The HAQ disability index in scleroderma trials.
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Disability Evaluation↗
Biomedical subjects
P Lee
Publications and source records attributed to P Lee.
Preventing pain on injection of propofol: a comparison between lignocaine pre-treatment and lignocaine added to propofol.
A randomized double-blind study compared two methods of preventing the pain from injection of propofol, lignocaine pre-treatment followed by propofol and lignocaine added to propofol. One hundred patients received a 4 ml solution intravenously with a venous tourniquet for 1 minute, followed by propofol mixed with 2 ml of solution. Patients were divided into two treatment groups of 50 patients each: 4 ml 1% lignocaine pre-treatment followed by propofol and 2 ml saline, or 4 ml saline followed by propofol and 2 ml 2% lignocaine. Pain was assessed with a 100 mm visual analogue scale after induction and in recovery. The incidence of injection pain was 8% in the propofol mixed with lignocaine group, and 28% in the lignocaine pre-treatment group. This difference is statistically significant (P=0.017). For those patients who had pain, the mean pain score was 26.5 on induction for the propofol with lignocaine group (n =4), while the mean score was 44.4 for the pre-treatment group (n=13). The difference was not statistically significant (P=0.25). None of the propofol mixed with lignocaine group recalled pain, while 13 of the pre-treatment group did so. Lignocaine pre-treatment does not improve the immediate or the recalled comfort of patients during propofol induction when compared to lignocaine added to propofol. It is recommended that lignocaine should be added to propofol for induction rather than given before induction.
Anesthetics, Intravenous↗
Audit of the detection and notification of meningococcal disease at a North London university district hospital.
The microbiology department at a North London hospital audited notifications of suspected meningococcal disease in response to a reported high rate, which it suspected was due to over-reporting out of hours to public health specialists. All cases notified over a 14-month period were assessed with regards to time of reporting and subsequent microbiological confirmation. Of 36 notifications, 18 were confirmed as bacterial, mostly meningococcal meningitis. Of the four types of sample readily obtainable on admission (blood culture, ethylene diamine tetra-acetic acid [EDTA] blood sample, throat swab and acute serum) all were obtained in only two cases. The reporting was considered appropriate, reflecting the relatively high incidence of meningococcal disease (MD) within the local population. Further cases might perhaps have been laboratory confirmed had all samples been sent on admission. A single form requesting all four samples in suspected meningococcal disease cases is recommended. Informing public health specialists out of hours could be rationalised.
Adolescent↗
Dissipation and offsite movement of forestry herbicides in plants of importance to Native Americans in California National Forests.
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California↗
The epidemiology of cigarette smoking in Hong Kong Chinese women.
BACKGROUND: Smoking in women is a well-recognized public health problem. In many developed countries, cigarette smoking is now the single most important preventable cause of premature death in women. There are relatively few data on the epidemiology of cigarette smoking in Asian women, and this study examined the prevalence of and factors predisposing Chinese women to smoke cigarettes in Hong Kong. METHOD: A territory-wide random telephone survey of 26,716 households in Hong Kong was conducted. A total of 1064 current smokers and 291 ex-smokers were identified in these household, and in-depth interviews of 791 current smokers, 221 ex-smokers, and 1012 controls were conducted. RESULTS: The prevalence of cigarette smoking was 4.5% in women who were 25 years or younger, 2.6% in women aged 46-65 years, and 2.2% in women aged 65 years or older. Sixty-four percent of current smokers started when they were 19 years or younger. The main reasons for the initiation of cigarette smoking were the influence of friends, curiosity, feeling bored, or being idle. Current smokers and ex-smokers tended to have positive images of women who smoked. The following risk factors were found to be significant for cigarette smoking: less than university education, unemployment, being divorced, having a husband who smoked, and a low score on the perceived harms of cigarette smoking. CONCLUSION: Cigarette smoking is more prevalent in younger women in Hong Kong; and psychosocial issues should be addressed to prevent future epidemics.
Adolescent↗
Efficacy comparison of intravenous artelinate and artesunate in Plasmodium berghei-infected Sprague-Dawley rats.
