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PubMed2000

Temporal variations in myopia progression in Singaporean children within an academic year.

PURPOSE: Excessive nearwork is believed to be associated with myopia development and progression. To investigate this further, we studied refractive error changes and their correlation with nearwork in a cohort of grade school children in Singapore. METHODS: Cycloplegic autorefraction was performed 5 times over 10 months on 168 children aged 7, 9, and 12 years who were further divided into myopic and nonmyopic subgroups based in their initial refractive errors. Information about nearwork was obtained through diaries filled out over 24 h at the commencement of the study. RESULTS: Myopia progression was high (overall mean: -0.87 D per year) and largely linear throughout the year, but significantly higher rates were seen after the final school examinations in 7-year-old myopes and nonmyopes. Overall, myopic groups exhibited higher progression rates than nonmyopic groups, although 33.6% of subjects from the latter groups had become myopic by the end of the study. Nearwork scores derived from the diaries were generally not well correlated with overall myopia progression. CONCLUSIONS: The tendency for myopia progression rates to increase after the final school examinations in 7-year-olds is interpreted as a delayed effect of the intense nearwork associated with preparing for them. The timing of nearwork-diary data collection at the beginning of the study could be responsible for the poor correlation between these data and overall myopia progression rates.

Child↗
PubMed2000

Factors related to the progression of myopia in Singaporean children.

PURPOSE: To examine the possible factors related to the progression of myopia in Singapore children. METHODS: One hundred fifty-three Singapore children aged 6 to 12 years were recruited to participate in a concurrent cohort study of the risk factors for the progression of myopia. Socioeconomic status, outdoor activity, and near-work activity were documented in a face-to-face clinic interview. The changes in cycloplegic subjective refraction and autorefraction were ascertained with the use of a Nidek ARK 900 over a 2-year period. RESULTS: The average rate of progression of myopia as measured by subjective refraction was -0.59 D per year (95% confidence interval -0.52, -0.66). Younger children and children who were more myopic at the beginning (refractive error worse than -2.0 D) of the study had higher myopia progression rates. CONCLUSIONS: Myopia progression was faster for younger children and for children who had more severe myopia at baseline. Socioeconomic status and near-work activity were not related to myopia progression.

Child↗
PubMed2002

Is Cobb angle progression a good indicator in adolescent idiopathic scoliosis?

STUDY DESIGN: A retrospective follow-up study of spine geometry after posterior instrumentation and fusion for adolescent idiopathic scoliosis (AIS). OBJECTIVES: To evaluate 1) if Cobb angle progression is a reliable indicator of the crankshaft phenomenon; 2) if significant growth of the spine can occur after surgery without the development of a crankshaft phenomenon? SUMMARY OF BACKGROUND DATA: Anterior fusion of the spine is often recommended for skeletally immature scoliotic patients to avoid the risk of a crankshaft phenomenon, a long-term loss of curve correction caused by residual growth of the spine combined with the constraints of a posterior fusion. The crankshaft phenomenon is usually assessed indirectly by documenting progression of the Cobb angle on frontal radiographs. Thus far, no study has directly measured the three-dimensional growth of the spine after surgery in AIS. METHODS: Cobb angle, spine length and spine height were obtained from three-dimensional radiographic reconstructions of the spine in 48 adolescent scoliotic patients undergoing posterior instrumentation and fusion. Measurements were done before surgery, after surgery and at skeletal maturity. A significant growth of the spine was defined as a > or = 10 mm increase in spine length, while a significant curve progression was defined as a > or = 10 degrees increase in Cobb angle at skeletal maturity. RESULTS: In the majority of patients (56%), there was no significant change in spinal length or in Cobb angle measurements at an average 2.4 years post surgery. A crankshaft phenomenon was detected in 6 patients (12%) for which significant increases both in spinal length and Cobb angle measurement were found. Significant curve progression without any change in spine length was noted in 9 patients (19%) while an increase in spine length with no evidence of curve progression was present in 6 patients at last follow-up. CONCLUSION: Spinal growth as indicated by an increase in spinal length can be measured in a significant proportion of adolescents with idiopathic scoliosis after posterior instrumentation and fusion. Some of these study participants will develop a crankshaft phenomenon but Cobb angle progression is not a reliable indicator of this complication, since it may occur without any detectable growth of the spine.

