Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Progression”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2000

Short-wavelength automated perimetry and standard perimetry in the detection of progressive optic disc cupping.

OBJECTIVE: To compare progression in short-wavelength automated perimetry (SWAP) and white-on-white (standard) perimetry in eyes with progressive glaucomatous changes of the optic disc detected by serial stereophotographs. METHODS: Forty-seven glaucoma patients with at least 2 disc stereophotographs more than 2 years apart, along with standard perimetry and SWAP examinations within 6 months of each disc photo of the same eye, were included in the study. The mean follow-up time was 4.1 years (range, 2.0-8.9 years). Baseline and follow-up stereophotographs were then graded and compared for the presence of progression. Progression in standard perimetry and SWAP, using the Advanced Glaucoma Intervention Study scoring system and a clinical scoring system, was compared between eyes with progressive change on stereophotographs and those without. RESULTS: Twenty-two of 47 eyes showed progressive change by stereophotographs. There was a statistically significant difference in the mean change in Advanced Glaucoma Intervention Study scores for both standard perimetry (P<.004) and SWAP (P<.001) between the progressed and nonprogressed groups. The sensitivity, specificity, and area under the receiver operator characteristic curve were higher using SWAP than standard perimetry when evaluated by either algorithm. This was statistically significant only in the area under the receiver operator characteristic curve for the Advanced Glaucoma Intervention Study scoring system (P =.04). CONCLUSIONS: Short-wavelength automated perimetry identified more patients than standard perimetry as having progressive glaucomatous changes of the optic disc. Compared with standard perimetry, SWAP may improve the detection of progressive glaucoma. Arch Ophthalmol. 2000;118:1231-1236

Aged↗
PubMed1997

Ability of ankle-brachial index to detect lower-extremity atherosclerotic disease progression.

BACKGROUND: Accurate determination of progression of lower-extremity arterial occlusive disease (LEAOD) is required for natural history studies and evaluation of therapies for atherosclerosis. OBJECTIVE: To determine if changes in the ankle-brachial index (ABI) correlated with progression of LEAOD as determined by arteriography or duplex scanning. DESIGN: In patients with prior suprainguinal or infrainguinal lower-extremity revascularization, progression of LEAOD in native arteries was determined by comparing a preoperative (baseline) arteriogram with late follow-up arteriography or duplex scanning. Superficial femoral and popliteal arteries were graded as having less than 50% stenosis, 50% to 99% stenosis, or as being occluded. Tibial arteries were graded as continuously patent or occluded. Operated and nonoperated extremities were included in the study. The baseline ABI was performed postoperatively and repeated at follow-up arteriography or duplex scanning. Progression of LEAOD by the ABI was defined as a decrease in the ABI of 0.15 or greater. Progression of LEAOD by imaging studies was defined as an increase in 1 category of stenosis. Extremities with suprasystolic pressures were excluded. SETTING: Tertiary vascular surgical service. EXTREMITIES AND PATIENTS: One hundred ninety-three extremities were studied in 114 patients during a mean follow-up of 3.3 years. RESULTS: Seventy-two lower extremities (37.3%) showed progression of atherosclerosis by late follow-up arteriography or duplex scanning. Using the imaging studies as the criterion standard, the ABI had 102 true negatives, 29 true positives, 42 false negatives, and 20 false positives (sensitivity, 41%; specificity, 84%; positive predictive value, 59%; negative predictive value, 71%; and accuracy, 68%) for determining the progression of LEAOD. CONCLUSIONS: The ABI is relatively insensitive in identifying the progression of LEAOD as demonstrated by the use of imaging studies. In studies of natural history or therapy for atherosclerosis, imaging studies should be used in preference to the ABI to evaluate the progression of LEAOD accurately.

Adult↗
PubMed1999

Antiapoptotic Bcl-2 family protein expression increases with progression of oligodendroglioma.

