Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis.

BACKGROUND AND PURPOSE: Clinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. METHODS: Demographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. RESULTS: The acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 ± 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. CONCLUSION: In autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.

Time to relief of episodic symptoms of gastro-oesophageal reflux disease. A crossover comparison of single doses of the effervescent and standard formulations of ranitidine.

BACKGROUND: The length of time until symptom relief and the consistency of response are important aspects of the management of episodes of gastro-oesophageal reflux disease (GORD). METHODS: In an open, randomized, crossover study 98 patients treated 3 episodes of GORD with ranitidine effervescent formulation and 3 with ranitidine standard formulation. The patients filled in a diary card during the 1st h after each study medication. Satisfaction with the formulations and the formulation of choice were determined at the end of the study. RESULTS: A higher percentage of episodes with acceptable symptom relief (82.4% versus 73.1% P=0.024) and a shorter time to acceptable symptom relief (27 min versus 36 min; P < 0.001) were achieved with the effervescent formulation. Sixty-five per cent preferred the effervescent formulation (P < 0.01). CONCLUSIONS: An increased consistency of response and a more rapid symptom relief were achieved with treatment with the ranitidine effervescent formulation, indicating it may be more appropriate for on-demand treatment in patients with episodes of GORD.

Pharmacokinetics and bioavailability of omeprazole after single and repeated oral administration in healthy subjects.

1. Ten healthy subjects were given 20 mg omeprazole EC (enteric coated) granules once daily for 8 days. An i.v. tracer dose of [14C]-omeprazole was given simultaneously with the first and last oral doses and blood sampling was performed thereafter. In order to study the extent of absorption at minimal acid exposure, a single dose of 20 mg omeprazole was also given as a buffered solution, before and after the treatment with EC granules. 2. Kinetic parameters of omeprazole after the i.v. tracer dose were unchanged on repeated dosing while AUC increased by approximately 40% for the solution and 60% for the EC granules. 3. The increased AUC is caused by an increased systemic availability, which may be explained by a decreased first-pass elimination during repeated treatment and/or by a reduced degradation of omeprazole in the stomach secondary to the profound decrease in intragastric acidity caused by the drug. 4. The implication of these findings is that the antisecretory effect of therapeutic doses of omeprazole must be studied during repeated administration and not judged from studies using single doses only.

Effect of omeprazole and cimetidine on plasma diazepam levels.

The effects of steady state dosing with omeprazole and cimetidine on plasma diazepam levels have been studied in 12 healthy males. Single doses of diazepam (0.1 mg.kg-1 i.v.) were administered after one week of treatment with omeprazole 20 mg once daily, cimetidine 400 mg b.d. or placebo, and the treatment was continued for a further 5 days. Blood was collected for 120 h after the dose of diazepam for the measurement of diazepam and its major metabolite desmethyl diazepam. The mean clearance of diazepam was decreased by 27% and 38% and its half-life was increased by 36% and 39% after omeprazole and cimetidine, respectively. Neither drug had any apparent effect on the volume of distribution of diazepam. Desmethyldiazepam appeared more slowly after both omeprazole and cimetidine. It is concluded that the decrease in diazepam clearance was associated with inhibition of hepatic metabolism both by omeprazole and cimetidine. However, since diazepam has a wide therapeutic range, it is unlikely that concomitant treatment with therapeutically recommended doses of either omeprazole or cimetidine will result in a clinically significant interaction with diazepam.

A study of the relationship between social network, perceived ill health and utilization of emergency care. A case-control study.

Several studies have shown that persons who repeatedly turn to somatic emergency departments, besides having ailments also often have social and psychological problems. It has also been shown that this group of patients differs from the general population and can be considered a psycho-socially exposed group. In the present study a group of recurrent users (4 + yearly visits) was compared to a group of first-time visitors to the general emergency department of a middlesized metropolitan hospital. Both patient groups were asked to complete a questionnaire that contained 45 items, covering socio-demographic and social network variables, social and personal problems, perceived state of health and contacts with other care-giving institutions. The results showed that the first-time visitors were significantly younger than the recurrent users, and more often actively employed. Only 2 percent of the first-time visitors developed a behaviour of recurrent use of the ED. The recurrent users were well-known at the hospital, not only in the emergency department but also at the out-patient clinics and the social work department. The multiple Odds ratio showed that alcohol abuse, lack of close friend, general health problems and deteriorating health were important risk factors for recurrent ED use. It is suggested that an individual treatment plan including medical, social and societal measures could be one alternative in an attempt to more efficiently treat these patients.

