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PubMed2006

Progression of atherosclerotic renovascular disease: A prospective population-based study.

OBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS). METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion. RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95% CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD. CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0% of kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and no prevalent RVD progressed to occlusion.

Aged↗
PubMed2006

Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial.

PURPOSE: To investigate whether increased fluctuation of intraocular pressure (IOP) is an independent factor for glaucoma progression. DESIGN: A cohort of patients was followed up in a randomized clinical trial. PARTICIPANTS: Two hundred fifty-five glaucoma patients from the Early Manifest Glaucoma Trial (EMGT; 129 treated and 126 control patients). METHODS: Study visits, conducted every 3 months, included ophthalmologic examinations, IOP measurements, and standard automated perimetry, with fundus photography every 6 months. Intraocular pressure values were included only until the time of progression in those eyes that showed such progression. Individual mean follow-up IOP and IOP fluctuation, calculated as the standard deviation of IOP at applicable visits, were the variables of main interest. Cox regression with time-dependent variables was used to evaluate the association between IOP fluctuation and time to progression, both with and without IOP mean in the models. These analyses also controlled for other significant variables. MAIN OUTCOME MEASURES: Glaucoma progression, as defined by a predetermined visual field criterion, worsening of the disk, assessed by an independent disc reading center, or both. RESULTS: Median follow-up time was 8 years (range, 0.1-11.1 years). Sixty-eight percent of the patients progressed. When considering mean follow-up IOP and IOP fluctuation in the same time-dependent model, mean IOP was a significant risk factor for progression. The hazard ratio (HR) was 1.11 (95% confidence interval [CI], 1.06-1.17; P<0.0001). Intraocular pressure fluctuation was not related to progression, with an HR of 1.00 (95% CI, 0.81-1.24; P = 0.999). CONCLUSIONS: These results confirm our earlier finding that elevated IOP is a strong factor for glaucoma progression, with the HR increasing by 11% for every 1 mmHg of higher IOP. Intraocular pressure fluctuation was not an independent factor in our analyses, a finding that conflicts with some earlier reports. One explanation for the discrepancy is that our analyses did not include postprogression IOP values, which would be biased toward larger fluctuations because of more intensive treatment. In contrast, in this EMGT report, no changes in patient management occurred during the period analyzed.

Aged↗
PubMed2004

Preoperative PSA level significantly associated with interval to biochemical progression after radical retropubic prostatectomy.

OBJECTIVES: To evaluate the association between the preoperative prostate-specific antigen (PSA) level and the interval to biochemical progression after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: We studied 5534 men who underwent RRP for prostate cancer during a 15-year period and were enrolled in prospective follow-up studies. Of these men, 857 (15%) subsequently had biochemical evidence of cancer progression (PSA greater than 0.2 ng/mL). All men with biochemical progression after RRP were arbitrarily stratified into five groups according to their preoperative PSA level: less than 2.6 ng/mL, 2.6 to 4 ng/mL, 4.1 to 10 ng/mL, 10.1 to 20 ng/mL, and greater than 20 ng/mL. The time to biochemical progression after RRP was the primary endpoint of the analysis. Other prognostic factors were also evaluated in multivariable analysis. RESULTS: The median time to progression for men with a PSA level greater than 20 ng/mL was significantly shorter (16 months) than for men with a PSA level of 10.1 to 20 ng/mL (27 months) or those with lower PSA levels (P = 0.0005). Men with a PSA level of 4.1 to 10 ng/mL did not have a statistically significantly different median time to progression (31 months) from men with a PSA level of 10.1 to 20 ng/mL (27 months; P = 0.3), 2.6 to 4 ng/mL (32 months; P = 0.8), or less than 2.6 ng/mL (38 months; P = 0.3). Also, no statistically significant difference was found in the median time to progression between men with a PSA level of 2.6 to 4 ng/mL and less than 2.6 ng/mL (P = 0.4). In an analysis of covariance multivariate analysis, the preoperative PSA level was not an independent predictor of the time to biochemical progression (P = 0.12), after accounting for tumor stage and Gleason grade. CONCLUSIONS: The preoperative PSA level was significantly associated with the interval to biochemical cancer progression after RRP; however, this association appeared to be because the preoperative PSA level serves as a surrogate marker for other prognostic factors, such as the tumor volume, tumor stage, and Gleason grade.

