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Biomedical subjects

M J Phillips

Publications and source records attributed to M J Phillips.

At least 19 recordsLinked to original sources
PubMed2005

Existing delays following the presentation of ruptured abdominal aortic aneurysm allow sufficient time to assess patients for endovascular repair.

OBJECTIVES: The greatest benefit of endovascular AAA repair (EVAR) may be in the management of rupture (RAAA). However, the detailed anatomical assessment required for EVAR has lead to concerns of surgical delay and death during cross-sectional imaging. In this study, we prospectively assessed patients with RAAA and correlated time of hospital arrival with time of surgery or death to ascertain whether these concerns are justified. METHODS: All patients presenting with RAAA between October 2000 and December 2002 were included. The hospital arrival time, onset of surgery or time of death, were recorded, as were demographic and physiological parameters. RESULTS: One hundred consecutive patients were studied, median age 75 years (range 54-94). Seventy-nine patients underwent attempted conventional surgical repair and 21 were palliated. The median delay from arrival to operation was 159 min (range 16-1450 min). Mortality in the surgical group was not affected by the length of delay (p = 1.0) or by CT scanning (p = 0.34). The median time from arrival to death in the non-surgical group was 435 min (15 min-6 days). CONCLUSIONS: Most patients who present with ruptured AAA experience a significant delay prior to surgery. This study suggests it is safe to assess the majority of RAAA patients for EVAR.

Aged↗
PubMed2004

Four new avian mitochondrial genomes help get to basic evolutionary questions in the late cretaceous.

Good phylogenetic trees are required to test hypotheses about evolutionary processes. We report four new avian mitochondrial genomes, which together with an improved method of phylogenetic analysis for vertebrate mt genomes give results for three questions in avian evolution. The new mt genomes are: magpie goose (Anseranas semipalmata), an owl (morepork, Ninox novaeseelandiae); a basal passerine (rifleman, or New Zealand wren, Acanthisitta chloris); and a parrot (kakapo or owl-parrot, Strigops habroptilus). The magpie goose provides an important new calibration point for avian evolution because the well-studied Presbyornis fossils are on the lineage to ducks and geese, after the separation of the magpie goose. We find, as with other animal mitochondrial genomes, that RY-coding is helpful in adjusting for biases between pyrimidines and between purines. When RY-coding is used at third positions of the codon, the root occurs between paleognath and neognath birds (as expected from morphological and nuclear data). In addition, passerines form a relatively old group in Neoaves, and many modern avian lineages diverged during the Cretaceous. Although many aspects of the avian tree are stable, additional taxon sampling is required.

Animals↗
PubMed2003

Predicting outcome in ruptured abdominal aortic aneurysm: a prospective study of 100 consecutive cases.

OBJECTIVES: Case selection for surgery in patients presenting with ruptured abdominal aortic aneurysms (RAAA) is often difficult. A previous retrospective review identified five pre-operative risk factors associated with mortality [J Vasc Surg 23 (1996) 123]. In this study we aimed to identify whether these criteria could be usefully applied prospectively in patients presenting with RAAA. METHODS: All patients presenting with RAAA from October 2000 to December 2002 were included. The criteria were recorded with the time they were available and the time surgery commenced. The decision to operate was made on clinical grounds and no patient was refused surgery on the basis of these criteria. RESULTS: One hundred consecutive patients were studied, median age 75 (range 54-94). The operative mortality was 32.9% (26/79 patients). Surgical mortality increased with the number of positive criteria and was 8% (2/24), 24% (7/29), 55% (11/20) and 100% (6/6) for scores, 0, 1, 2 and > or =3, respectively. Age and conscious level were available in every patient. However, an ECG, haemoglobin and creatinine results were only available in 94, 81, and 69%, respectively. CONCLUSIONS: The scoring system accurately predicted operative mortality. The score was available in the majority of cases and may help the surgeon give informed consent to patients and relatives prior to surgical intervention.

Aged↗
PubMed2003

Synthesis and characterization of nano-biomaterials with potential osteological applications.

The manufacture of high-surface area, un-agglomerated nano-sized (1-100 nm) bioceramic particles are of interest for many applications including injectable/controlled setting bone cements, high strength porous/non-porous synthetic bone grafts, and the reinforcing phase in nano-composites that attempt to mimic the complex structure and superior mechanical properties of bone. In the present study, we report on the manufacture of nano-particle hydroxyapatite powders by several wet chemical methods, which incorporate a freeze-drying step. In particular, it was found that the emulsion-based syntheses yielded powders with high surface areas and small primary particle sizes. Freeze drying rather than oven drying of powders prepared by conventional wet chemical synthesis yielded a nano-sized powder with a comparatively higher surface area of 113 m(2)/g. All powders were calcined in air in a furnace at 900 degrees C to investigate the effects of synthesis method on phase purity and surface area. The materials were characterized by a range of analytical methods including Fourier-transform infrared spectroscopy employing the photo acoustic (PAS-FTIR) sampling technique, BET surface area analysis, X-ray powder diffraction (XRD), and the particles were examined using a transmission electron microscope (TEM).

