Gastric and biliary excretion of meperidine in man

The role and importance of enterogastric secretion in the disposition and elimination of the weak base, meperidine (pKa 8.63), was studied after intravenous administration (50 mg) of the drug to 6 normal volunteers. Continuous collection of the gastric fluid over a 4-hr period demonstrated the establishment of high gastric fluid/plasma concentration ratios for meperidine (mean about 50, range, 10 to 200). However, the total amount of drug recovered, even after correction for incomplete collection, was only a small percentage of the administered dose. Under basal conditions a mean +/- SE of 1.9 +/- 0.3 mg, equivalent to 3.7% of the administered dose, was found in the total gastric aspirate. Stimulation of gastric secretion by subcutaneous injection of betazole (1.5 mg/kg) increased this recovery to 3.6 +/- 0.3 mg (7.2%) primarily due to the increase in gastric volumen output. Aspiration of the gastric fluid in either the basal or stimulated situation had no observable effect upon the plasma concentration/time profile of meperidine whether assessed by the terminal half-life, t 1/2 beta, or the plasma clearance; control values were 3.8 +/- hr and 1,190 +/- 130 ml/min, respectively. In 2 subjects "bile fluid" was also collected for 2.5 hr and found to contain less than 0.2% of the administered dose. Enterosystemic recycling is therefore of minor importance in the disposition and elimination of meperidine in man.     

The heroin epidemic in San Francisco: estimates of incidence and prevalence

Much attention has recently been focused on the question of the extent of heroin use in America. In a worthwhile effort to call public attention to the problem, many estimates of its size have evidenced a tendency toward exaggeration and aggrandizement. This paper presents methods of estimation of the extent of heroin addiction which, when carefully employed, should effectively correct such distorted estimates. Two general types of estimation are employed, incidence and prevalence. Incidence estimates are concerned with new cases of heroin addiction that occur in a specific population within a given amount of time. These estimates are based upon self-report data from addicts regarding date of first addiction. When corrected for the "lag phase" (that period of time between onset of first addiction and eventual visit to a treatment program), these data permit accurate retrospective charting of incidence trends. Prevalence estimates focus on all known cases of heroin addiction in a specific population within a given amount of time. Three separate types of prevalence estimates from three separate sources are outlined in this article: estimates based on overdose death data, estimates based on crime statistics, and estimates of "unknown" addicts. In outlining these methods, this article describes the fluctuations in heroin addiction in one major American city, San Francisco, California. After analyzing data gathered from a sample of 2,367 addicts contacted over a 3-year period, this study suggests that the incidence of heroin addiction seems to have declined after 1970. Possible factors underlying this apparent decline in heroin addiction are then discussed, including the post-1970 maturation of the "population at risk," the effectiveness of antidrug media messages, the changing drug fashions in the heroin subculture, and the gradual deterioration of the quality and potency of street heroin.     

Adherence to antiretroviral therapy and its impact on clinical outcome in HIV-infected patients.

We analyse data on patient adherence to prescribed regimens and surrogate markers of clinical outcome for 168 human immunodeficiency virus infected patients treated with antiretroviral therapy. Data on patient adherence consisted of dose-timing measurements collected for an average of 12 months per patient via electronic monitoring of bottle opening events. We first discuss how such data can be presented to highlight suboptimal adherence patterns and between-patient differences, before introducing two novel methods by which such data can be statistically modelled. Correlations between adherence and subsequent measures of viral load and CD4+T-cell counts are then evaluated. We show that summary measures of short-term adherence, which incorporate pharmacokinetic and pharmacodynamic data on the monitored regimen, predict suboptimal trends in viral load and CD4+T-cell counts better than measures based on adherence data alone.     

