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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 163 records · Page 9Linked to original sources
PubMed1998

The action profile of lispro is not blunted by mixing in the syringe with NPH insulin.

OBJECTIVE: To assess the effect of mixing the insulin analog lispro (Humalog) with NPH (Humulin I) before injection on lispro's fast, short action profile. RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers received subcutaneous abdominal injections of 0.1 U/kg regular insulin and 0.2 U/kg NPH insulin as follows: lispro and NPH injected separately (treatment group A), lispro and NPH mixed in the syringe up to 2 min before single injection (treatment group B), and human regular insulin and NPH mixed and injected as in group B (treatment group C), on separate occasions, in random order. Plasma glucose was maintained for 12 h by intravenous 20% glucose. Pharmacokinetic and pharmacodynamic parameters were compared by analysis of variance for repeated measures. RESULTS: Peak plasma insulin levels (2.6 +/- 0.8 vs. 2.2 +/- 0.6 vs. 1.9 +/- 0.6 ng/ml, P = 0.075), total glucose infused (121.5 +/- 32.8 vs. 135.0 +/- 49.0 vs. 117.3 +/- 39.9 mg.kg-1.min-1, P = 0.53), and maximum glucose infusion rate (GIRmax) (8.3 +/- 0.9 vs. 8.0 +/- 1.7 vs. 7.1 +/- 2.4 mg.kg-1.min-1, P = 0.65) were not significantly different between treatments. The times until peak insulin concentrations were similar in treatment groups A and B, but significantly shorter than in treatment group C (0.9 +/- 0.3 and 1.2 +/- 0.2 vs. 2.0 +/- 0.4 h, respectively, P = 0.042). The times until GIRmax were also not different (113.9 +/- 41 and 122.0 +/- 45 vs. 209.0 +/- 51.3 min, respectively, P = 0.002). The glucose infusion rate (GIR) then fell to 50% GIRmax more quickly in treatment groups A and B than in treatment group C (239.9 +/- 40.5 vs. 292.4 +/- 133.3 vs. 399.5 +/- 78.3, respectively, P = 0.005). CONCLUSIONS: The action profile of lispro is not attenuated by mixing lispro with NPH in the syringe immediately before injection. The advantages are available to those individuals who need to combine types of insulin before injection to achieve optimal diabetes control.

Adult↗
PubMed1998

Recruitment and retention of minority participants in the DASH controlled feeding trial. DASH Collaborative Research Group. Dietary Approaches to Stop Hypertension.

The Dietary Approaches to Stop Hypertension (DASH) study was a National Heart, Lung, and Blood Institute multicenter trial that compared the impact of three dietary patterns on blood pressure (BP) among adults with high normal blood pressure or mild (Stage I) hypertension. DASH's high minority representation (two-thirds of the 459 randomized participants came from minority populations, and 60% of the cohort were African American) offered a valuable opportunity to assess factors affecting minority enrollment and retention in clinical trials of lifestyle modification. Recruitment strategies included targeted mailings to specific groups, mass mailings, community and worksite screenings, and mass media advertising; the four DASH clinical centers also reimbursed participants from $150 to $160. The most productive recruitment strategies tended to be mass mailings directed at a broad audience that was weighted toward, but not limited to, minority participants. DASH's African-American participants overwhelmingly (89%) cited health and dietary factors, such as learning more about blood pressure and healthy eating habits, as their primary reason for participating, while only six percent listed the financial incentives as their primary reason for participating. Eighty-eight percent of African-American respondents reported they would participate again in a similar study. The insights from DASH should help inform future efforts to recruit minority participants.

Adult↗
PubMed1997

A functional CFTR protein is required for mouse intestinal cAMP-, cGMP- and Ca(2+)-dependent HCO3- secretion.