BACKGROUND: Altered expression of Bcl-2 family proteins has been associated with tumorigenesis and tumor progression as well as resistance to radiotherapy and chemotherapy. In the current study, Bcl-2 family protein expression was examined in oligodendrogliomas and anaplastic oligodendrogliomas, and an attempt was made to determine whether these proteins accumulate during disease progression and to search for protein expression patterns predictive of time to progression and overall survival. METHODS: A total of 42 oligodendroglioma tissue samples, 26 de novo World Health Organization (WHO) Grade 2 oligodendrogliomas, and 16 de novo WHO Grade 3 anaplastic oligodendrogliomas were studied. Nineteen Grade 2 tumors progressed: 10 again were Grade 2 oligodendrogliomas and 8 had progressed to higher grade lesions. Eight anaplastic oligodendrogliomas progressed: five again were WHO Grade 3 tumors and three were glioblastoma multiforme. Expression of Bcl-2, Bax, Bcl-X, and Mcl-1 proteins and of the proliferation marker Ki-67 was evaluated by immunohistochemistry. Apoptotic cells were quantified by in situ nick translation (ISNT). RESULTS: De novo WHO Grade 2 oligodendrogliomas had higher Bcl-2 scores (P = 0.037), lower MIB-1 scores (P = 0.0012), and lower ISNT scores (P = 0.049) compared with de novo WHO Grade 3 anaplastic oligodendrogliomas. In de novo oligodendrogliomas, low numbers of Bax positive cells were associated with a short time to disease progression (P = 0.043). In de novo anaplastic oligodendrogliomas, low numbers of Bcl-2 positive cells correlated with short survival (P = 0.029). In tumors that had progressed from WHO Grade 3 anaplastic oligodendrogliomas, the authors found significantly more Bcl-X positive (P = 0.005), Mcl-1 positive (P = 0.002), and Bax positive (P = 0.03) cells. CONCLUSIONS: The results of the current study show that progression of oligodendrogliomas and anaplastic oligodendrogliomas is associated with an enhanced expression of antiapoptotic Bcl-2 family proteins.

Adult↗
PubMed2004

Documenting damage progression in a two-year longitudinal study of rheumatoid arthritis patients with established disease (the DAMAGE study cohort): is there an advantage in the use of magnetic resonance imaging as compared with plain radiography?

OBJECTIVE: In early rheumatoid arthritis (RA), longitudinal studies have demonstrated that magnetic resonance imaging (MRI) is more sensitive than radiography in demonstrating progressive erosive joint damage. The present study evaluated the progression of erosive damage in patients with established RA by using limited field of view MRI and comparing the results with those obtained by radiography. METHODS: MRI and radiographic studies were available from 47 of 60 patients enrolled in a 2-year RA observational study. MRI of the metacarpophalangeal (MCP) joints was performed at baseline and 2 years later, and a single observer scored all of the MR images with the use of an MRI scoring method developed by the Outcome Measures in Rheumatology Clinical Trials MRI RA study group. MR images from 14 patients were reread by the same observer after 1 week to assess intraobserver reliability. Radiographs were obtained at baseline and at 2 years, and were scored by an observer using the Scott modification of the Larsen score. Radiographs from 14 patients were reread after 1 week to assess the intraobserver reliability. The smallest detectable difference (SDD) was calculated for the MRI scores, the total Larsen scores, and the Larsen scores of the dominant-hand MCP joints (MCPs 2-5) for direct comparison with the MRI results. RESULTS: The median disease duration was 5.1 years (range 0.5-29 years). Evidence of erosion progression was identified by MRI in 30 patients (64%). The SDD based on the intraobserver scores was calculated as +/-3.25 units. Using this result, 11 patients (23%) showed evidence of erosion progression on MRI that was greater than the SDD. The SDD for progression based on the intraobserver total Larsen radiographic scores was 0.77 units, and the SDD for the Larsen scores of the dominant-hand MCP joints was 1.55 units. On the basis of these results, radiographic progression was noted in 19 patients (40%) by the total Larsen score and 7 patients (15%) by the dominant-hand MCP Larsen score. The most striking finding was that although MRI and radiograph scores identified a similar group of patients as having progression of joint damage, the radiographs of both hands appeared to be more responsive to change, albeit with the caveat that radiographic progression was most marked outside the dominant-hand MCP joints. CONCLUSION: There was no clear advantage of MRI with a limited field of view as compared with radiographic imaging of both hands in detecting progression of joint damage over 2 years in this group of patients with established RA. The conclusion drawn from this study is not that radiographs are better than MRI or vice versa, but that careful analysis is required to determine the optimal imaging method, or combination of imaging methods, for each study population, depending on the objective and duration of the study.

