Outcome in offspring of women with mild hyperphenylalaninaemia.
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Birth Weight↗
Biomedical subjects
I Smith
Publications and source records attributed to I Smith.
No reduction in birth weight in phenylketonuria.
Birth weight in a total of 1886 British infants with phenylketonuria (PKU) born between 1964 and 1992 was examined in relation to sex, social class, gestational age, disease severity and birth year. Comparisons were made with two national surveys (British births 1970 and Office of Population Censuses and Surveys 1981). In contrast to a recent Dutch study, birth weight in British infants with PKU (mean 3307 g, median 3337 g) showed a similar distribution to population norms. Birth weight showed no temporal trends and no trends with disease severity. CONCLUSION. Birth weight is not reduced in British infants with PKU.
Birth Weight↗
No association between the c2 allele at the cytochrome P450IIE1 gene and alcohol induced liver disease, alcohol Korsakoff's syndrome or alcohol dependence syndrome.
Cytochrome P450IIE1 metabolises, and is induced by ethanol. The 5' regulatory sequence of the gene is polymorphic; that identified by the c2 allele has been shown by transfection studies to confer an increased rate of transcription. A recent report indicating an association between this allele and alcohol induced cirrhosis suggests that it may contribute to the genetic vulnerability to this disease. We have examined this polymorphism in patients of western European origin with alcohol induced cirrhosis, alcohol Korsakoff's syndrome and alcohol dependence syndrome. We were unable to detect any association between this allele and any of these diseases.
Alcohol Amnestic Disorder↗
Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine, and fentanyl.
STUDY OBJECTIVE: To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 micrograms when used as analgesic supplements to a propofol infusion during monitored anesthesia care (MAC). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ambulatory surgery facility at a university medical center. PATIENTS: 80 outpatients undergoing breast biopsy or inguinal herniorraphy procedures under MAC. INTERVENTIONS: All patients received midazolam 2 mg intravenously (IV) followed by 1 ml of the study medication containing either dezocine 3 mg IV, ketorolac 30 mg IV, fentanyl 50 micrograms IV, or normal saline. A propofol infusion was initiated at 75 micrograms/kg/min and then varied to maintain a stable level of sedation (i.e., Observer Assessment of Alertness/Sedation scale score of 3). An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution. During the operation, supplemental (rescue) medication consisted of fentanyl 25 micrograms IV, bolus injections in all four treatment groups. MEASUREMENTS AND MAIN RESULTS: Propofol infusion and supplemental fentanyl dosage requirements, oxygen saturation values, respiratory rates, recovery times, and postoperative side effects were recorded. Visual analog scales were used to assess sedation, anxiety, pain, and nausea preoperatively (baseline), upon entry into the postanesthesia care unit, and at 30-minute intervals until discharge. The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control (saline) group. The saline and ketorolac groups required rescue analgesic medication more frequently and/or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups. Compared with the three analgesic treatment groups, postoperative pain scores were only marginally higher in the control group. Ketorolac-treated patients had consistently (but not significantly) shorter recovery times to oral intake, ambulation, and discharge than those in the dezocine or fentanyl groups. No postoperative nausea, vomiting, or pruritus was reported in the ketorolac group. CONCLUSION: Compared with ketorolac 60 mg, fentanyl 100 micrograms and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC. However, the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile.
Adult↗
Alkalinization of local anaesthetic for intraarticular instillation during arthroscopy.
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Anesthesia, Local↗
Molecular detection of human cytomegalovirus and determination of genotypic ganciclovir resistance in clinical specimens.
The data presented in this article demonstrate how the polymerase chain reaction (PCR) can be used to detect human cytomegalovirus (HCMV) DNA in the plasma and cerebrospinal fluid (CSF) of infected individuals. Detection of HCMV DNA in plasma of transplant recipients and persons infected with human immunodeficiency virus identifies people with acute visceral disease and those at highest risk for development of HCMV disease. The detection of HCMV DNA in CSF is of particular help in identifying persons with HCMV-related central nervous system disease. In addition, specific mutations within the UL97 region, which encodes for a HCMV protein kinase, have been found to confer ganciclovir resistance and can be detected in plasma and CSF by direct sequencing of PCR products. These data will help provide tools for clinicians to better diagnose, manage, and treat persons with HCMV disease.
AIDS-Related Opportunistic Infections↗
Sevoflurane for outpatient anesthesia: a comparison with propofol.
