[A neonate with developmental retardation]. / Een neonaat met ontwikkelingsachterstand.

An 6-month-old boy was admitted to the hospital with hypotonia, hyperpnoeic and apnoeic episodes, and abnormal eye movements. Cranial MRI revealed prominent superior cerebellar peduncles with dysgenesis of the vermis and a deep interpeduncular fossa, resulting in the characteristic image of a 'molar tooth' malformation of the brainstem. This is a classical sign of Joubert syndrome.

Hyperhomocysteinemia and risk for peripheral arterial occlusive disease in young women.

OBJECTIVE: Few studies to date have examined the relationship between hyperhomocysteinemia and peripheral arterial occlusive disease (PAOD) in young women. In this study we assessed hyperhomocysteinemia as a risk factor for PAOD in young women. In addition, we evaluated the effect of joint exposure to hyperhomocysteinemia and traditional risk factors. METHODS: Two hundred twenty women, ages 18 to 49 years, with PAOD and 629 healthy women (control group) from a population-based case-control study filled out the same structured questionnaire and donated venous blood samples for determination of plasma homocysteine levels. Hyperhomocysteinemia was defined as nonfasting total plasma homocysteine level above the 90th percentile of the control range. RESULTS: Young women with hyperhomocysteinemia had a 2.5-fold (95% confidence interval [CI], 1.7-3.9) increased risk for PAOD. When presence of hyperhomocysteinemia was combined with presence of a traditional risk factor, relative risk strongly increased in smokers (odds ratio [OR], 18.9; 95% CI, 8.3-42.9) and in women with hypertension (OR, 10.3; 95% CI, 5.4-19.8), hypercholesterolemia (OR, 8.5; 95% CI, 4.2-17.1), and diabetes (OR, 8.9; 95% CI, 1.7-46.9). CONCLUSIONS: Hyperhomocysteinemia is a risk factor for PAOD in young women. There is a strong synergistic effect between hyperhomocysteinemia and all traditional vascular risk factors. Our findings may have implications for risk management in these young women.

Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction.

We investigated the effect of prothrombotic coagulation defects in combination with smoking and other conventional risk factors on the risk of myocardial infarction in young women. In 217 women with a first myocardial infarction before the age of 50 years and 763 healthy control women from a population-based case-control study, factor V Leiden and prothrombin 20210A status were determined. Data on major cardiovascular risk factors and oral contraceptive use were combined with the presence or absence of these prothrombotic mutations, and compared between patients and controls. The overall odds ratio for myocardial infarction in the presence of a coagulation defect was 1.1 [95% confidence interval (CI) 0.6-1.9]. The combination of a prothrombotic mutation and current smoking increased the risk of myocardial infarction 12-fold (95% CI 5.7-27) compared with non-smokers without a coagulation defect. Among women who smoked cigarettes, factor V Leiden presence versus absence increased the risk of myocardial infarction by 2.0 (95% CI 0.9-4.6), and prothrombin 20210A presence versus absence had an odds ratio of 1.0 (95% CI 0.3-3.5). We conclude that factor V Leiden and prothrombin 20210A do not add substantially to the overall risk of myocardial infarction in young women. However, in women who smoke, the presence of factor V Leiden increased the risk of myocardial infarction twofold.

Functional health and well-being of relatively young women with peripheral arterial disease is decreased but stable after diagnosis.

OBJECTIVE: This study was undertaken to investigate the extent to which health-related quality of life (HQOL) is reduced in young women with peripheral arterial disease (PAD) compared with age-matched and gender-matched control subjects. Moreover, potential determinants of HQOL in young women with PAD were studied, ie, traditional cardiovascular risk factors, location of stenosis and time since diagnosis. METHODS: This was a population-based case-control study. Subjects were 208 young (<50 years) women with PAD diagnosed at angiography and 471 population-based age-matched and gender-matched control subjects. All participants completed the RAND-36 questionnaire, which produces a HQOL profile. The questionnaire contains 36 items that assess 8 domains of HQOL. Each domain is given a mean score ranging from 0 to 100, with higher scores indicative of better quality of life. RESULTS: PAD had a deleterious effect on HQOL in young women. Ability to deal with the physical requirements of daily life was affected, and physical capabilities limited activity to a considerable extent. Mean differences observed for 2 domains, ie, Physical functioning and Role-physical, were -25.1 (95% confidence interval [CI], -28.8,-21.4) and -22.5 (95% CI, -28.9,-16.0). Within the group of young women with PAD, HQOL did not depend on age, smoking, hypercholesterolemia, or education. However, women with hyperglycemia, hypertension, or increased body mass index scored lower on 1 or more domains of RAND-36. Location of stenosis was also related to HQOL; patients with more proximal stenosis scored slightly higher on the domain Physical functioning, compared with women with more distal stenosis. Time (0-10 years) between diagnosis (1990-1999) and when RAND-36 was filled out (2000) is related to score on the Mental health domain; score increases over time. Scores on the other 7 domains of HQOL showed no significant relation to duration of disease. CONCLUSION: Quality of life in young women with PAD was statistically significant diminished for all domains of RAND-36 in comparison with HQOL in healthy age-matched control subjects. HQOL of patients with recently diagnosed PAD is comparable to that of patients in whom the diagnosis was made several years previously. Effective therapy might stabilize, albeit not improve, quality of life in this specific patient population.

