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Biomedical subjects

M T Nurmohamed

Publications and source records attributed to M T Nurmohamed.

At least 19 recordsLinked to original sources
PubMed2006

[Rheumatic diseases as risk factors for cardiovascular disease].

Cardiovascular disease is the leading cause of death in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Prospective intervention trials aimed at the modification of cardiovascular risk factors are needed to determine the impact of cardiovascular risk reduction in patients with rheumatic disease. In addition to SLE, RA and AS should be acknowledged as new risk factors for cardiovascular disease.

Arthritis, Rheumatoid↗
PubMed2006

Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. OBJECTIVE: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. METHODS: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep-frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. RESULTS: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p< or =0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. CONCLUSION: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.

Adult↗
PubMed2006

Increased disease activity is associated with a deteriorated lipid profile in patients with ankylosing spondylitis.

BACKGROUND: Cardiovascular mortality is increased in patients with ankylosing spondylitis. A possible explanation might be a more prevalent atherogenic lipid profile in patients with ankylosing spondylitis than in the general population. It has been postulated that inflammation deteriorates the lipid profile, thereby increasing cardiovascular risk. OBJECTIVE: To explore the association between disease activity and lipid profile in patients with ankylosing spondylitis. METHODS: Disease activity parameters for ankylosing spondylitis and lipid levels (total cholesterol, high-density lipoprotein cholesterol (HDLc) and triglycerides) were measured in 45 patients with ankylosing spondylitis for 6 months after starting treatment with leflunomide or placebo. Findings in this treatment group were compared with those in 10 patients with ankylosing spondylitis treated with etanercept. A specialised regression model, adjusting for repeated measurements, age and sex, was used to assess the influence of the disease activity variables on the lipid levels. RESULTS: Multilevel regression analyses showed significant associations between disease activity parameters and lipid levels-for instance, an increase of 30 mm at the end of the first hour in erythrocyte sedimentation rate was associated with a decrease of about 6% in total cholesterol level and a decrease of about 11% in HDLc levels. Similar significant associations were found between other disease activity parameters and lipid levels. CONCLUSION: Increase in disease activity was associated with decreases in lipid levels. The decrease in HDLc levels tended to be almost twice as large as the decrease in total cholesterol levels, resulting in a more atherogenic lipid profile. Hence, effective treatment of disease activity in patients with ankylosing spondylitis may lower the cardiovascular risk by improving the lipid profile.

Adult↗
PubMed2005

[Thromboprophylaxis in general surgical practices in the year 2004: perioperative use during hospitalisation, during out-patient care and following plaster cast immobilisation].

OBJECTIVE: To determine which thromboprophylactic modalities were used by general surgeons in the Netherlands; to check current clinical practice against national and international guidelines. DESIGN: Descriptive. METHOD: In April 2004 a questionnaire was sent to all 106 surgical practices in the Netherlands with questions regarding the use of thromboprophylaxis before, during and after various surgical interventions. Practice was compared with guidelines from the Dutch Institute for Healthcare Improvement CBO, the Dutch Surgical Association and the American College of Chest Physicians. RESULTS: We obtained data from 92 (87%) surgical practices. Low molecular weight heparin was initiated before surgery by 92% of respondents. Risk factors such as age (72%) and prior venous thromboembolism (76%) played an important role in determining the thromboprophylactic protocol used. During hospitalisation, variations were seen primarily for operations performed on an out-patient basis: 61% of surgeons gave thromboprophylaxis in this setting. Prolonged thromboprophylaxis after hospital discharge was seldom administered. 54% of surgeons used prolonged thromboprophylaxis after surgery for hip or femur fractures. During cast immobilisation of the upper leg, 79% of all surgeons prescribed thromboprophylaxis. CONCLUSION: Current practice regarding thromboprophylaxis during hospitalisation conformed consistently to the guidelines. The guidelines were followed moderately with regard to the use of prolonged thromboprophylaxis following hip fractures. In the absence of clear guidelines, there were striking differences among surgical practices regarding thromboprophylaxis during out-patient care and plaster cast immobilisation.

