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PubMed1999

Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group.

The natural history of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients has never been studied according to the concept of liver fibrosis progression. The aim of this work was to assess the fibrosis progression rate in HIV-HCV coinfected patients and in patients infected by HCV only. A cohort of 122 HIV-HCV coinfected patients was compared with a control group of 122 HIV-negative HCV-infected patients. Groups were matched according to age, sex, daily alcohol consumption, age at HCV infection, and duration and route of HCV infection. The fibrosis progression rate was defined as the ratio between fibrosis stage (METAVIR scoring system) and the HCV duration. The prevalence of extensive liver fibrosis (METAVIR fibrosis scores 2, 3, and 4) and moderate or severe activity were higher in HIV-infected patients (60% and 54%, respectively) than in control patients (47% and 30%, respectively; P <.05 and P <.001, respectively). The median fibrosis progression rate in coinfected patients and in control patients was 0.153 (95% confidence interval [CI], 0.117-0.181) and 0.106 (95% CI, 0.084-0.125) fibrosis units per year, respectively (P <.0001). HIV seropositivity (P <.0001), alcohol consumption (>50 g/d, P =.0002), age at HCV infection (<25 years old, P <.0001), and severe immunosuppression (CD4 count </=200 cells/microL, P <.0001) were associated with an increase in the fibrosis progression rate. In coinfected patients, alcohol consumption (>50 g/d), CD4 count (</=200 cells/microL), and age at HCV infection (<25 years old) (P <. 0001, respectively) were associated with a higher fibrosis progression rate. HIV seropositivity accelerates HCV-related liver fibrosis progression. In coinfected patients, a low CD4 count, alcohol consumption rate, and age at HCV infection are associated with a higher liver fibrosis progression rate.

Adult↗
PubMed2004

Differential expression of cell cycle regulatory molecules and evidence for a "cyclin switch" during progression of prostate cancer.

BACKGROUND: Deregulation of the cell cycle can be viewed as both cause and consequence of cancer. Cyclin expression regulates progression through the cell cycle and although some cyclins have been examined in prostate cancer, the spatial and temporal changes in expression of these molecules during progression of autochthonous disease has not been fully explored. METHODS: Expression patterns of cyclins and cyclin dependent kinases during the different stages of progression in the spontaneous autochthonous TRAMP model were examined by RNAse protection assay, Western blot analysis, and immunohistochemistry. RESULTS: Differential expression of cell cycle regulatory molecules was observed during prostate cancer progression. Levels of the D-type cyclins decreased during progression while expression of cyclin E increased both at the mRNA and protein levels. The level of cyclin A and cyclin B expression increased beginning in early stage tumors and continued to increase throughout progression. The levels of cyclin dependent kinases did not change substantially during progression of the TRAMP model. CONCLUSIONS: The spatial and temporal pattern of mitotic cyclin expression during prostate cancer progression suggests that these molecules represent potential therapeutic targets. The differential expression of D-type cyclins may have implications with respect to androgen receptor mediated gene expression.

Animals↗
PubMed2004

Multiple imputation to estimate the association between eyes in disease progression with interval-censored data.

In many ophthalmologic studies, progression of diseases such as diabetic retinopathy, age-related maculopathy, cataract, and glaucoma is only noted when each eye is examined at intervals that commonly vary between subjects. Such data are often analysed using continuous time survival methods with observed progression assumed to occur at the end of the interval. Tied times of progression can lead to substantial bias in estimation of the association between progression in right and left eyes. We describe a multiple imputation strategy to create multiple data sets without ties, based on drawing interval-censored progression times from a parametric gamma frailty model that accounts for continuous and discrete covariates. We illustrate the method with data from 478 patients with insulin-dependent diabetes mellitus who were followed for progression of diabetic retinopathy in the Sorbinil Retinopathy Trial. Resolution of tied failure times allows for valid estimation of the hazard of progression in one eye given the progression status of the other eye. A simulation study suggests that the method performs well. Results highlight the advantage of multiple imputation that data imputed under one model can be analysed under several alternative models.

Adolescent↗
PubMed2001

Serum inflammatory markers and clinical/MRI markers of disease progression in multiple sclerosis.

