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Biomedical subjects

A Heltberg

Publications and source records attributed to A Heltberg.

At least 19 recordsLinked to original sources
PubMed2006

A randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate whether the efficacy of interferon-beta (IFNbeta) treatment of relapsing-remitting MS (RR-MS) was influenced by type, dose, and frequency of administration. METHODS: From June 1996 through October 1997, the authors offered participation to all Danish RR-MS patients who met the following criteria: definite MS, at least two relapses within 2 years, age 18 to 55, and an Expanded Disability Status Scale (EDSS) score of < or = 5.5. The study was multicenter, controlled, open-label, randomized, head-to-head comparing IFNbeta-1a 22 microg once a week (n = 143) with IFNbeta-1b 250 microg every other day (n = 158), both subcutaneously, for 24 months. Patients who declined randomization were offered treatment with IFNbeta-1b 250 microg every other day (n = 120). The primary end-points were the annualized relapse rate, the time to first relapse, and neutralizing antibody formation. The secondary endpoint was time to sustained progression. RESULTS: The annual relapse rates were virtually equal in the two arms of the randomized study (IFNbeta-1a: 0.70; IFNbeta-1b: 0.71); so were the time to first relapse and the time to sustained progression. In the nonrandomized patients (IFNbeta-1b), the annual relapse rate was not significantly different, but the time to progression was shorter. CONCLUSION: In this study, 250 microg interferon-beta-1b administered every other day did not prove clinically superior to once-a-week administration of 22 microg interferon-beta-1a.

Adjuvants, Immunologic↗
PubMed2001

Multiple sclerosis in the Faroe Islands: an epitome.

The Faroe Islands are a semi-independent unit of the Kingdom of Denmark and are located in the North Atlantic Ocean between Norway and Iceland. Efforts to identify all cases of multiple sclerosis (MS) since 1900 among Faroese have been continuing for over a quarter century. As of 1998 prevalence was 66 per 100,000, age adjusted to 1960 US population, with a rate of 100 for women and 34 for men. Median survival was at 29 to 34 years with no significant difference by sex. Faroese with overseas residence indicated that at least 2 years of exposure from age 11 on in a high-risk area are required for acquisition of MS. Among native resident Faroese the first instance of symptom onset was in 1943, heralding a type 1 epidemic of 21 cases. This was followed by three successive epidemics of 10, 10, 13 cases, with membership in each epidemic defined by calendar time and age of exposure. Age at exposure for epidemic I was 11 to 45 years; for later epidemics age 11 was the minimum. We believe the source of MS on the Faroes was their occupation by British troops for 5 years in World War II. We think they introduced a widespread, specific, persistent (but unknown) infection, probably asymptomatic, which we call the primary multiple sclerosis affection (PMSA). Only a small proportion of those affected with PMSA will years later show any clinical signs of MS. Models of transmission of PMSA through successive cohorts of Faroese fit the data for epidemics II and III, and predicted the occurrence of epidemic IV. The Faroese provide an ideal location to determine the nature of PMSA, since the disease has remained geographically stable for 50 years without further spread throughout the islands.

Adult↗
PubMed1997

Expression of endogenous retroviruses in blood mononuclear cells and brain tissue from multiple sclerosis patients.

OBJECTIVES: To compare the expression of endogenous retroviruses in MS patients and controls. MATERIAL AND METHODS: Peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of matched healthy donors and five patients with other central nervous system disease. Also brain specimens from MS patients and controls were obtained. Transcripts of various endogenous retroviruses in these samples were detected by RNA-PCR. RESULTS: Several endogenous retroviral sequences were transcribed in peripheral blood mononuclear cells and brain tissue from MS patients as well as controls. A composite transcript of an endogenous retrovirus and a zinc finger sequence was more frequently found in healthy donors than in MS patients. CONCLUSION: Some endogenous retroviruses are normally transcribed in white blood cells and brain tissue. The significance of those findings, which concerned the composite transcripts of the zinc finger sequence and its associated endogenous retrovirus is uncertain.

Adult↗
PubMed1997

Multiple sclerosis in the Faroe Islands. 7. Results of a case control questionnaire with multiple controls.

