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Biomedical subjects

U Khan

Publications and source records attributed to U Khan.

At least 19 recordsLinked to original sources
PubMed2003

Differences in morphology, cytoskeletal architecture and protease production between zone II tendon and synovial fibroblasts in vitro.

Fibroblast migration is an integral component of the processes resulting in the formation of restrictive adhesions in the injured tendon, especially in Zone II. Pre-requisites for cell migration are an intact cytoskeleton and an ability to biochemically degrade the extra-cellular matrix. The relative characteristics of fibroblasts from the fibro-osseus sheath (SC), the tissue surrounding the tendon in Zone II, and the endotenon (TC) with respect to morphology, cytoskeletal structure and ability to produce matrix metalloproteinases (MMPs) 2 and 9 were compared in vitro. It was found that SCs were larger in size and demonstrated greater amounts of intra-cellular alpha-smooth muscle actin (alpha-SMA) and intra-membranous vinculin. Filamentous actin (F-actin) fibres in SCs were more densely packed and concentrated, resulting in stress fibres. The SCs also produce greater amounts of MMP-2 and MMP-9 compared to TCs. These observations imply that SCs play an active role in adhesion formation and should be specifically targeted to inhibit or treat tendon adhesions.

Actins↗
PubMed2002

Free radial forearm adipofascial flaps raised through limited incisions.

Free radial forearm adipofascial flaps were used for limb reconstruction in four cases. The flaps were harvested through limited skin incisions with the aid of lighted retractors. The mean surface area was 96 cm(2). The donor sites and the transferred tissue healed satisfactorily in all cases. Although the dissection through limited incisions is slightly awkward and prolongs the operating time, the technique offers significant benefits in terms of donor-site morbidity and aesthetics.

Adolescent↗
PubMed2001

RNase P-mediated inhibition of cytomegalovirus protease expression and viral DNA encapsidation by oligonucleotide external guide sequences.

External guide sequences (EGSs) are oligonucleotides that consist of a sequence complementary to a target mRNA and recruit intracellular RNase P for specific degradation of the target RNA. In this study, DNA-based EGS molecules were chemically synthesized to target the mRNA coding for the protease of human cytomegalovirus (HCMV). The EGS molecules efficiently directed human RNase P to cleave the target mRNA sequence in vitro. When EGSs were exogenously administered into HCMV-infected human foreskin fibroblasts, a reduction of about 80-90% in the expression level of the protease and a reduction of about 300-fold in HCMV growth were observed in the cells that were treated with a functional EGS, but not in cells that were not treated with the EGS or with a "disabled" EGS carrying nucleotide mutations that precluded RNase P recognition. Moreover, packaging of the viral DNA genome into the capsid was blocked in the cells treated with the functional EGS. These results indicate that HCMV protease is essential for viral DNA encapsidation. Moreover, our study provides direct evidence that exogenous administration of a DNA-based EGS can be used as a therapeutic approach for inhibiting gene expression and replication of a human virus.

Base Sequence↗
PubMed2001

Reduction in matrix metalloproteinase production by tendon and synovial fibroblasts after a single exposure to 5-fluorouracil.

This study investigated the effect of treatment with 5min exposures to 5-fluorouracil (5-FU) on the production of matrix metalloproteinases (MMPs) by endotenon and synovial fibroblasts. Fibroblasts were grown from the flexor tendons of New Zealand White rabbits and were then exposed to varying concentrations (ranging from 0.25 mg x ml(-1)to 25 mg x ml(-1)of 5-FU for 5 min. The treated fibroblasts were suspended in a three-dimensional collagen lattice. The conditioned media from these collagen lattices were then analysed for MMP production using gelatin zymography on days 1, 3 and 7 after treatment. In the majority of cases this treatment produced a dose- and time-dependent reduction in total MMP production by both cell lines, specifically in the production of MMPs 2 and 9. This reduction was significant for most concentrations (P< or =0.01-P< or =0.05) when compared to phosphate-buffered-saline-treated controls. We conclude that 5-FU may reduce adhesions by limiting the migratory capacity of synovial fibroblasts (extrinsic healing).

