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PubMedDate not supplied

The role of ACE gene polymorphism in rapidity of progression of focal segmental glomerulosclerosis.

BACKGROUND: The insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene has been associated with progression of renal diseases. AIMS: We investigated its role in the rate of progression of focal segmental glomerulosclerosis (FSGS). METHODS: Forty-seven patients with end-stage renal disease (ESRD) due to FSGS were evaluated. RESULTS: The distribution of ACE genotype was II-25.5%, ID-55.5%, and DD-19%, as compared to 40 controls with genotype of 7.5%, 60%, and 32.5%, respectively (p= NS). In African Americans (AA) the gene frequencies among patients and controls were I-43%, D-57% vs I-36%, D-64%, respectively. This was different than the gene frequencies in White/Hispanic (W/H) patients I-61.5%, D-38.5% vs I-38.6%, D-61.4%, in controls (P < 0.05). In 22 patients with rapid progression (RP) of FSGS to ESRD the genotype distribution was II-18%, ID -64%, and DD-18%. In 25 patients with FSGS who progressed slowly (SP) the genotype was similar (II-32%, ID-48% and DD-20%, P >0.05). With respect to rate of progression, D allele frequency was similar in AA patients (RP 64% vs SP 50%) and W/H patients (RP 36% vs SP 40%). CONCLUSION: Our study reveals no association between the I/D polymorphism of the ACE gene and the presence of and rapidity progression of FSGS.

Adolescent↗
PubMed2003

Prediction of native coronary artery disease progression following PTCA or CABG in the Emory Angioplasty Versus Surgery Trial.

BACKGROUND: The natural history of atherosclerosis progression following revascularization procedures (PTCA or CABG) limits the long-term benefits of these procedures and requires continuation of risk management. MATERIAL/METHODS: Of 392 patients with multivessel disease randomized to an initial strategy of PTCA or CABG in the Emory Angioplasty Versus Surgery Trial (EAST), 298 patients (152 PTCA and 146 CABG) completed 3-year angiographic follow-up. Native coronary artery disease progression was defined as lesions with <50% diameter stenosis (%S) at baseline, measured by QCA, that increased at least 10%S to become >or=50%S during the 3-year follow-up. Major ischemic events (new Q-wave myocardial infarction, a large reversible thallium defect or additional revascularization procedures) attributed to these new lesions were determined based on the ECG ischemic changes and/or the details of the coronary anatomy. RESULTS: Of 298 patients, 53 (18%) (15% of PTCA and 21% of CABG) developed at least one significant new native coronary artery lesion. Of 136 patients with events, 19 (14%) had such events due to progression. In multivariate analysis, native coronary disease progression was independently correlated with hypertension (OR=2.4, p=0.03), ST segment depression =1mm on baseline ETT (OR=2.7, p=0.01), and percent of small LDL particles (LDL IIIa-IVb) (OR=1.2 for every 5% increase, p=0.01). CONCLUSIONS: In EAST, the native CAD progression accounted for one in seven major ischemic episodes over a 3-year follow-up. Patients with metabolic atherogenic risk profiles were more likely to have disease progression. These findings indicate the importance of more aggressive risk factor modification following revascularization.

Angiography↗
PubMedDate not supplied

Imaging-based measures of disease progression in clinical trials of disease-modifying drugs for Alzheimer disease.

The authors review and assess imaging-based strategies for measuring the rate of progression of Alzheimer disease (AD). Such techniques may be useful in addition to the behavioral instruments typically used in these studies and may be more sensitive to treatment-related change. MEDLINE searches obtained relevant published literature. Articles were reviewed with particular attention to assessments of rate of disease progression and the effects of investigational drugs. Authors studied a variety of techniques, including volumetric magnetic resonance imaging, functional MRI, fluorodeoxyglucose positron emission tomography, and several target-specific radiopharmaceuticals. In cross-sectional as well as small longitudinal trials, many of these show promise not only in diagnosis, but also as measures of disease progression. The effects of drugs that provide symptomatic relief on these measures have not been fully characterized. Even less is known about the effects of investigational drugs that may slow disease progression. Several neuroimaging techniques have been studied that could improve the ability of clinical trials to quantify the rate of progression of AD. Clinical trials of investigational drugs would benefit from more systematic validation of image-based outcome measures. Several choices of imaging techniques are available. An understanding of the relationship between a statistically significant effect size in an imaging marker and a clinically significant change in rate of disease progression will require additional studies.

