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PubMed2006

Addition of the antioxidant probucol to angiotensin II type I receptor antagonist arrests progressive mesangioproliferative glomerulonephritis in the rat.

Angiotensin II (Ang II) and reactive oxidative species (ROS) that are produced by NADPH oxidase have been implicated in the progression of glomerulonephritis (GN). This study examined the effect of simultaneously interrupting Ang II and ROS with an Ang II receptor blocker (ARB), candesartan, and a free radical scavenger, probucol, in a model of progressive mesangioproliferative GN induced by the injection of anti-Thy-1 antibody into uninephrectomized rats. Nephritic rats were divided into four groups and given daily oral doses of the following: Vehicle, 1% probucol diet, 70 mg/L candesartan in drinking water, and probucol plus candesartan. These treatments lasted until day 56. Vehicle-treated nephritic rats developed progressively elevated proteinuria and glomerulosclerosis. Candesartan kept proteinuria significantly lower than vehicle or probucol. The addition of probucol to candesartan normalized urinary protein excretion. Increases in BP in nephritic rats were lowered by these treatments, except with probucol. It is interesting that both glomerular cell number and glomerulosclerosis were significantly decreased by candesartan and normalized by the addition of probucol. Immunohistochemical studies for TGF-beta1, collagen type I, and fibronectin revealed that the combined treatment abolished glomerular fibrotic findings compared with candesartan. In addition, glomerular expression of NADPH oxidase components and superoxide production suggested that the combined treatment completely eliminated NADPH oxidase-associated ROS production. In conclusion, our study provides the first evidence that the antioxidant probucol, when added to an Ang II receptor blockade, fully arrests proteinuria and disease progression in GN. Furthermore, the data suggest that NADPH oxidase-associated ROS production may play a pivotal role in the progression of GN. The combination of probucol and candesartan may represent a novel route of therapy for patients with progressive GN.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2001

Relationship between crevicular aspartate aminotransferase levels and periodontal disease progression.

BACKGROUND: Aspartate aminotransferase (AST), an enzyme released from necrotic cells, has been identified in gingival crevicular fluid (GCF), and elevated levels are associated with periodontal tissue destruction. The aim of this study was to examine the relationship between elevated GCF levels of AST and periodontal disease progression. METHODS: Over a 12-month period, 8 to 10 interproximal sites in 41 periodontitis subjects (PS) and 15 healthy subjects (HS) were monitored. Clinical measurements included relative attachment level (RAL), probing depth, and bleeding on probing (BOP). Semiquantitative levels of GCF AST (< 800 microIU, > or = 800 microIU, and > or = 1,200 microIU) were determined using a chairside assay. At the 6- and 12-month visits, scaling and root planing and prophylaxis were performed in the PS and HS, respectively. Sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were calculated for 2 diagnostic criteria (AST > or = 800 microIU, AST > or = 1,200 microIU) utilizing 4 thresholds of disease progression as determined by 2 methods (absolute change in relative attachment level and cumulative sum [CUSUM]). RESULTS: The percentage of sites exhibiting AST > or = 800 microIU, AST > or = 1,200 microIU, and BOP in the PS was significantly (P<0.02) lower at 6 and 12 months compared to baseline. The use of crevicular AST activity to monitor periodontal disease progression was associated with many false-positive results. Overall, low specificities, PPV, and odds ratios were demonstrated by the assay when using 2 diagnostic criteria and 4 thresholds of disease progression. The high NPV suggest that a negative AST test result was indicative of a periodontally stable site. CONCLUSIONS: These results demonstrate that elevated levels of AST were present at sites that did not subsequently exhibit disease progression. The high prevalence of AST-positive sites due to gingival inflammation diminished the test's ability to discriminate between progressive and stable, but inflamed, sites.

Adult↗
PubMed1995

Acute spondylolytic spondylolisthesis. Risk of progression and neurological complications.

