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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 181 records · Page 10Linked to original sources
PubMed1997

Dynamic interfragmentary motion in fractures during routine patient activity.

Natural interfragmentary motion was measured in tibial fractures during normal patient activity, and the results were interpreted using correlations from the literature to examine the influence of natural motion on healing. Ten patients were selected with reduced, diaphyseal tibial fractures stabilized with Orthofix external fixators. Three-dimensional motion was monitored with an instrumented spatial linkage during walking, standing, and muscle activities at 2 and 4 weeks postfixation. Fracture motion arising from dorsal to plantar flexion while supine produced peak cyclic displacements of the same order of magnitude as that seen during weightbearing activity. Thus, therapeutic exercise may be used to provide a stimulus to osteogenic repair processes in patients who are unable to bear weight. In 3 patients, maximum amplitudes of axial motion during walking were 1 mm or greater. This implied regular gap closure and high tissue strains within the 1 mm +/- 0.5 mm gaps. In 3 patients, axial motion was less than 0.25 mm. These 2 extremes may indicate a range of displacement relative to gap size that embraces inhibitive and stimulative influences on healing. Transverse shear displacements also varied greatly from between 0.6 and 0.75 mm in 3 patients to less than 0.2 mm in 5 patients.

Adult↗
PubMed1997

Whole cell Cl- conductances in mouse choroid plexus epithelial cells do not require CFTR expression.

Whole cell patch-clamp studies were performed with tissue isolated from the cystic fibrosis (CF) transgenic Cftrm1cam mouse, to determine whether anion currents in choroid plexus epithelial cells require the expression of cystic fibrosis transmembrane conductance regulator (CFTR). Inclusion of 0.25 mM adenosine 3',5'-cyclic monophosphate (cAMP) and 375 nM protein kinase A (PKA) in the pipette solution caused a significant activation of a Cl(-)-selective, inward-rectifying conductance in cells from wild-type and CF mice. The small, outward currents observed in wild-type and CF animals, however, were not activated by cAMP-PKA. There were no significant differences in the size of currents between wild-type, heterozygote, and CF cells in the presence or absence of cAMP-PKA. A second whole cell conductance was activated when cells from wild-type mice were swollen. These volume-activated currents were Cl- selective and exhibited outward rectification. They were Ca2+ independent and ATP dependent and blocked by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid. The volume-activated channels were also activated in CF mutant cells, and there was no significant difference in the size of the volume-activated currents between wild-type, heterozygote, and CF cells. It is concluded that CFTR neither contributes to the whole cell conductance nor regulates the other anion conductances in choroid plexus epithelial cells.

Animals↗
PubMed1997

Interpretive group psychotherapy and dependent day hospital patients: a preliminary investigation.

A small group of highly dependent day hospital patients, together with a small number of 'potential' day hospital referrals sharing similar characteristics, were treated in twice weekly interpretive group psychotherapy for between seven and nine months. At the end of treatment three of four day hospital patients had made a successful separation from the day hospital, and at nine month follow-up outcome appeared improved. Only two of the six non-day hospital patients remained in the group, the reasons for which are discussed. The method of evaluation proved manageable, although it would be more appropriate to studies involving larger numbers and possibly control interventions. It is suggested that the role of interpretive group psychotherapy in rehabilitation deserves further investigation.

Adult↗
PubMed1997

Altered hierarchy of protective responses against severe hypoglycemia in normal aging in healthy men.

