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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

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

Regulation of proximal tubular osteopontin in experimental hydronephrosis in the rat.

BACKGROUND: Osteopontin is a tubular-derived glycoprotein with macrophage chemoattractant properties. Our previous observations demonstrate that osteopontin is involved in the accumulation of macrophages within the renal cortex of rats following unilateral ureteral obstruction (UUO). METHODS: The present study performed Northern and Western blot analyses of isolated proximal tubular cells exposed to exogenous angiotensin II, and cultured rat proximal tubular cells subjected to one hour of cyclic mechanical stretch, which provided insight into mechanisms involving the proximal tubular renin-angiotensin system in the increased expression of cortical osteopontin following hydronephrosis. RESULTS: In situ hybridization, using a 35S-labeled antisense riboprobe, showed osteopontin mRNA transcription localized to the cortical tubules of the obstructed kidney. Freshly isolated proximal tubules incubated with angiotensin II (10-5 M) for one hour had increased osteopontin mRNA and protein expression by Northern and Western blot analyses, respectively. Pre-treatment of proximal tubules with losartan (10-5 M) for one hour prior to the addition of exogenous angiotensin II (10-5 M) decreased osteopontin mRNA and protein expression. Rat proximal tubule cells subjected to cyclic mechanical stretch for one hour exhibited a 2.1-fold increment in osteopontin mRNA levels, which was normalized following pre-treatment with losartan. CONCLUSIONS: This study provides evidence that angiotensin II, produced by the proximal tubule in the obstructed kidney as a result of mechanical injury, possibly mechanical stretch, may stimulate angiotensin II type I receptor activation, leading to up-regulated osteopontin expression and secretion by the proximal tubule, thereby facilitating macrophage recruitment into the renal interstitium.

Animals↗
PubMed1998

Streptococcal toxic shock syndrome presenting as suspected child abuse.

Natural disease processes can predispose individuals to develop external body lesions that mimic traumatic injury. This can be particularly problematic in pediatric cases in which clinicians are alerted to the problems of child abuse. Streptococcal toxic shock syndrome is a systemic infectious illness that can manifest itself with erythematous and necrotizing skin lesions. We report a fatal case of streptococcal toxic shock syndrome in a 4-year-old girl who presented with skin lesions that were initially thought to be traumatic in origin. A report of possible child abuse was filed with the state. Based on the morphologic findings and bacteriologic culture results at autopsy, these lesions and the cause of death in this case were instead determined to result from streptococcal toxic shock syndrome.

Cause of Death↗
PubMed1998

Progression of Pneumocystis carinii infection in an animal model.

The development of Pneumocystis carinii infection in immunosuppressed rats is important not only in understanding the infection, but also as a source of P. carinii antigen for use in diagnostic serological tests. The aims of this study were to monitor the progression of P. carinii infection in the Sprague Dawley rat model and then determine parameters that indicate the maximum production of P. carinii antigen. Seventeen Sprague Dawley rats were killed at intervals up to 9 weeks after the start of immunosuppressive therapy. The progression of P. carinii lung infection was observed by Giemsa staining of lung imprints and by a hemi-nested polymerase chain reaction (PCR). Body weight, food and water intake and the appearance and activity of the rats were measured daily. Seven control rats were kept under the same conditions. P. carinii infection was detected in the lung 2 weeks after immunosuppression by hemi-nested PCR and after 3 weeks by Giemsa staining. No P. carinii DNA was detected in any of the blood samples. Rats with moderate or severe lung infection had been immunosuppressed for > or = 6 weeks. Body weight was significantly greater in control rats than in the immunosuppressed rats. Six weeks of immunosuppression was used as a cut-off to determine measurements to identify those rats with moderate or severe infections in their lungs. A combination of > 34% body weight loss at 6 weeks after immunosuppression and the condition of the animals with scores < or = 9 used in conjunction with duration of immunosuppression may be useful to maximise the yield of P. carinii infection from individual rats.

Animals↗
PubMed1998

Gastric tonometry in septic shock.

