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Biomedical subjects

N Graham

Publications and source records attributed to N Graham.

At least 55 records · Page 3Linked to original sources
PubMed1996

Survival from early, intermediate, and late stages of HIV infection.

OBJECTIVE: To estimate expected survival time among homosexual men infected with the human immunodeficiency virus type 1 (HIV-1) by (1) the calendar period before (1985-1988) and after (1989-1993) the widespread availability of acquired immunodeficiency syndrome (AIDS) treatments with antiretroviral and prophylactic interventions, and (2) stage of HIV disease. DESIGN: A prospective cohort study. A group of HIV-1-infected homosexual men were followed from July 1985 through June 1993 and evaluated every 6 months for the presence of clinical symptoms and measurement of the CD4 cell count. To measure the effectiveness of AIDS therapies in this nonrandomized study, we used 2 calendar periods as proxy measures of relative intensity of exposure to antiretroviral therapy. Stage of infection was defined by CD4 cell count and presence of HIV-related clinical symptoms or AIDS. SETTING AND STUDY PARTICIPANTS: Homosexual men infected with HIV-1 from the Multicenter AIDS Cohort Study. MAIN OUTCOME MEASURE: Survival time based on stage of HIV infection. RESULTS: The percentage of HIV-1-infected individuals free of AIDS and clinical symptoms at baseline who survived 2.5 years according to baseline CD4 cell counts of 0 to 0.100, 0.101 to 0.200, and 0.201 to 0.350 x 10(9)/L was 22%, 53%, and 83%, respectively, for the 1985-1988 calendar period, compared with 54%, 71%, and 91%, respectively, for men in the 1989-1993 calendar period. Among men free of AIDS with CD4 cell counts of greater than 0.350 x 10(9)/L, the relative hazard of mortality was 1.6 to 2.3 times higher for those with clinical symptoms compared with those free of clinical symptoms. CONCLUSIONS: Survival of AIDS-free HIV-1-infected individuals with CD4 cell counts of less than 0.350 x 10(9)/L has improved since antiretroviral and HIV prophylactic treatments have become available, but the long-term prognosis remains poor.

Antiviral Agents↗
PubMed1996

Naming and knowing in dementia of Alzheimer's type.

We studied the relationship between naming and the integrity of physical and associative knowledge in a group of patients with dementia of the Alzheimer type (DAT) and matched normal controls. All subjects named 48 line drawings and later generated verbal definitions in response to the names of a subset of the 48 items, which included a minimum of six definitions for correctly named objects and six definitions for items that the subject failed to name. A comprehensive scoring system was designed for the definitions, including physical and associative features of a general and a specific type, a superordinate label, the core concept, and various categories of errors. The definitions generated by the DAT patients, even those in the minimal group, contained significantly less correct information than those of normal subjects, and definitions corresponding to unnamed items were more impoverished than those for named items. Particularly striking was the loss of core concept for unnamed items. There was also a disproportionate reduction in physical information on unnamed compared to named items. We conclude that quantitative assessment of verbal definitions is a sensitive index of semantic memory breakdown. Our findings offer some support for the hypothesis that successful naming depends upon integrity of the subset of semantic knowledge comprising physical features.

Aged↗
PubMed1996

Effect of spatial scale and background luminance on the intensive and spatial nonlinearities in texture segregation.

Perceived segregation between element-arrangement textures is affected both by spatial scale and background luminance. The effects on the spatial nonlinearity are consistent with the proposed structure for complex (second-order) channels. The effects on the intensive nonlinearity are not consistent with an early, local nonlinearity but are consistent with either (i) a relatively early, local, nonlinearity occurring before the spatial frequency channels but after a sensitivity-setting stage, or (ii) inhibitory interaction among channels modeled as a normalization network. Thus the texture intensive nonlinearity comes after sensitivity to spatial frequency and background luminance has been determined. For six of seven observers, the texture intensive nonlinearity was compressive by 10% contrast for both increments and decrements (at high background luminance, large spatial scale.

Adaptation, Ocular↗
PubMed1996

Discovery and optimization of nonpeptide HIV-1 protease inhibitors.