Adolescent↗
PubMed2002

Platelet calmodulin levels in adolescent idiopathic scoliosis: do the levels correlate with curve progression and severity?

STUDY DESIGN: This ongoing longitudinal study evaluates simultaneous radiographic and platelet calmodulin determinations for patients with idiopathic scoliosis who are skeletally immature. OBJECTIVES: To determine whether platelet calmodulin levels correlate with curve progression and severity. SUMMARY OF BACKGROUND DATA: A previous study based on a single calmodulin determination and a single radiograph identified higher calmodulin levels in progressive curves and in higher magnitude curves. A longitudinal study was needed to demonstrate the relation of calmodulin to curve changes for individual patients over time during the growth period. METHODS: In this study, 55 patients with idiopathic scoliosis of varying types and severity were followed longitudinally with serial radiographs and platelet calmodulin determinations. A Risser sign was recorded for each radiograph at each visit. RESULTS: Calmodulin levels increased in all the patients with progressive curves (13/13), remained stable in 73% of the patients with nonprogressive curves (11/15), and were higher generally in curves greater than 30 degrees and double structural curves. Calmodulin levels usually decreased in patients undergoing brace treatment (14/17) or spine fusion (9/10). CONCLUSIONS: It appears that platelet calmodulin levels correlate closely with curve progression and stabilization by bracing or spine fusion. Correlation with nonprogressive curves was not as consistent, with 27% noncorrelation. Longer follow-up evaluation and enrollment of additional patients will be necessary to determine whether calmodulin may serve as a biochemical marker of curve progression and to help identify stable and progressive curves.

Adolescent↗
PubMed2002

Cervical kyphosis: predictive factors for progression of kyphosis and myelopathy.

STUDY DESIGN: A retrospective study of 13 patients with cervical kyphosis. The authors propose new methods of measuring spinal cord compression and predicting the progression of kyphosis. OBJECTIVES: To ascertain predictive factors for progression of cervical kyphosis and myelopathy. SUMMARY OF BACKGROUND DATA: Cervical kyphosis may be congenital, result from decompression surgery, or occur as a posttraumatic deformity. Although there is the potential for progressive deformity and the development of myelopathy in all these situations, there are few previous reports of predictive factors for progression of cervical kyphosis and myelopathy in patients with cervical kyphosis. METHODS: The authors studied radiographs and magnetic resonance imaging scans of 13 patients with cervical kyphosis, including 9 who had been operated on and had postsurgical secondary kyphosis, and 4 with idiopathic kyphosis without any of the above causes. Compression of the spinal cord at the apex of the cervical kyphosis was evaluated by magnetic resonance imaging of the ratio between the anteroposterior diameter of the medulla-pons junction and the spinal cord at the apex. RESULTS: The mean ratio between the anteroposterior diameter of the medulla-pons junction and the spinal cord at the apex in five patients in whom myelopathy did not develop was 0.37, and was 0.21 in the patients in whom myelopathy developed. Progression of cervical kyphosis was associated with osteophyte formation at the anterior aspect of the vertebral body. CONCLUSION: A ratio below 0.3 between the anteroposterior diameter of the medulla-pons junction and the spinal cord at the apex was a risk factor for cervical myelopathy. One of the most predictable risk factors of progression of the cervical kyphosis was osteophyte formation at the anterior aspect of the vertebral body.

Adolescent↗
PubMed2002

Radiographic markers in spondyloptosis: implications for spondylolisthesis progression.

