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Biomedical subjects

D J Scott

Publications and source records attributed to D J Scott.

At least 73 records · Page 4Linked to original sources
PubMed2000

A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41.

Van der Woude syndrome (VWS) is a common form of syndromic cleft lip and palate and accounts for approximately 2% of all cleft lip and palate cases. Distinguishing characteristics include cleft lip with or without cleft palate, isolated cleft palate, bilateral lip pits, hypodontia, normal intelligence, and an autosomal-dominant mode of transmission with a high degree of penetrance. Previously, the VWS locus was mapped to a 1.6-cM region in 1q32-q41 between D1S491 and D1S205, and a 4.4-Mb contig of YAC clones of this region was constructed. In the current investigation, gene-based and anonymous STSs were developed from the existing physical map and were then used to construct a contig of sequence-ready bacterial clones across the entire VWS critical region. All STSs and BAC clones were shared with the Sanger Centre, which developed a contig of PAC clones over the same region. A subset of 11 clones from both contigs was selected for high-throughput sequence analysis across the approximately 1.1-Mb region; all but two of these clones have been sequenced completely. Over 900 kb of genomic sequence, including the 350-kb VWS critical region, were analyzed and revealed novel polymorphisms, including an 8-kb deletion/insertion, and revealed 4 known genes, 11 novel genes, 9 putative genes, and 3 psuedogenes. The positional candidates LAMB3, G0S2, HIRF6, and HSD11 were excluded as the VWS gene by mutation analysis. A preliminary gene map for the VWS critical region is as follows: [see text] 41-TEL. The data provided here will help lead to the identification of the VWS gene, and this study provides a model for how laboratories that have a regional interest in the human genome can contribute to the sequencing efforts of the entire human genome.

Animals↗
PubMed2000

Out-patient psychodynamic psychotherapy services: an analysis of patient discharge data.

OBJECTIVE: To investigate the functioning of a specialist out-patient Psychodynamic Psychotherapy Service by studying demographic characteristics of patient referrals and referral sources. To investigate the effect of number of treatment sessions on outcome; and to discuss the results in the light of some prevailing stereotypes about psychotherapeutic treatment. DESIGN: Analysis of discharge data on a cohort of patients discharged from a psychotherapy clinic. SETTING: An out-patient psychotherapy clinic serving the West Sector of the City of Glasgow. SUBJECTS: All patients discharged between mid 1993 and 1998. RESULTS: The clinic served all General Practices within eight postal code areas in West Glasgow (catchment population 260,000). Over a five year period 1648 patients were discharged from the clinic; 68% of referrals were from General Practitioners, 18% from Psychiatrists and the remainder from Clinical Psychologists, Consultant Physicians and Surgeons. A wide range of diagnostic conditions were encountered with personality disorder being diagnosed in more than one-third of patients seen. Successful outcome, assessed by patients' subjective ratings on a four point scale at termination of treatment, showed a 50% improvement rate achieved between 7-12 treatment sessions in the Non Personality Disorder group, and between 12-20 treatment sessions in the Personality Disorder group. In total the proportion of not improved and improved ratings was 61% and 39% respectively. Four hundred (73%) of the not improved group received, five sessions or less. CONCLUSIONS: The results indicated that the Psychotherapy Service treated a large number of patients, many from middle to high areas of deprivation, and that improvement could be effected over relatively short time periods. The data did not conform to existing stereotypes such as psychotherapy being confined to the treatment of "worried well", affluent groups. It took twice as many sessions to achieve a 50% improvement rate in patients with a diagnosis of personality disorder compared with patients without such a diagnosis.

Adult↗
PubMed1999

Quaternary re-arrangement analysed by spectral enhancement: the interaction of a sporulation repressor with its antagonist.

