Vitreoretinal surgery for retinal detachment in retinochoroidal colobomata.

PURPOSE: To report the management and outcome of retinal reattachment surgery in retinochoroidal coloboma. METHODS: Four patients with retinochoroidal colobomata presented to the Bristol Eye Hospital (a UK tertiary referral center for vitreoretinal surgery) with retinal detachment. INTERVENTION: All were type II colobomatous detachments (three patients with type IIB, one patient with type IID). All eyes underwent vitrectomy with endolaser and/or cryotherapy and three eyes underwent scleral buckling. Two eyes had internal tamponade with gas (SF6, C3F8) while the other two had silicone oil. Endolaser was applied over healthy retinal pigment epithelium. RESULTS: At last follow-up, all (100%) remained attached, with no recurrences. Three patients achieved visual acuity of 6/120 or better and were able to perform satisfactory near work with appropriate magnifiers. The last patient began with hand movement vision and retained similar vision but subjectively felt more navigational. CONCLUSIONS: Good anatomic and functional outcomes can be achieved in this patient group with combined vitrectomy with or without scleral buckling surgery. Endolaser retinopexy is effective over healthy RPE at the margin of the coloboma combined with either gas or oil internal tamponade.

Prevalence and risk factors of diabetic retinopathy in non-Hispanic whites and Hispanics with NIDDM. San Luis Valley Diabetes Study.

Diabetic retinopathy (DR) is the leading cause of blindness in adults in the United States. Because photocoagulation can reduce the incidence of blindness from severe DR by approximately 50%, it is important to identify people at increased risk for DR so that appropriate treatment can be accomplished. Use of populations at increased risk for diabetes may identify groups at increased risk for complications. A recent report from the San Antonio Heart Study showed that Mexican Americans were at greater risk for servere DR than non-Hispanic Whites. To compare the prevalence of DR between non-Hispanics and Hispanics in southern Colorado, 279 people with non-insulin-dependent diabetes mellitus (NIDDM) were identified, and retinal photographs identified the presence and severity of retinopathy. The worse eye was used to classify the severity of DR for each patient. Ninety percent of the subjects (166 Hispanics and 85 non-Hispanic Whites) were classified by retinopathy level. The duration-adjusted prevalence of any DR was 41.8% in Hispanics and 54.1% in non-Hispanic Whites. Severe DR (preproliferative and proliferative) occurred in 18.5% of the Hispanics and in 21.3% of the non-Hispanic Whites. The odds ratio for any DR, comparing Hispanics with non-Hispanic Whites adjusted for other risk factors, was 0.40 (95% confidence interval = 0.21, 0.76). Other risk factors for the presence of any retinopathy included use of exogenous insulin, increased duration of diabetes, younger age at diagnosis, increased glycosylated hemoglobin level, and increased systolic blood pressure. These data suggest that, compared with non-Hispanic Whites, Hispanics in Colorado may be at decreased risk for diabetic retinopathy.

Reduced risk of IDDM among breast-fed children. The Colorado IDDM Registry.

The hypothesis that breast-feeding can provide protection against the development of insulin-dependent diabetes mellitus (IDDM) and would, therefore, be less common among subjects with IDDM was tested with a retrospective design. Cases (n = 268) were selected from the Colorado IDDM Registry and the Barbara Davis Center for Childhood Diabetes (Denver, CO). Two control groups were recruited, one from physicians' practices throughout Colorado (n = 291) and the second through random-digit dialing from the Denver area (n = 188). Cases were less likely to have been breast-fed than controls after adjustment for birth year, maternal age, maternal education, family income, race, and sex [adjusted odds ratio (OR) = 0.70; 95% confidence interval (CI) = 0.50-0.97]. This finding was consistent for both control groups and by birth-year intervals. A greater decrease in risk of IDDM was seen among subjects who had been breast-fed to an older age (for breast-feeding duration of greater than or equal to 12 mo, adjusted OR = 0.54, 95% CI = 0.27-1.08). The amount of IDDM that might be explained by breast-feeding habits (population percentage attributable risk) ranged from 2 to 26%, varying according to the breast-feeding prevalence reported in other studies. Replication of this work in different populations, controlled for the strong secular trends in breast-feeding habits, is critical before the hypothesis of protection is accepted.

