Towards an exposure-dependent model of post-traumatic stress: longitudinal course of post-traumatic stress symptomatology and functional impairment after the 2011 Oslo bombing.

BACKGROUND: Our understanding of the dynamics of post-traumatic stress symptomatology and its link to functional impairment over time is limited. METHOD: Post-traumatic stress symptomatology (Post-traumatic Checklist, PCL) was assessed three times in 1-year increments (T1, T2, T3) following the Oslo bombing of 22 July, 2011, in directly (n = 257) and indirectly exposed (n = 2223) government employees, together with demographics, measures of exposure and work and social adjustment. The dynamics of post-traumatic stress disorder symptom cluster interplay were examined within a structural equation modelling framework using a cross-lagged autoregressive panel model. RESULTS: Intrusions at T1 played a prominent role in predicting all symptom clusters at T2 for the directly exposed group, exhibiting especially strong cross-lagged relationships with avoidance and anxious arousal. For the indirectly exposed group, dysphoric arousal at T1 played the most prominent role in predicting all symptom clusters at T2, exhibiting a strong relationship with emotional numbing. Emotional numbing seemed to be the main driver behind prolonged stress at T3 for both groups. Functional impairment was predominately associated with dysphoric arousal and emotional numbing in both groups. CONCLUSIONS: For directly exposed individuals, memories of the traumatic incident and the following intrusions seem to drive their post-traumatic stress symptomatology. However, as these memories lose their potency over time, a sequela of dysphoric arousal and emotional numbing similar to the one reported by the indirectly exposed individuals seems to be the main driver for prolonged post-traumatic stress and functional impairment. Findings are discussed using contemporary models within an exposure-dependent perspective of post-traumatic stress.

The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial.

Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.

Osteoprotegerin levels predict mortality in patients with symptomatic aortic stenosis.

OBJECTIVES: To examine the prognostic value of osteoprotegerin (OPG) levels in relation to all-cause mortality in patients with symptomatic severe aortic stenosis (AS). DESIGN: We measured plasma OPG levels in 136 patients with symptomatic severe AS and investigated associations with transvalvular gradients, valve area, valve calcification (using ultrasonic backscatter analysis as an estimate) and measures of heart failure. Then, we assessed the prognostic value of elevated plasma OPG in determining all-cause mortality (n = 29) in these patients. RESULTS: Elevated OPG was poorly correlated with the degree of AS but was associated with increased backscatter measurements and impaired cardiac function. Furthermore, OPG was associated with all-cause mortality in patients with symptomatic AS, even after adjustment for conventional risk markers. The strongest association was obtained by using a combination of high levels of both OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP), suggesting that these markers may reflect distinct pathways in the development and progression of AS. CONCLUSION: The level of circulating OPG is significantly associated with all-cause mortality alone and in combination with NT-proBNP in patients with severe symptomatic AS.

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis.

OBJECTIVE: Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. DESIGN AND SUBJECTS: We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. MAIN OUTCOME MEASURES: We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS. RESULTS: We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis. CONCLUSIONS: A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS.

Navigated ultrasound in laparoscopic surgery.

Laparoscopic surgery is performed through small incisions that limit free sight and possibility to palpate organs. Although endoscopes provide an overview of organs inside the body, information beyond the surface of the organs is missing. Ultrasound can provide real-time essential information of inside organs, which is valuable for increased safety and accuracy in guidance of procedures. We have tested the use of 2D and 3D ultrasound combined with 3D CT data in a prototype navigation system. In our laboratory, micro-positioning sensors were integrated into a flexible intraoperative ultrasound probe, making it possible to measure the position and orientation of the real-time 2D ultrasound image as well as to perform freehand 3D ultrasound acquisitions. Furthermore, we also present a setup with the probe optically tracked from the shaft with the flexible part locked in one position. We evaluated the accuracy of the 3D laparoscopic ultrasound solution and obtained average values ranging from 1.6% to 3.6% volume deviation from the phantom specifications. Furthermore, we investigated the use of an electromagnetic tracking in the operating room. The results showed that the operating room setup disturbs the electromagnetic tracking signal by increasing the root mean square (RMS) distance error from 0.3 mm to 2.3 mm in the center of the measurement volume, but the surgical instruments and the ultrasound probe added no further inaccuracies. Tracked surgical tools, such as endoscopes, pointers, and probes, allowed surgeons to interactively control the display of both registered preoperative medical images, as well as intraoperatively acquired 3D ultrasound data, and have potential to increase the safety of guidance of surgical procedures.

Navigation in laparoscopy--prototype research platform for improved image-guided surgery.