The protein/protein interaction between SinI and SinR has been studied by analytical ultracentrifugation and gel electrophoresis in an attempt to understand how these proteins contribute to developmental control of sporulation in Bacillus subtilis. SinR was found to be tetrameric, while SinI was found to exist as monomers and dimers in a rapidly reversible equilibrium. Labelling of SinR by incorporating the tryptophan analogue 7-azatryptophan (7AW) into the protein in place of tryptophan shifts the UV absorbance spectrum, thus allowing selective monitoring of 7AWSinR at 315 nm using the UV absorption optics of the analytical ultracentrifuge. Selective monitoring of SinR in mixtures of SinR and SinI enables the binding and stoichiometry of the interaction to be investigated quantitatively and unambiguously. We demonstrate that the oligomeric forms of SinR and SinI re-arrange to form a tight 1:1 SinR:SinI complex, with no stable intermediate species. A fragment of SinR, SinR(1-69), which contains only the DNA-binding domain, was found to be monomeric, showing that the protein appears not to oligomerise in a similar manner to the Cro repressor, a protein with which it shares a marked structural similarity.

Amino Acid Sequence↗
PubMed1999

Does angioplasty improve the quality of life for claudicants?: A prospective study.

This study aims to analyze the impact of percutaneous transluminal angioplasty (PTA) for claudication on patients' quality of life (QOL). The patients in this study included 108 claudicants, 74 men and 34 women, with a median age of 67 years (range 40-87 years), who were assessed prior to and at 1, 3, and 6 months following PTA. This is the first report to demonstrate that the previously well-documented improvements in the clinical indicators of lower-limb ischemia are accompanied by improvements in individual QOL domains and in overall global QOL. These findings are detectable within a month following PTA and last at least 6 months. The results of this study may go some way to provide proof of efficacy for the procedure and thus help justify the recently questioned widespread use of PTA in clinical practice.

Aged↗
PubMed1999

With advances in medical imaging can the radiologist reliably diagnose Wilms' tumours?

AIM: To evaluate whether radiologists can accurately differentiate Wilms' tumours from other paediatric abdominal masses with renal involvement using modern imaging methods alone. METHODS: From February 1993 to June 1997, 23 patients presented to the Paediatric Oncology Service at The Royal Hospital for Sick Children, Edinburgh with an intra-abdominal mass which had renal involvement. Nine patients had Wilms' tumours, 12 had neuroblastomas, one patient had xanthogranulomatous pyelonephritis and there was a single case of a mesoblastic nephroma. In each case, two radiologists retrospectively reviewed the initial imaging examinations and independently reached a radiological diagnosis. RESULTS: The radiologists were concordant and reached the correct diagnosis in 20/23 cases (87%), unsure of the diagnosis in one case (4.3 %) and discordant in two cases (8.7 %). Radiologists should be aware that a mesoblastic nephroma can have identical imaging features to a Wilms' tumour. In most cases, ultrasound and a chest X-ray were sufficient to reach the correct diagnosis although computed tomography (CT) and magnetic resonance imaging were superior for demonstrating the relationship of the mass to the great vessels, retroperitoneum and spinal canal. Inferior vena cava invasion was strongly predictive of a Wilms' tumour. Displacement of the great vessels, extension of the mass across the mid-line, renal displacement and tumour calcification on CT were more suggestive of a neuroblastoma although these features were also seen in a significant number of patients with Wilms' tumours. Encasement of vessels by tumour, a paravertebral mass and spinal canal invasion were highly predictive of neuroblastoma. CONCLUSION: In this study, radiologists were accurate at diagnosing Wilms' tumours using modern imaging methods, however, care should be taken in children who are less than 1 year of age as a mesoblastic nephroma may have identical imaging characteristics.

Child↗
PubMed1999

Macrophage accumulation within the cap of carotid atherosclerotic plaques is associated with the onset of cerebral ischemic events.

