COMPARISON OF SPEED OF ONSET OF FAZADINIUM, PANCURONIUM, TUBOCURARINE AND SUXAMETHONIUM

Under light general anaesthesia the speed of onset of actionof fazadinium, pancuronium, tubocurarine and suxamethonium hasbeen assessed by measuring the decrease in the twitch heightof the adductor pollicis muscle following administration ofthe drugs. Suxamethonium produced 95% depression of the twitchheigh significantly faster than any of the other drugs, whilethe onset of fazadinium was significantly more rapid than thatof the other non-depolarizing neuromuscular blocking drugs.     

INFLUENCE OF pH, TEMPERATURE, HALOTHANE AND ITS METABOLITES ON OSMOTIC FRAGILITY OF ERYTHROCYTES OF MALIGNANT HYPERTHERMIA-SUSCEPTIBLE AND RESISTANT PIGS

Erythrocyte fragility of malignant hyperthermia-susceptibleand resistant pigs has been examined as a function of pH andtemperature in the absence and presence of halothane and itsmetabolites. A decrease in pH from 7.40 to 6.95 increased thefragility of both susceptible and resistant pigs, but the increasein susceptible animals was significantly greater than that inresistant animals. An increase in temperature led to a reductionof erythrocyte fragility of both types of pig. The most consistentdifferences in haemolysis between susceptible and resistantpigs occurred at sodium chloride concentrations of 0.120 and0.l37mol litre^–1. At all pH values examined and at 39and 41°C, but not at 43°C, erythrocytes from susceptiblepigs showed greater haemolysis in sodium chloride 0.120 and0.l37 mol litre^–1 than did erythrocytes from resistantpigs. Halothane or its metabolites, at concentrations occurringduring anaesthesia, did not alter erythrocyte fragility.     

BIODEGRADATION OF HALOTHANE, ENFLURANE AND METHOXYFLURANE

The biodegradation of halothane, enflurane and methoxyfluranewas studied in 22 patients undergoing abdoninal surgery, bymeasuring the uptake and elimination of each agent and the fluorideexcretion in urine. Six control patients were anaesthetizedwith nitrous oxide in oxygen together with neuromuscular blockingdrugs, five patients with nitrous oxide in oxygen and 0.93%halothane, five with nitrous oxide in oxygen and 1.30% enflurane,and six with nitrous oxide in oxygen and 0.31% methoxyflurane.The ratio of the fluoride excretion in urine to the total amountof fluoride contained in the amount of each anaesthetic agentabsorbed during anaesthesia was estimated to be 17.7% for halothane,2.3% for enflurane and 46.3% for methoxyflurane. The serum fluorideconcentration increased to a maximum of 15.8±3.8 µmollitre^–1 (mean±SD) at 6 h after anaesthesia withmethoxyflurane, while it did not exceed 8 µmol litre^–1with the other anaesthetic agents.     

GLUTATHIONE DETERMINATION AND A STUDY OF THE ACTIVITY OF GLUTATHIONE-PEROXIDASE,GLUTATHIONE-TRANSFERASE,AND GLUTATHIONE-REDUCTASE IN RENAL TRANSPLANTS

The aim of this work is to study the temporary variation of oxidative stress in renal transplants, both in plasma and in erythrocytes (CR). In order to do so, we determined total glutathione (GST) levels, both oxidized (GSSG) and reduced (GSH), and the activity of enzymes, glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt), in renal transplant patients. Determinations were made 48 h before the transplant 1 week and 2 weeks after the renal transplant. The results obtained confirm a high “oxidative stress” rate, resulting from the equilibrium between the production of free radicals and the activity of antioxidants, the former being higher proportionally. Immediately after the transplant there is an increase of oxidative stress, which results in an increase of G-red, a marked decrease of G-px in plasma and in erythrocytes (CR) and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). As times goes on, after the transplant, there is a significant improvement in the activity of antioxidant enzymes, but there is no normalization, which is easily seen in the fact that total glutathione levels and the activity of the various enzymes approach the average values of the control group.     

