Meningeal cholesterol granulomas in two meerkats (Suricata suricatta).
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Animals↗
Biomedical subjects
M Waters
Publications and source records attributed to M Waters.
HIV-related knowledge and adherence to HAART.
Near perfect adherence is considered essential for patients on HAART, yet adherence to medical recommendations is rarely so high. Supportive services and reminder tools may help individuals to become adherent, yet it is difficult to determine who may need such interventions. In this study, based on data from the NYSDOH/AIDS Institute Treatment Adherence Demonstration Program, we look at the association between HIV-related knowledge and adherence, hypothesizing that a better understanding of HIV and its treatment is associated with better adherence. In analyses based on 997 participants, knowledge, as measured by five true/false questions, was significantly associated with self-reported adherence. In multivariate analysis, compared to persons with four or five items answered correctly, persons with fewer correct answers were more likely to report missed doses (OR = 1.72 for 2-3 correct, p < 0.01; OR = 2.92 for 0-1 correct, p < 0.05). Our data suggest that providers should include questions focused on knowledge of HIV in their assessments of medication readiness and need for adherence support. Similarly, providers should be diligent with respect to patient education, ensuring that each patient has the information needed to support reasoned decision making and adequate adherence.
Adolescent↗
Childhood vaccination against varicella: persistence of antibody, duration of protection, and vaccine efficacy.
OBJECTIVE: To document the duration of protection afforded by Oka/Merck varicella vaccine over a 7-year period. STUDY DESIGN: The subjects were healthy children 1 to 12 years of age originally enrolled in clinical studies to evaluate the primary immune response to varicella vaccine 6 weeks after vaccination. Each was monitored for antibody persistence, breakthrough infection, and household exposure to varicella to produce estimates of vaccine efficacy. RESULTS: The 6-year cumulative varicella antibody persistence rate was 99.5% (95% CI: 98.9%, 100.0%). The annual breakthrough rate through 7 years ranged from 0.2% to 2.3% per year; the estimated cumulative event rate was 6.5%. Comparison of the observed average annual breakthrough rate with the age-adjusted expected annual incidence rate of varicella in unvaccinated children corresponded to an estimated vaccine efficacy of 93.8% to 94.6%. Eighty vaccinated children were exposed to varicella in the household, resulting in 8 (10%) cases of infection. When compared with the historical attack rate of 86.8% in unvaccinated susceptible persons exposed to varicella in the household, this yields an estimated vaccine efficacy of 88.5% (95% CI: 80.9%, 96.1%). Varicella cases in vaccinated children generally were mild. CONCLUSION: The live attenuated varicella vaccine is highly effective in inducing persistent immunity and long-term protection against breakthrough varicella infection.
Age Distribution↗
Growth hormone (GH)/GH receptor expression and GH-mediated effects during early bovine embryogenesis.
Pituitary growth hormone (GH) stimulates postnatal growth and metabolism. The role of GH and its receptor (GHR) during prenatal development, however, is still controversial. As shown by reverse transcription polymerase chain reaction (RT-PCR), bovine in vitro fertilization embryos synthesized the transcript of GHR from Day 2 of embryonic life onwards. Real time RT-PCR revealed that synthesis of GHR mRNA was increased 5.9-fold in 6-day-old embryos compared with 2-day-old embryos. Using in situ hybridization, the mRNA encoding GHR was predominantly localized to the inner cell mass of blastocysts. The GHR protein was first visualized 3 days after fertilization. GH-specific transcripts were first detected in embryos on Day 8 of in vitro culture. As shown by transmission electron microscopy, GH treatment resulted in elimination of glycogen storage in 6- to 8-day-old embryos and an increase in exocytosis of lipid vesicles. These results suggest that a functional GHR able to modulate carbohydrate and lipid metabolism is synthesized during preimplantation development of the bovine embryo and that this GHR may be subject to activation by embryonic GH after Day 8.
Amylases↗
A 22 year old man admitted to intensive care with hyperthermia and seizures.
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Journal Article↗
The NIOSH/FAA Working Women's Health Study: evaluation of the cosmic-radiation exposures of flight attendants. Federal Aviation Administration.
Air crew are exposed to elevated levels of cosmic ionizing radiation of galactic and solar origin and are among the more highly exposed occupational groups to ionizing radiation in the United States. Depending on flight route patterns, the annual dose may range from 0.2 to 5 mSv. By comparison, the average annual radiation dose equivalent of occupationally exposed adults in the United States is estimated to be 1.1 mSv. Cosmic-radiation dose depends primarily on altitude and geomagnetic latitude and to a lesser degree on solar activity. Although the International Commission on Radiological Protection has recommended that air crew exposures to natural radiation in-flight be treated as occupational exposures, United States flight crew exposures to natural cosmic radiation are not regulated or typically monitored. There are approximately 148,000 air crew (flight deck crew and flight attendants) in the United States.
