Prospective Follow-Up of Cortical Interruptions, Bone Density, and Micro-structure Detected on HR-pQCT: A Study in Patients with Rheumatoid Arthritis and Healthy Subjects.

OBJECTIVES: The purpose of the study was to prospectively investigate change (repair or progression) in the number, surface area and volume of cortical interruptions, bone density (vBMD) and micro-structural parameters assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in finger joints of patients with rheumatoid arthritis (RA) treated with synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or biologic DMARDs (bDMARDs) over a 1-year follow-up period, and in comparison with healthy subjects (HS). METHODS: Thirty-two patients with RA (221 joints, 53% on bDMARDs) and 32 HS (117 joints) were assessed at baseline and after 1 year using semi-automatic analysis of HR-pQCT images. Mean changes (group level) and the proportion of joints (joint level) with changes beyond the least significant change were calculated. RESULTS: At baseline, 530 interruptions were identified in patients, and 136 in HS. The mean of the interruption parameters did not significantly change in either group Mean vBMD decreased more in patients than in HS (- 4.4 versus - 1.1 mgHA/cm3, respectively). In patients versus HS, proportionally more joints showed repair in interruption volume (6.6% versus 1.7%, respectively) and loss of vBMD (26.7% versus 12.9%, respectively). In patients on sDMARDs versus patients on bDMARDs, proportionally more joints showed progression in the number of interruptions and loss of vBMD (6.1% versus 1.8% and 31.3% versus 17.2%, respectively). CONCLUSIONS: HR-pQCT is able to quantify bone repair and progression. Cortical interruption-, vBMD-, and micro-structure were impaired in RA, of which vBMD and micro-structure further deteriorated, particularly in patients on sDMARDs.

An automated algorithm for the detection of cortical interruptions and its underlying loss of trabecular bone; a reproducibility study.

BACKGROUND: We developed a semi-automated algorithm that detects cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT), and extended it with trabecular void volume measurement. In this study we tested the reproducibility of the algorithm using scan/re-scan data. METHODS: Second and third metacarpophalangeal joints of 21 subjects (mean age 49 (SD 11) years, 17 early rheumatoid arthritis and 4 undifferentiated arthritis, all diagnosed < 1 year ago) were imaged twice by HR-pQCT on the same day with repositioning between scans. The images were analyzed twice by one operator (OP1) and once by an additional operator (OP2), who independently corrected the bone contours when necessary. The number, surface and volume of interruptions per joint were obtained. Intra- and inter-operator reliability and intra-operator reproducibility were determined by intra-class correlation coefficients (ICC). Intra-operator reproducibility errors were determined as the least significant change (LSCSD). RESULTS: Per joint, the mean number of interruptions was 3.1 (SD 3.6), mean interruption surface 4.2 (SD 7.2) mm2, and mean interruption volume 3.5 (SD 10.6) mm3 for OP1. Intra- and inter-operator reliability was excellent for the cortical interruption parameters (ICC ≥0.91), except good for the inter-operator reliability of the interruption surface (ICC = 0.70). The LSCSD per joint was 4.2 for the number of interruptions, 5.8 mm2 for interruption surface, and 3.2 mm3 for interruption volume. CONCLUSIONS: The algorithm was highly reproducible in the detection of cortical interruptions and their volume. Based on the LSC findings, the potential value of this algorithm for monitoring structural damage in the joints in early arthritis patients needs to be tested in clinical studies.

Structural damage and inflammation on radiographs or magnetic resonance imaging are associated with cortical interruptions on high-resolution peripheral quantitative computed tomography: a study in finger joints of patients with rheumatoid arthritis and healthy subjects.

