A cellulose-binding domain-fused recombinant human T cell connective tissue-activating peptide-III manifests heparanase activity.

The chemokine connective tissue-activating peptide (CTAP)-III, which belongs to the leukocyte-derived growth factor family of mediators, was previously shown to be mitogenic for fibroblasts. However, it has recently been shown that CTAP-III, released from platelets, can act like a heparanase enzyme and degrade heparan sulfate. This suggests that CTAP-III may also function as a proinflammatory mediator. We have successfully cloned CTAP-III from a lambdagt11 cDNA library of PHA-activated human CD4(+) T cells and produced recombinant CTAP-III as a fusion protein with a cellulose-binding domain moiety. This recombinant CTAP-III exhibited heparanase activity and released degradation products from metabolically labeled, naturally produced extracellular matrix. We have also developed polyclonal and monoclonal antibodies, and these antibodies against the recombinant CTAP-III detected the CTAP-III molecule in human T cells, polymorphonuclear leukocytes, and placental extracts. Thus, our study provides tools to examine further immune cell behavior in inflamed sites rich with extracellular moieties and proinflammatory mediators.

Clinical course of macular holes: the Eye Disease Case-Control Study.

OBJECTIVE: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes. PATIENTS: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study. MAIN OUTCOME MEASURES: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated. RESULTS: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up. CONCLUSIONS: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low.

Risk factors for hemiretinal vein occlusion: comparison with risk factors for central and branch retinal vein occlusion: the eye disease case-control study.

OBJECTIVE: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion. DESIGN: The design was a multicenter case-control study. METHODS: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. RESULTS: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha2-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion. CONCLUSION: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma.

Serum zinc and serum lipid profiles in 778 adults.

There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision.

Acceptable values of kappa for comparison of two groups.

A model was developed for a simple clinical trial in which graders had defined probabilities of misclassifying pathologic material to disease present or absent. The authors compared Kappa between graders, and efficiency and bias in the clinical trial in the presence of misclassification. Though related to bias and efficiency, Kappa did not predict these two statistics well. These results pertain generally to evaluation of systems for encoding medical information, and the relevance of Kappa in determining whether such systems are ready for use in comparative studies. The authors conclude that, by itself, Kappa is not informative enough to evaluate the appropriateness of a grading scheme for comparative studies. Additional, and perhaps difficult, questions must be addressed for such evaluation.

Extended use of prefilled humidifier reservoirs and the likelihood of contamination.

UNLABELLED: We sought to determine the potential for disposable prefilled humidifiers to become contaminated during extended patient use. METHODS & MATERIALS: We sampled the water in 55 humidifier reservoirs, which were being used by patients or which had been used by patients and then been placed on 'standby,' and had the samples cultured by a commercial clinical laboratory. RESULTS: None of the humidifiers showed contamination after 72 hours of continuous patient use, and 33 of the 55 were used by patients for an additional 3-9 days with no contamination. Fifteen humidifiers that had been in use on patients were put in a standby mode for 30-32 days, with 5 continuing for 60-62 days, with no contamination seen. CONCLUSIONS: An automatic 72-hour change-out for prefilled humidifiers used with low-flow oxygen (less than or equal to 4 L/min) is wasteful. Our study demonstrates that the use-time of humidifiers can be safely extended to as long as 6-12 days.

Grading of images in a clinical trial.

We developed a computer model to compare the power in clinical trials that use either of two grading schemes for objectively recorded dependent variables. The example we use is an eye lens photo. The first grading system consists of side by side comparison of the before and after treatment photos; the second involves separate grading of the two photos. This modelling experience suggests that separate grading may often yield more power than side by side comparison, and offers other advantages as well. For applications in which grading error is considerably smaller in the side by side method, power may be markedly better. Most importantly, strong prejudice in favour of one or the other approach in all situations seems unwarranted.

Surrogate endpoints in clinical trials: ophthalmologic disorders.

We examined three examples of surrogate observations in ophthalmology. The first represents a simple case: the status of one eye is used as a surrogate for the (unobservable) status of the opposite eye in the same individual. The second and third examples represent possible extrapolation of long term results on the basis of early changes. These examples are used to illustrate the assumptions intrinsic in the use of surrogate variables.

Factors associated with visual outcome after photocoagulation for diabetic retinopathy. Diabetic Retinopathy Study Report #13.

Six risk factors for severe visual loss despite panretinal (scatter) photocoagulation were identified by analyzing data collected during the first 5 years after randomization in the Diabetic Retinopathy Study. Proportional hazards regression revealed NVD (neovascularization on/around the optic disc) to be the most important risk factor. The risk of severe visual loss rose with increasing NVD, hemorrhages/microaneurysms, retinal elevation, proteinuria, and hyperglycemia and fell with increasing "treatment density." These results are similar to previous DRS findings on untreated eyes. The importance of "treatment density" as an independent predictor of visual outcome is a new finding and lends support to the common clinical practice of repeating photocoagulation if initial treatment does not reduce or stabilize retinal neovascularization.

Discussion of case-control studies of Peleg, Stähelin, and Willett.

The combined results from the case-control studies of Peleg, Stähelin, and Willett were found to provide no evidence of a relationship between serum retinol levels and the risk of cancer in all sites combined or of lung cancer. However, a relationship between serum retinol levels and the risk of gastrointestinal cancer was suggested.

Further results on a multiple-testing procedure for clinical trials.

O'Brien and Fleming (1979, Biometrics 35, 549-556) proposed a procedure for multiple testing in clinical trials for acute disease. We evaluated their procedure for chronic-disease models and found that it can be used without modification. Type I errors are unaltered and no loss of power is seen in comparison with single-sample procedures. However, average savings in sample size are less for the chronic-disease models than for the acute model. Finally, it is shown that for any specific disease model and fixed maximum number of inspections of the data, the percentage reduction in sample size can be readily predicted from the power.

Prevalence of myopia in the United States.

Data from the 1971 to 1972 National Health and Nutrition Examination Survey were used to estimate myopia prevalence rates for persons in the United States between the ages of 12 and 54 years. When persons were classified by the refractive status of their right eye, 25% were myopic. Significantly lower prevalence rates were found for male subjects than for female subjects and for blacks than for whites. Myopia prevalence rose with family income and educational level. The importance of income and educational level may result from their association with near work, a factor that has been implicated in the pathogenesis of myopia.