OBJECTIVE: To investigate the effect of normal aging on the protective responses against hypoglycemia, in view of the fact that type II diabetes is primarily a disease of aging, and its treatment is associated with risk of hypoglycemia with cognitive impairment. RESEARCH DESIGN AND METHODS: Plasma glucose was lowered stepwise from 5 to 2.4 mmol/l and restored by manipulation of an infusion of 20% glucose during 220-min intravenous infusion of 1.5 mU.kg-1.min-1 soluble insulin in 14 men; 7 were aged 60-70 years and the other 7 were 22-26 years. Changes in neurohumoral responses, subjective awareness, and choice reaction time were assessed. RESULTS: Hormonal responses were similar in the two groups, but symptoms began earlier in the younger men (at a plasma glucose of 3.6 +/- 0.1 vs. 3.0 +/- 0.2 mmol/l, P = 0.02) and were more intense (P = 0.03). Four-choice reaction time, a measure of psychomotor coordination, deteriorated earlier in the older men (at a plasma glucose of 3.0 +/- 0.1 vs. 2.6 +/- 0.1 mmol/l, P = 0.07) and to a greater degree. The difference between the glucose level for subjective awareness of hypoglycemia and the onset of cognitive dysfunction was lost in the older men (0.0 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P < 0.007). CONCLUSIONS: Older men are prone to more severe cognitive impairment during hypoglycemia than younger men and are less likely to experience prior warning symptoms if blood glucose falls. This effect of normal aging may contribute to the risk of severe hypoglycemia in older diabetic patients treated with sulfonylureas and insulin.

Adult↗
PubMed1997

Prevention of deformity during limb lengthening.

Deformity occurs frequently at the site of distraction during leg lengthening and can add to disability. The elastic and nonelastic displacements have been measured in a model that simulates leg lengthening in the laboratory. Measurements have been made for different fixator systems. The angulation in the vertical plane that occurs during leg lengthening is minimized if the distance between the bone and the fixator bar is kept as small as possible, if three screws are inserted in the proximal and distal bone fragments, and if the peak loads on the fixator are reduced by adjusting the rhythm of distraction. However, even if these precautions are taken, the results show that some fixators designed for leg lengthening will fail and lead to deformity at the osteotomy site. This may occur under the repeated cycles of high loads associated with the rises in soft tissue tension that are known to occur in certain groups of patients. This study suggests that deformity can be prevented by the proper selection of a suitable frame and the adjustment of its configuration to meet the loading requirements.

Bone Lengthening↗
PubMed1997

Treatment of depression in the elderly: effect of physical illness on response.

OBJECTIVES: To determine the response to treatment of different subgroups within a sample of physically ill elderly depressed patients. 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: Data were analysed in subgroups according to diagnosed physical problems and concomitant medication. A logistic regression analysis was performed to identify subgroups valid for separate analysis. Those reaching at least 5 weeks of treatment showed a significant improvement compared with the placebo group if they had serious life-threatening disease, cerebrovascular disease, were not demented, or were either on no analgesics or on analgesics stronger than paracetamol. CONCLUSION: While the response to treatment in these subgroups was encouraging, general physicians must not be led to believe that the answer to depression lies only in pharmacological intervention, just as the belief that the risk-benefit ratio of such treatment where indicated is too high must be discouraged.

Aged↗
PubMed1996

pUCS75, a stable high-copy-number Streptomyces--Escherichia coli shuttle vector which facilitates subcloning from pUC plasmid and M13 phage vectors.

A new Streptomyces-Escherichia coli shuttle vector, pUCS75, has been constructed to permit facile subcloning of DNA from the multiple cloning sites of the pUC plasmid and M13 phage vectors. In contrast to other commonly used shuttle vectors, pUCS75 retains the primary site for second-strand synthesis (ssi) of the parental streptomycete replicon, pIJ101. This sequence can not only enhance structural stability of the plasmid, but also confers on it an elevated copy number when replicated in Streptomyces. Consequently, the vector is useful for cloning sequences containing repeat structures and for allowing the high-level expression of cloned genes.

Bacteriophage M13↗
PubMed1996

The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway.

The edg-1 gene encodes an inducible G protein-coupled receptor (GPR) homologue that is induced during the in vitro differentiation of human endothelial cells. The aim of this study was to investigate the G protein-coupling and -signaling properties of the edg-1 polypeptide. The third cytosolic loop (i3) of edg-1 associates with G(i) alpha and G(o) alpha polypeptides in a guanosine 5'-O-(thiotriphosphate)-sensitive manner. Immunoprecipitation of the edg-1 polypeptide in transfected cells results in the co-precipitation of G(i) alpha 1 and G(i) alpha 3 polypeptides. These data strongly suggest that edg-1 is capable of coupling to the Gi pathway. Overexpression of the edg-1 GPR in human embryonic kidney 293 cells results in the sustained activation of the MAP kinase activity that is blocked by pertussis toxin treatment. Moreover, NIH3T3 cells permanently transfected with edg-1 exhibit enhanced MAP kinase and phospholipase A2 activities. These data suggest that the G(i)/mitogen-activated protein kinase pathway is a major signaling pathway regulated by the orphan receptor edg-1.

