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Biomedical subjects

C Cahill

Publications and source records attributed to C Cahill.

At least 19 recordsLinked to original sources

Interactions of poly(amino acids) in aqueous solution with charged model surfaces--analysis by colloidal probe.

Biomolecules in a confined solution environment may be subject to electrostatic forces with a range up to 100 nm, while van der Waals interaction will account for shorter-range forces. The response of two model poly(amino acids)--poly-L-lysine and poly-L-glutamic acid--has been investigated for a silica/Si-oxide surface at pH 6. The model amino acids were adsorbed, or covalently coupled, to colloidal probes consisting of a microsphere attached to a force-sensing lever. The methodology was based on sensing interaction between the probe and a flat surface through carrying out force versus distance analysis with a scanning force microscope. The results were analyzed within the framework of the conventional DLVO theory. The outcomes illustrate both repulsive and attractive long-range interactions that will hinder, or promote, colloidal biospecies in solution entering the region of attractive short-range interactions at the physical interface. Large 'snap-on' distances were observed for some systems and have been ascribed to compression of the 'soft' functionalized layers. Those observations and measurements of adhesion provided insight into conformation of the adsorbed species and strength of attachment. The results have implications for the efficacy of methods and devices that seek to exploit the properties of micro/nano-fluidic systems.

Data Interpretation, Statistical↗

Rationalizing radio medical advice for maritime emergencies.

The provision of radio medical advice by the National Health Service for British coastal waters has developed in an ad hoc fashion. In 1999, the closure of one of the two centres providing such advice led to unexpected problems. The demographic characteristics of the offshore population covered by each centre were markedly different and this resulted in a different spectrum of medical emergencies presenting to the sole remaining centre. Subsequent data collection of the details of medical emergencies presenting from offshore allowed an audit to inform the development of training packages for both base and remote practitioners. This has led to an ongoing national rationalization of ship-to-shore radio medical advice for the UK.

Data Collection↗

Imaging and force-distance analysis of human fibroblasts in vitro by atomic force microscopy.

The structure of human fibroblasts have been characterised in vitro by atomic force microscopy (AFM) operated in the imaging or in the force versus distance (F-d) modes. The choice of cell substrate is important to ensure good adhesion. Of greater significance in the context of AFM analysis, is the observation that the substrate affects the imaging conditions for in vitro analysis of live cells. For instance, very rarely will glass coverslips lead to acceptable outcomes (i.e., resolved cytoskeletal structure). Activated tissue culture dishes, on the other hand, promote conditions that routinely result in good quality images. Those conditions are then unaffected by adoption of relatively high force loadings (more than 10 nN), large fields of view (100 x 100 microm2) and high scan speeds (up to ca. 200 microm/sec), all of which exceed values recommended in the literature. Plasma membranes are fragile in the context of AFM analysis (F-d analysis gives an equivalent Young's Modulus of ca. 5 kPa). However, the present work suggests that fragility per se need not be a problem, rather it is the adhesive interactions with the tip, which under some circumstances may exceed 20 nN, that are the source of poor imaging conditions. The present results, being supported by a qualitative model, suggest that the activated substrate acts as a preferential scavenger of cellular debris thus preventing the tip from biofouling, and will therefore promote low adhesion between tip and membrane. Good imaging conditions provide non-destructive in vitro information about cytoskeletal structure and dynamics, as shown in two examples concerned with cytochalasin treatment and with the MTT assay.

Cell Division↗

The appreciation of visual jokes in people with schizophrenia: a study of 'mentalizing' ability.

It has been suggested that certain characteristic symptoms of schizophrenia reflect a specific deficit in the ability to attribute mental states to others ('mentalizing'). Patients with negative features, particularly social withdrawal and blunted affect, those with thought disorder and patients with paranoid symptoms have difficulties when they try to infer what is going on in the minds of other people. This study examines this notion using two sets of cartoon jokes. While the first set can be understood purely using physical and semantic analysis, the second set requires that the viewer appreciates the mental state of the main character in order to 'get' the joke. For control subjects there was no difference in the ability to understand the two types of joke, while the schizophrenic patients found the mental state jokes significantly more difficult to understand. This effect was most marked in patients with behavioural disorders and those reporting passivity experiences. Those with paranoid delusions also showed a selective comprehension deficit with the mental state stimuli. Patients who were symptom free at the time of testing showed normal performance.

