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William Hubbard

Publications and source records attributed to William Hubbard.

3 recordsLinked to original sources

Validity of symptom assessment in psychotic disorders: information variance across different sources of history.

BACKGROUND: Factors such as poor insight, amotivation, suspiciousness, disorganized speech and attentional problems may interfere with the ability of acutely ill individuals with psychotic disorders to provide a valid account of their symptoms. This study was designed to determine the degree to which history provided by such subjects is consistent with that obtained from other sources. METHOD: Fifty-five subjects presenting with psychotic disorders were multiply evaluated with a semi structured interview, the Comprehensive Assessment of Symptoms and History (CASH), which includes the Scales for the Assessment of Negative and Positive symptoms (SANS and SAPS). One interviewer assessed the severity of the patient's symptoms in the previous month based solely on information provided by the patient. A second rater made symptom ratings based on information obtained from a "best informant". Following this, a consensus rating was established based on an extensive evaluation and review of all sources of information. An item-by-item comparison of the three sets of symptom ratings was then quantified by paired t-tests, simple and multiple correlations. RESULTS: Positive and negative symptoms ratings based on the subjects' report were significantly lower than the corresponding consensus ratings. However, those based on the informants' report did not differ from consensus ratings for negative symptoms. Information obtained from subjects and from informants together accounted for a majority of the variance of the consensus ratings. CONCLUSIONS: These findings demonstrate that assessment limited to patients' own reports are likely to underestimate psychopathology in acutely ill patients with psychotic disorders. Obtaining corroborative history from a family member may substantially improve the validity of the assessment of negative symptoms.

Adult↗

The immune decision toward allograft tolerance in non-human primates requires early inhibition of innate immunity and induction of immune regulation.

Brief treatment of rhesus macaques with immunotoxin plus 15-deoxyspergualin has yielded exceptional numbers (54%) of stable tolerant kidney allograft recipients, surviving over 6 years without rejection or immunosuppression. An early increase in IL-10 and reduction in IFNgamma distinguished recipients that subsequently became tolerant. Furthermore, analysis suggested that this immune switch was programmed within hours of transplantation. Administering deoxyspergualin within 5 h of surgery gave a higher incidence of tolerance (76%) compared to administration >5 h before or after surgery (11%, P<0.01). Deoxyspergualin inhibits nuclear translocation of activated NF-kappaB through heat shock proteins. Lymph node biopsies from tolerant recipients showed significant reductions in cytoplasmic expression of Hsp70 and RelB and almost complete inhibition of nuclear translocation of both. The early timing effect of deoxyspergualin suggests a crucial limitation to induction of stable tolerance is activation of Hsp-dependent innate responses to damage by ischemia-reperfusion. This was supported by studies in murine kidney reperfusion injury, where deoxyspergualin given 5 h before reperfusion protected renal function and reduced levels of IL-6 and IL-12. The narrow timing window for initiating deoxyspergualin treatment suggests the innate immune system is poised to defeat allograft tolerance induction, so effective blockade of NF-kappaB-mediated innate immunity must be in place early, to enable development of a tolerogenic environment.

Animals↗