Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications.

AIMS: The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms. METHODS: The MNSI was performed by trained personnel at each of the 28 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications clinical sites. Neurologic examinations and nerve conduction studies were performed during the same year. Confirmed clinical neuropathy was defined by symptoms and signs of distal symmetrical peripheral neuropathy based on the examination of a neurologist and abnormal nerve conduction findings in ≥ 2 anatomically distinct nerves among the sural, peroneal and median nerves. RESULTS: We studied 1184 subjects with Type 1 diabetes. Mean age was 47 years and duration of diabetes was 26 years. Thirty per cent of participants had confirmed clinical neuropathy, 18% had ≥ 4 and 5% had ≥ 7 abnormal responses on the MNSI questionnaire, and 33% had abnormal scores (≥ 2.5) on the MNSI examination. New scoring algorithms were developed and cut points defined to improve the performance of the MNSI questionnaire, examination and the combination of the two. CONCLUSIONS: Altering the cut point to define an abnormal test from ≥ 7 abnormal to ≥ 4 abnormal items improves the performance of the MNSI questionnaire. The MNSI is a simple, non-invasive and valid measure of distal symmetrical peripheral neuropathy in Type 1 diabetes.

Biomedical risk factors for decreased cognitive functioning in type 1 diabetes: an 18 year follow-up of the Diabetes Control and Complications Trial (DCCT) cohort.

AIMS/HYPOTHESIS: In patients with type 1 diabetes, there has been concern about the effects of recurrent hypoglycaemia and chronic hyperglycaemia on cognitive function. Because other biomedical factors may also increase the risk of cognitive decline, this study examined whether macrovascular risk factors (hypertension, smoking, hypercholesterolaemia, obesity), sub-clinical macrovascular disease (carotid intima-media thickening, coronary calcification) and microvascular complications (retinopathy, nephropathy) were associated with decrements in cognitive function over an extended time period. METHODS: Type 1 diabetes patients (n = 1,144) who had completed a comprehensive cognitive test battery at entry into the Diabetes Control and Complications Trial were re-assessed at a mean of 18.5 (range: 15-23) years later. Univariate and multivariable models examined the relationship between cognitive change and the presence of micro- and macrovascular complications and risk factors. RESULTS: Univariate modelling showed that smoking history was modestly associated with decrements in learning, memory, spatial information-processing and psychomotor efficiency; hypertension was associated with only psychomotor slowing. Multivariable modelling demonstrated that HbA(1c) level, and retinal and renal complications were each independently associated with decrements in psychomotor efficiency. In contrast, no macrovascular risk factors were significant after correcting for multiple comparisons. No interactions were found between these predictors and sex, severe hypoglycaemic events or presence of the APOE ε4 allele. CONCLUSIONS/INTERPRETATION: In relatively healthy, middle-aged adults with type 1 diabetes who had been followed for an average of 18.5 years, long-term metabolic control and microvascular factors are independently associated with a decline in cognitive function specifically affecting measures of psychomotor efficiency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360893.

The associations of apolipoprotein E and angiotensin-converting enzyme polymorphisms and cognitive function in Type 1 diabetes based on an 18-year follow-up of the DCCT cohort.

AIMS: Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive dysfunction in the general population, yet little research has examined whether genetic factors influence risk of cognitive dysfunction in patients with Type 1 diabetes. The long-term follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) population provides an opportunity to examine if specific genetic variations in APOE and ACE alter risk for cognitive decline. METHODS: Neurocognitive function in Type 1 diabetic subjects from the DCCT/EDIC study was assessed at DCCT entry and re-assessed approximately 18 years later, using a comprehensive cognitive test battery. Glycated haemoglobin (HbA(1c)) and the frequency of severe hypoglycaemic events leading to coma or seizures were measured over the 18-year follow-up. We determined whether the APO epsilon4 and ACE intron 16 indel genotypes were associated with baseline cognitive function and with change over time, and whether they conferred added risk in those subjects experiencing severe hypoglycaemic events or greater glycaemic exposure. RESULTS: None of the APOE or ACE polymorphisms were associated with either baseline cognitive performance or change in cognition over the 18-year follow-up. Moreover, none of the genotype variations altered the risk of cognitive dysfunction in those subjects with severe hypoglycaemic episodes or high HbA(1c). CONCLUSIONS: In this sample of young and middle-aged adults with Type 1 diabetes, APO epsilon4 and ACE D alleles do not appear to increase risk of cognitive dysfunction.

