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Patterns of radiological progression in early rheumatoid arthritis: results of an 8 year prospective study.

OBJECTIVE: To describe the course of radiological progression in a cohort of 126 patients presenting with early nonerosive rheumatoid arthritis (RA). METHODS: Criteria for recruitment to the study were fulfillment of the 1958 American Rheumatism Association criteria, absence of erosive disease at presentation and duration of symptoms less than 3 years. Radiographs of hands and feet at 0, 1, 2, 5, and 8 years were available on 114 patients and were scored by Sharp's method for erosion (ERO) and joint space narrowing (JSN). Eighty-six patients were typed for the RA susceptibility shared HLA-DR epitope. RESULTS: The feet showed greatest initial radiological progression, but tended to reach an earlier and lower plateau. ERO progressed more rapidly than JSN in the first 2 years, but in parallel thereafter. The relative proportion of ERO:JSN varied, 1:1 for the wrists, 4:1 for the proximal interphalangeal joints. Thirty-eight percent of joints were eroded at 2 years, 63% at 8 years. Four patterns of radiological progression were identified: flat or nonerosive disease in 29 patients, linear in 51, lag in 13, and plateau in 19 (irregular in 2). Changes in the rate of radiological progression were reflected by the time-integrated C-reactive protein over the same period. Rheumatoid factor titer was higher in the progressive groups compared to the flat group (p = 0.01). The RA susceptibility shared HLA-DR epitope was more frequent in the linear compared to the flat group (p = 0.03). CONCLUSION: A large proportion of joints become eroded in the first 2 years of early RA. The subsequent course of radiological progression is highly variable and cannot be easily explained by any single model.

Adolescent↗

Longitudinal cohort analysis of lethal prostate cancer progression in transgenic mice.

PURPOSE: Human prostate cancer is variably lethal, shows heterogeneous progression, and exhibits a spectrum of histopathology. Traditional rodent models of prostate cancer lack these characteristics. An alternative, autochthonous model of prostate cancer consists of transgenic mice which develop prostate cancer due to prostatic expression of SV40 T antigen. Lethal progression of such cancers in individual mice has not been previously characterized. Studies were undertaken to characterize the longitudinal progression of prostate cancers in these transgenic mice. METHODS: A prospective longitudinal cohort study was undertaken to characterize prostate cancer volume, progression, lethality, and histological heterogeneity in a transgenic mouse model of prostatic adenocarcinoma. Fifty-one transgenic mice were followed prospectively to determine the age at onset of palpable tumor and age at cancer-related death. Tumor volume was followed longitudinally by magnetic resonance imaging (MRI) in a subset of these mice and lethal cancers were evaluated by histopathology. RESULTS: Primary tumors became palpable at 10-38 weeks of age. Palpable tumors always preceded lethal progression. Cancer death followed 2-9 weeks later, and age at cancer death varied from 24 to 39 weeks of age. The histopathological changes were heterogeneous. Primary tumors were detectable by MRI before they became detectable by palpation. MRI showed that, analogous to human prostate cancers, volume of early stage primary tumors did not necessarily predict age at cancer death. CONCLUSION: Prostate cancer in transgenic mice mimics heterogeneic tumor progression in human prostate cancer, providing a uniquely relevant pre-clinical model. Tumor detection by MRI and palpation are valid surrogate measures of tumor progression in this model.

Animals↗

Effect of gender, age, transmission category, and antiretroviral therapy on the progression of human immunodeficiency virus infection using multistate Markov models. Groupe d'Epidémiologie Clinique du SIDA en Aquitaine.

This article illustrates the use of time-homogeneous Markov models with covariates to estimate the AIDS incubation period distribution from prevalent cohorts and to evaluate the effect of factors such as gender, age, human immunodeficiency virus (HIV) transmission category, and antiretroviral therapy on disease progression. We applied this methodology to the analysis of data from a cohort of 3,027 patients enrolled from a hospital-based surveillance system of HIV infection in the Bordeaux University Hospital and four secondary public hospitals in southwestern France. A total of 998 individuals (33%) progressed to AIDS during a median follow-up period of 34 months. Based on a progressive three-state Markov model, the estimated mean and median incubation periods were 9.1 years [95% confidence interval (CI) = 8.7-9.6] and 7.5 years (95% CI = 7.2-7.9), respectively. Our analyses showed a similar disease progression in men and women; we observed a more rapid progression for older subjects compared with younger ones and for homosexual men compared with heterosexuals, intravenous drug users, and transfusion recipients, who had similar disease progression rates after adjusting for age. The use of antiretroviral therapy appeared to slow disease progression. Moreover, the results indicated that a combination therapy of zidovudine with another antiretroviral drug may be more efficient than zidovudine monotherapy.

