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Biomedical subjects

Adriaan O Grobbelaar

Publications and source records attributed to Adriaan O Grobbelaar.

8 recordsLinked to original sources

Practical nerve morphometry.

Histopathological examination of peripheral nerves is often complemented by morphometric analysis in both clinical and research settings. However, existing manual or semi-automated methods are highly tedious, labour intensive and time-consuming, whereas fully automated morphometry is prone to error from the conversion of maldetected particles to spurious data. Both fully and interactive-automated morphometry have significant hardware requirements and may be difficult to implement. A new method for nerve morphometry is described aiming to combine the speed of automated morphometry with the accuracy of manual or semi-automated methods, and requiring only a digital image of the nerve section and two widely available software packages. Comparison with a standard digitizer pen method of nerve morphometry without sampling yielded statistically similar axon counts, mean area assessments and axonal area frequency distribution histograms, with assessment times of the new method between 35% and 45% of those of the standard method. This has widespread potential experimental and clinical applications and offers a means of relieving much of the tedium currently associated with nerve morphometry.

Animals↗

5-fluorouracil selectively inhibits collagen synthesis.

BACKGROUND: Fibroproliferative disorders, such as Dupuytren's contracture of the hand, are characterized by excessive production of collagen. 5-Fluorouracil has been used to treat fibroproliferative disorders of the eye and skin and is thought to inhibit thymidylate synthetase blocking DNA replication. 5-Fluorouracil has been shown to down-regulate fibroblast proliferation and differentiation in vitro. METHODS: This study investigated the dose-dependent effect of 5-fluorouracil on fibroblast extracellular matrix production. Fibroblasts were derived from tendon and primary Dupuytren's disease of the hand, a fibroproliferative disorder of the palmar aponeurosis (n = 4 patients). Total collagen synthesis was determined by means of the incorporation of radiolabeled proline. Fibroblast secretion of the profibrotic factor transforming growth factor-beta1 (TGF-beta1) was measured by a sandwich enzyme-linked immunosorbent assay. Gene expression of collagen types I and III and TGF-beta1 were quantified by means of reverse-transcriptase polymerase chain reaction assays. RESULTS: The authors found that 5-fluorouracil caused a dose-dependent, selective, and specific decrease in collagen production by Dupuytren's fibroblasts compared with noncollagenous protein synthesis. By contrast, procollagen types I and III mRNA were unaffected by 5-fluorouracil treatment. These changes did not appear to be mediated by alterations in the endogenous secretion of TGF-beta1 or its autocrine effect on collagen metabolism. CONCLUSIONS: The clinical implication is that 5-fluorouracil could possibly reduce extracellular matrix production and therefore reduce recurrence of Dupuytren's disease of the hand.

Antimetabolites↗

Psychosocial outcome of patients after ear reconstruction: a retrospective study of 62 patients.

This was a retrospective study examining the psychosocial morbidity of patients before and after ear reconstruction. Semistructured questionnaires were sent to 90 patents with significant congenital or acquired auricular deformity 2.2 years (range 3 months to 5 years) following autogenous or osteointegrated reconstruction. Sixty-two patients (69%) responded. Twenty-two of the patients below 12 years, who had undergone reconstructive surgery, also completed the Childhood Experience Questionnaire. These were compared with a cohort of 362 normal patients. There was significant psychosocial morbidity in both children and adults with auricular deformity. Seventy-one percent of patients reported reduced self-confidence that affected both social life and leisure activity. Teasing was a prominent symptom in both children (88%) and adults (85%) but was a motivational factor for surgery in children only. Dissatisfaction with the appearance (73.1%), on the other hand, was the main reason for treatment in adults. Following ear reconstruction, 74% of adults and 91% of children reported an improvement in self-confidence resulting in enhanced social life and leisure activities in both adults and children. There was no difference between osteointegrated and autogenous reconstruction. Sixty percent of patients reported their result as excellent. The patients scored their result better than the surgeon. We conclude that auricular reconstruction has significant psychosocial benefit in the majority of children and adults despite donor-site morbidity and a range of technical result.

Adaptation, Psychological↗

The contractile properties and responses to tensional loading of Dupuytren's disease--derived fibroblasts are altered: a cause of the contracture?

Dupuytren's disease causes disability because of the development of finger flexion deformities, with distinct nodule and cord formation. This results in physical shortening of the diseased fascial tissue through a combination of cell-mediated contraction and matrix remodeling. It is this fixed tissue fabric shortening that prevents finger extension. In this experimental study, the relative contractile properties of Dupuytren nodule- and cord-derived fibroblasts were quantified in a culture force monitor model, in comparison with normal carpal ligament fibroblasts. Nine nodule, 10 cord, and four carpal ligament fibroblast cell lines were studied; each cell line was derived from a separate patient. The contractile forces generated by nodule and cord fibroblasts were significantly greater than the force generated by carpal ligament fibroblasts. There were also significant differences between nodule- and cord-derived fibroblasts, with the nodule cells demonstrating the greatest contractile force generation. The contraction profiles of both cord and nodule Dupuytren fibroblasts demonstrated delays in the attainment of tensional homeostasis, with an absence of a plateau phase by 20 hours. After the contraction phase, cell-seeded constructs were subjected to a series of four uniaxial mechanical overloads and cellular responses were monitored during each subsequent 30-minute period. Dupuytren nodule and cord fibroblast responses were significantly altered, compared with carpal ligament fibroblasts, exhibiting an increased and opposite response. Dupuytren fibroblasts, particularly nodule fibroblasts, exhibited increased force generation and a delay in reaching tensional homeostasis. The data suggest that these cells have an inherently higher basal tension and contractile ability. This results in increased shortening of the matrix, and the delay in reaching tensional homeostasis might exacerbate this response. These results represent a theoretical framework regarding the fundamental processes involved in the pathogenesis and progression of clinical flexion deformities in Dupuytren disease.

