A population-based study comparing multiple sclerosis clinic users and non-users in British Columbia, Canada.

BACKGROUND AND PURPOSE: Much clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada. METHODS: This was a retrospective record-linkage cohort study using prospectively collected data from the British Columbia Multiple Sclerosis database and province-wide health administrative databases. RESULTS: There were 2841 incident MS cases between 1996 and 2004 including 1648 (58%) that had registered at an MS clinic ('clinic cases') and 1193 (42%) that had not ('non-clinic cases'). Gender and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently and had a higher burden of comorbidity than clinic cases. Only 1% of the non-clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases. CONCLUSIONS: Our findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population-based health administrative data offers the opportunity to gain a broader understanding of MS.

Radiated power and soft x-ray diagnostics in the SMART tokamak.

A multi-energy soft x-ray diagnostic is planned to operate in the small aspect ratio tokamak (SMART), consisting of five cameras: one for core measurements, two for edge, and two for divertors. Each camera is equipped with four absolute extreme ultra-violet diodes, with three of them filtered by Ti and Al foils for C and O line emissions, respectively, and Be foils for temperature measurements. In addition, two spectrometers will be installed with a vertical line of sight for impurity control. This study introduces a synthetic model designed to characterize radiated power and soft x-ray emissions. The developed code extracts the radiated power and Zeff values by leveraging distributions of electron density, temperatures, and impurity concentrations. The investigation is centered on the predicted scenarios of SMART's first phase of operation (Ip = 100 kA; Bt = 0.1 T), employing a double-null configuration with positive and negative triangularity. The anticipated impurities encompass C (1%) and Fe (0.01%) from the vessel, as well as O and N (0.1%) from air and water. For simplicity, the distribution is assumed to be homogeneous within the plasma, considering different mixtures with Zeff values ranging between 1 and 2. Finally, the model estimates signal strength for the diagnostic design, proving its feasibility.

Comorbidity is associated with pain-related activity limitations in multiple sclerosis.

BACKGROUND: Comorbidities are common in multiple sclerosis (MS). The high prevalence of pain in MS is well-established but the influence of comorbidities on pain, specifically, pain-related interference in activity is not. OBJECTIVE: To examine the relationship between comorbidity and pain in MS. METHODS: We recruited 949 consecutive patients with definite MS from four Canadian centres. Participants completed the Health Utilities Index (HUI-Mark III) and a validated comorbidity questionnaire at 3 visits over 2 years. The HUI's pain scale was dichotomized into two groups: those with/without pain that disrupts normal activities. We used logistic regression to assess the association of pain with each comorbidity individually at baseline and over time. RESULTS: The incidence of disruptive pain over two years was 31.1 per 100 persons. Fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, migraine, chronic lung disease, depression, anxiety, hypertension, and hypercholesterolemia were associated with disruptive pain (p<0.006). Individual-level effects on the presence of worsening pain were seen for chronic obstructive pulmonary disease (odds ratio [OR]: 1.50 95% CI: 1.08-2.09), anxiety (OR: 1.49 95% CI: 1.07-2.08), and autoimmune thyroid disease (OR: 1.40 95% CI: 1.00-1.97). CONCLUSION: Comorbidity is associated with pain in persons with MS. Closer examination of these associations may provide guidance for better management of this disabling symptom in MS.

Intraperitoneal immunization against necrobacillosis in experimental animals.

Experiments employing recently developed mouse models indicated that intraperitoneal immunization with the cytoplasm (intracellular fraction) of Fusobacterium necrophorum protected the animals from a lethal challenge of the pathogen. The critical immunization schedule needed to achieve complete protection involved six weekly intraperitoneal doses of the intracellular antigen. Livers of immunized mice were cleared of infecting fusobacterial within 24 hours whereas those of nonimmunized mice harboured increasing numbers of hte bacteria. Sera from both groups did not protect recipient mice form developing liver abscesses after challenge. Sheep immunized intraperitoneally with 20 mg of cytoplasmic protein given in three doseases were protected against the development of abscesses induced by F. necrophorum.

The incidence and significance of clostridia isolated from ready-to-eat meats and rendered products.