OBJECTIVES: To investigate the prognostic value of intramucosal pH (pHi) and the relation among pHi, arterial pH, base excess, and lactate in children with septic shock. DESIGN: Children admitted to the paediatric intensive care unit with a diagnosis of septic shock were prospectively enrolled. A gastrointestinal tonometer (Tonometrics Division, Instrumentarium Corporation, Helsinki, Finland) was placed into the stomach and intramucosal pH, arterial pH, base deficit, and lactate were measured on admission and six hours later. Sequential data were analysed on 24 patients (17 survivors, seven non-survivors), median age 46 months (range: 2.8-168 months). RESULTS: Median pHi on admission was 7.39 (interquartile range 7.36-7.51) in survivors compared with 7.2 (interquartile range 7.18-7.35) in non-survivors (p = 0.01). There was no significant difference in arterial pH, base excess, or lactate among survivors and non-survivors. Admission pHi < 7.32 predicted mortality with sensitivity (57%), specificity (94%), and positive predictive value (80%). Patients with admission pHi < 7.32 who failed to improve > or = 7.32 within six hours (n = 3) had 100% mortality. CONCLUSION: In children with septic shock the admission pHi is significantly lower in non-survivors. pHi is a better prognostic indicator of mortality than either standard acid-base values or lactate. pHi < 7.32 that does not improve within six hours is associated with a poor prognosis.

Adolescent↗
PubMed1998

CSF-1 (M-CSF) enhances the inflammatory response of fibronectin-primed macrophages: pathways involved in activation of the cytokine network.

We have previously reported that the priming of thioglycollate-elicited peritoneal macrophages (PMphi), as a representative population of mononuclear phagocytes (MNP), by macrophage-colony-stimulating factor (M-CSF or CSF-1) rendered these cells more susceptible to secondary stimulation by extracellular matrix (ECM) proteins, in particular fibronectin (FN), and that at least two beta1 integrins, VLA 4 (alpha4beta1 or CD49d) and VLA 5 (alpha5beta1 or CD49e), regulate IL-6 gene expression when PMphi come into contact with FN. In this report, we focused our attention on resident PMphi, as a more mature/differentiated MNP subpopulation. By using granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-6-knockout (null) mice, we demonstrated that the cooperative effect between CSF-1 and FN in IL-6 release was a result of a sequential stimulation of the GM-CSF, but not the TNF-alpha, gene via interaction with VLA 5. We also showed that regardless of the presence or absence of CSF-1 or FN, IL-6 inhibits GM-CSF and TNF-alpha gene expression in an autocrine manner. The observed effects were specific because CSF-1 enhanced VLA 5 expression and blocking FN-treated resident PMphi in vitro with VLA 5 monoclonal antibodies inhibited the IL-6 response. We found that treatment of resident PMphi with the protein kinase C inhibitor, staurosporine, and the activator, phorbol myristate acetate (PMA), resulted in marked modulation of either FN- or FN/CSF-1-induced cytokine release. An increased level of VLA 5 expression was observed in PMA-treated resident PMphi. We concluded that in inflammatory processes, CSF-1 drives a number of pathways involved in the regulation of the expression of several genes and renders MNP highly susceptible to stimulation by ECM proteins that transform the MNP into secretory inflammatory cells.

Animals↗
PubMed1998

Effect of zafirlukast (Accolate) on cellular mediators of inflammation: bronchoalveolar lavage fluid findings after segmental antigen challenge.

The effect of zafirlukast (Z) to alter the inflammatory response to segmental antigen challenge (SAC) was assessed by bronchoalveolar lavage (BAL) in this double-blind, placebo-controlled, two-period, crossover trial in 11 allergic asthmatic patients. Patients with asthma and positive skin tests to antigen received 7 d of treatment with Z (20 mg twice daily) or placebo (P) during two trial periods 14 to 21 d apart. At steady state (Day 5), patients underwent SAC followed by BAL immediately after challenge and 48 h later. Purified alveolar macrophages were analyzed ex vivo for phorbol myristate acetate (PMA)-driven superoxide release. Results were analyzed by analysis of variance (ANOVA). Forty-eight hours after SAC, Z therapy was associated with significantly reduced BAL lymphocytes and alcian blue-positive cells (presumably basophils) compared with P (p < 0.01), with a trend toward reduced numbers of alveolar macrophages (p = 0.06). PMA-driven superoxide release by purified alveolar macrophages was significantly reduced 48 h after SAC in the Z versus P arms (p < 0.05). Reduction of basophil influx, mediator release, and cellular activation may be important in attenuating the late phase of asthma. Collectively, the data suggest that zafirlukast therapy alters cellular infiltration and activation associated with antigen challenge.

Adolescent↗
PubMed1998

Self-reported adherence, management behavior, and barriers to care after an emergency department visit by inner city children with asthma.

