当前期刊: Journal of Internal Medicine Go to current issue    加入关注   
显示样式:        排序: 导出
  • Incidence of myeloproliferative neoplasms – trends by subgroup and age in a population‐based study in Sweden
    J. Intern. Med. (IF 6.051) Pub Date : 2020-01-11
    M. Hultcrantz; A. Ravn Landtblom; B. Andréasson; J. Samuelsson; P. W. Dickman; S. Y. Kristinsson; M. Björkholm; T. M.‐L. Andersson
  • Familial chylomicronemia syndrome: an under‐recognized cause of severe hypertriglyceridaemia
    J. Intern. Med. (IF 6.051) Pub Date : 2020-01-08
    A. Baass; M. Paquette; S. Bernard; R.A. Hegele
  • Hospital‐diagnosed overweight and obesity related to cancer risk: a 40‐year Danish cohort study
    J. Intern. Med. (IF 6.051) Pub Date : 2020-01-07
    S. B. Gribsholt; D. Cronin‐Fenton; K. Veres; R. W. Thomsen; A. G. Ording; B. Richelsen; H. T. Sørensen
  • Apolipoprotein B48 metabolism in chylomicrons and very low‐density lipoproteins and its role in triglyceride transport in normo‐ and hypertriglyceridemic human subjects
    J. Intern. Med. (IF 6.051) Pub Date : 2020-01-07
    E. Björnson; C.J. Packard; M. Adiels; L. Andersson; N. Matikainen; S. Söderlund; J. Kahri; A. Hakkarainen; N. Lundbom; J. Lundbom; C. Sihlbom; A. Thorsell; H. Zhou; M.‐R. Taskinen; J. Borén
  • Phenotypic features of vascular calcification in chronic kidney disease
    J. Intern. Med. (IF 6.051) Pub Date : 2019-12-10
    L. Dai, M. Debowska, T. Lukaszuk, L. Bobrowski, P. Barany, M. Söderberg, D. Thiagarajan, J. Frostegård, L. Wennberg, B. Lindholm, A. R. Qureshi, J. Waniewski, P. Stenvinkel
  • 更新日期:2019-12-11
  • Evolutionary basis for the human diet: consequences for human health
    J. Intern. Med. (IF 6.051) Pub Date : 2019-12-09
    P. Andrews, R.J. Johnson
  • Plasma metabolite biomarkers of boiled and filtered coffee intake and their association with type 2 diabetes risk
    J. Intern. Med. (IF 6.051) Pub Date : 2019-12-09
    L. Shi, C. Brunius, I. Johansson, I.A. Bergdahl, O. Rolandsson, B. van Guelpen, A. Winkvist, K. Hanhineva, R. Landberg

    Habitual coffee intake has been associated with a lower risk of developing type 2 diabetes (T2D), but few studies used biomarkers to reflect intake and investigated different coffee brews, that is boiled and filtered, separately.

  • Low rate of new‐onset primary biliary cholangitis in a cohort of anti‐mitochondrial antibody‐positive subjects over six years of follow‐up
    J. Intern. Med. (IF 6.051) Pub Date : 2019-12-04
    S. Zandanell, M. Strasser, A. Feldman, J. Tevini, G. Strebinger, D. Niederseer, G. Pohla‐Gubo, U. Huber‐Schönauer, S. Ruhaltinger, B. Paulweber, C. Datz, T.K. Felder, E. Aigner
  • Beyond neurotransmission: acetylcholine in immunity and inflammation
    J. Intern. Med. (IF 6.051) Pub Date : 2019-12-03
    M. A. Cox, C. Bassi, M. E. Saunders, R. Nechanitzky, I. Morgado‐Palacin, C. Zheng, T. W. Mak
  • The epidemic of drug‐induced sarcoidosis‐like reactions: a side effect that we can live with
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-28
    M.A. Judson

    Click here to view the Rapid communication by Cohen Aubart et al.

  • Hypervirulent Klebsiella pneumoniae – clinical and molecular perspectives
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-21
    J. E. Choby, J. Howard‐Anderson, D. S. Weiss
  • Lack of an effective drug therapy for abdominal aortic aneurysm
    J. Intern. Med. (IF 6.051) Pub Date : 2019-07-29
    J. Golledge, J. V. Moxon, T. P. Singh, M. J. Bown, K. Mani, A. Wanhainen
  • PCSK9 decreases during experimental endotoxemia
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-14
    C. Schoergenhofer, P. Matzneller, J. Mühlbacher, L. Hell, M. Zeitlinger, B. Jilma

    Click here to view the Original article by Rannikko et al.

