Response to "Potentially flawed interpretation of data by Andriulli et al.".
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Gastrointestinal Hemorrhage↗
Biomedical subjects
John Marshall
Publications and source records attributed to John Marshall.
Heritability of macular pigment: a twin study.
PURPOSE: Several studies have reported higher levels of macular pigment (MP) in association with reduced risk for age-related macular degeneration (ARMD), a disease to which there is a genetic predisposition. A classic twin study was performed to determine the heritability of MP in the healthy eye. METHODS: One hundred fifty twin pairs (76 monozygotic [MZ] and 74 dizygotic [DZ]), aged 18 to 50 years, participated. MP optical density was measured psychophysically with heterochromatic flicker photometry (HFP) and also with an imaging method involving fundus autofluorescence (AF). The covariance of MP within MZ and DZ twin pairs was compared, and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in MP. RESULTS: The mean MP optical density, measured using HFP, was 0.43 +/- 0.21. Using AF, the mean MP optical density, measured at 1 degrees eccentricity, was 0.28 +/- 0.11. MP optical densities correlated more highly in MZ twins than in DZ twins, according to both HFP (MZ: 0.65; DZ: 0.24) and AF (MZ: 0.83; DZ: 0.50). A model combining additive genetic and unique environmental effects provided the best fit and resulted in MP heritability estimates of 0.67 (95% CI, 0.52-0.77) and 0.85 (95% CI, 0.78-0.90) for HFP and AF readings, respectively. CONCLUSIONS: This classic twin study demonstrates that genetic background is an important determinant of MP optical density, reflected in heritability estimates of 0.67 and 0.85 for HFP and AF measures, respectively.
Adolescent↗
Biologic therapy for colon cancer.
Targeted biologic therapy remains a very active and evolving field since the US Food and Drug Administration approved cetuximab, a recombinant, human/mouse chimeric monoclonal antibody against the endothelial growth factor receptor, and bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor, for the treatment of colorectal cancer. Benefits of these reagents in diverse clinic settings combined with different chemotherapeutic agents are being defined. Current research is focused on defining which patients will benefit from these treatments and how best to use them in the clinic. Additional preclinical and clinical studies will enable better usage of these biologic agents and lead to the development of new targeted therapies for the treatment of colon cancer.
Animals↗
Clinician discomfort with life support plans for mechanically ventilated patients.
OBJECTIVE: To examine the incidence and predictors of clinician discomfort with life support plans for ICU patients. DESIGN AND SETTING: Prospective cohort in 13 medical-surgical ICUs in four countries. PATIENTS: 657 mechanically ventilated adults expected to stay in ICU at least 72 h. MEASUREMENTS AND RESULTS: Daily we documented the life support plan for mechanical ventilation, inotropes and dialysis, and clinician comfort with these plans. If uncomfortable, clinicians stated whether the plan was too technologically intense (the provision of too many life support modalities or the provision of any modality for too long) or not intense enough, and why. At least one clinician was uncomfortable at least once for 283 (43.1%) patients, primarily because plans were too technologically intense rather than not intense enough (93.9% vs. 6.1%). Predictors of discomfort because plans were too intense were: patient age, medical admission, APACHE II score, poor prior functional status, organ dysfunction, dialysis in ICU, plan to withhold dialysis, plan to withhold mechanical ventilation, first week in the ICU, clinician, and city. CONCLUSIONS: Clinician discomfort with life support perceived as too technologically intense is common, experienced mostly by nurses, variable across centers, and is more likely for older, severely ill medical patients, those with acute renal failure, and patients lacking plans to forgo reintubation and ventilation. Acknowledging the sources of discomfort could improve communication and decision making.
APACHE↗
Your liability for a locum.
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Insurance, Liability↗
Attenuated type II TGF-beta receptor signalling in human malignant oral keratinocytes induces a less differentiated and more aggressive phenotype that is associated with metastatic dissemination.