Adult↗
Optimisation of growth hormone production by muscle cells using plasmid DNA.
The production of peptide hormones by skeletal muscle tissue is a promising area of gene therapy. Skeletal muscle myogenesis can be induced in vitro, resulting in the fusion of mononucleate myoblasts to form multinucleate myotubes, and delivery vectors are first tested in vitro. C2C12 myoblasts transfected with pcDNA3-GH, which used the human cytomegalovirus (CMV) promoter, secreted immunoreactive GH with comparable biological activity to pituitary GH. Mouse myeloid leukaemia cells, which express the mouse GH receptor were used for the bioassay, and activation of these cells by GH was measured by a colorimetric microculture tetrazolium assay. Cells were incubated with a tetrazolium salt (MTS) and an intermediate electron acceptor (phenazine methosulphate, PMS), and formazan production was measured as optical density (O.D.) at 490 nm. The efficiencies of several plasmid expression vectors were compared in differentiated and non-differentiated muscle cells, as a function of bioactive GH secreted by the transfected cells. Ten-day differentiated C2C12 myotubes transfected with pcDNA3E-GH, which used the CMV promoter and a rat myosin light chain enhancer element, secreted significantly more biologically active GH than myotubes transfected with pcDNA3-GH (0.82 O.D. units+/-0.06 vs 0.57+/-0.05 respectively, P<0.001). This was consistent with reduced CMV promoter activity in myotubes. Myoblasts transfected with pcDNA3-GH secreted more bioactive GH than 10-day transfected myotubes (1.1+/-0. 1 vs 0.77+/-0.07 respectively). However, the responses were indistinguishable (both 1.0+/-0.09) if both the myotubes and myoblasts had been transfected with pcDNA3E-GH. Substitution of the vector pMHLC-GH, which used a muscle-specific truncated rabbit myosin heavy chain promoter, and the myosin enhancer resulted in a marked decrease in the responses to the conditioned medium from fused myotubes compared with the vectors pcDNA3-GH and pcDNA3E-GH (0. 24+/-0.02 vs 0.57+/-0.05 vs 0.82+/-0.06 respectively). We concluded that the combination of CMV promoter and myosin light chain enhancer in pcDNA3E-GH had the greatest expression efficiency of the several plasmid vectors which we investigated.
Animals↗
Serum organochlorine levels and breast cancer: a nested case-control study of Norwegian women.
This study investigated the potential association between organochlorine exposure and breast cancer using stored sera collected from 1973 through 1991 from the Janus Serum Bank in Norway. Breast cancer cases were ascertained prospectively from among 25,431 female serum bank donors. A total of 150 controls were matched to cases by birth dates and dates of sample collection. One g of serum per subject was analyzed for a total of 71 organochlorine compounds. For 6 pesticides [B-hexachlorocyclohexane, heptachlor epoxide, oxychlordane, trans-nonachlor, p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, and p, p'-2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and 26 individual polychlorinated biphenyl (PCB) congeners there were >90% of samples over the limit of detection. There was no evidence for higher mean serum levels among cases for any of these compounds, nor any trend of increasing risk associated with higher quartiles of exposure. The remaining compounds (including dieldrin) were analyzed with respect to the proportion of cancer cases and controls having detectable levels; no positive associations were noted in these analyses. Our study did not confirm the recent findings of a Danish study of increased concentrations of dieldrin in the serum of breast cancer cases. The evidence to date on the association between serum organochlorines is not entirely consistent, but there is accumulating evidence that serum levels of p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and total PCBs are not important predictors for breast cancer in the general population. Studies to date have not been able to evaluate whether exposure to highly estrogenic, short-lived PCB congeners increases breast cancer risk, nor have they fully evaluated the risk associated with organochlorine exposure in susceptible subgroups or at levels above general population exposure, including women with occupational exposure.
Adenocarcinoma↗
Resolving ambiguity and uncertainty.
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Anti-Infective Agents, Local↗
Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy.
Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several clinical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy.
Adolescent↗
Improved wettability of an experimental silicone rubber denture soft lining material.
