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Biomedical subjects

L Yee

Publications and source records attributed to L Yee.

At least 19 recordsLinked to original sources
PubMed2006

Does sodium hyaluronate- and carboxymethylcellulose-based bioresorbable membrane (Seprafilm) decrease operative time for loop ileostomy closure?

BACKGROUND: Adhesions can result in serious clinical complications and make ileostomy closure, which is relatively simple procedure into a complicated and prolonged one. The use of sodium hyaluronate and carboxymethyl cellulose membrane (Seprafilm) was proven to significantly reduce the postoperative adhesions at the site of application. The aim of this study was to assess the incidence and severity of adhesions around a loop ileostomy and to analyze the length of time and morbidity for mobilization at the time of ileostomy closure with and without the use of Seprafilm. METHODS: Twenty-nine surgeons from 15 institutions participated in this multicenter prospective randomized study. 191 patients with loop ileostomy construction were randomly assigned to either receive Seprafilm under the midline incision and around the stoma (Group I), only under the midline incision (Group II), or not to receive Seprafilm (Group III). At ileostomy closure, adhesions were quantified and graded; operative morbidity was also measured. RESULTS: All 3 groups were comparable relative to gender, mean age and number of patients with prior operations (26, 25 and 19, respectively). Group II patients were significantly more likely to have pre-existing adhesions than Group III patients (30.6% vs. 14.1%, p = 0.025). At stoma mobilization, significantly more patients in Group III than in Group I had adhesions around the stoma (95.2% vs. 82.3%, p = 0.021). Mean operative times were 27, 25, and 28 minutes, respectively (p = 0.38), with significant differences among sites. There was no significant difference in the number of patients needing myotomy or enterotomy (29, 27 and 24 patients, respectively), nor in the number of postoperative complications (7, 9 and 7 patients, respectively). CONCLUSIONS: When consistently applied, Seprafilm significantly decreased adhesion formation around the stoma but not operative times without any increase in the need for myotomy or enterotomy. These findings were not seen in the overall study population possibly due to the large number of surgeons using a variety of application techniques.

Adjuvants, Immunologic↗
PubMed2001

Suppression of pRB expression in normal human mammary epithelial cells is associated with resistance to all-trans-retinoic acid but not N-(4-hydroxylphenyl)-retinamide.

Despite the widespread clinical use of synthetic and naturally occurring retinoids, the down stream targets of retinoids have not been fully characterized. We observe that G(1/0)-phase arrest induced by all-trans-retinoic acid (ATRA) in normal human mammary epithelial cells (HMECs) is temporally associated with a significant decrease in the levels of hyperphosphorylated retinoblastoma protein (pRB). Suppression of pRB protein expression in HMECs by retroviral-mediated expression of the E7 protein of the human papillomavirus strain 16 (HPV-16) was associated with resistance to ATRA-mediated growth arrest but not to the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR or fenretinide). 4-HPR but not ATRA induced apoptosis in HMECs independent of the level of pRB protein expression. These observations suggest that ATRA- but not 4-HPR-mediated growth arrest may be dependent on the coordinated expression of pRB and emphasize the chemotherapeutic potential of 4-HPR, particularly for suppressing growth of tumors lacking pRB function.

Antineoplastic Agents↗
PubMed2001

Stability of dopamine and epinephrine solutions up to 84 hours.

OBJECTIVES: The current practice of preparing fresh dopamine and epinephrine solutions every 24 hrs may lead to hemodynamic instability caused by the interruption of infusions with each change. We determined the stability of these catecholamines over an 84-hr period and whether stability was enhanced by dextrose-containing solutions. SETTING: Tertiary care teaching hospital. DESIGN: The stability of dopamine and epinephrine, each at three commonly used concentrations, was studied in three vehicles (10 gm/dl dextrose in water [D10W], 5 gm/dl dextrose in water [D5W], and 0.9% NaCl in water [NS]). To mimic clinical conditions, solutions were placed on syringe pumps infusing continuously into a closed system at ambient temperature for 84 hrs. MEASUREMENTS: Concentrations of dopamine in mg/ml and epinephrine in microg/ml were measured by high-performance liquid chromatography at 0, 24, 36, 48, 72, and 84 hrs. RESULTS: Dopamine and epinephrine concentrations did not change over the 84-hr period regardless of the vehicles in which the drugs were prepared. CONCLUSIONS: Clinically relevant concentrations of dopamine and epinephrine remain stable in dextrose- and saline-containing solutions for >or=84 hrs. These data suggest that solutions of these catecholamines may safely be used in clinical practice beyond the currently recommended 24 hrs.