We examined the effect of stable transfection of dominant negative TbetaR-II (dn TbetaR-II) cDNA in a human oral carcinoma cell line that contained normal Ras and was growth inhibited by TGF-beta1. Two clonal cell lines containing dn TbetaR-II were isolated and compared to the vector-only control and parent cell line. The treatment of cells with exogenous TGF-beta1 resulted in a decrease in ligand-induced growth inhibition and loss of c-myc downregulation in test cells compared to controls; transcriptional activation of certain genes including fra-1 and collagenase was retained. Cells containing dn TbetaR-II grew faster in monolayer culture, expressed less keratin 10 and exhibited increased motility and invasion in vitro compared to control cell lines. Endogenous TGF-beta1 production and the regulation of MMP-2 and MMP-9 by TGF-beta1 remained unchanged. After orthotopic transplantation to the floor of the mouth in athymic mice, cells containing dn TbetaR-II formed comparable numbers of primary tumours at the site of inoculation as controls but the tumours were less differentiated as demonstrated by the absence of keratin 10 immunostaining. Further, metastatic dissemination to the lungs and lymphatics was more evident in grafts of cells containing dn TbetaR-II than controls. Taken together, the results demonstrate that attenuation of TGF-beta signalling through transfection of dn TbetaR-II cDNA leads to an enhanced growth rate, a loss of tumour cell differentiation and an increase in migration and invasion, characteristics that corresponded to the development of the metastatic phenotype.
Cell Differentiation↗
Source control for surgical infections.
The concept of source control encompasses all of the physical interventions, surgical and otherwise, that are used to treat infection. Although source control is one of the most important aspects of the treatment of serious infection, it has received relatively little attention. It is the topic of this overview, which draws heavily on a book we edited recently: Source Control: A Guide to the Management of Surgical Infection (Springer-Verlag, 2002). The first section focuses on general considerations: historical perspective, scientific basis, and surgical principles of source control. The second section highlights specific considerations of source control in various situations.
Abscess↗
A phase I study of oral BMS-275291, a novel nonhydroxamate sheddase-sparing matrix metalloproteinase inhibitor, in patients with advanced or metastatic cancer.
PURPOSE: BMS-275291 is a novel broad-spectrum inhibitor of matrix metalloproteinase (MMPs) rationally designed to spare a class of closely related metalloproteinases known as sheddases. Inadvertent sheddase inhibition is hypothesized to play a role in the dose-limiting joint toxicities occurring with hydroxamate-based MMP inhibitors. This trial was conducted to establish the recommended phase II dose; determine safety, toxicity, and pharmacokinetics of BMS-275291; and to assess potential markers of sheddase activity [tumor necrosis factor-alpha (TNFalpha) release and TNFalpha-RII shedding]. EXPERIMENTAL DESIGN: This was an open label, single arm, phase I study conducted at two centers. Patients with advanced or metastatic cancer were treated with once-daily oral BMS-275291 at doses escalating from 600 to 2400 mg/day. Six to eight patients/dose level were to be studied with the recommended phase II dose level expanded to a total of 15 patients. Pharmacokinetic sampling was performed on days 1, 15, and 29 at 0, 0.5, 1, 2, 4, 6, 8, and 24 h after dosing. Radiological tumor assessment was performed every 8 weeks. RESULTS: Forty-four evaluable patients were enrolled in this study with the most frequent tumor types being colorectal cancer and non-small cell lung cancer. Dose limiting toxicities were observed at 600 mg/day (one of eight patients with grade 3 transaminitis) and at 1200 mg/day (1 of 15 patients with grade 3 rash and grade 4 shortness of breath), both in the context of predisposing conditions. No dose-limiting toxicities occurred at 900, 1800, or 2400 mg/day. The most frequent adverse events considered possibly, probably, or definitely drug-related were joint toxicity (myalgia/arthralgia), rash, fatigue, headache, nausea, and taste change, all of which were mild, grade 1, grade 2, and not dose-limiting. No objective tumor responses were observed. Twelve of forty-four patients received treatment for 4+ months, six for 8+ months, three for >1 year. Desired trough levels of parent BMS-275291 were maintained with once daily dosing. The mean plasma concentration of parent BMS-275291 at trough exceeded the calculated in vitro IC(80) value for MMP-2 and IC(90) value for MMP-9 at the recommended phase II dose of 1200 mg/day. No major changes in serum concentrations of sheddase enzymatic products, TNFalpha or TNFalpha-RII, were observed. CONCLUSIONS: BMS-275291 is a nonhydroxamate MMP inhibitor with a novel mercaptoacyl zinc-binding group. In this study, plasma concentrations of BMS-275291 continuously exceeded in vitro MMP IC(50) values without dose-limiting joint toxicity. In this refractory patient population, a suggestion of disease stabilization was observed in 12 patients. On the basis of preclinical, clinical, and pharmacokinetic data, the recommended phase II dose for future study is 1200 mg/day.
