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Biomedical subjects

D Walsh

Publications and source records attributed to D Walsh.

At least 199 records · Page 11Linked to original sources
PubMed1994

The use of chlorpromazine for symptom control in dying cancer patients.

Terminal restlessness is a significant problem in deaths from advanced cancer, it is difficult not only for patients, but for family and health-care providers also. Chlorpromazine is an antipsychotic phenothiazine, safe at high doses and by many routes. It has also been used as an adjunct to morphine in advanced cancer. We have conducted a study using chlorpromazine in 20 patients, in which the drug was administered intravenously (i.v.) or rectally (PR) in inpatients and outpatients for terminal restlessness and dyspnea. The median PR dose was 25 mg every 4-12 hr. The median IV dose was 12.5 mg every 4-12 hr. Eighteen patients had complete relief and two had partial relief before death. We find chlorpromazine safe and effective for the relief of terminal restlessness and dyspnea in advanced cancer.

Chlorpromazine↗
PubMed1994

Biases in the diagnosis of alcoholism by the family history method.

The authors explored the factors influencing the agreement of diagnoses of alcoholism obtained by a best-estimate (BE) procedure versus those obtained by family history (FH) only, based on data from the Roscommon Family Study. The participants were first-degree relatives of either schizophrenic subjects, subjects with affective disorders, or matched community controls. The FH information was obtained from first-degree relatives of the participants, whereas the BE diagnoses included personal interview and medical records as well as FH information. Two types of error were distinguished: false-negative FHs, who were diagnosed with alcoholism by BE but not by FH; and false-positive FHs, who were diagnosed with alcoholism by FH but not by BE. The risk of false-negative FHs was increased by young age of the subject and male gender of the informant, and decreased by a history of previous hospitalization of the subject. Conversely, the risk for false-positive FHs was increased by older age of the subject, male gender of the subject, female gender of the informant, and informant's diagnosis of alcoholism. Comorbid diagnosis of nonaffective psychosis increased the risk of both types of error. It is concluded that when validated against a BE diagnosis, the FH diagnosis of alcoholism is subject to several biases and that the FH method is not a satisfactory substitute for BE diagnoses.

Adolescent↗
PubMed1994

Clinical heterogeneity in schizophrenia and the pattern of psychopathology in relatives: results from an epidemiologically based family study.

Individuals with schizophrenia vary widely in their symptoms, course of illness and outcome. Family background is the strongest known risk factor for schizophrenia. We know little of the relationship between clinical variability in this disorder and the level of familial vulnerability to schizophrenia and other major mental disorders. Therefore, in schizophrenic probands meeting DSM-III-R criteria (n = 126) from the epidemiologically based Roscommon Family Study, we systematically assessed 9 major symptoms, course, global outcome, Schedule for Negative Symptoms and the Levels of Functioning Scale. These clinical characteristics were related t the risk of mental disorders in first-degree relatives assessed by personal interview or hospital records (n = 354) utilizing both the "familial/sporadic" and the Cox proportional hazard models. Using either statistical method, no consistent and significant relationship was found between any of our measures of symptoms, course or outcome and the risk for schizophrenia or schizophrenia spectrum disorders in relatives. Similarly, no relationship was found between these clinical measures and the risk for affective illness, alcoholism or anxiety disorders. Our results are not consistent with previously articulated hypotheses that negative symptoms or poor outcome in schizophrenia reflect a high familial liability to illness. While familial factors contribute substantially to an individual's vulnerability to schizophrenia, our results suggest that once an individual is affected, these same factors do not strongly influence either the kinds of symptoms displayed or the course and outcome of the illness.

Adult↗
PubMed1994

An analysis of the clinical features of familial schizophrenia.

Clinical features of familial schizophrenia were examined in 169 siblings from 80 families. Factor analysis of symptoms produced a negative symptom factor (affective flattening and negative thought disorder), a disorganization factor (inappropriate affect and positive thought disorder) and a reality distortion factor (delusions and hallucinations). The negative symptom factor correlated positively with duration of illness and poor outcome. The disorganization factor correlated positively with poor outcome and early age at onset. The only clear correlation between these factors and affective symptoms was a negative one between the negative symptom factor and mania. There were no significant gender differences in age at onset, factor scores or outcome. The implication of these findings in relation to recent research in the areas of psychopathology and epidemiology are discussed.