PURPOSE: Macrophage accumulation is associated with aortic and coronary plaque instability. The macrophage content of carotid plaques removed at carotid endarterectomy (CE) was assessed, and the relevance to the onset of ipsilateral cerebral ischemic events (CIE) was examined. METHODS: Carotid plaques from patients undergoing CE were examined (group I, symptomatic stenoses, n = 28; group II, high-grade asymptomatic stenosis, n = 7). The plaques were stained with monoclonal antimacrophage antibody (HAM56), and the interval since the last CIE was recorded. The percentage area of the cap, shoulder, and entire sclerotic region was quantified by computerized planimetry. RESULTS: The macrophage content of the cap, shoulder, and sclerotic region in all 35 plaques was 1.14% (interquartile range, 0.56 to 3.86), 1.03% (0.51 to 2.15), and 0.49% (0.27 to 0.63), respectively (cap vs sclerotic, P <.01; shoulder vs sclerotic, P <. 01; cap vs shoulder, P =.23). In 18 plaques that were removed less than 180 days after the last CIE, the macrophage content of the cap, shoulder, and entire sclerotic region was 2.41% (0.95 to 4.81), 0. 83% (0.40 to 2.52), and 0.53% (0.38 to 0.71), respectively (cap vs sclerotic, P =.01; cap vs shoulder, P =.01). The content in the cap of these plaques was greater than in plaques removed more than 180 days after symptoms, or asymptomatic plaques (n = 17; 0.62% [0.44 to 1.25], P =.01). The cap macrophage content was inversely related to the time since the last CIE (r = -0.414, P =.029). CONCLUSION: In patients requiring CE, macrophage accumulation was maximal within the cap of carotid plaques and greatest in plaques removed less than 180 days after the last CIE. These findings and the inverse relationship between macrophage content and the interval since symptoms support the hypothesis that macrophage accumulation is associated with plaque instability.

Aged↗
PubMed1999

Endovascular stent-grafts for superficial femoral artery disease: results of 1-year follow-up.

PURPOSE: To document a preliminary study to assess the deployment and outcomes of endoluminal stent grafting in the superficial femoral artery (SFA) with use of a prototype device. MATERIALS AND METHODS: Twenty patients with lifestyle-limiting intermittent claudication were selected for treatment with a balloon-mounted expansive polytetrafluoroethylene graft. All patients had angiographically proven SFA disease (median length, 17 cm) with normal arterial inflow and at least two calf vessels patent to the ankle. Follow-up was by means of ankle brachial pressure index (ABPI), duplex ultrasound, and angiography. RESULTS: Fourteen patients were successfully treated. Six patients were excluded: five by the study protocol and one because the procedure was a technical failure. ABPI rose from 0.6 before treatment to 1.0. The treated limbs became asymptomatic. Twelve-month primary, primary assisted, and secondary patency rates of treated patients were 29%, 50%, and 64%. CONCLUSION: Endovascular stent grafting of SFA lesions is technically feasible, but the patency rates obtained with this design are inferior to those obtained with conventional surgical bypass.

Aged↗
PubMed1999

Peritoneal cytology in the surgical evaluation of gastric carcinoma.