Journal Article↗
PubMed2000

Chiral high-performance liquid chromatographic analysis of fluoxetine and norfluoxetine in rabbit plasma, urine, and vitreous humor using an acetylated beta-cyclodextrin column.

Fluoxetine (Prozac) is a potent selective serotonin reuptake inhibitor used for the treatment of major depression. Both fluoxetine (F) and its demethylated metabolite, norfluoxetine (NF), are racemic. S-Fluoxetine (SF) and S-norfluoxetine (SNF) are more potent inhibitors of serotonin reuptake than R-fluoxetine (RF) and R-norfluoxetine (RNF). Quantitation of individual enantiomers may provide a greater understanding of pharmacokinetic properties. The objective of this study was to perform a limited chiral selectivity study using rabbit plasma, urine, and vitreous humor analyzed by a solid-phase extraction protocol and a newly developed chiral analysis with an acetylated beta-cyclodextrin (CD) column. Liquid chromatographic parameters for CD were as follows: a mobile phase composition of methanol/0.3% triethylamine buffer, pH 5.6, (30:70), a flow rate of 1 mL/min, detection at 214 nm, and a temperature of 40 degrees C. Elution order was SNF, SF, RNF, and RF with capacity factors of 6, 7, 8, and 9, respectively. The corresponding resolution factors were as follows: R1,2 = 0.8, R2,3 = 1.2, and R3,4 = 0.9. The conditions for solid-phase extraction were optimized for Varian Bond Elut Certify columns. Following sample application, the column was rinsed with water, acetic acid, and then with methanol. Drug enantiomers were eluted with methylene chloride, isopropanol, and ammonium hydroxide (78:20:2). After extract evaporation, the extract residue was reconstituted for high-performance liquid chromatographic analysis. To investigate chiral pharmacology, a biodistribution study was performed by administering 2 mg/kg of F to five rabbits. Blood, urine, and vitreous specimens were collected. Plasma samples collected 45 min postinjection showed nearly equal concentrations of RF and SE After 24 h, the only metabolite detected in plasma was RNF. Drugs were not detectable in vitreous humor. Urine concentrations of SNF, SF, RNF, and RF were 51, 76, 34, and 8 microg/L, respectively. The CD column along with the described extraction protocol may be used for a chiral selectivity study of fluoxetine.

Animals↗
PubMed2000

Follow up study eight years after diagnosis of sexual abuse.

AIM: To study the outcome over an eight year period of children determined by paediatricians in 1989 as definitely or probably sexually abused. METHOD: Information was obtained on 140 of 148 children diagnosed in 1989 when aged 7 or less. Sources were hospital medical records and school health records. School health records of a comparison group of 83 children were also examined. RESULTS: A variety of problematic characteristics were found significantly more often in the abused group than the comparison group. These included surname changes (30% v 2%), removal from home (25% v 1%), number of home addresses (2.8 v 1.4), and schools attended (3.4 v 2.2). Other significant findings included further abuse (35% v 0%), adverse behaviours (60% v 16%), educational problems (24% v 5%), chronic health problems (54% v 36%), and involvement of mental health services (32% v 1%).

Adolescent↗
PubMed2000

The clinical spectrum of Clostridium sordellii bacteraemia: two case reports and a review of the literature.

Clostridium sordellii is rarely associated with disease in humans. Since its first report in 1922 only a few cases of bacteraemia have been reported. This report describes two cases of C sordellii bacteraemia; the oldest and youngest patients reported to date. The first, is a previously well 81 year old woman presented with perianal infection, which was later complicated by thrombosis of the aorta, and the second is a 12 year old boy with epilepsy who presented with an ear infection. These cases are also highlighted to demonstrate the wide spectrum of presentation of sordellii bacteraemia.

Aged↗
PubMed1999

Overexpression of sialomucin complex, a rat homologue of MUC4, inhibits tumor killing by lymphokine-activated killer cells.

