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PubMed2006

Disability progression in multiple sclerosis is slower than previously reported.

OBJECTIVE: To investigate disease progression and risk factors in a large geographically based population with multiple sclerosis (MS), using two different inception points--clinical onset and date of birth. METHODS: The authors reviewed a database of subjects with definite MS and symptom onset prior to July 1988. The main outcome was sustained progression to Expanded Disability Status Scale (EDSS) 6 (requires a cane), using the date of birth and date of MS onset as inception points in separate analyses. Risk factors examined were sex, relapsing vs primary progressive course, onset age, and onset symptoms. RESULTS: The study included 2,837 patients, followed prospectively for 22,723 patient years. The median time to EDSS 6 was 27.9 years, 15 years after onset; only 21% reached EDSS 6, and by age 50, 28% required a cane. Men progressed 38% more quickly than women from onset (p < 0.0005), yet both required canes at similar ages: 58.8 years for men and 60.1 for women (p = 0.082). A younger onset age predicted a slower progression, but those older at onset were consistently older when reaching EDSS 6. A primary progressive course predicted a more rapid progression from both onset (p < 0.0005) and birth (hazard ratio = 2.7 [95% CI: 2.2 to 3.3]). No onset symptom consistently predicted progression. CONCLUSION: Disability progression in multiple sclerosis (MS) accrued more slowly than found in earlier longitudinal studies. The authors also challenged two fundamental concepts in MS, demonstrating that neither male sex nor older onset age was associated with worse disease outcome.

Adult↗
PubMed2002

Proton MR spectroscopic imaging predicts lesion progression on MRI in X-linked adrenoleukodystrophy.

BACKGROUND: The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. Multislice proton MRS imaging (MRSI) has previously detected more extensive brain abnormalities in X-ALD than conventional MRI, which has been suggested to predict impending demyelination. However, the significance of these changes is unclear. OBJECTIVE: The purpose of this study was to determine the long-term sensitivity and specificity of MRSI for disease progression in X-ALD. METHODS: Twenty-five patients with X-ALD were investigated (average age, 15 years; range, 2-43 years) with MRI and proton MRSI at baseline and follow-up MRI over a mean period of 3.5 years. Eight patients had normal MRI findings at baseline and on follow-up (noncerebral group), 11 had abnormal MRI at baseline and no change on follow-up (cerebral nonprogressive group), and 6 had progressive MRI abnormalities (cerebral progressive group). On MRSI, voxels were analyzed in the normal MRI-appearing perilesional white matter, or in the corresponding area in the noncerebral group. RESULTS: The concentration ratio of N-acetylaspartate (NAA) to choline was the most sensitive indicator of disease progression. The average NAA/choline ratio was 5.99 for the noncerebral group, 5.75 for the cerebral nonprogressive group, and 3.74 for the cerebral progressive group (p = 0.002). At a cut-off point of 5.0, the NAA/choline ratio predicted disease progression in all patients with six cerebral progressive disease (sensitivity 100%). The specificity was 83%, the positive predictive value was 66%, and the negative predictive value was 100%. CONCLUSIONS: Multislice proton MRS imaging is able to identify impending or beginning degeneration in white matter that still appears normal on conventional MRI. Multislice proton MRSI may be a suitable technique for the prediction of lesion progression on MRI in X-linked adrenoleukodystrophy.

Adolescent↗
PubMed2005

Factors associated with neurological outcome and lesion progression in traumatic subarachnoid hemorrhage patients.

