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Biomedical subjects

A M Phillips

Publications and source records attributed to A M Phillips.

At least 19 recordsLinked to original sources

Overview of the fracture healing cascade.

Fracture healing is a dynamic process being governed by a variety of cellular elements and stimulating agents. Our knowledge in understanding the molecular and cellular processes occurring in healing fractures has vastly expanded as a result of the advances made in all aspects of medicine. The ability to manipulate mesenchymal stem cells and to deliver locally growth factors in order to create new bone has led to a proliferation of research papers. The purpose of this article is to provide a brief overview of the current level of understanding of the physiological processes regulating the healing of fractures.

Animals↗

A randomized, placebo-controlled study of rofecoxib with paracetamol in early post-tonsillectomy pain in adults.

BACKGROUND AND OBJECTIVE: Effective and early treatment of postoperative pain and nausea have become pivotal for the early discharge of patients after tonsillectomy. Opioid-based analgesia is standard practice but the use of non-steroidal anti-inflammatory drugs is discouraged due to their platelet inhibiting properties. The cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs are effective analgesics and do not affect platelet function. We hypothesized that premedication with cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug in addition to paracetamol would provide effective analgesia and decrease opioid consumption during early recovery from tonsillectomy. METHODS: In a randomized, placebo-controlled study of adult tonsillectomy patients (n=40) one group (R-group; n=20) was premedicated with paracetamol 1.5 g and rofecoxib 50 mg and a control group (P-group; n=20) was premedicated with paracetamol 1.5 g and placebo. Morphine was used as rescue medication. Postoperative (24 h) pain scores (0--10), morphine consumption as well as intraoperative blood loss were recorded. RESULTS: We found no overall difference in pain scores between the groups but significantly more patients in the placebo group had pain scores >5 within the first 8 h. The rofecoxib group consumed less morphine during the first 12 h. A lower intraoperative blood loss was observed in the rofecoxib group. CONCLUSION: Our results suggest an early although clinically minor analgesic benefit of the addition of a cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drug to paracetamol as premedication for adult tonsillectomy.

Acetaminophen↗

On-line high-precision stable hydrogen isotopic analyses on nanoliter water samples.

We describe a new on-line chromium reduction technique for the measurement of stable hydrogen (deltaD) isotopes in waters using continuous-flow isotope ratio mass spectrometry. The on-line Cr reduction method has low intersample memory effects (< 1%) and excellent precision and accuracy for deltaD (+/-0.5% and was used to analyze waters samples as small as 50 nL. The on-line Cr method has a number of significant advantages over conventional offline Zn and U reduction and on-line carbon-based pyrolysis techniques. A single Cr reactor can be used to analyze approximately 1,000 water samples using an injection volume of 0.5 microL, with an individual sample analysis time of 4 min. Intersample memory effects are negligible. The Cr reactor temperature of 1050 degree C is easily attainable on standard elemental analyzers and so does not require the specialized and costly high-temperature furnaces of carbon-based pyrolysis reactors. Furthermore, hydrogen isotopes in extremely small water samples in the 100-nL range or less can be easily measured; hence, this new method opens up a number of exciting application areas in earth and environmental sciences, for example, natural abundance deltaD measurements of individual fluid inclusions in geologic materials using a laser source and measurements of body fluids in physiological and metabolic research.

Algorithms↗

Assessment of dermal exposure--empirical models and indicative distributions.

The Health and Safety Executive embarked upon a program of work to address the issue of exposure to nonagricultural pesticides in the United Kingdom. Early on it became clear that the primary route of exposure was via the skin. Empirical dermal exposure models have been developed which allow estimates of potential dermal exposure to be derived from distributions of rate of contamination with in-use formulations during typical use conditions in the workplace. Estimates of actual dermal exposure (what gets onto the skin) may also be anticipated and used in quantitative risk assessment to inform product registration. The key interpreted data from the empirical models are presented. Data are presented for six models. Separate summary data are presented for exposure to the body, hands, and feet. In the case of hand exposure, data are presented, in some cases, for contamination arising from wearing used (previously worn, of unknown history) and clean protective gloves. This article proposes a mechanism for addressing exposure assessment where little or no direct dermal exposure data are available--the indicative distribution approach. The empirical distributions of rate of contamination have been studied to seek commonalities which may allow the construction of a universal tool for use in screening level risk assessment. A simple 12-box matrix is proposed.

