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Biomedical subjects

S T Chambers

Publications and source records attributed to S T Chambers.

At least 37 records · Page 2Linked to original sources

Detection of Legionella DNA in guinea pig peripheral leukocytes, urine and plasma by the polymerase chain reaction.

Legionella DNA has been detected in respiratory tract, serum and urine samples from patients with pneumonia by the polymerase chain reaction. A guinea pig model was used to assess whether Legionella DNA could also be detected in peripheral leukocytes during active infection. Ten guinea pigs were infected intraperitoneally with Legionella pneumophila serogroup 1, and leukocyte, plasma and urine samples were collected immediately before inoculation and on days 1, 3, 7 and 14 thereafter. All samples were tested for Legionella DNA by the polymerase chain reaction. Overall, Legionella DNA was detected in 55% of leukocyte samples, 28% of urine samples and 21% of plasma samples collected after inoculation. The sensitivity of the polymerase chain reaction on leukocytes was highest for samples collected within 3 days of inoculation. Further studies testing leukocyte samples from human Legionella infection are required to confirm these observations.

Animals↗

Elevated glycine betaine excretion in diabetes mellitus patients is associated with proximal tubular dysfunction and hyperglycemia.

In an ambulatory population of diabetic subjects (Type 1 and Type 2), the urine excretion of the renal osmolyte, glycine betaine, was compared to known markers of glycemic control, renal dysfunction and to the excretion of related betaines, including trigonelline, proline betaine, carnitine and acetyl-carnitine. Of the 85 subjects, 20 patients had urine glycine betaine concentrations above the reference range for normal subjects. Plasma glycine betaine concentrations were within reference ranges for normal subjects. Patients with elevated glycine betaine excretion tended to have lower plasma glycine betaine concentrations, but this did not reach statistical significance. One way analysis of variance found excretion is independent of treatment, duration of diagnosed diabetes, blood pressure and body mass index (BMI). An association between glycine betaine excretion and glycemic control was observed with statistically significant correlations occurring with both plasma glucose (r = 0.43, P < 0.001) and glycated haemoglobin (HbA1c) (r = 0.35, P < 0.005). The excretion of carnitine, acetyl-carnitine and proline betaine were related to glycine betaine excretion (r = 0.49, P < 0.001; r = 0.40, P < 0.001; r = 0.27, P < 0.05, respectively). Urine carnitine and acetyl-carnitine concentrations were also related to plasma glucose concentrations (r = 0.30, P < 0.01). Increased urine retinol binding protein concentrations (RBP), a marker of proximal tubular dysfunction, correlated with elevated urine glycine betaine excretion and plasma HbA1c (r = 0.28, P < 0.01). These results suggest poor glycemic control is associated with the increase in urine glycine betaine, carnitine, acetyl-carnitine and RBP excretion in diabetic patients. However, < 50% of the observed increase in glycine betaine excretion has been accounted for by the variables measured, suggesting other unidentified processes may also be involved.

Adult↗

Inhibitors of bacterial growth in urine: what is the role of betaines?

It has long been recognised that some individuals produce urine that is inhibitory to uropathogens. This may be partly explained by inhibitors. Several inhibitors have been identified in urine including urea and organic acids. Bacteria adapt to high osmolarity by activating osmoregulated betaine porters and accumulating organic osmolytes intracellularly. The preferred substrate is glycine betaine, which is present in urine, and promotes rapid growth by balancing osmotic forces and stabilising macromolecular structures against the toxicity of urea and low pH. Other dietary betaines such as trigonelline may also be taken but enhance urea toxicity. The importance of such compounds in vivo is unknown.

Bacteria↗

Osmoprotective activity, urea protection, and accumulation of hydrophilic betaines in Escherichia coli and Staphylococcus aureus.

The hydrophilic betaines, deanol betaine, triethanol betaine, diethanolthetin and methylethanolthetin, and also thioxanium betaine and citrulline betaine, were accumulated by Escherichia coli. All betaines tested had significant osmoprotective activity for E. coli and, with the exception of citrulline betaine and diethanolthetin, also demonstrated urea protection. Staphylococcus aureus accumulated only methylethanolthetin, deanol betaine and thioxanium betaine: the first two had an osmoprotective effect but conferred no urea protection. Diethanolthetin and thioxanium betaine significantly decreased urea tolerance for S. aureus.

Betaine↗

Ciguatera fish poisoning.

