hyperproliferation. It was the aim of this study to investigate this. Ten white patients were treated with the Chromos 694-nm Depilation Ruby Laser, and biopsies taken before and after treatments to assess the presence of cell hyperproliferation, which normally accompanies epidermal damage, with immunohistochemical staining of keratin 16 and Ki67. No evidence of cell hyperproliferation was seen in all specimens examined after ruby laser irradiation. The authors conclude that despite the possible microscopic damages seen in the basal epidermis after laser hair removal, there is no evidence of cellular hyperproliferation. This is in contrast to ultraviolet-irradiated cell damage, in which increased basal cell turnover is seen.

Cell Division↗