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Biomedical subjects

S T Chambers

Publications and source records attributed to S T Chambers.

At least 73 records · Page 4Linked to original sources
PubMed1994

Demonstration of herpes simplex type 2 in the cerebrospinal fluid of two patients with recurrent lymphocytic meningitis.

AIMS: To investigate the aetiology of recurrent lymphocytic meningitis in two patients with a past history of recurrent genital herpes simplex infection. METHODS: Cerebrospinal fluid (CSF) obtained from two patients during an acute recurrent episode of lymphocytic meningitis was analysed by polymerase chain reaction for the presence of herpes simplex DNA. RESULTS: In both patients, the acute CSF was positive for herpes simplex type 2 DNA. A second CSF obtained 2 weeks later from one patient was negative for HSV DNA: CONCLUSIONS: Herpes simplex type 2 may be an important cause of recurrent lymphocytic meningitis. Available evidence suggests that viral DNA is cleared from the CSF between episodes and supports active viral replication as the pathological mechanism. The recurrences of meningitis need not coincide with clinical recurrences of genital herpes.

Adult↗
PubMed1994

Glycine betaine and proline betaine in human blood and urine.

In healthy human subjects, glycine betaine concentrations in the blood plasma are normally between 20 and 60 mumol/l, adult males tending to have higher concentrations than females. Proline betaine concentrations are more variable, ranging from undetectable to about 50 mumol/l. Both betaines are present in urine. Whereas the urinary excretion of proline betaine reflects plasma concentrations, with high clearance rates, there is no correlation between plasma and urine glycine betaine concentrations. The apparent clearance rates are low (usually less than 5%). The proline betaine content of human kidney tissue is less than 0.1% of the glycine betaine content, and this is true also of rabbit tissue despite high concentrations of both betaines in rabbit circulation and urine. These data suggest that glycine betaine, but not proline betaine, is important in human and other mammalian biochemistry.

Adolescent↗
PubMed1994

Relationship between osmoprotection and the structure and intracellular accumulation of betaines by Escherichia coli.

Naturally occurring betaines, especially glycine betaine and proline betaine, were accumulated by Escherichia coli from urine. In synthetic hyperosmotic medium, with an homologous series of added betaines, (CH3)3N(+)-(CH2)n-COO-, osmoprotective activity and intracellular accumulation decreased monotonically as n increased from 1 to 5. In contrast, alpha-substituted glycine betaines were accumulated in a similar manner to glycine betaine, but with different osmoprotective activities. Arsenobetaine, with a quaternary arsonium group, was also accumulated but amino acids which can become negatively charged in a chemically basic environment were not.

Betaine↗
PubMed1994

Bacterial killing by neutrophils in hypertonic environments.

The effects of hypertonic sodium chloride and urea solutions on the phagocytosis and killing of Escherichia coli by neutrophils were examined. Neutrophil function was progressively inhibited by increasing osmolarity, with sodium chloride more inhibitory than urea. However, neutrophils killed at 25% of normal rates in 500 mosmol/L NaCl, and in 300 mosmol/L NaCl with 800 mosmol/L urea. These concentrations would rarely be exceeded in the human urinary tract. Inhibition of neutrophil superoxide production and degranulation was similar to that observed with phagocytosis and killing. Neutrophils also phagocytosed and killed E. coli in isotonic and hypertonic urine, but no improvement in function attributable to the uptake of urinary osmoprotectants was evident. It is concluded that physiologic levels of sodium chloride and urea will slow, but not prevent, neutrophil activity at a hypertonic site of infection.

Cell Degranulation↗
PubMed1994

Efficacies of different vancomycin dosing regimens against Staphylococcus aureus determined with a dynamic in vitro model.

A dynamic in vitro model was used to assess four different vancomycin dosing regimens against Staphylococcus aureus. These regimens achieved peak drug concentrations of 48 micrograms/ml (single dose) and 30 micrograms/ml (dosed every 12 h) and constant concentrations of 16 and 8 micrograms/ml. Analysis of the area under the bacterial concentration-time curve, area under the first moment of the bacterial concentration-time curve, and bacterial elimination rate constant showed no difference in the rate or extent of bacterial killing. The optimal dosing method may be that which achieves the lowest area under the curve while concentrations are maintained above the MBC.