Arthritis, Rheumatoid↗
PubMed2004

Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal.

OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.

Antirheumatic Agents↗
PubMed2004

Thrust during ambulation and the progression of knee osteoarthritis.

OBJECTIVE: To determine whether the presence of varus thrust at baseline increases the risk of progression of medial tibiofemoral osteoarthritis (OA), whether knees with thrust have a greater adduction moment, whether thrust has any additional impact on top of static varus, and whether thrust is associated with poor physical function outcome. METHODS: Two hundred thirty-seven patients with knee OA (definite osteophytes and symptoms) underwent baseline gait observation to assess varus thrust and full-limb radiography to assess alignment. Sixty-four of these 237 patients also underwent quantitative gait analysis to determine the maximum knee adduction moment. Two hundred thirty patients (97%) returned for followup at 18 months. At baseline and 18 months, the 230 participants had semiflexed, fluoroscopically confirmed knee radiographs (with progression defined as worsening of medial joint space grade); self-reported and performance-based measures of function were also assessed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) for medial OA progression, after excluding knees that were not at risk for progression. RESULTS: Varus thrust was present in 67 of 401 knees. Thrust increased 4-fold (age-, sex-, body mass index-, and pain-adjusted OR 3.96, 95% confidence interval [95% CI] 2.11-7.43) the odds of medial progression, with some reduction after further adjustment for varus alignment severity. In varus-aligned knees, thrust increased the odds of OA progression 3-fold (adjusted OR 3.17, 95% CI 1.60-6.31). In the gait substudy, the adduction moment was greater in knees with a thrust compared with knees without a thrust. Having a thrust in both knees versus neither knee was associated with a 2-fold increase in the OR for poor physical function outcome (P not significant). CONCLUSION: Varus thrust is a potent risk factor, identifiable by simple gait observation, for disease progression in the medial compartment, the most common site of OA involvement at the knee. Varus thrust may also predict poor physical function outcome. Varus thrust increased the odds of progression among varus-aligned knees considered separately, suggesting that knees with a thrust are a subset of varus-aligned knees at particularly high risk for progression of OA.

Aged↗
PubMed2004

One-year protocol liver biopsy can stratify fibrosis progression in liver transplant recipients with recurrent hepatitis C infection.

Determinants of progression to cirrhosis in hepatitis C virus (HCV) infection have been well described in the immunocompetent population but remain poorly defined in liver transplant (LT) recipients. This cohort study determines the factors contributing to the development of fibrosis and its rate of progression in the allograft. Predictive factors analyzed include: demographics, host and donor factors, surgery-related variables (cold and warm ischemia time), rejection episodes, cytomegalovirus infection (CMV), and immunosuppression. Over 12 years, 842 adult LTs were performed at our institution; 358 for the indication of HCV. A total of 264 patients underwent protocol liver biopsies at month 4 and yearly after LT. Using the modified Knodell system of Ishak for staging fibrosis, the median fibrosis progression rate was .8 units/year (P < .001). Rapid fibrosis progression (> .8 units/year) was best identified by liver histology performed at 1 year. Donor age > 55 years was associated with rapid fibrosis progression and development of cirrhosis (P < .001). In contrast, donor age < 35 years was associated with slower progression of fibrosis (P = .003). Risk factors for graft loss due to recurrent HCV included recipient age > 35 years (P = .01), donor age > 55 years (P = .005), and use of female donor allografts (P = .03). In conclusion, fibrosis progression in HCV-infected LT recipients occurs at a rate of .8 units/year. Increased donor age has a major impact on disease progression, graft failure, and patient survival. A liver biopsy performed at 1 year posttransplant can help identify those patients more likely to develop progressive disease and may allow better targeting of antiviral therapy.