Adult↗

Improving management of anemia using CQI techniques.

During the last two years, the National Kidney Foundation's Dialysis Outcomes Quality Initiative (NKF-DOQI) Anemia Work Group has been developing clinical practice guidelines for the management of anemia in patients with chronic renal failure. After an in-depth critical analysis of the scientific literature, with a consensus of "expert opinion" used to support recommendations in areas with inadequate published data, evidence-based guidelines were developed. These clinical practice guidelines, regardless of how well-founded in scientific evidence, are likely to be disregarded if they are not applicable in the day-to-day care of patients. Thus, they must be practical, clearly stated, and usable, given available resources and constraints. The purpose of this article is to describe our experiences in implementing some of these guidelines over the last two years, as they were being developed, for the care of patients in our hemodialysis unit.

Anemia↗

Psychotic experiences induced in deluded patients using distorted auditory feedback.

The effect of hearing immediate auditory feedback of their own voice distorted in pitch was examined in 21 patients with a diagnosis of schizophrenia. Patients frequently reported that they heard a voice "speaking when I speak" and often attributed this "other" voice to an external agent: "I think it's an evil spirit speaking when I speak." The frequency of making these ''other''attributions was significantly related to degree of pitch distortion (rho = 0.62, P <.01) and to current severity of delusions (rho = 0.62, P <.01). However, the relationship with hallucinations was not significant (rho = 0.40) and there was no relationship with negative features such as psychomotor retardation. We conclude that the "hallucination-like" reports elicited by our paradigm resulted from an interaction between an unusual perceptual experience (distorted auditory feedback) and an abnormal mechanism for belief formation present in deluded patients. This formulation suggests a close relationship between delusions and hallucinations.

Journal Article↗

A functional neuroanatomy of hallucinations in schizophrenia.

Hallucinations, perceptions in the absence of external stimuli, are prominent among the core symptoms of schizophrenia. The neural correlates of these brief, involuntary experiences are not well understood, and have not been imaged selectively. We have used new positron emission tomography (PET) methods to study the brain state associated with the occurrence of hallucinations in six schizophrenic patients. Here we present a group study of five patients with classic auditory verbal hallucinations despite medication, demonstrating activations in subcortical nuclei (thalamic, striatal), limbic structures (especially hippocampus), and paralimbic regions (parahippocampal and cingulate gyri, as well as orbitofrontal cortex). We also present a case study of a unique, drug-naive patient with visual as well as auditory verbal hallucinations, demonstrating activations in visual and auditory/linguistic association cortices as part of a distributed cortical-subcortical network. Activity in deep brain structures, identified with group analysis, may generate or modulate hallucinations, and the particular neocortical regions entrained in individual patients may affect their specific perceptual content. The interaction of these distributed neural systems provides a biological basis for the bizarre reports of schizophrenic patients.

Adult↗

Transmission electron microscopic demonstration of vimentin in rat osteoblast and osteocyte cell bodies and processes using the immunogold technique.

