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S J Smith

Publications and source records attributed to S J Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

A survey of Australasian obstetric anaesthesia audit.

In order to develop a minimal obstetric anaesthesia dataset based on current Australasian clinical audit best practice, we carried out a postal survey of 69 Australasian anaesthetic departments covering an obstetric service. We asked about data being collected, specifically concerning the high risk obstetric patient, epidural analgesia and postoperative anaesthetic review. Examples of any data collection forms were requested. Of the 66 responses, 35 departments (53%) were not collecting any audit data. Twenty-six of the 31 departments (84%) performing obstetric anaesthesia audit responded to our follow-up telephone survey. Eighteen departments believed that there had been an improvement in patient care as a result of their audit and 13 felt that the benefits outweighed the costs involved. However, only six departments (9%) had performed an audit cycle. The importance of feedback to patients or hospital staff and the incidence of post dural puncture headache (PDPH) were cited by some as priorities for obstetric anaesthesia audit. There was however no consistency as to what data should be collected. Many responses suggested a perceived need to collect clinical data without knowing what to do with it. Our survey has highlighted confusion between three distinct objectives; a dataset for obstetric anaesthesia record keeping, data required for continuing patient management in hospital and, a specific minimal dataset for clinical audit purposes. We conclude that current Australasian obstetric anaesthesia audit strategies are inadequate to develop a minimal dataset for cost-effective clinical audit.

Analgesia, Epidural↗
PubMed1999

Pill-induced esophagitis caused by oral rifampin.

OBJECTIVE: To report a case of pill-induced esophagitis caused by oral rifampin. DATA SOURCES: English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles. DATA SYNTHESIS: A large number of oral medications have been reported to cause pill-induced esophagitis. This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture. CONCLUSIONS: Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients. Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications.

Administration, Oral↗
PubMed1999

Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages.

Pseudovitamin D-defiency rickets (PDDR) is an autosomal recessive disorder characterized by hypocalcemia, rickets (which are resistant to treatment with vitamin D), and low or undetectable serum levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). The symptoms are corrected with 1,25(OH)2D treatment, and the disease is now believed to result from a defect in the cytochrome P450 component (P450c1; CYP27B1) of the renal 25-hydroxyvitamin D-1alpha-hydroxylase (1-OHase). We have studied genomic DNA from three families with PDDR and have identified the same homozygous mutation in the P450c1 gene in two of the index cases, causing a frameshift in exon 8, resulting in a premature stop codon in the heme-binding domain. The two cases in the third kindred were compound heterozygotes with missense mutations in exons 6 and 9. We have also identified a C/T polymorphism in intron 6 of the P450c1 genomic DNA. Interferon gamma-inducible 1-OHase activity in blood-derived macrophages was shown by 1,25(OH)2D synthesis in all control cells tested (37-184 fmol/h/106 cells) and those from the PDDR family parents (34-116 fmol/h/106 cells) but was totally absent from the patients' cells, indicating a defect in their macrophage 1-OHase, similar to the presumed renal defect. The assumption of similarity between the renal and macrophage P450c1 was supported by our ability to clone a 514 bp sequence, including the heme-binding region of the macrophage P450c1 cDNA from controls, which was identical to that published for both the renal and keratinocyte P450c1 cDNAs.

24,25-Dihydroxyvitamin D 3↗
PubMed1999

Comparison of plasma total homocysteine measurements in 14 laboratories: an international study.