Adult↗
PubMed2005

Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model.

BACKGROUND: Cancer progression is usually facilitated by independent growth signals that may lead to increased cell survival and evasion of apoptosis. Phosphatidylinositol 3'-OH kinase (P I3 K)-Akt and transcription factor NF-kappaB are important signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis, and oncogenesis. Although P I3 K-Akt and NF-kappaB have been implicated in the development and progression of prostate cancer, expression of these molecules during progression of autochthonous disease has not been elucidated. METHODS: Prostate cancer growth and progression in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and male non-transgenic littermates were observed by magnetic resonance imaging (MRI). Expression patterns of P I3 K-Akt, NF-kappaB, I kappaB, and associated signaling molecules during different stages of cancer progression in these mice were examined by Western blot analysis, electrophoretic mobility shift assay (EMSA), enzyme-linked immunoabsorbent assay (ELISA), kinase assay, and immunohistochemistry. RESULTS: Sequential MRI and gross analysis of prostate gland exhibited increasing prostate volume associated with the development and progression of prostatic adenocarcinoma in TRAMP mice, compared to male non-transgenic littermates. Differential protein expression of P I3 K, phosphorylated-Akt (Ser 473), I kappa Balpha and its phosphorylation, IKK kinase activity, NF-kappaB/p65, p50, DNA binding, and transcriptional-regulated genes, viz., Bc l2, cyclin D1, MMP-9, and VEGF were observed during prostate cancer progression in TRAMP mice, compared to male non-transgenic littermates. Expressions of these molecules were significantly increased during cancer progression observed at 24 and 32 weeks of age. CONCLUSIONS: Differential expression pattern of P I3 K-Akt, NF-kappaB and I kappaB during prostate cancer progression in TRAMP mice suggest that these molecules represent potential molecular targets for prevention and/or therapeutic intervention.

Adenocarcinoma↗
PubMed1997

Progressive supranuclear palsy affects both the substantia nigra pars compacta and reticulata.

We have analyzed the neuropathology of the substantia nigra in four cases of progressive supranuclear palsy compared with age-matched controls and patients with Parkinson's disease. Although there are many reports of severe dopaminergic cell loss in progressive supranuclear palsy, the fate of the GABAergic pars reticulata neurones remains unclear. Serial section analysis and fractional counts of pars compacta neurones (identified by their neuromelanin pigment) and pars reticulata neurones (identified using parvalbumin immunohistochemistry) were performed, and the type and distribution of neuropathology were described. Severe neurodegeneration within the dopaminergic pars compacta was seen in all cases of progressive supranuclear palsy and all cases of Parkinson's disease compared with controls. Lewy body pathology was found only in cases of Parkinson's disease, while neurofibrillary tangles were seen only in cases of progressive supranuclear palsy. Tau-positive astrocytes and neuropil threads were occasionally seen in controls and cases of Parkinson's disease (particularly those of advanced age) but were extremely numerous in all cases of progressive supranuclear palsy. There was a similar decrease in parvalbumin immunoreactivity within the pars reticulata in both progressive supranuclear palsy and Parkinson's disease. However, there was a striking 70% reduction in the number of pars reticulata neurones in progressive supranuclear palsy, with no cell loss observed in Parkinson's disease compared with controls. Our results show that both the dopaminergic pars compacta and the GABAergic pars reticulata are significantly damaged in cases of progressive supranuclear palsy. The distribution of neurodegeneration in patients with Parkinson's disease and progressive supranuclear palsy is discussed with respect to the current theories on pathophysiology in basal ganglia circuitry.

