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Biomedical subjects

P Buckley

Publications and source records attributed to P Buckley.

At least 19 recordsLinked to original sources
PubMed1995

Basal ganglia T2 relaxation times in schizophrenia: a quantitative magnetic resonance imaging study in relation to tardive dyskinesia.

Transverse, or spin-spin, relaxation times (T2) from magnetic resonance images of basal ganglia structures were compared between control subjects and patients with schizophrenia, who were subdivided on the basis of the presence or absence of tardive dyskinesia. As a group, schizophrenic patients showed evidence of somewhat more prolonged T2 relaxation times in the right putamen and globus pallidus than did control subjects; there were no significant correlations between hemispheric T2 values and corresponding volumes of the lateral ventricles. Overall, there was little difference in T2 values between patients with and without tardive dyskinesia. These data extend the range of evidence for basal ganglia dysfunction in schizophrenia, but they do not support earlier reports of prominent T2 changes associated with tardive dyskinesia.

Adult↗
PubMed1995

Secretion of a large molecular-weight form of insulin-like growth factor by a primary renal tumor.

A 5-year-old boy with an abdominal mass was found to have a primary renal tumor of poorly identifiable histology. Prior to resection of the tumor, the patient exhibited several episodes of biochemical hypoglycemia. The hypoglycemia did not recur after operation. Analysis of tumor tissue and of pre- and post-operative sera by column chromatography showed elevated insulin-like growth factor II (IGF-II) levels in the tumor; an abnormal large-molecular weight precursor form of IGF-II (pro-IGF-II) comprised 53% of total IGF-II in the tumor and 42% in preoperative serum. No pro-IGF-II was found in the serum 6 weeks post-operatively. Abnormal IGF-II secreted by the tumor may have mediated the hypoglycemia seen prior to tumor resection. This pediatric renal tumor is the first to our knowledge for which an association of non-islet cell tumor-related hypoglycemia and elevated tumor IGF-II content has been described.

Carcinoma, Renal Cell↗
PubMed1995

Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression.

This study was carried out to examine some components of in vivo immune function in major depression and schizophrenia. Toward this end, plasma concentrations of interleukin-1 beta (IL-1 beta) and IL-6, soluble IL-2 receptor (sIL-2R), and transferrin receptor (TfR) were measured in 28 normal controls, 11 schizophrenics and 13 major-depressed patients. Schizophrenic and major-depressed patients showed significantly higher plasma sIL-2R and TfR than normal controls. There was a trend toward higher plasma IL-6 in the psychiatric patients, and particularly in schizophrenic patients, than in normal volunteers. In normal controls and in the total study group, there were highly significant and positive correlations between plasma TfR and sIL-2R concentrations. It is suggested that schizophrenia and major depression are characterized by immune disorders that may indicate activation of cell-mediated immunity such as T-cell activation.

Acute-Phase Reaction↗
PubMed1995

Lymphoproliferative disease of granular lymphocytes.

We report a case of lymphoproliferative disease of granular lymphocytes that was associated with cutaneous manifestations. Marker studies of skin and blood in this patient revealed that the circulating and infiltrating cells were negative for CD3 and T-cell antigen receptor but were positive for CD16, CD56, and CD57, suggesting natural killer cell origin. The patient had a rapidly progressive course and died within 1 month of presentation.

Aged↗
PubMed1995

Pathology considerations for, and subsequent risk assessment of, chemicals identified as immunosuppressive in routine toxicology.

Several proposals have been made with the aim of assisting in the early identification of chemicals with immunotoxic potential. The Organisation for Economic Cooperation and Development is now likely to incorporate enhanced immunopathology into the test guideline for the 28-day rat study, which may be regarded as a Tier I investigation. However, no guidelines have yet been proposed either for how the new data generated will be evaluated, or for how a subsequent risk assessment will be made. In this paper, considerations for the immunopathological assessment of the thymus, spleen, lymph nodes and bone marrow are described, together with comments on haematological and organ weight changes that may be associated with immunotoxicity. Their interpretation will depend on the doses at which changes are manifest, the quantity and quality of the effects observed and the presence and severity of other forms of toxicity. Lastly, risk assessment and the approach to Tier II testing in immunotoxicity is discussed. It is concluded that much of this work must be on a case-by-case basis, but should not in principle differ from the approach adopted for any other type of toxicity identified ina 28-day study.