  • The hospital frailty risk score in patients with heart failure is strongly associated with outcomes but less so with pharmacotherapy
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-14
    F. A. McAlister, A. Savu, J. A. Ezekowitz, P. W. Armstrong, P. Kaul
  • Periodontal disease is associated with carotid plaque area: the Malmö Offspring Dental Study (MODS)
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-13
    D. Jönsson, M. Orho‐Melander, R. T. Demmer, G. Engström, O. Melander, B. Klinge, P. M. Nilsson
  • Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren’s syndrome
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-12
    S. Jousse‐Joulin, F. Gatineau, C. Baldini, A. Baer, F. Barone, H. Bootsma, S. Bowman, P. Brito‐Zerón, D. Cornec, T. Dorner, S. de Vita, B. Fisher, D. Hammenfors, M. Jonsson, X. Mariette, V. Milic, H. Nakamura, W.‐F. Ng, E. Nowak, M. Ramos‐Casals, A. Rasmussen, R. Seror, C.H. Shiboski, T. Nakamura, A. Vissink, A. Saraux, V. Devauchelle‐Pensec
  • Interaction of chylomicron remnants and VLDLs during ultracentrifuge separation based on the Svedberg flotation rate – Authors’ response
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-12
    E. Björnson, C.J. Packard, M.‐R. Taskinen, J. Borén

    Click here to view the Letter to the Editor by Stellaard and Lütjohann

  • Profiling of immune‐related gene expression in children with familial hypercholesterolaemia
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-12
    I. Narverud, J. J. Christensen, S. S. Bakke, S. M. Ulven, A. Rundblad, P. Aukrust, T. Espevik, M. P. Bogsrud, K. Retterstøl, T. Ueland, B. Halvorsen, K. B. Holven
  • Iron deficiency anaemia revisited
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-12
    M. D. Cappellini, K. M. Musallam, A. T. Taher
  • 更新日期:2019-11-13
  • Interaction of chylomicron remnants and VLDLs during ultracentrifuge separation based on the Svedberg flotation rate
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-10
    F. Stellaard, D. Lütjohann

    Click here to view the Original article by Björnson et al.

  • Atrial fibrillation in the course of pulmonary embolism: just a little smoke, or fuel to the fire?
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-10
    Behnood Bikdeli, David Jiménez

    Click here to view the Original Article by Ebner and Rogge et al.

  • 更新日期:2019-11-11
  • Leisure‐time physical activity and life expectancy in people with cardiometabolic multimorbidity and depression
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-06
    Y. V. Chudasama, F. Zaccardi, C. L. Gillies, N. N. Dhalwani, T. Yates, A. V. Rowlands, M. J Davies, K. Khunti
  • Drug‐induced sarcoidosis: an overview of the WHO pharmacovigilance database
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-06
    F. Cohen Aubart, R. Lhote, A. Amoura, D. Valeyre, J. Haroche, Z. Amoura, B. Lebrun‐Vignes

    There is a documented association between drug exposure and sarcoidosis‐like reactions. In this study, we used the largest pharmacovigilance database to describe drug‐induced sarcoidosis.

  • Associations between chronotype, MTNR1B genotype and risk of type 2 diabetes in UK Biobank
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-06
    X. Tan, D.‐M. Ciuculete, H.B. Schiöth, C. Benedict
  • Women living with HIV in high‐income settings and breastfeeding
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-06
    E. Moseholm, N. Weis
  • Response to Letter to the Editor by Bartoloni et al: ‘Interplay of anti‐SSA/SSB status and hypertension in determining cardiovascular risk in primary Sjögren’s syndrome’
    J. Intern. Med. (IF 6.051) Pub Date : 2019-11-05
    J. Mofors, M. Wahren‐Herlenius, G. Nordmark

    Click here to view the Letter to the Editor by Bartoloni et al.

  • Fructose metabolism as a common evolutionary pathway of survival associated with climate change, food shortage and droughts
    J. Intern. Med. (IF 6.051) Pub Date : 2019-10-31
    R. J. Johnson, P. Stenvinkel, P. Andrews, L. G. Sánchez‐Lozada, T. Nakagawa, E. Gaucher, A. Andres‐Hernando, B. Rodriguez‐Iturbe, C. R. Jimenez, G. Garcia, D.‐H. Kang, D. R. Tolan, M. A. Lanaspa
  • 更新日期:2019-11-01
  • Globalization of Traditional Chinese Medicine: what are the issues for ensuring evidence-based diagnosis and therapy?
    J. Intern. Med. (IF 6.051) Pub Date : null
    R Fears,G E Griffin,D Larhammar,V Ter Meulen,J W M van der Meer

  • 更新日期:2019-11-01
  • Diagnosis and classification of idiopathic inflammatory myopathies.
    J. Intern. Med. (IF 6.051) Pub Date : 2016-06-21
    I E Lundberg,F W Miller,A Tjärnlund,M Bottai

    The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis-specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti-SRP and anti-HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables.

