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Biomedical subjects

S S Thomas

Publications and source records attributed to S S Thomas.

At least 19 recordsLinked to original sources

BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia.

Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c release and caspase 8 substrate, was expressed in brain, activated after an ischemic insult in vivo and in vitro, and contributed to ischemic cell death. We detected BID in the cytosol of mouse brain and primary cultured mouse neurons and demonstrated, by using recombinant caspase 8, that neuronal BID also is a caspase 8 substrate. After 2 h of oxygen/glucose deprivation, BID cleavage was detected in neurons concurrent with caspase 8 activation but before caspase 3 cleavage. Bid(-/-) neurons were resistant to death after oxygen/glucose deprivation, and caspase 3 cleavage was significantly reduced; however, caspase 8 cleavage did not differ from wild type. In vivo, BID was cleaved 4 h after transient middle cerebral artery occlusion. Infarct volumes and cytochrome c release also were less in Bid(-/-) mice (-67% and -41%, respectively) after mild focal ischemia. These findings suggest that BID and the mitochondrial-amplification pathway promoting caspase activation contributes importantly to neuronal cell death after ischemic insult.

Animals↗

FGF-2 regulation of neurogenesis in adult hippocampus after brain injury.

Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury. Using mice genetically deficient in FGF-2 (FGF-2(-/-) mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2(-/-) mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF-2(-/-) mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult.

Animals↗

Comparison of three ankle-foot orthosis configurations for children with spastic hemiplegia.

The purpose of this study was to examine the effectiveness of the hinged ankle-foot orthosis (HAFO), posterior leaf spring (PLS), and solid ankle-foot orthosis (SAFO), in preventing contracture, improving efficiency of gait, and enhancing performance of functional motor skills in 30 children (21 male, 9 female; mean age 9 years 4 months; age range 4 to 18 years,) with spastic hemiplegia. Following a 3-month baseline period of no ankle-foot orthosis (AFO) use, each AFO was worn for 3 months after which ankle range of motion, gait analysis, energy consumption, and functional motor skills were assessed. The HAFO and PLS increased passive ankle dorsiflexion and normalization of ankle rocker function during gait. Normalization of knee motion in stance was dependent upon the knee abnormality present and AFO configuration. The HAFO was the most effective in controlling knee hyperextension in stance, while PLS was the most effective in promoting knee extension in children with >10 degree knee flexion in stance. Energy efficiency was improved in 21 of the children, with 13 of these children demonstrating the greatest improvement in HAFO and PLS. Improvements in functional mobility were greatest in the HAFO and PLS.

Adolescent↗

Interobserver reliability of the gross motor performance measure: preliminary results.

Although assessment of the quality of movement in children with cerebral palsy (CP) is difficult, the development of the Gross Motor Performance Measure (GMPM) has facilitated this process. In order to determine the interobserver reliability of the GMPM, 36 children with spastic neuromuscular disorders (mean age 7 years, range 4 to 15 years) were evaluated using four of the five dimensions of the GMPM. Percent Agreement, Intraclass Correlations, and Kappas were calculated by both dimension and attribute to determine reliability. In addition, reliability measures were evaluated over time to determine whether reliability improved with continual use of the GMPM. Overall, interobserver reliability was in the 'fair to good' category regardless of the reliability measure used in the analysis. Reliability scores improved over time with a greater number of individual item scores moving from the 'fair to good' category to the 'excellent' category. Results from this study indicate that it is possible to assess reliably the quality of movement in children with CP.

Adolescent↗

Closed anterior scoring for prominent-ear correction revisited.

The closed-anterior-scoring technique has been used over the past 3 years to correct 56 prominent ears in 32 patients at the West Midlands Regional Plastic Surgery Unit at Wordsley Hospital. A review was carried out to assess the result of this surgical procedure. We briefly discuss the historical development of other surgical techniques for prominent-ear correction, and describe in detail the operative technique for this procedure, which includes closed scoring and suturing of the cartilage. We used this technique to treat 24 patients with bilateral prominent ears and eight patients with unilateral prominent ears. The series comprised 20 females and 12 males, 26 children and six adults. The age range was from 4 to 24 years old. There were two complications (an upper-pole recurrence and protrusion of a buried prolene suture). Patients were followed up for between 6 months and 3 years (mean: 1.5 years). This procedure is quick and technically easy to learn, with no anterior scars or posterior cartilage overlap. Minimal dissection is involved, leading to a low rate of complications. The learning curve is rapid; this paper represents the experience of a specialist trainee (SST) after he was taught the technique by the senior author.