Aged↗
PubMed2003

Correlation of single time-point damage scores with observed progression of radiographic damage during the first 6 years of rheumatoid arthritis.

OBJECTIVE: Aggressive treatment of early rheumatoid arthritis (RA) is recommended to prevent irreversible joint damage. We evaluated the usefulness of single time-point joint radiographs for deciding whether early RA is erosive or nonerosive. METHODS: In an observational study, 179 patients with recent onset of RA symptoms (median 5.1 mo), positive rheumatoid factor, and active polyarthritis had 2 to 8 radiographic observations of hands, wrists, and forefeet during 6 to 60 months of followup. Linear regression lines for all available radiographs were used to determine progression rates of total Sharp score (TSS), erosion score (ES), and joint space narrowing score (JSNS) of each patient. RESULTS: Using the average of 2 readers' scores, intraclass correlation coefficient was 0.97 and smallest detectable difference was 3.07 for ES, 0.93 and 7.52 for JSNS, and 0.90 and 12.71 for TSS. Mean progression rates per year were 1.20 (ES), 0.67 (JSNS), and 1.85 (TSS). Single time-point radiographs taken within 6 months of symptom onset did not correlate with progression rates (r = 0.01 to 0.07); between 7 and 18 months correlations were weak (r = 0.23 to 0.35), but were better for ES between 19 and 72 months (r = 0.60 to 0.81). Among 53 patients (31%) with no progression of TSS, only 10 of them had zero scores at baseline. Among all 630 radiographs with TSS > or = 1, 25% were associated with progression rates < or = 0. CONCLUSION: Erosion scores of single radiographic examinations done > 18 months after onset of RA symptoms correlated with progression rates, but earlier radiographs did not sufficiently predict erosive or nonerosive status to guide disease modifying antirheumatic drug treatment decisions.

Adult↗
PubMedDate not supplied

Association between the A1166C polymorphism of the angiotensin II receptor type 1 and progression of chronic renal insufficiency.

BACKGROUND: In some studies genetic variation in the renin-angiotensin-aldosterone system (RAAS) has been associated with hypertension and rapid progression of renal insufficiency to end-stage renal disease (ESRD). Most of these studies do not take into account covariables influencing progression. We studied retrospectively the role of angiotensinogen (AGT) M235T, angiotensin converting enzyme (ACE) insertion/deletion (I/D), angiotensin II type 1 receptor (AT1R) A1166C, aldosterone syntase (CYP11B2) -344C/T and intron 2 W/C polymorphisms in conjunction with clinical and biochemical covariables on the rate of progression of renal insufficiency in a group of patients with ESRD of various etiologies. METHODS: Genotyping was performed by polymerase chain reaction (PCR) in 104 ESRD patients (62 males and 42 females), aged 64 +/- 14 years (mean +/- SD) with mean initial serum creatinine of 2.6 +/- 1.1 mg/dL and a mean time to reach ESRD of 52 +/- 38 months. RESULTS: The univariate analysis showed that there was a significant difference in the values of the slopes among the AT1R A1166C polymorphism genotypes: AA -4.87 +/- 0.22, AC -5.09 +/- 0.65 and CC -5.52 +/- 0.66 (p<0.05). None of the remainder polymorphisms showed significant association with progression. Stepwise multiple regression analysis including all the clinical, biochemical and genetic variables showed that only systolic blood pressure (SBP), serum PTHi and AT1R genotype were independently associated with the rate of progression, excluding the other variables from the model. CONCLUSIONS: These results indicate that susceptibility to faster progression to ESRD is associated with the AT1R A1166C polymorphism. This association remains significant after adjustment for relevant covariates, highlighting the importance of analyzing genetic risk factors in the context of clinical and biochemical variables.

Aged↗
PubMed2003

Reduced hepatocyte proliferation is the basis of retarded liver tumor progression and liver regeneration in mice lacking N-acetylglucosaminyltransferase III.