Adenocarcinoma↗
PubMed2004

Pretumor progression: clonal evolution of human stem cell populations.

Multistep carcinogenesis through sequential cycles of mutation and clonal succession is usually described as tumor progression, or the clonal evolution of tumor cell populations. However, many mutations found in cancers are also compatible with normal appearing phenotypes and therefore genetic progression may precede tumor progression. To better characterize such pretumor progression (mutations in the absence of visible phenotypic changes), a quantitative model was developed that postulates most oncogenic cancer mutations first accumulate in normal appearing colon crypt niche stem cells. Each crypt contains multiple stem cells, and random niche stem cell loss with replacement eventually leads to the loss of all stem cell lineages except one. This niche succession or crypt clonal evolution is similar to the clonal succession of tumor progression except it does not require selection or change visible phenotype. Mutations may sequentially accumulate during stem cell clonal evolution either through drift (passenger mutations) or selection. To determine the feasibility of pretumor progression, mutation rates sufficient to recreate the epidemiology of colorectal cancer were estimated. Pretumor progression may completely substitute for visible tumor progression because it is theoretically possible for all cancer mutations to first accumulate in normal appearing colon with normal replication fidelity. Elevated mutation rates or tumorigenesis may be unnecessary for early progression.

Adult↗
PubMed1999

Genetically engineered neural networks for predicting prostate cancer progression after radical prostatectomy.

OBJECTIVES: To use pathologic, morphometric, DNA ploidy, and clinical data to develop and test a genetically engineered neural network (GENN) for the prediction of biochemical (prostate-specific antigen [PSA]) progression after radical prostatectomy in a select group of men with clinically localized prostate cancer. METHODS: Two hundred fourteen men who underwent anatomic radical retropubic prostatectomy for clinically localized prostate cancer were selected on the basis of adequate follow-up, pathologic criteria indicating an intermediate risk of progression, and availability of archival tissue. The median age was 58.9 years (range 40 to 87). Men with Gleason score 5 to 7 and clinical Stage T1b-T2c tumors were included. Follow-up was a median of 9.5 years. Three GENNs were developed using pathologic findings (Gleason score, extraprostatic extension, surgical margin status), age, quantitative nuclear grade (QNG), and DNA ploidy. These networks were developed using three randomly selected training (n = 136) and testing (n = 35) sets. Different variable subsets were compared for the ability to maximize prediction of progression. Both standard logistic regression and Cox regression analyses were used concurrently to calculate progression risk. RESULTS: Biochemical (PSA) progression occurred in 84 men (40%), with a median time to progression of 48 months (range 1 to 168). GENN models were trained using inputs consisting of (a) pathologic features and patient age; (b) QNG and DNA ploidy; and (c) all variables combined. These GENN models achieved an average accuracy of 74.4%, 63.1 %, and 73.5%, respectively, for the prediction of progression in the training sets. In the testing sets, the three GENN models had an accuracy of 74.3%, 80.0%, and 78.1%, respectively. CONCLUSIONS: The GENN models developed show promise in predicting progression in select groups of men after radical prostatectomy. Neural networks using QNG and DNA ploidy as input variables performed as well as networks using Gleason score and staging information. All GENN models were superior to logistic regression modeling and to Cox regression analysis in prediction of PSA progression. The development of models using improved input variables and imaging systems in larger, well-characterized patient groups with long-term follow-up is ongoing.

Adult↗
PubMed2003

[Clinical and biological progression of incidental prostatic cancer ( Stage T 1a)].