Adolescent↗
PubMed1994

TNF-alpha and IL-6 expression in perfused rat liver after intraportal candidemia vs. E. coli or S. aureus bacteremia.

We tested the hypothesis that regulation of tumor necrosis factor-alpha (TNF-alpha) and IL-6 by the liver differs after intraportal challenge with Candida albicans spp. vs. gram-negative or gram-positive bacteria, independent of microbial clearance kinetics or hepatic O2 consumption (VO2). Buffer-perfused rat livers were infected with equivalent inocula (10(9) colony-forming units) of viable Escherichia coli serotype 055:B5 (EC), exotoxin C-producing Staphylococcus aureus (SA), or two strains of yeast phase C. albicans (CA-1 and CA-2). Microbial clearance and circulating cytokine levels were assessed over 180 min while monitoring VO2 and functional parameters, after which organ-based microbial killing, cell-associated TNF-alpha, and cytokine mRNA levels were determined. Compared with saline controls (normal saline solution; NSS), circulating and cell-associated TNF-alpha and TNF-alpha transcripts minimally increased after CA. In contrast, large increases in perfusate TNF-alpha occurred after EC, peaking at 180 min [135 +/- 32 U/ml (mean + SE)], concomitant with rises in cell-associated cytokine and TNF-alpha transcripts (P < 0.01 vs. NSS). Circulating TNF-alpha also rose after SA but neither cell-associated nor mRNA levels exceeded NSS values. There were no pathogen-specific differences in microbial clearance or VO2. IL-6 gene expression paralleled that for TNF-alpha, but IL-6 bioactivity in perfusates was inhibited by TNF-alpha-dependent and -independent mechanisms. We conclude that hepatic TNF-alpha and IL-6 expression are differentially regulated after taxonomically diverse microbial challenges, with E. coli eliciting the strongest and Candida spp. the weakest stimulatory responses.

Animals↗
PubMed1994

An epidemiologic, clinical, and family study of simple schizophrenia in County Roscommon, Ireland.

OBJECTIVE: The authors sought to estimate the prevalence of simple schizophrenia, compare the clinical presentations and courses of simple and "typical" schizophrenia, and examine psychopathology in first-degree relatives of probands with simple schizophrenia, probands with typical schizophrenia, and community comparison subjects. METHOD: The authors followed up all individuals with a recorded diagnosis of schizophrenia (N = 285) and 75% of those with a diagnosis of severe affective illness (N = 99) from the Roscommon County Case Register, which includes all individuals seeking psychiatric care in a rural county in western Ireland. The authors interviewed all available first-degree relatives of these groups and of matched unscreened community comparison subjects. RESULTS: Eleven cases of simple schizophrenia were diagnosed in the probands, for an estimated population prevalence and morbid risk in County Roscommon of 5.3 (SE = 1.6) and 6.2 (SE = 1.9) per 10,000, respectively. Individuals with typical schizophrenia (N = 126) had more marked delusions, hallucinations, and positive thought disorder; individuals with simple schizophrenia had more pronounced negative thought disorder and a more chronic course. Neither social/occupational functioning nor negative symptoms differed between the two groups. The risks for schizophrenia and all nonaffective psychoses were greater in the relatives of the probands with simple schizophrenia than in the relatives of the community comparison subjects. CONCLUSIONS: In this sample, simple schizophrenia was relatively rare, was rather debilitating, and resembled typical schizophrenia in presentation and course except for the absence of positive psychotic symptoms. From a familial perspective, simple schizophrenia appears to be related to typical schizophrenia.

Adult↗
PubMed1994

Outcome and family study of the subtypes of schizophrenia in the west of Ireland.

