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PubMed1994

Blood pressure treatment slows the progression of carotid stenosis in patients with isolated systolic hypertension.

BACKGROUND AND PURPOSE: The Systolic Hypertension in the Elderly Program (SHEP) was a randomized trial testing the efficacy of treating systolic hypertension in older adults. A significant reduction in stroke risk was observed among participants assigned to active treatment. Serial carotid duplex scans were performed on 129 participants at the University of Pittsburgh center, and rates of progression and regression of carotid stenosis were observed. METHODS: Changes in blood flow velocity ratios were used to detect progression because they can be reliably measured and their relation to degree of residual lumen is known. Progression required the development of a 40% to 50% diameter stenosis when stenosis was not initially present or, if already present, further reduction in the lumen diameter. Regression required the absence of a 40% to 50% diameter stenosis when stenosis was initially present or a stenosis significantly less severe than that initially seen. RESULTS: Progression occurred in 22% (28/129) of participants and regression in 16% (8/49). Progression of carotid stenosis occurred more often among participants randomized to placebo as compared with active treatment (31% versus 14%, P = .020). All eight patients exhibiting-regression were randomized to active treatment. In multivariate analysis, participants assigned to placebo had 4.3 times greater odds of progressing than participants assigned to active treatment. Other factors significantly related to progression were higher degree of plaque at baseline, low high-density lipoprotein-3, high lipoprotein(a), and younger age. CONCLUSIONS: Treating systolic hypertension appears to slow progression of carotid stenosis. Similar effects occurring in the intracranial vessels may be one reason for the substantial decrease in stroke among SHEP participants assigned to active treatment.

Aged↗

PubMed1995

Influence of vascular risk factors for atherosclerotic carotid artery plaque progression.

BACKGROUND AND PURPOSE: Investigations regarding arteriosclerosis of carotid arteries showed an association between increased intima-media thickness and vascular risk factors. A newly developed three-dimensional ultrasound method increases the reproducibility of plaque volume measurements because more exact volume measurements can be performed with a reduction of the disadvantages of two-dimensional measurements. In a pilot study the influence of vascular risk factors on carotid artery plaque progression was examined. METHODS: Volumes of atherosclerotic plaques in carotid arteries in 54 patients were measured with a three-dimensional ultrasound system during a 12-month period to determine the relationship between progression or regression of plaque volume, vascular risk factors, dose of aspirin, and flow turbulence in the plaque region. RESULTS: A progression of plaque volume occurred in 67% (36/54) of all plaques. In no plaque was a regression of plaque volume seen. The optimal adjustment of all risk factors showed a significant influence on plaque progression (r = .31). Diastolic blood pressure was the strongest predictor of plaque progression (P < .01), followed by diabetes (P < .03). Turbulence in the plaque region was found in 78% of the patients in the progression group (n = 36) versus 61% in the nonprogression group (n = 18) but was not significant. Dose of aspirin (100 mg versus 250/300 mg) had no influence on plaque volume after 1 year. CONCLUSIONS: Treatment of vascular risk factors reduces the progression of carotid artery plaque volume in three-dimensional ultrasound. The most important factor for plaque progression is a high diastolic blood pressure. Turbulence in the flow pattern and the examined doses of aspirin showed no significant influence.

Aged↗

PubMed1984

Physicochemical and histological changes in the arterial wall of nonhuman primates during progression and regression of atherosclerosis.

