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Biomedical subjects

V Lee

Publications and source records attributed to V Lee.

At least 37 records · Page 2Linked to original sources

Globe conserving treatment of the only eye in bilateral retinoblastoma.

AIMS: To quantify the rates of eye preservation and patient survival, local tumour relapse and recurrence, and development of new tumours in the remaining eye of children with bilateral retinoblastoma with one eye already enucleated. Also, in the same children, to describe the types of primary and secondary treatment procedures, and to define the anatomical outcome. METHODS: This is a retrospective observational case series report. The study participants consisted of 107 patients with bilateral retinoblastoma with one eye enucleated within 1 month of baseline examination and had their remaining eye treated conservatively. The main outcome measure were: primary treatment failures, new tumours, enucleation of the only eye, death, remission, and anatomical outcomes (retinal detachment, vitreous haemorrhage, and cataract). RESULTS: The median age at diagnosis was 8.4 (range 0.2-44, SD 10.1) months with a median ophthalmic follow up of 44.3 (8.1-114, SD 10.1) months. In 22 of the 107 patients (21%) the treated eye was in Reese Ellsworth groups I or II and in the remaining 85 (79%) in groups III-V at diagnosis. The primary treatment was cryotherapy in 14% (15/107) of eyes, radioactive plaque brachytherapy in 3.7% (4/107), and chemotherapy in 10% (11/107). It was lens sparing radiotherapy in 37% (40/107), whole eye radiotherapy in 29% (31/107), combined radiotherapy and chemotherapy in 2.8% (3/107), chemothermotherapy in 0.9% (1/107), and combined focal therapy in 1.8% (2/107). The primary treatment failed to achieve local tumour control during the follow up period in 37% (40/107) of eyes. In 17 eyes failure was due to inadequate control of the presenting tumour, in 16 to development of a new tumour, and in eight eyes to a combination of both. 35 (88%) of the 40 failures were managed by secondary conservative treatment and the remaining five were treated by enucleation of the only eye. There were eight (7.4%) deaths and the 3 year survival rate was 93% (100/108). Anatomical results included vitreous haemorrhage in four cases, tractional retinal detachment also in four cases, and 24 children required cataract surgery. CONCLUSIONS: Aggressive conservative treatment achieved a good rate of globe salvage without impairing survival.

Brachytherapy↗

Role of posterior stabilisation in the management of tuberculosis of the dorsal and lumbar spine.

We present a prospective study of patients with tuberculosis of the dorsal, dorsolumbar and lumbar spine after combined anterior (radical debridement and anterior fusion) and posterior (instrumentation and fusion) surgery. The object was to study the progress of interbody union, the extent of correction of the kyphosis and its maintenance with early mobilisation, and the incidence of graft and implant-related problems. The American Spinal Injury Association (ASIA) score was used to assess the neurological status. The mean preoperative vertebral loss was highest (0.96) in the dorsal spine. The maximum correction of the kyphosis in the dorsolumbar spine was 17.8 degrees. Loss of correction was maximal in the lumbosacral spine at 13.7 degrees. All patients had firm anterior fusion at a mean of five months. The incidence of infection was 3.9% and of graft-related problems 6.5%. We conclude that adjuvant posterior stabilisation allows early mobilisation and rehabilitation. Graft-related problems were fewer and the progression and maintenance of correction of the kyphosis were better than with anterior surgery alone. There is no additional risk relating to the use of an implant either posteriorly or anteriorly even when large quantities of pus are present.

Adolescent↗

Haematopoietic stem cell transplantation for thalassaemia major in Hong Kong: prognostic factors and outcome.

From August 1992 to August 1999, 44 patients received allogeneic haematopoietic stem cell transplantation in a single institution. The donors were HLA-identical siblings except for one who was a phenotypically matched father. Thirty-eight patients received bone marrow stem cells and the others received peripheral blood stem cells or umbilical cord blood (UCB). The mean age at transplant was 10.7+/-5.1 years, ranging from 1.8 to 21 years. Patients received busulphan (16 mg/kg) and cyclophosphamide (150 to 200 mg/kg) as conditioning, and antithymocyte globulin was given to 42 patients to prevent graft rejection. All had engraftment except a patient who received a UCB transplant. Four patients died from early treatment-related mortality, and one died from interstitial pneumonitis 3 months after transplant. Two patients developed secondary graft rejection and both received a second transplant. Thirty-eight patients survived and all except one were transfusion independent. The 5-year overall and event-free survival rates were 86% and 82%, respectively. By multivariate stepwise Cox proportional hazard analyses, severe veno-occlusive disease (VOD) of liver and Pesaro class 3 features were the significant factors associated with survival. Patients aged more than 11 years were more inclined to develop VOD. In conclusion, haematopoietic stem cell transplantation should be performed early if an HLA identical sibling is available.

