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Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 109 records · Page 6Linked to original sources

Visual function in full-term infants with hypoxic-ischaemic encephalopathy.

Thirty-one full term infants with hypoxic-ischaemic encephalopathy (HIE) were studied with a battery of tests designed to evaluate visual function in infancy and with serial MRI. Their age ranged between 5 and 31 months. The aim of the study was to evaluate whether the degree of HIE or the site and size of lesions on MRI could predict visual outcome. Twenty of the 31 infants studied showed abnormal results on at least one of the visual tests used. While visual function was generally normal in grade I HIE and severely impaired in grade III, visual outcome was variable in grade II. MRI findings were better predictors of visual impairment than the degree of HIE. Normal scans tended to be associated with normal visual function, irrespective of the severity of HIE. All but one of the infants with diffuse hemispheric involvement also showed multiple visual abnormalities. The concomitant involvement of basal ganglia was always associated with more severe visual outcome. These results suggest that infants with generalised lesions secondary to global insults are at high risk of severe visual impairment even in presence of normal acuity and require early assessment of various aspects of visual function.

Basal Ganglia↗

Infant emmetropization: longitudinal changes in refraction components from nine to twenty months of age.

Rapid emmetropization is described in pediatrically normal infants from 9 months of age during the following year. The infants, obtained from various categories of the Cambridge population screening program, provided a broad range of refractive errors. The large group of 254 nonanisometropic infants studied allowed the mean rate of change and dependence on the initial refraction value to be determined. Refraction was measured by cycloplegic retinoscopy. Rapid emmetropization changes occurred in the following refractive components: mean spherical equivalent (MSE), astigmatism magnitude, the horizontal astigmatism component, the infant's most positive meridian, and the infant's most negative meridian. The MSE and astigmatism rates of change (diopters/year), were highly dependent on their respective initial powers (r = -0.61 and r = -0.76). The percentage weighted mean proportional rate of change for MSE was -30% (SE 4%) and for astigmatism magnitude it was -59% (SE 14%). There was much individual variation, with some exhibiting fast emmetropization and others not. The MSE and astigmatism changes, however, were almost independent of each other. The refractive errors of the most positive and most negative meridians emmetropize because they are both derived from the MSE and half the astigmatism. With-the-rule astigmatism was more prevalent than against-the-rule astigmatism at 9 months of age, and with-the-rule astigmatism exhibited a significantly greater proportional rate of change. The relationship of emmetropization and refractive screening is considered. A new component "MOMS" is introduced, the maximum ocular meridional separation, when both eyes are considered. Thus incorporating astigmatism and anisometropia may be a good single indicator of conditions associated with later amblyopia. The almost independent emmetropization of the MSE and astigmatism components is an important result to consider in theories of emmetropization, refractive screening, clinical prescribing, and the evaluation of infants in treatment trials.

Accommodation, Ocular↗

Basal ganglia damage and impaired visual function in the newborn infant.

AIM: To examine the effects of early lesions in the visual pathway on visual function; and to identify early prognostic indicators of visual abnormalities. METHODS: The visual function of 37 infants with perinatal brain lesions on magnetic resonance imaging was assessed using behavioural and electrophysiological variables. RESULTS: Normal visual behaviour was observed in most infants with large bilateral occipital lesions, but all the infants with associated basal ganglia involvement had abnormal visual function. Visual abnormalities were also present in six infants with isolated basal ganglia lesions. CONCLUSIONS: These observations suggest that basal ganglia may have an integral role in human visual development and that their presence on neonatal MRI could be an early marker of abnormal visual function.

Basal Ganglia↗

Inhibition of oxidative phosphorylation, vascular tone, and [Ca2+]i in the perfused rat tail artery.

We investigated the possibility that the inhibition of oxidative phosphorylation in vascular smooth muscle attenuates norepinephrine- or KCl-evoked vasoconstriction with no change in mobilization of intracellular calcium concentration ([Ca2+]i). Experiments were performed in perfused segments of the rat tail artery loaded with the intracellular calcium dye fura 2, in the absence and presence of dinitrophenol or sodium cyanide; inhibition of oxidative phosphorylation was evaluated from the fall in intracellular ATP levels. The metabolic inhibitors reduced vasoconstriction with no change in [Ca2+]i handling, suggesting that 1) inhibition of oxidative phosphorylation attenuates vasoconstriction via a mechanism downstream of [Ca2+]i, and 2) [Ca2+]i homeostasis (both increases and decreases in [Ca2+]i) can be maintained in the presence of inhibitors of oxidative phosphorylation.