An ecological study of the relationship between risk indicators for social disintegration and use of a somatic emergency department.

During the last decade a number of studies have been dedicated to the relationship between social support and ill health. In this study the relationship between risk indicators for social disintegration in defined geographical areas and the utilization of a hospital somatic Emergency Department (ED) by the inhabitants of these areas was analyzed. Six socio-demographic variables were used as risk indicators for social disintegration. To measure illness behaviour a register of 57,481 ED visits, made by 34,915 individuals, to the General Adult ED at St Göran's Hospital was utilized. The proportions of immigrants, of adult unemployed and of persons moving into the areas were significantly related to the illness behaviour of seeking care at the ED. The results also showed a significant correlation between the sum of the six risk indicators and use of ED services for three of the four studied subgroups.

Heavy users of an emergency department--a two year follow-up study.

Persons who repeatedly turn to emergency departments (ED) for medical services often have an unfavourable social situation. Very little is known about how their situation and utilization of ED services change with time. In the present study, 232 persons who had made 4+ visits to an ED during the previous year were followed for two years. In the first year 31% and in the second 19% of the original group remained heavy users of the ED. Patients diagnosed as having bronchial asthma remained heavy ED users to a greater extent than others. The mortality in the whole group was high, the standardized mortality rate (SMR) was 590% for the men and 740% for the women during the first follow-up year and 380% respectively 350% during the second. A sub-sample of the patients was interviewed both in the beginning and at the end of the study period with regard to psycho-social factors. The follow-up analysis showed that number of previous visits, contact with psychiatric care, living alone and perceived loneliness were predictive factors for continued ED use. Twenty-two percent of the variation in ED use could be accounted for by changes in the social network over time. The present study supports the hypothesis that the quality of the social network is related to the use of medical services, here expressed in ED use. The findings raise the question of how to handle the variety of psycho-social problems found among these ED users.

Effects of omeprazole in duodenal ulcer patients.

The efficacy of and tolerance to omeprazole, 40 mg/day, was studied in an open-label study in 18 patients with endoscopically verified duodenal ulcers. The effects of the drug on the oxyntic mucosa and pentagastrin-stimulated acid secretion during and after treatment were also studied. Fifteen patients completed the final endoscopy. The ulcers were healed in all after 4 weeks' treatment. Both basal and peak acid output were significantly reduced during omeprazole treatment, whereas 4 weeks after the cessation of treatment neither basal nor peak acid output differed from the pretreatment levels. Fasting serum gastrin levels rose by 56% during treatment but had returned to pretreatment values when tested again 4 weeks after the end of the treatment period. Histological examination of the biopsy specimens taken before and after treatment showed that omeprazole had no significant effect on the volume densities of either parietal or endocrine cells. We conclude that omeprazole is of value in the treatment of duodenal ulcer and that the effects of the drug on acid output and serum gastrin levels are fully reversible.

Heavy users of an emergency department: psycho-social and medical characteristics, other health care contacts and the effect of a hospital social worker intervention.

A small proportion of the patients coming to emergency departments of general hospitals account for a substantial share of the department's resources by making repeated visits. Repeater behaviour is a complex product of many, sometimes concurrent factors. This study has focused on the medical and psycho-social factors. A group of patients with repeated visits to an emergency department of a middle-sized Stockholm hospital was studied in 1980. The repeater group had a heavier load of psycho-social problems than the source population. The repeater behaviour profile included: feeling of loneliness, living alone, contacts with social agency, disability pension, high sick absenteeism from work and alcoholism. The repeater group had numerous contacts with health-care providers outside the emergency department. Some of the repeaters needed and received help by a social hospital worker. Of those that received such help 80% significantly decreased their emergency department visiting rate.