Mice lacking N-acetylglucosaminyltransferase III (GlcNAc-TIII) exhibit slightly but significantly retarded liver tumor progression after a single injection of 10 micro g/g diethylnitrosamine (DEN) and continued administration of phenobarbital (PB) in drinking water. A key question is whether the absence of GlcNAc-TIII inhibits cell proliferation or induces apoptosis. Because PB aids tumor progression, we tested whether it diminished the difference in tumor progression between Mgat3(+/+) and Mgat3(Delta/Delta) mice. Here, we show that in the absence of PB, control males developed about twice as many liver tumor nodules as males lacking GlcNAc-TIII. Both the size of liver tumors and liver weights were significantly greater in DEN-treated wild-type or heterozygous mice. Apoptosis assays performed monthly after DEN treatment showed no differences between mutant and wild-type. However, there was a marked retardation in liver regeneration after partial (70%) hepatectomy (PH). Wild-type mice incorporated bromodeoxyuridine in approximately 15% of hepatocyte nuclei at 48 h after PH, whereas mice lacking GlcNAc-TIII had only approximately 5% positive nuclei. This was not because of enhanced apoptosis in mutant mice after PH. Expression of the Mgat3 gene remained undetectable in wild-type liver by Northern analysis after tumor induction or after PH. In addition, transgenic overexpression of GlcNAc-TIII in hepatocytes did not enhance tumor progression in Mgat3(Delta/Delta) mice, and there were no differences in tumor progression or liver regeneration after PH between control and transgenic mice overexpressing GlcNAc-TIII in liver. Therefore, the nonhepatic action of GlcNAc-TIII promotes hepatocyte proliferation after PH, as well as the progression of DEN-induced tumors, providing evidence for a functional role of the bisecting GlcNAc on circulating glycoprotein growth factor(s) that stimulate hepatocyte proliferation.

Acetylglucosamine↗
PubMed1978

Progression of obstructive coronary artery disease 5 to 7 years after aortocoronary bypass surgery.

Changes in the native coronary circulation were evaluated 5 to 7 years (72 +/- 10 months) after aortocoronary bypass surgery in 108 patients; 104 had had previous angiographic controls between 6 and 18 months following surgery. Coronary artery narrowings were graded on a scale of 0 to 6, 0 being normal, grade 1 and 2, < or = 50%; grade 3, 51-75%; grade 4, 76-90%; grade 5, 91-99% narrowing and grade 6 total occlusion. Progression of disease was significant when a preexisting stenosis increased at least 1 grade or a new lesion > 50% developed. Nongrafted vessels were compared to arteries with patent or occluded grafts. During the first year following surgery, the rate of progression was much higher in grafted arteries with patent or occluded grafts than in nongrafted arteries 157 and 53% vs 9.5% respectively, P < 0.001). During the subsequent period of approximately 5 years, however, grafted arteries did not change, whereas the rate of progression in nongrafted arteries increased from 9.5 to 46%. At 5 to 7 years after surgery, grade 1 and 2 (< or = 50%) narrowings progressed slightly more frequently in grafted arteries because of surgically related events. However, for narrowings > 50% and for new lesions, there was no difference in the rate of progression between grafted and nongrafted vessels. In conclusion, the rate of progression of atherosclerosis in nongrafted coronary arteries is important. At 5 to 7 years after surgery, there is little or no difference in the severity of the disease in the proximal segments of grafted and nongrafted coronary arteries.

Coronary Artery Bypass↗
PubMed2004

Patient retention and hand-wrist radiograph progression of rheumatoid arthritis during a 3-year prospective study that prohibited disease modifying antirheumatic drugs.

