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PubMed2004

Positive proximal (bladder neck) margin at radical prostatectomy confers greater risk of biochemical progression.

OBJECTIVES: To identify the prognostic significance of positive bladder neck margin as the sole positive margin after radical retropubic prostatectomy for treatment of prostate cancer. METHODS: We retrospectively analyzed the data from patients who underwent radical retropubic prostatectomy at Johns Hopkins Hospital between 1984 and 2001. Of 164 patients with positive margins, 38 had a positive margin only at the bladder neck margin and 126 had a positive margin at one or more locations separate from the bladder neck margin. RESULTS: Kaplan-Meier analyses showed that patients with a positive bladder neck margin had a greater biochemical progression risk than patients with positive margins at one or more locations other than the bladder neck margin. The 5-year actuarial risk of progression in men with positive and negative bladder neck margins was 69.8% and 33.0%, respectively. A positive bladder neck margin was statistically an independently significant predictor of progression (P = 0.001), along with the prostatectomy Gleason score (P = 0.0001) in the multivariate analysis. The hazard ratio for predicting progression for postoperative Gleason score and bladder neck positivity was 2.1 and 2.5, respectively. Serum prostate-specific antigen values, clinical stage, age, and the percentage of tumor at the bladder neck margin were not predictors of progression in either univariate or multivariate analysis. CONCLUSIONS: Patients with a positive bladder neck margin as the sole positive margin at radical retropubic prostatectomy have a greater risk of biochemical progression than patients with one or more positive margins at other locations, although not as adverse as the risk reported for those with Stage T4 disease.

Adenocarcinoma↗
PubMed2005

Biopsy of men with PSA level of 2.6 to 4.0 ng/mL associated with favorable pathologic features and PSA progression rate: a preliminary analysis.

OBJECTIVES: To compare the pathologic outcomes and prostate-specific antigen (PSA) progression rates of patients who underwent radical prostatectomy because of prostate cancers and whose cancer was detected at a PSA level of 2.6 to 4.0 ng/mL versus those with cancer detected after the PSA level rose to greater than 4.0 ng/mL. Some studies have suggested that clinically significant prostate cancer is detected more frequently in an organ-confined stage with a PSA level between 2.6 and 4.0 ng/mL than with a PSA level greater than 4 ng/mL. However, it is uncertain whether this will affect clinical outcomes. METHODS: From 1991 to 2001, 20,788 men enrolled in a prostate cancer screening study had an initial PSA level of less than 2.6 ng/mL. Of these patients, 523 had a PSA level that rose to greater than 2.5 ng/mL and had prostate cancer detected. Of the 297 patients who subsequently underwent radical prostatectomy, 223 had a preoperative PSA level of 2.6 to 4.0 ng/mL and 74 had a preoperative PSA level greater than 4.0 ng/mL. The median follow-up was 4 years. The pathologic stage, mean tumor volume, Gleason score, possibly insignificant cancer rate, possibly rapidly progressive cancer rate, and PSA progression rate were compared between the two groups. RESULTS: The patients with a preoperative PSA level between 2.6 and 4.0 ng/mL had more favorable pathologic outcomes in terms of cancer volume, pathologic stage, and possibly rapidly progressive cancer rate. The possibly insignificant cancer rates were not different between the groups. A trend was noted for patients with a preoperative PSA level between 2.6 and 4.0 ng/mL to have a lower PSA progression rate. CONCLUSIONS: Biopsy in men with PSA levels between 2.6 and 4.0 ng/mL may detect clinically significant prostate cancer more frequently at an organ-confined stage, with a lower PSA progression rate. Additional study in a larger population with longer follow-up is needed to confirm this trend.

Adult↗
PubMed1996

Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study.

PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

Anticholesteremic Agents↗
PubMed2001

Risk factors for progression of visual field abnormalities in normal-tension glaucoma.

PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.

Aged↗
PubMed2003

Incidence and progression of cataract in the Melbourne Visual Impairment Project.

