ALTHESIN, KETAMINE AND METHOHEXITONE AT PRESSURE-DURATION OF ACTION OF A SINGLE I.V. DOSE

General anaesthesia for emergency surgery in a pressurized habitatis likely to involve the use of i.v. agents. The anaestheticproperty of such agents is known to be antagonized by pressure,but the effect on their duration of action is not easily predicted.The recovery of mice from a single i.v. dose of Althesin, ketamineor methohexitone was estimated by their ability to remain uprightin a rotating drum. At 35 atm abs. duration of action was significantlyreduced: P<0.05 for Althesin; P<0.0l for ketamine andmethohexitone. A number of animals in each group, however, displayedrecovery times that were comparable to control. The convulsionrate with methohexitone was 60% at 35 atm abs., whereas at 1atm abs. it was 20%. The clinical implications of these findingsare discussed.     

TRANSPLACENTAL DISTRIBUTION OF ATRACURIUM, LAUDANOSINE AND MONOQUATERNARY ALCOHOL DURING ELECTIVE CAESAREAN SECTION

Maternal venous (MV), umbilical venous (UV) and umbilical arterial(UA) blood samples were obtained for assay of atracurium, laudanosineand monoquaternary alcohol concentrations in 22 healthy patientsundergoing elective Caesarean section under general anaesthesia.At delivery (at a mean time of 8.2 min after atracurium 0.3mg kg^–1), the mean UV concentrations were 103 ng ml^–1(range 44–189 ng ml^–1) for atracurium, 26 ng ml^–1(range 6–60 ng ml^–1) for laudanosine and 59 ng ml^–1(range 21–148 ng ml^–1) for monoquaternary alcohol.The ratios of UV: MV, UA:MV and UA:UV blood concentrations wererelated positively to time since injection of atracurium forall three substances (P < 0.01 in each instance). The UV:MVratio at delivery was greatest for laudanosine: mean 19.4% (range1-35%), compared with 7% (range 2-21%) for atracurium and 10%(range 0-15%) for monoquaternary alcohol. These low values confirmthat, although atracurium crosses the placental barrier andits metabolites may be found in the fetus, the drug is safeto use during Caesarean section.     

Pharmacodynamic resistance to warfarin is associated with nucleotide substitutions in VKORC1

Summary. Background: Vitamin K epoxide reductase subunit 1 (VKORC1) is the molecular target of coumarin anticoagulants and mutations in VKORC1 have been identified previously in individuals who required high warfarin doses. Objective: Detailed characterization of the relationship between variation in VKORC1 and the warfarin resistance phenotype. Patients and methods: Serum warfarin concentration and coagulation parameters were determined in 289 subjects who required warfarin doses >20 mg day^?1. The VKORC1 sequence was studied in selected study subjects. Results: Twenty‐eight out of 289 (10%) subjects had serum warfarin >2.3 mg L^?1 during stable therapeutic anticoagulation indicating pharmacodynamic warfarin resistance. Detailed analysis of 15 subjects from this group showed that eight out of 15 (53%) had nucleotide substitutions in VKORC1 predictive of p.V66M, p.L128R, p.V54L or p.D36Y. VKORC1 was normal in the remaining seven out of 15 (47%) subjects and in nine out of nine (100%) subjects with high warfarin dose requirement not caused by pharmacodynamic resistance. At referral, subjects with VKORC1 mutations received a median warfarin dose of 32 mg day^?1 (range 22–55) and had a median serum warfarin concentration of 4.6 mg L^?1 (range 2.6–9.0). VKORC1 substitutions were associated with a requirement for high warfarin doses but not with adverse clinical events. Family members with VKORC1 nucleotide substitutions and not receiving warfarin had undetectable PIVKA‐II and K₁ epoxide (K₁O). Conclusions: Nucleotide variations in VKORC1 are a common cause of pharmacodynamic warfarin resistance but are not associated with adverse outcome during anticoagulation. Mutations associated with warfarin resistance do not cause a discernible defect in VKORC1 reductase function.     

Comparison of methods for measuring surface roughness of ceramic

SUMMARY The aim of this investigation was to compare two methods of assessing the surface texture of finished dental ceramic; a laser reflectivity method (LSR) and a contact stylus tracing method. Identical ceramic blocks (Dicor MGC) were finished using a variety of techniques and devices, and the surface texture characterized by LSR and contact stylus tracing to enable comparisons to be made between the two methods. The results indicate that there is little correlation between the two measuring methods. Therefore, laser reflectivity should not be exclusively used to measure the surface texture of contoured and finished ceramic materials. The development of sophisticated surface characterization parameters suggest that the surface characteristics of dental restorations and other related surfaces should be described using more than one surface measurement parameter. Surface parameters should be chosen which can both quantify surface roughness and provide information on the shape of the surfaceunder investigation.