Approximately 26% of rendered and 10% of ready-to-eat products contained species of the genus Clostridium. Eleven species of clostridia were isolated from a total of 524 products tested. Some products harboured more than one species.C. sporogenes, one of the most heat resistant organisms, was the most common type isolated.C. sordellii produced a transient illness in guinea pigs while all other species were innocuous.

Pathogenic microorganisms in soil: an old problem in a new perspective.

Early investigations on the survival of pathogenic bacteria in soil have been directed mainly to changes in the numbers of viable populations. More reliable techniques to assess the physiological, biochemical and pathogenic capabilities of such organisms are necessary to gain a better understanding of the nature of the diseases they cause and ultimately of the means to control them.

Hepatic lesions and bacterial changes in mice during infection of Fusobacterium necrophorum.

Liver abscesses were induced in male albino mice within 1 week after intraperitoneal inoculation of viable Fusobacterium necrophorum LA19 culture. Fusobacteremia was transitory and reached a peak 2 h after inoculation then sharply declined until its disappearance 24 h post inoculation. By contrast, the number of fusobacteria in the liver increased rapidly during the first 4 h post inoculation and continued to do so less rapidly until the last sampling time (48 h post inoculation). There were small or large areas of necrosis, usually surrounded by inflammatory cells, small focal accumulations of lymphocytes, plasma cells, and macrophages in areas of parenchyma with no degenerations, generalized proliferation of Kupffer cells, and a few accumulations of fibrin and leukocytes on the surface. Ultrathin sections of infected liver tissues reveled both intact and partially degraded F. necrophorum cells enclosed in phagocytic and digestive vacuoles of mononuclear cells, The results indicate that macrophages play a key role in the pathogenesis of liver abscesses.

A stable L-form of Haemophilus pleuropneumoniae.

A stable L-form of Haemophilus pleuropneumoniae (Shope) was isolated from primary pig kidney cell tissue cultures which had been inoculated 28 days previously with glycine induced spheroplasts of this organism.H. pleuropneumoniae was definitely cytopathic in primary pig kidney cell cultures, producing cell rounding, cytoplasmic vacuolation and nuclear enlargement with peripheral condensation of nuclear DNA. By contrast, the effect of spheroplasts was much less distinct, producing only loss of cytoplasmic granularity coincident with apparent loss of some cytoplasmic RNA, and slight nuclear enlargement. Both the organism and its L-form were shown to be related by cultural methods, antibiotic sensitivity tests, immunofluorescence and immunodiffusion. The L-form remained stable after 90 serial passages on agar and 45 in broth, each medium being capable of supporting the growth of both forms of the organism.

Application of immunofluorescence to studies on the ecology of Sphaerophorus necrophorus.

Sphaerophorus necrophorus (bovine liver abscess isolates) antiserum was fractionated and labeled with fluorescein isothiocyanate. The fluorescent-antibody (FA) conjugate proved to be species-specific and facilitated the detection of S. necrophorus cells in liver abscesses, viscera, and ruminal contents of cattle. Brightly fluorescing S. necrophorus cells were observed in experimentally inoculated soil incubated anaerobically at 37 and 4 C for 8 and 10 months, respectively. When incubated under moist conditions (80% water holding capacity) at 37 C, the test organism survived in both sterile and unsterile soil for as long as 8 weeks. Results strongly support the feasibility of using FA techniques concurrent with cultural methods for rapid detection of S. necrophorus infections.

Characterization of endotoxin from Fusobacterium necrophorun.