Adenosine Triphosphate↗

Cardiac function in a rat model of chronic aortic stiffness.

Cardiac function was investigated in conscious normotensive rats in which increased aortic stiffness was produced as a result of vascular calcium overload after treatment with vitamin D3 plus nicotine (VDN rats, n = 16; controls, n = 17). Baseline stroke volume, cardiac output, and cardiac response to a venous volume overload were unchanged after 1 mo of exposure to increased aortic stiffness, as were baseline venous return and total vascular capacitance. The latter was estimated from the change in mean circulatory filling pressure after modification of circulatory volume. Cardiovascular reflexes were modified in VDN rats. Bradycardia evoked by an increase in arterial PCO2 (PaCO2) or hypotensive hemorrhage was more pronounced. The PaCO2-induced bradycardia was accompanied by a fall in cardiac output in VDN rats but not in controls. In VDN rats, the attenuation of sympathetic reflexes may explain the slower recovery of blood pressure after hypotensive hemorrhage. In conclusion, a chronic increase in aortic stiffness does not compromise cardiac performance, but cardiovascular reflexes are impaired in VDN rats. Whether this is because of the increase in aortic stiffness or the effect of VDN treatment on the baroreceptors or other components of the reflex arc remains to be elucidated.

Animals↗

Calcification of medial elastic fibers and aortic elasticity.

We tested the hypothesis that a simple change in wall composition (medial calcium overload of elastic fibers) can decrease aortic elasticity. Calcium overload was produced by hypervitaminosis D plus nicotine (VDN) in the young rat. Two months later, measurement of central aortic mean blood pressure in the unanesthetized, unrestrained rat showed that the VDN rat suffered from isolated systolic hypertension but that mean blood pressure was normal. Wall thickness and internal diameter determined after in situ pressurized fixation were unchanged, as was calculated wall stress. Wall stiffness was estimated from (1) elastic modulus (determined with the Moens-Korteweg equation and values for aortic pulse wave velocity in the unanesthetized, unrestrained rat and arterial dimensions) and (2) isobaric elasticity (= slope relating pulse wave velocity to mean intraluminal pressure in the phenylephrine-infused, pithed rat preparation). Both increased after VDN, and both were significantly correlated to the wall content of calcium and the elastin-specific amino acids desmosine and isodesmosine. Left ventricular hypertrophy occurred in the VDN model, and left ventricular mass was related to isobaric elasticity. In conclusion, elastocalcinosis induces destruction of elastic fibers, which leads to arterial stiffness, and the latter may be involved in the development of left ventricular hypertrophy in a normotensive model.

Analysis of Variance↗

Vasodilators, aortic elasticity, and ventricular end-systolic stress in nonanesthetized unrestrained rats.

We evaluated the effect of different vasodilators on ventricular end-systolic stress by investigating the impact of sodium nitroprusside, nifedipine, and hydralazine on blood pressure, aortic stiffness, and wave reflection during drug-induced hypotension (to 80 mm Hg mean blood pressure) in normotensive (central aortic mean blood pressure, 116 to 119 mm Hg; systolic pressure, 133 to 137 mm Hg), nonanesthetized, unrestrained rats. Aortic stiffness was evaluated from the slope of the linear regression relating pulse wave velocity (PWV) to central aortic mean or pulse pressure. The fall in central aortic systolic blood pressure was less than the fall in mean pressure, especially after hydralazine (122+/-4 mm Hg; sodium nitroprusside, 107+/-2; and nifedipine, 112+/-3 mm Hg; P<.05). The PWV/mean pressure slope was linear, positive, and similar in all three groups (hydralazine, 3.3+/-0.2; sodium nitroprusside, 3.8+/-0.3; and nifedipine, 3.9+/-0.3 cm x s[-1]x mm Hg[-1]; P>.05). The PWV/pulse pressure slope was linear, negative, and less steep in the case of hydralazine (-4.9+/-0.6; sodium nitroprusside, -15.5+/-3.7; and nifedipine, -13.5+/-2.9 cm x s[-1] x mm Hg[-1]; P<.05). The travel time and augmentation index of the reflected wave were similar in all groups. In conclusion, sodium nitroprusside and nifedipine had a more beneficial effect on end-systolic stress than did hydralazine. This does not appear to be related to any specific effect on wave reflection or the "static" relationship between PWV and aortic mean blood pressure; it may be related to the effects of these drugs on the "dynamic" relationship between PWV and pulse pressure.

