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Optimal stimulatory doses of purified phenol-water extracted lipopolysaccharides (LPS) from 5 selected strains of 3 putative periodontopathogens (Fusobacterium nucleatum, Prevotella intermedia, and Veillonella), 3 strains of 2 nonoral bacterial species (Bacteroides fragilis and Salmonella enteritidis), and pokeweed mitogen (PWM ) iduced significantly higher maximum mitogenic responses and polyclonal Ig production in cultures of unfractionated spleen cells from nu/nu-BALB/c (nude) than from BALB/c (normal) mice. Compared with PWM, the LPS were stronger mitogens showing relative mitogenic capacities B. fragilis LPS> F. nucleatum LPS> S. enteritidis LPS, Veillonella LPS, and P. intermedia LPS B. fragilis LPS was the most and S. enteritidis LPS the least effective polyclonal B cell activator of total Ig, IgG2a, lgG2b, IgG3, IgA, and IgM secretion IgGI was not detected, P. intermedia LPS was the strongest IgA inducer Kinetic observations indicated mitogenic responses and polyclonal B cell activation in a close sequential order in nude and normal cells. The LPS were potent Ag- and T-cell Independent polyclonal B cell activators and LPS of subgingival plaque bacteria may therefore play a nonspecific role in the pathogenesis of periodontal diseases. [ABSTRACT FROM AUTHOR]

The concentration of metronidazole in the exudate of walled off Teflon chambers implanted in rabbits was compared with that of serum. The peak concentration of metronidazole in the exudate following intravenous injection was lower and appeared later than in serum. No accumulation of metronidazole in the exudate was observed after repeated doses of the agent. [ABSTRACT FROM PUBLISHER]

BACKGROUND Systemic capillary leak syndrome (SCLS) (Clarkson's disease) is a rare disorder of unknown etiology, characterized by transient episodes of hypotension, and the microvascular leak of fluids into the peripheral tissues, resulting in edema. Between 80-90% of patients with SCLS have a concomitant monoclonal gammopathy. Although translational in vitro studies have implicated vascular endothelial barrier dysfunction in the etiology of SCLS, the etiology and disease associations in clinical cases remain unknown. CASE REPORT We report a case of SCLS in a 49-year-old woman who initially presented with an upper respiratory tract infection, which was complicated by edema and compartment syndromes in the extremities that required fasciotomies. Serum levels of the cell surface heparan sulfate proteoglycan, syndecan-1 (CD138), a measure of endothelial surface glycocalyx (ESG) damage, were measured by enzyme-linked immunoassay (ELISA), peaked at up to 500 ng/mL (reference range, 50-100 ng/mL) and normalized on disease remission. CONCLUSIONS This case report supports the view that damage to the microvascular endothelium, has a role in the pathogenesis of acute SCLS. This case also indicated that monitoring serum levels of syndecan-1 (CD138) might be used to monitor the progression and resolution of episodes of SCLS.

Lipopolysaccharides (LPSs) from anaerobic gram-negative bacteria, including those of low endotoxic activity that are isolated from Bacteroides, Prevotella, and Porphyromonas are potent inducers of DNA replication and polyclonal immunoglobulin production in murine B lymphocytes. The activation is dose-dependent and T cell-independent. Replication of DNA and production of immunoglobulins were also stimulated by lipid A and by the LPS heteropolysaccharide that were isolated by mild acid hydrolysis of the LPSs of Bacteroides fragilis and Fusobacterium nucleatum. Combinations of LPS, lipid A, and acid-degraded polysaccharide amplified the blastogenic response. Antibodies that react with the polysaccharide part of LPSs isolated from members of the Bacteroidaceae are present in healthy human serum.

