Phencyclidine binding to striatal cocaine receptors

PCP and related compounds inhibit 3H-mazindol binding to the cocaine receptor on dopamine transporters. The relative potencies of these compounds are such that some of the behavioral effects of PCP could be related to its action at the cocaine receptor; however, the affinity of PCP at the cocaine site (Ki = 1.59 microM) is less than its affinity at its own receptor (Ki about 0.12 microM). More data will be needed to conclusively implicate the cocaine receptor in the action of PCP.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Quality in Clinical Practice

This paper reports the proceedings of the discussion panel assigned to look at clinical aspects of quality in emergency medicine. One of the seven stated objectives of the Academic Emergency Medicine consensus conference on quality in emergency medicine was to educate emergency physicians regarding quality measures and quality improvement as essential aspects of the practice of emergency medicine. Another topic of interest was a discussion of the value of information technology in facilitating quality care in the clinical practice of emergency medicine. It is important to note that this is not intended to be a comprehensive review of this extensive topic, but instead is designed to report the discussion that occurred at this session of the consensus conference.     

Differentiating Large-scale Surge versus Daily Surge

This breakout session at the Academic Emergency Medicine 2006 Consensus Conference examined how baseline overcrowding impedes the ability of emergency departments to respond to sudden, unexpected surges in demand for patient care. Differences between daily and catastrophic surge were discussed, and the need to invoke a hospital-wide response to surge was explored.     

Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction.

To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative.     

Relationship of plasma buprenorphine and norbuprenorphine to withdrawal symptoms during dose induction, maintenance and withdrawal from sublingual buprenorphine

Aims. Examine the relationship between buprenorphine and norbuprenorphine plasma concentrations with subject-reported withdrawalsymptomatology during buprenorphine dose induction, maintenance treatment (daily and alternate-day dosing) and withdrawal . Design. Two groups of randomly assigned subjects inducted onto buprenorphine and maintained on 8 mg daily by the sublingual route for 18 days. Group 1 continued to receive daily buprenorphine to day 36. Group 2 subjects received alternate-day dosing of buprenorphine and placebo on days 19 to 36. Both groups received placebo on days 37 to 52 . Setting. Inpatient facilities at the Addiction Research Center, Intramural Research Center, NIDA, Baltimore, MD . Participants. Eleven male, heroin-dependent volunteers participating in a research study . Intervention. Medications for treatment of withdrawal symptoms were prescribed as needed after day 39 (72 hours after the last dose of buprenorphine) . Measurements. Plasma concentrations of buprenorphine and norbuprenorphine, withdrawal symptomatology and pupil diameter . Findings. The mean steady-state buprenorphine plasma concentration (24 hours) after daily administration of sublingual buprenorphine for study days 21-35 was 0.80 ng/ml, and the mean alternate day steady-state buprenorphine plasma concentration (24 hours) was 0.77 ng/ml. Daily and alternate day steady-state norbuprenorphine plasma concentrations were 1.10 and 0.90 ng/ml, respectively. Predicted alternate day steady-state buprenorphine and norbuprenorphine plasma concentrations at 48 hours were 0.49 ng/ml and 0.57 ng/ml, respectively. Withdrawal scores varied inversely with plasma concentration. There were no significant differences between Groups 1 and 2 during steady-state (days 21-35) with regard to withdrawal scale scores or pupillary diameter. The overall, mean terminal elimination half-lives for buprenorphine and norbuprenorphine were 42 and 57 hours, respectively . Conclusions. During daily buprenorphine maintenance, plasma concentrations greater than 0.7 ng/ml of buprenorphine and norbuprenorphine were associated with minimal withdrawal symptoms. The long elimination half-life of buprenorphine suggested that increasing the buprenorphine dose with alternate-day administration may provide an effective, flexible therapy regimen for the treatment of opioid dependence.     

Serum TABM produced during anterior chamber-associated immune deviation passively transfers suppression of delayed-type hypersensitivity to primed mice

Injection of soluble protein antigen into the anterior chamber of the eye of primed mice induces anterior chamber-associated immune deviation (ACAID) which is manifested by suppression of delayed-type hypersensitivity (DTH) to the antigen. Recently, we found that ACAID induced in primed mice also results in a rapid rise in serum of soluble T lymphocyte-derived proteins specific for nominal antigen (TABM). Here, we demonstrate that serum TABM induced in primed mice during ACAID will transfer the suppression of DTH to mice primed to the same antigen. Sera from TNP-BSA-primed mice that received an anterior chamber injection of TNP-BSA, but not BSA alone, suppressed the DTH response to TNP when injected into other TNP-BSA-primed mice. Sera absorbed with Sepharose beads conjugated with either anti-TCR C(alpha), anti-TCR C(beta), anti-TABM or TNP-BSA did not contain TNP-specific TABM and did not transfer suppression of DTH. These results suggest that the antigen-specific, TCR C(alphabeta)+ TABM that appear in serum during ACAID are able to confer on or amplify the capacity of sensitized T cells to suppress DTH. We believe this to be the first demonstration of an in vivo immunologic function that is specifically associated with TABM produced in vivo.      

Diagnosis of rhabdomyosarcomas with HHF35, a monoclonal antibody directed against muscle actins.

The authors have recently developed a monoclonal antibody, HHF35, that recognizes the muscle-specific isoforms of actin. To determine its potential usefulness in the differential diagnosis of "small, round, blue cell" tumors of childhood, they immunolabeled formalinor B-5-fixed tissue sections from known cases of rhabdomyosarcoma or rhabdomyoma (30), neuroblastoma (9), retinoblastoma (2), and Ewing's sarcoma (9) with HHF35 and with antibodies to creatine kinase M, myoglobin, vimentin, and neuron-specific enolase. HHF35 reacted with 29 of 30 cases of rhabdomyosarcoma, whereas antibodies to creatine kinase M and myoglobin were positive on only 12 and 7 tumors, respectively. HHF35 did not react with any case of neuroblastoma, retinoblastoma, or Ewing's sarcoma when the antibody diluent contained 50 mM EDTA. These results indicate that HHF35 is a highly sensitive and specific marker for myogenic differentiation and that it will be useful in the differential diagnosis of rhabdomyosarcomas.     

Incomplete HIV-1 activation in latently infected U1 cells demonstrated by double in situ hybridization

Triple combination antiretroviral therapy can reduce HIV-1 infection to a relatively small pool of latently infected cells. To eliminate this residual source of virus, new therapies designed to activate latently infected cells are currently being tested. We therefore investigated the kinetics of in vitro HIV-1 RNA induction using chronically infected U1 cells. A new two-probe fluorescence in situ hybridization (double ISH) method was devised to simultaneously assess total HIV-1 RNA (T-RNA) and unspliced HIV-1 RNA (U-RNA) expression in individual cells. Activation of the U1 cells resulted in increasing expression of T-RNA between 0 and 24 h with lagging expression of U-RNA between 6 and 30 h. Both the positive area per cell and the number of positive cells increased with time. Although activation induced 98.5% of the cells to express HIV-1 T-RNA by 24 h, 52% remained negative for U-RNA. In contrast, 100% of 8E5 cells, which constitutively express HIV-1, scored positive for U-RNA as well as T-RNA with the double ISH. This study provides, for the first time, a semiquantitative cell-by-cell analysis of HIV-1 mRNA subsets in latently infected cells. Our results establish the advantages of using double fluorescence ISH to study gene expression and demonstrate that chronically infected U1 cells remain in a partially induced state despite potent activation.