Journal Article↗
PubMed2002

C-reactive protein is elevated in symptomatic compared with asymptomatic patients with carotid artery disease.

OBJECTIVES: to investigate the level of inflammatory markers between symptomatic and asymptomatic carotid stenosis patients. DESIGN: cross-sectional study. MATERIALS AND METHODS: a prospective study of 137 consecutive patients, admitted electively for carotid endarterectomy during 1997-2000, was conducted. 125 patients had cerebrovascular symptoms: either stroke (neurological deficit >24 h), Transient ischaemic attack (neurological deficit<24 h) or amaurosis fugax. Twelve patients were asymptomatic. A medical history and a fasting venous blood sample were taken from each patient around 6 weeks before surgery. The plasma concentrations of cholesterol and of inflammatory markers; (high sensitivity C-reactive protein (hs-CRP), sICAM-1, sVCAM-1, sE-selectin) were determined. RESULTS: the concentration of hs-CRP in the symptomatic group (3.9 mg/L) was significantly higher than in the asymptomatic group (2.1 mg/L; p = 0.04). These concentrations were within normal range (<10 mg/L). sICAM-1, sVCAM-1, sE-selectin and total cholesterol concentrations were not different between the two groups. CONCLUSION: plasma hs-CRP was elevated in symptomatic compared to asymptomatic patients with carotid artery disease. High sensitivity C-reactive protein has been shown to be of prognostic value in a number of cardiovascular conditions and this study suggests it may be of value to identify patient at high risk of developing neurological deficits.

Aged↗
PubMed2001

Serotonin, testosterone and alcohol in the etiology of domestic violence.

In a previous study we administered the panicogenic agent sodium lactate to a select group of perpetrators of domestic violence and comparison groups. Results of that study showed that perpetrators exhibited exaggerated lactate-induced fear, panic and rage. In this current study, we compared the cerebral spinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) and testosterone obtained from perpetrators of domestic violence and a group of healthy comparison subjects. All subjects were assessed for DSM-III-R diagnoses. Perpetrators with alcohol dependence (DV-ALC) (n=13), perpetrators without alcohol dependence (DV-NALC) (n=10) and healthy comparison subjects (HCS) (n=20) were clinically assessed using the Spielberger Trait Anxiety, Brown-Goodwin Aggression Scale, Buss Durkee Hostility Inventory and Straus Conflict Tactics. Following an overnight fast and bed rest, subjects received a lumbar puncture to obtain CSF concentrations of 5-HIAA and testosterone. Perpetrators scored significantly higher on measures of aggression than HCS. DV-NALC had significantly lower concentrations of CSF 5-HIAA and higher Straus Conflict Tactics (CT) physical violence scores than DV-ALC and HCS. DV-ALC had significantly higher concentrations of CSF testosterone than DV-NALC. DV-ALC also had significantly higher Straus CT physical violence scores than HCS. DV-NALC and DV-ALC differed on 5-HIAA concentrations, testosterone concentrations, Straus CT physical violence scores and alcohol dependence. These results suggest that DV-NALC and DV-ALC groups could have different biological mechanisms mediating domestic violence.

Adult↗
PubMed2001

Mitochondrial genomes of a bandicoot and a brushtail possum confirm the monophyly of australidelphian marsupials.

Recent molecular analyses suggest that the position of bandicoots is the major difficulty in determining the root of the tree of extant marsupials. To resolve this, we analyse mitochondrial genome sequences of a bandicoot (Isoodon macrourus) and a brushtail possum (Trichosurus vulpecula) together with the previously available marsupial mitochondrial genomes, the Virginia opossum (Didelphis virginiana) and the wallaroo (Macropus robustus). Analyses of mitochondrial protein-coding and RNA genes strongly support the bandicoot as sister to the wallaroo and the brushtail possum. This result, combined with other recent molecular analyses, confirms the monophyly of Australidelphia (Australasian marsupials plus Dromiciops from South America). Further, RY coding was found to nullify AGCT coding nucleotide composition bias.

Animals↗
PubMed2001

Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis.

