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Biomedical subjects

P B Christensen

Publications and source records attributed to P B Christensen.

At least 19 recordsLinked to original sources

Transfusion-acquired hepatitis C: the Danish lookback experience. The Danish HCV [hepatitis C virus] Lookback Group.

BACKGROUND: In 1996, the Danish National Board of Health recommended hepatitis C virus (HCV) lookback to identify recipients of blood components from donors found to be positive since the implementation of anti-HCV screening in 1991. STUDY DESIGN AND METHODS: The aim was to accumulate results of the lookback at a national level and to describe the morbidity of the infected recipients. Records of transfusion were identified for at least 10 years back, and recipients still alive were tested for hepatitis C. Those with positive results were referred for clinical evaluation. RESULTS: A total of 150 anti-HCV-positive Danish donors had donated blood to 1018 transfusion recipients, of whom 288 (29%) were still alive. Because of age, malignancy, or other severe diseases, 118 (41%) of these were not contacted. Of 157 recipients screened for HCV, 128 (82%) were anti-HCV positive on enzyme-linked immunosorbent assay, and 88 (56%) were HCV RNA positive. Among the HCV RNA-positive recipients, symptoms were present in 38 percent (25/66 reported), elevated alanine aminotransferase was found in 53 percent (41/77 tested), and cirrhosis was found in 11 percent (6/54 biopsied). Treatment with interferon alpha was initiated in 23 patients, corresponding to 26 percent of HCV RNA positive recipients. CONCLUSION: Among tested recipients in the Danish HCV lookback, most were anti-HCV positive and more than half were still viremic. The morbidity was considerable, and one-fourth of viremic recipients entered treatment.

Blood Banks

Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study.

OBJECTIVE: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus, making them potential candidates for endoscopic surveillance. METHODS: Rates of esophageal and gastric cancers were collected from the Danish Cancer registry for the period 1970-1991. The registry was used to identify all cases of esophageal adenocarcinoma in the period 1987-1992. Medical records were retrieved and details concerning previous diagnosis of reflux disease and Barrett's esophagus were recorded. RESULTS: The age- and gender-adjusted incidence of esophageal adenocarcinoma increased eightfold, from 0.3/10(5)/yr in 1970 to 2.3/10(5)/yr in 1990. This increase could not be explained by changes in classification or diagnostic routines. Medical data were retrieved for 524 of the 578 cases of esophageal adenocarcinoma reported during the period 1987-1992. A history of reflux symptoms or a diagnosis compatible with reflux was reported in 113 of 524 patients. A total of 119 patients (23%) had previously been investigated for dyspepsia or reflux symptoms, most often by endoscopy. A previous diagnosis of Barrett's esophagus was found in only 1.3% of the cancer patients. CONCLUSIONS: The rate of esophageal adenocarcinoma in Denmark has increased eightfold over a 20-yr period, and this increase is not explained by changes in classification or diagnostic routines. More than 98% of esophageal adenocarcinomas were found in patients who could not have entered endoscopic surveillance, as Barrett's esophagus had not been diagnosed before the cancer diagnosis. Endoscopic surveillance to detect dysplasia may be an option for the individual patient with Barrett's esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population.

Adenocarcinoma

Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers.

Our purpose was to clarify whether human colorectal cancer cells are equipped to present tumour-associated-antigens to the immune system, and whether this ability correlates with lymphoid infiltration, the Dukes' stage and Jass classification. Enzymatically dissociated tumour cells from 70 different colorectal cancers were monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression of the surface molecules HLA class I, HLA class II, CD80 (B7-1), CD54 (ICAM-I) and CD58 (LFA-3) was evaluated. In 60 of 70 tumours, all tumour cells expressed HLA class I, in 10 tumours 15-96% of the tumour cells expressed HLA class I. In 1 tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA class II, in 2 tumours none expressed HLA class II. Expression of CD58 was heterogeneous, and there was no or only sparse expression of CD80 and CD54. Expression of the HLA class I molecules, but not the class II, was correlated with lymphoid infiltration and the Jass classification. Expression of these surface molecules was not correlated with the Dukes' stage. The tumour cells were generally equipped to present antigens to the effector arm of the immune system since HLA class I is expressed, but the tumour cells were not optimal in stimulating an immune response, since HLA class II and CD58 were only marginally expressed and CD80 and CD54 were absent.

