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In a mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3, the 50% effective dose, ED50, after single doses one hour post-inoculation was considerably lower for ceftriaxone (CRO) than for cefuroxime (CXM) and cefotaxime (CTX), in spite of the same minimal inhibitory concentration, MIC, of 0.02 mcg/ml against the pneumococcus for all 3 drugs. The bactericidal activity as measured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was considerably higher for CRO (87%) than for both CTX (35%) and CXM (15%), respectively. Of pharmacokinetic parameters investigated on doses equal to the ED50s, the time the serum antibiotic concentration remained above the MIC (delta T(MIC)) was the factor that varied the least among 3 drugs. Therefore, the superior in vivo effect for CRO is not due to higher intrinsic activity against the pathogen but to the long serum-elimination half-life resulting in an extended delta T(MIC), probably related to the high serum protein binding.

In Denmark and probably in other countries as well, the infectious agent causing intercurrent death of rabbits by passages of Nichols pathogenic Treponema pallidum has been studied in rabbits in the absence of T. pallidum. This agent can be propagated in rabbits at intervals of 2 to 30 days and, depending on the interval between passages and the number of passages, the mortality may vary from zero to almost 70 per cent. Based on the post mortem findings in fatal cases, the name pleural effusion disease is suggested for this rabbit infection. Iridocyclitis, haematological and biochemical changes are signs of the disease not described previously. The source of the infectious agent is discussed.

Groups of red mice were injected intravenously with doses of from 3 viable units to 3times107 viable units of a virulent strain of M. bovis grown in Dubos Tween medium and exposed to ultrasonics. The course of the infection was evaluated by the survival times of animals that had died spontaneously and by quantitative culture from the organs of animals injected with the four smallest doses and killed at various times after the injection. M. bovis provoked progressive, fatal infection in all animals, even in those injected with 3 viable units. The median survival times of the animals injected with the three largest doses were 13, 17 and 18 days, i.e. increasing the lower the dose. For the animals injected with the three smallest doses, the median survival times were all about 3 months, independent of dosage. On autopsy, tuberculous lesions were found in spleen, lungs and lymph glands, but never in the liver. These lesions, which rapidly became caseous, were largest in the animals injected with a small dose, particularly in those which survived the longest. Smears from the organs contained enormous numbers of tubercle bacilli. Quantitative culture from the organs showed that the tubercle bacilli multiplied strongly during the first 3–4 weeks after the injection. Multiplication then ceased or became strongly inhibited. During the following 3 weeks, the number of viable units in the various organs remained at about the same level, being greatest in the spleen, smaller in the liver and lymph glands, and smallest in the lungs. During the rest of the experimental period, the number varied considerably from animal to animal, but generally it was almost unchanged in the lymph glands, liver and spieen, but increasing in the lungs. In some of the animals that lived longer than 3 months, the number of viable units in all the organs was extremely great.

The homology percentages between DNA from M. smegmatis ATCC 607 and DNA from nine various species of mycobacteria have been determined. DNA-DNA hybridization was measured in a spectrophotometer. The technique, calculation of results and the uncertainty of the method are described.

Skin reactivity to tuberculin has been studied during the course of experimental leptospirosis in guinea pigs. A depression of the delayed hypersensitivity to tuberculin was demonstrated in the infected animals. The depression was most pronounced when icterus had developed. The depression was not correlated with the amount of infectious units administered or with the demonstration of live leptospirae in the peritoneal cavity. In the infected animals there was no correlation between the initial and the final skin tests which is in contrast to findings in the control group.

We have examined the immunological activity of five affinity-purified protein antigens from Mycobacterium tuberculosis in seven inbred and one outbred guinea pig strains. The test systems were measurements of delayed-type hypersensitivity (Dth) responses, lymphocyte stimulation assays (LS), and antibody response measurements. The results showed significant differences in the immunogenicity of the single-protein antigens and, when the antigens were considered separately, highly significant guinea pig strain differences The outbred guinea pig strain behaved as a Dth high responder to all antigens studied. The order of magnitude of the Dth responses was not usually correlated with that of the corresponding antibody responses for the individual guinea pig strain-antigen combinations. In particular, when compared with the other strains, strain 2 guinea pigs generally gave the lowest Dth, but the highest antibody responses. A 38,000 molecular weight protein, possessing M. tuberculosis complex-specific B-cell determinants, appeared immunodominant in 5 out of 7 strains. Our Dlh data in the inbred strains further suggest the presence of an M. turberculosis-specific- T-cell epitope. A T-cell line, 11D9, derived from the high-responder guinea pig strain 13 reactive to this prolein, was shown to be able to confer a tuberculin-like skin reaction in vivo. LS assays with recombinant 38-kDa protein and truncated versions of the protein mapped the 1lD9-defined T-cell epitope to the middle parl of the molecule.