OBJECTIVE: To quantitate patient retention and radiographic progression rates in serial hand/wrist radiographs of patients with rheumatoid arthritis (RA) who were not being treated with disease modifying antirheumatic drugs (DMARD). METHODS: A total of 1433 RA patients with 1-7 years' disease duration entered a 3-year prospective randomized double-blind clinical trial comparing the nonsteroidal antiinflammatory drugs (NSAID) etodolac (300 or 1000 mg daily) and ibuprofen (2400 mg daily). Standardized hand/wrist radiographs were obtained yearly and at dropout if > 6 months after entry. DMARD were not permitted. Joint erosion, joint space narrowing (JSN), and total scores of 3 readers were averaged. RESULTS: At entry, mean duration of RA was 3.5 years (range 1-7); ages were 21-78 years; patients were 71% female, 84% Caucasian, 67% rheumatoid factor (RF) positive; tender joint count was 29, swollen joint count 22, Westergren erythrocyte sedimentation rate (ESR) 49, and C-reactive protein (CRP) 2.44. There were 824 (57.5%) patients who completed >or= 6 months and had paired radiographs; 46% completed 48 weeks; 31%, 98 weeks; and 19%, 147 weeks. Months between paired radiographs (time in study) averaged 23.1 (range 6-36). Mean progression rates for total, erosion, and JSN scores (5.08, 2.53, and 2.54 units per year, respectively) were significantly associated with time in study, baseline RF, ESR, CRP, swollen joint count, presence of erosions at entry, and with 20% and 50% composite clinical responses. Painful joint count and RA duration were weakly associated only with progression of erosions. Progression rates were not associated with age, sex, corticosteroid use, or prior DMARD use. Patients who completed the 3-year trial had less severe disease activity and radiographic progression than those who dropped out. CONCLUSION: In this 3-year prospective double-blind clinical trial that prohibited DMARD, retention rates (57.5%, 46%, 31%, and 19% at 0.5, 1, 2, and 3 years) were similar to those in the non-DMARD-treated placebo groups of recent published studies. Radiographic progression rates are reported for 824 non-DMARD-treated patients during RA of 1-10 years' duration. This information may be useful as background information in the interpretation of longterm clinical trials that evaluate joint radiographic outcomes.

Adult↗
PubMedDate not supplied

Risk factors for liver fibrosis progression in patients with chronic hepatitis C.

The major hepatological consequence of HCV infection is the progression to cirrhosis and its potential complications. Several factors have been clearly shown to be associated with fibrosis progression rate: duration of infection, age, male sex, consumption of alcohol, HIV coinfection and low CD4 count. As age and duration of infection increases, the risk of fibrosis increases and the impact of treatment (IFN) decreases. In conclusion, fibrosis progression has a progressive acceleration, sex, age and consumption of alcohol are strongly involved in this progression; the possibility to assess with non-aggressive biochemical markers the fibrosis stage will probably allow in the future to identify other factors related to fibrosis progression.

Age Factors↗
PubMedDate not supplied

[Clinical heterogeneity of Alzheimer's disease. Different clinical profiles can predict the progression rate].

INTRODUCTION: Alzheimer's disease (AD) is a degenerative dementia that may disclose different cognitive, behavioral, psychiatric and functional symptoms since onset. These distinct cognitive profiles support the conception of clinical heterogeneity and account for AD's highly variable rate of progression. In spite of strict diagnostic criteria NINCS ADRDA's and DSM IV the clinical certainty is only about 85%. Mayeux define 4 subtypes: a). Benign: mild cognitive and functional impairment without focal signs and late onset behavioral signs, slow progression; b). Myoclonic: usually of presenile onset with severe cognitive deterioration, mutism and early onset myoclonus; c). Extrapyramidal: early onset akineto rigid signs with severe cognitive, behavioral and psychiatric involvement; d). Typical: gradual and progressive cognitive, behavioral and functional impairment. The differentiation of these subtypes will allow us to define discrete patterns of progression, to define prognostic subgroups, and to homogenize them for clinical research and drug trials. DEVELOPMENT: We examined 1000 charts of probable AD patients from the Santojanni Center. We found 42% extrapyramidal, 35% typical, 15% benign and 8% myoclonic. The early onset of parkinsonism and myoclonus predict a rapidly evolving cognitive impairment and a more severe rate of progression with psychiatric disorders and dependency in activities of daily living. (DADL) Patients with low level of education, low cognitive performance at entry as well as those with rapid rate of cognitive deterioration had a faster rate of progression to DADL. CONCLUSION: Delusions, low level of education, extrapyramidal signs and motor hyperactivity but not hallucinations, and anosognosia were the best non cognitive predictors of DADL.

Activities of Daily Living↗
PubMed2004

Predictive value for disease progression of serum thyroglobulin levels measured in the postoperative period and after (131)I ablation therapy in patients with differentiated thyroid cancer.