Aged↗
PubMed2001

[Progression of coronary arteriosclerosis as monitoring the therapeutic success of hyperlipidemia].

BACKGROUND: Coronary calcium represents an integral part of coronary atherosclerosis. It results from an actively regulated process and already appears in early stages of the disease. Studies using electron-beam computed tomography (EBCT) have demonstrated that an accelerated progression of coronary calcified atherosclerosis is associated with an increased rate of clinical events. In experimental animal models, effective lowering of LDL cholesterol stops the progression of coronary calcified atherosclerosis. LDL CHOLESTEROL AND PROGRESSION OF CORONARY CALCIUM: A number of EBCT-derived retrospective analyses have consistently reported that LDL cholesterol values are the most important factor influencing the progression of coronary calcified atherosclerosis. In high-risk patients with no clinical coronary artery disease who were not specifically treated, a mean annual progression of coronary calcium of 52% was observed. In the presence of statin drug therapy, progression ranged from -7% through 22%, depending on the LDL cholesterol levels during therapy. A preliminary prospective investigation has confirmed these results and, in particular, suggested that reaching low LDL cholesterol levels < 100 mg/dl effectively stops the progression of coronary calcified atherosclerosis. LDL cholesterol independent ("pleiotropic") effects of statin drugs could not be demonstrated by using EBCT. At present, two large prospective, randomized trials are being conducted which analyze the effects of intensified versus standard statin drug therapy on the progression of coronary calcified atherosclerosis by EBCT. CONCLUSIONS: Serial EBCT studies enable analysis of the interaction between therapeutic measures, progression of coronary calcified atherosclerosis and clinical course of the patients by virtue of direct visualization of the activity of coronary plaque disease. This has already been successfully implemented in small patients groups. Validation in the individual patient is pending. Prospective, randomized therapeutic trials are expected to yield valuable knowledge for clinical practice.

Cholesterol, LDL↗
PubMed2004

Progressive idiopathic axonal neuropathy--a comparative clinical and histopathological study with vasculitic neuropathy.

Patients with a progressive disabling idiopathic axonal neuropathy could have a potentially treatable immune mediated neuropathy. To evaluate whether progressive idiopathic axonal neuropathy could be a pathologically difficult to prove vasculitic neuropathy pathologically difficult to prove or if it could be a separate clinical entity (i. e. with the axon as the primary immunological target), we performed a comparative clinical and histopathological study in 10 patients with progressive idiopathic axonal neuropathy, 10 patients with vasculitic neuropathy, and 12 patients with chronic idiopathic axonal polyneuropathy (CIAP). The clinical features and disease course in patients with progressive idiopathic axonal neuropathy and patients with vasculitic neuropathy were similar. Six patients with progressive idiopathic axonal neuropathy had been treated with prednisone and/or intravenous immunoglobulin. Disability decreased in all these six patients, but also in two of the four non-treated patients. Upon reviewing the sural nerve biopsy specimens, vasculitis was found in one patient with progressive idiopathic axonal neuropathy. Vasculitis-associated signs of ischemic injury or inflammation (most notably: large variation in fascicular axonal degeneration, perivascular inflammation, inflammation of the blood vessel wall without lumen obstruction) were found in four patients with progressive idiopathic axonal neuropathy, in all patients with vasculitic neuropathy, but were absent in patients with CIAP. The findings show that there is a small chance of finding sural nerve vasculitis upon scrutinising biopsy examination in progressive idiopathic axonal neuropathy. The presence of vasculitis-associated signs in progressive idiopathic axonal neuropathy suggests that some of these patients could have vasculitic neuropathy, even if vasculitic lesions cannot be demonstrated. However, if inflammatory changes cannot be demonstrated this does not preclude an immune-mediated origin.

Adolescent↗
PubMed2005

Disease progression in the contralateral carotid artery after endarterectomy.

