RESUMEN
Mastocytosis is an emerging differential diagnosis in patients with more or less specific mediator-related symptoms. In some of these patients, typical skin lesions are found and the diagnosis of mastocytosis can be established. In other cases, however, skin lesions are absent, which represents a diagnostic challenge. In the light of this unmet need, we developed a diagnostic algorithm for patients with suspected mastocytosis. In adult patients with typical lesions of mastocytosis in the skin, a bone marrow (BM) biopsy should be considered, regardless of the basal serum tryptase concentration. In adults without skin lesions who suffer from mediator-related or other typical symptoms, the basal tryptase level is an important parameter. In those with a slightly increased tryptase level, additional investigations, including a sensitive KIT mutation analysis of blood leucocytes or measurement of urinary histamine metabolites, may be helpful. In adult patients in whom (i) KIT D816V is detected and/or (ii) the basal serum tryptase level is clearly increased (>25-30 ng/ml) and/or (iii) other clinical or laboratory features suggest the presence of 'occult' mastocytosis or another haematologic neoplasm, a BM investigation is recommended. In the absence of KIT D816V and other signs or symptoms of mastocytosis or another haematopoietic disease, no BM investigation is required, but the clinical course and tryptase levels are monitored in the follow-up. In paediatric patients, a BM investigation is usually not required, even if the tryptase level is increased. Although validation is required, it can be expected that the algorithm proposed herein will facilitate the management of patients with suspected mastocytosis and help avoid unnecessary referrals and investigations.
Asunto(s)
Algoritmos , Mastocitosis/diagnóstico , HumanosRESUMEN
BACKGROUND: Risk indicators of indolent systemic mastocytosis (ISM) in adults with clinical suspicion of ISM without accompanying skin lesions [urticaria pigmentosa (UP)] are lacking. This study aimed at creating a decision tree using clinical characteristics, serum tryptase, and the urinary histamine metabolites methylimidazole acetic acid (MIMA) and methylhistamine (MH) to select patients for bone marrow investigations to diagnose ISM. METHODS: Retrospective data analysis of all adults, in whom bone marrow investigations were performed to diagnose ISM, was carried out. RESULTS: In total, 142 patients were included. SM was absent in all 44 patients with tryptase <10 µg/l, in 45 of 98 (46%) patients with tryptase ≥10 µg/l and in 18 of 52 patients (35%) with tryptase >20 µg/l. Above 43 µg/l, all patients had ISM (n = 11). Male gender, insect venom anaphylaxis as presenting symptom, tryptase, MIMA, and MH were independent ISM predictors. If tryptase was ≥10 µg/l, the diagnostic accuracy of MIMA and MH was high (areas under the ROC curve 0.92). CONCLUSIONS: In suspected patients without UP, the ISM risk is very low (if present at all) if tryptase is <10 µg/l. If tryptase is ≥10 µg/l, this risk depends on MIMA and MH, being low if these are normal, but high if these are elevated. Male gender and insect venom anaphylaxis are additional risk indicators. We recommend refraining from bone marrow examinations in suspected patients without UP if tryptase is <10 µg/l. Our results question the reliability of the minor diagnostic World Health Organization criterion of tryptase >20 µg/l.