Interchangeable combinations of Fusobacterium nucleatum Fev1 lipopolysaccharide (LPS) with its split products by acetic acid hydrolysis, i.e. lipid A (LA) and degraded polysaccharide (PS), amplified the blastogenic response in murine spleen cell cultures as measured by [3H]thymidine uptake. Athymic murine spleen cells precultured with LPS-Fev1 for 48 h (stage 1), washed twice and cultured together with fresh cells and either LA or PS for 72 h (stage 2) gave a synergistic response over that found in spleen cell cultures of thymic mice. Spleen cells pre-cultured with LA or PS and with fresh cells and LPS-Fev1 added to stage 2 cultures gave less significant amplification compared with precultures of LPS and either LA or PS together with fresh cells added to stage 2. Precultures with LA, PS or LPS-Fev1 and with pokeweed mitogen (PWM) and fresh cells added produced an additional increment of synergy which was most pronounced in spleen cell cultures of normal mice.

Lipopolysaccharide of Fusobacterium nucleatum strain Fevl was split by acid hydrolysis. The split products, i.e. lipid A and degraded polysaccharide were mitogenic for murine spleen cells as measured by uptake of [3H]thymidine. The uptake of [3H]thymidine was dose-dependent. Incubation of spleen cells with stimulants for 3 days resulted in a polyclonal activation of immunoglobulin synthesis. Higher mitogenic response and immunoglobulin production were found in spleen cells of athymic mice compared to those of thymic mice. The activity of lipid A in stimulating immunoglobulin synthesis was comparable with the parent lipopolysaccharide-Fevl, the degraded polysaccharide being the less potent stimulator.

This is a case report of a 20-year-old man with ranula, the size of an orange, in the floor of the mouth causing mandibular prognathism with fan-shaped mandibular teeth anterior to the premolars. The tumor was extirpated. The pathogenesis, differential diagnosis and treatment of ranulas are discussed.

The effects of iohexol, a new non-ionic contrast medium, after intravenous injection into humans are reported. After injection of small doses into 2 subjects, iohexol was injected intravenously into 20 healthy male volunteers in doses of 125 to 500 mg I/kg body weight. A large number of physiologic, biochemical, hematologic and pharmacokinetic parameters were analysed. The results indicated that iohexol was well tolerated and that clinical trials in patients could be undertaken.

Release of previously incorporated 45Ca from fetal rat bone in tissue culture was stimulated by preparations of the polymorphonuclear leukocyte chemotactic factor isolated from lipopolysaccharide (LPS)-induced inflammatory exudate in rabbits as well as by Bacteroides fragilis LPS. High concentrations of released hydroxyproline and lactate seemed to correlate well as a high percentage of 45Ca liberated into the culture medium. An active bone resorption was stimulated by a concentration of 1 microgram/ml of the chemotactic factor. The peak in amount of released 45Ca was at a concentration of 5 micrograms/ml of the chemotactic factor (LPS-CF) as well as of the LPS preparation, whereas the parathyroid hormone was most active at 1 IU/ml. Their effect was connected with the formation of osteoclasts. Neither LPS-CF nor LPS stimulated a release of 45Ca or hydroxyproline from heat-devitalized bones. Heparin added to LPS-CF did not enhance its resorptive potential, whereas when added to LPS it had a synergistic effect. It is suggested that the bone resorptive effect exerted by LPS may be caused by chemotactic factors elaborated by activation of the complement system, and that these factors may be of importance in the pathophysiology of periodontal disease.

A case report with simultaneous occurrence of neurofibromatosis, incomplete branchial arch syndromes, a branchial cleft cyst and a pseudocyst in connection with a vascular hamartoma anterior to the right ear of a 38-year-old woman is presented. A possible common pathogenesis of the vascular hamartoma and the incomplete branchial arch syndromes as well as that of the neurofibromatosis is suggested. The pseudocyst is interpreted as a branchial cleft cyst showing inflammatory changes due to a pharyngitis shortly before the preauricular tumor appeared.

The first experience with iohexol in urography in humans is reported. Injection of iohexol in a dose of 200 mg I/kg body weight into 34 patients with normal renal function was followed by only few and slight subjective adverse effects. A large number of laboratory tests revealed no toxic effects. High radiographic contrast was obtained.

