Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.

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Background and Purpose: New therapeutic interventions for acute ischemic stroke are aimed at improving cerebral blood flow in the first 3 to 6 hours after symptom onset. Single-photon emissioncomputed tomography (SPECT) performed in the setting of clinical therapeutic trials may give us a better understanding of the physiological response to new forms of treatment and could impact acute management decisions.Methods: We prospectively studied 15 patients with hemispheric ischemic stroke with SPECT within 6 hours of symptom onset and again at 24 hours. The ischemic defect was assessed in a semiquantitative manner that used computer-generated regions of interest (SPECT graded scale). This measure was correlated with clinical presentation (National Institutes of Health [NIH] Stroke Scale), initial clinical course (change in NIH Stroke Scale), long-term outcome (Barthel Index at 3 months), and complications of cerebral hemorrhage and edema.Results: The severity of the SPECT graded scale on the admission scan correlated with the severity of neurological deficit (admission NIH Stroke Scale) (P<.05) and was positively associated with poor long-term outcome as measured with the Barthel Index (P<.001) and the complications of cerebral hemorrhage and massive cerebral edema (P<.005). In fact, there was a threshold value for the SPECT graded scale above which all patients suffered poor long-term outcome and the complications of cerebral hemorrhage and edema.Conclusions: The measurement of an ischemic defect using SPECT is a valid assessment of hemispheric stroke severity in the hyperacute setting and may be useful for selecting or stratifying patients in clinical therapeutic trials. (Stroke. 1993;24:1322-1329

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The L-type calcium channel antagonist, isradipine, reduces brain ischemia in animal models of ischemic stroke. These effects of isradipine appear more pronounced in dopamine (DA) rich brain regions. These same DA-rich brain regions have also been shown to be the areas most affected by cocaine-induced ischemic changes. Using a novel quantified approach to single photon emission computerized tomography, we demonstrated that isradipine pre-treatment prevented cocaine-induced ischemic changes, especially in these DA-rich brain regions. This is the first demonstration that any medication, including isradipine, can prevent the ischemic effects of cocaine on brain blood flow. Isradipine may, therefore, be a useful therapeutic agent for the prevention of brain ischemia in cocaine addicts.

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