Asunto(s)
Imidazoles/orina , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/diagnóstico , Metilhistaminas/orina , Triptasas/sangre , Urticaria Pigmentosa/complicaciones , Adulto , Médula Ósea/metabolismo , Médula Ósea/patología , Femenino , Histamina/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , RiesgoRESUMEN
BACKGROUND: Indolent systemic mastocytosis (ISM) is a rare disease characterized by accumulation of abnormal mast cells in various tissues, including bone marrow. Symptoms are usually related to release of mast cell mediators. The aims are to establish the prevalence of osteoporotic fractures in ISM and to investigate the association with serum tryptase and the urinary histamine metabolites, methylhistamine (MH), and methylimidazole acetic acid. METHODS: The fracture prevalence in 157 patients (65 men; 92 women), mean age 54 ± 12 years, was assessed by vertebral morphometry and data from patient records, supplemented by a questionnaire. Bone mineral density (BMD) of lumbar spine and femoral neck was measured, and tryptase and histamine metabolites were analysed. RESULTS: We registered 235 lifetime fractures in 154 patients, including 140 osteoporotic (low-energy trauma) fractures, of which 62% were vertebral, 1% hip and 36% other nonvertebral fractures. Osteoporotic fractures and osteoporosis were found in 37% and 28% of the patients, respectively. In men, the prevalence of these osteoporotic manifestations (46% <50 years; 73% ≥50 years) was much higher compared with women (18% <50 years; 58% ≥50 years). Older age, male gender, and higher urinary MH were independently related to the osteoporotic manifestations. CONCLUSIONS: This first publication about prevalence of fractures and osteoporosis in patients with ISM shows that the risk of osteoporotic fractures is high, especially in men. Higher urinary MH levels are associated with a higher risk of osteoporotic manifestations. Routine measurements of BMD and vertebral morphometry are warranted in these patients for early detection of osteoporosis.
Asunto(s)
Fracturas Óseas/epidemiología , Osteoporosis/epidemiología , Triptasas/sangre , Adulto , Anciano , Densidad Ósea , Femenino , Cuello Femoral/diagnóstico por imagen , Fracturas Óseas/diagnóstico por imagen , Histamina/metabolismo , Humanos , Vértebras Lumbares/diagnóstico por imagen , Masculino , Mastocitosis Sistémica/diagnóstico por imagen , Mastocitosis Sistémica/epidemiología , Mastocitosis Sistémica/fisiopatología , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Prevalencia , Radiografía , Columna VertebralRESUMEN
BACKGROUND: Mastocytosis is an uncommon disease resulting from proliferation of abnormal mast cells infiltrating skin, bone marrow, liver, and other tissues. The aim of this study was to find differences in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis compared to healthy controls. The second aim was to define a specific gene expression profile in patients with mastocytosis. METHODS: Twenty-two patients with indolent systemic mastocytosis and 43 healthy controls were studied. Whole genome gene expression analysis was performed on RNA samples isolated from the peripheral blood. For amplification and labelling of the RNA, the Illumina TotalPrep 96 RNA Amplification Kit was used. Human HT-12_V3_expression arrays were processed. Data analysis was performed using GeneSpring, Genecodis, and Transcriptional System Regulators. RESULTS: Comparison of gene expression between patients and controls revealed a significant difference (P < 0.05 corrected for multiple testing) and the fold change difference >2 in gene expression in 2303 of the 48.794 analysed transcripts. Functional annotation indicated that the main pathways in which the differently expressed genes were involved are ubiquitin-mediated proteolysis, MAPK signalling pathway, pathways in cancer, and Jak-STAT signalling. The expression distributions for both groups did not overlap at all, indicating that many genes are highly differentially expressed in both groups. CONCLUSION: We were able to find abnormalities in gene expression in peripheral blood cells of patients with indolent systemic mastocytosis and to construct a gene expression profile which may be useful in clinical practice to predict the presence of mastocytosis and in further research of novel drugs.
