In-vitro antimicrobial activity of enoxacin and its metabolites.
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Biomedical subjects
Publications and source records attributed to R M Jones.
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The time to safe return of neuromuscular function after atracurium 0.3 mg/kg intravenously was assessed in 24 patients in whom anaesthesia was maintained with halothane 0.5%. Safe reversal (recovery to a T4 ratio greater than 0.5), after this dose of atracurium, could only be reliably and rapidly (less than 2 minutes) achieved with edrophonium if a period greater than 30 minutes elapsed since administration of the relaxant. This coincides with the appearance of four recognisable twitches if a train-of-four pattern of nerve stimulation is used. Thus, if no monitoring equipment is available, at least half-an-hour should elapse after administration of atracurium in a moderate dose (e.g. 0.3 mg/kg) before rapid and reliable reversal can be anticipated. Four twitches in a train-of-four should be recognisable, if a nerve stimulator is available.
We describe the case of a patient treated for hypertension with the angiotensin converting enzyme inhibitor enalapril, who developed hypotension after recovery from anaesthesia.
The ability to evoke reversal of dense vecuronium- and pancuronium-induced paralysis (T1 10% of control) with edrophonium 1.0 mg.kg-1 was studied using train-of-four nerve stimulation and electromyographic monitoring. Two different end-points, train-of-four ratios of 0.5 and 0.7, were used to define "adequate reversal", and the results for both relaxants were compared. Reversal was reliable and rapid for vecuronium if either ratio was used with times of 2.8 (1.5) and 9 (3) min required to achieve ratios of 0.5 and 0.7, respectively. However, if the block was due to pancuronium, reversal was unreliable with 2 of 9 and 4 of 9 patients not achieving ratios of 0.5 and 0.7, respectively. Reversal was also markedly prolonged in this group with a mean time of 37 (23) min to achieve a ratio of 0.7, and in almost half these patients a supplementary dose of edrophonium was required.
Twenty-five patients having a major liver resection at the Austin Hospital were reviewed, 18 of whom had their operation after 1986. The indications were for metastatic disease in 14, hydatid in six and primary tumour in five. There were no operative deaths. Dissection was performed with the Cavitron Ultrasound Surgical Aspirator (CUSA) and peroperative ultrasound used in 18 and without in seven. Mean blood loss was 1.75 u in the CUSA group and 6.5 u in the non-CUSA group (P less than 0.05). It is concluded that intra-operative ultrasound and use of the CUSA makes major liver resection a more precise and less hazardous procedure.
We investigated the mechanism of membrane phospholipid degradation during reperfusion of ischemic myocardium using isolated and perfused rat hearts. Thirty min of myocardial reperfusion after 30 min of normothermic global ischemia resulted in a significant decrease of phosphatidylcholine (PC) content associated with a small but significant increase in lysophosphatidylcholine (LPC) content. Myocardial ischemia for up to 60 min caused no significant loss of any of the major phospholipids. Isotopic incorporation of [14C]arachidonic acid (AA) as well as [3H]-glycerol into PC was significantly attenuated in the ischemic-reperfused heart compared with the normally perfused heart, suggesting that both reacylation and de novo pathways for PC synthesis were inactivated during reperfusion. In the heart prelabeled with [14C]AA, the radiolabeled PC was decreased significantly during reperfusion, associated with a small but significant increase in [14C]AA accumulation. The decreases of PC content and incorporation of [14C]AA into PC, as well as the increases of LPC content and the [14C]AA during reperfusion, were prevented by reperfusion with low Ca2+ (50 microM) buffer or by pretreatment with trifluoperazine (10 microM) or mepacrine (50 microM), but not with verapamil (1 microM). The inhibition of loss of PC was associated with significant diminution of creatine kinase release from the reperfused hearts. The present study indicates that the net loss of membrane phospholipids, especially with respect to PC during reperfusion, may result from 1) inhibition of reacylation of AA, 2) inhibition of de novo synthesis, and 3) stimulation of phospholipase activity. These results are consistent with an influx of Ca2+, although other interpretations are also possible.
Phenotype frequencies for the complement proteins C4A, C4B, Bf (factor B) and C3 were performed for 49 Caucasian patients with psoriasis. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of healthy regional Caucasian controls, p less than 0.001, relative risk = 6.28. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and to produce a non-functional gene product when it occurs with the B17 allele. HLA B17 is known to be associated with psoriasis in many Caucasian populations. Additional findings in the present study were a significant reduction in the C4B*2 allele frequency, a non-significant increase in the Bf*F allele frequency and no difference for Bf or C3 phenotype frequencies in the patients with psoriasis as compared to the controls.
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Phenotype frequencies for the complement proteins Bf (factor B), C4A and C4B were performed in a sample of 49 Caucasian patients with psoriasis followed in Memphis, Tennessee. The genes for these proteins are located in the major histocompatibility complex between the HLA-B and HLA-DR loci. Bf phenotype frequency did not differ significantly for the patients as compared to regional controls. The C4*A6 allele was present in 26.6% of the patients as compared to 5.4% of the controls, p less than 0.001, relative risk = 4.93. The C4*A6 allele is known to be in linkage disequilibrium with the HLA B17 allele and produces a functionally defective gene product. The role, if any, of C4*A6 in the pathogenesis of psoriasis is uncertain.
