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Biomedical subjects

U Khan

Publications and source records attributed to U Khan.

34 records · Page 2Linked to original sources
PubMed1999

Breast reconstruction using the free superficial inferior epigastric artery (SIEA) flap.

The lower abdominal wall has established itself as tissue that can mimic the breast to a high degree. Attention has, therefore, turned to harvesting and transferring this tissue, but with minimal donor site morbidity. We report on our experience with five transfers of this tissue based on the superficial inferior epigastric (SIE) vessels. This technique negates the harvest of any rectus muscle and thus its advantages become immediately obvious. The anatomy is reviewed as well as the techniques used. The limitations of this technique relate to the pedicle. The pedicle is shorter than the deep inferior epigastric (DIE) axis and presents itself on the anterior aspect of the tissue. However, these limitations can be overcome with simple adjustments.

Breast Neoplasms↗
PubMed1999

Decrease in adhesion formation by a single application of 5-fluorouracil after flexor tendon injury.

Using an animal model, the effect of a single intraoperative application of 5-fluorouracil on digital flexor tendon adhesions was assessed. After a standard partial division of the tendon and immobilization with a stitch, the synovial sheath in 30 rabbit tendons was treated with 5-fluorouracil solution (50 mg/ml)-soaked sponge pledgets for 5 minutes. Buffered saline was substituted for 5-fluorouracil in 30 control tendons. The tendons were harvested 1 week postoperatively, and histologic sections were assessed with a light microscope. There was a significant reduction in synovial sheath thickening (p < 0.001), cell counts (p < 0.001) and proportional length of adhesions (p < 0.001) in the treated tendons. The reduction in synovial reaction and adhesion formation using this "one touch" technique presents a novel strategy for the management of the clinical problem of postoperative adhesions complicating tendon injury and repair.

Animals↗
PubMed1998

Public consultation. Up and ATAM (aims, timing, audience, method).

Although the NHS has some shining examples of public and user involvement, many still view it as an optional extra. Policy makers need to adopt a broader strategy for involving users, carers, staff and the wider public. Badly done public consultation will cause problems for policy makers, alienate participants and fuel public cynicism.

Community Participation↗
PubMed1998

Differential cellular response within the rabbit tendon unit following tendon injury.

The cellular changes in the epitenon, endotenon and synovial sheath were investigated in a rabbit model after a partial transverse laceration was made on the plantar aspect of the flexor digitorum profundus proximal to the synovial sheath (which was not injured). Fibroblasts, macrophages and mast cells within the epitenon, endotenon and synovial sheath were counted on electron micrographs. The epitenon and uninjured synovial sheath became engorged with fibroblasts and macrophages following injury. The number of synovial fibroblasts showed the greatest increase during the first week after injury. In comparison, the endotenon exhibited a delay in cellular response with initial apoptosis, as judged by positive P53 staining. However, hypercellular activity was seen within the endotenon at 12 weeks postoperatively.

Animals↗
PubMed1998

Differences in proliferative rate and collagen lattice contraction between endotenon and synovial fibroblasts.

Injured and surgically repaired tendons heal with the formation of scar tissue. Scar tissue represents 1 of the most unpredictable factors contributing to postoperative morbidity. The main cell involved in scar formation is the fibroblast. The relative activity of fibroblasts from the fibro-osseous sheath (the tissue surrounding the tendon in zone II) and the endotenon (the core of the tendon) with respect to proliferation and the ability to contract a collagen lattice were compared in vitro. The fibroblasts derived from the fibro-osseous sheath were more active in both these respects. In addition, the amount of matrix metalloproteinase activity was found to be greater for the fibro-osseous sheath fibroblasts, implying a greater capacity to degrade and disorganize connective tissue and thus migrate. These results imply that the fibro-osseous fibroblasts represent a more active population of cells compared with endotenon fibroblasts, and perhaps should be specifically targeted in future modes of therapy.

Analysis of Variance↗
PubMed1997

IL-12 treatment attenuates T helper cell type 2 and B cell responses but does not improve vaccine-enhanced lung illness.

In humans and mice, sensitization to respiratory syncytial virus (RSV) Ags can result in severe inflammatory lung disease during subsequent infection with RSV. Although specific antiviral T cells are thought to be responsible for this augmentation of disease, the precise roles of different functional subsets are unknown, and no protective nonpathogenic subset has been defined. BALB/c mice sensitized to the major surface glycoprotein of RSV (G) expressed by recombinant vaccinia virus develop Th2-driven lung eosinophilia after intranasal challenge with RSV. In an attempt to manipulate the outcome of vaccination, we treated mice with IL-12 at various times during vaccination and challenge. IL-12 treatment reduced the vaccine-induced lung eosinophilia during RSV challenge, but increased the total lymphoid cell infiltration into the alveolar space. Analysis of intracellular cytokines by flow cytometry showed that IFN-gamma production during challenge was increased, and IL-4 and IL-5 levels were reduced by IL-12 treatment. In control treated mice, 40 to 50% of the lung lymphoid cells were B cells. Treatment with IL-12 reduced this figure to approximately 1.5%. Although IL-12 treatment reduced lung eosinophilia, illness (as assessed by weight loss) was not eliminated and, in some experiments, was increased. The present study shows that reversing Th2-associated pathology with IL-12 does not necessarily benefit the host.

