Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blinded, randomized controlled trial.

In this double-blinded, randomized controlled trial we tested if the addition of ketamine to morphine for patient-controlled analgesia (PCA) resulted in improved analgesic efficacy and lower pain scores compared with morphine PCA alone after major abdominal surgery. Seventy-one patients were randomly allocated to receive either morphine 1 mg/mL (Group M) or morphine 1 mg/mL plus ketamine 1 mg/mL (Group MK) delivered via PCA after surgery. No other analgesics or regional blocks were permitted during the 48-h study period. Postoperatively there were no differences between the groups for subjective assessment of analgesic efficacy, pain scores at rest, and on movement, opioid consumption, or adverse events. Group MK patients performed worse in cognitive testing (P = 0.037). There was an increased risk of vivid dreaming in patients who received ketamine (relative risk = 1.8, 95% confidence interval 0.78-4.3). We conclude that small-dose ketamine combined with PCA morphine provides no benefit to patients undergoing major abdominal surgery. Implications: We performed a randomized, controlled trial comparing the use of ketamine and morphine with morphine alone to relieve pain after major abdominal surgery.Ketamine did not improve pain relief and merely increased side effects.     

The selective kappa-opioid receptor agonist U50,488H attenuates voluntary ethanol intake in the rat

Non-selective opioid receptor antagonists are increasingly used in the treatment of alcohol dependence. The clinical effects are significant but the effect size is rather small and unpleasant side effects may limit the benefits of the compounds. Ligands acting at μ- and/or δ- receptors can alter the voluntary intake of ethanol in various animal models. Therefore, the attenuating effects of selective opioid receptor ligands on ethanol intake may be of clinical interest in the treatment of alcoholism. The objective of this study was to examine the effects of a selective κ-receptor agonist, U50,488H on voluntary ethanol intake in the rat. We used a restricted access model with a free choice between an ethanol solution (10% v/v) and water. During the 3-days baseline period, the rats received a daily saline injection (1 ml/kg, i.p.) 15 min before the 2 h access to ethanol. The animals had free access to water at all times. The control group received a daily saline injection during the 4-days treatment-period, whereas the treatment groups received a daily dose of U50,488H (2.5, 5.0 or 10 mg/kg per day). Animals treated with U50,488H dose-dependently decreased their ethanol intake. The effect of the highest dose of U50,488H was reduced by pre-treatment with the selective κ-antagonist nor-binaltorphimine (nor-BNI). These results demonstrate that activation of κ-opioid receptors can attenuate voluntary ethanol intake in the rat, and the data suggest that the brain dynorphin/κ-receptor systems may represent a novel target for pharmacotherapy in the treatment of alcohol dependence.     

Antimicrobial Activity of Essential Oils of Xylopia Aethiopica

Xylopia aethiopica is a medicinal plant of great repute in West Africa which produces a variety of complex chemical compounds. The fresh and dried fruits, leaf, stem bark and root bark essential oils showed various degrees of activity against the Gram positive bacteria, Bacillus subtilis and Staphylococcus aureus, the Gram negative bacteria Pseudomonas aeruginosa and the yeast-like fungus Candida albicans, using the cup plate method,. However, none of the oils showed activity against Escherichia coli.     

Tumor markers carcinoembryonic antigen, CA 50, and CA 19-9 and squamous cell carcinoma of the esophagus. Pretreatment screening

Pretreatment serum levels of the tumor markers carcinoembryonic antigen (CEA), CA 50, and CA 19-9 in 95 patients with squamous cell carcinoma of the esophagus and 32 age-matched controls were compared. Thirty-nine percent of the cancer patients showed elevated (greater than or equal to 5 micrograms/l) serum CEA levels, 41% had elevated (greater than or equal to 17 U/ml) CA 50 levels, and 13% showed elevated (greater than or equal to 37 U/ml) CA 19-9 levels. The tumor markers showed a considerable degree of complementarity, and combined tumor marker analysis increased the sensitivity to 59%. Raised CEA levels were found significantly more frequently in intrathoracically localized tumors than in cervical cancers. Patients surviving less than 6 months showed a higher rate of elevated CEA assays than those who survived 6 to 18 months. No certain correlation was established between tumor marker elevation and tumor stage or tumor differentiation.     

Extracellular matrix proteins (fibronectin, laminin, and type IV collagen) bind and aggregate bacteria.

The normal microbial colonization of sites in the body's tissues by certain bacteria requires that the bacteria first bind to extracellular secreted constituents, cell-surface membranes, or cell matrixes. This study examines two interactions of a variety of bacteria with the cell matrix noncollagenous proteins fibronectin and laminin and with basement membrane (Type IV) collagen. Adherence of bacteria to matrix proteins coated on tissue culture wells was examined with the use of radiolabeled bacteria. Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus sanguis bound well to fibronectin, laminin, and Type IV collagen, whereas a variety of gram-negative organisms did not bind. The interaction of soluble laminin, fibronectin, and Type IV collagen with bacteria was monitored by nephelometry with the use of a platelet aggregometer. S. aureus aggregated in response to fibronectin, laminin, or Type IV collagen. In contrast, gram-negative organisms did not aggregate with these proteins. It appears that fibronectin, laminin, and Type IV collagen can bind and aggregate certain gram-positive bacteria, and this binding is dependent on the surface characteristics of the organism. These adhesion molecules may play a role in the normal colonization of sites by microorganisms and in invasion during infections.     

