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Biomedical subjects

R Evans

Publications and source records attributed to R Evans.

At least 127 records · Page 7Linked to original sources

Allergy evaluation and immunotherapy.

Up to 10% of children and adolescents in the United States may have asthma and up to 40% may be affected by allergic rhinitis. Most people know that asthma is a serious disease, but "hay fever" is often mistakenly considered trivial. However, hay fever symptoms can significantly influence a patient's quality of life, causing fatigue, headache, and even cognitive impairment. Both asthma and allergic rhinitis can result in lost sleep, many missed school days, and the inability to participate in sports and other recreational activities in which young people engage. An appropriate diagnosis is the first step toward improving quality of life for these young patients. This article reviews diagnostic procedures for allergic disease, and-because compliance is frequently an issue with school-aged patients-it also reviews current thinking on allergen immunotherapy, a treatment that provides effective long-term control in appropriately selected patients.

Adolescent↗

Results of a phase II concurrent chemoradiotherapy study using three-dimensional conformal radiotherapy with cisplatin and oral etoposide in stage III nonsmall-cell lung cancer.

This phase II study was designed to utilize conformal radiation therapy with cisplatin and oral etoposide in patients with stage III or locally recurrent non-small-cell lung cancer to determine tolerance and toxicity of therapy. From April 1992-February 1996, 18 patients with pathologically confirmed stage IIIA, IIIB, or locally recurrent non-small-cell lung cancer (NSCLC) were entered on study. Metastatic workup included a CT scan of the thorax and upper abdomen as well as a bone scan. Chemotherapy consisted of IV cisplatin (100 mg/m2) with IV etoposide (25 mg/m2) on day 1; oral etoposide was given (50 mg/m2) days 2-14. Using three-dimensional planning, 40-45 Gy were delivered to the clinical target volume, followed by a boost to the gross tumor volume for a total of 70 Gy. Patients with recurrent disease received 40-50 Gy in total. Eighteen patients were enrolled: 16 patients were treated with curative intent and were evaluable for outcome. Two patients were treated for locally recurrent NSCLC and were not included in the outcome analysis. Stages included IIIA (44%) and stage IIIB (54%). Forty-four percent had T3/4 tumors, and 69% had N2/3 disease. Overall survival at 1 year was 64%, while 2-year overall survival was 50%. Distant metastasis-free survival at 1 year was 67%, and at 2 years 60%. The 1-year chest progression-free survival was 57%, and at 2 years 50%. Sixty-three percent required hospitalization for dehydration or neutropenia. Fifty-six percent developed leukopenia (<1,000 cells/microl) sometime during the therapy. We conclude that concurrent cisplatin and oral etoposide with conformal radiation therapy provide encouraging results in stage III lung cancer. The major toxicities of this therapy included leukopenia, thrombocytopenia, and mucosal esophagitis. Local progression of disease continues to be a problem with the current doses given. Future studies should evaluate dose escalation of radiation therapy with limited volumes, utilizing conformal radiation and chemotherapy to improve local control and potentially impact upon distant metastases.

Administration, Oral↗

Rates of growth and loss of bone mineral in the spine and femoral neck in white females.

This study characterizes the rates of growth and loss of bone mass as a function of age in white females. It combines longitudinal data from several studies of bone mass on healthy white female subjects ranging from age 6 to 90 years. Rates of change in bone area, bone mineral content (BMC) and bone mineral density (BMD) are estimated separately for the spine and the femoral neck of each individual using linear regression. The individual rates of change are then fitted as a nonparametric function of age using weighted moving averages, resulting in a curve of age-specific mean change as a function of age. When the curves of BMD were compared between the hip and the femoral neck, the cessation of bone growth and the onset of bone loss were found to occur at an earlier age at the hip than at the spine. No significant differences in the ages of maximum rates of growth or maximum loss were found between the two skeletal sites. This information will be useful for designing interventions to promote bone growth or retard bone loss.

Adolescent↗

Cell-culture system for continuous production of Toxoplasma gondii tachyzoites.

The aim of this study was to identify a sustainable cell line and culture method that could continuously provide a sufficient quantity of Toxoplasma gondii tachyzoites to serve the needs of a general hospital laboratory. Three continuous cell lines (HeLa, LLC and Vero) and three cell-culture methods (culture in conventional flasks, culture in membrane-based flasks and an automated culture system) were investigated. In multiplicity-of-infection and time-course experiments, HeLa was the cell line of choice. Harvests from HeLa cells had significantly higher tachyzoite yields than those from LLC cells (P<0.00005) or Vero cells (P<0.05). Membrane-based flasks gave higher yields (6.15x10(6) tachyzoites/ml) than conventional flasks (1-2x10(6) tachyzoites/ml) initially, but these were not sustained. The automated cell-culture system was unsuitable for parasite culture. Continuous passage in 25 cm2 flasks was successful, yielding 1x10(6) tachyzoites/ml; viability exceeded 90% after 96-120 h of infection throughout 38 passes, during which time the viability improved and the time to harvest became more consistent. Toxoplasma gondii grown in continuous culture in HeLa cells can provide a regular supply of viable tachyzoites. Demonstration that HeLa-derived tachyzoites could be used for the dye test confirms the potential of this in vitro system for use in general hospital laboratories.

