Search PubMed⌕ Search

Biomedical subjects

D Walsh

Publications and source records attributed to D Walsh.

At least 163 records · Page 9Linked to original sources
PubMed1996

Self-report measures of schizotypy as indices of familial vulnerability to schizophrenia.

While structured psychiatric interviews have generally succeeded in identifying higher rates of schizotypal personality disorder in relatives of schizophrenia versus control probands, self-report questionnaires designed to assess schizotypy have been less successful at distinguishing these groups of relatives. In the Roscommon Family Study, an epidemiologically based, case-controlled study conducted in the west of Ireland, relatives were administered a short form of Eysenck's Psychoticism scale and shortened and modified versions of the scales for magical ideation and social anhedonia developed by Chapman and colleagues. We compared, with relatives of matched controls, relatives of four proband groups: schizophrenia, other nonaffective psychoses (ONAP), psychotic affective illness (PAI), and nonpsychotic affective illness (NPAI). Only social anhedonia scores successfully differentiated, at modest levels of significance, relatives of schizophrenia versus control probands. Levels of magical ideation did not distinguish relatives of schizophrenia, ONAP, PAI, or NPAI probands from relatives of controls. Compared to controls, ONAP probands had significantly elevated psychoticism scores, but no such increase was seen in relatives of schizophrenia, PAI, or NPAI probands. Dimensions of schizotypy assessed at personal interview were significantly better at differentiating relatives of schizophrenia and control probands than our measures of social anhedonia, magical ideation, or psychoticism. Although psychiatric interviews in this sample have shown that clinically assessed schizotypal personality disorder and traits strongly aggregate in relatives of schizophrenia patients, of the three self-report instruments designed to assess schizotypy, only one even modestly identifies relatives of schizophrenia versus control probands. These results suggest that, compared with psychiatric interviews, self-report questionnaires are less successful at assessing underlying familial vulnerability to schizophrenia.

Family↗
PubMed1996

Neurotrophin-3 gene polymorphisms and schizophrenia: no evidence for linkage or association.

It has been suggested on the basis of neuropathological and epidemiological evidence that schizophrenia is, at least in part, a neurodevelopmental illness. Some patients show abnormalities in cell position in the medial temporal lobes of their brains. Neurotrophin-3 is one of many proteins essential for the proper growth and development of the nervous system. Therefore the finding of a polymorphism near the promoter region of the gene, alleles of which were associated with the disease, prompted us to attempt replication. In a linkage and association analysis of the same polymorphism using familial schizophrenics and population controls we found no evidence to support the finding. We conclude that mutations or polymorphisms at this gene are unlikely to be involved in the genetic aetiology of schizophrenia.

Alleles↗
PubMed1996

The risk for psychiatric illness in siblings of schizophrenics: the impact of psychotic and non-psychotic affective illness and alcoholism in parents.

Clarification of the nature of the liability to schizophrenia transmitted within families is a major goal of family studies. In the Roscommon Family Study, the risk in relatives of schizophrenic vs. control probands was significantly increased for psychotic affective illness (PAI), but not for non-psychotic affective illness (NPAI) or alcoholism (ALC). We attempt to confirm these findings independently by examining, within families of schizophrenia spectrum probands, the relationship between PAI, NPAI and ALC in parents and the risk for schizophrenia spectrum disorders in siblings. A parental diagnosis of PAI predicted a significantly increased risk for schizophrenia, affective illness and anxiety disorders in siblings. In particular, schizophrenia in siblings was predicted by a parental diagnosis of mood-incongruent PAI. By contrast, neither a parental diagnosis of NPAI nor a parental diagnosis of ALC was associated with an increased risk for schizophrenia spectrum disorders in siblings. Consistent with our earlier findings, these results suggest that (a) the familial liability to schizophrenia is neither extremely non-specific nor extremely specific and (b) PAI, and particularly mood-incongruent PAI, may occur particularly in parents of schizophrenics because, although it reflects a significant familial liability to schizophrenia, it does not markedly impair the ability to marry and reproduce.

Adult↗
PubMed1996

Do endogenous features in depression predict the risk of psychiatric illness in relatives?