OBJECTIVES: To study the relationship between structural damage and inflammatory features on magnetic resonance imaging (MRI) or radiography and other risk factors [anti-citrullinated protein antibody (ACPA) and/or rheumatoid factor (RF) seropositivity, hand dominance, disease duration] and the presence or number of cortical interruptions in finger joints on high-resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Finger joints of 38 healthy subjects and 39 patients with rheumatoid arthritis (RA) were examined through radiographs, MRI, and HR-pQCT. Radiographs were scored according to the Sharp/van der Heijde (SvH) method; MRI for the presence of cortical interruptions, bone marrow oedema (BMO), and synovitis; and HR-pQCT images for cortical interruptions. Descriptive statistics were calculated and associations examined using generalized estimating equations. RESULTS: Cortical interruptions were found in healthy subjects and patients with RA on HR-pQCT (mean ± sd 0.33 ± 0.63 vs 0.38 ± 0.64 per joint quadrant, respectively, p < 0.01). Structural damage on MRI (cortical interruptions) or radiographs (SvH ≥ 1) was associated with the presence of cortical interruptions on HR-pQCT [odds ratio (OR) 12.4, 95% confidence interval (CI) 7.5-21.4, p < 0.01 and OR 4.8, 95% CI 1.9-11.7, respectively, p < 0.01]. The presence of BMO or synovitis was associated with more cortical interruptions on HR-pQCT (ß 0.47, 95% CI 0.4-0.6, p < 0.01 and ß 1.9, 95% CI 0.6-3.1, p < 0.01). In patients with RA, ACPA, and/or RF seropositivity, hand dominance and disease duration were not associated with more cortical interruptions on HR-pQCT. CONCLUSION: Structural damage and inflammatory features on MRI and radiographs are associated with cortical interruptions on HR-pQCT. No association between other risk factors and cortical interruptions was demonstrated.

Vascular channels in metacarpophalangeal joints: a comparative histologic and high-resolution imaging study.

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and multiplane HR-pQCT images. Four 3-mm thick portions in three anatomic metacarpophalangeal joint specimens were selected for histologic sectioning. First, VCs identified with HR-pQCT were examined for confirmation on histology. Second and independently, VCs identified by histology were matched to single and multiplane HR-pQCT images to assess for presence of cortical interruptions. Only one out of five cortical interruptions suggestive for VC on HR-pQCT could be confirmed on histology. In contrast, 52 VCs were identified by histology of which 39 (75%) could be classified as cortical interruption or periosteal excavation on matched single HR-pQCT slices. On multiplane HR-pQCT images, 11 (21%) showed a cortical interruption in at least two consecutive slices in two planes, 36 (69%) in at least one slice in two planes and five (10%) showed no cortical interruption. Substantially more VCs were present in histology sections than initially suggested by HR-pQCT. The small size and heterogeneous presentation, limit the identification as VC on HR-pQCT.

An automated algorithm for the detection of cortical interruptions on high resolution peripheral quantitative computed tomography images of finger joints.

OBJECTIVES: To introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure). METHODS: Ten metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated. RESULTS: The median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring. CONCLUSION: The algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT.

The Reliability of a Semi-automated Algorithm for Detection of Cortical Interruptions in Finger Joints on High Resolution CT Compared to MicroCT.

We developed a semi-automated algorithm for the detection of cortical interruptions in finger joints using high-resolution peripheral quantitative computed tomography (HR-pQCT). Here, we tested its reliability compared to microCT (µCT) as gold standard. Nineteen joints of 10 female anatomic index fingers were imaged by HR-pQCT and µCT (82 and 18 µm isotropic voxel sizes, respectively). The algorithm was applied for detection of cortical interruptions of different minimum diameters (range >0.16 to >0.50 mm). Reliability was tested at the joint level with intra-class correlation coefficient (ICC) for the number of interruptions and interruption surface, and at the level of a single interruption for matching between HR-pQCT and µCT with a fixed interruption diameter (>0.10 mm) on µCT. The positive predictive value (PPV0.10mm) and sensitivity0.10mm were evaluated. The mean number of interruptions per joint depended on the diameter cut-off and ranged from 3.4 to 53.5 on HR-pQCT and from 1.8 to 45.1 on µCT for interruptions >0.50 to >0.16 mm, respectively. Reliability at the joint level was almost perfect (ICC ≥0.81) for both the number and surface of interruptions >0.16 and >0.33 mm. As expected, the PPV0.10mm increased with increasing interruption diameter from 84.9 to 100%, for interruptions >0.16 and >0.50 mm, respectively. However, the sensitivity0.10mm decreased with increasing interruption diameter from 62.4 to 4.7%. This semi-automated algorithm for HR-pQCT in finger joints performed best for the detection of cortical interruptions with a minimum diameter of >0.16 or >0.33 mm, showing almost perfect reliability at the joint level and interruptions matched with those on µCT.

Empty can and drop arm tests for cuff rupture : Improved specificity after subacromial injection.

Shoulder disorders are common in the general population : they occur in about 25 of every 1000 patients per year. A rather large majority are caused by cuff disorders. Differentiating between impingement and cuff rupture is essential to adequate treatment. Clinical tests have been developed, but their accuracy is limited. This study was performed to improve clinical accuracy by combining single tests and adding a subacromial injection. We postulated that the empty can and drop arm tests would result in higher sensitivity and specificity after subacromial injection. METHOD: We prospectively assessed 49 patients with the empty can and drop arm tests and used ultrasound to compare the individual and combined results. RESULT: The ultrasound found six cuff ruptures. Specificity improved and sensitivity decreased after subacromial injection. CONCLUSION: Only specificity improved after subacromial injection. Combining the test results led to an increase in both sensitivity and specificity without injection.