The mechanisms underlying the different sensitivity to respiratory anaphylaxis were studied in two inbred strains of guinea pigs with high (IMM/S) or low (IMM/R) sensitivity to ovalbumin (OA) aerosol-induced respiratory anaphylaxis. Guinea pigs were immunized with OA in Freund’s complete adjuvant and lymphocyte stimulation tests were done with cells from the tracheobroncheal lymph nodes (TBL) draining the airways, from peripheral blood lymphocytes and from the axillary and inguinal lymph nodes. The TBL of the IMM/R strain had a signficantly lower response than those of the IMM/S strain. This selectively low response, which was not antigen specific, could be increased by cyclophosphamide pretreatment. The high TBL response in the IMM/S strain was decreased by OA inhalations to the level of the IMM/R strain. OA inhalations decreased the IgE response in the IMM/S but not the IMM/R strain. Different interpretations of these findings are discussed, with emphasis on the possibility that an inherent suppressor cell population in the TBL are involved.

A total of 157 strains of Staphylococcus aureus of different phage patterns and penicillinase production were investigated for their susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin by an agar dilution method. Only strains of the 52, 52A, 80, 81 complex had significantly higher IC-50 values than the rest of the strains. No correlation was found between penicillinase production and the IC-50 values. Penicillinase susceptibility divided the antibiotics into two groups: one including methicillin, oxacillin and cephalothin, and the other included dicloxacillin, cloxacillin and flucloxacillin. Nineteen strains of S. aureus which existed in both a penicillinase producing and a penicillinase non-producing form were examined for susceptibility to the six antibiotics. The difference between penicillinase positive and penicillinase negative variants was especially marked for flucloxacillin and cephalothin. Methicillin induction prior to susceptibility testing had only a minor influence on the results. Investigation of the stability of methicillin and the four isoxazolyl penicillins against penicillinase production by 37 strains of S. aureus showed methicillin to be the most stable antibiotic. This was followed by dicloxacillin, cloxacillin, flucloxacillin, and oxacillin in that order. The order of stability was identical and independent of phage pattern and quantitative penicillinase production.

Resume Les auteurs ont entrepris d'analyser 148 families de deux enfants chez lesquelles la mere a ete immunisee par le facteur Rhesus au cours de la seconde grossesse et qui a donne le jour a un premier enfant Rhesus positif en bonne sante et un second enfant Rhesus positif malade. Cette analyse donne les resultats suivants. Les series d'enfants compatibles et incompatibles dans le systeme ABO avec le serum de la mere ont ete comparees avec le nombre relatif des differentes series de la population prises au hasard. L'augmentation relative des probabilites d'immunisation a ete estimee pour les differentes series et ensuite comparee deux a deux. Des differences significatives ont ete trouvees dans les cas ou la difference dependait du premier enfant seulement. Quand le premier enfant est incompatible (6 cas en tout) il semblerait que l'immunisation durant la seconde grossesse serait dependante a un certain degre de la compatibilite du second enfant. Le degre de l'immunisation Rhesus a ete evaluee sur la base du titre des anticorps dans les 10 jours qui precedaient la delivrance et de l'intensite du test de Coombs direct pratique avec le sang du cordon de l'enfant malade. Deux groupes ont ete compares: dans le premier les deux enfants sont compatibles avec la mere dans le systeme ABO; dans le second groupe, le premier enfant est compatible et le second incompatible avec la mere dans le systeme ABO. Le titre des anticorps anti-Rhesus et l'intensite de la reaction du test de Coombs direct sont nettement plus bas dans le second groupe. Toutes ces observations semblent confirmer la theorie selon laquelle dans l'immunisation Rhesus un foetus imcompatible dans le systeme ABO est un stimulus plus faible qu'un foetus compatible dans le meme systeme; en d'autres termes, cette difference est strictement d'ordre quantitatif. Zusammenfassung Es wird uber 148 Zwei-Kinder-Familien berichtet, bei welchen die Mutter wahrend der zweiten Schwangerschaft eine Rhesussensibilisierung erlitten und ein rhesuspositives gesundes und anschliesend ein rhesuspositives krankes Kind geboren hatten. In diesem Untersuchungsgut wurden die Reihenfolgen der Kinder bezuglich Kompatibilitat bzw. Inkompatibilitat im ABO-Blutgruppensystem gegenuber den Muttern mit den relativen Haufigkeiten der verschiedenen Reihenfolgen in der Durchschnittsbevolkerung verglichen. Die relative Grose der Sensibilisierungswahrscheinlichkeit wurde fur die verschiedenen Reihenfolgen geschatzt, und diese Werte wurden paarweise verglichen. Gesicherte Differenzen wurden nur in jenen Fallen beobachtet, bei denen der Kompatibilitatsunterschied das erste Kind betraf. Wenn das erste Kind inkompatibel war (6 Falle), schien die Sensibillisierungswahrscheinlichkeit bei der zweiten Schwangerschaft in einem gewissen Grade von der Kompatibilitat des zweiten Kindes abhangig zu sein. Der Schweregrad der Sensibilisierung wurde anhand des Antikorpertiters bei der Mutter wahrend der letzten 10 Tage vor der Geburt sowie anhand der Starke des direkten Coombstests des Nabelvenenblutes ermittelt. Es wurden die folgenden zwei Gruppen miteinander verglichen: In der ersten Gruppe waren beide Kinder gegenuber der Mutter in bezug auf das ABO-System kompatibel; in der zweiten Gruppe war nur das erstgeborene Kind kompatibel, das zweite jedoch inkompatibel. Der Rhesusantikorpertiter bei der Mutter sowie die Starke des direkten Coombstests beim Kind waren in der zweiten Gruppe signifikant geringer. Alle mitgeteilten Beobachtungen stutzen die Annahme, das ein ABO-inkompatibler Fot gegenuber der Mutter einen kleineren Rh-Antigenstimulus darstellt als ein ABO-kompatibler Fot. Der Unterschied ist jedoch rein quantitativ.