Adolescent↗

Human herpesvirus-6 encephalitis after unrelated umbilical cord blood transplant in children.

Three children developed human herpesvirus-6 (HHV-6), variant B encephalitis after unrelated umbilical cord blood transplant, in a single center. They developed clinical manifestations of encephalitis around day 17 post transplant. Impairment of consciousness, incoherent speech, episodic focal pruritus, motor weakness, convulsions and severe hyponatremia were features at presentation. Radiological investigation of brain ranged from unremarkable to extensive white matter and meningeal lesions. Diagnosis was established by the presence of HHV-6 DNA in cerebrospinal fluid (CSF). Retrospective analyses of plasma revealed the presence of viral DNAemia prior to the onset of disease in two subjects. Treatment with ganciclovir or foscarnet was given. Two subjects did not achieve engraftment and died of other transplant-related complications on day 38 and 56 post-transplant, respectively. One subject achieved disease-free survival for more than 1 year with a satisfactory neurological outcome. In conclusion, HHV-6 encephalitis is not uncommon among patients undergoing umbilical cord blood transplantation. It is worth conducting further studies on early diagnosis and optimal management of this potentially fatal disease.

Antiviral Agents↗

Primary orbital melanoma masquerading as vascular anomalies.

PURPOSE: To review two cases of primary orbital melanoma presenting like orbital vascular anomalies. METHODS: Retrospective review of clinical presentation, treatment, radiology and pathology for two patients under the care of the Orbital Clinic at Moorfields Eye Hospital. RESULTS: Both lesions presented with the appearance and behaviour of vascular anomalies. In one case, a spindle cell melanoma appeared to be a low flow vascular anomaly with a loculated secondary haemorrhage and, in the other case, a melanoma of soft parts was considered to be an arteriovenous malformation and responded partially to embolisation. CONCLUSION: Primary malignant melanoma may present as a secondary vascular lesion of the orbit and this very rare tumour should be considered in the differential diagnosis of any vascular anomaly.

Adult↗

Liver disease in transfusion dependent thalassaemia major.

AIMS: To study the prevalence and severity of liver diseases of transfusion dependent thalassaemia major patients, and correlate the histological and biochemical changes of iron overload in liver with the peripheral blood markers. METHOD: Liver biopsy was performed to assess the histological changes and liver iron content (LIC). RESULTS: One hundred patients were evaluated (median age 11.7 years, range 1.5-27). A total of 81 liver biopsies were performed in 73 patients; 43 samples were analysed for LIC. Grade 3-4 haemosiderosis and hepatic fibrosis was found in 44% and 30% of patients respectively; both were significantly associated with higher serum ferritin, liver enzymes, and LIC. Very high LIC (>15 mg/g dry weight) was present in 16.3% of patients. CONCLUSION: Severe haemosiderosis and hepatic fibrosis were common in patients with thalassaemia major despite the use of chelation therapy. Liver biopsy provided information on fibrosis and LIC which could not be accurately predicted from peripheral blood markers.

Adolescent↗

Knowledge about cataract, glaucoma, and age related macular degeneration in the Hong Kong Chinese population.

AIMS: Patients' knowledge and participation in their care are important in prevention of blindness from common eye diseases such as cataract, glaucoma, and age related macular degeneration (AMD). The aim of this study was to measure knowledge of these conditions in the Hong Kong Chinese population. METHODS: Subjects aged 40 and above in the Shatin district of Hong Kong were randomly selected as part of a larger study of causes of adult visual loss. The subjects received eye examinations in which the primary cause of visual disability was recorded. The respondents were asked by trained interviewers in a standardised fashion about their knowledge of cataract, glaucoma, and AMD. Their answers were rated for accuracy by a senior ophthalmologist. RESULTS: Out of the 2538 eyes examined, 7.0% had visual acuity less than 6/18. Fully 69.6% of the visual disability for those aged 60 or above was caused by cataract, AMD, or glaucoma. Awareness of cataract in particular was high, in that over 90% of respondents had heard of it. However, only 22.9% of them could describe cataract symptoms correctly, and these percentages were even lower in glaucoma (10.2%) and AMD (<1%). Over 40% of subjects did not know that surgery was an appropriate treatment for cataract. CONCLUSION: This sample of the Hong Kong Chinese population had limited knowledge of common eye diseases. Educational programmes to enhance public awareness may be needed to improve the effectiveness of health promotion and thus prevent unnecessary blindness.