To identify the temporal changes occurring during progression and regression of atherosclerosis in nonhuman primates, we have studied the physicochemical and histological characteristics of arterial wall lesions during a 30-mo progression period of diet-induced hypercholesterolemia and during a 12-mo period of regression. Three groups of cynomolgous monkeys (Macaca fascicularis) were studied. Control groups were fed a basal chow diet for 18, 24, and 30 mo and were compared with progression groups that were fed a high-cholesterol-containing diet for up to 30 mo. Regression groups were fed a high-cholesterol diet for 18 mo to induce atherosclerosis and then fed monkey chow for up to 12 mo. The progression group monkeys were killed at 6, 12, 18, 24, and 30 mo, and the regression animals were killed at 24 and 30 mo (i.e., after 6 and 12 mo of being fed a noncholesterol-containing chow diet). Histology and morphometry, physical microscopy for cholesterol monohydrate crystals, foam cell and droplet melting points and chemical composition studies were completed on a large number of individual arterial lesions. Control animals had very little cholesterol ester, rare foam cells, and no extracellular cholesterol ester droplets or cholesterol crystals. During progression, the arteries first increased cholesterol ester content to produce high melting (approximately 45 degrees C) foam cell-rich lesions essentially devoid of cholesterol crystals. With time, the number of cholesterol crystals increased so that by 30 mo large numbers were present. Foam cells decreased with time but their melting temperature remained high while that of extracellular droplets fell to approximately 38 degrees C. Between 18 and 30 mo necrosis appeared and worsened. After 6-mo regression, unexpected changes occurred in the lesions. Compared with 24-mo progression, the chemical composition showed a relative increase in free cholesterol, a decrease in cholesterol ester and microscopy revealed large numbers of cholesterol crystals. Concomitantly, foam cells decreased and the melting temperature of both intra- and extracellular cholesterol ester markedly decreased. After 12-mo regression cholesterol decreased, cholesterol crystals and necrosis diminished and collagen appeared increased. Thus, during progression there is initially an increase in the number of foam cells containing very high-melting intracellular cholesterol ester droplets. By 30 mo, cholesterol crystals and necrosis dominate and high-melting foam cells appear only at lesion margins, suggesting that the initial process continues at the lesion edge. The lower melting point of extracellular esters indicates a lipid composition different from intracellular droplets. Thus, the changes observed in these animals generally reflect those predicted for progression of human atherosclerosis. During the initial 6 mo of regression, necrosis remains, the number of foam cell decreases, and cholesterol ester content decreases; however the relative proportion of free cholesterol content increases, and large numbers of cholesterol content are formed. Thus, large and rapid decreases in serum cholesterol concentration to produce regression in fact may result in the precipitation of cholesterol monohydrate and an apparent worsening of the lesions. More prolonged regression (12-mo) tends to return the lipid composition of the artery wall towards normal, partially reduces cholesterol crystals, and results in an improved but scarred intima.

Animals↗

PubMed2004

Engagement, denial, and treatment progress among sex offenders in group therapy.

This study investigates the relationship between engagement, denial, and treatment progress among a sample of 61 male sex offenders in outpatient group therapy. Three hypotheses were posed: (1) that denial is inversely related to engagement in group therapy; (2) that denial is inversely related to treatment progress, and (3) that engagement is correlated with treatment progress. Results revealed a strong correlation between engagement in group therapy, measured by the Group Engagement Measure, and sex offender treatment progress, assessed by the Sex Offender Treatment Rating Scale. Denial, measured by the Facets of Sexual Offender Denial Scale, demonstrated a strong inverse relationship to treatment progress. Engagement and denial were also strongly inversely related. Together, engagement and denial explained a significant amount of the variance in treatment progress. The findings provide support for current standards of practice that maintain that admitting to a sex crime is a necessary condition for progress and engagement in treatment. Strategies for increasing engagement and treatment progress, and reducing denial, are discussed.

Adult↗

PubMed2006

Progressive non-infectious anterior vertebral fusion, split cord malformation and situs inversus visceralis.

BACKGROUND: Progressive non-infectious anterior vertebral fusion is a unique spinal disorder with distinctive radiological features. Early radiographic findings consist of narrowing of the anterior aspect of the intervertebral disk with adjacent end plate erosions. There is a specific pattern of progression. The management needs a multi-disciplinary approach with major input from the orthopaedic surgeon. CASE REPORT: We report a 12-year-old-female with progressive anterior vertebral fusion. This occurred at three vertebral levels. In the cervical spine there was progressive fusion of the lateral masses of the Axis with C3. Secondly, at the cervico-thoracic level, a severe, progressive, anterior thoracic vertebral fusion (C7-T5) and (T6-T7) resulted in the development of a thick anterior bony ridge and massive sclerosis and thirdly; progressive anterior fusion at L5-S1. Whereas at the level of the upper lumbar spines (L1) a split cord malformation was encountered. Situs inversus visceralis was an additional malformation. The role of the CT scan in detecting the details of the vertebral malformations was important. To our knowledge, neither this malformation complex and nor the role of the CT scan in evaluating these patients, have previously been described. CONCLUSION: The constellations of the skeletal abnormalities in our patient do not resemble any previously reported conditions with progressive anterior vertebral fusion. We also emphasise the important role of computerized tomography in the investigation of these patients in order to improve our understanding of the underlying pathology, and to comprehend the various stages of the progressive fusion process. 3D-CT scan was performed to improve assessment of the spinal changes and to further evaluate the catastrophic complications if fracture of the ankylosed vertebrae does occur. We believe that prompt management cannot be accomplished, unless the nature of these bony malformations is clarified.

