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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 235 records · Page 13Linked to original sources

Gentamicin-resistant Salmonella typhimurium phage type 204c: molecular studies and strain diversity in a putative bovine outbreak.

As part of the investigation of a putative bovine outbreak, 13 isolates of Salmonella typhimurium phage type 204c were subjected to plasmid analysis. Plasmid profiles suggested that several distinct strains were involved and these observations were supported by minor variations in antibiotic resistance pattern. Restriction enzyme fingerprinting and conjugational segregation of the plasmids confirmed these findings. Although 12 of the 13 isolates were resistant to gentamicin, resistance was conferred by 4 distinct plasmids; 3 of these belonged to Inc I and were distantly related on the basis of restriction fingerprints and the fourth was a resistant derivative of the 60 MDa S. typhimurium serotype-specific plasmid. The molecular evidence refuted the hypothesis that geographical and temporal clustering of these gentamicin-resistant isolates could be explained on the basis of a single epidmiological episode.

Animals↗

Alcohol and driving: is the 0.05% blood alcohol concentration limit justified?

This paper reviews the findings of experimental and laboratory research to determine whether there is sufficient evidence to support a uniform 0.05% blood alcohol concentration (BAC) as the legal limit for driving. Statistically significant and meaningful decrements in driving-related performance were identified at 0.05% BAC or below in many studies. Younger and inexperienced drinkers and drivers appear to be at greatest risk for alcohol-related traffic crashes. It is concluded that on scientific grounds, there is support for setting the legal limit at 0.05%. The setting of a uniform 0.05% BAC statutory limit should be but one effort within a comprehensive approach including other legal, social, behavioural and environmental strategies to deal with the drink driving problem.

Journal Article↗

Use of desflurane for outpatient anesthesia. A comparison with propofol and nitrous oxide.

Desflurane's induction and recovery characteristics were compared to those of propofol-nitrous oxide in outpatients undergoing laparoscopic procedures. Ninety-two healthy patients were randomized to receive either: 1) propofol induction and propofol-nitrous oxide maintenance (control), 2) propofol induction and desflurane-nitrous oxide maintenance, 3) desflurane-nitrous oxide, or 4) desflurane alone for induction and maintenance of anesthesia. Inhalation induction with desflurane-nitrous oxide was faster than with desflurane alone (100 +/- 35 vs. 124 +/- 43 s). Inhalation inductions were associated with a high incidence of apnea (17 and 26%), breath-holding (26 and 39%), and coughing (30 and 22%) in groups 3 and 4, respectively. The emergence time after discontinuation of desflurane in oxygen (4.5 +/- 2.1 min.) was significantly less than that after propofol-nitrous oxide (7.3 +/- 3.9 min.). However, times from arrival in the recovery room until the patients were judged fit for discharge were similar for all four treatment groups. Digit-symbol substitution test results and sedation visual analogue scores also were similar during the first 2 h in the recovery room. A lower incidence of moderate-to-severe nausea was reported in group 1 (15% vs. 52, 52, and 59% in groups 2, 3, and 4, respectively). In conclusion, induction of anesthesia with desflurane was rapid but is associated with a high incidence of airway irritation. Emergence and recovery profiles after maintenance of anesthesia with desflurane compared favorably to a propofol-nitrous oxide combination. However, propofol was associated with a lower incidence of nausea than was desflurane after outpatient anesthesia for laparoscopic surgery.

Adult↗

Post-transcriptional control of a sporulation regulatory gene encoding transcription factor sigma H in Bacillus subtilis.

The transcriptional regulatory gene spoOH encodes an RNA polymerase sigma factor called sigma H that directs gene expression at an early stage of sporulation in the Gram-positive bacterium Bacillus subtilis. We now report that conditions that induce sporulation cause a rapid increase in the cellular concentration of sigma H. This increase could account for the stimulated transcription of certain sigma H-controlled genes at the onset of sporulation. Experiments in which the expression of spoOH was monitored by use of a spoOH-lacZ fusion and in which expression of spoOH was artificially manipulated by use of an isopropyl-beta-D-thiogalacto-side-inducible promoter indicate that sporulation-induced increases in the amount of sigma H are not controlled at the level of the transcription of its structural gene. Rather, we infer the existence of post-transcriptional control mechanisms that govern sigma H levels, and we present evidence suggesting that increases in the amount of sigma H at the start of sporulation are due to increased translation or stability of the spoOH mRNA and, to a lesser extent, decreased turnover of spoOH protein.

Adenosine↗

Regulation of spo0H, a gene coding for the Bacillus subtilis sigma H factor.

