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Biomedical subjects

C Cahill

Publications and source records attributed to C Cahill.

At least 19 recordsLinked to original sources

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

Treatment of sexual abuse which occurred in childhood: a review.

This review is concerned with the individual and group treatment of clients who present with a history of sexual abuse in childhood. Almost all of the literature regarding the individual treatment of these clients is based on clinical reports; very little is experimentally based. Most of the reports of group treatment are of a similar nature, although some outcome research data are included. The clinical consensus, in terms of the issues, stages, goals and techniques of therapy, is described. In addition, an overview is provided of the identification of clients who may have a history of CSA, which includes guidelines for assisting disclosure. Finally, the issues raised for therapists in treating these clients are addressed. Much of the material reviewed in this article refers to the treatment of female, and in particular incestuously abused, victims; at the time of writing, very little information was available regarding the treatment of male victims.

Adolescent

Long-term effects of sexual abuse which occurred in childhood: a review.

The psychological problems and difficulties experienced by adults who report having been sexually abused in childhood are reviewed. These long-term effects include damage to the victims' emotional reactions and self-perceptions, relationship problems, problems with sexuality and difficulties in social functioning. Common presenting problems of victims of childhood sexual abuse (CSA) are described. Also discussed are the characteristics of incestuous abuse in terms of the victim, the abusive relationship and its termination; the contributions of the various aspects of CSA to the psychological impact of such abuse; and psychodynamic explanations of the development of long-term effects. The bulk of the published material regarding the long-term effects of CSA refers to female victims only, and this 'bias' is reflected in the review.

Child

Photopheresis for the treatment of cutaneous T cell lymphoma.

We investigated the use of extracorporeal chemotherapy (photopheresis) in eight patients with cutaneous T cell lymphoma. Initially described by Edelson et al. for the treatment of erythrodermic cutaneous T cell lymphoma, we have expanded the treatment to include patients with extensive patch/plaque disease as well as tumor-stage disease. Four of five patients with erythrodermic stage disease had either a complete or a partial clinical remission with photopheresis alone. One patient with extensive patch/plaque disease continued to have a partial clinical remission of 7 months' duration with photopheresis alone. Of the two patients with tumor-stage disease, one remained without evidence of clinical disease at 10 months with photopheresis alone, whereas the second patient had a partial clinical remission of 5 months with a combination of local radiation therapy followed by monthly photopheresis. The skin biopsy specimen obtained from the patient with tumor-stage disease in complete clinical remission did not show cutaneous T cell lymphoma. We conclude that photopheresis is an effective modality alone or in combination with adjunctive therapy for erythroderma, extensive patch/plaque disease, and some tumor-stage disease.

Adult

POMC in rhesus anterior pituitary and plasma: evidence of N-acetylated beta-endorphin and alpha-MSH.

Pro-opiomelanocortin (POMC) related peptides have been studied in rat tissue and plasma, but they have not been well characterized in the rhesus monkey. Since monkey pituitary may be more similar to the human pituitary than the rat, we have characterized POMC related peptides by immunocytochemical, multiple radioimmunoassays (RIA's) and molecular sieving chromatography. Immunocytochemical staining demonstrated N-acetylated- beta-endorphin (N-Ac- beta-End) and alpha-MSH in a few corticotrophs. RIA's of crude anterior pituitary extract and molecular sieving chromatography demonstrates that the major portion is beta-End sized with a significant proportion being N-acetylated and an alpha-MSH peak. Molecular sieving chromatography of extracted plasma demonstrated a similar pattern to that seen in the anterior pituitary. These data suggest that rhesus monkey processes POMC differently than rat or man.

Animals