Acquired Immunodeficiency Syndrome↗

Paucity of radiographic progression in rheumatoid arthritis treated with methotrexate as the first disease modifying antirheumatic drug.

OBJECTIVE: To determine disease progression in patients with rheumatoid arthritis (RA) using methotrexate (MTX) as the first disease modifying antirheumatic drug (DMARD). METHODS: Patients with RA treated with MTX as their first DMARD and in whom hand/wrist radiographs prior to MTX administration had been obtained and who had received MTX for at least 10 months were evaluated radiographically for disease progression. Coded radiographs were read for erosions by 2 experienced readers using the modified method of Sharp. Erosion scores and rate of progression (per month) were calculated. RESULTS: Of 24 patients studied, baseline radiographs showed erosions (one or more) in 11 and none in 13. Patients with and without erosions at baseline had comparable demographic and clinical features, although patients with erosions had longer disease duration and higher rheumatoid factor positivity than those without erosions (statistically nonsignificant, however). Half of all patients showed no progression; 73% of those patients with erosions at baseline but only 31% of those without erosions at baseline progressed (p = 0.049); progression rates were 0.017 (+/-0.033) and 0.049 (+/-0.078) for the 2 groups (p = 0.040). CONCLUSION: Patients with RA starting MTX before erosions have occurred are less likely to develop them; these patients also experienced a lesser degree of disease progression than patients who started MTX with erosions already present.

Antirheumatic Agents↗

Progressing neurological deficit secondary to acute ischemic stroke. A study on predictability, pathogenesis, and prognosis.

OBJECTIVES: To identify predictors and possible pathogenetic mechanisms of early neurological deterioration in patients with acute ischemic strokes and to evaluate their impact on clinical outcome. DESIGN: Case series. SETTING: University hospital's stroke unit. PATIENTS: A continuous series of 152 patients with first-ever ischemic hemispheric strokes were hospitalized within 5 hours of onset, evaluated with the Canadian Neurological Scale, and underwent a computed tomographic (CT) scan. The initial subset of 80 patients also underwent angiography. A repeated CT scan or autopsy was performed within 5 to 9 days of a patient's stroke. Progressing neurological deficit was defined as a decrease of one point or more in the global neurological scale score during hospitalization, when compared with that at entry. RESULTS: The conditions of 39 patients (26%) deteriorated during the initial 4 days; 20 patients (51%) had an impaired level of consciousness, and 19 patients (49%) had impaired limb strength and/or speech. They had been hospitalized earlier and had higher serum glucose levels at admission; the baseline CT scans of these patients showed an early focal hypodensity and initial mass effect more frequently. On the repeated CT scan (144 patients) or at autopsy (eight patients), patients with a progressing course more frequently had large infarcts, severe mass effect, and hemorrhagic infarction. We found no differences with regard to demographic data, medical history, and treatments that were given; only subcutaneous heparin calcium was more frequently administered to patients with a progressing course. Twenty-two (27%) of the 80 patients who underwent angiography had a progressing course, of whom 20 (91%) had an intracranial and/or extracranial arterial occlusion, with collateral blood supply in seven patients (35%). Logistic regression analysis showed that the independent predictors of progression were the serum glucose levels at admission and the early focal hypodensity with cortical and corticosubcortical locations, with the positive predictive values of the latter being 34% (95% confidence interval [CI], 26% to 42%) and 57% (95% CI, 47% to 67%), respectively. Among patients who underwent angiography, logistic regression analysis showed a significant correlation between carotid siphon occlusion and a progressing course. The 30-day case-fatality ratio and disability (Barthel index, < 60) were higher in patients with a progressing course (36% and 54% vs 12% and 35%, respectively). CONCLUSIONS: Early stroke deterioration is still an event that is difficult to predict; it is largely determined by cerebral edema following an arterial occlusion, as indicated by an early focal hypodensity and initial mass effect on the baseline CT scan. Since early deterioration anticipates a bad outcome in 90% of patients, it might be used as an early surrogate end point in therapeutic trials.