The aim of this study was to assess whether mean serum levels of inflammatory markers when measured serially correlate with disease progression or putative MRI markers of axonal loss in a cohort of well-characterised multiple sclerosis (MS) patients. Serial serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), nitric oxide metabolites nitrate and nitrite (NOx), C-reactive protein (CRP), neopterin and tumour necrosis factor alpha (TNF-alpha) were measured in 29 MS patients, 13 with a relapsing remitting (RR) and 16 with a secondary progressive (SP) course, who were participating in a phase II clinical trial of anti-CD4 therapy. Short-term whole blood stimulated TNF-alpha production was also measured. Patients were studied 12 times over an 18-month period. MRI variables included the number and volume of Gd-enhancing lesions and the change in T2-hyperintense, T1-hypointense lesions and cerebral volume between the baseline and exit studies. Disease progression required a sustained change in the EDSS. There was no correlation between mean levels of inflammatory markers over the study period and disease progression or changes in any of the MRI measures. However, mean sICAM-1 levels from the first 6 months of the study were higher in patients who progressed during the study than in those that did not (443 (SD439) vs. 235 (SD162) ng/mL, p=0.05). Mean levels of NOx were significantly higher in patients with RR MS than in patients with SP disease (59.1 micromol/L (SD 12.8) vs. 48.7 micromol/L (SD 11.9), p=0.02). Patients with either a single relapse or no relapse had significantly higher NOx levels than to patients with multiple relapses during the 18 month follow-up (59.0 micromol/L (SD 12.3) vs. 47.9 micromol/L (SD 12.0), p=0.02). The mean levels of the other inflammatory markers did not correlate with disease course or relapse-rate. Serum levels of many inflammatory markers do not correlate with short-term disease progression. Some of the data suggest that the effects of inflammation on disease progression are delayed. In addition raised levels of serum nitric oxide metabolites are associated with a lower number of clinical relapses and a non-progressive disease course. These findings, although preliminary, pose interesting questions on the role of nitric oxide in the pathogenesis of MS. Inducible NO production in the early stages of the disease may be beneficial.

Adult↗
PubMed2005

Progression of visual field defects and visual loss in trabeculectomized eyes.

PURPOSE: To evaluate progression of visual field (VF) defects and development of visual impairment (low vision and blindness) after trabeculectomy. METHODS: We evaluated retrospectively 138 eyes of 138 consecutive patients over 40 years of age with primary open-angle glaucoma (POAG) or exfoliation glaucoma (EG) operated on by trabeculectomy without antimetabolites. The mean follow-up period was 3.5 years (range 2-5). In 83 eyes, pre- and postoperative VF measured by the same technique were compared to detect progression. Visual acuities (VA) were recorded as Snellen decimal notations. VA of <0.3 to 0.05 was defined as low vision and VA of <0.05 or VF constricted to less than 20 degrees in diameter as blindness. RESULTS: In 34 (41%) of 83 eyes with comparable fields, VF defects progressed because of glaucoma. In logistic regression analysis, severity of preoperative VF loss (P=0.0047) and use of preoperative oral anti-glaucomatous medication (P=0.047) correlated significantly with VF progression. In univariate analysis, also initial intraocular pressure (IOP) reduction after surgery (P=0.023) and IOP reduction from preoperative to last postoperative examination (P=0.036) were significantly smaller in eyes with VF progression. Defect progression did not, however, correlate significantly with the last IOP (P=0.58). Six eyes (4.3%) were blind due to glaucoma preoperatively and 14 eyes (10.1%) at the last follow-up. Visual impairment correlated with the severity of initial VF loss (P=0.008). CONCLUSIONS: Progression of VF defects and development of visual impairment due to glaucoma was fairly common despite trabeculectomy. Both were associated with severity of initial VF defect. In this series, no significant correlation appeared between defect progression and the last IOP, but association between stability of VF and the amount of IOP reduction after surgery indicate that a lower target IOP level particularly in eyes with initially severe VF defect would, however, be needed.

Adult↗
PubMed2005

Towards an optimal perimetric strategy for progression detection in glaucoma: from fixed-space to adaptive inter-test intervals.

