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Biomedical subjects

J Friend

Publications and source records attributed to J Friend.

At least 37 records · Page 2Linked to original sources

Validation of methods for the assessment of cataract progression in the Roche European-American Anticataract Trial (REACT)

The Roche European-American Anticataract Trial (REACT) will assess the effect of antioxidants on progression of cataract in humans. This report evaluates the methods used in REACT. Seventy three subjects (139 eyes) with cortical (C), posterior subcapsular (P), nuclear (N) or mixed cataract were seen twice within two weeks for eye examinations, assessments of visual function, lens photographs and CCD images. The degree of cataract and nuclear color (NC) were assessed with subjective (LOCS III) and objective (computerized, CASE 2000 CCD) methods. Repeat visit values were used to calculate intraclass correlation coefficients (r1) and 95% tolerance limits (TL). A clinically significant change (CSC) was defined as one step in LOCS III. The relative power of each method to detect cataract change and sample sizes needed to achieve statistically significant results were calculated. The r1 values for visual function tests ranged from 0.76 to 0.88; if these tests of visual function were used to detect a clinically significant change in cataract severity, sample sizes of 840 to 2707 per group would be needed. The r1 values for LOCS III were 0.88 to 0.97, and sample sizes ranged from 50 to 135 per group. The r1 values for the CCD were 0.93 to 0.98, and sample sizes ranged from 1 to 42 with poorer values relating to measurement of P. We conclude that the methods used in REACT are reproducible. The analytical algorithms in the image analysis programs did not permit differentiation between C and P opacification; therefore, P cataract is best measured with LOCS III. REACT sample sizes are adequate to detect a difference of 0.2 LOCS III units/year between the mean rates of cataract progression in two groups.

Adult↗

The Lens Opacities Classification System III. The Longitudinal Study of Cataract Study Group.

OBJECTIVE: To develop the Lens Opacities Classification System III (LOCS III) to overcome the limitations inherent in lens classification using LOCS II. These limitations include unequal intervals between standards, only one standard for color grading, use of integer grading, and wide 95% tolerance limits. DESIGN AND RESULTS: The LOCS III contains an expanded set of standards that were selected from the Longitudinal Study of Cataract slide library at the Center for Clinical Cataract Research, Boston, Mass. It consists of six slit-lamp images for grading nuclear color (NC) and nuclear opalescence (NO), five retroillumination images for grading cortical cataract (C), and five retroillumination images for grading posterior subcapsular (P) cataract. Cataract severity is graded on a decimal scale, and the standards have regularly spaced intervals on a decimal scale. The 95% tolerance limits are reduced from 2.0 for each class with LOCS II to 0.7 for nuclear opalescence, 0.7 for nuclear color, 0.5 for cortical cataract, and 1.0 for posterior subcapsular cataract with the LOCS III, with excellent interobserver agreement. CONCLUSION: The LOCS III is an improved LOCS system for grading slit-lamp and retroillumination images of age-related cataract.

Aging↗

Contrast sensitivity and visual acuity in patients with early cataracts.

In a population of 188 nondiabetic patients with early cataracts or nuclear brunescence, we assessed the degree to which contrast sensitivity function (CSF) provided more information about a patient's visual disability than high contrast visual acuity measurements. Data collected included LOCS II cataract classification, Bailey-Lovie visual acuity (LogMAR score), Lotmar interferometric visual acuity (LI VA), and distance contrast sensitivity function (CSF) using the Vistech 6500. Generalized least squares regression models in which CS was the dependent variable and either LogMAR score or LI VA was among the independent variables were used to ascertain whether CSF provided additional information about visual disability to that provided by LogMAR score or LI VA. Contrast sensitivity function was decreased only by nuclear opalescence at high frequencies (12 to 18 cpd); for all other cataract types and nuclear color, CSF testing provided no more information about cataract-related visual loss than LI VA or LogMAR score. Measurement of CSF using the Vistech 6500 system in patients with early cataracts provides information on visual dysfunction beyond that provided by LogMAR score or LI VA only in patients with nuclear opalescence, and that may not be clinically significant.

Adult↗

Quantitating cataract and nuclear brunescence, the Harvard and LOCS systems.

