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Biomedical subjects

A Rees

Publications and source records attributed to A Rees.

At least 19 recordsLinked to original sources

Laminar organization of frequency-defined local axons within and between the inferior colliculi of the guinea pig.

We present a comprehensive description of the local (intrinsic and commissural) connections in the central nucleus of the inferior colliculi (CNICs) in guinea pig. Focal injections of the anterograde tracer biocytin were made into physiologically identified loci of the CNIC and the spatial organisation of the labeled fibres was revealed with computer-assisted three-dimensional (3-D) reconstruction. The intrinsic fibres form a series of V-shaped laminar plexuses composed of fibres bearing both terminal and en passant boutons. Each laminar plexus has a central wing located in the CNIC that extends into the dorsal cortex and an external wing located in the external cortex. The edge where the two wings intersect delimits the lateral border of the central nucleus with the external cortex. The density of labeled terminals was consistently lower in the cortices than in the CNIC. The laminar plexus connects points of similar frequency within the CNIC. Seen in 3-D, the location, orientation, shape, and area of the laminar plexus vary as a function of best frequency. The commissural fibres ending in the contralateral IC to the injection also form a laminar plexus which is symmetrical to the ipsilateral plexus. Electrolytic lesions placed in the contralateral IC at sites with best frequencies corresponding to those of the injection coincided with the terminals of the commissural fibres in most instances. Possible patterns for the organisation of these connections (point-to-point and diverging) are discussed. Three systems of peripheral axons to the laminar plexus are described: parallel, oblique, and perpendicular to the central wing. The novel parallel system has terminals in both ICs that run parallel to the central wing. It might constitute the anatomical basis for across-frequency interactions. The oblique and perpendicular systems are fibres of passage projecting to the commissure and brachium of the IC, respectively.

Acoustic Stimulation

Effects of treatment duration and severity of depression on the maintenance of gains after cognitive-behavioral and psychodynamic-interpersonal psychotherapy.

One hundred four clients completed a mailed follow-up 1 year after completing 8 of 16 sessions of treatment, either cognitive-behavioral (CB) or psychodynamic-interpersonal (PI) psychotherapy. Although mean scores on outcome measures at 1 year suggested that gains were, in general, well maintained, only 29% of clients were asymptomatic on all 3 occasions of testing (end of treatment, 3 months and 1 year later) without recourse to further treatment. However, only 11% of those asymptomatic at end of treatment experienced relapse or recurrence of depression, albeit on the limited evidence of just two follow-up assessments. The results of comparisons among treatment conditions at 1 year differed substantially from those obtained earlier: Eight-session PI treatment now appeared less efficacious than the other 3 treatment conditions, and there was now no measurable benefit of 16-session over 8-session CB, irrespective of initial severity of depression. These findings confirm the importance of follow-up in evaluation of psychotherapies for depression.

Adult

Histological changes associated with an artificial anterior cruciate ligament.

AIMS: To investigate the histopathological features of the synovial lining of the knee following implantation of an artificial cruciate ligament. METHODS: Eighty two patients underwent anterior cruciate ligament reconstruction for chronic, symptomatic instability of the knee. The cruciate ligament was reconstructed with a scaffold type prosthetic ligament. All patients underwent arthroscopy at the time of cruciate reconstruction and also as a "second look" procedure at a mean 26.5 months later, at which time synovial biopsy specimens were obtained in all cases. RESULTS: The most frequent histological finding was granulomatous synovitis in 48% (39/82) of patients. Particulate polyester debris produced a greater response than carbon fibres. In 24% (20/82), nonspecific inflammation was present and in 28% (23/82) the synovium was considered normal. When the prosthetic ligament was fully covered by soft tissue in-growth, a granulomatous reaction was present in 42% (24/57), irrespective of whether the ligament was partially or totally uncovered. Stabilisation of the joint did not prevent subsequent deterioration in the articular cartilage; other factors such as increasing patient age, interval between injury and reconstruction and altered knee kinematics after reconstruction are probably important. Granulomatous synovitis was not associated with progressive chondral changes. CONCLUSIONS: Although present in 48% of cases, granulomatous synovitis was not shown to have adverse effects on either chondral surface or the prosthetic material of the ligament. Rupture of the implant is caused by mechanical factors and granulomatous synovitis is not responsible for implant failure.

Adolescent

Bifocal surgery for deformity and bone loss after lower-limb fractures. Comparison of bone-transport and compression-distraction methods.

We report the results in the first 16 patients treated in Sheffield using bifocal techniques for diaphyseal bone loss and deformity secondary to trauma. Eight patients had bone-transport and eight had compression-distraction methods. At a mean follow-up of 24 months all 16 had excellent or good results with union of the fracture, correction of deformity and normal or near normal leg length. There were no major complications. Mean treatment times were 16 months for bone transport and 9.8 months for compression-distraction. Bone transport was more complicated requiring an average of 2.2 additional operations compared with only one for compression-distraction. Femoral cases had shorter treatment indices than tibial cases but had less favourable outcomes.

