Showing papers by "Queen's University Belfast published in 1993"

A molecular photoionic AND gate based on fluorescent signalling

Abstract: MOLECULES that perform logic operations are prerequisites for molecular information processing and computation1–11. We12,13 and others14–16 have previously reported receptor molecules that can be considered to perform simple logic operations by coupling ionic bonding or more complex molecular-recognition processes with photonic (fluorescence) signals: in these systems, chemical binding (the 'input') results in a change in fluorescence intensity (the 'output') from the receptor. Here we describe a receptor (molecule (1) in Fig. 1) that operates as a logic device with two input channels: the fluorescence signal depends on whether the molecule binds hydrogen ions, sodium ions or both. The input/output characteristics of this molecular device correspond to those of an AND gate.

Elevated consumption of carbon relative to nitrogen in the surface ocean

Abstract: UPTAKE of atmospheric CO2 by the ocean's 'biological pump' is driven by export of carbon from the euphotic zone to deeper waters1,2. As nitrate is a limiting nutrient in large regions of the ocean, measurements of nitrate uptake are often used to estimate the amount of carbon exported in this way3–6. This presupposes knowledge of the molar C: N ratio in the organic material exported from the upper waters, which is usually taken to be 6.6 (the Redfield ratio7,8). Recent studies have suggested, however, that the consumption ratio of C:N may deviate from this value in coastal waters9–11. Here we present time-series from both coastal waters and open-ocean sites which demonstrate that net organic carbon production greatly exceeded that predicted from nitrate consumption and the Redfield C:N ratio. We found a similar discrepancy in sections across broad regions of the North Atlantic during eutrophic periods. Our results suggest that extrapolating from nitrate consumption using the Redfield ratio leads to significant underestimates of organic carbon export from the euphotic zone.

Citizenship and the European Community

Abstract: National or European Citizenship? National Citizenship to European Civil Society The Constitutional Framework of Community Rights Economic and Social Cooperation Class and Citizenship Sex and Citizenship The Equal Protection of Community Laws Political Rights and Political Union

Evidence of persistent measles virus infection in Crohn's disease

Abstract: Transmission electron microscopy was used to examine the microvasculature of perfusion-fixed tissues from Crohn's disease and control patients. Paramyxovirus-like particles, and inclusions consisting of condensations of nucleocapsid, in giant cells and endothelium at foci of vascular injury were identified in all 9 Crohn's disease patients. Tissues from patients with Crohn's disease were also examined by either in situ hybridisation (n = 10) or immunohistochemistry (n = 15), and compared to inflammatory and noninflammatory controls (n = 22). Hybridisation for measles virus N-protein genomic RNA was positive in all cases of Crohn's disease localising to foci of granulomatous vasculitis and lymphoid follicles. Positive immunohistochemical staining for measles virus nucleocapsid protein was positive in 13 of 15 patients with Crohn's disease, localising to foci of granulomatous inflammation. Hybridisation for measles virus RNA was positive in a minority of control intestinal tissues; viral inclusions were not seen ultrastructurally. Immunostaining was negative in control cases of intestinal tuberculosis. These observations suggest that measles virus is capable of causing persistent infection of the intestine and that Crohn's disease may be caused by a granulomatous vasculitis in response to this virus.

Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study

Abstract: This investigation was designed to determine whether low dose radiation to the macular region could influence the natural course of age-related subfoveal neovascularisation. Nineteen patients with subfoveal membranes due to age-related macular degeneration (ARMD) were treated with 10 or 15 Gy of 6 MV photons and seven patients who declined treatment were followed up as controls. Six controls and all treated patients had completed follow up times of at least 12 months. Visual acuity was maintained or improved in 78% and 63% of treated patients at their 6 and 12 month follow up examinations respectively. By contrast visual acuity showed steady deterioration in six of seven controls. Significant neovascular membrane regression, as measured by image analysis, was recorded in 68% and 77% of treated patients at 6 and 12 months post-radiation, whereas the membranes in all seven control patients showed progressive enlargement. This study suggests that low doses of radiation can maintain central vision and induce regression of subfoveal neovascular membranes of ARMD in a significant proportion of patients. We now believe it appropriate to proceed to a prospective randomised study to test this hypothesis further.

