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Biomedical subjects

S Thorpe

Publications and source records attributed to S Thorpe.

At least 19 recordsLinked to original sources

Brain areas involved in rapid categorization of natural images: an event-related fMRI study.

Event-related fMRI was used to investigate brain activation during a visual go/no-go categorization task based on colored photographs of natural scenes, similar to a previous ERP study by Thorpe et al. (1996, Nature 381: 520-522). Subjects had to press a key when an animal was present in the display. Stimuli were flashed for 33 ms using an intertrial interval of 5 s and a design that carefully balanced targets and distractors in a pseudo-random sequence. Activation produced by targets and distractors was compared with two different techniques, one based on correlations with the stimulation pattern, the other using simple t score statistics to compare selected scans. The contralateral primary motor cortex and the ipsilateral cerebellum were both more active following target trials than following distractors, thus confirming the sensitivity of the method. Differential activity was also seen in the posterior cingulate cortex, the fusiform, and the parahippocampic gyri. Activity in such structures could underlie the differential evoked-potentials reported previously in the same task. Surprisingly, in these visual structures, the signal was stronger following distractor trials than target ones. This result could be due to more prolonged processing on distractor trials. Alternatively, it could be that target detection induces strong activation of a small proportion of neurons, which, because of competitive inhibitory mechanisms, could result in a decrease in activity for the population as a whole. We suggest that this kind of mechanism could also account for the decreases in signal observed in perceptual priming experiments.

Adult↗

Responsibility attitudes and interpretations are characteristic of obsessive compulsive disorder.

The cognitive-behavioural theory of Obsessive Compulsive Disorder (OCD) proposes that a key factor influencing obsessional behaviour is the way in which the intrusive cognitions are interpreted. The present paper reports an investigation of links between clinical symptoms (of anxiety, depression and obsessionality) and responsibility beliefs. These beliefs include not only measures of general responsibility attitudes (assumptions) but also more specific responsibility appraisals consequent on intrusive cognitions. The characteristics of two new questionnaires specifically designed to measure these beliefs were assessed in patients suffering from Obsessive Compulsive Disorder, in patients suffering from other anxiety disorders and in non-clinical controls. The scales measuring negative beliefs about responsibility were found to have good reliability and internal consistency. Comparisons between criterion groups indicate considerable specificity for both assumptions and appraisals with respect to OCD. There was also good evidence of specificity in the association between responsibility cognitions and obsessional symptoms across groups, and that this association was not a consequence of links with anxiety or depressive symptoms. Although the two measures were correlated, they each made unique contributions to the prediction of obsessional symptoms. Overall, the results are consistent with the hypothesis that responsibility beliefs are important in the experience of obsessional problems.

Adult↗

The use of a blood conservation pressure transducer system in critically ill patients.

We tried to determine if a blood conservation pressure transducer system reduced blood transfusions, increased haemoglobin concentration or reduced line infections in critically ill patients. One hundred patients were randomly allocated to conventional or blood conserving systems attached to systemic and pulmonary arterial catheters. Intravascular lines were cultured after removal. There were no significant differences in transfusions or haemoglobin concentration. Blood conservation: median units transfused, 2 (range 0-19); mean haemoglobin at 7 days, 11.2 g.dl-1 (SD, 1.0). Conventional: median units, 2 (range 0-34); mean haemoglobin at 7 days, 11.1 g.dl-1 (SD 1.0). Thirty-seven of 99 arterial lines were colonised in the controls compared with 29 of 96 in the blood conservation group. Patients who required haemofiltration in both groups had significantly increased transfusion requirements. Haemofiltration: median 6 units (range 0-34) vs. non-haemofiltered: median 1 (range 0-14; p < 0.001). There were no significant differences in transfusions, haemoglobin concentration or line colonisation with the blood conservation system. There is considerable potential for blood conservation during haemofiltration.

Adult↗

Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer.