  • The juvenile idiopathic inflammatory myopathies: pathogenesis, clinical and autoantibody phenotypes, and outcomes.
    J. Intern. Med. (IF 6.051) Pub Date : 2016-03-31
    L G Rider,K Nistala

    The aim of this review was to summarize recent advances in the understanding of the clinical and autoantibody phenotypes, their associated outcomes and the pathogenesis of the juvenile idiopathic inflammatory myopathies (JIIMs). The major clinical and autoantibody phenotypes in children have many features similar to those in adults, and each has distinct demographic and clinical features and associated outcomes. The most common myositis autoantibodies in JIIM patients are anti-p155/140, anti-MJ and anti-MDA5. Higher mortality has been associated with overlap myositis as well as with the presence of anti-synthetase and anti-MDA5 autoantibodies; a chronic illness course and lipodystrophy have been associated with anti-p155/140 autoantibodies; and calcinosis has been associated with anti-MJ autoantibodies. Histologic abnormalities of JIIMs detectable on muscle biopsy have also been correlated with myositis-specific autoantibodies; for example, patients with anti-MDA5 show low levels of inflammatory infiltrate and muscle damage on biopsy. The first genome-wide association study of adult and juvenile dermatomyositis revealed three novel genetic associations, BLK, PLCL1 and CCL21 and confirmed that the human leucocyte antigen region is the primary risk region for juvenile dermatomyositis. Here, we review the well-established pathogenic processes in JIIMs, including the type 1 interferon and endoplasmic reticulum stress pathways. Several novel JIIM-associated inflammatory mediators, such as the innate immune system proteins, myeloid-related peptide 8/14, galectin 9 and eotaxin, have emerged as promising biomarkers of disease. Advances in our understanding of the phenotypes and pathophysiology of the JIIMs are leading to better tools to help clinicians stratify and treat these heterogeneous disorders.

  • Pathogenic immunity in systemic lupus erythematosus and atherosclerosis: common mechanisms and possible targets for intervention.
    J. Intern. Med. (IF 6.051) Pub Date : 2015-02-28
    M Wigren,J Nilsson,M J Kaplan

    Systemic lupus erythematosus (SLE) is an autoimmune disorder that primarily affects young women and is characterized by inflammation in several organs including kidneys, skin, joints, blood and nervous system. Abnormal immune cellular and humoral responses play important roles in the development of the disease process. Impaired clearance of apoptotic material is a key factor contributing to the activation of self-reactive immune cells. The incidence of atherosclerotic cardiovascular disease (CVD) is increased up to 50-fold in patients with SLE compared to age- and gender-matched controls, and this can only partly be explained by traditional risk factors for CVD. Currently, there is no effective treatment to prevent CVD complications in SLE. Traditional preventive CVD therapies have not been found to significantly lower the incidence of CVD in SLE; therefore, there is a need for novel treatment strategies and increased understanding of the mechanisms involved in the pathogenesis of CVD complications in SLE. The pathogenic immune responses in SLE and development of atherosclerotic plaques share some characteristics, such as impaired efferocytosis and skewed T-cell activation, suggesting the possibility of identifying novel targets for intervention. As novel immune-based therapies for CVD are being developed, it is possible that some of these may be effective for the prevention of CVD and for immunomodulation in SLE. However, further understanding of the mechanisms leading to an increased prevalence of cardiovascular events in SLE is critical for the development of such therapies.

  • 25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study.
    J. Intern. Med. (IF 6.051) Pub Date : 2014-06-04
    A Granic,T Aspray,T Hill,K Davies,J Collerton,C Martin-Ruiz,T von Zglinicki,T B L Kirkwood,J C Mathers,C Jagger

    OBJECTIVE To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years. DESIGN, SETTING AND SUBJECTS Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts. RESULTS For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol L(-1) ) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates. CONCLUSION Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.

  • Low blood pressure and antihypertensive treatment are independently associated with physical and mental health status in patients with arterial disease: the SMART study.
    J. Intern. Med. (IF 6.051) Pub Date : 2013-03-27
    M Muller,H M Jochemsen,F L J Visseren,A M Grool,L J Launer,Y van der Graaf,M I Geerlings,

    OBJECTIVE To investigate the independent effects of antihypertensive treatment and blood pressure (BP) levels on physical and mental health status in patients with arterial disease. DESIGN AND SETTING Cross-sectional analyses were conducted within the single-centre Secondary Manifestations of ARTerial disease (SMART) study, in a hospital care setting. SUBJECTS A total of 5877 patients (mean age 57 years) with symptomatic and asymptomatic arterial disease underwent standardized vascular screening. MAIN OUTCOME MEASURE The primary outcome was self-rated physical and mental health assessed using the 36-item short-form health survey. RESULTS In the total population, antihypertensive drug use and increased intensity of antihypertensive treatment were associated with poorer health status independent of important confounders including BP levels; adjusted mean differences [95% confidence interval (CI)] in physical and mental health between n = 0 and n ≥ 3 antihypertensives were -1.2 (-2.1; -0.3) and -3.5 (-4.4; -2.6), respectively. Furthermore, both lower systolic and lower diastolic BP levels were related to poorer physical and mental health status independent of antihypertensive treatment. Mean differences (95% CI) in physical and mental health status per SD decrease in systolic BP were -0.56 (-0.84; -0.27) and -0.32 (-0.61; -0.03) and per SD decrease in diastolic BP were -0.50 (-0.78; -0.23) and -0.08 (-0.36; 0.20), respectively. The association between low BP and poor health status was particularly present in patients with coronary artery disease. CONCLUSIONS In a population of patients with asymptomatic and symptomatic arterial disease, antihypertensive treatment and lower BP levels are independently associated with poorer self-rated physical and mental health. These findings suggest that different underlying mechanisms may explain these independent associations.