Animals↗

Autopsy risk and acquisition of human immunodeficiency virus infection: a case report and reappraisal.

Autopsy findings have contributed greatly to our understanding of acquired immunodeficiency syndrome. To our knowledge, documented autopsy-acquired infection with human immunodeficiency virus type 1 has not been reported, suggesting autopsy performance is of limited risk. We present a well-documented case of autopsy-acquired human immunodeficiency virus infection in a pathologist who sustained a scalpel wound to the hand.

Accidents, Occupational↗

Inhaled nitric oxide prevents experimental platelet activating factor-induced shock.

OBJECTIVE: To investigate whether inhaled nitric oxide (INO) can prevent platelet activating factor (PAF)-induced pulmonary hypertension and shock. DESIGN: Randomized controlled animal trial. SETTING: Laboratory. SUBJECTS: Yorkshire swine. INTERVENTIONS: Animals received general anesthesia and invasive hemodynamic monitoring, then PAF only, 2.5 micrograms/kg intravenously over 45 minutes (PAF group, n = 9) or PAF in addition to INO, 20 ppm (PAF-INO group, n = 6). MAIN OUTCOME: Vascular pressures (mean arterial and mean pulmonary), vascular resistance indexes (systemic and pulmonary), cardiac indexes, and oxygen delivery and oxygen consumption. RESULTS: Mean arterial pressures, cardiac indexes, and oxygen delivery and consumption were significantly higher in the PAF-INO group. Mean pulmonary arterial pressures and systemic and pulmonary vascular resistance indexes were significantly lower in the PAF-INO group. There were 4 deaths (44%) in the PAF group vs none (0%) in the PAF-INO group (P = 10). CONCLUSIONS: The use of INO prevents pulmonary hypertension, circulatory failure, and death during PAF-induced shock.

Administration, Inhalation↗

A simulation model of the dynamics of HIV transmission in intravenous drug users.

The complex dynamics of HIV transmission and subsequent progression to AIDS make the use of traditional mathematical modeling techniques problematic. In a previous paper for this journal, Leslie and Brunham established the utility of a nonmathematical simulation language in modeling HIV transfer under conditions similar to those found among homosexual males. This study considers the application of such an approach in modeling HIV spread among intravenous drug users (IDUs) injecting within a "shooting gallery," a location providing a common needle supply to a large number of users. Modeling HIV transmission in this population involves not only consideration of heterogeneity in partnership selection, but also of the fact that spread of the virus is not directly from person to person, but via injection equipment. The General Purpose Simulation System was used to create a hypothetical cohort of IDUs, drawing from a common needle supply. Following introduction of an index case, the HIV infection rate in this cohort was followed over 5 simulated years. The model was then used to consider the effects of systematic variation in the frequency of injection and needle-cleaning behavior.

Acquired Immunodeficiency Syndrome↗

Water transport in native and transplanted porcine jejunum.

Adequate absorptive function of transplanted small intestine is essential for success of this procedure. This study compared water transport under basal and meal stimulated conditions in the transplanted swine jejunum to native jejunum. Six female adolescent Yorkshire swine were randomized to undergo construction of either a 25-cm native proximal jejunal Thiry-Vella Fistula (TVF), n=3, or a 25-cm proximal jejunal allograft TVF, n=3. Immunosuppression in the transplanted animals was accomplished with intravenous methylprednisolone, azathioprine, and cyclosporin. Jejunal absorption studies, each 4 hr long, were performed utilizing 14C-polyethylene glycol to calculate net water flux. Each animal underwent at least three fasting and three postprandial studies. New water flux was negative, i.e., secretory, in both the native and transplanted proximal swine jejunum. In the basal state, integrated hourly water transport was more secretory in the native bowel vs the transplanted bowel during the 2nd, 3rd, and 4th experimental hr (-4.6 +/- .8 vs -2.1 +/- .7 cc, P = 0.034; -4.4 +/- .7 vs -1.8 +/- .6 cc, P = 0.012; and -4.7 vs 1.3 +/- .5 cc, P < 0.005), respectively. In native jejunum, integrated hourly water transport was less secretory 2 and 3 hr postprandially compared to basal (-1.9 +/- .5 vs -4.4 +/- .7 cc, P = 0.016; and -2.0 +/- .5 vs -4.7 +/- .7 cc, P = 0.021), respectively. This postprandial proabsorptive response did not occur in the transplanted jejunum. Native and transplanted jejunal water flux in the postprandial state did not differ significantly. We conclude that there is higher secretion in native vs transplanted jejunum during fasting. The postprandial proabsorptive response of the proximal porcine jejunum is abolished by transplantation.