The Bacillus spo0H gene codes for sigma H, which, as part of the RNA polymerase holoenzyme E sigma H, is responsible for the transcription of several genes which are expressed at the beginning of the sporulation process. In this communication, we examined the regulation of the spo0H gene of Bacillus subtilis by using lacZ reporter gene assays, quantitative RNA determinations, and Western immunoassay. The expression of the spo0H gene increases as the culture enters the mid-logarithmic stage of growth. This increased expression requires the genes spo0A, spo0B, spo0E, and spo0F, and the requirement for at least spo0A and spo0B can be bypassed when the abrB gene is mutated. The expression of the spo0H gene is constitutive in the presence of the abrB mutation, being expressed at higher levels during vegetative growth. In addition, the sof-1 mutation, in the spo0A structural gene, can bypass the need for spo0F in spo0H expression. The transcriptional start site of spo0H was determined by using RNA made in vivo as well as in vitro. These studies indicate that spo0H is transcribed by the major vegetative RNA polymerase, E sigma A. spo0H RNA and sigma H levels during growth are not identical to each other or to the pattern of expression of spoVG, a gene transcribed by E sigma H. This suggests that spo0H is regulated posttranscriptionally and also that factors in addition to sigma H levels are involved in the expression of genes of the E sigma H regulon.

Bacillus subtilis↗

The Bacillus subtilis sin gene, a regulator of alternate developmental processes, codes for a DNA-binding protein.

The sin gene of Bacillus subtilis encodes a dual-function regulatory protein, Sin, which is a negative as well as a positive regulator of alternate developmental processes that are induced at the end of vegetative growth in response to nutrient depletion. Sin has been purified to homogeneity by using a simple two-step procedure. It was found to bind to the developmentally regulated aprE (alkaline protease) gene at two sites in vitro. The stronger Sin-binding site (SBS-1) is located more than 200 bp upstream from the transcription start site. It is required for Sin repression of aprE expression in vivo, as strains bearing SBS-1 deletions were not affected by the sin gene. The second, weaker Sin-binding site lies on a DNA fragment that contains the aprE promoter. Results of DNase I, exonuclease III, and dimethyl sulfate footprinting analysis of SBS-1 suggested that Sin binding involves two adjacent binding sites which appear to contain two different partial dyad symmetries. An analysis of the predicted amino acid sequence of Sin revealed a potential leucine zipper protein dimerization motif which is flanked by two helix-turn-helix motifs that could be involved in recognizing two different dyad symmetries.

Amino Acid Sequence↗

Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria.

A total of 599 children with phenylketonuria, who had been treated early, were followed up prospectively in order to examine the association between intellectual progress from 4 to 14 years of age and control of phenylalanine concentrations. The phenylalanine rose from around 400 mumol/l during the first four years to above 900 mumol/l by 12 years. The children were divided into two cohorts: cohort I comprised 224 children born in the United Kingdom between 1964 and 1971 and cohort II 375 children born between 1972 and 1978. In a previous study it was shown that by 4 years of age these children already had a mean intelligence quotient (IQ) over half a standard deviation below general population norms, and that IQ fell linearly as average phenylalanine concentrations rose. Multiple regression was used to estimate the size of the associations between IQ at later ages and average phenylalanine concentrations in the periods between assessments, after controlling for previous IQ and phenylalanine control, social class, type of phenylketonuria, and factors relating to diagnosis and early management. For each 300 mumol/l rise in average phenylalanine concentrations for those aged 5 to 8 years IQ at 8 years fell by 4-6 points. This compared with a 7-10 point fall in IQ at 4 years for a similar rise in phenylalanine. After 8 years of age the association between IQ and phenylalanine control disappeared in cohort I but persisted in cohort II and was significant up to 10 years of age, although the association was smaller than at 8 years.

Adolescent↗

Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia.

In 97 outpatients undergoing ambulatory arthroscopic procedures, we compared esmolol with alfentanil when used to supplement propofol-N2O-atracurium anesthesia according to a randomized, double-blind protocol. After an initial intravenous dose of 16 micrograms/kg alfentanil, or 2 mg/kg of esmolol, a variable-rate infusion of alfentanil or esmolol was administered to maintain a stable heart rate. After induction of anesthesia with 2.5 mg/kg of propofol, mean arterial pressure decreased to a larger extent in the alfentanil-treated patients. Although heart rate and mean arterial pressure increased in both groups after tracheal intubation, alfentanil more effectively blunted the hemodynamic response to this stimulus. Maintenance of anesthesia was adequate in both treatment groups. After discontinuation of anesthesia, patients in the esmolol group opened their eyes earlier (7.2 +/- 2.4 min vs 9.8 +/- 4.6 min) than those in the alfentanil group. Esmolol-treated patients also reported less sedation in the first 15 min of recovery than those receiving alfentanil. However, there were no differences in times to ambulation and discharge between the groups. Esmolol-treated patients reported more postoperative pain for the first 15 min of recovery and more esmolol-treated patients required postoperative opioid analgesia than those treated with alfentanil. There were no significant differences in the incidences of nausea and vomiting between the two groups. The authors conclude that esmolol may be used in place of alfentanil to supplement propofol-N2O-atracurium anesthesia in outpatients undergoing arthroscopic procedures. However, hemodynamic responses to tracheal intubation were larger with esmolol, and avoidance of alfentanil did not decrease the incidence of postoperative nausea and vomiting in this outpatient population.

Adjuvants, Anesthesia↗

Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.

The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.

