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Biomedical subjects

G Stewart

Publications and source records attributed to G Stewart.

At least 73 records · Page 4Linked to original sources
PubMed1996

Comparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links.

We have compared the use of new markers of bone turnover in the assessment and treatment of Paget disease and made observations on the mechanisms of bone resorption. Urine hydroxyproline (Hyp) as a bone resorption marker and serum alkaline phosphatase (ALP) as a bone formation marker have traditionally been used to biochemically assess and monitor treatment of Paget disease. Hyp and total ALP were compared with total urine pyridinoline (Pyd) and deoxypyridinoline (Dpd), free urine Pyd and Dpd, urine type I collagen N-terminal cross-linked telopeptide (NTX), type I collagen C-terminal propeptide (PICP), serum osteocalcin, and bone ALP in Paget patients treated with pamidronate. Patients were divided into three biochemical severity-based treatment groups by their fasting urine hydroxyprolline excretion (HypE) levels (Le., group 1, HypE < 5.0 mumol/l of glomerular filtrate [GF]; group 2, HypE of 5.0-9.9 mumol/l of GF; group 3, HypE > 10 mumol/l of GF). Group 1 received one 60 mg intravenous infusion of pamidronate, and groups 2 and 3 received four and six 60 mg infusions at weekly intervals, respectively. Fasting serum and morning urine specimens were taken before and at 2, 6, 13, and 26 weeks after starting treatment. Baseline Z scores were used to compare separation of patient results from normal, and the difference in Z scores from baseline to 13 weeks was used to compare response to treatment. Baseline discrimination and response to treatment at all disease activity levels was greatest for NTX and was poor for osteocalcin, PICP, and C-terminal cross-linked telopeptide of type I collagen (ICTP). The other markers showed good discrimination and response at medium and high levels of disease activity. NTX, total Pyd and Dpd, free Pyd and Dpd, and ICTP are all pyridinoline cross-link-based markers, but discrimination and response by NTX was generally much greater than for the others. Determination of the mechanism of the difference between NTX and other cross-link measures is necessary for appropriate use of the markers and may also lead to a better understanding of the bone resorption process. It has been proposed that the greater sensitivity and discrimination of NTX is because it is more bone-specific than the other cross-link markers with significant amounts of free Pyd and Dpd coming from nonbone sources. We propose another model where the proportion of peptide-bound cross-links such as NTX may be increased in high bone turnover states partly due to a rate-limiting step in their degradation to free cross-links. Conditions with high bone resorption rates would have high levels of NTX that would decline rapidly when resorption rates fall to a level where the capacity to degrade NTX matches the rate of production.

Aged↗
PubMed1996

Patient outcomes after reoperation on the lumbar spine.

A consecutive series of thirty-nine patients who had had a reoperation of the lumbar spine was followed up for an average of forty-eight months (range, twenty-four to eighty-six months). The patients were evaluated with regard to pain, functional status, and work status. Twenty-eight patients (72 percent) had a successful outcome, as determined by their ability to return to work, their lack of a need for narcotic analgesics, and their satisfaction with the operative results. Factors that were significantly associated with a successful outcome included a younger age (p < 0.02), working outside the home (p < 0.05), an initial period of improvement after the previous (index) operation (p < 0.01), fewer spinal levels operated on previously (p < 0.05), and a revision procedure incorporating anterior interbody arthrodesis (p < 0.02).

Adult↗
PubMed1995

Gender and estrous cycle effects of the 5-HT1A agonist, 8-OH-DPAT, on hypothalamic serotonin.