  • Relationship between vitamin D status and left ventricular geometry in a healthy population: results from the Baltimore Longitudinal Study of Aging.
    J. Intern. Med. (IF 6.051) Pub Date : 2012-10-16
    P Ameri,M Canepa,Y Milaneschi,P Spallarossa,G Leoncini,F Giallauria,J B Strait,E G Lakatta,C Brunelli,G Murialdo,L Ferrucci

    OBJECTIVES The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ventricular (LV) structure and function in community-dwelling subjects without heart disease. DESIGN The relationship between concentrations of 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease. RESULTS Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL(-1) ; only 15.5% of subjects had moderate or severe vitamin D deficiency [25(OH)D < 20 ng mL(-1) ]. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (β 0.095, SE 0.039, P < 0.05) and LV mass index (β 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels <30 ng mL(-1) [odds ratio (OR) 1.24; 95% confidence interval (CI) 0.83-1.85] or ≥38 ng mL(-1) (OR 1.73; 95% CI 1.13-2.65), compared with those with 30-37 ng mL(-1) 25(OH)D. Consistently, LV relative wall thickness was significantly lower (P for trend=0.05), and LV diastolic internal diameter index (P for trend<0.05) and end-diastolic volume index (P for trend<0.05) were significantly higher in subjects with 30-37 ng mL(-1) 25(OH)D compared to the rest of the study population. There was a significant interaction between 25(OH)D and hypertension on the risk of LV hypertrophy (P < 0.05). CONCLUSIONS In a population-based sample of predominantly vitamin D-sufficient subjects without heart disease, LV geometry was most favourable at intermediate 25(OH)D concentrations.

  • Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size The EPIC-InterAct study.
    J. Intern. Med. (IF 6.051) Pub Date : 2012-02-23
    J W J Beulens,Y T van der Schouw,M M Bergmann,S Rohrmann,M B Schulze,B Buijsse,D E Grobbee,L Arriola,S Cauchi,M-J Tormo,N E Allen,D L van der A,B Balkau,H Boeing,F Clavel-Chapelon,B de Lauzon-Guillan,P Franks,P Froguel,C Gonzales,J Halkjaer,J M Huerta,R Kaaks,T J Key,K T Khaw,V Krogh,E Molina-Montes,P Nilsson,K Overvad,D Palli,S Panico,J Ramón Quirós,O Rolandsson,O Ronaldsson,I Romieu,D Romaguera,C Sacerdote,M-J Sánchez,A M W Spijkerman,B Teucher,A Tjonneland,R Tumino,S Sharp,N G Forouhi,C Langenberg,E J M Feskens,E Riboli,N J Wareham,

    OBJECTIVE To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. DESIGN Multicentre prospective case-cohort study. SETTING Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. SUBJECTS A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. INTERVENTIONS Alcohol consumption assessed using validated dietary questionnaires. MAIN OUTCOME MEASURES Occurrence of type 2 diabetes based on multiple sources (mainly self-reports), verified against medical information. RESULTS Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78-1.05) for 6.1-12.0 versus 0.1-6.0 g day(-1) , adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1-96.0 g day(-1) with an HR of 0.86 (95% CI: 0.75-0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72-0.92) for 6.1-12.0 g day(-1) (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m(-2) ) than normal-weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79-1.03 for 6.1-12.0 g day(-1) ). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. CONCLUSIONS The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal-weight women and men.

  • Prevention of breast cancer in the context of a national breast screening programme.
    J. Intern. Med. (IF 6.051) Pub Date : 2012-02-02
    A Howell,S Astley,J Warwick,P Stavrinos,S Sahin,S Ingham,H McBurney,B Eckersley,M Harvie,M Wilson,U Beetles,R Warren,A Hufton,J Sergeant,W Newman,I Buchan,J Cuzick,D G Evans

    Breast cancer is not only increasing in the west but also particularly rapidly in eastern countries where traditionally the incidence has been low. The rise in incidence is mainly related to changes in reproductive patterns and lifestyle. These trends could potentially be reversed by defining women at greatest risk and offering appropriate preventive measures. A model for this approach was the establishment of Family History Clinics (FHCs), which have resulted in improved survival in younger women at high risk. New predictive models of risk that include reproductive and lifestyle factors, mammographic density and measurement of risk-associated single nucleotide polymorphisms (SNPs) may give more precise information concerning risk and enable better targeting for mammographic screening programmes and of preventive measures. Endocrine prevention using anti-oestrogens and aromatase inhibitors is effective, and observational studies suggest lifestyle modification may also be effective. However, referral to FHCs is opportunistic and predominantly includes younger women. A better approach for identifying older women at risk may be to use national breast screening programmes. Here were described pilot studies to assess whether the routine assessment of breast cancer risk is feasible within a population-based screening programme, whether the feedback and advice on risk-reducing interventions would be welcomed and taken up, and to consider whether the screening interval should be modified according to breast cancer risk.

