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Biomedical subjects

V Lee

Publications and source records attributed to V Lee.

At least 19 recordsLinked to original sources

Changing trends in cytomegalovirus retinitis with triple therapy.

PURPOSE: Cytomegalovirus retinitis (CMVR) has been the most common cause of visual loss in AIDS patients. We investigate whether the pattern of disease has changed since the introduction of triple therapy. METHODS: We reviewed the records of all patients with CMVR in one teaching hospital HIV unit over a 2 year period (n = 24). This included the opthalmic and systemic findings, HIV and CMV treatment, survival after diagnosis and CD4 results. RESULTS: There has been a marked decrease in the number of patients developing new CMVR: from 21 eyes (15 patients) to 4 eyes (4 patients) in two consecutive 12 month periods between January 1996 and December 1997, coinciding with the introduction of triple therapy in October 1996. Median survival has increased from 376 days in the deceased patients to 598 days in the survivors on triple therapy. Median time to CMVR relapse has lengthened from 79 to 179 days in the triple therapy cohort. The pattern of ocular morbidity in the 11 eyes of the 7 surviving patients is also changing, with no new zone 1 disease, and a marked rise in the incidence of uveitis, maculopathy and cataracts. CONCLUSION: Results suggest that triple therapy is associated with an increase in survival, a decrease in CMVR relapse and changes in ocular features. This transition has implications for current screening and treatment protocols.

AIDS-Related Opportunistic Infections

Versican enhances locomotion of astrocytoma cells and reduces cell adhesion through its G1 domain.

Versican is a large extracellular proteoglycan and is expressed in a variety of tissues including the central nervous system. A malignant astrocytoma cell line U87 with high motility expressed a higher level of versican than another malignant astrocytoma cell line U343 with lower motility. We observed that the U87 cells were less adherent to tissue culture plates than the U343 cells. To investigate the role of versican in astrocytoma cell migration, we generated recombinant products of a mini-versican construct expressed in COS-7 cells. We found that the mini-versican products enhanced astrocytoma cell migration. Furthermore, enhanced migration was promoted by the G1 domain but not the G3 domain of versican. We introduced culture medium containing products of the mini-versican, the G1, and the G3 constructs separately into the astrocytoma cell lines U87 and U343. The mini-versican and the G1 construct, but not the G3 construct, were shown to reduce astrocytoma cell adhesion. The present data suggest that versican exerts its effect on astrocytoma cell migration and adhesion through the G1 domain.

Astrocytoma

Ring melanoma--a rare cause of refractory glaucoma.

BACKGROUND: Ring melanoma of the ciliary body and iris is extremely rare and often has adverse histology. This tumour may cause raised intraocular pressure. METHODS: A review of four cases of ring melanomas with insidious presentations seen in the ocular oncology service over a 12 month period. RESULTS: All four patients presented with unilateral anterior segment abnormalities and refractory glaucoma. The misdiagnoses of the causes of the glaucoma included angle recession from previous blunt trauma (patient 1); iridocorneal endothelial (ICE) syndrome supported by endothelial specular microscopy (patients 2 and 3); and melanocytoma on ciliary body biopsy (patient 4). Two patients were treated by several cyclodiode ciliary body ablation treatments and the other two underwent trabeculectomies and Molteno tubes. Two of the four patients have since died from their disease. CONCLUSION: The ophthalmologist should re-evaluate the diagnosis in patients with anterior segment abnormalities and refractory ipsilateral glaucoma. Endothelial specular microscopy and biopsy of the suspicious lesion may give misleading reassurance. The potential presence of an anterior uveal melanoma must always be considered.

Adult

Proton beam therapy for posterior pole circumscribed choroidal haemangioma.

BACKGROUND: Macular and juxtapapillary circumscribed choroidal haemangiomas (CCH) have always posed a diagnostic and therapeutic challenge. Proton beam therapy has been advocated by Zografos and associates as optimal for treating these tumours in this critical region as charged particles have a highly localised and uniform dose distribution. PATIENTS: We present 3 cases of CCH treated with proton beam therapy. Two patients developed radiation optic neuropathy and maculopathy, and one had a persistent exudative macular detachment following treatment. CONCLUSION: Our experience with proton therapy of these tumours has been disappointing in preventing radiation optic neuropathy and maculopathy and offers little advantage over external irradiation. The majority of our patients with this condition are now treated with low-dose lens-sparing external beam radiotherapy or brachytherapy, which has encouraging visual results and is a far more cost-effective option.