Asunto(s)
Perfilación de la Expresión Génica , Mastocitosis Sistémica/genética , Transducción de Señal/genética , Transcripción Genética , Adulto , Anciano , Células Sanguíneas/metabolismo , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Mastocitosis Sistémica/sangre , Persona de Mediana Edad , ARN Mensajero/análisisRESUMEN
BACKGROUND: Anaphylaxis to insect venom (Hymenoptera) is most severe in patients with mastocytosis and may even lead to death. However, not all patients with mastocytosis suffer from anaphylaxis. The aim of the study was to analyze differences in gene expression between patients with indolent systemic mastocytosis (ISM) and a history of insect venom anaphylaxis (IVA) compared to those patients without a history of anaphylaxis, and to determine the predictive use of gene expression profiling. METHODS: Whole-genome gene expression analysis was performed in peripheral blood cells. RESULTS: Twenty-two adults with ISM were included: 12 with a history of IVA and 10 without a history of anaphylaxis of any kind. Significant differences in single gene expression corrected for multiple testing were found for 104 transcripts (P < 0.05). Gene ontology analysis revealed that the differentially expressed genes were involved in pathways responsible for the development of cancer and focal and cell adhesion suggesting that the expression of genes related to the differentiation state of cells is higher in patients with a history of anaphylaxis. Based on the gene expression profiles, a naïve Bayes prediction model was built identifying patients with IVA. CONCLUSIONS: In ISM, gene expression profiles are different between patients with a history of IVA and those without. These findings might reflect a more pronounced mast cells dysfunction in patients without a history of anaphylaxis. Gene expression profiling might be a useful tool to predict the risk of anaphylaxis on insect venom in patients with ISM. Prospective studies are needed to substantiate any conclusions.
Asunto(s)
Anafilaxia/genética , Insectos , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/genética , Ponzoñas/inmunología , Adulto , Anciano , Anafilaxia/etiología , Animales , Estudios de Casos y Controles , Femenino , Perfilación de la Expresión Génica , Humanos , Himenópteros , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
The most important causative factor for anaphylaxis in mastocytosis are insect stings. The purpose of this review is to analyse the available data concerning prevalence, diagnosis, safety and effectiveness of venom immunotherapy (VIT) in mastocytosis patients. If data were unclear, authors were contacted personally for further information. Quality of evidence (A: high, B: moderate, C: low and D: very low) and strength of recommendation (strong 1 and weak 2) concerning VIT in mastocytosis patients are assessed according to the Grading of Recommendations Assessment, Development and Evaluation and are marked in square brackets. Results of VIT were described in 117 patients to date. The mean rate of side-effects during treatment in studies published so far is 23.9% (7.6% requiring adrenaline) with an overall protection rate of 72%. Based on the review we conclude that (1) mastocytosis patients have a high risk of severe sting reactions in particular to yellow jacket, (2) VIT could be suggested [2] in mastocytosis, (3) probably should be done life long [2], (4) VIT in mastocytosis is accompanied by a higher frequency of side-effects, so (5) special precautions should be taken into account notably during the built up phase of the therapy [2], (6) VIT is able to reduce systemic reactions, but to a lesser extent compared to the general insect venom allergic population [2], so (7) patients should be warned that the efficacy of VIT might be less than optimal and they should continue carrying two adrenaline auto injectors [2].
Asunto(s)
Anafilaxia/inmunología , Venenos de Artrópodos/uso terapéutico , Mastocitosis/inmunología , Mastocitosis/terapia , Avispas/inmunología , Animales , Venenos de Artrópodos/efectos adversos , Humanos , Inmunoterapia/efectos adversos , Mordeduras y Picaduras de Insectos/inmunología , Mastocitosis/epidemiologíaRESUMEN
The high cardiovascular disease prevalence in western countries is largely attributable to the contemporary lifestyle. Interventions in the area of nutrition and physical activity have been shown to be effective in the prevention of cardiovascular disease. Successful implementation of lifestyle intervention programmes may be just as effective as drug treatment. In combination with drug treatment, intervention in the area of nutrition and physical activity is the recommended treatment for patients at a high risk of cardiovascular disease. Addition of new drugs to those presently available is associated with low absolute risk reductions and high costs, particularly in the presence of successful lifestyle interventions.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico/fisiología , Estilo de Vida , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/epidemiología , Dieta , Educación en Salud , Promoción de la Salud , Humanos , Factores de RiesgoRESUMEN
A 31-year-old woman presented with recurrent transient monocular blindness. As transient ischaemic attacks were suspected further investigations were targeted at evaluation of premature atherosclerotic lesions in the internal carotid artery. Initially laboratory tests were not performed. After referral to a cardiovascular-disease prevention outpatient clinic, laboratory evaluation disclosed a marked isolated polycythaemia that turned out to be secondary to right-left shunting through multiple pulmonary arteriovenous malformations. The ultimate diagnosis was hereditary haemorrhagic telangiectasia. Later on, physical signs such as telangiectasia and central cyanosis were noticed. In the clinical decision-making process, laboratory tests associated with causes of transient monocular visual loss were not carried out and therefore clues important for the ultimate diagnosis were not obtained. In only a minority of young patients with transient monocular visual loss can this be ascribed to premature atherosclerosis. For these reasons, a proper physical examination and laboratory tests directed towards other causes must be part of the initial diagnostic work-up in young patients with visual disturbances and suspected transient ischaemic attacks.
