Tourniquet inflation after intra-articular morphine and bupivacaine administration following knee arthroscopy

We performed a randomized doubled-blind study to evaluate whether there was a benefit in delay in tourniquet deflation with intra-articular administration of morphine and bupivacaine following operative arthroscopic surgery. In 34 patients the tourniquet was deflated immediately and in 38 patients the tourniquet remained inflated for 10 min following injection. The analgesic efficacy was assessed using pain scores and the amount of supplementary analgesia required. The results demonstrate no benefit in delay in tourniquet deflation.     

Sn-chlorin e6 antibacterial immunoconjugates. An in vitro and in vivo analysis.

Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site-selective covalent modification of the monoclonal oligosaccharide moiety. By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared. By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10. Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody. The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process. In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity. Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared. In vivo specificity was demonstrated using rats infected with Fisher immunotype I P. aeruginosa at a site in the left posterior thigh muscle. Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate. Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact.     

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.     

The effects of cocaine on food intake of baboons before, during, and after a period of repeated desipramine

Food intake of five adult male baboons (Papio c. anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. Following completion of the "procurement" component, the first response requirement, access to food, i.e., a meal, became available under the second, "consumption" component, during which each response produced a 1 g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for cocaine (0.50-4.0 mg/kg, IM) and desipramine (0.50-4.0 mg/kg, IM), were determined before, during, and after a period of repeated administration of desipramine. Cocaine produced dose-dependent increases in the latency to initiate feeding and decreases in food intake during the first eight hr of the session. Compensatory feeding occurred later in the session so that cocaine had no effect on total daily intake. There was no interaction between repeated desipramine and the acute effects of cocaine. Desipramine produced dose-dependent decreases in intake during the first two hr of the session, the size of the first meal and intake during the entire session. These measures, as well as number of meals and second meal size, remained below baseline during repeated desipramine. Thus, repeated desipramine, while having significant effects on feeding behavior itself, did not influence the effects of cocaine administration on food-maintained responding.     

Effects of buprenorphine on the self-administration of cocaine by humans

Seven male research volunteers reporting intravenous cocaine and morphine use participated in 12 cocaine self-administration sessions. A session consisted of sublingual buprenorphine pretreatment (0, 2, 4mg) 50min before seven self-administration trials. The first three trials were sampling trials, in which subjects were given each of the three reinforcers available for that session; the remaining four trials were choice trials in which subjects could choose between two doses of cocaine and tokens exchangeable for special privileges. Each buprenorphine dose was tested for four consecutive days under different cocaine dose/token combinations (e.g. 8mg vs 16mg vs two tokens). Following placebo, under all choice conditions, subjects reliably chose higher doses of cocaine over lower doses, and tokens about as often as high cocaine doses. Buprenorphine (4mg) significantly decreased high-dose cocaine choice and increased token choice, when the available cocaine doses were 16 and 32mg/70kg. Both buprenorphine doses significantly increased ratings of "sedated" and opiate symptoms and decreased ratings of "bad drug effect" following all cocaine doses. Both buprenorphine doses, in combination with cocaine doses greater than 8mg, significantly increased self-reported "high" and occasionally increased "stimulated" scores above values seen following cocaine alone. The results demonstrate that in the presence of non-drug alternative to cocaine (tokens), buprenorphine decreased high-dose cocaine choice. Despite the decrease, subjects were clearly intoxicated from a drug combination that mimicked a cocaine-heroin ("speedball") effect. Although buprenorphine may be useful in reducing cocaine use, the complex relationship between this reduction in use, behavioral alternatives, and the subjective effects of the drug combination remains unclear.     

Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia

BACKGROUND: Neuroimaging studies have provided evidence of abnormal frontal and temporal lobe function in schizophrenia. Frontal cortex abnormalities have been associated with negative symptoms and temporal lobe abnormalities with positive symptoms. The deficit and nondeficit forms of schizophrenia were predicted to differ in prefrontal cortical activity, but not in medial temporal lobe activity. METHODS: Regional cerebral blood flow was studied using oxygen 15 positron emission tomography during 3 different memory retrieval conditions in 8 control subjects, 8 patients with the deficit syndrome, and 8 patients without the deficit syndrome. Behavioral and positron emission tomography data were analyzed using a mixed-effects model to test for population differences. RESULTS: In all memory conditions, frontal cortex activity was higher in patients without the deficit syndrome than in patients with the deficit syndrome. During the attempt to retrieve poorly encoded words, patients without the deficit syndrome recruited the left frontal cortex to a significantly greater degree than did patients with the deficit syndrome. The 2 schizophrenia subtypes did not differ in the activity or recruitment of the hippocampus during memory retrieval. CONCLUSION: Frontal cortex function during memory retrieval is differentially impaired in deficit and nondeficit schizophrenia, whereas hippocampal recruitment deficits are not significantly different between the 2 schizophrenia groups.     

Targeted imaging of infection

The prompt identification, localization and characterization of focal sites of infection in the patients with fever is a critical step in clinical management, particularly, when localizing symptoms are not present. Although the classic signs of inflammation are suitable to localize injury at superficial sites or in the extremities, inflammation of internal structures, such as in the brain, chest and abdomen, can be difficult to localize without additional diagnostic procedures. Tissue injury, regardless of cause or anatomical site, results in a complex series of physiologic changes that we recognize as the inflammatory response. The inflammatory response is characterized by a series of biochemical events in the insulted cells and surrounding structures that results in the three major pathophysiological components: increased tissue perfusion, increased vascular permeability, and leukocytic exudation. Exploitation of the early attributes of the inflammatory process are not sufficient for the routine detection of inflammation. Currently, reagents for targeting infection represent cellular or protein components involved in the inflammatory process. Such approaches have met with some success as these agents comprise integral parts of the complex phenomena known as inflammation. This same fact also limits their utility. Improved agents for targeting infection will likely be based on small molecules whose diffusion into the lesion is not hindered by molecular size constraints and which bind to molecular targets at the site of infection/inflammation. In general, the lower molecular weight should also lead to enhanced blood clearance, avoiding elevated blood pool activity which contributes to background. New agents should also obviate the need to handle blood, as this represents potential hazards to both patient and the medical personnel alike.