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Biomedical subjects

M J Olek

Publications and source records attributed to M J Olek.

At least 19 recordsLinked to original sources
PubMed2004

Vitamin D intake and incidence of multiple sclerosis.

BACKGROUND: A protective effect of vitamin D on risk of multiple sclerosis (MS) has been proposed, but no prospective studies have addressed this hypothesis. METHODS: Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). Diet was assessed at baseline and updated every 4 years thereafter. During the follow-up, 173 cases of MS with onset of symptoms after baseline were confirmed. RESULTS: The pooled age-adjusted relative risk (RR) comparing women in the highest quintile of total vitamin D intake at baseline with those in the lowest was 0.67 (95% CI = 0.40 to 1.12; p for trend = 0.03). Intake of vitamin D from supplements was also inversely associated with risk of MS; the RR comparing women with intake of >or=400 IU/day with women with no supplemental vitamin D intake was 0.59 (95% CI = 0.38 to 0.91; p for trend = 0.006). No association was found between vitamin D from food and MS incidence. CONCLUSION: These results support a protective effect of vitamin D intake on risk of developing MS.

Adolescent↗
PubMed2001

Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study.

CONTEXT: Epidemiological studies suggest an association between infection with Epstein-Barr virus (EBV) and risk of multiple sclerosis (MS). OBJECTIVE: To determine whether elevation in serum antibody titers to EBV viral capsid antigen (VCA), nuclear antigens (EBNA, EBNA-1, and EBNA-2), and diffuse and restricted early antigen (EA-D and EA-R) as well as to cytomegalovirus (CMV) precede the occurrence of MS. DESIGN, SETTING, AND SUBJECTS: Prospective, nested case-control study. Of 62 439 women participating in the Nurses' Health Study (aged 30-55 years in 1976) and Nurses' Health Study II (aged 25-42 years in 1989) who gave blood samples in 1989-1990 and 1996-1999, respectively, and were followed up through 1999, 144 women with definite or probable MS and 288 healthy age-matched controls were included in the analysis. MAIN OUTCOME MEASURE: Serum antibody titers to the specific EBV and CMV antigens, compared between cases and controls. RESULTS: We documented 18 cases of MS with blood collected before disease onset. Compared with their matched controls, these women had higher serum geometric mean titers (GMTs) of antibodies to EBV but not CMV. Elevations were significant for antibodies to EBNA-1 (GMT, 515 vs 203; P =.03), EBNA-2 (GMT, 91 vs 40; P =.01), and EA-D (15.9 vs 5.9; P =.04). The strongest association was found for antibodies to EBNA-2; a 4-fold difference in titers was associated with a relative risk (RR) of MS of 3.9 (95% confidence interval [CI], 1.1-13.7). The corresponding RRs were 1.6 (95% CI, 0.7-3.7) for VCA, 2.5 (95% CI, 1.0-6.3) for EBNA, 1.8 (95% CI, 1.0-3.1) for EA-D, and 1.0 (95% CI, 0.6-1.7) for CMV. Significant but generally weaker elevations in anti-EBV antibodies were also found in analyses of 126 cases of MS with blood collected after disease onset and their matched controls. CONCLUSIONS: Our results support a role of EBV in the etiology of MS.

Adult↗
PubMed2001

Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women.

BACKGROUND: Antioxidant nutrients may reduce the risk of MS. In a recent case-control study, vitamin C intake was significantly inversely associated with MS risk among women. However, no prospective data are available. OBJECTIVE: To examine prospectively the associations of intakes of carotenoids, vitamin C, and vitamin E with the risk of MS among women. METHODS: The authors documented the occurrence of definite and probable MS within two large cohorts of women who completed detailed and validated semiquantitative food frequency questionnaires. One cohort (Nurses' Health Study) comprised 81,683 women aged 38 to 63 years in 1984, who were followed for 12 years; the other (Nurses' Health Study II) comprised 95,056 women aged 27 to 44 years in 1991, who were followed for 6 years. RESULTS: The authors documented a total of 214 cases of MS. After adjustments for age, latitude of birthplace, pack-years of smoking, and total energy intake, the pooled multivariate relative risks (95% CIs) comparing women in the highest quintile with those in the lowest quintile were 1.1 (0.7 to 1.7) for alpha-carotene, 1.1 (0.7 to 1.6) for beta-carotene, 1.4 (0.8 to 2.2) for beta-cryptoxanthin, 1.0 (0.6 to 1.5) for lycopene, 1.0 (0.7 to 1.6) for lutein/zeaxanthin, 1.4 (0.9 to 2.1) for total vitamin C, 1.3 (0.9 to 2.0) for dietary vitamin C, 0.8 (0.6 to 1.3) for total vitamin E, and 0.9 (0.6 to 1.4) for dietary vitamin E. The authors found no associations between intakes of fruits and vegetables and risk of MS. Use of vitamin C, vitamin E, and multivitamin supplements was also unrelated to risk of MS. CONCLUSIONS: These findings do not support hypotheses relating higher intakes of dietary carotenoids, vitamin C, and vitamin E to reduced risk of MS in women.