The manipulation of the surgical field in laparoscopic surgery, through small incisions with rigid instruments, reduces free sight, dexterity, and tactile feedback. To help overcome some of these drawbacks, we present a prototype research and development platform, CustusX, for navigation in minimally invasive therapy. The system can also be used for planning and follow-up studies. With this platform we can import and display a range of medical images, also real-time data such as ultrasound and X-ray, during surgery. Tracked surgical tools, such as pointers, video laparoscopes, graspers, and various probes, allow surgeons to interactively control the display of medical images during the procedure. This paper introduces navigation technologies and methods for laparoscopic therapy, and presents our software and hardware research platform. Furthermore, we illustrate the use of the system with examples from two pilots performed during laparoscopic therapy. We also present new developments that are currently being integrated into the system for future use in the operating room. Our initial results from pilot studies using this technology with preoperative images and guidance in the retroperitoneum during laparoscopy are promising. Finally, we shortly describe an ongoing multicenter study using this surgical navigation system platform.

Derivation and validation of a simple risk score for predicting 1-year mortality in stroke.

CONTEXT: Numerous models have been presented for the prognosis in acute stroke; however they have been criticized for being difficult to use, and few have been validated in independent samples. OBJECTIVES: To develop simple risk score models for 1-year mortality in acute stroke in patients > 60 years old and validate the models. DESIGN: From a cohort of 2321 consecutive patients > 60 years of age with acute stroke in one hospital, we randomly selected 800 patients for chart review. Among 737 patients with validated acute stroke, we randomly split the sample into (1) a derivation (60%; n = 442) and (2) a validation sample (40%; n=295). We used logistic regression to develop three models with 2-4 covariates and a corresponding risk score from the derivation sample. The models were validated using area under the receiver operating curves. RESULTS: Three risk score models for 1-year mortality after stroke were developed using combinations of age, Canadian Neurological Scale score (CNSscore) (< or = 3.5 = 0, >3.5 = 1), Charlson comorbidity index and stroke type (ischemic = 0, hemorrhagic = 1). Both 2-variable (Age - 60 + (30*CNSscore)), 3-variable (Age - 60 + (30*CNSscore) + 4*Charlson)) and 4-variable (Age - 60 + (25*CNSscore) + (5*Charlson) + (18*Stroke type)) models reliably predicted the outcome with an area under the receiver operating curve ranging 0.71 to 0.72. CONCLUSIONS: Simple models incorporating two to four covariates reliably predicted 1-year mortality. Such models can be used to stratify prognosis in clinical practice, research or intervention trials.

PyPop update--a software pipeline for large-scale multilocus population genomics.

Population genetic statistics from multilocus genotype data inform our understanding of the patterns of genetic variation and their implications for evolutionary studies, generally, and human disease studies in particular. In any given population one can estimate haplotype frequencies, identify deviation from Hardy-Weinberg equilibrium, test for balancing or directional selection, and investigate patterns of linkage disequilibrium. Existing software packages are oriented primarily toward the computation of such statistics on a population-by-population basis, not on comparisons among populations and across different statistics. We developed PyPop (Python for Population Genomics) to facilitate the analyses of population genetic statistics across populations and the relationships among different statistics within and across populations. PyPop is an open-source framework for performing large-scale population genetic analyses on multilocus genotype data. It computes the statistics described above, among others. PyPop deploys a standard Extensible Markup Language (XML) output format and can integrate the results of multiple analyses on various populations that were performed at different times into a common output format that can be read into a spreadsheet. The XML output format allows PyPop to be embedded as part of a larger analysis pipeline. Originally developed to analyze the highly polymorphic genetic data of the human leukocyte antigen region of the human genome, PyPop has applicability to any kind of multilocus genetic data. It is the primary analysis platform for analyzing data collected for the Anthropological component of the 13th and 14th International Histocompatibility Workshops. PyPop has also been successfully used in studies by our group, with collaborators, and in publications by several independent research teams.

The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections.

A multidrug-resistant clonal group (CgA) of Escherichia coli was shown to cause half of all trimethoprim-sulphamethoxazole (TMP-SMZ)-resistant urinary tract infections (UTIs) in a college community between October 1999 and January 2000. This second study was conducted to determine the fate of CgA. Urine E. coli isolates from women with UTI, collected between October 2000 and January 2001, were tested for antibiotic susceptibility, O serogroup, ERIC2 PCR and DNA macrorestriction patterns using pulsed-field gel electrophoresis. The proportion of UTIs caused by CgA declined by 38% (P<0.001) but the prevalence of resistance to TMP-SMZ did not change. Six additional clonal groups were identified and these were responsible for 32% of TMP-SMZ-resistant UTIs. The temporal decline in the proportion of UTIs caused by CgA provides evidence that CgA caused a community outbreak of UTI. The fluctuation and occurrence of other E. coli clonal groups in this community suggest that a proportion of community-acquired UTIs may be caused by E. coli disseminated from one or more point sources.