BACKGROUND: The aim was to compare two perimetric strategies for progression detection in glaucoma. METHODS: Two perimetric strategies for progression detection were compared by means of a thought experiment in a theoretical cohort. In strategy I, visual field testing is performed with fixed-space inter-test intervals at a frequency of two tests per year. In strategy II, the frequency of visual field testing is set to one test per year as long as the fields are apparently unchanged, whereas as soon as progression is suspected, confirmation or falsification is performed within a short time span. Outcome measures were the time delay between the progression event and the diagnosis of definite progression, and the number of visual field tests performed per patient per year. RESULTS: Average time delay between the actual progression event and the final diagnosis of definite progression was 15 months in the case of strategy I and 6 months in the case of strategy II. Maximum time delays were 18 and 12 months respectively. The frequency of visual field testing was 2 tests per patient per year for strategy I and 1.45 tests per patient per year for strategy II. CONCLUSIONS: Perimetry in glaucoma can be optimised by postponing the next test in the case of an apparently stable field and accelerating the next test in the case of a suspected progression. This results in an earlier diagnosis, a lower perimetric frequency and a shorter period of uncertainty for the patient.

Bayes Theorem↗
PubMed1998

Assessment of curve progression in idiopathic scoliosis.

In a 5-year prospective study on idiopathic scoliosis, an attempt was made to elucidate the natural history of the disease and to determine which factors contribute to curve progression. A total of 85,622 children were examined for scoliosis in a prospective school screening study carried out in northwestern and central Greece. Curve progression was studied in 839 of the 1,436 children with idiopathic scoliosis of at least 10 degrees detected from the school screening program. Each child was followed clinically and roentgenographically for one to four follow-up visits for a mean of 3.2 years. Progression of the scoliotic curve was recorded in 14.7% of the children. Spontaneous improvement of at least 5 degrees was observed in 27.4% of them, with 80 children (9.5%) demonstrating complete spontaneous resolution. Eighteen percent of the patients remained stable, while the remaining patients demonstrated nonsignificant changes of less than 5 degrees in curve magnitude. A strong association was observed between the incidence of progression and the sex of the child, curve pattern, maturity, and to a lesser extent age and curve magnitude. More specifically, the following were associated with a high risk of curve progression: sex (girls); curve pattern (right thoracic and double curves in girls, and right lumbar curves in boys); maturity (girls before the onset of menses); age (time of pubertal growth spurt); and curve magnitude (> or = 30 degrees). On the other hand, left thoracic curves showed a weak tendency for progression. In conclusion, the findings of the present study strongly suggest that only a small percentage of scoliotic curves will undergo progression. The pattern of the curve according to curve direction and sex of the child was found to be a key indicator of which curves will progress.

Adolescent↗
PubMed2006

Extensions to the modeling of initiation and progression: applications to substance use and abuse.

Twin data can provide valuable insight into the relationship between the stages of phenomena such as disease or substance abuse. Initiation of substance use may be caused by factors that are the same as, partially shared with, or completely independent of those that cause progression from use to abuse. Comparison of rates of progression among the cotwins of twins who do vs. do not initiate provides indirect information about the relationship between initiation and progression. Existing models for this relationship have been difficult to extend because they are usually expressed in terms of explicit integrals. In this paper, the problem is overcome by regarding the analysis of twin data on initiation and progression as a special case of missing data, in which individuals who do not initiate are regarded as having missing data on progression measures. Using the general framework for the analysis of ordinal data with missing values available in Mx makes extensions that include other variables much easier. The effects of continuous covariates such as age on initiation and progression becomes simple. Also facilitated are the examination of initiation and progression in two or more substances, and transition models with two or more steps. The methods are illustrated with data on the effects of cohort on liability to cannabis use and abuse, bivariate analysis of tobacco use and dependence and cannabis use and abuse, and the relationships between initiation of smoking, regular smoking and nicotine dependence. Other suitable applications include the relationship between symptoms and diagnosis, such as fears and the progression to phobia.

Age Factors↗
PubMed1995

The quantitation of altered hepatic foci during multistage hepatocarcinogenesis in the rat: transforming growth factor alpha expression as a marker for the stage of progression.

