Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta-analysis of randomised controlled trials

Spinal anaesthesia for caesarean section commonly causes maternal hypotension. This systematic review and network meta-analysis compared methods to prevent hypotension in women receiving spinal anaesthesia for caesarean section. We selected randomised controlled trials that compared an intervention to prevent hypotension with another intervention or inactive control by searching MEDLINE and Embase, Web of Science to December 2018. There was no language restriction. Two reviewers extracted data on trial characteristics, methods and outcomes. We assessed risk of bias for individual trials (Cochrane tool) and quality of evidence (GRADE checklist). We assessed 109 trials (8561 women) and 12 different methods that resulted in 30 direct comparisons. Methods ranked by OR (95%CI) from most effective to least effective were: metaraminol 0.11 (0.04–0.26); norepinephrine 0.13 (0.06–0.28); phenylephrine 0.18 (0.11–0.29); leg compression 0.25 (0.14–0.43); ephedrine 0.28 (0.18–0.43); colloid given before induction of anaesthesia 0.38 (0.24–0.61); angiotensin 2, 0.12 (0.02–0.75); colloid given after induction of anaesthesia 0.52 (0.30–0.90); mephentermine 0.09 (0.01–1.30); crystalloid given after induction of anaesthesia 0.78 (0.46–1.31); and crystalloid given before induction of anaesthesia 1.16 (0.76–1.79). Phenylephrine caused maternal bradycardia compared with control, OR (95%CI) 0.23 (0.07–0.79). Ephedrine lowered umbilical artery pH more than phenylephrine, standardised mean difference (95%CI) 0.78 (0.47–1.49). We conclude that vasopressors should be given to healthy women to prevent hypotension during caesarean section with spinal anaesthesia.     

Direct measurement of nitroxide pharmacokinetics in isolated hearts situated in a low-frequency electron spin resonance spectrometer: implications for spin trapping and in vivo oxymetry.

The pharmacokinetics of two nitroxides were investigated in isolated rat hearts situated in a low-frequency electron spin resonance spectrometer. The spin labels 2,2,3,3,5,5-hexamethyl-1-pyrrolidinyloxy and 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy were chosen for their physiochemical analogy to the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and its corresponding spin-trapped adduct, 2-hydroxy-5,5-dimethyl-1-pyrrolidinyloxy (DMPO-OH). The bioreductive rates of the two nitroxides were measured during constant perfusion as well as during ischemia and are discussed in terms of a two-compartment pharmacokinetic model. These data provide information necessary to the design and application of spin traps to detect oxy radicals during reperfusion of ischemic tissue and suggest the feasibility of monitoring free-radical processes in intact, functioning mammalian tissues by using a low-frequency electron spin resonance spectrometer.     

Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism

Abstract: Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. Methods: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). Results: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-α and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean±SE AST: 1499±18 vs 78±10 IU/1, p<0.001; TNF: 2500±250 vs 135± 15 pg/ml. p<0.001, IL-6: 12,200±300 vs 1260±140 pg/ml, p<0.001, respectively). Conclusions: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases.     

Existence of automaticity in anomalous bundle of Wolff-Parkinson-White syndrome.

Escape beats probably arising from the anomalous bundle were documented in 2 patients with the Wolff-Parkinson-White (WPW) syndrome. A third patient, in whom complete AV block developed both in the anomalous bundle and the normal pathway, showed the occurrence of escape beats (an escape-bigeminy pattern), as well as a regular idioventricular rhythm arising from the anomalous bundle. Phase 4 block in the anomalous bundle occurred in 7 other patients, in 4 of them spontaneously and in 3 only after the administration of ajmaline or amiodarone. Only 4 of 14 fully investigated patients (out of a total number of 23) showed absence of both escape beats and phase 4 block. The escape beats were considered as direct evidence, and the phase 4 block as indirect evidence, for the existence of automaticity in the anomalous bundle. Such evidence supports the view that the anomalous bundle, like the His bundle-branch system, may be composed of specialised tissue endowed with the property of automaticity.     

The Effect of Replacement of Methionine by Homocystine on Survival of Malignant and Normal Adult Mammalian Cells in Culture

In tissue cultures of normal adult and malignant mammalian cells, homocystine has been substituted for methionine in a medium rich in folic acid and cyanocobalamin. Normal adult cells thrive. Three highly malignant cell types from three different species, including man, die.     

Fatty acid bile acid conjugates (FABACs)--new molecules for the prevention of cholesterol crystallisation in bile

BACKGROUND: Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM: To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS: FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS: FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS: FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.     

Endogenous c-src as a determinant of the tumorigenicity of src oncogenes.

We have compared the tumorigenicity of two src oncogenes, v-src and c-src(527), whose respective protein products pp60v-src and pp60c-src(527) show a different spectrum of amino acid substitutions vis-à-vis the c-src protooncogene-encoded product pp60c-src. Whereas the extent of primary tumor growth induced by c-src(527) was quite similar in the two chicken lines tested, the extent of v-src-induced tumor growth showed a marked line dependence. As examined with a line of chickens that shows immune-mediated regression of v-src-induced tumors, a weaker tumor immunity, as correlated with a greater level of primary tumor growth, resulted from inoculation of c-src(527) DNA than of v-src DNA. These observations indicated that the v-src-specific amino acid substitutions define a major tumor antigenicity. That a separate src-associated antigenicity is also targetable by the tumor immune response followed from the finding that the level of protective immunity against the growth of c-src(527) DNA-induced tumors was augmented under conditions of the prior regression of v-src DNA-induced tumors. As this latter antigenicity may include one or more c-src(527)-encoded peptides that are equivalent to c-src-encoded self peptides, these observations suggest that a host tolerance to pp60c-src can be broken so as to permit a tumor immune response based on recognition of self peptides of pp60c-src(527).