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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

At least 145 records · Page 8Linked to original sources

What is right about the Canadian health care system?

Canadians tend to dwell on problems in their health care system, looking to the United States for magical fixes. Evidence on comparative system performance, which rarely surfaces in public debate, indicates that Canadians are healthier, not only because the social environment is more benign, but also because health care is allocated by need rather than ability to pay. Expenditures are much lower, but Canadians receive equivalent care because their system is more efficient. Although Canadian "waiting lists" are highly publicized, the United States avoids the issue by excluding those who cannot pay. Why, then, do American notions keep pushing north? All expenditures are someone's income. There is a great deal of money to be made by wrecking Canadian Medicare.

Canada↗

Restructuring asthma care in a hospital setting to improve outcomes.

STUDY OBJECTIVES: To restructure asthma care as the pilot program in hospital-wide redesign aimed at providing better and more standardized care. We chose asthma care to begin our reorganization because it is the highest-volume diagnosis at our hospital and it involves a broad spectrum of services. DESIGN: Key elements of our restructuring included the following: (1) establishing a pulmonary unit with expanded bed capacity from 8 to 22 beds for asthma patients; (2) standardized treatment protocols; (3) availability of direct admission by primary care physicians who maintained management of their patients with the option of consultation with a specialist; and (4) use of case managers who helped patients and their families overcome obstacles to optimum care. SETTING: A hospital serving a high proportion of Medicaid patients. PATIENTS/PARTICIPANTS: Children with asthma and their families. INTERVENTIONS: Standardized care for asthma; use of case managers to facilitate adherence to treatment. RESULTS: With the restructured asthma care program, parent satisfaction with treatment was sustained; the average length of stay and use of the emergency department (ED) were reduced; observation unit use increased; and there were fewer readmissions to both the inpatient unit and the ED. CONCLUSIONS: We conclude that an inner-city hospital can provide optimum care for asthma patients by standardizing treatment, aggregating asthma patients in one location, and providing education and follow-up through the use of case managers. The protocol shifts some costs from expensive services such as the pediatric ICU and the ED to less costly case management and outreach personnel. In the long run, this allocation of resources should help to lower costs as well as improve quality of care.

Asthma↗

Codeine intoxication in the neonate.

Although opiates can provide patients with relief from pain and the discomfort of cough, the routine prescription of these drugs for infants demands caution and concern. Infants, particularly neonates, are not merely small adults requiring smaller dosages, but rather uniquely different patients. Neonates present with an immature physiology and biochemistry with respect to drug metabolism. We report a case of codeine intoxication in the neonate, in which the drug was prescribed for cough control during an emergency department visit.

Codeine↗

Allergy: etiology and epidemiology.

The occurrence of atopic disease throughout the world is subject to many variables. Differences in methodology and diagnostic criteria for measuring the incidence could account for some disparities, but they cannot explain all of them. Despite our increasing knowledge of the atopic diseases, improved treatments, and early diagnosis, the incidence and prevalence of asthma, allergic rhinitis, and atopic dermatitis continue to rise. Ongoing research into the etiology and potential risk factors for atopic diseases could lead to the early diagnosis, effective treatment, and prevention.

Asthma↗

Evaluation of the biochemical effects of administration of intravenous nutrients using erythrocyte ATP/ADP ratios.

Regardless of clinical diagnosis, many acutely and chronically sick patients benefit from intravenous vitamins and minerals, which are usually administered in multiple infusions before observing obvious benefit. We hypothesized this effect was due to improved cellular energy, and attempted to find laboratory evidence via this study. Two groups of patients, chosen at random, received a single infusion of vitamins and minerals in two different dose schedules. Controls received no treatment. Study subjects were patients who presented specifically for a nutritional therapeutic approach, and although all were treated with multiple infusions, a single infusion was selected at random for this study. Thirty patients received a single infusion of a lower dose nutritional formula, sometimes known as a Myer's Cocktail (MC), and 34 had a single infusion of a higher dose nutritional I/V (NIV). Immediately prior to and after the infusion, blood was drawn and an erythrocyte ATP/ADP ratio (EADR) was determined. The results showed that in both infusion groups if the EADR was initially low, it would increase. If it were initially high, it would decrease. This effect was not observed in control subjects. Pre-test EADR boxplot analyses, derived from the results of each protocol, showed these results were statistically predictable. An analysis of variation (ANOVA) calculation indicated the differences were significant. The family error rate used was 0.05. We conclude that this regression of the EADR to the mean, as a result of either of the two infusions and not seen in control subjects, is biochemically significant.

Adenosine Diphosphate↗

Combination chemotherapy and IL-15 administration induce permanent tumor regression in a mouse lung tumor model: NK and T cell-mediated effects antagonized by B cells.