EFFECTS OF ALPROSTADIL AND PRAZOSIN ON MOTILITY, VIABILITY AND MEMBRANE INTEGRITY OF HUMAN SPERM

Purpose

We evaluated the effects of alprostadil, prazosin hydrochloride, and alprostadil/prazosin hydrochloride, agents used in the clinical treatment of male erectile dysfunction, on the motility, viability and membrane integrity of human sperm.

Materials and Methods

Ten healthy volunteers provided semen samples that were incubated with 0.4 mg./ml. alprostadil, 0.1 and 0.2 mg./ml. prazosin hydrochloride and 0.4 mg./ml. alprostadil plus 0.1 mg./ml. prazosin hydrochloride for 2 hours. Control incubations included polyethylene glycol 1450, the formulation vehicle for the clinical use of alprostadil and prazosin, and Ham's F-10 buffer. Serial evaluations of percent sperm motility, percent viability, membrane function (by hypo-osmotic swelling test) and several computer generated measurements of sperm motion, including straight line velocity, curvilinear velocity, linearity and amplitude of lateral head displacement, were made.

Results

None of the agents had a significant impact on the percentage of motile or viable sperm or on sperm membrane function. Incubation with 0.2 mg./ml. prazosin reduced straight line velocity and curvilinear velocity significantly compared with the other agents. These changes were most likely a direct result of the viscosity of the 0.2 mg./ml. prazosin solution and not a cellular or metabolic effect on the sperm.

Conclusions

Alprostadil and prazosin hydrochloride at doses used in transurethral therapy for erectile dysfunction have no effect on the motility, viability and membrane integrity of human sperm.     

INTERACTION OF CYCLOSPORIN AND ITS SOLVENT, CREMOPHOR, WITH ATRACURIUM AND VECURONIUM

Interactions between Sandimmun (formulated as cyclosporin (CyA)in Cremophor and ethanol) and atracurium or vecuronium wereinvestigated inanaesthetizedcats. Duringstable50% blockade andwith a constant rate of infusion of the neuromuscular blockingdrugs, Sandimmun 0.8 mg kg^–1 or an equivalent amount ofits solvent moiety was injected over 5 min. Sandimmun potentiatedthe blockade induced by vecuronium (median infusion rate 110µg kg^–1 h^–1) from 50.7% before injection tomaximum 95.2% 17.3 min after injection (median values), whereasthe median blockade in cats receiving atracurium (median 250pig kg^–1 h^–1) increased from 51.3% to 72.4% after32.9 min. At 45 min after the injection the median blockadeswere 93.1% and 69.8%, respectively. In cats receiving vecuronium(median 104 µg kg^–1 h^–1) the solvent producedan increase in effect of from 51.1% to maximum 78.0% blockadeafter 5.4min and 61.5% after 45 min (median values). Interactionwith solvent was negligible in cats receiving atracurium. Weattribute the effect of the solvent to the Cremophor component.The mechanism of the interaction related to the cyclosporinis unknown. ^*Present address: Apothekernes Laboratorium A. S, Harbnitzalleen3, N-0275 Oslo 2, Norway.     

THE DURATION OF ACTION OF BUPIVACAINE, PRILOCAINE AND LIGNOCAINE

The duration of analgesia and of hypoaesthesia produced by avariety of solutions has been examined by skin weal testing;each separate study was carried out in twenty female volunteersunder double-blind conditions. First, bupivacaine, lignocaineand prilocaine were compared with and without 1 in 200,000 adrenaline.Bupivacaine was found to give significantly longer analgesiathan prilocaine and significantly longer hypoaesthesia thanboth the other agents. Adrenaline significantly lengthened theaction of all three drugs, this prolongation being greatestwith lignocaine. The second part of the trial compared the durationof action of hospital-prepared and commercially prepared solutionsof the three local analgesics plus adrenaline. The commercialampoule preparations provided significantly longer action thanthe corresponding drugs in hospital-prepared multidose vials.The third group of experiments studied the effect of doublingthe concentrations of the solutions; there was no great increasein duration of analgesia but the duration of hypoaesthesia waslengthened, significantly so with bupivacaine. Throughout allthe above studies the individual results with bupivacaine showeda greater range of variation than those with the other agents.Finally the analgesic effect of saline (with and without adrenaline)was investigated; it was found that both agents generally produceda similar brief period of hypoaesthesia. The findings and theirpractical implications are discussed. Present address: Princess Alexandra Hospital, Harlow, Essex.,     