1. Most segments of the gastrointestinal tract secrete HCO3-, but the molecular nature of the secretory mechanisms has not been identified. We had previously speculated that the regulator for intestinal electrogenic HCO3- secretion is the cystic fibrosis transmembrane regulator (CFTR) channel. To prove this hypothesis, we have now measured HCO3- secretion by pH-stat titration, and recorded the electrical parameters of in vitro duodenum, jejunum and ileum of mice deficient in the gene for the CFTR protein ('CF-mice') and their normal littermates. 2. Basal HCO3- secretory rates were reduced in all small intestinal segments of CF mice. Forskolin, PGE2, 8-bromo-cAMP and VIP (cAMP-dependent agonists), heat-stable enterotoxin of Escherichia coli (STa), guanylin and 8-bromo-cGMP (cGMP-dependent agonists) and carbachol (Ca2+ dependent) stimulated both the short-circuit current (Isc) and the HCO3- secretory rate (JHCO3-) in all intestinal segments in normal mice, whereas none of these agonists had any effect on JHCO3- in the intestine of CF mice. 3. To investigate whether Cl(-)-HCO3- exchangers, which have been implicated in mediating the response to some of these agonists in the intestine, were similarly active in the small intestine of normal and CF mice, we studied Cl- gradient-driven 36Cl- uptake into brush-border membrane (BBM) vesicles isolated from normal and CF mouse small intestine. Both the time course and the peak value for 4,4'-diisothiocyanostilbene-2',2-disulphonic acid (DIDS)-inhibited 36Cl- uptake was similar in normal and CF mice BBM vesicles. 4. In summary, the results demonstrate that the presence of the CFTR channel is necessary for agonist-induced stimulation of electrogenic HCO3- secretion in all segments of the small intestine, and all three intracellular signal transduction pathways stimulate HCO3- secretion exclusively via activation of the CFTR channel.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

The immediate-early gene product MAD-3/EDG-3/IkappaB alpha is an endogenous modulator of fibroblast growth factor-1 (FGF-1) dependent human endothelial cell growth.

The tumor promoter phorbol 12-myristic 13-acetate inhibits the growth of human endothelial cells and induces the formation of capillary-like, tubular structures. We report the novel growth regulatory function of the immediate-early gene, edg-3, which is identical to the IkappaB alpha/MAD-3 gene. We employed phosphothioate oligonucleotides (PTO) directed against the translation initiation site of IkappaB alpha to inhibit its expression. The antisense IkappaB alpha PTO-treated cells exhibited an exaggerated growth response to fibroblast growth factor-1 (FGF-1). In contrast, IL-1-induced growth arrest response was not modulated. These data suggest that the early response gene IkappaB alpha is an endogenous regulator of endothelial cell growth in vitro.

Cell Division↗
PubMed1997

Placebo-controlled treatment trial of depression in elderly physically ill patients.

OBJECTIVES: To determine the response of physically ill elderly depressed patients to treatment. DESIGN: Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine. MAIN OUTCOME MEASURE: Response rate as defined by the 17-item Hamilton Depression Rating Scale. RESULTS: Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02). CONCLUSIONS: The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.

Aged↗
PubMed1997

Temporal changes in dynamic inter fragmentary motion and callus formation in fractures.

This study examined whether callus proliferation at long bone fractures is triggered by cyclical inter-fragmentary displacement which arises from routine activity. It also examined whether a growing callus increases the stability of a fracture, thereby reducing displacement amplitude during relative motion. Seven tibial fractures stabilised with external fixators were monitored up to and beyond fixator removal. An instrumented spatial linkage was developed which was attached to the bone screws to measure inter-fragmentary displacement at the fracture in all six degrees of freedom during routine walking. Callus index (final bone width/initial bone width) was measured at the posterior and lateral cortical surfaces from orthogonal radiographs. In all seven subjects, callus growth was initiated subsequent to a peak in displacement which occurred within the first 42 days; at nine of the 14 surfaces occurred callus initiation occurred within 14 days of the peak displacement. With the exception of two lateral surfaces, maximum callus size, subsequent to fixator removal (at up to 119 days after removal). Displacement reduced during callus growth in five out of six subjects. Since the reduction in displacement did not arise from reduced weight-bearing, increasing callus size must correlate with progressive mechanical union. This was confirmed by end point stiffness tests. Therefore, peak cyclical displacement appears to be the stimulus for callus growth, the effect of which is to reduce displacement and strain which allows the following stages of bone formation and remodelling to unite the fracture.

Adult↗
PubMed1997

A biomechanical study on five unilateral external fracture fixation devices.