Neural progenitor cells from postmortem adult human retina.

BACKGROUND: Given the presence of neural progenitor cells (NPC) in the retina of other species capable of differentiating into multiple neural components, the authors report the presence of NPC in the adult human retina. A resident population of NPC suggests that the retina may constitutively replace neurons, photoreceptors, and glia. METHODS: Adult human postmortem retinal explants and cell suspensions were used to generate cells in tissue culture that display the features of NPC. The phenotype of cells and differentiation into neurons was determined by immunocytochemistry. Dividing cells were labelled with 5-bromo-2-deoxyuridine (BrdU) and neurospheres were generated and passaged. RESULTS: Cells labelled with nestin, neurofilament M (NFM), rhodopsin, or glial fibrillary acidic protein (GFAP) grew out from explant cultures. BrdU labelling of these cells occurred only with basic fibroblast growth factor (FGF-2). Dissociated retina and pars plana generated primary neurospheres. From primary neurospheres, NPC were passaged to generate secondary neurospheres, neurons, photoreceptors, and glia. BrdU labelling identified dividing cells from neurospheres that differentiated to express NFM and rhodopsin. CONCLUSION: The adult human retina contains NPC and may have the potential to replace neurons and photoreceptors. This has implications for the pathogenesis and treatment of retinal disorders and degenerations, including glaucoma, and those disorders associated with retinal scarring.

Signal intensity, clinical activity and cross-sectional areas on MRI scans in thyroid eye disease.

The signal intensity from inflamed extra-ocular muscles on short tau inversion recovery (STIR)-sequence magnetic resonance imaging (MRI) is known to correlate with clinical scores of thyroid eye disease (TED) severity. Twenty-one patients who had undergone repeated MRI scanning for TED were studied retrospectively. Signal intensity of extra-ocular muscles (from STIR-sequence MRI) and cross-sectional area (from STIR and T1 MRI) were correlated with Mourits' clinical activity score (CAS). The area of highest signal intensity within the most inflamed extra-ocular muscle, and the average cross-sectional signal intensity of the most inflamed extra-ocular muscle reliably correlated with CAS, and this was maintained as disease activity changed over time. In contrast, isolated measures of muscle cross-sectional area did not correlate with CAS. The extra-ocular muscle cross-sectional area calculated from STIR-sequence MR images was greater than that measured on T1 images. This suggests that muscle area from STIR-sequence MRI may also detect peri-muscular inflammation. We conclude that the peak signal intensity from the most inflamed extra-ocular muscle remains the most reliable correlate of clinical disease activity obtained from these images. STIR-sequence MRI scans provide a number of useful measures of disease activity in TED.

Usual dietary fat intake and insulin concentrations in healthy women twins.

OBJECTIVE: To evaluate the associations between the usual intake of dietary fats and insulin concentrations. Insulin concentrations and insulin resistance have been positively related to risk for NIDDM, obesity, hypertension, dyslipidemia, and coronary heart disease, yet little is known of the environmental risk factors for relative hyperinsulinemia. Insulin resistance can be induced by high-fat feeding in laboratory animals; therefore, high-fat diets may increase risks for developing NIDDM. RESEARCH DESIGN AND METHODS: Subjects included 544 nondiabetic women who participated in the second examination of the Kaiser Permanente Women Twins Study (1989-1990). Fasting and 2-h post 75-g glucose load insulin levels were determined. Dietary fat intake was assessed by a food frequency questionnaire. Generalized least-squares regression analyses for unpaired twin data were used to determine the relationship between dietary fat intake and insulin levels after adjustment for total calories, age, several behavioral variables, and in some models, percentage of body fat and waist-to-hip ratio. Associations of dietary fat intake with insulin levels were also evaluated within the subset of monozygotic twin pairs (n = 164 pairs) after removal of genetic influences by regression analysis of intrapair differences. RESULTS: Among the 544 individual women, a 20 g/day increase in total dietary fat was associated with a higher fasting insulin level (9% [P < 0.001] before and 6% [P < 0.01] after adjustment for the obesity variables). Higher intakes of saturated fat, oleic acid, and linoleic acid were each positively related to higher fasting insulin values. The relation of dietary fat with fasting insulin was significantly attenuated among physically active women compared with those who were sedentary (P = 0.04), even after adjustment for obesity. Only saturated fat intake was significantly associated with 2-h postglucose load insulin level before (P = 0.004) but not after adjustment for obesity. Within identical twin pairs, total dietary fat was positively related to fasting insulin before (P = 0.03) but not after adjustment for obesity (P = 0.11). CONCLUSIONS: High intake of total dietary fat is positively related to relative fasting hyperinsulinemia in nondiabetic women, particularly those who are sedentary. This effect appears to be partly mediated by the relation of dietary fat with obesity.