Mutations in the sister of P-glycoprotein (Spgp) or bile salt export pump (BSEP) are associated with Progressive Familial Intrahepatic Cholestasis (PFIC2). Spgp is predominantly expressed in the canalicular membranes of liver. Consistent with in vitro evidence demonstrating the involvement of Spgp in bile salt transport, PFIC2 patients secrete less than 1% of biliary bile salts compared with normal infants. The disease rapidly progresses to hepatic failure requiring liver transplantation before adolescence. In this study, we show that the knockout of spgp gene in mice results in intrahepatic cholestasis, but with significantly less severity than PFIC2 in humans. Some unexpected characteristics are observed. Notably, although the secretion of cholic acid in mutant mice is greatly reduced (6% of wild-type), total bile salt output in mutant mice is about 30% of wild-type. Also, secretion of an unexpectedly large amount of tetra-hydroxylated bile acids (not detected in wild-type) is observed. These results suggest that hydroxylation and an alternative canalicular transport mechanism for bile acids compensate for the absence of Spgp function and protect the mutant mice from severe cholestatic damage. In addition, the spgp(-/-) mice display a significant increase in the secretion of cholesterol and phospholipids into the bile. This latter observation in spgp(-/-) mice suggests that intrahepatic, rather than intracanalicular, bile salts are the major driving force for the biliary lipid secretion. The spgp(-/-) mice thus provide a unique model for gaining new insights into therapeutic intervention for intrahepatic cholestasis and understanding mechanisms associated with lipid homeostasis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Estimation from censored data with incomplete information.

Phillips and Sweeting [J. R. Statist. Soc. B 58 (1996) 775-783.] considered estimation of the parameter of the exponential distribution with censored failure time data when there is incomplete knowledge of the censoring times. It was shown that, under particular models for the censoring mechanism and censoring errors, it will usually be safe to ignore such errors provided they are not expected to be too large. A flexible model is introduced which includes the extreme cases of no censoring errors and no information on the censoring values. The effect of alternative assumptions about knowledge of the censoring values on the estimation of failure rate is investigated.

Aviation↗
PubMed2001

A prospective, randomized, multicenter comparative study of clinafloxacin versus a ceftriaxone-based regimen in the treatment of hospitalized patients with community-acquired pneumonia.

In an open-label, phase 3, randomized, multicenter study, clinafloxacin (200 mg/d) was compared to ceftriaxone (2 g/d; with or without erythromycin) in 527 patients with acute community-acquired bacterial pneumonia (CAP). Primary efficacy parameters were clinical cure rate and microbiologic eradication rates (by pathogen and by patient) determined 5-9 d post-therapy (test of cure; TOC). Clinical cure rates at TOC for the 2 treatment groups were equivalent in the intention-to-treat (clinafloxacin 79.3, ceftriaxone 78.6%), clinically evaluable (clinafloxacin 88.1, ceftriaxone 85.0%), modified intention-to-treat (clinafloxacin 82.6, ceftriaxone 86.9%) and microbiologically evaluable populations (clinafloxacin 86.2, ceftriaxone 86.2%). Microbiologic eradication rates were similar in the 2 treatment groups. Both drugs were tolerated. Treatment of hospitalized CAP patients with clinafloxacin is a reasonable choice, especially when a resistant pathogen is anticipated.

Adolescent↗
PubMed2001

Revision total knee arthroplasty: planning, controversies, and management--infection.

Routine blood work that includes ESR, CRP, and glucose levels, and plain radiographs and knee aspirations are obtained from our patients who have clinical suspicion of infection. If the culture result is positive and blood tests suggest infection, the surgical plan is a two-stage revision with an interval period of intravenous antibiotic administration. Risk factors are identified, and the patient's condition optimized. An infectious disease consultant is also involved in the treatment care plan and advises the patient about the best antibiotic, management of proper antibiotic levels, and home care. If culture results are negative, cultures are repeated every week for 3 to 4 weeks after the patient stops taking antibiotics. If the cultures yield positive results, a two-stage revision protocol is initiated. In patients who have 3 to 4 negative culture results, normal blood tests and radiographs, and no history of any immunocompromised state, such as diabetes or rheumatoid arthritis, diagnoses such as polyethylene wear or synovitis can be considered. If patients have any involved risk factor or blood tests, equivocal or suggestive, isotope scintigraphy is requested. We examine tissue in patients with positive scans and equivocal blood test results with clinical suspicion of infection. We prefer an open arthrotomy, which allows us to take multiple specimens for frozen section, assess fixation of the implant, and look for any other signs of infection. If the frozen section reveals more than 10 PMNLs per high-power field, we proceed to stage 1 revision after obtaining intraoperative cultures. If an organism grows in the cultures, stage 2 protocol is initiated. If no cultures are obtained at 7 to 10 days of incubation, we may consider earlier stage 2 revision at 4 to 6 weeks (Fig. 1). In patients in whom the frozen section reveals less than 5 PMNLs per high-power field, component fixation should be assessed, and if they are loose, revision of the knee should be initiated. As with a septic revision, use of antibiotic-impregnated cement can be considered for fixation. If the components are well fixed, a polyethylene tibial tray is exchanged. In either circumstance, intraoperative cultures should be obtained, and if they yield positive results, antibiotics should be continued for 6 to 12 weeks.

