BACKGROUND Our aim was to estimate the completeness-that is, whether all patients were included in the system-and the validity-that is, whether the diagnostic criteria were fulfilled for the patients registered-of the diagnoses of Crohn's disease and ulcerative colitis in a Danish hospital system. METHODS Information in a regional hospital system, in the County of North Jutland, Denmark, was compared with hospital records and information in a pathology system. RESULTS The analysis of the completeness included 143 patients with Crohn's disease and 285 patients with ulcerative colitis. The completeness of the regional hospital system using the pathology system as a reference standard was 94% for both diseases. The analysis of the validity included 281 patients registered as having Crohn's disease and 506 patients registered as having ulcerative colitis. The validity of the two diagnoses was 97% and 90%, respectively. CONCLUSIONS The regional hospital system showed few misclassifications of the diagnoses of Crohn's disease and ulcerative colitis. Thus the nationwide hospital system (based on the regional hospital systems) may provide a unique study base for future research.

We studied the utilization of oral anticoagulants and the degree of completeness and validity of some key research variables from the Danish health service in the county of North Jutland (482 000 inhabitants), studying the records of 12 855 prescriptions of oral anticoagulants during 1991 and 1992. The utilization of oral anticoagulants showed an increase of 16% from 1991 to 1992, when 0.3% of all women and 0.4% of all men were treated during one year. The increase was less than expected based on newly introduced indications for treatment of atrial fibrillation. The following variables were studied: the name (ATC commodity number) and amount of the prescribed drug, the defined daily dose, the personal registration number of the patient, type of prescription (e.g. in writing or by telephone), number of repeat prescriptions, date of prescription issued by the doctor, the registration number of the GP or hospital department (if the prescription is made by a hospital doctor) and date of expedition from the pharmacy. The number of wrong and missing data was less than 1%. The study suggests that Danish prescription information is of such quality that it can be used for pharmacoepidemiological studies.

To evaluate the risk of addiction after prescription of a strong analgesic, we followed 90 patients during the year after they had received a prescription for a strong analgesic for the first time in September 1989 in North Jutland County, Denmark. The study was based on copies of all prescriptions of strong analgesics; these are sent to the National Health Service, which is responsible for the control of the prescribing of strong analgesics. Seven patients were excluded because the data registration was incomplete, while there was valid data on the remaining 83 patients, 12 of whom had cancer. All the cancer patients and 14 other patients died during the follow-up period. Of the remaining 57 patients, seven were still being treated (12.3%; 95 confidence limits: 5.1-23.7%) with strong analgesics. Addiction was not suspected by their general practitioners in any of these seven as the main reason for continued treatment with strong analgesics. We therefore conclude that addiction is rare after a first prescription of strong analgesics.

Jespersen MH, Jensen J, Rasmussen LH, Ejlersen E, M0ller-Petersen J, Sperlitig-Petersen HU. The reference range for complexed a2-macroglobulin in human plasma: development of a new enzyme-linked immunosorbent assay (ELISA) for quantitation of complexed a2-macroglobulin. Scand J Clin Lab Invest 1993; 53: 639-648.Purified α2-macroglobulin was complexed by reaction with methylamine and used to raise monoclonal murine antibodies. A four-step enzyme linked immunosorbent assay (ELISA) was developed to determine the antibody-specificity of the produced monoclonal murine antibodies towards human native and complexed α2-macroglobulin.Two monoclonal antibodies were selected, HI 1 All (specific towards complexed a2-macroglobulin) and 1CG4 (recognizes both forms of the molecule), and purified by affinity chromatography on protein G. The purified antibodies were used to develop a fast three-step ELISA for exact quantitation of complexed and total a2-macroglobulin in human plasma. The intra-assay coefficient of variation (CV) for measurement of complexed a2-macroglobulin is 2.2-9.9%, whereas the inter-assay CV was determined to be 3.7-10.5% and the recovery of the assay is 93-108%. The assay for total a2-macroglobulin has an intra-assay CV of 3.0-15.5%, an interassay CV of 5.1-21.2% and a recovery of 91-116%.Citrated plasma samples from 139 healthy blood donors were examined, resulting in a reference range for complexed a2-macroglobulin of 13.5 31.1 mgl−1 “with a median value of 21.7mgl”. The concentration of total a2-macroglobulin was measured by the same assay using the monoclonal antibodies 1CG4. For total a2-macroglobulin we determined the reference range to be 1.12-3.54g 1_1 with a median value of 2.14g 1_1. Based on these results the reference range for complexed a2-macroglobulin as a percentage of total a2-macroglobulin was calculated to be 0.8-1.9% with a median value of 1.0%.