Our objectives were to establish the incidence and progression of stenotic lesions in the contralateral carotid artery (CCA) after endarterectomy, to identify subpopulations of patients at risk of contralateral disease progression, and to evaluate the efficacy of duplex scanning surveillance at detecting these lesions. We performed a prospective study on 180 patients in whom the CCA to the operated artery was healthy or showed <70% stenosis. All patients had completed a clinical and hemodynamic follow-up program, including duplex scanning of both carotids, with sessions 3 and 6 months after surgery and then every semester until 2 years. Thereafter, examinations were scheduled according to the severity of stenosis. Mean follow-up time was 26.2 months (range 1.6-67.6). Disease progression was observed in 26 lesions (15%), nine of which (5.5%) progressed to severe stenosis (SS). Kaplan-Meier event-free rates of any disease progression were 89%, 88%, 82%, and 79% for 1, 2, 3, and 4 years, respectively. Event-free rates of progression to SS were 98%, 96%, 93%, and 90.6%, respectively, for 1, 2, 3, and 4 years. The risk of progression to SS was five times higher for stenoses that were moderate at the start of the study (p = 0.025). Severe contralateral stenoses were more common and appeared later during follow-up than ipsilateral restenoses. Progression of contralateral stenotic lesions is not uncommon and is essentially related to the presence of a moderate lesion at the start of follow-up. Indeed, moderate stenosis is a risk factor for progression to SS, which appears later and more frequently than ipsilateral restenosis. It therefore seems that patients with a moderate contralateral lesion would benefit from long-term duplex ultrasound surveillance.

Aged↗
PubMedDate not supplied

Factors influencing the rate of fibrosis progression in chronic hepatitis C.

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.

Adult↗
PubMed1995

Progression of aortic stenosis in 394 patients: relation to changes in myocardial and mitral valve dysfunction.

OBJECTIVES: This study reports the results of echocardiographic follow-up in a large cohort of patients with aortic stenosis and correlates the progression of aortic stenosis with changes in the degree of mitral regurgitation and left ventricular hypertrophy and systolic dysfunction. BACKGROUND: Progressive aortic stenosis often causes left ventricular dysfunction and mitral regurgitation. Doppler echocardiography has greatly assisted in the noninvasive evaluation and follow-up of aortic stenosis. Nevertheless, the longitudinal follow-up of patients with Doppler echocardiography for the progression of aortic stenosis and the significance of progressive ventricular hypertrophy and mitral regurgitation have not been reported. METHODS: Serial Doppler echocardiography was performed in 394 consecutive patients with valvular aortic stenosis at baseline and after a mean follow-up period of 37 +/- 16 months. Mean and peak aortic gradients, aortic valve area, left ventricular systolic and diastolic diameters and percent area change (shortening fraction) were expressed as continuous variables, and systolic dysfunction, mitral regurgitation, ventricular hypertrophy and filling properties were tabulated as categoric variables using a semiquantitative grading system. RESULTS: Peak and mean gradients increased by an average of 8.3 and 6.3 mm Hg/year, respectively; end-systolic and end-diastolic diameters increased by 1.9 and 1.6 mm/year, respectively; and aortic valve area decreased by 0.14 cm2/year during the follow-up interval (p < 0.001 for all), indicating progression of aortic stenosis and ventricular dilation. Patients in the lowest quartile of aortic valve area and highest quartiles of mean and peak gradients had the least change compared with those in the highest quartile of aortic valve area and lowest quartile of mean and peak gradients (p < 0.01 for all). Patients with more mitral regurgitation at follow-up than at baseline had higher mean percent increase in mean and peak gradients as well as more progression of ventricular dilation and worsening systolic function compared with those with stable or improving mitral regurgitation (p < 0.05 for all). Similarly, subjects with worsening left ventricular hypertrophy had larger mean percent increase in mean and peak gradients than those with stable left ventricular hypertrophy (p < 0.01) but maintained stable ventricular volumes and systolic function. There was no correlation between the amount of change in mean or peak gradients and degree of deterioration in systolic function. CONCLUSIONS: Aortic stenosis progresses predictably over time; however, systolic dysfunction is an inconsistent marker of the hemodynamic consequences of severe aortic stenosis. As an adaptive response to pressure overload, progressive hypertrophy appears to prevent ventricular dilation and development or worsening of mitral regurgitation. Conversely, progressive mitral regurgitation may be seen as a maladaptive consequence of increasing aortic stenosis.

