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PubMed1983

The difference between the effects of single and double applications of 12-O-tetradecanoylphorbol-13-acetate, a potent tumor promoter, on polyamine metabolism and nucleic acid synthesis in mouse epidermis.

Double applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin at intervals of greater than 48 h led to a larger induction of ornithine decarboxylase (ODC) and a smaller increase of DNA and RNA synthesis than did a single application. The largest induction of S-adenosylmethionine decarboxylase occurred at a 120 h interval between coupled TPA applications. The change in ODC activity was followed by a parallel change in putrescine level. At intervals less than 24 h, the first application of TPA appeared to induce a refractory state; the second application of TPA did not induce the polyamine biosynthetic enzymes nor cause an accumulation of polyamines. The effect of the second application of TPA on the synthesis of DNA and RNA was considerably less at all times than that of a single application.

Animals↗

PubMed2006

The effectiveness of a high output/short duration radiofrequency current application technique in segmental pulmonary vein isolation for atrial fibrillation.

AIMS: Segmental pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation has become a curative therapy for atrial fibrillation (AF). However, the long procedure time limits the wide application of this procedure. The aim of the current study was to compare a novel ablation technique with a high power output and short application time vs. a conventional technique using a low power output and long application time. METHODS AND RESULTS: The study included 90 consecutive patients (age 53+/-10 years; 66 men). Segmental PV isolation was performed by irrigated RF catheter ablation in both groups. In the conventional group (Group 1, 45 patients), the power output was limited to 30 W with a target temperature of 50 degrees C and an RF preset duration of 120 s. In the novel group (Group 2, 45 patients), the maximum power output was preset to 45 W, with a target temperature of 55 degrees C and duration of 20 s. In Group 2, a significant reduction in the PV isolation time (127+/-57 vs. 94+/-33 min, P<0.02), mean fluoroscopy time (73+/-23 vs. 55+/-16 min, P<0.001), and radiation dose was observed. According to the application time and number, Group 2 showed a reduction in RF application time, but a higher number of RF applications were required for creation of complete PV isolation. During a mean follow-up of 15+/-7 months, a total of 74% of patients in Group 1 and 76% of patients in Group 2 demonstrated stable SR. CONCLUSION: Segmental PV isolation using a high power output and short application time is safe and effective in PV isolation in patients with AF. This technique can significantly reduce the procedure and fluoroscopy time compared with a low-power output technique.

Atrial Fibrillation↗

PubMed2003

Emergence of adult northern and western corn rootworms (Coleoptera: Chrysomelidae) following reduced soil insecticide applications.

A 3-yr investigation was conducted in commercial corn, Zea mays (L.), fields in eastern South Dakota to determine how reduced application rates of planting-time soil insecticides would influence temporal emergence patterns and survival of northern and western corn rootworms, Diabrotica barberi Smith and Lawrence, and D. virgifera virgifera LeConte, respectively. Beetle emergence was monitored at 2-d intervals throughout the entire adult emergence period of three growing seasons from corn plots treated with planting-time applications of labeled (1X) and reduced (0.5 and 0.75X) application rates of terbufos, tefluthrin, and chlorethoxyfos. No consistent insecticide- or rate-related impacts on mean total emergence per trap were recorded for any of the compounds investigated. However, terbufos applications resulted in a 52% reduction in the number of beetles captured per trap, 53% reduction in maximum rate of adult emergence, and a 59% reduction in overall rate of emergence over time for male D. virgifera during 1994. Terbufos also significantly extended the time required for emergence to peak and linear emergence of female D. virgifera to end in 1994. Tefluthrin applications delayed onset, end, and time of maximum emergence of female D. barberi by 9.9, 14.1, and 12 d, respectively, during 1993. Tefluthrin also reduced emergence rates over time for male (38%) and female (46%) D. barberi during 1994. Overall, application rate was inconsequential regarding total emergence, seasonal emergence pattern, or level of plant protection provided for all insecticides we tested in this 3-yr investigation. Our findings demonstrate that, if properly applied, the reduced application rates used in this study provide adequate root protection and will not significantly impact the biology of these pest species.