OBJECTIVES: To analyze the biological and clinical progression of the prostate cancer stage T1a. MATERIAL AND METHODS: Retrospective study of 44 patients diagnosed of T1a prostate carcinoma between 1985 and 2001. We value biological and clinical progression, time up to the progression, mortality for tumour reason and survival, with the following stratification: patients without initial treatment and patients treated by means of external radiotherapy or radical prostatectomía. RESULTS: Of all 44 patients biological progression was observed in 5 (11.36%) and clinical progression in 4 (9.09%). The mortality to 5 years for tumour reason was of 2 (4.54%). Of all 38 patients without initial treatment biological progression was observed in 5 (13.15%), in an average time of 25.8 months and clinical progression in 4 (10.52%), in an average time of 34.5 months. The mortality to 5 years was of 2 (5.26%). In all 6 patients to whom radical treatment carried out them progression was not observed and they all live. There are no statistically significant differences between both groups of patients (p = NS). CONCLUSIONS: The biological and clinical progression of the T1a prostate cancer is low, 11.36% and 9.09%, respectively. The mortality to 5 years is of 4.54%. Differences of survival do not exist, statistically significant, between treated and not treated.

Adenocarcinoma↗
PubMed1997

The effect of paclitaxel on the progression of polycystic kidney disease in rodents.

Woo et al (Nature 368:750-753) reported that parenteral administration of paclitaxel arrested the striking renal enlargement and prolonged life in C57BL/6J-cpk/cpk mice with a rapidly progressive form of polycystic kidney disease (PKD). In the current study, we sought to determine whether paclitaxel could alter the progression of other forms of hereditary PKD in rodents. Paclitaxel was administered by intraperitoneal injection to C57BL/6J-cpk/cpk mice and Han:SPRD-Cy/Cy rats with rapidly progressive PKD and to DBA/2FG-pcy/pcy mice and Han:SPRD-Cy/+ rats with slowly progressive PKD. Paclitaxel (150 micrograms/wk) prolonged the survival of cpk/cpk mice from 24.5 days to more than 65 days and decreased kidney weight relative to body weight from 16.5% at 21 days of age to 8.2% at more than 65 days of age. Mortality attributable to paclitaxel was 12%. By contrast, the administration of paclitaxel (0.1 to 15 mg/kg/wk) to 7- to 10-day-old Han:SPRD-Cy/Cy rats with rapidly progressive PKD had no effect on the course of the disease; moreover, paclitaxel caused severe side effects and premature death in all the Cy/Cy animals. Heterozygous male Cy/+ rats develop slowly progressive renal enlargement and azotemia. Paclitaxel, administered at 7, 15, or 27 mg/kg/wk to male Cy/+ rats from 4 until 10 weeks of age, reduced body weight gain, had an inconsistent effect on kidney weight relative to body weight, and had no effect on the serum urea nitrogen concentration. Mortality associated with the 7, 15, and 27 mg/kg/wk doses of paclitaxel was 0%, 15.4%, and 28.5%, respectively. DBA/2FG-pcy/pcy mice of either sex developed slowly progressive renal enlargement and azotemia. The administration of paclitaxel (100 to 150 micrograms/wk) from 2 to 10 weeks of age to DBA/2FG-pcy/pcy mice with cystic disease had no effect on the increase in kidney weight or on the level of serum urea nitrogen in comparison to untreated cystic animals. Mortality associated with 100- and 150-micrograms/wk doses of paclitaxel was 0% and 20%, respectively. We conclude that paclitaxel diminished the rate of renal enlargement and increased the life span of cpk/cpk mice but not Cy/Cy rats with rapidly progressive forms of PKD. Paclitaxel had no apparent benefit in Cy/+ rats nor pcy/pcy mice with slowly progressive PKD. On the basis of these studies in rodents, it appears that paclitaxel has limited potential usefulness as a therapeutic agent in the treatment of PKD.

Animals↗
PubMedDate not supplied

Variations in psychosocial functioning associated with patterns of progression in cocaine-dependent men.