OBJECTIVE: The inability to adhere to a prescribed therapeutic program for the treatment of a chronic disease may be responsible in part for continued disease activity. This problem may be more of an issue in the treatment of asthma, a common, potentially lethal chronic condition in which the lack of symptoms may be interpreted as remission. Adherence was one of the key areas of interest for the National Cooperative Inner-City Asthma Study. The focus of this study was to identify those issues reported by families that could adversely affect their adherence to an asthma care program. The identification of barriers to adherence could then form the basis of a successful intervention program. This study describes barriers to adherence, asthma management behavior, and self-reported adherence. METHODS: Patients presenting during an acute attack of asthma at an emergency department (ED) were recruited for this study. The medical record of the ED encounter was abstracted and compared with information that was obtained during a baseline interview 3 to 5 weeks later. During the baseline interview, parents were asked about health care behaviors related to adherence. RESULTS: There were 344 children 4 to 9 years of age living in inner city census tracts in the study. Four areas of adherence (medicine use, appointment-keeping, emergency actions, and asthma attack prevention) were investigated. The parental report of medications prescribed at the ED and the information on the abstracted ED report agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for cromolyn. Among respondents, 85.4% of parents reported that they are able to follow the ED recommendations almost all of the time; side effects of medicines were a concern for 81.1% of caretakers who were adherent and for 89.5% of caretakers who were nonadherent. Doubts regarding the usefulness of medications occurred in 34.4% of those considered adherent and 54.2% who admitted nonadherence. Medications were forgotten some of the time by 45.2% of the children, and 52.8% tried to get out of taking medicine. Appointments for follow-up care were kept by 69% of those given an appointment in the ED, by an estimated 60.0% of those who were told specifically to call for an appointment, and by an estimated 25.2% of those who were neither given an appointment nor told specifically to make one. Only one third of parents report that they were able to keep the child away from known asthma triggers nearly all of the time. Approximately half avoided allergens; however, only 37.5% reported avoidance of cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a medicine and taking the child to a physician were reported as the first or second action during an acute attack of asthma by 72.1% of respondents. CONCLUSIONS: Adherence to an asthma-management program involves a number of areas: medication, appointment-keeping, prevention, and applying an emergency plan of action. Barriers to adherence may exist in one or all four of these areas, leading to ineffective control of asthma. Recommendations are made for improving the patient-physician partnership to improve adherence.

Asthma↗
PubMed1998

Transient basophilia following the application of lymphatic pump techniques: a pilot study.

Lymphatic pump techniques (LPTs) consisting of pectoral traction and splenic pump were performed on seven male medical students following blood collection for baseline value determinations. Blood was collected from each subject at 15, 30, 60, 120, and 240 minutes post-LPT. The samples were analyzed for serum chemistry and complete blood cell count. All subjects showed an increase in the percentage of basophils. There was variation in the time points for the initial occurrence of basophilia among the subjects. A separate cohort of five male medical students served as control subjects. The control group did not receive LPTs. Blood samples collected at the same time points as the experimental group did not show the basophilia.

Adult↗
PubMed1998

Evaluation of night vision disturbances in contact lens wearers.

PURPOSE: We quantitatively recorded and evaluated night vision disturbances with physiologically dilated pupils. We compared the amount of image degradation experienced in eyes wearing spherical soft contact lenses with the amount of image degradation experienced by subjects wearing spectacles. METHODS: We prospectively evaluated 69 eyes from 35 myopic subjects with no ocular pathology. The subjects ranged in age from 22 to 35 years. We designed a test to quantitatively record image degradation with physiologically dilated pupils in scotopic conditions of dim ambient light. Previously, we have shown that this test accurately measures image degradation. We used this test to compare image degradation between new spherical soft contact lens and spectacle correction. Hyperopes and eyes with greater than 1.50 D of astigmatism were excluded. RESULTS: Adequately correcting myopic refractive error decreased recorded image degradation (P < or = 0.0001). There was no significant difference in the amount of image degradation between spectacle trial frames and new spherical soft contact lenses (P < or = 0.2885). CONCLUSIONS: Our test offers an objective method of assessing night vision disturbances in contact lens wearers. Our results suggest that image degradation, which may contribute to the sensation of glare experienced by some patients, is influenced equally by contact lens and spectacle correction.

Adult↗
PubMed1998

The efficacy of spinal manipulation, amitriptyline and the combination of both therapies for the prophylaxis of migraine headache.