BACKGROUND: Information on interlaboratory variation and especially on methodological differences for plasma total homocysteine is lacking. METHODS: We studied 14 laboratories that used eight different method types: HPLC with electrochemical detection (HPLC-ED); HPLC with fluorescence detection (HPLC-FD) further subdivided by type of reducing/derivatizing agent; gas chromatography/mass spectrometry (GC/MS); enzyme immunoassay (EIA); and fluorescence polarization immunoassay (FPIA). Three of these laboratories used two methods. The laboratories participated in a 2-day analysis of 46 plasma samples, 4 additional plasma samples with added homocystine, and 3 plasma quality-control (QC) pools. Results were analyzed for imprecision, recovery, and methodological differences. RESULTS: The mean among-laboratory and among-run within-laboratory imprecision (CV) was 9.3% and 5.6% for plasma samples, 8.8% and 4.9% for samples with added homocystine, and 7.6% and 4.2% for the QC pools, respectively. Difference plots showed values systematically higher than GC/MS for HPLC-ED, HPLC-FD using sodium borohydride/monobromobimane (however, for only one laboratory), and EIA, and lower values for HPLC-FD using trialkylphosphine/4-(aminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole. The two HPLC-FD methods using tris(2-carboxyethyl) phosphine/ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F) or tributyl phosphine/SBD-F, and the FPIA method showed no detectable systematic difference from GC/MS. CONCLUSIONS: Among-laboratory variations within one method can exceed among-method variations. Some of the methods tested could be used interchangeably, but there is an urgent need to improve analytical imprecision and to decrease differences among methods.

Chromatography, High Pressure Liquid↗
PubMed1999

Validation of accuracy-based amino acid reference materials in dried-blood spots by tandem mass spectrometry for newborn screening assays.

BACKGROUND: Advances in technology and the earlier release of newborns from hospitals have pressed the demand for accurate calibration and improved interlaboratory performance for newborn screening tests. As a first step toward standardization of newborn screening aminoacidopathy tests, we have produced six-pool sets of multianalyte dried-blood-spot amino acid reference materials (AARMs) containing predetermined quantities of five amino acids. We describe here the production of the AARMs, validation of their amino acid contents, and characterization of their homogeneity and their stability in storage. METHODS: To each of six portions of a pool of washed erythrocytes suspended in serum we added Phe (0-200 mg/L), Leu (0-200 mg/L), Met (0-125 mg/L), Tyr (0-125 mg/L), and Val (0-125 mg/L). Six-pool sets (1300) were prepared, dried, and packaged. We used isotope-dilution mass spectrometry to estimate the endogenous amino acid concentrations of the AARMs and validate their final amino acid concentrations. We used additional tandem mass spectrometry analyses to examine the homogeneity of amino acid distribution in each AARM, and HPLC analyses to evaluate the stability of the amino acid contents of the AARMs. RESULTS: The absolute mean biases across the analytic range for five amino acids were 2.8-9.4%. One-way ANOVAs of the homogeneity results predicted no statistically significant differences in amino acid concentrations within the blood spots or within the pools (P >0.05). Regression slopes (0 +/- 0.01) for amino acid concentrations vs storage times and their P values (>0.05) showed no evidence of amino acid degradation at ambient temperatures, 4 degrees C, or -20 degrees C during the intervals tested. CONCLUSION: The validation, homogeneity, and stability of these blood spots support their use as a candidate national reference material for calibration of assays that measure amino acids in dried-blood spots.

Amino Acids↗
PubMed1999

Comparison of serum and plasma methylmalonic acid measurements in 13 laboratories: An international study.

BACKGROUND: Detection of cobalamin deficiency is increasingly important, and methylmalonic acid (MMA) appears to be a useful marker. Information on interlaboratory variation and on methodological differences for MMA in serum and plasma is limited. METHODS: Using gas chromatography/mass spectrometry, 13 laboratories participated in a 2-day analysis of 8 serum and 11 EDTA-plasma specimens. Results were analyzed for imprecision, recovery, and differences among laboratories and methods. RESULTS: The mean among-laboratory imprecision (CV) was 19% and 21% for serum and plasma samples, respectively, and 9.3% and 7.8% for serum and plasma samples with added MMA, respectively. The mean within-laboratory (among-run) CV was 13% for both serum and plasma samples and 5.2% and 4.9% for serum and plasma samples with added MMA. Within-method imprecision was the same or higher than among-method imprecision. The mean among-laboratory recovery of MMA was 105% and 95% in serum and plasma, respectively. Most laboratories showed a proportional bias relative to the consensus mean of up to 15%. Two laboratories reported results that on average were almost 30% higher than the consensus mean. CONCLUSIONS: No method differences were found, but significant among-laboratory imprecision was found in the present study. Improvements are needed to reduce the analytical imprecision of most laboratories, and attention must be focused on calibration issues. Differences among laboratories can be improved by introducing high-quality reference materials and by instituting external quality assessment programs.