Animals↗

PubMed1987

Changes in the qualifications of medical school applicants, 1981 to 1985.

The decline in the number of medical school applicants has prompted concerns among medical educators regarding the effects of this decrease on the qualifications of the applicant pool. Changes in the qualifications of medical school applicants were analyzed in terms of age, sex, and ethnicity or racial group using two measures of quality: Medical College Admission Test (MCAT) scores and grade-point averages. The distributions of these measures for 1981 and 1985 applicants were compared. The results showed that there were significant but modest gains over the years in the percentage of men and women applicants who scored from 10 to 15 on the MCAT biology, chemistry, physics, and science problems subtests. There were also significant percentage gains for applicants in all age categories, except applicants over age 32, and for all ethnic or racial groups except blacks. The authors conclude that a variety of sociodemographic, educational, and selection factors may account for these changes.

Adult↗

PubMed1995

Predicting subsequent employment status of SSA disability applicants with chronic pain.

OBJECTIVE: The study assessed the predictive ability of the standardized Multiperspective Multidimensional Pain Assessment Protocol (MMPAP). An assessment tool that predicts return to work with chronic pain patients is needed, as increasing numbers of disability applications are adjudicated in the courts. DESIGN: National randomized validation sample of disability applicants. Each MMPAP consisted of physical examinations by two physiatrists and the participant's subjective assessment. Criterion standards were Multidimensional Pain Inventory and McGill Pain Questionnaire. There was phone follow-up 6 months postdecision. SETTING: Six clinical sites were ambulatory referral centers, both public and private. PARTICIPANTS: Population-based random national sample of 710 Social Security disability applicants claiming chronic pain related to their disability, stratified by national Social Security Administration (SSA) applicant demographics. Seventy-eight were lost to follow-up, and 688 initially refused. INTERVENTIONS: No interventions were continued or initiated by the research team between assessment and follow-up. MAIN OUTCOME MEASURES: Claimant employment status 6 months after disability decision was primary outcome, change in pain intensity, and change in employment situation. RESULTS: The MMPAP predicted with 90% accuracy employment status of SSA disability applicants with chronic pain 6 months postdecision when assessed at application by two physicians trained in Physical Medicine and Rehabilitation (physiatry). Accuracy of employment situation change was 93%, and pain intensity change was 65%. Self-report measures, physical examination results, psychological status, functional limitations, and physician's subjective appraisal predict future employment. CONCLUSIONS: The MMPAP accurately predicts future employment of disability applicants claiming chronic pain. The introduction of this standardized protocol will assist in standardizing disability determination for claimants with chronic pain.

Chronic Disease↗

PubMed1998

Transrectal ultrasound of the prostate: innovations and future applications.

PURPOSE: We present a critical evaluation of the use of ultrasound for prostate disease examination in urological practice, and provide perspectives on ultrasound applications that may become important for the future evaluation of prostate problems. MATERIALS AND METHODS: Based on an evaluation of clinical data in cases suspicious for prostatic malignancy, we addressed the apparent shortcomings of transrectal ultrasound for accurately diagnosing prostate cancer. Future applications presented in the literature were noted. RESULTS: Evaluating the ultrasound data in cases suspicious for malignancy indicated that imaging has little advantage over digital rectal examination for detecting malignant areas. The new applications of ultrasound that hold great promise for use in the urology clinic include the injection of contrast agents to obtain information on blood supply, temperature estimation for the noninvasive assessment of temperature distributions during heat treatment and a therapeutic application for local treatment of prostate cancer. CONCLUSIONS: While differential diagnosis with ultrasound appears to result in disappointing sensitivity and specificity values, its use in volume measurement and biopsy guidance is unquestioned. The development of new applications may improve the clinical value of ultrasound in urological practice. The application of ultrasound contrast agents for the detection and clinical staging of prostate cancer is especially promising. Future research will indicate whether the promise evolves in clinical applications.

Animals↗

PubMed2000

An evaluation of fibrin tissue adhesive concentration and application thickness on skin graft survival.