  • Body fat mass is a predictor of risk of osteoporotic fractures in women but not in men: a prospective population study.
    J. Intern. Med. (IF 6.051) Pub Date : 2011-08-19
    A Moayyeri,R N Luben,N J Wareham,K-T Khaw

    OBJECTIVES Obesity has generally been associated with higher bone density and lower fracture risk. However, weight-related indices of obesity may be related differently to health end-points, compared with fat-related indices (such as body fat distribution and fat mass), as they may capture different dimensions of obesity and the associated biological effects. The aim of this study was to examine the association between percentage body fat (%BF) and prospective risk of fracture. METHODS The European Prospective Investigation into Cancer (EPIC) in Norfolk was a population-based prospective study. A total of 14 789 participants (6470 men, aged 42-82 years at baseline) were included. The main outcome measures were quantitative ultrasound of the heel and incident hip and any osteoporotic fractures. RESULTS A total of 556 participants suffered a fracture (184 hip fractures) during 8.7 ± 0.8 years of follow-up. Risk of hip fracture decreased linearly with increasing %BF amongst women but not men. After adjustment for age, history of fracture, height, smoking, alcohol intake and heel broadband ultrasound attenuation (BUA), the hazard ratio (95% CI) for a 10% higher %BF on risk of hip fracture was 0.56 (0.39-0.79) in women and 0.92 (0.39-2.21) in men. The effect size in women was approximately equivalent to a difference of 5 years in age or 1 standard deviation (17 dB MHz(-1) ) increased BUA. A nonlinear negative association was also observed between %BF and risk of 'any type of fracture' amongst women but not men. CONCLUSIONS The %BF appears to predict hip fracture risk in women with an effect size comparable to that of bone density as measured by heel ultrasound. This effect was not observed in men. Understanding the differences in relationships between different indices of obesity as well as sex differences may help to elucidate the metabolic and other underlying mechanisms involved in bone health and fracture risk.

  • Vascular imaging with positron emission tomography.
    J. Intern. Med. (IF 6.051) Pub Date : 2011-04-27
    F Joshi,D Rosenbaum,S Bordes,J H F Rudd

    Atherosclerosis is an inflammatory disease that causes most myocardial infarctions, strokes and acute coronary syndromes. Despite the identification of multiple risk factors and widespread use of drug therapies, it still remains a global health concern with associated costs. Although angiography is established as the gold standard means of detecting coronary artery stenosis, it does not image the vessel wall itself, reporting only on its consequences such as luminal narrowing and obstruction. MRI and computed tomography provide more information about the plaque structure, but recently positron emission tomography (PET) imaging using [(18) F]-fluorodeoxyglucose (FDG) has been advocated as a means of measuring arterial inflammation. This results from the ability of FDG-PET to highlight areas of high glucose metabolism, a feature of macrophages within atherosclerosis, particularly in high-risk plaques. It is suggested that the degree of FDG accumulation in the vessel wall reflects underlying inflammation levels and that tracking any changes in FDG uptake over time or with drug therapy might be a way of getting an early efficacy readout for novel anti-atherosclerotic drugs. Early reports also demonstrate that FDG uptake is correlated with the number of cardiovascular risk factors and possibly even the risk of future cardiovascular events. This review will outline the evidence base, shortcomings and emerging applications for FDG-PET in vascular imaging. Alternative PET tracers and other candidate imaging modalities for measuring vascular inflammation will also be discussed.

  • Lipoprotein-associated phospholipase A₂ activity and mass in relation to vascular disease and nonvascular mortality.
    J. Intern. Med. (IF 6.051) Pub Date : 2010-11-06

