More on epidural needle wings.
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Analgesia, Epidural↗
Biomedical subjects
C Miller
Publications and source records attributed to C Miller.
Identification and characterization of murine alternatively spliced tissue factor.
Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation and plays a critical role in regulating hemostasis and thrombosis. We have recently reported a naturally occurring, soluble form of human tissue factor (asTF) generated by alternative splicing. This splice variant has a novel C-terminus with no homology to that of the full-length TF (flTF), lacks a transmembrane domain, and is active in the presence of phospholipids. Mouse models offer unique opportunities to examine the relative importance of flTF and asTF in mediating thrombosis, the response to arterial injury, and ischemic damage. To that end, we have identified and characterized murine asTF (masTF). Like the human splice variant, masTF lacks a transmembrane domain and has a unique C-terminus. We have generated antibodies specific to masTF and murine flTF (mflTF) to examine the expression of both forms of TF. masTF antigen is widely and abundantly expressed, with a pattern similar to that of mflTF, in adult tissues, in experimentally induced thrombi, and during development. These studies demonstrate that masTF contributes to the pool of total TF and may thus play an important role in mediating TF-dependent processes.
Alternative Splicing↗
An unusual case of talonavicular dislocation with associated ipsilateral foot fractures.
We describe a previously unreported form of a talonavicular dislocation complicated by navicular, talar neck and open calcaneal fractures. Prompt recognition and rapid reduction of fractures and dislocations gives the best possible outcome. The presence of serious distracting injuries can alter priorities, however the "lesser" injuries often lead to long term morbidity after recovery from the life-threatening injuries.
Adult↗
High-performance liquid chromatography determination of alpha1-acid glycoprotein in small volumes of plasma from neonates.
In order to investigate how the alpha1-acid glycoprotein (AGP) concentrations of neonates change in response to surgical stress, a simple high-performance liquid chromatography (HPLC)-assay for the measurement of alpha1-acid glycoprotein levels was developed. A fraction containing alpha1-acid glycoprotein was isolated from the bulk of plasma protein by addition of 0.6M perchloric acid and was then analysed directly on a short PLRP-S 4000A reversed phase column column. The method was validated by analysis of pooled plasma from healthy adults both in comparison with a calibration curve and by standard additions. The procedure was able to isolate alpha1-acid glycoprotein rapidly (<30 min) and required only 50 microl of plasma. The mean extraction recovery was 79.1% (CV 6.4%). The within-run precision for the analysis of three replicates of quality control sample ranged from +/-1.2 to +/-3.8% and the between-run precision was +/-6.1%. The method was linear (r(2)=0.988) over a concentration range from 6 to 100.0 mg/100 ml. The AGP levels in neonatal samples ranged from 25 to 93 mg/100 ml.
Adult↗
The aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart.
Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) catalyze the production of aldosterone and corticosterone, respectively, in the rat adrenal cortex. Recently, there has been some debate as to whether these corticosteroids are also produced in the hearts of rodents and humans, possibly contributing to the development of hypertrophy and myocardial fibrosis. To investigate this, we have used our established, highly sensitive real-time quantitative RT-PCR method to measure CYP11B1 and CYP11B2 mRNA levels in adrenal and cardiac tissue from several rat models of cardiovascular pathology. We have also studied isolated adult rat ventricular myocytes treated with angiotensin II and ACTH. Total RNA was isolated from the adrenal and cardiac tissue of 1) male Wistar rats with heart failure induced by coronary artery ligation and sham-operated controls; 2) stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats as controls; 3) cyp1a1Ren-2 transgenic rats and Fischer controls; 4) isolated adult Sprague-Dawley ventricular myocytes incubated with 11-deoxycorticosterone (DOC), DOC plus angiotensin II, or DOC plus ACTH. Adrenal CYP11B2 expression was significantly increased in transgenic rats compared with Fischer controls (1.3 x 10(9)+/- 1.2 x 10(9) vs. 2.1 x 10(7) +/- 7.0 x 10(6) copies/microg RNA; P < 0.05). There were no other significant differences in adrenal CYP11B2 or CYP11B1 expression between the model animals and their respective controls. Cardiac CYP11B1 and CYP11B2 mRNA transcript levels from all in vivo and in vitro groups were never greater than 100 copies per microgram total RNA and therefore too low to be detected reproducibly. This suggests that cardiac corticosteroid production is unlikely to be of any physiological or pathological significance.
Adrenal Glands↗
Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis.
Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.
Absorptiometry, Photon↗
Synthesis and biological activity of GnRH antagonists modified at position 3 with 3-(2-methoxy-5-pyridyl)-alanine.
Degarelix is a potent very long-acting GnRH antagonist after subcutaneous administration. In this paper, we describe the synthesis of two analogs of degarelix incorporating racemic 3-(2-methoxy-5-pyridyl)-alanine (2-OMe-5Pal, 5) at position 3. The two diastereomers were separated by reverse-phase high-performance liquid chromatography (RP-HPLC) and the absolute stereochemistry at position 3 in the peptides was determined by enzymatic digestion with proteinase K. These analogs were tested in vitro for their ability to antagonize the GnRH receptor and in vivo for duration of action in a castrated male rat assay. Analog 7 with D2-OMe-5Pal was potent in vitro (IC50 = 5.22 nM); however, analog 8 with L2-OMe-5Pal at position 3 in degarelix lost potency as an antagonist of the human GnRH receptor (IC50 = 36.95 nM). Both the analogs were found to be short-acting in vivo.