Adult

Sclerosing canaliculitis after 5-fluorouracil breast cancer chemotherapy.

BACKGROUND: 5-Fluorouracil is a pyrimidine analogue that inhibits DNA synthesis and is commonly used in the treatment of carcinomas of the breast, gastrointestinal tract and genitourinary tract. Excessive tearing that resolves on cessation of treatment is commonly described as a side effect of the drug. Permanent stenosis of the punctum and canaliculus is extremely rare, with only 12 cases reported in the world literature. We present three cases of established lacrimal outflow obstruction in patients who were treated with CMF (cyclophosphamide, methotrexate, 5-fluorouracil), a widely used regimen for metastatic breast cancer. Patient 1 had right distal stenosis of her lower canaliculus and was syringed patent during dacryocystography with resolution of epiphora. Patient 2 had proximal blockage of all canaliculi and underwent bilateral canaliculodacryocystorhinostomy with silicone tubes that temporarily relieved symptoms until tube removal. The proximal canalicular blockage recurred due to underlying extensive fibrosis. Patient 3 had right proximal common canalicular stenosis and left distal canalicular blocks but declined surgery. CONCLUSION: With the rise in the incidence of breast carcinoma it is important that the attention of both ophthalmologists and oncologists should be drawn to the potential ocular toxicity of systemic 5-fluorouracil chemotherapy, which may lead to lacrimal canalicular fibrosis with permanent epiphora. The management of these patients is challenging as there is a continuous spectrum of canalicular involvement from focal to diffuse; therefore early referral is recommended. Moreover as no consensus has been reached as how best to manage this unique small group of patients, we review the literature and discuss the implications for treatment.

Aged

Low-dose intermittent factor replacement for post-operative haemostasis in haemophilia.

Recommendations for factor replacement therapy for postoperative haemostasis in haemophilia are often empirical and based on the physiological understanding of haemostatic requirements. This report describes the haemostatic management of patients with severe haemophilia undergoing major surgery using lower than usually recommended levels of factor replacement therapy. Eighteen adults (11 with FVIII and seven with FIX deficiency) with an average weight of 52 kg (range: 27-69) underwent 20 major surgical procedures. Factor concentrates were administered by intermittent bolus infusions. The dose of FVIII infused before surgery was 76 mu kg-1 (range: 51-113) and that of FIX was 77 mu kg-1 (range: 50-104). The preoperative levels achieved were 107% (range: 80-180) and 73% (range: 60-90), respectively. Between days 1 and 3 after surgery, an average of 29 mu kg-1 day-1 (range: 20-46) of FVIII and 23 mu kg-1 day-1 (range: 12-42) of FIX was used resulting in mean trough levels of 36% (range: 12-62) and 34% (range: 11-52), respectively. After day 4, an average of 19 mu kg-1 day-1 (range: 15-25) of FVIII and 18 mu kg-1 day-1 (range: 10-37) of FIX was administered until wound healing. The average duration of factor replacement was 11 days (range: 8-16). The mean dose of factor concentrate per patient was 260 mu kg-1 (range: 179-338) of FVIII and 300 mu kg-1 (range: 183-524) of FIX. The total amount of factor used per patient ranged from 12,380 to 19,980 units of FVIII and 8000 to 23,600 units of FIX. Only one patient had post-operative bleeding which was due to a surgical cause. It is concluded that it may be possible to use much lower than recommended levels of factor replacement therapy for postoperative haemostasis in severe haemophilia.

Adolescent

Patterns of smoking, risk factors for smoking, and smoking cessation among Vietnamese men in Massachusetts (United States).