Urinary tract infections in women with type 1 diabetes mellitus: survey of female participants in the epidemiology of diabetes interventions and complications study cohort.

PURPOSE: We determined the prevalence of and risk factors for urinary tract infection in women with type 1 diabetes, and compared the prevalence of cystitis to that in nondiabetic women. MATERIALS AND METHODS: Women enrolled in the Epidemiology of Diabetes Interventions and Complications study were surveyed at year 10 as part of the Uro-EDIC study to assess the prevalence of cystitis and pyelonephritis in the preceding 12 months. Multivariate logistic regression models including measures of glycemic control and vascular complications of type 1 diabetes were used for risk factor analyses. The prevalence of cystitis in Uro-EDIC women was compared to that in a nondiabetic subset of women participants in the National Health and Nutrition Examination Survey III (NHANES III). RESULTS: A total of 550 women participated in the Uro-EDIC survey. The prevalence of cystitis and pyelonephritis in the preceding 12 months was 15% and 3%, respectively. Duration of diabetes, hemoglobin A1C, retinopathy, neuropathy, nephropathy, composite vascular complication score and intensive glycemic therapy during the Diabetes Control and Complications Trial, and Diabetes Control and Complications Trial cohort were not associated with cystitis or pyelonephritis. Sexual activity was associated with increased cystitis risk (adjusted OR 8.28; 95% CI 1.45, 158.32; p = 0.01). The adjusted prevalence of cystitis was 19.1% in Uro-EDIC women and 23.1% in NHANES III participants (adjusted OR 0.78; 95% CI 0.51, 1.22; p = 0.28). CONCLUSIONS: In Uro-EDIC women sexual activity rather than measures of diabetes control and complications was the main risk factor for urinary tract infection. The prevalence of cystitis was similar to that in nondiabetic women participants in NHANES III.

Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial.

Levels of lipoprotein(a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P < 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.

Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial.

The relationships between long-term intensive control of glycemia and indicators of skin collagen glycation (furosine), glycoxidation (pentosidine and N(epsilon)-[carboxymethyl]-lysine [CML]), and crosslinking (acid and pepsin solubility) were examined in 216 patients with type 1 diabetes from the primary prevention and secondary intervention cohorts of the Diabetes Control and Complications Trial. By comparison with conventional treatment, 5 years of intensive treatment was associated with 30-32% lower furosine, 9% lower pentosidine, 9-13% lower CML, 24% higher acid-soluble collagen, and 50% higher pepsin-soluble collagen. All of these differences were statistically significant in the subjects of the primary prevention cohort (P < 0.006-0.001) and also of the secondary intervention cohort (P < 0.015-0.001) with the exception of CML and acid-soluble collagen. Age- and duration-adjusted collagen variables were significantly associated with the HbA1c value nearest the biopsy and with cumulative prior HbA1c values. Multiple logistic regression analyses with six nonredundant collagen parameters as independent variables and various expressions of retinopathy, nephropathy, and neuropathy outcomes as dependent variables showed that the complications were significantly associated with the full set of collagen variables. Surprisingly, the percentage of total variance (R2) in complications explained by the collagen variables ranged from 19 to 36% with the intensive treatment and from 14 to 51% with conventional treatment. These associations generally remained significant even after adjustment for HbA1c, and, most unexpectedly, in conventionally treated subjects, glycated collagen was the parameter most consistently associated with diabetic complications. Continued monitoring of these subjects may determine whether glycation products in the skin, and especially the early Amadori product (furosine), have the potential to be predictors of the future risk of developing complications, and perhaps be even better predictors than glycated hemoglobin (HbA1c).

Increased small dense LDL and intermediate-density lipoprotein with albuminuria in type 1 diabetes.