Several small, achiral nonpeptide inhibitors of HIV-1 protease with low micromolar activity were identified by mass screening of the Parke-Davis compound library. Two of the compounds, structurally similar, were both found to be competitive and reversible inhibitors [compound 1, 4-hydroxy-3-(3-phenoxypropyl)-1-benzopyran-2-one: Ki = 1.0 microM; compound 2, 4-hydroxy-6-phenyl-3-(phenylthio)-pyran-2-one: Ki = 1.1 microM]. These inhibitors were chosen as initial leads for optimization of in vitro inhibitory activity based on molecular modeling and X-ray crystallographic structural data. While improvements in inhibitory potency were small with analogues of compound 1, important X-ray crystallographic structural information of the enzyme-inhibitor complex was gained. When bound, 1 was found to displace H2O301 in the active site while hydrogen bonding to the catalytic Asps and Ile50 and Ile150. The pyranone group of compound 2 was found to bind at the active site in the same manner, with the 6-phenyl and the 3-phenylthio occupying P1 and P1', respectively. The structural information was used to develop design strategies to reach three or four of the internal pockets, P2-P2'. This work led to analogues of diverse structure with high potency (IC50 < 10 nM) that contain either one or no chiral centers and remain nonpeptide. The highly potent compounds possess less anti-HIV activity in cellular assays than expected, and current optimization now focuses on increasing cellular activity. The value of the HIV-1 protease inhibitors described is their potential as better pharmacological agents with a different pattern of viral resistance development, relative to the peptide inhibitors in human clinical trials.

Benzopyrans↗
PubMed1996

Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.

OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively.

Aged↗
PubMed1995

Investigating simple and complex mechanisms in texture segregation using the speed-accuracy tradeoff method.

Several recent models of texture segregation have proposed two mechanisms: simple, linear channels (first-order, Fourier mechanisms) and complex channels (second-order, non-Fourier mechanisms). We used the speed-accuracy tradeoff (SAT) method to examine the time course of texture segregation processing in simple and complex channels. The stimuli were texture patterns designed to segregate primarily as a result of activity in one set of channels or the other. We presented subjects with textures that were checked or striped arrangements of either Gaussian-blob or Gabor-patch elements. Subjects were required to identify the orientation of a rectangular texture region embedded in a background field of a different texture. A range of contrasts and a control task were used to equate visibility of the Gabor and Gaussian textures. SAT functions were obtained by requiring subjects to respond within 200 msec after an auditory cue. We found that when segregation depended primarily on simple channels, performance was faster than when it depended primarily on complex channels: the 75% correct level was reached 100-200 msec sooner and this extra speed was reflected both in smaller delay and higher rate parameters.

Contrast Sensitivity↗
PubMed1995

Testing a computational model of light-adaptation dynamics.

Experiments from the periodic and aperiodic traditions were used to guide the development of a quantitatively valid model of light adaptation dynamics. Temporal contrast sensitivity data were collected over a range of 3 log units of mean luminance for sinusoids of 2 to 50 Hz. Probe thresholds on flashed backgrounds were collected over a range of stimulus-onset asynchronies and background intensities from 0.1 to 1000 td. All experiments were performed foveally in the photopic range and used a consistent stimulus paradigm and psychophysical method. The resulting model represents a merging of elements from both traditions, and consists of a frequency-dependent front-end followed by a subtractive process and static nonlinearity.

Adaptation, Ocular↗
PubMed1995

Prevalence and course of depression among elderly residential home admissions in Mannheim and Camden, London.

A longitudinal study based on consecutive admissions to all residential homes for the elderly was conducted in the industrial city of Mannheim (Germany) and in the London borough of Camden (England). Inclusion criteria were that the elderly persons (65 years old and older) came directly from their own home or, if transferred from a hospital, had been there for less than 3 months. At each site, 60 home residents were interviewed at admission and 3 months and 8 months later. Depression and dementia were assessed with the aid of the Brief Assessment Scale. The prevalence of depression (Mannheim: 34.6%; Camden: 47.9%) was already high at admission and did not change significantly over time. Residents in Camden were more demented and more impaired in their activities of daily living at the time of admission, and the percentage of those who died or were transferred to a hospital or nursing home within 8 months thereafter was higher in Camden (30%) than in Mannheim (5%). Multiple regression analysis revealed that, in both study areas, depression at baseline was the best predictor for depression 3 months and 8 months later. This relationship was particularly strong in Camden, where a high percentage of the depressed at admission showed a chronic course of illness. Sex, age, home visits, social isolation, activities of daily living, cognitive impairment, and somatic symptoms at the time of admission were not significantly associated with depression 3 months later. Eight months after admission, a similar pattern was found in Mannheim. In Camden, however, in addition to depression, a lack of home visits by relatives and friends, and somatic symptoms at baseline, were significant predictors of depression 8 months after admission.

Aged↗
PubMed1995

Assessment of an inner city visual screening programme for preschool children.