BACKGROUND: The immunogold labeling technique and transmission electron microscopy were used to demonstrate the expression and position of the intermediate filament vimentin in rat osteoblast and osteocyte cell bodies and cell processes. Conventional light and transmission electron microscopic studies of bone cells demonstrated adjacent cell linkage to be mediated by osteoblast and osteocyte processes present within the canalicular system traversing the bone matrix. The cell processes were filled with densely packed filaments, many of which have been shown previously to be actin microfilaments. The appearance, however, of 10 nm diameter filaments in some cell processes and the fact the intermediate filament vimentin has been defined in many cells of mesenchymal origin raised the possibility that some of these filaments might be vimentin. The ultrastructural colloidal gold immunochemical technique allowed for demonstration in situ of the expression of vimentin filaments plus accurate definition of their position. METHODS: The studies were performed in newborn rat femoral and tibial diaphyseal cortical bone and in 1-week-old repair bone from 2.4 mm diameter defects made through the lateral cortex in 6-week-old rat femurs and tibias. The bone tissues for the immunochemical study were fixed in 1% glutaraldehyde, 4% paraformaldehyde, and 0.1 M phosphate buffer (pH 7.4) for 2 days. Decalcification was performed in 6% EDTA for 2-3 days. Infiltration involved use of Lowicryl resin K4M, and the embedding and curing processes were performed in a cryostat with temperatures -30 degrees C. An antivimentin monoclonal antibody was used for labeling using the postembedding technique. Effective antibody dilutions ranged from 1:10 to 1:200, with the dilutions of 1:25 and 1:100 showing the best combination of filament labeling with the least matrix background. The grids were exposed to 10 nanometer gold colloid conjugated goat anti-mouse IgM for demonstration of binding. RESULTS: Vimentin immunolabeling was defined clearly in relation to filaments within the osteoblast and osteocyte cell body cytoplasm, throughout the entire length of the osteoblast and osteocyte cell processes, and in close relationship to the intracellular gap junctions which were present within the cell processes both close to the cell bodies and within the canaliculi well away from them. CONCLUSIONS: Immunogold labeling demonstrates the presence of the intermediate filament vimentin in osteoblast and osteocyte cell bodies and processes of rat bone. Vimentin distribution is not concentrated to specific areas, is present throughout the extent of the bodies and processes, and is seen immediately adjacent to gap junctions.

Age Factors↗

Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.

BACKGROUND: This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD: Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS: In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION: These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

Adult↗

Imaging transient, randomly occurring neuropsychological events in single subjects with positron emission tomography: an event-related count rate correlational analysis.

Many neuropsychiatric symptom states are idiosyncratic, involuntary, randomly occurring, subjective, and transient. The brain states associated with these clinically important mental states cannot be imaged directly with existing positron emission tomography (PET) techniques. A new PET method that brings such mental/brain states under experimental control for analysis in single subjects is described. It utilizes a slow bolus H2 15O three-dimensional (3D) regional CBF imaging technique. The analysis focuses upon natural or experimentally induced variance in the temporal distribution of specific neuropsychological events over the course of a study session. For each scan, the amount of radioactivity entering the brain during these events is calculated to derive a score reflecting the contribution of the events to the image. A statistical analysis is then performed to identify those pixels in which the intensity covaries with the scan scores over the subject's scans. This permits the identification of the brain areas associated with the mental state of interest. The method is validated using an auditory sentence-monitoring task. The detection in single subjects of cerebral activations associated with recurrent events as brief as 2 s in duration is demonstrated. This method may be used as a means of imaging ephemeral neurologic or neuropsychiatric symptom states or as an alternative to a subtraction design for activation studies.

Adult↗

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Adult↗

Extracorporeal photochemotherapy in progressive systemic sclerosis.

BACKGROUND: Extracorporeal photochemotherapy, an immune-modulating form of therapy, has been shown to be effective in the treatment of autoimmune diseases. We evaluated the effects of extracorporeal photochemotherapy in the treatment of patients with progressive systemic sclerosis (PSS). METHODS: Nine patients with active progressive systemic sclerosis were treated with extracorporeal photochemotherapy on 2 successive days monthly. The duration of therapy ranged from 6 to 21 months. RESULTS: A significant improvement was noted in the skin, musculoskeletal system, functional index, and symptoms including Raynaud's phenomenon, dyspnea, fatigue, dysphagia, and arthralgias, as well as improvement of cutaneous ulcers. Stabilization of the pulmonary function studies was also noted in the majority of patients over the course of therapy. No serious side effects were noted throughout the course of therapy in the 9 patients. CONCLUSIONS: The results suggest that photopheresis may be beneficial in selected early cases of progressive systemic sclerosis.

