Determination of plasma concentrations of propofol associated with 50% reduction in postoperative nausea

BACKGROUND: Subhypnotic doses of propofol possess direct antiemetic properties. The authors sought to determine the plasma concentration of propofol needed to effectively manage postoperative nausea and vomiting. METHODS: Patients aged 18-70 yr who were classified as American Society of Anesthesiologists physical status 1 or 2 and had surgery during general anesthesia were approached for the study. Only patients who had nausea (verbal rating score > 5 on a 0- to 10-point scale), retching, or vomiting in the postanesthetic care unit participated. Propofol was administered to these patients to achieve target plasma concentrations of 100, 200, 400, and 800 ng/ml using a computer-assisted continuous infusion device. Target concentrations were increased every 15 min until patients described at least a 50% reduction in symptoms on the verbal rating score. An arterial blood sample was obtained at each step. The measured plasma propofol concentrations were used to analyze data. Blood pressure, heart and respiratory rates, arterial blood saturation, sedation score, and overall satisfaction with treatment were recorded. RESULTS: Of the 89 patients who consented to the study, 15 patients met entry criteria and were enrolled. Five of these patients also had retching or vomiting when they entered the study. Fourteen patients responded successfully to treatment. One patient did not achieve the required response at plasma concentrations of 830 ng/ml. Hence the success rate for the treatment of postoperative nausea and vomiting was 93%. Among patients who responded, the median plasma concentration associated with an antiemetic response was 343 ng/ml. There was no difference in sedation scores from baseline and no episodes of desaturation. Hemodynamic parameters were stable during the study. CONCLUSIONS: Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.     

Treating Alzheimer's disease. Pharmacologic options now and in the near future

Treatment of Alzheimer's disease has in the past been limited to empirical trials of psychotropics for relief of behavioral complications. At present, tacrine and doneprezil are the only FDA-approved antidementia agents available. In the very near future, however, other cholinesterases inhibitors (e.g., ENA 713, metrifonate, long-acting physostigmine) are expected to be approved for clinical use. The evidence at this point suggests that they have modest but meaningful clinical effects and possible long-term benefits. Clinical use of the newer agents is likely to be influenced by their side-effect profiles, which consist largely of cholinergic effects, although without the hepatotoxic effects associated with tacrine. To what extent these agents are accepted by patients and physicians remains to be seen. On the one hand, benefits are modest; on the other, these medications are increasingly safe. Continuing research is clarifying the role of cholinergic therapy in relieving behavioral symptoms, as well as the possible side effects on rates of illness progression, institutionalizaton, and even mortality. In the not-too-distant future, physicians can expect to see a variety of medications, now in early stages of development, that are intended to affect cholinergic systems in other ways. Further down the road, a host of mechanism-based therapeutic strategies, which hope to deal with the first cause of this devastating illness, will have been assessed in clinical trials.     

Ulceration of the ileum in Crohn''s disease: correlation with vascular anatomy

Forty-five cases of gastroschisis and 85 of omphalocele were reviewed. The survival of gastroschisis has dramatically improved over the past 20 years, however, that of omphalocele still remained in the lower value, because the size of the defect and the presence of associated anomalies are prognostic factors. The primary fascial closure was first employed for the patients with gastroschisis and a silo chimney was used for limited cases. On the other hand, for the patients with omphalocele, primary closure was possible in 34 cases, silo chimney was used in 17, and 45 cases had nonoperative management with epithelialization. Among them, nonoperative management using painting was the most reliable therapeutic for omphalocele.     

Isolation of xanthan from Xanthomonas campesteris B-1459 in mechanically agitated fermentors

Xanthan production from Xanthomonas campestris was studied by a mechanically shaken fermentor. Influence of glucose concentration, aeration of culture media, rheology of broths and pH control was evaluated. Different aeration conditions based on variation of stirring rates were assayed. Substrate concentration was determined according to the Miller method, and polymer production was performed by the Cadmus method. The higher xanthan levels (i.e. 2.3%) were obtained at 750 rpm, with 1 v/v. min. In such conditions, viscosity ranges about 7000 cPoise and a low level of dissolved oxygen were detected in the culture medium. Xanthan production was influenced by the glucose concentration and the presence of amaranth within the culture medium. In the processes wherein an automatic control of pH was performed, the polymer concentration did not increase regarding to processes involving regular pH evolution.     

Individual cognitive-behavioural interventions in early psychosis

BACKGROUND: Cognitive-behavioural treatments have previously been explored in the treatment of chronic psychotic problems, but recently, the effectiveness of these treatments has been investigated with regard to recent onset and acute psychosis. METHOD: The literature relating to cognitive-behavioural treatments in psychosis is explored and the application of the approach to recent onset psychosis is described in detail. RESULTS: There appears to be a growing body of evidence that the advances made in the treatment of people with chronic treatment resistant psychosis can be similarly applied to people with recent onset and acute psychosis. CONCLUSIONS: Cognitive-behavioural treatments are feasible with recent onset psychotic patients although further evaluation of their effectiveness is necessary.     

The roles of the N-linked glycans and extension regions of soybean beta-conglycinin in folding, assembly and structural features

Beta-conglycinin, one of the dominant storage proteins of soybean, is a trimer composed of three subunits, alpha, alpha' and beta. All subunits are N-glycosylated and alpha and alpha' contain extension regions in addition to the core regions common to all subunits. Non-glycosylated individual subunits and deletion mutants (alpha(c) and alpha'(c)) lacking the extension regions of alpha and alpha' were expressed in Escherichia coli. All recombinant proteins were purified to near homogeneity and appeared to have the correct conformation, as judged by CD, density-gradient centrifugation and gel-filtration profiles, indicating that the N-linked glycans and extension regions are not essential for the folding and the assembly into trimers of beta-conglycinin. Density-gradient centrifugation, gel-filtration and differential scanning calorimetry profiles of the recombinant proteins and the native beta-conglycinin indicated that the N-linked glycans and extension regions contribute to the dimension of beta-conglycinin but not to the density and the thermal stability. Comparing the solubilities of the individual subunits with those of deletion mutants, only the alpha and alpha' subunits were soluble at lower ionic strength (mu < 0.25) at around the pH value of the endoplasmic reticulum. This suggests that the extension regions play an important role in the prevention of aggregation in the endoplasmic reticulum in analogy with the N-linked glycans.     

Processing of adenosine receptor agonists in rat and human whole blood

A stability study of adenosine receptor agonists in rat and human whole blood was performed. The compounds were incubated at 37 degrees in fresh blood, and aliquots of the incubation mixture were hemolyzed at regular time intervals and analyzed with HPLC. N6-cyclopentyladenosine (CPA) and N6-cyclobutyladenosine (CBA) were degraded, whereas N6-cyclohexyladenosine, N6-cycloheptyladenosine and N6-sulfophenyladenosine were not. 2-Chloroadenosine had a half-life very similar to that of CPA. However, the 2'-, 3'-, and 5'-deoxyribose derivatives of CPA remained intact. The nucleoside transport inhibitor nitrobenzylthioinosine attenuated CBA and CPA metabolism in rat blood as did the inhibitor of adenosine deaminase erythro-9-(2-hydroxy-3-nonyl)adenine, albeit at relatively high concentrations. Complete blockade of CBA and CPA degradation was achieved by a preincubation of rat and human blood with the adenosine kinase (AK) inhibitor 5'-amino-5'-deoxyadenosine. We conclude that the two adenosine analogues are metabolized by AK both in rat and in human whole blood.