We sought to evaluate the hypothesis that endogenous symptoms define a form of depression that is relatively distinct from a familial perspective. Cox models examined the relationship between endogenous symptoms in 88 epidemiologically ascertained cases of treated major depression and the risk for a range of psychiatric disorders in relatives. Endogenicity did not predict risk of major depression, bipolar disorder, anxiety disorders, schizophrenia, or schizophrenia spectrum illnesses in relatives. Risk in relatives of illness as an external validator of endogenous depression is not supported by our family study data.

Depressive Disorder↗
PubMed1996

Accuracies and inaccuracies of the family history method: a multivariate approach.

This paper reports on 1459 first-degree relatives of probands with schizophrenia or affective illness and matched community controls. We sought (i) to validate psychiatric diagnoses obtained by family history (FH) against those obtained by a best estimate (BE) procedure based on personal interview and (ii) to explore the factors influencing the accuracy of the FH report. We found relatively poor agreement between the FH and BE diagnoses, and the disagreements were influenced by numerous factors, including gender, psychiatric status of the informant or proband's diagnosis. When validated against a BE diagnosis, the overall accuracy of the FH method is relatively poor, and is furthermore subject to several biases. Therefore, substituting the FH method for BE diagnosis may be an important source of error in the investigation of familial/genetic factors in psychiatric disorders.

Adolescent↗
PubMed1996

Byler-like familial cholestasis in an extended kindred.

Progressive familial intrahepatic cholestasis (PFIC) occurs in many communities and races. A form of PFIC in five children from two consanguineous marriages in an Irish kindred is described. In addition, a review of clinical information from the records of three deceased members of the kindred strongly implies that they also suffered from PFIC. The children had a history of neonatal diarrhoea, sepsis, and intermittent jaundice that ultimately became permanent. They suffered intractable pruritus and growth retardation. Despite evidence of severe cholestasis, serum gamma-glutamyl transferase and cholesterol were normal in these children. Sweat sodium concentration were raised in three children. Liver histology showed severe intrahepatic cholestasis and hepatocellular injury. Urinary bile acid analysis revealed a non-specific pattern consistent with chronic cholestasis. These children suffer from a form of PFIC remarkably similar to that occurring in members of the Byler kindred.

Bile Acids and Salts↗
PubMed1996

Evidence for a schizophrenia vulnerability locus on chromosome 8p in the Irish Study of High-Density Schizophrenia Families.

OBJECTIVE: This study was an attempt to replicate evidence for a vulnerability locus for schizophrenia and associated disorders in the 8p22-21 region reported by Pulver and colleagues. METHOD: The linkage sample of the Irish Study of High-Density Schizophrenia Families consists of 265 multiplex families containing 1,408 individuals. Fifteen markers covering 30 centimorgans on chromosome 8p were tested. Three statistical methods were used: two-point and multipoint heterogeneity lod scores and a multipoint nonparametric test. RESULTS: According to two-point heterogeneity lod scores, the strongest evidence for linkage was found for markers D8S1731 (maximum lod score = 2.00), D8S1715 (maximum lod score = 2.52), and D8S133 (maximum lod score = 2.08) by assuming a phenotypic definition of all psychiatric illness and a range of genetic models. According to multipoint heterogeneity lod scores, the strongest evidence for linkage (maximum lod score = 2.34), found by using a dominant genetic model and a broad definition of the schizophrenia spectrum, extended over a 10-cM region between markers D8S1715 and D8S1739. Multipoint nonparametric linkage found the strongest evidence (maximum z = 2.51) over a broader region when either a diagnosis of core schizophrenia or a narrow definition of the schizophrenia spectrum was used. This putative vulnerability locus was segregating in 10%-25% of the families studied. CONCLUSIONS: This study supports the existence of a vulnerability locus for schizophrenia on chromosome 8p. In this sample, this locus appears to influence the risk of illness in only a modest proportion of families and predisposes to a range of schizophrenia spectrum and possibly nonspectrum disorders.

Chromosomes, Human, Pair 8↗
PubMed1996

Quality of life assessment in advanced cancer.