STUDY DESIGN: Radiographic analysis of spinopelvic morphology and posterior element dysplasia in spondyloptosis. SUMMARY OF BACKGROUND DATA: Spondylolisthesis treatment protocols are based on age, symptomatology, and slippage degree. Spinopelvic morphology and dysplasia can determine progression. Frequency of two denominators of high-grade spondylolisthesis-degree of dysplasia and spinopelvic morphology-is unknown. OBJECTIVES: To determine common radiographic denominators of spondyloptosis-degree of posterior bony hook dysplasia and spinopelvic morphology-as prognostic factors for spondylolisthesis progression. METHODS: Patients with spondyloptosis were reviewed. Bony dysplasia at lumbosacral junction was graded. Pelvic incidence and sacral kyphosis were measured. RESULTS: A total of 53 patients had a mean sacral kyphosis of 56 degrees and pelvic incidence of 76 degrees; 62% of patients had posterior element dysplasia. CONCLUSION: Prognostic factors for spondylolisthesis progression, such as percent of slippage, do not identify lower-grade slips at risk for progression. Progression is linked to increased shear stress across the lumbosacral junction and inability to resist it. Increased stress is related to increased verticality of the lumbosacral joint, which is individually predetermined by pelvic incidence and sacral anatomy. Pelvic incidence is fundamental in determining sagittal spine curvature required for economic spinopelvic balance. Pelvic incidence is independent of adaptive changes in higher-grade spondylolisthesis. Pelvic incidence in our spondyloptosis series (76 degrees) is higher than in normal (48.2-53.2 degrees ) and low-grade spondylolisthesis (64.5 degrees). Posterior element dysplasia decreases mechanical resistance to lumbosacral shear stress. Incidence of dysplasia in our series (62%) is higher than that reported in low-grade spondylolisthesis. Analysis of pelvic incidence and posterior element dysplasia may aid in estimation of risk for progression of spondylolisthesis.

Adolescent↗
PubMed2001

The value of immune modulating parameters in predicting the progression from peritonitis to septic shock.

Intra-abdominal infection is one of the major causes of septic shock and multiple organ failure. To date, what causes the disease's progression remains unclear and therefore the relevance of immune modulating therapies remains speculative. The primary outcome measure of this study was to investigate immune modulating mediators at the onset of peritonitis before the development of subsequent septic shock. The secondary outcome measure was to investigate the usefulness of these immune parameters in predicting progression from peritonitis to septic shock. Fifty-eight peritonitis patients were included in this study: 14 patients subsequently developed septic shock. All patients were examined on "diagnosis of peritonitis" (<4 h within establishment of diagnosis), during "early septic shock" (<12 h following the onset of septic shock), and once again during "late septic shock" (within 72-98 h following the onset of septic shock). The immune modulating parameters tumor necrosis factor-alpha (TNF-alpha), the soluble TNF-alpha receptors I and II (sTNF-alpha RI and sTNF-alpha RII), interleukines (IL) -1beta, -6, -8, and -10, and the adhesions molecules endothelial-leukocyte-adhesion-molecule (E-Selectin), intercellular-adhesion-molecule-1 (ICAM-1), and vascular-adhesion-molecule-1 (VCAM-1), in addition to nitrate and nitrite, were determined. In the peritonitis group with subsequent septic shock, TNF-alpha, sTNF-alpha RI + RII IL-1beta, IL-8, IL-10, and nitrate were significantly increased before the onset of septic shock. TNF-alpha had an area under the receiver operating characteristics curve (AUC) of 0.84 and was reliable in predicting the progression from peritonitis to septic shock. The AUC of the other immune modulating parameters, despite being significantly elevated, ranged from 0.71 to 0.76. The AUC of the conventional laboratory markers such as leukocytes and C-reactive protein ranged from 0.64 to 0.68. In peritonitis that progressed to septic shock, an early immune response had already occurred before the onset of septic shock. The progression was best predicted by TNF-alpha. Therefore, mediator therapy might be considered in high-risk peritonitis patients who show an exaggerated immune response before the progression to septic shock.