Previous studies have demonstrated that IL-15 administration after cyclophosphamide (CY) injection of C57BL/6J mice bearing the i.m. 76-9 rhabdomyosarcoma resulted in a significant prolongation of life. In the present study, we investigated the immune response against the 76-9 experimental lung metastases after CY + IL-15 therapy. Administration of CY + IL-15, but not IL-15 alone, induced prolongation of life and cures in 32% of mice bearing established experimental pulmonary metastases of 76-9 tumor. The CY + IL-15 therapy resulted in increased levels of NK1.1+/LGL-1+ cells, and CD8+/CD44+ T cells in PBL. In vitro cytotoxic assay of PBL indicated the induction of lymphokine-activated killer cell activity, but no evident tumor-specific class I-restricted lytic activity. Survival studies showed that the presence of NK and T lymphocytes is necessary for successful CY + IL-15 therapy. Experiments using knockout mice implied that either alphabeta or gammadelta T cells were required for an antitumor effect induced by CY + IL-15 therapy. However, mice lacking in both alphabeta and gammadelta T cells failed to respond to combination therapy. Cured B6 and alphabeta or gammadelta T cell-deficient mice were immune to rechallenge with 76-9, but not B16LM tumor. B cell-deficient mice showed a significant improvement in the survival rate both after CY and combination CY + IL-15 therapy compared with normal B6 mice. Overall, the data suggest that the interaction of NK cells with tumor-specific alphabeta or gammadelta T lymphocytes is necessary for successful therapy, while B cells appear to suppress the antitumor effects of CY + IL-15 therapy.

Animals↗

Jarvik 2000 heart: potential for bridge to myocyte recovery.

BACKGROUND: Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose. METHODS AND RESULTS: The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft. CONCLUSIONS: The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.

Animals↗

Cytokine release by macrophages after interacting with CSF-1 and extracellular matrix proteins: characteristics of a mouse model of inflammatory responses in vitro.

Extracellular matrix (ECM) proteins play a key role at sites of inflammation where they regulate the inflammatory properties of infiltrating leukocytes. Previous data indicated that the macrophage colony-stimulating factor (CSF-1 or M-CSF) primed subpopulations of mononuclear phagocytes (MNP) for differential inflammatory responses and rendered defined populations extremely sensitive to secondary stimulation as measured by cytokine gene expression. In this report, we focus on the question whether CSF-1 modified the inflammatory responsiveness of elicited peritoneal macrophages (PM phi), as a defined subpopulation of MNP, to secondary stimulation by ECM proteins as a component of inflammatory lesions. It was seen that CSF-1-primed PM phi responded to fibronectin (FN) and collagen type IV (COL IV) in vitro by releasing large amounts of IL-6 but released only minimal quantities when exposed to vitronectin (VN) or to untreated plastic surfaces. TNF-alpha and GM-CSF proteins were not released. Preincubation of the PM phi with CSF-1 or 10% FBS for up to 12 h prior to exposure to ECM proteins was shown to further enhance the release of IL-6 when the cells were cultured with FN but to result in a loss of secretory activity when placed on COL IV. In addition, preincubated PM phi in contact with FN were shown to release TNF-alpha but not GM-CSF. CSF-1 did not enhance VLA 4 (alpha 4 beta 1 or CD49d) but enhanced VLA 5 (alpha 5 beta 1 or CD49e) expression. However, blocking with either anti-VLA 4 or VLA 5 monoclonal antibodies inhibited the IL-6 response. These data suggest that CSF-1 primes elicited PM phi for differential expression of adhesion molecules that are required for binding to individual ECM proteins and for modulating inflammatory responses of MNP.

Animals↗

Compliance with national asthma management guidelines and specialty care: a health maintenance organization experience.

BACKGROUND: To improve asthma disease management, the National Asthma Education Program (NAEP) Expert Panel published Guidelines for the Diagnosis and Management of Asthma in 1991. OBJECTIVES: To compare the current status of asthma disease management among patients in a large health maintenance organization with the NAEP guidelines and to identify the factors that may be associated with medical care (eg, emergency department visits and hospital admissions) and adherence to the guidelines. METHODS: Analyses of 1996 survey data from 5580 members with asthma (age range, 14 to 65 years) covered by a major health maintenance organization in California (Health Net). RESULTS: In general, adherence to NAEP guidelines was poor. Seventy-two percent of respondents with severe asthma reported having a steroid inhaler, and of those, only 54% used it daily. Only 26% of respondents reported having a peak flowmeter, and of those, only 16% used it daily. Age (older), duration of asthma (longer), increasing current severity of disease, and treatment by an asthma specialist correlated with daily use of inhaled steroids. Ethnicity (African American and Hispanic) correlated negatively with inhaled steroid use but positively with emergency department visits and hospital admissions for asthma. Increasing age and treatment by an asthma specialist were also identified as common factors significantly related to the daily use of a peak flowmeter and, interestingly, to overuse of beta2-agonist metered-dose inhalers. CONCLUSIONS: Although the NAEP guidelines were published 7 years ago, compliance with the guidelines was low. It was especially poor for use of preventive medication and routine peak-flow measurement. Furthermore, the results showed that asthma specialists provided more thorough care than did primary care physicians in treating patients with asthma. Combining the results of the regression analyses revealed that some of the variation in rates of emergency department visits and hospitalizations among some subpopulations can be explained by the underuse of preventive medication. This study serves the goal of documenting the quality of care and services currently provided to patients with asthma through a large health maintenance organization and provides baseline information that can be used to design and assess effective population-based asthma disease management intervention programs.