Ciguatera fish poisoning is one of a variety of non-bacterial forms of human seafood poisoning. Consuming large predatory fish from tropical reef ecosystems may be hazardous. We describe a case that is typical of the disease, and illustrates the persistence of neurological symptoms that occur in some patients.

Adult↗

Osmoprotective properties and accumulation of betaine analogues by Staphylococcus aureus.

Betaines were evaluated as potential antistaphylococcal agents for urinary tract infections. Staphylococcus aureus accumulated all tested betaines except trigonelline. S. aureus transport systems were less sensitive to carbon chain length than those of Escherichia coli. Betaines were accumulated in the absence of osmotic stress, and 10-fold more in hyperosmotic medium. Most betaines increased the osmotolerance of S. aureus in defined minimal medium. Unlike E. coli, S. aureus did not significantly accumulate a second betaine in the presence of glycine betaine. Betaines are less likely to be useful in treating staphylococcal than E. coli urinary infections.

Anti-Bacterial Agents↗

Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration.

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Administration, Intranasal↗

An audit of the assessment and management of adults admitted to Christchurch Hospital with community acquired pneumonia.

AIMS: To audit the management of adult patients admitted with community acquired pneumonia including the standards of clinical assessment, use of modified British Thoracic Society prognostic criteria and antibiotic therapy. METHODS: A prospective, 16 week, study of consecutive patients admitted to Christchurch Hospital with community acquired pneumonia. RESULTS: Ninety-six patients met the inclusion criteria. The median age was 70 years. A pathogen was identified in 28 (26%) patients. Forty two patients fulfilled the modified British Thoracic Society criteria for severe disease and all 9 deaths occurred in that subgroup. The management guidelines were followed without exception in only 15% of cases. Documentation of the prognostic criteria was often incomplete and therefore only 33% of those patients with severe disease were correctly identified. Seventy one percent of those with severe disease were treated with only one antibiotic and there was significant delay in administering the first dose in 44% of cases. A follow up chest radiograph was performed in 43 (51%) of those discharged. CONCLUSIONS: There was poor compliance with the management guidelines. There was a lack of awareness of the severity criteria leading to inadequate treatment in many cases. Further educational initiatives are indicated.

Adult↗

The cost of campylobacteriosis in New Zealand in 1995.

AIM: To estimate the financial impact of campylobacter infection in Canterbury and New Zealand in 1995. METHODS: The records of Canterbury Health Laboratories and hospital notes were searched to locate all inpatients admitted with campylobacteriosis in Christchurch in 1995 and to determine the costs involved. Further estimates of costs of outpatient care and costs due to lost productivity were made using local notification data. The computer database was searched for all cases of Guillain-Barré syndrome and reactive arthritis in 1995, and an estimate made of the cost attributable to campylobacter. RESULTS: There were 65 admissions for campylobacteriosis at a cost of $92,262. Notified cases in general practice were estimated to cost $61,911 and loss of work an additional $338,499. Of the eight admissions with Guillain-Barré syndrome in 1995, the estimated cost of cases due to campylobacter infection was $89,522. Inpatient costs of reactive arthritis were negligible. Overall costs in Canterbury in 1995 amounted to $582,194, with a corresponding national figure of $4.48 million. The true cost of campylobacter infection may be up to ten times higher. CONCLUSIONS: The current high incidence of campylobacter infection has considerable financial impact on the community. Further public health and research initiatives to decrease incidence and associated costs are encouraged.

Adolescent↗

Natural and synthetic betaines counter the effects of high NaCl and urea concentrations.

Escherichia coli was used as a model system to evaluate a range of betaines for their ability to protect against salt and urea stresses. Betaine structure determined the salt and urea protective effects. Dimethylthetin conferred salt protection similar to glycine betaine, whereas dimethylsulfoniopropionate (DMSP) was less effective than either glycine betaine or dimethylthetin, but similar to propionobetaine (its nitrogen analogue). Hydrophobic alpha-substituents altered salt tolerance. Valine betaine with an aliphatic side group conferred salt tolerance similar to glycine betaine. Betaines containing phenyl groups (phenylglycine, phenylalanine and N-phenylglycine betaines) did not confer salt protection, growth being similar to, or less than the control (no betaine). Hydrophobic groups decreased the ability to protect against urea stresses; valine betaine conferred poor urea tolerance. The addition of an hydroxyl group increased the ability of a betaine to protect against urea denaturation. Proline betaine, an effective salt protector, conferred poor urea tolerance. Increasing the charge separation in the betaine molecule decreased the ability to confer urea tolerance. Thiolanium, pyridinium and triethylglycine betaines, with larger cationic functions, conferred no urea tolerance to E. coli.