Visual detection of cortical breaks in hand joints: reliability and validity of high-resolution peripheral quantitative CT compared to microCT.

BACKGROUND: To study the reliability and validity of high-resolution peripheral quantitative CT (HR-pQCT) with microCT (µCT) as gold standard in the visual detection of cortical breaks in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. METHODS: Ten cadaveric fingers (10 MCP and 9 PIP joints) were imaged by HR-pQCT and µCT and visually analyzed by two independent readers. Intra- and interreader reliability were evaluated for the presence (yes/no, kappa statistics) and the total number (intraclass correlation coefficient, ICC) of cortical breaks. Sensitivity, specificity, positive and negative predictive value (PPV respectively NPV) of HR-pQCT in detecting cortical breaks were calculated. RESULTS: With HR-pQCT, mean 149 cortical breaks were identified and with µCT mean 129 (p < 0.05). Intrareader reliability for the presence of a cortical break per quadrant was 0.52 (95 % CI 0.48-0.56) and 0.71 (95 % CI 0.67-0.75) for HR-pQCT and µCT, respectively, and for the total number of cortical breaks 0.61 (95 % CI 0.49-0.70) and 0.75 (95 % CI 0.68-0.82). Interreader reliability for the presence of a cortical break per quadrant was 0.37 (95 % CI 0.33-0.41) and 0.45 (95 % CI 0.41-0.49) for HR-pQCT and µCT, respectively, and for the number of cortical breaks 0.55 (95 % CI 0.43-0.65) and 0.54 (95 % CI 0.35-0.67). Sensitivity, specificity, PPV and NPV of HR-pQCT were 81.6, 64.0, 81.6, and 64 % respectively. CONCLUSION: Cortical breaks were commonly visualized in MCP and PIP joints with HR-pQCT and µCT. Reliability of both HR-pQCT and µCT was fair to moderate. HR-pQCT was highly sensitive to detect cortical breaks with µCT as gold standard.

Multiplanar reconstruction computed tomography for diagnosis of scaphoid waist fracture union: a prospective cohort analysis of accuracy and precision.

OBJECTIVE: To examine reliability and validity concerning union of scaphoid fractures determined by multiplanar reconstruction computed tomography randomized at 6, 12, and 24 weeks after injury. MATERIALS AND METHODS: We used Fleiss' kappa to measure the opinions of three observers reviewing 44 sets of computed tomographic scans of 44 conservatively treated scaphoid waist fractures. We calculated kappa for the extent of consolidation (0-24 %, 25-49 %, 50-74 %, or 75-100 %) on the transverse, sagittal and coronal views. We also calculated kappa for no union, partial union, and union, and grouped the results for 6, 12, and 24 weeks after injury. As the reference standard for union, CT scans were performed at a minimum of 6 months after injury to determine validity. RESULTS: Overall inter-observer agreement was found to be moderate (κ = 0.576). No union (κ = 0.791), partial union (κ = 0.502), and union (κ = 0.683) showed substantial, moderate, and substantial agreement, respectively. The average sensitivity of multiplanar reconstruction CT for diagnosing union of scaphoid waist fractures was 73 %. The average specificity was 80 %. CONCLUSIONS: Our results suggest that multiplanar reconstruction computed tomography is a reliable and accurate method for diagnosing union or nonunion of scaphoid fractures. However, inter-observer agreement was lower with respect to partial union.

Performance of various criteria sets in patients with inflammatory back pain of short duration; the Maastricht early spondyloarthritis clinic.

AIM: To describe how patients presenting with inflammatory back pain (IBP) of short duration can be classified by different sets of classification criteria for spondyloarthritis (SpA) and ankylosing spondylitis, and which clinical and imaging features are of discernible importance. METHODS: 68 patients with IBP of a maximum of 2 years' duration were included in the early spondyloarthritis cohort. Detailed history, clinical examination and imaging of sacroiliac joints by plain radiography and magnetic resonance imaging (MRI) were obtained. The Berlin criteria set for SpA that has a prominent place for MRI and human leucocyte antigen B27 was used to quantify the relative contribution of MRI in classifying SpA. RESULTS: 14 of the 68 patients had ankylosing spondylitis according to the modified New York criteria, 57 patients fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for SpA, 48 patients fulfilled the Amor criteria for SpA (43 patients fulfilled both criteria sets) and 44 patients fulfilled the Berlin criteria for SpA. Only four patients did not fulfil any criteria set; 36 patients fulfilled ESSG, Amor and Berlin criteria. The 14 patients with ankylosing spondylitis fulfilled all three SpA criteria sets. CONCLUSION: Among our selected cohort of patients with early IBP, the prevalence of SpA according to three different criteria sets is high. The ESSG criteria were the most sensitive, followed by the Amor criteria and the Berlin criteria. The modified New York criteria for ankylosing spondylitis appeared to be the most specific. In this cohort, the contribution of MRI and human leucocyte antigen B27 to purely clinical criteria in making a diagnosis of axial SpA was limited.