OBJECTIVES: To examine the effects of fibrinogen concentration and application thickness of fibrin tissue adhesive on skin graft survival. STUDY DESIGN: Prospective controlled study. METHODS: Ten domestic pigs were included in the study. A 20 x 5-cm area of skin was harvested bilaterally along the flanks of the animals using a Padgett dermatome. The harvested grafts were trimmed into four 4 x 4-cm squares. Donor sites were treated according to group assignment and the non-meshed grafts were placed on the side opposite their initial orientation and secured with staples. Both single- and multiple-donor human fibrin tissue adhesive preparations, with low and high average fibrinogen concentrations of 30 mg/mL and 60 mg/ mL, were used. Adhesive preparations were applied in either a thin layer (0.015 mL/cm2) or a thick layer (0.06 mL/cm2) using a spray applicator. A constant thrombin concentration of 10 U/mL was used in the study. No adhesive was used in the control group and grafts were stabilized with staples. No topical dressings were applied to any of the treatment sites. Animals were sacrificed 4 weeks after graft application. RESULTS: Based on statistical analysis, thickness of adhesive application had a significant effect on skin graft survival. Percent mean graft survival in the control and thin application groups was found to be 92% and 97.8% respectively; the mean survival rate in the thick application group was 63.1%. Fibrinogen concentration, when evaluated independently within the thin and thick application groups, was found to have no significant effect on graft survival. CONCLUSION: Independent of fibrinogen concentration, a thin layer of fibrin tissue adhesive, when applied between two opposing surfaces, does not interfere with and may support the healing process, whereas a thick layer of adhesive inhibits skin graft healing.

Animals↗

PubMed2002

Entry of inflammatory cells into the mouse vagina following application of candidate microbicides: comparison of detergent-based and sulfated polymer-based agents.

BACKGROUND: Because topical microbicides designed to prevent the spread of sexually transmitted diseases may be applied frequently, it is important to ensure product safety as well as efficacy. A murine model was developed to test for induction of inflammatory responses following application of candidate microbicides. GOAL: A comparison was made of the induction of inflammation following vaginal application of detergent-based and sulfated polymer-based microbicides. STUDY DESIGN: Vaginal leukocytes were collected, identified, and quantified following microbicide application to detect the entry of inflammatory leukocytes into the vaginal lumen. RESULTS: Large numbers of neutrophils and macrophages entered the vaginal lumen following a single application of detergent-based microbicides. No significant increase in vaginal leukocytes was detected following a single or repeated application of sulfated polymer-based microbicides. CONCLUSION: Application of sulfated polymer-based microbicides was less likely to result in inflammatory responses than was application of detergent-based compounds. This murine model should prove useful as part of a screening process to prioritize candidate microbicides before clinical trial.

Administration, Intravaginal↗

PubMed2003

Substance P and prostaglandin E2 release after shock wave application to the rabbit femur.

The biologic action of extracorporeal shock wave application on the musculoskeletal system is poorly understood. To prove the hypothesis that alterations of tissue concentrations of substance P and prostaglandin E(2) are involved in the biologic action of shock waves, extracorporeal shock waves with energy flux density of 0.9 mJ/mm2 (1500 pulses at 1/second) were applied in vivo to the distal femur of rabbits. The concentrations of substance P and prostaglandin E(2) eluted from the periosteum of the femur were measured. Compared with the untreated contralateral hindlimbs, substance P release from the periosteum from the femur was increased 6 hours and 24 hours after extracorporeal shock wave application, but was decreased 6 weeks after extracorporeal shock wave application. By contrast, extracorporeal shock wave application did not result in altered prostaglandin E(2) release from the periosteum from the femur. Remarkably, there was a close relationship between the time course of substance P release found here, and the well-known clinical time course of initial pain occurrence and subsequent pain relief after extracorporeal shock wave application to tendon diseases. Accordingly, substance P might be involved in the biologic action of extracorporeal shock wave application on tissue of the musculoskeletal system. This is the first study providing insights into the molecular mechanisms of extracorporeal shock wave application to the musculoskeletal system.

Analysis of Variance↗

PubMed2006

Trends in HIV prevalence among white and African-American civilian applicants for United States Military Service, 1985 to 2003.