Acute spondylolytic spondylolisthesis was diagnosed after major trauma in five patients. The level of injury was between the third and fourth lumbar vertebrae in one patient and between the fifth lumbar and first sacral vertebrae in four. The initial spondylolisthesis was grade I in four patients and grade III in one. Four of the patients were initially managed non-operatively. The deformity did not progress in a five-year-old boy with grade-I spondylolisthesis who had been managed with immobilization in a body cast. The deformity progressed in two of the adolescents who had been managed non-operatively; the progression was from grade I to grade III in one of these patients and from grade III to grade V (spondyloptosis) in the other, in whom a cauda equina syndrome also developed. The latter patient was subsequently managed with posterior reduction and arthrodesis followed by an anterior arthrodesis, and the neurological deficits resolved. The deformity also progressed, from grade I to grade II over three years, in a fifty-seven-year-old woman who had been managed non-operatively. One patient who had a grade-I deformity was managed with immediate operative stabilization followed by immobilization in a thoracolumbosacral orthosis; the deformity did not progress. Although minor or repetitive trauma is often associated with spondylolysis, high-energy trauma may produce a more severe form of spondylolysis with spondylolisthesis. These deformities are more unstable, with instability similar to that of a fracture-dislocation, and they have a greater propensity to progress than the usual form of spondylolytic spondylolisthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed2004

Interferon-beta-1b: a review of its use in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Age Factors↗
PubMed2004

Spotlight on Interferon-beta-1b in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomized, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalizations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomized trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomized, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomized trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralizing anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Drug Administration Schedule↗
PubMed1997

Compensated cirrhosis due to viral hepatitis: using MR imaging to predict clinical progression.

OBJECTIVE: The goal of our study was to determine the relative value of multiple MR features in predicting clinical progression of disease in patients with compensated cirrhosis. MATERIALS AND METHODS: The MR examinations of 23 patients with compensated cirrhosis (Child A) were retrospectively reviewed independently by two radiologists and correlated with clinical progression after follow-up of all patients for more than 12 months each (12-87 months: average, 39 months) by the same experienced hepatologist. Clinical progression was defined as an increase of the Child grade or the Pugh score by at least two points (5- to 15-point scale). In the initial MR study of each patient, the following MR findings were assessed by each radiologist independently: volume indexes of the spleen and each segment of the liver (based on three-axis measurements), nodular surface, regenerative nodules, ascites, iron or fat deposition, and varices or collaterals. RESULTS: The volume index of the spleen was the most accurate predictor of clinical progression (p = .001), the next most accurate was the number of sites of varices or collaterals (p = .002), and the third most accurate was the ratio of caudate lobe to right lobe volume index (p = .02). Other MR findings failed to correlate with clinical progression. CONCLUSION: As revealed on MR imaging, the volume index of the spleen, the severity of varices, and the volume index ratio of caudate lobe to right lobe can be used to help predict clinical progression of disease in patients with compensated cirrhosis.

Adult↗
PubMed1996

Determinants of progression of microalbuminuria in adolescents with IDDM.

OBJECTIVE: To evaluate the significance of microalbuminuria in adolescents with IDDM and to study the relative importance of blood pressure (BP), metabolic control, and albumin excretion rate (AER) on progression of microalbuminuria. RESEARCH DESIGN AND METHODS: A cohort of 155/156 children and adolescents followed from onset up to 18.3 years of IDDM participated. In a previous follow-up in July 1991 (up to 15 years of duration), 17 patients had developed persistent microalbuminuria (> or = 20 micrograms/min). In these adolescents, we analyzed whether microalbuminuria had progressed (in mean > or = 5% per year), had remained unchanged, or had normalized (< 20 micrograms/min) after another 3 years. The predictive values of mean HbA1c, diastolic blood pressure (dBP), systolic blood pressure (sBP), overnight AER, sex, age, and duration of diabetes for the progression of microalbuminuria were determined using multiple regression modeling. RESULTS: Seven of 17 patients with microalbuminuria in July 1991 had normalized, 6 of 17 patients had progressed, and 4 of 17 patients had remained unchanged after 3 years. Progressors had higher mean HbA1c during the first 5 years of IDDM and higher mean sBP in 1991 than nonprogressors. Patients with normalized microalbuminuria all had AER < 30 micrograms/min in 1991, were younger at onset of microalbuminuria, had lower mean HbA1c, and had lower dBP before normalized AER than nonregressors at the same duration of microalbuminuria. In multivariate analysis, independent significant predictors for progression were first 5-year mean HbA1c, mean AER, and mean sBP in 1991 (R2 = 0.76, P = 0.001). CONCLUSIONS: Progression of microalbuminuria in adolescents with IDDM is predicted by early sustained hyperglycemia, later elevated sBP, and increased AER per se. Microalbuminuria is frequently normalized in adolescents, and this is associated with better prevailing metabolic control, younger age, and lower dBP.