Combining information obtained from magnetic resonance imaging and conventional radiographs to detect sacroiliitis in patients with recent onset inflammatory back pain.

OBJECTIVE: To compare the contribution of changes on magnetic resonance imaging (MRI) and conventional radiography (CR) in the sacroiliac joints of patients with recent onset inflammatory back pain (IBP) in making an early diagnosis of spondyloarthritides. METHODS: The study involved 68 patients with IBP (38% male; mean (SD) age, 34.9 (10.3) years) with symptom duration less than two years. Coronal MRI of the sacroiliac joints was scored for inflammation and structural changes, and pelvic radiographs were scored by the modified New York (mNY) grading. Agreement between MRI and CR was analysed by cross tabulation per sacroiliac joint and per patient. RESULTS: A structural change was detected in 20 sacroiliac joints by MRI and in 37 by CR. Inflammation was detected in 36 sacroiliac joints by MRI, and 22 of these showed radiographic sacroiliitis. Fourteen patients fulfilled the mNY criteria based on CR. Classification according to the modified New York criteria would be justified for eight patients if it was based on MRI for structural changes only, for 14 if it was based on structural changes on CR, for 14 (partly) different patients if it was based on inflammation on MRI only, for 16 if it was based on inflammation and structural changes on MRI, for 19 if it was based on inflammation on CR combined with MRI, and for (the same) 19 if it was based on inflammation and structural damage on CR combined with MRI. CONCLUSIONS: CR can detect structural changes in SI joints with higher sensitivity than MRI. However, inflammation on MRI can be found in a substantial proportion of patients with IBP but normal radiographs. Assessment of structural changes by CR followed by assessment of inflammation on MRI in patients with negative findings gives the highest returns for detecting involvement of the SI joints by imaging in patients with recent onset IBP.

Retinopathy and microalbuminuria in type 2 diabetes: determinants and time-dependency of the association.

Background: The aim of this study was to identify the independent determinants of diabetic retinopathy (RET) and microalbuminuria (MA) and to assess the time-dependency of the association of RET with MA. Methods: In 668 out-patients with type 2 diabetes, RET was assessed by stereoscopic fundoscopy and by measuring the level of MA in untimed, triplicate urine collections on at least two and four separate visits, respectively, during a period of at least 24 months. RET was defined as RET of any type and MA as a urinary albumin-to-creatinine ratio (ACR) between 2 and 30 mg/mmol. Multiple logistic regression analysis was used to determine odds ratios (OR) and 95% confidence intervals (CI). The extent of the association (OR(assoc)) was estimated by the odds that a patient with RET has MA divided by the odds that a patient without RET has MA. Results: Common determinants of RET and MA were: systolic BP, HbA(1c), and triglycerides. Age, non-Caucasian ethnicity, and RET were associated with MA, whereas duration of diabetes and ACR were associated with RET. We estimated an overall OR(assoc) of 2.36 (95% CI, 1.72-3.24). The time-dependency of OR(assoc) showed a hyperbolically shaped curve, reaching a maximum value of 2.5 at 9.8 years after the diagnosis of type 2 diabetes. Conclusions: Our study, which supports what is currently known about independent determinants of diabetic RET and MA, suggests a drastic increase in clustering of RET and MA over the first 5 years before the diagnosis of type 2 diabetes.

The prevalence of type 2 diabetes and gestational diabetes mellitus in an inner city multi-ethnic population.

