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MRI dynamics of brain and spinal cord in progressive multiple sclerosis.

OBJECTIVE: To assess the usefulness of serial cord MRI in patients with progressive multiple sclerosis. METHODS: Monthly MRI of the brain and spinal cord with and without gadolinium enhancement was carried out in 19 patients with progressive multiple sclerosis (10 primary progressive, nine secondary progressive) over the course of one year. RESULTS: During this period there were 132 active lesions in the brain and only six in the cord. One hundred and twelve (85%) active brain lesions occurred in the secondary progressive group; three new cord lesions occurred in each group. In the secondary progressive group MRI activity was high in patients who had superimposed relapses, whereas in those who progressed without relapse and in the primary progressive group it was low. Cross sectional areas of the cord decreased at the C5 level in both groups, implying progressive atrophy of fibre tracts. There was no relation between either brain or cord MRI activity and change in disability over the study period. CONCLUSIONS: Although the detection of new lesions by frequent cord imaging using current technology has little role in the monitoring of disease activity in progressive multiple sclerosis, the serial measurement of cord cross sectional area may be important. There is also evidence to suggest that the mechanism underlying irreversible disability in patients with progressive multiple sclerosis may be different in patients who continue to relapse than in those who do not.

Atrophy↗

Efficacy of rivastigmine in Alzheimer's disease patients with rapid disease progression: results of a meta-analysis.

BACKGROUND: Alzheimer's disease (AD) patients experiencing more rapid symptom progression are likely to have a poorer prognosis than those experiencing slow symptom progression. In a recent retrospective analysis, treatment effects of rivastigmine were more pronounced in AD patients with rapid cognitive decline than in those with slow cognitive decline. This warranted further investigation. METHODS: Rapidly and slowly progressing patients were identified by rates of cognitive decline [>/=4 points and <4 points, respectively, on the Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-cog)] during 26 weeks of placebo treatment in four randomized controlled trials (weeks 0--26). This meta-analysis evaluated rates of cognitive decline in both subgroups during subsequent open-label rivastigmine 26-week extension studies (weeks 26--52). A longitudinal mixed effects model compared cognitive decline in rapidly and slowly progressing patients, including correction for possible regression to the mean. RESULTS: 180 (75%) rapidly and 337 (78%) slowly progressing patients provided ADAS-cog data after 26 weeks of open-label rivastigmine treatment. Improvements in cognitive symptoms were observed during the first 12 weeks, which were more pronounced in patients with rapid progression than in those with slow progression. Rapidly progressing patients experienced significantly greater cognitive benefits than slowly progressing patients (p=0.029), who experienced a modest decline in cognitive symptoms at the end of the study. COMMENT: Patients experiencing rapid symptom progression may receive greater benefit from rivastigmine than those with slow progression. In this study, cholinesterase inhibition appeared to be of particular utility in the management of AD patients whose symptoms were rapidly worsening.

Alzheimer Disease↗

Longitudinal monitoring for disease progression of localized juvenile periodontitis.

The present study was performed to investigate the factors associated with disease progression in localized juvenile periodontitis (LJP) patients by longitudinal monitoring of microbiological changes. Following a 9-month period, 9 LJP patients were divided into 2 groups based upon attachment loss, progressing and non-progressing. Both groups received scaling, root planing, and modified Widman flaps. Clinical and microbiological data were obtained at baseline, following the observation period, and at 6 and 12 months post-treatment. At 6 and 12 months post-treatment significantly more cocci were persistent in the non-progressing group than in the progressing group. Actinobacillus actinomycetemcomitans was also more frequently isolated in the progressing group than in the non-progressing group initially and following the 9-month observation period. Also after treatment, A. actinomycetemcomitans recolonized earlier in the progressing group than in the non-progressing group. These studies suggest that A. actinomycetemcomitans may play a role in disease progression in LJP; however, they do not eliminate the possibility that other organisms may also play a role, since A. actinomycetemcomitans was not detected in all of the patients in whom disease progressed.

Adolescent↗

Progression of age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake.

