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Biomedical subjects

K Randall

Publications and source records attributed to K Randall.

At least 19 recordsLinked to original sources
PubMed2003

Drug errors in obstetric anaesthesia: a national survey.

We conducted a postal survey of lead obstetric anaesthetists in all consultant-led maternity units in the UK about drug errors and the measures taken to reduce or prevent them. Of the 179 out of 240 (75%) who responded, 70 (39%) knew of at least one drug error in their unit during the last year, with 28 of them (40%) experiencing more than one. Of the most recent errors, giving the wrong drug (most commonly thiopental instead of antibiotics or vice versa [14 cases], or suxamethonium instead of [Formula: see text] [8 cases] or other drugs [4 cases]) was the most common error, occurring in 27 units (15%). Errors involving epidural/spinal analgesia/anaesthesia (including drugs intended for these routes but given via other routes) occurred in 20 cases. Only 36 respondents (20%) described protocols for checking anaesthetic drugs. Methods described for reducing drug errors were use of coloured labels (20%) or pre-filled labelled syringes (6%), limiting the range of drugs available (6%) and keeping drugs in separate trays once drawn up (6%).

Journal Article↗
PubMed2003

Effect of the Confidential Enquiries into Maternal Deaths on the use of Syntocinon at Caesarean section in the UK.

The recommended dose of Syntocinon used for uterine contraction at Caesarean section is5 units intravenously, given slowly. We conducted a survey of the use of Syntocinon at Caesarean section among 240 lead obstetric anaesthetists in the UK in 2001 and found that 155 (87%) of the 179 (75%) respondents gave 10 units, 77 of them (50%) by rapid bolus. The risks of Syntocinon, especially given by rapid injection, were highlighted in the report of the Confidential Enquiries into Maternal Deaths in the UK (1997-99), which was published at the end of 2001, and so the survey was repeated in 2002. Of the 256 forms sent, 198 completed replies were returned (77%); these indicated a dramatic change of practice: only 30 (15%) now gave 10 units and only 7 of these (23%) by a rapid injection. One hundred and sixty-seven respondents to the second survey (84%) stated they had changed their practice and 159 of these (95%) gave the Confidential Enquiries report as the main reason for change. These results highlight the importance of the Confidential Enquiries as a means of improving practice.

Anesthesia, Obstetrical↗
PubMed2001

Near infra-red spectra of urea with glycine betaine or trimethylamine N-oxide are additive.

Glycine betaine and trimethylamine-N-oxide counteract urea denaturation in solutions containing urea and the methylamine in the mole ratio of 2:1. Near infra-red difference spectra (water spectrum subtracted) of solutions containing both urea with either glycine betaine or trimethylamine-N-oxide can be predicted from the spectra of the single solutes, with r(2)>0.999 both using the spectrum from 1200 to 2100 nm (where most absorbance is attributable to hydrogen bonding) and using an extended range 1000 to 2500 nm, which includes solute specific bands. Thus urea and the kosmotropes appear to interact with water independently and the counteraction cannot be attributed to specific interactions between them. The spectrum of aqueous glycine betaine can be predicted from tetramethylammonium and formate ions (r(2)=0.998), suggesting that independent interactions of the quaternary amine, and of the carboxyl function, with water are dominant. The exceptional properties of glycine betaine do not arise from specific intramolecular interactions between the charged groups.

Betaine↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1997

Carpal bone titanium implant arthroplasty. 10 years' experience.

In 1984, in an effort to address the silicone wear particle problem, titanium implants were developed for the scaphoid, lunate, and trapeziometacarpal joint. The design of these implants closely resembled their silicone counterparts, though some modifications were made to accommodate the properties of unalloyed titanium and enhance their stability. Carpal bone implants act as articulating spacers to help maintain the relationship of adjacent carpal bones after local resection procedures. Their use allows carpal stabilization procedures and provides functional mobility with good strength and pain relief. Their surgical application began in 1985. The 10-year clinical experience seems very promising to date.

Adult↗
PubMed1996

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↗
PubMed1996

Long-term expression of transforming growth factor TGF beta 1 in mouse skin after localized beta-irradiation.

The long-term expression of TGF beta 1 in mouse skin after localized irradiation with a beta-emitting source is reported. The skin of CBA/ca mice was exposed to 50 Gy superficial beta radiation from an 11 mm strontium-90 source. Such a dose produced an acute moist desquamation reaction in 100% of the animals, which was macroscopically resolved within 30 days. The acute response was followed by progressive remodelling of dermal tissues as characterized by histological means. The expression of TGF beta 1 was followed for 12 months after irradiation and showed three distinct waves of expression at the RNA level. Levels of expression initially rose to 230% above controls at 6 h before returning to control levels around 24-48 h. Expression then rose again to 169 and 234% above controls at 14 and 28 days post-irradiation respectively. Levels then declined to those of the controls by 2 months. A progressive increase in expression was then noted after 3 months, which peaked around 9 months and was resolved by 12 months. In a parallel study the skin of 144 CBA/ca mice was exposed to 50 Gy superficial beta radiation from 2 x 4 cm Thulium-170 source and compared with a similar group of sham-irradiated controls. The irradiated group showed a cumulative tumour incidence of 54.3% compared with 0% incidence in the sham-irradiated group. Of the 45 radiation-induced tumours a representative sample of 16 (nine malignant fibrous histiocytomas; three fibrosarcomas; two fibromas; one squamous cell carcinoma; one rhabdomyosarcoma) were selected for further study. Semiquantitative PCR on all these tumours showed elevated levels of TGF beta 1 expression ranging from 1.8 to 87-fold above the levels found in normal skin. This study is part of ongoing investigations into the long-term effects of single accidental exposures. The 50 Gy dose used is comparable with the surface doses obtained by some of the victims of the Chernobyl accident.