This paper reports the comparative antimalarial efficacy of intravenous artelinate and artesunate in rats. Prior to efficacy experiments, a Plasmodium berghei-Sprague-Dawley rat model of malaria was developed, in which the clearance effects of intravenous drugs could be readily compared. In efficacy experiments, groups of P. berghei-infected rats were given 3 daily intravenous treatments of artelinate or artesunate at molar equivalent dose rates (total of 0-191.2 micromoles/kg). Artelinate was superior to artesunate in terms of clearance (100% clearance dose of 95.6 micromoles/kg (40 mg/kg) versus 191.2 micromoles/ kg for AS (73.4 mg/kg)) and parasite clearance time (1.7 +/- 0.5 days for AL versus 2.7 +/- 0.5 days for AS at a dose rate of 191.2 micromoles/kg, P < 0.01). No frank clinical toxicity was observed, though both artesunate and artelinate induced dose-related vascular necrosis at the site of injection. The necrosis was less severe and reversible when the drugs were administered via femoral, rather than tail/foot veins. The data suggest that the P. berghei-7-week-old Sprague-Dawley rat model of malaria is reproducible and useful for assessing the efficacy of antimalarials and that artelinate is at least as potent, and safe, as artesunate, the leading clinical treatment for severe malaria.
Animals↗
Oral immunization of BALB/c mice with Giardia duodenalis recombinant cyst wall protein inhibits shedding of cysts.
The process of encystation is a key step in the Giardia duodenalis life cycle that allows this intestinal protozoan to survive between hosts during person-to-person, animal-to-person, waterborne, or food-borne transmission. The release of cysts from infected persons and animals is the main contributing factor to contamination of the environment. Genes coding for cyst wall proteins (CWPs), which could be used for developing a transmission-blocking vaccine, have been cloned. Since the immunogenicity of recombinant Giardia CWP is unknown, we have investigated the immunogenicity of recombinant CWP2 (rCWP2) and its efficacy in interfering with the phenomenon of encystation taking place in the small bowels of BALB/c mice vaccinated with the recombinant protein. Here we report that the immunization of BALB/c mice with rCWP2 stimulated the immune system in a manner comparable to that for a live infection with Giardia muris cysts. Fecal and serum anti-rCWP2 immunoglobulin A (IgA) antibodies were detected in the immunized mice. In addition, anti-rCWP2 IgG1 and IgG2a antibodies were detected in the serum. mRNAs coding for Th1 and Th2 types of cytokines were detected in spleen and Peyer's patch cells from immunized mice. When the vaccinated mice were challenged with live cysts, the animals shed fewer cysts. We conclude that rCWP2 is a possible candidate antigen for the development of a transmission-blocking vaccine.
Administration, Oral↗
Demographic and geographic variations of oral health among African Americans based on NHANES III.
UNLABELLED: As efforts continue to improve the health of all US citizens, oral health must not be overlooked. Oral health is an integral part of overall health status and oral diseases are among the most prevalent of all health problems. OBJECTIVES: To describe the oral health status and oral health behaviors of African Americans. METHODS: The National Health and Nutrition Examination Survey (NHANES III) data set was used to examine a range of oral health indicators of African Americans with specific attention to demographic and geographic factors. The original data set consisted of 20,050 subjects, gathered through the use of complex, multi-stage, stratified and clustered sampling techniques. Only African Americans were included in this study which resulted in a sample of 5,616. Statistical analysis was conducted to allow the proper modeling of the complex, stratified, multistage survey design and sample weights of NHANES III. RESULTS: Sixty-two percent of respondents indicated that they only visit the dentist when needed and had no regular visitation schedule. Dental health was worse for those individuals who were poor, unemployed, and uninsured. Regional differences in dental care appeared with individuals living in the south reporting poorer dental health. CONCLUSIONS: The findings from this study are useful for identifying sociodemographic and geographic factors related to oral health status. The insights gained from this study illustrate the need for tailoring oral health promotion programmes and services to specific groups within the African American community because service utilisation and response patterns and perceptions may be different.
Adolescent↗
Effect of hyperbaric oxygen therapy on exercise-induced muscle soreness.