Adolescent↗
PubMed1997

Transient impaired glucose tolerance in South African Indians does not carry a risk for progression to NIDDM.

OBJECTIVE: To evaluate the significance of transient impaired glucose tolerance (IGT) in terms of the risk of progression to NIDDM and the serum insulin response during oral glucose tolerance test (OGTT) in a prospective study on the natural history of IGT in South African Indians. RESEARCH DESIGN AND METHODS: This is a report on 87 subjects who formed part of a 4-year prospective study in 128 subjects classified with IGT at baseline (year 0) using World Health Organization criteria for glucose tolerance. Subjects were reexamined at years 1 and 4. At year 1, based on OGTT results, the subjects were divided into three groups: transient IGT (normal glucose tolerance [trIGT], n = 40), persistent IGT (pIGT, n = 47), and diabetes (n = 41). Analysis was performed on the 87 subjects who were classified as IGT at year 0, but who had not progressed to NIDDM by year 1 of the study At baseline (year 0), a modified OGTT was performed; between years 1 and 4, the OGTT included timed midtest samples for plasma glucose and serum insulin. Analysis of predictive factors for progression to diabetes or reversion to normal glucose tolerance was undertaken using year 0 as baseline. RESULTS: By year 4, 72 subjects (82.8%) completed the study Of the 32 subjects in the trIGT group, none (0%) had progressed to NIDDM, 11 (34.4%) had reverted to IGT (N-IGT), and 21 (65.6%) had persisted with normal glucose tolerance (N-N); of the 40 subjects in the pIGT group, 16 (40%) had progressed to NIDDM (IGT-D), 17 (42.5%) had persisted with IGT (IGT-IGT), and 7 (17.5%) had reverted to normal glucose tolerance (IGT-N). Significant predictive factors for reversion to normal glucose tolerance included absence of obesity (P = 0.0131, odds ratio [OR] 4.2, 95% CI 1.4-13.1) and 2-h plasma glucose level (P = 0.027, OR 2.4, 95% CI 1.11-5.13) at baseline (year 0). Intergroup (cross-sectional) analysis showed that the serum insulin response was higher in the pIGT than in the trIGT subgroup (fasting serum insulin: IGT-N vs. N-IGT and N-N, 16.9 +/- 1.9 vs. 6.8 +/- 2.1 and 6.1 +/- 2.4 microU/ml, respectively, P < 0.001; 2-h postload serum insulin: IGT-IGT vs. N-IGT, 116.8 +/- 2.2 vs. 60.3 +/- 1.7 microU/ml, P < 0.05). By contrast, the insulinogenic index was higher in the trIGT subgroups both at year 1 (90-min: N-N vs. IGT-D, 48.9 +/- 3.9 vs. 14.1 +/- 2.5; P < 0.05) and at year 4 (N-N vs. remaining four subgroups, P < 0.01 at 60 min and 90 min). Intragroup (prospective) comparisons showed that in the N-IGT subgroup, the mean 2-h insulinogenic index was lower at year 4 than at year 1 (19.9 +/- 1.7 vs. 66.0 +/- 2.7; P < 0.05). CONCLUSIONS: In this 4-year prospective study in South African Indians, transient IGT carries no risk of progression to NIDDM. The significant predictive factors for reversion to normal glucose tolerance include lower baseline obesity prevalence and 2-h postload plasma glucose level. Moreover, in this group, beta-cell secretory function appeared to deteriorate with worsening of glucose tolerance.

Adult↗
PubMed1998

Predictors of progression from normoalbuminuria to microalbuminuria in NIDDM.