Acute Disease↗

Progression of symptoms in the early and middle stages of Huntington disease.

OBJECTIVE: To delineate the progression of symptoms in the early and middle stages of Huntington disease (HD). DESIGN: A survey of individuals with symptomatic HD completed by a first-degree relative. SETTING: The National Huntington Disease Research Roster for Patients and Families, Indianapolis, Ind. PARTICIPANTS: The survey included 1238 individuals with a minimum of a 6-year history of symptomatic HD. MEASURES: Participating families completed a series of surveys, including the Affected Individual Questionnaire, which consists of 19 physical, emotional, and cognitive signs commonly thought to occur during disease progression. The respondent indicates if each of the symptoms occurred and, if so, at what time during the course of the disease: (1) within 1 year, (2) within 2 to 5 years, (3) within 6 to 10 years, (4) after more than 10 years, (5) has not occurred, or (6) "don't know." RESULTS: The symptoms are categorized into 6 onset periods. Involuntary movements are grouped alone as the earliest reported symptom. The second group is composed entirely of mental and emotional symptoms, including sadness, depression, and difficult to get along with. The third group includes clumsiness, sexual problems, lack of motivation, and suspiciousness/paranoia. As the disease progresses, a variety of motor, emotional/behavioral, and cognitive symptoms are experienced, including unsteadiness, trouble holding onto things, trouble walking, changes in sleeping patterns, delusions and hallucinations, intellectual decline, and memory loss. With the approach of late-stage HD, affected individuals begin to experience speech difficulty and weight loss. In the late stage, patients lose bowel and bladder control. CONCLUSIONS: Even though the symptoms of HD are fairly well characterized, their progression, especially in the early and middle stages, remains uncertain. Clarification of the disease progression is vital to improved understanding of the pathogenesis of HD and to the evaluation of therapeutic agents that are designed to slow the progression of disease. The results of this study assist in clarifying HD progression from early involuntary movements and emotional changes to more overt motor symptoms and difficulty with activities of daily living.

Activities of Daily Living↗

The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy.

OBJECTIVE: To examine the 10-year incidence and progression of diabetic retinopathy. DESIGN: Population-based incidence study. PARTICIPANTS: Seven hundred sixty-five insulin-taking diabetic persons diagnosed before age 30 years, 251 insulin-taking diabetic persons diagnosed at age 30 years or older, and 282 non-insulin-taking diabetic persons diagnosed at age 30 years or older who participated in baseline, 4-year, and 10-year follow-up examinations. MAIN OUTCOME MEASURES: The 10-year incidence of any retinopathy, progression of retinopathy, and progression to proliferative retinopathy were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study severity scheme. RESULTS: The 10-year incidence of retinopathy (89%, 79%, and 67%), progression of retinopathy (76%, 69%, and 53%), and progression to proliferative retinopathy (30%, 24%, and 10%) were highest in the group diagnosed before age 30 years, intermediate in the insulin-taking group diagnosed at age 30 years or older, and lowest in the non-insulin-taking group, respectively. Increased risk of proliferative retinopathy was associated with more severe retinopathy at baseline. CONCLUSIONS: These data suggest relatively high 10-year rates of incidence and progression of retinopathy, and despite changes in the treatment of diabetes, there has been little change in the incidence and progression of diabetic retinopathy during the 10-year study period.

Adolescent↗

An attempt to analyse progress in fold recognition from CASP1 to CASP3.

The Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment has been conducted for the third time. An obvious question is whether there has been progress from CASP1 to CASP3. An analysis depends on many variables, including prediction category, number and difficulty of targets, methods used to evaluate prediction success, and the rules for submission. It also depends on whether progress is measured in terms of all predictions submitted or in terms of the best predictions for each target. The progress made by individual groups is another interesting issue. In view of this complexity and the limited amount of data, an objective estimate of progress is difficult to obtain. Despite such difficulties, some estimate of progress is desirable. Here, we present an attempt to quantify progress in the fold-recognition category from CASP1 to CASP3. The numbers indicate clear progress from CASP1 to CASP2 but no improvement from CASP2 to CASP3. However, we argue that the targets in CASP3 are more difficult compared with CASP2, which translates into better performance of CASP3 over CASP2.

Autoantigens↗

A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group.