Genomic characterization of equine interleukin-4 receptor alpha-chain (IL4R).

Three overlapping fragments of the equine interleukin-4 receptor alpha chain gene (IL4R) were cloned and sequenced. The resulting 3553 bp cDNA sequence exhibited homology to human, murine and bovine IL4R. The equine IL4R exhibits many conserved features when compared to other species, including intron-exon boundary positions and amino acid sequence motifs characteristic of type I cytokine receptors. The IL4R gene was localized to horse chromosome ECA13 by synteny mapping on a somatic cell hybrid panel. Evidence for an alternative splice variant of IL4R was found in the genomic sequence and subsequently verified using RT-PCR on equine monocyte RNA. A polymorphism screen of the largest exon, homologous to exon 12 of the human IL4R gene, was performed using DNA from 60 horses of various breeds which yielded 11 coding-region single nucleotide polymorphisms (SNPs), 7 synonymous and 4 non-synonymous. Three of the four non-synonymous SNPs occur at high frequencies and are found very near a conserved tyrosine residue.

Epidermal growth factor receptor - but not histamine receptor - is upregulated in seasonal allergic rhinitis.

BACKGROUND: We were interested in exploring the molecular mechanisms underlying the observed difference in histamine (H) responsiveness between seasonal allergic rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than do NR subjects. In addition, we examined expression of genes involved in regulating the glandular response, including epidermal growth factor (EGF), EGF receptor (EGFR), and mucins (Muc5Ac and Muc5B). METHODS: Fourteen subjects, seven SAR and seven NR, were provoked during pollen season with doubling doses of H (0.125-8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior to provocation, nasal scrapings were obtained and mRNA quantified using two-step real-time PCR. RESULTS: The mean PD50 (concentration of H producing a 50% increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32 mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P = 0.93), and EGFR, 103.5 (P < 0.05). CONCLUSIONS: There were no significant differences in H1R or H2R mRNA levels between SAR and NR subjects in-season, despite observed differences in H reactivity. SAR subjects, however, did show a significant elevation in EGFR expression, consistent with the observation of mucus hypersecretion in allergic rhinitis.

[Mental health among refugees. Connection between symptoms, traumatization and exile]. / Psykisk helse blant flyktninger. Samspill mellom symptomer, traumatisering og eksil.

Traumatization and psychiatric symptoms among 346 refugees admitted to the outpatient unit at the Psychosocial Centre for Refugees from 1992 to 1996 were registered and analysed by means of systematic, clinical interviews. More than 50% reported exposure to physical torture, and more than 50% had also been involved in serious war actions. Most patients had experienced many forms of persecution. Approximately 10% of the patients had employment in their host country and 20-30% attended school or participated in language courses. Almost 40% were neither employed nor engaged in any kind of studies. 50% were diagnosed as having post-traumatic stress disorder. The relationship between demographic background, traumatization and exile situation, and symptoms and social dysfunction is illustrated by case histories.

Mental disorder among refugees and the impact of persecution and exile: some findings from an out-patient population.

BACKGROUND: Refugees have long been considered at risk for mental disorder. We sought to characterise this risk in an out-patient refugee sample by analysing the relationship between psychiatric symptoms and dysfunction, and between symptoms and the socio-demographic background and stressors specific to this refugee sample. METHOD: A consecutive sample of 231 refugee patients referred to the psychiatric out-patient unit at the Psychosocial Centre for Refugees, University of Oslo, was examined with a semi-structured interview guide, Brief Psychiatric Rating Scale (BPRS), Hopkins Symptom Check-List (HSCL-25) and a check-list for post-traumatic symptoms (PTSS-10). Global Assessment of Function (GAF) scores were obtained; and the data were analysed using nine predictor variables. RESULTS: It was found that 46.6% of the patients had a post-traumatic stress disorder according to the criteria for DSM-III-R as the main diagnosis, while the mean GAF score for the patients was 57.3. Analysis of the GAF and BPRS data did not reveal any predictor of psychotic behaviour. However, torture emerged as an important predictor of emotional withdrawal/retardation. Also, age, gender and no employment or education predicted for anxiety/depression, while refugee status and no employment or school predicted for hostility/aggression. CONCLUSIONS: The results confirm earlier findings that refugees constitute a population at risk for mental disorder. Past traumatic stressors and current existence in exile constitute independent risk factors. However, stressors other than those discussed here appear to be important also, particularly with regard to psychotic symptoms.

