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Biomedical subjects

S Whitehouse

Publications and source records attributed to S Whitehouse.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of early postoperative rehabilitation outcome following total knee arthroplasty using different surgical approaches and instrumentation.

PURPOSE: To assess early postoperative rehabilitation outcome following computer-assisted total knee arthroplasty (TKA) or standard instrumentation TKA using a medial parapatellar or subvastus approach. METHODS: A prospective controlled trial of 70 consecutive patients undergoing TKA with a low contact stress rotating platform prosthesis was conducted. Patients were randomised to receive surgery with either computer navigation or standard instrumentation. A medial parapatellar or subvastus approach was used according to the surgeons' preference. Outcome measures included preoperative knee function, intra-operative factors, and postoperative rehabilitation. RESULTS: Duration of surgery was significantly longer when using computer navigation; however, operating time decreased with greater experience. A higher incidence and duration of early postoperative quadriceps dysfunction was associated with computer-assisted TKA through the medial parapatellar approach than through the subvastus approach or TKA performed with standard instrumentation. No patient who received surgery through the subvastus approach had a lag of more than 20 degrees, at 48 hours postoperatively, regardless of the instrumentation used. CONCLUSION: Computer-assisted TKA through a medial parapatellar approach was associated with delayed recovery of the quadriceps during early postoperative rehabilitation. This was due to the additional quadriceps dissection required to place the femoral tracking array. The subvastus approach is therefore recommended for computer-assisted TKA.

Aged↗
PubMed2004

Infection after total knee arthroplasty.

The aim of our study was to determine the current incidence and outcome of infected total knee arthroplasty (TKA) in our unit comparing them with our earlier audit in 1986, which had revealed infection rates of 4.4% after 471 primary TKAs and 15% after 23 revision TKAs at a mean follow-up of 2.8 years. In the interim we introduced stringent antibiotic prophylaxis, and the routine use of occlusive clothing within vertical laminar flow theatres and 0.05% chlorhexidine lavage during arthroplasty surgery. We followed up 931 primary TKAs and 69 revision TKAs for a mean of 6.5 years (5 to 8). Patients were traced by postal questionnaire, telephone interview or examination of case notes of the deceased. Nine (1%) of the patients who underwent primary TKA, and four (5.8%) of those who underwent revision TKA developed deep infection. Two of nine patients (22.2%) who developed infection after primary TKA were successfully treated without further surgery. All four of the patients who had infection after revision TKA had a poor outcome with one amputation, one chronic discharging sinus and two arthrodeses. Patients who underwent an arthrodesis had comparable Oxford knee scores to those who underwent a two-stage revision. Although infection rates have declined with the introduction of prophylactic measures, and more patients are undergoing TKA, the outcome of infected TKA has improved very little.

Adult↗
PubMed2003

Do patients need to earn total knee arthroplasty?

Traditional orthopaedic thinking dictates that performing total knee arthroplasty (TKA) in patients with relatively early stages of osteoarthritis (OA) will lead to a poor outcome. Our goal was to test this perception, using radiologic parameters as a marker of the degree of OA. Our study involved 130 consecutive patients who underwent TKA for OA. The radiographs of each patient were graded according to the Ahlback classification. Outcome was measured prospectively using the Oxford Knee Score (OKS), which was recorded both preoperatively and 1 year after surgery. The degree of radiologic OA changes preoperatively was not found to influence the outcome of surgery at 1 year, with all patient groups improving to a similar extent. In addition, as has been seen in previous studies, no correlation was found between symptoms of OA and radiologic appearances. The results of this study would support a re-evaluation of traditional orthopaedic practice. This conclusion coincides with other recent work that suggests that TKA is underused and is performed too late in the natural history of OA of the knee.

Aged↗
PubMed2003

Infection after total hip arthroplasty. The Avon experience.

Our aim in this study was to determine the outcome of hip arthroplasty with regard to infection at our unit. Infection after total joint arthroplasty is a devastating complication. The MRC study in 1984 recommended using vertical laminar flow and prophylactic antibiotics to reduce infection rates. These measures are now routinely used. Between 1993 and 1996, 1727 primary total hip arthroplasties and 305 revision hip arthroplasties were performed and 1567 of the primary and 284 of the revision arthroplasties were reviewed between five and eight years after surgery by means of a postal questionnaire, telephone interview or examination of the medical records of those who had died. Seventeen (1.08%) of the patients who underwent primary and six (2.1%) of those who underwent revision arthroplasty had a post-operative infection. Only 0.45% of patients who underwent primary arthroplasty required revision for infection. To our knowledge this is the largest multi-surgeon audit of infection after total hip replacement in the UK. The follow-up of between five and eight years is longer than that of most comparable studies. Our study has shown that a large cohort of surgeons of varying seniority can achieve infection rates of 1% and revision rates for infection of less than 0.5%.

Aged↗
PubMed2002

A randomised comparison of a foot pump and low-molecular-weight heparin in the prevention of deep-vein thrombosis after total knee replacement.

