Biomedical subjects
A Rees
Publications and source records attributed to A Rees.
Evidence for a sound movement area in the human cerebral cortex.
Human listeners can localize sounds by the difference in both arrival time (phase) and loudness between the two ears. Movement of the sound source modulates these cues, and responses to moving sounds have been detected in animals in primary auditory cortex and in humans in other cortical areas. Here we show that detection of changes in the interaural phase or amplitude difference occurs through a mechanism distinct from that used to detect changes in one ear alone. Moreover, a patient with a right hemisphere stroke is unable to detect sound movement, regardless of whether it is defined by phase or by loudness cues. We propose that this deficit reflects damage to a distinct cortical area, outside the classical auditory areas, that is specialized for the detection of sound motion. The deficit is analagous to cerebral akinotopsia (motion blindness) in the visual system, and so the auditory system may, like the visual system, show localization of specialized functions to different cortical regions.
Aligning maps of visual and auditory space. Sensory maps.
Visual and auditory space are represented topographically in the superior colliculus in the midbrain. Recent experiments show that N-methyl-D-aspartate (NMDA) receptors play an important role in aligning auditory and visual maps during development.
Factors influencing plasma lipid profiles including lipoprotein (a) concentrations in renal transplant recipients.
Fasting plasma cholesterol, triglycerides, high-density lipoprotein (HDL) and apoprotein (apo) B were elevated in 214 nondiabetic renal transplant recipients when compared to a reference group. Apo (a) was slightly but not significantly lower in transplant recipients (median 118 mg/dl, range 16-1680 vs 130 mg/dl, 10-1176) and this difference could be predicted from Lp (a) isoform analysis. Cholesterol, triglyceride, apo B and apo (a) concentrations correlated negatively with creatinine clearance but none of these parameters showed a significant association with proteinuria. Patients treated with steroids had higher plasma HDL concentrations than those receiving cyclosporin monotherapy (P < 0.01). The use of diuretics was associated with raised triglycerides (P < 0.001) and cholesterol (P < 0.01) and with reduced HDL (P < 0.01) whilst patients receiving beta-blockers had significantly higher triglycerides (P < 0.01) and lower HDL levels (P < 0.02). In multiple regression analysis, age (P < 0.01), creatinine clearance (P < 0.05) and diuretic therapy (P < 0.005) were independent risk factors for increased cholesterol whilst apo (a) levels correlated negatively with creatinine clearance (P < 0.005). These results suggest that impaired renal function, steroids and non-immunosuppressive drugs contribute to lipid abnormalites in renal transplant recipients.
The topographical organization of descending projections from the central nucleus of the inferior colliculus in guinea pig.
We describe the descending projections from the central nucleus of the inferior colliculus (CNIC) in guinea pig. Focal injections of the tracer biocytin, made in physiologically defined frequency regions of the CNIC, labelled laminated axonal terminal fields in the ipsilateral dorsal nucleus of the lateral lemniscus, and bilaterally in the ventral nucleus of the trapezoid body and the dorsal cochlear nucleus. Labelling was also present in the rostral periolivary nucleus, but we could not distinguish a clear border between the terminal fields in this nucleus and those in the ventral nucleus of the trapezoid body. Labelling observed in the ventral nucleus of the lateral lemniscus, and to a lesser extent in the dorsal nucleus of the lateral lemniscus, was accompanied by retrogradely labelled somata and therefore we cannot conclude unequivocally that the CNIC projects to these lemniscal nuclei. Where the labelling was ordered topographically, its position varied as a function of the best frequency at the injection site. High-frequency regions in the CNIC project to the medial parts of the ventral nucleus of the trapezoid body and dorsal cochlear nucleus, while low-frequency regions in the CNIC project to the lateral parts of the ventral nucleus of the trapezoid body and dorsal cochlear nucleus. Additional axonal labelling with terminal boutons, but with no apparent topographical arrangement, was present in the ipsilateral horizontal cell group, sagulum, and also bilaterally in the superficial granule cell layer of the ventral cochlear nucleus and layer 2 of the dorsal cochlear nucleus. Our findings are consistent with the existence of tonotopically organised feedback projections from the CNIC to the brainstem nuclei that project to it.
Outcomes of time-limited psychotherapy in applied settings: replicating the Second Sheffield Psychotherapy Project.
