Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial

We studied the relation between diet, serum lipoproteins, and the progression of coronary lesions in 39 patients with stable angina pectoris in whom coronary arteriography had shown at least one vessel with 50 per cent obstruction before intervention. Intervention consisted of a two-year vegetarian diet that had a ratio of polyunsaturated to saturated fatty acids of at least 2 and that contained less than 100 mg of cholesterol per day. Dietary changes were associated with a significant increase in linoleic acid content of cholesteryl esters and a significant lowering of body weight, systolic blood pressure, serum total cholesterol, and the ratio of total to high-density lipoprotein (total/HDL) cholesterol. Angiographic examination was performed after 24 months; angiograms were assessed visually (with blinding) and by computer-assisted image analysis. Both types of assessment indicated progression of disease in 21 of 39 patients but no lesion growth in 18. Coronary lesion growth correlated with total/HDL cholesterol (r = 0.50, P = 0.001) but not with blood pressure, smoking status, alcohol intake, weight, or drug treatment. Disease progression was significant in patients who had values for total/HDL cholesterol that were higher than the median (greater than 6.9) throughout the trial period. No coronary-lesion growth was observed in patients who had lower values for total/HDL cholesterol (less than 6.9) throughout the trial or who initially had higher values (greater than 6.9) that were significantly lowered by dietary intervention.     

The influence of image enhancement and reconstruction on quantitative coronary arteriography

In the coming years, cinefilm will gradually be replaced by some digital medium for the archiving of angiographic images. However, not only the question which digital archiving medium will be used in the future is important, but also wich images are to be stored. Options are to either archive the raw, unprocessed images, or the enhanced images as they are displayed on the viewing monitor in the catheterization laboratory. In the first case, an off-line workstation will need additional hardware to display the images with the same image quality as they were acquired; in the second case, the question remains whether quantitative analysis programs still provide reliable results.Goal of this study was to investigate the possible effects of image enhancement and reconstruction on the results from quantitative coronary arteriographic (QCA) measurements with the Philips ACA-package (Automated Coronary Analysis). Image enhancement was achieved by an unsharp masking approach; the reconstruction of the original image from the enhanced image was attempted by an iterative deconvolution approach.The evaluation study consisted of two parts; a technical evaluation on eleven phantom tubes with known dimensions, and a clinical evaluation study on 48 coronary lesions. The results of the technical evaluation demonstrate that the measurement errors increase for the smaller vessel sizes (<1.2 mm) when QCA is applied to reconstructed images. The systematic difference on the smallest phantom tube (0.687 mm) on unprocessed images was limited to 0.050 mm, while it increased to 0.089 mm for the reconstructed images. Moreover, the random differences for the smaller vessel sizes increased for all processed images: for 0.159 mm for the unprocessed image to 0.189 mm for the enhanced and 0.204 mm for the reconstructed image (p<0.01). For the larger vessels, in general, no significant differences could be observed between the results of the unprocessed and processed images.The results of the clinical evaluation study demonstrate that especially the obstruction diameter is overestimated when QCA is applied to reconstructed images (0.113 mm). Although the measurements on the enhanced images did not show a significant overestimation of the obstruction diameter, the intra-observer random difference was much higher (0.199 mm for the enhanced images versus 0.140 mm for the unprocessed images, p<0.01). In more general terms, applying QCA on enhanced images increases the random difference values, while reconstructing the original image from the enhanced images increases the systematic errors in the measured diameters.This study has clearly demonstrated that especially the smaller diameter values (<1.2 mm) are influenced by image enhancement. Therefore, to obtain quantitative results with the desired small values for systematic and random differences, requires that the raw, unprocessed image data be archived.This work was supported in part by a grant from Philips Medical Systems, Best, The Netherlands     

Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantitation of coronary cineangiograms

A computer-assisted technique has been developed to assess absolute coronary arterial dimensions from 35 mm cineangiograms. The boundaries of optically magnified and video-digitized coronary segments and the intracardiac catheter are defined by automated edge-detection techniques. Contour positions are corrected for pincushion distortion. The accuracy and precision of the edge detection procedure as assessed from cinefilms of contrast-filled acrylate (Perspex) models were -30 and 90 micrometers, respectively. The variability of the analysis procedure itself in terms of absolute arterial dimensions was less than 0.12 mm, and in terms of percentage arterial narrowing for coronary obstructions less than 2.74%. Short-, medium-, and long-term variability measurements were assessed from repeated coronary angiographic examinations performed 5 min, 1 hr, and 90 days apart, respectively. For all studies the mean differences in absolute diameters were less than 0.13 mm. The variability in obstruction diameter ranged from 0.22 mm for the best-controlled study (medium-term) to 0.36 mm for the least-controlled study (long-term); variability in reference diameter ranged from 0.15 to 0.66 mm, respectively. It is concluded that the biological variations are a source of major concern and that further attempts toward standardization of the angiographic procedure are seriously needed.     

Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs

Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow theory) and neuroimmunology is reviewed to aid understanding and evaluation of CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference to albumin) are described in CSF/serum quotient diagrams with the hyperbolic reference range for blood-derived protein fractions in CSF. Clinical relevance of complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and brain-derived proteins) is briefly discussed. Integrated CSF data reports are shown with numerical and graphical data representation, reference range-related interpretation and diagnosis-related comments. The principles and rationale of general CSF analysis reported in this review should enable the reader to accurately interpret CSF data profiles, and to plan a proper evaluation of new brain- or blood-derived analytes in CSF.     

Trends in lower limb amputation in the Veterans Health Administration, 1989-1998

OBJECTIVE: To assess trends in lower limb amputation performed in Veterans Health Administration (VHA) facilities. METHODS: All lower limb amputations recorded in the Patient Treatment File for 1989-1998 were analyzed using the hospital discharge as the unit of analysis. Age-specific rates were calculated using the VHA user-population as the denominator. Frequency tables and linear, logistic, and Poisson regression were used respectively to assess trends in amputation numbers, reoperation rates, and age-specific amputation rates. RESULTS: Between 1989-1998, there were 60,324 discharges with amputation in VHA facilities. Over 99.9% of these were in men and constitute 10 percent of all US male amputations. The major indications were diabetes (62.9%) and peripheral vascular disease alone (23.6%). The age-specific rates of major amputation in the VHA are higher than US rates of major amputation. VHA rates of major and minor amputation declined an average of 5% each year, while the number of diabetes-associated amputations remained the same. CONCLUSION: The number and age-specific rates of amputations decreased over 10 years despite an increase in the number of veterans using VHA care.     

Geographic variation of lower-extremity major amputation in individuals with and without diabetes in the Medicare population

OBJECTIVE: To describe geographic variation in rates of lower-limb major amputation in Medicare patients with and without diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional population-based study used national fee-for-service Medicare claims from 1996 through 1997. The unit of analysis was 306 hospital referral regions (HRRs) representing health care markets for their respective tertiary medical centers. Numerators were calculated using nontraumatic major amputations and the diabetes code (250.x) for individuals with diabetes. Denominators for individuals with diabetes were created by multiplying the regional prevalence of diabetes (as determined using a 5% sample of Medicare Part B data identifying at least two visits with a diabetes code for 1995-1996) by the regional Medicare population. Denominators for individuals without diabetes were the remaining Medicare beneficiaries. Rates of major amputations were adjusted for age, sex, and race. RESULTS: Rates of major amputations per year were 3.83 per 1,000 (95% CI 3.60-4.06) individuals with diabetes compared with 0.38 per 1,000 (95% C1 0.35-0.41) individuals without diabetes. Marked geographic variation was observed for individuals with and without diabetes; however, patterns were distinct between the two populations. Rates were high in the Southern and Atlantic states for individuals without diabetes. In contrast, rates for individuals with diabetes were widely varied. Variation across HRRs for individuals with diabetes was 8.6-fold compared with 6.7-fold in individuals without diabetes for major amputations. CONCLUSIONS: Diabetes-related amputation rates exhibit high regional variation, even after age, sex, and race adjustment. Future work should be directed to exploring sources of this variation.     