Databases, Factual↗

Potential exposure of hands inside protective gloves-a summary of data from non-agricultural pesticide surveys.

The results of individual surveys are compared and general observations are made about the protective nature of protective gloves. A total of 190 measurements of contamination by involatile components of pesticide products were made inside the gloves. Protective gloves were nearly always found to be contaminated inside, except for public hygiene insecticide uses. Disposable gloves were sometimes used when applying public hygiene insecticides, while gloves worn for other applications were normally re-used. The data suggest that when expressing inner glove exposure as 'amount of product per unit time', the data distributions of the non-zero results appeared similar for all activities except for the application of antifoulings. A median value for all non-zero data was indicated at 1.36mg product per minute; a 75th percentile at 4.21mg min(-1) and a 95th percentile at 71.9mg min(-1), assuming product densities of 1.0g ml(-1). In default of better information, these indicators can be used in health-based risk assessment. A further 47 data related to exposure inside new gloves, and 21 data to deposition on outer gloves. These indicate that in general, gloves provide a reasonable degree of protection to non-agricultural pesticides. Due regard should be paid to 'human factors' when considering contamination inside gloves. When people take off dirty gloves, it is difficult to avoid touching the glove exterior. With gloves off, the subject can touch contaminated surfaces. Donning dirty gloves furnishes an inevitable contact with contamination on the outside of the gloves, and can introduce that contamination inside. A common mode of contamination could contribute to the similar distributions for hand contamination inside gloves, from very different uses.

Data Collection↗

The products of the Drosophila stoned locus interact with synaptic vesicles via synaptotagmin.

The stoned locus of Drosophila melanogaster encodes two novel proteins, stonedA (STNA) and stonedB (STNB), both of which are expressed in the nervous system. Flies with defects at the stoned locus have abnormal behavior and altered synaptic transmission. Genetic interactions, in particular with the shibire (dynamin) mutation, indicated a presynaptic function for stoned and suggested an involvement in vesicle cycling. Immunological studies revealed colocalization of the stoned proteins at the neuromuscular junction with the integral synaptic vesicle protein synaptotagmin (SYT). We show here that stoned interacts genetically with synaptotagmin to produce a lethal phenotype. The STNB protein is found by co-immunoprecipitation to be associated with synaptic vesicles, and glutathione S-transferase pull-downs demonstrate an in vitro interaction between the micro2-homology domain of STNB and the C2B domain of the SYTI isoform. The STNA protein is also found in association with vesicles, and it too exhibits an in vitro association with SYTI. However, we find that the bulk of STNA is in a nonmembranous fraction. By using the shibire mutant to block endocytosis, STNB is shown to be present on some synaptic vesicles before exocytosis. However, STNB is not associated with all synaptic vesicles. We hypothesize that STNB specifies a subset of synaptic vesicles with a role in the synaptic vesicle cycle that is yet to be determined.

Animals↗

Presynaptic glutamic acid decarboxylase is required for induction of the postsynaptic receptor field at a glutamatergic synapse.

We have systematically screened EMS-mutagenized Drosophila for embryonic lethal strains with defects in glutamatergic synaptic transmission. Surprisingly, this screen led to the identification of several alleles with missense mutations in highly conserved regions of Dgad1. Analysis of these gad mutants reveals that they are paralyzed owing to defects in glutamatergic transmission at the neuromuscular junction. Further electrophysiological and immunohistochemical examination reveals that these mutants have greatly reduced numbers of postsynaptic glutamate receptors in an otherwise morphologically normal synapse. By overexpressing wild-type Dgad1 in selected neurons, we show that GAD is specifically required in the presynaptic neuron to induce a postsynaptic glutamate receptor field, and that the level of postsynaptic receptors is closely dependent on presynaptic GAD function. These data demonstrate that GAD plays an unexpected role in glutamatergic synaptogenesis.

Alleles↗

Determination of spinosad and its metabolites in food and environmental matrices. 3. Immunoassay methods.