Adolescent↗

Increased susceptibility to ischemia-induced brain damage in transgenic mice overexpressing a dominant negative form of SHP2.

Cell culture studies have established SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) as an important factor in growth factor and cytokine-activated signaling pathways. However, the significance of SHP2 in the mammalian central nervous system (CNS) is not known since early embryonic lethality occurs in shp2 null mice. To bypass this embryonic lethality, transgenic animals containing a catalytically inactive mutant of SHP2 (SHP2-CS) under the control of a nestin intron II/thymidine kinase minimal promoter were generated. In the developing CNS of these animals, although high-level transgene expression was detected in the neuroepithelium, there was no obvious abnormality in progenitor cell proliferation or migration. In the adult brain, high-level transgene expression was detected in the subventricular zone, rostral migratory stream, dentate gyrus of hippocampus, and cerebellum. Because SHP2 function is likely important in cell survival pathways, we used a focal cerebral ischemia model to examined whether SHP2 is important during CNS injury. Ischemia-induced damage and neuronal death was found to be significantly greater in nestin-SHP2-CS mice than in wild-type littermates. These findings indicate that SHP2 is a required factor in signaling pathway(s) important for neuronal survival.

Animals↗

Dilute adrenaline infiltration and reduced blood loss in reduction mammaplasty.

The aim of this review was to assess the use of dilute adrenaline infiltration in reduction mammaplasty and to determine whether it had any associated complications. The closed technique for adrenaline infiltration was used with no reported infection. One hundred breast reductions in 50 patients were compared by dividing them into two groups of 25 patients each. Group A had 1:500,000 adrenaline in normal saline infiltration; group B did not. Both groups were matched equally for age and general health. Results showed that blood loss was less for group A when measured by the fall in postoperative hemoglobin (2.5 g per deciliter vs. 3.5 g per deciliter). This was statistically significant (p < 0.05). There was no significant difference in postoperative drainage (group A, 158 ml; group B, 182 ml). Group A required fewer blood transfusions (two vs. eight), without the risk of increased complications. Blood transfusions were given in the earlier part of the study, but currently are rarely needed. Adrenaline infiltration at this dilution is virtually free from any side effects. It decreases intraoperative blood loss and facilitates the operation without the need for blood transfusion.

Adult↗

Energy consumption in children with myelomeningocele: a comparison between reciprocating gait orthosis and hip-knee-ankle-foot orthosis ambulators.

This study compared the differences in energy efficiency (energy cost) in children with myelomeningocele ambulating with either reciprocating gait orthoses (RGOs) or hip-knee-ankle-foot orthoses (HKAFOs). There were 15 children who ambulated with RGOs and 11 children braced and ambulating in HKAFOs. Velocity was measured in m/s, energy consumption was measured in mL/kg/min, and energy cost (energy consumption/velocity) was measured in mL/kg/m. Children in HKAFOs had a significantly higher energy consumption rate than children in RGOs. However, children who swing through in a HKAFO have a significantly faster velocity than children who ambulate with the RGO using a reciprocating pattern. The increased energy cost in the RGO group is influenced by their slower velocity, just as the decreased energy cost in the HKAFO group is influenced by their increased velocity. Therefore it appears that children in HKAFOs are more energy efficient than children in RGOs.

Adolescent↗

Electrical burns of the mouth: still searching for an answer.

This report is a review of the literature and the clinical experience of electrical burns of the mouth in the West Midlands Regional Burns Unit at the Birmingham Accident Hospital, UK, over the past 10 years. There were five patients, four were children, 9 months to 5 years of age, and one adult. All patients had electrical conduction injuries involving the lips and perioral structures with involvement of the oral commissure. Electrical arc and flash burns were not included in this study. One child had a severe electrical injury and posed a difficult management problem. Although a variety of reconstructive procedures are available, the dilemma between conservative treatment and immediate reconstruction persists. Early intraoral splinting has been suggested in the literature. It was not used in any of the patients in this series and, though it may be beneficial, the patient compliance of a paediatric population may be questionable. The incidence of electrical burns has been on the decline, but those affecting the mouth still continue to be a major problem in management.

Adult↗

Vulvoperineal reconstruction after excision of anogenital multifocal intraepithelial neoplasia ("MIN").