BACKGROUND: Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large, growing segment of the elderly population. Evidence is sparse regarding modifiable factors that may decrease the risk of progression to the advanced forms of AMD. OBJECTIVE: To advise patients with a high risk for advanced forms of AMD about preventive measures through our evaluation of the relationship between dietary fat intake and the progression of early or intermediate AMD to the advanced stages of the disease associated with visual loss. DESIGN: A prospective cohort study with an average follow-up time of 4.6 years. SETTING: A hospital-based clinical retinal practice specializing in macular degeneration. Patients The 261 participants were aged 60 years and older and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least 1 eye. Main Outcome Measure Progression to advanced AMD, which was defined as having geographic atrophy or neovascular disease. RESULTS: Higher total fat intake increased the risk of progression to the advanced forms of AMD, with a relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest fat-intake quartile relative to the lowest fat-intake quartile, after controlling for other factors (P trend =.01). Animal fat intake was associated with a 2-fold increased risk of progression (RR, 2.29 for the highest quartile compared with the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for increasing risk with higher animal fat intake was not significant (P=.09). Higher vegetable fat intake had a stronger relationship with increased risk of AMD progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the highest quartile compared with the lowest quartile (P trend =.003). Saturated, monounsaturated, polyunsaturated, and transunsaturated fats increased the likelihood of progression (RR, 2.09 and P trend =.08; RR, 2.21 and P trend =.04; RR, 2.28 and P trend =.04; RR, 2.39 and P trend =.008, respectively). Higher fish intake was associated with a lower risk of AMD progression among subjects with lower linoleic acid intake. Processed baked goods, which are higher in some of these fats, increased the rate of AMD progression approximately 2-fold, and nuts were protective. CONCLUSIONS: Among individuals with the early or intermediate stages of AMD, total and specific types of fat intake, as well as some fat-containing food groups, modified the risk of progression to advanced AMD. Fish intake and nuts reduced risk. Since advanced AMD is associated with visual loss and reduced quality of life, these preventive measures deserve additional research and greater emphasis.

Aged↗

The effect of body weight on progression of knee osteoarthritis is dependent on alignment.

OBJECTIVE: Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment. METHODS: The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations. RESULTS: Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45). CONCLUSION: Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.

Aged↗

Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors.

BACKGROUND: In vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors. METHODS: MR spectroscopic imaging examinations were performed on 27 children with neuroglial brain tumors during therapy on a 1.5-Tesla MR system. Normalized rTBV values were measured in 11 of 27 patients. Each examination was rated as stable or progressive by clinical and imaging criteria. RESULTS: The percent change in normalized choline (Cho) was significantly greater in patients who had progressive examinations compared with patients who had stable examinations (P = 0.03). The percent change in Cho/N-acetylaspartate (Cho/NAA) was significantly higher in patients who had progressive outcomes (n = 18 patients) compared with patients who had stable outcomes (n = 32 patients; P < 0.001; sensitivity, 0.89; specificity, 0.88) and was identified as the most important prognostic indicator of tumor progression by logistic regression (likelihood ratio test, 33.4; P < 0.001). The odds of tumor progression were approximately 55 times greater for patients who showed at least a 20% change in Cho/NAA. rTBV distinguished between progressing and stable tumors (P = 0.03), and Cho/NAA and rTBV values showed interaction to predict the probability of a progressing clinical outcome. CONCLUSIONS: The percent change in Cho/NAA by proton MR spectroscopic imaging, assisted by rTBV, was useful in predicting tumor progression in children with brain tumors.

Adolescent↗

Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment.

BACKGROUND: Predictors of progression to dementia in individuals with mild cognitive impairment (MCI) define different groups with higher risks of progression. To date, efforts to differentiate those who will progress to dementia from those who will not have proved inconclusive, and while grades of risk have been identified, their generalizability is not clear. AIM: To examine the clinical and socio-demographical risk factors for progression of memory decline in a sample of subjects with referred memory complaints who met criteria for amnestic MCI. METHODS AND MATERIALS: Seventy-four subjects consecutively recruited who met the operational criteria for amnestic MCI. They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after one year. Memory decline was defined using the short story mean score change (at follow-up and at baseline). Subjects showing memory decline, with or without conversion to AD over time, were classified as having progressive MCI; subjects that remained unchanged or improved during follow-up were considered as having stable MCI. RESULTS: Subjects with progressive MCI (n = 39, 53%) were older (p = <0.001) and more educated (p = 0.01) compared to stable MCI (n = 35, 47%) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (p = 0.05). Antihypertensive drug prescription was greater in the stable MCI compared to progressive MCI (p = 0.01) and significant higher levels of plasma total homocysteine were observed in progressive MCI (p = 0.03). When analyzed in a logistic regression model, the prescription of Angiotensin Converting Enzyme Inhibitors (ACE) was found to be independently associated to the stability of cognitive function, whereas older age, higher education, higher levels of plasma total homocysteine and total ADAS-Cog basal score were independently associated with the progression of cognitive decline. CONCLUSIONS: Older age, higher education, poor global cognitive performance, higher levels of plasma total homocysteine are independently associated with the progression of memory decline while the prescription of ACE Inhibitors is a protective factor for cognitive deterioration.