BACKGROUND: A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death. METHODS: Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%). RESULTS: Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25). CONCLUSIONS: At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.

Adenocarcinoma↗

Epidemiologic features of rapidly progressing breast cancer in Tunisia.

A form of breast cancer characterized by rapid disease progression, inflammation, and edema is found in approximately 55% of the breast cancer patients presenting at the Institute Salah Azaiz, Tunis (Tunisia). In 581 patients seen between January 1, 1969, and December 31, 1974, we examined age, place of residence, reproductive history, delay in seeking treatment, and blood gropu as potential risk factors to determine the distinction between the rapidly progressing disease and the less aggressive form. Rural residence, blood type A, and recent pregnancy are risk factors among premenopausal women, but older age, rural residence, blood type A, late menarche, and delay in diagnosis are associated with postmenopausal rapidly progressing breast cancer. The most significant risk factors were rural residence and blood type A. Rapidly progressing breast cancer was diagnosed in two of every three breast cancer patients coming from a rural environment. Forty-three percent of 203 patients with rapid disease progression were blood type A, a significantly higher percentage than the 33% found in the general Tunisian population and the breast cancer patients without evidence of rapidly progressive disease. We observed that the risk factors for disease progression were quite different from those reported to influence the incidence of breast cancer.

Adult↗

Melanocyte tumor progression is associated with changes in angiogenesis and expression of the 67-kilodalton laminin receptor.

BACKGROUND: A number of experimental studies have substantiated changes in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model of tumor progression. METHODS: Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression were investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule). RESULTS: Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed "nevi with ADMA"), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvessels were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjacent tissue of metastatic foci. Expression of the laminin receptor, evaluated as percentages of positive lesions and positive cells per lesion, underwent upregulation in the course of progression. Changes in expression were associated mostly with nevi with ADMA, transformation, and deepening of the tumors into the dermis. CONCLUSIONS: These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.

Adult↗

Expression of squamous cell carcinoma-associated antigen in grade 3 pT1 transitional cell carcinoma of the bladder and prediction of its progression and intravesical recurrence.

BACKGROUND: Among superficial transitional cell carcinomas (TCC) of the bladder, Grade 3 pT1 disease is associated with a higher risk of progression and intravesical recurrence. The authors determined whether or not squamous cell carcinoma-associated antigen (SCC antigen) could predict clinical behavior of Grade 3 pT1 disease. METHODS: SCC antigen was immunohistochemically stained in Grade 3 pT1 TCC of the bladder that had been fixed in formaldehyde solution and embedded in paraffin. Patients were followed up, and disease progression and recurrence were identified. Disease progression was defined as histologically verified muscle invasion or clinically detectable distant metastasis, including pelvic lymph node metastasis. RESULTS: SCC antigen in the cytoplasm was positively identified with immunohistochemical staining in 21 of 55 patients with the disease. Of 21 patients with positive SCC antigen in the cytoplasm, 8 experienced disease progression, whereas there was progression in 5 of 34 patients with negative antigen. The nonprogression rate of Grade 3 pT1 carcinomas with positive antigen in the cytoplasm was significantly lower than that for those with negative antigen. The disease-free rate also was clearly lower in the positive carcinoma than in the negative. Multivariate analysis confirmed that SCC antigen in the cytoplasm was the only significant variable independently affecting progression and intravesical recurrence of the disease. CONCLUSIONS: The results suggested that immunohistochemical expression of SCC antigen in the cytoplasm is closely linked with a higher risk for progression and intravesical recurrence of Grade 3 pT1 disease. Detection of the antigen can help to more accurately predict the clinical course of the disease.

