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Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 37 records · Page 2Linked to original sources

Directional motion asymmetry in infant VEPs--which direction?

Monocular viewing during early infancy reveals asymmetries in optokinetic nystagmus (OKN) and visual evoked potentials (VEPs). This study investigates the VEP asymmetry to see if it is consistent in direction with the OKN asymmetry. Steady-state VEPs were recorded from infants (5-21 weeks) viewing gratings that underwent successive displacements in the same direction, leftward or rightward. In addition, transient VEPs were recorded to the two directions of an oscillating stimulus. Both tests produced larger VEP amplitudes for nasal-to-temporal compared to temporal-to-nasal movement. Horizontal eye movements were monitored by EOG while viewing these stimuli to test whether the asymmetry was a consequence of eye movements. No difference in eye movements as a function of the stimulus was found, excluding differences in retinal slip as an explanation of the asymmetry. The stronger neural response for nasal-to-temporal displacements is opposite to the asymmetry of OKN. Oculomotor and VEP asymmetries may be related; however this relationship is not simply that the stronger neural response, indicated by the VEP, leads to a stronger optokinetic response.

Adult↗

Scrotal abscess following appendectomy.

Postoperative infectious complications in children following perforated appendicitis present in diverse ways. We present two unusual complications of appendectomy for perforated appendicitis: an acute scrotum after open and laparoscopic appendectomy. A retrospective review of two cases of scrotal abscess following appendectomy at our hospital as well as a MEDLINE search was performed to review the clinical presentation, etiology, type of treatment, and outcome of these patients. Although scrotal inflammation occurring postoperatively in a patient with perforated appendicitis may be due to an incarcerated hernia, it is much more likely to be due to a scrotal abscess. Patients without a patent processus vaginalis or inguinal hernia at initial presentation of peritonitis must be carefully followed in the postoperative period and explored early if testicular or scrotal pain becomes manifest.

Abscess↗

Cushing's disease due to plurihormonal adrenocorticotropic hormone and gonadotropin-producing pituitary adenoma.

A 67-year-old woman presented with clinical features of hypercortisolism in association with an invasive pituitary macroadenoma. Adrenocorticotropic hormone (ACTH)-dependent Cushing's disease was documented, and the resected tumor was chromophobic, weakly positive with periodic-Schiff reagent, and showed immunostaining for ACTH and beta-endorphin in a minority of adenoma cells. Both luteinizing hormone and alpha-subunit staining were also observed, but no follicle-stimulating hormone reactivity was seen. Ultrastructurally, the tumor showed typical features of a gonadotroph adenoma of female type. Immunoelectron microscopy showed that ACTH was not produced in corticotrophs, but in cells with the characteristic features of gonadotrophs. This represents the second report of a plurihormonal gonadotroph adenoma producing sufficient ACTH to result in pituitary-dependent Cushing's disease.

Adenoma↗

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification.

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Adult↗

Interaction of hand use and spatial selective attention in children.

It has been argued that concurrent motor action can modulate visual spatial attention. The visual spatial biases of adult patients with unilateral neglect, for example, can be ameliorated by simultaneous use of the contralesional hand. Such improvements are most dramatic when the contralesional hand is moved within contralesional space. To date, evidence of such an interaction in neurologically healthy individuals has not been presented. Line bisection is a simple task that is sensitive to attentional spatial bias. When young children are asked to bisect horizontal lines using their right hands, they show a reliable, if small, bias that is consistent with the pattern seen in adult neglect. This bias is reversed when the left hand is used. Here, we show that these effects are significantly modulated by the location of the movements relative to the body mid-line - specifically that the conjunction of hand movements within ipsilateral space is necessary for the previously reported pattern to be observed. We further demonstrate that these effects are not present in the bisections of neurologically healthy adults. In a final study, we examined whether the hand movement effects seen in children's line bisections would persist in a purely visual task (that is when the movements were made irrelevant to the response). Again, significant modulation of children's perception by concurrent hand movements - and the relative location of those movements - was observed. The theoretical and clinical implications of the results are discussed.

Attention↗

Cerebrovascular structure and dementia: new drug targets.

Effective pharmacological treatment of cognitive disorders in dementia is lacking despite extensive efforts to produce active therapy aimed at neuronal and vascular targets. In this review, the evidence for the involvement of vascular mechanisms in the pathology and evolution of dementia will be examined and the potential importance of age-related changes in cerebrovascular structure and cerebral blood flow (CBF) autoregulation will be discussed. With a description of recent clinical results (on statins, angiotensin-converting enzyme inhibitors and Ca(2+) channel blockers) and experimental results (on beta-amyloid), the impact of drugs on cerebrovascular targets is examined. The working hypothesis that targeting vascular mechanisms in dementia is an option for future therapy is proposed.