PURPOSE: To determine the 5-year incidence and progression of cataract and cataract surgery in the Melbourne Visual Impairment Project. DESIGN: Prospective cohort study. methods: Demographic information including race, sex, age, and education level was collected at baseline. Cortical cataract was defined as 4/16 or greater opacity; progression was defined as a more than 2/16 increase. Nuclear cataract was defined as Wilmer standard grade 2 or higher; progression was defined as more than 0.5 increase. Posterior subcapsular (PSC) cataract was defined as opacity 1 mm(2) or greater; progression was defined as greater than 1 mm(2) increase. results: Of the 3040 participants eligible to attend follow-up examinations, 2594 (85% of those eligible) participated. The mean age of participants at follow-up was 62.5 years, and 55% were female. The percentage of patients who had at least one lens extracted over 5 years increased from 0.5% of those aged 40 to 49 years at baseline to 35.7% of those aged 80 years or more at baseline. The overall incidence of the three types of cataract was as follows: cortical 7.7% (95% confidence limits [CL] = 5.8-9.8), nuclear 16.4% (95% CL = 12.1-20.8), and PSC 7% (95% CL = 5.3-8.7). The overall progression of cataract was cortical 14.3% (95% CL = 10.2-18.3), nuclear 19.3% (95% CL = 15.9-22.7), and PSC 20% (95% CL = 8.7-31.1). The incidence and progression rates increased significantly by age, but the rates were not significantly different by sex. CONCLUSION: These cataract incidence data confirm the public health importance of cataract in Australia. The data also support the need to plan both primary prevention program and adequate surgical services to meet the anticipated increase in demand with the aging population.

Adult↗
PubMed2003

Rate of progression of glaucoma correlates with retrobulbar circulation and intraocular pressure.

PURPOSE: To evaluate the correlation between progression rate of glaucomatous damage and retrobulbar blood flow in an institutional setting. DESIGN: Retrospective, observational case series. METHODS: Twenty open-angle glaucoma patients with at least five visual field examinations and progressive damage in at least one eye were included in the study. Mean +/- standard deviation follow-up time was 4.3 +/- 1.6 years. As an indicator of progression rate of visual field damage, the angle to a horizontal line of the slope of the regression line of the visual field index mean defect over time was calculated for one randomly selected eye per patient. The association between this angle and intraocular pressure, as well as retrobulbar color Doppler imaging measurements obtained at the beginning of the observation period, was analyzed by a multiple linear regression analysis in a stepwise forward approach. RESULTS: With a faster rate in progression of glaucomatous damage, a lower baseline end diastolic blood flow velocity in the central retinal artery (partial r = -.63; P <.0037) and a higher baseline intraocular pressure (partial r =.59; P <.0078) were noted (multiple r =.69; P <.0043). Rate of progression was not related to the extent of preexisting visual field damage. CONCLUSIONS: Independent of the extent of glaucomatous damage and intraocular pressure, the progression rate of glaucomatous visual field damage statistically correlates with retrobulbar hemodynamic variables.

Antihypertensive Agents↗
PubMed1995

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

PURPOSE: A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. METHODS: Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. RESULTS: The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). CONCLUSION: Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

AIDS-Related Opportunistic Infections↗
PubMed1995

Progression of nuclear sclerosis and long-term visual results of vitrectomy with transforming growth factor beta-2 for macular holes.

PURPOSE: We studied the progression of cataracts and visual acuity up to 36 months after vitrectomy and instillation of transforming growth factor beta-2 for treatment of full-thickness macular holes. METHODS: Sixty-four eyes with idiopathic and two with traumatic macular holes in this prospective consecutive series were divided into the following two groups: 56 phakic eyes were treated with 70, 330, or 1,330 ng of transforming growth factor beta-2 to study the progression of cataracts, and 31 phakic or pseudophakic eyes were treated with 1,330 ng of transforming growth factor beta-2 to study the long-term visual acuity after macular hole surgery. RESULTS: Eyes in the cataract progression study had a mean preoperative nuclear sclerosis grade of 0.4, which increased to 2.4 on final lens examination at a mean of 12.4 months postoperatively. The amount of nuclear sclerosis increased progressively with duration of follow-up, and 16 (76%) of 21 eyes followed up for 24 months or more required cataract extraction. The mean preoperative posterior subcapsular cataract grade was 0.0 and increased only slightly to 0.25 on final lens examination. All eyes had initial successful closure of the macular hole, but the macular hole reopened in two eyes (between six and 12 months and at 19 months) for an overall success rate of 29 (93.5%) of 31 eyes at a mean of 19.5 months. The visual acuity increased two or more Snellen lines in 29 (93.5%) of 31 eyes. The final visual acuity was 20/40 or better in 23 (74%) of 31 eyes and the visual improvement was stable in eyes followed up for three years. CONCLUSIONS: Nuclear sclerotic cataracts progress substantially after macular hole surgery with a long-acting intraocular gas tamponade. The visual acuity often decreases 12 or more months after vitrectomy because of cataract progression, but the visual results of vitrectomy and transforming growth factor beta-2 for macular holes are excellent when the cataracts are removed.