Sialomucin complex (SMC) is a large heterodimeric glycoprotein complex composed of a mucin subunit ascites sialoglycoprotein-1 and a transmembrane subunit ascites sialoglycoprotein-2. It is a rat homologue of human mucin gene MUC4 and is abundantly expressed on the cell surface of highly metastatic ascites 13762 rat mammary adenocarcinoma cells. Because of their extended and rigid structures, mucin-type glycoproteins are suggested to have suppressing effects on cell-cell and cell-matrix interactions. During the metastatic process, these effects presumably cause tumor cell detachment from the primary tumor mass and facilitate escape of the tumor cells from immunosurveillance. Analyses of human breast cancer cells in solid tumors and tumor effusions showed that the more aggressive cells in effusions are stained with polyclonal antibodies against SMC more frequently than cells in solid tumors, suggesting a role for MUC4/SMC in tumor progression and metastasis. Previously, we generated recombinant cDNAs for SMC that vary in the number of mucin repeats to study the putative functions of SMC in tumor metastasis. These cDNAs were transfected into human cancer cell lines and tested for the effect of the expression of this gene. Here, using a tetracycline-responsive inducible expression system, we demonstrate that overexpression of SMC masks the surface antigens on target tumor cells and effectively suppresses tumor cell killing by cytotoxic lymphocytes. This effect results from the ability of SMC to block killer cell binding to the tumor cells and is dependent on both overexpression of the mucin and the number of mucin repeats in the expressed SMC. These results provide an explanation for the proposed role of SMC/MUC4 in tumor progression.

Animals↗
PubMed1999

Barriers to meeting the mental health needs of the Chinese community.

BACKGROUND: This study aimed to identify the barriers encountered by Chinese people with mental health needs in England which hindered their obtaining appropriate help from the National Health Service (NHS). METHODS: Attenders at Chinese community centres in health authority districts with resident Chinese population in excess of 2000 were invited to fill in a 12-item Chinese Health Questionnaire (12-CHQ). Individuals who scored two or above, indicating a high probability of a mental health problem, were invited to undertake a semi-structured interview. RESULTS: A total of 401 completed the 12-CHQ. Eighty-six (21.4 per cent) screened positive and 71 (82.6 per cent) agreed to be interviewed. Although 70 (98.6 per cent) were registered with a general practitioner (GP), there were long delays before they made contact with health professionals, and the GP was the first port of call for help in only 27 (38.6 per cent) interviewees. Fifty-two (74.3 per cent) had encountered difficulties when they sought professional help. The main barriers were language, interviewees' perceptions of symptoms as somatic rather than psychiatric in origin, lack of knowledge about statutory services, and lack of access to bilingual health professionals. Doctors, particularly GPs, were pivotal in the management of their conditions. The majority were prescribed psychiatric medication with only a small number in contact with community psychiatric services. Unemployment and social exclusion were common. Stigma associated with mental illness and limited knowledge in the community were identified as the causes for the widespread discrimination experienced by the interviewees. CONCLUSION: The mental health needs of these Chinese people were not adequately met by statutory services, nor could they rely on family and friends for care and support. Training for health service staff and access to health advocates are essential to maximize the effectiveness of health professional-patient contacts. The promotion of better understanding of mental illness by the Chinese community is important, and greater flexibility within the NHS is required to ensure those professionals with bilingual skills are used to the best effect.

Adult↗
PubMed1998

Health care costs of worksite health promotion participants and non-participants.

Total and lifestyle-related medical care costs for employees of a major corporation participating in a worksite health promotion (WHP) program over a three-year period were compared with the costs for non-participants in a cross-sectional study. The study population consisted of 8,334 active employees based in the Cincinnati headquarters of The Procter & Gamble Company. Adjusting for age and gender, participants (n = 3,993) had significantly lower health care costs (29% lower total and 36% lower lifestyle-related costs) when compared with non-participants (n = 4,341) in the third year of the program. Similarly, in the third year of the program, participants had significantly lower inpatient costs, fewer hospital admissions, and fewer hospital days of care when compared with non-participants. No significant differences in costs were found between participants and non-participants during the first two years of the WHP program. Conclusions drawn from this study are that long-term participation in a WHP that includes high-risk screening and intensive one-on-one counseling results in lower total and lifestyle-related health care costs, as well as lower utilization of hospital services.

Adult↗
PubMed1998

Phase I trial of weekly paclitaxel in advanced lung cancer.

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Adult↗
PubMed1998

Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor.