Cervical Vertebrae↗

PubMed2004

Magnitude of response with myeloma frontline therapy does not predict outcome: importance of time to progression in southwest oncology group chemotherapy trials.

PURPOSE: Four Southwest Oncology Group (SWOG) standard-dose chemotherapy protocols for multiple myeloma (MM) initiated between 1982 and 1992 were evaluated. The purpose was to clarify the predictive value of specific levels of myeloma-associated monoclonal protein reduction and time to first progression using mature data sets. PATIENTS AND METHODS: Study data on 1,555 eligible previously untreated patients with MM enrolled onto SWOG phase III trials 8229, 8624, 9028, and 9210 were used in these analyses. Six-month and 12-month landmark analyses were performed to evaluate the outcome for patients in each response category. RESULTS: The overall and event-free survivals for the four protocols combined were 33 months and 18 months, respectively. Using 6- and 12-month landmarks, the median survivals of 30 to 35 months were not different for responders (> or = 50% and > or = 75% regression) versus nonresponders in patients without disease progression before the landmarks. Conversely, at the 6- and 12-month landmarks, the median survivals for patients who had experienced disease progression were 13 and 15 months, respectively, versus a 34-month median for patients who did not experience progression. Using the Cox survival model, with response and progression considered as time-dependent covariates, survival duration was influenced more by the occurrence of progression than by the occurrence of response. CONCLUSION: The magnitude of response, as a single variable, does not predict survival duration. Patients with response and stable disease have equivalent outcome. Only patients with progressive disease have a poorer outcome. The best indicator of survival is time to first progression.

Adult↗

PubMed2002

Inhibition of cell cycle progression through specific phase by pancratistatin derivatives.

Pancratistatin derivatives, 1-O-(3-hydroxybutyryl)pancratistatin (HBP) and 1-O-(3-O-beta-D-glucopyranosylbutyryl)pancratistatin (GBP), showed strong cytostatic activity against rat embryo fibroblast 3Y1 at concentrations less than 1 microM. When the effect on cell cycle progression was examined in 3Y1 fibroblasts arrested at G0/G1 phase by serum deprivation, HBP, GBP, and pancratistatin inhibited the progression of 3Y1 fibroblasts from G0/G1 to S phase. In addition, when the effect on cell cycle progression was studied in 3Y1 fibroblasts synchronized at late G1/early S phases by treating with hydroxyurea, HBP blocked further progression through S phase, while GBP and pancratistatin did not affect the progression, but retarded it. On the other hand, when the effect of HBP and GBP on the progression was evaluated in promyelocytic leukemia HL-60RG cells synchronized at G0/G1 phase, the cells did not progress into S phase and accumulated in sub G0/G1 phase, which indicated apoptotic cells. These findings suggest that of Amaryllidaceae alkaloids, HBP blocks the progression of cell cycle at least at G0/G1 and S phases and GBP does at least at G0/G1 phase, resulting in apoptosis induction in tumor cells.

Amaryllidaceae Alkaloids↗

PubMed1988

Development of significant coronary artery lesions in areas of minimal disease. A common mechanism for coronary disease progression.

In 62 patients with coronary disease who had serial arteriograms without intervening coronary artery bypass graft (CABG) or percutaneous transluminal coronary arteriography (PTCA), progression was seen in 48 (77 percent). Progression from a normal or minimally narrowed lumen diameter to narrowing greater than or equal to 75 percent (to greater than or equal to 90 percent) in 21 patients) occurred in at least one vessel in 33 patients (69 percent) (group A, type I progression). Less striking progression and progression of initially more severe lesions was seen in 15 of 29 patients without type 1 progression (Group B) and in other vessels in 12 group A patients. Improvement in at least one vessel was seen in eight patients. There was no difference between groups A and B in the incidence of risk factors, intervening myocardial infarction, or recent unstable angina. It is concluded that progression of occlusive coronary disease occurs as commonly in areas of the coronary tree that are minimally diseased as in segments that are initially severely narrowed. Methods to stabilize the endothelium may prevent progression of coronary artery disease.