Adult↗

Aetiology and surgical treatment of childhood blepharoptosis.

AIMS: To describe the aetiology, demography, surgical management, and outcome of a cohort of paediatric ptosis patients in a large tertiary referral oculoplastic centre. METHODS: A case note review of all patients undergoing ptosis surgery below the age of 16 years in a tertiary referral oculoplastic unit documenting the laterality, aetiology, severity of ptosis, indications for and type of surgery undertaken, the proportion of good, suboptimal, and poor surgical outcomes, re-operations, and level of patient satisfaction. RESULTS: 340 patients (82% (280/340) unilateral, 18% (60/340) bilateral ptosis) with myogenic (79%, 269/340), aponeurotic (5%, 16/340), neurogenic (11%, 37/340), mechanical (2%, 6/340), apparent (1%, 2/340), and syndrome related (3%, 10/340) ptosis underwent anterior (41%, 141/340) and posterior (26%, 90/340) levator resection, frontalis suspension with mersilene (9%, 29/340) and autogenous fascia lata (17%, 59/340), levator transposition (5%, 15/340) and other surgery (1%, 6/340) for visual (43%, 141/333) and cosmetic (57%, 189/333) indications. 77% (260/340) of patients achieved a good outcome, 10% (35/340) a suboptimal outcome, and 13% (45/340) a poor outcome requiring re-operation. There was no statistically significant difference in surgical outcome between patients with mild, moderate, or severe ptosis and with good, moderate, or poor levator function. The level of recorded patient satisfaction with the surgical outcome was 90% (206/229). CONCLUSIONS: Results suggest that most groups of paediatric ptosis patients, including those with poor levator function and severe ptosis, achieve satisfactory results with the appropriate ptosis surgery.

Adolescent↗

Complement activation by neurofibrillary tangles in Alzheimer's disease.

Brain inflammation is widely documented to occur in Alzheimer's disease (AD), but its sources are still incompletely understood. Here, we present in vitro and in situ evidence that, like amyloid beta peptide (Abeta), tau, the major protein constituent of the neurofibrillary tangle, is a potent, antibody-independent activator of the classical complement pathway. Complement activation, in turn, is known to drive numerous inflammatory responses, including scavenger cell activation and cytokine production. Because Abeta deposits and extracellular tangles are present from early preclinical to terminal stages of AD, their ability to activate complement provides a ready mechanism for initiating and sustaining chronic, low-level inflammatory responses that may cumulate over the disease course.

Alzheimer Disease↗

Studies toward the total synthesis of the cytotoxic sponge alkaloid pyrinodemin A.

[structure: see text]. The syntheses of the proposed structure of pyrinodemin A (1) and its cis double bond positional isomer (C15'-C16') in racemic form are described. The key reaction involved an intramolecular nitrone/double bond cycloaddition. Our results suggest that neither 1 nor its double positional isomer is the correct structure of pyrinodemin A

Alkaloids↗

Roles of aggrecan domains in biosynthesis, modification by glycosaminoglycans and product secretion.

Aggrecan is a member of the chondroitin sulphate (CS) proteoglycan family, which also includes versican/PG-M, neurocan and brevican. Members of this family exhibit structural similarity: a G1 domain at the N-terminus and a G3 domain at the C-terminus, with a central sequence for modification by CS chains. A unique feature of aggrecan is the insertion of three additional domains, an inter-globular domain (IGD), a G2 domain and a keratan sulphate (KS) domain (sequence modified by KS chains), between the G1 domain and the CS domain (sequence modified by CS chains). The G1 and G3 domains have been implicated in product secretion, but G2, although structurally similar to the tandem repeats of G1, performs an unknown function. To define the functions of each aggrecan domain in product processing, we cloned and expressed these domains in various combinations in COS-7 cells. The results indicated that the G3 domain enhanced product secretion, alone or in combination with the KS or CS domain, and promoted glycosaminoglycan (GAG) chain attachment. Constructs containing the G1 domain were not secreted. Addition of a CS domain sequence to G1 reduced this inhibition, but GAG chain attachment was still decreased. The potential GAG chain attachment site in the IGD was occupied by GAGs, and IGD product was secreted efficiently. The KS domain was modified by GAG chains and secreted. Finally, the G2 domain was expressed but not secreted, and inhibited secretion of the IGD when expressed as an IGD-G2 combination.