Patients who undergo total knee replacement (TKR) are at high risk of venous thromboembolism. Low-molecular-weight heparins (LMWH) are the most suitable chemical prophylactic agents but there are some uncertainties about their safety and effectiveness. The foot pump offers an alternative. We randomised 229 patients undergoing primary, unilateral TKR to receive either the A-V Impulse foot pump or enoxaparin, a LMWH. Ascending venography was undertaken between the sixth and eighth postoperative day in 188 patients without knowledge of the randomisation category. The prevalence of venographic deep-vein thrombosis was 58% (57/99) in the foot-pump group and 54% (48/89) in the LMWH group which was not statistically significant. There were four cases of proximal thrombi and two of fatal pulmonary emboli in the foot-pump group and none in the LMWH group. There were fewer haemorrhagic complications and soft-tissue effects in the foot-pump group. We conclude that the neither method provides superior prophylaxis.

Aged↗
PubMed1999

Functional domains of the SYT and SYT-SSX synovial sarcoma translocation proteins and co-localization with the SNF protein BRM in the nucleus.

The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome. The SYT protein appears to act as a transcriptional co-activator and the SSX proteins as co-repressors. Here we have investigated the functional domains of the proteins. The SYT protein has a novel conserved 54 amino acid domain at the N-terminus of the protein (the SNH domain) which is found in proteins from a wide variety of species, and a C-terminal domain, rich in glutamine, proline, glycine and tyrosine (the QPGY domain), which contains the transcriptional activator sequences. Deletion of the SNH domain results in a more active transcriptional activator, suggesting that this domain acts as an inhibitor of the activation domain. The C-terminal SSX domain present in SYT-SSX translocation protein contributes a transcriptional repressor domain to the protein. Thus, the fusion protein has transcriptional activating and repressing domains. We demonstrate that the human homologue of the SNF2/Brahama protein BRM co-localizes with SYT and SYT-SSX in nuclear speckles, and also interacts with SYT and SYT-SSX proteins in vitro. This interaction may provide an explanation of how the SYT protein activates gene transcription.

Amino Acid Sequence↗
PubMed1997

The SYT protein involved in the t(X;18) synovial sarcoma translocation is a transcriptional activator localised in nuclear bodies.

The t(X;18)(p11.2;q11.2) translocation found in synovial sarcomas results in the fusion of the SYT gene on chromosome 18 to either of two closely related genes SSX1 and SSX2 on chromosome X. The resulting chimaeric genes express SYT-SSX1 or SYT-SSX2 fusion proteins in which the C-terminal amino acids of SYT are replaced by amino acids from the C-terminus of the SSX proteins. Using green fluorescent protein fusions we demonstrate that the SYT, SSX and the SYT-SSX proteins are nuclear proteins. We demonstrate that whilst the SSX1 protein has a uniform nuclear distribution the SYT protein has a speckled distribution in the cell nucleus, and this distribution is retained with the SYT-SSX2 fusion protein. Since the SYT speckles do not co-localise with PML-containing bodies (PODs) or spliceosomes it is possible that they represent a novel nuclear structure. Transfection of constructs expressing GAL4 fusion proteins demonstrate that the SYT domains present in the SYT-SSX fusion proteins can activate transcription of a luciferase reporter. It is proposed that the t(X;18) translocation results in the generation of an SYT-SSX transcriptional co-activator in which the addition of the C-terminal SSX domain to SYT provides a new interacting domain that redirects the SYT activation domain to different target promoters.

Cell Nucleus↗
PubMed1997

Symptomatic venous thromboembolism after total knee replacement.

Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis. We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis. One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40). Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.

Aged↗
PubMed1983

Mg X ATP2-dependent interaction of the inhibitor protein of the cAMP-dependent protein kinase with the catalytic subunit.

The interaction between the inhibitor protein and the catalytic subunit of the cAMP-dependent protein kinase has been investigated by steady state kinetics and by an assessment of the requirement of this interaction for ATP. By analysis for tightly bound inhibitors, inhibition by the inhibitor protein was shown to be competitive versus peptide substrate and uncompetitive versus Mg X ATP2-. This, together with the observations of Gronot et al. (Gronot, J., Mildvan, A.S., Bramson, H. N., Thomas, N., and Kaiser, E.T. (1981) Biochemistry 20, 602-610) and those given in the accompanying paper (Whitehouse, S., Feramisco, J.R., Casnellie, J.E., Krebs, E.G., and Walsh, D.A. (1983) J. Biol. Chem. 258, 3693-3701), would indicate that the probable reaction mechanism of the protein kinase is ordered with the nucleotide binding first and that the inhibitor protein blocks catalysis by interaction with the catalytic subunit-Mg X ATP complex. The Ki for this interaction at saturating Mg X ATP and zero peptide substrate is 0.49 nM. Multiple inhibition analysis in the presence of 5'-adenylimidodiphosphate (AMP X PNP) indicates that the inhibitor protein does not interact with a catalytic subunit-AMP X PNP complex. The requirement for ATP for the inhibitor protein-catalytic subunit interaction has also been demonstrated by direct binding measurements and by the observation that the efficiency of the inhibitor protein is increased by preincubation of the inhibitor protein, catalytic subunit, and ATP in the absence of peptide substrate. By either measurement, the catalytic subunit in the presence of the inhibitor protein, was shown to exhibit an apparent Kd of 20 approximately 60 nM for ATP; this value is two orders of magnitude higher than the affinity for ATP by the catalytic subunit alone. This high apparent affinity of the catalytic subunit for ATP (in the presence of the inhibitor) does not require that there be a specific binding site on the inhibitor protein for some moiety of the ATP but may simply be a reflection of the formation of a catalytic subunit-Mg X ATP X inhibitor protein complex with resultant displacement of the equilibrium of ATP binding to the protein kinase.