Coronary Angiography↗

PubMed1998

Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency.

Chronic renal failure is characterized by specific alterations of the lipoprotein metabolism. It has been suggested that renal dyslipoproteinemia contributes to the progression of renal dysfunction. The objective of this study was to investigate the impact of different apoB-containing lipoprotein families on the progressive decline of renal function in patients with moderately advanced chronic renal failure. As part of a larger prospective study, 44 adult nondiabetic patients with primary chronic renal disease were followed with repeated GFR measurements for an average of 2.4 (SD 1.0) yr. Patients' characteristic variables, including plasma levels of lipids, apolipoproteins (apo), and apoA- and apoB-containing lipoprotein families (LP), were determined at the beginning of the observation period. The baseline variables were prospectively related, using linear regression, to the rate of progression (deltaGFR). The patient study group had a mean GFR at baseline of 40.3 (SD 16.7) ml/min per 1.73 m2 body surface area. The average rate of progression was a yearly decline in GFR of -3.2 (SD 5.1) ml/min per 1.73 m2 body surface area. A strong association was observed between the plasma concentration of complex, triglyceride-rich apoB-containing lipoproteins (LP-Bc) and the rate of progression (r=0.43, P < 0.01), whereas there was no association between the cholesterol-rich apoB-containing lipoproteins (LP-B) and deltaGFR. The association between the levels of LP-Bc and the rate of progression was not dependent on the baseline values of GFR, BP, and the degree of proteinuria. The results of this study extend earlier observations regarding the importance of renal dyslipoproteinemia for progressive renal insufficiency. In particular, elevated levels of intact or partially metabolized triglyceride-rich apoB-containing lipoproteins of intermediate- and low-density ranges seem to promote the progression of human renal insufficiency.

Adult↗

PubMed1994

The effects of smoked marijuana on progressive-interval schedule performance in humans.

In three experiments, 8 human subjects participated in a study of the effects of smoked marijuana on progressive-interval schedule performance. A two-component chained progressive-interval fixed-interval schedule of point delivery was used. In the progressive-interval component, the interval length began at 20 s and increased either geometrically or arithmetically (by either 20 s, 40 s, 80 s, 100 s, or 160 s) on each subsequent interval. After this interval elapsed, a single button press produced the fixed-interval component, with a total of five reinforcers of varying magnitude ($0.05, $0.20, or $0.40) available on a fixed-interval 20-s schedule. After the five reinforcer deliveries, the schedule returned to the initial progressive-interval component. Several relationships were found among rates of responding, postreinforcement pauses and drug administration in the progressive-interval component: (a) Postreinforcement pauses increased as the temporal requirements of the progressive-interval schedule increased; (b) rates of responding during successive progressive-interval components rapidly decreased to low rates of responding after the first few progressions; (c) postreinforcement pauses decreased systematically as dose of smoked marijuana increased; and (d) rates of responding increased after smoking active marijuana but not after smoking placebo cigarettes. Results are discussed in the context of behavioral control and relevance to other studies that have investigated the effects of smoked marijuana on schedule performance.

Adult↗

PubMed1993

Critical aspects of initiation, promotion, and progression in multistage epidermal carcinogenesis.