Animals↗

A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.

OBJECTIVE: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. STUDY DESIGN: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline. RESULTS: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor. CONCLUSIONS: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.

Asthma↗

Transrectal ultrasound-guided intraprostatic injection of absolute ethanol with and without carmustine: a feasibility study in the canine model.

OBJECTIVES: To develop a reliable intraprostatic injection technique and to define the local and systemic toxicity of intraprostatic injection of dehydrated ethanol with and without carmustine. METHODS: Twenty-three random-source male canines were divided into a control group (n = 3), a dehydrated ethanol-alone group (group 1, n = 10), and a dehydrated ethanol-plus-carmustine group (group 2, n = 10). A reliable intraprostatic injection technique was developed with the control animals. The optimal volume of dehydrated ethanol for intraprostatic injection and the local tissue effects of dehydrated ethanol injection were defined with group 1. The local tissue effects of escalating doses of carmustine were defined with group 2. All animals were injected under general anesthesia using transrectal ultrasound (TRUS) guidance. Fourteen days after injection, a repeated TRUS of the prostate was done, the animals were killed, and the bladder, prostate, and periprostatic tissues were excised for pathologic examination. RESULTS: Sonographic changes in the prostate 2 weeks after injection were present in all group 1 and 2 animals. All prostates had varying amounts of hemorrhagic and coagulative necrosis, which correlated with the TRUS findings. There were no differentiating pathologic features between group 1 and group 2 specimens. The relative amount of necrosis varied with the doses of dehydrated ethanol and carmustine injected, but was not predictable on the basis of the doses administered. Subclinical prostatic microabscesses were identified in 6 of 10 group 1 animals and 4 of 10 group 2 animals. Only group 2 animals had alterations in their blood chemistry results, all of which were self-limited. Two had white blood cell nadirs of less than 2000 5 days after injection. No animals developed incontinence, and there were no rectal injuries. CONCLUSIONS: Intraprostatic dehydrated ethanol and carmustine injections were readily controllable under TRUS guidance and resulted in hemorrhagic and coagulative necrosis of prostatic tissue with minimal associated morbidity and no incontinence in the dog model. Hematologic changes observed in the animals that received carmustine were self-limiting.

Animals↗

The use of automated data to identify complications and comorbidities of diabetes: a validation study.

We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases, 9th edition, Clinical Modification and Current Procedural Terminology codes. The records of 471 randomly selected diabetic patients were reviewed for complications from January 1, 1993 to December 31, 1995; chart data served to validate automated data. The complications with the highest sensitivity determined by a diagnosis in the medical records identified within +/-60 days of the database date were myocardial infarction (95.2%); amputation (94.4%); ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the exception of amputation (82.9%), positive predictive value was low when based on a diagnosis identified within +/-60 days of the database date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purposes.

Adolescent↗

Further evidence from two families that craniofrontonasal dysplasia maps to Xp22.

Craniofrontonasal dysplasia (CFND) is a rare X-linked disorder that maps to a 13-cM region on Xp22. Phenotypic features include craniosynostosis, hypertelorism and a broad nasal root with or without a bifid nasal tip. Multiple examples have been reported of males having a less severe phenotype than females. We report haplotype analyses in two CFND families over the critical region to which the gene has been mapped. In pedigree 1, a clinically unaffected male inherited the affected marker haplotype spanning the critical region. We suggest that this individual does have the CFND mutation, but has an extremely mild phenotype that is not detectable with clinical examination. Under the assumption that he is an unknown phenotype, a combined two-point LOD score of 1.68 at zero recombination was obtained, increasing the previously reported total to 5.61 (DXS8022). The data do not narrow down the critical region. This result stresses the importance of subjecting fathers of apparently sporadic cases to a highly critical medical examination and may also explain the unequal ratio of reported female-to-male cases.

Craniofacial Abnormalities↗

Influence of temperature on tracheal tube cuff pressure during cardiac surgery.