Adult

A comparison of flow cytometry and immunohistochemistry in human colorectal cancers.

In human colorectal cancer it has been reported that some tumours lack the HLA-ABC antigens. This has been interpreted as reflecting tumour escape from the immune system. Earlier data have been obtained by immunohistochemistry. In this study, we compared the expression of HLA-ABC, HLA-DR, CD80 (B7-1) and CD54 (ICAM-1) in 20 tumours using both a conventional immunohistochemistry two-layer technique and multiparameter flow cytometry, gating on an epithelial cell marker. Colorectal cancer tissue used in flow cytometry was dissociated with collagenase, deoxyribonuclease and hyaluronidase. The intensity of expression of HLA-ABC, HLA-DR and CD80 was unaffected by the enzymes, but CD54 was decreased by 30%. The reproducibility of flow cytometry was good. Microscopy of sections revealed that about 5% of each tumour sample consisted of normal epithelium, but even after correction for this, flow cytometry was superior to immunohistochemistry in 33 out of 80 cases, and showed that tumours described as HLA-ABC negative by immunohistochemistry were in fact weakly positive for HLA-ABC. We conclude that flow cytometry and immunohistochemistry are complementary, and that flow cytometry is superior to immunohistochemistry for detecting antigens/epitopes present in low amounts.

Aged

Mortality and survival in myasthenia gravis: a Danish population based study.

OBJECTIVES: To study mortality and survival of patients with myasthenia gravis. METHODS: 290 patients with myasthenia gravis were studied, including 212 incident cases identified during a comprehensive epidemiological study of myasthenia gravis in western Denmark 1975-89. Follow up was performed on 31 December 1994. Survival curves were constructed using the life table method. Patient data were compared with data from the public Danish population statistics. Death certificates were provided from the National Registry of Death. RESULTS: The annual average crude mortality rate was 1.8 per million (range 1.5-2.2). The myasthenia gravis related mortality rate (myasthenia gravis as underlying or contributory cause) was 1.4 per million (range 1.1-1.8). The age specific mortality rates were low below 50 years. After this age the mortality increased with age in both sexes; after 60 years more rapidly in men than in women. The overall survival rates three, five, 10, and 20 years from diagnosis were 85%, 81%, 69%, and 63% respectively. The survival of both sexes was shorter than that of the corresponding Danish population. Old age at diagnosis, a classification in Osserman-Genkins group IIB or III, and the presence of a thymoma were associated with a less favourable prognosis. The three, five, 10, and 20 year survival rates of thymectomised patients were 94%, 94%, 86%, and 79% respectively. The corresponding figures for the non-thymectomised patients were 78%, 71%, 56%, and 51%. A Cox regression analysis showed that this apparently significant effect of thymectomy was because the thymectomised patients were younger than the non-thymectomised patients. Furthermore, at the time of diagnosis of myasthenia gravis the non-thymectomised patients had a higher frequency of serious conditions associated with myasthenia gravis than the thymectomised patients. CONCLUSION: Patients with myasthenia gravis generally have a relative good prognosis although their survival is shorter than that of the corresponding population. Old age, a classification in Osserman-Genkins group III, and the presence of a thymoma are associated with a less favourable prognosis. In this study, the apparently significant effect of thymectomy was because the thymectomised patients were younger than non-thymectomised patients and because the non-thymctomised patients had a higher frequency of serious conditions associated with myasthenia gravis.

Age Distribution

A clinical trial of dextromethorphan in amyotrophic lateral sclerosis.