Adult↗

Prognostic factors for radiographic progression, radiographic damage, and disability in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the rate of radiographic progression and identify prognostic factors of radiographic progression, radiographic damage, and physical disability in juvenile idiopathic arthritis (JIA). METHODS: Ninety-four JIA patients with a median disease duration of 1.1 years were followed up prospectively for a median of 4.5 years. Bilateral wrist radiographs were obtained at baseline, at 1 year, and at the last followup visit. Radiographic damage was assessed by the carpal length (Poznanski score), and physical disability by the Childhood Health Assessment Questionnaire (C-HAQ). Yearly radiographic progression, the Poznanski score at the final visit, and the C-HAQ score at the final visit were used as outcome measures. Baseline parameters included demographic, clinical, laboratory, and radiographic data. RESULTS: The mean +/- SD Poznanski score was -1.2 +/- 1.3 at baseline, -1.7 +/- 1.8 at the 1-year visit, and -1.9 +/- 2.2 at the final visit (P < 0.0001). Radiographic progression was greater during the first year (mean +/- SD -0.5 +/- 1.1) than between the 1-year visit and the final visit (-0.2 +/- 1.3). The mean yearly radiographic progression during the entire study period was -0.1 +/- 0.4. Logistic regression analysis revealed that radiographic progression during the first year was the only baseline parameter that was predictive of all 3 study outcomes. The final Poznanski score was also predicted by the baseline Poznanski score, whereas female sex was protective against radiographic progression. CONCLUSION: We identified the prognostic factors for poorer outcome in polyarticular-course JIA. The changes in the early Poznanski score can be used to predict long-term joint damage and physical disability.

Adolescent↗

An immunohistological study of cells infiltrating progressive and regressive tumors induced by two variant subpopulations of a rat colon cancer cell line.

In order to understand the mechanisms leading up to progression or regression, tumors resulting from the s.c. inoculation of progressive or regressive variants of a cell culture established from a chemically-induced rat colonic carcinoma were subjected to sequential histological study. As immunological factors have been previously described in this system of progressive or regressive tumors, special interest was given to inflammatory cells, T and B lymphocytes and macrophages, located inside and outside the tumor. Immunohistological methods using monoclonal or polyclonal antibodies and enzyme histology were performed to identify different populations of infiltrative cells. In both variants of tumors an accumulation of these cells were seen at the periphery of the tumor, surrounding the nodules. In contrast, very few inflammatory cells, macrophages or T lymphocytes were seen inside the clumps of tumor cells where cytolytic cells could have a contact-dependent tumoricidal effect. Only small differences were found between progressive and regressive tumors in the density of the various populations of T helper, T cytotoxic/suppressor, B lymphocytes or macrophages inside or around the tumor nodules. On the other hand, progressive and regressive tumors clearly differ in the relationship between tumor cells and the fibroblastic reaction they induce. Regressive tumors were rapidly encircled by a fibroblastic reaction isolating them from the peripheral tissues. The fibroblastic reaction was less dense around the progressive tumor cells which were able to migrate and invade the periphery. This suggests that immunological factors leading to tumor progression or regression could act indirectly through a control of the fibroblastic reaction, rather than through a direct cytotoxic effect on the tumor cells.

Animals↗

Use of backcalculation for estimation of the probability of progression from HIV infection to AIDS.

Backcalculation has been used to estimate the rate of past HIV infection and to predict future AIDS incidence. In this study we examine another use: estimating the probability of progression from HIV infection to AIDS as a function of time from infection. Given observed AIDS incidence data, the technique of backcalculation estimates the most likely number of persons infected with HIV in the past. Assumptions about probability of progression from HIV infection to AIDS are necessary. By varying these assumptions and examining the resulting goodness of fit to the AIDS incidence data, we can theoretically estimate parameters of progression. We report on implementation of this method and examine its practical utility in deciding among four competing progression models specified on a priori grounds. The four specific models comprise three Weibull distributions with medians of 8, 10, and 12 years, respectively, and one model that begins as a Weibull with 8 year median but where the hazard is level after 3.5 years. To employ asymptotic maximum likelihood methods, we define a two parameter family of progression models that includes all four a priori models. One parameter sets the scale for an initial Weibull progression (the shape parameter being fixed for all models), and the other specifies a levelling point after which the hazard remains constant. AIDS incidence data from Canada's national surveillance system provided the empiric data for this evaluation. First we corrected these data for reporting delay by Poisson modelling of the delay distribution. We used three parametric families of infection curves: step-function, log-logistic, and logistic. The results support the hypothesis of an early levelling of the hazard function. When we fixed the scale parameter to that of the Weibull curve with 8 year median, the maximum likelihood estimate of the levelling point was 2.7 years, and a clearly superior fit was produced compared to a pure Weibull progression with the same scale parameter (likelihood ratio chi-square of 10.6 on 1 degree of freedom, p = 0.001). The maximum was indistinguishable in fit from the levelling point of 3.5 years hypothesized in advance (chi-square = 0.30, d.f. = 1, p = 0.58). Backcalculation, however, could not determine the Weibull scale parameter itself because the likelihood was quite flat as a function of this parameter. We conclude that one must determine the parameters governing the initial shape of the hazard function from other kinds of data.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

Progressive joint damage during penicillamine therapy for rheumatoid arthritis.