Transport studies for the sorption of copper ions by chitosan

Abstract: The ability of chitosan, prepared from waste prawn shell, to sorb copper (II) ions from aqueous solutions has been studied. Equilibrium studies show that chitosan has a maximum sorption capacity for copper ions of about 40mg/g chitosan. The mass transport characteristics have been investigated by monitoring the kinetics in an agitated batch adsorber. An external mass transfer coefficient and an intraparticle diffusion rate parameter have been determined for a number of system variables including agitation, initial copper ion concentration, chitosan mass, chitosan particle size and solution temperature.

Dietary fish oil augments nitric oxide production or release in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Abstract: Decreased release of nitric oxide from damaged endothelium is responsible for the impaired endothelium-dependent vasodilator responses found in animal models of vascular disease. Dietary supplementation with fish oils has been shown to augment endothelium-dependent relaxations, principally by improving the release of nitric oxide from injured endothelium. Using forearm venous occlusion plethysmography we studied vascular responses to 60, 120, 180 and 240 nmol/min of acetylcholine (an endothelium-dependent vasodilator) and 3, 6 and 9 nmol/min of glyceryl trinitrate (an endothelium-independent vasodilator) infused into the brachial artery in 23 patients with Type 2 (non-insulin-dependent) diabetes mellitus. NG monomethyl-L-arginine was employed to inhibit stimulated and basal release of nitric oxide from the endothelium. On completion of the baseline studies patients randomly received either fish oil or matching olive oil capsules in a double-blind crossover fashion for 6 weeks followed by a 6-week washout period and a final 6-week treatment phase. Studies, identical to the initial baseline studies, were performed at the end of the active treatment periods at 6 and 18 weeks. Fish oil supplementation significantly improved forearm blood flow responses to each dose of acetylcholine when compared to the vasodilator responses recorded at baseline and after olive oil administration (p < 0.01). Neither fish oil nor olive oil supplementation produced any significant changes in forearm blood flow to the incremental infusions of glyceryl trinitrate when compared with responses recorded during the baseline studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Helicobacter pylori: comparison of DNA fingerprints provides evidence for intrafamilial infection.

Abstract: Although a high prevalence of antibodies to Helicobacter pylori has been documented within families, culture and DNA typing of strains from infected children and their parents has not been evaluated. This study aimed to analyse H pylori infection within family groups. Endoscopy, gastric biopsy, and H pylori culture were performed on all eight parents of four children who presented with dyspepsia and who had a positive H pylori culture. All biopsy specimens were cultured on Columbia based blood agar under microaerophilic conditions for four days. The DNA from each strain was extracted and electrophoretic patterns were compared after digestion with restriction endonucleases Hae III or Hind III. Ribotyping using a biotinylated cDNA probe prepared from 16S and 23S rRNA of H pylori NCTC 11638 was also used. Seven of the parents were positive for H pylori on urease testing, histology, and on culture. DNA typing showed the same or a similar strain to be present in at least two family members in three of the four family groups. In family 1, the mother, father, and child all had an identical strain; in family 2, father and son had a similar related strain; father and mother had the same strain in family 3; and all strains were unique in family 4. These data provide evidence for either intrafamilial cross infection or a common source of infection within family groups.

Newborn and fetal response to maternal voice

Abstract: The intrauterine environment presents a rich array of sensory stimuli to which the fetus responds. The maternal voice is perhaps the most salient of all auditory stimuli. The following experiments examined the movement response of the fetus and newborn to its mother's voice and a strange female's voice and to voices speaking normally and speaking 'motherese'. Newborns (2-4 days of age) discriminated, as measured by the number of movements exhibited to the presentation of the stimuli, between their mother's voice and a stranger's voice and between normal speech and 'motherese', in both cases the former being preferred. Fetuses, 36 weeks of gestational age, evidenced no ability to discriminate between their mother's and a stranger's voice played to them via a loudspeaker on the abdomen but did discriminate between their mother's voice when played to them by a loudspeaker on the abdomen and the mother's voice produced by her speaking. The results are further evidence of the ability of the fetus to l...