Animals↗
PubMed1997

Effects of wild-type and mutated copper/zinc superoxide dismutase on neuronal survival and L-DOPA-induced toxicity in postnatal midbrain culture.

Mutations in the free radical-scavenging enzyme copper/zinc superoxide dismutase (Cu/Zn-SOD) are associated with neuronal death in humans and mice. Here, we examine the effects of human wild-type (WT SOD) and mutant (Gly93 --> Ala; G93A) Cu/Zn-SOD enzyme on the fate of postnatal midbrain neurons. One-week-old cultures from transgenic mice expressing WT SOD enzyme had significantly more midbrain neurons and fewer necrotic and apoptotic neurons than nontransgenic cultures. In contrast, 1-week-old cultures from transgenic G93A mice expressing mutant SOD enzyme had significantly fewer midbrain neurons and more necrotic and apoptotic neurons than nontransgenic cultures. To subject postnatal midbrain neurons to oxidative stress, cultures were incubated with L-DOPA. L-DOPA at 200 microM caused approximately 50% loss of tyrosine hydroxylase (TH)-positive neurons in nontransgenic cultures and even greater loss in transgenic G93A cultures; no alterations were noted in GABA neuron numbers. In contrast, 200 microM L-DOPA did not cause any significant reductions in TH-positive or GABA neuron numbers in transgenic WT SOD cultures. L-DOPA at 50 microM had opposite effects, in that it significantly increased TH-positive, but not GABA neuron numbers in transgenic WT SOD and G93A and in nontransgenic cultures. These results indicate that increased amounts of WT SOD enzyme promote cell survival and protect against L-DOPA-induced dopaminergic neurotoxicity, whereas increased amounts of mutated Cu/Zn-SOD enzyme have inverse effects. As the spontaneous loss and L-DOPA-induced loss of postnatal dopaminergic midbrain neurons appear to be mediated by free radicals, our study supports the view that mutated Cu/Zn-SOD enzyme kills cells by oxidative stress.

Age Factors↗
PubMed1997

Single exposures to 5-fluorouracil: a possible mode of targeted therapy to reduce contractile scarring in the injured tendon.

After injury, adhesions may develop between the digital flexor tendons and their sheaths. Fibroblasts are key cells in this fibrotic adhesive process, and two possible sources for these cells are the synovial sheath and the endotenon tissue (tendon core). Fibroblasts seeded into a collagen lattice will contract the collagen. This fibroblast-populated collagen lattice contraction was used to investigate the ability of the fibroblasts from the synovial sheath and endotenon to reorganize collagen (an important function in the formation of adhesions). Endotenon and synovial fibroblasts isolated from 30 animals were used in the study. Synovial fibroblasts produced significantly greater collagen lattice contraction compared with endotenon fibroblasts (p < 0.05). The possibility of preventing collagen lattice contraction with a single, nontoxic 5-minute treatment of the fibroblast-populated collagen lattices with the antimetabolite 5-fluorouracil was investigated. Compared with controls the degree of fibroblast-populated collagen lattice contraction was significantly inhibited (p < 0.05) with the use of 5-fluorouracil for endotenon and synovial cells. These results demonstrate the potential for locally targeted therapy in tendon healing. Because of the different contractile properties of the two cell lines, a change in the balance between intrinsic and extrinsic healing might be achieved with this method of therapy; in turn, this might lead to better functional results following surgery.

Animals↗
PubMed1996

Quantitative analysis of collagen gel contractile forces generated by dermal fibroblasts and the relationship to cell morphology.

The force generated in granulation tissue during wound contraction is thought to be cell mediated; however, it is unclear whether contractile forces are generated by fibroblast locomotion or contraction of myofibroblasts. To help clarify this question the force of this contraction can now be determined accurately in a human dermal fibroblast collagen lattice system using a novel instrument known as a Culture Force Monitor. Three distinct phases of contraction of such collagen gels could be identified over the first 24 hours. Most of the force generated by human dermal fibroblasts was produced during the first stage in parallel with cell attachment and associated changes in cell shape, and the appearance of cell processes. During this initial 24 hours no evidence could be found for the presence of myofibroblasts, but stereoscopic and electron microscopic analysis at a range of time points indicated that migratory fibroblasts were present in the system. Comparison of the contraction profiles of cells extracted from other tissues (tendon and articular cartilage), and extracted by different means from the same tissue specimen, indicated that different populations of fibroblasts can be distinguished on the basis of their pattern of contractions. It would seem that most of the force generated in this model is a result of fibroblast attachment and movement within the collagen lattice. Furthermore, different groups of fibroblasts, even within the same tissue, may vary in their contraction (hence locomotory) activity.