The experimental three-stage hepatocarcinogenesis protocol of initiation, promotion, and progression, coupled with the analytical technique of stereology, permits quantitative analysis of the carcinogenic process, including the derivation of biologically based risk assessment models. The aberrant expression of the placental isozyme of glutathione S-transferase (PGST) is an efficient marker for initiated, preneoplastic, and neoplastic hepatocytes. Putatively initiated cells and their clonal progeny can be identified, enumerated, and their growth characteristics determined on the basis of their aberrant expression of this protein. A lack of suitable markers has made the identification and quantitation of hepatocytes in the early stage of progression more difficult. One characteristic of cells in the stage of progression is the evolution of relatively autonomous growth. The alteration of growth factor signalling pathways may provide one mechanism for this observation. The expression of transforming growth factor alpha (TGF alpha) is seen in many malignancies. The initiation-promotion-progression protocol has been used to induce progression in the rat liver. The focal expression of TGF alpha was found to correlate with areas of progression in rats subjected to this protocol. The ability to identify and quantitate cells in the stage of progression should facilitate application of the Moolgavkar-Venzon-Knudson model for assessing human risk from carcinogens active at each of these three stages. Validation of this model will require determination of the number and growth characteristics of hepatocytes in the stage of progression.

Animals↗
PubMed1996

Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: valve area and right heart disease.

OBJECTIVES: The purpose of this study was to determine, in a large referral population, the rate of echocardiographic change in mitral valve area (MVA) without interim intervention, to determine which factors influence progression of narrowing and to examine associated changes in the right side of the heart. BACKGROUND: Little information is currently available on the echocardiographic progression of mitral stenosis, particularly on progressive changes in the right side of the heart and the ability of a previously proposed algorithm to predict progression. METHODS: We studied 103 patients (mean age 61 years; 74% female) with serial two-dimensional and Doppler echocardiography. The average interval between entry and most recent follow-up study was 3.3 +/- 2 years (range 1 to 11). RESULTS: During the follow-up period, MVA decreased at a mean rate of 0.09 cm2/year. In 28 patients there was no decrease, in 40 there was only relatively little change (< 0.1 cm2/year) and in 35 the rate of progression of mitral valve narrowing was more rapid (> or = 0.1 cm2/year). The rate of progression was significantly greater among patients with a larger initial MVA and milder mitral stenosis (0.12 vs. 0.06 vs. 0.03 cm2/year for mild, moderate and severe stenosis, p < 0.01). Although the rate of mitral valve narrowing was a weak function of initial MVA and echocardiographic score by multivariate analysis, no set of individual values or cutoff points of these variables or pressure gradients could predict this rate in individual patients. There was a significant increase in right ventricular diastolic area (17 to 18.7 cm2) and tricuspid regurgitation grade (2 + to 3 +; p < 0.0001 between entry and follow-up studies). Progression in right heart disease occurred even in patients with minimal or no change in MVA. Patients with associated aortic regurgitation had a higher rate of decrease in MVA than did those with trace or no aortic regurgitation (0.19 vs. 0.086 cm2/year, p < 0.05). CONCLUSIONS: The rate of mitral valve narrowing in individual patients is variable and cannot be predicted by initial MVA, mitral valve score or transmitral gradient, alone or in combination. Right heart disease can progress independent of mitral valve narrowing.

Algorithms↗
PubMed1996

A prospective study of disease progression in patients with atherosclerotic renal artery stenosis.

The natural history of renal artery stenosis (RAS) has been difficult to document because serial arteriography is rarely justified. Duplex scanning is a noninvasive technique that is ideally suited for both screening and follow-up of RAS. In this approach, renal arteries are classified as normal, < 60% stenosis, > or = 60% stenosis, or occluded, and disease progression is defined as a change in the duplex classification. The purpose of this study was to determine the rate of disease progression in atherosclerotic RAS by serial duplex scanning. At least one abnormal renal artery was identified in each of 76 patients being screened for RAS. Of the 152 renal arteries, 20 were excluded (14 prior interventions, 5 occlusions, 1 technically inadequate duplex scan), leaving 132 for the natural history follow-up protocol. The patient group included 36 men and 40 women, with a mean age of 67 years, who were followed for a mean of 32 months (maximum 55 months). The initial status of the 132 renal arteries was normal in 36, < 60% stenosis in 35, and > or = 60% stenosis in 61. The cumulative incidence of progression from normal to > or = 60% RAS was 0% at 1 year, 0% at 2 years, and 8% at 3 years. The cumulative incidence of progression from < 60% to > or = 60% RAS was 30% at 1 year, 44% at 2 years, and 48% at 3 years. All 4 renal arteries that progressed to occlusion had > or = 60% stenoses at the initial visit, and for those arteries with a > or = 60% stenosis, the cumulative incidence of progression to occlusion was 4% at 1 year, 4% at 2 years, and 7% at 3 years. Progression of RAS occurred at an average rate of 7% per year for all categories of baseline disease combined. Progression of atherosclerotic RAS is relatively common, particularly from < 60% to > or = 60% stenosis.