Adult↗
Bimolecular interaction of insulin-like growth factor (IGF) binding protein-2 with alphavbeta3 negatively modulates IGF-I-mediated migration and tumor growth.
Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the alpha v beta 3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and alpha v beta 3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7 beta 3, which overexpressed the alpha v beta 3 integrin. Collectively, these results indicate that alpha v beta 3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.
Antibodies, Monoclonal↗
Mining biomarkers in human sera using proteomic tools.
One of the major difficulties in mining low abundance biomarkers from serum or plasma is due to the fact that a small number of proteins such as albumin, alpha2-macroglobulin, transferrin, and immunoglobulins, may represent as much as 80% of the total serum protein. The large quantity of these proteins makes it difficult to identify low abundance proteins in serum using traditional 2-dimensional electrophoresis. We recently used a combination of multidimensional liquid chromatography and gel electrophoresis coupled to matrix-assisted laser desorption/ionization-quadrupole-time of flight and Ion Trap liquid chromatography-tandem mass spectrometry to identify protein markers in sera of Alzheimer's disease (AD), insulin resistance/type-2 diabetes (IR/D2), and congestive heart failure (CHF) patients. We identified 8 proteins that exhibit higher levels in control sera and 36 proteins that exhibit higher levels in disease sera. For example, haptoglobin and hemoglobin are elevated in sera of AD, IR/D2, and CHF patients. The levels of several other proteins including fibrinogen and its fragments, alpha 2-macroglobulin, transthyretin, pro-platelet basic protein, protease inhibitors clade A and C, as well as proteins involved in the classical complement pathway such as complement C3, C4, and C1 inhibitor, were found to differ between IR/D2 and control sera. The sera levels of proteins, such as the 10 kDa subunit of vitronectin, alpha 1-acid glycoprotein, apolipoprotein B100, fragment of factor H, and histidine-rich glycoprotein were observed to be different between AD and controls. The differences observed in these biomarker candidates were confirmed by Western blot and the enzyme-linked immunosorbent assay. The biological meaning of the proteomic changes in the disease states and the potential use of these changes as diagnostic tools or for therapeutic intervention will be discussed.
Biomarkers↗
Targeting specific PDZ domains of PSD-95; structural basis for enhanced affinity and enzymatic stability of a cyclic peptide.
A cyclic peptide, Tyr-Lys-c[-Lys-Thr-Glu(betaAla)-]-Val, incorporating a beta-Ala lactam side chain linker and designed to target the PDZ domains of the postsynaptic density protein 95 (PSD-95), has been synthesized and structurally characterized by NMR while free and bound to the PDZ1 domain of PSD-95. While bound, the lactam linker of the peptide makes a number of unique contacts outside the canonical PDZ binding motif, providing a novel target for PDZ-domain specificity as well as producing a 10-fold enhancement in binding affinity. Additionally, the cyclization greatly enhances the enzymatic stability, increasing the duration that the peptide inhibits the association between PSD-95 and glutamate receptors, effectively inhibiting the clustering of kainate receptors for over 14 hr after application. Highly specific regulation of kainate receptor action may provide a novel route for treatment of drug addiction and epilepsy.
Enzyme Stability↗
Effect of exogenous keratinocyte growth factor on corneal epithelial migration after photorefractive keratectomy.
