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Relationship between antiphospholipid antibodies and progression of lower extremity arterial occlusive disease after lower extremity bypass operations.

PURPOSE: Antiphospholipid antibodies (APLs), which consist of anticardiolipin antibodies (ACLs) or lupus anticoagulant (LA), are associated with venous thrombosis, stroke, and cardiac events. Although they are present in many patients with lower extremity atherosclerotic occlusive disease (LEAOD), the relationship between APL and the progression of LEAOD has not been reported. A comparison of progression of LEAOD as determined with direct imaging studies in patients with and without APL forms the basis for this report. METHODS: APL+ patients (immunoglobulin M [IgM] or IgA or IgG ACL > 3 SD units above control mean or positive LA) who underwent lower extremity bypass grafting between January 1990 and June 1999 (n = 79) were compared with an APL control group (n = 68). Members of the study and control groups were similar with respect to age, procedure, sex, length of follow-up, and multiple atherosclerosis risk factors. Progression of LEAOD was determined by comparing preoperative arteriograms with postoperative imaging studies (arteriograms or duplex scanning). External iliac, common femoral, superficial femoral and popliteal arteries were graded as < 50% stenosis, > or = 50% stenosis, or occluded. Posterior tibial and anterior tibial arteries were graded as patent or occluded. Progression was defined as any increase in stenosis category. RESULTS: The mean follow-up period was 31 months for APL+ and 35 months for APL- patients (P = not significant). Progression of LEAOD occurred in 58 (73%) of 79 APL+ patients and in 25 (37%) of 68 APL- patients (P <.001). There was no difference in progression in external iliac or common femoral arteries. Differences in progression were noted in more distal arteries; APL+ patients had significantly more progression in superficial femoral (45% vs 16%, P <.01), popliteal (31% vs 12%, P <.01), posterior tibial (29% vs 13%, P <.05), and anterior tibial arteries (29% vs 14%, P <.05). Multivariate logistic regression analysis showed a significant independent association between the presence of APL and progression of LEAOD (P <.0001). CONCLUSION: In this study, the presence of APL in patients undergoing lower extremity bypass operations was a significant independent risk factor for progression of LEAOD. We conclude that this patient group should be closely monitored in the postoperative period and appears ideally suited for prospective studies of therapies to modify LEAOD progression.

Aged↗

Mean intraocular pressure and progression based on corneal thickness in primary open-angle glaucoma.

PURPOSE: The aim of this study was to evaluate the association of corneal thickness on the incidence of glaucomatous progression at individual levels of intraocular pressure. METHODS: A retrospective, noninterventional evaluation of patients with primary open-angle glaucoma who were either stable over 5 years or had glaucomatous progression before 5 years of follow-up was performed. Each patient had central thickness corneal measurements documented. RESULTS: We included 310 patients in this study. Patients with thicker (at least 0.571 mm, n = 77) and mid-range corneas (0.511-0.570 mm, n = 177) progressed in 14% (n = 11) and 18% (n = 31) of cases, respectively. The progression rate for patients with a mean pressure of less than 17 mmHg in both groups was 12%-13%. In contrast, the progression rate in patients with 18 mmHg or higher was 23% and 16% in the mid-range and thick corneal groups, respectively. In patients with thinner corneas (equal to or less than 0.510 mm, n = 56), the progression rate was 32% (n = 18). The progression rate was 60% (12 of 20) with mean pressures of at least 18 mmHg or higher, but 18% with mean pressures equal to or less than 17 mmHg. Univariant (P = 0.05), but not multivariant, analysis showed that corneal thickness was a risk factor for progression. CONCLUSIONS: This study suggests that the reduction of intraocular pressure helps to prevent progression in patients with primary open-angle glaucoma. However, for patients with thinner corneas, pressure reduction may potentially be of even greater importance to help avoid glaucomatous progression. Future study should clarify potential variables associated with thin corneas and glaucomatous progression.

Cornea↗

Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer.