OBJECTIVE: Traumatic subarachnoid hemorrhage (tSAH) is a frequent finding after closed-head injuries, and its presence is a powerful factor associated with poor outcome. The exact mechanism linking tSAH and an adverse outcome is poorly understood. The aim of this study was to identify the factors that may predict outcomes and changes in the computed tomographic (CT) scans of lesions in a selected population of tSAH patients. METHODS: We evaluated 141 patients admitted consecutively from January 1, 1997, to January 31, 1999, with a CT diagnosis of tSAH. The admission and "worst" CT scans were recorded. CT scan changes were reported as "significant CT progression" (changes in the Marshall classification) or "any CT progression." The amount of subarachnoid blood was recorded using a modified Fisher classification. Outcome was assessed at 6 months after injury with the Glasgow Outcome Scale. RESULTS: Twenty-eight patients (19.9%) had an unfavorable Glasgow Outcome Scale outcome. In the univariate analysis, prognosis was significantly related to age, admission Glasgow Coma Scale score, Marshall CT classification score at admission and on the worst CT scan, amount of tSAH, and volume of the associated brain contusions. From multivariate analysis, the only factors independently related to outcome were the Glasgow Coma Scale score (P < 0.01) and size of the tSAH at admission (P < 0.001). Thirty-four patients (24.1%) had significant CT lesion progression, and 66 patients (46.8%) had some lesion progression. Patients having significant progression of the lesion had a higher risk of an unfavorable outcome (32 versus 10%; P = 0.004). Unadjusted factors predicting CT progression were the Glasgow Coma Scale score at admission, the Marshall classification at admission, the amount of subarachnoid blood, and the presence or volume of associated brain contusions at admission. Independent factors associated with significant CT progression were the amount of tSAH (P < 0.001) and the presence or volume of brain contusions at admission (P < 0.001). CONCLUSION: The outcome of patients with tSAH at admission is related in a logistic regression analysis to the admission Glasgow Coma Scale score and to the amount of subarachnoid blood. These patients also have a significant risk of CT progression. The amount of subarachnoid blood and the presence of associated parenchymal damage are powerful independent factors associated with CT progression, thus linking poor outcomes and CT changes.

Aged↗
PubMed2006

Oncologic progression of bone plasmacytomas to multiple myeloma.

PURPOSE: To evaluate the clinical aspects, diagnoses, prognostic factors, and percent progression of plasmacytoma to multiple myeloma. MATERIALS AND METHODS: 103 medical records of patients suspected of plasmacytoma were surveyed covering the period between 1950 and 1998, and 30 were selected for analysis. Patients were classified into 2 groups: patients who did (n = 17) and did not (n = 13) progress to multiple myeloma. Comparative statistics regarding a variety of clinical aspects were developed. RESULTS: Patients who progressed to multiple myeloma were younger than those who did not (52.3 +/- 2.6 vs 62.6 +/- 3.4 years; mean +/- SEM; P = 0.02). There were no significant differences in gender between groups. A higher incidence of multiple recurrence was observed in patients who progressed to multiple myeloma (75%, P = 0.049). Both groups showed a prevalence of vertebral column injuries. No significant differences were found between groups regarding the disease period (from the onset of symptoms until diagnosis) (P = 0.20) and survival (P = 0.34). The average time to progression from plasmacytoma to myeloma was 41 +/- 39 months (mean +/- SD), and the progression rate was 57%. CONCLUSION: Patients who progressed to multiple myeloma were younger than those who did not. No significant differences were found between groups regarding sex, time from symptom onset to diagnosis, and survival time. In both groups, the most affected anatomic location was the vertebral column, and most affected sex was male. The average time to progression to multiple myeloma was 41 months. It was not possible to determine the factors that influenced the survival of patients with plasmacytoma or for those who progressed to multiple myeloma.

Age Factors↗
PubMed2005

Asymmetric dimethylarginine and progression of chronic kidney disease: the mild to moderate kidney disease study.

Reduced bioavailability of nitric oxide (NO) is thought to play an important role in progression of renal damage. The hypothesis that the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is involved in progression of kidney disease was tested. Plasma ADMA concentrations and other putative progression factors were assessed in 227 relatively young patients (45.7 +/- 12.6 yr) with nondiabetic kidney diseases and mild to moderate renal failure. Progression assessed as doubling of serum creatinine and/or renal replacement therapy was evaluated prospectively. Baseline plasma ADMA concentrations in renal patients correlated significantly with serum creatinine (r = 0.595), GFR (r = -0.591), age (r = 0.281), and proteinuria (r = 0.184; all P < 0.01). Patients who reached an end point during follow-up were significantly older (P < 0.05) and had significantly higher creatinine, ADMA, and parathyroid hormone blood concentrations and protein excretion rates at baseline, whereas GFR and hemoglobin were significantly lower (all P < 0.01). Cox regression analysis revealed baseline serum creatinine (odds ratio 2.00; 95% confidence interval [CI] 1.61 to 2.49; P < 0.001) and ADMA (odds ratio 1.47; 95% CI 1.12 to 1.93 for an increment of 0.1 mumol/L; P < 0.006) as independent predictors of disease progression. In patients with ADMA levels above median, progression was significantly faster (P < 0.0001), and their mean follow-up time to a progression end point was 52.8 mo (95% CI 46.9 to 58.8) as compared with 71.6 mo (95% CI 66.2 to 76.9) in patients with ADMA levels below the median. The endogenous NO synthase inhibitor ADMA is significantly associated with progression of nondiabetic kidney diseases. Lowering plasma ADMA concentrations may be a novel therapeutic target to prevent progressive renal impairment.