Animals↗
PubMed2001

Waterproofing in hypospadias: a refinement of the two-stage reconstruction.

A new technique for 'waterproofing' during the second stage of a two-stage hypospadias repair is described. It is simpler and involves less tissue dissection than other waterproofing techniques. The senior author has used it over a period of 6 years as standard practice. The technique has been used in a total of 24 cases, in which the fistula rate was 8% (two cases).

Child, Preschool↗
PubMed2001

The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision.

The possibility of altering the pathophysiology of keloid scars was investigated in 11 patients, using a single application of 5-fluorouracil solution for 5 minutes after extralesional excision was performed. Similar excisional wounds treated with phosphate-buffered saline for 5 minutes served as synchronous controls. An objective scoring system and subjective assessment were made to assay the change in the quality of the wound-healing and scar tissue produced by this treatment. A keloid scar score was used at regular time intervals after treatment to assess the quality of scar produced, thereby enabling the treated and control scars to be clinically compared. Biopsies were taken of the control and treated scars 1 month after treatment; the biopsy specimens were then subjected to immunohistochemical analysis as well as a functional assessment of cultured keloid fibroblasts. The immunohistochemical antigens assayed were Ki-67 (also called MIB-1; a marker of cell proliferation); vascular cell adhesion molecule-1 (a marker of inflammation); transforming growth factor beta-1 (a factor involved in scarring) and CD-68 (a macrophage-specific marker). Fibroblast-populated collagen lattices provided a functional assessment of fibroblast contraction. All treated and control wounds healed without any dehiscence or infection. The keloid scar score revealed that there was a perceived improvement in condition for those treated with 5-fluorouracil, compared with the control specimens, during the 6-month follow-up period in the five patients who attended all their clinic appointments; data on later recurrence are not complete as yet. The wounds treated with 5-fluorouracil produced scars that had a significant (p < 0.01) reduction in all the markers assayed, apart from CD-68. Functionally, the keloid fibroblasts from three of five of the treated patients showed reduced contractile capacity. This pilot study demonstrates that a "single-touch" technique with 5-fluorouracil can produce a change in the characteristics of the healing keloid wound after extralesional excision. Long-term studies are required to elucidate the correct dosage and time of exposure to improve the efficacy of this potential treatment.

Adult↗
PubMed2001

Group B streptococcal bacteremia in an adult: a case report from India.

The incidence of group B streptococcal bacteremia in adults has increased in recent years, particularly in patients with severe underlying diseases. However, group B still remains an unusual pathogen in adults in developing countries. We report a case of group B streptococcal bacteremia in a non-pregnant adult, the only case reported in our hospital. The organism was only isolated from the blood and responded to specific therapy.

Adult↗
PubMed2000

Use of an islanded fasciocutaneous flap in the lower limb following distraction callotasis.

Severe limb injuries present a challenge to the attending surgeon and there has been an emergence of complex modes of treatment. The Ilizarov technique for distraction osteogenesis is accepted as a worthwhile option in selected cases of massive segmental bone loss. The blood supply of the bone during this process has been studied experimentally but the response of the soft tissue envelope to the process of compression followed by slow and progressive elongation is not entirely understood. We present a case of lower limb trauma where a combined approach to reconstruction was required with acute shortening followed by distraction osteogenesis for a major segmental tibial defect. Late soft tissue reconstruction for persistent ulceration over the tibia was then undertaken using a distally based fasciocutaneous flap.

Adolescent↗
PubMed2000

Modulation of the formation of adhesions during the healing of injured tendons.

The formation of restrictive adhesions around the musculotendinous unit after injury is one of the most vexing processes faced by the surgeon. In flexor tendons it has been shown that the synovial tissue is the source of aggressive fibroblasts which contribute to this process. Using a rabbit model, we have examined the effects of treating the synovial sheath with the antimetabolite 5-fluorouracil (5-FU) for five minutes. Inflammatory, proliferative and molecular markers were compared in the response of the treated and control tendons to injury. Compared with a control group we found that the proliferative and inflammatory responses were significantly reduced (p < 0.001) in the treated tendons. Not only was there a reduction in the cellular and cytokine response, but there also was a significant (p < 0.001) reduction in the level of activity of the known pro-scarring agent, transforming growth factor beta 1 (TGF-beta1). These pilot studies indicate that the formation of restrictive adhesions may be modulated using a simple single-touch technique in the hope of producing a better return of function.