The purpose of this study was to improve the wettability of an experimental silicone rubber soft lining material (Sildent) to increase patient comfort. Sildent was modified by the addition of polyalkylene oxide poly(dimethylsiloxane) surfactants. The various surfactants were added directly to the polymeric matrix in the quantities 5, 10, 20% w/w. The surfactants were also added to a one part silicone sealant, which was then painted onto the surface of already cured Sildent. Contact angle measurements were made on samples using a dynamic contact angle analyzer. Results showed that incorporation of surfactants A (Silwet L7600) and B (Silwet L7607) effectively improved the wettability of Sildent. This improvement was still evident after 6 months storage in distilled water at 37 degrees C suggesting retention of the surfactants matrix via physio-chemical bonding. Formulations with surfactants added directly to the matrix showed unacceptable water absorption after 2 months in distilled water. Samples with surfactant charged sealant painted on the surface showed a lower water absorption. In conclusion, Sildent formulations modified with polyalkylene silicone surfactants showed improved wettability compared to unmodified Sildent. Further work is needed to reduce water uptake and determine the effect on key mechanical properties.
Catalysis↗
Using molecular epidemiology in assessing exposure for risk assessment.
Quantitative estimation of health risks depends on exposure characterization, the nature of the dose response relationships, and the toxicity of the agents involved. The greatest uncertainties in risk assessment almost always arise from sparse or inadequate exposure data, inadequate understanding of exposure mechanisms, and insufficient understanding of the exposure-dose-response pathway. Additional sources of uncertainty arise when mixed or multiple exposures are implicated in the disease pathway, and as a result of variability in both exposures and responses within and between individuals. Here we consider the role of exposure assessment in the risk assessment process, the use of biological markers or molecular epidemiology to contribute to improvements in exposure assessment for risk assessment, and uncertainties associated with the use of biological markers.
Biomarkers↗
Oral midazolam for conscious sedation of children during minor procedures.
OBJECTIVE: To compare the safety and efficacy of two doses of oral midazolam, and to assess the drug induced amnesia obtained, when used for conscious sedation of children undergoing minor procedures in the accident and emergency (A&E) setting. METHODS: A two stage trial was completed: an initial prospective, double blinded, randomised trial comparing 0.2 mg/kg midazolam suspension with 0.5 mg/kg, followed by further data collection on the higher dose. Children whom staff and parents felt required sedation for accurate and humane completion of minor procedures were selected. Anxiety was measured using physiological parameters, a behavioural anxiety score, a parental visual analogue scale, and a telephone questionnaire at 2-7 days after the procedure. RESULTS: Fifty patients in total were recruited. Randomisation between two doses ceased after 20 patients since staff, despite being "blinded", perceived there to be a wide variation in response to midazolam and attributed that to the difference in doses. On breaking the code these suspicions were partly supported. Due to reluctance to continue with the lower dose all children subsequently received 0.5 mg/kg. At this higher dose oral midazolam had an onset of action of 15 minutes and was effective in 76% of children (as measured by anxiety score and/or subsequent amnesia). Amnesia was reported in 66% of children. There were no adverse side effects except paradoxical hyperagitation in three (6%); this did not require any specific treatment. General anaesthesia was avoided in at least eight children in whom the procedure would not have been attempted without midazolam. Altogether 90% of parents said they would like it to be used again should similar circumstances arise. CONCLUSIONS: At 0.5 mg/kg oral midazolam appears safe and is effective in sedating most children for minor procedures. Its use should be considered by all A&E departments dealing with children.
Administration, Oral↗
Dynamic mechanical thermal analysis of maxillofacial elastomers.
STATEMENT OF PROBLEM: Maxillofacial prosthetic materials should simulate the oral tissues as much as possible and therefore have a similar flexibility and resilience. In light of the oral tissues constantly moving, the dynamic deformation properties of maxillofacial materials would seem the most relevant. PURPOSE: In this study, dynamic mechanical thermal analysis was used to evaluate the deformation properties of five silicone rubber materials used to construct facial prostheses. The technique involves the application of a sinusoidally oscillating stress to a material and analyzes how the material elastically or viscoelastically responds to the stress. The dynamic mechanical thermal analysis can operate at a fixed frequency or range of frequencies over a specific temperature range and also isothermally as a function of time. RESULTS: Cosmesil and A-2186 materials were the most resilient materials and Silbione had the greater energy absorption capacity, which was particularly noticeable at the higher frequencies. Silbione also had a lower shear modulus (G'), which indicated it was more flexible than the other materials. CONCLUSION: The dynamic mechanical thermal analysis proved to be a rapid, reliable, and convenient method for the determination of viscoelastic properties of maxillofacial materials.
Analysis of Variance↗
Cost savings with nonthoracotomy implantable cardioverter-defibrillators.