Adult↗
PubMed1998

The effect of different diagnostic thresholds on incidence of disease progression.

Detection of periodontal disease progression occurs when a predetermined threshold of attachment loss is exceeded during longitudinal monitoring. The incidence of disease progression in a population may be dependent on the method and threshold utilized to identify significant changes in attachment level measurements. The aim of this study was to investigate the effect of utilizing different methods and thresholds on the incidence of disease progression in an untreated periodontitis population. The relationship between baseline clinical parameters and disease progression was also examined. A total of 411 interproximal sites in 46 individuals were monitored monthly over a 6-month period. Disease progression was determined by the cumulative sum (CUSUM) method and by the absolute change in relative attachment level between months 0 and 6 utilizing 3 different thresholds for attachment level change (0.58 mm, 1.16 mm, and 1.74 mm) based upon examiner repeatability using an automated probe. Utilizing the CUSUM method, 49 of 411 sites (11.9%) demonstrated attachment loss over the 6-month observation period. When attachment level changes > or = 0.58 mm, > or = 1.16 mm, and > or = 1.74 mm were used to identify disease progression, the percentage of sites exhibiting deterioration were 19.5%, 8.8%, and 2.9%, respectively. These results demonstrate that the apparent incidence of disease progression was dependent on the method and threshold utilized to detect progressive sites. When utilizing the CUSUM and 0.58 mm thresholds a significant (P < 0.05), but weak relationship (r = -0.26) was observed between baseline relative attachment level measurements and sites exhibiting disease progression. This finding suggests that sites with significant but relatively less attachment loss may be more likely to experience further breakdown compared to sites with a history of greater periodontal destruction.

Analysis of Variance↗
PubMed1997

Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study.

OBJECTIVE: To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS: Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS: The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.

Albuminuria↗
PubMed2002

Chromosomal imbalances in primary oligodendroglial tumors and their recurrences: clues about malignant progression detected using comparative genomic hybridization.

OBJECT: Despite the rapid increase in knowledge concerning the genetic basis of malignant progression in astrocytic tumors, progression of oligodendroglial tumors (including both pure oligodendrogliomas and mixed oligoastrocytomas) is still poorly understood. The aim of the present study is the elucidation of chromosomal imbalances involved in the progression of oligodendroglial tumors toward malignancy. METHODS: Using comparative genomic hybridization (CGH) on snap-frozen tumor tissue, the tumor genomes of five primary oligodendroglial tumors and associated recurrent tumors were screened for chromosomal imbalances. This information was correlated with clinical data (including follow-up data) and histopathological malignancy grade. In all cases an increase in chromosomal imbalances was detected in the recurrent tumor, indicating genetic progression. In three of the five cases this correlated with malignant progression detected at the histopathological level. The results indicate that, similar to what occurs in astrocytic tumors, chromosomal imbalances harboring genes involved in the cell proliferation control mechanism at the G1-S border are involved in the progression of oligodendroglial tumors. Additionally, although gains of genetic material on chromosome 7 and losses on chromosome 10 are most frequently detected in the course of malignant progression of astrocytic tumors, either or both of these can also occur during malignant progression of typical oligodendroglial tumors that contain losses involving chromosome 1p and/or chromosome 19q. CONCLUSIONS: When performed on optimally preserved material from a small set of primary oligodendroglial tumors and associated recurrent tumors, CGH detects chromosomal aberrations that potentially play a mechanistic role in the malignant progression of these tumors.

Adult↗
PubMed1999

Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study.