Subjective and objective systems are used to quantify cataract at The Center for Clinical Cataract Research. We have described each system and its use, presented data on reproducibility and validity, and for objective systems, demonstrated the correlation to the subjective grade of the cataract as defined by the Lens Opacities Classification Systems, Versions II and III (LOCS II and III). The subjective systems are used to classify nuclear color, nuclear opalescence, cortical cataract, and posterior subcapsular cataract. Reported kappa scores for LOCS II range from 0.85 to 1.0. Intraclass correlation coefficients for LOCS III (r1) range from 0.67 to 0.94. The computerized objective system are: (1) fast spectral scanning colorimetry (FSSC) for assessment of nuclear color (r1 = 0.96 to 0.98); (2) nuclear mean density (NMD) for assessment of nuclear opalescence (r1 = 0.97); and (3) percent area opacity (anterior = a; posterior = p) (OPAC-a and OPAC-p) for assessment of cortical and posterior subcapsular cataract (r1 = 0.92 to 0.96).

Adult↗

Classification and protein distribution in a series of intracapsular cataracts.

The crystallin profiles of the cortices and nuclei of intracapsular cataractous lenses were studied by high pressure liquid chromatography (HPLC), polyacrylamide gel electrophoresis (PAGE), and dot blotting. The complete personal and medical history of 381 patients and the Cooperative Cataract Research Group (CCRG) classification of each were obtained. Few statistically significant associations between patient personal history and cataract types were found. Protein profiles of selected cataracts which had specifically located opacities (i.e., nuclear only, cortical only, etc.) were studied in detail. Sodium dodecyl sulphate-PAGE revealed few differences in lens-soluble proteins between cataractous and normal cortices or nuclei. By HPLC, the proteins of cataractous cortices and their nuclei differed very little from age-matched controls. The cortical proteins of nuclear cataracts appeared normal. However, two major alterations of proteins were observed in the nuclei of dense nuclear cataracts. Increased high molecular weight protein and increased components with molecular weights < 20,000 Da were found in cataractous nuclei as compared with normal age-matched control lens nuclei. Dot blot (immunological) analyses identified the crystallins of normal lenses that eluted from the HPLC column more efficiently than those of cataractous lenses. Cortical protein HPLC samples had the most specificity. Nuclear protein HPLC samples of older normal and cataractous lenses had little if any alpha crystallin specificity in the void volume peak. A relation between the presence of opacities and changes in molecular weight distribution of crystallins was found in the opaque nuclei but not in the opaque cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lovastatin and the human lens; results of a two year study. The MSDRL Study Group.

Lovastatin has been associated with development of subcapsular cataract in dogs given high doses. To test the cataractogenic potential of lovastatin in humans, 192 patients were divided into 2 groups, A (N = 94) and B (N = 98), 1 taking 40 mg/day of lovastatin and 1 taking placebo. Both groups were enrolled for 2 years in this double-blind, randomized study and were followed with eye examinations including assessment of visual function, Lens Opacities Classification System II (LOCS II) cataract and nuclear color classification, and computerized lens image analysis. There were no statistically significant differences in visual function between the two groups. Similarly, cataract progression, assessed by LOCS II measurement and by computerized measurements of cataract, showed no important differences between the treatment groups. These data show no cataractogenic effect of lovastatin in humans.

Cataract↗

Loss of contrast sensitivity in diabetic patients with LOCS II classified cataracts.

Contrast sensitivity function (CSF) was assessed in a population of diabetics with moderate cataracts to determine if CSF testing provides more information about visual dysfunction than Snellen or Lotmar interferometric visual acuity. With the Lens Opacities Classification Systems Version II (LOCS II) of cataract classification it was possible to grade accurately the type and severity of cataract and nuclear brunescence. The presence of statistically significant relationships between increasing LOCS II classification (worsening cataract) and diminished function, even when the regression model was controlled for Snellen visual acuity, supports the thesis that CSF measurements do provide more information about cataract related visual loss than Snellen acuity alone. Statistically significant (p < or = 0.05) relationships existed between different morphological types of cataract, nuclear colour, and CSF at specific frequencies. The frequencies affected differed with cataract type or nuclear colour, and with distance and near CSF.

Adult↗

Social effects of wheeze in childhood: a 25 year follow up.

OBJECTIVES: To determine the outcome of childhood wheeze in terms of education, employment, housing, and social class. DESIGN: 25 year follow up study. SETTING: Community study based at the department of thoracic medicine, Aberdeen Royal Infirmary. PARTICIPANTS: Three groups of subjects who had been identified in a random community survey in 1964: those who had had asthma in childhood (n = 97), those who had wheezed only in the presence of upper respiratory tract infections (n = 132), and a comparison group who had had no respiratory symptoms as children (n = 131). Subjects were aged 34 to 40 years at the time of the current study. MAIN OUTCOME MEASURES: Interview and questionnaire data on education, employment, housing and social class, ventilatory function, and peak flow rate. RESULTS: Pulmonary function testing showed that only the "asthmatic" group had airways obstruction; this group showed greater peak flow variation than the "wheezy" group, which did not differ from the comparison group. The asthmatic subjects were more likely to have experienced respiratory problems during their school years and associated with their work. Despite these problems, educational attainment, employment, housing, and eventual social class were similar for all three groups. CONCLUSION: Childhood wheeze did not adversely affect education, employment, housing, or social class in this population.