We assessed the use of clinical stage, serum prostate specific antigen, DNA ploidy, proliferation, and traditional histologic findings from the biopsy to predict prostate cancer progression after radical retropubic prostatectomy. Between 1995 and 1998, 454 consecutive patients with cancer on biopsy were treated by radical retropubic prostatectomy. Preoperative serum prostate specific antigen, clinical stage, Gleason score, percentage of cores and surface area positive for cancer, perineural invasion, and DNA ploidy and MIB-1 immunostain quantitation by image analysis were evaluated in a multivariate Cox proportional hazards regression model to predict cancer progression. Cancer progression was defined as a postoperative serum prostate specific antigen level of > or = 0.4 ng/mL, local recurrence, or systemic progression. Mean follow-up was 3.4 years (range 17 days to 5.8 years). Cancer progression was observed in 73 patients with a mean time to progression of 2.1 years (range 33 days to 5.1 years). Gleason score (p <0.001), MIB-1 cancer proliferation (p = 0.008), and perineural invasion (p = 0.008) were significantly associated with progression. Patients with cancer Gleason scores of 7 and >7 had a 2.5-fold and nearly 4-fold increased risk, respectively, of cancer progression compared with patients with cancer Gleason scores of < or = 6. Patients with perineural invasion at biopsy were twice as likely to progress compared with patients without perineural invasion. Each 1-unit increase in MIB-1 on the natural logarithmic scale increased the risk of cancer progression by 64%. Cancer progression models that include serum prostate specific antigen and clinical stage may require revision to incorporate perineural invasion and MIB-1 proliferative activity in addition to Gleason score.

Adult↗

Progression of lumbosacral isthmic spondylolisthesis in adults.

STUDY DESIGN: A retrospective clinical and radiographic review of adult patients with progressive isthmic lumbosacral spondylolisthesis. OBJECTIVES: To describe the clinical presentation of adult-onset progression of isthmic spondylolisthesis and to analyze its causes. SUMMARY OF BACKGROUND DATA: Until recently, progression of lumbosacral spondylolisthesis in adults was rarely reported. On the contrary, although slip progression before skeletal maturity has been widely recorded, its occurrence in adults has been doubted. Only sporadic case reports of adult slip progression and only brief notes on the subject in clinical studies describing other aspects of spondylolisthesis have been published. METHODS: Patients with isthmic lumbosacral spondylolisthesis who had serial radiographs of the lumbar spine on which slip progression during adult life was noted were evaluated. The amount of vertebral slip was calculated in millimeters from decubitus lateral spinal radiographs. The calculation was expressed as the percentage of slipped vertebral body length. RESULTS: From 1989 to 1995, 18 patients (9 women and 9 men), ages 32 to 55 years, with documented adult isthmic slip progression were identified at the Spinal Surgery Unit of the Hadassah University Hospital. All patients reported incapacitating low back pain, accompanied in most by significant sciatica. Documented slip progression ranged from 9% to 30% (average, 14.6%), and occurred during a period of 2 to 20 years (average duration, 6.8 years). Slip progression started after the third decade of life and coincided with marked disc degeneration at the olisthetic level. Slip progression associated with disc degeneration (i.e., intervertebral space narrowing and the formation of spondylophytes and vacuum phenomenon) brought about severe clinical symptomatology related to segmental instability and spinal stenosis. Of the 18 patients in this study, 14 were treated with surgery. All these patients except 1 underwent decompression, pedicle screw fixation, and bilateral lateral fusion. One patient underwent posterolateral fusion without instrumentation. Immediate postoperative complications were observed in three patients, including two superficial wound infections and one transient foot drop. Solid fusion was obtained in 11 of the 14 patients who underwent surgery. CONCLUSIONS: The concurrent occurrence of disc degeneration at the slip level and adult slip progression explains how an asymptomatic developmental lesion, present for at least two to three decades, may become symptomatic.

Adult↗

Progression of coronary artery calcification in diabetics with and without chronic kidney disease.

BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION: Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.

Calcinosis↗

Site progression of loss of attachment over 5 years in 14- to 19-year-old adolescents.

The aims of this study were (1) to monitor the progression and patterns of progression of loss of attachment > or = 1 mm on a site basis over a 5-year period in adolescents, and (2) to relate the presence of oral deposits and inflammation to the subsequent development and progression of loss of attachment on a site basis. 167 subjects were examined at ages 14, 16 and 19 years. Loss of attachment > or = 1 mm, plaque, subgingival calculus, gingival bleeding and gingival colour change were assessed on the mesio-buccal sites of the 1st molars, 1st premolars and central incisors. Each site was treated separately in the analysis to avoid the problem of within-subject site dependence. Sites were classed as progressing, non-progressing or fluctuating according to the probing attachment level measurements at each of the 3 examinations. During the 5 years of this study, a total of 542 sites in 128 subjects progressed; 1136 sites in 162 subjects did not progress; 43 sites in 30 subjects had fluctuating attachment level measurements. Sites which subsequently progressed had significantly more plaque, subgingival calculus and gingival inflammation than non-progressing sites at the baseline examination and throughout the study (p < 0.001). Between 55-57% of the maxillary 1st molars and 46-49% of the mandibular incisors progressed. In contrast, there was no progression of loss of attachment on over 80% of the maxillary central incisors and mandibular 1st premolars.

Adolescent↗

Radiological progression and its predictive risk factors in silicosis.

OBJECTIVES: To investigate the risk factors predicting radiological progression in silicosis in a prospective cohort study of patients with silicosis who were previously exposed to silica from granite dust. METHODS: From among a total of 260 patients with silicosis contracted from granite work, 141 with available serial chest x ray films of acceptable quality taken over a period of 2 to 17 (mean 7.5) years, were selected for study. Ninety four (66.7%) had ended exposure 5 or more years previously (mean 10.1 years, maximum 28 years). Radiological progression was assessed by paired comparison of the initial and most recent radiographs, with two or more steps of increase in profusion of small opacities according to the 12 point scale of the International Labour Organisation (ILO) classification of radiographs of pneumoconiosis, taken from the majority reading by a panel of three independent readers. RESULTS: Overall, 37% of patients with silicosis had radiological evidence of progression. From the initial radiographs, 24 (31.6%) of those with radiological profusion category 1, 15 (37.5%) of those with radiological profusion category 2, and 13 (52%) of those with complicated silicosis (including all seven with category 3 profusion of small opacities) showed radiological progression. As expected, progression was more likely to be found after longer periods of follow up (the interval between the two chest x ray films) with a 20% increased odds of progression for every additional year of follow up. After adjustment for varying intervals of follow up, the probability of radiological progression was found to be significant if large opacities were present in the initial chest x ray film. Progression was also less likely to be found among those who had ended exposure to silica longer ago, although the result was of borderline significance (p=0.07). Tuberculosis was also associated with increased likelihood of progression (borderline significance). CONCLUSIONS: There is a high probability of radiological progression in silicosis after high levels of exposure to granite dust among workers who were followed up for up to 17 years. A significant risk factor is the extent of radiological opacities in the initial chest x ray film. The probability of progression is also likely to be reduced with longer periods after the end of exposure.

Adolescent↗

Progression of unilateral moyamoya disease: A clinical series.

