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The effect of the point of application of anterior tibial loads on human knee kinematics.

Coupled axial tibial rotation in response to an anterior tibial load has been used as a common diagnostic measurement and as a means to load the ligamentous structures during laboratory tests. However, the exact location of the point of application of these loads as well as the corresponding sensitivity of the coupled tibial rotation to this point can have an effect on the function of the soft tissues at the joint. Therefore, the purpose of this study was to determine the effects of four different points of application of the anterior tibial load on the anterior tibial translation and coupled axial tibial rotation. The four points include: (1) geometric point - midway between the collateral ligament insertion sites on the tibia, (2) clinical point - a position that attempts to simulate clinical diagnostic tests, (3) medial point - a position medial to the geometric point and (4) lateral point - a position lateral to the clinical point. A robotic/universal force-moment sensor testing system was used to apply the anterior tibial load at the four points of application and to record the resulting joint motion. Anterior tibial translation in response to an anterior tibial load of 100N was found not to vary between the four points of application of the anterior tibial load at all flexion angles examined. However, internal tibial rotation was found for the lateral point (13+/-10 degrees at 30 degrees of knee flexion) in all specimens and clinical point (8+/-10 degrees at 30 degrees of knee flexion) while external rotation resulted when the load was applied at the medial point (-8+/-7 degrees at 30 degrees of knee flexion). Both internal and external tibial rotations occurred throughout the range of flexion when the tibial load was applied at the geometric point. The results suggest that the clinical point should be used as the point of application of the anterior tibial load whenever clinical examinations are simulated and multi-degree-of-freedom joint and soft tissue function are examined.

Aged↗

A prospective evaluation of prehospital 12-lead ECG application in chest pain patients.

The objective of this study was to prospectively determine the utility, efficiency, and reliability of early prehospital 12-lead electrocardiogram (ECG) application, the improvement in prehospital diagnostic accuracy, and paramedic and base physician opinions regarding early application of prehospital 12-lead ECGs in a broad range of stable chest pain patients. The patient population consisted of cooperative, stable adult prehospital patients with a chief complaint of nontraumatic chest pain of presumed ischemic origin. From July 17, 1989 through January 1, 1990 paramedics acquired prehospital 12-lead ECGs on 680 stable adult chest pain patients. Factors affecting prehospital 12-lead ECG application were evaluated. Paramedic application of prehospital 12-lead ECGs was found to be efficient and reliable, and it can be applied to most cooperative stable adult prehospital chest pain patients. Prehospital 12-lead ECGs significantly improve base physicians' diagnostic accuracy in myocardial infarction, angina, and nonischemic chest pain patients. Paramedic and base physicians' opinions regarding early application of prehospital 12-lead ECGs during patient evaluation were favorable.

Chest Pain↗

The effect of the interval between dose applications on the observed specific-locus mutation rate in the mouse following fractionated treatments of spermatogonia with ethylnitrosourea.

Our earlier analyses have suggested an apparent threshold dose-response for ethylnitrosourea-induced specific-locus mutations in treated spermatogonia of the mouse to be due to a saturable repair process. In the current study a series of fractionated-treatment experiments was carried out in which male (102 x C3H)F1 mice were exposed to 4 x 10, 2 x 40. 4 x 20 or 4 x 40 mg ethylnitrosourea per kg body weight with 24 h between applications; 4 x 40 mg ethylnitrosourea per kg body weight with 72 h between dose applications; and 2 x 40, 4 x 20 and 4 x 40 mg ethylnitrosourea per kg body weight with 168 h between dose applications. For all experiments with 24-h intervals between dose applications, there was no effect due to dose fractionation on the observed mutation rates, indicating the time interval between dose applications to be shorter than the recovery time of the repair processes acting on ethylnitrosourea-induced DNA adducts. In contrast, a fractionation interval of 168 h was associated with a significant reduction in the observed mutation rate due to recovery of the repair process. However, although reduced, the observed mutation rates for fractionation intervals of 168 h were higher than the spontaneous specific-locus mutation rate. These observations contradict the expectation for a true threshold dose response. We interpret this discrepancy to be due to the differences in the predictions of a mathematical abstraction of experimental data and the complexities of the biological system being studied. Biologically plausible explanations of the discrepancy are presented.

Animals↗

Pregnancy after tubal sterilization with silicone rubber band and spring clip application.

