Mutagenicity of nitrodibenzopyranones in the Salmonella plate-incorporation and microsuspension assays.
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Biomedical subjects
Publications and source records attributed to D Walsh.
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Malignant ascites is a common complication of advanced cancer. It is associated with distressing symptoms and poor prognosis. Treatment may be aimed at the underlying cancer but is rarely successful. Therapeutic success for the available symptomatic treatment options for ascites is often limited. Control of symptomatic malignant ascites is possible with the use of diuretics in selected patients, is well tolerated, and should be tried first.
There is ongoing clinical research on prognostic parameters relevant to stage IA melanoma. The object is to identify those factors associated with an increased risk of recurrence. The charts of 197 patients first treated at our Institute between 1980 and 1992 along with 62 patients referred for follow-up or treatment of recurrent disease, all having been initially diagnosed with stage IA disease, were reviewed. Only one patient (0.5%) of those first treated at our Institute manifested recurrence and this was a local recurrence. No statistically significant differences were found between patients who relapsed and those who did not with regard to lesion thickness, level of invasion, evidence of ulceration, location of the primary lesion, gender, or age. Generally, stage IA melanomas have excellent prognosis. However, there are patients who experience recurrent and metastatic disease. At the present time, there are no reliable indicators available for use in predicting which patients are at risk.
Between 1980 and 1992, 68 patients with clinical indications of involvement of the gastrointestinal (GI) tract with metastatic melanoma were treated at Roswell Park Cancer Institute. Presenting symptoms were anaemia, abdominal pain, nausea and vomiting. Sites commonly involved were the small bowel (75%), the large intestine (25%), and the stomach (16%). Twenty-one patients were considered unsuitable for surgery; their median survival after diagnosis of GI metastases was 2.9 months. Forty-seven patients underwent abdominal surgery; effective palliation was achieved in most of them. Complete resection of GI metastases was accomplished in 47% of patients. The median survival after operation was 27.6 months for patients with complete resection of GI metastasis and no other disease, 5.1 months for patients with resection of involved GI tract and other metastases present, and 1.9 months for patients who had a by-pass procedure only. The 5-year survival for patients with complete resection of GI metastases and no other evidence of disease was 28.3%. The other groups had only 1-year survivors. Surgical intervention is justified on the basis of these findings, and extended palliation can be achieved in patients with complete resection of metastatic disease.
In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24-22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non-parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.
With on exception, previous studies examining the familial relationship between schizotypal personality disorder (SPD) and schizophrenia have compared rates of SPD in relatives of probands with schizophrenia versus control probands. In the Roscommon Family Study, an epidemiologically based family study of major psychiatric disorders conducted in the west of Ireland, we used a Cox proportional hazards model to examine the impact of a parental diagnosis of SPD on the risk for psychiatric disorders in siblings of probands with schizophrenia or schizophrenia spectrum disorders. In siblings of probands with schizophrenia or schizophrenia spectrum, a parental diagnosis of SPD significantly increased the risk for schizophrenia and schizophrenia spectrum disorders, but not for affective illness or anxiety disorders. These findings replicate our previous results from the Roscommon Family Study, further supporting the hypothesis that SPD has a substantial familial relationship with schizophrenia and other schizophrenia spectrum disorders, but not with affective illness.
Using case register data, the overall marital rate among 5158 patients with mental illness was found to be comparable to the general population. The proportion of those ever married was markedly reduced in the schizophrenic group relative to those with a manic or neurotic illness. Men with schizophrenia had a particularly low rate of marriage. The overall marital fertility of the 3 groups was comparable to each other and appeared to be higher than that in the general population. In the schizophrenic group only, married men, particularly those with a family history of mental disorder, produced more children than married women. Men might represent a more fertile group of schizophrenic patients with some biological advantage of increased fecundity, which may help to compensate for negative selection pressures.
The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI.(ABSTRACT TRUNCATED AT 250 WORDS)
This study reports on the endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) in the central nervous system (CNS) early after experimental infection of rhesus monkeys (Macaca mulatta) with pathogenic and nonpathogenic simian immunodeficiency virus (SIV). Diffuse endothelial expression of VCAM-1 was observed in the CNS in all animals receiving pathogenic SIV. These findings demonstrate the rapidity with which pathogenic SIV is able to enter the CNS and induce endothelial cell activation.