The purpose of this study was to examine the effects of HBO2 therapy on exercise-induced muscle soreness. Subjects (n = 6 male and 10 female university student volunteers) were randomly divided into an experimental group that received HBO2 therapy and a control group that did not receive any treatments. HBO2 treatments consisted of 5 sessions of breathing 95% oxygen at 2.5 atm abs for 100 min. Temporary muscle soreness was created using a single-leg eccentric exercise task involving the quadriceps femoris. Over the next 14 days, measurements were obtained on muscle soreness, leg circumference, quadriceps peak torque, quadriceps average power, fatigue and plasma creatine kinase. After eccentric exercise, plasma creatine kinase (CK) levels and perceived muscle soreness were elevated but were not different between HBO2 and control groups. HBO2 therapy did not alter leg circumference, quadriceps peak torque, average power or fatigue compared to the control group. Faster recovery was observed in the HBO2 group on day 3 following the exercise protocol with perceived muscle soreness still elevated for the control group but not different from baseline for the HBO2 group. The data indicated that five HBO2 treatments did not speed recovery following eccentric exercise that induced temporary muscle soreness.
Adult↗
Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy.
BACKGROUND: Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population. METHODS AND RESULTS: Plasma alpha-galactosidase A (alpha-Gal) was measured in 79 men with HCM who were diagnosed at > or =40 years of age (52.9+/-7.7 years; range, 40-71 years) and in 74 men who were diagnosed at <40 years (25.9+/-9.2 years; range, 8-39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at <40 years had low alpha-Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low alpha-Gal activity had alpha-Gal gene mutations. CONCLUSION: Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.
Adolescent↗
Myringoplasty: does the size of the perforation matter?
Does the size of a tympanic membrane defect influence the success rate in myringoplasty? Many studies which have suggested that size does not affect results have included only small numbers of patients. After a power analysis to identify the size of groups needed to detect a clinically significant difference between the success rate of small and large perforations, a retrospective study was carried out to answer the question. A retrospective study of 423 myringoplasty-only operations showed that size does influence success; the success rate for small perforations was 74.1% compared with 56.0% for large perforations (P = 0.0003). Size also influences the change in four-frequency air conduction thresholds (small perforations +7.2 dB, large perforations +10.2 dB; t = 2.08, P = 0.039) in successful myringoplasties, a positive value indicating an improvement in hearing. This change is unlikely to be clinically significant. Patients should be made aware of these facts when informed consent is being obtained.
Audiometry↗
[Effect of weightlessness and movement restraint on structure and metabolism of M. soleus in monkeys after space flight].
After staying in real and simulated weightlessness, the most obvious changes were recorded in the "slow" tonic muscles like m. soleus, the protein loss in the fibres being greater than the loss of other components, water included.
Animals↗
An assessment of the role of exhaled carbon monoxide in acute asthmatic exacerbations in hospitalised patients.
Exhaled carbon monoxide is a useful marker of airway inflammation in untreated asthma. Whether exhaled CO is clinically useful in steroid treated patients in a hospital setting is uncertain. We therefore studied exhaled CO as a marker of asthma severity in clinical practice. Non-smoking "acute" asthmatics (hospitalised; n=33), "stable" asthmatics (n=35), and healthy controls (n=22) were recruited. Exhaled CO, peak expiratory flow (PEF) and FEV1 were measured daily (hospitalised cases) or once only (stable outpatients). Inpatients were managed without knowledge of the results. Exhaled CO levels in acute asthmatics (initial levels), stable asthmatics and controls were similar (median=2.0 ppm, h=5.05, p=0.08). In acute asthmatics, initial exhaled CO did not correlate with duration of hospitalisation, doses of intravenous corticosteroids, doses of nebulised salbutamol, PEF (% predicted) or FEV1 (% predicted). In stable asthmatics, exhaled CO did not correlate with corticosteroid dosage, PEF (% predicted) or FEV1 (% predicted). In the setting of acute hospitalised asthma patients, exhaled CO may not add any further to clinical management. This may in part be due to prior treatment with corticosteroids.