Adult↗
PubMed2001

Cigarette smoking and incidence of multiple sclerosis.

Experimental data suggest that cigarette smoking may play a role in the development of multiple sclerosis (MS), but epidemiologic studies have been small and inconclusive. The authors assessed the association between MS incidence and smoking in two cohort studies of US women, the Nurses' Health Study (121,700 women aged 30-55 years at baseline in 1976) and the Nurses' Health Study II (116,671 women aged 25-42 years at baseline in 1989). Smoking history was assessed at baseline and updated on biennial questionnaires. A total of 315 definite or probable cases of MS were documented. Compared with that for women who never smoked, the relative incidence rate was 1.6 (95% confidence interval: 1.2, 2.1) among current smokers and 1.2 (95% confidence interval: 0.9, 1.6) among past smokers after adjustment for age, latitude, and ancestry. The relative rate increased significantly with cumulative exposure to smoking (p for trend < 0.05), from 1.1 (95% confidence interval: 0.8, 1.6) for 1-9 pack-years to 1.5 (95% confidence interval: 1.2, 2.1) for 10-24 pack-years and 1.7 (95% confidence interval: 1.2, 2.4) for 25 or more pack-years. Similar results were obtained after adjustment for other potential confounding factors. Although these prospective results do not prove a cause-and-effect relation, they suggest that smoking is associated with an increased risk of MS.

Adult↗
PubMed2001

Hepatitis B vaccination and the risk of multiple sclerosis.

BACKGROUND: Reports of multiple sclerosis developing after hepatitis B vaccination have led to the concern that this vaccine might be a cause of multiple sclerosis in previously healthy subjects. METHODS: We conducted a nested case-control study in two large cohorts of nurses in the United States, those in the Nurses' Health Study (which has followed 121,700 women since 1976) and those in the Nurses' Health Study II (which has followed 116,671 women since 1989). For each woman with multiple sclerosis, we selected as controls five healthy women and one woman with breast cancer. Information about hepatitis B vaccination was obtained by means of a mailed questionnaire and was confirmed by means of vaccination certificates. The analyses included 192 women with multiple sclerosis and 645 matched controls and were conducted with the use of conditional logistic regression. RESULTS: The multivariate relative risk of multiple sclerosis associated with exposure to the hepatitis B vaccine at any time before the onset of the disease was 0.9 (95 percent confidence interval, 0.5 to 1.6). The relative risk associated with hepatitis B vaccination within two years before the onset of the disease was 0.7 (95 percent confidence interval, 0.3 to 1.8). The results were similar in analyses restricted to women with multiple sclerosis that began after the introduction of the recombinant hepatitis B vaccine. There was also no association between the number of doses of vaccine received and the risk of multiple sclerosis. CONCLUSIONS: These results indicate no association between hepatitis B vaccination and the development of multiple sclerosis.

Case-Control Studies↗
PubMed2001

Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

Adult↗
PubMed2001

Multiple sclerosis and age at infection with common viruses.

Increased risk of multiple sclerosis has been reported among individuals with a history of measles and other common childhood diseases during adolescence, infectious mononucleosis, or exposure to the canine distemper virus. We investigated these associations in a case-control study nested within the Nurses' Health Study (121,700 women traced since 1976) and the Nurses' Health Study II (116,671 women traced since 1989). Age at diagnosis of common viral diseases and birth order were obtained through a questionnaire. Our results include 301 cases with multiple sclerosis and their (up to six) matched controls. Except for infectious mononucleosis, which was a moderate risk factor (odds ratio = 2.1, 95% confidence interval = 1.5-2.9), we found little association between history of common viral diseases or exposure to canine distemper virus and risk of multiple sclerosis. We did find a relation between mumps after 15 years of age (odds ratio = 2.3, 95% confidence interval = 1.2-4.3) or measles after age 15 years of age (odds ratio = 2.8, 95% confidence interval = 0.8-9.1) and multiple sclerosis. Birth order was not materially related to multiple sclerosis. Our findings support the hypothesis that individuals who suffered from infectious mononucleosis, a marker of late infection with the Epstein-Barr virus, have an increased risk of multiple sclerosis. Late infection with other common viruses may also be associated with increased risk.

