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1.
Science ; 350(6261): aad0210, 2015 Nov 06.
Article in English | MEDLINE | ID: mdl-26542576

ABSTRACT

Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.

2.
Science ; 350(6261): aad0459, 2015 Nov 06.
Article in English | MEDLINE | ID: mdl-26542579

ABSTRACT

The Mars Atmosphere and Volatile Evolution (MAVEN) mission, during the second of its Deep Dip campaigns, made comprehensive measurements of martian thermosphere and ionosphere composition, structure, and variability at altitudes down to ~130 kilometers in the subsolar region. This altitude range contains the diffusively separated upper atmosphere just above the well-mixed atmosphere, the layer of peak extreme ultraviolet heating and primary reservoir for atmospheric escape. In situ measurements of the upper atmosphere reveal previously unmeasured populations of neutral and charged particles, the homopause altitude at approximately 130 kilometers, and an unexpected level of variability both on an orbit-to-orbit basis and within individual orbits. These observations help constrain volatile escape processes controlled by thermosphere and ionosphere structure and variability.

3.
Clin Microbiol Infect ; 16(2): 186-9, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19673963

ABSTRACT

VIM-6, previously reported in two strains from Singapore recovered in 2000, was detected in 16 isolates collected in 2006 in India (12 isolates), Indonesia (two), Korea and the Philippines (one each). High genetic variability was observed among VIM-6-producing isolates (12 ribotypes and 11 pulsed-field gel electrophoresis types), but clones were observed in India and Indonesia; bla(VIM-6)-carrying integrons of 3.9 kb and 5 kb were detected, and two of five Indian hospitals yielded isolates with both integrons. These two integrons, bla(VIM-6) was located in the first position, followed by bla(OXA-10) and aacA4. The 5-kb integrons also harboured aadA1 and a 331-bp open reading frame encoding a putative efflux pump.


Subject(s)
Bacterial Typing Techniques , Polymorphism, Genetic , Pseudomonas Infections/epidemiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/classification , Pseudomonas aeruginosa/enzymology , beta-Lactamases/biosynthesis , Asia, Southeastern/epidemiology , DNA Fingerprinting , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Genes, Bacterial , Genotype , Humans , Integrons , Molecular Sequence Data , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Sequence Analysis, DNA
4.
Infect Control Hosp Epidemiol ; 29(9): 859-65, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18684094

ABSTRACT

OBJECTIVE: To describe an outbreak of invasive methicillin-resistant Staphylococcus aureus (MRSA) infection after percutaneous needle procedures (acupuncture and joint injection) performed by a single medical practitioner. SETTING: A medical practitioner's office and 4 hospitals in Perth, Western Australia. PATIENTS: Eight individuals who developed invasive MRSA infection after acupuncture or joint injection performed by the medical practitioner. METHODS: We performed a prospective and retrospective outbreak investigation, including MRSA colonization surveillance, environmental sampling for MRSA, and detailed molecular typing of MRSA isolates. We performed an infection control audit of the medical practitioner's premises and practices and administered MRSA decolonization therapy to the medical practitioner. RESULTS: Eight cases of invasive MRSA infection were identified. Seven cases occurred as a cluster in May 2004; another case (identified retrospectively) occurred approximately 15 months earlier in February 2003. The primary sites of infection were the neck, shoulder, lower back, and hip: 5 patients had septic arthritis and bursitis, and 3 had pyomyositis; 3 patients had bacteremia, including 1 patient with possible endocarditis. The medical practitioner was found to be colonized with the same MRSA clone [ST22-MRSA-IV (EMRSA-15)] at 2 time points: shortly after the first case of infection in March 2003 and again in May 2004. After the medical practitioner's premises and practices were audited and he himself received MRSA decolonization therapy, no further cases were identified. CONCLUSIONS: This outbreak most likely resulted from a breakdown in sterile technique during percutaneous needle procedures, resulting in the transmission of MRSA from the medical practitioner to the patients. This report demonstrates the importance of surveillance and molecular typing in the identification and control of outbreaks of MRSA infection.