Adult

Molecular cloning of a proteolytic antibody light chain.

The cDNA for an antibody light chain raised by immunization against vasoactive intestinal peptide (VIP) was cloned in a bacterial expression vector, and the recombinant light chain was purified to electrophoretic homogeneity. The light chain catalyzed the hydrolysis of VIP efficiently owing to its comparatively high affinity for the substrate. In control experiments, the catalytic activity was preserved at a constant level after further chromatography of the light chain on anion-exchange and gel-filtration fast protein liquid chromatography columns, and it was removed by immunoadsorption with immobilized anti-mouse light chain antibody. The amide bond linking methylcoumarinamide (MCA) and arginine in a tripeptide unrelated in sequence to VIP was cleaved by the light chain with lower affinity and kinetic efficiency (kcat/Km). Hydrolysis of the peptidyl-MCA conjugate was inhibited competitively by the alternate substrate, VIP. The Ki and Km values for VIP were in the same range, indicating that peptide-MCA and VIP hydrolysis occurs at a common catalytic site in the light chain. Molecular modeling suggested the presence of a serine protease-like site in the light chain. This was supported by inhibition of the hydrolytic activity by serine protease inhibitors, but not by inhibitors of other classes of proteases. These observations suggest a poorly discriminatory catalytic site, with specificity for VIP arising chiefly by means of the antigen recognition function of the light chain combining site.

Amino Acid Sequence

Inadequate management of hyperlipidaemia after coronary bypass surgery shown by medical audit.

OBJECTIVE: To audit the detection and management of hyperlipidaemia in patients who have had coronary bypass surgery. PATIENTS: 100 consecutive patients (81 men), mean age 61, who had survived at least 3 months after coronary bypass surgery. METHODS: Retrospective review of case notes and computerised biochemistry records. RESULTS: 83 patients had at least one lipid measurement in the hospital, and of the remaining 17 patients, 10 had undergone urgent or emergency surgery. The median (range) total cholesterol was 6.7 (4.0-11.7) mmol/l and the triglyceride concentration was 2.1 (0.6-18.4) mmol/l. Only 30 patients were referred to a dietician, and 12 were given a lipid lowering drug--these interventions were no more frequent in patients with a cholesterol concentration above than below the median. CONCLUSIONS: Although a high proportion of patients who undergo routine coronary bypass surgery have their plasma lipid concentrations measured, many patients with raised cholesterol concentrations, who would benefit from lipid lowering interventions, are not offered them.

Adult

Binaural masking and sensitivity to interaural delay in the inferior colliculus.

The binaural masking level difference (BMLD) is a psychophysical effect whereby signals masked by a noise at one ear become unmasked by sounds reaching the other. BMLD effects are largest at low frequencies where they depend on signal phase, suggesting that part of the physiological mechanism responsible for the BMLD resides in cells that are sensitive to interaural time disparities. We have investigated a physiological basis for unmasking in the responses of delay-sensitive cells in the central nucleus of the inferior colliculus in anaesthetized guinea pigs. The masking effects of a binaurally presented noise, as a function of the masker delay, were quantified by measuring the number of discharges synchronized to the signal, and by measuring the masked threshold. The noise level for masking was lowest at the best delay for the noise. The mean magnitude of the unmasking across our neural population was similar to the human psychophysical BMLD under the same signal and masker conditions.

Acoustic Stimulation

Insulin receptor and insulin-responsive glucose transporter (GLUT 4) mutations and polymorphisms in a Welsh type 2 (non-insulin-dependent) diabetic population.

We have recently examined the exons encoding the insulin receptor tyrosine kinase domain and GLUT 4 in 30 subjects with Type 2 (non-insulin-dependent) diabetes mellitus using a molecular scanning approach. The variant sequences Val-Met985 and Lys-Glu1068 of the insulin receptor and Val-Ile383 of GLUT 4 were each separately found in three different diabetic subjects. In a study of a Welsh population, the GLUT 4(383) variant was found in three of 160 diabetic and none of the 80 control subjects. In this study, the same group of Welsh Type 2 diabetic and control subjects was analysed using allele-specific oligonucleotide hybridisation, single nucleotide primer extension and allele-specific restriction digestion to ascertain the frequency of the two insulin receptor mutations. The Val-Met985 mutation was found in none of the 160 Welsh Caucasian Type 2 diabetic subjects and two of 80 control subjects. The Lys-Glu1068 mutation removes a Sty 1 site and digestion of amplified exon 18 with Sty 1 confirmed the presence of the mutation in the heterozygous state in the original subject. None of the Welsh diabetic or control subjects had the Glu1068 mutation. The discovery of a very common silent polymorphism at codon 130 of GLUT 4 allowed examination of the association of this locus with Type 2 diabetes using allele-specific oligonucleotide hybridisation in a subset of the Welsh subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles

Surgical management of infective endocarditis in children.