Gas chromatographic analysis revealed that polyunsaturated fatty acids such as arachidonic acid and total tissue free fatty acids isolated from an aminopropyl bonded-phase column yield a two- to three-fold higher recovery of arachidonic acid as compared to those isolated from thin-layer chromatographic plates. This method was further improved by packing the aminopropyl bonded phase in glass columns, since the glass column significantly eliminated the other contaminants (from polypropylene columns) coeluting with fatty acids in both a neutral lipid thin-layer chromatographic system and on a 5% DEGS-PS column of gas chromatographic analysis. In aminopropyl bonded-phase columns, the standard triglycerides and phospholipids were completely separated from free fatty acids as judged by gas chromatographic analysis. These results warrant the use of an aminopropyl bonded-phase column for the isolation of free fatty acids to obtain better recovery of polyunsaturated fatty acids.
We describe the isolation by reversed-phase h.p.l.c. of a number of products of the degradation of insulin by insulin proteinase and their direct analysis by fast atom bombardment mass spectrometry (f.a.b.-m.s.). Various semisynthetically labelled insulins were used, including [[2H2]GlyA1]insulin and [18O]LysB29]insulin. The results obtained confirm and extend the results obtained by non-mass-spectrometric methods [Davies, Muir, Rose & Offord (1988) Biochem. J. 249, 209-214, and papers cited therein]. Cleavage sites were identified between positions A13-A14, A14-A15, B9-B10, B13-B14, B24-B25 and B25-B26. The advantages and disadvantages of the application of f.a.b.-m.s. to such studies are discussed.
One hundred consecutive first (n = 72) and regrafted (n = 28) cadaver renal allograft recipients were immunosuppressed with cyclosporin, azathioprine and prednisolone (triple therapy) and followed for a median of 17.3 months (range, 7-26 months). Actuarial patient survival at 12 and 24 months was 97.7 per cent. Actuarial graft survival at 12 and 24 months was 79.5 per cent (first graft recipients 81.3 per cent and regrafted recipients 75 per cent). HLA-DR matching significantly improved graft survival which was 93 per cent at 1 year in patients given HLA-DR compatible kidneys, compared with 83 and 54 per cent, respectively, in patients who received kidneys mismatched for one or two HLA-DR antigens. There were 0.8 (s.d. = 0.7) episodes of acute rejection per patient during the first 3 months after transplantation. Triple therapy provides effective immunosuppression without evidence of over immunosuppression and reduces the incidence of cyclosporin side-effects. Although acute nephrotoxicity was uncommon, serum creatinine remained elevated 6 and 12 months after transplantation.
A total of 12,988 adolescents completed a questionnaire which assessed experience with cigarettes, inhalants, alcohol, marijuana, cocaine, and level of ego identity (EOM-EIS). Discriminant analyses of substance use, across the achievement, moratorium, foreclosure, and diffusion identity statuses, yielded significant functions for each grade comparison (7th to 12th). Frequencies of experience for diffused respondents were consistently higher than estimates for the achieved and moratorium respondents; and, foreclosed adolescents reported the lowest frequency of experience. Diffused adolescents were about twice as likely to have tried cigarettes and alcohol, three times as likely to have tried marijuana, four times as likely to have tried inhalants, and five times as likely to have used cocaine than their foreclosed peers. The achieved, moratorium, and unclassified respondents reported frequencies of experience that fell between the two extreme groups. Implications for identifying adolescents "at risk", and tailoring prevention/intervention efforts to address developmental differences are addressed.
The characteristics of the train-of-four (TOF) response have been studied electromyographically during the onset and the spontaneous offset of neuromuscular blockade induced with vecuronium or gallamine. During the onset of blockade, at 75% depression of initial twitch height, gallamine was associated with significantly more TOF fade than vecuronium. Both agents were associated with significantly less fade during onset than during spontaneous offset. When the two neuromuscular blocking drugs were compared during spontaneous offset they showed a similar degree of fade during early offset (up to 50% recovery of initial twitch height). However, during late spontaneous offset, when the initial twitch height had recovered to 75% of control values, vecuronium was associated with more fade than gallamine.
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The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.
Biosynthetic human proinsulin (obtained by recombinant DNA techniques) was used as the starting material for the preparation, by semisynthetic methods, of [3H]proinsulin with the label at the N-terminal phenylalanine residue. The labelled proinsulin was characterized by its retention time on reversed-phase h.p.l.c., by polyacrylamide-gel electrophoresis, by the time course of its enzymic conversion into insulin and by chromatographic analysis after extensive proteolytic degradation. The specific radioactivity of the product was 5 Ci/mmol. Experimental details of the preparation of human [[3H]Phe1]proinsulin, the isolation of this product by isocratic h.p.l.c. and gel filtration, and further characterization of protein intermediates have been deposited as supplement SUP 50138 (12 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on prepayment [see Biochem. J. (1987) 241, 5].