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PubMed2002

HLA-DR3 and DR4 and their relation to the incidence and progression of diabetic retinopathy.

PURPOSE: Cross-sectional data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy indicated that patients with HLA-DR4, but not DR3, were more likely to have prevalent proliferative retinopathy than those without both antigens. We describe the relation of HLA-DR3 and DR4 antigens to the 14-year incidence and progression of diabetic retinopathy and macular edema in this cohort. DESIGN: A population-based cohort study. PARTICIPANTS: A probability sample of male and female patients receiving primary care for diabetes in 11 counties of southern Wisconsin. METHODS: Participants were invited for a baseline examination in 1980 to 1982, with follow-up examinations at 4, 10, and 14 years later. At the 4-year examination, a random sample of participants (n = 428) diagnosed with diabetes before the age of 30 and taking insulin were selected for HLA-DR typing. MAIN OUTCOME MEASURES: Fourteen-year incidence and progression of diabetic retinopathy and macular edema based on masked stereoscopic fundus photographic grading. RESULTS: There was no relation between HLA-DR3 and DR4 status with the 14-year incidence and progression of diabetic retinopathy, progression to proliferative retinopathy, and incidence of macular edema. Patients with either HLA-DR3 or DR4 were less likely to progress to proliferative retinopathy compared with those who were negative for both, although these relations were not statistically significant. The associations did not vary after adjusting for hypertension status, baseline retinopathy, and glycosylated hemoglobin levels, or after stratifying by duration of diabetes (less than 10 years vs. 10 years or more) and age at diagnosis of diabetes (less than 15 years vs. 15 years or more). Furthermore, 10-year mortality and 14-year nephropathy rates did not differ by HLA-DR3 or DR4 status, suggesting that selective mortality did not explain the pattern of associations seen. CONCLUSIONS: In contrast to the initial cross-sectional findings, these data suggest that HLA-DR3 or DR4 status is unrelated to 14-year incidence and progression of diabetic retinopathy. The discrepancy may be related to increasing homogeneity of retinopathy and diminishing power to detect small differences, but it may also reflect the uncertain and inconsistent effects of HLA-DR3 or DR4 on the development and progression of diabetic retinopathy.

Adult↗
PubMed2002

Small neuroretinal rim and large parapapillary atrophy as predictive factors for progression of glaucomatous optic neuropathy.

PURPOSE: To evaluate which morphologic features of the optic disc are predictive factors for progressive neuroretinal rim loss in chronic open-angle glaucoma. DESIGN: Prospective, observational case series. PARTICIPANTS: The study included 394 eyes of 257 white patients with chronic open-angle glaucoma. Mean follow-up time was 31.8 months (median, 39.7 months). Progression of glaucoma was defined as loss of neuroretinal rim as detected by disc photographs. Presence of optic disc hemorrhages was not taken into account. METHODS: All patients underwent repeated qualitative and morphometric evaluation of color stereo optic disc photographs. Statistical analysis included Kaplan-Meier curves, and bivariate and multivariate Cox regression analysis adjusted for patients' ages. Dependency of left and right eyes from the same subject was taken into account. MAIN OUTCOME MEASURES: Qualitative and quantitative morphologic optic nerve head parameters. RESULTS: Progression of glaucomatous optic nerve changes was detected in 42 eyes (11%). At baseline of the study, neuroretinal rim area (total area, P = 0.03) was significantly smaller, and beta zone of parapapillary atrophy (total area, P = 0.04) was significantly larger in the progressive study group compared with the nonprogressive study group. Neither study group varied significantly in size and shape of the optic disc, optic cup depth, alpha zone of parapapillary atrophy, and diameter of the retinal arteries and veins (P > 0.05). Multiple Cox regression analysis revealed that the progression of glaucoma depended significantly on the area of the neuroretinal rim (temporal sector, P = 0.003) and beta zone of parapapillary atrophy (temporal inferior sector, P = 0.02). CONCLUSIONS: Important morphologic predictive factors for progression of the glaucomatous appearance of the optic nerve head in white persons are small size of neuroretinal rim and large area of beta zone of parapapillary atrophy. Progression of glaucomatous optic nerve head changes is independent of size and shape of the optic disc, size of alpha zone of parapapillary atrophy, retinal vessel diameter, and optic cup depth.