Percutaneous radiologic drainage of pancreatic abscesses

OBJECTIVE: The purpose of our study was to review and report the patient selection, techniques, and results of percutaneous drainage of pancreatic abscesses by retrospective review. MATERIALS AND METHODS: Fifty-nine patients (46 men and 13 women) with a mean age of 44 years old had 80 pancreatic abscesses that were drained percutaneously under radiologic guidance (CT, n = 77; sonography, n = 2; and fluoroscopy, n = 1). Abscesses had a wide spectrum of causes, with alcoholic pancreatitis being most common, trauma second most common, and gallstones third. Ten patients had undergone surgery for pancreatic necrosis or abscess. Patients with pancreatic pseudocysts, necrosis, or acute fluid collections were excluded from this study. RESULTS: Of the 59 patients, 51 (86%) were cured with percutaneous drainage and antibiotic therapy. Of the patients who were not cured with percutaneous drainage, seven required surgery and one underwent repeat percutaneous drainage. In the 59 patients, complications included non-life-threatening bleeding in three patients. Ten of 59 patients (17%) had fistulas that spontaneously formed into the gastrointestinal tract. The duration of catheterization ranged from 4 to 119 days, with a mean duration of 33 days. The rate of mortality at 30 days after completion of percutaneous drainage was 8% (5 of 59). CONCLUSION: Percutaneous drainage was an effective therapy for this defined group of patients with pancreatic abscesses. Factors leading to the relatively high success rate described in this study likely included selection of patients; catheters of adequate size, number, and location; careful follow-up with appropriate catheter manipulations; and an integrated, cooperative approach whereby surgeons were willing to permit drainage to effect its benefits, rather than operating prematurely.     

PRACTICAL INCONSISTENCY MANAGEMENT FOR CRITICAL-TASKS DECISION-SUPPORT SYSTEMS

Abstract

In this paper, the problem of logical consistency in critical-tasks decision systems is addressed. It is shown how local search techniques can be used to check the (in)consistency of very large propositional knowledge bases (KBs). Using new heuristic findings. we can now implement efficient forms of diagnostic reasoning in the context of very large ICBs modeling deep models of complex devices and including patterns of default reasoning.     

Dynamic response of full-scale sandwich composite structures subject to air-blast loading

Glass-fibre reinforced polymer (GFRP) sandwich structures (1.6 m × 1.3 m) were subject to 30 kg charges of C4 explosive at stand-off distances 8–14 m. Experiments provide detailed data for sandwich panel response, which are often used in civil and military structures, where air-blast loading represents a serious threat. High-speed photography, with digital image correlation (DIC), was employed to monitor the deformation of these structures during the blasts. Failure mechanisms were revealed in the DIC data, confirmed in post-test sectioning. The experimental data provides for the development of analytical and computational models. Moreover, it underlines the importance of support boundary conditions with regards to blast mitigation. These findings were analysed further in finite element simulations, where boundary stiffness was, as expected, shown to strongly influence the panel deformation. In-depth parametric studies are ongoing to establish the hierarchy of the various factors that influence the blast response of sandwich composite structures.     

L-733,060, a novel tachykinin NK1 receptor antagonist; effects in [Ca2+]i mobilisation, cardiovascular and dural extravasation assays

Short RNA species that encompass the psi domain of the retroviral genome spontaneously form dimers in vitro, and the retroviral nucleocapsid protein activates this dimerization in vitro. Addition of gag RNA sequences downstream of the 3' end of the psi domain decreases the level of spontaneous dimerization. Here, we report the effects of RNA length on dimerization in vitro, studied with RNA fragments from Moloney murine leukaemia virus that contain the psi domain and all or part of the gag sequence. Extension of the RNA leads to progressive inhibition of the in vitro dimerization process. Sequences located downstream of the 3' end of the psi domain seem to stabilize the monomeric structures. This stabilization participates in dimerization of the RNA sequences involved in the recognition of two RNA molecules. We studied the ability of nucleocapsid protein 10 to promote dimerization of such long RNA fragments, and found that the protein greatly enhances their dimerization in vitro. We propose that nucleocapsid protein 10 stimulates the overall dimerization process by reduction of the energy barrier that must be overcome to allow dimer formation. Our results show that dimerization of RNA form Moloney murine leukaemia virus in vitro is enhanced by nucleocapsid protein 10. This finding is in agreement with the involvement of the nucleocapsid protein in RNA dimerization in vivo.