The effect of slurry storage and anaerobic-digestion on survival of pathogenic bacteria

Abstract: The decline in viable numbers of Salmonella typhimurium, Yersinia enterocolitica and Listeria monocytogene in beef cattle slurry is temperature-dependent; they decline more rapidly at 17 degrees C than at 4 degrees C. Mesophilic anaerobic digestion caused an initial rapid decline in the viable numbers of Escherichia coli, Salm. typhimurium, Y. enterocolitica and L. monocytogenes. This was followed by a period in which the viable numbers were not reduced by 90%. The T90 values of E. coli, Salm. typhimurium and Y. enterocolitica ranged from 0.7 to 0.9 d during batch digestion and 1.1 to 2.5 d during semi-continuous digestion. Listeria monocytogenes had a significantly higher mean T90 value during semi-continuous digestion (35.7 d) than batch digestion (12.3 d). Anaerobic digestion had little effect in reducing the viable numbers of Campylobacter jejuni.

The levering laryngoscope

Abstract: This is a report of a modification of the standard Macintosh laryngoscope blade to facilitate tracheal tube placement in cases of difficult visualisation of the larynx. The modification offers the unique advantage of a hinged blade tip, controlled by a lever on the handle of the laryngoscope which allows elevation of the epiglottis while decreasing the overall laryngoscopic elevation or levering movement required. It is an adaptation which can be applied to most laryngoscope blades, does not require any special training in its use and will prove useful for both routine intubations as well as those which may be difficult and associated with an anterior larynx.

Reliability of reported family history of myocardial infarction.

Abstract: OBJECTIVE--To assess the reliability of reported family histories of myocardial infarction. DESIGN--A case-control study in which reported histories of first degree relatives were validated from death certificates, general practitioners9 records, and hospital notes. SETTING--Participants enrolled in the Belfast centre of the World Health Organisation9s study monitoring trends and determinants in cardiovascular disease (MONICA). SUBJECTS--200 men who survived myocardial infarction and 200 age matched controls drawn randomly from the population. MAIN OUTCOME MEASURES--The sensitivity, specificity, positive predictive value, and proportion of overall agreement with validated records of reported family histories of myocardial infarction in first degree relatives; odds ratios for myocardial infarction, given at least one reported relative or at least one verified relative being affected. RESULTS--349 of the 400 probands provided detailed family histories, reporting on 2812 first degree relatives. The overall sensitivity, specificity, and positive predictive value of reported histories were 67.3%, 96.5%, and 70.5% for cases and 68.5%, 97.7%, and 73.8% for controls. The kappa coefficients were modest: 0.65 for cases and 0.68 for controls. The odds ratios for myocardial infarction, given at least one affected relative, were not substantially inflated by recall bias. Some recall bias was evident for the probands9 reports of their siblings9 histories of myocardial infarction, the odds ratio for a reported history being 1.67 (95% confidence interval 1.09 to 2.57) and for the validated history 1.54 (1.01 to 2.37). CONCLUSIONS--Although the relative risk of disease is correctly estimated, the predictive accuracy of a casual family history of myocardial infarction may limit the effectiveness of targeted screening programmes. They may, however, complement other strategies based on genetic testing.

The effects of weather, seed rate and cultivar on lodging and yield in winter wheat

Abstract: Winter wheat cultivars Apollo, Hornet, Longbow and Norman were each sown at 50, 100, 200, 400, 800 and 1600 seeds/m2 in a field experiment conducted in Northern Ireland over the 1989/90 crop year. No growth regulators were applied and the wheat received 178 kgN/ha top-dressing in the spring. Hourly rainfall, windspeed and wind direction data were recorded and lodging was visually assessed from the end of May to harvest. Lodging first occurred in the 1600 seed-rate plots as the ears were emerging in early June and then progressively increased in the 800, 400 and 200 plots during June, July and August. Lodging did not occur suddenly but took several hours, with the stems first lying at an angle before lodging completely. Stem buckling or breakage did not appear to be the principal form of structural failure. The longest strawed cultivar, Longbow, lodged most severely. The shorter-strawed Norman also lodged badly in contrast with Hornet which had a similar straw length. Apollo, which was taller than Norman and Hornet and produced more ears per square metre than the other cultivars, lodged least but tended to lean at c. 30° from the vertical. Lodging occurred during or within 24 h of periods of rainfall which, in many cases, coincided with windspeeds at crop height averaging > 25 km/h and occasionally > 50 km/h. Lodging also occurred following rainfall when the windspeed did not exceed 16 km/h. The grain yield was negatively correlated with the average lodging from ear emergence to harvest, there being a 1 t/ha decline in yield for each 10% increase in average area lodged. The 50 and 100 seed-rate plots yielded 10 t/ha and had little or no lodging. The decline in yield with increased lodging and seed rate was attributed to the effect of lodging rather than to seed rate and was associated with a fall in the number of grains/ear and 1000-grain weight from 56 and 53·5 g at the lowest seed rate to 15 and 42·7 g at the highest, respectively. A comparison of the plants from lodged and unlodged plots of the 1600 and 800 seed rates, and subsequently of the 800 and 400 seed rates, indicated that at the higher seed rate, lodged plots had less fresh weight per unit area, basal internodes with smaller diameters, fewer support roots per stem, and a lower root dry weight per stem.