Adolescent↗
PubMed2002

Classification and prediction of the progression of thyroid-associated ophthalmopathy by an artificial neural network.

OBJECTIVE: We have used an artificial neural network in an attempt to classify and predict the progression of thyroid-associated ophthalmopathy (TAO) at the first clinical examination. DESIGN: This retrospective comparative case series included a group of patients examined by the ophthalmologist only once because of the absence of signs of progressive disease (GR1), as subsequently monitored by an endocrinologist, and a group of patients on follow-up because of progressive disease (GR2). PARTICIPANTS AND METHODS: We examined 242 patients, of whom 207 were women and 35 were men. GR1 included 129 patients (257 eyes) who, on ophthalmologic assessment, were further classified as having no TAO (n = 53; GR1a) and only lid signs or inactive, stable TAO (n = 76; GR1b). GR2 included 113 patients (219 eyes). One hundred three normal subjects (205 eyes), 50 women and 53 men, were tested to provide normal ranges for proptosis values. We applied a model of back propagation neural network with 17 input variables, a training matrix of 414 observations, a randomly selected test group of 115 observations, and, as output, the progression of disease. The ophthalmologic assessment included (1) lid fissure measurement, (2) Hertel, (3) color vision, (4) cover test and Hess screen, (5) visual acuity, (6) tonometry, (7) fundus examination, (8) visual field, and (9) orbital computed tomography scan or ultrasonography. Other parameters included in the neural analysis were gender and age of the patients, their cigarette smoking, and the interval between follow-up visits. RESULTS: The prevalence of smokers among patients without TAO was significantly lower than that among those with TAO (P < 0.03). Mean proptosis values (Hertel) were significantly different in GR1, in GR2, and in a group of normal eyes (P < 0.0001), and the changes of values in consecutive measurements were associated with progression of the disease (P < 0.01). Differences of the proptosis values in the two groups of patients were not related to smoking. The neural network correctly classified 78.3% of 115 eyes (87 patients) and predicted TAO progression in 69.2% of 39 eyes (28 patients). CONCLUSIONS: In our opinion, neural network analysis can be successfully applied for classifying TAO and predicting progression at the first clinical examination.

Adolescent↗
PubMed2003

Visual field and optic disc progression in patients with different types of optic disc damage: a longitudinal prospective study.

OBJECTIVE: To evaluate the incidence of visual field and optic disc progression in glaucoma patients with distinct patterns of optic disc damage. DESIGN: Prospective, observational case series. PARTICIPANTS: One hundred five patients with open-angle glaucoma. METHODS: Baseline optic disc photographs of 105 study eyes of 105 patients were reviewed by 2 masked observers and classified according to patterns of disc damage into the following categories: focal, myopic, senile sclerotic, and generalized disc damage. Patients were followed up every 6 months with standard automated perimetry (SAP), high-pass resolution perimetry (HRP), and scanning laser tomography (SLT) with the Heidelberg Retina Tomograph. MAIN OUTCOME MEASURES: Visual field (SAP and HRP) and optic disc (SLT) progression were determined according to predefined criteria. RESULTS: Twenty-four eyes were classified into the focal, 8 into the myopic, 12 into the senile sclerotic, and 28 into the generalized group. Eyes from 33 patients could not be classified by the observers into any of these groups and were excluded from further analysis. Although intraocular pressure during follow-up was similar among the four groups, some differences in frequency of progression were observed. Patients with senile sclerotic discs had the lowest rates of visual field progression (both with SAP and HRP) and optic disc progression, although the differences were significant only for optic disc progression (P = 0.05). CONCLUSIONS: Patients with senile sclerotic discs showed a tendency towards less visual field and optic disc progression when compared with patients with other types of disc damage.

Aged↗
PubMed1998

Patterns of visual field progression in patients with retinitis pigmentosa.

