Idiotypic interactions and immunopathology.
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Biomedical subjects
Publications and source records attributed to M Goldman.
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There is an increasing need for practical instruments that can rapidly and accurately assess the effectiveness of treatments for mental illness in clinical settings. Symptom rating scales used in clinical research are too complex and time-consuming to be useful in these settings. In contrast, single-item global measures of severity such as the Clinical Global Impression-severity scale (CGI) and the Global Assessment of Function scale (GAF) are brief and easy to complete, but little is known about their relationship with the specific symptoms of severe mental illnesses. In this study, we examine the extent to which CGI and GAF scores reflect the severity and the change in severity of positive, negative, depressive, and agitation symptoms in a sample of 102 schizophrenia inpatients at the University of Michigan Medical Center. At admission, positive symptoms were the strongest correlates of both CGI and GAF scores, followed by negative symptoms, and agitation. Depressive symptoms did not correlate significantly with either global measure. The three symptom scores together explained 58% of the variation in CGI and 39% of the variation in GAF. A similar pattern of association was found for the scores measured at discharge and for the relationships between the change in global measures and change in specific symptom clusters. Thus, by demonstrating that single-item global measures, particularly the CGI, can be reasonably good indicators of psychopathology, this study suggests that these measures may be practical tools for routine monitoring of the effectiveness of treatments for severe mental illness in community settings.
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An in vitro technique using color flow imaging and continuous wave Doppler was developed to measure the initial regurgitant flow jet diameter and velocity integral to yield the parameters for a volume calculation. Jets were produced by volume-controlled injection through tubes of various diameters (1.3, 1.9, 2.8, and 3.5 mm) to deliver volumes from 1 to 7 ml over 100 to 300 msec at pressures from 40 to 200 mm Hg. One hundred forty-five samples were obtained. Flow jet diameter consistently overestimated tube diameter by 2 mm when injected volume was 1.5 to 7 ml and by 1.5 mm when injected volume was less than 1.5 ml. This offset was stable with various transducers (2.5, 3.5, 5.0 MHz) at normal gain setting (just under noise). Therefore, corrected flow jet diameter (FJD) = FJD - 2 mm, and Doppler volume = corrected flow jet area x velocity integral. A range of injectates from 1.1 to 7 ml generated Doppler volume of 1.0 to 8.2 ml. The relation between Doppler volume (DV) and injected volume (IV) was DV = 1.079 IV - 0.22, r2 = 0.945, p less than 0.01. This relation was not altered by tube diameter. Thus a method combining color flow imaging and continuous wave Doppler provides a reliable and accurate measure of in vitro flow volume.
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In three cases of acute disseminated toxoplasmosis developing soon after renal (two patients) or hepatorenal (one patient) transplantation, Toxoplasma gondii trophozoites were visualized on Giemsa-stained smears of bronchoalveolar lavage fluid. Trophozoites were also found in bone marrow smears in one instance. Seroconversion occurred late in two cases and was not detected before the patient's death in the third. These observations underline the potential of bronchoalveolar lavage as a diagnostic procedure for disseminated toxoplasmosis.
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Interleukin (IL) 10 inhibits endotoxin (lipopolysaccharide; LPS) induced tumor necrosis factor (TNF) production in vivo and in vitro. In turn, IL-10 is induced by LPS and acts as a negative feedback to limit TNF production. We investigated the effects of IL-10 on brain TNF and IL-1 beta production induced by a central LPS administration in mice. Because central LPS also induces peripheral TNF, we also measured the serum TNF levels. A single intracerebroventricular injection of murine recombinant IL-10 (75 ng/mouse) simultaneously with LPS (2.5 micrograms/mouse) almost completely inhibited brain TNF production. The brain IL-1 beta production was also inhibited, as was the serum concentration of the acute-phase protein serum amyloid A. On the other hand, intracerebroventricular administration of an anti-IL-10 monoclonal antibody (JES5-2A5; 60 micrograms/mouse) potentiated brain TNF and IL-1 beta production. Identical results were obtained when the serum TNF levels were measured. IL-10 did not affect the LPS-induced increase of serum corticosterone, the main endogenous inhibitor of TNF production, or the induction of IL-6. These results indicate that LPS-induced IL-10 can act as an important endogenous inhibitor of brain TNF production and suggest an anti-inflammatory role for IL-10 in the central nervous system.