Animals↗

Visual and visuospatial development in young children with Williams syndrome.

This study investigated the relation between sensory visual problems and the severity of visuospatial difficulties in a large group of young children with Williams' syndrome (WS). A questionnaire describing visual and associated problems was completed by the families of 108 children with WS and detailed follow-up assessments were conducted, including visual, spatial, motor, visuocognitive, and linguistic tests of 73 of these children (mean age 7 years 3 months; 40 males, 73 females). Children with WS showed a much higher incidence of common paediatric sensory vision problems (strabismus, visual acuity loss, amblyopia, reduced stereopsis) than normally developing children. It was found that delays with respect to age normative values increased with age on all tests. No significant correlation was found between the presence of a visual deficit and the severity of the visuospatial problems, suggesting that the difficulties children with WS have in understanding spatial arrangements are not simply a result of their earlier sensory visual problems. Results confirm the dissociation between visuospatial and language abilities in children with WS, and support the neurobiological model of a split between ventral and dorsal stream processing of visual information with a generalized deficit in dorsal stream processing in young children with WS.

Amblyopia↗

The development of reaching and looking preferences in infants to objects of different sizes.

Reaching and looking preferences and movement kinematics were recorded in 5-15-month-old infants, who were divided into 3 age groups. Infants were presented with pairs of cylinders of 3 different diameters: small (1-cm diameter), medium (2.5-cm diameter), and large (6-cm diameter). Whereas infants between 5 and 12 months of age showed a preference for looking first at the large object, a significant preference for reaching to smaller (graspable) objects was observed in 81/2-12-month-old infants. Kinematic measures suggest that the onset of object-oriented action requires a slowing down of the reach and an extended "homing-in" phase. The divergent looking and reaching preferences in infants at different ages may reflect a dissociation during development of visual processing streams subserving object-related action from those related to visual orienting.

Choice Behavior↗

Melatonin increases pial artery tone and decreases the lower limit of cerebral blood flow autoregulation.

We studied a possible link between the melatonin-induced increase in cerebral arteriolar tone and the melatonin-induced shift in cerebral blood flow (CBF) autoregulation to a lower pressure level. Using the cranial window technique, we showed that intravenous infusion of melatonin constricted pial arterioles (-5.1 +/- 1.3 and -5.4 +/- 0.7 microm at 60 and 600 ng/kg/h, respectively). Perivascular application of luzindole alone had no significant effect but abolished vasoconstriction induced by melatonin (-0.5 +/- 0.7 and + 3.0 +/- 1.2 microm at 60 and 600 ng/kg/h respectively). Using a combination of the hydrogen clearance and cranial window techniques, we showed that intravenous infusion of melatonin had no effect on baseline CBF but shifted the lower limit (LL) of CBF autoregulation (stepwise hypotension) to a lower pressure (90 +/- 2 mmHg in vehicle vs. 71 +/- 3 and 51 +/- 5 mmHg, both P < 0.05, after melatonin at 60 and 600 ng/kg/h, respectively). As melatonin had no effect on systemic blood pressure yet shifted the LL of CBF autoregulation, the security margin increased (28 +/- 5 in controls vs. 38 +/- 3 and 55 +/- 5% after melatonin at 60 and 600 ng/kg/h, respectively, both P < 0.05). The higher i.v. infusion rate of melatonin increased the relative arteriolar dilatory response to hypotension but did not increase absolute diameter at any given pressure level. Our results show that melatonin shifts the LL of CBF autoregulation to a lower systemic pressure level. This effect does not appear to be explained by the effect of melatonin on cerebral arteriolar diameter.

Animals↗

Brain areas sensitive to coherent visual motion.

Detection of coherent motion versus noise is widely used as a measure of global visual-motion processing. To localise the human brain mechanisms involved in this performance, functional magnetic resonance imaging (fMRI) was used to compare brain activation during viewing of coherently moving random dots with that during viewing spatially and temporally comparable dynamic noise. Rates of reversal of coherent motion and coherent-motion velocities (5 versus 20 deg s-1) were also compared. Differences in local activation between conditions were analysed by statistical parametric mapping. Greater activation by coherent motion compared to noise was found in V5 and putative V3A, but not in V1. In addition there were foci of activation on the occipital ventral surface, the intraparietal sulcus, and superior temporal sulcus. Thus, coherent-motion information has distinctive effects in a number of extrastriate visual brain areas. The rate of motion reversal showed only weak effects in motion-sensitive areas. V1 was better activated by noise than by coherent motion, possibly reflecting activation of neurons with a wider range of motion selectivities. This activation was at a more anterior location in the comparison of noise with the faster velocity, suggesting that 20 deg s-1 is beyond the velocity range of the V1 representation of central visual field. These results support the use of motion-coherence tests for extrastriate as opposed to V1 function. However, sensitivity to motion coherence is not confined to V5, and may extend beyond the classically defined dorsal stream.