OBJECTIVES: To measure the prevalence and patterns of, and risk factors for, smoking and other tobacco use among Vietnamese men in Massachusetts (United States). METHODS: Data were obtained via a telephone interview of 774 Vietnamese men in 1994. DESIGN: Cross-sectional survey administered via telephone in 1994. SETTING: Massachusetts, United States. SUBJECTS: Randomly selected Vietnamese men (n = 774). MAIN OUTCOME MEASURES: Present and past use of tobacco products, knowledge and attitudes regarding tobacco, and risk factors for tobacco use. Results were compared with data from the Massachusetts general population. RESULTS: Vietnamese men smoked at a rate 1.9 times that of the Massachusetts general men's rate (43% vs 24%). The smoking rate did not decrease with increasing length of residence in the United States. In a logistic regression, risk factors for current smoking were: age in the thirties; history of parental smoking; lower educational level; higher depression score; low level of exercise; lack of health insurance; and geographical origin from the south coast of Vietnam. Smoking cessation declined with increasing depression score. Most smokers (76%) had no plans to quit smoking. CONCLUSIONS: Vietnamese men smoke at much higher rates than the general population, and are much less likely to be planning cessation. High rates of depression and sociocultural barriers to smoking cessation must be addressed in efforts to reduce tobacco use among this high-risk population.

Acculturation

Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes.

OBJECTIVE: The redox-sensitive transcription factor nuclear factor-kappa B (NF-kappa B) is believed to contribute to late diabetic complications. It is unknown whether NF-kappa B is influenced by glycemic control. RESEARCH DESIGN AND METHODS: To determine whether NF-kappa B is activated in patients with insufficient glycemic control (HbA1c > 10%), we developed a tissue culture-independent electrophoretic mobility shift assay (EMSA)-based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells (PBMCs). We included 43 patients with type 1 diabetes in this cross-sectional study. 10 of those received the antioxidant thioctic acid (600 mg/day p.o.) for 2 weeks. RESULTS: Monocytes of patients with HbA1c levels > 10% demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6-8%. The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity. CONCLUSIONS: Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kappa B activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid significantly lowered the extent of NF-kappa B binding activity.

Adult

Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts.

Refined ensembles of solution structures have been calculated for the N-terminal SH3 domain of Grb2 (N-SH3) complexed with the ac-VPPPVPPRRR-nh2 peptide derived from residues 1135 to 1144 of the mouse SOS-1 sequence. NMR spectra obtained from different combinations of both 13C-15N-labeled and unlabeled N-SH3 and SOS peptide fragment were used to obtain stereo-assignments for pro-chiral groups of the peptide, angle restraints via heteronuclear coupling constants, and complete 1H, 13C, and 15N resonance assignments for both molecules. One ensemble of structures was calculated using conventional methods while a second ensemble was generated by including additional direct refinements against both 1H and 13C(alpha)/13C(beta) chemical shifts. In both ensembles, the protein:peptide interface is highly resolved, reflecting the inclusion of 110 inter-molecular nuclear Overhauser enhancement (NOE) distance restraints. The first and second peptide-binding sub-sites of N-SH3 interact with structurally well-defined portions of the peptide. These interactions include hydrogen bonds and extensive hydrophobic contacts. In the third highly acidic sub-site, the conformation of the peptide Arg8 side-chain is partially ordered by a set of NOE restraints to the Trp36 ring protons. Overall, several lines of evidence point to dynamical averaging of peptide and N-SH3 side-chain conformations in the third subsite. These conformations are characterized by transient charge stabilized hydrogen bond interactions between the peptide arginine side-chain hydrogen bond donors and either single, or possibly multiple, acceptor(s) in the third peptide-binding sub-site.

Adaptor Proteins, Signal Transducing

Antigen presentation in retroviral vector-mediated gene transfer in vivo.

We have examined mechanisms involved in gene transfer, protein expression, and antigen presentation after direct administration of retroviral vectors using a variety of antigen systems. We have identified transduced infiltrating cells at the injection site, and the majority of the infiltrating cells were of the monocyte/macrophage lineage. We found that the splenic dendritic cell fraction contained proviral DNA, expressed antigenic proteins, and was able to present antigens efficiently to the immune system. Furthermore, the dendritic cell fractions from retroviral vector-immunized mice were able to prime naive T cells in vitro, and adoptive transfer of in vitro-transduced dendritic cell fractions elicited antigen-specific cytotoxic T lymphocytes. These data suggest a role for dendritic cells in induction of immune responses elicited by retroviral vector-mediated gene transfer.