Subject(s)
Acupuncture Therapy/adverse effects , Disease Outbreaks , Infectious Disease Transmission, Professional-to-Patient , Injections/adverse effects , Methicillin Resistance , Staphylococcal Infections , Staphylococcus aureus/drug effects , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/therapy , Female , Health Personnel , Humans , Infection Control/methods , Male , Middle Aged , Pyomyositis/therapy , Shoulder Joint/drug effects , Shoulder Joint/microbiology , Staphylococcal Infections/diagnosis , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/transmission , Staphylococcus aureus/classification , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Western Australia/epidemiology
5.
Antimicrob Agents Chemother ; 48(6): 2049-55, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15155198

ABSTRACT

Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 microg/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 microg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 microg/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 microg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.


Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Bacterial Infections/microbiology , Fluoroquinolones/pharmacology , Asia/epidemiology , Bacteria/genetics , Bacterial Infections/epidemiology , DNA Gyrase/genetics , DNA Topoisomerase IV/genetics , DNA, Bacterial/genetics , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Pacific Ocean , Population Surveillance , Reverse Transcriptase Polymerase Chain Reaction , South Africa/epidemiology
6.
Heredity (Edinb) ; 92(3): 242-8, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14666135

ABSTRACT

Pollinators often visit several flowers in sequence on plants with large floral displays. This foraging pattern is expected to influence the rate of self-fertilization in self-compatible taxa. To quantify the effects of daily floral display on pollinator movements and selfing, we experimentally manipulated flower number in four replicate (cloned) arrays of Mimulus ringens (Scrophulariaceae), each consisting of genets with unique combinations of homozygous marker genotypes. Four display classes (two, four, eight and 16 flowers) were present in each array. Pollinator visitation rate per flower and seed set per fruit were unaffected by display. However, flower number strongly influenced the frequency of within-plant pollinator movements, which increased from 13.8% of probes on two-flower displays to 77.6% of probes on 16-flower displays. The proportion of within-plant movements was significantly correlated with selfing (r = 0.993). The increase from 22.9% selfing on two-flower displays to 37.3% selfing on 16-flower displays reflects changes in the extent of geitonogamous self-pollination. We estimate that approximately half of all selfing on 16-flower displays resulted from geitonogamy. Selfing also varied dramatically among fruits within display classes. Nested ANOVA indicates that differences among flowers on two-flower ramets accounted for 45.4% of the variation in selfing, differences among genets accounted for 16.1% of the variation, and statistical and sampling error accounted for 38.5% of the variation. Differences among flowers within ramets may reflect the order of sequential floral probes on a display.


Subject(s)
Crosses, Genetic , Flowers/physiology , Mimulus/genetics , Mimulus/physiology , Pollen/physiology , Fruit/genetics , Fruit/growth & development , Genetic Variation , Phenotype , Reproduction/genetics , Reproduction/physiology
7.
Antimicrob Agents Chemother ; 47(12): 3989-93, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14638518

ABSTRACT

Enterobacter cloacae strains from hospitalized patients with a range of infections were collected by 17 laboratories in the Asia-Pacific region and South Africa. Isolates for which ceftriaxone MICs were above 1 microg/ml and/or ceftazidime MICs were above 2 microg/ml, as well as 46 strains for which ceftriaxone and/or ceftazidime MICs were at or below these values, were screened for levels of extended-spectrum beta-lactamase (ESBL) production through the use of broth microdilution for the detection of clavulanate enhancement of the activity of ceftriaxone, ceftazidime, and cefepime. Of the isolates examined, ceftriaxone and/or ceftazidime had elevated MICs for 44%, of which 36% were ESBL positive. ESBL-positive strains were commonly susceptible to piperacillin-tazobactam and more frequently resistant to several other antimicrobials studied. A cefepime MIC above 0.25 microg/ml had the highest sensitivity (100%) and specificity (74%) for predicting the presence of an ESBL.


Subject(s)
Enterobacter cloacae/drug effects , Enterobacter cloacae/enzymology , Enterobacteriaceae Infections/epidemiology , beta-Lactamases/metabolism , Asia/epidemiology , Cephalosporins/pharmacology , Clavulanic Acid/pharmacology , Cross Infection/epidemiology , Cross Infection/microbiology , Enterobacteriaceae Infections/microbiology , Enzyme Inhibitors/pharmacology , Humans , Microbial Sensitivity Tests , Pacific Islands/epidemiology , Penicillins/pharmacology , Phenotype , South Africa/epidemiology , beta-Lactamase Inhibitors
8.
Int J Antimicrob Agents ; 19(2): 125-32, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11850165

ABSTRACT

From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.


