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Biomedical subjects

G Harris

Publications and source records attributed to G Harris.

At least 37 records · Page 2Linked to original sources

Comprehension of signs by dolphins (Tursiops truncatus).

The authors assessed the ability of 6 captive dolphins (Tursiops truncatus) to comprehend without explicit training 3 human communicative signs (pointing, directed gaze, and replica). Pointing consisted of indicating the target item with the index finger and a fully extended arm. Directed gaze consisted of orienting the head and eyes toward the target item while the rest of the body remained stationary. The replica signal consisted of holding up an exact duplicate of the target item. On the initial series of 12 trials for each condition, 3 dolphins performed above chance on pointing, 2 on gaze, and none for replica. With additional trials, above chance performance increased to 4 dolphins for pointing, 6 for gazing, and 2 for replica. The replica sign seemed to be the most taxing for them (only 2 dolphins achieved results significantly above chance). Taken together, these results indicate that dolphins are able to interpret untrained communicative signs successfully.

Animals↗

Botulinum toxin to the lateral rectus for the treatment of esotropia with paradoxical diplopia.

A retrospective review of six patients with paradoxical diplopia in the presence of esotropia was carried out. All patients were treated with botulinum toxin to the lateral rectus of the affected side. Five patients had no diplopia post toxin and the remaining patient had diplopia which could be ignored. The number of injections per patient ranged between 3 and 34. Three patients went on to have surgery to increase the angle of esotropia, with relief of diplopia. We conclude that botulinum toxin has a role in the treatment of esotropic patients with paradoxical diplopia.

Adolescent↗

The silent sinus syndrome: a case series and literature review.

PURPOSE: The purpose of this study is to describe the clinical and pathologic features of a form of chronic maxillary atelectasis referred to as the silent sinus syndrome, which is characterized by progressive enophthalmos secondary to maxillary collapse resulting from maxillary sinus hypoventilation. METHODS: A retrospective medical record analysis was carried out to identify patients with enophthalmos secondary to maxillary collapse. Clinical records, including ophthalmology and otolaryngology evaluations as well as computed tomography scans and operative reports, were carefully examined. A complete literature review for relevant studies was performed to examine possible pathophysiology and similar cases. RESULTS: Four patients with enophthalmos and asymptomatic maxillary sinus disease were identified. On computed tomography, all four of the patients had opacified, partially collapsed maxillary sinuses with osteopenia of the sinus walls and orbital floor displacement resulting in enophthalmos. All four underwent successful functional endoscopic sinus surgery and transconjunctival orbital floor repair. CONCLUSION: In some instances, chronic maxillary atelectasis can present with enophthalmos secondary to collapse of the maxillary sinus. For reasons that are unclear, the sinus component of the disease remains asymptomatic and is discovered only after thorough evaluation of the enophthalmos.

Adult↗

DPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants.

Human immunodeficiency virus (HIV) protease inhibitors (PIs) are important components of many highly active antiretroviral therapy regimens. However, development of phenotypic and/or genotypic resistance can occur, including cross-resistance to other PIs. Development of resistance takes place because trough levels of free drug are inadequate to suppress preexisting resistant mutant variants and/or to inhibit de novo-generated resistant mutant variants. There is thus a need for new PIs, which are more potent against mutant variants of HIV and show higher levels of free drug at the trough. We have optimized a series of substituted sulfonamides and evaluated the inhibitors against laboratory strains and clinical isolates of HIV type 1 (HIV-1), including viruses with mutations in the protease gene. In addition, serum protein binding was determined to estimate total drug requirements for 90% suppression of virus replication (plasma IC(90)). Two compounds resulting from our studies, designated DPC 681 and DPC 684, are potent and selective inhibitors of HIV protease with IC(90)s for wild-type HIV-1 of 4 to 40 nM. DPC 681 and DPC 684 showed no loss in potency toward recombinant mutant HIVs with the D30N mutation and a fivefold or smaller loss in potency toward mutant variants with three to five amino acid substitutions. A panel of chimeric viruses constructed from clinical samples from patients who failed PI-containing regimens and containing 5 to 11 mutations, including positions 10, 32, 46, 47, 50, 54, 63, 71, 82, 84, and 90 had mean IC(50) values of <20 nM for DPC 681 and DPC 681, respectively. In contrast, marketed PIs had mean IC(50) values ranging from 200 nM (amprenavir) to >900 nM (nelfinavir).

Administration, Oral↗

Cerebral cortex: a topographic segmentation method using magnetic resonance imaging.

