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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 55 records · Page 3Linked to original sources

Search for neutrino oscillations at the palo verde nuclear reactors

We report on the initial results from a measurement of the antineutrino flux and spectrum at a distance of about 800 m from the three reactors of the Palo Verde Nuclear Generating Station using a segmented gadolinium-loaded scintillation detector. We find that the antineutrino flux agrees with that predicted in the absence of oscillations excluding at 90% C.L. nu;(e)-nu;(x) oscillations with Deltam(2)>1.12x10(-3) eV(2) for maximal mixing and sin (2)2straight theta>0.21 for large Deltam(2). Our results support the conclusion that the atmospheric neutrino oscillations observed by Super-Kamiokande do not involve nu(e).

Journal Article↗

Modeling of separations by closed-loop steady-state recycling chromatography of a racemic pharmaceutical intermediate.

Closed-loop steady-state recycling (SSR) is a cyclic, one-column process that is similar to simulated moving bed (SMB) chromatography in several respects. Both processes are cyclic. In both SMB and SSR, fractions are collected from the leading and trailing portions of the circulating chromatographic profile, and fresh sample is injected into the interior of the profile. However, SMB is a continuous process whereas SSR is a discontinuous, repetitive process. This paper presents a model for the closed-loop SSR process and its experimental validation in a case of practical importance. For this last purpose, we used the closed-loop SSR separation of the enantiomers of a racemic pharmaceutical intermediate. The experimental determination of the competitive adsorption equilibria was performed by frontal analysis in a system composed of a chiral HPLC column as the stationary phase and pure acetonitrile as the mobile phase. All the adsorption data were well correlated by the Langmuir model. The Langmuir model was used to calculate overloaded band profiles corresponding to the separation of racemic mixtures at both analytical and preparative scales. Theoretical band profiles were calculated using the equilibrium-dispersive model. With proper corrections for the contributions of the sources of extra-column band broadening, the model properly predicts the experimental band profiles obtained in the closed-loop SSR setup and demonstrates that a cyclic steady-state develops after the completion of a finite number of cycles. The results also show that the extra-column effects must be accounted for in order to model the closed-loop SSR process accurately.

Chromatography, High Pressure Liquid↗

Ectopic gestation following emergency contraceptive pill administration.

Emergency contraceptive pill prescription following rape is common. We report a case of ectopic gestation after emergency contraceptive pill failure and review the literature on this rare complication. A 26-year-old woman with a normal menstrual period 2 weeks before was administered an emergency contraceptive pill 8 hours after a single sexual assault. The assault was her only sexual activity before and after the emergency contraceptive pill use. Forty-six days following the assault, the patient presented with a right ampullary tubal pregnancy of 59 days gestation and underwent emergent surgery for ectopic gestation. To prevent a delay in the diagnosis of ectopic pregnancy, we recommend that providers and the package insert advise women, that ectopic gestation can occur with emergency contraceptive pill failure.

Adult↗

Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium.

OBJECTIVE: To identify the effects of depomedroxyprogesterone acetate (DMPA) on vaginal microbial flora and epithelium. METHODS: Women who desired DMPA for contraception were evaluated before and at 3 and 6 months after initiation of 150-mg DMPA injections every 3 months. At each visit, we assessed genital symptoms, vaginal signs, vaginal microflora, and histopathology by vaginal biopsies. RESULTS: Among 38 women observed for 6 months, there was significant reduction in mean serum estradiol level (99.9 +/- 9.3 pg/mL to 26.6 +/- 1.6 pg/mL, P <.001). The number of subjects with any Lactobacillus did not change, but the number with hydrogen peroxide (H(2)O(2))-positive Lactobacillus decreased from 20% before to 12% after 6 months of DMPA (P =.005). The log concentration in colony-forming units per milliliter of vaginal fluid of H(2)O(2)-positive Lactobacillus decreased in a linear manner from 4. 0 +/- 0.6 at baseline to 2.5 +/- 0.6 after 6 months of DMPA use (P =. 006). The mean number of cell layers in the epithelium was reduced slightly from 28.1 +/- 0.7 to 25.9 +/- 0.9 (P =.05), epithelial thickness decreased from 1.02 +/- 0.04 mm to 0.89 +/- 0.05 mm (P =. 005), and the glycogen-positive thickness decreased from 0.81 +/- 0. 04 mm at baseline to 0.66 +/- 0.05 after 6 months of DMPA use (P =. 005). CONCLUSION: Depomedroxyprogesterone acetate produced a systemic hypoestrogenic state associated with decreased H(2)O(2)-positive Lactobacillus colonization and slight thinning of the glycogen vaginal epithelial layer. Such changes possibly compromise the vaginal barrier to infection.