OBJECTIVE: The purpose of the study was to determine whether distinct patterns of visual field progression are present in patients with retinitis pigmentosa (RP) and to evaluate the correlation between these patterns, if present, and different genetic subtypes of RP. DESIGN: A retrospective analysis of patterns of visual field progression in RP was performed. PARTICIPANTS: Visual fields of 162 patients with RP, including 55 with type 2 Usher syndrome, who had at least 3 Goldmann visual field examinations during a period of at least 3 years were reviewed. MAIN OUTCOME MEASURES: Goldmann visual fields. RESULTS: Visual fields of 86 patients could be classified into one of three specific patterns of visual field progression. Pattern I included those patients with a progressive concentric loss of visual fields; pattern II included those with visual field loss that began superiorly and subsequently developed an arcuate scotoma that progressed either from the nasal (IIA) or the temporal (IIB and IIC) side; and pattern III included patients whose visual field loss was characterized initially by a complete or incomplete midperipheral "ring scotoma" that broke through into the periphery. The end stage of all these patterns was a residual central visual field, sometimes also associated with a small peripheral island. In 53 of the 162 patients, the pattern of visual field loss could not be categorized because of an advanced stage of field loss at the time of the initial examination. CONCLUSIONS: Distinctive patterns of visual field progression can be observed in patients with retinitis pigmentosa and type 2 Usher syndrome. There were no intrafamilial variations in the pattern of visual field loss in our data on 24 patients from 11 families. Within certain genetic subtypes, there was a predilection for a preponderance of a specific pattern of visual field progression. Future studies may be able to correlate these patterns of visual field loss with different genetic mutations. A greater understanding as to why certain patterns of field loss exist could potentially provide greater insight into the various pathogenetic mechanism(s) by which photoreceptor cells degenerate in this group of patients.

Deafness↗
PubMed1999

Scoring systems for measuring progression of visual field loss in clinical trials of glaucoma treatment.

OBJECTIVES: To compare the statistical properties of two visual field scoring systems used by clinical trials of glaucoma treatments with a view to their performance as longitudinal measures of visual field progression. DESIGN: Cohort study comparing the scoring systems used by the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS) using pairs of visual fields (C-30-2 of the Humphrey Analyzer) spaced 1 year apart. PARTICIPANTS: Sixty-seven eyes of 56 subjects with glaucomatous visual field loss from a natural history study of glaucoma were examined. METHODS: Because both scoring systems are scaled so that they range from 0 to 20, the AGIS and CIGTS scores were compared by scatterplot, Pearson correlation, and the mean difference between scores. The difference between pairs of scores 1 year apart was used to compare the temporal variability of each scoring system. The proportion of subjects whose visual field "deteriorated" in 1 year by the amount specified for unconfirmed progression in each clinical trial was calculated. MAIN OUTCOME MEASURES: Mean difference in scores 1 year apart and the variance of these differences were measured. RESULTS: The median scores for the first of the two fields was 5.2 (interquartile range [IQR] = 9.8) for CIGTS and 5.0 (IQR = 7.0) for AGIS. The CIGTS scores were slightly larger than AGIS scores by an average of 0.5 (P = 0.06). The mean CIGTS score of the baseline fields was 0.06 (standard deviation = 3.8) higher than the mean of the second fields and 0.12 (standard deviation = 2.8) higher for AGIS. Fifteen percent of eyes had CIGTS scores that deteriorated by three or more (the cutoff for unconfirmed progression) over 1 year, while 7.5% of eyes had AGIS scores that deteriorated by four or more (the AGIS cutoff for unconfirmed progression) over the same period. Twenty-one percent improved by CIGTS criteria, while 12% improved by AGIS criteria. CONCLUSIONS: CIGTS scores are systematically slightly higher than AGIS scores. The CIGTS scoring system has higher temporal variability than the AGIS system. The CIGTS criterion for unconfirmed progression over a 1-year period is likely to lead to higher estimated rates of progression than the AGIS criteria. This is mostly because of the difference in the definition of progression between the two study criteria.

Clinical Trials as Topic↗
PubMed2003

Cytokeratin 7 staining of hepatocytes predicts progression to more severe fibrosis in alcohol-fed baboons.