Brain↗

Relationships between clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine human cervix carcinoma cell lines.

PURPOSE: To compare clonogenic cell survival, DNA damage and chromosomal radiosensitivity in nine cervix carcinoma cell lines. MATERIALS AND METHODS: Initial and residual (after 24h repair) radiation-induced DNA damage was evaluated using pulsed field gel electrophoresis. Chromosome damage was measured by micronucleus (MN) induction in cytochalasin-B-induced binucleate cells. RESULTS: Significant differences between the cell lines were obtained in the induced levels of initial damage, residual damage and MN. Values for SF2 for the nine cell lines ranged from 0.36 to 0.92. No correlation was found between clonogenic measurements of radiosensitivity and initial DNA damage dose response slopes. However, borderline significant correlations were seen between clonogenic radiosensitivity data and the levels of residual DNA damage. There was no correlation between clonogenic radiosensitivity and the levels of radiation-induced MN. Cell lines with high levels of initial damage had high yields of MN induced by radiation and the correlation seen was significant. CONCLUSIONS: The poor correlation between the different endpoints precludes their use in a clinical setting on primary tumour samples in vitro. It may be that tumour cell lines in vitro are a poor model for tumours in vivo. Studies aimed at assessing assays for measuring tumour radiosensitivity therefore should employ clinical samples. In vitro cell line work should concentrate on unravelling the complex mechanisms involved in determining a radiosensitive or radioresistant phenotype.

Cell Nucleus↗

Laparoscopic and thoracoscopic esophagomyotomy for children with achalasia.

BACKGROUND: Minimally invasive esophagomyotomy, consisting of a laparoscopic or thoracoscopic approach, has become a preferred surgical treatment for adults with achalasia. This multicenter study reports on the clinical status of children who have undergone minimally invasive esophagomyotomy for achalasia. METHODS: Symptomatology for achalasia was assessed in 22 pediatric patients who underwent minimally invasive esophagomyotomy for achalasia between 1995 and 2000. All patients were evaluated for duration of hospitalization, postoperative resumption of feeds, postoperative complications, and symptomatic relief. Participants were assigned pre-and postoperative symptom severity scores ranging from 0 (no symptoms) to 3 (severe). RESULTS: The median age of the 10 females and 12 males at time of surgery was 11.3 years +/- 3.4 (standard deviation). Transabdominal laparoscopic esophagomyotomy with fundoplication was performed in 18 patients, and thoracoscopic esophagomyotomy without fundoplication was performed in 4. Two patients required conversion from transabdominal laparoscopic esophagomyotomy to open esophagomyotomy because of intraoperative esophageal perforation. The mean duration of postsurgical follow-up was 17 +/- 16 (standard deviation) months (range, 1-54 months). Mean duration of hospitalization (days +/- standard error or mean) was less for transabdominal laparoscopic esophagomyotomy than for converted open esophagomyotomy (2.7 +/- 0.3 vs. 9.0 +/- 3.0 days; P < 0.05) or for thoracoscopic esophagomyotomy (4.8 +/- 1.7 days; P = not significant). Mean time to resumption of soft feedings (days +/- standard error or mean) occurred sooner after transabdominal laparoscopic esophagomyotomy than after converted open esophagomyotomy (2.0 +/- 0.2 vs. 5.5 +/- 0.5 days; P < 0.001) or after thoracoscopic esophagomyotomy (4.0 +/- 1.3 days; P = not significant). Patients experienced significant pre-to postoperative improvement in mean severity score with regard to dysphagia (2.6 vs. 0.4; P < 0.001) and regurgitation (1.7 vs. 0.2; P < 0.001). CONCLUSIONS: Minimally invasive esophagomyotomy can provide excellent symptomatic relief from dysphagia and regurgitation for children with achalasia.

Adolescent↗

Melatonin potentiates NE-induced vasoconstriction without augmenting cytosolic calcium concentration.