Subject(s)
Anti-Infective Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Fluoroquinolones , Haemophilus influenzae/drug effects , Indoles , Moraxella catarrhalis/drug effects , Quinolones , Respiratory Tract Diseases/microbiology , Streptococcus pneumoniae/drug effects , Asia , Haemophilus Infections/microbiology , Humans , Microbial Sensitivity Tests , Neisseriaceae Infections/microbiology , Pneumococcal Infections/microbiology , Population Surveillance , Prevalence , South Africa
9.
Endocr Pract ; 7(6): 454-8, 2001.
Article in English | MEDLINE | ID: mdl-11747282

ABSTRACT

OBJECTIVE: To determine whether weekly fructosamine testing at home by patients with type 2 diabetes, combined with therapeutic intervention when necessary on the basis of the results, would lead to improved glycemic control in comparison with usual care during a 3-month period. METHODS: In a prospective study, 25 patients with glycosylated hemoglobin (HbA1c) values above 8.0% were randomized into 2 groups. Both groups, a glucose-only testing group (14 patients with an initial mean HbA1c of 9.4 +/- 0.9%) and a combined glucose plus fructosamine testing group (11 patients with an initial mean HbA1c of 9.2 +/- 0.7%), received therapeutic intervention at the time of randomization. Both groups were instructed to perform blood glucose testing up to four times per day. The combined glucose plus fructosamine testing group was also instructed to perform weekly fructosamine testing in addition to the glucose testing and to telephone the investigator if their home-testing fructosamine value exceeded 350 mmol/L (approximately equivalent to HbA1c of 7.8%), whereupon the investigator implemented further interventions. Both groups returned in 3 months, at which time HbA1c testing was repeated in order to determine whether glycemic control had changed. RESULTS: The study results after 3 months showed that the HbA1c values in the combined glucose plus fructosamine testing group decreased from 9.2 +/- 0.7% to 8.0 +/- 0.5% (P<0.0001). In contrast, the HbA1c values in the glucose-only testing group declined from 9.4 +/- 0.9% to 9.1 +/- 1.3%, a difference that was not significant. CONCLUSION: In the 3 months after a change in therapy for type 2 diabetes, weekly home testing of fructosamine, combined with therapeutic interventions based on the results, led to a more rapid and significant improvement in glycemic control than did the usual regimen of glucose-only testing.


Subject(s)
Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 2/blood , Fructosamine/blood , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Prospective Studies
10.
Am J Med Genet ; 105(5): 404-5, 2001 Jul 08.
Article in English | MEDLINE | ID: mdl-11449390

ABSTRACT

A novel allele of the GXAlu tetranucleotide repeat in intron 27b of the neurofibromatosis 1 (NF1) gene has recently been reported to be present in 4.7% of autistic patients but not in controls. We have found the novel GXAlu allele absent in 204 patients from the South Carolina Autism Project and 200 controls. The autism population studied includes a significant number of patients with hypotonia, stereotyped behaviors, or postural, gait, and motor abnormalities similar to those seen in the patients previously reported to possess the novel GXAlu allele. This suggests that the novel (AAAT)6 GXAlu allele is not associated with autism.


Subject(s)
Alleles , Autistic Disorder/genetics , Genes, Neurofibromatosis 1/genetics , Introns/genetics , Microsatellite Repeats/genetics , Autistic Disorder/pathology , Base Sequence , Female , Gene Frequency , Humans , Male
11.
J Neurochem ; 77(3): 796-803, 2001 May.
Article in English | MEDLINE | ID: mdl-11331408

ABSTRACT

Both (Li(+)) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li(+) reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/kg, i.p. for 30 days). Like Li(+), VPA treatment significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Thus, both mood stabilizers, Li(+) and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.