The methods used for obtaining bacterial cultures from the normal conjunctiva were reviewed. A comparison was made between four methods: a) platinum loop, b) calcium alginate swab c) dry, and d) wet cotton wool swab, using agar (all methods) and serum-bouillon (methods b, c, d) as culture media. The comparisons were based on the isolation rate of Staphylococcus albus and corynebacteria. At the same time, four topical anaesthetics (benoxinate, tetracaine, proparacaine, cocaine) and one vital stain (tetrazolium - alcian blue mixture) instilled into the conjunctiva immediately before taking samples, were studied for their effects on the isolation rate of Staphylococcus albus and corynebacteria. For isolating Staphylococcus albus, method d was found to be superior to the others when the methods were used in the above mentioned order, and when agar was the only culture medium used. On the other hand, after instillation of the above mentioned eyedrops, causing the so-called “washing-out” effect (Fahmy et al. 1974), method a was found better than the others, providing the methods were used in the a-b-c-d order and when agar only was used. When considering the growth of Staphylococcus albus in serum boullion as well, methods b, c, and d were found equal in effect, but somewhat superior to a. Corynebacteria showed nearly the same isolation rate with all the methods before as well as after the instillation of eye drops.

Forty-nine clinical strains of coagulase-negative staphylococci were investigated for susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin. The highest level of resistance was found to methicillin and the lowest to cephalothin. The resistance-level of the isoxazolyl penicillins showed a high degree of uniformity. However more strains were resistant to cloxacillin and oxacillin than to dicloxacillin and flucloxacillin. Only a weak correlation was found between beta-lactamase production, and resistance to the six antibiotics. Methicillin was the most stable. The inactivation of cephalothin differed from that of the other antibiotics.

Groups of red mice were injected intravenously with doses varying from 11 viable units to about 108 viable units of a virulent strain of M. tuberculosis grown in Dubos Tween medium and dispersed by means of ultrasonics. The course of the infection was determined by quantitative culture from the organs of animals killed at various times after the injection and by the survival times of animals that died spontaneously. Quantitative culture showed that the tubercle bacilli multiplied strongly in the organs during the first 2–3 weeks after the injection. Multiplication then ceased completely in liver, spleen and lungs; in the lymph glands the bacilli continued to multiply but at a very slow rate. After the period of initial multiplication, the number of bacteria in liver and spleen decreased gradually during the whole experimental period (1 year), although it varied considerably from animal to animal after the second month. In the lungs, the number remained almost constant in the animals injected with large doses, but in those given doses ≥ 104 viable units, it became reduced from the second month, and in some cases the bacteria disappeared completely. Total elimination of the bacteria was also observed in the liver and spleen of a few animals but never in the lymph glands. The mean survival times of animals injected with the four largest doses were prolonged from 81 to 310 days the smaller the dose. In the animals injected with doses ≥ 104 viable units, the mean survival times, which were independent of dosage, were not significantly different and not significantly less than those of a group of non-infected animals. The macroscopical tuberculous lesions were small in all groups. Enlargement of the spleen, slightly enlarged lymph glands and possibly tubercles in the lungs were the most frequent findings. The number of bacteria in the organs was large in all animals injected with the large doses, but only in about half of those given small doses.

In Denmark and probably in other countries as well, the infectious agent causing intercurrent death of rabbits by passages of Nichols pathogenic Treponema pallidum has been studied in rabbits in the absence of T. pallidum. This agent can be propagated in rabbits at intervals of 2 to 30 days and, depending on the interval between passages and the number of passages, the mortality may vary from zero to almost 70 per cent. Based on the post mortem findings in fatal cases, the name pleural effusion disease is suggested for this rabbit infection. Iridocyclitis, haematological and biochemical changes are signs of the disease not described previously. The source of the infectious agent is discussed.