Betaine↗

Evaluation of alpha interferon for the treatment of chronic hepatitis B infection in Christchurch.

AIM: To evaluate alpha interferon for the treatment of chronic replicative hepatitis B infection in Christchurch patients. METHODS: Ten patients were divided into two groups depending upon whether their average pretreatment ALT levels were greater than twice the upper limit of normal (group 1, 6 subjects) or less than twice the upper limit of normal (group 2, 4 subjects). Interferon alpha-2a (4.5 mega units) was administered three times a week for 24 weeks with the addition of a preceding priming course of prednisone in group 2. RESULTS: At 6 months post treatment only one patient in group 1 had seroconverted (HBeAg to anti-HBe), however, the remaining five patients seroconverted from 18-32 months after therapy. This response was associated with normalisation of the transaminases and in 5/6 subjects a fall in the HBV DNA levels. In group 2 one subject seroconverted by 6 months despite a shortened course of Interferon. A delayed seroconversion (18 months) was observed in one patient and another had a partial response with the development of anti-HBe but associated with persistence of HBeAg. The remaining patient has not responded. CONCLUSIONS: Interferon alpha-2a was effective in promoting a seroconversion HBeAg to anti-HBe in patients with chronic hepatitis B and transaminases elevated to twice the upper limit of normal, although in most cases this response was delayed. Larger studies will be required to determine the role of steroid priming in those with less active disease.

Adult↗

The association between colicinogenicity and pathogenesis among uropathogenic isolates of Escherichia coli.

Colicins have previously been thought to play an indirect role in bacterial pathogenesis. We describe here an association between colicinogenicity and pathogenesis among uropathogenic E. coli strains based on 568 clinical isolates. Significantly more strains isolated from patients with the symptomatic infections pyelonephritis and cystitis produced colicin, 44.4% (P < 0.05) and 51.5% (P < 0.01), respectively, than those strains isolated from patients with asymptomatic infections (32.5%). Attempts to identify new colicins produced by the 232 colicin+ isolates showed that 57.3% did not belong to any known colicin type. The colicin V genotype was found in only 10.8% of the colicin+ isolates, suggesting the possibility of different colicinogenic plasmids predominating during urinary tract infections.

Colicins↗

Is the ability of urinary tract pathogens to accumulate glycine betaine a factor in the virulence of pathogenic strains?

The regulation of intracellular concentrations of organic solutes, including glycine betaine, is an important adaptive response to osmotic stress for Escherichia coli. The clinical significance of glycine betaine to uropathogens is not clear. Clinical isolates of E. coli, Klebsiella pneumoniae, Enterobacter species, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, S. saprophyticus, and Enterococcus faecalis accumulated glycine betaine from hyperosmotic media. The addition of glycine betaine to hyperosmotic minimal medium accelerated the growth rates of all species tested except P. mirabilis. However, when clinical strains of E. coli were transferred from urine with low osmolality to hyperosmotic urine, there was no slowing of the growth rate. There was no difference in growth rates of E. coli isolates from acute pyelonephritis, cystitis, and asymptomatic bacteriuria nor from fecal isolates. The ability to accumulate osmolytes, although it may be a factor in the adaptation to hypertonic environments, was not related to virulence.

Adolescent↗

Use of the polymerase chain reaction to detect Legionella DNA in urine and serum samples from patients with pneumonia.

Legionella pneumonia can be difficult to diagnose. Existing laboratory tests for detecting Legionella species lack sensitivity or provide only a retrospective diagnosis. We used the polymerase chain reaction (PCR) with primers that amplify a 104-base pair segment of the coding region of the 5S tRNA gene to detect Legionella DNA in urine and serum samples from patients with pneumonia. Stored urine and serum samples from patients enrolled in two prospective studies of pneumonia were tested. Legionella DNA was detected in urine and/or serum samples from 18 (64%) of 28 patients with legionella pneumonia diagnosed by conventional tests, but it was not detected in urine or serum samples from 24 patients with pneumonia due to other organisms. The sensitivity of PCR improved to 73% if testing was restricted to samples taken within 4 days of the onset of symptoms. Detection of Legionella DNA in urine and serum promises to be a valuable tool for the rapid diagnosis of legionella pneumonia.

Adult↗