Many patients undergoing surgery for gastric carcinoma will develop peritoneal metastases. A method to identify those patients at risk of peritoneal recurrence would help in the selection of patients for adjuvant therapy. Peritoneal cytology has received little attention in the West, but may prove a useful additional means of evaluating patients with gastric cancer. The aims of this study were to evaluate sampling techniques for peritoneal cytology in patients with gastric cancer, to assess the prognostic significance of free peritoneal malignant cells and to discover the effect of the operative procedure on dissemination of malignant cells. The study is based on 85 consecutive patients undergoing surgical treatment of gastric cancer and followed up for 2 years or until death. Peritoneal cytology samples were collected at laparoscopy, and at operation prior to resection by intraperitoneal lavage and serosal brushings. After resection, samples were taken by peritoneal lavage, imprint cytology of the resected specimen and post-operatively by peritoneal irrigation via a percutaneous catheter. Malignant cells were diagnosed by two independent microscopists. Preoperative peritoneal lavage yielded malignant cells in 16 out of 85 cases (19%). The yield of free malignant cells was increased by using serosal brushings (by four cases) and imprint cytology (by two cases); all of the cases had evidence of serosal penetration. One serosa-negative case exhibited positive cytology in the post-resection peritoneal specimen in which the preresection cytology specimen was negative. Survival was worse in the cytology-positive group (chi2 = 25.1; P< 0.0001). Among serosa-positive patients, survival was significantly reduced if cytology was positive, if cases yielded by brushings and imprint cytology were included (log-rank test = 8.44; 1 df, P = 0.004). In conclusion, free peritoneal malignant cells can be identified in patients with gastric cancer who have a poor prognosis; the yield can be increased with brushings and imprint cytology in addition to conventional peritoneal lavage. Evaluation of peritoneal cytology by these methods may have a role in the selection of patients with the poorest prognosis who may benefit most from adjuvant therapy.

Adult↗
PubMed1999

Remodeling of the AB site of rat parvalbumin and oncomodulin into a canonical EF-hand.

Parvalbumin (PV) and the homologous protein oncomodulin (OM) contain three EF-hand motifs, but the first site (AB) cannot bind Ca2+. Here we aimed to recreate the putative ancestral proteins [D19-28E]PV and [D19-28E]OM by replacing the 10-residue-long nonfunctional loop in the AB site by a 12-residue canonical loop. To create an optical conformational probe we also expressed the homologs with a F102W replacement. Unexpectedly, in none of the proteins did the mutation reactivate the AB site. The AB-remodeled parvalbumins bind two Ca2+ ions with strong positive cooperativity (nH = 2) and moderate affinity ([Ca2+]0.5 = 2 microM), compared with [Ca2+]0.5 = 37 nM and nH = 1 for the wild-type protein. Increasing Mg2+ concentrations changed nH from 2 to 0.65, but without modification of the [Ca2+]0. 5-value. CD revealed that the Ca2+ and Mg2+ forms of the remodeled parvalbumins lost one-third of their alpha helix content compared with the Ca2+ form of wild-type parvalbumin. However, the microenvironment of single Trp residues in the hydrophobic cores, monitored using intrinsic fluorescence and difference optical density, is the same. The metal-free remodeled parvalbumins possess unfolded conformations. The AB-remodeled oncomodulins also bind two Ca2+ with [Ca2+]0.5 = 43 microM and nH = 1.45. Mg2+ does not affect Ca2+ binding. Again the Ca2+ forms display two-thirds of the alpha-helical content in the wild-type, while their core is still strongly hydrophobic as monitored by Trp and Tyr fluorescence. The metal-free oncomodulins are partially unfolded and seem not to possess a hydrophobic core. Our data indicate that AB-remodeled parvalbumin has the potential to regulate cell functions, whereas it is unlikely that [D19-28E]OM can play a regulatory role in vivo. The predicted evolution of the AB site from a canonical to an abortive EF-hand may have been dictated by the need for stronger interaction with Mg2+ and Ca2+, and a high conformational stability of the metal-free forms.

Amino Acid Sequence↗
PubMed1999

High impact of nephropathy on five-year mortality rates among patients with Type 2 diabetes mellitus from a multi-ethnic population in New Zealand.