Detailed questionnaires were completed in 1978-79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no differences, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.

Adolescent↗
PubMed1996

Possible association between multiple sclerosis and the human T cell leukemia virus (HTLV)-related endogenous element, HRES-1.

In the present study we searched for an association between the human endogenous retroviral element HRES-1 and multiple sclerosis (MS). Fragments of this endogenous retrovirus were amplified for subsequent examination by single strand conformational analysis. We did not find HRES-1 markers exclusively linked with MS and only the two already known polymorphisms, which define three alleles of HRES-1, were detected. However, we found a significant difference in the distribution of these alleles between a group of 87 MS patients and a control group of 158 healthy individuals (P = 0.014). There were no differences in the distribution of the HRES-1 allelic forms between MS patients with a relapsing-remitting course and patients with chronic progressive MS. Our results provide evidence of an association between HRES-1 and MS. Possible explanations for this are discussed.

Alleles↗
PubMed1996

Three allelic forms of the human endogenous retrovirus, ERV3, and their frequencies in multiple sclerosis patients and healthy individuals.

A possible association between the endogenous retrovirus, ERV3, and multiple sclerosis (MS) was examined. Samples of DNA from 74 MS patients and 159 healthy blood donors were subjected to enzymatic amplification followed by single strand conformational analysis to detect polymorphisms in the long terminal repeats of ERV3. Using this approach we detected six single base pair variations and a drop-out of a nucleotide. The linkage pattern of these base pair variations enabled us to define three allelic forms of ERV3. Polymorphisms exclusively present in the group of patients were not found and the distribution of the three allelic forms did not differ significantly between the group of controls and the MS group. Neither was there a significant difference in the distribution of the three alleles between MS patients with the progressive form and patients with relapsing/remitting MS. Our results are not in support of an association between ERV3 and MS.

Alleles↗
PubMed1995

Multiple sclerosis in the Faroe Islands: transmission across four epidemics.

As of 1991 we had ascertained 42 native resident Faroese plus 12 non-resident "migrant" Faroese with clinical onset of MS in this century. The resident series comprised four successive epidemics beginning in 1943 and then at 13-year intervals thereafter, a separation of very high statistical significance (p < 0.00001). We concluded that the first epidemic in the Faroes resulted from the introduction of a specific but unknown infection which we call the "primary MS affection" (PMSA) by occupying British troops during World War II. Clinical neurologic MS (CNMS) is then the rare late sequel of infection with PMSA. The first epidemic defined age of susceptibility to PMSA as age 11 to 45 at onset of exposure. Models of transmission used for the first three epidemics included the need for two years of exposure before PMSA acquisition and limitation of transmissibility of PMSA to age 13 to 26. With these conditions successive cohorts of susceptible Faroese were defined to account for the second and third epidemics, and they also predicted the occurrence of the fourth epidemic. Further consideration of these models suggests transmissibility is even more limited, perhaps to age 20 to 26 or so.

Adolescent↗
PubMed1995

Expression of endogenous retroviruses in blood mononuclear cells and brain tissue from multiple sclerosis patients.

The aim of the present study was to examine whether there is an abnormal expression of certain endogenous retroviruses in MS patients. For this purpose samples of peripheral blood mononuclear cells were obtained from 22 MS patients, a corresponding number of age and sex-matched healthy donors and five patients with other diseases affecting the central nervous system. In addition, brain specimens of macroscopic normal white and gray matter from four MS patients and a similar number of controls were included in the study. Using an enzymatic amplification technique, we found expression of the endogenous retroviral sequences, HRES-1, HERV-K10 and ERV3 in most samples of peripheral blood mononuclear cells from MS patients and controls without obvious differences between these two groups. In contrast, composite transcripts of ERV3 and a zinc finger sequence were more frequently detected in healthy donors than in MS patients. At present, the possible significance of this is uncertain. The retroviral element 4-1 was not transcribed or only transcribed at a very low level in peripheral blood cells of controls and MS patients. Transcripts of various endogenous retroviruses were also detected in the brain samples, but a different pattern was not apparent in the MS group as compared with controls. Aspects concerning a possible association between endogenous retroviruses and autoimmunity are considered.