Benzylacyclouridine (BAU, IND 039655) is a potent and specific inhibitor of uridine phosphorylase (UrdPase; EC 2.4.2.3). This enzyme plays a major role in regulating uridine homeostasis and also catalyzes the conversion of fluoropyrimidine nucleosides to their respective bases. Inhibition of UrdPase enzyme activity 18-24 h after 5-fluorouracil (5-FU) administration increased plasma levels of uridine and enhanced the therapeutic index of 5-FU by rescuing normal tissues. Moreover, in vitro preclinical studies have also shown that inhibiting UrdPase enzyme activity by BAU prior to administration of 5-FU increased cytotoxicity in a number of human cancer cell lines. A series of preclinical studies was performed in dogs and pigs to evaluate the pharmacological and pharmacodynamic properties of BAU. These data showed a sustained elevation in plasma uridine concentration in both animal models. The rapid degradation of a tracer dose of uridine into uracil was virtually arrested by BAU administered both p.o. or i.v. The t1/2 of BAU was 1.8-3.6 h in dogs, with bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg). In pigs, the half-life varied from 1.6 to 2.3 h, with a bioavailability of 40% at 120 mg/kg. The drug was distributed into most tissues with a tissue: plasma ratio of approximately 0.7. On the basis of these preclinical studies, we performed a Phase I clinical trial of BAU in patients with advanced cancer. Patients received 200, 400, 800, and 1600 mg/m2 BAU as a single oral dose. Toxicities included grade 2 anemia, grade 1 fever, grade 1 fatigue, grade 1 constipation, and grade 1 elevation in alkaline phosphatase; none of these toxicities were observed to be dose dependent. The maximum tolerated dose and dose-limiting toxicity were not reached at the doses given. BAU plasma concentrations and area under the curve correlated linearly with the oral dose level. The pharmacokinetics of BAU were consistent with a first-order clearance, with average peak concentrations ranging from 19 microM (200 mg/m2) to 99 microM (1600 mg/m2) and tbeta1/2 ranging from 3.0 to 3.9 h at the four dose levels. Compared with baseline plasma uridine, treatment of patients with 200, 400, 800, and 1600 mg/m2 BAU increased peak uridine concentrations by 120, 150, 250, and 175%, respectively. On the basis of this clinical study, the suggested Phase II starting dose of BAU in combination with 5-FU is 800 mg/m2. Studies combining BAU with 5-FU and incorporating appropriate molecular and biochemical end points to assess the effects of this drug combination on tumor and/or surrogate tumor tissue are under way.

Aged↗
PubMed1997

Measles virus serology in Crohn's disease.

BACKGROUND: There is evidence that measles virus infection in early life may predispose to Crohn's disease. AIMS: To examine using serological methods a potential association between measles virus infection in early life and predisposition to Crohn's disease. SUBJECTS: Forty five patients with Crohn's disease and forty five healthy controls were studied prospectively. METHODS: Clinical data were recorded and serum was analysed for measles virus, cytomegalovirus (CMV), adenovirus and herpes simplex virus (HSV) antibody titres by a complement fixation test (CFT), and for measles virus IgM by enzyme linked immunosorbent assay (ELISA). RESULTS: Reciprocal CFT titres for measles virus were lower in patients with Crohn's disease compared with controls (p < 0.05); there was no significant difference in titres for other viruses. None of the subjects studied had a level of measles virus IgM suggestive of acute infection, and there was no significant difference in measles virus IgM levels between patients and controls. The measles virus CFT titres and IgM levels in the patients with Crohn's disease did not correlate with any of the clinical features recorded. CONCLUSION: This study does not provide supportive evidence for a role for measles virus in the aetiology of Crohn's disease.

Adenoviridae↗
PubMed1997

Prophylactic cranial irradiation in small cell lung cancer: rationale, results, and recommendations.

The utility of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) constitutes one of the longest running debates in oncology. Despite dozens of prospective and retrospective studies and decades of individual experience, a consensus has been reached on only two issues: (1) when administered to all patients with SCLC, PCI decreases the likelihood of developing brain metastases by about half, but (2) PCI does not significantly prolong survival. Uncertainty persists over many critical questions, including whether, when, and how to administer PCI; whether identifiable subgroups of patients benefit more tangibly from PCI; how frequent and severe the long-term side effects of PCI are; whether withholding treatment until brain metastases are diagnosed is clinically responsible and cost effective; and how newer forms of treatment for brain metastases should be integrated into the picture. In this review, we discuss the epidemiology and natural history of brain metastases in patients with SCLC, the results of studies examining the efficacy of PCI, data on the early and late toxicities of PCI, and the status of alternative therapies for patients with brain metastases from SCLC. Based on this information, an approach to newly diagnosed patients is suggested, and recommendations for future study are made.