Effects of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.04, 0.25, or 1.0 mg/kg), on hypothalamic serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and their ratio were determined in adult male rats and in diestrous, proestrous, and estrous female rats. Consistent with its action at the somatodendritic 5-HT1A autoreceptor, 8-OH-DPAT decreased the 5-HIAA/5-HT ratio, but the decrease was least evident in proestrous females and in males. Similar to hypothalamic tissue, there was also a decline in the 5-HIAA/5-HT ratio in the hippocampus after treatment with 0.25 mg/kg 8-OH-DPAT. When ovariectomized rats were treated with oil or estradiol benzoate followed 48 h later by oil or progesterone, 0.25 mg/kg 8-OH-DPAT produced a decrease in the hypothalamic 5-HIAA/5-HT ratio in every group except those rats treated with progesterone without estrogen priming. Treatment with estradiol benzoate increased hypothalamic 5-HIAA, and both progesterone and 8-OH-DPAT reduced the metabolite to the level of the ovariectomized control. These results suggest that both estrogen and progesterone contribute to an estrous cycle modulation of the 5-HT1A somatodendritic autoreceptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1995

Resistance to Onchocerca volvulus: differential cellular and humoral responses to a recombinant antigen, OvMBP20/11.

Persons putatively immune (PI) to Onchocerca volvulus (Ov) infection were identified in Ecuador on the basis of epidemiologic, clinical, and parasitologic findings. Immune responses of PI subjects to a recombinant onchocercal protein, OvMBP20/11, were determined and compared with those of a comparable infected (INF) group from the same Ov-endemic area. PI subjects had significantly less antibody reactivity to this molecule; however, not all INF subjects had an antibody response. IgG1 and IgG4 were the predominant IgG subclasses induced to this molecule, and the amount of IgG1 produced was the only significant difference between the PI and INF groups. In contrast to the antibody responses, proliferative responses to OvMBP20/11 were significantly higher in PI than in INF subjects. Cytokine analysis of peripheral blood mononuclear cell culture supernatants revealed that INF subjects produced significantly more interleukin-10 in response to OvMBP20/11 than did PI subjects. This antigen induced few other cytokines, and there were no differences between study groups.

Animals↗
PubMed1995

Soft tissue swelling with fractures: abuse versus nonintentional.

The objectives were to 1) define the amount of postfracture swelling at presentation in long bone fractures, and 2) to study the relationship between suspected abuse and/or neglect (A/N) and degree of postfracture swelling at presentation. This was a prospective study of 37 patients less than 11 years of age presenting with long bone fractures to the emergency department (ED) of the Children's Hospital of Michigan between August 1992 and December 1992. Data were recorded at the time of the ED visit and from medical records which were reviewed four to six months later. Of the patients enrolled in the study, eight were categorized as A/N and 29 as nonintentional. There was no difference in reported injury age between the two groups (15.5 +/- 24.5 hours vs 14.0 +/- 17.7, P = 0.8). At presentation the mean increase in circumference from post-fracture swelling was 9.6 +/- 7.1%, using the uninjured extremity as the control. The abuse group had a lesser increase in circumference compared to the nonintentional group, even after adjusting for injury age (3.8 +/- 3.6% vs 11.2 +/- 7.0%, P < 0.006). We concluded that patients with long bone fractures had a mean swelling of 9.6 +/- 7.1% at presentation. Injuries induced by A/N present with less swelling than similar injuries sustained nonintentionally, and we speculate that this difference indicates that the history and/or time of injury may not be reliable.

Acute Disease↗
PubMed1995

The Functional Independence Measure: a comparative validity and reliability study.

The majority of measurement scales used to evaluate outcome in rehabilitation are ordinal in nature and consequently statistically valid assessments of change are difficult to make. The Functional Independence Measure (FIM) can be weighted to possess interval properties, potentially allowing more accurate analysis of change. In this study the FIM was compared to the Barthel Index (BI) to determine its validity, reliability and ease of use in two groups of 25 patients undergoing neurorehabilitation. The FIM was considered to be more valid than the BI, and equally reliable in the assessment of disability. When the two disability scores were compared using subjective and objective assessment the agreement between them was comparable, although neither was high.

Activities of Daily Living↗
PubMed1995

Transient global amnesia and cortical blindness after vertebral angiography: further evidence for the role of arterial spasm.