OBJECTIVE: The authors sought to clarify differences in outcome and familial psychopathology among the classical subtypes of schizophrenia. METHOD: In the epidemiologically based Roscommon Family Study, personal interviews were conducted with 88% of traceable living probands (N = 415) an average of 16 years after illness onset and with 86% of traceable living first-degree relatives (N = 1,753). Probands meeting the DSM-III-R criteria for schizophrenia were subtyped by DSM-III-R and ICD-9. RESULTS: By both diagnostic systems, age at onset differed significantly across subtypes, being earliest in the subjects with the hebephrenic and catatonic subtypes and latest in the paranoid subjects. The probands with the paranoid subtype had substantially better outcome, especially in occupational functioning and capacity for self-care. The DSM-III-R criteria for paranoid schizophrenia were considerably more successful than the ICD-9 criteria in selecting good-outcome cases. Neither the risk for schizophrenia nor the risk for schizophrenia spectrum disorders significantly differed in relatives as a function of the proband subtype. The subtypes of schizophrenia did not "breed true" within families. CONCLUSIONS: Paranoid schizophrenia, especially when narrowly defined, as in DSM-III-R, has a substantially better outcome than other subtypes. From a familial perspective, 1) paranoid schizophrenia is not a milder form of schizophrenia and 2) catatonic schizophrenia is probably closely related to typical schizophrenia. The subtypes of schizophrenia are not, from a familial perspective, etiologically distinct syndromes.

Adult↗
PubMed1994

The cancer anorexia-cachexia syndrome.

PURPOSE: To review the research related to the anorexia-cachexia syndrome in patients with cancer, with attention to the etiology and symptomatic treatment. DESIGN: A comprehensive literature review using MEDLINE. RESULTS AND CONCLUSION: The anorexia-cachexia syndrome is a common problem in advanced cancer. Although many possible etiologies have been investigated, the cause has not been determined. Appropriate clinical evaluation is necessary to identify those patients who may respond to available, symptomatic treatments.

Animals↗
PubMed1994

Palliative care: management of the patient with advanced cancer.

The incidence and mortality of cancer are increasing worldwide. Changes in lifestyle and living standards have contributed to this phenomenon, as have other factors, such as an increase in the high-risk elderly population in Western Europe and North America. This, coupled with the decline of the family unit and an escalation in the numbers of Americans living alone, is creating a significant health care problem in the United States; namely, how will we be able to provide adequate care for the increasing numbers of aged expected to develop cancer in the 21st century in ways compatible with cost-saving and cost-effective strategies currently being used in the health care industry? The bulk of current cancer research is directed at developing new curative strategies, while improving palliative measures for the treatment of the symptomatology of cancer is largely ignored. We will have to refocus our priorities if we are to be successful in addressing this problem. This paper provides an overview of current trends in the palliative management of patients with advanced cancer and offers insights into how we may begin to prepare ourselves to meet the challenges of cancer care in the years ahead.

Hospices↗
PubMed1994

Increase in blood lactate during ramp exercise: comparison of continuous and threshold models.

Controversy persists regarding the mechanism underlying the lactate threshold. It has recently been argued that there is in fact no "threshold" and that blood lactate increases as a continuous function during exercise (Hughson J. Appl. Physiol. 62:1975-1981, 1987). In comparing continuous and threshold models, questions have been raised regarding the ramp rate, data sampling, and the mathematical models employed (Morton J. Appl. Physiol. 67:885-888, 1989). To address some of these concerns, we evaluated 61 subjects (mean age 45 +/- 15), who underwent maximal ramp treadmill tests with the ramp rate individualized such that test duration was approximately 10 min for each subject. The relationship between changes in blood lactate and oxygen uptake were evaluated using a modification of the log-log transformation model described by Beaver (J. Appl. Physiol. 59:1936-1940, 1985) and a continuous exponential plus constant model described by Hughson et al. (J. Appl. Physiol. 62:1975-1981, 1987). Model fitting, using mean squared error (MSE) and coefficient of determination (CD) for each method were as follows: [table: see text] The modified log-log model had a better fit as indicated by the lower MSE and higher CD, suggesting the change in lactate was better described by this model. However, the differences were so slight as to suggest: 1) a meaningful difference does not exist between the two; or 2) these methods may not be capable of detecting a difference, if one exists.

Adult↗
PubMed1994

A phase II study of delta-9-tetrahydrocannabinol for appetite stimulation in cancer-associated anorexia.