3T3 Cells↗
PubMed1996

T cell rescue of monocytes from apoptosis: role of the CD40-CD40L interaction and requirement for CD40-mediated induction of protein tyrosine kinase activity.

Circulating monocytes have a limited life span and will undergo apoptosis in the absence of specific stimuli. Recent studies have demonstrated that monocytes can be rescued from apoptosis via lipopolysaccharide (LPS) activation or stimulation with interleukin-1 or tumor necrosis factor-alpha. Based on previous studies from our laboratory, we hypothesized that, in nonseptic (e.g., autoimmune) inflammation, the presence of activated T cells may enhance monocyte longevity through T cell contact-dependent signaling. Plasma membranes prepared from 6 h activated (TmA) and resting (TmR) purified CD4+ T cells were added to resting elutriation-purified monocytes cultured in serum-free medium. Cells were assayed for degree of apoptosis occurring over a 72-h incubation using both agarose gel electrophoresis and flow cytometry. The addition of TmA (but not TmR) was capable of blocking monocyte apoptosis and the ability of TmA to rescue monocytes was abrogated by the addition of anti-CD40L antibodies. Rescue of monocytes from apoptosis could also be mediated by direct cross-linking of monocyte CD40. Inhibitors of tyrosine kinase activity blocked both TmA and anti-CD40-mediated rescue of monocytes from apoptosis, suggesting a primary role of a tyrosine kinase signaling pathway in the events controlling monocyte longevity.

Apoptosis↗
PubMed1996

The safety evaluation of fluvastatin, an HMG-CoA reductase inhibitor, in beagle dogs and rhesus monkeys.

Fluvastatin is a potent synthetic competitive inhibitor of beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the biosynthetic pathway for hepatic cholesterol synthesis. The therapeutic indication is reduction of elevated total and low-density lipoprotein cholesterol levels. Results from four toxicity studies in beagle dogs and one study in rhesus monkeys following oral administration of fluvastatin are reported. In two 26-week dog studies, doses were 0, 1, 8, or 48 mg/kg/day (reduced to 36 mg/kg/day in Week 7) and 0, 6, 24, or 36 mg/kg/day (reduced to 30 mg/kg/day in Week 2). In a 2-year dog study, doses were 0, 1, 8, or 16 mg/kg/day. Dose levels in the 26-week monkey study were 0, 0.6, 12, and 48 mg/kg/day (raised to 84 mg/kg/day in Week 17 and to 108 mg/kg/day in Week 22). In these studies, evaluations included clinical and physical examinations, body weight and food consumption, electrocardiography, ophthalmoscopy, hematology and clinical chemistries, urinalysis, blood drug concentration, and macroscopic and microscopic examinations of observed lesions and representative tissues. In the 26- and 52-week dog studies and the monkey study, lenticular biochemistry, the HMG-CoA reductase activity of liver microsomes, and serum lipid concentrations were investigated. The fourth dog study was a single-dose toxicokinetic study in which 48 mg/kg [3H]-fluvastatin was monitored for up to 2 weeks. Sampling was limited to ocular tissues for enzyme analysis. Doses of > or = 24 mg/kg/day were lethal in dogs. At lethal doses, ataxia, convulsions, fecal blood, multifocal congestion and hemorrhage, isolated foci of malacia in the medulla oblongata, and liver necrosis were observed. Reduced weight gain, emesis, cataracts, elevated liver enzymes, reduced cholesterol, and gallbladder inflammation with mucosal hyperplasia occurred at > or = 8 mg/kg/day. In contrast to other HMG-CoA reductase inhibitors, fluvastatin did not cause significant central nervous system hemorrhage or testicular changes in dogs. Monkeys tolerated exposure to fluvastatin well with only mild gallbladder changes observed. Reduced serum cholesterol and slight hyperplasia of the gallbladder mucosa occurred in the 12 and 48/84/108 mg/kg/day groups.