BACKGROUND: The natural history of unilateral moyamoya disease (MMD) in adult patients is not clearly described in the literature. We present a series of 18 patients with unilateral MMD and analyze the risk factors for progression to bilateral disease. METHODS: A retrospective review of 157 MMD patients treated at Stanford University Medical Center from 1991 to 2005 identified 28 patients with unilateral MMD (defined as none, equivocal or mild involvement on the contralateral side). RESULTS: Eighteen patients (5 males and 13 females) were identified with unilateral MMD and angiographic follow-up of > or =5 months. Mean radiologic follow-up (+/- standard error of the mean) was 19.3 +/- 3.4 months and mean clinical follow-up was 24.5 +/- 3.7 months. Five patients had childhood onset MMD and 13 patients had adult onset disease. Angiographic progression from unilateral to bilateral disease was seen in 7 patients (38.9%) at a mean follow-up of 12.7 +/- 2.4 months. Four of the 7 patients had significant clinical and radiologic progression requiring surgical intervention. Five of 7 patients that progressed had adult onset MMD. The presence of equivocal or mild stenotic changes of the contralateral anterior cerebral artery (ACA), middle cerebral artery (MCA) or internal carotid artery (ICA) was an important predictor of progression (p < 0.01); 6 of 8 patients (75%) with equivocal or mild contralateral disease progressed, whereas only 1 of 10 patients (10.0%) with no initial contralateral disease progressed to bilateral MMD. One patient had mild or equivocal MCA, ICA and ACA stenosis at the time of initial diagnosis and this patient progressed. CONCLUSIONS: Contralateral progression in the adult form occurs more commonly than previously reported. The presence of minor changes in the contralateral ACA, intracranial ICA and MCA is an important predictor of increased risk of progression. Patients with a completely normal angiogram on the contralateral side have a very low risk of progression.

Adolescent↗

Process of progression of coronary artery lesions from mild or moderate stenosis to moderate or severe stenosis: A study based on four serial coronary arteriograms per year.

BACKGROUND: The process of progression in coronary artery disease is unknown. METHODS AND RESULTS: The subjects were 36 patients with 36 objective vessels with clinically significant progression of coronary artery disease (>/=15% per year) in whom 4 serial coronary arteriograms (CAGs) were performed at intervals of approximately 4 months in a 1-year period. The degree of progression of percent stenosis between each of 2 serial CAGs was classified as marked (M: >/=15%), slight (S: 5% to 14%), and no progression (N: <5%). From the pattern of progression, the 36 vessels were classified as 14 type 1 vessels with marked progression (N-->N-->M in 13 vessels and S-->S-->M in 1 vessel) and 22 type 2 vessels without marked progression (S-->S-->S in 18 vessels, N-->S-->S in 4). Percent stenosis at the first, second, third, and final CAGs was 44+/-14%, 46+/-13%, 46+/-13%, and 88+/-10% (P<0.05 versus first CAG) in type 1 vessels and 44+/-11%, 50+/-9%, 59+/-9%, and 67+/-9% in type 2 vessels (P<0.05 for second, third, and final CAGs versus first CAG). Type 1 vessels featured the sudden appearance of severe stenosis due to marked progression, angina pectoris, or myocardial infarction (71%) and Ambrose type II eccentric lesions indicating plaque rupture or thrombi (57%). Type 2 vessels featured continuous slight progression of stenosis with smooth vessel walls; angina pectoris (14%) occurred when the percent stenosis reached a severe level. An increase in serum C-reactive protein was observed only in the type 2 vessel group, which suggests a relation between continuous slight progression and inflammatory change. CONCLUSIONS: Two types of stenosis progression provide a new insight into the mechanism of coronary artery disease.

Aged↗

Rapid angiographic progression of coronary artery disease in patients with angina pectoris. The role of complex stenosis morphology.