OBJECTIVE: Our objective was to establish the clinical, genetic, metabolic, and immunologic risk factors for the progression of the albumin excretion rate (AER) in normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS: We recruited 108 NIDDM patients with normal AER after a diabetes duration of 9 years to participate in a prospective 9-year follow-up. In addition to conventional clinical and metabolic variables, we assessed microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary heart disease, peripheral vascular disease) diabetic complications, genetic markers (HLA genotypes), and organ-specific autoimmune markers, including islet cell antibodies. Multiple logistic regression was used to determine independent predictors of progression of AER. RESULTS: A total of 21 patients (19%) died during the follow-up. There was an overrepresentation of men (61 vs. 39%; P = 0.044) and smokers (55 vs. 27%; P = 0.01) in patients who progressed to micro- or macroalbuminuria versus those who did not progress. In addition, progressors had higher fasting plasma glucose (P = 0.002) and HbA1 (P = 0.0002) concentrations at baseline than did nonprogressors. Neuropathy was more often seen in progressors than in nonprogressors at baseline (53 vs. 16%; P = 0.0004). Frequency of HLA genotypes and autoimmune markers did not differ between progressors and nonprogressors. In a multiple logistic regression analysis, HbA1 (P = 0.0005) and a history of smoking (P = 0.011) were independent predictors of progression of AER. CONCLUSIONS: This study reemphasizes the importance of poor glycemic control and smoking as independent risk factors for progression of AER. Furthermore, development of micro- or macroalbuminuria in NIDDM was associated with neuropathy and male sex.

Adult↗
PubMed1999

Progression of retinopathy after improved metabolic control in type 2 diabetic patients. Relation to IGF-1 and hemostatic variables.

OBJECTIVE: To determine the impact of improved glycemic control on the development and progression of retinopathy after the institution of insulin therapy in patients with type 2 diabetes and to assess the relation to IGF-1 and hemostatic variables. RESEARCH DESIGN AND METHODS: In a prospective observational study, 45 type 2 diabetic patients were examined at baseline and 1, 3, 6, 12, and 24 months after change to insulin therapy. Retinopathy was graded on fundus photographs using the Wisconsin scale; HbA1c, IGF-1, and hemostatic variables were measured. RESULTS: During the observation period of 2 years, 23 patients progressed in the retinopathy scale; 8 progressed > or = 3 levels. After 2 years of insulin treatment, HbA1c and IGF-1 were significantly lower than at baseline, whereas the hemostatic variables had not changed significantly. Progression of retinopathy > or = 3 levels was related to the degree of HbA1c reduction, the duration of diabetes, a higher prothrombin fragment 1 + 2 levels (F1 + 2), but not to other hemostatic variables or IGF-1. The relative risk for progression > or = 3 levels was 2.6 when HbA1c had been reduced > or = 3 percent units (95% CI 1.1-6.1). CONCLUSIONS: The magnitude of improvement of HbA1c by the institution of insulin treatment over a 2-year period may be associated with progression of retinopathy in patients with type 2 diabetes.

Diabetes Mellitus, Type 2↗
PubMed2005

Continuous infusion propofol general anesthesia for dental treatment in patients with progressive muscular dystrophy.

Progressive muscular dystrophy may produce abnormal reactions to several drugs. There is no consensus of opinion regarding the continuous infusion of propofol in patients with progressive muscular dystrophy. We successfully treated 2 patients with progressive muscular dystrophy who were anesthetized with a continuous infusion of propofol. In case 1, a 19-year-old, 59-kg man with Becker muscular dystrophy and mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained by a continuous infusion of 6-10 mg/kg propofol per hour and an inhalational mixture of 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. In case 2, a 5-year-old, 11-kg boy with Fukuyama type congenital muscular dystrophy and slight mental retardation was scheduled for dental treatment under general anesthesia. General anesthesia was maintained with a continuous infusion of 6-12 mg/kg propofol per hour and an inhalational mixture of 0.5-1.5% sevoflurane in 67% nitrous oxide and 33% oxygen. No complications were observed during or after the operation. It is speculated that a continuous infusion of propofol in progressive muscular dystrophy does not cause malignant hyperthermia because serum levels of creatine phosphokinase and myoglobin decreased after our anesthetic management. Furthermore, our observations suggest that sevoflurane may have some advantages in patients with progressive type muscular dystrophies other than Duchenne muscular dystrophy and Becker muscular dystrophy. In conclusion, our cases suggest that a continuous infusion of propofol for the patients with progressive muscular dystrophy is a safe component of our anesthetic strategy.