Adolescent↗

Transplant vasculopathy: viral anti-inflammatory serpin regulation of atherogenesis.

BACKGROUND: Surgical and ischemic injury to the artery wall initiates vascular wound-healing responses that stimulate atherosclerotic plaque growth. The plasminogen activators have cellular chemotactic, adhesion, and proteolytic activity. Serp-1 is a secreted myxoma virus glycoprotein serpin that binds and inhibits plasminogen activators. We have examined the effects of Serp-1 on plaque growth and inflammatory cell invasion in animal models after balloon injury and after aortic allograft transplant. METHODS: We used histologic analysis to assess 4 animal models of angioplasty-mediated injury and 2 models of aortic allograft transplant for intimal hyperplasia and cellular invasion. We assessed plasminogen activator (uPA and tPA) and inhibitor (PAI-1) expression in rat iliofemoral arteries after balloon injury using Western blot, enzyme activity, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Plaque growth after balloon injury decreased after Serp-1 treatment in all balloon-injury models tested. Transplant vasculopathy also significantly decreased in 2 rat models of aortic allograft transplant. Infusion of a Serp-1 active site mutant, that lacked plasminogen activator inhibiting activity, did not inhibit plaque growth. Quantitative RT-PCR detected increased transcription of PAI-1 mRNA. Increased PAI-1 protein and enzyme-inhibitory activity was also detected in Serp-1-treated arteries by activity assay and Western blot. CONCLUSIONS: Thrombolytic serpins are central regulatory agents in vascular wound-healing responses. Investigation of the inhibitory mechanisms of viral serpins may provide new insights into atherogenesis.

Angioplasty, Balloon↗

Identification of quantitative trait loci influencing alcohol consumption in the high alcohol drinking and low alcohol drinking rat lines.

Selective breeding has been employed to develop high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to discourage inbreeding (Li et al, 1993). To identify quantitative trait loci (QTLs) contributing to alcohol consumption, reciprocal HAD and LAD matings in conjunction with F1 intercrosses were used to create 459 F2 progeny. Using selective genotyping of 151 F2 progeny with extreme alcohol consumption scores and a novel least squares method developed by Haley et al (1994), five chromosomal regions (1, 5, 10, 12, and 16) were identified with lod scores greater than 2.0. Genotyping of the entire sample of 459 F2 progeny produced maximum lod scores of 3.5 on chromosome 5, 2.4 on chromosome 10, 4.7 on chromosome 12 and 2.9 on chromosome 16. The evidence of linkage to chromosome 1 diminished substantially to a maximum lod score of 0.5 when all F2 progeny were genotyped. This study is the first genome-wide study for QTLs underlying alcohol consumption that has employed noninbred lines. Further localization of these QTLs will likely provide insight and candidate genes for the study of human alcoholism.

Alcohol Drinking↗

Identification of complement receptor one (CR1) polymorphisms in west Africa.

Complement receptor one (CR1) is a ligand for the rosetting of Plasmodium falciparum infected red cells with uninfected cells. Since CR1 exhibits three known polymorphisms, we studied European-Americans (n = 112) and African-Americans (n = 330) and Malians (n = 158) to determine if genetic differences existed in an area endemic for malaria that could offer a survival advantage. The frequencies of Knops blood group phenotypes McC(b+) and Sl(a-) were greatly increased in Africans vs Europeans. Although the frequency of McC(b+) was similar between Africans from the USA or Mali, the Sl(a-) phenotype was significantly higher in Mali (39% vs 65%, respectively). There was an increased frequency of the largest size (250 kD) of CR1 in Mali, but this did not differ significantly from the USA (P = 0.09). Both cohorts of Africans had higher expression of red cell CR1 than European-Americans but this showed little difference between the USA and Mali groups. Thus, the most important CR1 polymorphism relevant to rosetting of malaria infected cells appears to be the Knops blood group.

Blood Group Antigens↗

Pre-eclampsia and premature labour among pregnant wowen with haematuria.