OBJECTIVE: This population study examines the relationship between LDL density and persistent albuminuria in subjects with type 1 diabetes at the end of the Diabetes Control and Complications Trial (DCCT). RESEARCH DESIGN AND METHODS: Subjects were classified as persistently normoalbuminuric (albumin excretion rate [AER] < 30 mg/d, n = 1,056), microalbuminuric (AER > or = 30-299 mg/day, n = 80), and macroalbuminuric (AER = 300 mg/day, n = 24) based on the last two AER measures. RESULTS: Triglyceride (P < 0.01) and LDL cholesterol (P < 0.01) levels were higher in macroalbuminuric subjects compared with normoalbuminuric subjects. Cholesterol distribution by density-gradient ultracentrifugation showed an increase in intermediate-density lipoprotein (IDL) and a shift in peak LDL from buoyant toward more dense particles with progressive albuminuria. In the entire group, there was a significant negative correlation between the peak buoyancy of LDL particles and albuminuria (r = -0.238, P < 0.001, n = 1,160). This correlation persisted in the normoalbuminuric DCCT group (r = -0.138, P < 0.001, n = 1,056). CONCLUSIONS: As albuminuria increases in subjects with type 1 diabetes, dyslipidemia occurs with an increase in IDL and dense LDL that may lead to increased cardiovascular disease.

Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group.

OBJECTIVE: Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. DESIGN: Prospective multicenter clinical trial. SETTING: Referral centers. PATIENTS AND METHODS: Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). RESULTS: Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. CONCLUSIONS: We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias.

Optic neuritis treatment trial. One-year follow-up results.

OBJECTIVE: To determine the efficacy of corticosteroids as treatment for acute demyelinative optic neuritis after completion of 1 year of patient follow-up in the Optic Neuritis Treatment Trial. DESIGN: Randomized placebo controlled multicenter clinical trial. SETTING: Fifteen university or hospital-based centers throughout the United States. PATIENTS: Four hundred fifty-seven patients with acute demyelinative optic neuritis between 18 and 46 years of age. INTERVENTION: Either intravenous methylprednisolone sodium succinate (250 mg every 6 hours) for 3 days followed by oral prednisone (1 mg/kg per day) for 11 days, oral prednisone (1 mg/kg per day) for 14 days, or oral placebo for 14 days. The first two regimens were followed by a short taper of corticosteroid therapy. MAIN OUTCOME MEASURES: Visual acuity, visual field, contrast sensitivity, and color vision. RESULTS: Visual acuity at 1 year was 20/40 or better in 95% of the placebo group, 94% of the intravenous group, and 91% of the oral prednisone group. Comparing each corticosteroid group with the placebo group, there were no statistically significant differences in the distributions of any of the four measures of visual function. Patients in the oral prednisone group suffered a higher rate of new attacks of optic neuritis than patients in either of the other two groups. CONCLUSIONS: The visual benefit from treating acute optic neuritis with intravenous followed by oral corticosteroids is short term, limited to an accelerated rate of recovery. The decision whether to prescribe this regimen for optic neuritis, or to prescribe no treatment, must be made for each patient on an individual basis. Oral prednisone alone, in the dose range used in the Optic Neuritis Treatment Trial, should not be prescribed.

Contrast sensitivity and other vision tests in the optic neuritis treatment trial.

PURPOSE: To determine the intercorrelation, prevalence of abnormality, and incremental detection value of vision tests in optic neuritis. METHODS: We calculated the linear correlation of paired vision tests and prevalence of abnormal test values from baseline and six-month measurements of Snellen visual acuity, Pelli-Robson contrast sensitivity, Humphrey Field Analyzer mean deviation, and Farnsworth-Munsell 100-hue color vision in 438 patients entered in the Optic Neuritis Treatment Trial from 1988 to 1991. The incremental detection value of nonvisual acuity tests was defined as their frequency of abnormality when visual acuity was 20/20 or better. RESULTS: All four vision-test results were highly intercorrelated at baseline and at six months. At baseline, contrast sensitivity had the highest prevalence of abnormality, but all vision tests were so often abnormal that differences were not clinically relevant. At six months, when visual recovery had occurred, contrast sensitivity was most often abnormal (2.2 X visual acuity; 1.8 X mean deviation; 1.5 X Farnsworth-Munsell 100-hue color vision test); when contrast sensitivity, mean deviation, or Farnsworth-Munsell 100-hue color vision was normal, visual acuity was 20/25 or better in 98% of patients. CONCLUSIONS: The high intercorrelation of four vision tests suggests that optic neuritis affects a broad range of visual functions. Among non-visual acuity tests, Pelli-Robson contrast sensitivity proved to be a particularly practical and sensitive indicator of visual dysfunction in optic neuritis.

