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S Orme

Publications and source records attributed to S Orme.

12 recordsLinked to original sources
PubMed2000

A comparison of a low-dose warfarin induction regimen with the modified Fennerty regimen in elderly inpatients.

OBJECTIVES: To compare a new low-dose warfarin induction regimen with the Fennerty regimen in elderly inpatients. DESIGN: Age-stratified, randomized prospective study. SUBJECTS: 120 age-stratified elderly inpatients. INTERVENTIONS: Each patient was randomized to either the new induction regimen or to a modified Fennerty regimen. MAIN OUTCOMES MEASURES: Days to therapeutic International Normalized Ratio (INR >2); days in the therapeutic range (INR 2-3) during induction; number of patients with INR >4.5; ability of day 4 INR to predict day 8 warfarin dose. RESULTS: The mean time to therapeutic INR was longer for the new induction regimen than modified Fennerty regimen in patients aged 65-75 years [4.6 (mean) +/- 1.6 (SD) days vs 3.8 +/- 0.8 days; P = 0.03] and in patients aged >75 years (4.5 +/- 1.4 days vs 3.5 +/- 0.7 days; P = 0.003). Patients spent more time in the therapeutic INR range with the new induction regimen [3.0 +/- 1.3 days vs 2.7 +/- 1.3 days (P = 0.03) for those aged 65-75 years and 2.9 +/- 1.1 days vs 2.4 +/- 1.3 days (P = 0.04 for those aged >75 years]. Fewer patients using the new regimen had INRs >4.5 in the first 8 days [1 (3%) vs 6 (20%) for 65-75 years (P < 0.05) and 1 (3%) vs 11 (37%) for >75 years (P < 0.01)]. The ability to predict the maintenance dose to within 1 mg was 55% for both regimens. CONCLUSION: The low-dose regimen has important clinical advantages over the Fennerty regimen for anticoagulating elderly inpatients.

Aged↗
PubMed1999

Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain.

TRAF2 is a signal transducing adaptor molecule which binds to the CD40 cytoplasmic domain. We have found that it is phosphorylated, predominantly on serine residues, when transiently overexpressed in 293 cells. The phosphorylation appears to be related to the signaling events that are activated by TRAF2 under these circumstances, since two nonfunctional mutants were found to be phosphorylated significantly less than the wild-type protein. Furthermore, the phosphorylation status of TRAF2 had significant effects on the ability of the protein to bind to CD40, as evidenced by our observations that the CD40 cytoplasmic domain interacted preferentially with underphosphorylated TRAF2 and that phosphatase treatment significantly enhanced the binding of TRAF2 to CD40. We conclude from these studies that the phosphorylation of TRAF2 is likely to play an important role in regulating signaling by virtue of its ability to influence the CD40-TRAF2 interaction.

Amino Acid Substitution↗
PubMed1999

Diffuse female hair loss: are androgens necessary?

Diffuse hair loss in women is generally regarded as the female equivalent of male balding and is often referred to as female androgenetic alopecia. In this article we report the case of a young woman with hypopituitarism who presented with the clinical and histological features of female androgenetic alopecia in the absence of detectable levels of circulating androgens or other signs of postpubertal androgenization, showing that this pattern of hair loss is not necessarily androgen dependent.

Adolescent↗
PubMed1999

The normal range for inter-arm differences in blood pressure.