Adult↗
PubMed2003

Anaemia as a risk factor for the progression of chronic kidney disease.

PURPOSE OF REVIEW: About a dozen controlled clinical trials examined the effect of anaemia correction on the progression of chronic kidney disease. None of these studies fulfilled the stringent criteria of a randomized controlled trial as suggested by the CONSORT statement, yet evidence emerged that anaemia sustains mitogenic and fibrogenic stimuli by lowering local partial oxygen tension. This review addresses the question of why and how anaemia could possibly enhance the progression of chronic kidney disease, and summarizes relevant clinical trials. RECENT FINDINGS: The discovery of hypoxia-inducible factor, a transcription factor stabilized under hypoxic conditions, with DNA-binding properties towards about 50 target genes including erythropoietin, has largely encouraged the hypothesis that tissue hypoxia may serve as another common mechanism for the progression of chronic kidney disease besides hypertension or proteinuria. In addition, anaemia-mediated alterations of renal sympathetic nerve activity and anaemia-related increments of oxidative stress may contribute to a progressive nephron loss. Conclusive evidence from clinical trials is scarce. SUMMARY: Pathophysiological concepts suggest some impact of anaemia on the progression of chronic kidney disease. The urge for more sound clinical intervention trials is met by the ongoing ECAP study (Effect of early Correction of Anaemia on the Progression of chronic kidney disease).

Anemia↗
PubMed1998

Disease progression in a cohort of infants with vertically acquired HIV infection observed from birth: the Women and Infants Transmission Study (WITS).

BACKGROUND: The Women and Infants Transmission Study is an ongoing prospective cohort study of HIV-infected pregnant women and their infants. We used the 1994 U.S. Centers for Disease Control and Prevention (CDC) classification system for HIV infection in children to describe HIV disease progression in 128 HIV-infected children, and examined maternal and infant characteristics associated with disease course. METHODS: The Kaplan-Meier method was used to calculate probabilities of entry into CDC clinical classes A, B, and C (mild, moderate, and severe HIV disease); CDC immunologic stages 2 and 3; and death. Relative risks of progression for selected predictor events were estimated using the Cox proportional hazards model. RESULTS: With a median 24 months of follow-up, the median ages at entry into clinical classes A, B and C were 5, 11, and 48 months, respectively. Increased risk of progression to class C was seen in infants who had: onset of class B events (p < .001); progression to immunologic stage 2 (p < .001) or 3 (p < .001); early culture positivity (in first 48 hours, p < .01; in first 7 days, p = .03); and early appearance (within the first 3 months of life) of lymphadenopathy, hepatomegaly, or splenomegaly (p < .001). CONCLUSIONS: Reaching specific clinical or immunologic stages were strong predictors of progression to AIDS or death. Early onset of clinical signs (onset of lymphadenopathy, hepatomegaly, or splenomegaly < or =3 months of age), and early culture positivity (within the first 48 hours or within the first week of life), defined the infant with highest risk of disease progression.

Cohort Studies↗
PubMed2004

Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial.

PURPOSE OF REVIEW: This review summarizes factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of treatment. EMGT randomized patients with early glaucoma either to argon laser trabeculoplasty plus betaxolol (n = 129) or to no immediate treatment (n = 126) and followed them every 3 months. RECENT FINDINGS: Treated patients had delayed progression, as compared with controls. In Cox regression, EMGT treatment halved the risk of progression (hazard ratio = 0.50; 95% confidence interval: 0.35, 0.71). Risk decreased about 10% with each millimeter mercury of intraocular pressure (IOP) reduction from baseline; the higher (or lower) the IOP at follow-up, the higher (or lower) the risk. Baseline factors increasing progression were higher IOP, exfoliation, bilateral disease, worse perimetric mean deviation and older age; frequent disc hemorrhages at follow-up also increased risk. SUMMARY: EMGT treatment reduced progression risk in half, demonstrating the value of IOP lowering in early glaucoma. Age and indicators of disease severity also predicted progression.