Remarkable developments in magnetic resonance imaging (MRI) technology provide a broad range of potential applications to explore in vivo morphological characteristics of the human cerebral cortex. MR-based parcellation methods of the cerebral cortex may clarify the structural anomalies in specific brain subregions that reflect underlying neuropathological processes in brain illnesses. The present study describes detailed guidelines for the parcellation of the cerebral cortex into 41 subregions. Our method conserves the topographic uniqueness of individual brains and is based on our ability to visualize the three orthogonal planes, the triangulated gray matter isosurface and the three-dimensional (3D) rendered brain simultaneously. Based upon topographic landmarks of individual sulci, every subregion was manually segmented on a set of serial coronal or transaxial slices consecutively. The reliability study indicated that the cerebral cortex could be parcelled reliably; intraclass correlation coefficients for each subregion ranged from 0.60 to 0.99. The validity of the method is supported by the fact that gyral subdivisions are similar to regions delineated in functional imaging studies conducted in our center. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in circumscribed cortical subregions. The description of a thorough map of regional structural and functional cortical abnormalities will provide further insight into the role that different subregions play in the pathophysiology of brain illnesses.

Cerebral Cortex↗

An MRI-based parcellation method for the temporal lobe.

The temporal lobe has long been a focus of attention with regard to the underlying pathology of several major psychiatric illnesses. Previous postmortem and imaging studies describing regional volume reductions or perfusion defects in temporal subregions have shown inconsistent findings, which are in part due to differences in the definition of the subregions and the methodology of measurement. The development of precise reproducible parcellation systems on magnetic resonance images may help improve uniformity of results in volumetric MR studies and unravel the complex activation patterns seen in functional neuroimaging studies. The present study describes detailed guidelines for the parcellation of the temporal neocortex. It parcels the entire temporal neocortex into 16 subregions: temporal pole, heschl's gyrus, planum temporale, planum polare, superior temporal gyrus (rostral and caudal), middle temporal gyrus (rostral, intermediate, and caudal), inferior temporal gyrus (rostral, intermediate, and caudal), occipitotemporal gyrus (rostral and caudal), and parahippocampal gyrus (rostral and caudal). Based upon topographic landmarks of individual sulci, every subregion was consecutively traced on a set of serial coronal slices. In spite of the huge variability of sulcal topography, the sulcal landmarks could be identified reliably due to the simultaneous display of three orthogonal (transaxial, coronal, and sagittal) planes, triangulated gray matter isosurface, and a 3-D-rendered image. The reliability study showed that the temporal neocortex could be parceled successfully and reliably; intraclass correlation coefficient for each subregion ranged from 0.62 to 0.99. Ultimately, this method will permit us to detect subtle morphometric impairments or to find abnormal patterns of functional activation in the temporal subregions that might reflect underlying neuropathological processes in psychiatric illnesses such as schizophrenia.

Adolescent↗

Homebirth and independent midwifery.

Why do women choose to give birth at home, and midwives to work independently, in a culture that does little to support this option? This article looks at the reasons childbearing women and midwives make these choices and the barriers to achieving them. The safety of the homebirth option is supported in reference to analysis of mortality and morbidity. Homebirth practices and level of success are compared in Australia and New Zealand (NZ), in particular, and The Netherlands, England and America. The success of popularity of homebirths is analysed in terms of socio-economic status. The current situation and challenges of independent midwifery in Darwin are described.

Australia↗

Using a computer-based clinical management system to improve effectiveness of a homeopathic service in a fundholding general practice.

UNLABELLED: Problems which the development attempts to address. This study's overall objectives were to determine whether: * The aims of collaboration between General Practitioner (GPs) and a homeopath can be made explicit and service delivery optimised by using computer-based data collection in a multi-disciplinary primary care team that includes a homeopathic practitioner. * Outcomes of the homeopathic service can be evaluated in a practical way, which allows quality assurance through rapid audit cycles. METHOD: The primary care team (PCT) explored the problems of developing a rational and quality assured complementary therapy service in a series of meetings in an NHS practice where complementary therapists are members of the PCT. This led to the defining of data-collection structures and processes needed. The researchers designed and supervised their implementation and evaluation through a series of action research cycles. A database was designed which allowed the clinicians to track interventions and outcomes using the Measure Your Own Medical Outcome Profile (MYMOP). Critical incidents were brought to fortnightly clinical meetings and methods were continually adapted as problems arose and new options emerged at six-weekly audit meetings. RESULTS: GPs tended to refer patients who do not fit easily into biomedical disease categories. Patients referred tend to self-rate themselves as experiencing notably poor wellbeing. MYMOP has to be used skillfully with homeopathic patients, especially where psychological distress is identified as one of their main complaints. CONCLUSIONS: It is possible to introduce rigour and reflectiveness when providing a homeopathic service in general practice by assessing the needs of patient and practitioners, agreeing intake guidelines, developing referral processes, implementing audit cycles. Clear lines of communication can be established and a patient-centred outcome measure can be introduced into the treatment cycle.