Calibration↗
PubMed1999

Video-EEG telemetry: apparent manifestation of both epileptic and non-epileptic attacks causing potential diagnostic pitfalls.

Video-EEG telemetry is often used to support the diagnosis of non-epileptic seizures (NES). Although rare, some patients may have both epileptic seizures (ES) and NES. It is crucially important to identify such patients to avoid the hazards of inappropriate anticonvulsant withdrawal. To delineate the electroclinical characteristics and diagnostic problems in this group of patients, we studied the clinical, EEG and MRI features of 14 consecutive patients in whom separate attacks, considered to be both NES and ES were recorded using video-EEG telemetry. Only two patients were drug-reduced during the telemetry. Most patients had their first seizure (ES or NES) in childhood (median age 7 years; range: 6 months-24 years); 8/14 patients were female. Brain MRI was abnormal in 10/14 patients. Interictal EEG abnormalities were present in all patients; 13/14 had epileptiform and 1/14 only background abnormalities. Over 70 seizures were recorded in these 14 patients: in 12/14 patients, the first recorded seizure was a NES (p < 0.001), and 7 of these patients had at least one more NES before an ES was recorded. Only 3/14 patients had more than 5 NES before an ES was recorded. Recording a small number of apparently NES in an individual by no means precludes the possibility of additional epilepsy. Particular care should be taken, and multiple (> 5) seizure recording may be advisable, in patients with a young age of seizure onset, interictal EEG abnormalities, or a clear, potential aetiology for epilepsy.

Adolescent↗
PubMed1998

Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis.

Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined; during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation.

3T3 Cells↗
PubMed1998

Mechanisms of epithelial cell-cell adhesion and cell compaction revealed by high-resolution tracking of E-cadherin-green fluorescent protein.

Cadherin-mediated adhesion initiates cell reorganization into tissues, but the mechanisms and dynamics of such adhesion are poorly understood. Using time-lapse imaging and photobleach recovery analyses of a fully functional E-cadherin/GFP fusion protein, we define three sequential stages in cell-cell adhesion and provide evidence for mechanisms involving E-cadherin and the actin cytoskeleton in transitions between these stages. In the first stage, membrane contacts between two cells initiate coalescence of a highly mobile, diffuse pool of cell surface E-cadherin into immobile punctate aggregates along contacting membranes. These E-cadherin aggregates are spatially coincident with membrane attachment sites for actin filaments branching off from circumferential actin cables that circumscribe each cell. In the second stage, circumferential actin cables near cell-cell contact sites separate, and the resulting two ends of the cable swing outwards to the perimeter of the contact. Concomitantly, subsets of E-cadherin puncta are also swept to the margins of the contact where they coalesce into large E-cadherin plaques. This reorganization results in the formation of a circumferential actin cable that circumscribes both cells, and is embedded into each E-cadherin plaque at the contact margin. At this stage, the two cells achieve maximum contact, a process referred to as compaction. These changes in E-cadherin and actin distributions are repeated when additional single cells adhere to large groups of cells. The third stage of adhesion occurs as additional cells are added to groups of >3 cells; circumferential actin cables linked to E-cadherin plaques on adjacent cells appear to constrict in a purse-string action, resulting in the further coalescence of individual plaques into the vertices of multicell contacts. The reorganization of E-cadherin and actin results in the condensation of cells into colonies. We propose a model to explain how, through strengthening and compaction, E-cadherin and actin cables coordinate to remodel initial cell-cell contacts to the final condensation of cells into colonies.

Actins↗
PubMed1998

Glia help synapses form and function.

A sophisticated new cell-culture system has shown that glial cells can promote synaptogenesis and enhance the efficacy of synaptic transmission. These effects are not secondary to increased neuronal survival but probably involve changes in neuronal activity levels and a secreted glial factor.