Antihypertensive Agents↗
PubMed2004

Immunophenotypic and genotypic characterization of progression in follicular lymphomas.

Progression of follicular lymphomas (FLs) is often accompanied by a spectrum of histologic changes and an aggressive clinical course. Although molecular alterations have been implicated in this event, the underlying factors are largely unknown. We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients. Eleven patients progressed from grade I or II FL to aggressive B-cell lymphomas with diffuse morphology, whereas 5 patients presented with diffuse aggressive lymphomas and recurred with indolent lymphomas. Immunoreactivity for P53 correlated with higher histologic grade in lymphomas progressing from indolent to aggressive; however, only 1 patient who presented with aggressive lymphoma demonstrated a P53 gene mutation. Neither P53 immunoreactivity nor genotypic alterations correlated with presentation with an aggressive histology and relapse with FL. Growth fraction, as assessed by Ki-67 staining, and Trump expression correlated with histologic grade. Immunoreactivity for RB, BCL2, and MYC was seldom associated with progression. Eight of 9 cases tested exhibited identical immunoglobulin heavy and light chain rearrangements or identical BCL2 gene rearrangements in the sequential lymphomas. We conclude that P53 and Trump protein expression and proliferation activity correlate with histologic grade, but not with recurrence or progression of FL. Our results further indicate that progression of FL to diffuse aggressive lymphomas and presentation of an aggressive B-cell lymphoma followed by FL are clonally related.

Antigens, Neoplasm↗
PubMedDate not supplied

Progression of chronic renal disease.

Progressive chronic renal disease is characterized histologically by the accumulation of extracellular matrix proteins within the renal interstitium and progressive tubular atrophy. A number of kidney diseases and their progression to end-stage renal failure are driven by the intercrine, autocrine, paracrine, and endocrine effects of angiotensin II. Growth factors appear to have an important role in the development and progression of diabetic nephropathy. Substantial evidence indicates that induction of transforming growth factor beta (TGF-beta) is mediated by high levels of glucose. TGF-beta is pivotal for the hypertrophy of mesangial and tubular cells. Other factors such as hypertension, protein glycation products, and other mediators may further amplify the synthesis of TGF-beta and/or the expression of its receptors in the diabetic state. Other cytokines, such as tumor necrosis factor alpha also contribute to the progression of chronic renal disease. The overall picture derived from several studies of chronic renal disease suggests that treatment of the progression of the renal fibrosis may require the use of several strategies to prevent the advent of end-stage renal disease.

Angiotensin II↗
PubMed2005

A slowly progressive and reproducible animal model of intervertebral disc degeneration characterized by MRI, X-ray, and histology.