Data from 5,699,590 white and African-American civilian applicants who applied for service in the US military between 1985 and 2003 were used to analyze HIV prevalence trends. The overall HIV prevalence was 0.72/1000, which declined from 2.63/1000 in 1985 to 0.29/1000 in 1995, after which it remained stable until 2003 (0.30/1000). Larger and more significant declines in annual HIV prevalences were observed among the 4.5 million white applicants (-15.7% per year) compared with the 1.2 million African-American applicants (-10.0% per year). The HIV prevalence decline was also greater among male applicants (-12.4% per year) than female applicants (-7.1% per year). In the most recent 4 years study period, HIV prevalences increased among white applicants 25 to 29 years of age among African-American applicants 30 years of age or older. These data suggest that despite the overall consistent decreases in HIV prevalence from the 1980s to the late 1990s, an increase in HIV prevalence has taken place older African-American and white subgroups in more recent years.

Adolescent↗

PubMed1992

Optimal power deposition with finite-sized, planar hyperthermia applicator arrays.

Improved hyperthermia applicator technology is allowing finer spatial power resolution within the heated tissue volume. Effective utilization of these planar applicator arrays requires an understanding of the interrelationships between the lateral dimensions of the tumor and the applicators, the power field produced by the applicators, the amount of surface cooling, the tumor tissue blood perfusion, and the normal tissue blood perfusion. These interrelationships are investigated using three-dimensional power patterns and temperature fields produced by optimizing the power amplitudes of the individual applicators located within an array of small, but finite, planar applicators. Five major conclusions are obtained. First, optimization works and is effective in determining optimal power fields. Second, for optimal treatments the lateral dimensions of a single superficial applicator need to extend beyond the tumor boundary. Third, surface cooling is needed to reduce the high normal tissue temperatures at shallow depths. Fourth, finer power resolution becomes more important as the tumor size decreases, but, little improvement in the temperature field is achieved beyond a 3 x 3 array configuration. Fifth, increasing the normal blood perfusion rate can decrease the temperature on the tumor boundary if direct power deposition on that boundary is unavailable.

Equipment Design↗

PubMed2005

A clinical water-coated antenna applicator for MR-controlled deep-body hyperthermia: a comparison of calculated and measured 3-D temperature data sets.

A magnetic resonance (MR)-compatible three-dimensional (3-D) hyperthermia applicator was developed and evaluated in the magnetic resonance (MR) tomograph Siemens MAGNETOM Symphony 1.5 T. Radiating elements of this applicator are 12 so-called water coated antenna (WACOA) modules, which are designed as specially shaped and adjustable dipole structures in hermetically closed cassettes that are filled by deionized water. The WACOA modules are arranged in the applicator frame in two transversal antenna subarrays, six antennas per subarray. As a standard load for the applicator an inhomogeneous phantom was fabricated. Details of applicator's realization are presented and a 3-D comparison of calculated and measured temperature data sets is made. A fair agreement is achieved that demonstrates the numerically supported applicator's ability of phase-defined 3-D pattern steering. Further refinement of numerical models and measuring methods is necessary. The applicator's design and the E-field calculations were performed using the finite-difference time-domain (FDTD) method. The calculation and optimization of temperature patterns was obtained using the finite element method (FEM). For MR temperature measurements the proton resonance frequency (PRF) method was used.

Computer Simulation↗

PubMed1985

The responses of normal and psoriatic skin to single and multiple topical applications of leukotriene B4.

Topical application of single doses of leukotriene B4, (5-500 ng) under occlusion to the skin of normal volunteers and to the clinically normal skin of patients with untreated stable plaque psoriasis caused an inflammatory reaction lasting several days. Histologically, intraepidermal neutrophil microabscesses were seen in both groups following 50 ng applications of leukotriene B4, but there were significantly fewer intraepidermal neutrophils in the psoriatic than in the normal subjects. Nine repeated daily applications of leukotriene B4 (50 ng) to the same site were associated with a reduction of the visible inflammatory response in both volunteer groups, although application of a single 50 ng dose of leukotriene B4 to an adjacent, previously untreated site at the end of the multiple dose experiments elicited acute erythema and edema. Histologically, there were significantly fewer intraepidermal neutrophils in biopsies from sites to which 9 applications of leukotriene B4 were made than in sites to which 1 dose had been applied at the end of the multiple-dose experiments in both psoriatic and normal volunteers. Therefore, repeated application of leukotriene B4 is associated with decreased responsiveness which is due to a local mechanism in the repeatedly treated skin. No subject developed psoriasis following single or multiple applications of leukotriene B4, suggesting that the production of leukotriene B4 in the epidermis is unlikely to be a primary pathogenic event in this disease.