Coronary risk factors in schoolchildren.

Abstract: Death rates from coronary heart disease (CHD) in Northern Ireland are among the highest in the world. However, no data have been available to test the hypothesis that the high prevalence of CHD is reflected by the risk status of the childhood population. A randomly selected 2% population sample of 1015 children aged 12 and 15 years was studied to obtain baseline information on blood pressure, lipid profile, cigarette smoking, family history, physical activity, cardiorespiratory fitness, and dietary fat intake. Using available criteria thresholds, 15-23% displayed increased blood pressure, 12-25% had unfavourable lipid profiles, and 18-34% were overfat. In 15 year old children, 16-21% admitted being regular smokers, 26-34% displayed poor cardiorespiratory fitness, and 24-29% reported little physical activity in the previous week. Dietary analysis revealed relatively low polyunsaturated to saturated fatty acid ratios and high mean fat intakes, accounting for approximately 40% total daily energy. Despite the exclusion of family history from the analysis, 16% of the older children exhibited three or more risk factors. These results justify major concern about the level of potential coronary risk in Northern Ireland schoolchildren. Broadly based primary prevention strategies aimed at children are essential if future adult CHD mortality is to be reduced.

Peptidases, Peptides, and the Mammalian Blood–Brain Barrier

Abstract: The blood-brain barrier (BBB) helps to maintain a constant internal environment for the brain by regulating the passage of substances between the general circulation and the brain tissue. After considerable research into the location and properties of this barrier (for reviews see, e.g., Davson, 1976; Bradbury, 1984, 1986), it was finally established by electron microscopy that its principal site is the endothelial cell layer of blood capillaries supplying the brain (Reese and Karnovsky, 1967; Brightman and Reese, 1969; Reese et al., 197 1). These cells possess several unique features that serve this purpose; most importantly they have been shown to be joined by tight junctions forming zona occludens around each cell (Brightman and Reese, 1969). In contrast, systemic capillaries often have pores or slits between the endothelial cells through which water and solutes can pass freely by nonspecific, passive processes such as diffusion. Cerebral capillaries contain few, if any, such pores (Patlak and Paulson, 198 1). This continuous physical barrier prevents nonspecific intercellular transport, and pinocytosis is also severely limited (Reese and Karnovsky, 1967). Intracellular or transcellular transport, i.e., directly through the endothelial cell membrane, is the principal route into and out of the CNS, though the choroid plexuses are also involved in the transport of solutes from brain to CSF, and vice versa. As a result the BBB exhibits a low permeability to hydrophilic substances such as small ions and polar nonelectrolytes that do not have specific transport mechanisms. Hydrophobic substances, because of their high lipid solubility, can generally diffuse freely across the barrier. Other types of cells including pericytes, astroglia, and smooth muscle cells are closely associated with the cerebral microvasculature. Perhaps the most important of these, and certainly the most extensively studied, are the astroglial cells. Astrocytic processes completely engulf cerebral microvessels so that the membranes of the astrocyte and the capillary endothelial cell are closely apposed, separated only by a basement membrane and a thin layer of interstitial substance (Dempsey and Wislocki, 1955). Although astroglia probably have no actual physical role in the functioning of the BBB, Davson and Oldendorf (1967) have speculated that they might influence the structural and functional characteristics of the cerebral endothelium (see, e.g., Stewart and Wiley, 1981; Janzer and Raff, 1987). The intimate association of astroglia and the capillaries has important implications for experimental work on the BBB because preparations of brain microvessels may contain astrocytic end-feet still attached, which may lead to erroneous conclusions about the exact cellular localization of BBB-associated substances. For example, the surfaces of isolated intact microvessels have been shown to stain for the astrocytic marker, glial fibrillary acidic protein (GFAP) (White et al., 198 I), presumably because glial filaments remain trapped within astrocyte end-feet that have remained associated with the vessels. However, our own work with bovine microvessels suggests that GFAP may not always give an accurate indication of such contamination. Although a 40-fold enrichment of y-glutamyl transpeptidase (a marker enzyme for brain capillaries) is routinely achieved in these preparations, and no more than 4% of the total cortical glutamine synthetase activity (a glial marker) remains, the intensity of staining of GFAP on western blots of microvessel protein was found to be somewhat greater than that obtained from an equal amount of whole cerebral cortical protein (Brownlees and Williams, unpublished observations). This sug-