OBJECTIVE: This study examines plastic, slip and fatigue failures in external fixator frames. DESIGN: Failure was examined in five commonly used unilateral external fixators using experimental models that simulated both stable and unstable diaphyseal fractures. BACKGROUND: Plastic failure arises from permanent deformation of a frame initiated by bending of frame components, while slip failure arises from slip at clamping interfaces. Such failure may lead to refracture or to malalignment of the bone (transverse or angular). Fatigue failure arises from the loosening or wear of components under long-term cyclic loading; this can lead to variable interfragmentary displacement and impairment of fracture stability. METHODS: Axial loads were measured at which plastic or slip failure occurred, as were changes in interfragmentary motion due to 10 000 load cycles simulating walking activity. RESULTS: In four fixators, plastic or slip failure initiated bone malalignment at only 50% of average adult weight bearing (650 N). Additionally, in three fixators a third screw at the clamp centre was found to reduce retention of the two adjacent screws, causing premature slip failure. Evidence of fatigue was found in all the fixators after only 10 000 load cycles. In one fixator, the amplitude of elastic interfragmentary motion increased progressively by 30% transversely, 15% angularly and 100% torsionally. In another fixator it increased by 10% in all directions while the column was locked (non-dynamizing), and it increased a further 10% while it was unlocked and able to slide telescopically (dynamizing). Clamp slip occurred at the column of a third fixator almost immediately after commencing the cyclic loading. CONCLUSION: Plastic or slip failure of frames may occur prematurely during routine weight-bearing on unstable fractures, and frame fatigue may affect long-term interfragmentary stability.

Journal Article↗
PubMed1997

The use of SCID mice for the growth of retinoblastoma cell lines and for the establishment of xenografts from primary tumours.

We investigated the possibility of growing primary retinoblastoma tumour tissue in SCID mice. In preliminary experiments with the WERI retinoblastoma cell line injected subcutaneously in SCID mice, tumours arose at only 25% of the inoculation sites. After mixing these cells with a reconstituted basement membrane extracellular matrix (Matrigel) prior to inoculation, tumours arose at 100% of inoculated sites. When primary retinoblastoma cells were injected subcutaneously into SCID mice in the presence of Matrigel, tumours arose in 5/8 cases. On average, the latency period was 4 months before the tumours were palpable. Histopathological examination of the tumours showed that they resembled surgically resected human retinoblastomas and one of the tumours formed pseudo-rosettes which is a characteristic of these tumours. Unfortunately, when these xenografted tumours were introduced into tissue culture, it was not possible to establish cell lines directly and the cultures were soon overgrown by mouse cells which could clearly be shown to be infiltrating the tumour. The ability to grow retinoblastoma cell lines and primary tissue subcutaneously in SCID mice offers a convenient model system to study the genetics of tumorigenesis in this tumour type and possibly an opportunity to study the role of chemotherapy in the treatment and progression of the disease.

Animals↗
PubMed1997

A method of examining the magnitude and origin of "soft" and "hard" tissue forces resisting limb lengthening.

Complications arising from limb-lengthening procedures such as muscle contracture, axial malalignment of the bone and traction injuries to the nerves and vessels, are often severe. Often complications arise from the build-up of forces in the biological tissues which are resisting lengthening. Little is known about the origin and magnitude of these forces, although three studies have identified the regenerate (new bone tissue) as the dominant resisting tissue. This study describes the development of a method to examine these forces. It employs load measurement devices in the structural columns of Ilizarov fixators which measure the compressive load on the frame exerted by the biological tissues. The distribution of this load between the columns of the frame, in conjunction with a transverse radiograph of the limb at the regenerate site, is used to examine the origin of the resisting force. Accuracy was determined by a laboratory simulation which found the predicted position of the force to be within 5 mm of the actual position in all four cases tested. Mean error in the total measured force was 2 N (SD, 1 N). A pilot study on a patient undergoing a 60 mm femoral lengthening revealed a peak force of 717 N originating in the Vastus Lateralis or the illiotibial tract. Negligible contribution to resistance was provided by the regenerate, contrary to that found with other studies.

Adult↗
PubMed1997

Normotensive blood pressure in mice with a disrupted renin Ren-1d gene.

Renin is an aspartyl protease that is involved in the conversion of angiotensinogen to angitensin II and hence participates in the regulation of blood pressure. Mice are polymorphic for the number of renin genes with some strains harbouring two renin genes, Ren-1d and Ren-2. To study the role of renin Ren-1d in regulating cardiovascular homeostasis, mice with a disrupted Ren-1d gene were created. Analyses of kidney renin mRNA expression in Ren-1d-/-/Ren-2+/+ mice demonstrated that only Ren-2 transcripts were present. Mean arterial blood pressures of Ren-1d+/+/Ren-2+/+, Ren-1d+/-/Ren-2+/+ and Ren-1d-/-/Ren-2+/+ mice showed no significant differences. These observations demonstrate that the Ren-1d gene product is not essential for normal blood pressure maintenance under normal physiological conditions.

Animals↗