Endotoxin liberation from Neisseria meningitidis correlates to their ability to induce procoagulant and fibrinolytic factors in human monocytes.

Endotoxin released from different strains of Neisseria meningitidis were studied for their ability to induce procoagulant (tissue factor, TF), fibrinolytic (plasminogen activator, PA) and antifibrinolytic (plasminogen activator inhibitor 2, PAI-2) factors in human monocytes. Two meningococcal strains that liberate endotoxin (E+; 270+ and 840+) and 2 non-liberating (E-; 270- and 840-) strains were used. The endotoxin activity in culture filtrates of these strains was monitored with the Limulus amoebocyte lysate (LAL) test. There was a marked difference between E+ and E- strains in their ability to liberate endotoxin. Suspensions of whole bacteria of all 4 strains induced a significant (14-19-fold) increase in monocyte TF expression when present in concentrations > 10(5) CFU/ml. At lower concentrations (10(4) CFU/ml), E+ strains were clearly more potent stimulators of TF synthesis than E- strains. Culture filtrates of E+ strains were up to 10(4)-fold more potent in inducing TF synthesis than filtrates from E- strains. This marked difference in inducing potency between E+ and E- strains was also observed when monocyte PAI-2 synthesis was examined. The PA expression, on the other hand, was suppressed when monocytes were incubated in the presence of culture filtrates, especially filtrates from the E+ strains. The increased procoagulant and antifibrinolytic activity, together with reduced profibrinolytic activity of monocytes, was closely correlated to the amount of endotoxin measured in the culture filtrates. These changes may contribute substantially to the coagulopathic state seen during systemic meningococcal disease.

Comparing aerobic with nonaerobic forms of exercise in the treatment of clinical depression: a randomized trial.

We compared aerobic with nonaerobic forms of exercise in the treatment of clinical depression. Ninety-nine inpatients, who met the DMS-III-R criteria for major depression, dysthymic disorder, or depressive disorder not otherwise specified (NOS), took part in the study. They were randomly assigned to two different physical training conditions, aerobic and nonaerobic. In both conditions, one hour of training was performed three times a week for a period of 8 weeks. There was a significant increase in maximum oxygen uptake (VO2 max) in the aerobic group; there was no change in the nonaerobic group regarding this variable. Depression scores in both groups were significantly reduced during the study, but there was no significant difference between the groups. The correlation between increase in physical fitness and reduction in depression scores was low. The study indicates that the antidepressive effects associated with exercises are not restricted to aerobic forms of training.

Endotoxin liberation studied by biological and chemical methods. Chemical characterization of six meningococcal lipopolysaccharides.

Release of endotoxin (or lipopolysaccharides, LPS) from four meningococcal strains was studied with a chemical and a biological technique. Two strains were endotoxin-liberating (E+; 270E+ and 840E+) and two had no or low endotoxin release E-; 270E- and 840E-). LPS was quantitated by gas chromatography (GC) of LPS-specific hydroxy fatty acid, in parallel with assay of endotoxin by Limulus Amebocyte Lysate (LAL), in cell suspensions of equal O.D. and in filtered samples. The GC and LAL methods showed a reasonably good agreement in the determination of LPS in filtrates, which had distinctly higher levels (approx. 10-100 times) for the E+ strains than the E- strains, in accordance with earlier LAL studies. This difference was not due to overproduction of LPS in the E+ strains, since all four strains had the same level of LPS (by GC) in cell suspensions of equal O.D. Here the agreement between the GC and LAL methods was substantially less, with lower values by LAL for the two E-strains. The chemical composition of purified LPS was determined by methanolysis and GC for the four strains and for two additional strains 247 and 714 with a high degree of genetic similarity with strains 270E- and 840E-, respectively. Amounts of unphosphorylated L-glycero-D-mannoheptose and 2-keto-3-deoxyoctonic acid were the same in all 6 LPS. Otherwise distinct differences were found between LPS of the 6 strains. LPS of the two E+ strains formed one group with about 2.4 mol of galactose (gal), 1.4 mol of glucose (glc) and 2.8 mol of glucosamine (glcN) in the carbohydrate chain. Another group, LPS of all the E- strains except 270E-, had 1.1 mol of gal, 2.8 mol of glc and 1.3 mol of glcN in the LPS chain. LPS 270E- also had 1.3 mol of glcN but deviated strongly form all other LPS by a complete lack of gal and glc. On the basis of genetic evidence strain 270E- is regarded as a "rough" LPS mutant of strain 247. The atypical chemistry of LPS 270E- may explain an observed hydrophobicity of this LPS, and it may be related to the previously described sulfonamide sensitivity. Whether the chemical difference observed for LPS of the E+ and E- strains is a mere coincidence remains to be elucidated by detailed studies of more strains of known tendency of endotoxin liberation.