Adolescent↗
PubMed1999

Progression of defects in the central 10-degree visual field of patients with retinitis pigmentosa and choroideremia.

PURPOSE: To determine the progression of defects in the central 10-degree visual field in patients with retinitis pigmentosa and choroideremia by means of univariate linear regression with respect to the mean deviation. METHODS: In a retrospective study, results of automated static perimetry in the central 10-degree visual field were reviewed for patients with retinitis pigmentosa and choroideremia. Univariate linear regression of mean deviation was undertaken for each eye that had field data from at least five tests in addition to the prior static perimetric experience during a period of 3.5 years or more. Data from 30 eyes of 16 patients fulfilled eligibility requirements; the mean number of fields was 5.8 (range, five to 10) and the mean follow-up period was 64 months (range, 42 to 97 months). Eyes were classified as progressive if the regression coefficient was negative and significantly different from zero, with a P value of less than .05. RESULTS: Among 14 patients in whom both eyes were eligible for univariate linear regression analysis, a statistically significant progression was demonstrated in both eyes in four patients, only in one eye in five patients, and in neither eye in five patients. One of two patients, in whom only one eye was eligible for the study, showed significant progression in the eye. Overall, 14 (47%) of 30 eyes showed statistically significant progression with respect to the mean deviation. No eye showed significant improvement. CONCLUSIONS: Automated static perimetry of the central 10-degree visual field measured approximately once or twice a year demonstrated the progressive nature of the disease with the use of univariate linear regression of mean deviation in 47% of eyes with retinitis pigmentosa and choroideremia during the follow-up period of 3.5 years or more. These results may be useful in understanding the clinical course of the diseases and counseling patients.

Adolescent↗
PubMed2005

Massive apoptosis in lymphoid organs in animal models for primary and secondary progressive multiple sclerosis.

The mechanism(s) responsible for generating the different forms of multiple sclerosis, primary progressive (PP) and secondary progressive (SP) versus relapsing-remitting (RR), is not well understood. Using myelin oligodendrocyte glycoprotein (MOG)(92-106), we have established animal models that mimic the different types of multiple sclerosis. A.SW mice develop PP or SP-experimental allergic encephalomyelitis (EAE) with large areas of demyelination and high titers of MOG antibody whereas SJL/J mice develop RR-EAE with perivascular T cells and mild demyelination. In A.SW progressive EAE, we found atrophy of the thymus, spleen, and lymph nodes with depletion of T and B cells and massive apoptosis, as demonstrated by immunohistochemistry, terminal dUTP nick-end labeling, and DNA agarose gel electrophoresis. To test whether lymphoid apoptosis itself contributes to disease progression, we injected SJL/J mice with apoptotic thymocytes. Injection of apoptotic cells resulted in greater than 20% of mice developing SP-EAE with ataxia. SJL/J mice with SP-EAE had large areas of demyelination, high MOG antibody titers and atrophic lymphoid organs. Spleen cells from mice with progressive EAE produced less interferon-gamma than those from RR-EAE when stimulated with mitogen. We suggest that induction of lymphoid apoptosis alters the balance of Th1 versus Th2 immune responses and increases MOG antibody production, leading to exacerbation of demyelination and subsequent disease progression.

Animals↗
PubMed2001

Tumor progression of skin carcinoma cells in vivo promoted by clonal selection, mutagenesis, and autocrine growth regulation by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.

Tumor microenvironment is crucial for cancer growth and progression as evidenced by reports on the significance of tumor angiogenesis and stromal cells. Using the HaCaT/HaCaT-ras human skin carcinogenesis model, we studied tumor progression from benign tumors to highly malignant squamous cell carcinomas. Progression of tumorigenic HaCaT-ras clones to more aggressive and eventually metastatic phenotypes was reproducibly achieved by their in vivo growth as subcutaneous tumors in nude mice. Their enhanced malignant phenotype was stably maintained in recultured tumor cells that represented, identified by chromosomal analysis, a distinct subpopulation of the parental line. Additional mutagenic effects were apparent in genetic alterations involving chromosomes 11 and 2, and in amplification and overexpression of the H-ras oncogene. Importantly, in vitro clonal selection of benign and malignant cell lines never resulted in late-stage malignant clones, indicating the importance of the in vivo environment in promoting an enhanced malignant phenotype. Independently of their H-ras status, all in vivo-progressed tumor cell lines (five of five) exhibited a constitutive and stable expression of the hematopoietic growth factors granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, which may function as autocrine/paracrine mediators of tumor progression in vivo. Thus, malignant progression favored by the in vivo microenvironment requires both clonal selection of subpopulations adapted to in vivo growth and mutational events leading to stable functional alterations.

