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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 37 records · Page 2Linked to original sources
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC.

This multicenter study enrolled 73 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively. Of the 32 patients in phase I portion of the trial, six received irinotecan 40 mg/m2 plus carboplatin at an area-under-curve (AUC) of 6 and paclitaxel 225 mg/m2 on an every-3-week schedule (regimen A). Due to the unexpectedly severe toxicity associated with this regimen, the carboplatin and paclitaxel doses were reduced, while the irinotecan doses were escalated from 40 to 80 to 125 mg and reduced to 100 mg/m2 (regimen B). In the phase II portion of the trial, irinotecan was dosed at 100 mg/m2 because 3 of 8 patients who received the 125 mg/m2 dose in phase I experienced first-course grade 3/4 toxicities. However, the toxicity of regimen B proved unacceptably severe in phase II; 13 of the 40 patients (35%) experienced grade 3/4 neutropenia and 30% suffered febrile or septic neutropenia. The unconfirmed objective response rate in phase I was 64.5%; median time to progression and median survival were 7.1 months and 11.6 months, respectively, and 1-year survival was 46.9%. The unconfirmed objective response rate in phase II was 60.6%, including one complete response (CR) and 19 partial responses (PRs); one CR and 16 PRs were subsequently confirmed. The efficacy and toxicity of this triple combination strongly suggest significant pharmacokinetic and/or pharmacodynamic interactions, warranting continued clinical investigation.

Adult↗
PubMed1999

Preparative chromatographic resolution of enantiomers using polar organic solvents with polysaccharide chiral stationary phases.

The preparative chromatographic resolution of racemic mixtures is rapidly becoming a standard approach for the generation of enantiomers in pharmaceutical research and development. This paper will discuss the optical resolution of numerous pharmaceutical intermediates and final products using polar organic solvents with polysaccharide chiral stationary phases. The advantages of this approach compared to more traditional mobile phases for preparative separations will be presented. In addition the ability to reverse elution order using polar organic solvents will be presented.

Chromatography, High Pressure Liquid↗
PubMed1999

Chromatographic resolution of the enantiomers of a pharmaceutical intermediate from the milligram to the kilogram scale.

The preparative chromatographic resolution of racemic mixtures is rapidly becoming a standard approach for the generation of enantiomers in pharmaceutical R&D. This paper will discuss the optical resolution of a pharmaceutical intermediate as the separation is scaled up from the milligram to the kilogram scale. Difficulties encountered and their solutions at each scale will be discussed. In addition, the exploration of Simulated Moving Bed (SMB) for the separation will also be discussed. Finally, a comparison of the productivities and solvent consumption for each method and scale will be presented.

Chromatography↗
PubMed1999

Peripheral blood allogeneic microchimerism in lung and cardiac allograft recipients.

We have been investigating two parameters, donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism, to determine whether these parameters will predict a chronic rejection-free state and which recipients may be candidates for steroid withdrawal. We have identified donor antigen-specific hyporeactivity for 33% (16/48) of lung and 23% (11/47) of heart recipients. For both organ groups, the hyporeactive subgroup experienced a lower incidence of chronic rejection. The probability of donor antigen-specific hyporeactivity predicting a chronic rejection-free state is 100% for lung and 91% for heart recipients. We have identified peripheral blood allogeneic microchimerism for 77% (20/26) of lung and 36% (9/25) of heart recipients tested at 12-18 months posttransplant. Donor antigen-specific hyporeactivity correlates with a critical level of donor cells in lung recipients; the probability of high peripheral blood allogeneic microchimerism levels predicting a chronic rejection-free state in lung recipients is 100%. The results in heart recipients are not as clear with a short-, but not long-term, trend of higher chimerism levels correlating with the development of donor antigen-specific hyporeactivity. These results illustrate the usefulness of immmune parameters to predict long-term graft outcome in an organ-specific manner.

Bronchiolitis Obliterans↗
PubMed1999

Some clinical applications of religious development in adolescence.

The use of religion in the lives of adolescents to repair problematic or disrupted attachments is discussed in the context of attachment theory and Kohut's self-psychology theory, with particular reference to the self-object. It is proposed that adolescents do not seek to break ties with parents or adults so much as to revise their relationships in a more adult direction. Two adolescent cases, one beginning treatment in childhood and the other in early adolescence, are presented and discussed in the context of attachment theory and self-psychology.

Adolescent↗
PubMed1999

Methotrexate compared with mercaptopurine for early induced abortion.

OBJECTIVE: To compare the antimetabolites methotrexate and 6-mercaptopurine as single-agent medical abortifacients using clinical and immunohistochemical analyses. METHODS: Twenty-seven women with gestations less than 7 weeks from the last menstrual period (LMP) were randomized to receive intramuscular methotrexate, 50 mg/m2, or oral 6-mercaptopurine, 200 mg. Forty-six additional women received methotrexate after randomization was discontinued. Women returned at 2-week intervals. Those without fetal cardiac activity were followed until complete abortion. Those with fetal cardiac activity were considered failures and underwent suction abortions. Tissue collected at the time of suction abortion was analyzed with the cell-proliferation immunohistochemical assay Ki-67. RESULTS: All 12 women in the 6-mercaptopurine group had fetal cardiac activity at follow-up and underwent suction abortion; therefore, this arm of the study was discontinued. Six of the 61 women who received methotrexate had fetal cardiac activity at follow-up and also underwent suction abortion. Fetal cardiac activity was present after methotrexate in three of 55 women at less than 6 weeks from the LMP and in three of six between 6 and 7 weeks from the LMP (P < .01). Women who aborted after methotrexate started bleeding on day 19 (standard deviation [SD] 7.8), bled for 9 days (SD 4.0), and used minimal pain medications. Tissues exposed to methotrexate showed decreased Ki-67 activity compared with tissues exposed to 6-mercaptopurine (P = .003). CONCLUSION: In oral doses of 200 mg, 6-mercaptopurine did not induce early abortion. A single intramuscular dose of methotrexate used without prostaglandins induced abortion in most women at gestational ages of less than 6 weeks. Ki-67 activity was lower in a small sample of fetal tissues exposed to methotrexate than in tissues exposed to 6-mercaptopurine.

Abortifacient Agents↗