This study examined the relationship between patterns of progression of cocaine use and psychosocial functioning in a sample of cocaine-dependent men who were veterans. Four patterns of progression were examined: mild-severe, moderate-severe, mild-moderate-severe, and severe only. Analysis of variance and post hoc analysis with Duncan grouping revealed significant differences among cocaine users with different patterns of progression in terms of negativism, problem index for situations involving unpleasant emotions, problem index for situations involving urges, depression, somatic anxiety, and medical problems in the family. However, there were no significant differences on sensation seeking, confidence to resist taking cocaine in different situations, obsessive compulsiveness, somatization, attention deficit, and social adjustment. Cocaine users with a severe-only pattern of progression were significantly more dysfunctional than those with mild-moderate-severe progression in terms of negativism, problem index for situations involving unpleasant emotions, depression, and somatic anxiety. Cocaine users with mild-moderate-severe progression had significantly less somatic anxiety than those with mild-severe progression and had less negativism and a lower problem index for urges than those with moderate-severe progression. Logistic regression analysis revealed unique behavioral variables associated with different patterns of progression. The implications of these findings for treatment are discussed.

Adaptation, Psychological↗
PubMed1999

Progression of asymptomatic carotid stenosis: a natural history study in 1004 patients.

PURPOSE: The purpose of this study was to delineate the natural history of the progression of asymptomatic carotid stenosis. METHODS: In a 10-year period, 1701 carotid arteries in 1004 patients who were asymptomatic were studied with serial duplex scans (mean follow-up period, 28 months; mean number of scans, 2.9/patient). At each visit, stenoses of the internal carotid artery (ICA) and the external carotid artery (ECA) were categorized as none (0 to 14%), mild (15% to 49%), moderate (50% to 79%), severe (80% to 99%), preocclusive, or occluded. Progression was defined as an increase in ICA stenosis to >/=50% for carotid arteries with a baseline of <50% or as an increase to a higher category of stenosis if the baseline stenosis was >/=50%. The Cox proportional hazards model was used for data analysis. RESULTS: The risk of progression of ICA stenosis increased steadily with time (annualized risk of progression, 9.3%). With multivariate modeling, the four most important variables that affected the progression (P <.02) were baseline ipsilateral ICA stenosis >/=50% (relative risk [RR], 3.34), baseline ipsilateral ECA stenosis >/=50% (RR, 1.51), baseline contralateral ICA stenosis >/=50% (RR, 1.41), and systolic pressure more than 160 mm Hg (RR, 1. 37). Ipsilateral neurologic ischemic events (stroke/transient ischemic attack) occurred in association with 14.0% of the carotid arteries that were studied. The progression of ICA stenosis correlated with these events (P <.001), but baseline ICA stenosis was not a significant predictor. CONCLUSION: In contrast to recently published studies, we found that the risk of progression of carotid stenosis is substantial and increases steadily with time. Baseline ICA stenosis was the most important predictor of the progression, but baseline ECA stenosis also was identified as an important independent predictor. Contralateral ICA stenosis and systolic hypertension were additional significant predictors. We found further that the progression of ICA stenosis correlated with ischemic neurologic events but not baseline stenosis. The data provide justification for the use of serial duplex scans to follow carotid stenosis and suggest that different follow-up intervals may be appropriate for different patient subgroups.

Aged↗
PubMed2003

Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis.

We have previously shown that patients with primary progressive multiple sclerosis (MS) have significantly elevated plasma levels of antibody to GM3 ganglioside compared to patients with relapsing-remitting MS, healthy subjects and patients with other neurological diseases. Anti-GM3 antibody levels were elevated also in patients with secondary progressive MS but to a lesser extent than in primary progressive MS. As gangliosides are particularly enriched in the axonal membrane, these findings suggested that antiganglioside immune responses might contribute to the axonal damage in progressive forms of MS. The present study was performed to determine whether peripheral blood T cell responses to GM3 are also increased in progressive MS. Blood was collected from 98 untreated patients with MS (40 with relapsing-remitting, 27 with secondary progressive and 31 with primary progressive MS), 50 healthy subjects and 24 patients with other disorders of the CNS, and reactivity to GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed by 6-day T cell proliferation assays. Increased T cell reactivity to GM3 and GQ1b occurred significantly more often in patients with primary progressive MS than in healthy subjects and patients with other CNS diseases. These findings suggest that ganglioside-specific T cells may contribute to the axonal damage in primary progressive MS.