Aged↗

Impact of steatosis on progression of fibrosis in patients with mild hepatitis C.

In patients with mild hepatitis C, the usefulness of antiviral therapy is subject of debate, as a low risk for progression of fibrosis is assumed. Several studies have shown that steatosis is a strong and independent predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. Therefore, this study assessed the impact of steatosis on the progression of fibrosis between paired liver biopsies in untreated patients with mild hepatitis on index biopsy. One hundred thirty-five untreated patients (mean age, 38 years; M/F sex ratio, 1.43) with one known risk factor of infection (68 transfusions, 67 injecting drug use) had 2 liver biopsies after a median interval of 61 months (18-158). All had METAVIR score of A1F1 or lower at first liver biopsy. Unequivocal progression of fibrosis was considered if patients had a fibrosis score of 3 or 4 at the second liver biopsy. The probability of progression of fibrosis was estimated by using the Kaplan-Meier method. During follow-up, progression of fibrosis occurred in 21 patients (16%) after a median delay of 65 months. Cumulative probabilities of the progression of fibrosis at 4 and 6 years were 5.2% and 19.8%, respectively. In multivariate analysis, steatosis was the only independent factor predictive of progression of fibrosis (RR, 4.8; CI, 1.3-18.3). Probability of progression of fibrosis was significantly related to the percentage of hepatocytes with steatosis. In conclusion, steatosis is a major determinant of the progression of fibrosis in mild hepatitis C, regardless of the genotype. Our results argue for antiviral treatment in the subgroup of patients with mild hepatitis and steatosis.

Adult↗

Differential modulation by interferon gamma of the sensitivity of human melanoma cells to cytolytic T cell clones that recognize differentiation or progression antigens.

Human melanoma is a highly immunogenic tumor capable of inducing a specific immune response. A number of melanoma-associated antigens have been characterized during the past several years and can be classified into two groups: differentiation antigens-present also in normal melanocytes-and tumor-specific antigens, which, with the exception of testis, are present only in tumor cells. In a previous publication [Kirkin A. F., Petersen T. R., Olsen A. C., Li L., thor Straten P., Zeuthen J. (1995) Cancer Immunol Immunother 41:71] we have described the production of clones of cytotoxic T lymphocytes (CTL) against the highly immunogenic human melanoma cell line FM3. Using these clones we have defined four previously unknown melanoma-associated antigens, which could be subdivided into differentiation and progression antigens. In the experiments reported in this paper, we have further compared CTL clones from different groups and shown that the sensitivity of melanoma cells to CTL that recognize differentiation or progression antigens is differentially modulated during tumor progression as well as by the lymphokines interferon gamma (IFN gamma) and interleukin-10 (IL-10). The interaction of CTL clones recognizing progression antigens was strongly increased after treatment of melanoma cells with IFN gamma, while the recognition by CTL clones specific for differentiation antigens either was unchanged or significantly decreased. IL-10 treatment of melanoma cells induced up-regulation with respect to recognition by CTL clones specific for differentiation antigens without affecting the recognition of melanoma cells by CTL clones specific for progression antigens. Using cellular systems at different stages of tumor progression, we demonstrated that the progressed state of melanoma cells is associated with increased sensitivity to recognition by CTL clones detecting progression antigens, and with decreased sensitivity to CTL clones recognizing differentiation antigens. Mimicking tumor progression, treatment with IFN-gamma induced apparent down-regulation of differentiation antigens. A hypothesis is suggested in which IFN-gamma plays different roles in the immune response against poorly immunogenic and highly immunogenic melanoma cells, increasing the progression of poorly immunogenic tumor cells or promoting a strong immune response and regression of highly immunogenic melanoma cells.