BACKGROUND: Rapid disease progression commonly underlies acute coronary events, and "complex" stenosis morphology may play a role in this phenomenon. METHODS AND RESULTS: We studied the role of complex stenosis morphology in rapid disease progression in 94 consecutive patients awaiting routine coronary angioplasty. Coronary arteriography was repeated at 8 +/- 3 months' follow-up, immediately preceding angioplasty (68 patients) or after an acute coronary event (26 patients). Disease progression of 217 stenoses, of which 79 (36%) were "complex" and 138 (64%) were "smooth," was assessed by computerized angiography. At presentation, 63 patients had stable angina pectoris and 31 had unstable angina that settled rapidly with medical therapy. At follow-up, 23 patients (24%) had progression of preexisting stenoses and 71 (76%) had no progression. Patients with progression were younger (55 +/- 12 years) than those without (58 +/- 9 years) but did not differ with regard to risk factors, previous myocardial infarction, or severity and extent of coronary disease. Twenty-three lesions (11%) progressed, 15 to total occlusion (11 complex and 4 smooth; 65%). Progression occurred in 17 of the 79 complex stenoses (22%) and in 6 of the 138 smooth lesions (4%) (P = .002). Mean stenosis diameter reduction was also significantly greater in complex than in smooth lesions (11.6% versus 3.9% change; P < .001). Acute coronary events occurred in 57% of patients with progression compared with 18% of those without progression (P < .001) and were more frequent in patients who presented with unstable angina (P = .002). CONCLUSIONS: Rapid stenosis progression is not uncommon, and complex stenoses are at risk more than smooth lesions.

Angina Pectoris↗

Progression of atherosclerosis in patients with peripheral arterial disease as a function of angiotensin-converting enzyme gene insertion/deletion polymorphism.

Angiotensin-converting enzyme insertion/deletion (I/D) gene polymorphism plays a role in determining the inter-individual variability of circulating angiotensin-converting enzyme activity and intracellular angiotensin-converting enzyme levels. Angiotensin-converting enzyme, as a key enzyme in the renin-angiotensin system, catalyzes the activation of the vasoconstricting and proliferation-stimulating angiotensin II and breaks down the vasodilatory peptide bradykinin. It is assumed that the excess supply of angiotensin II (due to the deletion polymorphism of the angiotensin-converting enzyme gene) contributes to endothelial dysfunction and in this way promotes the onset and progression of atherosclerosis. The aim of this study was to test whether the presence of the deletion allele of the angiotensin-converting enzyme gene predisposes a more rapid systemic progression of a preexisting peripheral arterial disease. To this end, the course of disease was surveyed for an average of 5 years in 97 patients who were angiotensin-converting enzyme gene-typed and suffered from a stable stage II peripheral arterial disease according to Fontaine. These patients did not suffer from an additional coronary artery disease, a cerebrovascular disease, or other serious illness. A local progression in the periphery or a systemic progression in the coronary or cerebrovascular areas was regarded as study endpoints. Of the patients, 49.5% showed an atherosclerosis progression during the surveillance period. With II-carriers, a progression was registered in 42.1% and with DD carriers, progression was seen in 59.4%. D/I allele frequencies were seen in patients with progression at a level of 0.60/0.40 vs 0.55/0.45 for patients without progression. The average duration of disease in stable stage II (before progression appeared) amounted to 108 +/- 14 months for II carriers, 88 +/- 8 months for ID carriers, and 92 +/- 11 months for DD carriers (p = 0.21). Based on these findings, the deletion polymorphism of the angiotensin-converting enzyme gene is not an independent risk factor for progression of atherosclerosis in patients with peripheral arterial disease.

Arteries↗

Progression of ossification of the posterior longitudinal ligament following en bloc cervical laminoplasty.

BACKGROUND: Ossification of the posterior longitudinal ligament often causes compressive myelopathy. Ossification is a progressive disease, and it has been reported that the area of ossification increases after decompressive surgery. However, it is uncertain how the progression of ossification affects the long-term outcome after cervical laminoplasty. This study was performed to clarify the relationship between the progression of ossification of the posterior longitudinal ligament and the clinical results following en bloc cervical laminoplasty. METHODS: Forty-five patients who were followed for more than ten years after laminoplasty participated in this study. Radiographs and tomograms of the cervical spine of each patient were made before and after the operation and at the time of the latest follow-up. The extent of ossification in the longitudinal and sagittal axes was evaluated. Neurological function was graded with use of the Japanese Orthopaedic Association scoring system. The relationship between the progression of ossification and the score-based rate of recovery was analyzed. RESULTS: Thirty-three (73%) of the patients had progression of ossification of the posterior longitudinal ligament after laminoplasty. Progression was frequent in patients with the mixed type of ossification and in those with the continuous type, whereas it was rare in patients with the segmental type. The patients with progression of the ossification were significantly younger than those without progression (p = 0.018). The Japanese Orthopaedic Association score improved rapidly within one year and continued to improve up to five years after surgery. The score tended to decrease thereafter. For thirteen patients, the score had worsened at the time of the latest follow-up. Three patients had neurological deterioration following an increase in the thickness of the ossification. CONCLUSIONS: Progression of ossification of the posterior longitudinal ligament was often observed during the long-term follow-up period after laminoplasty. Young patients with mixed and continuous types of ossification had the greatest risk for progression. Preventive measures, such as the use of a wider laminar opening during the laminoplasty, should be considered for patients who are at risk for progression of ossification.