Puriified lipopolysaccharides (LPS) from strains of Bacteroides, Fusobacterium and Veillonella incubated with guinea pig serum, were tested for chemotatic activity against rabbit polymorphonuclear leukocytes (PMNs) in modified Boyden chambers. Comparisons were made to a Salmonella LPS (S. enteriditis S-795). Submicrogram amounts of LPS induced positive chemotaxis, and a typical dose-response relationship up to certain dose levels was observed. The difference in chemotactic activity between the Veillonella LPS and LPS-S-795 was not statistically significant. The Fusobacterium LPS showed either a non-significant or a highly significantly lower chemotatic capacity than LPS-S-795. The Bacteroides LPS were also clearly chemotactic, but considerable less when compared to the Salmonella LPS. When serum was not added, the LPS preparation showed no chemotactic activity.

The first experience in patients (phase II studies) with iohexol (Omnipaque) - a new non-ionic contrast medium - in intravenous urography (34 patients), cardioangiography (45 patients) and cerebral angiography (38 patents) is collectively reported. A non-comparative, multicentre design was used in all 3 applications. The objective was to assess the efficacy (the opacity to X-rays) and the tolerability of iohexol using routine contrast medium doses in a well defined adult population. No unexpected or severe reactions occurred in the 117 included or 9 excluded patients. Good efficacy was confirmed, and the contrast medium was well tolerated. The results warrant advancing iohexol into comparative phase III trials. The iohexol phase II studies and initial research in patients with contrast media in general are discussed.

A clinical study of local anesthetic solutions with and without epinephrine was conducted involving 32 healthy adults requiring removal of bony impacted mandibular third molars. The time elapsing from the administration of the anesthetic solution until analgesia was obtained was significantly shorter in the vasoconstrictor group (P less than 0.001). Additional anesthetic was necessary in 44% of the patients in the control group. The blood loss in the vasoconstrictor group was significantly lower (P less than 0.001) than in the group receiving anesthetic solution without the vasoconstrictor. No statistically significant difference in operation time between the groups was found, although the profuse bleeding in the control group impeded to some extent the surgical procedure. A positive correlation coefficient between operation time and blood loss of r = 0.65 in the vasoconstrictor group (P less than 0.006) and r = 0.77 in the control group (P less than 0.001) was found. Hemorrhage occurring 24 h postoperatively was recorded in 37% of the subjects in the vasoconstrictor group, and of these 83% revealed a healing of the socket by second intention.

Iohexol was compared with Amipaque (metrizamide) in a double-blind study in one pair of injections in each of 20 patients referred for routine cerebral angiography. Catheter position, patient position, injection pressure, contrast medium volume, and concentration (300 mg l/ml) were the same in the two injections, with iohexol and Amipaque being used alternately. Except for these two injections iohexol was used throughout. The parameters studied included diagnostic information obtained (quality of the examination), circulation time, and comparison of patient reactions to the pair of injections (e.g., electrocardiogram, heart rate, and subjective reactions). The patients' reactions to the noncomparative part of the examination were evaluated also, and the patients were observed for possible adverse reactions after the examination. No difference could be detected between the two contrast media in this series. No serious adverse reactions occurred.

The clearance of bacterial lipopolysaccharide (LPS) from Bacteroides fragilis was studied, using wound chambers implanted subcutaneously in rabbits. The primary skin inflammatory reaction, the Limulus amoebocyte lysate test and the haemagglutination inhibition test all demonstrated a more rapid elimination of LPS from the wound chambers after the second injection, compared to the elimination rate after the first injection given three days earlier. The clearance rate of LPS was significantly higher (0.003 greater than or equal to p greater than or equal to 0.0006) and the number of accumulated leukocytes in the inflammatory exudate significantly lower (p less than or equal to 0.05) after the second injection. Antibodies to B. fragilis LPS in the exudate before the second endotoxin injection was of the 19S IgM class. This suggests that phagocytes in the granulation tissue lining the chamber walls may be of importance in the elimination of endotoxin.