Progressive joint damage characterises rheumatoid arthritis despite treatment with slow-acting drugs such as penicillamine. We examined a cohort of 145 RA patients, treated with 250 or 500 mg penicillamine daily for 18 months to study progressive joint damage measured using Larsen's standard radiographs. Overall damage increased significantly over 18 months at both doses of penicillamine. Radiological changes between 6-18 months were studied in detail in 55 cases. They were divided into rapidly progressive (increases in Larsen score of more than 5) or slowly progressive (increases in Larsen score of 5 or less). Overall clinical response, visual analogue pain score, ESR, haemoglobin and platelet count were significantly lower in the slowly progressive patients; articular index and duration of morning stiffness were slightly lower; latex titre, RAHA titre, joint size and white cell count showed no differences between groups. There is an indirect relationship between progressive joint damage and some clinical and laboratory measures. The reasons underlying our failure to control progression in some cases need further definition.

Adult↗

Patterns of progression: unpredictability and risk of decompensated cirrhosis.

Hepatitis C virus (HCV) infection appears to have a slow but progressive evolution to chronic hepatitis and cirrhosis in a significant percentage of patients. Chronic hepatitis develops in 60-80% of patients. Worldwide prospective studies have shown that a further 20-30% of patients with chronic active hepatitis will develop cirrhosis regardless of the possible source of HCV infection. The percentage of cirrhotics is generally believed to increase progressively as the length of follow-up increases. In patients with chronic HCV, there also is high risk for the development of hepatocellular carcinoma. Factors influencing the rate of progression from chronic hepatitis to cirrhosis appear to include age at time of exposure, duration of infection, degree of liver damage at initial biopsy, immunological status, and possibly HCV genotype. The mean intervals between the time of initial infection and the diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma have been estimated to be 10, 20, and 30 years, respectively. The progression of disease is variable and is not always orderly and sequential. Patients can progress from chronic persistent hepatitis or chronic active hepatitis directly to hepatocellular carcinoma without first developing cirrhosis, especially those with genotype 1b. In addition, cirrhosis does not appear to lead to clinically apparent hepatic failure in all patients. Because of the variability in the clinical presentation and clinical progression of chronic HCV, long-term follow-up studies may be necessary to fully assess the sequelae of chronic HCV infection. Most patients with chronic HCV have abnormal liver histology but can present as otherwise healthy individuals. In contrast, patients with chronic HCV who have normal hepatic chemistries can have substantial hepatocellular damage. Consequently, treatment at diagnosis offers the greatest likelihood of eliminating the virus and preventing progression to more severe liver disease.

Carcinoma, Hepatocellular↗

Progression of coronary artery disease after percutaneous transluminal coronary angioplasty.

Thirty-nine patients underwent coronary arteriography 1 to 20 months (mean 7 months) after percutaneous transluminal coronary angioplasty (PTCA). At the time of the repeat study, 35 patients (90%) had recurrent angina or myocardial infarction, and 4 patients (10%) were asymptomatic. Restenosis, defined as greater than 50% loss of PTCA gained diameter, was found in 19 patients (49%). In addition, 20 patients had new lesions or marked progression of existing lesions (defined as greater than 20% or increasing greater than 20% obstruction in coronary diameter) in the previously normal or mildly diseased coronary segments. The new or progressive lesions occurred both in patients with restenosis at the PTCA site (nine of 19) and in patients without restenosis (11 of 20). New or progressive lesions tended to occur more commonly in the artery on which PTCA was performed (13 of 40) than in the artery that did not have PTCA (10 of 77) (p less than 0.02 by chi 2). In arteries that had PTCA, new or progressive lesions occurred more often in the segment proximal to the angioplasty site (seven of 13 or 54%) than in the peri-PTCA segment (two of 13 or 15%) and in the segments distal to it (four of 13 or 31%), but this observation did not reach statistical significance. No other clinical, angiographic, or PTCA procedure variables affected the occurrence of new or progressive lesions. In patients with recurrent angina or myocardial infarction after PTCA, both restenosis and new or progressive lesions are common. New lesions or marked progression of existing lesions tended to occur in the vessel subjected to PTCA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