LACK OF CORRELATION BETWEEN THE ANAESTHETIC AND ANTI-CONVULSANT POTENCIES OF ALTHESIN, KETAMINE AND METHOHEXITONE

Using Sprague-Dawley rats, the anti-convulsant potencies ofAlthesin, ketamine and methohexitone were determined for bicuculline-and strychnine-induced seizures and compared with their effectson hyperbaric seizures. All three anaesthetics protected againstboth types of chemical convulsants; the degree of protectionvaried from 34 to 151 %, with Althesin being the most effective.However, there was no correlation between their anti-convulsantand anaesthetic potencies, and no relationship between the effectson chemical convulsions and the interactions of the same agentswith hyperbaric convulsions. These data suggest that the orderof anti-convulsant potencies at equivalent anaesthetic concentrationis Althesin >> ketamine = methohexitone, and that neitherbicuculline- nor strychnine-induced seizures are a good modelfor hyperbaric convulsions.     

LOCAL EXCISION OF CARCINOMAS OF THE RECTUM,ANUS, AND ANAL CANAL

Local resection has a place in the treatment of selected patients with carcinoma of the rectum, anus and anal canal. Selection depends on the ability of the surgeon to assess accurately the stage of the tumour. Favourable lesions are those which are small, exophytic, and mobile on the surrounding tissues. A transphincteric approach has been advocated for these tumours, but this seems unnecessarily destructive. The present series consists of 18 highly selected patients who were treated by transanal local removal. There have been two recurrences, one of which has been treated by abdominoperineal resection and the other by further local excision. All of these patients were diagnosed clinically as suffering from carcinoma before operation. Patients who had a preoperative diagnosis of carcinoma and were later found to have benign adenomas, and patients who were diagnosed as benign and later found to have histological malignancy, have been excluded.     

EFFECTS OF EXTRADURAL BLOCK: COMPARISON OF THE PROPERTIES, CIRCULATORY EFFECTS AND PHARMACOKINETICS OF ETIDOCAINE AND BUPIVACAINE

Five healthy, unmedicated male volunteers, aged 19–25yr, participated in a double-blind, crossover study. Each subjectreceived, on separate occasions and via a catheter placed atL2, 1.5% etidocaine HC120 ml with adrenaline 5 g/ml, or 0.75%bupivacaine HC1 20 ml with adrenaline 5 g/ml for extraduralanalgesia. In addition, in order to calculate the absorptionrate of the local anaesthetic agent, each subject received ontwo further occasions etidocaine HC175 mg and bupivacaine HC175mg respectively by i.v. infusion, over a period of 10 min. Spreadof sensory analgesia to four segments above and below the siteof injection was faster with etidocaine (13± 3 min) (mean±SD) than with bupivacaine (22 ± 8 min). Two-segment regressionoccurred later for bupivacaine (260±57 min) than foretidocaine (180±96 min). Caudal spread of analgesia wasmore extensive with etidocaine than with bupivacaine. The onsetof motor blockade tended to be faster with etidocaine (5.8±3.0min), than with bupivacaine (10.0 ± 3.5 min); regressionof motor blockade by one unit was longer with etidocaine (306±103min) than bupivacaine (238± 75 min). Sudo-motor blockoccurred earlier with etidocaine (4.0±2.1 min) than bupivacaine(13.7±4.8 min). Significant changes in cardiac strokework and stroke volume occurred. For etidocaine these measurementsremained below control values for 120–210 min after injection.The mean maximum arterial plasma concentration of etidocainewas 1.52 ± 0.64 g/ml, at 14 ± 2 min and of bupivacainewas 1.35±0.63 g/ml, achieved at 20±4 min. Thesystemic absorption of both drugs occurred in a biphasic patternwith a fast and slow half-life of 0.3 and approximately 8 hrespectively. ^*Present addresses: Department of Anesthesiology, Universityof Massachusetts Medical Center, 55 Lake Avenue North, Worcester,Mass. 01605, U.S.A. Unit of Anaesthesia and Intensive Care, The Flinders Universityof South Australia, Bedford Park S.A. 5042, Australia. Department of Therapeutics, Academic Division of Medicine, TheUniversity of Sheffield, Royal Infirmary, Sheffield, Yorks S63DA.     

