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K C Murphy

Publications and source records attributed to K C Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1998

Association between functional psychosis and expanded CAG/CTG repeats is not explained by health stratification.

A number of studies have reported an association between large CAG/CTG repeats and both schizophrenia and bipolar disorder. Recently, we reported an inverse correlation between CAG/CTG repeat size and age in a health-selected population, raising the possibility that selection of control groups for physical health was a confounding factor in our previous association studies. We investigated this by health-selection of patients with schizophrenia and bipolar disorder. The maximum CAG/CTG repeat size remained significantly larger in probands with functional psychosis compared with control individuals, and in probands with a diagnosis of schizophrenia compared with control individuals. The number of probands in the healthy bipolar group was small, and although on average this group also had longer CAG/CTG repeats than control individuals, this failed to reach statistical significance. Our findings do not support the notion that the original results with psychosis as a whole, and schizophrenia specifically, are attributable to a stratification effect consequent on health selection. Nevertheless, we are unable formally to reject the hypothesis that the previously observed difference between bipolar probands and control individuals is the result of this phenomenon.

Bipolar Disorder↗
PubMed1998

Use of bacteriophage lambda recombination functions to promote gene replacement in Escherichia coli.

Replacement of Escherichia coli's RecBCD function with phage lambda's Red function generates a strain whose chromosome recombines with short linear DNA fragments at a greatly elevated rate. The rate is at least 70-fold higher than that exhibited by a recBC sbcBC or recD strain. The value of the system is highlighted by gene replacement with a PCR-generated DNA fragment. The deltarecBCD::Plac-red kan replacement allele can be P1 transduced to other E. coli strains, making the hyper-Rec phenotype easily transferable.

Bacteriophage lambda↗
PubMed1998

Chromosome 22qII deletions. An under-recognised cause of idiopathic learning disability.

BACKGROUND: Velo-cardio-facial syndrome (VCFS), a syndrome of multiple congenital abnormalities including characteristic dysmorphology, congenital heart defects and learning disability, is associated with small interstitial deletions of chromosome 22qII. We tested the hypothesis that VCFS may be significantly under-diagnosed by screening a learning disabled population for chromosome 22qII deletions. METHOD: Two hundred and sixty-five people with learning disability residing in two learning disability hospitals in South Wales were reviewed. They were selected for inclusion in the study if they fulfilled any of the following criteria: psychotic disorder (schizophrenia or affective disorder), family history of psychotic disorder, cleft palate and/or lip, congenital heart disease, broadly defined facial dysmorphism or a history of hypocalcaemia. Fluorescence in situ hybridisation studies were performed on 74 selected individuals. RESULTS: Cytogenetic analysis revealed that two people demonstrated a previously undetected chromosome 22qII deletion. A third person demonstrated a previously undetected cytogenetically visible deletion on chromosome 15. CONCLUSIONS: VCFS appears to be aetiologically significant in a proportion of individuals with idiopathic learning disability, especially in those where psychosis is associated with mild learning disability. We suggest that clinicians should consider a chromosome 22qII deletion in people who meet selection criteria.

Adult↗
PubMed1998

Polydactyly and psychosis. Five cases of co-occurrence.

BACKGROUND: Abnormalities presumed to occur during foetal life have been associated with schizophrenia. Polydactyly is a developmental abnormality but no previous association has been reported between polydactyly and functional psychotic illness. METHOD: Individuals with both polydactyly and a functional psychosis were ascertained during a study of familial schizophrenia. RESULTS: Five such individuals were ascertained in the course of assessing 234 individuals with familial psychosis, giving a rate of polydactyly in the sample of around 10 times the general population rate. CONCLUSIONS: This study provides preliminary evidence that polydactyly is over-represented in individuals with familial schizophrenia and related psychotic illnesses.

Adult↗
PubMed1997

Linkage study of chromosome 6p in sib-pairs with schizophrenia.

Following reports of linkage between schizophrenia and markers in the chromosomal region 6p24-22 we have studied nine microsatellite markers spanning 40 cM of this region in our sample of 102 affected sibling pairs from 86 families. Allele sharing identity by descent was examined using likelihood based sib-pair analysis as implemented by the program SPLINK. No evidence for linkage was obtained and the highest lod score was only 0.192 for D6S309. We conclude that if there is a susceptibility locus for schizophrenia in this region then its effect size is so small as to render our study insufficiently powerful to detect it.

Adult↗
PubMed1997

No evidence for an allelic association between schizophrenia and markers D22S278 and D22S283.

We report a case control association study using markers D22S278 and D22S283 in 90 unrelated patients with DSMIII-R schizophrenia and 90 controls matched for ethnicity, age and sex. No differences between allele frequencies for either marker were observed when the two groups were compared (D22S278: chi 2 = 6.53, df = 7, P = 0.51; D22S283: chi 2 = 14.73, df = 15, P = 0.48). These findings fail to support previous work by others suggesting the presence of allelic association between the markers D22S278 and D22S283 and schizophrenia.

Alleles↗
PubMed1997

Association between schizophrenia and a microsatellite polymorphism at the dopamine D5 receptor gene.