    OBJECTIVES To assess whether associations of circulating lipoprotein-associated phospholipase A₂ (Lp-PLA₂) with vascular disease are independent of other risk factors. METHODS Lp-PLA₂ activity and mass, lipids and other characteristics were measured at baseline in 19,037 individuals at high risk of vascular disease in a randomized trial of simvastatin with 5-year average follow-up. RESULTS Lp-PLA₂ activity and mass were correlated with each other (r = 0.56), lipids and other vascular risk factors. The moderate association of Lp-PLA₂ activity with occlusive coronary events (n = 2531) in analyses adjusted for nonlipid factors (hazard ratio per 1 SD [HR] 1.11, 95% CI 1.06-1.15) became nonsignificant after further adjustment for apolipoproteins (HR 1.02, 0.97-1.06). Such adjustment also attenuated HRs with Lp-PLA₂ mass from 1.08 (1.03-1.12) to 1.05 (1.01-1.09). By contrast, the HR with apolipoprotein-B100 of 1.15 (1.10-1.19) was only slightly attenuated to 1.14 (1.09-1.19) after further adjustment for apolipoprotein A₁ and Lp-PLA₂. Age- and sex-adjusted HRs for other cardiac events (n = 1007) with either Lp-PLA₂ activity or mass were about 1.20, but HRs reduced after adjustment for nonlipid factors (activity: 1.11, 1.04-1.18; mass: 1.08, 1.02-1.15). Adjusted HRs for ischaemic stroke (n = 900) were weak and nonsignificant and for nonvascular mortality (n = 1040) were 1.01 (0.94-1.09) with activity and 1.12 (1.05-1.19) with mass. Simvastatin reduced Lp-PLA₂ levels by about one-quarter, but simvastatin's vascular protection did not vary with baseline Lp-PLA₂ concentration. CONCLUSIONS Associations of Lp-PLA₂ with occlusive coronary events depend considerably on lipid levels, whereas those with other cardiac events appear to reflect confounding from cardiovascular medication and prior vascular disease.

  • Cystatin C and risk of vascular and nonvascular mortality: a prospective cohort study of older men.
    J. Intern. Med. (IF 6.051) Pub Date : 2010-03-27
    J R Emberson,R Haynes,T Dasgupta,M Mafham,M J Landray,C Baigent,R Clarke

    OBJECTIVE To assess the relevance of cystatin C, as a marker of mild-to-moderate renal impairment, for vascular and nonvascular mortality in older people. DESIGN Prospective cohort study. SETTING Re-survey in 1997 to 1998 of survivors in the 1970 Whitehall study of London civil servants. SUBJECTS Five thousand three hundred and seventy-one men (mean age at resurvey: 77 years) who took part in the resurvey and had plasma cystatin C concentration measured. MAIN OUTCOME MEASURES Cause-specific mortality over subsequent 11 years (1997 to 2008). METHODS Cox regression was used to estimate the associations of cystatin C with vascular and nonvascular mortality, before and after adjustment for prior disease and other risk factors (including lifetime blood pressure). RESULTS During an 11.0-year follow-up period, there were 1171 deaths from vascular causes [26 per 1000 per year (py)] and 1615 deaths from nonvascular causes (36 per 1000 py). Compared with men with cystatin C in the bottom fifth of the distribution, men in the top 10th had about two-fold higher mortality rates from vascular and nonvascular mortality (fully adjusted P both <0.001) even after adjustment for prior disease and all measured confounders, including lifetime blood pressure. The fully adjusted relative risks per 50% higher cystatin C concentrations were 1.66 [95% CI 1.48 to 1.85] for vascular mortality, 1.92 [95% CI 1.66 to 2.22] for ischaemic heart disease mortality and 1.46 [95% CI 1.31 to 1.61] for nonvascular mortality. CONCLUSIONS In older men, plasma concentration of cystatin C, probably as a marker of mild renal disease, is a strong independent predictor of both vascular and nonvascular mortality.

  • The genetics of ischaemic stroke.
    J. Intern. Med. (IF 6.051) Pub Date : 2010-02-24
    M Matarin,A Singleton,J Hardy,J Meschia

    In this review, we discuss the genetic factors in both the aetiology and treatment of ischaemic stroke. We discuss candidate gene association studies, family linkage studies and the more recent whole genome association studies and whole genome expression studies. We also briefly discuss genetic testing for stroke risk and genetic analysis of treatment complications.

  • 更新日期:2019-11-01
  • Modulating T-cell homeostasis with IL-7: preclinical and clinical studies.
    J. Intern. Med. (IF 6.051) Pub Date : 2009-07-23
    C M Capitini,A A Chisti,C L Mackall

    Interleukin-7 (IL-7) is required for the development and survival of T cells and plays a critical role in modulating T-cell homeostasis. This review will address current understanding of IL-7 biology, review recent clinical experiences and discuss potential future clinical applications of IL-7, or IL-7 blockade, in the setting of disease.

  • SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma-paraganglioma syndromes.
    J. Intern. Med. (IF 6.051) Pub Date : 2009-06-16
    B Pasini,C A Stratakis