BACKGROUND: The effect of previous CD4 cell count nadir on clinical progression in patients with increases in CD4 cell counts has not been investigated. OBJECTIVE: To assess risk for progression of HIV disease in patients with CD4 counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count) and compare the rate of progression in patients with CD4 counts less than 50 cells/mm3 with that in patients whose CD4 counts rebounded from less than 50 cells/mm3 to at least 200 cells/mm3. DESIGN: Prospective, observational multicenter study. SETTING: 52 HIV outpatient clinics in Europe. PATIENTS: Two groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A) and those with CD4 counts less than 50 cells/mm3 (group B). Group A was stratified according to the lowest previous CD4 count: at least 150 cells/mm3 (stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3), and 1 to 50 cells/mm3 (stratum 4). MEASUREMENTS: Patients were followed until a progression event occurred (first AIDS-defining event, new AIDS-defining event, or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A) or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a patient-years analysis and reported as events per 100 patient-years of follow-up; the relative hazards for progression were based on Cox proportional hazards models. RESULTS: The overall rate of disease progression in group A was 3.9 per 100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient-years]). In group A, the rate increased in patients with previous low CD4 cell count nadirs, resulting in a significant increase in the relative hazard for progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to 4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively. CONCLUSIONS: Increases in CD4 counts from very low levels to at least 200 cells/mm3 are associated with a much reduced rate of disease progression. However, a previously low CD4 cell count nadir remains associated with a moderately higher risk for disease progression among patients with CD4 counts of at least 200 cells/mm3.

Adult↗
PubMed2003

Quadriceps strength and osteoarthritis progression in malaligned and lax knees.

BACKGROUND: Quadriceps muscle strengthening is a common goal in the management of knee osteoarthritis. In healthy knees, strength protects against new osteoarthritis. In arthritic knees, greater strength may protect joints and thereby delay osteoarthritis progression. Alternatively, in certain joint environments, such as malalignment or laxity, greater strength may translate into damaging joint reaction forces. The relationship between quadriceps strength and progression of knee osteoarthritis may differ according to these factors. OBJECTIVE: To determine whether greater quadriceps strength is associated with greater probability of tibiofemoral osteoarthritis progression in malaligned knees and in high-laxity knees. DESIGN: Prospective, longitudinal cohort study. SETTING: Academic medical center. PARTICIPANTS: 237 persons with primary knee osteoarthritis, definite tibiofemoral osteophytes, and at least some difficulty with knee-requiring activity. Two hundred thirty completed the 18-month evaluation. The current study primarily involved those without advanced osteoarthritis in either knee (n = 171). MEASUREMENTS: Quadriceps strength, knee laxity and alignment, and osteoarthritis progression. RESULTS: The predicted probability of tibiofemoral progression was 0.153 (95% CI, 0.100 to 0.228) in high-strength knees and 0.098 (CI, 0.061 to 0.155) in low-strength knees. In malaligned knees, high strength was associated with a significant increase (P = 0.03) in the likelihood of progression (predicted probability, 0.406 [CI, 0.226 to 0.615] vs. 0.187 [CI, 0.081 to 0.375] in high-strength vs. low-strength knees). Strength was also associated with increased likelihood of progression in high-laxity knees (P = 0.003 when high laxity was defined as > or =6.75 degrees). The probability of patellofemoral progression did not differ between high- and low-strength knees in the full sample or within subsets. CONCLUSIONS: Greater quadriceps strength at baseline was associated with increased likelihood of tibiofemoral osteoarthritis progression in malaligned knees and lax knees. Subset-specific approaches beyond strengthening exercises should be developed to enhance joint-protective muscle activity.

Body Mass Index↗
PubMed2003

Bone marrow edema and its relation to progression of knee osteoarthritis.

BACKGROUND: While factors affecting the course of knee osteoarthritis are mostly unknown, lesions on bone scan and mechanical malalignment increase risk for radiographic deterioration. Bone marrow edema lesions on magnetic resonance imaging correspond to bone scan lesions. OBJECTIVE: To determine whether edema lesions in the subarticular bone in patients with knee osteoarthritis identify knees at high risk for radiographic progression and whether these lesions are associated with limb malalignment. DESIGN: Natural history study. SETTING: A Veterans Administration hospital in Boston, Massachusetts. PATIENTS: Persons 45 years of age and older with symptomatic knee osteoarthritis. MEASUREMENTS: Baseline assessments included magnetic resonance imaging of the knee and fluoroscopically positioned radiography. During follow-up at 15 and 30 months, patients underwent repeated radiography; at 15 months, long-limb films were obtained to assess mechanical alignment. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semi-quantitative grading. Generalized estimating equations were used to evaluate the relation of medial bone marrow edema lesions to medial progression and lateral lesions to lateral progression, before and after adjustment for limb alignment. RESULTS: Of 256 patients, 223 (87.1%) participated in at least one follow-up examination. Medial bone marrow lesions were seen mostly in patients with varus limbs, and lateral lesions were seen mostly in those with valgus limbs. Twenty-seven of 75 knees with medial lesions (36.0%) showed medial progression versus 12 of 148 knees without lesions (8.1%) (odds ratio for progression, 6.5 [95% CI, 3.0 to 14.0]). Approximately 69% of knees that progressed medially had medial lesions, and lateral lesions conferred a marked risk for lateral progression. These increased risks were attenuated by 37% to 53% after adjustment for limb alignment. CONCLUSION: Bone marrow edema is a potent risk factor for structural deterioration in knee osteoarthritis, and its relation to progression is explained in part by its association with limb alignment.