The authors conducted a retrospective cohort study of pregnant women to estimate the prevalence and associated risk of adverse pregnancy outcomes among pregnant women with microhaematuria. Between 1 January 1993 and 15 March 1993 at University of Washington Medical Center, 328 consecutive births were identified, and demographic data, medical history, laboratory data and pregnancy outcomes were abstracted from hospital charts. The presence or absence of haematuria was determined in 276/328 cases. Sixteen per cent (44/276) of the women were found to have haematuria. Those with haematuria were at increased risk of developing pre-eclampsia (odds ratio [OR] = 9.5, 95% confidence interval [CI] 3.1, 28.2) and premature labour (OR = 3.8, 95% CI 1.5, 9.7). These associations persisted after controlling for age, race, and urinary tract infection (UTI) (pre-eclampsia OR=9.1, 95% CI 2.5, 33.7; premature labour OR = 4.2, 95% CI 1.2, 15.3). Infants of women with haematuria were at a non-significantly increased risk of low Apgar scores (OR = 2.8, 95% CI 0.7, 11.9) and low birthweight (OR=1.9, 95% CI 0.7, 4.7). In this observational study, microscopic haematuria was prevalent among pregnant women and was independently associated with an increased risk of adverse maternal complications.

Adult↗

A comparison of four repair techniques for Camper's chiasma flexor digitorum superficialis lacerations: tested in an in vitro model.

The relative strengths of 4 methods for repair of the flexor digitorum superficialis tendon were examined in 14 fresh-frozen cadaver hands (40 tendons). All tendons underwent sharp zone II transection at Camper's chiasma. All transections were repaired with 4.0 Ethibond (Ethicon Inc, Sommerville, NJ) using modified Becker, modified Kessler, horizontal mattress, or simple sutures. Flexion of the repaired digit at a constant excursion rate was rendered up to tendon rupture. The modified Becker technique withstood breaking forces (57.9 N) significantly greater than the other techniques examined. Forces up to 34 N have been measured in vivo during unresisted active finger motion. Thus, the modified Becker technique appears to provide adequate strength for early active flexor digitorum superficialis motion.

Analysis of Variance↗

Accidental and nonaccidental femur fractures in children.

A retrospective review of 207 patients younger than 6 years of age who sustained nonpathologic diaphyseal femur fractures was done, which emphasized the characteristics of accidental versus nonaccidental injury. There were 214 fractures in 123 boys and 83 girls (the gender of one patient was unknown). The average age of the patients was 2.73 years. Mechanisms of injury were pedestrian struck by a car (62 patients), falls (92 patients), and motor vehicle accidents (10 patients). Nineteen patients did not have a history of trauma. Seventy-six cases were investigated for child abuse. The results of 13 investigations were positive. Overall, the morphologic features of the fractures were transverse (38%), spiral (27%), and oblique (17%). In the investigated group, 27% of the fractures were transverse, 39% were spiral, and 15% were oblique. In those cases with positive results of the investigation, 36% of the fractures were transverse, 36% were spiral, and 7% were oblique. Although transverse fractures are most common in accidental and nonaccidental injuries, many practitioners think spiral fractures are pathognomonic of abuse. The current data show that although spiral fractures were less common than transverse fractures overall, and no more common in the cohort of patients in whom the results of the child abuse investigations were positive, they were overrepresented in the cohort that was investigated. This suggests that spiral fractures are viewed as particularly suspicious, which may lead to missed cases of nonaccidental injury in children with transverse fractures.

Child Abuse↗

Religiosity and substance use and abuse among adolescents in the National Comorbidity Survey.

OBJECTIVE: To replicate previous findings among adults of an inverse association between religiosity and substance use among a nationally representative sample of adolescents. METHOD: Subjects were 676 (328 female and 348 male) adolescents in the National Comorbidity Survey who were assessed for substance use and abuse with the Composite International Diagnostic Interview. Religiosity was assessed through affiliation with religious denomination and through response to 7 questions concerning belief and practice. RESULTS: Confirmatory factor analyses replicated in adolescents the 2 religiosity factors of personal devotion and personal conservatism previously identified by Kendler among adults, although the 2 factors were more highly correlated in adolescents than in adults. Personal devotion (a personal relationship with the Divine) and affiliation with more fundamentalist religious denominations were inversely associated with substance use and substance dependence or abuse across a range of substances (alcohol, marijuana, cocaine, or any contraband drug). Personal conservatism (a personal commitment to teaching and living according to creed) was inversely associated with use of alcohol only. CONCLUSION: Low levels of religiosity may be associated with adolescent onset of substance use and abuse.

Adolescent↗

Nitric oxide inhibits chondrocyte response to IGF-I: inhibition of IGF-IRbeta tyrosine phosphorylation.