INTRODUCTION: Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, excitotoxicity mediated by glutamate has been implicated. Dextromethorphan is a NMDA-glutamate receptor antagonist with neuroprotective properties. MATERIAL AND METHODS: The effect of treatment with dextromethorphan (150 mg daily) in ALS patients was evaluated in a randomized, double-blind, placebo-controlled study. Forty-five patients were included in the analysis. RESULTS: At the end of the treatment period, 12 months after randomization, 15 patients (65%) in the placebo group and 12 patients (55 %) in the dextromethorphan group were still alive (log rank test, P=0.49). Rates of disease progression, as expressed by rates of decline in pulmonary function and in functional disability, were similar in both groups except for a significantly less pronounced rate of decline in the ability scores for the lower extremities in the dextromethorphan group. CONCLUSION: Treatment with a relatively low dose of dextromethorphan did not result in an improvement in 12-month survival in ALS.

Adult

Interferon-alpha 2b therapy in low-activity hepatitis C: a pilot study.

BACKGROUND: Many patients with chronic hepatitis C have long periods of normal or near-normal liver enzyme levels, even though histologic alterations have been confirmed. The recommendation today is not to treat this patient group. METHODS: In a pilot study 23 hepatitis C virus (HCV) RNA-positive patients with alanine aminotransferase (ALAT) levels less than 1.5 times upper normal limits for at least 6 months on more than three occasions and with histologic liver abnormalities compatible with chronic hepatitis C were treated with 3 MU of interferon-alpha 2b three times a week for 6 months. RESULTS: Nine patients (39%) became HCV RNA-negative in serum during treatment, but only two (8.7%) remained so after 6 months' follow-up. Significantly more patients with genotype other than type 1 became HCV RNA-negative than patients with genotype 1 during treatment (P = 0.005). CONCLUSIONS: Patients with low-activity chronic hepatitis C have a response to interferon-alpha treatment similar to that of patients with increased ALAT levels. Genotype seems to influence the rate of response.

Adult

Associated autoimmune diseases in myasthenia gravis. A population-based study.

During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe.

Arthritis, Rheumatoid

Pen injected apomorphine against off phenomena in late Parkinson's disease: a double blind, placebo controlled study.

The effect, therapeutic dose range, and pharmacokinetics of apomorphine, given as subcutaneous injections by a single use pen, were evaluated in the treatment of off phenomena in 22 patients with idiopathic Parkinson's disease. At study entry a placebo controlled apomorphine test was performed, and apomorphine doses were then individually titrated (mean 3.4 (range 0.8-6.0) mg) and compared with placebo in a double blind cross over phase. With apomorphine compared with placebo the mean daily duration of off periods was reduced by 51% as assessed by the patients and by 58% as assessed by the staff. The severity of off periods was also significantly reduced. The effect was unchanged after a maintenance phase of eight weeks. At study termination 13 of 14 patients were able to inject themselves and 11 of 14 patients found that their feeling of freedom had increased. The most common adverse events were nausea, subcutaneous nodules, and increased frequency of involuntary movements. Pharmacokinetics were linear and did not change with repeat dosing. The tmax ranged from five to 45 minutes (16 patients). It is concluded that pen injected apomorphine is a valuable treatment for patients with advanced Parkinson's disease with on-off phenomena.

Adult

[Varying prescriptions of benzodiazepines in general practice].

The aim of this study was to describe differences in patterns of benzodiazepine prescription in Svendborg. All benzodiazepine prescriptions filled by the two pharmacies in Svendborg between February and 31 March 1990 were registered. During the period, 3364 prescriptions were issued to 2262 persons (1837 tranquillizers and 1272 sedatives). General practitioners provide about 90% of benzodiazepine prescriptions. Practices with a high prescription level accounted for four times as many prescriptions as did practices with a low prescription level. By comparing the prescription level and the composition of the practice population we found that practices with a high prescription level had more women and elderly people enrolled than had the practices with a low prescription level. After standardization for age and sex the difference was reduced from 3.8 to 2.8, but practices with many elderly and female patients still provided more benzodiazepine prescriptions. Major benzodiazepine consumers (> 2 DDD/per day) constricted for 8.8% of the total amount of consumers and accounted for about 25% of the benzodiazepines prescribed during the investigation period. The number of major consumers enrolled in a practice varied between 2.8 to 13.0 per/1,000 patients. The difference in the prescription pattern could to a certain extent be explained by this difference, but there would still be a difference that can not be accounted for in our study. However, we anticipate that this variation could be due to differences in procedures and attitudes to the prescription of benzodiazepines.