OBJECTIVE: To determine risk factors for pregnancy after tubal sterilization with silicone rubber bands or spring clips. METHODS: A total of 3329 women sterilized using silicone rubber bands and 1595 women sterilized using spring clips were followed for up to 14 years as part of a prospective cohort study conducted in medical centers in nine US cities. We assessed the risk of pregnancy by cumulative life-table probabilities and proportional hazards analysis. RESULTS: The risk of pregnancy for women who had silicone rubber band application differed by location of band application and study site. The 10-year cumulative probabilities of pregnancy varied from a low of 0.0 per 1000 procedures at one study site to a high of 42.5 per 1000 procedures in the four combined sites in which fewer than 100 procedures per site were performed. The risk of pregnancy for women who had spring clip application varied by location of clip application, study site, race or ethnicity, tubal disease, and history of abdominal or pelvic surgery. The probabilities across study sites ranged from 7.1 per 1000 procedures at 10 years to 78.0 per 1000 procedures at 5 years (follow-up was limited to 5 years at that site). CONCLUSION: The 10-year cumulative probability of pregnancy after silicone rubber band and spring clip application is low but varies substantially by both clinical and demographic characteristics.

Adult↗

Design and in vitro results of a high intensity ultrasound interstitial applicator.

Interstitial technologies were proposed for the treatment of deep-seated and unresectable tumours. This study was designed to demonstrate the possibility of producing coagulation necrosis for a short exposure duration (20s) and a large volume with an interstitial ultrasonic applicator equipped with a plane transducer. The applicator was evaluated in terms of electroacoustic efficiency (58% at 10.7 MHz), temperature pattern and in vitro pig liver tissues destruction. The temperature elevation reached 52, 39, 22 and 15 degrees C at, respectively, 2.5, 7.5 and 10 mm from the applicator surface along the propagation axis. The evident cigar-shaped lesions spread on a depth of (8 +/- 2) mm from the surface applicator, (10 +/- 1) mm high and (3 +/- 1) mm high and (3 +/- 1) mm wide. The temperature measurements showed the limitations encountered with a 10 MHz transducer. The high increase in temperature of tissues close to the transducer can induce vaporisation and a gaseous barrier opaque to ultrasound. Owing to the shape and the operating frequency of the transducer, we hope to obtain the same satisfactory performances in vivo with weakly perfusion-dependent lesions. Axial and longitudinal applicator motions will enable us to treat more important volumes.

Acoustics↗

The accumulation of potentially toxic elements in edible body tissues of lambs grazing after a single application of sewage sludge.

The application of sewage sludge to grassland can lead to the accumulation of potentially toxic elements (PTEs) at the soil surface that may be ingested, together with soil and herbage, by grazing ruminants. To investigate the extent to which the method of application of sludge to grassland might influence the accumulation of PTEs in body tissues of grazing sheep, two experiments were undertaken using grassland overlying two contrasting types of soil. At both sites, plots were either untreated or given liquid digested sludge in a single application in either autumn or spring by surface spreading or by injection. Weaned lambs were grazed on the experimental sites for 149 days (Experiment 1) or 160 days (Experiment 2). Muscle, kidney and liver tissues were assayed for concentrations of PTEs at each slaughter date. Applications of sludge were reflected in elevated concentrations of Pb and Cu in soil in Experiment 1 only (P < 0.05). Total loadings of PTEs for the treated grasslands did not exceed UK statutory limits to annual additions to soil. No significant differences were observed in the concentrations of PTEs in herbage between untreated and treated sites, with the exception of the concentration of Cu in herbage after surface application in the spring (Experiment 2). At the end of Experiment 1 the concentration of Cd tended to be higher in kidney tissues of lambs grazed on the pastures amended with sludge in the autumn compared to lambs grazed on untreated pastures. No other treatment effects were evident. Concentrations of PTEs in edible tissues of lambs grazed on grassland given a single dose of sludge were generally low and unlikely to pose a significant risk to the food chain. However, reduced food intake was observed in lambs grazed on grassland which had received sludge recently, indicating that the 21-day UK statutory no-grazing period should be reviewed in relation to grassland given sewage sludge in the spring.

Animals↗

Quantifying characteristics of information-technology applications based on expert knowledge for detection of oestrus and mastitis in dairy cows.