Aged↗
PubMed2004

The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma.

BACKGROUND: We sought to determine whether or not there are differences in disease progression after radical or nonradical (debulking) surgical procedures for malignant pleural mesothelioma. METHODS: Over a 49-month period, 132 patients with malignant pleural mesothelioma underwent surgery. Fifty-three underwent extrapleural pneumonectomy and 79 underwent nonradical procedures. Time to evidence of clinical disease progression was recorded, as was the site(s) of that disease. RESULTS: One-hundred nineteen patients were evaluable, of which 59% (22 radical; 48 nonradical) had disease progression. Overall 30-day mortality was 8.5% (7.5% radical; 9% nonradical). The median time to overall disease progression was considerably longer after extrapleural pneumonectomy than debulking surgery (319 days vs 197 days, p = 0.019), as was the time to local disease progression (631 days vs 218 days, p = 0.0018). There was no preponderance of earlier stage disease in the radical surgery group. There was a trend toward prolonged survival in those undergoing radical surgery, but no significant difference between the groups (497 days vs 324 days, p = 0.079). In those who had extrapleural pneumonectomy, time-to-disease progression significantly decreased with N2 disease compared with N0/1 involvement (197 days vs 358 days, p = 0.02). CONCLUSIONS: Extrapleural pneumonectomy may be preferable to debulking surgery in malignant pleural mesothelioma to delay disease progression and give greater control of local disease. Involvement of N2 nodes is associated with accelerated disease progression and is therefore a contraindication to extrapleural pneumonectomy.

Abdominal Neoplasms↗
PubMed2005

Cervical squamous intraepithelial lesions of low-grade in HIV-infected women: recurrence, persistence, and progression, in treated and untreated women.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are more predisposed than HIV-negative women to develop squamous intraepithelial lesions (SIL) of the uterine cervix, and cervical dysplasia may be of higher grade in HIV-positive women than in HIV-negative subjects, with more extensive and multi-centric involvement of the lower genital tract by human papillomavirus (HPV)-associated lesions. Moreover, recurrence and progression rate of cervical intraepithelial neoplasia (CIN) is particularly higher in immunocompromised women. DESIGN: Retrospective case-control study of HIV-positive women and HIV-negative controls, all affected by low-grade SIL of the uterine cervix, treated by loop excision or followed-up without treatment. Correlation of progression and recurrence of SIL with HIV status and CD4+ count. PATIENTS: From September 1990 to October 1997, 75 HIV-positive low-grade-SIL patients, 47 treated and 28 followed-up without treatment, and 75 HIV-negative low-grade-SIL controls, 45 treated and 30 followed-up. RESULTS: Among treated patients, 17/47 (36.2%) HIV-positive and 5/45 (11.1%) controls had recurrence (P < 0.0101, O.R. = 4.53, 95% CI = 1.5-13.7), progression of untreated lesion was seen in 15/28 (53.6%) HIV-positive and 7/30 (23%) controls (P < 0.05, O.R. = 3.79, 95% CI = 1.23-11.69). The risk of recurrence or progression of low-grade SIL linked to HIV seropositivity is about 4-5 times higher in comparison with seronegative counterpart, matched for age, risk factors and lesion size. More significantly, considering the cut-off of 200 CD4+/mm(3) in HIV-positive women, 13/17 cases of recurrence (P < 0.05, O.R. = 4.88, 95% CI = 1.28-18.58) and 10/15 cases with progression (P < 0.05, O.R. = 6.67, 95% CI = 1.24-35.73) were immunocompromised (<200 CD4+/mm3), with a significant higher risk of recurrence or progression linked to immunodeficiency status. Considering time of progression or recurrence, during follow-up, Kaplan-Meier curves shows that HIV-positive status and immunodeficiency are correlated with more rapid evolution of cervical dysplasia and HPV-related lesions: comparison of recurrence in treated patients report P < 0.005 and progression in untreated P<0.05 (Mantel-Haenszel log-rank test). CONCLUSIONS: Immunological status seems to be a determinant factor in prognosis of cervical SIL, HIV-positive women affected by this lesion, even if low-grade, need more aggressive management than the immunocompetent counterpart. Strict cytologic and colposcopic screening is recommended and CD4+ count and HPV-DNA testing may be useful risk indicators. Excisional procedures are preferred, while ablative treatments or wait and see policy may expose to some risk this type of population with poor compliance to follow-up.