Subject(s)
Antimanic Agents/pharmacology , Arachidonic Acid/metabolism , Brain/drug effects , Brain/metabolism , Phospholipids/metabolism , Valproic Acid/pharmacology , Acyl Coenzyme A/analysis , Animals , Antimanic Agents/administration & dosage , Arachidonic Acid/administration & dosage , Brain Chemistry , Fatty Acids/blood , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/blood , Gene Expression/drug effects , Kinetics , Lithium/pharmacology , Male , Phospholipases A/analysis , Phospholipases A/genetics , Rats , Rats, Inbred F344 , Tritium , Valproic Acid/administration & dosage , Valproic Acid/blood
12.
Pathology ; 33(1): 53-60, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11280610

ABSTRACT

The in vitro activity of cefepime was compared to that of a range of other broad-spectrum agents, using a gradient diffusion MIC method, against 995 recent clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, other nonfermentative gram-negative bacilli, staphylococci (except oxacillin-resistant Staphylococcus aureus), streptococci, enterococci, and aerobic gram-positive bacilli. Cefepime had excellent activity against Enterobacteriaceae, including eight presumptive extended-spectrum beta-lactamase producers and 33 stably derepressed mutants of natural cephalosporinases. Activity against Pseudomonas aeruginosa was similar to ceftazidime and superior to cefpirome. Its activity against gram-positive cocci was also good, being more active against staphylococci and only slightly less active against streptococci than ceftriaxone. Cefepime maintained activity against bacteria resistant to aminoglycosides and ciprofloxacin. Enterococci, Bacillus species, Burkholderia cepacia and Stenotrophomonas maltophilia were predicably resistant. Cefepime has a spectrum of activity almost as broad as that of the carbapenems.


Subject(s)
Cephalosporins/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Cefepime , Drug Resistance, Microbial , In Vitro Techniques
13.
Antimicrob Agents Chemother ; 44(11): 3224-8, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11036060

ABSTRACT

Enterococcus faecalis strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 microgram/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (vanA, vanB, vanC, vanD, and vanE). We have isolated and sequenced a novel putative vancomycin resistance locus (designated vanG), which contains seven open reading frames, from this strain. These are organized differently from those of all the other enterococcal van loci, and, furthermore, the individual vanG gene products exhibit less than 50% amino acid sequence identity to other van gene products.


Subject(s)
Bacterial Proteins/genetics , Drug Resistance, Microbial , Enterococcus faecalis/genetics , Peptide Synthases , Vancomycin Resistance/genetics , Amino Acid Sequence , Carbon-Oxygen Ligases/genetics , Enterococcus faecalis/drug effects , Molecular Sequence Data , Open Reading Frames , Sequence Homology, Amino Acid
14.
Microb Drug Resist ; 6(3): 223-9, 2000.
Article in English | MEDLINE | ID: mdl-11144422

ABSTRACT

Australia has a long association methicillin-resistant Staphylococcus aureus (MRSA). Its unique geographic and demographic features have led to the emergence and spread of three types of MRSA over 35 years. Classical multiresistant hospital-acquired MRSA were first noted in Australia in 1965. By the end of the 1970s, strains of this type of MRSA were well established in the complex tertiary care hospitals in the capital cities on the eastern seaboard of mainland Australia. Characterized by resistance to beta-lactams, erythromycin, tetracycline, gentamicin, and trimethoprim-sulfamethoxazole, these strains have persisted and diversified genetically and have acquired a variety of new resistances. They have proven pathogenicity and are a prominent cause of hospital infection in the endemic institutions. More recently they have become endemic in some central state tertiary care hospitals. Community-acquired strains of MRSA first appeared in the north of Western Australia in the mid-1980s. Strains have subsequently appeared in the south of the state and in the two adjacent central states, and are more frequently isolated from Aboriginal patients. Although harboring few or no additional resistances apart from resistance to beta-lactams initially, these strains are also accumulating additional resistances. A different variety of community-acquired MRSA has recently been noted in eastern Australia. It has a similar antibiogram to the western strains, but an entirely different epidemiology, resembling that currently being experienced in parts of New Zealand, and associated with patients of south Pacific island origin.