Brain Neoplasms↗
PubMed1996

Asymmetric corneal toricity and pseudokeratoconus in videokeratography.

BACKGROUND: The diagnosis of asymmetric corneal toricity in video- keratography is based on the occurrence of an asymmetric bow tie pattern in the corneal map, which is usually attributed to corneal radial asymmetry but can be an artifact produced by misalignment of the videokeratograph with the corneal apex. METHODS: This study determined whether asymmetric bow tie patterns in 16 subjects (ages 24 to 40 years with corneal toricity of 0.37 to 1.50D) could be converted to symmetric bow tie patterns by changing the alignment of the videokeratograph so that it was directed at the corneal apex. RESULTS: In changing from regular to apex alignment the corneal map became more symmetric in 11 eyes, had no change in 3 eyes and increased in 2 eyes. No radius change could be measured centrally, but there were significant changes of greater than 1.00D in the peripheral corneal radii of 8 eyes. CONCLUSIONS: An asymmetric or angled bow tie appearance of a corneal map suggests a decentered apex rather than corneal asymmetry and may lead to a misdiagnosis of the type or magnitude of corneal toricity, keratoconus or other corneal irregularities.

Adult↗
PubMed1995

Cutaneous infection with Mycobacterium abscessus.

Cutaneous infection with rapidly growing mycobacteria is uncommon and diagnosis may be difficult. However, the histopathological features are distinctive and may aid diagnosis. The three pathogenic species, Mycobacterium fortuitum, M. chelonae and M. abscessus, show major differences in their antimicrobial sensitivities, and species identification is therefore important. We describe a case of infection with M. abscessus, and discuss the clinical and pathological features of such infections, and approaches to their treatment.

Aged↗
PubMed1995

Combined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation.

Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. Paclitaxel was administered as a 3-hour infusion, repeated weekly for 6 weeks with the usual premedication regimen for hypersensitivity prophylaxis. The starting dose of paclitaxel was 10 mg/m2/wk, which was increased by 10 mg/m2 in successive cohorts of three new patients, as tolerated. Radiation therapy was delivered as 40 Gy in 20 fractions to the original volume with a boost of 20 Gy in 10 fractions to the primary tumor. Doses were escalated from 10 to 70 mg/m2/wk. Of the 23 patients evaluable for response, one had stage II NSCLC, four had stage IIIA, 17 had stage IIIB, and one had stage IV. Severe esophagitis (grade 4) occurred in two of the three patients treated at 70 mg/m2 and was dose limiting. One patient discontinued therapy due to hypersensitivity, two developed grade 3 neutropenia, and one developed radiation pneumonitis. With a median follow-up of 7 months, 15 of the 23 patients remain alive. Four had a complete response and 13 had a partial response, for an overall response rate of 74% (95% confidence interval, 52% to 90%). The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.

Ambulatory Care↗
PubMed1994

Tissue and tumor expression of a cell surface glycoprotein complex containing an integral membrane glycoprotein activator of p185neu.

Ascites 13762 rat mammary adenocarcinoma cells contain an abundant heterodimeric cell surface glycoprotein complex. It is composed of a transmembrane subunit and a sialomucin subunit and is the product of a single gene. The transmembrane subunit has two EGF-like domains and activates the proto-oncogene receptor kinase p185neu. Southern blot comparisons of the ascites tumor and rat liver demonstrated the presence of the gene encoding the complex in normal tissues and showed an amplification of about fivefold in the ascites tumor. Polymerase chain reaction assays showed the presence of mRNA for the complex in rat brain and lung, but not in liver, pancreas, placenta, intestine, kidney, ovary and uterus. Northern blot analyses showed that the 9 kb transcript for the complex is expressed at an approximately 500-fold higher level in the ascites cells than in rat brain. Immunocytochemical studies using antiserum directed against the transmembrane subunit showed its presence in bronchial epithelium, brain ependymal and neurons of four day old animals and in the endoderm and neuronal cells of embryos. Similar immunocytochemical studies showed the presence of the transmembrane subunit in some human breast tumors. These results suggest that the gene encoding this complex is regulated in a tissue-specific manner, is overexpressed in some tumors and may play a role in tumor progression.

Animals↗