The progesterone receptor antagonist, Onapristone, is an effective endocrine agent in experimental breast cancer models. This study aimed to investigate this agent as first-line endocrine therapy in patients with breast cancer. However, owing to the recognition in this and other clinical studies that some patients on Onapristone developed liver function test abnormalities, the development of this drug and recruitment to the study stopped in 1995. 19 patients either with locally advanced breast cancer (n = 12) or who were elderly, unfit patients with primary breast cancer (n = 7) received Onapristone 100 mg/day. Seventeen of the 19 tumours expressed oestrogen receptors (ER) whilst 12 of the 18 tumours tested expressed progesterone receptors (PgR). Tumour remission was categorised by International Union Against Cancer criteria. One patient was withdrawn after 4.5 months while her disease was static. Of the remaining 18 patients, 10 (56%) showed a partial response and 2 (11%) durable static disease (> or = 6 months), giving an overall tumour remission rate of 67%. The median duration of remission was 70 weeks. Transient liver function test abnormalities developed in a number of patients, mainly during the first 6 weeks of treatment. In conclusion Onapristone can induce tumour responses in human breast cancer.

Antineoplastic Agents↗

Radiotherapy enhances laser palliation of malignant dysphagia: a randomised study.

BACKGROUND/AIMS: A major drawback of laser endoscopy in the palliation of malignant dysphagia is the need for repeated treatments. This study was designed to test whether external beam radiotherapy would reduce the necessity for repeated laser therapy. PATIENTS/METHODS: Sixty seven patients with inoperable oesophageal or gastric cardia cancers and satisfactory swallowing after initial laser recanalisation were randomised to palliative external beam radiotherapy (30 Gy in 10 fractions) or no radiotherapy. All patients underwent a 'check' endoscopy five weeks after initial recanalisation and were subsequently reendoscoped only for recurrent dysphagia, which occurred in 59 patients. RESULTS: Dysphagia was relieved equally well in both groups and the improvement was maintained with further endoscopic treatment. The initial dysphagia controlled interval and the duration between procedures required to maintain lifelong palliation (treatment interval) increased from five to nine weeks (median) in the radiotherapy group (p < 0.01 both parameters). Radiotherapy was well tolerated in all but three patients. One perforation occurred and two fistulae opened after dilatation in patients who received radiotherapy. CONCLUSION: Additional radiotherapy reduces the necessity for therapeutic endoscopy for a patient's remaining life. It has an important role in relatively well patients who are likely to survive long enough to benefit.

Aged↗

The effects of spatial frequency on binocular fusion: from elementary to complex images.

Factors limiting binocular fusion were studied using 2-dimensional difference of Gaussian (2D-DOG) stimuli. The proportion of fused stimuli and observer's response time were determined for stimuli that varied in spatial frequency composition between 0.22 and 4.8 cycles per degree. At small disparities, mean fusion response times were short and relatively stable but increased rapidly once the disparity reached a certain critical value. This 2-phase function implies the existence of 2 separate fusional mechanisms: a rapid neurally based fusional process, which operates at small disparities, and a second mechanism involving reflexive vergence movements operating at disparities 2 to 3 times larger. Both mechanisms are highly influenced by spatial frequency, being 4 to 5 times more effective at low spatial frequencies. Additional experiments demonstrated that with compound stimuli, the fusion limit is not determined by the highest spatial frequency components (as had been reported previously) but, rather, can take advantage of the additional fusional range associated with low spatial frequencies. Such cooperation may be obvious only in the case of 2-dimensional stimuli.

Depth Perception↗

Speed of processing in the human visual system.

How long does it take for the human visual system to process a complex natural image? Subjectively, recognition of familiar objects and scenes appears to be virtually instantaneous, but measuring this processing time experimentally has proved difficult. Behavioural measures such as reaction times can be used, but these include not only visual processing but also the time required for response execution. However, event-related potentials (ERPs) can sometimes reveal signs of neural processing well before the motor output. Here we use a go/no-go categorization task in which subjects have to decide whether a previously unseen photograph, flashed on for just 20 ms, contains an animal. ERP analysis revealed a frontal negativity specific to no-go trials that develops roughly 150 ms after stimulus onset. We conclude that the visual processing needed to perform this highly demanding task can be achieved in under 150 ms.

Adult↗

Neural processing of stereopsis as a function of viewing distance in primate visual cortical area V1.