PURPOSE: To investigate the effect of topical keratinocyte growth factor (KGF) on wound healing after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, Rayne Institute, St. Thomas' Hospital, London, United Kingdom, St. Erick's Eye Hospital, Stockholm, Sweden, and the University of Regensberg, Regensberg, Germany. METHODS: In a placebo-controlled trial, 24 New Zealand white female rabbits were divided into 3 equal groups. Group 1 (n=8) had myopic PRK (6.0 diopters [D]) using the Technolas 217z laser (Bausch & Lomb). Group 2 and Group 3 had myopic LASIK (6.0 D) with a flap depth of 140 microm and 180 microm, respectively. Topical KGF (20 microg/mL) was administered to half the treated eyes in each group intraoperatively and postoperatively; the other half received placebo eyedrops. Epithelial closure, corneal haze, and keratocyte activation in the rabbit eyes were analyzed and compared with those in placebo-controlled eyes for 5 weeks postoperatively. RESULTS: In Group 1, the mean reepithelialization after PRK was 0.10 mm2/h +/- 0.02 (SD) in the KGF group and 0.33 +/- 0.05 mm2/h in the control group (P=.001). There was no significant difference in the mean backscatter between the KGF eyes (154 +/- 45.95) and the control eyes (141 +/- 38.45) after PRK (P=.42). Histology revealed reduced epithelial cell layers in the KGF group and comparable keratocyte density as in the control group. In Groups 2 and 3, there was no significant difference in backscatter, epithelial layers, and keratocyte density between KGF and control eyes after LASIK. CONCLUSIONS: Topical KGF (20 microg/mL) delayed reepithelialization after PRK. It had no effect on stromal wound healing in LASIK eyes with an intact epithelial barrier.
Administration, Topical↗
A long-term study of photorefractive keratectomy; 12-year follow-up.
OBJECTIVE: To evaluate long-term refractive stability of excimer laser myopic photorefractive keratectomy (PRK). DESIGN: A long-term (12 years) prospective follow-up study. PARTICIPANTS: Sixty-eight patients (56.6%) of the original cohort of 120 who participated in the first United Kingdom excimer laser clinical trial underwent detailed clinical assessment at 12 years after myopic PRK. INTERVENTION: Myopic PRK was performed using the Summit Technology UV 200 excimer laser with a 4-mm ablation zone. Patients were allocated to 1 of 6 treatment groups based on their preoperative refraction. Each group received one of the following spherical corrections: -2, -3, -4, -5, -6, or -7 diopters (D). Patients in each group received an identical treatment, and therefore, emmetropia was not the primary aim. MAIN OUTCOME MEASURES: Refractive stability, refractive predictability, best spectacle-corrected visual acuity (BSCVA), and corneal haze. RESULTS: The postoperative refraction remained stable at 12 years, with no significant change in mean spherical equivalent refraction between 1, 6, and 12 years. Seventy-five percent of patients who underwent a -2-D correction and 65% of patients who received a -3-D correction were within 1 D of intended correction at 12 years. Fifty-seven percent of the -4-D group and 50% of the -5-D group were within 1 D, and this was further reduced to 25% and 22% in the -6-D and -7-D groups, respectively. Four percent had residual corneal haze, and 12% had persistent nighttime halos at 12 years. Dry eyes were encountered in 3% of patients, and none of the eyes developed corneal ectasia in the long term. CONCLUSIONS: In myopic PRK, refractive stability achieved at 1 year was maintained up to 12 years with no evidence of hyperopic shift, diurnal fluctuation, or late regression in the long term. Corneal haze decreased with time, with complete recovery of BSCVA. Night halos remained a significant problem in a subset of patients due to the small ablation zone size.
Adult↗
Risk quantification of early outcome after lung transplantation: donor, recipient, operative, and post-transplant parameters.
BACKGROUND: Because there is no reliable evaluation system of recipient acuity after lung transplantation, comparing patients among centers is difficult. The purpose of our study was to identify risk factors for 30-day mortality and prolonged intensive care unit stay and to develop a scoring system to evaluate the severity of impairment and to predict surgical outcomes. METHODS: We prospectively collected data from 122 lung transplant recipients and from 119 donors from January 1997 to June 2000. We assessed donor, recipient, and operative factors; ischemic time; and immediate post-operative physiologic parameters to identify risk factors for 30-day mortality and prolonged intensive care unit stay. Furthermore, we sub-classified these factors into grades to develop a scoring system for predicting surgical outcomes. RESULTS: Cardiopulmonary bypass use, body mass index >25 kg/m2, immediate post-operative systolic pulmonary arterial pressure, trend of oxygenation index from 12 to 24 hours after transplantation, and the Acute Physiology and Chronic Health Evaluation II score correlated significantly with outcomes, and the sum of these 5 scores correlated strongly with outcomes (p < 0.0001). CONCLUSIONS: We conclude that the total score of these 5 risk factors could be used to predict 30-day mortality and prolonged intensive care unit stay. This scoring system also will facilitate standardization among transplant centers in evaluating post-transplant severity of illness.