Relationship between habitual physical activity and insulin levels among nondiabetic men and women. San Luis Valley Diabetes Study.

OBJECTIVE: To determine whether higher levels of physical activity would be associated with lower fasting insulin and C-peptide levels in a free-living nondiabetic population. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted with a Hispanic and non-Hispanic white population of 442 men and 489 women with normal glucose tolerance (by World Health Organization criteria) in two rural Colorado counties. Total physical activity was assessed by a 7-day physical activity recall from which metabolic equivalents were estimated. Relationships between metabolic equivalents and fasting insulin and C-peptide were assessed while considering obesity, age, and other risk factors known to influence fasting insulin levels. RESULTS: Among all subjects, univariate analyses showed that higher activity levels were associated with lower mean fasting insulin and C-peptide levels (P less than or equal to 0.05). Multiple linear regression showed that higher activity was significantly associated with lower values of log fasting insulin and C-peptide levels in men only (P less than 0.001) independent of obesity, fat distribution, and age. Men in the highest tertile of activity had an adjusted mean fasting insulin level of 59.2 pM and fasting C-peptide level of 0.5 nM compared with a fasting insulin level of 72.7 pM and fasting C-peptide level of 0.6 mM for men in the lowest tertile of activity. The magnitude of the inverse association between activity and insulin was greatest in older rather than younger men. Physical activity was not associated with fasting insulin or C-peptide levels in women in the multivariate analyses. CONCLUSIONS: Based on cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower fasting insulin and C-peptide levels in Hispanic and non-Hispanic white men.

Microvascular complications of NIDDM in Hispanics and non-Hispanic whites. San Luis Valley Diabetes Study.

The goal of this article was to examine the differences in the rates of microvascular complications of non-insulin-dependent diabetes mellitus (NIDDM) in Hispanic and non-Hispanic white subjects. This was a geographically based case-control study where prevalent cases of NIDDM were identified in medical records. Subjects attended a 4-h clinic to confirm NIDDM diagnosis and assess complication end points. Retinopathy was defined by stereofundus photographs. Distal symmetric neuropathy was determined by standardized clinical examination. Nephropathy was indicated by serum creatinine level, urine protein-creatinine ratio, and urine albumin concentration. This study consisted of 279 NIDDM subjects confirmed by oral glucose tolerance test and World Health Organization criteria aged 20-74 yr (187 Hispanic and 92 non-Hispanic white subjects). Duration-adjusted prevalence of retinopathy was significantly higher in non-Hispanic white subjects (54.1 per 100, 95% confidence interval [CI] 44.4-63.7) than in Hispanics (41.8 per 100, 95% CI 34.8-48.8). This excess occurred only in non-Hispanic white subjects with background retinopathy but not in those with more severe retinopathy. Hispanics and non-Hispanic white subjects did not differ significantly for the prevalence of neuropathy (31.6 per 100 in non-Hispanic white subjects and 26.3 per 100 in Hispanics) or nephropathy by any measure. There were no significant differences in duration of diabetes or mean glycohemoglobin levels between ethnic groups. Microvascular complications of NIDDM are not in excess among Colorado Hispanics, and retinopathy may be somewhat more common in non-Hispanic white people.

Relationship between habitual physical activity and insulin area among individuals with impaired glucose tolerance. The San Luis Valley Diabetes Study.