Zeeburg', a multiethnic town borough in the Amsterdam-East region, has one of the city's highest rates of immigrants. In the total population of 19,825 Surinam (mainly Creole), Turkish, Moroccan, and Dutch adults the prevalence of known type 2 diabetes in 1994 and of gestational diabetes mellitus (GDM) between January 1992 and January 1997 was investigated. Based on World Health Organization (WHO) criteria of 1985, the age-standardized prevalence of type 2 diabetes was similar in men (6.4%; 95% confidence interval [CI]: 5.6-7.2) and women (6.4%: 95% CI: 5.8-7.0) for all ethnic groups combined. However, the age- and sex-standardized prevalence of type 2 diabetes was significantly greater in the non-Dutch inhabitants than in the Dutch inhabitants (17.3% [95% CI: 12.9-21.6] in Surinam inhabitants, 10.9% [95% CI: 9.7-12.2] in Turkish inhabitants, 12.4% [95% CI: 9.7-15.0] in Moroccan inhabitants, and 3.6% [95% CI: 3.2-3.9] in Dutch inhabitants). The odds ratios for type 2 diabetes for the separate immigrant groups relative to the Dutch group were 5.88 (95% CI: 4.54-7.69) for Surinam inhabitants, 4.00 (95% CI: 2.86-5.55) for Turkish inhabitants, and 4.17 (95% CI: 3.03-5.55) for Moroccan inhabitants. GDM was present in 2.59% of women of non-Dutch origin compared with 0.62% of women of Dutch origin. A significant positive association was found between the non-Dutch origin and the occurrence of GDM (chi2 = 6.7; p < 0.01). The study highlights a high prevalence of known type 2 diabetes and GDM in the immigrant inhabitants and emphasizes that appropriate interventions are necessarily with implications for health targets and capitation based budgets.

On the prediction of the histologic composition of benign prostatic hyperplasia based on clinical and MRI parameters.

BACKGROUND: The histologic composition of prostate adenoma seems related to the development of clinical benign prostatic hyperplasia (BPH). Therefore, a new noninvasive prediction model as an alternative for biopsies was investigated. METHODS: In 19 patients, the data of a routine preoperative workup for transurethral resection (TURP) and of an additional MRI-examination were related to the results of morphometry on TURP-tissue. RESULTS: Statistical analysis identified age of the patient and MRI-volumetrics of the prostate adenoma as best predictors of the epithelial fraction, with a 95% confidence interval of at least 5% (range, 9-14%) (R2 = 50%). CONCLUSIONS: This prediction model is sufficiently accurate to categorize a population of patients into histologic subgroups. It seems very likely that this method will be of use as an investigative tool in medical trials to provide insight into the pathogenesis of clinical BPH and into treatment strategies for the individual patient.

Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study.

OBJECTIVE: To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS: Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS: The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.

Vascular complications in relation to ethnicity in non-insulin-dependent diabetes mellitus.

The purpose of this study was to investigate the effect of ethnicity on the development of diabetic retinopathy and nephropathy as markers for microvascular complications and of angina pectoris as a marker for macrovascular complications. We evaluated data from 1124 patients with non-insulin-dependent diabetes mellitus (NIDDM) of Caucasian, Mongoloid, Asian, Armenian, Northern African and Negroid origin who were referred between January 1993 and December 1994. Logistic regression analyses showed that the occurrence of microvascular complications was significantly associated with duration of NIDDM. In addition, retinopathy was significantly associated with glycated haemoglobin A1c (HbA1c) and nephropathy with triglycerides (P < 0.05 and P < < 0.001 respectively). Northern African origin was associated with retinopathy (P < 0.05) and Asian origin with nephropathy (P < 0.005). Macrovascular complication was associated with age and triglyceride level (P < 0.001 and P < 0.05 respectively). Northern African and Negroid ethnicity exclusively did not show a gradual increase in the risk for angina pectoris with increasing age. Moreover, a negative association between Northern African as well as Negroid ethnicity and macrovascular complication was observed (P = 0.05 and P < 0.05 respectively). In support of these observations, we found a favourable lipid profile in both mentioned groups. In summary, we have shown that, in patients with NIDDM, ethnicity is associated with macrovascular complications and duration of the disease with microvascular complications.

Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?

The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.

Influence of heparin, protamine and polybrene on the time integral of thrombin generation (endogenous thrombin potential).

We investigated the anticoagulating and heparin-neutralizing properties of protamine and polybrene (hexadimethrine bromide), using the endogenous thrombin potential (ETP) as the parameter to access plasma coagulability. The hypocoagulability induced by high doses of heparin (3 IU/ml) could be reversed by addition of protamine to a very limited extent only. Polybrene on the other hand did neutralize heparin at the equivalent concentration and a two-fold excess did not influence the ETP parameters. In vivo neutralization of high-dose heparin with protamine should therefore be reconsidered. Our experiments suggest polybrene to be superior over protamine with respect to neutralization of high doses of heparin.