Infective endocarditis occurs infrequently in the general pediatric population, occurring mostly in patients with congenital heart disease. This study reviews our surgical experience with infective endocarditis based on a policy of aggressive intervention, conservative operative debridement, and creative reconstruction options using pericardium and prosthetic heart valves. From 1982 to 1989, 16 patients, 3 weeks to 16 years of age, underwent 19 intracardiac operations for infective endocarditis therapy at Kosair Children's Hospital. Eight (42%) were for resection of vegetations alone; an additional 11 operations (58%) involved more extensive debridements requiring either valve replacement or valvuloplasty using pericardium for exclusion of an abscess cavity, closure of a fistula, or for valve repair. Operative mortality was 25% (4 patients) and related to preoperative disease severity. There was one late death. Offending organisms included Staphylococcus species (31%), Haemophilus influenzae (13%), pneumococcus (5%), gram-negative organisms (13%), and Candida (13%); no organism grew on culture in 25%. We conclude that aggressive surgical exploration in patients with infective endocarditis is indicated and often requires resection of vegetations alone. More extensive procedures should preserve as much valvular tissue as possible. Pericardium is useful for reconstruction after debridement.

Adolescent

Components of major depression examined via the Beck Depression Inventory.

Although more than 20 factor analytic studies have been published on the Beck Depression Inventory (BDI), only Steer and co-workers (1987) have used a sample composed exclusively of patients diagnosed with depression. The component structure found in their study of depressed patients differs in important respects from the structure summarised in several reviews. The main aim of the present study was to investigate whether this structure could be confirmed with the BDI responses of an independent sample of 139 patients diagnosed with DSM-III Major Depressive Episode. Three principal components were extracted and rotated to maximum congruence with a target based on the results of Steer et al. (1987). The significance of the fit to this target was then evaluated by rotating the same matrix of loadings to 5000 random permutations of the target. The fit was found to be highly significant, though some possible improvements could be identified ad hoc. An alternative factor structure for the BDI, derived from covariance structure analysis by Tanaka and Huba (1984), was also tested but could not be confirmed.

Adolescent

Glomerular mesangial cells and inflammatory macrophages ingest neutrophils undergoing apoptosis.

Apoptosis or programmed cell death of senescent neutrophils leading to their uptake by phagocytes is a general mechanism by which neutrophils may be removed from inflamed sites in vivo, promoting resolution rather than persistence of inflammation. We now report morphological evidence of neutrophil apoptosis leading to uptake by glomerular cells in rats with experimental glomerulonephritis. In addition to confirming that inflammatory macrophages take up apoptotic neutrophils, these studies indicated that glomerular mesangial cells can also participate in this mode of neutrophil clearance. Furthermore, human neutrophils which had been "aged" in vitro so as to undergo apoptosis were ingested by 31.5 +/- 1.3% (mean +/- SE) of cultured human mesangial cells, but there was minimal recognition of freshly isolated neutrophils (2.2 +/- 0.1%). Centrifugal elutriation of aged neutrophil populations yielded fractions with varying degrees of apoptosis (from 11.1 to 79.4%). Uptake of these fractions (by 8.2% to 59.8% of mesangial cells) was closely correlated with apoptosis (r = 0.96, P less than 0.0001). This demonstrated that recognition was dependent upon apoptosis, as in previous reports of macrophage recognition of aged neutrophils. However, by contrast, a partial requirement for serum was observed. These data indicate a hitherto unexpected function for the mesangial cell in clearance of senescent neutrophils from the glomerulus which may supplement inflammatory macrophage uptake of leucocytes undergoing apoptosis.

Animals

Glycosylated haemoglobin in the diagnosis of diabetes mellitus in elderly people.

An oral glucose tolerance test (OGTT, 75 g WHO criteria) was applied to healthy elderly subjects (mean age 76 years) within a week of measurement of random blood glucose and glycosylated haemoglobin (HbA1). The 'Corning' method was used to assay HbA1 (established normal range for our laboratory 5-8%). Sixty-five subjects (38 women) of whom 54 were not diabetic on WHO criteria for OGTT participated in the study. Five of the 54 patients with non-diabetic OGTT results had abnormal HbA1 (greater than 8%). These five subjects had no evidence of impaired glucose tolerance. Eleven subjects had diabetic OGTT results of whom only four had raised HbA1 assay results. Seven subjects had normal HbA1 in spite of diabetic OGTT. The mean HbA1 in the group of subjects with normal OGTT (n = 52) was 6.7% (SD 1.05, range 4.6-8.7%). It appears from our study that the normal range of HbA1 in elderly subjects is not markedly different from established normal values. The poor sensitivity (36%) and predictive value (44%) of abnormal HbA1 in detecting diabetes, as shown in our study, would not permit its use for screening purposes nor as a confirmatory test for diabetes in elderly subjects.

Aged