Basal Ganglia Diseases↗

Effects of local anesthesia on recovery after outpatient arthroscopy.

The effects of intraarticular bupivacaine administration on postoperative pain and mobilization were evaluated in 97 healthy outpatients undergoing knee arthroscopy under general anesthesia. After completion of the operation, which was performed using a standardized general anesthetic technique, the patient's knee was injected with 30 mL of either 0.5% bupivacaine or saline solution (control), according to a randomized, double-blind protocol. Although there were no statistically significant differences in the patient's assessment of postoperative pain, patients receiving bupivacaine required significantly less opioid analgesic medication in the postoperative period. More importantly, ambulation occurred more rapidly in those patients treated with bupivacaine (versus saline solution), permitting them to be discharged earlier than the control patients (145 +/- 51 min vs 173 +/- 50 min). No adverse effects were noted after the 150-mg intraarticular dose of bupivacaine. On the day after operation, no differences in physical activity or analgesic requirements were detected between the two treatment groups. In conclusion, bupivacaine reduced the opioid requirements and facilitated earlier mobilization after knee arthroscopy without altering the patients' perception of postoperative pain.

Adult↗

Neurological deterioration in young adults with phenylketonuria.

7 patients with phenylketonuria who developed neurological disability in adolescence or early adult life are described. 4 had been diagnosed by routine neonatal screening and started a low phenylalanine diet in infancy. 3 were diagnosed in early childhood because of developmental delay, and then started dietary treatment. Dietary control deteriorated in later years and was withdrawn in mid to late childhood. The late neurological deterioration cannot be directly ascribed to poor compliance with or cessation of dietary treatment in this small, retrospective study--but other likely causes have been excluded and 2 patients showed a striking clinical improvement when a strict diet was resumed. Serial magnetic resonance images from one of these patients show abnormalities that appeared after cessation of dietary treatment and resolved after diet was resumed. If these findings are confirmed, strict dietary control into adult life would be indicated for at least some patients with phenylketonuria.

Adult↗

Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection.

To assess methyl-group metabolism in the central nervous system in infection with human immunodeficiency virus (HIV), levels of 5-methyltetrahydrofolate, methionine, and S-adenosylmethionine were measured by high-performance liquid chromatography in cerebrospinal fluid (CSF) from six children with congenital HIV infection and neurological complications. Total neopterins were also measured, as a marker of macrophage activation. In all six children concentrations of one or more methyl-group carriers were lower than those in a reference population of children, and all of the five in whom CSF neopterins were measured had higher than normal levels. Defective methylation may play a part in the neurological damage caused by HIV infection.

Biopterins↗

A randomized study to determine complications associated with duration of insertion of heparin locks.

A randomized trial was conducted to assess the effect of leaving heparin locks in place longer than 72 hours. Three hundred and one patients were randomly assigned to one of two groups. Group A had the lock changed every 72 hours and Group B had the lock left in place up to 168 hours. Due to withdrawals following randomization, Group A contained 116 subjects and Group B 140 subjects. No significant differences were found between the two groups in relation to age, sex, medical condition, drug used, entries into the lock, minor complications, or incidence of phlebitis. The findings suggest that consideration could be given to extending insertion time up to 96 hours and possibly up to 118 hours.

Adult↗

Fetal damage due to maternal phenylketonuria: effects of dietary treatment and maternal phenylalanine concentrations around the time of conception (an interim report from the UK Phenylketonuria Register).

In 94 infants born to women with PKU, birth weight and head circumference were inversely and linearly related to the mothers' phenylalanine concentrations close to conception; with each 200 mumols/L rise in phenylalanine concentrations, birth weight fell by 98 g and head circumference by 0.46 cm. This relationship was highly significant and appeared to be the same whether or not the mother received a low phenylalanine diet. Even in the 28 infants whose mothers conceived on a strict low phenylalanine diet, birth weights and head circumferences, corrected for sex and gestation, were a little below the population norms (3421 g and 34.7 cm compared with 3600 g and 35.2 cm respectively) although the differences were not statistically significant. Optimal fetal growth occurred only in infants whose mothers had phenylalanine concentrations close to the normal range at conception. Dietary treatment started after conception did not appear to confer any benefit.

Adolescent↗

A long term view of myringoplasty in children.

Fifty-nine type 1 tympanoplasties in children under 14 years of age were assessed by recall to a special follow-up clinic up to 15 years post-operatively. Overall 78 per cent of tympanic membranes were found to be intact with a late failure of grafts noted in 6 per cent of cases. An improvement in the audiological threshold was found in 51 per cent, 24 per cent were unchanged, the remaining 25 per cent suffered a deterioration which was seen both immediately post-operatively and thereafter until reviewed in the special clinic. The age at operation, size of the perforation, grade of surgeon carrying out the operation and prior adenoidectomy had no statistically significant influence on the success rate or the audiological outcome. Revision procedures achieved similar graft take rates to the initial procedures but fared worse audiologically. We conclude that in the majority the operation was successful but hearing gain was not as good as expected and subject to late deterioration. A long term follow-up is important to detect this and other complications.

Adolescent↗