Animals↗
PubMed1996

Patterns of cellular activation after tendon injury.

Mechanisms which lead to disabling adhesions following flexor tendon surgery of the hand were investigated in a rabbit model which was used to assess the relative response of the cells of the synovial sheath, epitenon and the endotenon to injury. A transverse laceration, cutting through 50% of the tendon, was made just outside the synovial sheath on the flexor aspect of the flexor digitorum profundus tendon. The synovial sheath was preserved intact. Using monoclonal antibodies for localizing specific inflammatory markers, we were able to follow the response and activity of the synovial sheath, epitenon and endotenon with respect to these markers at various times after surgery. Our findings suggest that the synovial sheath and the epitenon are relatively more reactive in the early period after injury, as judged by a range of inflammatory indices with the notable exception of the expression of the potent neovascularizing agent, basic fibroblast growth factor (bFGF).

Animals↗
PubMed1996

Increased superoxide dismutase activity improves survival of cultured postnatal midbrain neurons.

Copper/zinc superoxide dismutase (Cu/Zn-SOD) is a major free radical scavenging enzyme. Increased Cu/Zn-SOD activity protects cells against oxidative stress mediated by different mechanisms. However, there is also in vitro and in vivo evidence that, in the absence of abnormal oxidative stress, chronic increased Cu/Zn-SOD activity is detrimental to living cells. To address this issue, we examined the fate of mature midbrain neurons from transgenic mice expressing human Cu/Zn-SOD and from their nontransgenic littermates. Midbrain from transgenic pups had about threefold higher Cu/Zn-SOD activity than that from nontransgenic pups. Virtually all transgenic neurons were strongly immunoreactive for human Cu/Zn-SOD protein in their cell bodies and processes. The number of midbrain neurons decreased over time in both transgenic and nontransgenic cultures, but to a significantly smaller extent in the transgenic cultures. Postnatal midbrain neurons died by either necrosis or apoptosis, and increased Cu/Zn-SOD activity attenuated both forms of cell death. Furthermore, increased Cu/Zn-SOD activity better prevented the loss of dopaminergic neurons than GABAergic neurons. We also found that neuronal processes were dramatically denser in transgenic cultures than in nontransgenic cultures. These results indicate that chronic increased Cu/Zn-SOD activity does not appear to be detrimental, but rather promotes cell survival and neuronal process development in postnatal midbrain neurons, probably by providing more efficient detoxification of free radicals. They also show that increased Cu/Zn-SOD activity does not seem to play a critical role in determining the mode of cell death in this culture system.

Animals↗
PubMed1995

Sural nerve grafting for lower extremity nerve injuries.

Fourteen consecutive patients who had sural nerve grafts to reconstruct the sciatic or peroneal nerve were retrospectively evaluated to determine the functional return of reinnervation. A standardized functional evaluation to assess motor and sensory return of the injured compared with the contralateral side was employed as a means of normalizing the data. The dorsiflexion and plantar flexion strength were quantitatively measured to determine the recovery of muscle strength, and recorded as a percentage of the strength of the contralateral extremity as well as by assigning a motor grade. Sensory recovery was evaluated by sensory grade, two-point discrimination, and response to Semmes-Weinstein monofilaments. The average age of these 14 patients was 20 years (range 8-63 years). All but one of the patients regained protective sensation and five patients regained useful motor function. Four of the five patients regaining useful function were pediatric patients. Improved functional outcome was correlated to the nerve injured, patient age, mechanism of injury, length of graft, and the delay to grafting. The return of lower extremity function, obviating the need for bracing, can occur in children but is a rare occurrence in the adult patient although protective sensation is routinely gained and disabling paresthesias from neuromas are avoided.

Adolescent↗
PubMed1990

Selective growth of hippocampal neurites on cryostat sections of rat brain.

Dissociated rat hippocampal neurons were cultured on horizontal cryostat sections from neonatal and adult rat brain and their growth patterns visualized by brightfield and interference contrast microscopy. Cells adhered to the sections as individuals or in small clusters and grew extensive neurites. Neurites grew over all areas of neonatal sections without apparent selectivity. For adult sections, however, neurites grew almost exclusively on areas of grey matter: there was no neurite growth on areas of white matter, irrespective of the location of that white matter within the brain. The transition from the neonatal to the adult pattern of growth occurred for sections from animals aged between 14 and 21 days.

Animals↗