Animals↗
PubMed1996

Accumulation of natural and synthetic betaines by a mammalian renal cell line.

Intracellular accumulation of different betaines was compared in osmotically stressed Madin Darby canine kidney (MDCK) cells to model the betaine accumulation specificity of the mammalian inner medulla and to show how this accumulation differed from that of bacteria. All betaines accumulated less than glycine betaine. Arsenobetaine (the arsenic analogue of glycine betaine) accumulated to 12% of the glycine betaine levels and the sulphur analogue dimethylthetin accumulated to >80%. Most substituted glycine betaine analogues accumulated to 2-5% of intracellular glycine betaine concentrations, however, serine betaine accumulated to <0.5% of glycine betaine levels. Inhibition studies to distinguish the betaine ports were performed by the addition of proline. Butyrobetaine and carnitine accumulation was not proline sensitive, whereas that of other betaines was. As with glycine betaine, the accumulation of propionobetaine and dimethylthetin was proline sensitive and osmoregulated. Pyridinium betaine was accumulated by both proline-sensitive and -insensitive systems, with a small increase under osmotic stress. High concentrations (10 times that of glycine betaine) of the dietary betaines proline betaine and trigonelline inhibited total betaine accumulation. Because alpha-substituted betaines are accumulated by bacteria and not by MDCK cells, these betaines may be the basis for design of antimicrobial agents.

Animals↗
PubMed1995

Competitive accumulation of betaines by Escherichia coli K-12 and derivative strains lacking betaine porters.

Escherichia coli was grown in hyperosmotic media containing both glycine betaine and one other betaine. E. coli K-12 derivative WG439 (putP- proP- proU-) did not accumulate any of 15 betaines. Strains WG445 (putP- proP- proU+), WG443 (putP- proP+ proU-) and the control strains all accumulated less betaine, (CH3)3N(+)-(CH2)n-COO-, when n was greater than 1. Accumulation was not detectable when n = 5. Both L- and D-isomers of alpha-substituted betaines were accumulated by both strains WG443 and WG445, the D-isomers more slowly. Hydroxylated alpha-substituted betaines were accumulated relatively more through the osmoregulated transport protein ProU than through ProP. In actively growing cultures glycine betaine appeared to be the preferred substrate for accumulation, but the proportion of the second accumulated betaine increased as cultures approached stationary phase.

Amino Acid Transport Systems↗
PubMed1995

Expression of transforming growth factor-beta 1 in mouse skin during the acute phase of radiation damage.

Transforming growth factor-beta (TGF beta 1) plays a central role in wound healing, so its perturbation by radiation may contribute to the acute and late effects seen in irradiated skin. TGF beta 1 mRNA expression was measured by PCR, in the skin of the CD1 and CBA mouse, exposed to Sr-90 beta from an 11-mm diameter source. TGF beta 1 mRNA expression increased sharply after doses between 1 and 10 Gy and plateaued at approximately 200% above controls after doses between 20 and 50 Gy. Immunohistochemistry showed that the TGF beta 1 protein was confined to the dermis and suprabasal cells with none in basal cells. A dose of 50 Gy produces an acute desquamative reaction in 100% of mice that is resolved in 30 days. After the same dose, TGF beta 1 mRNA expression fell below the controls at 3 h (-9.4% in the CD1 and -44% in the CBA mouse); rose sharply at 6-12 h (+124% CD1, +230% CBA), returned to control levels by 24-48 h, then rose progressively to approximately 200% above the controls between days 7 and 14. TGF beta 1 mRNA expression remained elevated at 100-200% above controls until the end of the experiment at 55 days. The significance of these changes in TGF beta 1 is discussed in the context of the early stress response reaction to radiation, the acute inflammatory and the later chronic fibrosis of the skin.

Acute Disease↗
PubMed1995

Fracture of the anterior colliculus.

The authors retrospectively reviewed 33 cases of fracture involving the anterior colliculus of the medial malleolus to examine clinical results of operative treatment for these fractures. Although this injury appears innocuous, it can be difficult to obtain stable fixation of the fragment intraoperatively, and painful nonunion can result. A simple reduction maneuver and method of tension band fixation are described.

Ankle Injuries↗
PubMed1995

The cortical neuritic pathology of Huntington's disease.

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1992

The effect of whole-body gamma-irradiation on localized beta-irradiation-induced skin reactions in mice.

The combined effects of whole-body radiation and localized radiation trauma have received scant experimental attention. However, in the recent accidents at Chernobyl and Goiania skin damage from beta-contamination was combined with total-body radiation and in many cases the skin lesions which covered large surfaces of the body were severe and recovery was prolonged. This paper models the immunosuppressive effects of whole-body gamma-radiation in the sublethal to lethal range (1-11 Gy) on the skin reactions produced by 50 Gy of superficial beta-radiation. For gamma ray doses < 4 Gy no synergistic effects were detectable. For gamma-ray doses of 4, 6 and 8 Gy there was a 4-5-day prolongation in time-course of the skin reaction but no significant exacerbation of its severity. The overall time for the resolution of the skin reaction (45 days) was also unaffected by the relatively high whole-body doses. These rather surprising findings of minimal synergy between whole-body exposure and a localized severe beta burn to the skin are perhaps explained by the mismatch between the maximal immunosuppression at 2-10 days postirradiation and the timing of the skin damage at 10-25 days.

Animals↗