Carcinogenesis in mouse skin can be divided into three distinct stages: initiation, promotion, and progression (malignant conversion). Initiation, induced by a single exposure to a genotoxic carcinogen, can result from a mutation in a single critical gene (e.g., rasHa), apparently in only a few epidermal cells. The change is irreversible. Promotion, resulting in the development of numerous benign tumors (papillomas), is accomplished by the repeated application of a nonmutagenic tumor promoter. The effects of single applications of tumor promoters are reversible since papillomas do not develop after insufficient exposure of initiated skin to promoters or when the interval between individual promoter applications is increased sufficiently. The reversibility of promotion suggests an epigenetic mechanism. Promoter treatment provides an environment that allows the selective clonal expansion of foci of initiated cells. The conversion of squamous papillomas to carcinomas (termed progression or malignant conversion) occurs spontaneously at a low frequency. The rate of progression to malignancy can be significantly increased by treatment of papilloma-bearing mice with certain genotoxic agents. These progressor agents or converting agents are likely to act via a second genetic change in papillomas already bearing the initiating mutation. Progression in the skin is characterized by genetic changes that result in several distinct changes in the levels or activity of structural proteins, growth factors, and proteases. The mechanisms involved in progression are being studied in epidermal cell culture. In order to determine the in vivo phenotype of cultured cells, a grafting system was developed in which the cells were transferred from culture to a prepared skin bed in athymic mice. Introduction of an activated v-fos oncogene into initiated cells bearing an activated rasHa gene produced cells with a carcinoma phenotype, i.e., carcinomas formed when the cells were grafted as part of reconstituted skin. Grafted keratinocytes containing the rasHa gene alone produced papillomas; with v-fos alone, normal skin formed when grafted. The rasHa/fos carcinomas showed changes in differentiation markers characteristic of chemically induced carcinomas. A cell culture assay utilizing cells initiated by the introduction of an activated rasHa oncogene was developed to study progression. After exposure of initiated cells to progressor agents under conditions in which the proliferation of the rasHa-initiated cells was suppressed, proliferating foci developed, with a good correlation of activity in the assay with activity in the progression stage in vivo. The cell culture assay provides a quantitative model to study chemically induced neoplastic progression and may be useful to identify potential progressor agents.

Animals↗

PubMed2026

Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk.

A major challenge in Alzheimer's disease (AD) research is predicting who will develop AD, how it progresses, and how to slow, prevent, or reverse progression. Here, we apply a data-driven timeline inference framework to sparse longitudinal blood metabolomics data to reconstruct AD timelines and derive individual-specific timeline progression rates. Inferred temporal locations for each metabolomics sample along the AD timeline closely track clinical severity, while timeline progression rates capture inter-individual differences in the speed of pathophysiological progression. Genome-wide association studies of timeline progression rate identify novel loci distinct from those in AD case-control studies, notably showing no effect of the major risk locus APOE. These findings support a multidimensional paradigm of AD risk in which disease potential and progression act as partially independent factors. By explicitly modeling disease dynamics, this work reveals genetic contributions not captured by traditional approaches and provides a framework for studying AD and other progressive disorders.

Journal Article↗

PubMed1999

[Radical prostatectomy in clinically localized prostatic adenocarcinoma. Factors influencing biochemical progression free survival].

MATERIAL AND METHOD: Study of biochemical progression (PSA > 0.5 ng/ml) and biochemical progression-free survival in 160 patients diagnosed with clinically localized prostate adenocarcinoma who underwent radical prostatectomy at the University Clinic in Navarra between 1988-1997. RESULTS: At the end of the study, 120 patients (75%) are alive and free of progression, 33 (20%) are alive and in progression, 3 (1.9%) died of cancer, and 4 (2.5%) died for other causes. Biochemical progression occurred in 43/160 (27%) patients. Progression is related to previous PSA, both in absolute terms and divided into greater or smaller than 15 ng/ml; to Gleason grade greater or smaller than 7 or divided into 2-4, 5-7, 8-10; to pathological stage and to urethro-vesical junction stenosis. Biochemical progression-free survival (BPFS) in the univariate study is related to PSA (the ideal prognostic cut-off value being 15 ng/ml); to Gleason, specially when divided into 2-4, 5-7, 8-10; to the pathological stage and to margins. The multivariate study evidences that the single most influential factors are PSA (divided as greater or smaller than 15 ng/ml), Gleason grade (divided into: 2-4, 5-7, 8-10) and margins involvement. There are 3 highly reliable risk groups based on PSA, Gleason and clinical stage. When these are introduced as variables in the multivariate study, they appear as the strongest predictive variables. CONCLUSIONS: The influential factors on progression-free survival are PSA (15 ng/ml being the best prognostic cut-off value), Gleason grade (divided into 2-4, 5-7, 8-10) and margins' positivity, which are the single most significant pathological factor ahead of clinical stage. Serum PSA, clinical stage and Gleason grade allow to define three reliable risk groups.

Adenocarcinoma↗

PubMed1995

Impact of pathologic extraprostatic disease on local and systemic progression following radical prostatectomy.