UNLABELLED: The aim of our study was to evaluate and compare in thyroid cancer patients the predictive value for disease progression of thyroglobulin (Tg) levels measured under thyroid-stimulating hormone (TSH) stimulation, in the postoperative period just before (131)I ablative therapy and at the time of control 6-12 mo later. METHODS: Two-hundred twelve consecutive patients treated for a well-differentiated thyroid carcinoma (184 papillary, 28 follicular) with no initial distant metastases were retrospectively studied. All patients had a total or near-total thyroidectomy followed by ablation with 3.7 GBq (131)I. Tg levels were determined just before ablative therapy (Tg1) and 6-12 mo later (Tg2). Thresholds of 30 and 10 ng/mL were used for Tg1 and Tg2, respectively. Univariate and multivariate analyses were performed to assess the predictive value for disease progression of the 2 Tg determinations. RESULTS: Thirty patients had a Tg1 level > 30 ng/mL. Six to 12 mo later, 30 patients had a Tg2 level > 10 ng/mL, 19 of whom had initially a Tg1 level > 30 ng/mL. Disease progression was reported in 20 patients (9%). Progression-free survival rates were significantly lower in patients with a low Tg1 or Tg2 level but the difference was more important with Tg2. With univariate analysis, 5 variables were significantly associated with disease progression: Tg2, Tg1, node invasion, extrathyroidal extension, and tumor size. With multivariate analysis, only Tg2 (odds ratio [OR] = 16.4; 95% confidence interval [95% CI] = 5.7-47.4; P < 0.001) and node invasion (OR = 2.7; 95% CI = 1.0-7.2; P = 0.04) had an independent prognostic value. When only initial parameters were considered, Tg1 and node invasion were the 2 independent prognostic factors. The OR decreased for Tg1 (OR = 10.1; 95% CI = 4.0-25.7; P < 0.001) but increased for node invasion (OR = 4.4; 95% CI = 1.7-11.2; P = 0.002). CONCLUSION: Among all clinical and tumoral variables, lymph node invasion and serum Tg level are 2 important parameters to define the risk of disease progression. Although Tg2 appears more significant than Tg1, both Tg levels measured under TSH stimulation, in the postoperative period and a few months after ablative therapy, have a predictive value. In clinical practice, patients at risk can be selected as soon as the initial lymph node status and Tg1 level are known.

Adolescent↗
PubMed2004

Expression levels of melanoma inhibitory activity correlate with time to progression in patients with high-grade glioma.

Melanoma inhibitory activity (MIA) is related to disease progression in patients with malignant melanoma and to invasion and metastasis of melanoma in vivo and in vitro. An alternative splice product termed MIA(splice) was described recently. In addition to melanoma, both proteins are expressed in a substantial subset of high-grade gliomas. We hypothesize that expression levels of both proteins correlate with early tumor progression and parameters of disseminated disease in patients with high-grade glioma. We examined the correlation of expression levels of MIA and MIA(splice) with time to progression and morphological and clinical markers of disseminated disease (defined as multifocal occurrence, gliomatosis, invasion or metastasis) in a series of 24 newly-diagnosed human high-grade gliomas. Homogenates of surgical specimens, cell cultures and blood samples were analyzed. Significant levels of MIA and MIA(splice) protein were detected in 71% of homogenates of high-grade glioma, but not in the related blood samples. Patients with early tumor progression had lower expression levels of MIA than patients with late progression, and the expression level of MIA was inversely related to time to progression. In addition, MIA expression correlated with a high fiber content of the extracellular matrix, suggesting a role in dissemination as known from malignant melanoma. Expression levels of MIA in homogenates of surgical specimen directly relate to a more benign clinical prognosis in patients with high-grade glioma. While a mechanistic relation has not yet been verified, factors such as a high fiber content of the extracellular matrix may explain this observation.

Adult↗
PubMed2005

The role of p53 and anaplastic lymphoma kinase genes in the progression of cutaneous CD30(+) lymphoproliferative diseases.