Adult↗
PubMed2003

Measuring visual field progression in the Early Manifest Glaucoma Trial.

AIMS: The Early Manifest Glaucoma Trial (EMGT) (316 eligible eyes) has used a new set of criteria to define visual field progression in glaucoma. This paper provides estimates of the amount of visual field worsening required to reach the EMGT definition of definite perimetric progression. METHODS: In the 148 eyes that reached definite progression, we first determined changes between baseline and the time of definite EMGT progression, both for mean deviation (MD) and for number of highly (p < 0.5%) significantly depressed test points in pattern deviation probability maps. Second, we studied whether such changes depended on baseline MD, intraocular pressure (IOP), age and time to progression, all of which are factors that affect the rate of field progression. RESULTS: In eyes reaching progression, the mean change in MD from baseline was -1.93 dB (SE +/- 0.20) and the mean change in number of significant points was +4.85 (SE +/- 0.35). These changes did not show linear dependency on baseline MD, IOP or time to progression. CONCLUSIONS: The average amount of field deterioration needed to reach EMGT visual field progression has been measured and expressed in more conventional units (i.e. a loss of about - 2dB in MD and an increase in about five highly significant points). These estimates will facilitate the clinical interpretation of the results of EMGT.

Aged↗
PubMed1995

Infiltration of the kidney by alpha beta and gamma delta T cells: effect on progression in IgA nephropathy.

We have studied renal biopsies from three groups of patients to determine if alpha beta T cells or gamma delta T cells are present, and whether their presence is correlated with disease progression in IgA nephropathy (IgAN). Group one comprised thin basement membrane disease biopsies (non-immunological control, N = 7); group two were patients with IgAN and stable renal function one year following biopsy (stable, N = 7); and group three were IgAN patients with rapidly declining renal function after one year (progressive, N = 7). Immunohistochemical staining using monoclonal antibodies (CD3, TcR beta, TcR delta) and molecular studies utilizing polymerase chain reaction amplification of cDNA transcribed from biopsy RNA, with primers specific for either the alpha beta TcR or gamma delta TcR, were undertaken. On immunohistochemistry a significant increase in CD3 + cells in progressive biopsies was seen (vs. control P = 0.002, vs. stable P = 0.002). The progressive biopsies infiltrate consisted of both alpha beta TcR (vs. control P = 0.001, vs. stable P = 0.003) and gamma delta TcR cells (vs. control P = 0.01). The RNA study demonstrated an increase in TcR C alpha transcription in the progressive (vs. control P = 0.003) biopsies. Increased TcR C delta transcription was seen in the progressive group (vs. control P = 0.01, vs. stable P = 0.02). We confirm that the presence of lymphocytes in IgAN biopsies predicts progressive disease. While alpha beta T cells are found in both stable and progressive disease, the presence of gamma delta T cells is only associated with progressive IgAN.

Adult↗
PubMed2006

Characteristics of progression of early age-related macular degeneration: the cardiovascular health and age-related maculopathy study.

AIMS: To determine the risk of age-related macular degeneration (AMD) progression posed by the presence of each early AMD characteristic. METHODS: A prospective cohort study of 254 participants aged 50 years and older, all with early AMD features at their baseline visit followed for an average of 7 years. Stereoscopic colour fundus photographs were graded for early AMD features using the International Classification System. AMD status was stratified into six exclusive levels along a continuum of disease severity according to drusen type, pigmentary abnormalities, or late AMD. Progression was assessed according to three definitions: a change between or within a severity level, or by side by side grading. RESULTS: The progression rate of early AMD ranged between 3.4 and 4.67% per annum depending upon the definition used. In total, 15 (6%) cases progressed from early AMD to the late complication of AMD. After controlling for age and smoking, cases with soft indistinct drusen at baseline were at a greater risk of progressing from early to late AMD than were cases without this characteristic (OR=3.72, 95%CI 1.20-11.54; P=0.02). CONCLUSION: Our proposed definitions of AMD progression give rates that are consistent with current knowledge of progression and its determinants. Each early AMD characteristic conveys its own risk of progression to an eye, with soft indistinct drusen carrying the greater risk. An international consensus on what defines AMD progression would greatly help the research community when trying to assess the importance of new risk factors and the effectiveness of novel interventions.