Adolescent↗

Cervical lymphadenopathy: sonographic differentiation between tuberculous nodes and nodal metastases from non-head and neck carcinomas.

PURPOSE: Clinical examination alone cannot differentiate between cervical tuberculous lymphadenitis and cervical nodal metastases from non-head and neck (NHN) carcinomas because the distributions of involved lymph nodes are similar. We evaluated the sonographic features of cervical lymph nodes that could be used to differentiate between the 2 categories of nodes. METHODS: We retrospectively reviewed sonograms of abnormal cervical lymph nodes in 47 patients with proven cervical tuberculous lymphadenitis and in 22 patients with proven nodal metastases from NHN carcinomas. RESULTS: Abnormal nodes in tuberculous lymphadenitis and nodal metastases from NHN carcinomas were commonly found in the supraclavicular fossa (15% and 38%, respectively) and the posterior triangle (70% and 41%, respectively). Statistically significant (p < 0.05) features for differential diagnosis were lymph nodes' longest diameter, echogenicity, short-to-long axis ratio, appearance of surrounding soft tissues, and presence of intranodal cystic necrosis, matting, and posterior enhancement. Nodal size, echogenicity, presence of an echogenic hilum, calcification, coagulation necrosis, and sharpness of borders helped in identifying the abnormal lymph nodes. CONCLUSIONS: Sonographic features that helped to differentiate between the 2 categories of nodes were shape, edema of surrounding soft tissue, homogeneity, intranodal cystic necrosis, matting, and posterior enhancement.

Adult↗

CSF-1 (M-CSF) differentially sensitizes mononuclear phagocyte subpopulations to endotoxin in vivo: a potential pathway that regulates the severity of gram-negative infections.

CSF-1 is known to prime mononuclear phagocytes (MNP) for inflammatory stimuli in vitro. We hypothesized that CSF-1 in vivo can sensitize the host to the increased production of endotoxic shock mediators such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Indeed, when CSF-1-primed mice were challenged with lipopolysaccharide (LPS), increased levels of serum IL-6 and TNF-alpha were detected. Both intravenous and intraperitoneal injections of CSF-1 resulted in increased sensitivity to LPS challenge, which induced maximum increases in serum IL-6 when administered via the intraperitoneal route. The peak serum IL-6 production in control and CSF-1-primed mice occurred 2-3 h after LPS injection, whereas that of TNF-alpha occurred by 1-2 h. When peripheral blood leukocytes, spleen cells, and resident peritoneal cells (PC) were isolated from CSF-1-primed mice injected with LPS, only the PC were shown to release IL-6 constitutively and none released TNF-alpha. A comparison of mRNA isolated from various cells and tissues after intraperitoneal CSF-1 priming indicated that only PC expressed IL-6 mRNA, whereas PC, liver, and spleen expressed TNF-alpha mRNA. All tissues showed increased levels of IL-6 and TNF-alpha mRNA in response to LPS challenge. Only liver and kidney showed an enhanced level of IL-6 expression in CSF-1-primed mice challenged with LPS, whereas liver, lung, and kidney showed enhanced TNF-alpha expression. These data indicate that CSF-1 primes tissue MNP but not circulating MNP to transcribe mRNA and release IL-6 and TNF-alpha. Overall, the data suggest that CSF-1 plays an important role in regulating the sensitivity of the host to the pathophysiological effects of endotoxin.

Animals↗

CSF-1 regulation of Il6 gene expression by murine macrophages: a pivotal role for GM-CSF.