OBJECTIVE: The authors sought to evaluate whether the pattern of schizophrenia and related disorders in probands and their relatives can be explained by a single underlying continuum of liability to the "schizophrenia spectrum." METHOD: In the epidemiologically based Roscommon Family Study, the authors separately examined--in siblings, parents, and relatives of index and comparison probands--the familial aggregation and coaggregation of five hierarchically defined disorders: schizophrenia, schizoaffective disorder, schizotypal/paranoid personality disorder, other nonaffective psychoses, and psychotic affective illness. A multiple threshold model was fitted to these contingency tables by maximum likelihood. RESULTS: The multiple threshold model that constrained resemblance to be the same in siblings and parents fit the data well and estimated the correlation in liability to schizophrenia spectrum disorders between probands and first-degree relatives at 0.36. Parents, however, required higher levels of liability to manifest schizophrenia spectrum disorders than siblings. While schizophrenia and psychotic affective illness could be clearly assigned to the two extremes of the schizophrenia spectrum, the proper ordering of schizoaffective disorder, schizotypal/paranoid personality disorder, and other nonaffective psychoses could not be unambiguously determined. CONCLUSIONS: These results are consistent with the existence of a schizophrenia spectrum in which these five disorders are manifestations, of varying severity, of the same underlying vulnerability. This vulnerability is strongly transmitted within families.
OBJECTIVE: The authors sought to assess whether the DSM-III-R category of schizoaffective disorder differs meaningfully from schizophrenia and affective illness in clinical features, outcome, and familial psychopathology. In addition, the authors evaluated the validity of two proposed subtyping systems for schizoaffective disorder: 1) bipolar versus depressive (based on presence or absence of a full manic syndrome in the past) and 2) good versus poor interepisode recovery. METHOD: In the epidemiologically based Roscommon Family Study, index probands with diagnoses of schizophrenia or affective illness were selected from a case registry. Personal interviews were conducted with 88% of traceable, living probands and 86% of traceable, living first-degree relatives. RESULTS: Probands with schizoaffective disorder differed significantly from both those with schizophrenia and those with affective illness on lifetime psychotic symptoms as well as on outcome and negative symptoms assessed as follow-up. Relatives of probands with schizoaffective disorder had significantly higher rates of affective illness than relatives of schizophrenic probands and significantly higher rates of schizophrenia than relatives of probands with affective illness. Probands with bipolar and depressive schizoaffective disorder did not differ substantially with respect to psychotic symptoms, negative symptoms, outcome, or family history. Schizoaffective disorder probands with good interepisode recovery had fewer negative symptoms and a better outcome than those with poor recovery, but there were no significant differences in family history. Both the epidemiologic and family data are consistent with the hypothesis that schizoaffective disorder results from the co-occurrence of a high liability to both schizophrenia and affective illness. CONCLUSIONS: On the basis of the validators examined, DSM-III-R criteria for schizoaffective disorder define a syndrome that differs meaningfully from both schizophrenia and affective illness. The division of schizoaffective disorder into bipolar and depressive subtypes was, however, not validated. The separation of schizoaffective disorder into subtypes based on level of interepisode recovery defined subtypes that differed clinically but not with respect to familial psychopathology.
BACKGROUND: The season of birth phenomenon in schizophrenia was reexamined in relation to place of birth, in order to test the hypothesis that a seasonal factor might operate preferentially among those who were urban-born. METHOD: The seasonal distribution of births was examined among 3253 patients in two case registers having an ICD-9 diagnosis of schizophrenia and compared with the distribution of births among the normal population born in those catchment areas over the same period; those subjects born in population centres greater than 50,000 were defined as urban-born. RESULTS: Patients who were urban-born showed an excess of winter births relative to controls that was absent among their rural-born counterparts. On comparing patient groups, those who were urban-born were more likely to be born in the winter, while those who were rural-born were more likely to be born in the spring; this urban-rural distinction was confined essentially to female patients. CONCLUSIONS: These findings might be accommodated most readily in terms of a spatially as well as seasonally varying environmental factor that is associated with urbanicity and to which female offspring are more vulnerable.