Meningococcal disease is increasing in incidence in many countries, and effective vaccines for serogroup B strains will not be available for at least 5 to 10 years. In the interim, it is attention to principles of good clinical practice, particularly in the early management of the disease, that have the potential to reduce by half the current case fatality rate of approximately 10%. As discussed in this article, those principles include increased awareness, understanding of the disease and its early symptoms by parents and healthcare professionals, and careful attention to the patient before admission and during the hospital stay.

Based on general practitioners' referral letters and hospital records, we made a retrospective analysis of a cohort of 177 consecutive cases of meningococcal disease that occurred during a period of 10 years in the County of North Jutland, Denmark. The analysis concerned diagnostic problems in general practice, prognosis, pre-hospital antibiotic treatment and its effect on subsequent cultures, and degree of obligatory notification. The referring doctor suspected meningococcal disease/central nervous infection in 123 patients (69.5%). Neck stiffness and petechiae were related to a correct referral diagnosis, in contrast to the occurrence of a non-petechial rash. The presence of disseminated intravascular coagulation was associated with the mortality rate, which was 0.062. The therapeutic recommendations of the Danish Health Authorities were followed in only 25 of the 98 patients who fulfilled the criteria for pre-hospital parenteral antibiotic treatment. Pre-hospital antibiotic treatment was related to negative culture of spinal fluid or blood. Seven of the 177 patients were not notified according to the rules. Difficulties in pre-hospital diagnosis seem not to influence the lethal course of the disease.

Data from the Danish National Health Service records on activities of each of 146 general practices in the county of North Jutland, Denmark, were studied to determine whether the use of proctoscopy influenced the stage at which cancer of the rectum was recognized. Information for all patients in the county who received the diagnosis of cancer of the rectum was obtained from the Danish Cancer Registry. Proctoscopy was performed significantly more often in partnership practices (96%) than in single practices (81%). The frequency with which the test was used varied from 1 to 107 proctoscopies per general practitioner per year. In the 95 patients with cancer of the rectum, no relationship was found between the stage (Dukes') at the time of diagnosis and work-load, size and activity of practice, or use of proctoscopy.

We reviewed the case records of 48 patients aged 60 years and older with a diagnosis of acute bacterial meningitis made during the period 1976-88. Predisposing conditions were present in 26 patients (54%) and concurrent infections in 24 patients (50%). Streptococcus pneumoniae accounted for 41% of all isolates and 56% were Gram-positive organisms. The most common symptoms were fever (79%), meningism (54%) and change in mental status (69%). Sixty-three per cent of the patients survived. Increased fatality was associated with absence of typical symptoms and signs and was presumably due to a delay in diagnosis. Other clinical and biochemical variables and antimicrobial therapy before admission to hospital and the presence of underlying disease were not associated with outcome.

The effect of budesonide, 1, 2, and 4 mg/100 ml in daily enemas, on active distal ulcerative colitis was compared with that of prednisolone disodium phosphate enemas, 25 mg/100 ml, in a multicentre, randomized, group-comparative trial. A total of 146 patients with active disease were treated for 2 weeks. Data from 139 were valid for statistical analyses. Bowel habits, proctoscopy findings, and histologic pictures were evaluated, and plasma cortisol was determined for measurement of influence on the hypothalamic-pituitary-adrenal axis. Clinical symptoms and proctoscopy findings improved within all treatment groups. The improvement of these effect variables tended to be less after treatment with the lowest dose of budesonide, 1 mg/100 ml, than after the other treatments. Plasma cortisol did not change in any of the budesonide groups, whereas a mean reduction of 30% (P = 0.07) was observed after prednisolone. It can be concluded that budesonide enemas of 2 mg/100 ml constitute an attractive alternative to prednisolone enemas for topical treatment of distal ulcerative colitis.