OBJECTIVE: To determine whether higher levels of physical activity are associated with lower fasting insulin levels and lower insulin areas under the oral glucose tolerance curve in individuals with impaired glucose tolerance (IGT) in a community setting. RESEARCH DESIGN AND METHODS: Data from a cross-sectional study of a population consisting of 219 Hispanic and non-Hispanic white men and women with IGT (by World Health Organization criteria) in two rural Colorado counties were analyzed. Total physical activity was assessed by a 7-day physical activity recall, from which metabolic equivalents (METs) were estimated (expressed as MET h/week). Relationships of MET h/week with fasting insulin levels and insulin areas were assessed while considering obesity, age, and other risk factors known to influence fasting insulin level and insulin area. RESULTS: Among all subjects, univariate analyses showed that higher physical activity levels were associated with lower mean insulin areas and fasting insulin levels (both P < 0.05). Multiple linear regression showed that higher levels of physical activity were significantly associated with lower values of of the insulin area (P < 0.001) but not with fasting insulin levels. The relationship between insulin area and habitual physical activity was independent of obesity, fat distribution, and age. CONCLUSIONS: On the basis of cross-sectional data, we conclude that higher levels of habitual physical activity are associated with lower insulin areas in a population of individuals with IGT. Understanding the impact of physical activity on markers of insulin action in individuals with IGT is important because of the greatly enhanced risk of non-insulin-dependent diabetes mellitus and, hence, cardiovascular disease in this population.

Integration of the delta-endotoxin gene of Bacillus thuringiensis into the chromosome of root-colonizing strains of pseudomonads using Tn5.

The delta-endotoxin gene (tox) from Bacillus thuringiensis subsp. kurstaki HD-1 was cloned into Tn5 and the resulting Tn5-tox element transposed from a vector plasmid into the chromosome of six corn-root-colonizing strains of Pseudomonas fluorescens and Agrobacterium radiobacter. Chromosomal integration of the tox gene maximized stability and minimized the potential for horizontal transfer of the tox gene to other bacterial species. Expression of the tox gene was demonstrated by Western blot analysis and by toxicity against larvae of the tobacco hornworm (Manduca sexta). The method described illustrates how a given gene can be stably integrated into the chromosome of diverse bacterial species.

IS50L as a non-self transposable vector used to integrate the Bacillus thuringiensis delta-endotoxin gene into the chromosome of root-colonizing pseudomonads.

Insertion sequence IS50L of transposon Tn5 was used as a non-self transposable vector to integrate the delta-endotoxin gene (tox) from Bacillus thuringiensis subsp. kurstaki HD-1 into the chromosome of two corn-root colonizing strains of Pseudomonas fluorescens (112-12 and Ps3732-3-7). A DNA fragment containing the KmR gene from Tn5 and tox was inserted into an IS50L element (IS50L-tox) contained on a suicide plasmid. Transposition of IS50L-tox into the chromosome of P. fluorescens 112-12 and Ps3732-3-7 occurred by selecting for KmR transconjugants and supplying transposase in cis from a linked IS50R element. A frameshift mutation in the transposase gene of the IS50L-tox element was also constructed to decrease the likelihood that suppression or a spontaneous reversion at the UAA (ochre) termination codon of IS50L would create an active transposase. The inability of IS50L-tox to transpose further minimizes the potential for horizontal gene transfer of the tox gene to other bacterial species. Expression of the Tox protein in strains 112-12 and Ps3732-3-7 was demonstrated by an immunological assay (Western blot) and toxicity against larvae of the tobacco hornworm (Manduca sexta).

Physical-activity-assessment measures compared in a biethnic rural population: the San Luis Valley Diabetes Study.

We evaluated the consistency of three questionnaire methods of assessing work and leisure activity in the rural biethnic population of the San Luis Valley Diabetes Study. A 7-d physical activity recall (PAR), a ranking of usual activity, and a history of usual participation in vigorous activity were used. Energy expenditure (kJ.kg-1.wk-1) (EE) was estimated from PAR. Subjects were 503 adults [49% non-Hispanic white (NHW), 51% Hispanic]. Physical activity at work rather than leisure-time activity largely determined total energy expenditure. Average EE at work increased with work rank for all subjects combined [mean EE (SEE) for rank 1 (low) = 324.2 (24.4), rank 4 (high) = 874.0 (102.1)] and within sex, ethnic, and occupational subgroups. Leisure EE increased with leisure rank only for NHW men and employed women. Similar patterns were observed in comparisons of PAR data with history of vigorous activity. Further development and validation of instruments appropriate for use across population subgroups are needed.