Adult↗
PubMed1993

Multiple sclerosis in the Faroe Islands. VI. Studies of HLA markers.

Occurrence of clinical neurologic multiple sclerosis (CNMS) among resident Faroese began between 1943 and 1973 and comprised three epidemics. The occupation by British forces for 5 years during World War II was interpreted to have been of major importance for the occurrence of these epidemics and led us to believe that CNMS is the rare, late result of a single, widespread, systemic and specific infectious disease which we have labelled the primary MS affection (PMSA). In this study we describe the occurrence of genetic markers of the HLA system in 16 Faroese MS patients, 25 of their siblings, 30 unrelated healthy neighbors and spouses to MS patients, 18 healthy controls from areas where no MS cases have been detected, and 80 unrelated normal Faroese. These studies show no significant deviations of HLA class I antigens, whereas the class II antigens do deviate: 50% of the Faroese MS patients carry the HLA-DR2 (DQ1/DRB 15) antigen, compared to a frequency of 15-20% among the control groups. Also the group of siblings of MS patients showed an increased frequency of DR4 (72%) compared to normal frequency among MS patients and other normal controls (43-47%). However, if DR15-positive individuals were excluded, this difference was further reduced. If PMSA was widespread within this group, DR4 or some closely associated genetic marker may confer protection against PMSA developing into CNMS. The occurrence of CNMS in these epidemics seems therefore associated to HLA class II-linked genetic factors similar to those found in studies of other caucasians with MS. This observation seems important in understanding the pathogenesis of this disease.

Cohort Studies↗
PubMed1993

Effects of neuropsychological treatment in patients with multiple sclerosis.

The chronic and progressive nature of multiple sclerosis (MS) often excludes patients from neuropsychological treatment. At the Multiple Sclerosis Rehabilitation Hospital, Haslev, 40 patients with mild to moderate cognitive and behavioral impairment associated with MS were randomized to either specific cognitive treatment (20 pts) by direct training, compensatory strategies and neuropsychotherapy, or to non-specific, deliberately diffuse mental stimulation (20 pts). Treatment was for a mean of 46 days. The effects of treatment were evaluated by neuropsychological tests before treatment, immediately after treatment (short-term effects) and 6 months later (long-term effects). After short-term treatment, effects on cognitive measures were not convincing, but on the Beck Depression Inventory (BDI) the specific cognitive treatment group reported significantly less depression. After 6 months only this group showed an effect, since the visuo-spatial memory was improved. However, the depression ratings (BDI) were almost maintained from the short-term level. Interestingly, the non-specific treatment group rated themselves as significantly more depressed. Conclusively, it is worth while to offer specific neuropsychological treatment to MS patients with cognitive and behavioral dysfunction.

Adult↗
PubMed1993

Multiple sclerosis in the Faroe Islands. 5. The occurrence of the fourth epidemic as validation of transmission.

Based on 32 cases with clinical onset 1943-73, we previously described the occurrence of clinical neurologic multiple sclerosis (CNMS) on the Faroe Islands as constituting three consecutive epidemics, with 20, 9, and 3 cases respectively. As of 1991 there were seven additional cases of CNMS with clinical onset 1984-1989 constituting the fourth epidemic, as well as three more members of epidemic III. We have proposed that CNMS is the rare late result of infection with PMSA (the primary multiple sclerosis affection), a state requiring some two years of exposure from age 11+ for acquisition by Faroese, and that PMSA was first transmitted during World War II by affected but asymptomatic British troops to Faroese residents; part of this (F1) cohort of affected asymptomatic Faroese transmitted PMSA to the next (F2) cohort comprising Faroese reaching age 11 in the interval when that F1 subset was present, and the F2 cohort similarly transmitted PMSA to the third (F3) cohort. Cases of CNMS defining epidemic I-III were members of the respective F1-F3 cohorts. The existence of epidemic IV within the F4 cohort of Faroese may be taken as validation of our transmission models and of our theses as to the nature of multiple sclerosis.

Adolescent↗
PubMed1991

Localized in vivo proton spectroscopy in the brain of patients with multiple sclerosis.