Asunto(s)
Amaurosis Fugax/etiología , Policitemia/etiología , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Adulto , Malformaciones Arteriovenosas/complicaciones , Malformaciones Arteriovenosas/diagnóstico , Malformaciones Arteriovenosas/genética , Diagnóstico Diferencial , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Ataque Isquémico Transitorio/diagnósticoRESUMEN
BACKGROUND: Homocysteine is a cardiovascular disease risk factor. We investigated, both in subjects with past plasma total homocysteine (tHcy) test indications and healthy adults, the diagnostic value of a fasting (tHcy) (f-tHcy) and the added value of a post-methionine-load tHcy (postload-tHcy). METHODS: Plasma homocysteine cut-off values were retrospectively used for hyperhomocysteinemia assessment in 3477 subjects with past tHcy test indications and 177 apparently healthy subjects. Cut-off values were based on reference limits (f-tHcy < or = 15.0; postload-tHcy < or = 50.0 micro mol/l), relative risk (f-tHcy < or = 12.0, postload-tHcy < or = 38.0; or f-tHcy < or = 10.0 micro mol/l) and vitamin-optimized reference limits (f-tHcy < or = 9.3; postload-tHcy < or = 35.1 micro mol/l). RESULTS: Use of the American Heart Association 10 micro mol/l f-tHcy cut-off value gave hyperhomocysteinemia prevalences of 65% in subjects with past tHcy test indications and 50% in healthy subjects. The combination of the vitamin-optimized reference limits for f-tHcy and postload-tHcy gave a hyperhomocysteinemia prevalence of 79% in subjects with tHcy test indications, of which only 5% was on account of increased postload-tHcy. Corresponding values for healthy subjects were 68% and 3%, respectively. CONCLUSIONS: Employment of a 10 micro mol/l (American Heart Association) or 9.3 micro mol/l (vitamin-optimized reference) cut-off value leaves no indications for tHcy testing from an evidence-based point-of-view.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Ayuno/sangre , Homocisteína/sangre , Hiperhomocisteinemia/sangre , Metionina/administración & dosificación , Adulto , Femenino , Humanos , Hiperhomocisteinemia/diagnóstico , Hiperhomocisteinemia/epidemiología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Prevalencia , Valores de Referencia , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
UNLABELLED: Autoimmunity is suggested to play a pathogenetic role in premature atherosclerosis. Since atherosclerosis and vasculitis seem pathogenetically related, we hypothesized that ANCA, an important antibody in vasculitis, plays a role in atherosclerosis as well. We therefore investigated the prevalence of ANCA in patients with premature atherosclerosis and related the presence of these antibodies to levels of AECA and markers of inflammation. METHODS & RESULTS: In a cohort of 286 patients with premature atherosclerosis the prevalence of ANCA was 5.6% (16/286). All had perinuclear ANCA. More females were ANCA-positive (8M/8F vs. 200M/70F, p = 0.03). In a nested case-control study, comparing the 16 ANCA-positive patients with 32 controls, levels of AECA were higher in the first (7.32 +/- 0.91U vs. 5.52 +/- 0.41U, p < 0.05). CONCLUSION: ANCA does not seem to play a major role in premature atherosclerosis. Whether elevated levels of AECA in ANCA-positive patients with premature atherosclerosis reflect more extended vascular disease remains to be determined.