Three different anesthetic techniques were compared in 146 healthy outpatients undergoing ambulatory surgery. In Groups I and II, anesthesia was induced with propofol (1.5-2.0 mg/kg, intravenously [iv]) and maintained with nitrous oxide (N2O) 60% in oxygen and either a propofol infusion, 75-160 micrograms.kg-1.min-1 IV, or sevoflurane, 1%-2% end-tidal, respectively. In Group III, anesthesia was induced and maintained with sevoflurane, 1%-4% end-tidal and N2O 60% in oxygen. In addition to 60% N2O in oxygen at a total gas flow of 3 L/min, all patients received fentanyl, 2-3 micrograms/kg IV, and vecuronium, 0.1 mg/kg IV. IV induction of anesthesia with propofol (90 +/- 53 s and 94 +/- 48 s in Groups I and II, respectively) was significantly faster than inhalation induction with sevoflurane (153 +/- 100 s). There were no significant differences in the incidence of coughing, airway irritation, or laryngospasm during induction of anesthesia. Although the mean arterial blood pressure values were similar in all three groups, the use of sevoflurane was associated with consistently lower heart rate values during the early maintenance period. Early and intermediate recovery times were the same in all three treatment groups. The use of sevoflurane for induction and/or maintenance of anesthesia was associated with a higher incidence of postoperative emetic sequelae compared with propofol. Finally, the times at which patients were considered "fit for discharge" and the actual discharge times were similar in all three groups. Sevoflurane is an acceptable alternative to propofol for induction and maintenance of outpatient anesthesia.
Adult↗
Sevoflurane versus desflurane for outpatient anesthesia: a comparison of maintenance and recovery profiles.
The recovery characteristics of desflurane and sevoflurane were compared when used for maintenance of ambulatory anesthesia. After obtaining informed consent, 42 healthy, unpremedicated women undergoing laparoscopic sterilization procedures were studied. Anesthesia was induced with propofol, 1.5-2.0 mg/kg, and maintained with either desflurane 3%-6% (n = 21) or sevoflurane 1%-2% (n = 21) with 60% nitrous oxide in oxygen. Intraoperative analgesia and neuromuscular block was achieved using fentanyl and vecuronium, respectively. The inhaled anesthetics were titrated to achieve an adequate clinical "depth of anesthesia" and to maintain mean arterial pressure (MAP) within 20% of the preinduction baseline values. Visual analog scales (VAS) and the digit-symbol substitution test (DSST) were performed preoperatively and at 30-min intervals during the recovery period. There were no differences between the two groups in the total doses of propofol, fentanyl, or vecuronium. Heart rate (HR) values were lower in the sevoflurane group during the induction-to-incision period. However, HR and MAP were otherwise similar during the maintenance and recovery periods. Use of desflurane led to a more rapid emergence (4.8 +/- 2.4 vs 7.8 +/- 3.8 min) and shorter time to extubation (5.1 +/- 2.2 vs 8.2 +/- 4.2 min) compared to sevoflurane (mean values +/- SD). Intermediate recovery times, postoperative VAS and DSST scores, and side effects were similar in the two treatment groups. Although sevoflurane was associated with a slower emergence from anesthesia than desflurane after laparoscopic surgery, recovery of cognitive function and discharge times were similar in the two anesthetic groups. Thus, it would appear that sevoflurane is an acceptable alternative to desflurane for maintenance of outpatient anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The role of sevoflurane in outpatient anesthesia.
Sevoflurane appears to have several properties that make it an attractive alternative to the currently available anesthetics for outpatient anesthesia. The relative low solubility of sevoflurane, as well as an impressive lack of airway irritation, makes it a very useful anesthetic for inhalation induction of anesthesia. This feature is likely to make sevoflurane a population choice for pediatric outpatient anesthesia. For adult outpatients, the relatively low solubility of sevoflurane permits rapid alterations in alveolar concentration during the maintenance period (even when administered at relatively low flow rates of 2-3 L/min), thereby improving control of the depth of anesthesia. Low solubility should also allow for a more predictable emergence from anesthesia (versus isoflurane), thereby facilitating patient turnover in a busy ambulatory surgery center. The commercial development of sevoflurane has been slow because of concerns regarding the potential toxicity of its metabolites and breakdown products (24). However, the large body of clinical experience from Japan and the worldwide Phase II and III clinical development programs suggests that these concerns may be unfounded. The short duration of exposure in the outpatient setting should further decrease the risk of nephrotoxicity. The relatively low solubility of sevoflurane will facilitate its use with total gas flow rates of 2-3 L/min. In the final analysis, clinicians will have to balance the cost of sevoflurane (versus halothane, enflurane, isoflurane, and desflurane) against its potential advantages in the ambulatory surgery population. Although the search for anesthetics that are more ideally suited for use in the outpatient setting will continue, sevoflurane clearly represents a step in the right direction (3).