Localized proton spectroscopy was performed in 15 patients with acute or chronic multiple sclerosis (MS). Some of the patients were investigated serially, being given a total of 22 spectroscopic investigations. Resonances corresponding to free lipids were observed in six plaques. This was distinctly seen in two plaques at Days 70 and 85 after the occurrence of the plaques. A lesser content of lipids in plaques was observed as early as Day 10 and as late as nearly 1 year after occurrence. The relative concentration of N-acetyl asparate (NAA) was significantly lower in patients than in controls, and the relative concentration of choline (Cho) was significantly higher in patients than in controls. These differences were most pronounced in older plaques. MR spectroscopic demonstration of lipids in a MS plaque probably reflects disintegration of myelin, and a decreased NAA/Cho ratio may be related either to gliosis or to axonal degeneration, which sometimes occurs in longstanding MS.

Acute Disease↗
PubMed1989

Serum sex hormone and gonadotropin concentrations in premenopausal women with multiple sclerosis.

Dysfunctions within the hypothalamic-pituitary-gonadal axis occur frequently among women with multiple sclerosis (MS) and may induce menstrual disturbances and subsequent infertility. We have measured serum concentrations of prolactin. gonadotropins and sex hormone binding globulin (SHBG) as well as free and bound oestrogen and androgen levels in 14 women of fertile age with MS. These women all displayed regular cycles without having experienced fertility problems. As controls 14 normal women with regular periods and ideal body weight of 91% (range 80-101) were included. Serum from both groups was sampled during the early follicular phase. The MS-patients had significantly (P less than 0.05) higher concentrations of prolactin, LH, FSH, total and free testosterone (P less than 0.01) and a significantly lower serum concentration of oestrone sulphate (P less than 0.01). The abnormal hormone concentrations were not related to clinical status of the disease. We propose that the increased androgen levels are of ovarian origin as adrenal androgens were normal. The reason for the slight increase of prolactin and the marked increase of gonadotropins in women with MS is speculative. As oestradiol levels, however, were within normal range, we assume that a peripheral resistance to gonadotropins combined with an abnormal central regulation causes the increased pituitary secretion.

Adult↗
PubMed1989

Long-term prognosis and quality of life after reversible cerebral ischemic attacks.

The long-term prognosis and quality of life of 201 patients admitted to hospital with reversible ischemic attacks (RIA) were estimated in a prospective study. The median follow-up time was 58 months. Further RIAs were reported by 91 patients (45%) and 48 (24%) suffered a stroke. The risk of stroke was markedly higher in the first 6 months after RIA, after which the annual stroke rate was rather constant with an average of 4.8%, about 8 times higher than expected. The average annual mortality rate for the RIA patients was 5.9%, which is significantly higher than expected. Cardiovascular deaths accounted for more than half of all deaths, stroke for one fourth. Life-table analysis of subgroups disclosed a much more favorable prognosis for women under 60 years. High systolic blood pressure, diabetes, and previous myocardial infarction were identified as risk factors. The occurrence of RIA had significantly influenced the quality of life and occupational status for the majority of the patients, even for those who did not suffer a subsequent stroke. Decreased working capacity, general asthenia and fatigue and impaired memory were the most common complaints. We conclude that RIA may be a more serious vascular event than generally believed. Apart from carrying a substantial risk of stroke and death, even a single RIA can cause permanent psychological dysfunction influencing the quality of life.

Actuarial Analysis↗
PubMed1987

Twin studies in multiple sclerosis.

The classical method of evaluating whether genetic factors are involved in the etiology of a given disease and to what extent is the twin method. However, methodological problems are great, and it is possible only in a few countries to apply this method to multiple sclerosis (MS) research. To draw genetical conclusions it is of fundamental importance that the material should be an unselected, unbiased material derived from a twin population. Another fundamental point is the diagnosis of twin zygosity. In MS research the twin method has been applied by several authors, but a Mendelian mode of inheritance has not been shown to exist. However, an association of MS to the genetic HLA system has been demonstrated, and this suggests that genetical factors are of some importance in the development of MS. Methodological problems are discussed and the most important twin studies in MS, including the Danish twin study.

Denmark↗