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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

Outbreak of Hepatitis B among injecting drug users in Denmark.

BACKGROUND: The incidence of hepatitis B is low in Denmark, but injecting drug users (IDUs) remains a high-risk group for this infection. OBJECTIVES: The aim of the study was to describe a hepatitis B outbreak among IDUs by comparing existing registers. Additionally, we wanted to analyze the genetic variation of the hepatitis B virus involved in the outbreak. STUDY DESIGN: In the County of Funen, registers of laboratory diagnosis, hospital records and reports from clinicians to the Medical Officer of Health (MOH) were compared between 1992 and 1998. HBsAg positive sera recovered from the epidemic were sequenced and compared to known HBV strains. RESULTS: We identified 648 cases of hepatitis B of which 51% (332) were acute infections. The laboratory database identified 96% (319/332) of these, 45% (150/332) were admitted to hospital and 38% (127/332) were reported to public health. By capture-recapture analysis based on MOH reports and hospital records the estimated total number of acute cases were 334 (95% C.I. 283-385). We sequenced 75 HBsAg positive samples and identified two very similar strains of genotype D (serotype ayw3) among IDUs involved in the outbreak. CONCLUSIONS: The current surveillance system did not detect the majority of acute hepatitis B cases in County of Funen. We suggest laboratory-based surveillance of hepatitis B to be implemented at a national level as this may identify new outbreaks faster and more complete than the current surveillance system.

Denmark↗

Hepatitis B core antibodies in Danish blood donors: a surrogate marker of risk behaviour.

BACKGROUND AND OBJECTIVES: The aim of this work was to determine the prevalence of antibodies to hepatitis B core antigen (anti-HBc) among Danish blood donors and to correlate this with risk factors for blood-borne and sexually transmitted diseases. MATERIALS AND METHODS: During a 5-month period, 10 862 consecutive donors in the County of Funen were screened for anti-HBc, and repeat-reactive samples were confirmed by supplementary testing. Information on risk factors was assessed by questionnaire in 585 consecutive anti-HBc-negative blood donors and compared with information obtained from confirmed positive donors. RESULTS: The prevalence of confirmed positive anti-HBc among donors was 0.70% (76/10 862, 95% confidence interval [CI]: 0.55-0.87). One donor was positive for anti-HBc immunoglobulin M (IgM); none tested positive for hepatitis B virus (HBV) DNA. In a logistic regression analysis, age, female gender, tattoos and commercial sexual relations, were independent predictive factors for the presence of anti-HBc. CONCLUSION: Anti-HBc is a surrogate marker for previous risk behaviour in the Danish blood donor population. We suggest that screening for anti-HBc may be used among new donors to supplement interviews on risk behaviour.

Adult↗

[Transfusion-related hepatitis C. The Danish "look back" survey].

This study accumulated results of the HCV lookback in Denmark and described the morbidity of the infected recipients. Donor records were identified for at least ten years back, and recipients still alive were tested for hepatitis C. Those with positive results were referred for clinical evaluation. A total of 150 Danish anti-HCV positive donors had donated blood to 1018 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 and 88 (56%) were HCV-RNA positive. Among the HCV-RNA positive recipients symptoms were present in 38% (25/66 reported), elevated ALT was found in 53% (41/77 tested) and cirrhosis was found in 11% (6/54 biopsied). Treatment with interferon-alpha was initiated in 23 patients, corresponding to 26% of HCV-RNA positive recipients.

Blood Donors↗

Prevalence and incidence of bloodborne viral infections among Danish prisoners.

In order to determine the prevalence and incidence of bloodborne viral infections among prisoners, we conducted a prospective study in a Danish medium security prison for males. The prisoners were offered an interview and blood test for hepatitis and human immunodeficiency virus HIV at inclusion as well as at release from prison or end of study. Of 403 prisoners available 325 (79%) participated in the initial survey and for 142 (44%) a follow-up test was available. 43% (140/325) of the participants were injecting drug users (IDUs) of whom 64% were positive for hepatitis B (HBV) and 87% for hepatitis C (HCV) markers. No cases of HIV or human T lymphotropic virus (HTLV) were found. 32% of all prisoners could transmit HBV and/or HCV by blood contact. 70% of IDUs had shared injecting equipment, and 60% had injected inside prison. Only 2% of IDUs were vaccinated against HBV. Duration of injecting drug use, numbers of imprisonments, and injecting in prison were independently and positively associated with the presence of HBV antibodies among IDUs by logistic regression analysis. The HBV incidence was 16/100 PY (95% CI: 2-56/100 PY) and the HCV incidence 25/100 PY (1-140) among injecting drug users (IDUs). We conclude that IDUs in prison have an incidence of hepatitis B and C 100 times higher than reported in the general Danish population. They should be vaccinated against hepatitis B and new initiatives to stop sharing of injecting equipment in and outside prison is urgently needed.

Adult↗

Haemophilic patients with hepatitis C have higher viral load compared to other well-defined patient groups.

Comparison of hepatitis C viral load between different patient populations has been hampered by the use of different technology in individual studies. We had the impression that haemophilic (HAEM) patients had a higher serum load of hepatitis C virus (HCV) compared to other HCV-infected patients. We therefore studied viral load and genotypes in active illicit drug users (IDU), HAEM patients and patients with post-transfusion hepatitis (PTH). The study comprises 225 HCV-RNA positive patients, 117 IDU, 60 HAEM patients and 48 PTH patients. All patients were anti-HIV negative. HCV-RNA was measured with a quantitative reverse transcription polymerase chain reaction (RT-PCR) method, HCV-genotypes were determined with genotype specific primers in RT-PCR in 221 patients. Four patients could not be genotyped with our assay and were excluded. Overall viral load was higher in genotypes 1 and 2 compared to genotype 3, median values of HCV-RNA were 1,400 x 10(3) geq ml(-1), 2,700 x 10(3) geq ml(-1) and 270 x 10(3) geq ml(-1), respectively. HAEM patients had significantly higher viral load for both genotypes 1 and 3 compared to the IDU and PTH patients. In a multiple linear regression model HCV-RNA viral load was independently associated with HAEM and genotype, but not to age, gender or disease duration. In conclusion, HAEM patients have higher viral load than IDU and PTH patients. The reason for this is unknown, but it may be due to host factors or mode of transmission with multiple inoculations.

Adult↗

Characterisation of tumour infiltrating lymphocytes and correlations with immunological surface molecules in colorectal cancer.

Using flow cytometry, we studied the phenotype of tumour infiltrating lymphocytes (TILs) in 41 enzymatically dissociated colorectal cancers and compared this to the expression of HLA class I and II and CD80 on tumour cells. We studied the possible enzymatic damage to various surface markers after enzymatic dissociation. The reproducibility of flow cytometric determinations obtained from TILs was good (kappa value: 0.79). The median CD4+/CD8+ ratio was 2.2. Approximately 43-45% (median of cells in each tumour) of both the CD4(+)- and the CD8(+)-TILs expressed HLA class II; 14.2% of the CD4(+)-TILs expressed CD25 and none of the CD8(+)-TILs expressed CD25. CD3-/CD16+/CD56(+)-TILs were very infrequent. Expression of HLA class II did not correlate with any lymphocyte surface markers. Since TILs are "turned off" rather than stimulated when tumour cells express HLA class II but not CD80, the lack of correlations could be due to anergy.

Adult↗

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↗