Adult↗
Characterization of RNA polymerase and two sigma-factor genes from Mycobacterium smegmatis.
A search for Mycobacterium smegmatis genes showing similarity to the conserved family encoding major sigma factors in diverse prokaryotes has identified two such determinants. Both genes are expressed in exponentially growing cells, as judged by Western immunoassays. A series of chromatographic steps was used to purify M. smegmatis RNA polymerase holoenzyme and it was shown that its ability to initiate in vitro transcription with a heterologous Bacillus subtilis promoter is dependent on the presence of these sigma factor(s). Reconstitution of specific in vitro transcription activity was obtained upon mixing of M. smegmatis core RNA polymerase with the major sigma factor of Bacillus subtilis. We also demonstrated in vitro transcription of the M. smegmatis rrnB promoter by the M. smegmatis RNA polymerase. Significantly, highly active B. subtilis RNA polymerase holoenzyme was unable to transcribe this gene.
Amino Acid Sequence↗
Characterization of an iron-dependent regulatory protein (IdeR) of Mycobacterium tuberculosis as a functional homolog of the diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae.
The DtxR protein from Corynebacterium diphtheriae is an iron-dependent repressor that regulates transcription from the tox, IRP1, and IRP2 promoters. A gene from virulent Mycobacterium tuberculosis H37Rv was recently shown to encode a protein, here designated iron-dependent regulator (IdeR), that is almost 60% homologous to DtxR from C. diphtheriae. A 750-bp PCR-derived DNA fragment carrying the M. tuberculosis ideR allele was subcloned to both high- and low-copy-number vectors. In Escherichia coli, transcription from the C. diphtheriae tox, IRP1, and IRP2 promoters was strongly repressed by ideR under high-iron conditions, and ideR restored normal iron-dependent expression of the corynebacterial siderophore in the C. diphtheriae dtxR mutant C7(beta)hm723. The M. tuberculosis IdeR protein was overexpressed in E. coli and purified to near homogeneity by nickel affinity chromatography. Gel mobility shift experiments revealed that IdeR bound to a DNA fragment that carried the C. diphtheriae tox promoter/operator sequence. DNAse I footprint analysis demonstrated that IdeR, in the presence of Cd2+, Co2+, Fe2+, Mn2+, Ni2+, or Zn2+, protected an approximately 30-bp region on DNA fragments carrying the tox, IRP1, or IRP2 promoter/operator sequences. IdeR reacted very weakly in Western blots (immunoblots) with antiserum against the C. diphtheriae DtxR protein, suggesting that the immunodominant epitopes of DtxR may be located in its poorly conserved carboxyl-terminal domain.
Bacterial Proteins↗
The Bacillus subtilis SinR protein is a repressor of the key sporulation gene spo0A.
SinR is a pleiotropic DNA binding protein that is essential for the late-growth processes of competence and motility in Bacillus subtilis and is also a repressor of others, e.g., sporulation and subtilisin synthesis. In this report, we show that SinR, in addition to being an inhibitor of sporulation stage II gene expression, is a repressor of the key early sporulation gene spo0A. The sporulation-specific rise in spo0A expression at time zero is absent in a SinR-overproducing strain and is much higher than normal in strains with a disrupted sinR gene. This effect is direct, since SinR binds specifically to spo0A in vitro, in a region overlapping the -10 region of the sporulation-specific Ps promoter that is recognized by E-sigma H polymerase. Methyl interference and site-directed mutagenesis studies have identified guanine residues that are important for SinR recognition of this DNA sequence. Finally, we present evidence that SinR controls sporulation through several independent genes, i.e., sp0A, spoIIA, and possibly spoIIG and spoIIE.
Bacillus subtilis↗
Evaluation of the efficacy of the VEEP regimen in adult Hodgkin's disease with assessment of gonadal and cardiac toxicity.