Administration, Topical↗

PubMed1988

Multiple topical applications of arachidonic acid to mouse ears induce inflammatory and proliferative changes.

The response to daily topical applications of arachidonic acid (0.25-4 mg/ear/day) to the ears of outbred CD-1 mice was monitored. The first application produced erythema, extravasation of plasma proteins resulting in an increase in ear weight, and some neutrophil accumulation (detected histologically and quantified by myeloperoxidase content). The second application produced minimal edema but did cause erythema and a greater accumulation of neutrophils. Subsequent daily application caused erythema, neutrophil accumulation, and an increase in ear weight predominantly due to cell proliferation (epidermis and connective tissue). Daily applications of other unsaturated fatty acids did not match the response induced by arachidonic acid. Mast cell deficient mice (W/Wv) exhibited a smaller edema response to the first dose of arachidonic acid compared to either their wild-type controls or CD-1 mice. In addition, W/Wv mice exhibited a smaller ear weight increase and myeloperoxidase accumulation following eight daily doses of arachidonic acid. However, epidermal proliferation was similar in all the strains of mice tested. These data suggest that the edema caused by the first topical application of arachidonic acid is partly mast cell mediated. Mast cells also appear to be involved in the neutrophil infiltration induced by multiple topical applications, but not in the epidermal proliferation.

Administration, Topical↗

PubMed2000

Experimental irritant contact dermatitis due to cumulative epicutaneous exposure to sodium lauryl sulphate and toluene: single and concurrent application.

In clinical practice, cutaneous exposure to a variety of irritants such as surfactants and solvents is frequent. Although the induction of irritant dermatitis by single irritants has been extensively studied in recent years, our knowledge of the effects of simultaneous application of different irritants is limited. Using non-invasive techniques for measurements of transepidermal water loss (TEWL) and skin colour reflectance, we quantified the irritant effects of single and concurrent application of 0.5% sodium lauryl sulphate (SLS) and undiluted toluene (TOL) in vivo. The irritants were applied twice daily for 30 min to the volar forearms of 20 volunteers. Repeated application of SLS and TOL induced an irritant reaction, as indicated by an increase in TEWL and skin redness. In contrast to SLS alone, the application of TOL alone induced only a moderate increase in TEWL, confirming previous results. Concurrent application of SLS/TOL and TOL/SLS induced significantly stronger reactions than those caused by twice daily application of each irritant on its own. Our results demonstrate that a mixed application of an anionic detergent and an organic solvent has an additive effect on skin irritation. It is suggested that pretreatment with SLS causes an increased susceptibility to TOL irritation and vice versa. Thus, the necessity for special precautions against skin absorption of TOL when handling detergents such as SLS is emphasized.

Administration, Cutaneous↗

PubMed2004

Assessment of spray application of Saint GERVAIS water effects on skin wettability by contact angle measurement comparison with bidistilled water.

BACKGROUND: The skin is responsible for protecting the body from physical, chemical and microbial injuries. The stratum corneum is the top layer of the epidermis and it plays a key role in helping to contain moisture. When the skin becomes damaged, its ability to perform these functions is compromised. Dry skin is a common form of skin damage. Contact angle 0 between a surface and water is a good indicator of hydrophobic or hydrophilic tendency of surfaces. OBJECTIVE: To quantify the influence of spray application of an isotonic mineral water (Saint GERVAIS water) on the hydrophobic tendency of dry skin and to compare spreading of both types of water on the skin through 0 measurement of each water drop on the skin before and after mineral spray application. MATERIALS AND METHODS: Contact angles theta between skin surface and the two types of water (bidistilled and mineral water) were measured before and after application of mineral water by a system allowing the measurement of theta in vivo and in vitro. The cutaneous hydration, the temperature and pH were also measured before and after mineral water application. RESULTS: As for the application of mineral water, the cutaneous pH significantly increased so the strong skin acidity decreased. The cutaneous temperature was modified (a decrease of 2 degrees C was noted) and the cutaneous hydration was also increased (+47AU). The hydro-phobic tendency of the dry skin tested in this study was strongly decreased after mineral water application. This parameter was illustrated by a decrease of contact angle theta value. CONCLUSION: Saint GERVAIS water application allowed a regulation of skin pH, a fresh sensation on the skin and an increase in the cutaneous hydration. Moreover, the contact angle measurement with bidistilled water illustrated the increased wettability of the skin.