Autocrine Communication↗
PubMed1999

Colorectal adenoma and cancer divergence. Evidence of multilineage progression.

Colorectal cancer progression involves changes in phenotype and genotype. Although usually illustrated as a linear process, more complex underlying pathways have not been excluded. The object of this paper is to apply modern quantitative principles of molecular evolution to multistep tumor progression. To reconstruct progression lineages, the genotypes of two adjacent adenoma-cancer pairs were determined by serial dilution and polymerase chain reaction at 28-30 microsatellite (MS) loci and then traced back to their most recent common ancestor. The tumors were mismatch repair deficient, and therefore relatively large numbers of MS mutations should accumulate during progression. As expected, the MS genotypes were similar (correlation coefficients >0.9) between different parts of the same adenoma or cancer, but very different (correlation coefficients <0. 2) between unrelated metachronous adenoma-cancer pairs. Unexpectedly, the genotypes of the adjacent adenoma-cancer pairs were also very different (correlation coefficients of 0.30 and 0.36), consistent with early adenoma-cancer divergence rather than direct linear progression. More than 60% of the divisions occurred after this early adenoma-cancer divergence. Therefore, the tumor phylogenies were not consistent with sequential stepwise selection along a single most "fit" and frequent lineage from adenoma to cancer. Instead, one effective early progression strategy creates and maintains multiple evolving candidate lineages, which are subsequently selected for terminal clonal expansion.

Adenoma↗
PubMed2002

Association of polymorphisms of the transforming growth factor-beta1 gene with the rate of progression of HCV-induced liver fibrosis.

BACKGROUND: The objective of the present study was to elucidate possible relationships between four polymorphisms of the TGF-beta1 gene (-800G>A; -509C>T; Leu10Pro; Arg25Pro) and stage, histological activity grade and progression rate of liver fibrosis, classified according to the METAVIR-score. METHODS: Three study groups, i.e. 48 patients with hepatic fibrosis (26 with known duration of hepatitis C virus infection), 47 patients with non-fibrotic diseases and 50 healthy blood donors, were analyzed for TGF-beta1 polymorphisms using ARMS-PCR and sequence analysis. The concentrations of total TGF-beta1 in plasma and of hyaluronan, P-III-NP and activities of transminases in serum were measured. RESULTS: The presence of proline at codons 10 and/or 25 was associated with a faster progression of fibrosis than other polymorphisms. Patients with the genotype (25)ArgPro developed fibrosis significantly faster (0.23 units/year) than those having (25)ArgArg (0.08 units/year). Similarly, the fibrosis progression rate of patients with genotypes (10)LeuPro and (10)ProPro was almost three times as fast as of those having genotype (10)LeuLeu. Stage and histological activity grade of fibrosis in (25)ArgPro in comparison to (25)ArgArg were higher. Also (10)LeuPro showed a higher average stage of fibrosis than (10)LeuLeu. The TGF-beta1 plasma concentrations of patients with hepatic fibrosis were not significantly different between carriers of (25)ArgArg and (25)ArgPro genotypes. The frequency of the genotype (25)ArgPro in liver fibrotic patients was about three times that of the control group whereas the frequency distribution of the genotype (25)ArgArg tended to lower frequency in the fibrosis group. TGF-beta1-promoter polymorphisms did not show any correlation with stage, grade or progression of liver fibrosis. CONCLUSION: Our results indicate that the heterozygous ArgPro of codon 25 predicts significantly faster fibrotic progression of chronic hepatitis C than the homozygous (25)ArgArg genotype. The homozygous LeuLeu genotype of codon 10 showed a slow progression of fibrosis.

Adult↗
PubMed2000

Role of gastric acid secretion in progression of acute gastric erosions induced by ischemia-reperfusion into gastric ulcers.