B-type natriuretic peptide and its molecular precursor in myocardial infarction complicated by cardiogenic shock

BackgroundPlasma measurement of cardiac natriuretic peptides and their biosynthetic precursors is helpful in chronic heart failure patients. In contrast, information on circulating B-type natriuretic peptide (BNP) and its molecular precursor (proBNP) in patients with cardiogenic shock is scarce. We therefore examined proBNP-derived peptides in plasma from patients with myocardial infarction complicated by cardiogenic shock.Methods and ResultsPatients were referred for early, invasive therapy because of myocardial infarction complicated by cardiogenic shock (n = 13). Plasma proBNP was measured with an automated assay (NT-proBNP) and an in-house radioimmunoassay (proBNP); BNP concentrations were quantitated with an immunoradiometric assay. The median NT-proBNP concentration was 8.2-fold higher than the corresponding BNP concentration (873 pmol/L [range 41–12,486] versus 107 pmol/L [1–1041], P < .001). Moreover, the NT-proBNP concentration was 3.3-fold higher compared with proBNP (268 pmol/L [19–12,220], P < .01). Despite the molar differences, there was a strong correlation between NT-proBNP and proBNP (r = 0.84, P < .0001) and BNP (r = 0.82, P < .0001) concentrations. Gel filtration chromatography suggested that the proBNP immunoreactivity reflect a molecular form larger than the N-terminal 1-76 fragment.ConclusionsThe study reveals the plasma profile of proBNP-derived peptides during myocardial infarction complicated by cardiogenic shock. Peripheral concentrations of NT-proBNP, proBNP, and BNP were highly correlated despite marked differences between assays. The results also suggest an increase in cardiac proBNP processing after myocardial infarction and cardiogenic shock.     

Cyclosporin metabolism in human liver microsomes and its inhibition by other drugs

The metabolism of cyclosporin was studied in human liver microsomes. There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes. The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil. These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo. Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions.     

Influence of nutritional status on plasma and erythrocyte sulphur amino acids, sulph-hydryls, and inorganic sulphate in end-stage renal disease.

BACKGROUND: The metabolism of sulphur amino acids and sulph-hydryls is altered in end-stage renal disease (ESRD). Previous studies have focused on the role of vitamin status in the development of hyperhomocysteinaemia in such patients, but little information exists about the influence of global nutritional status and hypoalbuminaemia on sulphur-containing compounds in ESRD. As considerable fractions of sulph-hydryls in blood are present in erythrocytes (RBC), which among others participate in intra-organ amino acid transport, the relationship between plasma and RBC levels of several of these compounds and various nutritional parameters were evaluated in the present study. METHODS: Thirty-seven ESRD patients (24 males, 13 females) on dialysis treatment (18 haemodialysis, 19 continuous ambulatory peritoneal dialysis) and 21 healthy subjects (seven males, 14 females) were examined. The subjective global nutritional assessment (SGNA) showed that 10 (27%) patients were malnourished and 27 (73%) had normal nutritional status. RESULTS: All the ESRD patients had high plasma total homocysteine (tHcy) levels. The plasma concentrations of methionine (Met) and taurine (Tau) were low, but the levels of the other sulphur-containing compounds were high. In the RBC, the patients had higher levels of tHcy and Tau than in healthy subjects, but no difference was seen in the concentrations of glutathione (GSH), cysteinylglycine (Cys-Gly), Met, and Cys. The plasma inorganic sulphate concentrations were five times higher in the patients than in healthy subjects, but the levels did not differ significantly between the malnourished patients and those with normal nutritional status. The malnourished patients had lower plasma, but not RBC, levels of tHcy, GSH, and Cys-Gly than those with normal SGNA. Plasma tHcy correlated positively with serum (s)-albumin and anthropometric parameters and negatively with SGNA. RBC and whole blood, but not plasma, GSH concentrations were correlated with haematocrit and were significantly lower in low haematocrit patients (< or = 37%, n = 19) than in those with a high haematocrit (> 37%, n = 18). CONCLUSIONS: These results show that nutritional status and s-albumin influence plasma, but not RBC, concentrations of sulph-hydryls in ESRD patients. This should be considered when the relationships between cardiovascular disease and plasma tHcy or other sulphur-containing compounds are assessed. The study also shows that GSH concentrations in RBC and whole blood are related to haematocrit and not to nutritional parameters, indicating that anaemia status rather than nutritional status determines RBC and whole blood GSH levels in ESRD patients.     

黄蜈散治疗宫颈糜烂的临床研究

分组对比观察黄蜈散治疗宫颈糜烂的临床作用及其对宫糜修复过程的影响,发现黄蜈散治疗组显效率(85.5%)显著高于清洁处理组(18.5%)和无处理对照组(10.8%)。黄蜈散具有消炎、消肿、促进宫糜局部正常鳞状上皮再生,加快宫糜自然修复的作用,对宫颈组织无明显腐蚀和破坏,并不引起宫颈间质的异常纤维化。