Database Management Systems↗

Effect of growth hormone therapy on feeding problems and food intake in children with growth disorders.

UNLABELLED: To assess the effect of therapeutic doses of growth hormone (GH) on the feeding problems, food intake, body fat and mealtime interactions of children with growth disorders, an age-matched group of 46 children with Turner syndrome (TS) or Silver Russell syndrome (SRS) was examined using questionnaire measures and direct observation. The children's body fat was measured using bio-electrical impedance analysis and skinfold thickness measurements. Children receiving GH consumed significantly more energy, protein, fat and carbohydrate than did the children who were not receiving GH, independent of the extent of the child's feeding problems. Children receiving GH had less body fat than did children who were not receiving GH. Children who were not receiving GH distracted their parents from the mealtime significantly more often and received more negative prompting and coaxing from their parents to eat than did children who were receiving GH. This study provides evidence to support the theory that appetite and intake is determined in part by growth and growth potential. Feeding problems seen in children with growth disorders are partly due to parental attempts to impose control over their child's intake, when their child consumes less than the parent believes to be adequate. CONCLUSION: GH has a significant impact on both the food intake and parent-child interaction at mealtimes of children with SRS and TS.

Animals↗

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Antifungal Agents↗

Comparison of three isolation systems for the culture of mycobacteria from respiratory and non-respiratory samples.

AIMS: To compare the recovery of mycobacteria from clinical samples using the MB/BacT rapid culture system with that obtained using egg medium or the Bactec radiometric method. METHODS: The three methods were compared using 681 clinical samples (462 respiratory and 219 non-respiratory samples) and eight external quality control strains. Culture media were incubated at 35-37 degrees C for six weeks in the MB/BacT system and for 12 weeks in the Bactec system and on egg medium. Solid media were examined macroscopically once a week and the Bactec vials were read six times in the first two weeks, and then weekly for the next 10 weeks (a growth index > 50 indicated a positive vial). The MB/BacT system positive vials were unloaded from the machine as soon as possible after detection. Confirmation of growth for all systems was by Ziehl-Neelson stained smears. Isolates were identified by a combination of phenotypic and molecular methods. RESULTS: Of the 681 clinical samples, 59 (8.7%) were positive on culture, including 23 strains of Mycobacterium tuberculosis. None of the three systems recovered all of the isolates, but each recovered mycobacteria not detected by either of the other two systems. After six weeks incubation, isolation rates were 87%, 78%, and 90%, and mean times to detection were 13, 19, and nine days for the MB/BacT, egg medium, and Bactec systems, respectively. Although the MB/BacT system was slightly slower than the Bactec system, the biomass was greater, allowing earlier use of molecular probes and earlier inoculation of susceptibility tests. CONCLUSIONS: The MB/BacT system provides comparable performance to the Bactec radiometric system, without the problems of disposal of radioactive waste. Optimal recovery is obtained when culture on egg medium is used in conjunction with a rapid culture system.

Bacteriological Techniques↗

Kaiser Permanente Tele-Home Health Research Project.

In summary, the quality of care and satisfaction measures of the two systems are remarkable for what they are not--that is, not different. They suggest no difference between a culturally accepted model of care, with roots extending deep into human experience, both personal and traditional, and one based on a radical departure therefrom--care in the physical absence of a carer. They suggest, they do not indicate, because the study was not designed as a direct comparison. Numbers were small. Other flaws are evident. But Barb Johnston and her colleagues have opened the door for larger groups with deeper pockets to prove to conclusion what they have suggested--that telecare works. They have succeeded in providing telecare with what it has hitherto lacked: a solid suggestion of equivalence with the established system, and perhaps for markedly less cost. And they have done so in the face of difficulties and barriers which may have prevented them from achieving even better results. The study is a notable achievement, and its authors and Kaiser Permanente deserve the gratitude of the entire telemedicine community.

California↗

Human frontal cortex: an MRI-based parcellation method.