PURPOSE: The aim of this phase II study was to investigate the potential of the vincristine, epirubicin, etoposide, and prednisolone (VEEP) regimen to reduce the risks of long-term sequelae of chemotherapy such as sterility, cardiopulmonary damage, and second malignancies, while maintaining efficacy in terms of response and survival. PATIENTS AND METHODS: Eighty-five adult patients with newly diagnosed and previously untreated stage II to IV Hodgkin's disease (HD) were entered and monitored for a minimum of 1 year. Patients were treated to maximum response plus two further courses, and if they had not attained a complete response (CR) or CR-unconfirmed/uncertain [CR(u)] were changed to second-line chemotherapy. Adjuvant radiotherapy was administered to patients with bulky disease and those with postchemotherapy residual masses. Measurements of left ventricular ejection fraction (LVEF), gonadotropins in females, and sperm count in males were taken both before and after treatment with VEEP. RESULTS: The maximum rates of response were as follows: CR, 32%; CR(u), 47%; and PR, 21% [CR + CR(u), 79%]. The median follow-up duration is 45 months, with a 5-year overall survival (OS) rate of 89% and failure-free survival (FFS) rate of 62%. Patients in CR at the end of chemotherapy had a higher FFS at 5 years compared with patients in CR(u) (88% v 56%). Acute toxicity was mild, with no pulmonary toxicity or treatment-related deaths. The median LVEF was 62% before VEEP and 57% after VEEP. Gonadal function tests following treatment were normal in 92% of males and 100% of females. No second malignancies have been observed. CONCLUSION: VEEP is an active combination with tolerable acute toxicity that preserves fertility and cardiopulmonary function. The efficacy of VEEP is comparable to that of established regimens, but a definitive evaluation of its potential to reduce second malignancies will require a longer follow-up duration.
Adolescent↗
Effect of NHS and Community Care Act. No significant change in discharges.
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Aftercare↗
Relation between biochemical severity and intelligence in early treated congenital hypothyroidism: a threshold effect.
OBJECTIVES: To assess whether early treatment of congenital hypothyroidism fully prevents intellectual impairment. DESIGN: A national register of children with congenital hypothyroidism who were compared with unaffected children from the same school classes and matched for age, sex, social class, and first language. SETTING: First three years (1982-4) of a neonatal screening programme in England, Wales, and Northern Ireland. SUBJECTS: 361 children with congenital hypothyroidism given early treatment and 315 control children. MAIN OUTCOME MEASURES: Intelligence quotient (IQ) measured at school entry at 5 years of age with the Wechsler preschool and primary scale of intelligence. RESULTS: There was a discontinuous relation between IQ and plasma thyroxine concentration at diagnosis, with a threshold at 42.8 nmol/l (95% confidence interval 35.2 to 47.1 nmol/l). Hypothyroid children with thyroxine values below 42.8 nmol/l had a mean IQ 10.3 points (6.9 to 13.7 points) lower than those with higher values and than controls. None of the measures of quality of treatment (age at start of treatment (range 1-173 days), average thyroxine dose (12-76 micrograms in the first year), average thyroxine concentration during treatment (79-234 nmol/l in the first year), and thyroxine concentration less than 103 nmol/l at least once during the first year) influenced IQ at age 5. CONCLUSIONS: Despite early treatment in congenital hypothyroidism the disease severity has a threshold effect on brain development, probably determined prenatally. The 55% of infants with more severe disease continue to show clinically significant intellectual impairment; infants with milder disease show no such impairment. The findings predict that 10% of early treated infants with severe hypothyroidism, compared with around 40% of those who presented with symptoms in the period before screening began, are likely to require special education.
Child, Preschool↗
Intelligence in mild atypical phenylketonuria.
In 82 children with mild phenylketonuria (PKU) (blood phenylalanine (Phe) concentrations consistently below 900 mumol/l throughout follow up) the relationship between intelligence at age 4 (IQ by Stanford-Binet) and average blood Phe concentrations from birth to 4 years was examined. Of the 82 children 24 had received no treatment. In the group as a whole, and in the 24 untreated subjects alone, mean IQs were significantly below population norms, with deficits of approximately 4.5 points and 9 points respectively. After allowing for social class IQ fell progressively by approximately 6 points for each 100 mumol/l rise in mean Phe concentrations in both the treated and untreated subjects. This relationship resembled that previously reported in early treated children with more severe forms of PKU, except that the scale of the relationship was even greater. We conclude that all children whose blood Phe concentrations reach 400 mumol/l or above should receive a low Phe diet, at least during the preschool years, and that the aim should be to control blood Phe levels below 400 mumol/l throughout early childhood in all forms of PKU.
Child, Preschool↗
Submandibular gustatory sweating.
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Adult↗
Anesthetic Considerations for Laparoscopic Surgery.
Laparoscopic surgery presents attendant challenges for the anesthesiologist. Cardiovascular and respiratory function may be affected adversely by the presence of a pneumoperitoneum; airway management may be difficult because of the patient's position; and postoperative pain, although less than that experienced after traditional, open surgery, can still result in considerable discomfort. These complications, and several choices of anesthetic technique, are discussed.
Journal Article↗