Activities of Daily Living↗

Photopheresis for ARC: a nursing perspective.

Photopheresis, an approved treatment for cutaneous T-cell lymphoma (CTCL), is the basis of a trial involving patients with AIDS-related complex (ARC). This study has provided the opportunity to identify unique nursing challenges along with satisfaction from innovative nursing interventions.

AIDS-Related Complex↗

Memory for what it is and memory for what it means: a single case of Korsakoff's amnesia.

A single case of Korsakoff's syndrome, showing classic circumscribed amnesia on traditional neuropsychological tests, performed a number of learning tasks previously used in primates to demonstrate the different anatomical basis of memory systems used to learn about the properties of objects or to learn about rules of responding. The patient (CJ) performed in a manner very similar to lesioned monkeys in that he could learn evaluative tasks (e.g. a red object is nice), but not rule based tasks (e.g. a red object means go left). In consequence CJ learned an object discrimination task in a manner qualitatively different from a group of non-amnesic controls. Although he could not learn rule based tasks, CJ could perform them once he had been given the rule. Detailed analysis of learning showed that CJ could choose the object he had chosen previously, but could not say where it had been or whether he had been rewarded. Furthermore he could recognise a word as familiar, while not remembering its source. We propose that he has a specific impairment in a memory system concerned with the representation of the signification of objects in particular contexts, while representation of the properties of objects remains intact.

Alcohol Amnestic Disorder↗

Viral-specific immunization in AIDS-related complex by photopheresis.

The potential for therapeutic intervention in 7 patients with AIDS-related complex (ARC) was evaluated through the use of photopheresis. The rationale for the study was based on: 1. the demonstration that psoralen and UVA could inactivate HIV/virus in vitro; 2. CD4 cells are the primary target population effected by HIV and photopheresis; and 3. reinfusion of inactivated virus and cell-associated virus might serve to engender an immune response. Preliminary results in 7 patients with ARC over 6 to 18 months revealed a virus-specific response with an elevation of HIV antibodies, while EBV and CMV titers remained unchanged. The immunologic results revealed an increase in the CD8 lymphocyte population, stable activation markers (B2 microglobulin neopterin), a decrease in p24 antigen titers and inability to culture HIV virus in 3 patients. All of these results were in the context of a stable or increasing CD4+ percent. Six patients did not reveal a generalized inhibition of other immune responses as demonstrated by recovery of DTH. In addition, the resolution of lymphadenopathy, night sweats, fever and weight loss, paralleled the immunologic response.

AIDS-Related Complex↗

Detection of major group rhinoviruses by soluble intercellular adhesion molecule-1 (sICAM-1).

Soluble intercellular adhesion molecule-1 (sICAM-1) was shown to be the receptor for the major subgroup of rhinoviruses. It was demonstrated that this molecule can inhibit the binding and subsequent infection of target cells by rhinoviruses belonging to the major but not the minor subgroup. The data reported now describe an ELISA-based system utilizing biotinylated sICAM-1 as a means of detecting rhinoviruses belonging to the major subgroup.

Bacterial Proteins↗

Infection of a polarized epithelial cell line with wild-type reovirus leads to virus persistence and altered cellular function.

The mechanisms and consequences of persistence of non-transforming viruses are poorly understood. Reovirus infections are usually regarded as cytocidal and infection is associated with inhibition of cellular protein and DNA synthesis. Reovirus infection of the polarized epithelial MDCK cell line is not associated with inhibition of protein synthesis, and cells become persistently infected and continue to grow without c.p.e. after infection. After several passages, virus persistence is associated with profound morphological and functional changes. The cells lose their usual cobblestone appearance and acquire a fibroblastic, undifferentiated morphology. This is associated with an inability to form tight junctions. In addition, expression of epidermal growth factor receptors and one adhesion protein is altered in the persistently infected cells. These results demonstrate that reovirus persistence will occur readily, and that infection of differentiated cells with a non-transforming virus can lead to loss of differentiation and abnormal protein expression.

Animals↗