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Biomedical subjects

E Young

Publications and source records attributed to E Young.

At least 37 records · Page 2Linked to original sources
PubMed2001

Direct optometrist referral of cataract patients into a pilot 'one-stop' cataract surgery facility.

OBJECTIVES: To determine the feasibility of a) direct optometrist referral of patients with cataract, and b) combined assessment with same day cataract surgery ('one stop' cataract surgery). METHODS: Evaluation of 169 patients referred directly by optometrists into a pilot 'one stop' cataract surgery facility. RESULTS: Of 169 referrals, 160 patients (94.7%) were given confirmed appointments for the 'one stop' cataract service and 9 patients (5.3%) were appointed conventionally. Of 160 patients attending the 'one stop' cataract service, 154 patients (96.3%) underwent cataract surgery at the same visit, in 4 patients (2.5%) cataract surgery was indicated but deferred and in 2 patients (1.3%) cataract surgery was not indicated. The referral was supplemented with information regarding the patient's medical history forwarded by the general practitioner for 3 patients (1.8%). There were no systemic or sight-threatening complications. 151 patients (98.1%) achieved a visual acuity of 6/12 or better at a mean of 31 days post-operatively. CONCLUSION: Optometrists can accurately predict the need for cataract surgery and refer directly into a pilot 'one stop' cataract surgery facility, without the need for general practitioner involvement. 'One stop' cataract surgery is feasible; benefits to the patient include the abolition of the need to visit the general practitioner for consultation and referral, and the hospital for pre-assessment.

Ambulatory Surgical Procedures↗
PubMed2000

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Employment↗
PubMed2000

Pathologic gene expression in Gaucher disease: up-regulation of cysteine proteinases including osteoclastic cathepsin K.

Deficiency of lysosomal acid beta-glucosidase induces glycolipid storage in the macrophages of Gaucher disease but the pathways of multisystem tissue injury and destruction are unknown. To investigate the cognate molecular pathology of this inflammatory disorder, genes that were differentially expressed in spleen samples from a patient with Gaucher disease (Gaucher spleen) were isolated. Of 64 complementary DNA (cDNA) fragments sequenced from an enriched Gaucher cDNA library, 5 encode lysosomal proteins (cathepsins B, K, and S, alpha-fucosidase, and acid lipase), 10 encode other known proteins, and 2 represent novel sequences from human macrophage cell lines. Transcript abundance of the cathepsins, novel genes, pulmonary and activation-regulated chemokine (PARC), and NMB, a putative tumor suppressor gene, was greatly increased. Immunoblotting showed increased mature forms of all 3 cathepsins found in samples of Gaucher spleens. Immunofluorescence microscopy showed strong cathepsin B and K reactions in sinusoidal endothelium and Gaucher cells. The respective means, plus or minus SD, of cathepsin B, K, and S activities were 183 +/- 35, 97 +/- 39, and 91 +/- 45 nmol/min/mg protein in 4 Gaucher spleens, and 26 +/- 4, 10.5 +/- 2, and 4.0 +/- 2.1 nmol/min/mg protein in 3 control spleens. Plasma cathepsin B, K, and S activities were also elevated in Gaucher disease plasma (P <.001), but compared with control plasma samples, neither cathepsin B nor K activities were significantly elevated in 8 patients with nonglycosphingolipid lysosomal storage diseases or in 9 patients with other glycosphingolipidoses, which suggests disease specificity. All 3 cathepsin activities were increased 2-fold to 3-fold in Gaucher sera compared with control sera. In all 6 patients treated by enzyme replacement for 16-22 months, serum cathepsin activities decreased significantly (P <.01). Longitudinal studies confirmed the progressive reduction of proteinase activities during imiglucerase therapy but in 3 Gaucher patients with mild disease not so treated, serum cathepsin activities remained constant or increased during follow-up. Enhanced expression of cysteine proteinases may promote tissue destruction. Moreover, the first identification of aberrant cathepsin K expression in hematopoietic tissue other than osteoclasts implicates this protease in the breakdown of the matrix that characterizes lytic bone lesions in Gaucher disease. (Blood. 2000;96:1969-1978)

Adult↗
PubMed2000

Adolescent onset of the gender difference in lifetime rates of major depression: a theoretical model.

Prepubescent boys are, if anything, more likely than girls to be depressed. During adolescence, however, a dramatic shift occurs: between the ages of 11 and 13 years, this trend in depression rates is reversed. By 15 years of age, females are approximately twice as likely as males to have experienced an episode of depression, and this gender gap persists for the next 35 to 40 years. We offer a theoretical framework that addresses the timing of this phenomenon. First, we discuss the social and hormonal mechanisms that stimulate affiliative needs for females at puberty. Next, we describe how heightened affiliative need can interact with adolescent transition difficulties to create a depressogenic diathesis as at-risk females reach puberty. This gender-linked vulnerability explains why adolescent females are more likely than males to become depressed when faced with negative life events and, particularly, life events with interpersonal consequences.