Adult↗

The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging.

The natural history of progression from normal glucose tolerance (NGT) to impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes is not well defined. We studied this progression using biennial oral glucose tolerance tests performed in the Baltimore Longitudinal Study of Aging and survival analysis to assess progression from NGT to abnormal fasting plasma glucose (FPG; > or =6.1 mmol/l), abnormal 2-h plasma glucose (2hPG; > or =7.8 mmol/l), IFG (FPG 6.1-6.9 mmol/l, 2hPG < or =7.8 mmol/l), and IGT (FPG <6.1 mmol/l, 2hPG 7.8-11.0 mmol/l), and from IFG-IGT to diabetes (FPG > or =7.0 mmol/l or 2hPG > or =11.1 mmol/l). At baseline, the 815 subjects had a mean age of 57 years, 35% were women, and 60% had NGT. Of the 488 subjects with NGT, over half were followed for at least 10 years. By 10 years, 14% had progressed to abnormal FPG and 48% to abnormal 2hPG. Of the 267 subjects who progressed to IFG-IGT, 216 had additional follow-up. By 10 years, 8% of these progressed to diabetes by FPG whereas 27% progressed by 2hPG. In subsidiary analyses, we defined "abnormal" FPG as > or =5.55 mmol/l and "diabetic" FPG as > or =6.1 mmol/l, making the baseline prevalence of IFG similar to that of IGT. By these criteria, 43% progressed to abnormal FPG and 43% to abnormal 2hPG by 10 years of follow-up; among subjects developing impaired FPG or 2hPG, 22% progressed to diabetes by FPG whereas 17% progressed by 2hPG at 10 years. Nonetheless, 42% of subjects developing abnormal FPG did not develop abnormal 2hPG, and vice versa. We conclude that, although phenotypic differences in rates of progression are partly a function of diagnostic thresholds, fasting and postchallenge hyperglycemia may represent phenotypes with distinct natural histories in the evolution of type 2 diabetes.

Aged↗

Prediction of curve progression in a goat scoliosis model.

OBJECTIVES: Currently, prediction of progression in scoliosis is accomplished by analysis of several factors, which provide only a broad percentage chance, rather than an accurate risk assessment, of deformity progression. A model for prediction of scoliosis progression was investigated using an experimental scoliosis: A goat model was used to predict curve progression based on the percentage of vertebral body wedging in the region of maximal deformity. METHODS: Structural, lordoscoliotic curves of significant magnitude (> or = 30 degrees) convex to the right in the thoracic spine were created in 15 immature goats using a rigid posterior asymmetric tether in combination with convex rib resection and concave rib tethering. At 12 weeks, all posterior tethers were removed, and the goats were observed for an additional 4-week period. Serial radiographs were used to document progression (defined as > or = 5 degrees) and vertebral body wedging within the maximal scoliotic deformity. RESULTS: During the additional 4-week observation period following removal of the tether, seven goats developed progressive curves (mean progression: +10.1 degrees, range: +6 degrees to +17 degrees) and eight goats developed nonprogressive curves (mean: -1.6 degrees, range: -8 degrees to +4 degrees). At the beginning of the observation period, the percentage of vertebral body wedging was 60.4% versus 50.2% in the progressive versus nonprogressive groups (P = 0.002). Thus, at 55.3% vertebral body wedging, prediction of curve progression was possible for 85% of progressors and 88% of nonprogressors. CONCLUSIONS: Prediction of curve progression is often difficult when based on skeletal maturity and curve magnitude alone. In an immature goat scoliosis model, however, in which these two factors are relatively well controlled, curve progression can be predicted based on the percentage of vertebral body wedging in the region of maximal deformity.