BACKGROUND: Lateral wall pressure may cause tracheal injury by affecting tracheal capillary blood flow. Damage to the trachea is less severe when lateral wall pressure exerted by the endotracheal tube cuff does not exceed the mean capillary perfusion pressure of the mucosa. The purpose of this study was to determine the effects of hypothermic and normothermic cardiopulmonary bypass (CPB) on tracheal tube cuff pressure dynamics. METHODS: Twenty-two patients were studied during normothermic CPB (pulmonary artery blood temperature in the CPB period between 36 and 35 degrees C), and 22 patients during hypothermic CPB (pulmonary artery temperature in the CPB period between 32 and 28 degrees C). A Mallinckrodt Medical Lo-Contour Murphy tracheal tube, with high-volume, low-pressure cuff was used without lubricant. Intracuff pressure (ITCP) was recorded at end-expiration before, during and after cardiopulmonary bypass. RESULTS: ITCP measurements were different between groups during CPB at aortic cross-clamping (13.9 +/- 0.8 mmHg in the normothermic group versus 11.3 +/- 0.4 mmHg in the hypothermic group, P < 0.05), and respectively during CPB after aortic declamping (15.3 +/- 0.8 mmHg and 12.6 +/- 0.8 mmHg, P < 0.05) and after CPB at the end of surgery (16.8 +/- 0.7 mmHg and 18.6 +/- 0.3 mmHg, P < 0.05). CONCLUSION: We conclude that the ITCP is higher in normothermic CPB than in hypothermic CPB; however, the clinical significance of this observation needs further investigation.

Aged↗

Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein.

Rb protein inhibits both cell cycle progression and apoptosis. Interaction of specific cellular proteins, including E2F1, with Rb C-terminal domains mediates cell cycle regulation. In contrast, the nuclear N5 protein associates with an Rb N-terminal domain with unknown function. The N5 protein contains a region of sequence similarity to the death domain of proteins involved in apoptotic signaling. We demonstrate here that forced N5 expression potently induces apoptosis in several tumor cell lines. Mutation of conserved residues within the death domain homology compromise N5-induced apoptosis, suggesting that it is required for normal function. Endogenous N5 protein is specifically altered in apoptotic cells treated with ionizing radiation. Furthermore, dominant interfering death domain mutants compromise cellular responses to ionizing radiation. Finally, physical association with Rb protein inhibits N5-induced apoptosis. We propose that N5 protein plays a role in the regulation of apoptosis and that Rb directly coordinates cell proliferation and apoptosis by binding specific proteins involved in each process through distinct protein binding domains.

Amino Acid Sequence↗

Effects of dopexamine on blood flow in multiple splanchnic sites measured by laser Doppler velocimetry in rabbits undergoing cardiopulmonary bypass.

Decreased gut perfusion has been reported during cardiopulmonary bypass (CPB). Studies of treatments to avoid splanchnic ischaemia during CPB have given conflicting results. We studied 12 rabbits during mild hypothermic non-pulsatile CPB. Tissue blood flow in three different splanchnic areas (gastric, jejunum and ileum) was measured by laser Doppler velocimetry (LDV) before CPB (T0), after steady state (T1), after administration of dopexamine 2 micrograms kg-1 min-1 (T2) and 4 micrograms kg-1 min-1 (T3), and after return to baseline (T4). Splanchnic blood flow decreased during CPB. Dopexamine increased significantly jejunum LDV (100% at T1 to mean 271 (SD 210)% at T2) and ileum LDV (100% at T1 to 187 (112)% at T2). Gastric LDV was not altered by infusion of dopexamine during CPB. This could partly explain the conflicting results on the value of gastric tonometry as an index of splanchnic injury.

Adrenergic beta-Agonists↗

Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations.

We have measured serum procalcitonin (PCT) concentrations after cardiac surgery in 36 patients allocated to one of three groups: group 1, coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) (n = 12); group 2, CABG without CPB (n = 12); and group 3, valvular surgery with CPB (n = 12). Serum PCT and C-reactive protein (CRP) concentrations were measured before operation, at the end of surgery and daily until postoperative day 8. Serum PCT concentrations increased, irrespective of the type of cardiac surgery, with maximum concentrations on day 1: mean 1.3 (SD 1.8), 1.1 (1.2) and 1.4 (1.2) ng ml-1 in groups 1, 2 and 3, respectively (ns). Serum PCT concentrations remained less than 5 ng ml-1 in all patients. Concentrations returned to normal by day 5 in all groups. To determine the effect of the systemic inflammatory response (SIRS) on serum PCT concentrations, patients were divided post hoc, without considering the type of cardiac surgery, into patients with SIRS (n = 19) and those without SIRS (n = 17). The increase in serum PCT was significantly greater in SIRS (peak PCT 1.79 (1.64) ng ml-1 vs 0.34 (0.32) ng ml-1 in patients without SIRS) (P = 0.005). Samples for PCT and CRP measurements were obtained from 10 other patients with postoperative complications (circulatory failure n = 7; active endocarditis n = 2; septic shock n = 1). In these patients, serum PCT concentrations ranged from 6.2 to 230 ng ml-1. Serum CRP concentrations increased in all patients, with no differences between groups. The postoperative increase in CRP lasted longer than that of PCT. We conclude that SIRS induced by cardiac surgery, with and without CPB, influenced serum PCT concentrations with a moderate and transient postoperative peak on the first day after operation. A postoperative serum PCT concentration of more than 5 ng ml-1 is highly suggestive of a postoperative complication.