Fifty patients underwent radical prostatectomy for localized prostate cancer (Stages A2, B) between 1977 and 1982. Surgical specimens were examined for tumor grade and extraprostatic extension of the disease. Forty-one of the 50 patients had capsular involvement (82%), 26 (52%) positive margins and 14 (28%) seminal vesicular involvement. Six patients progressed locally, six systematically and three both. Eight patients progressed at five years and an additional seven at ten years. In all 15 progressors tumor involved the capsule yet four patients with capsular involvement alone progressed. Eleven of the 26 patients (42%) with positive margins progressed. Five of the 14 patients (37%) with seminal vesicle involvement progressed, all five had positive margins as well. None of the patients with disease confined within the capsule progressed. Gleason score for non-progressors ranged between three and nine with a median of six while for progressors it ranged between five and nine with a median of seven. Long rank test and Cox Proportional Hazard Model statistical analysis were employed among all the factors: capsular involvement, positive margins, positive seminal vesicles and grade of tumor. Positive margins was the only statistically significant factor affecting local progression of the disease in both univariate and multivariate analysis at a 95% confidence (p=0.04). All factors were statistically insignificant in affecting systemic progression (p>0.5).

Journal Article↗

PubMed2004

Progression of rheumatoid arthritis on plain radiographs judged differently by expert radiologists and rheumatologists.

OBJECTIVE: In a former study a panel of rheumatologists was used to assess which progression in radiological joint damage due to rheumatoid arthritis (RA) on hand and foot radiographs taken at one-year intervals was considered the minimally clinically important difference (MCID). We compare the judgments of the panel of rheumatologists with the judgments of 2 musculoskeletal radiologists. METHODS: Two experienced musculoskeletal radiologists evaluated independently the same hand and foot radiographs as assessed by the panel of rheumatologists. Progression was defined as important if the radiologist would state it as substantial progression in their report. Two readers, different from the radiologists and rheumatologists, independently obtained the Sharp/van der Heijde scores. Receiver operating characteristic curve analyses were performed to quantify the minimally important progression defined by the radiologists expressed in Sharp/van der Heijde change-scores. The change-score with the highest accuracy represented the minimally important progression and was compared with the MCID defined by the panel of rheumatologists for 4 different settings (early versus advanced RA and mild versus high disease activity). RESULTS: The minimally important progression defined by the radiologists was estimated at 6.5 Sharp/van der Heijde units. This was larger than the MCID defined by the panel of rheumatologists in 3 of the 4 clinical settings (3.0-4.5 units) and similar to the setting "advanced RA, mild disease activity." The panel of rheumatologists was inclined to change therapy in cases not reported as substantially progressive by the radiologists. The Sharp/van der Heijde progression scores of the radiographs on which the radiologists and rheumatologists disagreed related better with the rheumatologists' opinions. CONCLUSION: Changes that were not regarded as substantial by the radiologists were judged clinically important by the rheumatologists in 3 of the 4 clinical settings. Thus, the radiologists appeared to be reserved in judging changes as important.

Arthritis, Rheumatoid↗

PubMed2005

Depression and clinical progression in HIV-infected drug users treated with highly active antiretroviral therapy.

OBJECTIVE: To disentangle the impact of adherence from that of injecting drug status and depressive syndrome on HIV clinical progression in a cohort of highly active antiretroviral therapy (HAART)-treated HIV patients infected through drug use. DESIGN: MANIF 2000 is a French cohort of HIV-infected drug users with scheduled medical visits every 6 months. Only patients enrolled in the MANIF 2000 cohort who had a CD4 cell count >200 cells/microl at HAART initiation were selected. The follow-up period included all post-HAART initiation visits. METHODS: HIV clinical progression was defined as either AIDS-related death or reaching a CD4 level <200 cells/microl. Adherence was assessed using a self-administered questionnaire and a structured face-to-face interview. Depressive symptoms were evaluated by a Center for Epidemiologic Studies Depression Scale (CES-D) score at each visit. Cox proportional hazards model was used to calculate crude and adjusted relative hazards and 95% confidence intervals and thus identify independent predictors of clinical progression. RESULTS: Of the 305 HAART-treated patients in the cohort, 243 had CD4 cell count >200 cells/microl at HAART initiation. At the first visit after HAART initiation, median CD4 cell count was 466 cells/microl and 45% had undetectable viral load. Injecting drug users accounted for 17% of the study group. Over the follow-up period, 32 patients experienced HIV clinical progression. Probable depression was encountered in 46% of patients and non-adherence in 31% of the sample. After adjustment on baseline CD4 cell count, predictors of clinical progression were: having a higher level of cumulative non-adherence over the follow-up period [HR (95% CI)=1.2 (1.1-1.3) per 10% increase] and having a high score of depressive symptoms following HAART initiation [HR (95% CI)=5.3 (2.21-3.0)]. CONCLUSIONS: Although depressive syndrome is known to influence non-adherence behaviours that are amongst the major reasons for clinical progression, it is also a predictor of clinical progression in HIV-infected intravenous drug users on HAART, independently of non-adherence behaviours. HIV care providers should be more sensitive to depressive symptoms in order to detect them early and supply HIV patients with specific care. Further research is needed to determine whether treating depressive symptoms may improve adherence and thus delay disease progression and mortality.