Asthma↗

Ventral and dorsal horn acetylcholinesterase neurons are maintained in organotypic cultures of postnatal rat spinal cord explants.

Transverse sections of postnatal rat spinal cord have been cultured using the organotypic roller tube method. These explant cultures retain identifiable anatomical landmarks, allow identification of individual neurons, can be maintained for up to 8 weeks, and undergo maturational changes in vitro. Putative ventral horn motoneurons were identified in these cultures by localization to ventral horn regions analogous to those of motoneurons in vivo and by staining for choline acetyltransferase (ChAT) immunoreactivity and acetylcholinesterase (AChE) activity. Morphometric studies of the photomicrographic areas of cell bodies of these ventral horn neurons in intact cultures show a range of sizes up to 1635 microns 2 with the average size being 245 +/- 7 microns 2 (n = 724) (average +/- S.E.M.). The size ranges are roughly comparable to cross-sectional areas determined previously for ventral horn motoneurons in vivo. Dorsal horn regions of these cultures also developed prominent AChE activity that was absent at explantation. Biochemical analysis of ChAT and AChE activity in pooled samples of whole cultures showed ChAT activity to be 0.48 +/- 0.08 (n = 7) mumol/min/g protein and AChE activity to be 12.2 +/- 2.0 (n = 7) mumol/min/g protein at 37 degrees C (averages +/- S.E.M.). These values are comparable to previously reported values for neonatal rat spinal cord in situ. Organotypic roller tube cultures of postnatal rat spinal cord provide an attractive system for studies of survival, morphology, growth and differentiation of mammalian ventral horn neurons in vitro.

Acetylcholinesterase↗

Interactive radio instruction: developing instructional methods.

The USAID has, since 1972, funded the development of a new methodology for educational radio for young children through 3 projects: the Radio Mathematics PRoject of Nicaragua, the Radio Language Arts Project of Kenya, and the Radio Science PRoject of Papua New Guinea. These projects developed math programs for grades 1-4 and English as a second language for grades 1-3; programs to teach science in grades 4-6 are now being developed. Appropriate techniques were developed to engage young children actively in the learning process. Lessons are planned as a "conversation" between the children and the radio; scripts are written as 1/2 of a dialogue, with pauses carefully timed so that written as 12 of a dialogue, with pauses carefully timed so that students can contribute their 1/2. Teaching techniques used in all 3 projects include choral responses, simultaneous individual seatwork, and activities using simple materials such as pebbles and rulers. Certain techniques were specific to the subject being taught, or to the circumstances in which the lessons were to be used. Patterned oral drill was used frequently in the English lessons, including sound-cued drills. "Deferred" oral responses were used often in the math lessons. In this method, the children are instructed to solve a problem silently, not giving the answer aloud until requested, thus allowing time for even the slower children to participate. "One-child" questions were used in both English and science: the radio asks a question to be answered by a single child, who is selected on the spot by the classroom teacher. This allows for open-ended questions, but also requires constant supervision of the classroom teacher. Songs and games were used in all programs, and extensively for didactic purposes in the teaching of English. Instructions for science activities are often more complex than in other courses, particularly when the children are using science apparatus, especially when they work in pairs to share scarce equipment, a cost-saving device developed specifically for use in the science course.

Adolescent↗

Comparison of limbal and peripheral human corneal epithelium in tissue culture.

Peripheral human corneal epithelium grows better in tissue culture than central epithelium, but it is not known whether ocular limbal epithelium grows even better than does the peripheral corneal epithelium. In this work we compared the growth kinetics of limbal and peripheral human corneal epithelial cells in tissue culture. Four 1-2 mm2 explants, removed from the limbus or from peripheral cornea (1-2 mm inside the limbus) of eye bank eyes, were grown to confluence in primary culture. Cells were then passaged at 2 X 10(5) cells per dish. At intervals thereafter, the cells were counted in a hemocytometer to determine plating efficiency and growth curves. Mitotic activity was determined 4 days after passaging by labeling cultures with 3H-thymidine and counting aliquots using the hemocytometer and scintillation counter. In the primary cultures, limbal epithelium grew as small, uniformly polygonal cells. Peripheral corneal cells grew to a variety sizes. The 24 hr plating efficiency and doubling time of limbal epithelial cells were 47 +/- 8% and 80 +/- 14 hr, respectively, while those of peripheral corneal cells were 41 +/- 10% (P less than 0.1) and 131 +/- 25 hr (P less than 0.001). The mitotic activity of limbal cells was significantly higher than that of peripheral (2.9 +/- 1.2 vs. 0.8 +/- 0.6) (P less than 0.01). These results indicate that human ocular limbal epithelium grows better in culture than does peripheral human corneal epithelium.