The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results.

The Insulin Resistance Atherosclerosis Study (IRAS) is the first epidemiologic study designed to assess the relationships between insulin resistance, insulinemia, glycemia, other components of the insulin resistance syndrome, and prevalent cardiovascular disease (CVD) in a large multiethnic cohort. Over 1600 men and women were recruited from four geographic areas to represent a range of glucose tolerance (normal, impaired, and diabetic) and ethnicity (hispanic, non-Hispanic white, and African-American). Insulin resistance was assessed directly using the frequently sampled intravenous glucose tolerance test with minimal model analysis. Intimal-medial carotid artery wall thickness, an indicator of atherosclerosis, was measured using B-mode ultrasonography. Prevalent CVD was assessed by questionnaire and resting electrocardiography. This report describes the design of the study and provides the recruitment results. Forthcoming cross-sectional analyses will help to disentangle the association between insulin resistance and CVD, apart from the concomitant hyperinsulinemia and related CVD risk factors.

Structural studies on phospholamban and implications for regulation of the Ca(2+)-ATPase.

The cardiac sarcoplasmic reticulum (SR) protein phospholamban (PLB) is an endogenous inhibitor of the SR Ca(2+)-ATPase. Phosphorylation of PLB relieves this inhibition and up-regulates calcium transport. PLB has proved remarkably difficult to study by conventional solution-state nuclear magnetic resonance (NMR) methods, due primarily to the extreme hydrophobic nature of the protein and its propensity to form pentamers. That the C-terminal domain of PLB is helical and membrane spanning is now well established; the structure of the cytoplasmic domain is relatively ill defined. In order to discern the effect of phosphorylation on the structure of the cytoplasmic domain, we have characterized a variety of model peptides in several structure-inducing and/or lipid-mimicking environments using circular dichroism and solution-state NMR. The resolution of peptide structures obtained in aqueous trifluoroethanol was markedly improved by the incorporation of 15N labels into the peptide backbone, allowing a variety of isotope edited, filtered, and resolved techniques to be applied. Molecular dynamics simulations on the full-length protein were combined with an analysis of published data to suggest a revised model for the structure of PLB.

Nestin positive cells in adult human retina and in epiretinal membranes.

BACKGROUND/AIM: Nestin is an intermediate filament marker for neural progenitor cells. The authors aimed to identify nestin positive cells in adult human retina and within surgically removed epiretinal membranes. METHODS: Adult human retina and epiretinal membranes were studied. Tissue was fixed and processed for semithin sections or whole mount preparations for immunohistochemical detection of nestin and glial fibrillary acidic protein (GFAP) expression. RESULTS: Nestin positive cells are most prominent at the ora serrata, possess fibrillary processes, small amounts of perinuclear cytoplasm, and are arranged radially within or superficially on the retina. In the posterior retina, speckled cytoplasmic nestin staining is seen around the nuclei of neurons. In the peripapillary retina most of the cells in the retinal ganglion cell layer are nestin positive. These cells appear to represent nestin positive neurons. Speckled cells are also seen in the myelinated portion of the optic nerve. In epiretinal membranes patches of elongated nestin positive cells were found. These cells were also positive for GFAP. CONCLUSIONS: Some neurons and glia in the adult human retina are nestin positive. Their pattern in anterior retina suggests an analogy with the ciliary marginal zone found in many other species. The role of these cells in pathological responses to retinal disease is suggested by the presence of large numbers of ectopic nestin positive cells in epiretinal membranes. The authors hypothesise that nestin positive cells represent a population of progenitor cells from normal adult human retina that differentiate to make up retinal scar tissue.

Novel corneal features in two males with incontinentia pigmenti.

Incontinentia pigmenti (IP) is a rare X linked genetic disorder, which predominantly affects females. The mutations are usually lethal in males. Two male cases are presented; a genetic mosaic for the common IP deletion and another in whom the genetic abnormality has not yet been characterised. Emphasis is placed on the ocular features present in this disorder and in particular a novel corneal feature and its possible aetiology.

Effects of Hot shot on recovery after hypothermic ischemia in neonatal lamb heart.