BACKGROUND: Migraine headache affects approximately 11 million adults in the United States. Spinal manipulation is a common alternative therapy for headaches, but its efficacy compared with standard medical therapies is unknown. OBJECTIVE: To measure the relative efficacy of amitriptyline, spinal manipulation and the combination of both therapies for the prophylaxis of migraine headache. DESIGN: A prospective, randomized, parallel-group comparison. After a 4-wk baseline period, patients were randomly assigned to 8 wk of treatment, after which there was a 4-wk follow-up period. SETTING: Chiropractic college outpatient clinic. PARTICIPANTS: A total of 218 patients with the diagnosis of migraine headache. INTERVENTIONS: An 8-wk course of therapy with spinal manipulation, amitriptyline or a combination of the two treatments. MAIN OUTCOME MEASURES: A headache index score derived from a daily headache pain diary during the last 4 wk of treatment and during the 4-wk follow-up period. RESULTS: Clinically important improvement was observed in both primary and secondary outcomes in all three study groups over time. The reduction in headache index scores during treatment compared with baseline was 49% for amitriptyline, 40% for spinal manipulation and 41% for the combined group; p = .66. During the posttreatment follow-up period the reduction from baseline was 24% for amitriptyline, 42% for spinal manipulation and 25% for the combined group; p = .05. CONCLUSION: There was no advantage to combining amitriptyline and spinal manipulation for the treatment of migraine headache. Spinal manipulation seemed to be as effective as a well-established and efficacious treatment (amitriptyline), and on the basis of a benign side effects profile, it should be considered a treatment option for patients with frequent migraine headaches.

Adolescent↗
PubMed1997

Priming of mouse macrophages with the macrophage colony-stimulating factor (CSF-1) induces a variety of pathways that regulate expression of the interleukin 6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm) genes.

Recent data have indicated that resident mouse peritoneal macrophages (PMo) transcribed the interleukin 6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm) genes in response to stimulation with the monocyte-macrophage colony-stimulating factor (CSF-1) but only Il6 mRNA was translated into secreted protein. In this paper, we extend these observations. It is shown that resident PMo incubated with protein kinase (PK)C inhibitors, staurosporine (SP) and its derivative GF109203-X, showed a several fold increase in the levels of Il6 mRNA in control and CSF-1-primed PMo and a parallel release of large amounts of protein. In contrast, SP was shown to have no effect on the release of GM-CSF from control or CSF-1-primed PMo, although it increased by approximately twofold the amount of Csfgm mRNA in CSF-1-primed Mo. When SP was added 4 h after CSF-1 priming to block CSF-1-induced protein kinase pathways, an increased amount of IL-6 release was again seen but without any increase in Il6 mRNA levels. Under these conditions, Csfgm gene expression was relatively unaffected. Activation of PKC by phorbol myristate acetate (PMA) also resulted in increased Il6 gene expression by control and CSF-1-primed PMo. PMA had no apparent effect on Csfgm transcription but appeared to influence translation at a low level, as measured by the release of small amounts of GM-CSF protein. The addition of lipopolysaccharide (LPS) to CSF-1-primed PMo resulted in a synergistic increase in the expression of both genes at the levels of transcription and protein release. The addition of SP to CSF-1-primed Mo before LPS, however, further enhanced IL-6 release but not GM-CSF release from the cells. The data indicate that CSF-1-priming drives a number of pathways involved in the regulation of expression of both genes and renders PMo highly susceptible to appropriate secondary stimulatory agents that transform the PMo into secretory inflammatory cells.

Animals↗
PubMed1997

IL-15 mediates anti-tumor effects after cyclophosphamide injection of tumor-bearing mice and enhances adoptive immunotherapy: the potential role of NK cell subpopulations.

The daily administration of IL-15 to cyclophosphamide (CY)-injected mice bearing the 76-9 rhabdomyosarcoma was shown to prolong the period of remission induced by CY. In addition, IL-15 was shown to enhance the efficacy of adoptive immunotherapy. Cytotoxicity assays using spleens from normal and tumor-bearing mice indicated that IL-15 enhanced NK cell activity but there was no evidence for class I-restricted cytolytic T cell activity. To determine whether IL-15 was likely to induce different cytotoxic effectors at the tumor site compared with the spleen, tumors were removed after CY injection and cell suspensions were incubated with IL-15 in parallel with isolated spleen cells. Both populations were seen to expand to yield predominantly cells coexpressing NK1.1 and B220 antigens. However, tumor-associated NK cells were shown to differ from expanded spleen NK cells in terms of the proportions of LGL-1+ cells and cells expressing early and late NK cell differentiation antigens. Both expanded populations expressed high NK cell cytotoxic activity but only the spleen cells expressed lymphocyte-activated killer cell activity. It was apparent that the expanded tumor-associated NK cells expressed low-level class I-restricted lytic activity. The potential of activated NK cells in the circulation to exert anti-tumor effects was shown by the adoptive transfer of expanded NK cells to tumor-bearing mice after CY injection when significant prolongation of life was seen in all cases. The data indicate that IL-15 may serve as a useful anti-cancer adjuvant by activating initially the NK cell arm of the immune network.