AIMS: Type 2 diabetes mellitus and its complications are common among Polynesians in New Zealand. This study investigated the mortality from diabetes among indigenous Maori and recent migrants from the South Pacific. METHODS: Death certificates and other reports were collected to enumerate those who had died in an across-community cohort study of 765 diabetic patients aged 40-79 years in 1991. Five year mortality status was ascertained in 99.7% and death certificates were obtained from 129 (88%) of the 146 who had died. Diabetes was missed from 36% of death certificates. RESULTS: Compared to Europeans with Type 2 diabetes, Maori with Type 2 diabetes were 2.66 (1.63-4.35) fold as likely to die from diabetes-related conditions, including a 13.1 (3.7-46.4) fold greater risk of death from nephropathy. Pacific Islands Polynesians with Type 2 diabetes had a similar mortality to Europeans with Type 2 diabetes (hazards ratio 1.06 (0.68-1.65)). After 6 years, 10.7 (2.2-19.3)% more Maori had died than Pacific Islands Polynesians. CONCLUSIONS: Maori with Type 2 diabetes are dying from diabetic complications, particularly nephropathy, at an alarming rate. The magnitude of the difference between Maori and Pacific Islands Polynesians suggests environmental rather than inherited factors are involved and these need further investigation.

Adult↗
PubMed1999

Does soluble intercellular adhesion molecule-1 (ICAM-1) affect neutrophil activation and adhesion following ischaemia-reperfusion?

OBJECTIVES: To examine the effect of reperfusion plasma and sICAM-1 on neutrophil integrin expression and neutrophil adhesion to determine if sICAM-1 has a potential role in the regulation of neutrophil adhesion. MATERIALS: Twenty-seven patients, 17 men and 10 women undergoing femorodistal surgery. Blood was taken preoperatively and from the femoral vein following the release of the cross-clamp. Neutrophils were obtained from five volunteers and incubated with phosphate buffered saline (PBS), preoperative plasma or reperfusion plasma with and without sICAM-1. Neutrophil expression of CD11b and adhesion were measured. MAIN RESULTS: Neutrophil CD11b expression did not change following incubation in the three media. Neutrophil adhesion increased significantly following exposure to reperfusion plasma compared to PBS or preoperative plasma (45.5 adhesion vs. 12.75%, p < 0.01 Mann-Whitney U-test). Soluble ICAM-1 decreased CD11b expression and adhesion in neutrophils exposed to reperfusion plasma only (CD11b expression fell from 15.9 to 3.4 mcf, p < 0.01 Mann-Whitney U-test and adhesion fell to 11.6% cells adhered, p < 0.01). CONCLUSION: An increase in CD11b expression is not required for an increase in neutrophil adhesion. The change in neutrophil adhesion produced by reperfusion plasma can be blocked by sICAM-1. Soluble ICAM-1 may have a physiological role in the regulation of neutrophil adhesion.

Aged↗
PubMed1999

Duplex-derived evidence of reflux after varicose vein surgery: neoreflux or neovascularisation?

BACKGROUND: Recurrent varicose veins remain a problem in surgical practice despite improvements to the preoperative investigation of, and surgery for varicose veins. Neovascularisation accounts for some cases of recurrence within a few years of surgery, but other factors relating to disease progression must also play a part. We investigated whether new venous reflux (neoreflux) could occur in the early postoperative period (within 6 weeks) following successful varicose vein surgery. METHODS: Eighteen-month prospective observational study in the dedicated vascular surgery unit of a university teaching hospital. Forty-six patients, with primary saphenofemoral junction reflux, awaiting varicose vein surgery were chosen consecutively from the waiting list. All saphenofemoral surgery was performed in a standardised fashion. Assessments were performed prior to, at 6 weeks and at 1 year after surgery. Duplex ultrasound was used to identify and locate sites of reflux. RESULTS: Neoreflux was present at the 6-week postoperative scan in nine limbs after varicose vein surgery (19.6%), and resolved in 55.6% of patients within 1 year. Neovascularisation was noted in two limbs at the 1-year scan. CONCLUSION: New sites of reflux, which may resolve spontaneously, occur in the early postoperative period despite adequate varicose vein surgery. It is our hypothesis that this is a manifestation of the effect of altered venous haemodynamics in a system of susceptible veins.

Adult↗
PubMed1999

Axial flow fields in cuffed end-to-side anastomoses: effect of angle and disease progression.