BACKGROUND/AIMS: Not all alcoholic patients develop severe liver disease with fibrosis progressing to cirrhosis. It is of practical importance to determine whether some markers can predict progression of liver fibrosis. METHODS: We used a baboon model that mimics human alcoholic liver disease. Cytokeratin 7 and 19 expression and fat deposition were investigated in serial liver biopsies of 18 animals undergoing prolonged alcohol administration (range 2-17 years) and in four controls. Fibrosis was graded histologically and was also assessed quantitatively by image analysis. RESULTS: Ten animals did not show a progression of liver disease even after 17 years of alcohol administration, but eight animals fed alcohol exhibited a progression of liver disease from no fibrosis or perivenular fibrosis to septal fibrosis or cirrhosis within 7 years. In normal liver, cytokeratin 7 and cytokeratin 19 immunostaining is restricted to bile duct cells. Hepatocellular cytokeratin 7 was observed only in those animals which progressed to more severe stages of fibrosis and it anticipated this progression by 4.2 years on average. CONCLUSIONS: In alcohol-fed baboons, cytokeratin 7 staining of hepatocytes (but not cytokeratin 19, nor fat deposition) predicts with a high degree of sensitivity and specificity progression to more severe liver disease.

Animals↗
PubMed2003

[Multivariate analysis of recurrence and progression in stage T1 transitional-cell carcinoma of the bladder. Prognostic value of p53 and Ki67].

OBJECTIVE: To establish prognostic factors of recurrence and progression in stage T1 transitional cell bladder carcinoma, paying special attention to prognostic value of p53 and ki67. MATERIALS AND METHODS: 175 patients with incident bladder tumour at T1 category. The immunohistochemical study was performed using the monoclonal antibodies DO-7, for p53 and MIB-1, for ki67. Kaplan-Meier methodology was used, and a multivariate analysis using Cox's proportional hazards model was carried out in order to determine the variables associated with recurrence and progression. ROC curves were also drawn up. RESULTS: The average follow up period was 8.55 years. 5 and 12-year recurrence-free survival rates were 57.98% and 48.47%. The independent variables for recurrence were histological grade, tumour multifocality, tumour size > 3 cm, presence of carcinoma in situ and ki67 expression. 5 and 12-year progression-free survival rates were 83.12% and 75.63%. The independent variables for progression were age, tumour multifocality, solid microscopic morphology, p53 expression and ki67 expression. CONCLUSIONS: Solid microscopic pattern and p53 expression are the variables which best predict progression. A positive relationship was observed between p53 and progression: the greater the expression of p53, the greater the progression. Tumour multifocality and ki67 expression > 27% are the main prognostic factors for recurrence.

Aged↗
PubMed2002

Syrinx size and duration of symptoms predict the pace of progressive myelopathy: retrospective analysis of 103 unoperated cases with craniocervical junction malformations and syringomyelia.

OBJECTIVE: the clinical course of syringomyelia associated with craniocervical junction abnormalities is variable. About half of the unoperated patients have benign course. This is difficult to explain on the basis of the present pathogenetic theories. Therefore, to understand the mechanism of syrinx progression better, we studied the value of syrinx size, syrinx morphology, and the syrinx/spinal cord size ratio in predicting the rate of progression and the severity of myelopathy in these patients. METHODS: 103 adult patients with syringomyelia associated with Chiari 1 malformation and/or radiographic signs of underdeveloped posterior cranial fossa were clinically and MRI examined. Patients were subdivided according to the type of disease progression. Severity of neurological deficits, and MRI features (the extent of cerebellar tonsillar displacement, anteroposterior diameter of cavities, the spinal cord and cyst/cord ratio and the shape of cavities) were measured. RESULTS: a significant relationship was found between the mid-sagittal diameter of the syrinxes and the type of disease course; patients with short duration and rapid progression had the largest diameters of cavities, whereas patients with longer duration as well as with slow rate of progression had smaller diameters (chi(2)=28.90, P<0.05; chi(2)=29.89, P<0.01; r=-0.24, P<0.05). In addition, a correlation was found between the anteroposterior diameter of the spinal cord and cyst/cord ratio and the disease duration (r=0.52, P<0.05 and r=0.48, P<0.05, respectively). CONCLUSIONS: the initial years for the development of symptomatic syringomyelia associated with CCJ malformations are characterized by relatively rapid clinical progression accompanied with distended cavities. In the later periods of unoperated syringomyelia, some patients show delay in the progress of syrinxes accompanied with collapse of cavities, probably either due to a spontaneous formation of drainage between the syrinx and the subarachnoidal space, or due to the restoration of abnormal CSF dynamics at the CCJ level.