Animals↗
PubMed1998

Molecular epidemiology of p53 protein mutations in workers exposed to vinyl chloride.

The production of mutations in cellular tumor suppressor genes such as p53 is involved in the development of many human cancers. These mutations result in the expression of mutant forms of the encoded p53 protein which can potentially serve as a biomarker for this carcinogenic process. Workers exposed to vinyl chloride who are at risk for the development of the sentinel neoplasm angiosarcoma of the liver represent a model population for the study of such a mutant p53 biomarker, since vinyl chloride is known to cause specific p53 mutations in persons with angiosarcoma of the liver. To determine the relation between vinyl chloride exposure and this p53 biomarker, the authors examined serum samples collected between 1987 and 1992 from a cohort of 225 French vinyl chloride workers and 111 unexposed controls (matched according to age, sex, race, smoking, and alcohol drinking) for the presence of mutant p53 protein, using an enzyme-linked immunosorbent assay. Stratification of the exposed workers by quartile of vinyl chloride exposure (in estimated ppm-years) yielded a statistically significant trend of increasing odds ratios for p53 biomarker seropositivity with increasing exposure. These results suggest that this serum biomarker for mutant p53 protein is related to vinyl chloride exposure and may be an early indicator of carcinogenic risk in exposed individuals.

Adult↗
PubMed1998

Brain endothelial cell enzymes cleave platelet-retained amyloid precursor protein.

We have previously demonstrated that thrombin-activated platelets from patients with advanced Alzheimer's disease (AD) retain significantly more surface membrane-bound amyloid precursor protein (mAPP) than platelets from non-demented age-matched individuals (AM). We have studied interactions between these platelets and the cerebrovascular endothelium to which activated platelets adhere in a model system, investigating their involvement in the formation of amyloid beta peptide (Abeta) deposits in AD patients. We report here that there appear to be alpha and beta secretase-like activities in primary human blood brain barrier endothelial cell (BEC) cultures from both AD patients and AM control subjects (AD-BEC and AM-BEC, respectively) as well as a gamma secretase-like activity that appears only in AD-BEC. No such activities were observed in human umbilical vein endothelial cells (HUVECs). Furthermore, there is more penetration of the platelet-released products platelet factor 4 and soluble APP through the BEC layer grown from AD patients than that grown from AM individuals, whereas none penetrate through a HUVEC layer. Thus the interaction between platelets, the APP they have retained or released, and cerebral vascular endothelial cells may be at least partially responsible for amyloidogenic deposits around the cerebral vasculature of AD patients.

Adult↗
PubMed1998

Firearm ownership in households with children.

BACKGROUND/PURPOSE: Increased morbidity and mortality rates in children injured by firearms has been well documented during this past decade. The aim of this study was to determine the socioeconomic factors affecting firearm ownership in families with children living in suburban/rural versus inner-city environments, and to identify predictors of firearm ownership in these families. METHODS: Parents of children less than 19 years old seen in a suburban (n = 751) or inner-city hospital (n = 406) anonymously completed a questionnaire regarding firearm ownership. RESULTS: Firearm ownership was 54% in rural locations, versus 18% among inner-city residents (P< .05). Firearm ownership in white households was 45% versus 20% in African-American households (P< .05). Mean number of all types of firearms in white households was 3.38 versus 1.78 in black households (P< .001). Firearm ownership was 19% in the less than $20,000 income bracket, significantly lower than households with greater incomes, and was significantly lower in households in which parents had the least education (19.7%) versus those with college degrees (38.5%; P< .05). Firearm owners of rifles and shotguns significantly more often cited hunting, collection, and target shooting as reasons for owning firearms, in contrast to revolver owners who cited protection and collection as reasons for firearm ownership (P < .05). CONCLUSIONS: Firearm ownership is higher in rural, caucasian versus inner-city African-American residents and is significantly less in households with lower income and educational levels. Significant predictors for firearm ownership were number of parents in households, educational level of parents, and population of residence.

Adult↗
PubMed1998

The costs of treating breast cancer in the United Kingdom: implications for screening.