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Arteriosclerosis/inmunología , Autoanticuerpos/sangre , Adulto , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Autoimmunity is suggested to play a role in premature atherosclerosis. Antineutrophil cytoplasmatic antibodies (ANCA) are a group of autoantibodies found in several inflammatory disorders in which they supposedly amplify the inflammatory process. In this study the hypothesis is tested that ANCA play a role in premature atherosclerosis. DESIGN: Cross-sectional study followed by nested case-control study. In a total of 286 consecutive patients with premature atherosclerosis (age < 55 years) ANCA were tested. Within the same cohort, a nested case-control study in 16 ANCA-positive patients and 32 ANCA-negative controls matched for sex, and site of atherosclerosis, was executed. SETTING: University hospital outpatient clinic for lipids and premature atherosclerosis. SUBJECTS: A total of 286 consecutive patients with premature atherosclerosis (age < 55 years). RESULTS: Prevalence of ANCA was 5.6% (16 of 286). All cases had perinuclear ANCA (pANCA); no cytoplasmatic ANCA was found. Mean age was 42 +/- 7 in the ANCA-positive vs. 42 +/- 9 years in the ANCA-negative group (P=ns). More female parents were ANCA-positive (8M/8F vs. 200M/70F, P=0.03). Patients with ANCA had more often peripheral vascular disease (37.5 vs. 15.2%, P=0.03). In the case-control study levels of Lp(a) were higher (43.8 vs. 15.6% >300 mg x L(-1), P=0.05), whereas levels of HDL-c were lower in ANCA-positive patients (0.84 +/- 0.26 vs. 1.06 +/- 0.27 mmol x L(-1), P=0.01). Markers of inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), did not differ, nor did antibodies against oxidized-LDL and malondialdehyde (MDA)-LDL, markers for the extent of atherosclerosis. CONCLUSIONS: Our results suggest that ANCA do not appear to play a major role in premature atherosclerosis as there was no increased prevalence of the autoantibody. Moreover, no differences in the incidence of classical cardiovascular risk factors nor in serum levels of markers of inflammation were found between the ANCA-positive group as compared with the ANCA-negative group.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/análisis , Arteriosclerosis/inmunología , Adulto , Análisis de Varianza , Arteriosclerosis/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Regresión , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Treatment of hypercholesterolaemia with HMG-CoA reductase inhibitors results in an earlier reduction of morbidity and mortality than expected from trials using conventional cholesterol-lowering therapies. Possible explanations for this effect include stimulation of angiogenesis, improvement of endothelial function, plaque stabilisation, inhibition of coagulation and/or thrombocyte aggregation and inhibition of the inflammatory response associated with atherosclerosis. METHODS: We investigated whether statins exert their effects by inhibition of endothelial activation, inflammation and/or monocyte/macrophage activation by measuring plasma levels of soluble cell adhesion molecules, neopterin and C-reactive protein upon treatment with fluvastatin for a period of 12 months in patients with established atherosclerosis and hypercholesterolaemia. RESULTS: Blood samples were taken at baseline and at 3 and 12 months after starting treatment with fluvastatin 80 mg daily. Upon treatment, a reduction of s-ICAM-1 (956.3+/-123.6 vs. 745.4+/-127.4 vs. 674.9+/-70.8 ng/ml, P<0.05) and s-E-selectin (58.6+/-6.7 vs. 47.0+/-6.1 vs. 44.9+/-3.2 ng/ml, P<0.01) was observed. In addition, levels of neopterin decreased, albeit transiently (7.1+/-0.7 vs. 6.0+/-0.5 vs. 6.5+/-0.8 nmol/l, P=0.02), suggesting a reduction in monocyte/macrophage activity. Moreover, we found a decrease in levels of C-reactive protein during follow-up (5.21+/-2.0 vs. 3.18+/-0.7 vs. 1.95+/-0.3 mg/l, P<0.05), compatible with a reduction in inflammatory activity. CONCLUSION: We conclude that statins have a combined beneficial effect on monocyte/macrophage activity, endothelial function and systemic inflammatory activity.