In a replication and extension of the Second Sheffield Psychotherapy Project (SPP2), a collaborative psychotherapy project (CPP) was carried out at 3 sites within the National Health Service of the United Kingdom. Clients (N = 36) stratified at 3 levels of severity of depression were randomly assigned to one of 2 treatment approaches (psychodynamic-interpersonal or cognitive-behavioral) of 2 time-limited durations (8 or 16 sessions). Gains in both treatment approaches were approximately equivalent and were similar for CPP and SPP2 clients when measured at the end of treatment. However, CPP patients did not maintain their gains to the extent that the SPP2 clients did at 3-month and 1-year follow-up assessments. In the CPP, clients given 16 sessions showed a statistically significant advantage over clients given 8 sessions on some measures at some assessments; in the SPP2, similar effects were noted only among some subgroups of clients.
Dose-effect relations in time-limited psychotherapy for depression.
Criteria for reliable and clinically significant improvement were applied to standard and individually tailored outcome measures data from 212 depressed clients who had been randomly assigned to receive either 8 or 16 sessions of time-limiting psychotherapy. The data were used to address 2 questions: (a) Is the dose-effect curve for psychological symptoms negatively accelerated? and (b) is there a differential rate of response for acute, chronic, and characterological/interpersonal components of depression? The results supported the differential rate of response of different components of depression and suggested qualifications to the acute, chronic, and characterological/interpersonal components and evidence that both supported and qualified previous suggestions that the dose-effect curve is negatively accelerated.
Dexamethasone-suppressible adrenal tumour in untreated 21-hydroxylase deficiency.
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Successful double bypass grafting in a child with coronary artery obstruction due to Kawasaki disease.
We describe the clinical evaluation and surgical treatment of a 7-year-old child who had severe coronary artery obstructions that occurred as a sequela of previously diagnosed Kawasaki disease.
Genetics and molecular biology.
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Stroke and transient ischaemic attacks in association with substance abuse in a young man.
A 22-year-old man with a five-year history of drug and alcohol abuse presented with a left hemiparesis preceded by three transient ischaemic attacks, two of which occurred whilst smoking cannabis. Substance abuse was the only identifiable risk factor for cerebrovascular disease.
Contribution of GABA- and glycine-mediated inhibition to the monaural temporal response properties of neurons in the inferior colliculus.
1. To determine the contribution of inhibition to the generation of the temporal response patterns of neurons in the inferior colliculus (IC), the effects of iontophoretically applied gamma-aminobutyric acid (GABA), glycine, and the GABAA and glycine receptor antagonists, bicuculline and strychnine were studied on 121 neurons in the IC of urethan-anesthetised guinea pig. 2. The neurons temporal discharge patterns were classified into six categories on the basis of their peristimulus time histograms (PSTHs). 1) Onset units fired at the stimulus onset and could be divided into two subtypes: narrow (1-2 spikes only) or broad (response lasting up to approximately 30 ms). 2) Pauser units had a precisely timed onset peak separated from a lower level of sustained activity by either a marked reduction or complete cessation of firing. 3) Chopper units had three or more clearly defined peaks near stimulus onset or evidence of regularly spaced peaks over the duration of the stimulus. 4) Onset-chopper units had three clearly defined peaks at onset but no sustained firing. 5) On-sustained units had a clearly defined single onset peak followed by a lower level of sustained activity. 6) Sustained units fired throughout the stimulus, but lacked an onset peak. 3. Iontophoretic application of GABA and glycine produced a dose-dependent reduction in firing rate in 76% (42/55) and 79% (11/14) of units, respectively. Application of bicuculline or strychnine increased the discharge rate in 91% (64/70) and 94% (16/17) of neurons, respectively. 4. The effects of bicuculline and strychnine on PSTH class were studied in detail on 70 neurons. Changes in discharge rate were accompanied by changes in PSTH in 49% (34/70) of neurons tested with bicuculline and 41% (7/17) tested with strychnine. Pauser units were the most affected with 69% changing their PSTH class, but some units in all PSTH classes, except the chopper group, exhibited changes in PSTH pattern after application of bicuculline. The majority of units (approximately 50%) that changed PSTH pattern in the presence of bicuculline became chopper units. Units of all PSTH classes could become choppers, but the proportion of units showing this change was dependent on the unit's control response pattern. All seven units that changed PSTH class with strychnine also became choppers. Changes in PSTH, including the appearance of a chopper pattern, did not depend on either a unit's control discharge rate or the magnitude of the change in discharge rate induced by the antagonists. 5. Bicuculline and strychnine had no significant effect on latency for units in the chopper, onset-chopper, onset, pauser, and on-sustained groups. A few sustained and unclassified units that had long predrug latencies did show marked reductions in latency when tested with bicuculline. 6. The majority of units did not fire spontaneously, and neither bicuculline or strychnine produced a significant increase in spontaneous rate. 7. In many units, the changes in firing rate did not occur equally over the duration of the response. Firing rates at the onset and in the last quarter of the sustained response were compared. Three effects of bicuculline and strychnine were observed. For 80% of units the largest change in firing rate occurred in the sustained response, while in 14% of units the change was greatest at onset.