STUDY DESIGN: The progression of intervertebral disc degeneration following anterolateral "stab" of adult rabbit lumbar discs by 16-gauge hypodermic needle to a limited (5-mm) depth was studied for up to 24 weeks using magnetic resonance imaging, radiograph, and histologic outcome measures. OBJECTIVES: To develop a slowly progressive, reproducible rabbit model of intervertebral disc degeneration suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel approaches to the treatment of intervertebral disc degeneration (e.g., growth factors, gene therapy, cell therapy, and tissue engineering). SUMMARY OF BACKGROUND DATA: Numerous animal models of intervertebral disc degeneration have been proposed in the literature, each with attendant advantages and disadvantages. The classic "stab model," involving full-thickness stab of anterior anulus fibrosus of adult rabbit lumbar discs by a number 11 scalpel blade, appears to produce changes in certain biochemical and histologic outcome measures that are similar to changes seen in human intervertebral disc degeneration. However, the immediate herniation of nucleus pulposus on full-thickness stab renders this model less suitable for 1) studying effects of less precipitous changes in nucleus pulposus and anulus fibrosus that may be important in the onset and progression of intervertebral disc degeneration and 2) testing novel therapeutic approaches that target the processes of early intervertebral disc degeneration. METHODS: The L2-L3, L3-L4, and L4-L5 lumbar intervertebral discs of 18 skeletally mature female New Zealand White rabbits were stabbed by 16-gauge hypodermic needle to a depth of 5 mm in the left anterolateral anulus fibrosus. Serial magnetic resonance imaging scans of the stabbed discs and intact L1-L2 and L5-L6 control discs were performed at 3, 6, 12, and 24 weeks post surgery and compared with preoperative magnetic resonance images. Supplemental radiograph and histologic analyses were performed. RESULTS: The stabbed discs exhibited a progressive decrease in "magnetic resonance imaging index" (the product of nucleus pulposus area and signal intensity from T2-weighted midsagittal plane images) starting at 3 weeks post stab and continuing through 24 weeks, with no evidence of spontaneous recovery or reversal of magnetic resonance imaging changes. Radiograph findings included early osteophyte formation by 6 weeks post stab and extensive, bridging osteophytes by 24 weeks. Histologic analysis revealed progressive loss of notochordal cells from the nucleus pulposus, filling of the nucleus pulposus space with fibrocartilage, and derangement of anulus fibrosus. CONCLUSIONS: Stabbing the anterolateral anulus fibrosus of adult rabbit lumbar discs with a 16-gauge hypodermic needle to a limited (5-mm) depth results in a number of slowly progressive and reproducible magnetic resonance imaging, radiograph, and histologic changes over 24 weeks that show a similarity to changes seen in human intervertebral disc degeneration. This model would appear suitable for studying pathogenesis and pathophysiology of intervertebral disc degeneration and testing safety and efficacy of novel treatments of intervertebral disc degeneration.

Animals↗
PubMed2005

Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the Chingford cohort.

STUDY DESIGN: A candidate gene association study in a longitudinal cohort. OBJECTIVE: To investigate the association between polymorphisms at 25 candidate genes and progression of individual radiographic features of lumbar disc degeneration (LDD). SUMMARY OF BACKGROUND DATA: LDD is characterized radiographically by the presence of osteophytes and disc space narrowing and is known to have a genetic component. Because of the high prevalence of radiographic features, progression may be a more useful phenotype clinically to study than prevalence itself. METHODS: We tested the effect on radiographic progression of LDD of polymorphisms in 25 genes, 24 of which had been previously tested with regards to knee osteoarthritis. The progression traits used were the change in radiographic grade over 9 years in osteophytes, disc space narrowing, and summary Kellgren-Lawrence grade. Lumbar spine radiographs (L1-L5) at baseline and at follow-up were read for 720 women genotyped at the 25 genes participating in the Chingford study. RESULTS: Polymorphisms in MMP3, TIMP1, and COX2, which encode molecules involved in inflammatory pathways, were associated with radiographic progression of LDD. The strongest associations observed (statistically significant after correcting for multiple comparisons) were between COX2 and change in osteophyte grade (P < 0.001) and Kellgren-Lawrence grade (P < 2 x 10(-5)), and between the genes for vitamin D receptor (P < 0.002) and a thrombospondin (THSD2) (P < 0.002) and change in osteophyte grade. CONCLUSIONS: Our results suggest a role for genes regulating inflammatory pathways in the radiographic progression of spine degeneration. This could prove a fruitful area for future therapeutics for the spine and other joints.

Cyclooxygenase 2↗
PubMed2006

Mechanical modulation of vertebral growth in the fusionless treatment of progressive scoliosis in an experimental model.