RESUMEN
BACKGROUND: Hyperhomocysteinemia is a cardiovascular disease (CVD) risk factor. We determined plasma homocysteine (Hcy) reference values at optimized vitamin status and investigated their influence on the prevalence of hyperhomocysteinemia in healthy adults. Results were compared with those obtained using European Concerted Action Project (ECAP) cutoff values. METHODS: Healthy adults (n = 101) received folic acid (5 mg/day) and vitamin B(12) (1 mg/day) for 2 weeks and the same dosages of folic acid and vitamin B(12) plus vitamin B(6) (1 mg. kg(-1). day(-1)) during the following 2 weeks. Hcy concentrations, both fasting and 6-h post-methionine load, were determined at baseline and after 4 weeks. RESULTS: Baseline (4 weeks) fasting and 6-h postload Hcy reference values were 4.7-14.6 (4.1-9.3) and 18.8-49.7 (12.9-35.1) micromol/L, respectively. Mean fasting and 6-h postload Hcy decreased after 4 weeks of vitamin supplementation by 3.5 micromol/L (33.5%) and 8.5 micromol/L (26.3%), respectively. The percentages of subjects exhibiting significant decreases in fasting Hcy following vitamin supplementation were 88% (all subjects), 92% (non-vitamin users), and 72% (vitamin users). The prevalences of hyperhomocysteinemia with use of ECAP cutoff values were 29% for all groups, 29% for men, 27% for premenopausal women, and 53% for postmenopausal women. With vitamin-optimized cutoff values, prevalences were 58%, 58%, 76%, and 89%, respectively. Use of vitamin-optimized cutoff values increased the diagnostic value of fasting Hcy and decreased that of a 6-h postload Hcy compared with use of ECAP cutoff values. CONCLUSIONS: Use of vitamin-optimized cutoff values gives rise to high hyperhomocysteinemia pretest probabilities in the general population and, therefore, precludes any meaningful role for Hcy testing. Future demonstration of a beneficial effect of decreasing Hcy on CVD risk would justify use of vitamin-optimized cutoff values for assessment of CVD risk.
Asunto(s)
Homocisteína/sangre , Hiperhomocisteinemia/epidemiología , Vitaminas/farmacología , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Femenino , Ácido Fólico/administración & dosificación , Ácido Fólico/farmacología , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/complicaciones , Masculino , Persona de Mediana Edad , Prevalencia , Piridoxina/administración & dosificación , Piridoxina/farmacología , Vitamina B 12/administración & dosificación , Vitamina B 12/farmacología , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: Unstable coronary syndromes, such as acute myocardial infarction and unstable angina pectoris are mostly due to rupture of an atherosclerotic plaque. Recently mast cells were found to participate actively in the inflammatory process of atherosclerosis by excreting proteolytic and pro-inflammatory substances with the ability to cause plaque instability and rupture. Mast cell activity can be determined by measuring serum levels of tryptase, as has been demonstrated in patients with anaphylaxis and mastcytosis. HYPOTHESIS: Acute coronary events (acute myocardial infarction and unstable angina pectoris) are associated with increased mast cell activity, reflected by elevated serum tryptase levels. METHODS: Serum levels of tryptase were determined in the following three groups of patients: 13 patients with acute myocardial infarction, 10 patients with unstable angina pectoris, and 14 patients without ischaemic cardiovascular disease who were used as controls. Patients with known IgE mediated allergic diseases and/or anti-histaminical drugs were excluded. RESULTS: The groups were comparable for sex, blood pressure, smoking and cholesterol levels. The controls tended to be younger (P=0.05). Levels of tryptase did not differ between patients with acute myocardial infarction (7.9+/-4.6 microg/l), unstable angina pectoris (6.0+/-2.1 microg/l) or controls (6.9+/-4.1 microg/l), nor could a relation with levels of C-reactive protein be demonstrated. CONCLUSION: Serum levels of tryptase are not elevated in patients with acute coronary syndromes. This implies that increased mast cell activity, if any, in unstable coronary syndromes is not reflected systemically. Other, more specific methods will be needed to determine the activity of the mast cell in vivo.