We test the hypothesis that the monocyte-macrophage colony-stimulating factor (CSF-1 or M-CSF) plays a major role in the inflammatory responses of Mphi by acting as a priming agent that heightens their responsiveness to secondary stimulation by other mediators. We previously reported that CSF-1 induced peritoneal Mphi (PMphi) to transcribe several genes including interleukin-6 (Il6) and granulocyte-macrophage colony-stimulating factor (Csfgm). It was reported that the Il6 and Csfgm genes were individually regulated by different pathways but it was not clear to what extent the two genes interacted during Mphi-mediated inflammatory responses. We now show that CSF-1 induces the release of bioactive GM-CSF from mouse resident PMphi. GM-CSF induces Il6 gene expression and synergizes with CSF-1 to induce the release of large amounts of IL-6. PMphi from C57BL/6J-Csfgm(null) mice were shown to release minimal IL-6 in response to CSF-1 and to express a much reduced response to the highly stimulatory combination of CSF-1 and lipopolysaccharide (LPS). Exogenous recombinant GM-CSF restored the IL-6 response of GM-CSF null PMphi to a great extent but not completely. As controls, three other recombinant proteins were tested but of these only tumor necrosis factor alpha (TNF-alpha) was shown to synergize with both CSF-1 and GM-CSF. Using PMphi from mice deficient in the expression of the Il6 gene, it was shown that they released two- to threefold more GM-CSF in response to CSF-1 than their control counterparts. However, an exogenous supply of recombinant IL-6 had no effect on GM-CSF release. The data indicate that the pathways regulating Il6 gene expression are under the control of a complex network of cytokine interactions involving at least CSF-1, GM-CSF, and TNF-alpha, with the added possibility that IL-6 may exert modulatory activity within this network.

Animals↗

Trauma admissions in the elderly: how does a patient's age affect the likelihood of their being admitted to hospital after a fracture?

In two projects we have studied patients presenting to Accident and Emergency (A&E) departments with a fracture, to examine how their age influences their likelihood of admission. Over 1 year from April 1994 we collected data on all 6467 Cardiff residents who presented to the city's A&E department with a fracture. In total 1226 (19%) were admitted. Overall, only 12% of those under 65, but 47% of older patients required admission. This was largely a reflection of the age-distribution of hip fracture, an injury for which admission is inevitable. In a subsequent study of eight A&E departments in South Wales we therefore considered the proportion of patients admitted following fractures at specific anatomical sites. In people over the age of 55 we identified 6889 fractures, 2115 (31%) of which led to admission. After standardisation to control for the age-distribution of incidence for different fracture sites, we found that the likelihood of admission was 22% greater for people aged over 65 years. Elderly people very often require hospital admission after a fracture, primarily as a consequence of the types of fractures that they tend to sustain. Admissions directly attributable to the effects of age and age-related medical, psychiatric and social comorbidity appear of more limited significance.

Adolescent↗

The United Kingdom pre-hospital study of active compression-decompression resuscitation.

This prospective, controlled trial with crossover group design compares the effectiveness of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of victims of prehospital cardiac arrest. In three UK cities, victims of non-traumatic, out of hospital cardiac arrest, over the age of 8 years received either standard or ACD-CPR on arrival of ambulance personnel. Main outcome measures were return of spontaneous circulation, survival to be admitted to the intensive care unit, survival to hospital discharge, and neurological outcome. A total of 576 patients (STD-CPR, n=309; ACD-CPR, n=267) were analysed. The treatment groups were similar with respect to age, gender, proportion of witnessed arrests, initial cardiac rhythm, and call to advanced life support interval. The proportion of patients receiving bystander CPR was higher in the ACD group (37.1% vs. 28.5%; P=0.028). The interval between collapse and defibrillation was longer in the ACD group (12.3 min vs. 10.4 min; P=0.028). There was no difference between the STD-CPR and ACD-CPR groups in survival to admission to the intensive care unit (13.6% vs. 13.8%; P=0.93) or hospital discharge (4.8% vs. 6.0%; P=0.67). There was no difference between the groups with respect to the neurological outcome of those patients surviving to hospital discharge. Analysis of important subgroups also showed no benefit for ACD-CPR. We conclude that there was no improvement in outcome with ACD-CPR when used by ambulance personnel in Cardiff and Portsmouth.

Aged↗

Three new ellagic acid derivatives from the bark of Eschweilera coriacea from the Suriname rainforest.

Bioassay-guided fractionation of Eschweilera coriacea collected in the lowland wet forest of Suriname yielded the new but only weakly active ellagic acid derivative eschweilenol A (1) and the two new but inactive ellagic acid derivatives eschweilenol B (2) and eschweilenol C (3). The four known compounds, sucrose, ellagic acid, 3-O-galloylepigallocatechin, and epigallocatechin, were also isolated. The structures of the three new compounds were determined by spectrometric methods, primarily from the HMQC, HMBC, NOESY, and ROESY NMR techniques, and chemical methods, including methylation and triethylsilylation. The location of a hydroxyl group in one ellagic acid derivative was determined by a new technique involving an NOE correlation of the protons of a triethylsilyl derivative with a proton on a neighboring aromatic ring.

Antifungal Agents↗