Adult↗
PubMed1996

The progression of myopia in school age children: data from the Columbia Medical Plan.

The purpose of this study was to characterize the clinical course of myopia in a selected pediatric population. The computerized records of a health maintenance organization provided longitudinal data on 501 children aged 5 to 15 years. We examined the influence of age at diagnosis, gender, race, and initial refraction on progression of myopia. Mean follow-up was 34 months, with 75% of children having follow-up longer than 16 months. The mean rate of myopic progression was greater for children whose myopia was diagnosed at a younger age (5-7 years, -0.56 diopters/year versus 11-15 years, -0.28 diopters/year; p < 0.0001). Children with more than one diopter of myopia at first diagnosis progressed faster than children with less than or equal to one diopter of myopia (mean rate -0.48 diopter/year versus -0.41 diopter/year; p = 0.05). Cumulative event rate curves suggest a gender effect in the prepuberty years of 8 to 10, with myopia progressing faster in girls than boys (p = 0.003). Progression of myopia did not differ between white and non-white children. More rapidly progression of myopia is associated with younger age at initial diagnosis and greater severity of initial myopic refraction.

Adolescent↗
PubMed1995

Clinical course and outcome of patients with Hodgkin's disease who progress after autologous transplantation.

Twenty-six of fifty-eight patients undergoing autologous bone marrow transplantation (autoBMT) or peripheral stem cell transplantation (PSCT) for Hodgkin's disease had progression of lymphoma (Hodgkin's or non-Hodgkin's) during the course of their follow-up. The majority of progressions, 81% (21/26), occurred within the first year of transplant; 12% (3/26) occurred at three years or more. Three patients developed a non-Hodgkin's lymphoma; all B-cell tumors primarily involving the gastrointestinal tract. The majority of patients (23/26) received at least one therapy after progression and 65% (17/26) of patients received multiple therapies. One patient who received a second BMT is alive without evidence of disease at 49 months following the second autologous BMT. The median survival for the entire group is 11 months. Forty-six percent (12/26) of patients survived more than one year and twenty-three percent (6/26) survived more than two years after disease progression. Post-progression survival is significantly related to time to progression.

Adolescent↗
PubMed1996

Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma.

Chronic lymphocytic leukemia (CLL) and immunocytoma (IC) are remarkably heterogeneous with regard to their clinical course. The current staging systems can distinguish prognostic subgroups, but do not seem to predict the risk of disease progression of an individual patient with sufficient accuracy. Given the increase of treatment options for CLL and IC, additional parameters are needed to decide which patients may benefit from early or intensified treatment. It has been shown that two biochemical markers, serum beta 2-microglobulin (s-beta 2M) and serum thymidine kinase (s-TK), might identify CLL and IC patients at high risk of disease progression. Therefore, the prognostic value of these two serum parameters was compared with a panel of several established prognostic factors in a prospective clinical trial. 113 patients with CLL and 41 patients with IC (mean age +/- SD 63.9 +/- 10.7 years) were included. The following parameters were determined: histopathological diagnosis (IC vs. CLL), age, sex, performance status (Karnofsky index), B symptoms, peripheral blood lymphocyte count, platelet count, blood hemoglobin, serum lactate dehydrogenase (s-LDH), s-beta 2M, s-TK, serum creatinine, number of lymph node areas involved, prior therapy, and the time from diagnosis to inclusion in the study. Univariate analyses showed that nine parameters (Karnofsky index, peripheral blood lymphocytosis, platelet count, blood hemoglobin, lymph node areas involved, pretreatment, s-LDH, s-beta 2M, and s-TK) significantly predicted progression-free survival. In a Cox regression model, only four of these parameters provided independent prognostic information on progression-free survival: 1. s-beta 2M, 2. Karnofsky index, 3. platelet count, and 4. s-TK. The results show that s-beta 2M and s-TK independently predict progression-free survival in patients with CLL and IC, and suggest that these prognostic factors may allow an improved prediction of progression-free survival, particularly in early disease stages.

Biomarkers, Tumor↗
PubMed1997

Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas.