Animals↗

Glomerular CD8+ cells predict progression of childhood IgA nephropathy.

The aim of this study was to evaluate whether the infiltrating T-lymphocyte can be a predictor in the disease progression of IgA nephropathy (IgAN). Twenty children with IgAN, followed for more than 5 years, were divided into progressive (n=5) and non-progressive groups (n=15). We assessed glomerular and interstitial infiltration of T-lymphocytes (CD4+ and CD8+ cells) and expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta) using an indirect immunofluorescence method on the renal biopsies. We analyzed their relationship to the degree of proteinuria, histological changes, and prognosis. The number of CD8+ cells in glomeruli and in interstitium was higher in the progressive group than in the non-progressive group. The glomerular alpha-SMA staining was more intensive in the progressive group than in the non-progressive group. Urinary protein and the degree of histological changes were also higher in the progressive group than in the non-progressive group. Among these markers, the number of glomerular CD8+ cells was the most apparent difference between the two groups. In conclusion, these results indicate that the number of glomerular CD8+ cells is the most sensitive predictor of disease progression in childhood IgAN.

Actins↗

Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs.

Our objective was to assess the progression of osteoarthritis (OA) using scoring systems based on the anatomical changes recorded in the finger joints on standard radiographs and to test how far these scoring systems could be used to evaluate the effects of candidate "disease modifying osteoarthritis drugs" (DMOAD). The appearance and growth of osteophytes, narrowing of the joint space and subchondral bone changes allowed the classic OA-associated anatomical lesions to be used to score the progression of finger joint OA. Progression of OA in the finger joints was also assessed by the their evolution through previously described and predictable anatomical phases on standard X-rays. These phases were characterised by complete loss of the joint space preceding or coinciding with the appearance of subchondral cysts eroding the entire subchondral plate, and have been described in "inflammatory" or "erosive" OA. The erosive episodes were followed by processes of remodelling. In order to interfere with the progression of osteoarthritis, two chondroitin sulphates with possible DMOAD effects were used in two series of patients with OA of the finger joints. The patients were included in two separate randomised, double-blind placebo-controlled trials: 46 of them received chondroitin polysulphate and 34 received chondroitin sulphate. Eighty-five patients were kept on placebo medication and were used as controls. All 165 patients were followed for 3 years. Posteroanterior X-rays of the metacarpophalangeal and interphalangeal (IP) finger joints were obtained at the start of this prospective study and at yearly intervals thereafter. Almost 80% of the distal IP and 50% of the proximal IP were affected at study entry. In approximately 40% of the patients the classic picture of OA of the IP joints was complicated by manifest erosive OA changes. The two systems to score the progression of OA (Anatomical Lesion and Anatomical Phase Progression Score System) showed definite progression within 3 years of follow-up, especially in the IP joints. When compared with the placebo controls, none of the chondroitin sulphates prevented OA from occurring in previously normal finger joints. However, when the classic OA-associated anatomical lesions were considered, OA was less progressive in both active treatment groups. Furthermore, fewer patients from both chondroitin sulphate- and chondroitin polysulphate-treated groups developed "erosive" osteoarthritis. In conclusion, conventional radiographs can be used to assess the morbidity and progression of hand OA. The systems used to score the progression of finger joint OA allowed the DMOAD effects of both chondroitin sulphates to be evaluated. The data recorded during these pilot studies should help investigators to design future long-term clinical experiments.

Adult↗

Prognostic factors of radiographic progression in early rheumatoid arthritis: a two year prospective study after a structured therapeutic strategy using DMARDs and very low doses of glucocorticoids.