Aged↗
PubMed2004

Lipid profile of patients with aortic stenosis might be predictive of rate of progression.

BACKGROUND: Aortic stenosis is one of the most commonly encountered valvular pathology requiring surgery in developed countries. There are similarities between risk factors for coronary atherosclerosis and the development of aortic stenosis. We designed a retrospective study, evaluated the lipid profile and previous echocardiographic recordings of patients with aortic stenosis, and searched the association of rate of progression and lipid profile. METHODS AND RESULTS: The annual rates of progression in the peak and mean aortic gradients were 8.5 +/- 3.2 and 6.7 +/- 2.2 mm Hg/year, respectively. We classified the annual rate of progression of peak aortic gradient into 2 groups, group 1 with <10 mm Hg ("slow progressors") and group 2 with > or =10 mm Hg annual rate of progression ("fast progressors"). The annual rate of progression in group 1 was significantly higher than that in group 2, both in peak and mean aortic gradients (12 +/- 2 mm Hg and 6.4 +/- 1.6 mm Hg; 9 +/- 1.3 mm Hg and 5.2 +/- 1.1 mmHg; P <.001 for both). There was a highly significant difference between group 1 and group 2 for total cholesterol/high-density lipoprotein (HDL) cholesterol level ratio (7.1 +/- 1.4 vs 5.2 +/- 1.3, P <.001). There was a significant correlation between annual rate of progression in peak gradient and total cholesterol/HDL cholesterol level ratio (r = 0.399, P =.009). Smoking (P =.024, Beta = 0.26), presence of coronary heart disease (P =.011, Beta = 0.31), and total cholesterol/HDL cholesterol level ratio (P =.004, Beta = 1.98) were independently predictive of fast progression of the peak aortic gradient in the regression analysis. CONCLUSION: In a small group of patients from Turkey with aortic stenosis, there seems to be an association between the rate of progression and total cholesterol/HDL cholesterol level ratio, with fast progression occurring in the group with higher ratios.

Aged↗
PubMedDate not supplied

Mechanisms of epilepsy progression: current theories and perspectives from neuroplasticity in adulthood and development.

Clinical and epidemiological studies have repeatedly demonstrated that a subset of patients with epilepsy have progressive syndromes with increasing seizure frequency and cumulative adverse effects despite optimal anticonvulsant therapy. Recent longitudinal imaging studies and long-term neuropsychological studies have confirmed that a substantial subset of people with epilepsy undergo progressive brain atrophy accompanied by functional declines that worsen with duration of epilepsy. As further evidence of the progressive and adverse effects of inadequately controlled epilepsy, chronic experimental models of epilepsy and the phenomenon of kindling have provided abundant evidence that neural circuits undergo long-term progressive structural and functional alterations in response to seizures. This long-term seizure-induced plasticity in neural circuits appears to be "bidirectional", inducing progressive damage while also inducing resistance to additional damage, as a function of timing or inter-seizure interval. Seizure-induced plasticity has pronounced age-dependence, and influences long-term cognitive consequences of seizures during early life and acquired susceptibility to epilepsy in adulthood. While it is clear from clinical and epidemiological studies that human epilepsy is a heterogeneous disorder and that not all epileptic syndromes are progressive, emerging results from studies of activity-dependent and seizure-induced plasticity and perspectives from "complex systems" analysis are providing new insights into systematic neurobiological processes that are likely to influence the progressive features of epileptic syndromes and patterns of progression in individual patients. The emerging perspective is that phenomena of plasticity and genetic background exert powerful effects in development and adulthood through regulation of activity-dependent structural and functional remodeling of neural circuitry, and that these effects not only influence progression and consequences of seizures, but also offer new opportunities for therapeutic intervention.