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 +/- 6% at 2 years and 68 +/- 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 +/- 11% vs. 75 +/- 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 +/- 7% compared with a rate of 39 +/- 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

Adolescent↗
PubMedDate not supplied

Progressive keratectasia after laser in situ keratomileusis.

PURPOSE: We describe ten patients who developed progressive keratectasia following laser in situ keratomileusis (LASIK) and identify possible factors that may lead to ectasia. METHODS: In this retrospective study, we reviewed the files of 3,634 patients (6941 eyes) who had LASIK between March 2000 and April 2003. Ten patients (14 eyes, 0.2%) developed progressive keratectasia. We also evaluated consequent therapeutic measures and final visual status of these patients. RESULTS: Patients were examined at a mean 24.9 +/- 8.1 months after LASIK. Ectasia developed within a mean 14 +/- 0.3 months after surgery. At baseline, mean keratometric power was 44.7 +/- 2.30 D, mean corneal thickness was 516 +/- 18.9 microm, and mean attempted correction was -10.85 +/- 3.20 D. We found a statistically significant correlation between residual stromal thickness, attempted correction, and occurrence of progressive keratectasia. We also found that preexisting abnormal corneal topography was a risk factor for progressive keratectasia. Ultimately, most patients had reasonable visual acuity after penetrating keratoplasty. CONCLUSION: Progressive keratectasia is a vision threatening complication of LASIK that may occur in previously healthy or diseased eyes. The most important risk factors are residual stromal thickness and preexisting abnormal corneal topography. Penetrating keratoplasty may be a reasonable therapeutic measure for severe cases of progressive keratectasia.

Adult↗
PubMed1998

High level of lipoprotein(a) is a strong predictor for progression of coronary artery disease.

Elevated levels of serum lipoprotein(a) [Lp(a)] are reported to be associated with risk of atherosclerosis and thrombosis. Little is known about the influence of Lp(a) on the progression of coronary artery disease. We evaluated the association of serum Lp(a) and the long-term changes of angiographic severity in patients who underwent repeated coronary angiography at intervals of more than 2 years. We evaluated 70 patients, and divided them into 3 groups by angiographic findings. Median Lp(a) concentration was significantly higher in the progression group (N=36) than in the no-change group (N=23) or the regression group (N=11) (32.4 vs 22, 19.3 mg/dl, p<0.05). Furthermore, the progression group had more patients whose Lp(a) levels were greater than 30 mg/dl (p=0.006), while in the regression group all patients were under 30 mg/dl. Stepwise logistic regression analysis for progression of lesions showed that Lp(a) > or =30 mg/dl remained significant, giving an estimated odds ratio (OR) of 2.46 (p= 0.005). In the subgroup analysis, OR in patients with mild lesions was reduced to 2.05 (p<0.05) while in patients with severe lesions OR was increased to 3.39 (p=0.003). The serum Lp(a) level has a close correlation with angiographic progression, and may be an important predictor for progression.

Aged↗
PubMedDate not supplied

Effect of regular exercise on the radiographic progression of foot osteoarthritis.

Among the elderly, osteoarthritis often causes chronic pain and disability. Although research has addressed the association between exercise and osteoarthritis, few studies have examined the effect of exercise on the radiographic progression of osteoarthritis. We investigated the relationship between ongoing exercise and radiographic progression of foot osteoarthritis. The first metatarsophalangeal and medial cuneiform-first tarsometatarsal joints were assessed. Joint-specific osteoarthritis radiographic progression scores were determined using four assessments: joint space narrowing, osteophytes, sclerosis, and a composite score. This cohort study included a subset of 221 men and women aged 40 to 91 years participating in a community-based osteoarthritis study. Adjusted risk estimates (95% confidence intervals) summarizing the relationship between ongoing exercise and radiographic progression in the first metatarsophalangeal joint ranged from 0.34 (0.11-0.99) for osteophytes to 0.66 (0.23-1.92) for sclerosis; because only eight individuals experienced medial cuneiform-first tarsometatarsal joint progression, these estimates were less stable, ranging from 2.41 (0.49-11.83) for composite to 4.29 (0.11-166.52) for osteophytes. Overall, our findings do not suggest that regular exercise is a risk factor for foot osteoarthritis progression. Future replication studies are warranted to confirm these findings.

Aged↗