Asunto(s)
Angina Inestable/fisiopatología , Mastocitos/fisiología , Infarto del Miocardio/fisiopatología , Adulto , Anciano , Angina Inestable/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Proyectos Piloto , Serina Endopeptidasas/sangre , TriptasasRESUMEN
Several studies have demonstrated the beneficial effects of 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors on vascular properties, but little is known about treatment intensification. We compared patients in whom statins were started (INITIAL, n=30) for hypercholesterolaemia (>6.5 mmol l(-1)) with a matched patient group of long-time statin users, with similar baseline characteristics for lipids, intima-media thickness (IMT), and pulse wave velocity, in whom treatment with statins was intensified (LONG-TERM, n=54). At baseline and after 1 year, lipid profile, IMT of the carotid and femoral arteries, aortic distensibility using pulse-wave velocity and various properties of the peripheral vascular bed using a recently developed bio-impedance method were measured. After 1 year the relative changes in lipid profile were significantly better in the INITIAL compared with the LONG-TERM-group. The relative changes in IMT of the mean internal carotid and common femoral arteries significantly differed between the INITIAL and LONG-TERM-group (-8 and +11%, -11 and +22%, respectively). After 1 year, in both groups, most other vascular wall characteristics were unaltered compared with baseline. In conclusion, the beneficial structural alterations of the vascular wall were greater after starting than after intensifying already existing lipid-lowering treatment. This suggests that other effects of HMG-CoA reductase inhibitors than lipid-lowering alone must be involved in vascular changes.
Asunto(s)
Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/diagnóstico por imagen , Arteria Femoral/efectos de los fármacos , Arteria Femoral/diagnóstico por imagen , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Pravastatina/uso terapéutico , Simvastatina/uso terapéutico , Adulto , Velocidad del Flujo Sanguíneo , Arterias Carótidas/fisiopatología , Impedancia Eléctrica , Arteria Femoral/fisiopatología , Estudios de Seguimiento , Humanos , Hipercolesterolemia/diagnóstico por imagen , Hipercolesterolemia/fisiopatología , Persona de Mediana Edad , Pulso Arterial , Estudios Retrospectivos , Factores de Tiempo , Túnica Íntima/patología , Túnica Media/patología , UltrasonografíaRESUMEN
OBJECTIVE: To examine the maternal and neonatal outcome of pregnancies of women with type I diabetes mellitus. DESIGN: Retrospective. METHODS: The medical records of pregnancies (> or = 16 weeks) in women with type I diabetes mellitus between 1986/'97 were studied in University Medical Center Utrecht, Academic Hospital Groningen and Isala Clinics, location 'De Weezenlanden', Zwolle, the Netherlands. RESULTS: During the study period, 172 women had 220 pregnancies: 212 single and 8 twin pregnancies. The mean age was 29.1 years (SD: 4.1), the mean duration of standing of the diabetes was 12 years (range: 1-32) and the mean concentration of glycosylated haemoglobin (HbA1c) was 6.3% at 10 weeks of pregnancy. The incidence of children with congenital malformations was 4 times higher (n = 19; 9.0%) than that in the Dutch population (2%). Macrosomia occurred in 92 children (43.4%) and perinatal mortality in 7 (3.3%). Maternal hypertensive complications occurred in 39 single pregnancies (18.4%), which is 2-3 times more often than in the Dutch population. CONCLUSION: In type I diabetic women maternal complications, perinatal morbidity and mortality are increased, despite near optimal glycaemic control.