The objective of the study was to analyze the prognostic factors of radiographic progression in a series of patients with early rheumatoid arthritis (RA) after 2 years of therapy with a structured algorithm using disease-modifying antirheumatic drugs (DMARDs) and very low doses of oral glucocorticoids. One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for 2 years. The outcome variable was radiographic progression after 2 years of DMARD therapy using the modified Larsen method. Clinical, biological, immunogenetic, and radiographic data were analyzed at study entry and after 1 and 2 years of follow-up. Radiographic progression (increase of four or more units in the Larsen score) was observed in 32% of patients after 2 years of follow-up. The percentage of erosive disease increased from 18.3% at baseline to 28.9% at 12 months and 44.6% at 24 months, in spite of a significant improvement in disease activity. New erosions appeared in 33% of patients after 2 years. Several baseline parameters were associated with radiographic progression in the univariate analysis: shared epitope (SE) homozygozity, HLA-DRB*04 alleles, female gender, hemoglobin, erythrocyte sedimentation rate, and anticyclic citrullinated peptide antibodies (anti-CCP). In the multivariate analysis, female gender [odds ratio (OR) 5.5, 95% confidence interval (CI): 1.1-28.2, p = 0.04], DRB1*04 alleles (OR 3.1, 95% CI 1.1-9, p = 0.03) and, marginally, anti-CCP antibodies (OR 3.6, 95% CI 0.9-14.5, p = 0.06), were associated with progression. Female patients with both DRB1*04 alleles and anti-CCP antibodies showed the highest scores in radiographic progression. The presence, but not the titer, of anti-CCP antibodies predicted progression. The positive predictive value of the multivariate model for progression was only 53.9% whereas the negative predictive value was 80.3%. In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, radiographic progression was observed in one third of patients after 2 years. Female gender, DRB1*04 alleles (rather than the SE), and the presence of anti-CCP antibodies at baseline (independently of the titer) were the most important predictors of progression. The utility of these parameters in clinical practice is limited by their relatively low positive predictive value.

Antirheumatic Agents↗

Rapid angiographic progression of "target" and "nontarget" stenoses in patients awaiting coronary angioplasty.

OBJECTIVES: Our aim was to compare the short-term evolution of "target" versus "nontarget" stenoses in patients awaiting coronary angioplasty. BACKGROUND: Coronary angioplasty is effective therapy for angina pectoris, but coronary events occur after successful angioplasty that are caused by both restenosis and progression of mild preexisting nontarget stenoses. METHODS: We prospectively studied 161 consecutive patients with stable angina (124 men and 37 women). After diagnostic angiography, target stenoses for angioplasty and nontarget lesions were identified. Patients were put on a routine waiting list and followed up regularly until repeat coronary arteriography was performed (mean +/- SD 7 +/- 3 months), either immediately before angioplasty (138 patients) or soon after an acute coronary event (23 patients), if one occurred. Stenosis diameter was measured by using computerized arteriography. Progression of disease was defined as > or = 20% lesion diameter reduction, new total occlusion or development of a "new" stenosis > or = 30%. RESULTS: At study entry, the mean diameter of target (n = 207) and nontarget (n = 184) lesions was 68 +/- 9% and 38 +/- 9%, respectively (p < 0.001). Disease progression occurred in 33 patients (20%). Seven new lesions (one total occlusion) developed. Eighteen target (9%) and 15 nontarget (8%) stenoses progressed. The power of the study to detect a difference of 1% between the risks of progression of target and nontarget stenoses with a 90% probability was < 0.1. Total occlusion developed in 15 (83%) of the 18 target and 6 (40%) of the 15 nontarget stenoses (p = 0.03). During follow-up, a myocardial infarction developed in 3 patients (2%) and unstable angina in 20 (12%). These coronary events were associated with progression of target stenoses in 10 patients and nontarget stenoses in 7 and with the development of new lesions in 1. In five patients coronary events were not associated with stenosis progression. CONCLUSIONS: Despite differences in baseline severity, a similar proportion of target and nontarget lesions progressed rapidly. However, target stenoses were more likely than nontarget lesions to progress to total occlusion. Progression of nontarget stenoses may contribute to recurrence of angina and new coronary events after successful angioplasty and should be considered when developing strategies aimed at improving outcome after angioplasty.

Aged↗

Comparability of two fundus photograph reading centers in grading cytomegalovirus retinitis progression.