Animals↗

Effects of cyclic flexion of coronary arteries on progression of atherosclerosis.

The purpose of this investigation was to test the hypothesis that cyclic flexion of the coronary arteries contributes to the progression of atherosclerotic plaques. Coronary arteriograms were evaluated in 33 unselected patients who underwent 2 studies over a period of 25 +/- 16 months (mean +/- SD). Among the 33 patients, 103 plaques were identified. Plaques that showed progression were compared with plaques that showed no progression. The angle of flexion that occurred during systole at the site of the plaque was measured on the first arteriogram. In comparing progression versus no progression, the interval between arteriograms was 29 +/- 18 versus 23 +/- 14 months (p = NS) and percent stenosis at the first arteriogram was 42 +/- 28 versus 45 +/- 19% (p = NS). Percent stenosis at the time of the second arteriogram among plaques that progressed was 78 +/- 21%, and by definition, it remained 45 +/- 19% among those that did not progress. Among arteries with plaques that showed a progression of stenosis, the angle of flexion during systole was 19 +/- 13 degrees versus 9 +/- 15 degrees among arteries with plaques that did not progress (p < 0.01). Linear regression showed that the correlation of the angle of flexion with percent change of stenosis was relatively low (r = 0.32) but statistically significant (p < 0.005). Mathematic modeling of flexible and stiff plaques showed stresses approximately 1.5 to 1.9 times greater with 20 degrees than with 10 degrees flexion. Stresses due to flexion were usually greatest proximal and distal to the plaque along the subendothelial layer of the inner wall of the curved vessel. Data show that the angle of cyclic flexion, and consequently the stresses due to cyclic flexion of the artery were greatest in the region of plaques that progressed over the period of observation. Such stresses may have contributed to tissue damage of fatigue resulting in a more rapid progression of the atheromatous plaques.

Aged↗

A longitudinal analysis from bite-wing radiographs of the rate of progression of approximal carious lesions through human dental enamel.

Four to ten years of serial bite-wing radiographs from over 700 children from five groups, three in Sweden and two in the U.S., were interpreted. By analysing changes in the depth of unfilled lesions over time, the mean time and probability distribution for the time a lesion remains in both the outer half and inner half of the enamel were estimated. The procedure incorporated information on filled lesions and non-progressing lesions and thus minimized bias that results in overestimation of the progression rate. In primary teeth, in both the U.S. and Swedish groups, it took on average 12 months for a lesion to progress through the outer half of the enamel and on average 10-12 months for a lesion to progress through the inner half. In newly-erupted first permanent molars, it took 21-23 months for a lesion to progress through the outer half of the enamel and between 19 (U.S. data) and 28 months (Swedish data) for progression through the inner half. In older adolescents in the two Swedish groups, progression was slower: 38-41 months through the outer-half and 47-56 months through the inner-half. In older U.S. adolescents, progression appeared to be more rapid: 16 months through the outer half of the enamel and 27 months through the inner half. The duration of time a lesion remains in different halves of the enamel could be approximated by a piecewise exponential or exponential probability distribution, which exhibits extreme variability. Assuming duration in each half of the enamel follows an exponential distribution with a mean of 2 yr, about 10 per cent of new lesions will progress through the enamel in one year and 25 per cent in two years. However, over 40 per cent of the lesions will not have progressed in 4 yr. There were no consistent differences in the rate of progression by sex, between upper and lower dentitions, for premolars versus molars, or between high and low-risk individuals.