Adenosine Triphosphatases↗
PubMed1983

Studies on the kinetic mechanism of the catalytic subunit of the cAMP-dependent protein kinase.

The kinetic mechanism of the catalytic subunit of the cAMP-dependent protein kinase has been investigated employing the heptapeptide Kemptide (Leu-Arg-Arg-Ala-Ser-Leu-Gly) as substrate. Initial velocity measurements performed over a wide range of ATP and Kemptide concentrations indicated that the reaction follows a sequential mechanistic pathway. In line with this, the results of product and substrate inhibition studies, the patterns of dead end inhibition obtained employing the nonhydrolyzable ATP analogue, AMP X PNP (5'-adenylylimidodiphosphate), and equilibrium binding determinations, taken in conjunction with the patterns of inhibition observed with the inhibitor protein of the cAMP-dependent protein kinase that are reported in the accompanying paper (Whitehouse, S., and Walsh, D.A. (1983) J. Biol. Chem. 258, 3682-3692), are best fit by a steady state Ordered Bi-Bi kinetic mechanism. Although the inhibition patterns obtained employing the synthetic peptide analogue in which the phosphorylatable serine was replaced by alanine were apparently incompatible with this mechanism, these inconsistencies appear to be due to some element of the structure of this latter peptide such that it is not an ideal dead end inhibitor substrate analogue. The data presented both here and in the accompanying paper suggest that both this substrate, analogue and the ATP analogue, AMP X PNP, do not fully mimic the binding of Kemptide and ATP, respectively, in their mechanism of interaction with the protein kinase. It is proposed that, as with some other kinase reactions, the configuration of the terminal anhydride bond of ATP assumes a conformation once the nucleotide is bound to the protein kinase that assists in the binding of either Kemptide or the inhibitor protein but not the alanine-substituted peptide and that AMP X PNP, because of its terminal phosphorylimido bond, cannot assume this conformation which favors protein (or peptide) binding.

Adenylyl Imidodiphosphate↗
PubMed1983

Influence of obesity on basal glucagon levels in non-diabetic and diabetic Nauruans.

Basal plasma glucagon (IRG), insulin (IRI) and glucose levels were measured in normal weight (Body Mass Index (BMI) less than 30) and obese (BMI greater than or equal to 30) non-diabetic and diabetic Micronesians (n = 30) on Nauru Island. This population has a high prevalence of diabetes mellitus. IRG levels were significantly higher (P less than 0.02) in the non-diabetic obese, compared to the non-diabetic lean subjects (109 +/- 19 vs 44 +/- 12 SEM pg/ml, respectively) and there was a significant positive correlation between basal IRG and BMI (r = 0.79, P less than 0.001). IRG levels were similar in diabetic obese and diabetic lean subjects. The pathophysiological significance of the hyperglucagonaemia in these obese subjects is not known, although it may be related to the frequent development of diabetes in this unique population.

Adult↗
PubMed1982

Purification of a physiological form of the inhibitor protein of the cAMP-dependent protein kinase.

The inhibitor protein of the cAMP-dependent protein kinase exists in two forms which can be distinguished by separation techniques that characterize proteins on the basis of size (McPherson, J. M., Whitehouse, S., and Walsh, D. A. (1979) Biochemistry 18, 4835-4845). To date, only one of these forms has been purified and the form obtained was not the species that is present in the initial extracts of tissues. This paper reports the purification to homogeneity of the form of the inhibitor that is present in initial cell extracts and which, in consequence, appears to be a physiological size species of this protein.

Amino Acids↗
PubMed1982

Prevalence rates of impaired glucose tolerance and diabetes mellitus in various Pacific populations according to the new WHO criteria.

This report gives the prevalence rates of impaired glucose tolerance (IGT) and diabetes mellitus (DM) for several Micronesian, Polynesian, and Melanesian populations in the Pacific region according to the new WHO criteria.The Micronesian population of Nauru show the highest prevalence rates of both IGT (22.7%) and DM (30.3%) - 53% of the adult population thus demonstrating abnormal glucose tolerance. The lowest prevalence rates of both IGT (4.5%) and DM (1.5%) were seen in the rural Melanesian population of the main island of New Caledonia.

Adult↗