Ischemia followed by reperfusion is known to produce gastric lesions due to oxidative stress, but the role of gastric H(+) secretion in the formation of this mucosal injury remains unknown. We studied alterations in gastric acid secretion and gastric histamine content, as well as the expression of histidine-decarboxylase and interleukin-1beta during the mucosal recovery from ischemia-reperfusion erosions. Gastric secretion was studied in rats (series A) with gastric fistula before, during and after the ischemia induced by clamping of celiac artery for 0.5 h followed by reperfusion in animals pretreated with vehicle (saline), omeprazole, a proton pump inhibitor, or ranitidine, a histamine (H(2)) receptor antagonist. In series B, the animals were submitted to 0.5 h of ischemia followed by 1 h of reperfusion and then anesthetized at 0, 3, 12 and 24 h or 3, 5, 10 or 15 days after the end of ischemia-reperfusion to determine gastric blood flow by H(2)-gas clearance technique, area of gastric lesions, plasma gastrin and interleukin-1beta levels, histamine content by radioimmunoassay (RIA) and expression of histidine-decarboxylase and interleukin-1beta mRNA by reverse transcription polymerase chain reaction. Clamping of celiac artery caused cessation of gastric blood flow and almost complete suppression of basal gastric acid secretion (series A) that returned gradually to the control value at day 3 after ischemia-reperfusion, accompanied by the rise in plasma gastrin levels, pronounced expression of histidine-decarboxylase mRNA and increased mucosal histamine content. Ischemia, followed by 1 h of reperfusion, produced gastric erosions (series B) that reached maximum at 12 h, but then declined at 24 h. These erosions progressed at day 3 into deeper ulcers whose area declined progressively within the next 5-15 days. The gastric blood ceased to flow (series B) during 30 min of clamping and was reduced throughout the period of healing of acute erosions, being accompanied by a gradual rise in mucosal interleukin-1beta mRNA content and in plasma interleukin-1beta levels. Treatment with omeprazole or ranitidine, which completely suppressed gastric acid secretion and significantly raised plasma gastrin level, greatly reduced the formation of erosive lesions preventing the progression of these lesions to chronic gastric ulcers, and this was accompanied by the rise in gastric blood flow and plasma gastrin levels and the significant attenuation of plasma interleukin-1beta levels. The ranitidine and omeprazole-induced suppression of ischemia-reperfusion erosions were abolished by the instillation of exogenous 0.2 N HCl into the stomach of these rats. The histidine-decarboxylase was faintly expressed in the intact gastric mucosa, but strongly upregulated during mucosal recovery from the damage induced by ischemia-reperfusion. We conclude that following ischemia-reperfusion: (1) gastric acid secretion, gastric microcirculation and histamine production markedly decline, while interleukin-1beta release significantly increases, probably playing an important role in the progression of acute lesions into chronic gastric ulcerations; (2) the suppression of gastric acid secretion by omeprazole and ranitidine, that induces hypergastrinemia, prevents the progression of gastric erosions into ulcers; and (3) the addition of exogenous acid restores the progression of the acute lesions into gastric ulcers, indicating that gastric acid plays a key role in ulcerogenesis induced by ischemia-reperfusion.

Acute Disease↗
PubMed1999

Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. The Multivirc Group.

BACKGROUND & AIMS: Impact of hepatitis C treatment has never taken into account the dynamics of fibrosis progression. This study assessed the impact of interferon on liver fibrosis progression in patients with chronic hepatitis C according to 3-month aminotransferase activity response. METHODS: We recruited 287 patients, 185 treated and 102 control, with paired biopsy specimens. Before follow-up, the fibrosis progression rate per year was estimated as the ratio between fibrosis stage in METAVIR units (1 U, 1 stage; 4 U, cirrhosis) and the duration of infection. During follow-up, fibrosis progression was assessed by the observed difference between stages divided by duration between biopsies. RESULTS: The median fibrosis progression rate in treated patients decreased compared with the rate before treatment from 0.103 F METAVIR U/yr (95% confidence interval [CI], 0.087-0.120) to 0.000 (95% CI, 0.000-0.000; P </= 0.0001). Among 91 treated responders, fibrosis stage worsened in 19 (22%), compared with 21 (22%) of 94 treated nonresponders and 57 of 102 controls (56%; P </= 0.0001 compared with treated patients), and improved in 26 (29%), 17 (18%), and 8 (8%; P = 0.0002 compared with 29% and P = 0.03 compared with 18%), respectively. These observed differences persisted after genotype, viremia, sex, age at infection, duration of infection, and alcohol consumption were taken into account. CONCLUSIONS: Interferon treatment changes the natural fibrosis progression rate in patients with chronic hepatitis C independently of genotype and early response.

Adult↗
PubMed2001

Impact of vascular branching sites on focal progression of allograft vasculopathy in transplanted hearts.