Animals↗
PubMed2000

Respiratory distress secondary to both amphotericin B deoxycholate and lipid complex formulation.

A 73-y-old female with a history of adenocarcinoma of colon and refractory anemia developed febrile neutropenia following chemotherapy. Therapy with iv infusion of amphotericin B deoxycholate (AmBd) was initiated on day 8 of hospital admission. Premedications included acetaminophen, diphenhydramine and meperidine. Patient developed rigor, chill and elevated temperature approximately 100 min into the infusion. The infusion was temporarily discontinued and rigors subsided following administration of 25 mg meperidine im. Infusion was continued after cessation of the rigors with no further sequelae. During each infusion of AmBd over the next 3 d, the patient developed rigor, chill and elevated temperature which was managed with meperidine. However, on day 4 she developed respiratory distress, bronchospasm and visible cyanosis with oxygen saturation of 88% while on 2 L oxygen. The infusion was stopped and the symptoms subsided with administration of albuterol via nebulizer. Amphotericin lipid formulation infusion was reinstituted after 3 d because of the patient's worsening clinical status. However, the patient developed severe respiratory distress approximately 130 min into the infusion. The infusion was discontinued and she was treated with albuterol via nebulizer. Itraconazole therapy was instituted without any adverse sequelae. Clinicians should be aware of this potential adverse event since it can occur with all formulation of amphotericin.

Adenocarcinoma↗
PubMed1999

Describing severe limb trauma.

Seventy-nine severe limb injuries were retrospectively reviewed to compare the AO/ASIF and the Gustillo classifications. Specifically, the suitability of these classifications with respect to prognosis and management of these cases was compared. A healed and stable wound was the ultimate outcome measure. Surrogate outcome measures used were: the time to healing; the number of anaesthetics until the wounds were healed; and the number of operations until the wounds were healed. Any change in lifestyle following the injury was also assessed. The primary healing rates of the AO/ASIF groups showed significant (P < 0.001) inter-group differences. However, when the injuries were classified using the Gustillo system, the primary healing rates did not show any differences between the groups. Also, differences in the other outcome measures were most pronounced when using the AO/ASIF system. Importantly, changes in lifestyle correlated with the injury score when using the AO/ASIF system (P < 0.05). Unlike the AO/ASIF system, the Gustillo system was not applicable in 100% of cases. A modified AO/ASIF scoring system is proposed which provides a good predictor of outcome.

Acute Disease↗
PubMed1999

Rational selection of flaps from the abdomen in breast reconstruction to reduce donor site morbidity.

Reconstruction of the female breast following mastectomy has become commonplace. The number of donor sites have increased as the quest both for improving reconstruction and reducing morbidity continues. There are a number of donor sites which resemble breast tissue in terms of skin texture, suppleness and colour. The 'gold standard' for transfer in breast reconstruction, however, is the lower abdominal skin and fat. The tissue can be moulded into virtually any breast shape desired. The lower abdomen can provide enough material for total autologous reconstruction of small, moderate sized or even large breasts. This tissue can be transferred onto the chest wall for breast reconstruction using four vascular axes. These are the superior epigastric artery (SEA), the deep inferior epigastric artery (DIEA), a perforator of the deep inferior epigastric artery (DIEP) or the superficial inferior epigastric artery (SIEA). The main problem with the majority of these techniques is that they may be associated with significant donor site morbidity due to harvest of some or all of the rectus muscle. An order of decreased muscle harvest is as follows; pedicled TRAM > free TRAM > DIEP > SIEA. It is envisaged that morbidity will be reduced if the aponeurosis and musculature of abdominal wall is kept intact. This can be achieved in selected cases if the 'abdominoplasty' flap is harvested on the SIE vessels. We present a logical approach to harvesting the lower abdominal wall tissue in order to reduce donor site morbidity.

Abdomen↗
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↗