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Biomedical subjects

S E Stewart

Publications and source records attributed to S E Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Practice MRI: reducing the need for sedation and general anaesthesia in children undergoing MRI.

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non-GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non-diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty-four children undertook a practice MRI (age range 4.1-16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non-GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.

Adolescent↗
PubMed2004

Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature.

OBJECTIVE: To review the extant literature on the long-term outcome of child/adolescent-onset obsessive-compulsive disorder (OCD). METHOD: Medline and Psychlit databases were systematically searched for articles regarding long-term outcomes of child/adolescent-onset OCD. Meta-analysis regression was applied to evaluate predictors and persistence of OCD. RESULTS: Sixteen study samples (n = 6-132; total = 521 participants) in 22 studies had follow-up periods ranging between 1 and 15.6 years. Pooled mean persistence rates were 41% for full OCD and 60% for full or subthreshold OCD. Earlier age of OCD onset (z = -3.26, P = 0.001), increased OCD duration (z = 2.22, P = 0.027) and in-patient vs. out-patient status (z = 2.94, P = 0.003) predicted greater persistence. Comorbid psychiatric illness and poor initial treatment response were poor prognostic factors. Although psychosocial function was frequently compromised, most studies lacked comprehensive outcome measures. CONCLUSION: Long-term persistence of pediatric OCD may be lower than believed. Future studies should include broader measures of outcome including symptomatic persistence and functional impairment in multiple domains.

Adolescent↗
PubMed2001

Timing and magnitude of frontal activity differentiates refixation and anti-saccade performance.

EEG data were recorded while 10 subjects generated refixation saccades towards a visual target and antisaccades away from a visual cue. Theoretically, the same basic neural circuitry supports refixation and correct anti-saccade performances, with additional activity in primarily dorsolateral prefrontal cortex circuitry supporting antisaccade-associated inhibitory processes. Analyses demonstrated that sensory registration of visual stimuli is similar for refixation and anti-saccade conditions. Increased frontal brain activity at 5 and 15 Hz was observed preceding correct antisaccades when compared to refixation saccades. These analyses provide specific information suggesting that 160-60 ms before saccade generation is the critical period for response inhibition.

Adult↗
PubMed2001

Suicidal children and adolescents with first emergency room presentations: predictors of six-month outcome.

OBJECTIVE: To examine risk of future documented suicide attempts and emergency room (ER) returns among children and adolescents with first suicidal ER presentations. METHOD: A total of 548 consecutive ER presentations of suicidal 5- to 19-year-olds to a Canadian center over a 1-year period (1997-1998) were reviewed. Relative risk analyses were performed on 224 first-time patients (mean age 14.6+/-2.1) to determine the strength of associations between predictors and outcomes (ER return and suicide attempts). RESULTS: At 6-month follow-up, 32.6% (n = 73) had returned to the ER, 24.1% (n = 54) had a documented suicide attempt, and 14.3% (n = 32) required psychiatric hospitalization. Predictors for both ER return and future documented suicide attempts included 15- to 19-year age range, past foster/group home placement, past mental health care, a suicide plan, reported mood symptoms, sobriety at ER visit, and general substance use. Child welfare guardianship and abuse history were also predictors of ER returns. CONCLUSIONS: Clinicians should be aware of these risk factors when assessing and managing suicidal youths with first ER presentations.

Adolescent↗
PubMed1999

Clinical and biochemical response following withdrawal of a long-acting, depot injection form of octreotide (Sandostatin-LAR).

OBJECTIVE: Monthly injections of Sandostatin-LAR have been shown to be an effective therapy for patients with acromegaly. Because of an ongoing need to assess a patients response to definitive therapy such as surgery and/or radiotherapy, we aimed to evaluate GH levels and acromegaly symptom scores in patients withdrawing from Sandostatin-LAR. DESIGN AND PATIENTS: 12 patients with acromegaly previously treated with Sandostatin-LAR, 20-40 mg intramuscularly every 28 (n = 9) or 42 (n = 3) days for 12-36 months were studied at monthly intervals for 4 months following the withdrawal of the drug. MEASUREMENTS: Hourly fasting serum GH measurements between 0800 h and 1200 h, serum IGF-1 and symptom scores were undertaken at 4, 8, 12 and 16 weeks following the last injection of Sandostatin-LAR. MRI/CT scans of the pituitary were undertaken at 16 weeks and compared to scans taken on Sandostatin-LAR within the previous 10 months. RESULTS: Serum GH rose progressively from 7.7 (1.5 to 14.6) (median (range)) mIU/l at 4 weeks to 9.9 (1.5-21.8), to 12.6 (4.9-31.9) (P < 0.05 vs 4 weeks) and to 13.1 (6.0-39.1) mIU/l (P < 0.002) at 8, 12 and 16 weeks, respectively, following cessation of Sandostatin-LAR. IGF-1 rose from 38.5 (12.6-73.8) nmol/l at 4 weeks to 62.4 (37.4-159) at 16 weeks (P < 0.002) and mean symptom score (comprising headache, sweating, arthralgia, paraesthesiae, tiredness) from 4.0 (0 to 10) (4 weeks) to 4.5 (0-9) (8 weeks) to 6.0 (2-10) (12 weeks) to 6.5 (4-12) (16 weeks, P < 0.05). Individual GH profiles indicated a rise in GH in 5/12 patients between weeks 4-8 and between weeks 8-12 in a further 5/12 patients. There were no changes in pituitary tumour size following discontinuation of Sandostatin-LAR. CONCLUSIONS: GH and symptom scores rise progressively following discontinuation of Sandostatin-LAR in acromegalic patients. However, GH and symptom scores remain suppressed in some patients for at least 8 weeks following cessation of Sandostatin-LAR. We suggest that a withdrawal period of 3 months from Sandostatin-LAR is required in order to perform a meaningful re-assessment of GH and clinical status.