The nonionic contrast medium, iohexol, was released by Nyegaard, Oslo, in 1980 for clinical testing. Results of a three-phase clinical trial program carried out in Europe and the U.S. through December 1983 are summarized. Evaluation of phase I studies of human tolerance and excretion--and phase II studies of effects on pharmacologic and physiologic parameters--indicated that iohexol was well tolerated and effective. Phase III consisted mainly of controlled parallel and crossover studies comparing iohexol with conventional ionic media and with other nonionic agents in a variety of radiographic studies. Image quality was as good or better with iohexol than with ionic media. Iohexol was tolerated significantly better than ionic agents. Patients consistently reported fewer and less intense pain and heat sensations. Iohexol had less effect on blood pressure, blood flow, heart rate, and electrophysiologic parameters, and caused fewer adverse reactions than ionic media for all types of reactions observed.

Purified lipopolysaccharide (LPS) from Veillonella incubated in normal rabbit serum was tested for chemotactic activity on rabbit polymorphonuclear leukocytes (PMNs) in modified Boyden chambers. In doses above those giving optimal response (over-optimal dose), a decrease of the PMN migration activity was found. This decrease also correlated well with an increase in the migration inhibition of the PMNs as demonstrated with the capillary tube assay. The PMN chemotactic factor isolated from LPS-induced inflammatory exudate (LPS-CF) in rabbits, produced both a decrease in chemotactic response and a migration inhibition of PMNs in over-optimal doses. This inhibitory effect was not due to cytotoxicity, proved by the trypan blue exclusion test. Also, a reduced locomotion of PMNs first preincubated with chemoattractants and then reactivated, was shown when the same PMNs were restimulated to migration using the same chemoattractants. This was interpreted as a deactivation of the cells. A cross-deactivation was demonstrated between LPS-CF and casein. The results from the experiments reported show that the Boyden chamber may be used to disciminate directional chemotaxis and migration inhibition. It may also be concluded from the study that the reduced migration activity of PMNs at over-optimal doses of chemoattractants is not due to cytotoxicity, but most probably is caused by a deactivation of the cells.

A purified polypeptide antigen from Staphylococcus simulans CCM 2705 produced one precipitation line by double diffusion in agar with rabbit antiserum against homologous whole bacteria. The purified antigen did not induce antibody production in rabbits. However, when the antigen was complexed with methylated bovine serum albumin, antibodies with specificity against the polypeptide were produced. The antigen did not sensitize normal or tanned erythrocytes for agglutination in antiserum. The polypeptide antigen induced a primary skin reaction and was toxic for mice. It also induced production of MIF as demonstrated by the migration inhibition test. The polypeptide was found to be a leukotaxigen. No difference between C4 normal and C4 deficient serum was noted. C5 was found to be necessary for the induction of chemotaxis.

In order to assess the vascular clinical trial program of iohexol (Omnipaque) in Europe, the results from the first 49 vascular trials are collectively reported. The included iohexol material comprises 1742 patients. In 40 comparative trials, other contrast media like metrizamide (Amipaque), ioxaglate (Hexabrix) and various monomeric ionic media were administered in 1292 patients included in this analysis. No severe or unexpected adverse reactions related to iohexol were encountered. No clinically significant differences in radiographic image quality between the media were documented. The overall tolerability of iohexol was superior to that of monomeric ionic media and seemed to be as good as that of metrizamide.

A double-blind clinical study of analgesic drugs was conducted involving 47 healthy adults requiring removal of 90 bony impacted mandibular third molars. The analgesic effect of paracetamol plus codeine (P + C) 350 + 20 mg was compared to that of acetylsalicylic acid (ASA) 500 mg and placebo. A standardized surgical procedure under local anesthesia was used. Insufficient analgesic effect was noted in 16% of the ASA group and in 69% of the placebo group but in none in the P+C group. On the first postoperative day, patients given P+C suffered less pain compared with those given ASA (P less than 0.01). No relationship could be demonstrated between the type of impaction and intensity of pain. Trismus, however, was found to be associated with difficulty of extirpation. Drowsiness and an increased sleeping tendency were the main side effects found in the P+C group. The incidence of secondary hemorrhage was high in the ASA group, compared with the P+C group a significance of 0.01 less than P less than 0.05 was found on various postoperative days. Registration of swelling revealed less postoperative edema in the P+C group than in the ASA group (0.01less thanPless than0.05). The main conclusion from this study is that the analgesic effect of P+C orally administered after a specific oral surgical procedure is superior to ASA and placebo. P+C also appears to have a more marked antiphologistic effect than ASA.