Subject(s)
Evolution, Molecular , Methicillin Resistance , Staphylococcal Infections/epidemiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Australia/epidemiology , Humans , Prevalence , Staphylococcal Infections/microbiology
15.
Neurochem Res ; 24(7): 833-41, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10403622

ABSTRACT

Our laboratory has reported that pentobarbital-induced anesthesia reduced the incorporation of intravenously injected radiolabeled palmitic acid into brain phospholipids. To determine if this decrease reflected a pentobarbital-induced decrease in palmitate turnover in phospholipids, we applied our method and model to study net flux and turnover of palmitate in brain phospholipids (1). Awake, light and deep pentobarbital (25-70 mg/kg, iv) anesthetized rats were infused with [9,10-3H]palmitate over a 5 min period. Brain electrical activity was monitored by electroencephalography. An isoelectric electroencephalogram characterized deep pentobarbital anesthesia. Net incorporation rates (J(FA,i)) and turnover rates (Fi) of palmitate were calculated. J(FA,i) for palmitate incorporated into phospholipids was dramatically reduced by pentobarbital treatment in a dose-dependent manner, by 70% and 90% respectively for lightly and deeply anesthetized animals, compared with awake controls. Turnover rates for palmitate in total phospholipid and individual phospholipid classes were decreased by nearly 70% and 90% for lightly and deeply anesthetized animals, respectively. Thus, pentobarbital decreases, in a dose-dependent manner, the turnover of palmitate in brain phospholipids. This suggests that palmitate turnover is closely coupled to brain functional activity.


Subject(s)
Adjuvants, Anesthesia/pharmacology , Brain/metabolism , Palmitates/metabolism , Pentobarbital/pharmacology , Phospholipids/metabolism , Animals , Electroencephalography , Male , Models, Biological , Rats , Rats, Inbred F344
16.
Neurochem Res ; 24(3): 399-406, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10215514

ABSTRACT

Using a method and model developed in our laboratory to quantitatively study brain phospholipid metabolism, in vivo rates of incorporation and turnover of docosahexaenoic acid in brain phospholipids were measured in awake rats. The results suggest that docosahexaenoate incorporation and turnover in brain phospholipids are more rapid than previously assumed and that this rapid turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA pool due to release and recycling of unlabeled fatty acid from phospholipid metabolism. Fractional turnover rates for docosahexaenoate within phosphatidylinositol, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h(-1), respectively. Chronic lithium treatment, at a brain level considered to be therapeutic in humans (0.6 micromol.g(-1)), had no effect on turnover of docosahexaenoic acid in individual brain phospholipids. Consistent with previous studies from our laboratory that chronic lithium decreased the turnover of arachidonic acid within brain phospholipids by up to 80% and attenuated brain phospholipase A2 activity, the lack of effect of lithium on docosahexaenoate recycling and turnover suggests that a target for lithium's action is an arachidonic acid-selective phospholipase A2.


Subject(s)
Brain/drug effects , Brain/metabolism , Docosahexaenoic Acids/metabolism , Lithium/pharmacology , Acyl Coenzyme A/metabolism , Animals , Arachidonic Acid/metabolism , Docosahexaenoic Acids/blood , Fatty Acids, Nonesterified/metabolism , Lipid Metabolism , Lithium/administration & dosage , Male , Phospholipases A/metabolism , Phospholipases A2 , Phospholipids/metabolism , Rats , Rats, Inbred F344
17.
Med J Aust ; 170(4): 152-5, 1999 Feb 15.
Article in English | MEDLINE | ID: mdl-10078178

ABSTRACT

OBJECTIVE: To examine the prevalence of resistance in Streptococcus pneumoniae to key antimicrobials in Australia during 1997. DESIGN: Prospective, Australia-wide, laboratory-based survey. SETTING: 11 microbiology laboratories from seven Australian States and Territories (five private laboratories and six public hospital laboratories) between March and November 1997. STRAINS: Up to 100 consecutive, clinically significant strains of S. pneumoniae isolated by each laboratory. MAIN OUTCOME MEASURES: Susceptibility to penicillin, amoxycillin-clavulanate, cefaclor, ceftriaxone, erythromycin, tetracycline, and sulfamethoxazole-trimethoprim (cotrimoxazole), measured by a gradient diffusion, minimum inhibitory concentration technique. RESULTS: Of 1020 strains, 16.8% had intermediate susceptibility to penicillin and 8.6% were resistant. Rates of resistance to other drugs were: amoxycillin-clavulanate, 3.1%; cefaclor, 21.4%; ceftriaxone, 3.1%; erythromycin, 15.6%; tetracycline, 15.7%; and cotrimoxazole, 33.4%. Non-invasive isolates harboured more resistances than invasive isolates, and resistance was more prevalent in isolates from children under two years. Multiple resistance was also common, with 21.2% of strains resistant to two or more classes of drug, and 9.3% of non-invasive and 1.7% of invasive isolates resistant to four classes. There were no obvious differences in resistance rates between private and public hospital laboratories. CONCLUSIONS: Rates of antimicrobial resistance are rising rapidly in S. pneumoniae in Australia. Recommendations for empiric treatment of invasive and respiratory infection need to take account of these changes.