Age Factors↗
PubMed2005

Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is associated with an unexplained increased risk of cardiovascular disease (CVD). Antibodies against human 60 kDa heat shock protein (anti-HSP60) are associated with the presence and severity of CVD. OBJECTIVES: To investigate whether anti-HSP60 antibodies are associated with prevalent CVD in patients with rheumatoid arthritis. METHODS: In a nested case-control design, anti-HSP60 antibody levels were measured in the serum samples of 192 rheumatoid patients. In a regression analysis the association between prevalent CVD and anti-HSP60 antibodies was examined, along with the possible influence on this association of several demographic, rheumatoid arthritis, and CVD related variables. RESULTS: In a random sample of 326 patients with rheumatoid arthritis, 48 cases were identified who also suffered from CVD. Three controls per case with rheumatoid arthritis but without CVD (n = 144) were matched for sex, age, disease duration, and smoking habits. A regression analysis showed no significant association between prevalent CVD and anti-HSP60 antibodies (odds ratio = 1.00 (95% confidence interval, 0.997 to 1.004)). After correcting for possible confounding variables, still no association was found. CONCLUSIONS: In contrast to the general population, anti-HSP60 antibody titres are not associated with prevalent CVD in patients with rheumatoid arthritis. These findings could be the result of an altered immune response to HSP60 in rheumatoid arthritis.

Aged↗
PubMed2005

Double blind, randomised, placebo controlled study of leflunomide in the treatment of active ankylosing spondylitis.

OBJECTIVE: To assess the efficacy and safety of leflunomide in active ankylosing spondylitis (AS) compared with placebo in a 24 week pilot study. METHODS: In a single centre randomised, double blind, placebo controlled study, 45 patients with active AS were randomised to either leflunomide 20 mg daily (n=30) or placebo (n=15). Active disease was defined as a score of >or=4 on the Bath ankylosing spondylitis disease activity index (0-10), and pain of >or=4 on a visual analogue scale (0-10). The primary efficacy variable at week 24 was the 20% response rate, as recommended by the Assessments in Ankylosing Spondylitis (ASAS) working group. Secondary outcome variables included general wellbeing, metrology index, swollen joint count, erythrocyte sedimentation rate, and C reactive protein. RESULTS: In all, 13 women and 32 men were studied. Demographic and disease indices were comparable between the two treatment groups at baseline. The rate of ASAS 20% responders was not significantly different: 27% in the leflunomide treated patients and 20% in the placebo group (95% confidence interval, -32% to 19%). No significant differences were found between the treatment groups in mean changes of the secondary outcome variables. Eleven patients were withdrawn prematurely from the study because of adverse events (7), lack of efficacy (3), and non-compliance (1). Most frequently adverse events were gastrointestinal side effects and skin disorders. CONCLUSIONS: In this placebo controlled study, leflunomide treatment did not result in a significant improvement of the ASAS 20% response in active ankylosing spondylitis. No unexpected or severe adverse events occurred.

Adult↗
PubMed2004

Relationship between serum trough infliximab levels, pretreatment C reactive protein levels, and clinical response to infliximab treatment in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between serum trough infliximab levels and clinical response to infliximab treatment in patients with rheumatoid arthritis (RA). METHODS: Disease activity and serum trough infliximab levels before and 2, 6, and 14 weeks after initiation of infliximab treatment at a dose of 3 mg/kg in a cohort of 105 patients with RA were assessed. Serum trough infliximab levels in responders and non-responders were compared. Additionally, the clinical responses of patients with high, intermediate, and low serum trough infliximab levels at 14 weeks were compared. RESULTS: After 14 weeks of treatment non-responders had lower serum trough levels of infliximab than responders (median (interquartile range) 0.5 (0.2-2.2) v 3.6 (1.4-8.2) mg/l; p<0.01)). Patients with low serum trough infliximab levels at 14 weeks had significantly less improvement in the 28 joint count Disease Activity Score (DAS28) score than patients with intermediate or high serum trough infliximab levels at 14 weeks. Pretreatment C reactive protein (CRP) levels correlated negatively with serum trough infliximab levels at 14 weeks after the start of treatment (Spearman rank correlation r(s) = -0.43, p<0.001). CONCLUSION: Serum trough levels of infliximab correlate with the clinical response to treatment with infliximab and pretreatment CRP levels. This study indicates that patients with high pretreatment CRP levels might benefit from higher dosages of infliximab or shorter dosing intervals.

Adult↗
PubMed2003

[Thrombosis prevention in orthopaedic surgery: clinical practice in the Netherlands in 2002].