OBJECTIVE: to visualise the axial flow fields in standard and cuffed end-to-side anastomoses (ESA). DESIGN: in vitro experiments using a flow rig, custom-built glass models and frame-by-frame video analysis of flow patterns in standard and cuffed ESA. SUBJECTS: glass models of standard or cuffed (1 cm or 2 cm high) ESA of angles 15, 30, 45 and 60 degrees. RESULTS: the cross-sectional area of standard ESA is much smaller than that of ESA between graft and cuff. The size of the vortex in the anastomotic zone of both standard and cuffed ESA increased with increasing ESA angle and cuff height, but did not change with flow rate. The presence of the vortex maintains a zone of flow separation and low shear at the heel of standard and graft/cuff anastomoses. CONCLUSIONS: the observations explain the clinical findings of intimal hyperplasia (IH) at the heel of PTFE/cuff anastomoses. The improved patency rates of cuffed ESA may be due not to decreased IH, but to an increased ability of the cuff to accommodate IH before causing a significant stenosis.

Anastomosis, Surgical↗
PubMed1999

Subclavian stents and stent-grafts: cause for concern?

PURPOSE: To report cases of stent and stent-graft fracture in the subclavian vessels. METHODS AND RESULTS: Three patients with self-expanding stents of 3 different types in 1 subclavian artery and 2 subclavian veins presented with recurrent symptoms 6 months to 2 years after stenting. All devices showed signs of compression with stent fracture. The covered stent in the subclavian artery was excised. Of the 2 venous patients, 1 was treated with first rib resection and the other refused further treatment. CONCLUSIONS: The subclavian vessels are prone to flexion during movement, and the vessels may be compressed by external structures, including the clavicle and first rib. Stents that have not been designed to withstand these forces may be damaged.

Adult↗
PubMed1999

Measuring serum total cholesterol: do vascular surgeons know what they are doing?

Raised serum total cholesterol (TC) is an accepted risk factor for both coronary and peripheral vascular disease and three landmark trials have shown the benefit of lowering TC using statins. Vascular surgeons tend to measure TC, but little is known about how they manage hypercholesterolaemia or whether they believe treatment will be of benefit. A questionnaire was sent to listed members of the Vascular Surgical Society of Great Britain and Ireland seeking responses to a range of questions on the measurement and management of raised TC. In all, 374 questionnaires were sent out. The response rate was 67%. Over 90% of respondents said they measured TC and considered a level below 5.5 mmol/l as normal. The cut-off for initiating drug therapy, referral to a dietician or to a lipid specialist varied from 5.5 to 7.5 mmol/l. Most (62%) believed that lowering TC improved coronary mortality, but fewer (26%) that it prevented worsening of claudication. Although most vascular surgeons check for raised TC, the level at which treatment begins and the form it takes varies; in many cases being at odds with recommendations. Few surgeons are convinced of the benefits of lowering TC for claudication and nearly one-fifth do not believe it improves coronary mortality.

Age Factors↗
PubMed1999

A prospective randomised trial of PIN versus conventional stripping in varicose vein surgery.

A prospective, randomised trial was carried out to examine the efficacy of perforate invagination (PIN, Credenhill Ltd, Derbyshire, UK) stripping of the long saphenous vein (LSV) in comparison to conventional stripping (Astratech AB, Sweden) in the surgical management of primary varicose veins. Eighty patients with primary varicosities secondary to sapheno-femoral junction (SFJ) incompetence and LSV reflux were recruited. Patients were randomised to PIN or conventional stripping with all other operative techniques remaining constant. Follow-up was performed at 1 and 6 weeks postoperatively. There were no statistically significant differences between the two techniques in terms of time taken to strip the vein, percentage of vein stripped or the area of bruising at 1 week. The size of the exit site was significantly smaller with the PIN device (P < or = 0.01). Optimal use of the conventional stripper provides results comparable to the PIN device. Choice of stripping device remains the surgeon's, bearing in mind that the PIN stripper achieves slightly better cosmesis.

Adult↗