Aged↗

Isolation of Borrelia burgdorferi from ticks in the Highlands of Scotland.

Borrelia burgdorferi, the causative agent of Lyme disease, was first isolated in 1982 and since then has been regularly isolated from ticks and clinical material in both Continental Europe and the USA. However, only three isolations have been reported in Britain. During the summer of 1997, 128 ticks were collected from two sites in the Highlands of Scotland and examined by the polymerase chain reaction (PCR) and culture. Eleven fresh isolates were obtained from culture and passed up to 22 times. Seven of the tick emulsions were also positive by flagellin gene PCR, and a further one was positive by PCR but negative on culture. All 11 isolate cultures were positive by the flagellin gene PCR. Further studies on four of these isolates confirmed their identity by immunofluorescence, but also detected possible differences between them and B. burgdorferi ACA-1 by enzyme profiles and by PCR with OspA gene primers. Culture of these new strains provides antigens that should improve diagnostic serological tests in Britain.

Animals↗

Phase diagram of highly asymmetric binary hard-sphere mixtures.

We study the phase behavior and structure of highly asymmetric binary hard-sphere mixtures. By first integrating out the degrees of freedom of the small spheres in the partition function we derive a formal expression for the effective Hamiltonian of the large spheres. Then using an explicit pairwise (depletion) potential approximation to this effective Hamiltonian in computer simulations, we determine fluid-solid coexistence for size ratios q=0.033, 0.05, 0.1, 0.2, and 1.0. The resulting two-phase region becomes very broad in packing fractions of the large spheres as q becomes very small. We find a stable, isostructural solid-solid transition for q< or =0.05 and a fluid-fluid transition for q< or =0.10. However, the latter remains metastable with respect to the fluid-solid transition for all size ratios we investigate. In the limit q-->0 the phase diagram mimics that of the sticky-sphere system. As expected, the radial distribution function g(r) and the structure factor S(k) of the effective one-component system show no sharp signature of the onset of the freezing transition and we find that at most points on the fluid-solid boundary the value of S(k) at its first peak is much lower than the value given by the Hansen-Verlet freezing criterion. Direct simulations of the true binary mixture of hard spheres were performed for q > or =0.05 in order to test the predictions from the effective Hamiltonian. For those packing fractions of the small spheres where direct simulations are possible, we find remarkably good agreement between the phase boundaries calculated from the two approaches-even up to the symmetric limit q=1 and for very high packings of the large spheres, where the solid-solid transition occurs. In both limits one might expect that an approximation which neglects higher-body terms should fail, but our results support the notion that the main features of the phase equilibria of asymmetric binary hard-sphere mixtures are accounted for by the effective pairwise depletion potential description. We also compare our results with those of other theoretical treatments and experiments on colloidal hard-sphere mixtures.

Journal Article↗

Effects of confinement on critical adsorption: absence of critical depletion for fluids in slit pores.

The adsorption of a near-critical fluid confined in a slit pore is investigated by means of density functional theory and by Monte Carlo simulation for a Lennard-Jones fluid. Our work was stimulated by recent experiments for SF6 adsorbed in a mesoporous glass, which showed the striking phenomenon of critical depletion, i.e., the adsorption excess Gamma first increases but then decreases very rapidly to negative values as the bulk critical temperature T(c) is approached from above along near-critical isochores. By contrast, our density functional and simulation results, for a range of strongly attractive wall-fluid potentials, show Gamma monotonically increasing and eventually saturating as the temperature is lowered toward T(c) along both the critical (rho=rho(c)) and subcritical isochores (rho T(+)(c). For rho<rho(c) we find that in the fluid the effective bulk field, which is negative and which favors desorption, is insufficient to dominate the effects of the surface fields which favor adsorption. We compare this situation with earlier results for the lattice gas model with a constant (negative) bulk field where critical depletion was found. A qualitatively different behavior of the density profiles and adsorption is found in simulations for intermediate and weakly attractive wall-fluid potentials, but in no case do we observe the critical depletion found in experiments. We conclude that the latter cannot be accounted for by a single pore model.

Journal Article↗