1. The influence of viewing distance on disparity selectivity was investigated in area V1 of behaving monkeys. While the animals performed a fixation task, cortical cells were recorded extracellularly in the foveal representation of the visual field. Disparity selectivity was assessed by using static random dot stereograms (RDSs) through red/green filters flashed over the central fixation target. To determine the influence of the viewing distance, a color video monitor was positioned at fixed distances of 20, 40, or 80 cm. The same RDSs with the same angular size of dots were used at the three distances. 2. Disparity sensitivity was tested on 139 cells, of which 78 were analyzed at two or more distances and the rest (61) at a single distance. When disparity selectivity was analyzed at a given distance, about half the cells were found to be selective at 40 or 80 cm, but only a third at 20 cm. Near cells were > or = 1.5 times more common than far cells at all three distances. The latency distribution of the responses of disparity-selective (DS) cells was similar at all three distances, with a mean distribution centered around 60 ms. 3. Changing the viewing distance drastically affected the neural activity of the V1 neurons. The visual responsiveness of 60 of 78 cells (77%) was significantly changed. Disparity selectivity could be present at a given distance and absent at other(s), with often a loss of visual response. This emergence of disparity coding was the strongest effect (28 of 78 or 36%) and occurred more frequently from short to long distances. Among the cells that remained disparity insensitive at all recorded distances (31 of 78 or 40%), about half also showed modulations of the amplitude of the visual response. For cells that remained DS at all recorded distances (13 of 78 or 17%), changing the viewing distance also affected the sharpness (or magnitude) of disparity coding in terms of level of visual responsiveness and those changes were often combined with variations in tuning width. In only two cells did the peak of selectivity type change. Finally, the activity of four DS cells was not affected at all by the viewing distance. 4. Another effect concerned the level of ongoing activity (OA), defined as being the neural activity in darkness preceding the flash of the visual stimulus while the monkey was fixating the small bright target. Changing the viewing distance resulted in significant changes in OA level for more than half of the cells (41 of 78 or 53%). The most common effect was an increase in OA level at the shorter distance. The modulations of both visual responsiveness and OA could occur simultaneously, although they often had opposite signs. Indeed, the two effects were statistically independent of each other, i.e., modulations of visual responses were not related to the level of excitability of the neurons. 5. Control experiments were performed that showed that the effects of changing the viewing distance were not due to the retinal patterns in that the modulations of visual responsiveness were independent of the dot density. Seventeen cells were also tested for a possible effect of vergence by the use of prisms. When there was an effect of distance, it could be closely or partially reproduced by using prisms. These controls, together with the effects observed on OA, strongly suggest that the modulations of neural activity of the V1 neurons by the viewing distance are extraretinal in origin, probably proprioceptive. 6. The modulation of visual responsiveness by the viewing distance in the primary visual cortex indicates that integration of information from both retinal and extraretinal sources can occur early in the visual processing pathway for cortical representation of three-dimensional space. A functional scheme of three-dimensional cortical circuitry is discussed that shows cortical areas where disparity selectivity and modulations of visual activity by the angle of gaze have been described so far.

Animals↗

The efficacy of the Prescription of Gain/Output (POGO) in fitting hearing aids to mild and moderate sensorineural hearing losses.

This study investigated the effectiveness of the application of the Prescription of Gain/Output (POGO) in hearing aid fittings. Six subjects were tested. Each presented with binaural mild to moderate sensorineural hearing losses and were previously fitted monaurally with behind-the-ear aids using modifications of the traditional Carhart (1946) approach. Functional gain requirements stipulated by POGO were calculated from unaided thresholds and compared to actual functional gain measurements. Five subjects, whose functional gain measures were not within prescribed limits, were referred for modification of the gain and frequency responses of their hearing aids and earmoulds. Post-modified functional gain measurements were analysed. The extent to which the required functional gain measurements were met, was investigated statistically in relation to word recognition scores and subjective ratings of perceived benefit. The conclusion reached was that the application of POGO results in improved word recognition scores and self-reported user satisfaction.

Acoustics↗

Radiation enhancement of laser palliation for advanced rectal and rectosigmoid cancer: a pilot study.

Laser palliation for advanced rectal or rectosigmoid cancer requires repeat treatments every four to six weeks. Thirteen patients (seven men, six women) age range 65-91 (median 81) received additional external beam radiotherapy in an attempt to reduce the frequency of laser treatments required. After successful laser recanalisation, patients were treated with a dose of 30-55 Gy in 10-20 fractions. Bowel symptoms were well controlled for prolonged periods in 11 patients (85%) and further laser procedures were only required every 19 weeks median (range 6-53 weeks). The laser energy required after radiotherapy was only 800 J/month (median). Survival was 14 months (median, range 2.5-20 months) for the seven patients who have died. Seven patients received laser treatment only for three months or more (median 14 weeks, range 13-39). In this group control of symptoms required procedures every four weeks (median) before radiotherapy and 20 weeks (median) afterwards. The laser energy required before radiotherapy was 15,000 J/month and 2000 J/month afterwards (Wilcoxon rank sum test, p < 0.01 for both). Radiotherapy was well tolerated in all but one patient. Three patients developed strictures after radiotherapy but all were dealt with endoscopically. There were no complications solely due to endoscopic procedures. Additional radiotherapy enhances laser palliation for inoperable rectal or rectosigmoid cancer.