Administration, Topical↗

PubMed1997

Effect of application volume and area on the absorption of phenol red, as a model drug, from the liver surface in rats.

To determine the influence of the method of administration of a pharmaceutical formulation we have examined the importance of application volume and area in the absorption of phenol red, as a model drug, from the rat-liver surface. When 1 mg phenol red was applied to the rat-liver surface, in-vivo, in three volumes (0.1, 0.2 or 0.334 mL) using a cylindrical glass cell (i.d. 9 mm), the shape of the plasma concentration profile differed greatly, particularly the maximum concentration. These patterns were well fitted by a two-compartment model with first-order absorption, and the absorption-rate constant Ka obtained was inversely proportional to the application volume. The absorption ratio and biliary recovery of phenol red after 6 h increased with glass cell area (i.d. 6, 9 or 14 mm; area 0.28, 0.64 or 1.54 cm2). Furthermore, the permeability coefficient Papp derived from Ka did not depend on application area, indicating no difference in the absorption characteristics of the liver surface. This also implies transport of the drug by passive diffusion from the liver surface. After intraperitoneal administration to the rat-liver surface for clinical application, increasing the application volume resulted in the delayed disappearance of phenol red from the plasma. However, the difference was not as marked as that obtained by use of the glass cell. The assumption that the effective area relating to the absorption changed with the application volume enabled us to estimate Papp. Consequently, we speculate that absorbability can be estimated precisely by consideration of application volume and area.

Adsorption↗

PubMed2001

Evaluation of multielement catheter-cooled interstitial ultrasound applicators for high-temperature thermal therapy.

Catheter-cooled (CC) interstitial ultrasound applicators were evaluated for their use in high-temperature coagulative thermal therapy of tissue. Studies in ex vivo beef muscle were conducted to determine the influences of applied electrical power levels (5-20 W per element), catheter flow rate (20-60 ml min(-1)), circulating water temperature (7-40 degrees C), and frequency (7-9 MHz) on temperature distribution and thermal lesion geometry. The feasibility of using multiple interstitial applicators to thermally coagulate a predetermined volume of tissue was also investigated. Results of these studies revealed that the directional shape of the thermal lesions is maintained with increasing time and power. Radial depths of the thermal lesions ranged from 10.7 +/- 0.7 mm after heating for 4 min with an applied power level of 5 W, to 16.2 +/- 1.4 mm with 20 W. The axial length of the thermal lesions is controlled tightly by the number of active transducers. A catheter flow rate of 20 to 40 ml min(-1) (52.2 +/- 5.5 kPa at 40 ml min(-1)) with 22 degrees C water was determined to provide sufficient cooling of the transducers for power levels used in this study. In vivo temperatures measured in the center of a 3-cm-diam peripheral implant of four applicators in pig thigh muscle reached 89.3 degrees C after 4 min of heating, with boundaries of coagulation clearly defined by applicator position and directivity. Conformability of heating in a clinically relevant model was demonstrated by inserting two directional CC applicators with a 2 cm separation within an in vivo canine prostate, and generating a thermal lesion measuring 3.8 cm x 2.2 cm in cross section while directing energy away from, and protecting the rectum. Maximum measured temperatures at midgland exceeded 90 degrees C within 20 min of heating. The results of this study demonstrate the utility of single or multiple CC applicators for conformal thermal coagulation and high temperature thermal therapy, with potential for clinical applications in sites such as prostate, liver, breast, or uterus.

Animals↗