Adult↗
PubMed2000

Dietary fat in relation to risk of multiple sclerosis among two large cohorts of women.

Ecologic correlations suggest that higher intake of saturated fat and lower intake of polyunsaturated fat might increase the risk of multiple sclerosis (MS), but the results of case-control studies have been inconsistent. Because no prospective data are available, the authors examined these associations in two large cohorts, the Nurses' Health Study, which consisted of 92,422 women with 14 years of follow-up (1980-1994) and the Nurses' Health Study II, which consisted of 95,389 women with 4 years of follow-up (1991-1995). They documented 195 new cases of MS. The pooled multivariate relative risks comparing women in the highest quintile with those in the lowest were 1.1 (95% confidence interval: 0.7, 1.7) for total fat, 0.7 (95% confidence interval: 0.5, 1.2) for animal fat, 1.2 (95% confidence interval: 0.7, 2.1) for vegetable fat, 0.8 (95% confidence interval: 0.5, 1.3) for saturated fat, 1.1 (95% confidence interval: 0.7, 1.7) for monounsaturated fat, 1.7 (95% confidence interval 1.0, 2.8) for n-6 polyunsaturated fat, 1.3 (95% confidence interval: 0.8, 2.0) for trans unsaturated fat, and 0.7 (95% confidence interval: 0.4, 1.1) for cholesterol. Omega-3 fatty acids from fish were also unrelated to risk. However, the authors observed a nonsignificantly lower risk of MS for a higher intake of linolenic acid. These findings do not support relations between intakes of total fat or major specific types of fat and the risk of MS.

Adult↗
PubMed2000

Oral contraceptives and the incidence of multiple sclerosis.

BACKGROUND: Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS. METHODS: We assessed whether MS incidence was associated with oral contraceptive use or parity in two cohort studies of U.S. women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55 years at baseline in 1976) and the Nurses' Health Study II (NHS II; 116,671 women aged 25 to 42 years at baseline in 1989). Participants with a diagnosis of MS before baseline were excluded. Oral contraceptive history and parity were assessed at baseline and updated biennially. During follow-ups of 18 years (NHS) and 8 years (NHS II) we documented a total of 315 definite or probable cases of MS. RESULTS: Neither use of oral contraceptives nor parity were significantly associated with the risk of MS. As compared with women who never used oral contraceptives, the age-adjusted relative risk (95% CI) was 1.2 (0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users. Similar results were obtained after adjustment for latitude, ancestry, and other potential confounding factors. There was no clear trend of MS risk with either increasing duration of use or time elapsed since last use. Age at first birth was also not associated with the risk of MS. CONCLUSIONS: These prospective results do not support a lasting protective effect of oral contraceptive use or pregnancy on the risk of MS. The decision to use hormonal contraception should not be affected by its effects on the risk of MS.

Adult↗
PubMed1999

Geographic variation of MS incidence in two prospective studies of US women.

OBJECTIVE: To estimate the incidence of MS and its relation to latitude in two ongoing prospective studies of US women. BACKGROUND: A higher incidence of MS has been found in northern areas compared with southern areas of the United States and other countries, but the attenuation of this gradient in Europe in the last few decades and the consideration of ethnic factors have led some authors to question the existence of a strong association between MS and latitude. METHODS: The authors identified new cases of MS among participants in the Nurses' Health Study (NHS), which took place between 1976 and 1994, and in the Nurses' Health Study II (NHS II), which took place between 1989 and 1995. The NHS included women born between 1920 and 1946, and the NHS II included women born between 1947 and 1964. RESULTS: The incidence of MS among NHS participants (181 definite/probable patients) increased significantly with latitude (p = 0.03, trend). Adjusted rate ratios were 3.5 (95% CI, 1.1, 11.3) for the north and 2.7 (95% CI, 0.8, 8.9) for the middle tiers relative to the southern tier. Among NHS II women (131 definite/probable patients), no association between latitude and MS was found (p = 0.89, trend). Adjusted rate ratios were 0.8 (95% CI, 0.4, 1.6) for the northern areas and 0.9 (95%, 0.4, 1.8) for the middle areas, relative to the southern areas. CONCLUSION: The association between latitude and risk of MS in the United States was corroborated, but there was an attenuation of the north-south gradient over time. If confirmed, this finding could provide new clues to identifying environmental causes of the disease.

Adult↗
PubMed1999

Treatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: response to therapy is linked to the duration of progressive disease.