Aged↗

Modulation of neural stereoscopic processing in primate area V1 by the viewing distance.

Accurate binocular depth perception requires information about both stereopsis (relative depth) and distance (absolute depth). It is unclear how these two types of information are integrated in the visual system. In alert, behaving monkeys the responsiveness of a large majority of neurons in the primary visual cortex (area V1) was modulated by the viewing distance. This phenomenon affected particularly disparity-related activity and background activity and was not dependent on the pattern of retinal stimulation. Therefore, extraretinal factors, probably related to ocular vergence or accommodation, or both, can affect processing early in the visual pathway. Such modulations could be useful for (i) judging true distance and (ii) scaling retinal disparity to give information about three-dimensional shape.

Animals↗

Radiation enhancement of laser palliation for malignant dysphagia: a pilot study.

Laser therapy offers rapid relief of dysphagia for patients with cancers of the oesophagus and gastric cardia but repeat treatments are required approximately every five weeks to maintain good swallowing. To try to prolong the treatment interval, 22 elderly patients were given additional external beam radiotherapy. Nine had squamous cell carcinoma and 13 adenocarcinoma: five had documented metastases. Six received 40 Gy and 16,30 Gy in 10-20 fractions. A 'check' endoscopy was performed three weeks after external beam radiotherapy. Dysphagia was graded from 0-4 (0 = normal; 4 = dysphagia for liquids). The median dysphagia grade improved from 3 to 1 after laser treatment. This improvement was maintained in the 30 Gy group but there was a noticeable deterioration in three of those who had received the higher radiation dose. A lifelong dysphagia grade of 2 or better was enjoyed by 14 of 16 patients in the 30 Gy group but only two of six in the 40 Gy group. The dysphagia controlled interval was 9 weeks (median) after check endoscopy and subsequent endoscopic procedures were required every 13 weeks to maintain good swallowing. There were no endoscopy related complications. Combined treatment is a promising approach for reducing the frequency of endoscopic treatments. The 30 Gy dose seems more appropriate and may prolong survival. A randomised study to test these conclusions is in progress.

Aged↗

Cellular analogs of visual cortical epigenesis. I. Plasticity of orientation selectivity.

A differential pairing procedure was applied in vivo to individual neurons in the primary visual cortex of anesthetized paralyzed cats, in order to produce changes in their relative orientation preference. While we recorded from a single cell, its visual response to a light bar was driven iontophoretically to a "high" level when stimulating with an initially nonpreferred orientation (S+), and alternately reduced to a "low" level when stimulating with the preferred orientation (S). This associative procedure was devised to test the possible role of neuronal coactivity in controlling the plasticity of orientation selectivity. Among 87 cells tested, 35 (40%) showed significant long-lasting changes, either in the relative orientation preference for the two "paired" stimuli S+ and S-, in the global orientation tuning profile, or in both. Measurements of relative orientation preference demonstrated significant effects in 27 cells (31%), all in favor of the positively reinforced orientation (S+). Modifications of orientation selectivity (studied over the entire orientation spectrum in 45 of the conditioned cells) usually consisted (21 out of 25 modified cells) of a competitive reorganization of the orientation tuning curve: the preferred orientation shifted toward S+, and a loss of relative visual responsiveness was observed for orientations close to the negatively reinforced orientation (S-). The largest changes were found in deprived kittens at the peak of the critical period, although the probability of inducing a significant change studied during the first year of postnatal life was independent of age. These functional modifications demonstrated at the cellular level are analogous to those induced by a global manipulation of the visual environment, when only a restricted spectrum of orientations is experienced during the critical period. Our results support the hypothesis that covariance levels between pre- and postsynaptic activity determine the sign and the amplitude of the modification of efficacy of cortical synapses.

Animals↗

A cellular analogue of visual cortical plasticity.