PURPOSE: To evaluate the appetite-stimulating properties of delta-9-tetrahydrocannabinol (THC) in patients with anorexia due to advanced cancer. PATIENTS AND METHODS: Nineteen patients with various malignancies were entered. All had cancer-associated anorexia and a life expectancy greater than four weeks. Patients were started on THC 2.5 mg p.o. t.i.d. one hour after meals for four weeks. Evaluations for side effects, efficacy, acceptability and satisfaction were conducted at two and four weeks. RESULTS: 18 patients were evaluable. Ten patients completed the entire 28-day study. Four patients experienced grade I toxicity and three withdrew at their request. Thirteen patients reported an improved appetite. CONCLUSION: THC is an effective appetite stimulant in patients with advanced cancer. It is well tolerated at low doses. Further studies are needed to determine the most appropriate dose and the specific population most likely to respond.

Administration, Oral↗
PubMed1994

Symptom management in esophageal cancer.

Most patients with esophageal cancer present late with regional or distant metastases and have a poor prognosis. They have many debilitating physical and psychosocial problems. Proper symptom management improves quality of life. The continuity of health care in advanced disease can be best provided by hospice home care programs. Appropriate comfort measures will alleviate terminal restlessness in a dying patient and permit them to die with dignity.

Anorexia↗
PubMed1994

Kinetic expression of endothelial adhesion molecules and relationship to leukocyte recruitment in two cutaneous models of inflammation.

BACKGROUND: Adhesive interactions between circulating leukocytes and endothelium is requisite for subsequent leukocyte extravasation at inflammatory sites. These adhesive events are mediated by a repertoire of proteins and carbohydrate moieties on both leukocyte and endothelial membranes. Understanding the kinetic expression of these adhesion molecules during an inflammatory cascade in vivo is important for the design and testing of rational therapeutic approaches directed at the blockade of adhesion molecule function in inflammatory disease. EXPERIMENTAL DESIGN: Two cutaneous inflammatory models were examined using healthy rhesus monkeys. Acute cutaneous injury was studied during a 72-hour period by intradermal injection of endotoxin (lipopolysaccharide) and subsequent biopsy. These tissues were then compared with those obtained from a cutaneous delayed-type hypersensitivity reaction (DHR), elicited by intradermal injections of mammalian tuberculin in sensitized animals and followed for up to 11 days. Expression of E-selectin, P-selectin, VCAM-1, and ICAM-1 was assessed using immunohistochemistry and compared with leukocyte localization and immunohistochemical expression of interleukin (IL) 1, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Finally, relevant adhesion ligands on leukocytes were assessed using flow cytometry. RESULTS: The lipopolysaccharide model was characterized by early (0.5 hours) and sustained (up to 72 hours) expression of E-selectin on the superficial dermal vasculature, with maximal expression by 8 hours. The expression of VCAM-1 was either not detected or minimal. Neutrophil localization, as detected by elastase immunoreactivity, paralleled E-selectin expression with a 4- to 12-hour lag phase, being maximal by 24 hours. In contrast, DHR was characterized by the dual asynchronous expression of both E-selectin and VCAM-1. Localization of CD2+ lymphocytes, representing the predominant cell type recruited, kinetically followed the expression of E-selectin and VCAM-1, being maximal in number at approximately 48 hours after peak expression of both of these endothelial proteins. Neutrophil recruitment in lipopolysaccharide-induced injury was associated with immunohistochemical localization of TNF-alpha, IL-1, and IL-8, whereas only TNF-alpha was consistently detected in DHR. During DHR, blood lymphocyte expression of L-selectin, VLA-4 (CD49d; alpha chain), and lymphocyte function-associated antigen 1 (both CD11a (alpha chain) and CD18 (beta chain)) did not change. CONCLUSIONS: The results from this study demonstrate that cutaneous inflammatory infiltrates of varying cellular compositions are associated temporally and spatially with unique patterns of endothelial adhesion molecule and cytokine expression.

Animals↗
PubMed1993

The Roscommon Family Study. I. Methods, diagnosis of probands, and risk of schizophrenia in relatives.