Female↗
Clinician predictions of intensive care unit mortality.
OBJECTIVE: Predicting outcomes for critically ill patients is an important aspect of discussions with families in the intensive care unit. Our objective was to evaluate clinical intensive care unit survival predictions and their consequences for mechanically ventilated patients. DESIGN: Prospective cohort study. SETTING: Fifteen tertiary care centers. PATIENTS: Consecutive mechanically ventilated patients > or = 18 yrs of age with expected intensive care unit stay > or = 72 hrs. INTERVENTIONS: We recorded baseline characteristics at intensive care unit admission. Daily we measured multiple organ dysfunction score (MODS), use of advanced life support, patient preferences for life support, and intensivist and bedside intensive care unit nurse estimated probability of intensive care unit survival. MEASUREMENTS AND MAIN RESULTS: The 851 patients were aged 61.2 (+/- 17.6, mean + SD) yrs with an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 21.7 (+/- 8.6). Three hundred and four patients (35.7%) died in the intensive care unit, and 341 (40.1%) were assessed by a physician at least once to have a < 10% intensive care unit survival probability. Independent predictors of intensive care unit mortality were baseline APACHE II score (hazard ratio, 1.16; 95% confidence interval, 1.08-1.24, for a 5-point increase) and daily factors such as MODS (hazard ratio, 2.50; 95% confidence interval, 2.06-3.04, for a 5-point increase), use of inotropes or vasopressors (hazard ratio, 2.14; 95% confidence interval, 1.66-2.77), dialysis (hazard ratio, 0.51; 95% confidence interval, 0.35-0.75), patient preference to limit life support (hazard ratio, 10.22; 95% confidence interval, 7.38-14.16), and physician but not nurse prediction of < 10% survival. The impact of physician estimates of < 10% intensive care unit survival was greater for patients without vs. those with preferences to limit life support (p < .001) and for patients with less vs. more severe organ dysfunction (p < .001). Mechanical ventilation, inotropes or vasopressors, and dialysis were withdrawn more often when physicians predicted < 10% probability of intensive care unit survival (all ps < .001). CONCLUSIONS: Physician estimates of intensive care unit survival < 10% are associated with subsequent life support limitation and more powerfully predict intensive care unit mortality than illness severity, evolving or resolving organ dysfunction, and use of inotropes or vasopressors.
APACHE↗
Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients?
BACKGROUND: An analysis from the prospective multicenter randomized controlled trial (Transfusion Requirements in Critical Care Trial) compared the use of restrictive and liberal transfusion strategies with resuscitated critically ill trauma patients. METHODS: Critically ill trauma patients with a hemoglobin concentration less than 90 g/L within 72 hours of admission to the intensive care unit were randomized to a restrictive (hemoglobin concentration, 70 g/L) or liberal (hemoglobin concentration, 100 g/L) red blood cell transfusion strategy. RESULTS: The baseline characteristics in the restrictive (n = 100) and liberal (n = 103) transfusion groups were comparable. The average hemoglobin concentrations (82.7 +/- 6.2 g/L vs. 104.3 +/- 12.2 g/L; p < 0.0001) and the red blood cell units transfused per patient (2.3 +/- 4.4 vs. 5.4 +/- 4.3; p < 0.0001) were significantly lower in the restrictive group than in the liberal group. The 30-day all-cause mortality rates in the restrictive group were 10%, as compared with 9% in the liberal group (p = 0.81). The presence of multiple organ dysfunction (9.2 +/- 6.3 vs. 9.0 +/- 6.0; p = 0.81), the changes in multiple organ dysfunction from baseline scores adjusted for death (1.2 +/- 6.1 vs. 1.9 +/- 5.7; p = 0.44), and the length of stay in the intensive care unit (9.8 +/- 8.1 vs. 10.2 +/- 8.7 days; p = 0.73) and hospital (31.4 +/- 17.1 vs. 33.7 +/- 17.7 days; p = 0.34) also were similar between the restrictive and liberal transfusion groups. CONCLUSIONS: A restrictive red blood cell transfusion strategy appears to be safe for critically ill multiple-trauma patients. A randomized controlled trial would provide the appropriate level of evidence with regard to the daily use of blood in this population of patients.