Alanine↗
Full-body gaze control mechanisms elicited during locomotion: effects of VOR adaptation.
We have previously shown that multiple, interdependent, full- body sensorimotor subsystems aid gaze stabilization during locomotion. In the present study we investigated how the full-body gaze control system responds following exposure to visual-vestibular conflict known to adaptively modify vestibulo-ocular reflex (VOR) function. Subjects (n = 14) walked (6.4 km/h) on a motorized treadmill before and after they were exposed to 0.5X minifying lenses worn for 30 minutes during self-generated sinusoidal vertical head rotations performed while seated. Results indicate that, following the exposure the major changes that subjects showed were to: 1) decrease the amplitude of head pitch and vertical translation of the torso movement with respect to space; 2) increase the amount of knee and ankle flexion during the initial stance phase of the gait cycle. A correlation analysis showed that: 1) changes in the head pitch significantly co-varied with that of the vertical torso translation 2) changes in the knee flexion significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle 3) changes in the vertical torso translation significantly co-varied with that of the ankle flexion during the initial stance phase of the gait cycle. Thus we infer that the changes in the magnitude after VOR adaptation in comparison to their pre adaptation responses serve to aid gaze stabilization during locomotion. The significant covariation of the changes between subsystems provides further evidence that the full body contributes to gaze stabilization during locomotion, and its different functional elements are subject to adaptive reorganization following exposure to visual-vestibular conflict.
Adaptation, Physiological↗
Comparison of selected analytical techniques for protein sizing, quantitation and molecular weight determination.
Protein analysis techniques are developing fast due to the growing number of proteins obtained by recombinant DNA techniques. In the present paper we compare selected techniques, which are used for protein sizing, quantitation and molecular weight determination: sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), lab-on-a-chip or microfluidics technology (LoaC), size exclusion chromatography (SEC) and mass spectrometry (MS). We compare advantages and limitations of each technique in respect to different application areas, analysis time, protein sizing and quantitation performance.
Chromatography↗
Hepatic allograft salvage with early doppler ultrasound diagnosis of acute vena cava thrombosis.
Postoperative inferior vena cava obstruction is an uncommon complication after liver transplantation. Outflow obstruction, if not rapidly corrected, can lead to graft failure and the patient's death. We report a case in which Doppler ultrasound showed the thrombus inside the vessel, excluding extrahepatic causes of venous outflow obstruction, and permitted early surgical correction of the complication without graft loss.
Acute Disease↗
Accurate method for clinical assessment of right lobe liver weight in adult living-related liver transplant.
INTRODUCTION: Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. METHODS: Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 x body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). RESULTS: Mean actual right lobe weight (n = 90) was 855.83 +/- 183.4 g. Estimated right lobe weight was 858.08 +/- 90.80 (R-57, P = NS); 1077.35 +/- 263.07 mL for CT (P = .0001), and 1185.07 +/- 350.10 mL for MRI (P = .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies (P = .0001). CONCLUSION: With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping.
Adult↗
The epidemiology of subacute sclerosing panencephalitis in England and Wales 1990-2002.
AIM: To assess the impact of measles/mumps/rubella (MMR) vaccine on the epidemiology of subacute sclerosing panencephalitis (SSPE) in England and Wales. METHODS: Cases of SSPE resident in England and Wales with onset between 1990 and 2002 were reviewed. RESULTS: A total of 47 cases were identified, 31 male and 16 female. There was an average annual decline of 14% in SSPE onset over the period, consistent with the decline in notified measles over the last 20 years. A history of measles was present in 35 (median age 1.3 years), the most recent recorded date being 1994; the interval from measles to onset of SSPE ranged from 2.7 to 23.4 years. Four children with a history of receipt of a measles containing vaccine were reported not to have had measles; two of these cases had a brain biopsy, and nucleotide sequence data confirmed wild measles infection. Brain biopsy specimens from a further three cases with a history of measles, of whom two had also had a history of vaccination, showed wild-type strain. CONCLUSION: The prevention of endemic circulation of measles virus in England and Wales through the high coverage achieved with MMR vaccine, together with the measles/rubella vaccination campaign of 1994, has resulted in the near elimination of SSPE. However, the recent decline in MMR vaccine coverage, with the associated increase in localised measles outbreaks and cases in young infants, is of concern. It underlines the importance of maintaining high vaccine coverage in order to protect indirectly those most vulnerable to SSPE, namely infants too young to be vaccinated.
Adolescent↗
Case report: polycythaemia vera presenting as massive splenic infarction and liquefaction.
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Abdominal Pain↗
Stable transformation of Theobroma cacao L. and influence of matrix attachment regions on GFP expression.