Because little is known of the intracellular mechanisms involved in the vasoconstrictor effect of melatonin (Mel), we examined the in vitro effects of Mel by using perfused cylindrical segments of the rat tail artery loaded with the intracellular Ca(2+) concentration ([Ca(2+)](i))-sensitive fluorescent dye, fura 2. Mel (10(-14) to 10(-4) M) had no effect on baseline perfusion pressure or [Ca(2+)](i) but increased, at submicromolar concentrations, the vasoconstrictor effect of norepinephrine (NE) (P = 0.0029). Mel did not modify NE-induced [Ca(2+)](i) mobilization, and thus the [Ca(2+)](i) sensitivity of NE-induced contraction increased in the presence of Mel. Mel consistently increased KCl-induced vasoconstriction and [Ca(2+)](i) sensitivity of contraction, but differences were not statistically significant. In conclusion, Mel increases the [Ca(2+)](i) sensitivity of vasoconstriction evoked by NE suggesting that Mel may amplify endogenous vasoconstrictor responses to sympathetic outflow.

Animals↗

Cerebral arteriolar structure and function in pinealectomized rats.

We examined cerebral arteriolar structure and autoregulation of cerebral blood flow (CBF) in control (n = 8), sham-operated (n = 8), pinealectomized (n = 10), and pinealectomized plus melatonin-treated (0.51 +/- 0.01 mg x kg(-1) x day(-1) in drinking water, n = 9) young Wistar rats. The lower limit of CBF autoregulation (LLCBF) was determined by measurement of CBF (in arbitrary units, laser Doppler) during stepwise hypotensive hemorrhage; the arteriolar internal diameter (ID; in microm, cranial window) was also measured. Measurements of ID were repeated during a second stepwise hypotension after smooth muscle cell deactivation (67 mmol/l EDTA). The cross-sectional area (CSA) was measured by histometry. CSA and EDTA-induced vasodilatation decreased after pinealectomy (517 +/- 21 vs. 819 +/- 40 microm(2) in sham and 829 +/- 55 microm(2) in control, P < 0.05, and 81 +/- 4 vs. 102 +/- 5 microm in sham and 104 +/- 4 microm in control, P < 0.05, respectively) and were restored by melatonin (924 +/- 39 microm(2) and 102 +/- 5 microm, respectively). These results suggest that melatonin deprival makes the arteriolar wall thinner and stiffer. However, these changes had little effect on LLCBF. In conclusion, pinealectomy of young rats induces atrophy and decreases distensibility of the cerebral arteriolar wall; these effects are prevented by melatonin. They do not modify LLCBF.

Animals↗

Aortic wall mechanics and composition in a transgenic mouse model of Marfan syndrome.

In Marfan syndrome, mutations of the fibrillin gene (FBN1) lead to aneurysm of the thoracic aorta, making the aortic wall more susceptible to dissection, but the precise sequence of events underlying aneurysm formation is unknown. We used a rodent model of Marfan syndrome, the mgR/mgR mouse (with mgR: hypomorphic FBN1 mutation), which underexpresses FBN1, to distinguish between a defect in the early formation of elastic fibers and the later disruption of elastic fibers. The content of desmosine plus isodesmosine was used as an index of early elastogenesis; disruption of elastic fibers was analyzed by histomorphometry. Because disruption of the medial elastic fibers may produce aortic stiffening, so amplifying the aneurysmal process, we measured thoracoabdominal pulse wave velocity as an indicator of aortic wall stiffness. Both mgR/mgR and wild-type (C57BL/6J-129SV) strains were normotensive, and wall stress was not significantly modified because the increase in internal diameter (0.80+/-0.06 vs 0.63+/-0.03 mm in wild type, P<0.05) was accompanied by increased medial cross-sectional area. The aortic wall stiffened (4-fold increase in the elastic modulus-to-wall stress ratio). Desmosine content was not modified (mgR/mgR 432+/-31 vs wild type 492+/-42 microg/mg wet weight, P>0.05). Elastic fibers showed severe fragmentation: the percentage of the media occupied by elastic fibers was 18+/-3% in mgR/mgR mice vs 30+/-1% in wild-type mice, with the number of elastic segments being 1.9+/-0.2 vs 1.4+/-0.1x10(-6)/mm(2) in the wild type (both P<0.05). In conclusion, underexpression of FBN1 in mice leads to severe elastic network fragmentation but no change in cross-linking, together with aortic dilatation. This result suggests that fragmentation of the medial elastic network and not a defect in early elastogenesis is 1 of the determinants of aortic dilatation in Marfan syndrome.

Animals↗