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Biomedical subjects

Anthony Johnson

Publications and source records attributed to Anthony Johnson.

34 records · Page 2Linked to original sources

On the mechanism by which epinephrine potentiates lidocaine's peripheral nerve block.

BACKGROUND: Adding epinephrine to lidocaine solutions for peripheral nerve block potentiates and prolongs the action, but by incompletely understood mechanisms. In an effort to discriminate the pharmacokinetic from the pharmacodynamic effects of epinephrine, the authors measured the lidocaine content of peripheral nerve over the course of block produced by 0.5% lidocaine, with and without epinephrine, and correlated it with the degree of analgesia. METHODS: Percutaneous sciatic nerve blocks were performed in 18 groups of rats (10 in each) with 0.1 ml of either 0.5% lidocaine or 0.5% lidocaine with epinephrine (1:100,000). Over the full course of nerve block, the authors regularly measured analgesia to toe pinch and then rapidly removed nerves to assay intraneural lidocaine content at 2-120 min after injection. RESULTS: The kinetics of lidocaine's clearance from nerve was composed of a fast-decaying transient superimposed on a very slowly decaying component. The effect of epinephrine on the intraneural lidocaine content was to increase the amount of lidocaine in the slow-decaying component by threefold to fourfold, although the total neural content was not altered by epinephrine for the first 10 min after injection. Epinephrine prolonged blockade by almost fourfold and enhanced the intensity of peak analgesia, as well as the fraction of rats with complete block, almost throughout the 2-120-min period of behavioral observation. CONCLUSIONS: Adding epinephrine to lidocaine solutions increases the intensity and duration of sciatic nerve block in the rat. The early increase in intensity is not matched with an increase in intraneural lidocaine content at these early times, although the prolonged duration of block by epinephrine appears to correspond to an enlarged lidocaine content in nerve at later times, as if a very slowly emptying "effector compartment" received a larger share of the dose. The increase in early analgesia without increased lidocaine content may be explained by a pharmacodynamic action of epinephrine that transiently enhances lidocaine's potency, but also by a pharmacokinetic effect that alters the distribution of the same net content of lidocaine within the nerve.

Algorithms↗

Nasal bone evaluation in fetuses with Down syndrome during the second and third trimesters of pregnancy.

OBJECTIVE: This study examined the use of three-dimensional ultrasonography for evaluating the fetal nasal bone, as a sonographic marker of Down syndrome, during the second and early third trimesters of pregnancy. METHODS: Forty fetuses, including 20 with trisomy 21, were scanned once by three-dimensional ultrasonography. A midline sagittal view of the facial profile was used to analyze the volume data. Independent examiners reviewed blinded and randomly allocated volume data sets for the nasal bone. Interobserver reliability was evaluated for the sonographic presence or absence of the nasal bone. Logistic regression determined the contribution of this parameter to the presence of Down syndrome. RESULTS: Both examiners showed substantial agreement in scoring whether the nasal bone was visualized by three-dimensional ultrasonography (P < .001). They identified 40% to 45% of fetuses with abnormalities using the absence of the nasal bone as a sonographic marker. However, a substantial number of fetuses with abnormalities were also found to have a nasal bone present. The nasal bone was visualized in 80% to 90% of fetuses without abnormalities. CONCLUSIONS: Three-dimensional ultrasonography can be used to evaluate the fetal nasal bone with substantial interobserver agreement during the second and early third trimesters of pregnancy. A nonvisualized nasal bone identified 40% to 45% of fetuses with Down syndrome in this study.

Down Syndrome↗

Three-dimensional power Doppler ultrasonography during pregnancy.

OBJECTIVES: To present the appearance of fetal and placental vascular anatomic structures by three-dimensional power Doppler ultrasonography. METHODS: Three-dimensional multiplanar imaging, surface rendering, and volume rendering were combined with power Doppler ultrasonography to show the methods, imaging artifacts, and diagnostic potential of this technology during pregnancy. RESULTS: Fetuses with normal and abnormal vascular anatomic structures were evaluated by three-dimensional power Doppler ultrasonography. The combination of several imaging modalities (e.g., three-dimensional multiplanar imaging, surface rendering, and volume rendering) with power Doppler ultrasonography is shown. CONCLUSIONS: Three-dimensional power Doppler ultrasonography is an important adjunctive method that can be used to characterize normal vascular development and circulatory anomalies of the fetus.

Female↗

Ganstigmine. Chiesi.

Ganstigmine (CHF-2819) is being developed by Chiesi as a potential treatment for neurodegenerative and cognitive disorders. The drug was in phase IIa studies in the US for senile dementia associated with Alzheimer's disease (AD) by mid-2000, and phase IIb trials in AD patients were scheduled for early 2001, with these ongoing in 2002.

Alkaloids↗

Pre-eclampsia and expression of heparin-binding EGF-like growth factor.

BACKGROUND: Pre-eclampsia is a disorder of pregnancy associated with poor extravillous cytotrophoblast invasion and above-normal rates of apoptosis in the trophoblast. Heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) has strong cytoprotective activity and is an important signalling protein that regulates trophoblast invasion during early placentation. We aimed to establish whether HB-EGF expression is altered in placentae of pre-eclamptic women. METHODS: We assessed the expression of HB-EGF mRNA and protein by in-situ hybridisation and immunohistochemical techniques, respectively, in archived placental tissues from pregnancies terminated at around 20 weeks of gestation, and from women delivering between weeks 19 and 35 of gestation with preterm labour, small for gestational age infants, or pre-eclampsia. FINDINGS: HB-EGF mRNA and protein were expressed in villous and extravillous cytotrophoblast cells up to week 35 of gestation in placentae from women who delivered preterm. Similar levels of HB-EGF protein were found in the placentae of women who were not in labour. HB-EGF expression was reduced about five-fold (p=0.0001) in pre-eclamptic pregnancies. Fetal growth retardation, which has been linked with shallow trophoblast invasion and moderate apoptosis, was associated with placentae expressing intermediate levels of HB-EGF. INTERPRETATION: In pre-eclampsia, deficient HB-EGF signalling during placental development could impair trophoblast survival, differentiation, and invasion, leading to poor placental perfusion and hypertension.