Our purpose is to examine how applicable current quality of life instruments are in advanced cancer. Quality of life (QOL) is difficult to define and measure; it is a multidimensional, dynamic and subjective concept. An acceptable QOL instrument for advanced disease should be simple to administer and easy to explain, complete and analyse. In our view, the present instruments used in oncology do not serve the needs of advanced cancer patients. Based on our review, we believe a single question posed on a linear or categorical scale should be used to assess QOL in advanced cancer in preference to other available methods.

Humans↗
PubMed1996

Testing the effect of season of birth on familial risk for schizophrenia and related disorders.

BACKGROUND: An excess of late winter and early spring births in schizophrenia has been repeatedly demonstrated. Previous evidence has suggested that the risk for schizophrenia may differ in relatives of schizophrenic probands born in this high risk period v. at other times of the year. METHOD: In an epidemiologically based family study conducted in the west of Ireland, we examined the relationship between season of birth in schizophrenia and schizophrenia spectrum probands and the risk for schizophrenia and related disorders in first-degree relatives. Risk was assessed using the Cox proportional hazard method. We examined four birth seasons previously shown to significantly predict risk for schizophrenia. RESULTS: Neither the risk for schizophrenia nor that for schizophrenia spectrum disorders in relatives was significantly associated with season of birth in probands. CONCLUSIONS: Season of birth does not, in this sample, identify schizophrenic probands with particularly high or low familial vulnerability to illness.

Adult↗
PubMed1996

Age at onset in schizophrenia and risk of illness in relatives. Results from the Roscommon Family Study.

BACKGROUND: For many common medical and neuropsychiatric disorders, early age at onset reflects high familial liability to illness. However, for schizophrenia, most studies do not find such a relationship. METHOD: Using Cox proportional hazard modes, we investigate this question in the epidemiologically-based Roscommon family study. RESULTS: No relationship was found between age at onset in schizophrenic probands and the hazard rate for schizophrenia in their relatives. Similar results were obtained when the definition of illness was expanded to include schizoaffective disorder and other non-affective psychoses. CONCLUSIONS: For schizophrenia, a 'common-sense' model for age of onset (i.e. those with highest familial liability to illness succumb first while those with lower liability survive longer before falling ill) does not seem to apply. Our results are more consistent with a model in which variation in age at onset of schizophrenia is due to random developmental effects or to environmental experiences unique to the individual.

Adult↗
PubMed1996

In vitro characterization of DNA adducts formed by foundry air particulate matter.

This study is part of an ongoing investigation of biomarkers in iron foundry workers exposed to polycyclic aromatic compounds. Foundry workers with the highest exposures had elevated levels of DNA adducts in their white blood cells in previous studies. The purpose of this study was to characterize the nature of DNA reactive chemicals in foundry air samples through incubating the foundry filter extract with DNA and activation enzymes. Calf thymus DNA was incubated with foundry filter extract and activated by either rat liver activation mixture (S9 mix) or xanthine oxidase. A complex pattern of adducts was observed on thin-layer chromatography (TLC) by the 32P-postlabeling assay. Two selected polycyclic aromatic hydrocarbons (PAHs)--1-NP-and anti(+/-)benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide [anti(+/-) BPDE]-DNA adducts--were used as marker compounds in characterizing the postlabeled DNA adducts by TLC combined with high-performance liquid chromatography (HPLC). After an initial separation of DNA adducts by TLC, individual spots were isolated and separated further on HPLC. HPLC analysis and spiking with anti(+/-)BPDE-DNA standard confirmed the co-migration of the anti(+/-)BPDE-DNA standard with one PAH adduct formed by the S9 mix-activated DCM extract in calf thymus DNA.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

Sodium picosulphate compared with polyethylene glycol solution for large bowel lavage: a prospective randomised trial.

Mechanical efficiency, patient acceptability and minimal biochemical perturbation are important factors in the choice of lavage solution for bowel preparation. This prospective randomised trial of 59 patients compared a polyethylene glycol bowel lavage solution (Klean Prep) to a sodium picosulphate solution (Picolax) considering their efficacy from both colonoscopists' and radiologists' points of view, patient acceptibility, and plasma biochemical changes. The sodium picosulphate solution was more acceptable to patients than the polyethylene glycol, and resulted in significantly less nausea and vomiting (p = 0.0025), and far fewer consumption difficulties (p < 0.0001). Mean plasma biochemical changes were significantly different for magnesium (p < 0.001), chloride (p < 0.01) and potassium (p < 0.02). Because neither lavage solution displayed a marked advantage for the colonoscopist or radiologist, and sodium picosulphate was more acceptable to patients, sodium picosulphate is the preferred solution for bowel preparation. The changes in plasma biochemistry values are unlikely to cause clinical problems.