Anticonvulsants↗
PubMed2004

Treatment of progressive forms of multiple sclerosis by cyclophosphamide: a cohort study of 490 patients.

There are no generally effective disease-modifying drugs for progressive forms of multiple sclerosis (MS). Some MS centres use cyclophosphamide (CYC) in secondary progressive (SP) forms of MS, especially after interferon beta-1b (INFbeta-1b) treatment failure. Moreover, there are currently no approved drugs for primary progressive (PP) MS. Using the collected data of patients with progressive MS, we studied clinical patterns that predicted a good response to CYC treatment. Secondly, we compared the therapeutic response of SPMS and PPMS patients to the treatment. Data from 490 MS patients were collected. All patients presented an SP (n = 362) or PP (n = 128) form of the disease and 476 had been treated for at least one year with a monthly pulse of CYC associated with methylprednisolone (MP). CYC treatment was justified because of at least a 1-point worsening on the Expanded Disability Status Scale (EDSS) during the previous year. The EDSS score was assessed at baseline and after 6 months (M6) and 12 months (M12) of treatment. After 12 months of CYC treatment, 78.6% of SPMS and 73.5% of PPMS patients had stabilised or had an improved EDSS score. Response to CYC was not significantly different in the two progressive forms of MS. Twenty-two patients presented noticeable drug side effects, one of whom withdrew from the treatment due to intolerance. Patients with an improved EDSS at M12 had a shorter mean progressive time course (5.1 years) than patients who stabilised or worsened (7.1 years) (p = 0.02). We also observed that poor responders at M6 were also poor responders at M12 (p < 0.001). This large cohort study showed that CYC treatment was well tolerated and suggested that a better response occurred in cases with a short progressive time course. We did not find any difference in treatment response between the two progressive forms of MS. To date, no treatment is approved for PPMS and we therefore propose a trial to test the use of CYC treatment early in the course of the disease in PPMS patients with disability progression.

Adult↗
PubMed2005

Study of the venous reflux progression.

BACKGROUND: Patients with chronic venous disease (CVD) often ask whether elective vein surgery could be delayed without consequences. Because the natural history of CVD is not well known, this study was designed to determine its progression in such patients. METHODS: One hundred and sixteen limbs in 90 patients who had at least 2 exams with duplex ultrasound (DU) scanning prior to vein surgery at a university medical center were studied. These were patients who were offered an operation but for various reasons were treated at a later stage. Patients were classified by the CEAP system. RESULTS: The mean age of the patients was 49 years (range, 23 to 81 years). A second DU scan was performed 1 to 43 months after the initial exam (median, 19 months). Eighty-five limbs (73.3%) were unchanged. Thirteen limbs (11.2%) had progression of clinical stage, and seven had progression on DU scanning as well. Seven limbs progressed from C2 to C3, four limbs from C3 to C4, and two limbs from C4 to C6. Thirty-four limbs had a documented change on repeat DU scanning. In 3 of these limbs, reflux was missed on the initial exam; therefore, 31 limbs had progression of disease. The great saphenous vein and tributaries were the most often anatomic sites affected by a change, followed by perforators. Seventeen limbs (14.7%) had extension of pre-existing reflux, and 14 (12.1%) had reflux in a new segment. In 11 of these limbs, a change in the initial plan for treatment was required. Symptomatic or DU changes were noted 6 months or later in 95% of limbs and 74.2% of limbs with disease progression were diagnosed at 12 months or later. All but one of the 13 symptomatic limbs developed symptoms at least a year later. CONCLUSION: Nearly one third of patients with venous reflux had progression. Anatomic extension is frequent with disease progression but not a pre-requisite. Progression was found in most limbs 6 months after the initial study. Patients undergoing treatment for their veins may need another DU exam if this time interval is exceeded.

Adult↗