BACKGROUND: Terminal warm blood cardioplegia, "Hot shot", is the method for providing an energy replenishment and/or early recovery of aerobic metabolism without electromechanical activity at initial reperfusion. The mechanism of beneficial effects of this Hot Shot is multifactorial. This study was designed to assess the effects of terminal warm blood cardioplegia by comparing with oxygenated terminal warm crystalloid cardioplegia. METHODS: In Group HS-B, n=8 (oxygenated blood; 37 degrees C, Ht: 20%, K+ 20 mEq/l, pH 7.237, PO2 219 mmHg) and in Group HS-C, n=8 (bloodless oxygenated (5% CO2+95%O2) crystalloid, 37 degrees C, K+ 20 mEq/l, pH 7.435, PO2 624 mmHg), terminal warm cardioplegia (20 ml/kg for 5 minutes) was studied in the isolated blood perfused neonatal lamb heart following 2 hr of cardioplegic ischemia. Another eight hearts served as control without any kind of terminal cardioplegia. After 60 min of reperfusion, LV function was measured. Coronary blood flow (CBF), oxygen content, and oxygen consumption (MVO2) were measured and the oxygen extraction ratio was calculated in Group HS-B and HS-C during terminal cardioplegia and/or reperfusion. Results are given as % recovery of preischemic values. RESULTS: HS-B as well as HS-C groups showed better functional recovery in maximum developed pressure (DP: 78.0+/-8.3 in HS-B vs 65.2+/-9.2%; p=0.018), maximum dp/dt (67.3+/-6.2 in HS-B, 65.3+/-7.4 in HS-C vs 55.8+/-5.0%; p=0.003, p=0.02), DP V10 (87.1+/-8.5 in HS-B vs 67.2+/-9.9%; p=0.0001), and peak dp/dt V10 (76.4+/-7.6 in HS-B, 69.8+/-8.1 in HS-C vs 58.6+/-6.9 %; p=0.0001) than the control group. Between the HS-B and HS-C groups, HS-B showed better functional recovery in terms of DP V10 (p=0.01). Oxygen delivery of terminal cardioplegia was almost four times higher in HS-B group (90.4+/-17.7 vs 18.7+/-1.1 mcl/ml), contrarily, HS-C group showed four times higher oxygen extraction ratio compared to HS-B group (0.78+/-0.06 vs 0.18+/-0.11), thus oxygen consumption during hot shot was maintained at the same level in both groups. CBF in the control group was lower than that in the other groups at 60 min of reperfusion. CONCLUSIONS: Reperfusion with both terminal warm cardioplegia including blood and oxygenated crystalloid cardioplegia resulted in better recovery of function and higher levels of CBF with slightly better function in terminal warm blood cardioplegia.

The effect on visual function of Hydroview intraocular lens opacification: a cross-sectional study.

PURPOSE: Hydroview intraocular lenses (IOLs) have been associated with symptomatic opacification of the optic necessitating IOL exchange. Glare and misty vision have been noted as common presenting symptoms. This study's purpose was to investigate the impact of IOL opacification on objective measurements of visual function, including glare, and on vision-related quality of life. METHODS: All patients who underwent Hydroview IOL implantation at Bristol Eye Hospital between December 2000 and the end of February 2001 were invited for assessment along with patients found to have Hydroview IOL opacification in routine ophthalmic clinics. Glare, visual acuity, contrast sensitivity, visual field, and colour vision were assessed. Vision-related quality of life and subject's symptoms were determined by questionnaire. IOL opacification was assessed by slit lamp bio-microscopy and anterior segment photography. RESULTS: Data from 129 patients were analysed. Fifty subjects had opacified IOLs and 79 clear IOLs. Subjects with opacified IOLs showed dramatically higher levels of glare (adjusted mean difference of 0.63 log units 95% CI, 0.45-0.82; P<0.001) with only mildly reduced visual acuity (adjusted mean difference of 0.09 logMAR units 95% CI, 0.03-0.15; P=0.002). Opacification was associated with poorer contrast sensitivity (P<0.001), visual field (P<0.001), and with lower vision-related quality of life (P<0.001). CONCLUSIONS: This study highlights the significant impact IOL opacification has on visual performance and experience, in particular glare and consequent impact on quality of life. The study shows that to quantify accurately the effect of IOL opacification on vision glare must be assessed.