One hundred and seventy-nine consecutive patients referred for upper gastrointestinal endoscopy were investigated for the presence of Helicobacter pylori in the oesophagus, and for oesophagitis. In 46 patients, biopsy specimens were initially obtained from the stomach and subsequently from the oesophagus (Method 1) and in 133 patients, this process was reversed (Method II). A significantly greater frequency of H. pylori in the oesophagus was found in patients biopsied in accordance with Method I than those biopsied according to Method II (26% versus 4.5%, P < 0.001). There was no significant difference between patients with and without oesophagitis. All patients with H. pylori positive oesophageal cultures had an H. pylori positive culture from their gastric specimens. Only one out of 11 patients with Barrett's oesophagus had H. pylori positive culture from the oesophageal specimen. We conclude that H. pylori is not associated with oesophagitis. The occurrence of H. pylori in the oesophagus is not frequent, and probably the result of gastro-oesophageal reflux or contamination during the endoscopy. The biopsy technique is of great importance regarding the measured prevalence of H. pylori positive specimen from the oesophagus.

A survey was carried out in Portsmouth to find out what general practitioners knew about colorectal cancer and what their views were on screening. A random sample of general practitioners was interviewed by questionnaire and the remainder asked to complete the questionnaire themselves. The overall response rate was 62%. There was a higher response rate from women doctors and from the group that was interviewed. For some questions there was a difference in the pattern of responses given by the interview group and the group who completed the questionnaire themselves.The level of knowledge of colorectal cancer varied according to which aspect was questioned. The general practitioners knew the symptoms well but were less aware of the vital statistics and risk factors. Most doctors were not in favour of screening by testing for faecal occult blood.

The two most frequent forms of epidemiological investigation are the cohort study and the case control study, which was reviewed in a previous article. This article examines the most commonly used methods of statistical analysis of these studies applied to the 2 x 2 table.

The prognostic value of plasma prekallikrein activity, prothrombin time, and serum albumin with regard to survival in chronic liver insufficiency was evaluated in 21 consecutive patients. Twenty patients had liver cirrhosis, and one patient had malignant liver disease (hepatocellular carcinoma). Eight patients died between 4 and 43 days after the time of blood sampling. These patients had a prekallikrein value less than 0.42. There were no overlapping prekallikrein values between patients who died and patients who survived (overlap index 0; p less than 0.001). Overlap index for prothrombin time was 0.35 (p less than 0.02), and for serum albumin 0.34 (p less than 0.02). In conclusion, plasma prekallikrein seems to indicate whether death is imminent in patients with liver insufficiency due to cirrhosis. Longitudinal studies of prekallikrein activity in different subgroups of patients with chronic and acute liver disease are recommended.

Abstract Lervang H-H, Møller-Petersen J, Ditzel J (Section of Endocrinology, Department of Medicine and Department of Clinical Chemistry, Aalborg Hospital. Aalborg, Denmark). Serum β 2 -microglobulin levels in thyroid diseases. Serum β 2 -microglobulin was measured in 38 patients with thyroid diseases. Serum levels of β 2 -microglobulin were significantly increased in patients with untreated Graves’ disease (median: 200 nmol l −1 ; P < 0.0002), and in patients with untreated toxic adenomas (222 nmol l −1 ; P < 0.0005) compared to 60 healthy control subjects (147 nmol l −1 ). Following antithyroid treatment of euthyroidism, serum β 2 -microglobulin decreased significantly in both Graves’ disease (162 nmol 1 −1 ) and toxic adenomas (175 nmol l −1 ); values which were not significantly different from that of the control group. The level of serum β 2 -microglobulin in 12 patients with hypothyroidism was not different from that of the control group. However, in untreated hypothyroidism serum β 2 -microglobulin was positively correlated with serum thyroxine (T 4 ) (rho = 0.69: P < 0.05) and free thyroxine index (FT 4 I) (rho = 0.72; P < 0.02). It is concluded that elevated levels of serum β 2 -microglobulin may reflect the increased metabolism in patients with thyrotoxicosis. Increased levels in active Graves’ disease may also partly be caused by immunological activation.