Adult↗
PubMed1996

Radiotherapy for prevention of disease progression in early-stage Dupuytren's contracture: initial and long-term results.

PURPOSE: Radiotherapy (RT) was given to prevent disease progression in early-stage Dupuytren's contracture. Initial response, long-term outcome, and treatment toxicity were evaluated. METHODS: Between 1982 and 1993, 96 patients (142 hands) received orthovoltage RT, which consisted of two courses with daily fractionation of 5 x 3 Gy (total dose 30 Gy) separated by a 6-week interval. The extent of disease was staged according to the classification of Tubiana et al.. Initial evaluation was performed 3 months after completion of RT; long-term outcome was analyzed at last follow-up (i.e., between February and April 1994). The mean follow-up was 6 +/- 2 (range 1-12) years. Fifty-seven patients with a minimum follow-up of 5 (median 7.5; mean 9.5-12) years were separately evaluated for long-term outcome (i.e., prevention of disease progression). Acute and late treatment toxicity was assessed using the Radiation Therapy Oncology Group/EORTC criteria. RESULTS: According to stage, 130 cases (92%) remained stable at 3 months follow-up, 10 improved (7%), and 2 progressed (1%). An objective reduction of symptomatic cords and nodules was achieved in 107 cases (75%) at 3 months follow-up. Moreover, 87% of the patients reported a subjective relief of symptoms. In long-term follow-up, only 16 of 142 cases (11%) had progressed according to stage. In the group with minimum follow-up 5 years (n = 57), 44 patients (77%) experienced no disease progression, whereas 13 progressed (23%) inside [8 cases (14%)] or outside [5 cases (9%)] of the RT field. Most failures could have been avoided with appropriate choice of larger safety margins included in the treated portals; however, the failures outside were still amenable for another RT course. CONCLUSION: Radiotherapy is effective to prevent disease progression for early-stage Dupuytren's contracture. Thus, it helps to avoid an otherwise necessary surgical procedure which is performed in adavanced stages of Dupuytren's contracture.

Adult↗
PubMed2000

Prognostic factors for atherosclerosis progression in saphenous vein grafts: the postcoronary artery bypass graft (Post-CABG) trial. Post-CABG Trial Investigators.

OBJECTIVES: The study was done to assess patients in the Post-Coronary Artery Bypass Graft (Post-CABG) trial to determine prognostic factors for atherosclerosis progression. BACKGROUND: Saphenous vein grafts (SVGs) are effective in relieving angina and, in certain patient subsets, in prolonging life. However, the progression of atherosclerosis in many of these grafts limits their usefulness. METHODS: The Post-CABG trial studied moderate versus aggressive lipid-lowering and low-dose warfarin versus placebo in patients with a history of coronary artery bypass surgery and found that more aggressive lipid lowering was effective in preventing progression of atherosclerosis in SVGs, but warfarin had no effect. Using variables measured at baseline, we sought the independent prognostic factors for atherosclerosis progression in SVGs, employing the statistical method of generalized estimating equations with a logit-link function. RESULTS: Twelve independent prognostic factors for atherosclerosis progression were found. In the order of their importance they were: maximum stenosis of the graft at baseline angiography, years post-SVG placement; the moderate low-density lipoprotein-cholesterol (LDL-C) lowering strategy; prior myocardial infarction; high triglyceride level; small minimum graft diameter; low high-density lipoprotein-cholesterol (HDL-C); high LDL-C; high mean arterial pressure; low ejection fraction; male gender; and current smoking. CONCLUSIONS: This study identified Post-CABG patient and SVG characteristics associated with saphenous vein graft atherosclerosis progression. These data provide a basis for rational risk factor management to prevent progression of SVG atherosclerosis.

Aged↗
PubMed2000

Etiologic factors in progression of carotid stenosis: a 10-year study in 905 patients.