By chromatographic separation on Sephadex gels a peptide, termed the lipopolysaccharide-induced chemotactic factor (LPS-CF), has been isolated from inflammatory exudate. The exudate was obtained from Teflon chambers implanted subcutaneously in rabbits 3 h after LPS from Bacteroides fragilis ss. fragilis had been injected. Three chemotactic peaks were eluted by fractionation of the exudate on Sephadex G-200 columns; one major peak with molecular weight of approximately 16,000 and two minor peaks with molecular weights of approximately 68,000 and 7,000. Refiltration of the major peak on G-75 showed the same elution profile as that found on G-200 columns. By addition of 8 M urea to the elution fluid only the major and the low molecular weight peaks appeared. The molecular weight of the major chemotactic peak was calculated to 16,000 on Sephadex gels, and also using SDS-polyacrylamide gel electrophoresis and equilibrium centrifugation. The chemotactic factor was quite heat-stable and was also non-dialyzable, and freezing and thawing as well as storage at 4 degrees C for several weeks did not impede its activity. This chemotactic factor is probably identical to the cytotaxic fragment split off from C5 upon interaction with LPS.

The incidence of side-effects produced by meglumine diatrizoate and meglumine-, meglumine-calcium-, and sodium-calcium-magnesium metrizoate, was compared in 800 urographies. Patients older than 60 years seem to have less side-effects than younger patients. The incidence of sensation of warmth seems to be higher in patients who have had previous urographies, compared to those who are examined for the first time. The incidence of this effect is higher for the sodium-calcium-magnesium salt of metrizoate, than for other salts of metrizoate.

The lateral soft tissue profile was recorded in 10 patients with slight to moderate degrees of mandibular prognathism, preoperatively, and 6 weeks after subcondylar sliding osteotomy had been performed. The recording method was mechanical. Only small and insignificant profile changes were found in the submandibular and occlusal plane regions as well as in the ramus region. The only significant change of profile was found in the mandibular body region, probably as a result of firm connection between soft tissue and underlying distally moved bone. The lack of significant profile change in the osteotomy region was in accordance with subjective observations and was probably due to local remodelling and adaptation processes. The facial width was thus found to be unaltered 6 weeks postoperatively.

The atypical Bacteroides fragilis lipopolysaccharide is chemotactic for polymorphonuclear leukocytes. The chemotactic activity is mediated by complement activated through the alternative pathway. This mediator has been isolated. It is a polypeptide with a molecular weight of 16,000 and is most likely the complement component C5a.

A review of the initial 76 clinical trials with Amipaque in vascular radiology and in examinations of the body cavities, mostly performed in the Scandinavian countries, is given. The clinical material presented comprises a total of 2,661 Amipaque examinations, 1,784 examinations performed intravascularly and 515 in body cavities. In addition, 362 vascular examinations with Amipaque in children are presented. Generally, no difference in visualization compared to ionic media was found. However, improved visualization was reported in some few angiographic studies and higher contrast density was indicated in the urograms. Compared to ionic media, Amipaque caused considerably less subjective reactions and less hemodynamic effects. A remarkable reduction in post-phlebographic thrombosis following leg phlebography was found with Amipaque. No death related to Amipaque occurred, and few contrast medium reactions have been recorded. Thus, the good tolerability of the non-ionic Amipaque shown in animal studies has also been confirmed clinically outside the subarachnoid space.

The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (51Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.

Wound chambers implanted subcutaneously in rabbits proved suitable for measurements of leukocyte chemotaxis. Injection of bacterial lipopolysaccharide (LPS) in the chambers the sixth day after implantation was followed by a marked increase of polymorphonuclear leukocytes in the wound chamber fluid, the number of which was dependent on the time after application of LPS. Up to a certain amount of LPS, the concentration of leukocytes in the chamber fluid was dose-dependent. The histopathological appearance of the granulation tissue lining the chamber wall one day after the injection of LPS from Veillonella revealed aggregation of blood cells plugging the lumina of small vessels and many eosinophilic leukocytes.