An association study of 97 patients with DSM-III-R schizophrenia and 97 matched controls was performed using a polymorphic microsatellite repeat at the dopamine D5 receptor gene. We observed a significant difference between the allele frequencies of patients and controls (chi 2 = 23.4, df = 12, p = 0.019). This reflects an excess of allele 4 (140 bp) in the patients when compared with the control sample (chi 2 = 7.087, p < 0.01; odds ratio = 2.98, 95% CI 1.29-6.86). However, this association remains tentative until confirmation in other samples.

Alleles↗
PubMed1996

Factor analysis of schizophrenic symptoms using the OPCRIT checklist.

Factor analysis was performed on OPCRIT checklist psychotic symptoms rated on 102 patients with DSM-III-R schizophrenia. An initial three-factor solution produced positive, negative, and disorganisation factors. However, application of the scree test suggested five substantive factors, with the positive factor dividing into three factors characterised, respectively, by paranoid symptoms, first rank delusions and first rank hallucinations.

Adult↗
PubMed1996

The molecular genetics of schizophrenia.

There is overwhelming evidence for a significant genetic contribution to the etiology of schizophrenia. Molecular genetic techniques are now sufficiently advanced to be applied to complex genetic disorders with uncertain phenotypes, such as schizophrenia. In this article we first briefly discuss certain pertinent background issues: the evidence that schizophrenia has a heritable basis, the possible modes of inheritance involved, and how best to define schizophrenia in the light of this evidence; we then review the current status of research in the field. Large collaborative studies are currently underway that pave the way for the detection of genes of both major and minor effects. We may now be seeing the first consistently replicated results from chromosome 6 and 22 and from candidate genes, such as the dopamine D3 receptor gene.

Chromosome Mapping↗
PubMed1996

No evidence for allelic association between schizophrenia and a polymorphism determining high or low catechol O-methyltransferase activity.

OBJECTIVE: Catechol O-methyltransferase (COMT) inactivates catecholamines by methylating their m-hydroxy group. Some previous studies using biochemical methods have found higher levels of COMT activity in schizophrenic patients. Recently, the genetic polymorphism that underlies variation in COMT activity, which results in the creation of a NlaIII restriction site in the low-activity allele, has been elucidated. METHOD: This study investigated this polymorphism in 78 unrelated schizophrenic patients and 78 comparison subjects matched for age and ethnicity. High-molecular-weight DNA was isolated from lymphocytes with routine procedures, and each individual was typed for high and low COMT activity. RESULTS: The frequency of the NlaIII polymorphism was 0.51 in the schizophrenic patients and 0.53 in the comparison subjects, and no significant allelic or genotypic associations were observed. CONCLUSIONS: There was no evidence for variation in COMT activity between a group of schizophrenic patients and matched comparison subjects.

Alleles↗
PubMed1996

Minor physical anomalies and their relationship to the aetiology of schizophrenia.

BACKGROUND: Previous reports have suggested an increased prevalence of minor physical anomalies (MPAs) in schizophrenia. METHOD: A review of the literature was performed to examine the relationship between MPAs, schizophrenia and other disorders. RESULTS: Previous studies demonstrate a number of methodological shortcomings. Moreover, MPAs are found in several other psychiatric disorders. Proponents of the neurodevelopmental model of schizophrenia have focused on an environmental explanation for the increased prevalence of MPAs. We argue that this may be overly simplistic and propose various ways in which genetic factors may also be involved. CONCLUSIONS: Better studies should be performed to examine more precisely the nature of MPAs in schizophrenia and other disorders and also the relationship between MPAs and other developmental abnormalities. At present, it is unclear if MPAs are directly related to the pathogenesis of the disorder or even if they are related to the timing of critical events.

Adult↗
PubMed1996

Expanded CAG/CTG repeats in schizophrenia. A study of clinical correlates.

BACKGROUND: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia. METHOD: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist. Patient's maximum CAG/CTG repeat length was measured using repeat expansion detection (RED). Significant differences were sought for repeat lengths in subjects categorised according to dimensional and categorical schizophrenia subsyndromes, affective episodes, individual symptoms, and a range of demographic variables. RESULTS: Maximum CAG/CTG repeat length did not differ significantly for any of the clinical or demographic variables studied. CONCLUSION: There are no subsyndromes or other clinical features of schizophrenia associated with CAG/CTG repeat expansion. Therefore, the identification of the gene(s) that contain expanded CAG/CTG repeats and which are associated with schizophrenia is unlikely to be facilitated at present by using any subsyndromes of schizophrenia as phenotypes.

Adult↗
PubMed1996

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE: To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS: We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS: Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION: Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Adenocarcinoma↗
PubMed1996

Psychosocial morbidity and survival in adult bone marrow transplant recipients--a follow-up study.

Previous reports have suggested that the presence of depression and other psychosocial variables may be associated with a poorer prognosis post bone marrow transplantation. Fifty-six patients had both unstructured clinical interviews and interviews using a structured diagnostic instrument (the Composite International Diagnostic Interview) and were followed up a mean of 82.1 months post-BMT. Of these, 42 patients were also interviewed using the Mental Attitude to Cancer Scale. Survival analysis revealed that factors such as depression or the presence of fighting spirit as the predominant coping style did not correlate with length of survival. Our results imply that survival may be more closely related to physical rather than psychosocial factors.

Adaptation, Psychological↗