Diagnosis of Hirschsprung's disease.
OBJECTIVE: Our aims were to determine the validity of using low-osmolality water-soluble contrast enemas (WSCE) in neonates and infants with suspected Hirschsprung's disease (HD) and to devise a scoring system that uses a checklist of radiologic signs to determine the probability of HD. MATERIALS AND METHODS: The records of all patients referred by pediatric surgeons from 1988 through 1992 for the radiologic investigation of possible HD were retrospectively reviewed. Thirty-eight patients who were from 2 days to 9 months old were studied; 20 of them were neonates (less than 1 month old). Of all the patients, 24 underwent WSCE and the other 14 underwent barium enema. For all patients, HD had been diagnosed by rectal biopsy or excluded by biopsy, clinical follow-up, or both. Radiographs were read by a gastrointestinal radiologist who used a checklist of diagnostic criteria reported in the literature. The sensitivity had specificity of the findings were compared with those in the literature. RESULTS: Of the 18 patients with HD, 12 were neonates. All reported radiologic diagnostic criteria were seen; the frequency, sensitivity, and specificity of the findings were reported. Twenty percent (n = 2) of HD patients in the WSCE group (n = 10) had negative findings. Two of the 12 neonates developed colonic perforation, one during the enema and the other within 24 hr of the procedure. CONCLUSION: WSCE has a sensitivity and specificity equivalent to those of the barium enema for the detection of HD. For the two patients with perforation, the use of WSCE was of considerable benefit, avoiding the problems associated with barium spillage into the peritoneal cavity. A scoring system for diagnostic enemas is feasible.
Substrate-driven formation of a proteolytic antibody light chain.
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Molecular cloning of a proteolytic antibody light chain.
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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.
Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis.
Low-density-lipoprotein (LDL) apheresis has the theoretical advantage over anion-exchange resins and hydroxymethylglutaryl coenzyme A inhibitors of decreasing lipoprotein(a) as well as LDL. To confirm this advantage, patients with heterozygous familial hypercholesterolaemia and coronary artery disease were randomised to receive LDL apheresis fortnightly (with disposable dextran sulphate/cellulose columns) plus simvastatin 40 mg daily, or colestipol 20 g plus simvastatin 40 mg daily. Quantitative coronary angiography was repeated after a mean of 2.1 years in 20 patients undergoing apheresis and in 19 on combination drug therapy. Changes in serum lipoproteins were similar in both groups apart from greater lowering by apheresis of LDL cholesterol (3.2 vs 3.4 mmol/L in drug group, p = 0.03) and lipoprotein(a) (geometric means 14 vs 21 mg/dL, p = 0.03). There were no significant differences in primary angiographic endpoints per patient but lesion-based and segment-based secondary endpoints were biased in favour of the drug group (change in minimum lumen diameter of lesions 0.07 vs -0.004 mm, p = 0.046; change in mean lumen diameter of segments 0.02 vs -0.06 mm, p = 0.01). None of the angiographic changes correlated with lipoprotein(a) concentrations. Per patient changes in % diameter stenosis and minimum lumen diameter in the two groups were as or more favourable than those observed in five published trials that assessed lipid-lowering drug therapy by quantitative coronary angiography. Although LDL apheresis combined with simvastatin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influencing coronary atherosclerosis and should be reserved for patients unresponsive to drugs. Decreasing lipoprotein(a) seems to be unnecessary if LDL cholesterol is reduced to 3.4 mmol/L or less.
Detection of mitochondrial DNA mutations in patients with diabetes mellitus.
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