Total treatment costs by stage at diagnosis are estimated for a sample of breast cancer patients. At 4 years, stage 4 cancers emerge as being more expensive to treat than those at earlier stages, although this difference fails to achieve significance when expected lifetime costs are considered. The inclusion of treatment cost estimates in a screening model indicates that screening may increase expected treatment costs by a marginal amount, although the model also suggests that the cost-effectiveness ratio of breast cancer screening might be better than had originally been thought.

Adult↗
PubMed1998

Primary sequence and molecular model of the variable region of a mouse monoclonal anti-Der p 1 antibody showing a similar epitope specificity as human IgE.

BACKGROUND: Der p 1, a major mite allergen, elicits IgE antibody responses in 80% of patients suffering from dust mite allergy. Given the potent IgE eliciting properties of Der p 1, there is considerable interest in studying the molecular architecture of the variable (Fv) region of IgE antibodies specific for this allergen. OBJECTIVES: IgE is present in human serum at extremely low concentrations, and as such it is practically impossible to purify sufficient quantities for structural studies. We have therefore sought to sequence and model a representative murine monoclonal (MoAb) anti-Der p 1 antibody, as a surrogate human IgE. METHODS: The cDNA coding for the Fv region of an anti-Der p 1 MoAb (2C7), that mimics the binding of human IgE to Der p 1, was amplified by PCR, cloned and sequenced. The predicted amino acid sequences were then compared with a directory of human germline V-gene segments. Modelling of the Fv region of MoAb 2C7 was carried out using the extensive database of existing immunoglobulin structures in the Brookhaven PDB. RESULTS: The MoAb 2C7 heavy chain showed greater than 70% homology with three members of the VH3 family, DP-35, DP-53 and DP-54. Similarly, the light chain showed greater than 70% homology with 11 VK sequences, including the VKII sequences DPK18, DPK19 and DPK28. A molecular model of the Fv region of MoAb 2C7 was generated and can be accessed from the EMBL databank. CONCLUSIONS: Antibodies similar to MoAb 2C7 could be generated as part of the human repertoire. The availability of 3-dimensional model of MoAb 2C7, as a surrogate human IgE antibody, combined with further data on its epitope specificity, will facilitate studies into IgE antibody responses to Der p 1.

Amino Acid Sequence↗
PubMed1998

Nonlinear analysis of EEG in septic encephalopathy.

Electroencephalograms (EEG) were recorded in fourteen patients who experienced a severe septic encephalopathy (SE). EEG analysis included visual inspection, spectral analysis and a recently developed nonlinear analysis (the Kaplan test). All EEGs showed decreased fast activity and an increase of slow wave activity on visual inspection. There was a nonsignificant trend of negative correlation between the spectral EEG analysis and the severity of the acute systemic illness (based on the sum score of 14 variables known as APACHE II score) (standard coefficient = -0.43, p = 0.118). However, a much more pronounced and significant negative correlation was observed between the Kaplan test and the APACHE II score (standard coefficient = -0.94, p = 0.005). The EEG abnormalities seen in these patients were independent of the sedation level. Neither the EEG parameters, nor the APACHE II score, predicted outcome. Nonlinear analysis is more powerful than spectral analysis to extract clinical relevant information from EEGs in patients who experience a severe SE. The nonlinear EEG analysis suggest that brain dynamics in SE may be characterized by a shift into a fundamentally different level of cortical information exchange which can be summarized in nonlinear terminology as a loss of deterministic structure in the EEG.

APACHE↗
PubMed1998

Case of the month: April 1998--30 year old male with perineal numbness.

A 30-year-old male presented with a 2 year progressive course of bowel and bladder dysfunction, mild leg weakness and sensory abnormalities in sacral dermatomes. MRI showed an intra-axial conus medullaris lesion which was excised and identified as a ganglioglioma. The case presents the typical clinical course and histopathology of this unusual lesion which carries a favorable prognosis after gross total removal. Preoperative neurological function in such patients is highly predictive of post-operative outcome.

Adult↗