PURPOSE: To compare grading of cytomegalovirus retinitis progression by two different fundus photograph reading centers (FPRCs). DESIGN: Patients with AIDS followed in an ophthalmology service were enrolled in a prospective epidemiologic study of the prevalence and incidence of resistant cytomegalovirus in vitro. METHODS: We compared masked replicate gradings by two different FPRCs of monthly fundus photographs for retinitis progression (onset of a separate new lesion or expansion of an existing lesion by > or =one-half disk diameter). RESULTS: For 77 patients, Kaplan-Meier plots of progression over time were similar between FPRCs (median time to progression, 65 vs 69 days). Agreement between FPRCs was 51% (kappa [kappa] =.37, "fair") on exact visit of progression (28 patients) or on absence of progression through follow-up (11 patients) and 62% (kappa =.38) on progression visit +/- 1 month. Eight of 12 patients with progression graded as more than 1 month apart were only 2 months apart. Considering each monthly visit as a choice point, overall agreement on progression was 78% (kappa =.55, "moderate"). Baseline evaluation of retinitis showed 95% agreement on presence/absence and a concordance correlation coefficient of.75 for extent in combined zones 1 and 2. Rates of retinal loss over follow-up were estimated as 2.8%/month vs 2.0%/month (P =.015). CONCLUSIONS: By adopting similar protocols and procedures, different FPRCs can achieve good agreement on presence and extent of cytomegalovirus retinitis. Further efforts to harmonize evaluation through ongoing comparison of gradings would likely improve agreement on retinitis progression.

AIDS-Related Opportunistic Infections↗

Plasma homocysteine predicts progression of atherosclerosis.

UNLABELLED: MINI ABSTRACT: Three emerging risk factors potentially useful in predicting future cardiac events are electron-beam computed tomography (EBT), homocysteine(HCY), and C-reactive Protein (CRP). We evaluated a cohort of 133 serial asymptomatic patients, who underwent two consecutive EBT scans (8-84 months apart) and a comprehensive cardiac risk factor assessment, including measurements for lipids, ultrasensitive CRP and homocysteine. Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden. BACKGROUND: Despite the availability of effective preventive therapies, coronary artery disease (CAD) remains the leading cause of morbidity and mortality. Use of traditional cardiovascular risk factors is imprecise and predicts less than one half of future cardiovascular events. Three 'emerging risk factors', as potential means of identifying subclinical atherosclerosis and predicting future cardiovascular events, are electron-beam computed tomography, homocysteine, and C-reactive protein. Given the evidence that HCY and CRP are involved in atherogenesis, we hypothesized that significant progression of EBT calcium score (a measure of atherosclerotic plaque burden) is associated with higher levels of these markers. METHODS: We evaluated 133 asymptomatic patients (100 men, 33 women; mean age was 61 +/- 9 years) who underwent previous EBT calcium score testing at Harbor-UCLA 8-80 months prior to enrollment (mean follow-up 20 months). Exclusion criteria included those with known or symptomatic CAD and chronic renal disease. During enrollment, we measured risk factors, serum HCY, serum lipids, ultrasensitive-CRP, and repeat EBT calcium scan. Statistical analysis was performed using probable Chi square method, and Student's t-test. RESULTS: Individuals with elevated HCY (> or =12 micromol/L) demonstrated a mean increase in CC progression of 35% per year, while those with HCY <12 micromol/L (median) progressed at 17% per year (p = 0.0008). Patients with a level equal to or lower than the median value of CRP (0.8 mg/L) had a median yearly progression of 22%, compared to 21% for those with CRP value = 0.9-11 mg/L (p = ns). Neither cholesterol values, body mass index, gender, age nor presence of individual risk factors predicted progression of coronary calcium. CONCLUSION: Presence of elevated HCY (>12 micromol/L) strongly and independently predicts progression of coronary plaque burden.

Adult↗

An implication of hypertriglyceridemia in the progression of diabetic nephropathy in metabolically obese, normal weight patients with type 2 diabetes mellitus in Korea.