Dose-Response Relationship, Drug↗
PubMed1994

Primary biliary cirrhosis presenting with granulomatous skin lesions.

A case is described of primary biliary cirrhosis in a 59 year old woman who initially presented with a rash over her lower legs 18 months before diagnosis. Skin biopsy examination showed non-caseating granulomas of the sarcoid type. It is believed that this is the first reported case of primary biliary cirrhosis presenting with a granulomatous rash.

Female↗
PubMed1993

Organic osmolytes in human and other mammalian kidneys.

Osmotically-active organic solutes, or osmolytes, have been found in high concentration in the renal inner medulla of a wide variety of mammalian species, but their existence in human kidneys has not yet been shown. The aim of this study was to demonstrate the presence of osmolytes in the human kidney. Human tissues were obtained from kidneys removed surgically for diseases which involved only one pole of the kidney; in most cases this was a tumor. Animal kidneys analyzed were from dogs, pigs and rabbits. Inner medulla and cortex tissue samples were analyzed and found to contain the organic osmolytes glycine betaine, myo-inositol, sorbitol and glycerophosphorylcholine. The levels were much higher in the medulla than in the cortex. Further dissection of the human kidneys showed that sorbitol, glycerophosphorylcholine and glycine betaine were maximally concentrated at the papillary tip, while myo-inositol was found in highest concentration at the papillary base. Osmolytes were in low concentrations or undetectable in rabbit skeletal muscle, ureter and bladder. The organic osmolytes detected are likely to be physiologically important in humans. Studies in other mammals can be used as models for the investigation of the osmolyte system in human kidney function.

Animals↗
PubMed1993

Effects of betaines and urine on the antibacterial activity of aminoglycosides.

Urine has long been known to inhibit the activity of aminoglycosides against urinary tract pathogens. Glycine betaine which is present in urine confers resistance against high osmolarity to Gram-negative organisms. We postulated that glycine betaine might contribute to the aminoglycoside resistance found in hypertonic urine. Escherichia coli became extremely resistant to gentamicin (40 x MIC in 0.9 M sodium chloride) when cultured in minimal medium supplemented with 10(-4) M glycine betaine and 0.1-1.0 M sodium chloride. Resistance was increased in the presence of high glucose concentrations but to a lesser extent (3 x MIC in 1.0 M glucose). This effect was not produced by other polyols or urea. These results suggest the observed synergism is mediated by the osmoprotective effects of glycine betaine and the inhibitory effect of sodium chloride or glucose against the aminoglycoside. Other betaines tested had a less marked effect. The betaines in urine permit the expression of increased resistance to aminoglycosides in concentrated urine.

Acetylcarnitine↗
PubMed1993

How vancomycin is used in Australasia--a survey.

BACKGROUND: Vancomycin serum concentrations have been monitored over the last 30 years in an attempt to avoid dose-dependent toxicity and enhance efficacy. Current literature recommendations for peak and trough concentrations are usually in the range of 20-40 mg/L and 5-10 mg/L, respectively. Literature recommendations regarding the time at which peak concentrations are measured are highly variable, ranging from immediately after the end of the infusion to three hours post-dose. AIMS: To identify how vancomycin dosing is being monitored and assess variability in the current practice. METHODS: A survey of microbiology departments and infectious disease physicians in major Australasian hospitals was undertaken. The variability in the current practice was assessed by fitting mean recommendations to a two compartment Bayesian model. RESULTS: Of the 83 (70%) who replied 71 (86%) monitored vancomycin concentrations. Fifty-four percent targeted peak concentrations within the range of 20-40 mg/L, and 73% targeted trough concentrations < or = 10 mg/L. The time of sampling of peak concentrations varied considerably ranging from immediately (12%) to 120 minutes (12%) post-infusion (median 30 minutes [40%]). The concentration-time curves resulting from three sets of mean recommendations ('peaks' drawn at: 0, 30 and 120 minutes aiming for a concentration of 35 mg/L with a trough concentration of 10 mg/L) were modelled using a two compartment Bayesian programme. The predicted true peak (maximum) concentrations ranged from 30 to 86 mg/L, despite aiming for identical target concentrations, indicating marked variation in the actual dosing practice. CONCLUSIONS: There is thus considerable variation in the practice of vancomycin therapeutic monitoring which has a major effect on dosing. The main contributing factor is the variable timing of sampling peak concentrations.