Acute Disease↗
Role of the nonspecific DNA-binding region and alpha helices within the core domain of retroviral integrase in selecting target DNA sites for integration.
Retroviral integrase plays an important role in choosing host chromosomal sites for integration of the cDNA copy of the viral genome. The domain responsible for target site selection has been previously mapped to the central core of the protein (amino acid residues 49-238). Chimeric integrases between human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) were prepared to examine the involvement of a nonspecific DNA-binding region (residues 213-266) and certain alpha helices within the core domain in target site selection. Determination of the distribution and frequency of integration events of the chimeric integrases narrowed the target site-specifying motif to within residues 49-187 and showed that alpha 3 and alpha 4 helices (residues 123-166) were not involved in target site selection. Furthermore, the chimera with the alpha 2 helix (residues 118-121) of FIV identity displayed characteristic integration events from both HIV-1 and FIV integrases. The results indicate that the alpha 2 helix plays a role in target site preference as either part of a larger or multiple target site-specifying motif.
Amino Acid Motifs↗
Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma.
PURPOSE: Forty-eight patients with high-risk re-sected stage III or IV melanoma were immunized with two tumor antigen epitope peptides derived from gp100(209-217)(210M) (IMDQVPSFV) and tyrosinase(368-376)(370D) (YMDGTMSQV) emulsified with incomplete Freund's adjuvant (IFA). Patients received peptides/IFA with or without interleukin (IL)-12 30 ng/kg to evaluate the toxicities and immune responses in either arm with time to relapse and survival as secondary end points. PATIENTS AND METHODS: Immunizations were administered every 2 weeks for 8 weeks, then every 4 weeks for 12 weeks, and then once 8 weeks later. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was done before and after vaccination. Skin testing with peptides and recall reagents was performed before and after vaccinations. RESULTS: Local pain and granuloma formation, fever, and lethargy of grade 1 or 2 were observed. Transient vaccine-related grade 3-but no grade 4-toxicity was observed. Thirty-four of 40 patients developed a positive skin test response to the gp100 peptide but none to tyrosinase. Immune responses were measured by release of gamma-interferon in an enzyme-linked immunosorbent assay (ELISA) by effector cells in the presence of peptide-pulsed antigen-presenting cells or by an antigen-specific tetramer flow cytometry assay. Thirty-three of 38 patients demonstrated an immune response by ELISA after vaccination, as did 37 of 42 patients by tetramer assay. Twenty-four of 48 patients relapsed with a median follow-up of 20 months, and 10 patients in this high-risk group have died. CONCLUSION: These data suggest a significant proportion of patients with resected melanoma mount an antigen-specific immune response against a peptide vaccine and indicate that IL-12 may increase the immune response and supporting further development of IL-12 as a vaccine adjuvant.
Adolescent↗
Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease.
BACKGROUND: Fabry's disease, lysosomal alpha-galactosidase A deficiency, results from the progressive accumulation of globotriaosylceramide and related glycosphingolipids. Affected patients have microvascular disease of the kidneys, heart, and brain. METHODS: We evaluated the safety and effectiveness of recombinant alpha-galactosidase A in a multicenter, randomized, placebo-controlled, double-blind study of 58 patients who were treated every 2 weeks for 20 weeks. Thereafter, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy end point was the percentage of patients in whom renal microvascular endothelial deposits of globotriaosylceramide were cleared (reduced to normal or near-normal levels). We also evaluated the histologic clearance of microvascular endothelial deposits of globotriaosylceramide in the endomyocardium and skin, as well as changes in the level of pain and the quality of life. RESULTS: In the double-blind study, 20 of the 29 patients in the recombinant alpha-galactosidase A group (69 percent) had no microvascular endothelial deposits of globotriaosylceramide after 20 weeks, as compared with none of the 29 patients in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had decreased microvascular endothelial deposits of globotriaosylceramide in the skin (P<0.001) and heart (P<0.001). Plasma levels of globotriaosylceramide were directly correlated with clearance of the microvascular deposits. After six months of open-label therapy, all patients in the former placebo group and 98 percent of patients in the former recombinant alpha-galactosidase A group who had biopsies had clearance of microvascular endothelial deposits of globotriaosylceramide. The incidence of most treatment-related adverse events was similar in the two groups, with the exception of mild-to-moderate infusion reactions (i.e., rigors and fever), which were more common in the recombinant alpha-galactosidase A group. IgG seroconversion occurred in 88 percent of patients who received recombinant alpha-galactosidase A. CONCLUSIONS: Recombinant alpha-galactosidase A replacement therapy cleared microvascular endothelial deposits of globotriaosylceramide from the kidneys, heart, and skin in patients with Fabry's disease, reversing the pathogenesis of the chief clinical manifestations of this disease.