Acromegaly↗
PubMed1999

A convergent validity study of Cloninger's Temperament and Character Inventory with the Coolidge Axis II Inventory.

This study examined the convergent validity of the Temperament and Character Inventory (TCI), a measure of four biosocial temperaments and three character dimensions with the Coolidge Axis II Inventory (CATI), a measure of 14 personality disorders. A nonclinical sample of 163 college students was given both measures, and the data were analyzed with bivariate and multivariate statistics. Hypotheses generated from the findings of Svrakic, Whitehead, Przybeck, and Cloninger (1993, Archives of General Psychiatry, 50, 991-999) were confirmed for a majority of the relationships between the two measures. The preliminary results provide qualified support for the TCI and Cloninger's biosocial theory in the assessment of personality disorders.

Adolescent↗
PubMed1998

Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the management of acromegaly.

OBJECTIVES: To evaluate the efficacy and safety of a long-acting preparation of the somatostatin analogue octreotide, Sandostatin-LAR (SMS-LAR) for the treatment of acromegaly. DESIGN AND PATIENTS: Thirteen patients with acromegaly received intramuscular injections of SMS-LAR 20-40 mg at 4-6 week intervals for a period of up to 3 years. MEASUREMENTS: Serial measurement of serum GH and IGF concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study. RESULTS: One patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6-week intervals for 36 months; hence data is presented for n = 12 for up to 12 months; and thereafter n = 8. SMS-LAR significantly reduced serum GH and IGF-1 values: for the whole group GH concentrations fell from 24.8 +/- 4.2 mU/l (mean +/- SE) at baseline to 5.2 +/- 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 +/- 6.1 mU/l at baseline to 4.2 +/- 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to < 10 mU/l in all subjects and was < 5 mU/l in 50% after both 1 and 3 years. IGF-1 concentrations fell from 95 +/- 13 nmol/l at baseline to 63 +/- 13 nmol/l after 1 year (P < 0.01, n = 12; reference range < 65 nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119 +/- 14 nmol/l at baseline to 60 +/- 13 nmol/l after 3 years (P < 0.001, n = 8). IGF-1 was < 65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2 patients (15%) developed gallbladder sludge which was asymptomatic; no patient developed gallstones. CONCLUSIONS: We conclude that SMS-LAR is a safe, effective and well tolerated treatment, making it an important therapeutic option in the management of acromegaly.

Acromegaly↗
PubMed1997

Sequence and expression pattern of J chain in the amphibian, Xenopus laevis.

We have determined the cDNA sequence encoding J chain, a polypeptide accessory molecule associated with polymeric Ig, from the anuran amphibian, Xenopus laevis (South African clawed frog). The translated polypeptide consists of 164 amino acid residues, including the signal sequence, and is somewhat longer than the corresponding sequence in mouse and cow, the two mammalian species in which the signal sequence of J chain has been determined. J chain in several mammalian species (human, mouse, cow and rabbit) has eight Cys residues. In the human chain, two of these Cys residues, the second and third in the sequence, have been shown to form disulfide bridges to heavy chains in IgM or IgA; the remaining Cys residues form intrachain disulfide bonds. The Xenopus J chain contains only seven of these Cys residues. Ser is found at the position corresponding to the third Cys in mammalian J chains. Northern blot analysis, performed on RNA isolated from various organs of 3-month old frogs, indicated that the highest level of expression was in the intestine. Transcripts corresponding to J chain were also detected in the spleen and at very low levels in the thymus.

Amino Acid Sequence↗
PubMed1995

Depot long-acting somatostatin analog (Sandostatin-LAR) is an effective treatment for acromegaly.