    A genetic predisposition for paragangliomas and adrenal or extra-adrenal phaeochromocytomas was recognized years ago. Beside the well-known syndromes associated with an increased risk of adrenal phaeochromocytoma, Von Hippel Lindau disease, multiple endocrine neoplasia type 2 and neurofibromatosis type 1, the study of inherited predisposition to head and neck paragangliomas led to the discovery of the novel 'paraganglioma-phaeochromocytoma syndrome' caused by germline mutations in three genes encoding subunits of the succinate dehydrogenase (SDH) enzyme (SDHB, SDHC and SDHD) thus opening an unexpected connection between mitochondrial tumour suppressor genes and neural crest-derived cancers. Germline mutations in SDH genes are responsible for 6% and 9% of sporadic paragangliomas and phaeochromocytomas, respectively, 29% of paediatric cases, 38% of malignant tumours and more than 80% of familial aggregations of paraganglioma and phaeochromocytoma. The disease is characterized by autosomal dominant inheritance with a peculiar parent-of-origin effect for SDHD mutations. Life-time tumour risk seems higher than 70% with variable clinical manifestantions depending on the mutated gene. In this review we summarize the most recent knowledge about the role of SDH deficiency in tumorigenesis, the spectrum and prevalence of SDH mutations derived from several series of cases, the related clinical manifestantions including rare phenotypes, such as the association of paragangliomas with gastrointestinal stromal tumours and kidney cancers, and the biological hypotheses attempting to explain genotype to phenotype correlation.

  • Parafibromin--functional insights.
    J. Intern. Med. (IF 6.051) Pub Date : 2009-06-16
    P J Newey,M R Bowl,R V Thakker

    Parafibromin is a predominantly nuclear protein with a tumour suppressor role in the development of hereditary and nonhereditary parathyroid carcinomas, and the hyperparathyroidism-jaw tumour syndrome, which is associated with renal and uterine tumours. Parafibromin is a component of the highly conserved PAF1 complex, which regulates transcriptional events and histone modifications. The parafibromin/PAF1 complex regulates genes involved in cell growth and survival, and via these, parafibromin plays a pivotal role in embryonic development and survival of adults.

  • The triad of paragangliomas, gastric stromal tumours and pulmonary chondromas (Carney triad), and the dyad of paragangliomas and gastric stromal sarcomas (Carney-Stratakis syndrome): molecular genetics and clinical implications.
    J. Intern. Med. (IF 6.051) Pub Date : 2009-06-16
    C A Stratakis,J A Carney

    Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumours (GISTs) and pulmonary chondromas (PCH). A number of other lesions have been described in the condition including pheochromocytomas, oesophageal leiomyomas and adrenocortical adenomas; CT is a novel form of multiple endocrine neoplasia (MEN), a genetic condition with a female predilection. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC and SDHD have been found in familial and sporadic PGLs, and gain-of-function mutations of the oncogenes c-kit (KIT) and platelet-derived growth factor receptor A (PDGFRA) cause sporadic and familial GISTs. We recently reported an international series of patients with CT, 34 females and three males (median age of presentation 21 years) who did not carry SDHA, SDHB, SDHC, SDHD, KIT or PDGFRA gene mutations. Comparative genomic hybridization revealed a number of DNA copy number changes. The most frequent and greatest contiguous change was a deletion within the 1pcen13-q21 region, which harbours the SDHC gene. Another frequent change was loss of 1p. Although GISTs showed more frequent losses of 1p than PGLs, the pattern of chromosomal changes was similar in the two tumours despite their different tissue origin and histology; the findings were consistent with a common genetic aetiology of these two tumours in CT. In a separate condition, in which the association (or dyad) of GISTs with PGLs is inherited in an autosomal dominant manner (Carney-Stratakis syndrome, CSS), germline mutations of the SDHB, SDHC and SDHD genes (but not KIT or PDFGRA) were found; GISTs in this condition were caused by SDH deficiency. We conclude that CT is a novel MEN syndrome whose genetic defect remains elusive. CSS is caused by SDH defects, suggesting that sarcomas (GISTs) can be caused by defective mitochondrial oxidation, consistent with recent data implicating this enzyme in a variety of endocrine and other tumours. The above have clinical implications (i) for patients with GISTs that are cKIT- and PDGFRA-mutation negative: these tumours are usually resistant to treatment with currently available tyrosine kinase inhibitors and may be part of a syndrome such as CT or CSS; and (ii) for patients with an inherited PGL syndrome, family history should be explored to identify any other tumours in the family, and in particular other endocrine lesions and GISTs.

  • Multiple endocrine neoplasias: advances and challenges for the future.
    J. Intern. Med. (IF 6.051) Pub Date : 2009-06-16
    M Alevizaki,C A Stratakis

    Several important advances have been made over the last 2 years, since the last international workshop on multiple endocrine neoplasias (MENs) that was held in Marseilles, France (MEN2006). The series of articles that are included in this issue summarize the most important of these advances as they were presented in Delphi, Greece, during the 11th International Workshop on MENs, September 25-27, 2008 (MEN2008). This editorial summarizes some of these advances: the identification of the AIP, and the PDE11A and PDE8B genes by genome-wide association (GWA) studies as predisposing genes for pituitary and adrenal tumours, respectively, the discovery of p27 mutations in a new form of MEN similar to MEN type 1 (MEN 1) that is now known as MEN 4, the molecular investigations of Carney triad (CT), a disorder that associates paragangliomas (PGLs), gastrointestinal stromal tumour (GISTs), and pulmonary chondromas (PCH) with pheochromocytomas and adrenocortical adenomas and other lesions, and the molecular elucidation of the association of GISTs with paragangliomas (Carney-Stratakis syndrome) that is now known to be because of SDHB, SDHC, and SDHD mutations. Molecular investigations in Carney complex (another MEN also described by Dr. Carney, who during the meeting, along with Dr. Charles E. ('Gene') Jackson was honoured for his life-long and many contributions to the field) have also revealed the role of cyclic AMP signalling in tumorigenesis. As our knowledge of the molecular causes of MENs increases, the challenge is to translate these discoveries in better treatments for our patients. Indeed, new advances in the preventive diagnosis and molecular treatment of MEN 1 and MEN 2, respectively, continued unabated, and an update on this front was also presented at MEN2008 and is included in this issue.