Multilocus genotypes of two strains of Neisseria meningitidis and their presumed variants obtained upon subcultivation.

Loss of sulfonamide resistance and endotoxin liberation have been described in two strains of Neisseria meningitidis serogroup B, upon subcultivation every 1 to 2 months over an 18-month period. Subsequently, the two laboratory variants, designated 270E- and 840E-, were also found to differ from the parent strains, 270E+ and 840E+, in serotype, outer membrane protein pattern, and virulence in mice. We report here the multilocus genotypes determined by enzyme electrophoresis, of the four isolates 270E+, 270E-, 840E+, and 840E-, and demonstrate that 270E- and 840E- strains could not have originated from subcultivation of 270E+ and 840E+, respectively, but that a mix-up of strains has occurred.

Endotoxin liberation associated with growth, encapsulation and virulence of Neisseria meningitidis.

Endotoxin liberation, encapsulation and growth was studied in 123 isolates of Neisseria meningitidis. Free endotoxin appeared in culture filtrates during exponential growth. Meningococci with free endotoxin titre greater than or equal to 10(2) (E+) showed a higher mean number of viable bacterial counts (CFU/ml) during growth than isolates with titre less than 10(2) (E-), p less than 0.001. Differences in endotoxin liberation was, however, far more pronounced than what was indicated by growth differences alone. E+ property and increased growth rate was significantly more often found among encapsulated than non-encapsulated meningococci. Within the serogroup B isolates, there tended to be a higher mean number of CFU/ml during growth in E+ than E- meningococci, particularly among carrier isolates studied separately (p = 0.009). Case isolates of B meningococci, which had generally a higher amount of capsular material and a higher proportion of E+ strains, had also higher mean CFU/ml than B carrier isolates. This indicates that the endotoxin liberation and growth may be correlated to presence and amount of capsular polysaccharide. Endotoxin liberation, presence of capsular polysaccharide and growth ability are 3 factors which are likely to coincide in meningococci. This combination of properties may be of importance for the development of meningococcal disease.

Endotoxin release from invasive meningococci related to sulfonamide resistance, serogroup and serotype.

The relationship between endotoxin liberation, sulfonamide resistance, serogroups and serotypes was studied in 28 Neisseria meningitidis strains isolated from patients with meningococcal disease. Sulfonamide resistance was present in 15/28 strains. 22 strains belonged to serogroup B, and 5 to group C; 1 strain was non-groupable. Free endotoxin activity in growing cultures of meningococci with endotoxin titre of greater than or equal to 10(2) was found in 27/28 strains. A high endotoxin activity was present in both sulfonamide-sensitive and -resistant invasive meningococci. A high endotoxin release with titre greater than or equal to 10(3) seemed to be more associated with serogroup C than B, and more to the serotypes 2 and 15/16 than to the non-typable strains.

Endotoxin liberation from Neisseria meningitidis isolated from carriers and clinical cases.

Endotoxin liberation was studied in a blinded material of 121 Neisseria meningitidis isolates; from nasopharynx of 58 carriers and from cerebrospinal fluid or blood of 63 cases with meningococcal disease. Endotoxin activity in culture filtrates was determined by a Limulus lysate test. Meningococci isolated from clinical cases were significantly more frequently endotoxin-liberating (E+) (84.1%) than in carriers (25.9%); p less than 0.001. Serogroupable carrier isolates had a significantly higher frequency of E+ meningococci (61.9%) than non-groupable ones (5.4%); p less than 0.002. Serogroup B case isolates, which generally had a larger amount of capsular polysaccharide than B meningococci from carriers, had a significantly higher proportion of E+ meningococci than group B from carriers; p = 0.007. All 7 serogroup C isolates were E+ (5 cases and 2 carriers). No correlation was found between endotoxin liberation and the serotype: subtype 15:P1.16, tested by a selection of monoclonal antibodies, or between endotoxin liberation and sulfonamide resistance, when carrier and case isolates were studied separately. Meningococci isolated from cases had the following mean endotoxin titres: 320.5 in the meningitis group, 408.2 in the septicaemic group, 462.1 in the septicaemic and meningitis group, and 123.7 in the group with other systemic disease. E+ meningococci were isolated from 5/6 fatal cases. Thus, endotoxin liberation from meningococci is strongly, but not completely associated with establishment of meningococcal disease and with the presence of capsular polysaccharide.