We describe a series of six patients who experienced severe retrograde amnesia (five cases) or cortical blindness (one case) during selective vertebral angiography. All angiograms were obtained with the same nonionic contrast medium. Analysis of the contrast batch demonstrated no abnormalities, but investigation of the angiographic suite revealed a faulty contrast warming cabinet resulting in injection of contrast material above body temperature. The warming cabinet was withdrawn, and the complication has not recurred. We believe that these symptoms reflect ischemia caused by vertebral arterial spasm.

Adult↗
PubMed1995

Use of dexamethasone in the outpatient management of acute laryngotracheitis.

OBJECTIVE: Recent studies have demonstrated that a single intramuscular injection of dexamethasone (0.6 mg/kg) shortens the duration and severity of illness in hospitalized patients with acute viral laryngotracheitis (croup). Our objective was to determine if dexamethasone has a role in the outpatient management of patients with acute viral croup of moderate severity. METHODS: Patients, 6 months to 5 years of age, who came to the emergency department (ED) with acute viral croup, a croup score of at least 2 (range 0 to 17), and a disposition of discharge were randomized in a double-blind fashion to receive a single intramuscular injection of dexamethasone, 0.6 mg/kg, or an equal volume of normal saline before discharge from the ED. Patients were excluded if they had any structural abnormalities, had received any steroids in the preceding 24 hours, or if they required beta-agonist therapy, more than one racemic epinephrine treatment, or hospitalization. Patients were followed up by telephone 24 hours and 7 to 10 days after discharge to determine whether additional medical attention was sought for perceived lack of improvement or worsening of symptoms. Secondary outcome included the parents' perception of how the child was doing at 24 hours, based on a 4-point ordinal scale: worse (1), same (2), improved (3), symptoms resolved (4), and the number of days it took for complete recovery. RESULTS: Of the 38 patients comprising the study group, 19 received dexamethasone. The median age was 19 months (range 6 to 66 months), and median pretreatment croup score was 3 (range 2 to 5) for both groups. The number of patients requiring racemic epinephrine was similar in both groups. Five patients sought additional medical attention within 48 hours. Four of the five patients had received placebo (21% of the placebo group) and one had received dexamethasone (5% of the steroid group) (not statistically significant). At the 24-hour telephone follow-up, significantly more patients in the dexamethasone group had a score consistent with improvement compared with placebo (84% vs 42%, P = .003). There was no difference in the number of days for symptoms to completely resolve between the two groups. CONCLUSION: The use of dexamethasone in the outpatient management of viral croup was associated with a reduction in severity of illness within 24 hours after treatment. Patients with viral croup of moderate severity should be considered as candidates for the use of dexamethasone before discharge from the ED.

Ambulatory Care↗
PubMed1994

HIV infection in recipients of blood products from donors with known duration of infection.

From a registry of people with transfusion-acquired HIV infection, 25 recipients were identified for whom the dates of HIV infection in the 8 corresponding donors could be established. Longer times to AIDS and to death in recipients were independently associated (p < 0.01) with the receipt of blood from donors who developed AIDS more than 10 years after HIV infection, as well as with older age and fewer transfusions. Sex, zidovudine treatment, and severity of illness at transfusion were not significantly associated with survival.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Mutations in the zinc-finger region of the yeast regulatory protein ADR1 affect both DNA binding and transcriptional activation.

The expression of the yeast ADH2 gene is controlled by the transcriptional activator ADR1, a zinc-finger protein that binds to an upstream activating sequence (UAS1) in the ADH2 promoter. We report here the isolation of seven mutations in the ADR1-5c allele, defining five different amino acid changes, that suppress the enhanced ADH2 expression caused by the ADR1-5c allele. Each of the mutations was shown to reduce the activation of ADH2 by a wild-type ADR1 gene, suggesting the mutations disrupt a domain important to the function of both the ADR1 and ADR1-5c proteins. All five amino acid changes occurred within the DNA-binding domain of ADR1 and were shown to severely inhibit the ability of ADR1 to bind UAS1 in vitro. These mutations were found, however, to also affect the ability of ADR1 to activate transcription independent of its ability to bind DNA. These results indicate that the DNA-binding region of ADR1 is involved in both transactivation and DNA binding.

Amino Acid Sequence↗