Adolescent↗
Dual role of inflammatory stimuli in activation-induced cell death of mouse microglial cells. Initiation of two separate apoptotic pathways via induction of interferon regulatory factor-1 and caspase-11.
We have previously shown that mouse microglial cells undergo apoptosis upon inflammatory activation and that nitric oxide (NO) is the major autocrine mediator in this process (Lee, P., Lee, J., Kim, S., Yagita, H., Lee, M. S., Kim, S. Y., Kim, H., and Suk, K. (2001) Brain Res. 892, 380-385). Here, we present evidence that interferon regulatory factor-1 (IRF-1) and caspase-11 are the essential molecules in activation-induced cell death of microglial cells. The apoptogenic action of inflammatory stimuli such as lipopolysaccharide (LPS) and interferon-gamma (IFNgamma) was mediated through the induction of IRF-1 and caspase-11 expression in two separate events. Although IRF-1 was required for NO synthesis, caspase-11 induction was necessary for NO-independent apoptotic pathway. Microglial cells from IRF-1-deficient mice showed markedly decreased NO production, and they were partially resistant to apoptosis in response to LPS/IFNgamma but were sensitive to NO donor exposure. LPS/IFNgamma treatment resulted in the induction of caspase-11 followed by activation of caspase-11, -1, and -3. Inactivation of caspase-11 by the transfection of dominant-negative mutant or treatment with the caspase inhibitors rendered microglial cells partially resistant to LPS/IFNgamma-induced apoptosis. Inhibition of both NO synthesis and caspase-11 completely blocked LPS/IFNgamma-induced cytotoxicity. These results indicated that LPS/IFNgamma not only induced the production of cytotoxic NO through IRF-1 but also initiated the NO-independent apoptotic pathway through the induction of caspase-11 expression.
Animals↗
NO as an autocrine mediator in the apoptosis of activated microglial cells: correlation between activation and apoptosis of microglial cells.
Abnormal activation of microglial cells has been implicated in various neurodegenerative diseases. Microglial activation needs to be tightly regulated for physiological maintenance and normal functioning of the central nervous system. Potential mechanisms for the down-regulation of activated microglial cells are the deactivation or elimination of activated cells. We hypothesized that the elimination of activated microglial cells by apoptosis is one of the key mechanisms of auto-regulation of activated microglial cells. To test this hypothesis, we utilized BV-2 mouse microglial cells and rat primary microglial cultures exposed to activating agents such as lipopolysaccharide and interferon-gamma, and investigated a possible correlation between apoptosis and activation of these cells. We found that the activation of microglial cells led to apoptotic death, and the activation state of microglial cells inversely correlated with cell viability. We have also demonstrated that: (i) NO was produced by activated microglial cells in a manner dependent on time and dose of activating agents; (ii) inhibition of NO synthesis by iNOS inhibitor blocked the apoptosis of activated microglial cells; (iii) an exogenous NO donor induced apoptosis of microglial cells; and (iv) inhibition of TNFalpha or FasL using neutralizing antibodies did not affect activation-induced apoptosis of microglial cells. These results indicated that activation of microglial cells leads to the production of NO, which in turn acts as the major mediator of cellular apoptosis in an autocrine fashion. Our work suggests the presence of auto-regulatory mechanism for microglial activation, which may have relevance in the pathogenesis of various neurodegenerative diseases possibly resulting from 'over-activation' of microglial cells.
Animals↗