Neuronal activity plays an important role in the development of the visual pathway. The modulation of synaptic transmission by temporal correlation between pre- and postsynaptic activity is one mechanism which could underly visual cortical plasticity. We report here that functional changes in single neurons of area 17, analogous to those known to take place during epigenesis of visual cortex, can be induced experimentally during the time of recording. This was done by a differential pairing procedure, during which iontophoresis was used to artificially increase the visual response for a given stimulus, and to decrease (or block) the response for a second stimulus which differed in ocularity or orientation. Long-term modifications in ocular dominance and orientation selectivity were produced in 33% and 43% of recorded cells respectively. Neuronal selectivity was nearly always displaced towards the stimulus paired with the reinforced visual response. The largest changes were obtained at the peak of the critical period in normally reared and visually deprived kittens, but changes were also observed in adults. Our findings support the role of temporal correlation between pre- and postsynaptic activity in the induction of long-lasting modifications of synaptic transmission during development, and in associative learning.

Afferent Pathways↗

Adjuvant treatment of postmenopausal patients with high risk primary breast cancer. Results from the Danish adjuvant trials DBCG 77 C and DBCG 82 C.

The efficacy of adjuvant treatment with tamoxifen was evaluated in protocol DBCG 77 C. Postmenopausal high risk patients (tumor greater than 5 cm, positive axillary nodes, or invasion to skin/fascia) were randomized after total mastectomy and axillary sampling to postoperative radiotherapy (control) or to radiotherapy plus treatment with tamoxifen (TAM), 30 mg daily for 1 year. A total of 1,716 patients entered the study. At 8 years of follow-up, (7 years median time of observation), we observed a significant increase of recurrence-free survival for the TAM treated group and a reduction in mortality, which is significant for patients less than 70 years of age. Retrospectively, an increased recurrence-free survival in TAM treated patients was significant in the following subgroups: tumor less than 5 cm, positive lymph nodes, anaplasia grade II and estrogen receptor level greater than 100 fmol/mg cytosol protein. In the subsequent trial (DBCG 82 C), 1,347 postmenopausal patients less than 70 years were randomized to one of the following 3 regimens: radiotherapy + tamoxifen, 30 mg daily for 1 year (TAM), TAM alone, or TAM + CMF (CMF i.v. day 1 every 4 weeks x 9). The survival is similar in the 3 groups at 4 years (2 years median time of observation).

Aged↗

DNA ploidy and S-phase fraction in primary breast carcinomas in relation to prognostic factors and survival for premenopausal patients at high risk for recurrent disease.

Fine needle aspiration on small tumour pieces from 153 premenopausal women with primary breast cancer at high risk for developing recurrent disease has been used for flow cytometric DNA analysis; 133 of the tumours had either one or more cell populations different from diploid or a single, diploid cell population with an aspiration cytology showing presence of typical tumour cells. The distribution of tumour cell populations in this material was rather unusual with a high number of tetraploid populations. There were significant differences between various DNA ploidy classes with respect to prognostic factors such as lymph node involvement and oestrogen and progesterone receptor status. The S-phase fraction was significantly lower for diploid tumour cell populations compared to aneuploid populations. Diploid tumours with high S-phase fraction were not correlated to prognostic factors usually indicating a poor prognosis. Patients with an aneuploid tumour cell population classified as medium aneuploid had a significantly shorter recurrence-free survival than the rest of the patients. No conclusion on the effect of adjuvant treatment for patients with different tumour cell populations can be made at present.

Breast Neoplasms↗

Altered progesterone/estrogen receptor ratios in endometriosis. A comparative study of steroid receptors and morphology in endometriosis and endometrium.

In a comparative study of endometriosis and endometrium, specimens were taken from both endometriotic and endometrial tissue in 14 patients. Receptor assays and histological examinations were performed on both specimens. Cytosolic estrogen receptors (ERc) as well as cytosolic progesterone receptors (PRc) were detected in 9/14 and 12/12 cases of endometriosis respectively. Nuclear estrogen receptors (ERn) were detected in 4/4 cases of endometriosis. Expressed as fmol/mg cytosol protein, significantly higher values of both ERc and PRc were found in endometrium than endometriosis (p less than 0.01). However, when the ratio between PRc and ERc was considered, significantly higher PRc/ERc ratios were found in the cytosol of endometriotic tissue (p less than 0.01). Thus the lower receptor concentrations found in endometriosis cannot be explained solely as ectopic endometrium being diluted by nonreceptor-containing tissue. In spite of high PRc/ERc ratios in endometriosis, secretory changes similar to those found in endometrium were observed in only one of 7 cases (p less than 0.05).

Adult↗