Subject(s)
Drug Resistance, Microbial , Pneumococcal Infections/drug therapy , Streptococcus pneumoniae/drug effects , Australia , Humans , Laboratories , Meningitis, Pneumococcal/drug therapy , Microbial Sensitivity Tests , Pneumonia, Pneumococcal/drug therapy , Prospective Studies , Streptococcus pneumoniae/isolation & purification
18.
Brain Res ; 807(1-2): 177-81, 1998 Oct 05.
Article in English | MEDLINE | ID: mdl-9757030

ABSTRACT

Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A2, that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input.


Subject(s)
Brain/physiology , Fatty Acids/metabolism , Parkinson Disease, Secondary/physiopathology , Signal Transduction/physiology , Animals , Basal Ganglia/metabolism , Brain/metabolism , Brain Mapping , Caudate Nucleus/metabolism , Cerebral Cortex/metabolism , Disease Models, Animal , Functional Laterality/physiology , Globus Pallidus/metabolism , Male , Parkinson Disease, Secondary/metabolism , Phospholipases A/metabolism , Phospholipases A2 , Putamen/metabolism , Rats , Rats, Sprague-Dawley
19.
J Clin Microbiol ; 36(8): 2187-90, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9665988

ABSTRACT

Enterococci with resistance to glycopeptides have recently emerged in Australia. We developed multiplex PCR assays for vanA, vanB, vanC1, and vanC2 or vanC3 in order to examine the genetic basis for vancomycin resistance in Australian isolates of vancomycin-resistant Enterococcus faecium and E. faecalis (VRE). The predominant genotype from human clinical E. faecium isolates was vanB. The PCR van genotype was consistent with the resistance phenotype in all but six cases. One vanA E. faecalis isolate had a VanB phenotype, one vanB E. faecium isolate had a VanA phenotype, and four E. faecalis isolates were consistently negative for vanA, vanB, vanC1, and vanC2 or vanC3, even though they exhibited a VanB phenotype. These four isolates were subsequently examined for the presence of vanD by published methods and were found to be negative. No vancomycin-susceptible strains produced a PCR product. On the basis of our findings the epidemiology of VRE in Australia appears to be different from that in either the United States or Europe. Our multiplex PCR assays gave a rapid and accurate method for determining the genotype and confirming the identification of glycopeptide-resistant enterococci. Rapid and accurate methods are essential, because laboratory-based surveillance is critical in programs for the detection, control, and prevention of the transmission of glycopeptide-resistant enterococci.


Subject(s)
Anti-Bacterial Agents/pharmacology , Enterococcus/drug effects , Gram-Positive Bacterial Infections/microbiology , Vancomycin/pharmacology , Australia/epidemiology , Bacterial Proteins/genetics , Bacterial Typing Techniques , Carbon-Oxygen Ligases/genetics , Drug Resistance, Microbial/genetics , Enterococcus/classification , Enterococcus/genetics , Enterococcus/isolation & purification , Enterococcus faecalis/drug effects , Enterococcus faecalis/genetics , Enterococcus faecalis/isolation & purification , Enterococcus faecium/drug effects , Enterococcus faecium/genetics , Enterococcus faecium/isolation & purification , Genes, Bacterial , Genotype , Gram-Positive Bacterial Infections/epidemiology , Humans , Phenotype , Polymerase Chain Reaction/methods , Teicoplanin/pharmacology
20.
Pediatr Radiol ; 28(4): 237-40, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9545478

ABSTRACT

BACKGROUND: Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. OBJECTIVE: The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. MATERIALS AND METHODS: Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. RESULTS: All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. CONCLUSION: MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow.


Subject(s)
Bone Marrow/pathology , Gaucher Disease/diagnosis , Magnetic Resonance Imaging , Adult , Bone Marrow/drug effects , Child , Child, Preschool , Gaucher Disease/drug therapy , Glucosylceramidase/therapeutic use , Humans , Infant
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