Case-Control Studies↗
PubMed2004

A dietary and exercise intervention slows menopause-associated progression of subclinical atherosclerosis as measured by intima-media thickness of the carotid arteries.

OBJECTIVES: The object of this study was to assess the effects of menopause and a diet/exercise intervention on subclinical atherosclerosis progression. BACKGROUND: Subclinical atherosclerosis has been linked to higher coronary heart disease and stroke rates and is greater among postmenopausal women according to cross-sectional analyses. Whether menopause is associated with an accelerated progression of subclinical disease is unknown, as is the extent to which lifestyle intervention can alter the course of progression. METHODS: Intima-media thickness (IMT) measures of the common carotid artery (CCA), internal carotid artery (ICA), and bulb segments of the carotid arteries were measured twice during the course of 4 years in 353 women from the Women's Healthy Lifestyle Project, a dietary and exercise clinical trial designed to prevent adverse risk factor changes through the menopause. A third measure was obtained 2.5 years later for 113 women. RESULTS: The progression of IMT was observed for the average of all segments (AVG), the CCA, and the bulb (0.007 mm/year, 0.008 mm/year, and 0.012 mm/year; p < 0.01 for all), but not for the ICA. Among controls, menopause was associated with accelerated IMT progression (0.003 mm/year for premenopausal women vs. 0.008 mm/year for perimenopausal/postmenopausal women for AVG IMT; p = 0.049). Additionally, among the 160 perimenopausal/postmenopausal women, the intervention slowed IMT progression (0.008 mm/year for the control group vs. 0.004 mm/year for the intervention group for AVG IMT; p = 0.02). Similar results were found for the CCA and bulb segments. CONCLUSIONS: These data demonstrate that the menopause transition is associated with accelerated subclinical atherosclerosis progression and that a diet/exercise intervention slows menopause-related atherosclerosis progression.

Arteriosclerosis↗
PubMed2006

Is biopsy Gleason score independently associated with biochemical progression following radical prostatectomy after adjusting for pathological Gleason score?

PURPOSE: Biopsy Gleason score is known to be associated with prostate specific antigen failure following radical prostatectomy. However, it is unclear whether it remains associated with outcome after surgery when the pathological Gleason score is known. MATERIALS AND METHODS: We determined the association between biopsy Gleason score and biochemical progression after correcting for preoperative and postoperative characteristics, including pathological Gleason score, in 1,931 men treated with radical prostatectomy between 1988 and 2005 in the Shared Equal Access Regional Cancer Hospital Database Study Group database. Gleason score was examined as a categorical variable of 2 to 6, 3 + 4 and 4 + 3 or greater. RESULTS: Higher biopsy Gleason scores were positively associated with extracapsular extension (p <0.001), positive surgical margins (p <0.001), seminal vesicle invasion (p <0.001), positive lymph nodes (p <0.001) and biochemical progression (log rank p <0.001). After adjusting for only preoperative characteristics biopsy Gleason 3 + 4 and 4 + 3 or greater were associated with increased risk of biochemical progression compared to biopsy Gleason 6 or less (p = 0.001 and <0.001, respectively). After further adjusting for multiple pathological characteristics, including pathological Gleason score, the association between higher biopsy Gleason score and progression was little changed, in that men with biopsy Gleason 3 + 4 and 4 + 3 or greater were significantly more likely to experience progression (p = 0.001 and <0.001, respectively). Furthermore, when stratified by pathological Gleason score, higher biopsy Gleason scores were associated with an increased risk of biochemical progression in each pathological Gleason score category (log rank p </=0.007). CONCLUSIONS: Biopsy Gleason score remained strongly associated with progression even when the pathological Gleason score was known and controlled for. If confirmed at other centers, incorporation of biopsy Gleason score into postoperative nomograms designed to estimate the progression risk might improve model precision.

Aged↗
PubMed2004

Accelerated progression of carotid stenosis in patients with previous external neck irradiation.