BACKGROUND: Gender may have a significant impact on the prevalence, age at onset, symptoms, course and outcome of schizophrenia, as well as on the pattern of psychopathology in relatives. METHOD: We examined these questions in the Roscommon Family Study, in which the probands were epidemiologically sampled from a case registry and followed up an average of 15 years after onset. Face-to-face interviews were conducted with 86% of traceable living relatives. RESULTS: The treated lifetime prevalence of DSM-III-R schizophrenia was 0.54 +/- 0.06% in men and 0.28 +/- 0.04% in women. No significant differences were seen in the age at onset, symptoms, course or outcome of schizophrenia. The risks for schizophrenia, schizophrenia spectrum disorders, affective illness and alcoholism were similar in relatives of male and female schizophrenic probands. CONCLUSIONS: Gender has little impact on the presentation and course of schizophrenia in the west of Ireland. The familial liability to schizophrenia did not differ in affected men and women. No evidence was found that schizophrenia in women, compared to men, is, from a symptomatic or familial perspective, more closely related to affective illness. The substantial gender difference in the prevalence rate of schizophrenia in Ireland cannot be explained by women having a greater resistance to the familial predisposition to illness.
The incidence and mortality of cancer are increasing. In advanced cancer when cure is impossible, symptoms should be the focus of attention. We review our recent prospective studies on symptom prevalence and severity in 1,000 patients with advanced cancer. Advanced cancer patients are polysymptomatic. Symptom prevalence differs with age, gender, and cancer site. The pattern of gastrointestinal symptoms is related to gender and severe weight loss. Specific symptoms are associated with reduced survival. There is a gender difference in survival favoring females. Pain, easy fatigue, and anorexia are consistently among the 10 most prevalent symptoms at all 17 primary sites. When pain, anorexia, weakness, anxiety, lack of energy, easy fatigue, early satiety, constipation, and dyspnea were present, 60% to 80% of patients rated them as moderate or severe, ie, of clinical importance. The most common symptoms also are the most severe. In general, the same symptoms are clinically important at most primary sites.
In advanced cancer, when cure is impossible, symptoms should be the focus of attention. We report the first prospective, systematic analysis of the severity of 37 symptoms in 1000 patients with advanced cancer, using the Paradox relational database. Pain, easy fatigue, and anorexia were consistently among the 10 most prevalent symptoms associated with cancer at all sites. When pain, anorexia, weakness, anxiety, lack of energy, easy fatigue, early satiety, constipation, and dyspnea were present 60%-80% of patients rated them as moderate or severe, i.e. of clinical importance. The most common symptoms were also the most severe. In general the same symptoms were clinically important at most primary sites. Clinically important dyspnea, hoarseness, hiccough, and dysphagia were more common in men; anxiety, nausea, vomiting, and early satiety in women. Clinically important dyspepsia, nausea, and vomiting occurred more frequently in gynecological cancers.
This study reports on a systematic statewide effort to determine the residential needs and preferences of two important groups: primary consumers of mental health services and family members of consumers. Two comparable surveys regarding the residential needs of consumers were conducted. In all, 314 consumers and 459 family members participated in the survey. A comparison of the preferences of family members and consumers suggests that family members more often prefer congregate living situations and more staff support than do consumers. Consumers more often express a desire to reside by themselves without staff and without other persons who are mentally ill. While the direct comparison of preferences from these two constituencies has limitations, these data do suggest significant variability in needs and preferences voiced by consumers and their family members; discrepancies that need to be addressed by mental health policymakers and planners.
Today's health-care environment demands that palliative-care programs operate in a businesslike manner. This report summarizes the business plan and the process followed to develop the Palliative Care Program at the Cleveland Clinic Foundation (CCF). The benefits generated from this effort and the lessons learned that may be helpful to other program managers are described. By disciplining itself to focus on financial, marketing, and operational issues, the Palliative Care Program is in a better position to advance its clinical services within the organization and in its market area, and can thereby serve its patients more effectively.