OBJECTIVE: to establish the mean and normal range for the difference in simultaneous systolic and diastolic blood pressure measurements between the right and left arm. SUBJECTS: 462 subjects, age range 20-89 years, in sinus rhythm and with no history of stroke, 98 of whom had a history of cardiovascular disease or were taking vasoactive medication. METHODS: four simultaneous recordings of blood pressure in both arms were made using two automated sphygmomanometers with the subject supine after resting for 10 min. RESULTS: inter-arm systolic and diastolic blood pressure differences show a near normal distribution of values. Some individuals had clinically important differences in systolic and diastolic blood pressure between their arms. The magnitude of these differences was not related to the mean baseline blood pressure. Linear regression analysis did not demonstrate any significant relationship between inter-arm systolic or diastolic blood pressure difference and age in patients of either sex. For systolic blood pressure the mean difference between the right and left arm was 1.1 mmHg and the normal range was -9 mmHg to 11 mmHg. For diastolic blood pressure the mean difference was 0 mmHg and the normal range -10 mmHg to 10 mmHg. CONCLUSION: the frequency of significant inter-arm systolic and diastolic blood pressure differences suggests that the blood pressure should be taken in both arms at the initial consultation. At subsequent visits, the arm in which measurements are taken should be recorded in the case notes. The higher of the two readings should be used to guide further management decisions.

Adult↗
PubMed1997

CD40-mediated signals inhibit the binding of TNF receptor-associated factor 2 to the CD40 cytoplasmic domain.

TNF receptor-associated factor 2 (TRAF2) is a signal-transducing protein associated with the CD40 cytoplasmic domain. It has been hypothesized that during signal transduction, TRAF2 must be released from CD40 in order for it to interact with downstream signaling molecules. We found that CD40 and TRAF2 were constitutively associated with each other in a human B cell line. Following stimulation with an anti-CD40 Ab, a decrease in the amount of CD40-associated TRAF2 was observed that could not be explained by a change in total level of either of the proteins. These results, as well as similar findings obtained with 293 cells overexpressing CD40 and TRAF2, suggested that CD40-mediated signals inhibited the CD40-TRAF2 interaction. We then conducted binding studies using CD40 cytoplasmic domain fusion proteins and TRAF2 derived from either control or CD40-stimulated cell lines. These in vitro studies also indicated that the binding of TRAF2 to the CD40 cytoplasmic domain was inhibited by CD40 stimulation. The results of these experiments, as well as differences between the in vitro and in vivo findings, indicated that multiple mechanisms were involved in the inhibition of the CD40-TRAF2 interaction by CD40 signals. Possible mechanisms of inhibition are discussed based on mapping of the TRAF2 binding site on the CD40 cytoplasmic domain.

B-Lymphocytes↗
PubMed1993

The effects of insulin-like growth factor-1 on plasminogen activator inhibitor-1 synthesis and secretion: results from in vitro and in vivo studies.

In vitro studies have shown that insulin and IGF-1 releases the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1) from cells of hepatic origin. To investigate the effects of IGF-1 on fibrinolysis: 1) cultured hepatoma cells were grown in the presence of IGF-1 and media collected for secreted PAI-1 and cells probed for PAI-1 mRNA, 2) 8 hypopituitary patients were treated with recombinant human growth hormone (rhGH) and 3) 5 type 2 diabetic patients were treated with recombinant human IGF-1 (rhIGF-1). Treatment of Hep G2 cells with IGF-1 (1000 ng/ml) increased secretion of PAI-1 from a median value of 80 ng/10(6) cells (range 21-91) to 144 ng/10(6) cells (range 128-169) after 24 h (p < 0.01). Synthesis of PAI-1 mRNA increased in a similar fashion. Treatment of hypopituitary patients with rhGH led to an increase in circulating IGF-1 from a mean value of 166 (range 41-324) ng/ml at baseline to 322 (77-575) ng/ml at 4 weeks and 259 (104-533) ng/ml after 8 weeks (p < 0.02). Despite this, no changes in circulating PAI-1 or fibrinolysis occurred. Type II diabetic patients treated with rhIGF-1 showed an increase in circulating IGF-1 from a mean value of 120 ng/ml (range 109-196), at baseline to 823 ng/ml (585-894) after 5 days. This also was not associated with changes in circulating PAI-1 or in fibrinolysis. The results confirm that IGF-1 induces the synthesis of PAI-1 in Hep G2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