Animals↗
PubMed1995

Tardive dyskinesia in schizophrenia. Relationship to minor physical anomalies, frontal lobe dysfunction and cerebral structure on magnetic resonance imaging.

BACKGROUND: It was hypothesised that schizophrenic patients with tardive dyskinesia show an excess of neurodevelopmental disturbance, particularly minor physical anomalies, in association with cognitive dysfunction and abnormalities of cerebral structure. METHOD: Forty-seven out-patients with a DSM-III diagnosis of schizophrenia were examined for tardive dyskinesia using the Abnormal Involuntary Movement Scale; they were examined also for minor physical anomalies and neuropsychological test performance. Cortical atrophy, signal hyperintensities and lateral ventricular volume were determined on magnetic resonance imaging. RESULTS: Patients with and without tardive dyskinesia could not be distinguished by age, gender distribution or a number of clinical measures; however, patients with tardive dyskinesia sorted fewer categories on the Wisconsin Card Sorting Test (P = 0.04). Cerebral structure in patients with and without tardive dyskinesia could not be distinguished on magnetic resonance imaging but those with dyskinesia, all of whom showed involvement of the orofacial region, showed more evident minor physical anomalies of the head relative to those of the periphery (P = 0.02). CONCLUSIONS: Tardive orofacial dyskinesia in schizophrenia appears to be associated particularly with poorer frontal lobe function, while predominance of craniofacial dysmorphogenesis may constitute a vulnerability factor that is related to the early origins of the disease process.

Adult↗
PubMed1994

2D and 3D high resolution gradient echo functional imaging of the brain: venous contributions to signal in motor cortex studies.

Recent emphasis on high resolution gradient echo studies in functional imaging has led to the conclusion that there are likely three domains of response to the blood circulation in the brain when considering field inhomogeneity effects of the venous blood pre- and during activation. The first is a coherent effect due to large or macroscopic vessels on the order of the size of the voxel (ca 200-500 microns in most studies). These can lead to very large signal changes (up to 100%). The second is at the venule level (ca 50-200 microns) and is associated with smaller parenchymal changes (usually ca 10% or less). The third is at the capillary level and is associated with much smaller signal changes at 1.5 T and even up to 4 T. The actual signal changes depend on field strength and sequence design. In this paper, we present our experience in detecting the first two domains with 2D and 3D gradient echo imaging at 1.5 T. We find that high resolution enables visualization of the larger small veins in motor cortex studies and that, on occasion, it is possible to see the venule effects as well. We suggest a simple model to explain the large signal changes based on susceptibility changes and partial volume effects. Comparisons of the functional imaging data to this model and to MR angiographic studies are also shown as evidence of the venous sources of the susceptibility changes.

Brain↗
PubMed1994

Substance abuse among patients with treatment-resistant schizophrenia: characteristics and implications for clozapine therapy.

OBJECTIVE: The goals of this study were 1) to determine the extent of substance abuse in patients with treatment-resistant schizophrenia and 2) to assess the relevance of such abuse to subsequent response to treatment with clozapine. METHOD: The subjects were 118 treatment-resistant patients with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder who underwent detailed demographic, clinical, and psychopathological evaluations before commencing treatment with clozapine. Lifetime and current histories of substance abuse were also systematically evaluated and characterized according to the Research Diagnostic Criteria and DSM-III-R. Response to clozapine treatment at 6 months was determined with measures of psychopathology and psychosocial function. RESULTS: An antecedent or current history of substance abuse was determined for 29 patients. Although predominantly male, the abusers did not differ from the nonabusers on other demographic features. The substance abusers actually showed less psychopathology (negative and disorganization symptoms) and better psychosocial functioning at baseline; however, both groups attained similar improvements on these measures after 6 months of clozapine therapy. CONCLUSIONS: A modest extent of previous or current substance abuse was observed among neuroleptic-resistant schizophrenic patients who subsequently received treatment with clozapine. This antecedent history of substance abuse did not appear to negatively influence subsequent response to clozapine treatment.

Adult↗
PubMed1994

Self psychology, object relations theory and supportive psychotherapy.