Aged↗
PubMed2000

Genetic progression and clonal relationship of recurrent premalignant head and neck lesions.

We constructed a preliminary genetic progression model for head and neck squamous cell carcinoma (HNSC) based on the frequency of genetic alterations in preneoplastic and neoplastic lesions from single biopsy specimens. To firmly establish the temporal order of established genetic events in HNSC, we sampled serial biopsies from five patients with recurrent premalignant lesions at a single anatomic site over a period of time (1 month to 144 months). These lesions were examined by microsatellite analysis of the minimal regions of loss on the 10 most frequently lost chromosomal arms in HNSC. Each set of serial biopsies from all five patients demonstrated LOH (loss of heterozygosity) of identical alleles at multiple loci with identical boundaries between areas of LOH and retention of heterozygosity, indicating a common clonal origin for each set. Three patients demonstrated genetic progression (new regions of LOH) over time correlating with histopathological progression, one patient demonstrated lack of genetic progression associated with unchanged histopathological morphology, and one patient demonstrated histopathological progression without detection of a corresponding genetic progression event. For one of these patients with a laryngeal tumor, at least four separate steps in progression to malignancy could be determined, accompanied by spatial expansion of an increasingly altered clonal population from the ipsilateral to the contralateral side, ultimately resulting in a malignancy. Microsatellite-based genetic analysis of recurrent premalignant lesions indicates that these lesions arise from a common clonal progenitor, followed by outgrowth of clonal populations associated with progressive genetic alterations and phenotypic progression to malignancy.

Biopsy↗
PubMed2000

The role of systemic hypertension in the progression of nondiabetic renal disease.

BACKGROUND: A role for hypertension in the progression of renal disease has been convincingly shown in experimental animals only. In human studies, the relation between hypertension and progression is difficult to demonstrate due to several confounding factors: age, gender, race; the difficult choice of blood pressure (BP) parameters that correlate with progression; the abnormal circadian BP pattern; and the many non-hemodynamic factors of progression. An important role for hypertension in progressive nondiabetic renal disease has been suggested by observational studies and clinical trials originally intended to evaluate the effect of dietary protein restriction on progression. In addition, several studies, summarized by a recent meta-analysis, have shown that pharmacological agents which lower both BP and proteinuria, mainly the angiotensin-converting enzyme inhibitors (ACEI), significantly slow the rate of progression in these diseases. METHODS: In this article we review the effect of lowering BP on the progression of nondiabetic chronic renal disease, the patient characteristics that are associated with a greater or lesser benefit of blood pressure reduction, and the choice of antihypertensive regimens associated with better outcomes in patients with renal disease. RESULTS: Lower levels of achieved BP are associated with a slower decline in renal function, both in patients with and without proteinuria. ACEI are effective BP lowering agents and are associated with better preservation of renal function as opposed to antihypertensive regimens without ACEI. This protective effect of ACEI is in addition to their BP and urine protein lowering effects. The protective effect of ACEI on renal function is more pronounced in patients with proteinuria. CONCLUSION: In patients with nondiabetic renal disease and proteinuria, the risk of progression can be minimized by lowering both BP and proteinuria. ACEI have an additional beneficial effect.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

The role of underlying nephropathy in the progression of renal disease.