Expert opinions were elicited about the characteristics at the commercial-farm level of on-line information technology (IT) applications that are able to detect oestrus and mastitis in dairy cows. Since actual data of these characteristics are not available, judgmental data provided an alternative means to interpret the implications of research results for commercial farms. Applications included were activity measurement, milk-production measurement, electrical conductivity of quarter milk, automated concentrate feeders and milk-temperature measurement. Sensitivity and specificity of detection of oestrus (OD), clinical-mastitis (CMD) and subclinical-mastitis (SCMD) were ascertained. Conjoint-analysis was used to assess the effect of each application indirectly by decomposing the evaluated overall detection characteristics of a predefined number of IT combinations. The individual experts were consistent in evaluating the alternatives, but there was variation in estimates among experts. Estimations of the main effects of the applications and important first-order interactions were incorporated into the detection models. Implementation of all applications under study resulted in overall sensitivities and specificities of 82% and 90%, 73% and 87%, 58% and 82% for OD, CMD and SCMD, respectively. Further research is necessary that should take into account costs and benefits of the different detection systems based on the current status of farm performance (e.g. OD and mastitis incidence) and farm structure (e.g. farm size, years in operation of the milking parlour and parlour layout). Research to do this is currently in progress.

Animals↗

Screens in ovoids of a Selectron cervix applicator.

The addition of screens in the vaginal source holders of a cervix applicator for intracavitary brachytherapy reduces the dose to rectum and bladder and therefore diminishes the number of rectal and vesical complications. Shielding properties of tungsten rectal and bladder screens of a Selectron cervix applicator, loaded with spherical cesium sources, were determined for verification of dose calculations. Transmission characteristics of half-disk shaped tungsten screen segments in a single ovoid were measured in a water phantom. The minimum transmission ratios are 60, 70 and 80% for segment thickness of 5.0, 3.5 and 2.0 mm, respectively. The accuracy of the new screen correction algorithm of the Selectron Planning System was assessed by comparing measured and calculated dose rates and was found to be better than +/- 4%. The correction algorithm provides a method to analyse the efficacy of screens in the ovoids for various segment geometries and orientations without extensive phantom measurements. Isotransmission and isodose calculations were made for a typical clinical applicator set-up and source distribution. The dose reduction to rectum and bladder, near the bottom and top of the ovoids was analysed in detail. A 3.5 mm thick rectum and bladder screen in each ovoid reduces the dose approximately by 20% to the rectum and by 15% to the bladder. A distance enlargement of about 5 mm between ovoid and rectum or bladder, e.g. by packing, results in a comparable dose reduction. Shielding properties of a Selectron cervix applicator, provided with screens, were compared with those of some Fletcher-type applicators. Significant differences between the transmission ratios and shielded areas of the screens of both systems near rectum and bladder were observed.

Brachytherapy↗

Improved skin oxygenation after benzyl nicotinate application in different carriers as measured by EPR oximetry in vivo.

The development of formulations, which increase skin oxygenation and of methods for measuring oxygen levels in skin are important for dealing with processes affected by the level of oxygen, e.g., rate of healing and efficiency of radiation oncology. In this study we have investigated the role of carriers on the efficacy of benzyl nicotinate (BN) action in skin after dermal application in different formulations by EPR oximetry in vivo. The time course of pO2 in the skin after application of rubefacient is followed directly for the first time. The results obtained proved the applicability of in vivo EPR oximetry as a sensitive method by which small alterations in pO2 can be detected. We have found that the type of vehicle significantly influences the time when BN starts to act, the duration of its action, and the maximal increase in pO2. The ranking of vehicle efficiency was: lipid nanoparticles in hydrophilic gel>liposomes in hydrophilic gel>hydrophilic gel>hydrophobic ointment>hydrophobic cream. Primarily the semi-solid vehicle determines the lag-time of action, but the maximal oxygen level is influenced decisively by the particulate carrier systems. BN effectiveness was dose dependent. 2.5% w/w concentration of BN appears to be the most appropriate for therapeutic application. After repeated application a successive increase of pO2 base line in skin and of the maximal pO2 was noticed.

Administration, Cutaneous↗

Prior experience of morphine application alters the c-fos response to MDMA ('ecstasy') and cocaine in the rat striatum.