A clinical theory of supportive psychotherapy that provides an explanatory model for its mode of therapeutic action can be developed through an examination of the work of Heinz Kohut and object relations theorists such as Ronald Fairbairn and D.W. Winnicott. Central to Kohut's theory of therapy is the premise that in the treatment situation a "good object" is provided for the patient in the form of a therapist who will be internalized, and thus mitigate or repair deficits in the self-structure resulting from inadequate early parenting. The object relations theorist Ronald Fairbairn also emphasizes the importance of the "satisfactory transference situation" to therapeutic change consistent with the author's view that fostering and maintaining the positive transference is a critical technical component in at least the earlier phases of supportive psychotherapy. D.W. Winnicott's conception of the "holding environment" is particularly relevant to the "frame" of supportive psychotherapy through such elements as ensuring the "safety" of the therapeutic situation, and the therapist not allowing anxiety and other affects to mount to intolerable and disorganizing levels. Central to the therapeutic posture of these clinicians is the adoption of an intensely emphatic introspective stance vis-a-vis the patient, which is seen was a critical component of supportive psychotherapy. The effective use of empathy aids the maintenance of the positive transference and facilitates the internalization by the patient of aspects of the interactive process in supportive psychotherapy, thus effecting therapeutic change.

Ego↗
PubMed1994

Observing the other: reflections on anthropological fieldwork.

Aspects of anthropological fieldwork are examined from a psychoanalytic viewpoint using two sources: (1) Malinowski's A Diary in the Strict Sense of the Term, a fieldwork journal he kept in New Guinea and the Trobriand Islands "as a means of self-analysis"; (2) the analysis of an anthropologist both before and after she returned from the field. Malinowski's Diary, written in a virtually free-associative form, illustrates how fieldwork stimulates derivatives of significant early infantile conflicts. The patient's analysis revealed the unconscious meaning of, and motivation for, fieldwork for this particular individual. Based on these data, it is postulated that during fieldwork a new, emotionally charged object relationship, with its concomitant transference responses, may be unconsciously established by the anthropologist with the alien society being studied.

Anthropology, Cultural↗
PubMed1994

Substance abuse and clozapine treatment.

Among 118 patients with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder who received treatment with clozapine, 29 patients had an antecedent or current history of substance abuse. Substance abusers and nonabusers showed similar improvements on measures of psychopathology and psychosocial functioning after 6 months of clozapine therapy. The implications of this finding are discussed.

Adult↗
PubMed1993

Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine.

Cognitive functions and psychopathology were assessed in 36 treatment-refractory schizophrenic patients before initiation of clozapine, and at 6 weeks and 6 months, thereafter. Before treatment, cognitive impairment was found in each measure of memory, attention, and executive function as compared with 26 normal controls. After both 6 weeks and 6 months of treatment, significant improvement occurred in the Controlled Oral Word Association Test, a measure of retrieval from reference memory. Improvement was also noted at 6 months in the Category Instance Generation Test, another measure of retrieval from reference memory, and in some, but not all, tests of executive function, attention, and recall memory. Clozapine treatment also resulted in significant improvement in Brief Psychiatric Rating Scale (BPRS) Total and Positive symptom scores at both 6-week and 6-month assessment points. There was some evidence for a relationship between improvement in psychopathology and cognitive function. The improvement in cognitive function during clozapine treatment could have consequences for capacity to work and social function.

Adult↗
PubMed1993

Identification of vascular structures as a major source of signal contrast in high resolution 2D and 3D functional activation imaging of the motor cortex at 1.5T: preliminary results.

We have measured the T2* signal response associated with cortical activation due to finger motion at 1.5 Tesla. Both thin slice 2D and 3D images show signal intensity changes which vary from 2% to 32% depending on volunteer, echo time, slice thickness, and in-plane resolution. The largest signal change occurred for the thinnest slices and highest resolution (2 mm3). This is consistent with reducing partial volume effects and a simple difference in phase between the intravascular signal and surrounding parenchyma. No inflow enhancement was seen on the 2D or 3D scans, confirming the nature of the signal difference for this approach was due to local field inhomogeneity effects. Using 3D imaging, multiple effects can be seen simultaneously. With a 3D MRA method, it was possible to locate the vessel that was the source of the T2* behavior; it was in each case a vein on the surface of the cortical parenchyma.

Brain↗
PubMed1993

13C alpha-NMR assignments of melittin in methanol and chemical shift correlations with secondary structure.