Spinosad is an insect control agent that is derived from a naturally occurring soil bacterium and is effective on several classes of insects, especially Lepidopteran larvae. Spinosad is registered in many countries for use on a variety of crops, including cotton, corn, soybeans, fruits, and vegetables. Residue methods utilizing a magnetic particle-based immunoassay (IA) test kit have been developed and validated for determining spinosad in environmental and food matrices. These methods involve an extraction of the residues from the matrices with appropriate solvents. For some matrices, the sample extracts can be diluted and measured directly by IA without any cleanup. For other matrices, sample extracts are purified using liquid-liquid partitioning and/or solid phase extraction prior to measurement by IA. The methods determine the total residue of spinosad, which includes the active ingredients (spinosyns A and D) and several minor metabolites, including spinosyn B, spinosyn K, and N-demethylspinosyn D. The methods have validated limits of quantitation of 0.0001 microgram/mL in water, 0.05 microgram/g in sediment, and 0.010 microgram/g in crops, crop processed commodities, and animal tissues. This paper briefly summarizes the residue methodology and method validation data for spinosad in 34 food, feed, and environmental matrices.

Animals↗

The pathologic features and mechanism of traumatic dislocation of the hip.

The term traumatic dislocation of the hip encompasses a heterogenous group of dislocations, and more commonly, fracture-dislocations which have been subclassified. The current study describes the pathologic features in terms of an anatomic description of the displaced parts of the joint and what is known of the associated injured structures in each of the subtypes. The events that lead to traumatic dislocation of the hip are well documented, but understanding of the mechanics of the injury can only be presumptive.

Hip Dislocation↗

Brain stem stroke causing baroreflex failure and paroxysmal hypertension.

BACKGROUND: Paroxysmal neurogenic hypertension has been associated with a variety of diseases affecting the brain stem but has only rarely been reported after brain stem stroke. The mechanism is thought to involve increased sympathetic activity and baroreflex dysfunction. We undertook microneurographic recordings of muscle sympathetic nerve activity (MNSA) during beat-to-beat blood pressure (BP) monitoring to investigate this hypothesis. CASE DESCRIPTION: We investigated a 75-year-old woman who developed paroxysmal hypertension (BP 220/110 mm Hg) after a large left-sided medullary infarct. The paroxysms were triggered by changes in posture and were accompanied by tachycardia, diaphoresis, and headache. Serum catecholamines were substantially increased (norepinephrine level, 23.9 nmol/L 9 days after stroke; normal level, <3.8 nmol/L), and heart rate variability, measured by spectral analysis, was decreased in both low- and high-frequency domains (0.04 and 0.06 ms(2), respectively; normal level, 0.14+/-0.02 ms(2)). MNSA was increased in frequency (61 bursts per minute; normal level, 34+/-18 bursts per minute), and the burst amplitude was not inversely related to diastolic BP. BP and MNSA responses to cold pressor and isometric handgrip stimuli were intact. CONCLUSIONS: Extensive unilateral infarction of the brain stem in the region of the nucleus tractus solitarius may result in partial baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal hypertension.

Aged↗

Acromioclavicular dislocation. Conservative or surgical therapy.

A literature review was performed to clarify available information which influences decisions whether to advise a young adult patient to undergo surgery for a severely displaced acromioclavicular dislocation. Twenty-four papers were retrieved yielding 1172 patients of whom the mean followup for the 833 surgically treated patients was 43.7 months and not surgically treated was 60.4 months. Of the 24 papers, only five reported surgical and conservative outcomes; two of these papers used prospective randomized methodology and three used nonrandomized methodology. Fourteen papers reported surgical outcome only and five papers reported conservative outcome only. Overall, 88% of surgically treated patients and 87% of nonsurgically treated patients had a satisfactory outcome. Complications most commonly listed were (surgically treated versus nonsurgically treated): need for further surgery (59% versus 6%), infection (6% versus 1%), and deformity (3% versus 37%). Return to activity was no quicker with surgery. Pain was not any more common without surgery. Range of movement was more frequently normal or near normal without surgery (95% versus 86% if surgically treated) and so was strength (92% versus 87%). Meta-analysis of the four studies including data from surgical and conservative therapy showed on significant benefit from surgery. Power studies suggest that to show a statistically significant benefit from surgery, large studies would be required, which, given the relative incidence of these injuries, would probably be multicenter and therefore vulnerable to methodologic difficulties. There does not seem to be any reason to recommend an operative procedure to a patient with a Rockwood et al Type III injury based on the evidence currently available.