Endotoxic lipopolysaccharides (LPS) isolated from Fusobacterium are similar to those of Salmonella with respect to chemical composition, O-antigenic specificity and endotoxic activity. Bacteroides LPS are highly atypical with respect to the chemical composition, and their endotoxic activity is low. O-Antigenic specificity is present. B. fragilis LPS is chemotactic for polymorphonuclear leukocytes in vitro and in vivo. The chemotactic activity is brought about by activation of the alternative complement pathway.

Preparations of the polymorphonuclear leukocyte (PMN) chemotactic factor isolated from lipopolysaccharide (LPS)-induced inflammatory exudate in rabbits were immunogenic in guinea pigs. Complete fusion of the precipitation lines produced against anti-CF by LPS-CF (molecular weigth 16,000) and material eluted on Sephadex G-200 columns with molecular weights (MW) of 68,000, 16,000 and 7,000 was found. Also, the chemotactically active material with MW of 68,000 and 7,000 eluted on G-75 columns after fractionation of the fraction of MW 16,000 from the G-200 eluate was antigenically identical to LPS-CF in double diffusion in agar. Normal rabbit serum (NRS) incubated with LPS, LPS-induced wound chamber exudate and NRS alone gave lines of precipitation against the anti-LPS-CF sera identical to that of LPS-CF. The capacity of LPS-CF to attract PMNs was significantly higher than that of LPS, and a peak in the number of PMNs in the exudate of wound chambers implanted in rabbits was found 4 h after the local injection of LPS-CF. When injected intraperitoneally in C5 deficient mice, LPS-CF stimulated a PMN migration which was only slightly below that in C5 normal mice. Antisera to LPS-CF inhibited the chemotactic activity of LPS-CF as well as that of LPS-NRS when the supernatants were tested using the Boyden's technique. Also, preincubation of PMNs with LPS-CF suppressed the migration towards a chemotactic gradient of LPS-CF molecules of these PMNs.

Chambers implanted subcutaneously in C5 normal (C5 N) and C5 deficient (C5 D) mice were used to examine the migration of polymorphonuclear leukocytes (PMNs) into the wound chamber fluid in response to injected Bacteroides fragilis lipopolysaccharide (LPS). The difference in PMN migration was highly significant between the two mouse strains, the C5 D mice showing no initial, but a low, delayed migration. The results from the study indicated that chemotaxis plays a major role in the accumulation of PMNs in the acute inflammatory response. Intraperitoneal endotoxin stimulation also showed a significantly lower total number of leukocytes in the exudate from C5 D mice as well as a delayed migration of cells compared to C5 N mice. No leukotactic mediators were elaborated in C5 D serum or exudate upon incubation with LPS when tested in a modified Boyden chamber. However, endotoxin-induced wound chamber fluid in C5 D mice showed an increasing leukotactic activity at the same time as the acute inflammatory response subsided in C5 N mice. Incubation of B. fragilis LPS in C4 deficient (C4 D) guinea pig serum indicated that the LPS was able to activate complement components to generated split products chemotacic for rabbit PMNs via the alternative complement pathway.

The effect on hemostatic parameters of two non-ionic contrast media, iopentol and iohexol in concentrations of 350 mg I/ml, were tested in vitro. The new medium iopentol had similar effects to those of iohexol, both with respect to the intrinsic coagulation system and platelet aggregation. As part of a human pharmacologic study the effects of iopentol on hemostatic parameters were tested in 8 volunteers in vivo. Iopentol induced a slightly decreased coagulability and aggregability in venous blood. It was concluded that the effects were of very little consequence for hemostasis as a whole.