This study was undertaken to investigate diverse risk factors affecting the progression of diabetic nephropathy (DN) by observing the changes of 24 h urinary albumin excretion (24 h UAE) in 90 abdominally obese, normal weight, type 2 diabetic patients with normo- or micro-albuminuria. Patients were divided into three groups according to the 24h UAE; normo-, micro-, and macro-albuminuria group. After 4 years of follow-up, patients were divided into either progression or non-progression group according to the changes of 24 h UAE. About 37% of the normo-albuminuria group and 18% of the micro-albumiuria group were classified into the progression group. The initial serum creatinine levels and the initial and follow-up post-prandial plasma glucose levels were significantly higher in the progression group than in the non-progression group. Most remarkably, the initial and follow-up serum triglyceride (TG) levels (190 +/- 132 versus 132 +/- 49 mg/dl and 191 +/- 124 versus 133 +/- 41 mg/dl, P < 0.01 in both) were significantly higher in the progression group than in the non-progression group, suggesting hypertriglyceridemia might be included in the progression factors of DN. The increases in 24-hour UAE were positively associated with the initial and follow-up post-prandial plasma glucose levels (P < 0.05 in both), the initial and follow-up serum creatinine levels (P < 0.05 in both), and the initial serum TG levels (P < 0.05). Whereas, insulin users or patients with retinopathy at follow-up (P < 0.05 in both) showed more rapid progression of albuminuria, ACE inhibitors or acarbose (P < 0.05 in both) use turned out to protect against it.

Albuminuria↗

The natural progression and remission of erectile dysfunction: results from the Massachusetts Male Aging Study.

PURPOSE: Erectile dysfunction affects more than 150 million men and is strongly associated with cardiovascular disease. A 1992 National Institutes of Health consensus development panel identified erectile dysfunction progression and spontaneous remission as priorities for investigation, but there are few data describing the natural course of the disorder following its initial presentation. This analysis estimates the frequency of erectile dysfunction progression and remission among aging men, and assesses the relation of progression/remission to demographics, socioeconomic factors, comorbidities and modifiable lifestyle characteristics. MATERIALS AND METHODS: Data from the Massachusetts Male Aging Study, a longitudinal study of men (401) 40 to 70 years old, were analyzed to assess erectile dysfunction severity following initial presentation of symptoms. Logistic regression was used to estimate the odds of erectile dysfunction progression/remission as a function of covariates. RESULTS: A total of 141 subjects (35%) exhibited erectile dysfunction remission (95% CI: 30%, 40%). Of 323 subjects with minimal or moderate baseline erectile dysfunction 107 (33%) exhibited erectile dysfunction progression (95% CI: 28%, 38%). The 78 subjects with complete erectile dysfunction were considered ineligible for progression and 45 (58%) of these exhibited complete erectile dysfunction at followup. Age and body mass index were associated with progression and remission, while smoking and self-assessed health status were associated with progression only. CONCLUSIONS: Natural remission and progression occur in a substantial number of men with erectile dysfunction. The association of body mass index with remission and progression, and the association of smoking and health status with progression, offer potential avenues for facilitating remission and delaying progression using nonpharmacological intervention. The benefits of such interventions for overall men's health may be far-reaching.

Aged↗

Plaque blush, branch location, and calcification are angiographic predictors of progression of mild to moderate coronary stenoses.

BACKGROUND: Angiographic predictors of plaque progression are weak and few: length, irregular surface, turbulence, low shear, and (in some studies) eccentricity and calcification. Having noted plaques that briefly retained dye after angiography, we interpreted these as plaques with a fissured surface or neovascularization and hypothesized that progression would be predicted by "plaque blush." METHODS: Plaques (<50% diameter stenosis) in 68 pairs of angiograms, 5.6 +/- 4.8 months apart, were reviewed by 2 blinded observers. The presence of plaque blush, calcification, clot (mobile defect), eccentricity, and a branch point location were compared between progressing (> or =20% stenosis increase) and nonprogressing plaques. RESULTS: Sixteen lesions in 15 patients progressed from 29% +/- 13% to 68% +/- 14% over a period of 8.1 +/- 7.9 months. Patients with and without progression were similar in sex, age, congestive heart disease risk factors, medications, interval between angiograms, clinical presentation, and initial stenosis severity. By logistic regression, plaque blush (BL) (P =.002), calcification (CA) (P =.024), and a branch (BR) point location (P =.001) predicted plaque progression. The odds ratio for plaque progression (ORp) was calculated as ORp = e(2.5 x BL + 1.8 x CA + 2.6 x BR). Using an ORp of 1/3, the model has 81% sensitivity and 77% specificity. A second analysis in which each progressive lesion was compared with proximal and distal lesions and with one in a different coronary artery yielded similar results. CONCLUSIONS: In mild to moderate coronary stenoses, studied retrospectively, plaque blush (a new sign) and a branch point location were strong predictors of plaque progression, whereas calcification was a weak predictor of progression.

Calcinosis↗