Adult↗
Noninvasive assessment of corneal sensitivity in young and elderly diabetic and nondiabetic subjects.
PURPOSE: To investigate the effect of age and diabetes on corneal sensitivity using the noncontact corneal aesthesiometer (NCCA). METHODS: One hundred sixteen nondiabetic subjects and 111 diabetic subjects (33 type I and 78 type II) were recruited and divided into three age groups: Young ( or=60 years). The exclusion criteria included patients with severe retinopathy requiring treatment, a history of invasive ocular surgery, or a history of conditions known to affect corneal sensitivity. The corneal cooling sensation threshold, for the right eye of each subject, was assessed with a double-staircase method-of-limits technique with the NCCA. This instrument uses a controlled pulse of air to produce a small, localized reduction in the surface temperature of the eye, which is detected by the nerves in the corneal epithelium. RESULTS: Analysis of the scatterplot of each subject's central cooling sensation threshold revealed a gradual loss of sensitivity with increasing age (nondiabetic, r(2) = 0.349; diabetic, r(2) = 0.131). Within the nondiabetic group, inter-age-group comparisons found significant differences between the central corneal cooling sensation thresholds for the three age groups (t-test, P < 0.01). Within the diabetic group, a significant difference was found between the Middle and Older categories only (t-test, P < 0.05). In summary, the Young group was more sensitive than the Middle group, which was more sensitive than the Older group. Within both type I and type II diabetic subjects, there was neither a significant relationship between duration of the disease and corneal sensitivity (t-test, P > 0.05) nor a gender-based difference (t-test, P > 0.05). CONCLUSIONS: There is a gradual reduction in corneal sensitivity with increasing age in both nondiabetic subjects and diabetic subjects, along with an increasing variation in the measured threshold. There is no relationship between corneal sensitivity and the time since diagnosis of diabetes for a thermally cooling stimulus, suggesting that the A partial differential and C fibers of the corneal innervation are affected differently by abnormal glucose metabolism in the diabetic cornea.
Adult↗
The influence of path length and matrix components on ageing characteristics of transport between the choroid and the outer retina.
PURPOSE: To determine the relative influence of path length and matrix components on the movement of small solutes and water between the choroid and the outer retina. METHODS: Human and bovine Bruch's membrane-choroid (BC) tissue samples were mounted in modified Ussing chambers, and the diffusion of taurine and hydraulic conductivity (Lp) was determined. In humans, diffusion of taurine was determined as a function of age of the donor. The relative contribution of Bruch's membrane in the BC complex to transport processes was measured after its removal by laser ablation. Similarly, the effect of choroidal path length was determined. In humans, tracking the trend of age-related thinning provided samples of various path lengths. In young bovine animals (< or =2 years old), choroidal thickness was adjusted by laser ablation. RESULTS: Diffusion of taurine across human BC decreased linearly from 162.7 to 105.9 nanomoles/h per 3 mm between 10 and 90 years of age (P < 0.05). Ablation of Bruch's membrane increased diffusion of taurine from 129 to 287.9 nanomoles/h per 4 mm in human (donor age 55, 74, and 82 years; P < 0.005) but caused no statistically significant change in bovine BC. Diffusion of taurine across bovine BC was greater in samples with partially ablated choroid (218 nanomoles/h per 4 mm) than in normal control samples (128.75 nanomoles/h per 4 mm). Lp was not measurable in bovine samples after complete ablation of Bruch's membrane, but did not change significantly as the choroid thinned. CONCLUSIONS: The data suggest that both path length and matrix components contribute to the decline of diffusion of small solutes across BC with age. The importance of matrix components was also demonstrated in restricting the movement of water while choroidal thickness played little if any role.
Adolescent↗