OBJECTIVES: We sought to examine, in a rural county in the West of Ireland, the degree of familial relationship between schizophrenia and other nonaffective psychoses and affective illness (AI). DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: This study included three proband groups: (1) all cases with a clinical diagnosis of schizophrenia from the Roscommon County Case Register born from 1930 onward (n = 285); (2) a random sample of cases from the register with a clinical diagnosis of severe AI (n = 99); and (3) a matched, random sample of Roscommon residents ascertained from the electoral register (n = 150). Face-to-face structured interviews were conducted with 86% of traceable, living relatives (n = 1, 753) and 88% of traceable, living probands (n = 415). RESULTS: In interviewed relatives, the lifetime risks (+/- SE) for schizophrenia, as a function of the "blind" proband diagnosis, were as follows: schizophrenia, 6.5% +/- 1.6%; schizoaffective disorder, 6.8% +/- 2.5%; schizotypal personality disorder, 6.9% +/- 3.9%; other nonaffective psychoses, 5.1% +/- 2.4%; psychotic AI, 2.8% +/- 1.2%; nonpsychotic AI, 0.6% +/- 0.6%; and control, 0.5% +/- 0.3%. Individuals with schizophrenia reproduced at a rate about one quarter that of controls and the risk for schizophrenia in parents of probands was much less than that found in siblings. CONCLUSIONS: These results support the following hypotheses: (1) in the West of Ireland, as in other populations, schizophrenia is a strongly familial disorder; (2) schizophrenia shares a familial predisposition with a spectrum of clinical syndromes that includes schizoaffective disorder, other nonaffective psychoses, schizotypal personality disorder, and probably psychotic AI, but not nonpsychotic AI; and (3) the diminished reproductive rates associated with schizophrenia have a large impact on the pattern of risk of illness in relatives.

Adult↗
PubMed1993

The Roscommon Family Study. II. The risk of nonschizophrenic nonaffective psychoses in relatives.

OBJECTIVE: We sought to clarify the familial relationship between the nonschizophrenic, nonaffective psychoses (schizoaffective disorder [SAD], schizophreniform disorder, delusional disorder, and atypical psychosis) and schizophrenia and affective illness (AI). DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. RESULTS: Compared with relatives of unscreened controls, the risk of nonschizophrenic, nonaffective psychoses was significantly elevated in relatives of probands with schizophrenia, SAD, schizotypal personality disorder, and psychotic AI. No significant elevation in risk to these disorders was seen in relatives of probands with nonpsychotic AI. The risk for SAD alone was significantly increased in relatives of probands with psychotic or bipolar AI. CONCLUSIONS: The nonschizophrenic, nonaffective psychoses have a significant familial relationship with both schizophrenia and schizotypical personality disorder. Schizoaffective disorder, as defined by DSM-III-R, shares familial etiologic factors with at least some forms of AI.

Adolescent↗
PubMed1993

The Roscommon Family Study. III. Schizophrenia-related personality disorders in relatives.

OBJECTIVES: We sought to clarify the familial relationship between five putative schizophrenia-related personality disorders (schizotypal [SPD], paranoid, schizoid, avoidant, and borderline) and schizophrenia, other nonaffective psychoses, and affective illness. DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria. PARTICIPANTS: Five hundred thirty-four probands selected from a psychiatric case register or electoral register, of whom 415 were personally interviewed, and 2043 living and traceable relatives, of whom 1753 were personally interviewed. RESULTS: Compared with relatives of unscreened controls, relatives of probands with schizophrenia had a highly significantly increased prevalence of SPD, and modest, but significant, increased prevalences of paranoid, schizoid, and avoidant personality disorders. Borderline personality disorder was rare, with a modest clustering of cases in relatives of affective disorder probands. The prevalence of SPD was also significantly elevated in relatives of probands with SPD and with other nonaffective psychoses but not in relatives of probands with psychotic or nonpsychotic affective illness. In contrast to the pattern seen for schizophrenia, the prevalence rate of SPD was substantially greater in parents than in siblings of schizophrenic probands. CONCLUSIONS: Schizotypal personality disorder has a strong familial relationship with schizophrenia. Paranoid, schizoid, and avoidant, but not borderline, personality disorders may have a significant familial relationship with schizophrenia. Schizotypal personality disorder also reflects the familial liability to other psychotic disorders but probably not to affective illness. Fitness effects may substantially influence the pattern of schizophrenia-related personality disorders in relatives.

Adolescent↗