Adult↗
PubMed2000

Lactate-induced rage and panic in a select group of subjects who perpetrate acts of domestic violence.

BACKGROUND: Perpetrators of domestic violence frequently report symptoms of autonomic arousal and a sense of fear and/or loss of control at the time of the violence. Since many of these symptoms are also associated with panic attacks, we hypothesized that perpetrators of domestic violence and patients with panic attacks may share similar exaggerated fear-related behaviors. To test this hypothesis, we employed the panicogenic agent sodium lactate to examine the response of perpetrators to anxiety fear induced by a chemical agent. METHODS: Using a double-blind, placebo-controlled design, we infused 0.5 mol/L sodium lactate or placebo over 20 min on separate days to a select group of subjects who perpetrate acts of domestic violence and two nonviolent comparison groups. We compared their behavioral, neuroendocrine, and physiologic responses. RESULTS: Lactate administration elicited intense emotional responses in the perpetrators of domestic violence. Perpetrators evidenced more lactate-induced rage and panic and showed greater changes in speech, breathing, and motor activity than did nonviolent control subjects. There were no significant differences between the groups for any neuroendocrine or physiologic measure. CONCLUSIONS: These results are consistent with our hypothesis that some perpetrators of domestic violence have exaggerated fear-related behavioral responses.

Adult↗
PubMed2000

Hepatitis C virus (HCV) infection and cryoglobulinemia: analysis of whole blood and plasma HCV-RNA concentrations and correlation with liver histology.

The influence of cryoprecipitate (CP) on liver histology and peripheral titers of hepatitis C virus (HCV) RNA was evaluated for 115 patients with chronic hepatitis. Fifty-four patients had measurable CP levels whereas 61 did not. Assessment of liver biopsies for grade of fibrosis revealed that patients with CP had increased fibrosis (P <.001) and incidence of cirrhosis (P =.001) compared with those without CP. In contrast, there was not a significant difference in the inflammatory activity score between the 2 groups. HCV RNA in whole blood (WB) and plasma (Pl) was evaluated in patients with or without CP by end-point-limiting dilution titer. Among patients with CP, WB titers were significantly higher than Pl titers (P <.001); however, there was no difference in WB or Pl titers in patients without CP (P =.068). Histological activity and fibrosis scores of patients from either group were compared with peripheral viral titers of WB and Pl, percentage of CP, rheumatoid factor (RF) titer, and serum alanine transaminase (ALT). There were significant correlations between the amount of fibrosis and the percentage of CP and rheumatoid factor titer, yet neither of the latter parameters was correlated with inflammatory activity. These data suggest that patients with CP and chronic hepatitis owing to HCV are more likely to have progressive disease than patients without CP. Furthermore, the presence of CP in patients infected with HCV appears to influence the amount of virus detected in patient Pl, suggesting that WB assays may be more reliable for HCV-RNA quantitation in patients with CP.

Adult↗
PubMed2000

Molecular and functional analysis of the human prothrombinase gene (HFGL2) and its role in viral hepatitis.

In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.

Adolescent↗
PubMed2000

Severe hepatic Wilson's disease in preschool-aged children.

A 3-year-old girl presented with hemolytic anemia, hepatosplenomegaly, ascites, and evidence of decompensated chronic liver disease. Genotypic DNA analysis revealed that the patient was homozygous for a splice site mutation now designated IVS4-1:G>C, expected to destroy completely the functional gene product of ATP7B, the gene responsible for Wilson's disease. We suggest that this severe mutation caused very early liver disease. Wilson's disease should be considered in the differential diagnosis of established liver disease in the preschool-aged child.

Adenosine Triphosphatases↗
PubMed2000

Hypertonic inhibition of exocytosis in neutrophils: central role for osmotic actin skeleton remodeling.

Hypertonicity suppresses neutrophil functions by unknown mechanisms. We investigated whether osmotically induced cytoskeletal changes might be related to the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the mobilization of all four granule types induced by diverse stimuli, suggesting that it blocks the process of exocytosis itself rather than individual signaling pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin, induced the formation of a submembranous F-actin ring, and abolished depolymerization that normally follows agonist-induced actin assembly. Several observations suggest a causal relationship between actin polymerization and inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the osmotic actin response and restored exocytosis, and 3) actin polymerization induced by jasplakinolide inhibited exocytosis under isotonic conditions. The shrinkage-induced tyrosine phosphorylation and the activation of the Na(+)/H(+) exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation and actin polymerization are independent phenomena. Thus cytoskeletal remodeling appears to be a key component in the neutrophil-suppressive, anti-inflammatory effects of hypertonicity.

Actins↗