An allotransplantation of a partly developed premolar from a 12-year-old daughter to her mother is reported. The tooth graft was selected by the use of HLA-A, -B, -C and DR typing and the MLC tests. Follow-up over a 3-year period included periodic identically taken radiographs, electric and galvanic pulp tests and tests for cytotoxic antibodies. Almost complete closure of the apex of the tooth has occurred with no sign of root resorption. The transplant has remained vital, and no production of antibodies against the graft has occurred.

Lipopolysaccharides (LPS) isolated from oral strains of Veillonella, Fusobacterium and Bacteroides stimulated the release of 45Ca from prelabeled fetal rat bones in culture. There was a typical dose-response relationship between the quantities of released 45Ca and LPS used for stimulation. Bacteroides-LPS proved to be the less active inducer of 45Ca release. LPS had no stimulating effect on the release of 45Ca from devitalized bone. The stimulated 45Ca release was paralleled by an increase in the culture medium of hydroxyproline and lactate. This, together with the findings of numerous osteoclasts in stained histological specimens of the experimental bones, indicates that LPS stimulated the osteoclasts to bone resorption. Heparin, which did not directly induce 45Ca release, potentiated the bone resorption stimulating capability of LPS. The lipid A and the polysaccharide portion of Fusobacterium LPS also stimulated bone resorption and, remarkably, the polysaccharide portion showed the greatest activity. This may explain the mode of action of LPS lacking a typical lipid A. It is suggested that stimulation of osteoclasts by LPS may result from activation of complement components by lipid A or its polysaccharide portion.

Phenol-water extracted lipopolysaccharides (LPS) from Veillonella, Fusobacterium nucleatum, Bacteroides fragilis and Bacteroides melaninogenicus were lethal for mice and 11-days-old chick embryos, pyrogenic in rabbits, and gelated Limulus amoebocyte lysate. Mouse lethality was considerably enhanced by actinomycin-D. In all test systems the endotoxin activity of Veillonella and Fusocbacterium LPS was comparable to that of LPS from Salmonella enteritidis, which was included as a reference endotoxin. The endotoxicity of the Bacteroides LPS was very low. While nanograms of the Veillonella and Fusobacterium LPS killed the chick embryos and gelated the Limulus lysates, microgram amounts of the Bacteroides LPS were needed to give positive reaction in the same test systems. As much as 74 microgram of the most active B. fragilis LPS were required to give a typical biphasic fever response in rabbits. A significant correlation was found between all test results (r = 0.90-0.98, p less than 0.001).

Exudate aspirated from wound chambers implanted subcutaneously on rabbits at different time intervals after local lipopolysaccharide (LPS) injection, showed a peak of chemotactic mediator concentration in vitro about two hours before the peak of polymorphonuclear lekocytes accumulated in vivo was demonstrated. Injection of LPS locally into the wound chambers three days after the first injection of LPS showed a reduced number of PMNs accumulated in the exudate. Antibodies to the LPS preparation were demonstrated in the exudate and serum by indirect haemagglutination of sheep erythrocytes before the second LPS injection. This antibody titre increased up to two weeks after the first LPS injection, and was slightly higher in the serum than in the exudate. Also, a migration inhibition factor (MIF) activity was demonstrated in the exudates formed. This MIF activity of the exudates increased after the second LPS injection. The increased titre of specific antibody may indicate an accelerated clearance of LPS, and the MIF activity may indicate a reduced response of PMNs to chemotactic mediators. However, the involvement of other biological mechanisms contributing to the decreased response, cannot be excluded.

The new non-ionic contrast medium iohexol 350 mg I/ml was compared with the ionic contrast medium metrizoate 350 mg I/ml in a double blind, two-group urographic study performed on 20 patients with stable, impaired renal function. A dose of contrast medium of 500 mg I/kg body weight was given to each patient. Iohexol resulted in significantly fewer subjective adverse reactions than metrizoate. A similar image quality was obtained with the two contrast media. No clinically significant difference existed between the two contrast media with respect to influence on blood pressure, pulse or clinical chemical parameters. A tendency to deterioration of renal function after urography was found in both groups, but no difference of statistical significance existed between the two contrast media with respect to possible nephrotoxicity. Inadequate hydration may have been partly responsible for the nephrotoxic effect of the urographic procedure.