  • The Interleukin-23 / Interleukin-17 axis in intestinal inflammation.
    J. Intern. Med. (IF 6.051) Pub Date : 2008-05-16
    Kevin J Maloy

    Although the precise aetiology of inflammatory bowel disease (IBD) remains unclear, recent discoveries have led to an improved understanding of disease pathogenesis. Whilst these findings have underscored the central role of innate and adaptive immune responses in intestinal inflammation, they have also precipitated a paradigm shift in the key cytokine pathways that drive disease. The prevailing dogma that IBD was mediated by interleukin (IL)-12-driven T-helper (Th)1 CD4 T cell responses towards the bacterial flora has been largely dispelled by findings that the closely related cytokine IL-23 appears to be the key mediator of intestinal inflammation. IL-23 is associated with a novel subset of IL-17-secreting CD4 T cells termed Th17 cells and rodent studies have implicated the IL-23/IL-17 axis in autoimmune inflammation. Genome-wide association studies in IBD patients have confirmed the predominant role of the IL-23 pathway, indicating that this could represent an important future therapeutic target.

  • 更新日期:2019-11-01
  • Inhibition of HIV-1 entry by antibodies: potential viral and cellular targets.
    J. Intern. Med. (IF 6.051) Pub Date : 2007-06-30
    S Phogat,R T Wyatt,G B Karlsson Hedestam

    Vaccine-induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. HIV-1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody-mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV-infected individuals. We also describe the nonvariable cellular receptors involved in the HIV-1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV-1 entry.

  • Progress in the development of immunotherapy for the treatment of patients with cancer.
    J. Intern. Med. (IF 6.051) Pub Date : 2002-03-21
    S A Rosenberg

    Several recent developments have hallmarked progress in tumour immunology and immunotherapy. The use of interleukin-2 (IL-2) in cancer patients demonstrated that an immunological manipulation was capable of mediating the regression of established growing cancers in humans. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing patients against these antigens has opened important new avenues of exploration for the development of effective active and cell-transfer immunotherapies for patients with cancer.

  • Management of oral anticoagulation in patients with atrial fibrillation: newer agents, newer conundrums?
    J. Intern. Med. (IF 6.051) Pub Date : 2018-04-17
    M Leggio,A Fusco,S D'Emidio,P Severi,M Lombardi,E Caldarone,M Armeni,D Mereu,M G Bendini,A Mazza

  • Unique case of cerebrotendinous xanthomatosis revisited: All the mutations responsible for this disease are present in the CYP27A1 gene.
    J. Intern. Med. (IF 6.051) Pub Date : 2017-11-03
    H Jiao,M Olin,M Hansson,G Eggertsen,M Eriksson,B Angelin,I Björkhem

  • Reversal of warfarin era thinking.
    J. Intern. Med. (IF 6.051) Pub Date : 2017-10-06
    J J Shatzel,M M Daughety,V Prasad,T G DeLoughery

  • Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial.
    J. Intern. Med. (IF 6.051) Pub Date : 2017-07-12
    I R Reid,A M Horne,B Mihov,G D Gamble,F Al-Abuwsi,M Singh,L Taylor,S Fenwick,C A Camargo,A W Stewart,R Scragg

    BACKGROUND Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density (BMD) or fracture risk in adults. OBJECTIVE To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels. METHODS Two-year substudy of a trial in older community-resident adults. A total of 452 participants were randomized to receive monthly doses of vitamin D3 100 000 IU, or placebo. The primary end-point was change in lumbar spine BMD. Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified. RESULTS Intention-to-treat analyses showed no significant treatment effect in the lumbar spine (between-groups difference 0.0071 g cm-2 , 95%CI: -0.0012, 0.0154) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2% over 2 years. There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect (P = 0.04). With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 (n = 46), there were between-groups BMD changes at the spine and femoral sites of ~2%, significant in the spine and femoral neck, but there was no effect on total body BMD. When baseline 25-hydroxyvitamin D was >30 nmol L-1 , differences were ~1/2% and significant only at the total hip. CONCLUSIONS This substudy finds no clinically important benefit to BMD from untargeted vitamin D supplementation of older, community-dwelling adults. Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults.

Contents have been reproduced by permission of the publishers.
上海纽约大学William Glover