In addition to cytotoxic and proinflammatory mediators, eosinophils can produce a variety of cytokines and growth factors. Besides interleukin (IL)-5, we show in the present work that human eosinophils can synthesize interferon (IFN)-gamma and IL-10, by RT-PCR, in situ hybridization and immunostaining. Double-labelling procedures revealed the coexpression of IL-5 and IL-10 but not IL-5 and IFN-gamma, indicating the existence of subpopulations of eosinophils expressing type 1 or type 2 cytokines. IFN-alpha efficiently used for the treatment of hypereosinophilic syndromes can significantly decrease eosinophil degranulation and IL-5 release by eosinophils, through binding to a receptor for IFN-alpha. Thus, eosinophils can represent major sources of cytokines with regulatory functions, especially in allergic diseases and parasitic infections.
We have evaluated carotid gamma imaging using 111Indium-labelled platelets in the diagnosis of carotid artery disease and measured the accumulation of labelled platelets on endarterectomy specimens. Autologous 111In labelled platelets were injected in 25 patients with TIA. Gamma images were then taken daily and independently interpreted by two observers. Carotid endarterectomy was performed in 11 patients allowing measurement of the radioactivity on the operative specimen. These results were compared to the findings on angiography and Doppler spectral analysis. All endarterectomy specimens accumulated platelets with the most active equivalent to platelets from 1.8 ml blood. Atheromatous ulcers were more active than stenoses with mean (+/- SEM) activities of 1.12 +/- 0.37 and 0.38 +/- 0.10 respectively. These radioactivity levels were at the threshold of gamma camera resolution in a theoretical model. Both observers agreed that 22 of the 50 carotid bifurcations showed platelet accumulation on gamma imaging. Of the 12 atheromatous ulcers demonstrated by angiography 11 were visualized, but only five of ten stenoses greater than 80% were detected. As Doppler identified all stenoses only one angiographically diseased carotid was not detected by combining ultrasound with platelet scanning. Atherosclerotic arteries accumulate 111In platelets and the more thrombogenic ulcerated plaques are identified more frequently than stenoses. Long-term follow-up is required to establish the clinical relevance of platelet deposition.
Patients with symptoms of cerebral ischemia are often evaluated with non-invasive carotid artery testing. An abnormal carotid Doppler ultrasound frequency shift pattern of early systolic flutter (ESF) was demonstrated by auscultation and velocity wave form analysis in patients with normal carotid bifurcations. Ten of these patients were studied with echocardiography (echo) and eight had mitral valve prolapse (MVP). To evaluate the association between ESF and MVP, a prospective blinded study was performed, recording carotid Doppler frequency shift in 50 patients referred for routine echocardiography. A total of 18 patients had ESF: 9/12 patients with MVP by echocardiography had ESF. Nine additional patients without MVP had ESF (two with mitral regurgitation and two with redundant mitral valves). The association of ESF with MVP was significant (p less than 0.001). The findings of ESF with a normal carotid artery by non-invasive testing suggests a possible mitral valve origin for symptoms of cerebrovascular disease.
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(1) This study indicated that both GK-101 and GK-101E exerted a statistically significant chemical action in the removal of carious material, in addition to any mechanical effects of the delivery system and applicator tip. (2) The superiority of GK-101E over saline in caries removal was noted, regardless of lesion consistency. (3) GK-101 was statistically superior to saline in caries removal in medium-hard lesions; it was not statistically superior to saline in lesions of medium consistency.
In a retrospective study of critical ischaemia of the lower limb, sympathectomy appeared to be of value in the majority of patients. We therefore assessed sympathectomy by measuring skin blood flow before and after the procedure using laser Doppler flowmetry (LDF) and transcutaneous oxygen tension (TCpO2) techniques. Twenty patients underwent chemical sympathectomy and there was one surgical procedure. Measurements were performed before and 1 week after sympathectomy below the knee and on the forefoot. Symptomatic improvement occurred in 20 of 21 patients. This study demonstrates that skin blood flow in the leg and foot is improved by sympathectomy and confirms objectively our clinical impression.
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