The influence on the formation of unstable haemoglobin by the immunomodulating 2-cyanaziridines azimexone and BM 41.332 in mice

Azimexone causes in mice the formation of unstable haemoglobins after a single dose of 20 mg/kg. BM 41.332, another immunomodulating drug of the 2-cyanaziridine class, induces these unstable haemoglobins only after a single oral administration of 500 mg/kg. Subsequently to the formation of unstable haemoglobins we observed a development of Heinz bodies. These effects of the 2-cyanaziridines were elicited neither by methaemoglobin formation nor by an impairment of the components protecting haemoglobin against oxidation (G6PD, catalase, glutathione). The elimination of the altered haemoglobin in the spleen could be followed by measurement of the rise in the iron content of the spleen.     

Comparative effects of cefpirome (HR 810) and other cephalosporins on experimentally induced pneumonia in mice

The chemotherapeutic efficacy of cefpirome (HR 810), a new polar aminothiazolylcephalosporin and that of ceftazidime, cefotaxime, cefoperazone, latamoxef and cefodizime were examined against experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. When compared in terms of MIC values against the infecting organism and the pharmacokinetic pattern, cefpirome showed equal activity and a similar pharmacokinetic behavior to ceftazidime and cefotaxime in mice. Trials to assess the bactericidal activity in vivo, however, showed that cefpirome displayed a more marked bactericidal effect in pneumonic mice than the other cephalosporins tested. Only cefodizime, a cephalosporin with extremely high and prolonged blood and tissue levels in experimental animals exerted chemotherapeutic effects similar to cefpirome. After cefpirome or cefodizime medication (50 mg/kg), the viable counts in the lungs of experimental animals fell steadily to 1/10,000 of the pretreatment level and, in contrast to the reference compounds, no regrowth of the challenge organisms could be observed with both drugs. Moreover, with ED50s ranging from 1.1 to 59.1 mg/kg in treatment studies, cefpirome as well as cefodizime were two to ten times more effective than ceftazidime and cefotaxime, whereas cefoperazone and latamoxef were considerably less effective.     

Thrombocytopenia and platelet functional defects in pre-eclampsia: implications for regional anaesthesia

A prospective, observational study of forty pre-eclamptic patients was conducted to confirm or refute reports of a platelet functional defect superimposed on the consumptive thrombocytopenia of pre-eclampsia. Investigations included a platelet count, in vivo platelet function as assessed by a Duke bleeding time, and in vitro platelet function as assessed by thromboxane B2 and Platelet Factor 3 (PF 3). The overall incidence of thrombocytopenia was 15%. Prolonged bleeding time and slightly decreased availability of PF 3 (evidence of possible platelet dysfunction) was present in 2.5% of patients while 21% had evidence of fibrinolysis with an elevated monoclonal D-dimer. In the assessment of suitability for regional blockade, a platelet count is essential. If the platelet count is between 50 and 100 x 10(9)/l a bleeding time is indicated.     

Oxygen saturation and cardiovascular changes during fibreoptic intubation under general anaesthesia

Sixty patients who required fibreoptic nasotracheal intubation were studied. Arterial oxygen saturation, arterial blood pressure and heart rate were monitored continuously during fibreoptic intubation under deep halothane anaesthesia. There were significant decreases (p less than 0.001) in arterial blood pressure and heart rate despite administration of intravenous colloid and atropine. Almost one third of the patients (18 out of 60) suffered a decrease in arterial oxygen saturation below 90% during the intubation sequence and in five patients the saturation fell below 80%. The episodes of desaturation were not related to the induction-intubation time or to the grade of laryngeal visibility at direct laryngoscopy.     

Effect of adrenaline, fentanyl and warming of injectate on shivering following extradural analgesia in labour

This prospective, controlled study was undertaken to determine whether addition of adrenaline or fentanyl to bupivacaine or warming of the injectate had any effect on the incidence of shivering following extradural analgesia in the labouring parturient. Eighty-four patients were sequentially allocated to four groups (control, warm injectate, extradural adrenaline and extradural fentanyl). The adrenaline group had the highest incidence of shivering, the warm injectate and fentanyl groups the lowest. Extradural fentanyl also seemed promising in reducing shivering in pre-block shiverers. This paper also explores the rapidity of temperature decay of solutions of bupivacaine in different clinical situations.     

Comparative Investigations of Various Immunoregulatory Substances in the Delayed Type Hypersensitivity Test of the Mouse

The substances D-penicillamine, auranofin, chloroquine, levamisole, BM 41.332, azimexone, bestatin, methisoprinol (inosiplex), thymosine (fraction 51, indomethacin and cyclophosphamide were examined comparatively in the delayed type hypersensitivity test after oxazolone sensitisation in mice. It was found, that only the basal antirheumatic drugs D-penicillamine, auranofin, chloroquine and levamisole and also BM 41.332 led to a potentiation of the DTH reactions. Methisoprinol, bestatin, azimexone, thymosine fraction 5 and indomethacin had no effect on the DTH, whilst the immunosuppressant cyclophosphamide led to an inhibition of the DTH reaction.

It is concluded that this pharmacological model is suitable for screening of new basal drugs for rheumatoid arthritis.     

RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro.

The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin-sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram-positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective.     

Thiosulphate and hydroxocobalamin prophylaxis in progressive cyanide poisoning in guinea-pigs

The duration of action of the cyanide antidotes sodium thiosulphate and hydroxocobalamin was investigated in guinea-pigs after prophylactic administration before a long-term infusion of NaCN. The parameter for the diminution of the antidote action was the point of time at which the concentration of HCN in the exhaled air of the animals exceeded 100 nmol/kg per min. The time taken to reach this threshold level in the control animals was 12 min. While the threshold level could be extended only to 35 min with hydroxocobalamin (300 mg/kg i.v.) the protective action of sodium thiosulphate (100, 500 and 1000 mg/kg i.v.) persisted dose dependently for about 1, 2 and 4 h, respectively. Additionally we found a plasma half-life of sodium thiosulphate in guinea-pigs of 26 min. This value corresponds approximately to the plasma half-life of sodium thiosulphate in humans given in the literature. Because of the large injection volume necessary, sodium thiosulphate is not suitable for prophylactic use in man.