STUDY DESIGN: Wedging of apical spinal segments was measured during creation and correction of an experimental scoliosis in a goat model. OBJECTIVES: To create and correct apical vertebral wedge deformities in a progressive experimental scoliosis model by purely mechanical means. SUMMARY OF BACKGROUND DATA: The creation and correction of vertebral wedge deformities has been previously described in a rat tail model using external fixation. METHODS: Experimental scoliosis was created in 14 goats using a posterior asymmetric tether with convex rib resection and concave rib tethering. After a period of up to 13 weeks, all tethers were removed and goats were randomized into treated (n = 8) and untreated (n = 6) groups. Treated goats underwent anterior thoracic stapling with four shape memory alloy staples along the convexity of the maximal curvature. Goats were followed for an additional 7 to 13 weeks during treatment. Serial radiographs were used to document progression or correction of the maximal scoliotic deformity as well as to measure the wedging of the apical spinal segment (two adjacent vertebrae and the intervening disc). RESULTS: During the tethering period, all goats achieved a progressive, structural, lordoscoliotic curve of significant magnitude (mean: 61 degrees, range: 49 to 73 degrees). Wedging of the apical spinal segment measured 11.1 degrees at the beginning and 22.4 degrees at the end of the tethering period. The increase in apical spinal segment wedging of +11.3 degrees (10.7 degrees vertebral/0.6-degree disc) was significant (P = 0.001). During the treatment period, the scoliosis in the stapled goats measured 56.8 degrees at the beginning and 43.4 degrees at the end for an average correction of -13.4 degrees (range: 0 to-22 degrees) (P = 0.001), whereas the untreated goats measured 67.0 degrees at the beginning and 59.8 degrees at the end for an average correction of -7.2 degrees (range: +7 to -21 degrees) (P = 0.19). Additionally, wedging of the apical spinal segment in the stapled goats measured 22.5 degrees at the beginning and 20.3 degrees at the end for an average correction of -2.2 degrees (-0.6 degrees vertebral/-1.6-degree disc); wedging of the apical vertebral segment in the untreated goats measured 22.3 degrees at the beginning and 25.8 degrees at the end of the treatment period for an average progression of +3.5 degrees (3.5 degrees vertebral/0.0-degree disc). The difference in apical spinal segment correction versus progression in the stapled (-2.2 degrees) versus control (+3.5 degrees) goats was significant (P < 0.05). CONCLUSIONS: This study demonstrates the ability to create wedge deformities at the apex of an experimental scoliosis in a large animal model and to control the progression of these deformities using anterior thoracic staples.

Animals↗
PubMed2006

Diagnosing glaucoma progression: current practice and promising technologies.

PURPOSE OF REVIEW: An update on recent work is provided that has broadened our understanding of the evaluation of visual function and structure, and their use in evaluating glaucoma progression. RECENT FINDINGS: The challenge of determining visual-field progression and the implications of long-term fluctuation are reviewed and data to support the magnitude of the fluctuation are cited. The use of confirmatory testing can limit the over diagnosis of glaucoma progression. Focusing visual-field testing on the locations of present scotomas or using frequency doubling technology may provide new approaches to assessing visual function. New standardized techniques to interpret visual fields, including neural networks, unsupervised machine learning and pointwise linear regression, may provide more quantitative means for visual-field interpretation. These techniques, along with structural evaluation of the optic nerve and nerve fiber layer, are essential in glaucoma management. Optic-nerve-head photography is still a mainstay in evaluating glaucoma progression, although many technologies including scanning laser tomography, scanning laser polarimetry and optical coherence tomography offer more quantitative means to follow structural change. These modalities, in different ways, show promise in providing additional information regarding the stability of glaucoma. SUMMARY: Identifying the functional visual component as well as structural changes is essential in evaluating glaucoma progression. New techniques of testing and evaluating visual fields, the optic-nerve head, and the retinal nerve fiber layer offer exciting opportunities to more accurately identify glaucoma progression, and are likely to become more central as imaging devices and software support develop further.

Diagnostic Techniques, Ophthalmological↗
PubMed2003

The role of Ras superfamily proteins in bladder cancer progression.