OBJECTIVE: Radiotherapy to the head and neck often results in carotid stenosis, but the course of disease is unknown. We investigated the natural history and progression of asymptomatic carotid stenosis induced by external irradiation. Patients and methods The study included 130 carotid arteries in 95 patients who had received external radiation therapy to the head and neck area and who had asymptomatic, mild internal carotid artery or common carotid artery stenosis. Stenosis of 15% to 49% on duplex ultrasound (US) scans defined mild (<50%) disease. Another 95 arteries in 74 patients with matched degree of carotid artery stenosis but who had not received radiation therapy were used as control. Both groups were followed up prospectively with serial duplex US scanning, and degree of carotid artery stenosis was categorized as 15% to 49%, 50% to 69%, 70% to 99%, and occlusion. Progression of carotid artery stenosis was defined as increase in stenosis from less than 50% to 50% or greater at ultrasonography. Secondary end points included progression to higher disease category, new cerebrovascular symptoms, and death. Data from irradiated arteries was compared with control data with the life table method. A Cox regression model was used to analyze disease progression, adjusted for covariates of sex, age, smoking, diabetes, and hypertension. RESULTS: Mean follow-up was 36 months. Adjusted freedom from progression rates at 3 years were 65% for irradiated arteries and 87% for control arteries at life-table analysis (P =.035; odds ratio, 3.1). The annualized progression rate from less than 50% to 50% or greater in irradiated arteries was 15.4%, compared with 4.8% in nonirradiated arteries. A long history of cervical irradiation (>6 years) was the only significant risk factor for disease progression. There was no difference between the two groups regarding development of new symptoms or mortality. CONCLUSIONS: Carotid stenosis associated with external irradiation progresses more rapidly compared with nonirradiated atherosclerotic arteries. Aggressive surveillance is recommended.

Aged↗
PubMed2004

Somatic symptom progression in idiopathic Parkinson's disease.

The substantia nigra (SN) pars compacta is arranged somatotopically. Symptoms of idiopathic Parkinson's disease (IPD) are caused by a lesion in this nucleus, which spreads in a stereotyped spatio-temporal pattern during the course of the disease. We investigated the order of somatic symptom progression in a group of 30 patients with IPD to determine if progression of symptoms was consistent with ordered spread of pathology through the SN pars compacta. Thirty outpatients with IPD were interviewed retrospectively about the progression of their symptoms using a semi-structured questionnaire. All the patients experienced somatic symptom progression in one of two distinct patterns, which was dependent on the location of the initial symptom. The typical pattern of progression for patients with lower limb onset was: (i) foot, (ii) leg, (iii) arm, (iv) hand, (v) face, (vi) voice and (vii) swallowing. For patients whose first symptom was in the upper limb progression to the face and lower limbs occurred roughly simultaneously or sequentially, with the typical pattern of progression: (i) hand/arm, (ii) foot/leg and face, (iii) speech and (iv) swallowing. These patterns of disease progression may reflect two distinct patterns of neuropathology within the SN pars compacta. Although the sample size was relatively small, this is the first time this phenomenon has been described in a full-length article.

Adult↗
PubMed2005

Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease.

Although hyperuricemia has long been associated with renal disease, uric acid has not been considered as a true mediator of progression of renal disease. The observation that hyperuricemia commonly is associated with other risk factors of cardiovascular and renal disease, especially hypertension, has made it difficult to dissect the effect of uric acid itself. However, recent epidemiologic evidence suggests a significant and independent association between the level of serum uric acid and renal disease progression with beneficial effect of decreasing uric acid levels. Furthermore, our experimental data using hyperuricemic animals and cultured cells have provided robust evidence regarding the role of uric acid on progression of renal disease. Hyperuricemia increased systemic blood pressure, proteinuria, renal dysfunction, vascular disease, and progressive renal scarring in rats. Recent data also suggest hyperuricemia may be one of the key and previously unknown mechanisms for the activation of the renin-angiotensin and cyclooxygenase-2 (COX-2) systems in progressive renal disease. Although we must be cautious in the interpretation of animal models to human disease, these studies provide a mechanism to explain epidemiologic data that show uric acid is an independent risk factor for renal progression. Although there is no concrete evidence yet that uric acid bears a causal or reversible relationship to progressive renal disease in humans, it is time to reevaluate the implication of hyperuricemia as an important player for progression of renal disease and to try to find safe and reasonable therapeutic modalities in individual patients based on their clinical data, medication history, and the presence of cardiovascular complications.

Animals↗