Octreotide (Sandostatin) is a synthetic analog of somatostatin, an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly. When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of somatostatin analogs may be more effective in lowering GH. We have evaluated Sandostatin-LAR, a new long-acting preparation of Sandostatin, in eight patients with acromegaly. After an initial pharmacokinetic study, patients received a minimum of 10 im injections of Sandostatin-LAR (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight patients. This was associated with significant improvements in headache, arthralgia, and sweating. There was no evidence of octreotide accumulation, and the drug was well tolerated. To date, no gallstones have occurred, and serial pituitary imaging has revealed no increase in the size of the initial pituitary tumor. In particular, two previously untreated patients have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. Sandostatin-LAR is an effective and well-tolerated treatment for patients with acromegaly. Undoubtedly the initial indication for Sandostatin-LAR will be in the patient who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics.

Acromegaly↗
PubMed1993

Diversity of expressed V and J regions of immunoglobulin light chains in Xenopus laevis.

In Xenopus laevis, two immunoglobulin light chain isotypes, designated L1 or rho and L2 or sigma, have been identified. The genomic organization of the L1 locus has been described previously: a constant (C) gene segment is preceded by a joining (J) gene segment; in addition, there are many cross-hybridizing variable (V) gene segments. To evaluate the extent of sequence diversity of L1 V regions, we screened three cDNA libraries, constructed from mitogen-stimulated Xenopus splenocytes, with probes for the C or the J gene segment. Eighteen cDNA clones that contain complete or truncated V regions were chosen for sequence analysis. The C regions of all clones are identical or nearly identical to the genomic C gene segment; the V regions are greater than 80% identical in nucleotide sequence and are presumably derived from a single family of V gene segments. Although framework regions are nearly identical, complementarity-determining regions are quite diverse. The expressed J segments fall into distinct groups, suggesting the presence of more than one germ-line J segment. Therefore, a genomic library was screened with a J region probe. A clone overlapping with the previously identified J-C clone, and containing four additional J gene segments, was isolated. All five J gene segments are very similar and three are identical in nucleotide sequence. Each of the three distinct germ-line J sequences is represented in the set of cDNA clones, suggesting that combinatorial diversification occurs; imprecision of V-J joining also appears to contribute to variability. Overall, these results suggest that the immunoglobulin repertoire in this species is not significantly restricted by a limitation in the diversity of light chain V regions.

Amino Acid Sequence↗
PubMed1992

Genes encoding Xenopus laevis Ig L chains. Implications for the evolution of kappa and lambda chains.

Xenopus laevis Ig contain two distinct types of L chains, designated rho or L1 and sigma or L2. We have analyzed Xenopus genomic DNA by Southern blotting with cDNA probes specific for L1 V and C regions. Many fragments hybridized to the V probe, but only one or two fragments hybridized to the C probe. Corresponding C, J, and V gene segments were identified on clones isolated from a genomic library prepared from the same DNA. One clone contains a C gene segment separated from a J gene segment by an intron of 3.4 kb. The J and C gene segments are nearly identical in sequence to cDNA clones analyzed previously. The C segment is somewhat more similar and the J segment considerably more similar in sequence to the corresponding segments of mammalian kappa chains than to those of mammalian lambda chains. Upstream of the J segment is a typical recombination signal sequence with a spacer of 23 bp, as in J kappa. A second clone from the library contains four V gene segments, separated by 2.1 to 3.6 kb. Two of these, V1 and V3, have the expected structural and regulatory features of V genes, and are very similar in sequence to each other and to mammalian V kappa. A third gene segment, V2, resembles V1 and V3 in its coding region and nearby 5'-flanking region, but diverges in sequence 5' to position -95 with loss of the octamer promoter element. The fourth V-like segment is similar to the others at the 3'-end, but upstream of codon 64 bears no resemblance in sequence to any Ig V region. All four V segments have typical recombination signal sequences with 12-bp spacers at their 3'-ends, as in V kappa. Taken together, the data suggest that Xenopus L1 L chain genes are members of the kappa gene family.

Amino Acid Sequence↗
PubMed1989

Transcription by RNA polymerase I stimulates mitotic recombination in Saccharomyces cerevisiae.

The recombination-stimulating sequence HOT1 is derived from the ribosomal DNA array of Saccharomyces cerevisiae and corresponds to sequences that promote transcription by RNA polymerase I. When inserted at a chromosomal location outside the ribosomal DNA array, HOT1 stimulates mitotic recombination in the adjacent sequences. To investigate the relationship between transcription and recombination, transcription promoted by HOT1 was directly examined. These studies demonstrated that transcription starts at the RNA polymerase I initiation site in HOT1 and proceeds through the chromosomal sequences in which recombination is enhanced. Linker insertion mutations in HOT1 were generated and assayed for recombination stimulation and for promoter function; this analysis demonstrated that the same sequences are required for both activities. These results indicate that the ability of HOT1 to enhance recombination is related to, and most likely dependent on, its ability to promote transcription.