Adolescent↗
PubMed2000

The molecular basis of lysosomal storage diseases and their treatment.

The lysosomal system is the main intracellular mechanism for the catabolism of naturally occurring endogenous and exogenous macromolecules and the subsequent recycling of their constituent monomeric components. It also plays an important part in processing essential metabolites. A genetic defect in a protein responsible for maintaining the lysosomal system results in the accumulation within lysosomes of partially degraded molecules, the initial step in the process leading to a lysosomal storage disease. The defective protein can be a luminal lysosomal enzyme or protein cofactor, a lysosomal membrane protein or a protein involved in the post-translational modification or transport of lysosomal proteins. Over 40 lysosomal storage diseases are known and they have a collective incidence of approximately 1 in 7000-8000 live births. Most of the genes for the lysosomal proteins have been cloned, permitting mutation analysis in individual cases. This information can be used for genotype/phenotype correlation, genetic counselling and the selection of patients for novel forms of therapy, such as substrate deprivation or dispersal, enzyme replacement, bone-marrow transplantation and gene transfer.

1-Deoxynojirimycin↗
PubMed2000

Disruption of the myocardial extracellular matrix leads to cardiac dysfunction.

MMP activity with disruption of structural collagen has been implicated in the pathophysiology of dilated cardiomyopathy. To examine the role of this enzyme in cardiac function, a transgenic mouse was created that constitutively expressed human collagenase (MMP-1) in the heart. At 6 months of age, these animals demonstrated compensatory myocyte hypertrophy with an increase in the cardiac collagen concentration due to elevated transcription of type III collagen. Chronic myocardial expression of MMP-1 produced loss of cardiac interstitial collagen coincident with a marked deterioration of systolic and diastolic function at 12 months of age. This is the first animal model demonstrating that direct disruption of the extracellular matrix in the heart reproduces the changes observed in the progression of human heart failure.

Age Factors↗
PubMed1999

The binding of unfractionated heparin and low molecular weight heparin to thrombin-activated human endothelial cells.

The binding of unfractionated heparin to endothelium is thought to be responsible for the rapid and saturable phase of unfractionated heparin clearance. Thrombin can induce endothelial cells to express and/or secrete a number of heparin binding proteins that have the potential to increase the binding of unfractionated heparin and to a lesser extent the binding of low molecular weight heparin. To explore this possibility, we examined the binding of unfractionated heparin and low molecular weight heparin to thrombin-activated endothelial cells. Cultured human umbilical vein endothelial cells were used to determine the binding of 125I-labeled unfractionated heparin and low molecular weight heparin to untreated and to thrombin-activated cells. After thrombin treatment, we obtained a time-dependent increase in the binding of radio-labeled unfractionated heparin. In contrast, there was much less binding of low molecular weight heparin, and a time-dependent increase was not apparent. After 30, 45, and 60 minutes of thrombin treatment, the binding of unfractionated heparin was significantly higher than that of low molecular weight heparin. The increase in binding of unfractionated heparin to thrombin-activated cells also was demonstrated using fluorescently labeled unfractionated heparin followed by fluorescence microscopy. The average fluorescence intensity of thrombin-treated cells increased by 44% when compared with resting cells. The present results indicate that thrombin can increase the binding of unfractionated heparin to human umbilical vein endothelial cells. Thus, an activated endothelium may contribute to the variability of the anticoagulant response to unfractionated heparin. In contrast, the binding of low molecular weight heparin is much less affected, which may account for its better bioavailability and longer half-life.

Binding Sites↗
PubMed1999

A histomorphometric evaluation of heparin-induced bone loss after discontinuation of heparin treatment in rats.

Although it is well established that long-term heparin therapy causes osteoporosis, it is unknown whether heparin-induced bone loss is reversible when heparin treatment is stopped. To address this question, we randomized rats to once daily subcutaneous injections of either unfractionated heparin (1.0 U/g or 0.5 U/g) or saline for 28 days and then followed the rats for an additional 28 days off treatment. Based on histomorphometric analysis of the distal third of the right femur proximal to the epiphyseal growth plate, 1.0 U/g heparin caused a 30% loss in cancellous bone volume over the first 28 days. This was accompanied by a 137% increase in osteoclast surface and a 60% decrease in both osteoblast and osteoid surface. One month after cessation of heparin treatment, no recovery in these parameters was observed. Similarly, serum levels of alkaline phosphatase, a biochemical marker of bone formation, which continued to decrease over the course of heparin treatment, showed no signs of recovery in the subsequent 28 days off treatment. To explore the mechanism responsible for the prolonged effect of heparin on bone, we repeated the experiment giving 125I-labeled heparin in place of unlabeled heparin. 125I-labeled heparin was found to accumulate in bone during the course of its administration, and be retained in bone for at least 56 days after stopping heparin treatment. These findings suggest that heparin-induced osteoporosis is not rapidly reversible because heparin is sequestered in bone for an extended period.