Adolescent↗
PubMed1996

DNA adducts and chronic degenerative disease. Pathogenetic relevance and implications in preventive medicine.

Chronic degenerative diseases are the leading causes of death in developed countries. Their control is exceedingly difficult due to their multiplicity and diversity, the interconnection with a network of multiple risk factors and protective factors, the long latency and multistep pathogenesis, and the multifocal localization. Adducts to nuclear DNA are biomarkers evaluating the biologically effective dose, reflecting an enhanced risk of developing a mutation-related disease more realistically than the external exposure dose. The localization and accumulation of these promutagenic lesions in different organs are the composite result of several factors, including (a) toxicokinetics (first-pass effect); (b) local and distant metabolism; (c) efficiency and fidelity of DNA repair; and (d) cell proliferation rate. The last factor will affect not only the dilution of DNA adducts but also the possible evolution towards either destructive processes, such as emphysema or cardiomyopathies, or proliferative processes, such as benign or malignant tumors at various sites. They also include heart tumors affecting fetal myocytes after transplacental exposure to DNA-binding agents, blood vessel tumors, and atherosclerotic plaques. In this article, particular emphasis is given to molecular alterations in the heart, which is the preferential target for the formation of DNA adducts in smokers, and in human aorta, where an extensive molecular epidemiology project is documenting the systematic presence of adducts to the nuclear DNA of smooth muscle cells from atherosclerotic lesions, and their significant correlation with known atherogenic risk factors. Exocyclic DNA adducts resulting from lipid peroxidation, and age-related indigenous adducts (I-compounds) may also originate from endogenous sources, chronic infections and infestations, and inflammatory processes. Type II I-compounds are bulky DNA lesions resulting from oxidative stress, whereas type II-compounds are presumably normal DNA modifications, which display positive correlations with median life span and are decreased in cancer and other pathological conditions. Profiles of type II-compounds strongly depend on diet and are related to the antidegenerative effects of caloric/ dietary restriction. Even broader is the possible meaning of adducts to mitochondrial DNA, which have been detected in rodents exposed to genotoxic agents and complex mixtures, as well as in untreated rodents, in larger amounts when compared to the nuclear DNA of the same cells. Mutations in mitochondrial DNA increase the number of oxidative phosphorylation-defective cells, especially in energy-requiring postmitotic tissues such as brain, heart and skeletal muscle, thereby playing an important role in aging and a variety of chronic degenerative diseases. A decreased formation of DNA adducts is an indicator of reduced risk of developing the associated disease. Therefore, these molecular dosimeters can be used as biomarkers in the prevention of chronic degenerative diseases, pursued either by avoiding exposure to adduct-forming agents or by using chemopreventive agents. Interventions addressed to the human organism by means of dietary measures or pharmacological agents have encountered a broad consensus in the area of cardiovascular diseases, and are deserving a growing interest also in cancer prevention. The efficacy of chemopreventive agents can be assessed by evaluating inhibition of nuclear DNA or mitochondrial DNA adduct formation in vitro, in animal models, and in phase II clinical trials in high-risk individuals.

Animals↗
PubMed1995

Enhanced levels of DNA adducts in the liver of woodchucks infected with hepatitis virus.