Base Sequence↗
PubMed1988

Lithium carbonate--a competitive aldosterone antagonist?

Plasma renin activity (PRA), aldosterone (aldo) levels, electrolyte levels, and blood pressures were measured in 16 patients with affective disorders taking lithium prophylactically, and in 16 age and sex-matched control subjects. PRA and aldo levels were significantly elevated in the lithium-treated group. There was no difference between the groups in plasma electrolytes or erect and supine blood pressures, arguing against secondary aldosteronism. In the lithium-treated group, there was a significant positive correlation between both PRA and plasma aldo vs serum lithium. We postulate that lithium inhibits the action of aldosterone on the distal tubule in the kidney. Activation of the renin angiotensin system maintains normal blood pressure and plasma electrolytes.

Adult↗
PubMed1987

High sodium intake increases platelet aggregation in normal females.

Platelet activation and aggregation appear to play an important part in the development of vascular disease. We studied the effect of varying sodium intake on total plasma serotonin and in vitro aggregation of blood platelets. A total of 12 normal female volunteers were studied after 5 days on a 10 or 200 mmol/day sodium diet. Aggregation studies were performed by incubating stirred platelet-rich plasma (PRP) with adenosine diphosphate (ADP) at final concentrations of 1 and 4 mumol/l; we also studied the effect of pre-incubating PRP with ketanserin or saralasin (1 mumol/l and 1 nmol/l final concentration, respectively). Salt-loading produced a significant increase in platelet aggregation induced by both 1 and 4 mumol/l ADP, and also a significant fall in PRP in serotonin concentration; since there was also a significant drop in the yield of platelets in PRP during salt-loading, the difference in serotonin concentration was not significant when expressed as pmol serotonin/10(8) platelets. There was a significant negative correlation between log serotonin levels (nmol/l) and % aggregation induced by 4 mumol/l ADP. Ketanserin decreased aggregation (induced by 4 mumol/l ADP) in PRP obtained during high salt intake; saralasin had no effect on aggregation, but did cause a decrease in light transmission. These results indicate that in normal females: (1) in vitro platelet aggregation is increased with high sodium intake, and this effect was reduced by addition of ketanserin; (2) PRP platelet count and total plasma serotonin levels are both significantly altered by changes in sodium status; (3) aggregation (%) is inversely proportional to log serotonin concentration (nmol/l).

Adult↗
PubMed1982

Cold-sensitive cell-division-cycle mutants of yeast: isolation, properties, and pseudoreversion studies.

We isolated 18 independent recessive cold-sensitive cell-division-cycle (cdc) mutants of Saccharomyces cerevisiae, in nine complementation groups. Terminal phenotypes exhibited include medial nuclear division, cytokinesis, and a previously undescribed terminal phenotype consisting of cells with a single small bud and an undivided nucleus. Four of the cold-sensitive mutants proved to be alleles of CDC11, while the remaining mutants defined at least six new cell-division-cycle genes: CDC44, CDC45, CDC48, CDC49, CDC50 and CDC51.--Spontaneous revertants from cold-sensitivity of four of the medial nuclear division cs cdc mutants were screened for simultaneous acquisition of a temperature-sensitive phenotype. The temperature-sensitive revertants of four different cs cdc mutants carried single new mutations, called Sup/Ts to denote their dual phenotype: suppression of the cold-sensitivity and concomitant conditional lethality at 37 degrees. Many of the Sup/Ts mutations exhibited a cell-division-cycle terminal phenotype at the high temperature, and they defined two new cdc genes (CDC46 and CDC47). Two cold-sensitive medial nuclear division cdc mutants representing two different cdc genes were suppressed by different Sup/Ts alleles of another gene which also bears a medial nuclear division function (CDC46). In addition, the cold-sensitive medial nuclear division cdc mutant csH80 was suppressed by a Sup/Ts mutation yielding an unbudded terminal phenotype with an undivided nucleus at the high temperature. This mutation was an allele of CDC32. These results suggest a pattern of interaction among cdc gene products and indicate that cdc gene proteins might act in the cell cycle as complex specific functional assemblies.

Cell Cycle↗
PubMed1980

Biologic interaction of gamma radiation with phenylbutazone, phenytoin, or hydralazine.

Combination of repeated administration of phenylbutazone (7 mg/kg for two weeks) or phenytoin (20 mg/kg for four weeks) and acute exposure to gamma radiation (696 REM) induced increased lethality in mice much greater than that observed fro use of either drug or radiation alone. Lethality in chronic hydralazine (10 mg/kg for four weeks) treated mice subjected also to gamma radiation was not different than that observed after either drug or radiation alone. Decrease in liver glutathione was observed in mice receiving combined drug-radiation treatment as also were leucocyte counts, but neither of these parameters supported as assumption of site of common lethal mechanism.

Animals↗