BACKGROUND: Disease-specific pathogenic mechanisms may be major determinants of the spontaneous rate of progression of chronic renal failure (CRF). To clarify the role of different underlying renal diseases, we examined the rate of CRF progression in 886 patients with chronic nephropathies. METHODS: Secondary analysis of two multicenter, prospective randomized trials: the Northern Italian Cooperative study (NIC) and the AIPRI study (ACE-Inhibition in Progressive Renal Insufficiency). Univariate and multivariate analyses of variance were used to select the covariates possibly related to CRF progression (estimated by means of the slope of the reciprocal of SCr against time), focusing on the contributory role of primary renal diseases. RESULTS: The overall rate of CRF progression was relatively low but there was a considerable difference in the slopes relating to the underlying nephropathy (particularly evident in the patients with chronic glomerulonephritis (CGN)). The median rate of CRF progression in both studies was more rapid in patients with polycystic kidney disease (PKD) and CGN than in those with other nephropathies. Multivariate analysis showed PKD as an independent predictor of the CRF progression rate only in the NIC Study (P < 0.0015); the selected variables in both studies predicted a variation of only 15-18% in the CRF progression rate. CONCLUSION: The underlying renal disease certainly plays a role in the natural history of CRF, but the variability of the CRF progression rates related to different renal diseases and between individuals with the same diagnosis underlines the need for caution in evaluating risk factors and predicting single patient outcomes.

Adult↗
PubMed2000

Rapid coronary artery disease progression and angiographic stenosis morphology.

It is established that the progression of coronary artery disease is neither linear nor predictable. The unpredictable and often episodic nature of coronary disease progression can be explained by rapid increase of stenosis severity due to thrombosis, which occurs as a complication of the atherogenic process. Rapid coronary stenosis progression is most often responsible for the acute clinical manifestations of coronary artery disease, i.e. sudden cardiac death, acute myocardial infarction and unstable coronary syndromes. Recently, it has been shown that stenosis progression, whether clinically "silent" or associated with acute coronary events, is a strong predictor of cardiovascular risk. Atheromatous plaques associated with rapid coronary artery disease progression have well defined anatomo-pathological characteristics and are usually termed "vulnerable" or "unstable", terms which indicate both their propensity to acute disruption and increased thrombogenicity that may lead to the development of acute coronary events. Plaques have been regarded, in the past, as being inert and staying almost unchanged for years. However, they are very active entities. The fibrous cap is in a balance between smooth muscle cells producing collagen and the macrophages degrading collagen. The thickness of the cap depends on the relative activity of those two components and there is, therefore, a danger of the fibrous cap rupturing. Although only a relatively small proportion of all coronary artery lesions in patients with angina pectoris undergo complications that lead to fibrous cap disruption and acute coronary events, these stenoses are responsible for the majority of cases of serious coronary events. Thus the identification of vulnerable plaques that may lead to increased risk of coronary events will most certainly help in the rational management of patients with coronary artery disease. Angiographic studies have indicated that "complex" lesion morphology is associated with increased risk of myocardial infarction and "ulcerated" plaques identify vulnerable lesions. We therefore reasoned that the identification of angiographically complex coronary stenoses could provide a valuable marker of cardiovascular risk in relation to rapid disease progression. Our group sought to investigate the role of angiographically complex lesions as a marker of rapid disease progression in different clinical settings. We took advantage of the fact that patients with stable angina pectoris requiring routine myocardial revascularisation in our institution are put on waiting lists. We observed that complex lesions progressed more than smooth stenoses of similar severity both in patients presenting with stable angina and in patients presenting with unstable angina. Why complex plaques should be particularly vulnerable to rapid stenosis progression is speculative. In this paper we discuss the possible mechanisms that may explain an association between complex stenosis and acute coronary events.

Coronary Angiography↗
PubMedDate not supplied

[Genetic determinant factors of resistance to HIV infection and of control of progression to AIDS: implications on pathogenesis and therapeutic approaches for the eradication of HIV. A review].