OBJECTIVE: Establish the use of thromboprophylaxis in orthopaedic surgery both during and after the hospital admission. DESIGN: Cross-sectional study. METHOD: In April 2002, a letter was sent to all orthopaedic surgeons in the Netherlands announcing that at every hospital with a Department of Orthopaedic Surgery, an orthopaedic surgeon would be approached for a telephone survey. They were phoned in the months April-June 2002. This study included hospitals where major orthopaedic surgery (e.g. the insertion of hip or knee prostheses and hip fracture surgery) took place (n = 124) as well as clinics that only performed day treatments (n = 5). RESULTS: For major orthopaedic operations, 91% of the hospitals used low molecular weight heparin (LMWH) during the admission period: 36% as monotherapy and 55% in combination with coumarin derivates. In 85% of cases the use of LMWH was started preoperatively. Coumarin derivates were used as a monotherapy in 9% of the hospitals. In 37% of the hospitals the use of NSAIDs was continued, particularly in patients with rheumatoid arthritis. In 94% of the hospitals, the use of acetylsalicylic acid was always stopped. In 97% of the hospitals prophylaxis was given after discharge in the form of LMWH (37% of the cases) or coumarin derivates (63% of the cases). The use of thromboprophylaxis with respect to arthroscopies and plaster immobilisation was variable.

Anticoagulants↗
PubMed2003

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.

BACKGROUND: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. OBJECTIVE: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. METHODS: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). RESULTS: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. CONCLUSION: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.

Adult↗
PubMed2000

Thromboprophylaxis in neurosurgical patients.

Neurosurgical patients constitute one of the highest risk groups for postoperative thromboembolic complications. Physical methods of thromboprophylaxis have been successful in reducing the incidence of postoperative deep vein thrombosis (DVT) but the residual incidence remains considerable. Many neurosurgeons are reluctant to use perioperative anticoagulant prophylaxis, despite its proven success in reducing DVT rates, because of the potentially serious consequences of even a small intracranial bleed. Recent studies have indicated that a combination of graduated compression stockings (GCS) and low-molecular-weight heparin (LMWH), started in the postoperative period, significantly reduces the incidence of DVT compared with GCS alone. Postoperative regimens avoid the risk of surgical hemorrhage and appear to offer increased protection for this group of patients.

Anticoagulants↗
PubMed2000

Long-term thromboprophylaxis in practice: how can it be implemented?

Prolonging thromboprophylaxis after hospital discharge following surgery reduces the incidence of venographic and symptomatic venous thromboembolism (VTE), although the effects on post-thrombotic syndrome are not yet clear. Oral anticoagulants and low-molecular-weight heparins (LMWHs) may be used for extended outpatient therapy, but oral anticoagulants require frequent laboratory monitoring and may cause major gastrointestinal bleeding. Conversely, LMWHs are effective and safe at a fixed, once-daily dosage without monitoring. Four studies have shown that extended prophylaxis with LMWHs significantly reduces the incidence of post-discharge VTE following total hip replacement. However, the need for subcutaneous injection potentially limits home use of LMWHs outside clinical trials because the amount of drug administered may vary between injections if patients self-inject, while administration by nurses would be too costly. An auto-injection device is now available for administering the LMWH enoxaparin. The device is simple to use and delivers a precise pre-determined dose. During studies with such devices, volunteers successfully performed mock injections and patients with indications for thromboprophylaxis showed high levels of acceptance with administration for up to 3 weeks. Ongoing studies are assessing longer periods of self-administration.

Aged↗
PubMed1997

Magnesium pyridoxal-5'-phosphate glutamate, "A vitamin B6 derivative", does not affect lipoprotein levels in patients with familial hypercholesterolaemia.

OBJECTIVE: In this double-blind, randomized, placebo-controlled, dose-finding study we assessed the short-term efficacy and safety of increasing dosages of magnesium pyridoxal-5'-phosphate glutamate (MPPG) compared to placebo in patients with familial hypercholesterolaemia (FH). Twenty-three patients of either sex, over the age of 18 years and suffering from heterozygous FH, were treated with MPPG for a period of 16 weeks. RESULTS: Baseline characteristics and lipoprotein profiles of the patients were comparable in the two treatment groups. Overall compliance was 90%. Neither after the first 8 weeks treatment period with 450 mg MPPG daily nor after the second 8 weeks treatment period with 600 mg MPPG daily were statistically significant changes in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or triglyceride levels observed between the treatment and placebo groups. Plasma levels of lipoprotein (Lp)(a), apolipoprotein (apo) A1, apo B100, very low density lipoprotein (VLDL) cholesterol and VLDL triglyceride also did not change. CONCLUSION: Although it has been demonstrated that MPPG improves lipoprotein levels in patients with different forms of dyslipidaemia, MPPG is not effective for the treatment of FH patients.

Adult↗