Adult↗

Association of the SULT1A1 R213H polymorphism with colorectal cancer.

1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild-type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N-OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer. 2. Genotyping, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis. 3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p-nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence. 4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population.

Aged↗

4-1BB co-stimulation enhances human CD8(+) T cell priming by augmenting the proliferation and survival of effector CD8(+) T cells.

Interactions between 4-1BB and its ligand, 4-1BBL, enhance CD8(+) T cell-mediated antiviral and antitumor immunity in vivo. However, mechanisms regulating the priming of CD8(+) T cell responses by 4-1BB remain unclear, particularly in humans. The 4-1BB receptor was undetectable on naive or resting human CD8(+) T cells and induced in vitro by TCR triggering. Naive cord blood cells were therefore primed in vitro against peptides or cellular antigens and then co-stimulated with 4-1BBL or agonistic antibodies. Co-stimulation enhanced effector function such as IFN-gamma production and cytotoxicity by augmenting numbers of antigen-specific and effector CD8(+) T cells. OKT3 responses also showed reduced cell death and revealed that the proliferation of CD8(+) T cells required two independently regulated events. One, the induction of IL-2 production, could be directly triggered by 4-1BB engagement on CD8(+) T cells in the absence of accessory cells. The other, expression of CD25, was induced with variable efficacy by accessory cells. Thus, suboptimal accessory cells and 4-1BB co-stimulation combined their effects to enhance IL-2 production and proliferation. Reduced apoptosis observed after co-stimulation in the presence of accessory cells correlated with increased levels of Bcl-X(L) in CD8(+) T cells, while Bcl-2 expression remained unchanged. Altogether, 4-1BB enhanced expansion, survival and effector functions of newly primed CD8(+) T cells, acting in part directly on these cells. As 4-1BB triggering could be protracted from the TCR signal, 4-1BB agonists may function through these mechanisms to enhance or rescue suboptimal immune responses.

Antigen-Presenting Cells↗

A clinical overview of removable prostheses: 3. Principles of design for removable partial dentures.

Removable partial dentures (RPDs) should not be made for patients unless they are necessary. Most partial dentures have the potential to cause some damage to the teeth and supporting tissues, however well they are designed and constructed; the criteria for selecting such devices were described in a previous article. In general there is merit in, wherever possible, reducing tissue coverage as much as possible when RPDs are being planned. This article, the third in a series on the prescription of RPDs, discusses the design principles involved.

Dental Abutments↗

A clinical overview of removable prostheses: introduction.

This series of articles has been written with the intention of simplifying the processes involved in the prescription of removable partial dentures. The scene is set in this introduction, and the first article addresses basic clinical and patient-related factors involved in decision-making before commencing active prosthodontic treatment. The second paper will outline a variety of impression techniques for primary and definitive impressions, while the third discusses designing principles. The fourth article is a brief overview of some technological aspects of removable partial denture-making and the fifth attempts to provide a useful guide showing how to diagnose and manage common clinical problems associated with removable partial dentures.

Denture, Partial, Removable↗

A clinical overview of removable prostheses: 1. Factors to consider in planning a removable partial denture.

This is the first article in a series on the prescription of removable partial dentures. It addresses basic clinical and patient-related factors involved in decision-making before commencing active prosthodontic treatment. Further papers will outline a variety of impression techniques for primary and definitive impression, discuss designing principles, give an overview of some technological aspects of removable partial denture-making and provide guidelines on how to diagnose and manage common clinical problems associated with removable partial dentures.

Adaptation, Psychological↗

A diagnostic approach for the evaluation of spina bifida by three-dimensional ultrasonography.

OBJECTIVE: To describe a prenatal diagnostic method for evaluating spina bifida by three-dimensional ultrasonography. METHODS: Two- and three-dimensional ultrasonography were used to determine the extent of vertebral defects among fetuses with spina bifida. Spinal levels were independently counted from the most caudal thoracic vertebra with a rib (e.g., 12th thoracic rib). A virtual cutting plane was manipulated through a volume-rendered spine to generate optimal multiplanar views for this blinded analysis. Prenatal diagnosis was compared with a postnatal analysis of bony spine defects derived from radiographic films or magnetic resonance imaging. RESULTS: Nine fetuses were examined by two-dimensional ultrasonography (21.8 +/- 3.4 menstrual weeks) and three-dimensional ultrasonography (22.8 +/- 4.4 menstrual weeks). For two-dimensional ultrasonography, the spinal level agreed to within 1 vertebral segment in 6 of 9 infants. In contrast, three-dimensional ultrasonography agreed to within 1 vertebral segment in 8 of 9 infants. Three fetuses had vertebral defect levels on two-dimensional ultrasonography that were 1.5 to 2 segments away from postnatal findings. The same fetuses had results that were within 1 vertebral segment on three-dimensional ultrasonography. Volume rendering showed splayed vertebral pedicles and disrupted vertebrae. An intact meningeal sac was easily rendered in 5 of 9 subjects. CONCLUSIONS: Multiplanar views are generally more informative than rendered views for localizing bony defects of the fetal spine. The level of the defect on three-dimensional ultrasonography correlates well with those on two-dimensional ultrasonography and postnatal imaging studies. This approach may improve characterization of spina bifida by adding diagnostic information that is complementary to the initial assessment by two-dimensional ultrasonography.

Female↗