In this review, we describe and discuss the genetic factors that, up to some point, determine resistance to the infection and control the progression of the disease in HIV-infected individuals. Genetic factors may account for non-progression or slow progression of the disease in some of so called long-term non progressors HIV-infected individuals. In general, this group shows no symptoms for more than 10 years, while their circulating T CD4+ cells levels remain stable and they usually have a low virus load. Even though non-progression and rapid progression phenomenon are still not fully understood, there probability exists that some class I and class II MHC alleles are associated with a greater or smaller risk to develop AIDS. Class I HLA-B*35 and Cw*04 alleles are the ones commonly associated with the rapid transition of the infection into AIDS. In contrast, heterozygosity for class I HLA alleles and, particularly, the absence of HLA-B*35 and Cw*04 may contribute to non-progression. Studies which set forward other HLA alleles as possibly taking part of the pathogenic mechanism of non-progression are also described; although, relevant methodological problems can be noticed. Furthermore, this review explains and discusses allelic variations for some of the components of the chemokine receptors family, particularly the genes which codify for CCR5 and CCR2 and other genetic factors such as the SDF1-3'. A variant of the alpha SDF1 chemokine gene that have been associated with AIDS' slow progression or non-progression in HIV-infected individuals. As a whole, the factors described in this review are those that influence the natural history of the disease due to HIV and give an example of what genetic or multigenetic influence can have over the pattern of evolution of HIV infection. Finally, we mention the possible implications that the identification of the genetic markers has in the pathogenesis of HIV disease and in the development of the new therapeutic strategies to control or eliminate HIV.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Clinical and biological disease progression in vertically acquired paediatric HIV infection.

With available interventions in Europe, mother-to-child, or vertical transmission of HIV has been reduced from 15-20%, but still occurs in around one or two of every 100 pregnancies of HIV infected women. Progression of disease in vertically-infected children is most rapid in early life and without early treatment about one-fifth progress to serious clinical illness or die before one year of age. However, those surviving the first few years of life, including the ones with previous serious illness are generally clinically well throughout childhood, sometimes even without antiretroviral treatment. With the increasingly common use of aggressive therapy at an early stage of infection, progression to serious disease or death is now rare. Clinical disease progression is closely associated with HIV RNA viral load which peaks at around age three months, with a subsequent decline thereafter in vertically-infected children. Levels in girls are different to those of boys, but the pattern of this difference is not consistent over age. Progression of HIV infection is also related to the levels of immunological components such as CD4, CD8 and absolute lymphocyte cell counts. Patterns over age differ by both gender and race in both infected and uninfected children with absolute lymphocyte values and subsets being generally higher for girls and white children. Levels in infected children differ markedly to those of uninfected children but much of the ranges of measurements are common to both. Early-life measurements of CD4 percentage and absolute lymphocyte count independently predict rapid progression to serious disease or death during the first year of life, while early persistent hepatomegaly or splenomegaly is prognostic of serious disease progression thereafter. However, there are no differences in progression by gender and race, nor are the prognostic abilities of markers altered by gender or race, which would suggest that clinical guidelines need not account for such factors. Of the early prognostic indicators, CD4 percentage measurement is the most useful and beyond six months of age a CD4 percentage cut-off of 10% best informs subsequent disease progression risk.

Adolescent↗
PubMed2005

Measurable predictive factors for progression to AIDS among HIV-infected patients in Singapore.

INTRODUCTION: This study identifies measurable factors at the time of diagnosis that predict the progression to Acquired Immunodeficiency Syndrome (AIDS) among Human Immunodeficiency Virus (HIV)-infected patients in Singapore. MATERIALS AND METHODS: We carried out a retrospective study of 790 HIV-infected patients from 16 May 1985 to 31 December 2001. The end-point was the onset of AIDS-defining illness listed in the 1987 and 1991 revised Centers for Disease Control and Prevention criteria, but excluded CD4 cell counts as a criterion. Using the Kaplan-Meier method, AIDS-free survival curves were plotted for age groups at diagnosis, baseline CD4 counts and periods for utilisation of antiretroviral treatment. A Cox regression model was constructed to determine independent predictors of disease progression. RESULTS: Univariate analysis showed that patients of older age at diagnosis had a significantly higher risk of progression compared to younger patients, and patients with higher baseline CD4 cell counts had a lower risk of progression to AIDS. Adjusting for the simultaneous influence of several covariates on the rate of HIV progression to AIDS, multivariate analysis using the Cox model showed a significantly higher risk of progression for older patients at diagnosis, and the progressive lowering of risk with increasing baseline CD4 cell counts. CONCLUSIONS: This study found older age at diagnosis and baseline CD4 cell counts to be measurable predictors for HIV progression to AIDS at time of diagnosis. Identification of these risk factors enables physicians to provide counselling and advice, and to start appropriate treatment early. This could lower the risk of progression and improve survival.

Acquired Immunodeficiency Syndrome↗