Nursing research conventions : objectivity or obfuscation ?

Abstract: This paper is a critique of naive realism, the philosophy which animates much nursing research, and which leads researchers to assume that the attainment of objective knowledge is possible The nature of naive realism, and its relationship to objectivity, is discussed Central to this outlook is the belief that the values and interests of the researcher can and should be divorced from the prosecution of research This is reflected in the literary convention of referring to the researcher in the third person Contrary to this position, I argue that the interpretations, values and interests of the researcher are central to the research process Moreover, nursing research may be affected by the interests of managers, educationalists, and those who wish to see nursing attain professional status Nursing researchers should accept that they are part of the social situations which they study They should therefore become reflexive in their outlook This entails recognizing and attempting to understand the effects of the researcher, rather than trying to eliminate or ignore them

Chronic constipation in long stay elderly patients: a comparison of lactulose and a senna-fibre combination

Abstract: OBJECTIVES--To compare the efficacy and cost effectiveness of a senna-fibre combination and lactulose in treating constipation in long stay elderly patients. DESIGN--Randomised, double blind, cross over study. SETTING--Four hospitals in Northern Ireland, one hospital in England, and two nursing homes in England. SUBJECTS--77 elderly patients with a history of chronic constipation in long term hospital or nursing home care. INTERVENTION--A senna-fibre combination (10 ml daily) or lactulose (15 ml twice daily) with matching placebo for two 14 day periods, with 3-5 days before and between treatments. MAIN OUTCOME MEASURES--Stool frequency, stool consistency, and ease of evacuation; deviation from recommended dose; daily dose and cost per stool; adverse effects. RESULTS--Mean daily bowel frequency was greater with the senna-fibre combination (0.8, 95% confidence interval 0.7 to 0.9) than lactulose (0.6, 0.5 to 0.7; t = 3.51 p < or = 0.001). Scores for stool consistency and ease of evacuation were significantly higher for the senna-fibre combination than for lactulose. The recommended dose was exceeded more frequently with lactulose than the senna-fibre combination (chi 2 = 8.38, p or = 0.01). As an index of the standard daily dose, the dose per stool was 1.52 for lactulose and 0.97 for the senna-fibre combination, at a cost per stool of 39.7p for lactulose and 10.3p for senna-fibre. Adverse effects were no different for the two treatments. CONCLUSIONS--Both treatments were effective and well tolerated for chronic constipation in long stay elderly patients. The senna-fibre combination was significantly more effective than lactulose at a lower cost.

Tumours of the Spermatic Cord and Paratesticular Tissue. A Clinicopathological Study

Abstract: A total of 85 patients with paratesticular tumours were diagnosed over a period of 36 years at this hospital; 66 patients (78%) had benign tumours, usually either an adenomatoid tumour or a lipoma. Of the remaining 19 malignant cases, 10 were primary neoplasms and 9 were metastases. A rare mucin-secreting epididymal adenocarcinoma was the only primary malignant epithelial tumour, the others being of mesenchymal origin. In 4/9 metastatic cases the initial presentation of a paratesticular swelling led to the discovery of the occult primary neoplasm following histological examination. Clinical features of a painful or painless mass, with or without an accompanying hydrocele, do not help to distinguish a benign from a malignant lesion. The prognosis of malignant tumours of mesenchymal origin depends mainly on the histological grade. Surgical resection remains the mainstay of treatment and adjuvant therapy significantly improves the chances of survival only in young patients with paratesticular rhabdomyosarcomas. Older patients with high grade tumours usually succumb to their disease despite chemotherapy and/or radiotherapy.

Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (org 9426) during isoflurane anaesthesia in patients with and without renal failure

Abstract: We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg−1 in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPL C. Onset time for maximum block, duration of clinical relaxation (T125) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kg−1 min−1 and 3.7(1.4) ml kg−1 min−1 respectively) and the mean residence times (97.1 (48.7) min and 58.3(9.6) min) (P

Survival of pathogenic bacteria during mesophilic anaerobic digestion of animal waste

Abstract: The survival of pathogenic bacteria was investigated during the operation of a full-scale anaerobic digester which was fed daily and operated at 28 degrees C. The digester had a mean hydraulic retention time of 24 d. The viable numbers of Escherichia coli, Salmonella typhimurium, Yersinia enterocolitica, Listeria monocytogenes and Campylobacter jejuni were reduced during mesophilic anaerobic digestion. Escherichia coli had the smallest mean viable numbers at each stage of the digestion process. Its mean T90 value was 76.9 d. Yersinia enterocolitica was the least resistant to the anaerobic digester environment; its mean T90 value was 18.2 d. Campylobacter jejuni was the most resistant bacterium; its mean T90 value was 438.6 d. Regression analysis showed that there were no direct relationships between the slurry input and performance of the digester and the decline of pathogen numbers during the 140 d experimental period.

Development of a random amplification of polymorphic DNA typing method for Listeria monocytogenes.

Abstract: The 10-mer primer OPM-01 (5'-GTT GGT GGC T-3') was used to generate random amplification of polymorphic DNA (RAPD) profiles by polymerase chain reaction for 91 strains of Listeria monocytogenes from raw milk, food, and veterinary, medical, and food-environmental sources. The profiles obtained contained 1 to 10 bands within the molecular size range of 0.5 to 5.0 kbp. Reproducibility was enhanced by annealing at low stringency and introducing a 1-min ramp time between annealing and extension temperatures. Thirty-three RAPD profiles were observed, with specific profiles being observed for strains from each source. RAPD profiles allowed discrimination within serogroups, although five RAPD profiles which were not confined to one serotype were found. Within food strains, one RAPD profile was more common than others, suggesting this to be a common type among strains from this source.

Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial).

Abstract: A randomised trial was conducted in 82 centres using the porcine surfactant extract, Curosurf, to compare two regimens of multiple doses to treat infants with respiratory distress syndrome and arterial to alveolar oxygen tension ratio 40% did attain significance; 48.4% of babies in the low dose group needed > 40% oxygen after three days compared with 42.6% of those in the high dose group. The total amount of surfactant administered in the low dose regimen (mean 242 mg phospholipid/kg) was probably enough to replace the entire pulmonary surfactant pool. Adopting the low dose regimen would lead to considerable cost savings, with no clinically significant loss in efficacy.

Pathogenesis of Multiple Sclerosis—The Immune Diathesis and the Role of Viruses

Abstract: Although the evidence of involvement of viruses in the pathogenesis of MS is largely circumstantial, the pattern of association is constant, with little evidence for direct viral infection of the CNS but with a consistent immune response to several common viruses. In parallel with these studies, epidemiological studies, while indicating genetic predisposition, favor an environmental pathogenetic factor and experimental models indicate that viruses can induce demyelination either by oligodendrolysis or by a variety of immune mechanisms with or without persistence in the CNS. In elucidating the pathogenesis of MS, the challenge is to understand the basis of the immune abnormalities, with intrathecal synthesis of viral antibodies and abnormal immune responses to some viruses, and to relate these to the MRI abnormalities which indicate periodic BBB breakdown. There is strong evidence that the breakdown is associated with inflammation. and that cytokines, particularly TNF, may play a role in demyelination. In conclusion, therefore, several factors are probably key in our understanding of MS. These include: (i) the genetic control of the immune system and its interaction with viral antigen; (ii) related effects on cerebral endothelium including cytokine and adhesion molecule regulation; and (iii) associated glial and axonal responses. Such an approach to the pathogenesis of MS may not identify a specific cause. It may, however, indicate that a pathological cascade can be "triggered" by several common viral infections and that therapy can be used to intervene at several points in the pathological response.