Adult↗

PubMed1990

An analysis of the effect of the Zielke operation on S-shaped curves in idiopathic scoliosis. A follow-up study revealing some skeletal and soft tissue factors involved in curve progression.

This article analyzes the fate of S-shaped idiopathic spinal curves during follow-up in 18 patients having the Zielke VDS operation. The spinal radiographs were evaluated by Cobb angle, end-vertebra angles (EVAs), vertebral rotation, and by a new method using the tilt of the surgically fused spinal block in the frontal plane. Spinal growth was measured. Using the conventional criterion for Cobb angle progression, 83% of the lower curves and 50% of the upper curves progress. The use of EVAs shows that progression occurs mainly in the middle (thoracolumbar) segment of the spine. Curve progression occurs in the frontal plane without any significant change in vertebral rotation. The progression of the upper curve Cobb angle is not related to the progression of the Cobb angle of the lower curve; but it is related to 1) tilt of the spinal block, 2) growth of the spine below the block and 3) overall linear spinal growth (T1-S1). Progression of the upper EVA of the upper curve is associated with skeletal immaturity. The key features leading to curve progression after the Zielke operation appear to be spinal asymmetry in the frontal plane, linear spinal growth, and concave lumbar muscle tether (myostatic contracture). The surgical implications of the findings are outlined.

Adolescent↗

PubMedDate not supplied

Progression of coronary atherosclerosis in patients with probable familial hypercholesterolemia. Quantitative arteriographic assessment of patients in NHLBI type II study.

A computer-assisted method for quantitatively assessing progression and regression of coronary atherosclerosis has been applied, in a fully blinded fashion, to a set of 116 5-year-interval coronary arteriograms obtained between 1972 and 1981 in the National Heart, Lung, and Blood Institute (NHLBI) Type II Study. Coronary changes are described in 54 of these patients who had tendinous xanthomata and hypercholesterolemia consistent with the diagnosis of familial hypercholesterolemia. Among 468 patent lesions of all degrees of severity and among 25 total occlusions identified on the initial arteriogram, 11% progressed by the 95% confidence criterion for assessing change in percent stenosis (+/- 17%), and 1% regressed by using the same criterion. Among 54 patients, 50% had progression only, 6% had regression only, and 4% had mixed progression and regression. Because half of these patients were treated with cholestyramine, these frequencies may underestimate the natural history of their disease progression. Comparable frequencies were obtained by using the 95% confidence criterion for change in stenosis resistance (Rp ratio outside range, 0.35 to 2.9). In properly obtained arteriograms, the Rp parameter is physiologically relevant and is a sensitive index of lesion change with a high signal-to-noise ratio; we advocate its use for detection of progression and regression. Morphologic features, including luminal irregularity and ulceration, increased the likelihood of progression by 1.8- to 5-fold. Surprisingly, significant arterial flexing at the site of the lesion predicted anatomic stability. A lumen narrowed by visible thrombus was 100-fold more likely to regress than were those without it. The initial severity of stenosis correlated strongly with new total occulusion and with disease progression as assessed by Rp change. Because lesion-specific features are important determinants of lesion change, intervention trials that statistically account for the contributions of lesion morphology are likely to provide a more insightful assessment of the therapeutic benefit.

Angiography↗