Non-alcoholic steatohepatitis: a childhood case

INTRODUCTION: A significant part of cryptogenic cirrhosis among adult patients shows that it can be the result of "burn-out" non-alcoholic steatohepatitis beginning in childhood. AIM: Describing the case of a 15-year-old boy the aim of the authors is to raise attention to the fact that doctors should think of the possibility of having a fatty liver in presence of certain etiological features. PATIENT: Although he was asymptomatic, the screening test revealed an elevated serum aspartate aminotransferase level. Abdominal ultrasound examination raised the possibility of a diffuse liver damage. The liver biopsy demonstrated the features of steatosis in the absence of alcohol abuse. RESULTS: On the basis of these results, NASH was diagnosed. The presence of a severe fatty liver at such an early age is quite unusual. In the background, the authors verified familial combined hyperlipidaemia and heterozygous mutation of the cystic fibrosis gene for delta F508 as genetic predisposing factor. The clinical condition was accelerated and worsened by the fact, that the patient has grown fat since his infancy. It did not prove possible to achieve a weight reduction with a fat- and cholesterol-poor diet, increased physical activity and medical treatment. However, there was significant improvement in the laboratory findings. CONCLUSIONS: The conclusion drawn from this case, on one hand, is that doctors should think of the possibility of a fatty liver in case of an elevated isolate serum transaminase level in connection with obese or over weight patients. On the other hand the role of other coexisting etiological features must emerge in the background of severe steatohepatitis.     

Pathways to diabetic limb amputation. Basis for prevention

We defined the causal pathways responsible for 80 consecutive initial lower-extremity amputations to an extremity in diabetic patients at the Seattle Veterans Affairs Medical Center over a 30-mo interval from 1984 to 1987. Causal pathways, either unitary or composed of various combinations of seven potential causes (i.e., ischemia, infection, neuropathy, faulty wound healing, minor trauma, cutaneous ulceration, gangrene), were determined empirically after a synthesis by the investigators of various objective and subjective data. Estimates of the proportion of amputations that could be ascribed to each component cause were calculated. Twenty-three unique causal pathways to diabetic limb amputation were identified. Eight frequent constellations of component causes resulted in 73% of the amputations. Most pathways were composed of multiple causes, with only critical ischemia from acute arterial occlusions responsible for amputations as a singular cause. The causal sequence of minor trauma, cutaneous ulceration, and wound-healing failure applied to 72% of the amputations, often with the additional association of infection and gangrene. We specified precise criteria in the definition of causal pathway to permit estimation of the cumulative proportion of amputations due to various causes. Forty-six percent of the amputations were attributed to ischemia, 59% to infection, 61% to neuropathy, 81% to faulty wound healing, 84% to ulceration, 55% to gangrene, and 81% to initial minor trauma. An identifiable and potentially preventable pivotal event, in most cases an episode involving minor trauma that caused cutaneous injury, preceded 69 to 80 amputations. Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.     

Providing Complementary and Alternative Medicine in primary care: the primary care workers' perspective

BACKGROUND: The use of Complementary and Alternative Medicine (CAM) in primary care is growing, but still not widespread. Little is known about how CAM can/should be integrated into mainstream care. OBJECTIVES: To assess primary care health professionals' perceptions of need and of some ways to integrate CAM in primary care. METHOD: Questionnaire survey of primary health care workers in Northwest London. General Practitioners (GPs) were targeted in a postal survey, other members of the primary care team, such as district and practice nurses, were targeted via colleagues. The questionnaire assessed health care professionals' perspective on complementary medicine, referrals, ways to integrate complementary medicine into primary care and interest in research on CAM. RESULTS: Responses were obtained from 149 GPs (40% response rate after one reminder) and 24 nurses and 32 other primary care team members. One hundred and seventy-one (83%) respondents had previously referred (or influenced referral) for CAM treatments, the main reasons cited were: patients request (68%), conventional treatments failed (58%) and evidence (36%) (more than one reason could be given). Acupuncture and homoeopathy were the therapies for which patients were most frequently referred, followed by manual therapies. There was a significant interest in more training/information on CAM (66%). Only 12 respondents (6%) were against any integration of CAM in mainstream primary care. Most respondents felt that CAM therapies should be provided by doctors (66%) or other health professionals trained in CAM (82%). Twenty-six percent of respondents agreed with provision of CAM by non-state-registered practitioners. It was felt that the integration of CAM could lead to cost savings (70%), particularly in conditions involving pain, but also cost increases (55%) particularly in 'poorly defined conditions'. Fifty-six percent of respondents would consider participating in studies investigating CAM. The greatest interest was in acupuncture (41% of those who expressed an interest in research), homoeopathy (30%) and therapeutic massage/aromatherapy (26%). CONCLUSIONS: There is considerable interest in CAM among primary care professionals, and many are already referring or suggesting referral. Such referrals are driven mainly by patient demand and by dissatisfaction with the results of conventional medicine. Most of our respondents were in favour of integrating at least some types of CAM in mainstream primary care. There is an urgent need to further educate/inform primary care health professionals about CAM.