Biomechanical Phenomena↗

Mapping of vascular endothelium in the human flexor digitorum profundus tendon.

PURPOSE: Previous techniques to delineate the human flexor digitorum profundus (FDP) vasculature have been innovative but potentially imprecise, resulting in uncertainty as to the existence of avascular zones in the flexor tendon. We aimed to use a novel immunohistochemical technique to determine more accurately the vasculature of the human flexor tendon. METHODS: Thirty fresh cadaveric human FDP tendons were harvested, fixed, wax embedded, sectioned, and stained using the anti-CD31 monoclonal antibody to allow vessel visualization. Vessel numbers and vascularity density ratios were determined by computed image analysis. RESULTS: Vessel density ratios varied with anatomic location, with a decrease between the A2 and A4 pulleys. There also was variation in vascularity ratios in the anteroposterior plane, with the palmar surface of the tendons having a lower vessel density. CONCLUSIONS: We have shown that although areas of low vascularity exist on the palmar aspect of the tendon, there are no truly avascular zones.

Endothelium, Vascular↗

Synovial sheath cell migratory response to flexor tendon injury: an experimental study in rats.

PURPOSE: We aimed to investigate the degree of participation of synovial sheath cells in the process of tendon healing by selective cell labeling and direct observation of migrational pathways. METHODS: We designed a novel rat animal model that employed vital dye staining of synovial sheath cells. The flexor digitorum profundus (FDP) tendon was removed from its sheath and vital dye was applied directly to the synovial sheath cells. A window was cut in the removed tendon before being returned to the sheath, thus placing a tendon injury adjacent to the labeled synovial sheath cells. The synovium remained intact at all times, and labeling was confirmed to be localized to the synovium. The migrational response of the synovial sheath cells to the tendon injury was observed by harvesting the tendons at 1, 3, 5, and 7 days (n = 6 for each time period) after injury and assessing tendon response with frozen sections under ultraviolet microscopy. RESULTS: Labeled synovial sheath cells were observed within the substance of the healing tendon 24 hours after injury, with numbers increasing with time for up to 5 days, but decreasing by day 7. CONCLUSIONS: This study confirms that in the rat model synovial sheath cells move into the healing tendon area and then migrate into the tendon core.

Animals↗

The early surface cell response to flexor tendon injury.

PURPOSE: The migratory response of surface fibroblasts to flexor tendon injury was studied by their selective labeling with a vital dye. METHOD: The surfaces of 30 rat deep flexor tendons were bathed in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholate (DiI), a vital dye for 5 minutes. The residual dye was removed by thorough irrigation. A partial tenotomy was made in the stained section by cutting out a central window. Semiquantitative cell counts and position of stained fibroblasts were noted by examination under fluorescent light at 0, 1, 3, 5, and 7 days. RESULTS: The surface fibroblasts readily took up the vital dye at day 0. By day 1 dyed cells had moved into the cut. By day 3 they had migrated laterally into the core substance of the tendon. Core dyed cell counts at days 1, 3, 5, and 7 were significantly different compared with day 0 core dyed cell counts. CONCLUSIONS: This cell migration from the surface of the cut to the tendon core is likely to be vital in the early stages of tendon healing.

Animals↗

The long-term results of ruby laser depilation in a consecutive series of 346 patients.

The goal of this study was to prospectively assess the long-term results of ruby laser depilation in 346 consecutive patients who underwent hair removal at 402 anatomical sites. The patients were treated using a ruby laser, with mean power ranging from 8.6 J to 15.7 J according to skin type. Results were assessed using two outcome measures-the percentage reduction in hair density and the hair-free interval. The median reduction in hair density was 55 percent (range, 0 to 100 percent) at a median time of 1 year after the last treatment session. The median hair-free interval was 8 weeks. Patients underwent a median number of four treatment sessions. Forty-three of the 346 patients were treated at more than one anatomical site. Of the sites treated, 75 percent reduction in hair density was achieved in 22 percent, 90 percent reduction was achieved in 2.2 percent, and complete depilation was achieved in only 0.7 percent. Darker colored hair was more effectively treated. Treatment efficacy was not affected by anatomical site, with the exception of the faces of male patients, which were found to be particularly resistant to treatment. There was a significant correlation between the number of treatments given and the outcome. The overall complication rate was 9.0 percent (36 of 402 sites) with respect to pigmentary changes and blistering, but varied according to Fitzpatrick skin type. The complication rate was highest in skin types V and VI (24.7 percent), with no complications in skin type I. Although a greater than 50 percent reduction in hair density was achieved in half of the 346 patients treated, complete depilation was achieved in only an extremely limited number of patients.

Adult↗