Acromioclavicular Joint↗

Protective gloves for use in high-risk patients: how much do they affect the dexterity of the surgeon?

Twenty-five orthopaedic surgeons underwent eight motor and sensory tests while using four different glove combinations and without gloves. As well as single and double latex, surgeons wore a simple Kevlar glove with latex inside and outside and then wore a Kevlar and Medak glove with latex inside and outside, as recommended by the manufacturers. The effect of learning with each sequence was neutralised by randomising the glove order. The time taken to complete each test was recorded and, where appropriate, error rates were noted. Simple sensory tests took progressively longer to perform so that using the thickest glove combination led to the completion times being doubled. Error rates increased significantly. Tests of stereognosis also took longer and use of the thickest glove combination caused these tests to take three times as long on average. Error rates again increased significantly. However, prolongation of motor tasks was less marked. We conclude that, armed with this quantitative analysis of sensitivity and dexterity impairment, surgeons can judge the relative difficulties that may be incurred as a result of wearing the gloves against the benefits that they offer in protection.

Clinical Competence↗

Orthopaedic surgery in hemophilic patients with human immunodeficiency virus.

Patients registered at the author's hemophilia center between 1982 and 1994 were studied to establish whether major orthopaedic surgical procedures accelerate the fall of CD4 lymphocyte counts of patients with hemophilia who are infected with the human immunodeficiency virus, and whether patients who had surgery had different rates of development of acquired immune deficiency syndrome or death when compared with patients who did not have surgery. The patients were divided into four groups: Group 1, 22 patients who were human immunodeficiency virus positive undergoing orthopaedic surgery; Group 2, 89 patients who were human immunodeficiency virus positive not undergoing orthopaedic surgery; Group 3, 18 patients who were human immunodeficiency virus negative undergoing orthopaedic surgery; and Group 4, 135 patients who were human immunodeficiency virus negative not undergoing orthopaedic surgery. There was no significant difference between the rates of decline of CD4 lymphocyte counts for patients who were human immunodeficiency virus positive who underwent surgery when compared with human immunodeficiency virus positive patients who did not undergo surgery, nor was there any significant difference between the two human immunodeficiency virus negative groups. There were no significant differences in the rate of development of acquired immune deficiency syndrome or mortality rates between patients who had surgery and those who did not.

Acquired Immunodeficiency Syndrome↗

Drosophila melanogaster contains both X-linked and autosomal homologues of the gene encoding calcineurin B.

A transcription unit was identified in the 43E polytene band region of the second chromosome of Drosophila melanogaster (Dm) whose putative translation product has 85% amino acid (aa) identity with the B subunit of the calcineurin protein (CnB) from humans. Unlike the previously described intronless Dm CnB gene homologue, which is located within the 4F band region of the X chromosome, the coding region of this second CnB is found to be interrupted by three introns. Conceptual translation of both Dm CnB genes predict proteins of identical size that are 98% identical in aa sequence. Northern blot analyses indicate that Dm pupae and adults express two different CnB-encoding transcripts that are differentially regulated.

Amino Acid Sequence↗

Hemophilic ankle arthropathy.

Ankle arthropathy remains a frequent source of disability in the hemophilic patient. Bleeding into the ankle most commonly commences in the second decade, and, once established as a target joint, progressive damage leads to significant pain, stiffness, and deformity affecting general mobility and leisure and occupational pursuits. Review of cohorts of hemophilic patients at the Royal Free Hospital has monitored this deterioration and there is no evidence that, despite improvements in medical treatment, the pattern of insidious decline in hindfoot function has changed during the past 4 decades. Based on these observations, a combined clinical and radiologic scoring system has been developed, incorporating ankle specific features, such as talar tilt, tibial osteophytes, and talar dome flattening, which give a better correlation than traditional systems with objective measures, such as treadmill walking. There is no substitution for prophylactic treatment in arresting ankle function decline, and surgical interventions are rare. However, the types of potential procedures are numerous and choices must be made according to the degree of disability and state of overall damage to the joint and adjacent soft tissues.

Ankle Joint↗