Animals↗

Sustained pulmonary vasodilation after inhaled nitric oxide for hypoxic pulmonary hypertension in swine.

It has been shown that pulmonary vasodilation is sustained after discontinuation of inhaled nitric oxide (INO) during moderate hypoxic pulmonary hypertension (HPH) in swine. The present investigations demonstrated how INO dose, hypoxia duration, and endogenous NO production influence this important phenomenon. Fifteen adolescent Yorkshire swine were randomly assigned to three groups (n = 5 each) and underwent the following phasic experimental protocol: (I) Baseline ventilation (FIO2 = .3); (II) Initiating HPH (FIO2 = .16 to .18, PaO2 = 45 to 55 mm Hg); (III) INO at 10 ppm; (IV) Posttreatment observation; (V) INO of 80 ppm; and (VI) Posttreatment observation. Phase II (pretreatment hypoxia) lasted 30 minutes in group A (short hypoxia) and 120 minutes in group B (long hypoxia). N-nitro-L-arginine methyl ester (NAME) was used to inhibit nitric oxide synthase (NOS) throughout the experiment in group C (short hypoxia + NAME). Hemodynamics and blood gases were monitored by systemic and pulmonary artery catheters placed by femoral cutdown. Analysis of variance with post-hoc adjustment was used to compare groups at each phase, and the paired t test was used for comparisons within a group. With respect to baseline mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR), there were no significant differences among the three groups. MPAP and PVR were significantly higher in group C than in group A during phase II, (MPAP, 76% +/- 8% v 33% +/- 2%; PVR, 197% +/- 19% v 78% +/- 10%; P < .05). There were no significant differences in MPAP or PVR during phases III through VI. When MPAP was expressed as percent dilation, 80 ppm caused significantly more dilation than did 10 ppm in all three groups. Groups A and C had significantly higher sustained pulmonary artery dilation after 80 ppm than after 10 ppm (A, 82% +/- 31% v 17% +/- 11%; C, 68% +/- 10% v 42% +/- 12%; both P < .05), but group B did not (43% +/- 15% v 30% +/- 9%; P = .25). High dose results in stronger vasodilation than low dose during and after INO for moderate HPH of short duration. Long hypoxia blunts this high-dose advantage. Endogenous NO inhibition augments HPH but does not decrease pulmonary vasodilation during or after INO.

Administration, Inhalation↗

Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening.

Two infant vision screening programmes on total populations in the Cambridge Health District have been designed to identify manifest strabismus and strabismogenic and amblyogenic refractive errors at 7-9 months of age. The first, completed, programme used the isotropic photorefractor with cycloplegia together with a standard orthoptic examination. The second, current, programme uses the VRP-1 isotropic videorefractor to identify infants with accommodative lags which are followed up by refraction under cycloplegia. Both programmes show good agreement between infants identified at screening and retinoscopic refractions at follow-up, showing that photo- and videorefraction (with or without cycloplegia) can be effective methods for screening for ametropia in infants and young children. In each programme 5-6% of infants showed abnormal levels of hyperopia (> or = 3.5 D in any meridian), less than 1% showed anisometropia > or = 1.5 D; very few infants (0.25%) showed -3D myopia or greater. Less than 1% showed manifest strabismus. Hyperopic and anisometropic children entered a randomised controlled trial of partial refractive correction. All children identified at screening, alongside appropriate control groups, are extensively followed up to age 4 years. The first programme has found that children who were hyperopic in infancy were 13 times more likely to become strabismic, and 6 times more likely to show measurable acuity deficits by 4 years, compared with controls. Wearing a partial spectacle correction reduced these risk ratios to 4:1 and 2.5:1 respectively. The impaired acuity can be attributed, in part, to meridional amblyopia resulting from persisting astigmatism. Both hyperopic and myopic infants showed refractive changes in the direction of emmetropia between 9 months and 4 years. Wearing a partial spectacle correction did not affect this process of emmetropisation, but does provide the possibility of reducing the incidence of common pre-school vision problems.

Aging↗

Visual function and perinatal focal cerebral infarction.