Adult

Inter-observer variation in the evaluation of neurological signs: patient-related factors.

The influence of patient-related factors on inter-observer variability in the evaluation of neurological signs was investigated. Two hundred and two consecutive unselected inpatients were examined by two senior neurologists who were unaware of the neurological case history. Eight signs were evaluated: anisocoria, jerky eye movements, facial palsy, difference in elbow extension force, abnormal finger-nose test, Barré sign, difference in knee jerk, and extensor plantar reflex. Agreement rates were calculated in order to compare the inter-observer variability with reference to the patients' sex, age, mode of admission, and diagnosis at discharge. Observed agreement rates for the eight examined signs only sporadically showed statistically significant differences between the chosen patient-related factors. In general, inter-observer variation does not appear to be influenced by the sex, age, mode of admission or diagnosis at discharge of the patients.

Adolescent

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. MATERIAL & METHODS--Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. RESULTS--Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. CONCLUSION--The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.

Adolescent

[Delays in admissions for observation in suspected acute myocardial infarction].

One hundred and fifty-three patients hospitalized for observation and treatment of suspected acute myocardial infarction (AMI) were studied. The time delay from debut of symptoms until the decision was taken as to whether the patient was a candidate for treatment with thrombolysis or not was registered. The decision was made within four hours for 55.5% of the patients, and for 81.0% the decision was made within 12 hours of debut of symptoms. In all, 47 (30.1%) of the patients were treated with thrombolysis. Fifty-six (36.6%) of the patients had an AMI or unstable angina pectoris, and 39 (69.6%) were treated with thrombolysis. Seventeen patients with AMI did not receive the treatment, and for one of these the only reason for not receiving thrombolysis was a time delay longer than 12 hours. The median time for patient delay was 60 minutes, doctors' delay 39 minutes, and transport delay 29 min. At the hospital the first ECG was done 14 minutes after arrival, and the decision about whether to treat with thrombolysis or not was taken 25 minutes after arrival. It is still possible to diminish the time delays for patients suspected of AMI. The longest delay is due to the patient, and public education is needed to minimize patient delay. Doctors are recommended to refer patients suspected of AMI directly to the hospital, omitting a delaying visit to the patient.

Adult

[Prescription of benzodiazepines in general practice].

General practitioners are responsible for about 90% of all prescriptions for psychotropic drugs which benzodiazepines account for approximately 75%. In order to obtain a quantitative and qualitative assessment of the consumption in Svendborg, all benzodiazepine prescriptions were registered during a two-month period (February and March 1990). A total of 3364 prescriptions were issued to 6% (2262 persons) of the population. Of these, 1837 (54.6%) were prescriptions for tranquillizers, 1272 (37.8%) for hypnotics and 255 (7.6%) for both tranquillizers and hypnotics. The prevalence of benzodiazepine users increased with age and women were responsible for about 2/3 of the total consumption. Small but frequent prescriptions were issued to the younger users of benzodiazepines while older users generally received prescriptions for greater quantities at longer intervals. One in four persons over 80 years of age used sedatives. On account of the pharmaceutical, social and economic consequences of the widespread use of benzodiazepines in the elderly population, restrain should be observed in prescribing benzodiazepines.

Adult

Incidence and prevalence of myasthenia gravis in western Denmark: 1975 to 1989.

We studied the epidemiology of myasthenia gravis (MG) in western Denmark from 1975 to 1989, basing case identification on records from all hospitals in the survey area. The population surveyed was 2.80 million in 1985. The average annual incidence rate was 5.0 per million population (women, 5.9; men, 4.2). The point-prevalence rate (January 1, 1990) was 78 per million population (women, 102; men, 53). In men, the incidence increased after 40 years. In women, the incidence rates showed a bimodal pattern with a peak of 7.0 in the age group 20 to 29 years and a second peak of 11.7 in the age group 70 to 79 years. The differences in sex- and age-specific incidence rates suggest that younger women are more susceptible to MG than younger men. Old men and postmenopausal women had similar rates. When last examined, 21% of the 220 prevalent cases were in remission and 18% were moderately or severely disabled.

Adolescent