Adolescent↗

The effect of biological effective dose on time to symptom progression in metastatic renal cell carcinoma.

AIMS: Renal cell carcinoma is commonly thought to be a radioresistant malignancy. Retrospective studies report conflicting results on the effect of radiotherapy dose escalation on response and time to progression in symptomatic metastatic disease; studies using the linear quadratic model have used alpha/beta ratios that are inappropriate for slow growing tumours. We aim to describe our experience with palliative radiotherapy in this context, relating Biological Effective Dose to outcome. MATERIALS AND METHODS: From December 1995 to April 2001, 143 independent palliative radiotherapy treatments were delivered to 78 patients in a single institution. Retrospective data was obtained on the radiotherapy schedule used, symptom response and time to symptom progression. The biological effective dose (BED) was calculated using alpha/beta ratios of 3 and 7 Gy (BED3 and BED7). The Log-Rank test was used to assess any differences in time to progression, and the Cox Proportional Hazards analysis to determine prognostic factors of time to progression. RESULTS: Overall symptomatic response rate was 73%, with most responses being partial (67%). Forty-three (38%) patients had symptomatic progression after a median follow-up of 425 days. BED (BED3 or BED7) was not significantly different across response types (complete, partial or no response; P=0.90 and 0.88, respectively) and was not predictive for time to symptomatic progression (P=0.99 for BED3 and P=0.70 for BED7). Patients with bone metastases received less total dose (P=0.001), less BED (BED3, P=0.0013, and BED7, P=0.0005) and had a significantly longer time to progression than other sites of metastases (hazard ratio (HR) 0.4; 95% confidence interval (CI) 0.2-0.7; P=0.004). Initial treatment with interferon-alpha alone in patients presenting with metastatic disease, before palliative radiotherapy, was also associated with a shorter time to symptom progression (HR 4.6; 95% CI 1.5-14.1; P=0.007). On removal of these criteria, brain metastases became a significant predictor of progression time, with an HR of 2.5 (95% CI 1.0-5.9; P=0.05), showing an increased risk of progression with brain metastases compared with metastases elsewhere. Time from primary diagnosis to development of metastatic disease was not predictive of time to symptom progression (P=0.29). CONCLUSION: Despite the widespread assumption that renal cell carcinoma is radioresistant, retrospective assessment showed high response rates to palliative radiotherapy. On the basis of our data, higher BED does not seem to be a predictor of response or of duration of response in the palliative treatment of renal cell carcinoma. Palliation of bone pain seems to be particularly durable compared with the palliation of symptoms at other sites of metastases. A trend for shorter duration of palliative effect of whole-brain radiotherapy was noted.

Adult↗

Continued drug use and other cofactors for progression to AIDS among injecting drug users.

OBJECTIVE: To evaluate the effects of continued drug use and other cofactors on progression to AIDS among HIV-infected injecting drug users. DESIGN: A prospective study. SETTING: The Muirhouse Medical Group in Edinburgh, Scotland, UK. SUBJECTS: A total of 156 HIV-infected injecting drug users. MAIN OUTCOME MEASURES: Progression to AIDS and low absolute CD4 counts. RESULTS: Of this group, 48% will have progressed to AIDS 10 years after seroconversion. Age and low absolute T4 counts had a significant effect on progression to AIDS, with older patients progressing more rapidly. Sex had no significant effects on progression. Absolute CD4+ counts and the CD4:CD8 ratio were significant predictors of progression among the group. Concurrent heroin injecting increased the risk of progression to AIDS. No significant effects were observed for use of other drugs. CONCLUSIONS: Our findings suggest that continued drug use may have an accelerating effect on progression to AIDS. Age also had an accelerating effect on progression, but sex had no significant effects. In general, the study group did not appear to progress at a different rate from other similar groups of HIV-infected individuals, despite the fact that this was a relatively young cohort. These data were based on accurate estimates of seroconversion dates.

Acquired Immunodeficiency Syndrome↗