Aged↗
PubMed1997

The progression of nonsegmental vitiligo: clinical analysis of 318 patients.

BACKGROUND: Vitiligo is an acquired disorder with destruction of melanocytes and is characterized by cutaneous depigmentation with a progressive clinical course. We attempted to evaluate whether there was a relationship between the initial site and ultimate progression of nonsegmental vitiligo. METHODS: Three hundred and eighteen nonsegmental vitiligo patients were examined. Questionnaires regarding age, sex, duration of disease, family history, distribution of initial lesions, progression, and clinical type were recorded from personal interviews and case notes. RESULTS: Two hundred and eighty nine (90.9%) of the 318 patients showed progression of vitiligo at the time of examination. When the initial sites were the posterior trunk, hands, or feet, there was more progression of vitiligo to other body areas. The progression pattern was usually contiguous to the initial site. When the hands were the initial site, however, vitiligo most commonly progressed to the face. CONCLUSIONS: There may be a possible relationship between the initial site and ultimate progression of nonsegmental vitiligo. The progression pattern is usually contiguous to the initial site.

Back↗
PubMed2001

Increased plasma endothelin levels in angina patients with rapid coronary artery disease progression.

AIMS: To investigate the association between plasma endothelin levels and rapid coronary artery disease progression, as assessed by quantitative angiography. METHODS AND RESULTS: Changes in diameter were assessed in 224 coronary stenoses of 92 consecutive patients (62 men) with chronic stable angina pectoris who were on a waiting list for routine coronary angioplasty and underwent coronary angiography on two occasions: the first (diagnostic) angiogram was carried out at study entry and the second 5.5+/-3.0 months later, immediately prior to coronary angioplasty. A digital quantitative angiographic analysis system was used to assess differences in stenosis diameter between the first and second angiogram. Plasma immunoreactive endothelin levels were estimated by radioimmunoassay at study entry. Rapid coronary artery disease progression occurred in 29 (31.5%) patients according to pre-established criteria: 12 (41%) had a > or =10% diameter reduction of at least one pre-existing stenosis > or =50%, 10 (34%) had a > or =30% diameter reduction of a pre-existing stenosis <50%, 5 (17%) patients developed a new stenosis and 2 (7%) had progression of a lesion to total occlusion by the second angiogram. Baseline demographic, clinical and angiographic data were similar in patients with and without stenosis progression. Plasma endothelin levels were significantly higher in patients with rapid disease progression than in those without (5.7+/-2.0 pg. ml(-1)vs 3.9+/-1.6 pg. ml(-1), P<0.001). Multiple logistic regression analysis revealed that endothelin was an independent predictor of disease progression (P=0.001). Moreover, endothelin levels above 4.26 pg. ml(-1)(the median of the total endothelin concentrations) were associated with a sixfold increase in the risk of developing rapid stenosis progression. CONCLUSIONS: Plasma endothelin is raised in patients with coronary artery disease progression and may be a marker of risk of rapid stenosis progression. Endothelin may also play a pathogenic role in this process.

Aged↗
PubMed2003

Progression of fibrosis in chronic hepatitis C.