Liver DNA specimens from woodchucks kept in captivity, 10 naturally infected with hepatitis virus (WHV) and five WHV-free, were examined for the presence of carcinogen-DNA adducts by 32P-postlabeling. The number of adducts was significantly higher in WHV carriers than in uninfected animals, and the total amounts of adducts per 10(9) nucleotides were also considerably enhanced by WHV infection, when using both butanol extraction (22.2 +/- 7.1 vs. 12.6 +/- 2.8, means +/- S.D.) and nuclease P1 enrichment (8.5 +/- 5.9 vs. 2.8 +/- 1.7). Two individual adducts were also significantly higher in WHV carriers. No significant variation occurred as related to age, sex or time length of captivity. These findings are consistent with our previous studies supporting an enhanced metabolism of chemical hepatocarcinogens in both human and woodchuck hepadnavirus infections. Several significant and remarkable correlations were pointed out by relating DNA adduct data to more than 30 virological, histopathological and metabolic parameters which had been previously evaluated in the same animals. For instance, numbers and/or levels of adducts were positively related to the amounts of virus present in hepatocytes, to cell damage (gamma-glutamyltranspeptidase activity), to the severity of the liver histopathological picture, and to monooxygenase activities, while they were inversely related to cellular glutathione concentrations and to detoxification of the direct-acting mutagen 4-nitroquinoline 1-oxide. The major adduct significantly correlated with the metabolic activation of the aromatic amine 2-aminofluorene and of the heterocyclic amines 3-amino-1-methyl-5H-pyrido(4,3)indole (Trp-P-2) and 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ), whereas another adduct significantly correlated with the metabolic activation of the mycotoxin aflatoxin B1. Thus, the enhanced metabolism of chemical hepatocarcinogens and the increased formation of carcinogen-DNA adducts in the liver of WHV carriers appear to represent one of the mechanisms contributing to the association between chronic hepadnavirus infection and development of primary hepatocellular carcinoma.

4-Nitroquinoline-1-oxide↗
PubMed1995

Schizotypal symptoms and signs in the Roscommon Family Study. Their factor structure and familial relationship with psychotic and affective disorders.

BACKGROUND: Although schizotypal personality disorder aggregates in relatives of schizophrenic probands, the criteria for this disorder may not be optimal either in describing the dimensions of schizotypal phenomena or in identifying those with a high familial liability to schizophrenia. METHODS: In the Roscommon Family Study, an epidemiologically based family study of major psychiatric disorders conducted in the west of Ireland, we examined 25 individual schizotypal symptoms and signs, assessed by structured personal interview, in 1544 first-degree relatives (without chronic psychosis or mental retardation) of five proband groups: schizophrenia; other nonaffective psychoses; psychotic affective illness; nonpsychotic affective illness; and matched, unscreened controls. RESULTS: We obtained seven meaningful schizotypal factors: negative schizotypy, positive schizotypy, borderline symptoms, social dysfunction, avoidant symptoms, odd speech, and suspicious behavior. Taken individually, all of these factors, except borderline symptoms, significantly discriminated relatives of schizophrenic probands from relatives of controls; in descending order of the odds ratios, they were odd speech, social dysfunction, suspicious behavior, negative schizotypy, avoidant symptoms, and positive schizotypy. In a multivariate analysis, four of these factors remained significant: odd speech, negative symptoms, social dysfunction, and avoidant symptoms. These schizotypal factors differed in their specificity. Three of the four most predictive schizotypal factors also significantly discriminated relatives of probands with other nonaffective psychoses from relatives of controls. CONCLUSION: "Schizotypy" is a complex, multidimensional clinical construct, whose various dimensions differ widely both in the degree and specificity with which they reflect the familial liability to schizophrenia. Subpsychotic thought disorder; negative schizotypal signs, such as poor rapport and odd behavior; deficient occupational functioning; and social isolation/avoidance best characterized relatives of schizophrenic probands compared with relatives of matched controls.

Adolescent↗
PubMed1995

Malignant melanoma of the anorectal region.

The charts of 15 patients with malignant melanoma of the anorectal region treated at Roswell Park Cancer Institute in the period 1975-1991 were reviewed. All the lesions except one developed at the pectinate line, in the area of transitional mucosa. Two of the patients at the time of initial presentation had distant metastases. Of the remaining 13, 8 were treated with abdominoperineal resection (APR) and 5 with local excision (LE). The incidence of local recurrence was 50% in the LE group and 22% in the APR group. Patients treated with APR had a 25%, 5-year survival rate compared with 0% for those treated with LE, although one of the latter group died 55 months following LE due to unrelated causes without recurrence. The median survival of those with LE was 15.7 months and of those with APR 13.7 months.

Adult↗