Asunto(s)
Anomalías Congénitas/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/mortalidad , Complicaciones Cardiovasculares del Embarazo/epidemiología , Embarazo en Diabéticas/epidemiología , Adulto , Edad de Inicio , Anomalías Congénitas/etiología , Diabetes Mellitus Tipo 1/sangre , Femenino , Macrosomía Fetal/epidemiología , Hemoglobina Glucada/metabolismo , Humanos , Incidencia , Mortalidad Infantil , Recién Nacido , Masculino , Registros Médicos , Países Bajos/epidemiología , Vigilancia de la Población , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , GemelosRESUMEN
The D9N substitution is a common mutation in the lipoprotein lipase (LPL) gene. This mutation has been associated with reduced levels of HDL cholesterol and elevated triglycerides (TG) in a wide variety of patients. We investigated the influence of this D9N mutation on lipid and lipoprotein levels and risk for cardiovascular disease (CVD) in patients with familial hypercholesterolemia (FH). A total of 2091 FH heterozygotes, all of Dutch extraction, were screened for the D9N mutation using standard polymerase chain reaction techniques, followed by specific enzyme digestion. A total of 94 FH subjects carried the D9N mutation at a carrier frequency of 4.5%. Carriers of other common LPL mutations, such as the N291S and the S447X were excluded. Clinical data on 80 FH individuals carrying the D9N were available and were compared with a FH control group matched for age, sex, and body mass index (n=203). Analysis revealed significantly higher TG (P=0.01) and lower HDL-cholesterol levels (P=0.002). Dyslipidemia was more pronounced in D9N carriers with higher body mass index. Moreover, FH patients carrying this common LPL mutation were at higher risk for CVD, (odds ratio=2.8; 95% CI, 1.43 to 5.32; P=0.002). The common D9N LPL mutation leads to increased TG and decreased HDL plasma levels in patients with FH. These effects are most apparent in those FH heterozygotes with an increased body mass index. Furthermore, this mutation, present in 4.5% of Dutch FH heterozygotes, leads to increased risk for CVD.
Asunto(s)
Hipercolesterolemia/genética , Lipoproteína Lipasa/genética , Mutación Puntual , Adolescente , Adulto , Anciano , Apolipoproteínas A/sangre , Índice de Masa Corporal , Enfermedades Cardiovasculares/enzimología , Enfermedades Cardiovasculares/genética , Niño , Preescolar , HDL-Colesterol/sangre , Estudios de Cohortes , Susceptibilidad a Enfermedades , Salud de la Familia , Femenino , Frecuencia de los Genes , Humanos , Hipercolesterolemia/enzimología , Lipoproteína Lipasa/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenotipo , Triglicéridos/sangreRESUMEN
Obstetrical problems sometimes portend manifestations of atherosclerosis, as illustrated by two case reports. The first patient had the combination of hyperhomocysteinaemia due to chronic vitamin deficiencies in the diet, and smoking. The second was also a smoker and had a genetically determined mild hyperhomocysteinaemia, aggravated by chronic vitamin deficiencies resulting from poor dietary habits; she also had an increased folic acid requirement because of use of anti-epileptic drugs in combination with a familial predisposition for premature atherosclerotic manifestations. The first patient had four pregnancies, two of which ended in intrauterine foetal death due to placental infarction, and one in the birth of a dysmature boy. The second patient's four pregnancies ended twice in abortion and twice in the birth of a dysmature child; in one of the latter cases placental infarction was observed. Both women subsequently suffered cerebrovascular accidents while in addition, older cerebral infarctions were found to be present. Women with recurrent abortion, pre-eclampsia, placental infarction, placental detachment and foetal growth retardation should be examined, even if other risk factors are also present, for (mild) hyperhomocysteinaemia, and treated for it with vitamin suppletion (folic acid, vitamins B6 and B12), even although admittedly more research is necessary to make certain that such treatment has a preventive effect on the manifestations of this disorder.