AIMS: The efficiency of preschool visual screening programmes to detect amblyopia is questionable. In this study such a programme in an inner city was assessed to determine its effectiveness. METHODS: The results of screening and hospital treatment of 712 patients who were considered to require referral were entered into a database for analysis. Default rates were assessed and the efficacy of treatment determined. RESULTS: The only effective screening test for the detection of amblyopia was visual acuity. A large proportion of referred patients had refractive problems only. High default rates, particularly in geographical areas of lower socioeconomic grading, severely handicapped any attempt to reduce the incidence of amblyopia. CONCLUSION: A fresh approach to the detection and care of amblyopia in the inner city community is required, perhaps by performing screening of children in their first year of attendance at school to reduce default rates. Cycloplegic refraction of children who are found to have reduced visual acuity before their referral to hospital is also recommended.

Amblyopia↗
PubMed1995

Use of integrated, general education, and community settings as primary contexts for skill instruction for students with severe, multiple disabilities.

Four students with severe, multiple disabilities learned to use four to five new skills at critical moments within age-appropriate activities. Instruction was provided only at moments critical to the continuation of the activities when natural cues and consequences delineated the need for the target behaviors. This method of intervention was combined with a more traditional package of antecedent prompt-fade procedures and, in a few instances, time delay. The purpose of the study was to analyze the effects of instruction given only at natural critical moments on the acquisition of basic sensory, motor, social, and communication behaviors. A multiple baseline design across skills within separate activities for four participants was employed. Fifteen of 17 skills were acquired to criterion. In addition, "learning to learn" effects occurred within each activity as instruction of new target behaviors was introduced. The outcomes are important for the participant population because they document the effect of integrated educational models for teaching the most basic skills. Discussion of the motivation provided by activity routines in general education and community settings, as well as interpretation of data when participants have the most severe disabilities, is presented.

Behavior Therapy↗
PubMed1994

Non-linearities in texture segregation.

The existence of complex (non-Fourier, second-order) channels is suggested by some characteristics of segregation perceived between regions distinguished by visual texture. These complex channels consist of two linear-filtering stages separated by a rectification-type non-linearity. We have investigated (i) the spatial frequency selectivity and orientation selectivity of their first-stage filters; (ii) the relationship between the preferred values of orientation and spatial frequency at the first and second filters; (iii) spatial pooling and its implications for the non-linearity at the middle of the complex channel; and (iv) the dynamics of complex and simple linear channels. An intensive non-linearity is also necessary to explain perceived region segregation. This intensive non-linearity might arise from an early local non-linearity preceding the channels (perhaps retinal light adaptation) or from normalization among the channels themselves (perhaps due to intracortical inhibition). Deciding between these two candidates has been more difficult than we had hoped. It appears that: (i) this intensive non-linearity operates for both simple and complex channels; (ii) the effects on it of changing mean luminance or spatial scale may be accounted for by a sensitivity parameter; (iii) it can be dramatically compressive even at contrasts less than 25% for high mean luminances and large scales; and (iv) at even lower contrasts there is an accelerating non-linearity that acts before the second filter of the complex channels.

Animals↗
PubMed1994

Dietary calcium intake in 18-year-old women: comparison with recommended daily intake and dietary energy intake.

Average dietary calcium intake and energy intake of 113 18-year-old university students in Western Australia was examined. Four-day, weighted diet records, including 1 weekend day, were completed by the subjects. A large proportion of the students (68%) had an average daily calcium consumption below the 800 mg recommended by the National Health and Medical Research Council of Australia. A strong positive association was also found between dietary calcium and dietary energy intakes. Many young women on self-imposed energy reduction diets are at risk of a dietary calcium intake deficit at a time when it should be enhanced. These findings are significant for nursing practice as they indicate the need for further health education concerning the importance of dietary calcium in young women.

Adolescent↗
PubMed1993

Spatial-frequency- and orientation-selectivity of simple and complex channels in region segregation.

Models incorporating spatial-frequency- and orientation-selective channels explain many texture-segregation results, particularly when known nonlinearities are included. One such nonlinearity is complex channels. A complex channel consists of two stages of linear filtering separated by a rectification-type nonlinearity. Here we investigate the spatial-frequency- and orientation-selectivity of simple (linear) channels and of the complex channels' first stage. Observers rated the degree of segregation between two "textures" both composed of elements which were Gabor patches. When the textures differed in type of element (e.g. one composed of vertical and the other of horizontal Gabor patches), the segregation results yield bandwidth estimates for simple channels of approx. 0.5-1.0 octave on the spatial-frequency dimension and 5-20 deg of rotation on the orientation dimension. When the textures differ in the arrangement of elements (e.g. striped vs checkerboard arrangements, both of horizontal and vertical patches), the segregation results yield bandwidth estimates for the first stage of complex channels. These estimates, while differing substantially from one observer to another, were always substantially wider than those for simple channels (by at least a factor of two) but narrower than bandwidths of LGN cells (particularly on the orientation dimension where LGN cells show little selectivity at all).

Contrast Sensitivity↗