Adjuvants, Immunologic↗
PubMed1997

Safety of surfaces and equipment for children in playgrounds.

BACKGROUND: The safety of playgrounds is important to protect children from injury, but studies are mostly done mainly under laboratory conditions without epidemiological data. We investigated the safety of different playground surfaces, and types and heights of equipment in public playgrounds in the City of Cardiff, UK. METHODS: We did a correlational study of 330 children aged between 0 and 14 years. All children were hurt when playing in playgrounds in Cardiff and presented to the Accident and Emergency Department in Cardiff Royal Infirmary during summer (April to September) 1992 and 1993, and the whole of 1994. We studied the children's hospital records to establish the type of injury and interviewed their parents to find out the playground and type of equipment involved. The main outcome measures were the number of children injured whilst playing, and injury rates per observed number of children on different surfaces, types, and heights of equipment. FINDINGS: Children sustained significantly more injuries in playgrounds with concrete surfaces than in those with bark or rubberised surfaces (p < 0.001). Playgrounds with rubber surfaces had the lowest rate of injury, with a risk half that of bark and a fifth of that of concrete. Bark surfaces were not significantly more protective against arm fractures than concrete. Most injuries were equipment related. Injury risk due to falls from monkey bars (suspended parallel bars or rings between which children swing) was twice that for climbing-frames and seven times that for swings or slides. The height of the equipment correlated significantly with the number of fractures (p = 0.005) from falls. INTERPRETATION: Rubber or bark surfacing is associated with a low rate of injuries and we support their use in all public playgrounds. Bark alone is insufficient, however, to prevent all injuries, particularly arm fractures. Rubberised impact-absorbing surfaces are safer than bark. We believe that playing on monkeys bars increases the risk of injury in playgrounds and that they should generally not be installed. Safety standards should be based on physical and epidemiological data. Our data suggest that the proposed raising of the maximum fall height from 2.5 m to 3.0 m in Europe is worrying.

Accidental Falls↗
PubMed1997

Mosaicism in pseudoachondroplasia.

Pseudoachondroplasia (PSACH) is a spondylo-epi-metaphyseal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, and precocious osteoarthritis. PSACH is caused by mutations in the cartilage oligomeric matrix protein (COMP) gene, which codes for a noncollagenous protein expressed in the territorial matrix of chondrocytes. Autosomal dominant inheritance has been demonstrated in many families; however, autosomal recessive inheritance has been suggested in some severe familial cases. Alternatively, germline/somatic mosaicism has been proposed and is credible, since it has been shown that dominantly inherited and sporadic cases of PSACH are caused by the same genetic defect. Here, we present evidence demonstrating somatic mosaicism in two PSACH families that were originally considered to represent autosomal recessive inheritance. The results of this study suggest that autosomal recessive inheritance is unlikely and all cases of PSACH should be studied for mutations in COMP.

Achondroplasia↗
PubMed1997

CSF-1-induced and constitutive Il6 gene expression in mouse macrophages: evidence for PKC-dependent and -independent pathways.

It has been recently shown that CSF-1 enhanced the constitutive expression of the Il6 gene in resident mouse peritoneal macrophages (PM phi) but little is known about the pathways involved. In this report, we show that both constitutive and CSF-1-induced IL-6 release were enhanced and prolonged in the presence of the PKC inhibitors, staurosporine (SP) and its derivative, GF-109203X. Enhancement of constitutive IL-6 release required higher concentrations of inhibitors, while enhanced CSF-1-induced release was diminished when inhibitor concentrations exceeded defined limits. SP was also shown to activate constitutive IL-6 release by blood monocytes and elicited PM phi but had no effect on their responsiveness to CSF-1. Activation of PKC by exposure of resident PM phi to phorbol myristate acetate (PMA) also resulted in enhanced IL-6 release and PMA was shown to synergize with CSF-1. These data indicate that CSF-1 does not induce Il6 gene expression by amplifying the constitutive pathway in all mononuclear phagocyte subpopulations. It exerts its effects independently of PKC, which may activate Il6 gene expression in its own right by an alternative pathway. While CSF-1 and PKC are involved in separate pathways, the synergistic IL-6 response seen when PMA and CSF-1 interact suggests convergence of the two pathways. It is also apparent that multiple PKs, excluding PKC, may be involved in repressing constitutive and CSF-1-induced Il6 gene expression.

Animals↗