BACKGROUND AND OBJECTIVES: Molecular events that precede transformations from lymphomatoid palulosis (LyP) to mycosis fungoides (MF) or to cutaneous anaplastic large cell lymphoma (ALCL) in the CD 30(+) cutaneous lymphoproliferative diseases (LPDs) are not known. Altered p(53) gene may be responsible since overexpression of the p(53) gene product has been reported in higher, but not in lower grades of cutaneous lymphomas. Expression of the anaplastic lymphoma kinase (ALK) gene product has also been described as an important prognostic indicator in ALCL. ALK positive systemic nodal ALCL are associated with a good prognosis. However, primary cutaneous ALCL that are ALK negative have a better overall survival. The current study was done to see if mutated p(53) gene or ALK reactivity were poor prognostic indicators in those patients with CD 30(+) cutaneous LPD who showed progression of the disease. METHODS: Mutations of the p(53) gene and expression of the ALK gene product were analysed in 36 patients (23 of LyP and 13 of CD30(+) cutaneous ALCL). Follow up data were available up till 5 yr in all patients. RESULTS: Clinical progression or histological transformation in sequential biopsy specimens was found in 9 of 36 patients. Transformation occurred in 5 patients (4 from LyP to ALCL and 1 from MF to ALCL) and clinical progression in 4 patients with ALCL. Mutations of the p(53) gene were found in two biopsy specimens of LyP. ALK gene products were not detected in any of the biopsy specimens of LyP and primary cutaneous ALCL. INTERPRETATION AND CONCLUSION: Although 9 of 36 patients with cutaneous CD30(+) LPDs had progression of their disease, neither mutations of the p(53) gene nor ALK immunoreactivity were found in any of these biopsies. The two cases of LyP that had mutated p(53) gene in their biopsy specimens showed no progression of their disease in the 5 yr follow up period. It appears that these molecular events may not play any significant role in the pathogenesis, progression or transformation of cutaneous CD30(+) LPD.

Anaplastic Lymphoma Kinase↗
PubMed2005

[Clinical predictors of chronic chagasic myocarditis progression].

INTRODUCTION AND OBJECTIVES: Previous prognostic studies of Chagas' disease have focused on mortality associated with end-stage cardiopathy (i.e., heart failure). Our aim was to identify indicators of progression in early-stage Chagas' heart disease. MATERIAL AND METHOD: The study included 856 patients with 3 positive anti-Trypanosoma cruzi test results. Those with heart failure were excluded. Patients were divided into 3 clinical groups: those without heart disease (Group I); those with heart disease but without left ventricular enlargement (Group II); and those with left ventricular enlargement but without heart failure (Group III). The endpoint was progression to a more severe clinical stage or death due to cardiovascular disease. A Cox regression model was used to derive a clinical risk score from clinical, electrocardiographic and echocardiographic variables. RESULTS: At study entry, the patients' mean age was 43.7 years. They were followed up for a mean of 8 years. The following were predictors of heart disease progression: age at entry (HR=1.05; 95% CI, 1.02-1.07; P<.001), left ventricular systolic diameter (HR=1.06; 95% CI, 1.04-1.09; P<.001), intraventricular conduction abnormalities (HR=1.85; 95% CI, 1.02-3.36; P=.04), and sustained ventricular tachycardia (HR=3.97; 95% CI, 1.65-9.58; P=.002). Treatment with benznidazole reduced the risk of progression (HR=0.40; 95% CI, 0.23-0.72; P=.002). The devised clinical risk score was effective in stratifying the likelihood of cardiopathy progression. CONCLUSIONS: Specific clinical indicators and a derived clinical risk score can be used to predict the progression of chronic chagasic myocarditis in patients without heart failure.

Adult↗
PubMed2005

Chronic allograft nephropathy (CAN) in early renal protocol biopsies: does treatment of borderline and subclinical acute rejections prevent development and progression of CAN?

Histological markers of chronic allograft nephropathy (CAN) in early protocol biopsies may ultimately result in deterioration of graft function. The aim of our study was to evaluate risk factors of early CAN histology and to determine whether treatment of borderline and subclinical acute rejections (BR/SAR) at 1-month posttransplant, prevents development and/or progression of CAN at 6-month biopsy. Thirty-five paired kidney allograft biopsies at 1 and 6 months after transplantation were blindly reviewed using Banff'97 criteria. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6-month biopsy (1.83 +/- 1.46 vs 4.66 +/- 2.35; p < 0.01). No CAN was present in 27/70 biopsies (38.6%), 71.4% showed progression and 28.6% were with stable CAN at 6-month biopsy. When compared according to the progression, mean histological index (HI) score (sum of acute/chronic changes) in progressed CAN group (pCAN) increased significantly at 6-month biopsy (5.0 +/- 3.0 vs 9.5 +/- 2.8; p < 0.001). At 1-month biopsy, BR/SAR were found in 68% and 70%, in the pCAN and stable (sCAN) groups, respectively. The percentage of treated BR/SAR in sCAN group was significantly higher (57.1 vs 23.5%; p < 0.05), and the score of acute histological lesions lower (1.08 +/- 0.95 vs 0.35 +/- 0.66; p < 0.01) at 6-month biopsy. In conclusion, 1-month protocol biopsy may be valuable to uncover BR/SAR and the presence of early CAN in stable renal allografts. Progression of CAN at 6-month biopsy in our study was found to be associated with a greater number of untreated BR/SAR at 1-month biopsy. This observation may have important implications in the design of clinical trials aimed to prevent the progression of CAN.