PURPOSE: The purpose of this study was to determine the etiologic factors in the progression of carotid stenosis. METHODS: We performed prospective serial duplex scan surveillance of 1470 carotid arteries in 905 asymptomatic patients during a 10-year period, with an average follow-up interval of 29 months and an average of 3.0 scans per carotid artery. Vascular laboratory and hospital records were used to collect risk factor information. The data were analyzed with proportional hazards modeling. RESULTS: We examined several demographic, clinical, and laboratory risk factors that were chosen because of their potential relevance to atherosclerotic disease. These factors were analyzed with univariate proportional hazards modeling, in which time to progression of stenosis was the outcome variable. The six significant predictors (P <.05) were age, sex, systolic pressure, pulse pressure (systolic pressure - diastolic pressure), total cholesterol, and high-density lipoprotein (HDL). All, except HDL, were positive predictors of time to disease progression. With multivariate modeling, only pulse pressure and HDL remained as significant independent predictors of stenosis progression. The risk ratio for a 10-mm Hg rise in pulse pressure was 1.12, and the risk ratio for a 10-mg/dL decrease in HDL was 1.20. CONCLUSION: In this large cohort of patients who were followed prospectively for carotid stenosis, pulse pressure and HDL were found to be the key risk factors for carotid stenosis progression. The fact that pulse pressure superseded systolic pressure in multivariate modeling may shed light on the biology of carotid plaque progression. Further, our identification of these modifiable risk factors may help in the design of therapeutic trials for the prevention of progression of carotid atherosclerosis.

Age Factors↗
PubMed1999

Cataract progression in patients with atopic dermatitis.

PURPOSE: To evaluate the possible causes of cataract progression in Japanese patients with atopic dermatitis. SETTING: Department of Ophthalmology, Toyama Medical and Pharmaceutical University, Toyama, Japan. METHODS: This prospective study comprised 41 patients (81 eyes) with atopic dermatitis. Cataract progression was determined by photographs and visual acuity results. Mean follow-up was 2.5 years (range 1.0 to 3.5 years). RESULTS: Of 41 patients, 10 (24.4%) had progression of cataract. Of 81 eyes, 10 (12.3%) had slow progression and 9 (11.1%), rapid. Cataract progression was not statistically significantly related to patient sex or severity of systemic skin lesions but was to facial skin lesions. Soft contact lens wear and eye rubbing were also correlated with cataract progression. CONCLUSION: Patients with facial atopic dermatitis, contact lenses, or both may rub their eyes more frequently than those with lesions on other body parts, increasing their risk of cataract progression.

Adolescent↗
PubMed2002

Progression to AIDS, a clinical AIDS condition and mortality: psychosocial and physiological predictors.

BACKGROUND: The primary aim of this study is to examine prospectively the association of stressful life events, social support, depressive symptoms, anger, serum cortisol and lymphocyte subsets with changes in multiple measures of human immunodeficiency virus (HIV) disease progression. METHODS: Ninety-six HIV-infected gay men without symptoms or anti-retroviral medication use at baseline were studied every 6 months for up to 9 years. Disease progression was defined in three ways using the Centers for Disease Control (CDC) classifications (e.g. AIDS, clinical AIDS condition and mortality). Cox regression models with time-dependent covariates were used, adjusting for control variables (e.g. race, age, baseline, CD4 T cells and viral load, number of anti-retroviral medications). RESULTS: Higher cumulative average stressful life events and lower cumulative average social support predicted faster progression to both the CDC AIDS classification and a clinical AIDS condition. Higher anger scores and CD8 T cells were associated with faster progression to AIDS, and depressive symptoms were associated with faster development of an AIDS clinical condition. Higher levels of serum cortisol predicted all three measures of disease progression. CONCLUSIONS: These results suggest that stressful life events, dysphoric mood and limited social support are associated with more rapid clinical progression in HIV infection, with serum cortisol also exerting an independent effect on disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Motor evoked potentials and disability in secondary progressive multiple sclerosis.