Aggrecans↗

Versican modulates embryonic chondrocyte morphology via the epidermal growth factor-like motifs in G3.

This investigation was designed to characterize the effect of the extracellular matrix molecule versican on chondrocyte morphology, using the well-studied chondrocyte cell culture system. When cultured chondrocytes reverted or "dedifferentiated" to a fibroblast-like morphology, we found that versican expression was significantly enhanced. Transfection of chondrocytes, isolated from embryonic chicken sterna, with a chicken miniversican construct accelerated the reversion process, while expression of an antisense construct inhibited it. A mutant miniversican lacking two epidermal growth factor-like motifs (versicanDeltaEGF) promoted differentiation, as shown by morphological changes and changes in the expression of other extracellular matrix molecules. A truncated versican mutant, the G3DeltaEGF, a G3 domain lacking its two epidermal growth factor-like motifs, also enhanced differentiation. This effect is related to G3DeltaEGF-induced change in cytoskeleton, since transfected cells exhibited misassembly of actin filaments. This article thus provides the first evidence that versican modulates chondrocyte morphology via changes in cytoskeletal structure, and may imply that extracellular matrix molecules play an important role in cell differentiation.

Actins↗

Identification of the motif in versican G3 domain that plays a dominant-negative effect on astrocytoma cell proliferation through inhibiting versican secretion and binding.

This study was designed to investigate the mechanisms by which mutant versican constructs play a dominant-negative effect on astrocytoma cell proliferation. Although a mini-versican or a versican G3 construct promoted growth of U87 astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87 cell surface. G3DeltaEGF products exhibited decreased binding activity, but higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to the cell surface. G3DeltaEGF expression inhibited secretion of endogenous versican in astrocytoma cells and also inhibited the secretion of mini-versican in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs. The effect seems to depend on the expression efficiency of G3DeltaEGF, and it occurred via the carbohydrate recognition domain.

Amino Acid Motifs↗

Vascular ultrasound surveillance after endovascular intervention for occlusive iliac artery disease.

This paper describes vascular ultrasound surveillance after endovascular intervention for occlusive iliac artery disease. There were 105 patients who had 198 procedures in 155 limbs, consisting of 110 balloon dilatations and 88 stentings. The patients were referred to the vascular diagnostic service by several surgeons. All procedures had been considered to be initially technically successful. Colour-Doppler duplex ultrasound studies were performed shortly before and at serial intervals after operation to determine patency rates. Univariate life table analysis showed 69% primary and 96% assisted primary patency at four years. Primary patency rates at four years were significantly worse for stentings (60%) compared to balloon dilatations (71%) (P<0.05). Maximum peak systolic velocities (PSV) were recorded from the treated arteries. Receiver operating characteristics curves showed that PSV >300 cm/s was most accurate for predicting technical failure. Haemodynamic success rates at four years were 72% for PSV >300 cm/s. Results for procedures that were initially successful indicate that long-term primary patency rates for iliac endovascular intervention are acceptable and that assisted primary patency rates are excellent.

Aged↗

Impact of a toxicology service on a metropolitan teaching hospital.

OBJECTIVE: To evaluate the impact of a toxicology service on a major metropolitan teaching hospital. METHOD: A descriptive comparative study of all patients presenting with poisoning or suspected poisoning 12 months before and after the commencement of a toxicology service. Data on length of stay in the emergency department, disposition, length of stay of admitted patients and substance(s) involved were examined. RESULTS: A total of 1,316 poisoned patients were studied. There was a statistically significant increase in self-poisonings from 612 to 704 (P = 0.002) and in the number of admissions from 113 to 192 (P < 0.05). There was no significant change in emergency department length of stay. The average length of stay for patients admitted under the care of the toxicology service decreased, especially for complicated patients. CONCLUSION: In the first 12 months of operation the toxicology service treated more patients than the 12-month period prior to commencement, achieving a decrease in average length of stay for those patients admitted to the service. The emergency department length of stay was not altered. We surmise that by decreasing average length of stay for the patients under the care of the toxicology service, the net increase in the general pool of unoccupied beds improves bed access for all emergency department patients.

Emergency Service, Hospital↗