BACKGROUND: Cardiac allograft vascular disease (CAVD) represents one of the most accelerated progressing coronary syndromes in the human heart. A variety of risk factors have been identified over recent years; however, little is known about the influence of physical forces. As a model for differences in focal blood flow dynamics, we analyzed progression of intimal hyperplasia at vascular bifurcational sites using intravascular ultrasound (IVUS). METHODS: The most diseased vascular sites ("worst sites") in 59 coronary arteries were assessed (30 MHz, motorized pull back) in 25 consecutive heart transplant recipients at baseline (52.8+/-15.3 days postoperatively) and after 1 year of follow up (360.5+/-24.9 days). Progression of intimal hyperplasia was compared between branching and non-branching lesions as well as in focal relation to the position of the flow divider. RESULTS: A total of 41 (69.5%) worst sites were identified at branching locations. Progression of intimal hyperplasia was found to be significantly more severe at bifurcational sites with an increase in plaque area by 1.5+/-1.8 mm(2) in branching versus 0.4+/-0.6 mm(2) in non-branching lesions (P=0.015). The highest rate in focal progression was found at the opposite site of the flow divider with an increase in maximal intimal thickness by 0.3+/-0.23 mm (180 degrees ) as compared to 0.11+/-0.15 mm (90 degrees, P<0.001) and 0.15+/-0.15 mm (P=0.014) at 270 degrees. CONCLUSIONS: Using serial intravascular ultrasound examinations, vascular branching sites could be identified to be predisposing locations not only for a donor related arteriosclerosis, but also for progression of intimal hyperplasia within transplanted hearts. The highest regional increase in intimal thickness was found at the outer wall of the flow divider, suggesting focal shear or wall stress to be involved in pathogenesis.

Coronary Disease↗
PubMed2003

Does elevated body mass modify the influence of postmenopausal estrogen replacement on atherosclerosis progression: results from the estrogen in the prevention of atherosclerosis trial.

OBJECTIVE: To determine whether the estrogen-related reduction in atherosclerosis progression demonstrated in the estrogen in the prevention of atherosclerosis trial (EPAT) is modified by body mass index (BMI). STUDY DESIGN: Subgroup analyses were performed using data from EPAT, a randomized, double-blind, placebo-controlled trial designed to determine whether unopposed 17beta-estradiol administered for a 2-year treatment period reduces the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary trial endpoint was the rate of change of common carotid artery intima-media thickness (IMT). In this subgroup analysis, the sample was divided into 122 women with BMI<30 kg/m(2) and 77 women with BMI> or =30 kg/m(2). Statistical analysis was performed using mixed general linear models to evaluate whether the treatment effects on IMT progression rates differed in the two BMI groups. RESULTS: There was no significant difference in the estradiol treatment effect on IMT progression rates between postmenopausal women with BMI<30 vs. > or =30 kg/m(2) (P=0.52). In the 77 subjects who did not use lipid-lowering therapy, there was significant improvement in IMT with estradiol treatment that was evident in both BMI groups (P=0.48 for differences between BMI groups). CONCLUSIONS: In contrast to the epidemiological observation that obese postmenopausal women do not derive benefit from estrogen replacement therapy, results of this study indicate that estradiol treatment is beneficial in preventing progression of atherosclerosis regardless of initial BMI. CONDENSATION: Estradiol treatment is beneficial in preventing progression of atherosclerosis in postmenopausal women not receiving lipid-lowering therapy, regardless of their initial body mass index.

Biomarkers↗
PubMed1999

Serial evoked potential studies and MRI imaging in chronic progressive multiple sclerosis.

Measurements of serial evoked potential latencies and plaque burden on MRI scans are often obtained during clinical studies of multiple sclerosis patients to provide additional information to the disability-based primary endpoints. The ideal laboratory-based marker of progression would be expected to significantly change over the time period of study. Serial visual (VEP) and brainstem auditory evoked potentials (BAEP) and MRI scans of 11 chronic progressive MS patients were obtained over a 1.5 year period in a clinical study. Over this period, there was no significant change in disability as measured by the Kurtzke EDSS, Ambulation Index or Neurological Rating Score. The VEP P100 significantly progressed over the period of study. However, the MRI T(2) plaque burden and BAEP I-V intrapeak latency did not significantly progress over the 1.5 years. We conclude that, in chronic progressive MS, serial visual evoked potential tests may complement standard disability-based endpoints to assess disease progression.

Disability Evaluation↗