Australia↗
PubMed1993

Inclusion body myositis presenting solely as dysphagia.

Two patients presenting with dysphagia due to cricopharyngeal muscle dysfunction developed limb weakness 2 to 3 years later. Cricopharyngeal and limb muscle biopsies demonstrated changes typical of inclusion body myositis (IBM). Both patients improved following cricopharyngeal myotomy. IBM should be considered in patients presenting with dysphagia.

Biopsy↗
PubMed1992

Which cephalosporin?

Explore the source record for details and available documents.

Bacterial Infections↗
PubMed1992

Same-day batch measurement of glycine betaine, carnitine, and other betaines in biological material.

Glycine betaine, carnitine, carnitine esters, butyrobetaine, and proline betaine (stachydrine) concentrations in biological materials can be reliably measured in 100-microliters samples, with a detection limit below 1 mumol/liter. The procedure is suitable for batches of more than 30 specimens and it is possible to obtain a single result within 2 h. The betaines are extracted into an acetonitrile:methanol mixture, dried with anhydrous disodium hydrogen phosphate containing argentous oxide. The 4-bromophenacyl ester derivatives are formed using 4-bromophenacyl triflate as reagent, in the presence of solid magnesium oxide as base. The derivatives are separated by high-performance chromatography on a silica column, in a mixed partition and ion-exchange mode.

Animals↗
PubMed1992

Comparison of gentamicin dosing regimens using an in-vitro model.

An in-vitro model which simulates in-vivo pharmacokinetics was used to compare the efficacy against Pseudomonas aeruginosa of dosing regimens of gentamicin which achieve different peak/trough concentrations but use the same total dose over 24 h. First exposure to gentamicin produced a rapid bactericidal effect which was proportional to the initial peak concentration. Subsequent doses of gentamicin produced a smaller bactericidal effect. Regrowth occurred with all dosing regimens, even after very high initial concentrations (26 mg/L). The time to reach bacterial counts above starting values was prolonged in relation to peak concentrations. Regrowth was also demonstrated in continuous infusion experiments which maintained very high concentrations (26 mg/L), although an inhibitory effect was evident compared with single dose experiments and the experiments mimicking in-vitro pharmacokinetics. There was little evidence of a post-antibiotic effect. The data supports the use of larger initial and longer interval bolus dosing compared with current recommendations.

Drug Administration Schedule↗
PubMed1992

Adaptive resistance following single doses of gentamicin in a dynamic in vitro model.

Adaptive resistance is a phenomenon recently described for Pseudomonas aeruginosa and other gram-negative bacilli following exposure to aminoglycoside antibiotics. It is a reversible form of resistance which develops within 1 to 2 h of initial exposure to an aminoglycoside and disappears several hours after removal of the antibiotic. We investigated adaptive resistance in P. aeruginosa ATCC 27853 following single doses of gentamicin by using a dynamic in vitro model which mimics in vivo pharmacokinetics. The initial peak gentamicin concentrations were 2.5, 8, and 25 mg/liter, and these were followed by an exponential decay in the concentration, with a half-life of 2.5 h. The degree of adaptive resistance was greater and the duration was longer with higher initial gentamicin concentrations. Maximal adaptive resistance occurred between 2 and 10 h following 8 mg/liter and between 2 and 16 h following 25 mg/liter. Full recovery of susceptibility occurred at approximately 36, 39, and 43 h following 2.5, 8, and 25 mg/liter, respectively, at which times the gentamicin concentrations were extremely low. Longer dosing intervals for aminoglycosides may improve efficacy by allowing time for adaptive resistance to resolve.

Drug Resistance, Microbial↗