AIMS: To evaluate the visual function of infants with perinatal cerebral infarction in whom the site and size of the lesion has been determined using magnetic resonance imaging (MRI). METHODS: Twelve infants with cerebral infarction on MRI were studied with a battery of tests specifically designed to evaluate visual function in infancy. This included tests: for visual attention (fixation shifts); of cerebral asymmetry (optokinetic nystagmus, visual fields); for assessment of acuity (forced choice preferential looking); and neurophysiological measures of vision (phase reversal and orientation reversal visual evoked potential). RESULTS: A considerable incidence of abnormalities on at least one of the tests for visual function used was observed. The presence or severity of visual abnormalities could not always be predicted by the site and extent of the lesion seen on imaging. CONCLUSIONS: Early focal lesions affecting the visual pathway can, to some extent, be compensated for by the immature developing brain. These data suggest that all the infants presenting with focal lesions need to be investigated with a detailed assessment of various aspects of vision.

Cerebral Infarction↗

A new technique for study of impact of arterial elasticity on left ventricular mass in rats.

We investigated possible links between left ventricular mass and central arterial elasticity in the adult spontaneously hypertensive rat (SHR) and in a subgroup of SHR in which blood pressure was normalized by chronic antihypertensive drug treatment; results were compared with those of age-matched normotensive Wistar-Kyoto rats. Two indexes of arterial elasticity, based on the measurement of aortic pressure pulse wave velocity, were used. First, the slope relating carotidofemoral pulse wave velocity to blood pressure in the phenylephrine-infused pithed preparation was used as a pressure-independent index of wall elasticity. Second, to account for hypertension- and treatment-induced aortic remodeling, elastic modulus was determined from the pulse wave velocity recorded when blood pressure reached that measured in awake animals before anesthesia and pithing, together with values for wall thickness and lumen diameter evaluated by histomorphometric analysis after in situ fixation at the same pressure. In control SHR, regression analysis of variance revealed significant correlations between left ventricular mass and both wave velocity/pressure slope and elastic modulus. Chronic antihypertensive treatment normalized all three parameters. In conclusion, this new technique provides experimental evidence of a link between left ventricular mass and central arterial elasticity.

Animals↗

Six-month supervised intermittent tuberculosis therapy in Haitian patients with and without HIV infection.

We enrolled 427 consecutive patients with tuberculosis diagnosed in Cité Soleil, Haiti in a trial of short-course intermittent therapy. All patients received supervised therapy with isoniazid, rifampin, pyrazinamide, and ethambutol thrice weekly for 8 wk, followed by isoniazid and rifampin thrice weekly for 18 wk. At entry, the 177 human immunodeficiency virus (HIV)-infected patients (42%) were found significantly more likely to have extrapulmonary tuberculosis and negative tuberculin skin tests (p < 0.05). Treatment was well tolerated by both groups of patients, and adherence to the treatment regimen was over 90%. Among patients with pulmonary or intrathoracic tuberculosis, 9% of HIV-seropositive and 1% of HIV-seronegative patients died during therapy (p < 0.001), whereas 81% and 87%, respectively, of those in the two groups were cured. Relapses occurred in 5.4% of HIV-seropositive and 2.8% of HIV-seronegative patients who completed treatment (p = 0.36). Survival after tuberculosis was poorer in HIV-seropositive patients, whose probability of dying was 33% at 18 mo after diagnosis as compared with 3% for HIV-seronegative patients (p < 0.001). HIV-seropositive patients who died had significantly lower median CD4 lymphocyte counts than did HIV-seropositive patients who survived (p < 0.001). Treatment of tuberculosis with short-course, thrice-weekly, supervised therapy in the setting of a developing country is highly efficacious in both HIV-seropositive and -seronegative patients.

AIDS-Related Opportunistic Infections↗

Economic perceptions and expectations of out-of-treatment drug users.

The effect on mainstream behavior of current economic conditions and expectations for the future is frequently the subject of public opinion polls. However, economic perceptions may also influence the behaviors of those in "hidden" populations, such as drug users. An Economic Perceptions Index (EPI) was developed and administered to 261 out-of-treatment drug users in Houston, Texas. Results suggest that drug users' general perceptions of the economy are based on their own economic situation, and that there is a relation between a pessimistic view of the economy and drug use. They also suggest that lack of municipal infrastructure may pose more of a barrier to users' seeking employment than job search skills.

Adult↗