Acute Disease↗
PubMedDate not supplied

Association of cyclooxygenase-2 immunoreactivity with tumor recurrence and disease progression in superficial urothelial bladder cancer.

AIMS AND BACKGROUND: The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. METHODS: In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. RESULTS: COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. CONCLUSIONS: COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.

Adult↗
PubMed2006

The effect of stromal cell-derived factor 1 (SDF1/CXCL12) genetic polymorphism on HIV-1 disease progression.

The human immunodeficiency virus type 1 (HIV-1) epidemic is increasing in Brazil, and little information has been reported about the genetic host factors related to HIV-1 infection in the Brazilian population. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor 1 (SDF1/CXCL12) gene has been related either to resistance to HIV-1 infection and delayed progression to AIDS or to rapid disease progression and death. A longitudinal study was conducted to evaluate the association of the SDF1 polymorphism and the progression of HIV-1 infection in 161 asymptomatic patients infected with HIV-1 (ASYMPT) and 617 patients with AIDS (SYMPT) from Londrina and the surrounding region, southern Brazil. The endpoints used were the development of AIDS, death, and the slopes of the CD4+ T cell counts and HIV-1 RNA plasma levels. Among the 161 ASYMPT patients, all of the 7 patients (4.3%) homozygous for the mutation remained asymptomatic (p=0.1906); 6 of them had not initiated antiretroviral therapy. Among the 617 patients with AIDS, 40 (6.5%) progressed to death. Of these, 33/388 (8.5%) did not have the SDF1-3'A allele, 6/196 (3.1%) were heterozygous and 1/33 (3.0%) was homozygous for the SDF1-3'A allele (p=0.029). The SDF1 genotypes were not associated with the surrogate markers of HIV-1 disease progression such as the CD4+ T cell decline and plasma HIV-1 RNA levels. The results observed in this study support the hypothesis that the mutation of SDF1-3'A could have a possible late-stage protective effect on HIV-1 disease progression in the Brazilian population.

Adolescent↗
PubMed1990

Lipids and the progression of renal disease.

The mechanisms involved in progressive renal injury have been the subject of intense investigation during the past decade. Hemodynamic and nonhemodynamic factors have been implicated in progressive renal damage, including abnormalities of lipid metabolism. The idea that abnormal lipid metabolism may be important in the development and progression of renal injury has intrigued investigators for over 100 years. Studies in models of progressive renal insufficiency have demonstrated that abnormalities in lipid metabolism may participate in the development of glomerular and tubular alterations leading to nephron destruction. This concept has been supported by the demonstration that pharmacologic intervention with different classes of lipid-lowering agents is associated with a reduction in the extent and severity of glomerular and tubular injury. The mechanism whereby hyperlipidemia contributes to renal injury are at present unknown. Morphologically, marked expansion of the mesangial matrix, prior to the development of glomerulosclerosis, suggests the possibility that altered production of mesangial matrix proteins may contribute to glomerular injury. Increased numbers of glomerular monocyte-derived macrophages and foam cells in hyperlipidemic rats have been described. The role that these cells may play in the development of proteinuria and glomerular damage has not been clarified. Biochemically, increased renal tissue content of cholesterol esters and reduced concentrations of essential fatty acids have been described. Whether these changes in tissue lipids contribute to renal injury is also unknown. In addition, persistent hyperlipidemia, particularly hypercholesterolemia, may also lead to glomerular hypertension, possibly through alterations in eicosanoid metabolism. Finally, preliminary data have suggested that oxidized lipoproteins may contribute to the hemodynamic and structural changes described in lipid-induced renal injury. The roles of altered platelet function and other lipid-derived inflammatory mediators are yet to be explored. In conclusion, experimental studies have indicated that hyperlipidemia is an important modulator of nephron damage and may contribute to the progression of renal disease. Whether alterations in lipid metabolism participate in progressive renal insufficiency in humans remains to be determined.

Animals↗