Meta-analysis of sero-epidemiologic studies of the relation between Chlamydia pneumoniae and atherosclerosis: does study design influence results?

BACKGROUND: The results of sero-epidemiologic studies of the relation between Chlamydia pneumoniae and atherogenesis vary considerably. A meta-analysis was performed to calculate the overall odds ratio (OR) and to identify potential sources of variability. METHODS: The MEDLINE database was searched from January 1997 to December 2000 for studies describing the seroprevalence of IgG antibodies to C pneumoniae in relation to clinically manifest atherosclerosis. Data extracted included 1) the study design used, 2) the number of included patients, 3) the type of disease (or end point), 4) the number of control subjects, 5) the type of control subjects, 6) the follow-up duration, 7) the crude and adjusted ORs (and 95% CI), and 8) the extent of adjustment for potential confounders. RESULTS: Thirty-eight studies were included in the meta-analysis. The overall OR was 1.6 (95% CI 1.3-2.0). The overall OR of cross-sectional case-control studies (2.0, 95% CI 1.5-2.6) was higher than that of prospective (nested) case-control studies (1.1, 95% CI 0.8-1.4). Moreover, the duration of follow-up in prospective studies was inversely related to the strength of the relation (beta = -0.04, 95% CI -0.08, -0.01). Adjustment of risk estimates for potentially confounding factors did not influence the strength of the relation. CONCLUSIONS: The relation between C pneumoniae and clinically manifest atherosclerosis is not durable. This probably is due to a lack of causality, although results may have been influenced by the design of the component studies.

Novel risk factors for peripheral arterial disease in young women.

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.

Increased pregnancy loss in young women with aortoiliac disease.

BACKGROUND: During clinical evaluation of young women with peripheral arterial occlusive disease, we were surprised by the high prevalence of pregnancy loss in women with segmental stenosis confined to the aortoiliac segment. We wondered if increased occurrence of miscarriage is the result of high expression of vascular and obstetrical risk factors in these patients, or if it is related to localization of disease. In a case-control study designed to investigate risk factors for peripheral arterial occlusive disease in young women, we assessed the risk of miscarriage in these patients according to level of obstruction. METHODS: A total of 202 female patients, aged 18-49 years and 466 healthy control women from a population based case-control study, donated venous blood samples and filled out a structured questionnaire concerning classical cardiovascular risk factors and obstetrical history. In all patients, diagnosis of peripheral arterial occlusive disease was confirmed by intra-arterial angiography. Patients were classified into two groups: those with and those without stenosis of the aortoiliac segment (aortoiliac disease). RESULTS: In 77 of the 202 patients (38%) with peripheral arterial occlusive disease, the obstruction was confined to the aortoiliac segment. The occurrence of miscarriage was high (42%) in young women with aortoiliac disease. Compared to healthy controls, the risk of miscarriage increased 3-fold (OR 3.1; 95% CI 1.8-5.6) in these patients. Adjustment for obstetrical and vascular risk factors did not affect the risk estimate. CONCLUSION: This is the first study that identifies aortoiliac disease as a risk factor for pregnancy loss in young women. The risk of miscarriage is increased 3-fold in women with aortoiliac disease. The presence of vascular and obstetrical risk factors did not affect the strength of the association. Pregnancy loss could be the first sign of insufficient aortic circulation in these patients.

Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus infections and the risk of peripheral arterial disease in young women.

Sero-epidemiological case control studies have observed positive relations between infections with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus (CMV) and the occurrence of coronary artery disease (CAD) and stroke. Moreover, positive relations between 'infection burden' and CAD and the role of inflammation have recently been described. However, the relations between infection, inflammation and the occurrence of peripheral arterial disease (PAD) have not been reported so far. We performed a multi-centre population-based case-control study, using serum samples of 228 young female PAD patients and 643 control women to determine IgG antibody titres and C-reactive protein. The odds ratios for PAD in women with serological evidence for infection with C. pneumoniae, H. pylori or CMV were 2.0 (95% CI; 1.3-3.1), 1.6 (95% CI; 1.1-2.2) and 1.6 (95% CI; 1.1-2.3), respectively. The cumulative number of infections was positively related to the risk of PAD; the odds ratio was 1.5 (95% CI; 1.0-2.4), 2.7 (95% CI; 1.6-4.4) and 3.5 (95% CI; 1.5-8.1) for women with one, two or three infections, respectively. This increased risk, related to the 'infection burden', was found again in the subgroup of women with a high CRP level, but not in the subgroup with a low CRP level. Infections might be a causal component in the development of PAD. The risk of PAD is not only related to a single pathogen in particular, but also to the cumulative number of infections. The positive relation between 'infection burden' and PAD was only found in women with a high CRP level, which indicates that inflammation might be involved in the process that leads to PAD.