Reproducibility of a comprehensive diet history in the Diabetes Control and Complications Trial. The DCCT Research Group.

OBJECTIVE: To evaluate the reproducibility of a modified Burke-type diet history within the context of a long-term, randomized, 29-center clinical diabetes study. DESIGN: Diet histories were collected by trained interviewers at the end of years 1 and 2 after subjects were randomly assigned to the intensive treatment group or the conventional treatment group. Mean daily intakes of energy, protein, carbohydrate, total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, and dietary fiber were calculated for each treatment group at each time period. SUBJECTS: The study population consisted of 139 subjects in the intensive treatment group and 128 subjects in the conventional treatment group. Ages ranged from 13 to 39 years; groups included men and women. Distribution by age, sex, race, proportion of smokers, weight reported as percent ideal body weight, and duration of IDDM were similar in both groups. STATISTICAL METHODS: Differences in nutrient intake between the conventional and intensive treatment groups at each time period were tested for significance using the Wilcoxon rank-sum test. The Wilcoxon paired differences test was used to assess changes between time periods within treatment groups. Linear agreement between repeated administrations of the diet history was evaluated using Pearson's correlation coefficient, and the extent of within-subject reproducibility was assessed by intraclass correlation. RESULTS: No statistically significant differences in energy and nutrient intakes were observed between the two groups at either year 1 or year 2. Within each treatment group, energy and nutrient intake differences between times were not statistically significant. Correlation coefficients between years 1 and 2 ranged from .51 for dietary fiber to .72 for dietary cholesterol; within-subject reproducibility was slightly higher. APPLICATIONS: These results demonstrate long-term reproducibility for the meal-based diet history in the DCCT population.

Physiological adjustments to higher- or lower-intensity exercise in elders.

A program of physical activity for people over 60 yr of age was developed to determine whether exercising at lower intensities (LI) is a significant conditioning stimulus. In addition, differences in aerobic capacities (VO2max) elicited by training at LI, as opposed to training at higher intensities (HI), were evaluated. Thirty-two volunteers over 60 yr of age (mean = 67.8 yr) participated in a 9-wk exercise program. After initial testing of VO2max on a cycle ergometer, subjects were assigned randomly to the HI, LI, or control group. Endurance training of the two exercise groups on cycle ergometers was maintained at 30-45% (N = 14) or 60-75% (N = 14) of the range (HRR) between the subject's resting and maximum heart rate for 25 min during each exercise session. These training intensities represented 57 and 70% of the VO2max of the LI and HI groups, respectively. Participants averaged three exercise sessions per week. Non-exercising volunteers served as control subjects. A one-way ANOVA with repeated measures was utilized for comparisons of retest, groups, and interaction. As a result of the exercise program, significant changes (P less than 0.005) in absolute (VO2max, 1 X min-1) and relative (VO2max, ml X min-1 X kg-1) aerobic capacities were realized within each training group while initial and post-training VO2max were not significantly different between the two groups. Similar changes were documented by a reduction in heart rate at submaximal exercise intensities and during recovery. It was concluded that exercising at LI (30-45% HRR) is an adequate training stimulus in older individuals and produces changes in VO2max that are comparable to those elicited by HI (60-75% HRR) training.

Progestins and oral contraceptive-induced lipoprotein changes: a prospective study.

In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for one year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups (p less than 0.05). ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol (LDL-C), a 13% fall in high density lipoprotein cholesterol (HDL-C) and a 27% decline in HDL2 cholesterol (HDL2-C) (p less than 0.05). Apoprotein A-I (Apo A-I) increased by 9% with ENA and by 11% with EED (p less than 0.05), but did not change significantly with ENG. This prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasma lipoproteins.