The frontal lobe is not a single anatomical and functional brain region. Several lines of research have demonstrated that particular subregions within the frontal lobe are associated with specific motor and cognitive functions in the human being. Our main purpose is to develop a magnetic resonance image (MRI)-based parcellation method of the frontal lobe that permits us to explore plausible abnormalities in functionally relevant frontal subregions in brain illnesses. We describe a procedure using MRI for subdividing the entire frontal cortex into 11 subregions: supplementary motor area (SMA), rostral anterior cingulate gyrus (r-ACiG), caudal anterior cingulate gyrus (c-ACiG), superior cingulate gyrus (SCiG), medial frontal cortex (MFC), straight gyrus (SG), orbitofrontal cortex (OFC), precentral gyrus (PCG), superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and middle frontal gyrus (MFG). Our method posits to conserve the topographic uniqueness of individual brains and is based on our ability to visualize both the three-dimensional (3D) rendered brain and the three orthogonal planes simultaneously. The reliability study for gray matter volume and surface area of each subregion was performed on a set of 10 MR scans by two raters. The intraclass R coefficients for gray matter volume of each subregion ranged between 0.86 and 0.99. We describe here a reproducible and reliable topography-based parcellation method of the frontal lobe that will allow us to use new approaches to understand the role of particular frontal cortical subregions in schizophrenia and other brain illnesses.

Brain Diseases↗

Immunohistochemical localization of types 1 and 2 5alpha-reductase in human scalp.

The predominant form of 5alpha-reductase (5aR) in human scalp is 5aR1. None the less, clinical studies have shown that finasteride, a selective inhibitor of 5aR2, decreases scalp dihydrotestosterone and promotes hair growth in men with androgenetic alopecia. Immunolocalization studies were thus carried out to examine 5aR isozyme distribution within scalp and, in particular, to determine whether 5aR2 might be associated with hair follicles. 5aR2 was localized using both a rabbit polyclonal and a mouse monoclonal antibody. 5aR1 was detected with a mouse monoclonal antibody. The specificity of these reagents was demonstrated both by immunofluorescence and Western blot analyses of COS cells overexpressing human 5aR1 or 5aR2. When cryosections of scalp from men with androgenetic alopecia were stained with antibody against 5aR2, using immunoperoxidase avidin-biotin complex methodology, immunostaining was observed in the inner layer of the outer root sheath and, in more proximal regions of the follicle, in the inner root sheath. Staining was also prominent in the infundibular region of the follicle, with less intense staining extending throughout the granular layer of the epidermis. Some staining was also seen in sebaceous ducts. Similar results were obtained with both the polyclonal and monoclonal 5aR2 antibodies. In contrast, in scalp cryosections stained with antibody to 5aR1, no immunostaining was observed within hair follicles. Intense staining for the type 1 isozyme was, however, detected within sebaceous glands. Our immunolocalization data suggest that the results seen in clinical trials of men with male pattern hair loss treated with finasteride may be due, at least in part, to local inhibition of 5aR2 within the hair follicle.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging.

Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.

Adolescent↗

DSM-IV AD/HD: confirmatory factor models, prevalence, and gender and age differences based on parent and teacher ratings of Australian primary school children.

Based on parent and teacher ratings of primary school children on a scale comprising the 18 DSM-IV AD/HD symptoms, this study used confirmatory factor analysis to compare three models: all items in one factor; inattention in one and hyperactivity and impulsivity items in a separate factor; and inattention, hyperactivity, and impulsivity items in three separate factors. It also examined the prevalence rates of the three AD/HD Types, and gender and age differences. Results supported both the two- and three-factor models, with the three-factor model only slightly better than the two-factor model. Based on parent-teacher agreement, the prevalence rates were 1.6, 0.2 and 0.6% for the Inattentive, Hyperactive-Impulsive, and Combined Types, respectively. Overall, the male to female ratio was 5: 1, and boys were rated higher than girls by both parents and teachers. Age differences were minimal. The implications of the findings in relation to some of the assumptions made in DSM-IV for AD/HD are discussed.

Age Factors↗

Post-traumatic stress responses following liver transplantation in older children.

Eighteen children aged between 7 and 16 years who had undergone a liver transplantation were interviewed using the Child Post-Traumatic Stress Reaction Index (CPTS-RI) to discover if they had post-traumatic stress symptoms. A case control design was used to define which factors were important for the development of post-traumatic stress. Results of a one-way analysis of variance (ANOVA), with post-traumatic stress symptom intensity as measured on the CPTS-RI as the dependent variable, revealed a significant difference between the liver transplantation group compared with children who had a chronic life-threatening illness or had undergone a routine surgical operation. A post hoc (Tukey's HSD test) statistical analysis was performed and significance at the .05 level was found between the liver transplantation group and both the chronic illness group and the routine surgical operation group. Our results indicate that the acute life-threat involved in the liver transplantation contributed to the development of post-traumatic stress. It was thought that dissociation may be important in preventing the resolution of the trauma. Additional investigations are needed with larger numbers in a longitudinal study beginning before the transplant to determine the course of the PTSD symptoms and the appropriate timing of interventions to reduce the harmful effects of these symptoms.

Adolescent↗