BACKGROUND: To investigate the mechanisms underlying disability in multiple sclerosis (MS), 40 patients with the relapsing-remitting form of the disease and 13 patients with secondary progressive MS underwent multimodal evoked potential (EP), motor evoked potential (MEP), and spinal motor conduction time evaluation. Clinical disability was evaluated by the expanded disability status scale (EDSS) and functional system scales. In secondary progressive MS patients, magnetic resonance imaging (MRI) was used to obtain a semiquantitATive estimate of the total lesion load of the brain. RESULTS: Spinal motor conduction time was significantly longer in secondary progressive MS patients than controls (p < 0.001) and relapsing-remitting MS patients (p < 0.05), but did not differ between relapsing-remitting patients and controls. Spinal motor conduction times also correlated directly with EDSS scores (p < 0.001) and pyramidal functional system scores (p < 0.001). Brain lesion load (4960.3 +/- 3719.0 mm2) and the total number of lesions (67.7 +/- 37.0) in secondary progressive MS did not correlate with disability scores. For the following EPs, the frequencies of abnormalities were significantly higher in secondary progressive MS patients than relapsing-remitting patients: visual evoked potentials (p < 0.05), somatosensory evoked potentials and upper limb motor evoked potentials (p < 0.01), and brainstem auditory evoked potentials, lower limb somatosensory evoked potentials and lower limb motor evoked potentials (p < 0.001). CONCLUSIONS: These findings suggest that disability in secondary progressive MS patients is mainly due to progressive involvement of corticospinal tract in the spinal cord.

Adult↗
PubMed1999

Progression to proliferative retinopathy and macular oedema requiring treatment. Assessment of the alternative classification of the Wisconsin Study.

PURPOSE: To study the ability of the alternative classification of the Wisconsin Study to predict progression to retinopathy requiring laser treatment in patients with diabetes. METHODS: A total of 1585 diabetic patients were included in the study. Of them, 294 (19%) were diagnosed with diabetes before and 1291 (81%) after age 30 years. Retinopathy was diagnosed on fundus photographs using a modification of the Wisconsin scale, and graded into 6 levels according to the worse eye. The first visit during the study period was used to represent baseline examination. The time points for detection of proliferative retinopathy (PDR) and clinically significant macular oedema (CSME) were recorded during a mean follow-up time of 2.9 years. RESULTS: Progression to PDR and/or CSME was significantly related to increasing severity of retinopathy at baseline (p<0.001; test for trend). Fifty per cent of patients with severe non-proliferative retinopathy (NPDR) (level 51) at entry progressed within one year to PDR and/or CSME; the 3-year risk for such progression in patients with mild (level 31) and moderate NPDR (level 41) was 25 and 60%, respectively. The incidence of progression to PDR and to CSME was 0.95 and 2.3/100 person-years, respectively. Progression to PDR and/or CSME was furthermore associated with a higher level of glycosylated haemoglobin, longer duration of the diabetes and use of antihypertensive treatment. CONCLUSION: Increasing severity of retinopathy as recorded by this modification of the alternative classification of the Wisconsin Study was significantly associated with increased risk of progression to retinopathy requiring treatment.

Diabetes Complications↗
PubMed1996

Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.

Adolescent↗
PubMed2006

Glomerular expression of neuronal activity-regulated pentraxin precedes the development of anti-Thy-1-induced progressive glomerulosclerosis.

Although it is clear that genetic predispositions play a role in progressive glomerulosclerosis, identification of specific genes is difficult because of natural genetic heterogeneity among individuals. We have reported a differential susceptibility to progressive glomerulosclerosis after induction of experimental glomerulonephritis anti-Thy-1 nephritis in Lewis rat substrains. Glomerular lesions in Lewis/Møllegard rats resolve spontaneously, whereas Lewis/Maastricht (Lew/Maa) rats develop progressive glomerulosclerosis. This predisposition for progressive glomerulosclerosis is governed by unknown genes that are expressed by renal cells. Here, differential gene expression analysis using a rat complementary DNA micro array revealed neuronal activity-regulated pentraxin (Narp) as a candidate gene involved in the remodeling or progression of damaged glomeruli. Glomerular Narp mRNA expression was monitored during disease in both Lewis sub strains. Immunohistochemistry revealed that Narp protein is exclusively expressed in Lew/Maa glomeruli 7 and 14 days after induction of anti-Thy-1 nephritis. Double-immunofluorescent staining showed that proliferating mesangial cells and parietal epithelial cells (PECs) at sites of adhesion to podocytes are partially Narp-positive, whereas podocytes fail to express Narp. Immunohistochemistry in nephritic Wistar, unilaterally nephrectomized Wistar and Sprague-Dawley rats showed that Narp protein is present only in strains that develop progressive glomerulosclerosis but never in strains that show remodeling. We conclude that Narp is a predictor for anti-Thy-1 nephritis-induced glomerulosclerosis and its expression by PECs may be involved in the progression to glomerulosclerosis.

Animals↗