OBJECTIVE: To determine if there are variables linked to responsiveness to pulse cyclophosphamide/methylprednisolone therapy in progressive Multiple Sclerosis (MS). BACKGROUND: MS is a presumed autoimmune disease of the CNS in which immunosuppressive and immunomodulatory treatments are being used. We have treated patients with the progressive form of MS using a regimen consisting of pulse cyclophosphamide/methylprednisolone that is given as an outpatient at 4 - 8 week intervals similar to lupus nephritis protocols. DESIGN/METHODS: We investigated a series of 95 consecutive progressive MS patients treated in an open label fashion in an effort to identify factors linked to response to treatment. Clinical outcome measures included status at 12 months and time to failure determined by EDSS change and global physician impression. For each endpoint, associations were examined between outcome and patient characteristics including gender, age at onset of disease and treatment, EDSS 1 year previously and at start of treatment, duration of MS, previous treatment, age at onset and duration of progression, and primary vs secondary progressive MS. RESULTS: Of the variables studied, age, gender, age at onset, and age at treatment did not correlate with response to therapy. The most significant variable that correlated with response was length of time the patient was in the progressive phase (P=0.048, 12 month change in EDSS; P=0.017, risk for time to failure). Patients that improved on therapy at 12 months had progressive disease for an average of 2.1 years prior to treatment, whereas those stable or worse had progressive disease for 5.0 and 4.1 years respectively. There was a trend (P=0.08) favoring positive clinical responses in secondary progressive as opposed to primary progressive patients. CONCLUSIONS: Our data suggest that progressive MS may become refractory to immunosuppressive therapy with time and early intervention when patients enter the progressive stage should be considered. Furthermore, in trials of immunosuppressive agents for progressive MS, duration of progression should be considered as a randomization and analysis variable.

Adult↗
PubMed1999

Multiple sclerosis--Part I. Overview, pathophysiology, diagnostic evaluation, and clinical parameters.

A review article on multiple sclerosis (MS) is difficult because the pace of current research in the evaluation and treatment of the disease has accelerated greatly in the past 5 years. The rapidly expanding field of immunology together with the plethora of new drug trials makes the task of including all relevant material impossible. This first of a two-part article will include several sections on MS, including an overview, pathophysiology, diagnostic evaluation, and clinical parameters. The second part, to appear in the December issue, will look at treatment strategies and future directions.

Adult↗
PubMed1999

Multiple sclerosis--Part 2. Treatment strategies.

Because it is a chronic, relapsing or progressive disease, multiple sclerosis has an unpredictable clinical course generally spanning 10 to 20 years. During that time, neurologic disability is cumulative. Therefore, it is difficult to evaluate the efficacy of a given mode of treatment in an individual patient. This second part of a two-part series reviews current and emerging modes of therapy for multiple sclerosis. Future treatment directions in multiple sclerosis will require a better understanding of the pathophysiology of the disease. Future therapeutic modalities will also rely on more accurate clinical markers, such as improved magnetic resonance imaging techniques or specific immune markers to follow the disease progression. Part 1 of this series appearing in the November 1999 issue of JAOA included several sections on multiple sclerosis, including an overview, pathophysiology, diagnostic evaluation, and clinical parameters.

Cyclophosphamide↗
PubMed1999

Charcot-Marie-Tooth disease type I diagnosed in a 5-year-old boy after vincristine neurotoxicity, resulting in maternal diagnosis.

Charcot-Marie-Tooth disease type 1, also known as hereditary motor sensory neuropathy type 1, is an uncommon autosomal dominant disease that causes destruction of peripheral nerves with a varied clinical course, but often leads to muscle weakness. If the peroneal muscle is involved, the patient may develop a characteristic slapping gait. The dose-limiting side effect of the chemotherapeutic agent vincristine is usually its neurotoxicity. We report the case of a 5-year-old patient with leukemia who developed an acute polyneuropathy after treatment with vincristine. Charcot-Marie-Tooth disease type 1 was diagnosed in the patient and, subsequently, in his mother only after vincristine toxicity was observed.

Adult↗
PubMed1998

Seasonal variation of interferon-gamma production in progressive multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. There is increased interferon (IFN)-gamma secretion in MS patients in vitro, and IFN-gamma administration induces exacerbations of disease suggesting a link between IFN-gamma and disease activity. We observed significantly increased IFN-gamma production in the autumn and winter months compared with the spring and summer months in chronic progressive MS, and this increase was linked to endogenous interleukin (IL)-12 production. Increased seasonal IFN-gamma was not observed in normal control subjects, and there were no seasonal changes in IL-10 in progressive MS. These results suggest a potential environmental link between dysregulated IFN-gamma production and MS disease progression and pathogenesis.

Cells, Cultured↗