PRE- AND POSTJUNCTIONAL BLOCKING EFFECTS OF AMINOGLYCOSIDE, POLYMYXIN, TETRACYCLINE AND LINCOSAMIDE ANTIBIOTICS

The effects of seven antibiotics (streptomycin, amikacin, polymyxinB, lincomycin, clindamycin, tetracyc-line and oxytetracycline)were compared with those of magnesium, tubocurarine and lignocainein the frog sciatic nerve - sartorius muscle preparation, usingintraceUular recording techniques All compounds except tubocurannedecreased end-plate potential quantal content. The prejunctionaleffects of magnesium, streptomycin, amikacin, polymyxin B andoxytetracydine (but not the other drugs) were well reversedby increasing the calcium concentration At concentrations whichdepressed quantal content, only magnesium, tetracycline andoxytetracydine did not reduce postjunctional sensitivity. Furtherpostjunctional effects of the drugs were revealed by alterationsin the time-courses of end-plate potentials. All the drugs testedexcept magnesium, tubocurarine and lincomycin produced changesin muscle action potentials. None of the compounds had anticholinesteraseactivity. The results confirm that aminogrycoside, polymyxin,tetracyc-Une and lincosamide antibiotics produce neuromuscularblock by a combination of both pre- and postjunctional actions. ^* Present address: School of Natural Resources, University ofthe South Pacific, Suva, Fiji.     

NEUROMUSCULAR BLOCKING AND HYPOTENSIVE ACTIONS OF STREPTOMYCIN, AND THEIR REVERSAL

Large doses of streptomycin injected in 20 dogs anaesthetizedwith chloralose or pentobarbitone caused neuromuscular blockade,as judged by the response of the tibialis anterior muscle toperipheral nerve stimulation. Marked arterial hypotension invariablyoccurred. In all of four dogs pholedrine restored and maintainedblood pressure, but the amplitude of respiration and tibialistwitch still decreased with large doses of streptomycin. Neostigmineled to a slow and incomplete recovery of twitch response andlittle increase in blood pressure. Calcium chloride alone, andafter neostigmine, caused a quick and complete recovery of twitchresponse and restored the blood pressure. It is suggested thatsmall doses of calcium chloride may be of use clinically whenhypotension and neuromuscular block occur due to large dosesof streptomycin.     

肾脏病患者血清脂蛋白,载脂蛋白变化及血透对其影响的临床观察

本实验测定了３４例慢性肾衰（ＣＲＦ）、２７例肾病综合征（ＮＳ）患者和１００例正常人血清脂质、脂蛋白（Ｌｐ）和载脂蛋白（Ａｐｏ）的含量，并观察了血透（ＨＤ）和非透析（ＮＤ）患者血清脂质、Ｌｐ、Ａｐｏ的浓度变化。结果显示：（１）与正常组比较，ＮＳ和ＣＲＦ患者血清脂质、Ｌｐ及Ａｐｏ的绝大多数指标有明显异常（Ｐ＜０．０１或０．０２或０．００１）；（２）比较ＨＤ和ＮＤ组，ＮＤ对ＣＲＦ血清脂质、Ｌｐ、Ａｐｏ含量的影响无显著意义（Ｐ＞０．０５）。     

乳腺积乳囊肿的病因及诊治

本文报告乳腺积乳囊肿56例。年龄23～52岁,平均27.5岁。术前50例诊断正确,误诊6例。特别提出局部肿块波动感试验阳性,A超显示液平段,B起显示无回声,试穿抽出乳汁,对诊断有一定价值。治疗以手术切除为主;仅有7例穿刺抽吸乳汁得以治愈。