BACKGROUND & AIMS: Fibrosis is the hallmark of hepatic cirrhosis, worsening of which is probably the best surrogate marker for progression of chronic liver disease. We evaluated a large cohort of patients with chronic hepatitis C (CHC) using liver histology to assess the rate and predictors of progression of fibrosis. METHODS: The cohort consisted of 123 patients with CHC who underwent 2 liver biopsies 4-212 months (mean, 44 months) apart without intervening treatment. Liver histology was graded using the histology activity index (score, 0-18) and fibrosis staged using a scoring system of 0 (no fibrosis) to 6 (cirrhosis). RESULTS: Among 123 patients, 48 (39%) showed progression in fibrosis scores, 46 (37%) showed no change, and 29 (24%) showed improvement. Of those with worsening fibrosis, 75% had a 1-point increase and 25% a 2-point or greater increase in scores, and 9% showed progression to cirrhosis. The overall rate of progression was 0.12 fibrosis units per year, a rate that predicts progression to cirrhosis in 50 years if progression was linear. The rate of fibrosis progression was variable, and it was higher among older patients, those with higher serum alanine and aspartate aminotransferase levels, and those with the most extensive periportal necrosis on initial liver biopsy. CONCLUSIONS: The best predictors of fibrosis progression in CHC are the extent of serum aminotransferase elevations and the degree of hepatocellular necrosis and inflammation on liver biopsy. These findings support the recommendation that patients with normal aminotransferase levels and mild liver histology can safely defer treatment.

Adult↗
PubMed2002

Fibrosis and disease progression in hepatitis C.

The progression of fibrosis in chronic hepatitis C determines the ultimate prognosis and thus the need and urgency of therapy. Fibrogenesis is a complex dynamic process, which is mediated by necroinflammation and activation of stellate cells. The liver biopsy remains the gold standard to assess fibrosis. Scoring systems allow a semiquantitative assessment and are useful for cross-sectional and cohort studies and in treatment trials. The rate at which fibrosis progresses varies markedly between patients. The major factors known to be associated with fibrosis progression are older age at infection, male gender, and excessive alcohol consumption. Viral load and genotype do not seem to influence significantly the progression rate. Progression of fibrosis is more rapid in immunocompromised patients. Hepatic steatosis, obesity, and diabetes may also contribute to more rapid progression of fibrosis. There are no tests that reliably predict the rate of progression of fibrosis in an individual patient. High serum alanine aminotransferase (ALT) levels are associated with a higher risk of fibrosis progression, and worsening of fibrosis is uncommon in patients with persistently normal serum aminotransferase levels. Serum markers for fibrosis are not reliable and need to be improved and validated. Liver biopsy provides the most accurate information on the stage of fibrosis and grade of necroinflammation, both of which have prognostic significance. Repeating the liver biopsy, 3 to 5 years after an initial biopsy is the most accurate means of assessing the progression of fibrosis.

Disease Progression↗
PubMed2001

Histological recurrence and progression of hepatitis C after orthotopic liver transplantation: influence of immunosuppressive regimens.

Post-orthotopic liver transplantation (OLT) recurrence of hepatitis C is virtually universal, but histological progression of disease is not. This study examines long-term clinical and liver histological features at and after OLT to elucidate factors predictive of hepatitis C recurrence and progression after OLT. A blinded retrospective review of clinical, serological, and histopathologic features of 65 patients who underwent OLT for hepatitis C and Non A Non B hepatitis was conducted. Histological findings of recurrent hepatitis C and progression (fibrosis, >or= grade 2 by last follow-up) were correlated with clinical parameters. Histological recurrence of hepatitis C was seen in 43 of 65 patients, with progression in 19 patients. Histological findings in the native liver and post-OLT biopsy specimen at the time of recurrence showed no correlation with hepatitis C recurrence and progression. Patients treated with azathioprine (AZA)-containing immunosuppressive regimens experienced less recurrence (6 of 17 v 37 of 48 patients; P < .005) and progression (1 of 17 v 18 of 48 patients; P = .014) than those without AZA as part of their immunosuppressive regimen. No difference was seen between patients treated with cyclosporine versus those administered FK506 (P > .05). Histological recurrence of hepatitis C after OLT is seen in 66% of patients with progressive disease and 29% of all patients. The grade of inflammation in the native liver at the time of OLT and time of recurrence is not predictive of progression. AZA-containing regimens reduce histological recurrence and progression of hepatitis C in post-OLT patients.

Adolescent↗