Chondrocytes in arthritic cartilage respond poorly to insulin-like growth factor I (IGF-I). Studies with inducible nitric oxide synthase (iNOS) knockout mice suggest that NO is responsible for part of the cartilage insensitivity to IGF-I. These studies characterize the relationship between NO and chondrocyte responses to IGF-I in vitro, and define a mechanism by which NO decreases IGF-I stimulation of chondrocyte proteoglycan synthesis. Lapine cartilage slices, chondrocytes, and cartilage from osteoarthritic (OA) human knees were exposed to NO from the donors S-nitroso-N-acetylpenicillamine (SNAP) or (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1- ium-1, 2-diolate] (DETA NONOate), by transduction with adenoviral transfer of iNOS (Ad-iNOS), or by activation with interleukin-1 (IL-1). NO synthesis was estimated from medium nitrite, and proteoglycan synthesis was measured as incorporation of (35)SO(4). IGF-I receptor phosphorylation was evaluated with Western analysis. SNAP, DETA NONOate, endogenously synthesized NO in Ad-iNOS-transduced cells, or IL-1 activation decreased IGF-I-stimulated proteoglycan synthesis in cartilage and monolayer cultures of chondrocytes. OA cartilage responded poorly to IGF-I; however, the response to IGF-I was restored by culture with N(G)-monomethyl-L-arginine (L-NMA). IGF-I receptor phosphotyrosine was diminished in chondrocytes exposed to NO. These studies show that NO is responsible for part of arthritic cartilage/chondrocyte insensitivity to anabolic actions of IGF-I; inhibition of receptor autophosphorylation is potentially responsible for this effect.

Animals↗

Re-engineering the soft machine: the impact of developing technology and changing practice on diagnostic radiographer skill requirements.

This paper describes research to investigate the extent to which new technology and changing work practices in diagnostic imaging have changed the skill requirements of working radiographers. Interviews were conducted with radiography managers, radiologists and industry representatives. While changes in technology were viewed as having a significant impact on skill requirements, levels of resourcing and both national and local policy were seen as key factors driving changes in work practice. Respondents believed that significant changes would be required to pre- and post-registration training requirements for radiographers in the light of changing practice.

Clinical Competence↗

The effects of breed and level of nutrition on whole-body and muscle protein metabolism in pure-bred Aberdeen angus and Charolais beef steers.

Eighteen pure-bred steers (live weight 350 kg) from each of two breeds, Aberdeen Angus (AA) and Charolais (CH), were split into three equal groups (six animals each) and offered three planes of nutrition during a 20-week period. The same ration formulation was offered to all animals with amounts adjusted at 3-week intervals to give predicted average weight gains of either 1.0 kg/d (M/M group) or 1.4 kg/d (H/H group). The remaining group (M/H) were offered the same amount of ration as the M/M group until 10 weeks before slaughter when the ration was increased to H. Data on animal performance, carcass characteristics and fibre-type composition in skeletal muscle are presented elsewhere (Maltin et al. 2000; Sinclair et al. 2000). On three occasions (17, 10 and 2 weeks before slaughter) the animals were transferred to metabolism stalls for 1 week, during which total urine collection for quantification of Ntau-methylhistidine (Ntau-MeH) elimination was performed for 4 d. On the last day, animals were infused for 11 h with [2H5]phenylalanine with frequent blood sampling (to allow determination of whole-body phenylalanine flux) followed by biopsies from m. longissimus lumborum and m. vastus lateralis to determine the fractional synthesis rate of mixed muscle protein. For both breeds, the absolute amount of Ntau-MeH eliminated increased with animal age or weight (P < 0.001) and was significantly greater for CH steers, at all intake comparisons, than for AA (P < 0.001). Estimates of fractional muscle breakdown rate (FBR; calculated from Ntau-MeH elimination and based on skeletal muscle as a fixed fraction of live weight) showed an age (or weight) decline for M/M and H/H groups of both breeds (P < 0.001). FBR was greater for the H/H group (P = 0.044). The M/H group also showed a lower FBR for the first two measurement periods (both at M intake) but increased when intake was raised to H. When allowance was made for differences in lean content (calculated from fat scores and eye muscle area in carcasses at the end of period 3), there were significant differences in muscle FBR with intake (P = 0.012) but not between breed. Whole-body protein flux (WBPF; g/d) based on plasma phenylalanine kinetics increased with age or weight (P < 0.001) and was similar between breeds. The WBPF was lower for M/M compared with H/H (P < 0.001) based on either total or per kg live weight0.75. Muscle protein fractional synthesis rate (FSR) declined with age for both breeds and tended to be higher at H/H compared with M intakes (intake x period effects, P < 0.05). Changing intake from M to H caused a significant increase (P < 0.001) in FSR. The FSR values for AA were significantly greater than for CH at comparable ages (P = 0. 044). Although FSR and FBR responded to nutrition, these changes in protein metabolism were not reflected in differences in meat eating quality (Sinclair et al. 2000).

Age Factors↗