PIP: In order to determine the effects on plasma lipoproteins of oral contraceptives containing progestins with varying androgenic potency, 136 healthy women were randomized into 3 groups and followed prospectively for 1 year while receiving either 50 mcg ethinyl estradiol and 1.0 mg ethynodiol diacetate (EED), 50 mcg ethinyl estradiol and 1.0 mg norethindrone acetate (ENA), or 50 mcg ethinyl estradiol and 0.5 mg d-1 norgestrel (ENG). Comparison was made to a self-selected group of 50 women using alternative means of contraception. Plasma cholesterol increased by 7-9% and triglycerides by 32-57% in all 3 groups. ENG use resulted in other significant lipoprotein changes including an 18% increase in low density lipoprotein cholesterol, a 13% fall in high density lipoprotein cholesterol and a 27% decline in high density lipoprotein-2 cholesterol. Apoprotein A-1 increased by 9% with ENA and by 11% with EED, but did not change significantly with ENG. Khis prospective study demonstrates that in oral contraceptive agents with identical estrogen, progestins with different androgenic potency produce major and different changes in plasms lipoproteins.

Clinical laboratory test standards for a sample of schizophrenics.

The normal ranges for 15 clinical laboratory tests for a pooled sample of 325 schizophrenics, largely chronic and hospitalized, are presented. Laboratory data came from pretreatment blood samples of subjects who were all participants in clinical psychotropic drug trials conducted through the Early Clinical Drug Evaluation Unit (ECDEU) Program of the National Institute of Mental Health. Both parametric means and ranges (mean +/- 2 standard deviations) and non-parametric medians and percentile ranges (2.5 and 97.5 percentiles) are reported. The results generally confirm the finding of increased variability in schizophrenic laboratory test data noted in the past. This, and implications of the method are discussed.

Factorial invariance across gender for the primary symptom dimensions of the SCL-90.

The present study was focused on an evaluation of factorial invariance across gender for the primary symptom dimensions of the SCL-90-a multidimensional self-report symptom inventory. The argument is advanced that evidence of invariance across relevant subject parameters is an essential component of reliability for dimensional constructs. Findings indicated subtantial levels of invariance across gender for eight of the nine primary symptom dimensions of the SCL-90 with moderate levels for the ninth. The implications of invariance, for the SCL-90 in particular, and clinical measurement in general are related and discussed.

The course of visual recovery after optic neuritis. Experience of the Optic Neuritis Treatment Trial.

PURPOSE: To define the time course of visual recovery after optic neuritis and factors predictive of this course in the patients enrolled in the Optic Neuritis Treatment Trial. METHODS: The cohort for this study consisted of the 438 patients who completed the 6-month follow-up visit. Visual acuity was measured at baseline and at seven follow-up visits during the first 6 months. Factors predictive of recovery were evaluated with univariate and multivariate statistical tests. RESULTS: Visual recovery was rapid in all three treatment groups. In almost all patients, regardless of treatment group and initial severity of visual loss, improvement began within the first month. Among the 278 patients with baseline visual acuity of 20/50 or worse, all patients improved at least one line of visual acuity, and all except six improved at least three lines, during the 6-month follow-up period. Baseline visual acuity was the best predictor of the 6-month visual acuity outcome (P = 0.0001). Older age was statistically associated with a slightly worse outcome (P = 0.02), but this appeared to be of no clinical importance. CONCLUSIONS: In most patients with optic neuritis, visual recovery is rapid. The only factor of value in predicting the visual outcome is initial severity of visual loss. However, even when initial loss is severe, visual recovery is still good in most patients. Patients not following the usual course of visual recovery should be considered atypical. For such patients, further investigation in regard to etiology of the visual loss may be appropriate.

Lack of correlation between serum lipoproteins and biliary cholesterol saturation in patients with gallstones.

It has been suggested that elevated serum lipoprotein cholesterol levels may be a determinant of biliary cholesterol saturation and cholesterol gallstone disease. The aim of this study was to correlate serum lipoprotein cholesterol and apolipoprotein levels with biliary cholesterol saturation in patients with gallstones who participated in the National Cooperative Gallstone Study. Baseline serum lipoprotein and biliary lipid levels were studied in 181 of these patients before they received treatment for dissolution of their gallstones. Neither low- or high-density lipoprotein cholesterol nor apolipoprotein levels correlated with biliary cholesterol saturation. This study, therefore, does not support the concept that serum lipoproteins are a determinant of biliary cholesterol saturation. It is possible, however, that a significant effect of lipoprotein levels is obscured by the greater effects of more important determinants of biliary cholesterol saturation.