We describe a protocol for Agrobacterium-mediated genetic transformation of Theobroma cacao L. using cotyledonary explants from primary somatic embryos (SEs) and A. tumefaciens strain AGL1. Transgenic plants carrying the visible marker, gene green fluorescent protein ( EGFP), the selectable marker gene neomycin phosphotransferase II ( NPTII), the class I chitinase gene from cacao ( Chi), and tobacco nuclear matrix attachment regions (MARs) in different combinations were successfully produced via regeneration of secondary SEs. The presence of the Chi gene or MARs did not influence the number of transgenic plants produced compared to the marker genes alone. However, the inclusion of MARs contributed to increased mean GFP expression in the population of transgenics. Additionally, the presence of MARs reduced the occurrence of gene silencing and stabilized high levels of GFP expression in lines of transgenic plants multiplied via reiterative somatic embryogenesis. Ninety-four transgenic plants were acclimated in a greenhouse and grown to maturity. Detailed growth analysis indicated that there were no differences in various growth parameters between transgenic and non-transgenic SE-derived plants. Seeds produced from two genetic crosses with one of the transgenic lines were analyzed for EGFP expression-a near-perfect 1:1 segregation was observed, indicating that this line resulted from the insertion of a single locus of T-DNA.
Base Sequence↗
Living donor liver transplantation--overview after 178 cases.
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Adult↗
Case management models and the care programme approach: how to make the CPA effective and credible.
The care programme approach (CPA), a form of case management, is a key mental health policy in England. Yet after over 10 years, it remains poorly and unevenly implemented with few benefits for service users, carers or mental health staff. This paper reviews the wider literature on case management and identifies and considers the principal models that might have informed the development of the CPA. After discussing the evidence for each of the clinical, strengths, intensive and assertive case management models, the paper identifies the key components that appear to be central to effective case management across these models. These components are then considered in relation to the CPA. It is argued that the CPA has been undermined by a failure to incorporate and build on certain important features of the major models of case management. The paper concludes by suggesting the key developments required to make the CPA more effective and to underpin the policy with a unifying philosophy while endorsing it with much needed credibility among both clinicians and service users.
Attitude of Health Personnel↗
The beta fibrinogen gene G-455-A polymorphism is a risk factor for Legg-Perthes disease.
Legg-Perthes disease is a pediatric hip disorder characterized by avascular necrosis of the femoral head. The etiology of Legg-Perthes disease may involve repeated interruptions of the blood supply to the proximal femur. Thus, the role of thrombosis in Legg-Perthes disease is of interest. The focus of this analysis is an evaluation of the relationship between Legg-Perthes disease and the beta fibrinogen gene G-455-A polymorphism in 55 cases of Legg-Perthes disease and 56 age, race, and gender-matched healthy controls. Parents of subjects completed a questionnaire about their child's lifestyle and medical history. Blood was obtained for plasma and DNA analysis. Study subjects were predominantly white (93%), male (77%) and under age 16 (70%). Cases were more likely to be exposed to passive smoke than were controls (odds ratio 5.6, 95% confidence interval 2.0-12.0). Assuming a dominant genetic model, individuals who possessed either the G/A or A/A genotype were over three times more likely to have Legg-Perthes disease compared to those without the polymorphism (odds ratio 3.4, 95% confidence interval 1.5-7.8). Separate analyzes by smoke exposure revealed that the excess risk of the G-455-A polymorphism occurred in those exposed (odds ratio 7.0) as opposed to those unexposed to passive smoke (odds ratio 1.9). Although this difference in the odds ratios is not statistically significant (P=0.2), it suggests a possible interactive effect of cigarette smoke and the b fibrinogen gene G-455-A polymorphism in the risk of developing Legg-Perthes disease.
Adolescent↗
Surviving the sex trade: a comparison of HIV risk behaviours among street-involved women in two Canadian cities who inject drugs.
In Canada, very little is known about the factors and processes that cause drug-related harm among female intravenous drug users (IDUs). Women who inject drugs and participate in the survival sex trade are considered to be at increased risk for sexual and drug-related harms, including HIV infection. Between September 1999 and September 2000, women participating in the VIDUS cohort in Vancouver and the St. Luc Cohort in Montreal completed interviewer-administered questionnaires. Analyses were conducted to compare the demographic characteristics, sexual risk behaviours, risky injection practices and drug use patterns among women who self-identified as participating in the sex trade with those who did not identify as participating in the sex trade. Logistic regression was used to identify factors independently associated with exchanging sex for money or drugs. HIV prevalence at the study visit (September 1999-2000) was 29% for sex trade workers and 29.2% for non-sex trade workers. While patterns of sexual risk were similar, the risky injection practice and drug use patterns between sex trade workers and non-sex trade workers were markedly different. Logistic regression analysis of cross-sectional data revealed that independent behaviours associated with the sex trade included: greater than once per day use of heroin (adjusted OR 2.7), smokeable crack cocaine (adjusted OR = 3.3) and borrowing used syringes (adjusted OR = 2.0). Creative, client-driven interventions are urgently needed for women who trade sex for money or for drugs.
Adolescent↗