Administration, Oral↗
PubMed1996

Nonimmune hydrops fetalis, pulmonary sequestration, and favorable neonatal outcome.

BACKGROUND: The association of pulmonary sequestration and nonimmune fetal hydrops reportedly carries a very poor prognosis for survival. We describe three newborns with good outcomes despite the diagnosis of pulmonary sequestration; two cases were associated with hydrops fetalis and one with isolated fetal ascites. CASES: Two neonates with severe hydrops fetalis had pulmonary sequestration diagnosed postnatally. A third infant presented early in gestation with marked fetal ascites that regressed spontaneously before delivery; this infant also had pulmonary sequestration. Despite severe respiratory insufficiency requiring aggressive management, all three infants survived after surgical resection of the sequestered lung mass. CONCLUSION: These cases demonstrate the difficulties associated with antenatal counseling regarding long-term prognosis for infants with nonimmune hydrops and pulmonary sequestration. With optimal care in a tertiary perinatal center, a less pessimistic outlook than previously described in the literature may be appropriate.

Adult↗
PubMed1996

Presence of a variant form of the estrogen receptor in peripheral blood mononuclear cells from normal individuals and lupus patients.

Estrogen may participate in the pathogenesis of systemic lupus erythematosus (SLE) via its intracellular receptor. To investigate the presence of various isoforms of the estrogen receptor (ER) in SLE we isolated RNA from mononuclear cells of lupus patients and normal controls. Using RT-PCR we were able to identify both the full length wild-type form and an isoform of the ER which precisely lacks exon V in both patient and normal individuals. Our results, although limited, suggest that normal individuals can express both the wild-type and truncated version at the same time, whereas lupus patients only express either the wild-type or the truncated ER. This finding may lead to a better understanding of the reasons for the prevalence of lupus in females and of the estrogenic effects on SLE disease activity.

Base Sequence↗
PubMed1996

The influence of external fixators on fracture motion during simulated walking.

This experimental study examines the relative influence of five unilateral external fixators on tibial fracture stability during simulated walking. Stability during routine patient activity is important, because cyclic inter fragmentary motion, or strain, has been shown to affect fracture healing. In model stable fractures simulating early healing (six weeks), it was found that fixators do little to constrain against axial inter fragmentary strains as great as 100% at only nominal weight-bearing (6.0 kg). These strains may occur repeatably at peak amplitudes of motion during walking. Similarly, peak angular movements may lead to additional axial strains of up to 25% at the external cortex and shear movements may lead to shear strains of up to 100%. Such strains are great enough to yield and possibly refracture the intra gap fracture tissue that may be composed of a combination of granulation tissue, fibrous cartilage, cartilage and bone. It was also shown that the procedure of releasing the fixator column to telescope (dynamize) has little influence on peak cyclic axial motion and on loading at the fracture, although increases occurred in peak transverse and torsional shear strains of up to 100%. Since permanent inter fragmentary translation also arises from the consequent compaction of the intra gap tissue, it may be permanent displacement rather than any change in the amplitude of motion that is responsible for the beneficial effect on healing claimed for the dynamizing procedure. In unstable fractures that are unable to support tibial load at the fracture, the peak amplitudes of cyclic movement were as great as those reported for fractures stabilized by plaster casts, and were approximately twice the movement of the stable fractures simulating early healing. Therefore, patients with unstable fractures supported by external fixators, may be expected to have similar patterns of healing to plaster-casted patients with similar fractures.

Biomechanical Phenomena↗
PubMed1996

Intestinal obstruction as a complication of Kawasaki disease.

Kawasaki disease is a syndrome characterized by multiple organ system inflammation and diffuse arteritis. Although gastrointestinal complications have been described, bowel obstruction rarely has been reported. The authors describe the case of a 1-year-old girl with Kawasaki disease who, after her acute illness, returned with mechanical bowel obstruction. During laparotomy, complete obstruction was found at the level of the jejunum, and resection was performed. Pathological examination of the resected specimen confirmed complete luminal obstruction with proliferation of granulation tissue, findings compatible with ischemic enteritis.

Acute Disease↗