Melittin is a naturally occurring hexacosa peptide which forms an amphiphilic helix in methanol, a random coil in water, and a tetramer of helices at basic pH or in the presence of a high salt concentration. The monomeric structure in methanol has been well characterized by proton NMR (Pastore et al. (1989) Eur. Biophys. J., 16, 363-367). In the present paper, chemical shifts of the backbone alpha-carbons of melittin in methanol were determined by mapping previously published alpha-proton shifts (Bazzo et al. (1988) Eur. J. Biochem., 173, 139-146), to natural abundance (1H)13C cross peaks appearing in the 2D heteronuclear multiple-quantum NMR spectrum. Changes in chemical shifts consequent to stepwise increases in the percentage of water in a mixed methanol/water solvent system were observed in similar spectra. The alpha-carbon shifts varied more smoothly than the corresponding alpha-proton shifts and were found to correlate with the transition from the helix to the random coil conformer in parallel with changes in the circular dichroism spectrum. Chemical shifts of this peptide are interpreted with regard to the current database of assignments in proteins of known 3D structure (Wishart et al. (1991) J. Mol. Biol., 222, 311-333). The N-terminal region of the peptide shows increased flexibility at lower methanol concentrations, as evidenced by the merger of the alpha-proton resonances of G1 (at 40% and 15% methanol) and G3 (at 15% methanol). Conformational exchange rates for G1 and G3 were estimated by comparison of the experimental spectra with simulated spectra and found to be as large as 4000 s-1 for G1 in 40% and 15% methanol and 600 s-1 for G3 in 15% methanol. Overall, these 1H and 13C chemical shift data support the description of monomeric melittin in methanol currently evolving in the literature and suggest a structure composed of a linked pair of helices with different structural stabilities, each of which experiences dynamical fraying at its free terminus.

Calcium Isotopes↗
PubMed1993

Bipolar affective disorder prior to the onset of multiple sclerosis.

The frequent association of affective disorder and multiple sclerosis raises important aetiological and clinical considerations. Reported here are seven patients who presented with symptoms of multiple sclerosis and who had a preceding history of bipolar affective disorder. The hypothesis that bipolar illness may be the initial manifestation of multiple sclerosis is discussed with reference to relevant clinical and epidemiological research on the topic.

Adult↗
PubMed1993

Magnetic resonance imaging of schizophrenia-like psychoses associated with cerebral trauma: clinicopathological correlates.

Three patients with schizophrenia-like psychosis and two with schizoaffective-like psychosis who experienced cerebral trauma before the onset of their illness underwent clinical and magnetic resonance imaging evaluation. Each patient with a schizophrenia-like psychosis, but neither of those with a schizoaffective-like psychosis, showed abnormalities confined to or including the left temporal lobe. These observations complement recent findings in schizophrenia.

Adult↗
PubMed1992

Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study.

OBJECTIVE: To determine whether obstetric complications occur to excess in the early histories of individuals who go on to develop schizophrenia when compared with controls, and to seek clinical correlates of any such excess. DESIGN: Contemporaneous maternity hospital records were identified and extracted verbatim, and these extracts evaluated for obstetric complications by two independent assessors who were blind to subjects' status. SUBJECTS: 65 patients having an ICD-9 diagnosis of schizophrenia, the records of the previous same sex live birth being deemed to be those of a control subject. MAIN OUTCOME MEASURE: Presence of one or more obstetric complications recorded in maternity notes of patients and controls. RESULTS: When two recognised scales for specifying obstetric complications were used the patients with schizophrenia were significantly more likely than controls to have experienced at least one obstetric complication (odds ratio 2.44, 95% confidence interval 1.08 to 6.03). Patients also showed a greater number and severity of and total score for obstetric complications, fetal distress being the only complication to occur to significant individual excess (present in five (8%) patients, absent in controls). There was a marked sex effect, male patients being more vulnerable (odds ratio 4.24, 1.39 to 12.90) to such complications. Obstetric complications in patients were unrelated to family history or season of birth but were associated with a significantly younger age at onset of illness (mean difference--4.5 years,--1.2 to--7.8 years). CONCLUSIONS: Patients with schizophrenia, particularly males, have an excess of obstetric complications in their early developmental histories, and such complications are associated with a younger age at onset of their disease. Though the data are not conclusive, they also suggest that obstetric complications may be secondary to yet earlier events.

Adult↗