PURPOSE: The prognosis of patients with bladder cancer is strongly dependent on whether the lesion is superficial or invasive at initial presentation. In addition, a significant fraction of patients presenting with superficial disease have invasive tumor during followup. Understanding how superficial bladder cancer progresses to invasive forms of the disease is of paramount importance for early diagnosis and successful treatment. Molecular mechanisms underlying bladder cancer progression are being elucidated. We reviewed the roles that members of the Ras superfamily of monomeric G proteins, an important class of cellular regulator, have in bladder cancer and its progression. MATERIALS AND METHODS: We performed MEDLINE searches focusing on members of the Ras superfamily of monomeric G proteins and their involvement in transitional cell carcinoma, which is the most common form of bladder cancer. General involvement in cancer of key superfamily members, focusing on mechanisms and downstream pathways, was also reviewed through MEDLINE and manual bibliographic searches. RESULTS: With more than 100 members in humans the Ras superfamily is a diverse group of monomeric G proteins. These proteins regulate many cellular processes, such as cell cycle progression, actin cytoskeletal dynamics and membrane traffic. Members of the Ras and Rho family are also known to be involved in human cancer through mutation, over expression and dysregulation. In this review we focus on bladder cancer. In particular we focus on how H-Ras, RalA/B and RhoGDI2, a regulator of Rho family members, participate in bladder cancer progression and how their participation may be related to other molecules associated with bladder cancer progression, such as epidermal growth factor receptor, p53 and PTEN (phosphatase and tensin homologue deleted on chromosome 10). CONCLUSIONS: The findings discussed offer the hopeful possibility that signaling pathways mediated by Ras superfamily members may offer new opportunities for diagnostic and therapeutic interventions in bladder cancer.

Carcinoma, Transitional Cell↗
PubMed2005

Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial.

PURPOSE: We determined if a third of the dose of intravesical bacillus Calmette-Guerin (BCG) has the same efficacy than a standard dose for decreasing the risk of recurrence and progression after transurethral resection in patients with superficial high risk (stages T1G3 and carcinoma in situ) bladder cancer. Also, we evaluated toxic side effects. MATERIAL AND METHODS: A total of 155 patients with a mean age +/- SD of 67 +/- 10.1 years with superficial bladder cancer, including stages T1G3 in 90, a Tis primary tumor in 23 and associated Tis disease in 42, were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG, Connaught strain (weekly x 6 and fortnightly x 6 thereafter) with the standard dose of 81 mg or with the decreased dose of 27 mg. RESULTS: Median followup was 61 months (range 3 to 102). Disease recurred in 32 patients (39%) treated with the standard dose and in 33 (45%) treated with the decreased dose. Median time to recurrence was not attained in the standard dose arm and it was 63 months in the decreased dose arm. Kaplan-Meier estimates for time to recurrence did not reveal differences between the 2 doses (p = 0.405). Tumor progressed in 20 patients (24.7%) with the standard dose and in 19 (26%) with the decreased dose. Four patients (6.1%) with Tis had local extension into the prostatic urethra and ducts, including 3 (8.3%) treated with the standard dose and 1 (3.4%) treated with the decreased dose. Median time to progression was not attained in either arm. Kaplan-Meier estimates for time to progression did not differ significantly (p = 0.7997). Deferred cystectomy for progression was performed in 7 patients (8.4%) treated with the standard dose and in 7 (9.5%) of those treated with the decreased dose. Subgroup analysis by patient age, tumor status, number, size and T stage (T1G3 vs Tis) did not differ significantly. The groups did not differ in disease specific mortality, which was 12.2% in the standard dose arm and 16.4% in the decreased dose arm. Mean disease specific survival +/- SE was 86.96 +/- 4.14 and 83.73 +/- 4.73 months, respectively. CONCLUSIONS: Our results suggest that a 3-fold decreased dose of intravesical BCG is as effective as the standard dose against progression in patients with high risk stages T1G3 and Tis superficial bladder carcinoma but with significantly less toxicity.

Adjuvants, Immunologic↗