Adoptive Transfer

Combined radiofrequency ablation-cooling catheter for reversible cryothermal mapping and ablation.

Reversible cryothermal mapping of cardiac arrhythmias has been performed intraoperatively. However, a steerable cooling catheter for reversible mapping has not yet been developed. We therefore developed and tested a cooling system consisting of a -15 degrees C hypertonic saline reservoir and a 7F steerable catheter also capable of radiofrequency (RF) ablation. Using excised ovine hearts placed in a 37 degrees C circulating saline bath, we measured the temperatures at depths of 0 mm, 1 mm, and 2 mm. The temperature after 90 seconds of cooling was 16.5 +/- 2.1 degrees C at 0 mm compared to 23.9 +/- 4.1 degrees C at 1 mm and 31.1 +/- 3.9 degrees C at 2 mm depth (p < 0.01). These data suggest that a 7F steerable combined RF ablation-cooling catheter may achieve temperatures suitable for mapping arrhythmias such as atrial tachycardias and right ventricular outflow tract tachycardias. Further enhancements to achieve lower temperatures at depth may be needed to reversibly map other arrhythmias such as left ventricular tachycardias.

Animals

Differential expression of two beta-galactoside-binding lectins in the reproductive tracts of pregnant mice.

Two beta-galactoside-binding proteins were isolated from uteroplacental complexes of pregnant mice and identified as the S-Lac lectins galectin-1 and galectin-3. The spatiotemporal pattern of appearance of those proteins was determined by immunocytochemistry. Galectin-1 was present in all tissue compartments of the uterus except the luminal and glandular epithelium. It was found in the uteri of animals from all preimplantation stages of pregnancy, as well as in those from nonpregnant, ovariectomized, or sexually immature animals. After implantation of the embryo, cells of the decidua basalis were labeled, as were granular metrial gland cells, all trophoblastic elements of the placenta, the myometrium, and nondecidualized endometrium. By contrast, there was little evidence of galectin-3 in the uteri of nonpregnant animals or during the preimplantation stages of pregnancy. However, immunoreactive material was observed in endometrial cells of the primary decidual zone immediately after implantation and at later stages of pregnancy in the decidua basalis, metrial gland, and all trophoblastic elements of the placenta. There was no evidence of galectin-3 in the myometrium or nondecidualized endometrium. After parturition, amounts of galectin-3 in the endometrium and metrial triangle appeared to decrease as the implantation sites were resorbed. These data suggested that the function of galectin-1 is one of tissue maintenance, whereas the function of galectin-3 is related specifically to pregnancy.

Amino Acid Sequence

Occupational stress and organizational commitment in nurse administrators.

OBJECTIVE: The authors explore levels of occupational stress (burnout) and organizational commitment (intent to stay), their inter-relationships, and their relationships to personal and organizational factors in nurse administrators. BACKGROUND: Although the concepts of burnout and turnover have been studied and reported for staff nurses, relatively few such studies exist in relation to nurse administrators. METHODS: Consequently, the Maslach Burnout Inventory, the Organizational Commitment Questionnaire, and a personal data sheet were completed by respondents to a mailed survey representing 65.6% of the membership of the state's nurse executive organization and 58.2% of the state's hospitals (N = 78). RESULTS: Scores indicate that half the respondents experience low levels of burnout whereas a third have high levels of burnout. Commitment scores were high for most nurse executives and were correlated inversely with burnout scale scores (depersonalization, personal accomplishment, emotional exhaustion), with the amount or phase of burnout, and with non-nursing management experience. Those with few opportunities to meet with colleagues scored higher on emotional exhaustion and lower on personal accomplishment scales. Intent to stay (high commitment scores) was related positively to perceived organizational support and to religiosity. CONCLUSIONS: Findings are consistent with those reported in other studies; however, the administrative role may require unique approaches to avoid or correct organizational stress. The role of social support, the determination of organizational/individual fit, and the adaptation of traditional organizational development techniques to the administrative role are discussed and proposed as areas for further study.

Adult