Animals↗
PubMed1999

Vasoflux, a new anticoagulant with a novel mechanism of action.

BACKGROUND: Heparin and direct thrombin inhibitors, such as hirudin, have limitations in the treatment of acute coronary syndromes. Heparin does not inactivate fibrin-bound thrombin, whereas hirudin fails to block thrombin generation. In contrast, Vasoflux is a novel anticoagulant that inactivates fibrin-bound thrombin and attenuates factor Xa generation. METHODS AND RESULTS: Vasoflux is prepared by depolymerization of heparin, restricting molecular size to between 3000 and 8000 Da, and reducing antithrombin affinity by periodate oxidation. Vasoflux catalyzes fibrin-bound thrombin inactivation by heparin cofactor II (HCII) and inhibits factor IXa activation of factor X independently of antithrombin and HCII. Compared with other anticoagulants in a thrombogenic extracorporeal circuit, Vasoflux maintains filter patency at concentrations that produce an activated clotting time (ACT) of 220 seconds. In contrast, to maintain filter patency, heparin, low-molecular-weight heparin (LMWH), and hirudin require concentrations that produced an ACT of 720, 415, and >1500 seconds, respectively, whereas dermatan sulfate was ineffective at concentrations that produced an ACT of 360 seconds. CONCLUSIONS: Vasoflux is more effective than heparin and LMWH because it inactivates fibrin-bound thrombin and is superior to hirudin and dermatan sulfate because it also blocks factor Xa generation.

Anticoagulants↗
PubMed1999

Bone marrow transplantation for Maroteaux-Lamy syndrome (MPS VI): long-term follow-up.

We describe the results of bone marrow transplantation (BMT) in four patients with mucopolysaccharidosis type VI (MPS VI, McKusick 253200)--Maroteaux-Lamy disease. The indications for transplantation were cardiomyopathy in three patients and severe obstructive sleep apnoea in one. The follow-up period ranges between 1 and 9 years, and three of the patients are at mainstream schools. In all of the patients the facial features have become less coarse and the cardiac manifestations have improved or remained stable. However, skeletal changes have persisted or even progressed, although posture and joint mobility have improved and all the patients have remained ambulatory and active. BMT appears to prolong survival and improve the quality of life in MPS VI patients, but careful selection of patients is essential.

Bone Marrow Transplantation↗
PubMed1999

Long-term follow-up following bone marrow transplantation for Hunter disease.

Bone marrow transplantation (BMT) was performed in 10 patients with Hunter disease (mucopolysaccharidosis type II, iduronate-2-sulphatase deficiency). The donor was an HLA-identical sibling in 2 cases, an HLA-nonidentical relative in 6 cases, a volunteer unrelated donor in 1 case, and details were not available in 1 case. Only three patients have survived for more than 7 years post BMT; however, this high mortality probably resulted from poor donor selection. In two, there has been a steady progression of physical disability and mental handicap. One patient has maintained normal intellectual development, with only mild physical disability. It is possible that BMT may be useful in selected patients with MPS II.

Adolescent↗
PubMed1999

Clinical and biochemical correlates of starting "daily" hemodialysis.

BACKGROUND: Daily hemodialysis has been proposed to improve outcomes for patients with end-stage renal disease. There has been increasing evidence that daily hemodialysis might have potential advantages over intermittent dialysis. However, despite these potential advantages, daily hemodialysis is infrequently used in the United States, and published accounts on the technique are few. METHODS: We describe patient outcomes after increasing their hemodialysis frequency from three to six times per week in a cohort of 72 patients treated at nine centers during 1972 to 1996. Analyses of predialysis blood pressure and laboratory parameters from 6 months before until 12 months after starting frequent hemodialysis used a repeated-measures statistical technique. RESULTS: Predialysis systolic and diastolic blood pressures fell by 7 and 4 mm Hg, respectively, after starting frequent hemodialysis (P = 0.02). Reductions were greatest among patients being treated with antihypertensive medications, despite a reduction in their dosage of medications. Postdialysis weight fell by 1.0% within one month of starting frequent hemodialysis and improved control of hypertension. After the initial drop, postdialysis weight increased at a rate of 0.85 kg per six months. Serum albumin rose by 0.29 g/dl (P < 0.001) between months 1 to 12 of treatment with daily hemodialysis. Hematocrit rose by 3.0 percentage points (P = 0.02) among patients (N = 56) not treated with erythropoietin during this period. Two years after the start of daily hemodialysis, Kaplan-Meier analyses showed a patient survival of 93%, a technique survival of 77%, and an arteriovenous fistula patency of 92%. Vascular access patency was excellent despite more frequent use of the access. CONCLUSIONS: These results suggest that in certain patients, daily hemodialysis might have advantages over three times per week hemodialysis.

Adolescent↗