Endotoxic lipopolysachharide (LPS) was obtained from phenol-water extraction of cell walls prepared from mass-cultivated Fusobacterium necrophorum. The LPS was relatively free of nucleic acids and low in protein, and constituted about 4% of the cell walls. Upon acid hydrolysis, some of the components detected were hexosamines (7.0%), neutral and reducing sugars (50.5%), heptose (6.4%), 2-keto-3-deoxyoctonate (0.8%), lipid A (21.0%), and phosphorus (1.7%). Under electron microscopy the LPS appeared mainly as ribbon-like trilaminar structures, and upon chemical treatment it displayed a behavior resembling that reported in certain enterobacterial LPS. The LPS was lethal to mice, 11-day-old chicken embryos, and rabbits. Endotoxicity in mice was enhanced at least 1,380-fold by the addition of 12.5 mug of actinomycin D. Induced tolerance to lethal effect of the endotoxin and rapidly acquired resistance to infection by F. necrophrum viable cells were also demonstrated in mice. The endotoxin produced both localized and generalized Shwartzman reactions as well as biphasic pyrogenic responses in rabbits. These results firmly establish the presence of a classical endotoxin in F. necrophorum, thus providing strong support to our recent suggestion that cell wall-associated components may contribute significantly to the pathogenicity of F. necrophorum.

Biological characterization of Fusobacterium necrophorum. Cell fractions in preparation for toxin and immunization studies.

Fusobacterium necrophorum isolated from bovine liver abscesses was grown in bulk at 37 C for 24 h under a strict anaerobic atmosphere. Harvested washed cells were disrupted ultrasonically and fractionated by differential centrifugation into the intracellular (cytoplasm) and cell wall fractions. Both intact cells and cell fractions induced generalized cytopathic effect on primary pig kidney cultures and caused a variety of signs of illness and/or death of intraperitoneally injected mice. The intact cells, disrupted cells, and cell walls produced necrotic lesions and erythema on intradermally injected guinea pigs and rabbits, whereas the cytoplasm mainly erythema. By contrast, the used culture medium (culture filtrate) of F. necrophorum did not show any detectable toxicity. The toxic component of the cytoplasm appears to be associated with nondialyzable, hemolytic, high-molecular-weight proteins and its toxicity is reduced by trypsin and pronase. Heating at 60 C for 10 min decreased markedly its erythemal and cytotoxic ability, wheras the toxicity of the cell walls appeared to be only slightly affected even when heated at 100 C for 1 h. These results suggest that at leasttwo distinct cell-bound toxic factors are present in F. necrophorum cells.

Glasser's disease of swine produced by the intracheal inoculation of haemophilus suis.

The intracheal inoculation of pigs with Haemophilus suis led to the production of Glasser's disease at every attempt without significant pulmonary involvement. Isolation of this organism from the experimental animals was possible only in the acute phase of the disease. The indirect fluorescent antibody technique when applied to frozen sections of tissues obtained from the experimentally infected pigs at autopsy, revealed a few rod forms but mostly "round bodies" of H. suis in animals from which the organism was isolated, and "round bodies" only in the pigs from which the organism was not isolated. Attention is drawn to the similarities between the lesions caused by H. suis and Mycoplasma hyorhinis, and to the confusion which may result therefrom. It is stressed that the laboratory diagnosis of these two diseases is complicated by the fact that both agents may not be isolated on the media commonly used in diagnostic laboratories. Both organisms necessitate the use of special media where the clinical and autopsy results indicate polyserositis and arthritis.

Results of a preliminary trial with Sphaerophorus necrophorus toxoids to control liver abscesses in feedlot cattle.

A preliminary field experiment was undertaken to evaluate the efficacy of alum precipitated toxoids of Sphaerophorus necrophorus prepared from sonicated whole cells and cell fractions to reduce the incidence of bovine abscesses. A total of 108 calves were divided into five groups and treated as follows: I. uninoculated control, II. adjuvant inoculated control, III. 15.5 mg protein of sonicated (fragmented cells) toxoid, IV. 10.5 mg protein of cytoplasmic toxoid. V. 15.5 mg protein of cytoplasmic toxoid. All animals were maintained under similar conditions to those prevailing in feedlots in Alberta. Livers were examined at slaughter. The most promising result was achieved with the injection of 15.5 mg protein of cytoplasmic toxoid. In this treatment group, no scars (healed lesions) were found in the liver and the incidence of liver abscesses was reduced to 10% from the average 35% liver abscesses and scars found in the uninoculated and adjuvant inoculated groups. The toxoid from sonicated whole cells did not reduce liver abscess incidence. These data suggest that the incidence of liver abscesses in cattle fattened in feedlots may be reduced by immunization.