Over the past 7 years, 12 women have been treated utilising a radical surgical approach for extensive vulval involvement as a component of multifocal intraepithelial neoplasia (MIN) of the female genital tract. The patients were analysed with respect to the anatomical site of involvement, age, presenting complaints and their duration, colposcopic examination, histopathology and surgical treatment. Gynaecologists, general surgeons and plastic surgeons were involved in the surgical treatment which was an initial colostomy followed by a definitive vulvoperineal resection and simultaneous vulval reconstruction using meshed split skin grafts or a combination of skin grafts and local flaps. 17 vulvoperineal reconstructions were done for 12 patients. Three had an incomplete histopathological clearance at the initial operation. Apart from these three patients, one had recurrence of symptoms alone, without any evidence of MIN, which was possibly due to human papilloma virus infection. One patient developed malignant squamous invasion 4 years later, which was cured with surgical excision and reconstruction. Colostomy closure was done after achieving local control of the disease. This staged approach does achieve the objectives of eliminating disease and alleviating symptoms. It preserves function and attempts to reconstruct normal anatomy without compromising the principles of surgical oncology and results in a high patient satisfaction.

Adult↗

Influence of monosaccharide derivatives on liver cell glycosaminoglycan synthesis: 3-deoxy-D-xylo-hexose (3-deoxy-D-galactose) and methyl (methyl 4-chloro-4-deoxy-beta-D-galactopyranosid) uronate.

An improved, convenient synthesis of 3-deoxy-D-xylo-hexose (3-deoxy-D-galactose) has been developed, and the chemical synthesis of a novel monosaccharide derivative, methyl (methyl 4-chloro-4-deoxy-beta-D-galactopyranosid)uronate (compound 10), is described. Using primary hepatocytes in culture, each was used to explore its effect on glycosaminoglycan (GAG) synthesis. In the absence of analogues hepatocytes synthesize primarily (92-95%) heparan sulphate. At 1 mM, 3-deoxy-D-galactose had little observable effect on either liver cell GAG or protein synthesis. At 10 mM and 20 mM, 3-deoxy-D-galactose reduced [3H]glucosamine and 35SO4 incorporation into hepatocyte cellular GAGs to, respectively, 75% and 60% of the control cells. This inhibition of GAG synthesis occurred without any effect on hepatocyte protein synthesis, indicating that 3-deoxy-D-galactose's effect on GAG synthesis is not mediated through an inhibition of proteoglycan core protein synthesis. Furthermore, GAGs in the presence of 20 mM of the analogue were significantly reduced in size, 17 kDa vs. 66 kDa in untreated cells. These results reflect either impaired cellular GAG chain elongation, and/or altered GAG chain degradation. Compound 10 exhibited a concentration-dependent inhibition of both hepatocyte cellular GAG and protein synthesis. At concentrations of 5, 10 and 20 mM, compound 10 inhibited GAG and protein synthesis by 20, 65 and 90%, respectively. Exogenous uridine was able to restore partially the inhibition of protein synthesis, but was unable to reverse the effect of compound 10 on GAG synthesis. These results show that part of the effect of compound 10 on GAG synthesis is not mediated by an inhibition of proteoglycan core protein synthesis. GAGs in the presence of compound 10 are half as large as those in the absence of this compound (33 and 66 kDa, respectively). These results again may reflect either impaired cellular GAG chain elongation and/or altered GAG chain degradation. Potential metabolic routes for each analogue's effect are presented.

Animals↗

Injuries suffered by dogs from riding in the back of open pickup trucks: a retrospective review of seventy cases.

Case records of 70 dogs injured while riding in the back of open pickup trucks during the period January 1, 1982, to May 1, 1993, were reviewed. Most dogs were young (mean age 2.4 y) and of medium to large size (average weight 22.6 kg). Sixty-five dogs (93%) were injured during the months of April through October. Forty-nine dogs (70%) had single injuries and 21 dogs (30%) sustained multiple injuries. Fractures were the most frequent injury incurred, with fractures of the femur the most common. Surgical repair was recommended in all but 2 cases.

Animals↗

Squamous cell carcinoma of the pinna: a 6-year study.

Over a 6-year period, 54 sequential lesions of squamous cell carcinoma of the pinna were studied in 44 patients with regard to the side, clinical features and their duration, TNM clinicopathological classification, treatment and follow-up. Treatment delay, types of surgical procedures, anaesthesia and postoperative complications were all analysed. The overall incidence of residual and recurrent cancer was 25.92%. The regional lymph node recurrence was 9.26%, though only 5.56% had clinically persistent cancer. Six patients subsequently died; two of these deaths were due to the cancer.

Aged↗