We analyzed hospital and physician charges for 99 consecutive patients who underwent implantable cardioverter-defibrillator (ICD) implantation at our institution. Eighteen patients received an epicardial lead system and 81 were scheduled to receive a nonthoracotomy lead system, the generator being implanted either abdominally (n = 62) or pectorally (n = 19). The epicardial group had a significantly longer convalescent stay (11.6 +/- 2.5 days; mean +/- SEM) than the abdominal nonthoracotomy group, analyzed by intention to treat (4.6 +/- 0.5 days) or by treatment received (3.8 +/- 0.2 days; p <0.0001). Postoperative stay for the pectoral group was shorter still (2.9 +/- 0.4 days; p <0.033). Total charges for the epicardial group were $99,081 +/- $25,094, significantly higher than those for any of the nonthoracotomy groups (p <0.017). Total charges for the pectoral group were $44,128 +/- $2,465, significantly less than those for the abdominal nonthoracotomy group, analyzed by intention to treat ($59,961 +/- $1,369; p <0.05) or by treatment received ($56,679 +/- $635; p <0.05). Cost reductions in the nonthoracotomy groups were primarily due to decreased in-hospital convalescence period, lower surgeon and anesthesiologist fees, and lower procedure-day hospital charges in the pectoral group. The use of ICDs with nonthoracotomy leads can result in significantly shorter in-hospital convalescence and a reduction in total implant-related charges of 40% to 55%. The use of pectorally implanted ICDs results in further reduction in hospital stay and further cost reduction of 22% to 26%. The trend toward shorter convalescent stay without postimplant testing is likely to reduce further the overall costs of ICD implantation.
Anesthesiology↗
Induced nitric oxide synthesis is dependent on induced alternatively spliced CAT-2 encoding L-arginine transport in brain astrocytes.
The inducible isoform II of nitric-oxide synthase (iNOS) was recently cloned from brain and identified in astroglial cells. Induced nitric oxide biosynthesis occurs in brain cells only if extracellular cerebrospinal fluid contains -arginine. This study demonstrates for the first time that induced iNOS activity is strictly dependent on concomitant induction of an alternatively spliced transcript of the cat-2 gene encoding high affinity -arginine transporter System y+ in cultured rat astrocytes. Inhibition profiles of radiolabeled -arginine and -leucine uptake identified the dominance of Na+-independent transport System y+ serving cationic amino acids, with insignificant activities of Systems y+L, bo,+, or Bo,+. A reverse transcription-polymerase chain reaction/sequencing/cloning strategy was used to identify a single 123-base nucleotide sequence coding the high affinity domain of alternatively spliced CAT-2 (not CAT-2a) in astrocytes activated by lipopolysaccharide/interferon-gamma. Using this sequence as a cDNA probe, it was determined that CAT-2 mRNA, iNOS mRNA, and System y+ activity were concomitantly and strongly induced in astrocytes. Constitutive CAT-1 mRNA was weakly present in neurons and astrocytes, was not inducible in either cell type, and contributed <3% to total System y+ activity. Although astroglial iNOS Km approximately 10 microM L-arginine for intracellular substrate, hyperbolic kinetics of inducible iNOS activity measured as a function of extracellular L-arginine concentration gave Km approximately 50 microM L-arginine with intact cells. The same Km approximately 50 microM was obtained for induced membrane transport System y+ activity. iNOS activity was reduced to zero in the absence of extracellular L-arginine uptake via System y+. These findings expand the current understanding of NO biosynthesis modulation and implicate a coordinated regulation of intracellular iNOS enzyme activity with membrane L-arginine transport in brain.
Alternative Splicing↗
Dynamic mechanical thermal analysis of denture soft lining materials.
The purpose of this study was to characterize the deformation properties of a range of long-term denture soft lining materials using dynamic mechanical thermal analysis. Specimens were subjected to sinusoidal shear deformation at a frequency of 1 Hz and a strain of 64 microns peak to peak over a temperature range of 30-70 degrees C. The technique simulated the type and rate of deformation soft lining materials would experience clinically, thus producing more relevant results than previously used methods. Shear modulus G', dissipative modulus G' and mechanical loss tangent G'/G' were obtained for each material. With increasing temperature the moduli of the acrylic materials decreased, indicating an increased compliance and greater deformation. The silicone (Molloplast B) and alternative formulation (Novus) properties were generally insensitive to temperature over the range chosen. The mechanical loss tangent values of the acrylics fell continuously with temperature, suggesting that the plasticization process lowered the Tg values below 30 degrees C, the lowest temperature of testing.
Acrylates↗