Adult↗

Response of ocular surface epithelium to corneal wounding in retinol-deficient rabbits.

The purpose of this study was to explore the nature and time course of the functional effects of early retinol deficiency on the ocular surface epithelium. To this end, the conjunctival epithelial healing rate, mitotic rate, and goblet cell frequency were determined following experimental ocular surface epithelial wounding in 15 rabbits sustained on a retinol-deficient diet and in 12 pair-fed controls. The animals were sacrificed at 2, 7, and 14 days after wound closure. The mean serum retinol level (+/- SEM) prior to wounding was 6.0 +/- 0.9 microgram/dl for the group fed the deficient diet. The mean serum and liver retinol levels for this group following defect closure were 4.0 +/- 0.5 micrograms/dl and 0 micrograms/g, respectively. These values are all significantly less than the analogous respective control values of 83.2 +/- 2.4 micrograms/dl, 77.6 +/- 2.3 micrograms/dl and 35.1 +/- 3.0 micrograms/g (P less than 0.001 for each pair, student t-test). In the retinol-deficient animals, the unwounded eyes had an abnormally high rate of conjunctival epithelial cell mitosis, the earliest ocular surface cellular abnormality detected. Hypermitosis of the unwounded corneal epithelium was also noted, though somewhat later than in the conjunctiva. Epithelial wound healing was delayed considerably in the retinol-deficient group, with only 33% of eyes in this group healed within the same time period as the controls (P less than 0.05, Chi-square). Normal numbers of goblet cells were noted in the conjunctiva of retinol-deficient animals, despite at least 5, and up to 8 weeks of profoundly depleted retinol stores.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An ultrastructural study of rabbit ocular surface transdifferentiation.

When debridement of the rabbit cornea is followed by re-epithelialization from the conjunctiva, a process of transdifferentiation of the endothelium occurs. Goblet cells appear peripherally 1 week after healing of the epithelial defect, are widespread at 2 weeks, and disappear centrally at 3 to 4 weeks. Six weeks after closure of the defect, the epithelium has reverted to the customary corneal appearance. The morphology of the regenerating epithelium was studied by light, transmission and scanning electron microscopy. The precursor cells for the goblet cells were identified in stage 1, before PAS-positive cells were present, as pairs of cells with dark cytoplasm and prominent Golgi. Subsequently, goblet cells were present in pairs, indicating that goblet cells are derived from non-goblet epithelial cells, and that they do not simply migrate onto the cornea. At the time of transdifferentiation, loss of goblet cells was shown to occur both by desquamation from the surface and by in situ cell death.

Animals↗

Conjunctival goblet cells and mitotic rate in children with retinol deficiency and measles.

To study the effect of retinol deficiency and measles on the conjunctival epithelium, we determined the epithelial mitotic rate (MR) and goblet cell frequency (GCF) in conjunctival biopsy specimens from preschool children in Hyderabad, India. We studied three groups of children: normal appearing, clinically retinol deficient (defined by the presence of superficial fine punctate keratitis), and clinically retinol deficient with measles. The last group was subdivided into those with low serum retinol levels (less than or equal to 20 micrograms/dL [less than or equal to mumol/L]) and those with normal serum retinol levels (greater than 20 micrograms/dL [greater than 0.70 mumol/L]). In the control group of seven normal-appearing children with a mean age of 4.6 years, the mean MR was 1.3% +/- 0.4%, and the mean GCF was 8.0% +/- 3.6% of the basal epithelial cells. In seven children with clinical retinol deficiency, the mean MR was 15.4% +/- 1.2%, and the mean GCF was 1.0% +/- 0.5%, values significantly different from normal ones. Among 11 children with clinical retinol deficiency, measles, and low serum retinol levels, the mean MR was 9.0% +/- 1.9%, and the mean GCF was 3.1% +/- 1.1%, values not statistically different from those in children with clinical retinol deficiency alone. Five children with clinical retinol deficiency, measles, and normal serum retinol levels had a mean MR of 10.2% +/- 3.7% and a mean GCF of 1.9% +/- 1.7%, values similar to those in the other disease groups. This indicates that retinol deficiency sufficient to cause clinical signs without subepithelial scarring or keratinization is associated with hyperproliferation of the conjunctiva whether or not there is a superimposed measles infection.

Biopsy↗