Repeated morphine application usually leads to the development of tolerance but under certain circumstances sensitization may arise simultaneously. This phenomenon becomes obvious in behavioral tests as increasing locomotor activity and increasing drug self-administration during a course of chronic morphine application. It was suggested recently that sensitization could contribute to addiction. The molecular mechanisms of sensitization may include the long lasting increase in neuronal responsiveness to morphine which was observed in defined brain areas after repeated morphine injections. In this work, we studied whether morphine-sensitized Wistar rats also display an enhanced neuronal activity in response to other drugs of abuse (so called co-sensitization). The substances to be tested were injected as single doses 4 weeks after completion of a 10-day morphine pretreatment. MDMA (3, 4-methylenedioxymethamphetamine, 6 mg/kg) as a single test dose yielded a c-fos response in a wide range of brain areas. In the caudate putamen, the expression pattern of c-fos was clearly altered if the rats had received repeated morphine application previously. In this case, the MDMA-induced c-fos expression was markedly confined to the centromedial, mesolimbic aspect of the striatum whereas it had a diffuse appearance in rats not exposed to the opiate earlier. Cocaine application (50 mg/kg) elicited an intense c-fos expression in the medial striatum if the animals were morphine-pretreated; it was virtually absent in drug-naive rats after the same cocaine dose. Ten mg/kg cocaine had a similar but weaker effect. No difference in the c-fos expression pattern between morphine and saline pretreated animals was observed in the case of a THC (Delta(9)-tetrahydrocannabinol, 25 mg/kg) or an LSD (lysergic acid diethylamide, 1 mg/kg) test application. These findings imply that morphine sensitizes the brain towards other addicting drugs. In consequence, morphine sensitization obviously does not solely reflect alterations in mu-opioid receptor signaling. Rather, it seems to reflect further rearrangements within the mesolimbic system.

Animals↗

Modulation of type II collagen-induced arthritis in DBA/1 mice by intravenous application of a peptide from the C1q-A chain.

In this report we are able to show that intravenous (i.v.) application (day 0) of a nonapeptide (residues 26-34) from the human C1q A-chain (designated peptide A-C1q) prior to intradermal (i.d.) administration of chicken type II collagen (CII) in arthritis-susceptible DBA/1 mice (H2q), leads to abrogation of polymorphonuclear neutrophil (PMN) invasion into the joints. This nonapeptide exhibits epitope characteristics and high homology to residues 137-147 of CB11 (a cyanogen bromide fragment of chicken CII, known to contain both arthritis inducing and suppressing determinants). Arthritis index was lowest in animals pretreated i.v. with CII (as internal control), though animals pretreated i.v. with peptide K (residues 137-147 with an additional glycine residue from CB11) or peptide A-C1q exhibited comparative arthritic indices. Only in the arthritis-positive control group (day 0: PBS i.v.) did i.d. application of CII lead to invasion of PMN into the synovial layer and the joint space. Analysis of antibody (Ab) responses at day 48 after i.v. immunization (day 0) and CII challenge (day 7) revealed IgE-Abs to native CII and also to native C1q. IgG titers to CII were highest in animals pretreated with peptide A-C1q. Abs from this group, exhibiting activity to peptide A-C1q (immunizing antigen), were of mainly IgG1 and IgG3 isotypes. Evaluation of the immune response following i.v. application of peptide A-C1q or CII, prior to i.d. CII administration, in DBA/1 mice, revealed IgM responses to peptide A-C1q and peptide K, but not to CII. Intravenous application of peptide A-C1q led to generation of IgG3-Abs reacting only with peptide A-C1q and peptide K, but not with native CII. Additionally, i.v. application of peptide A-C1q elicited IgG responses to a pentapeptide, resembling amino acid residues 26-30 (K-G-E-Q-G) of the C1q A-chain. This five residue antigenic determinant is present in peptide K, in chicken and human CII as well as in human C1q. No specific IgE response to any of the antigens tested could be detected. Since a peptide from the C1q A-chain is both capable of eliciting immune responses and modulating CII-induced arthritis in mice, we postulate that the collagen-like complement component C1q is involved in the development of CII-induced inflammatory arthritic lesions, and may represent, in vivo, the early antigen responsible for inducing anticollagen antibodies prior to CII in hyaline cartilage becoming available as antigen.

Adjuvants, Immunologic↗

An applicant's evaluation of an emergency medicine internship and residency.

Applicants to emergency medicine residencies face an increasingly difficult task of evaluating a greater number of training programs. High-quality information must be obtained by applicants prior to their submission of a ranking list to the National Intern and Residency Matching Program. Resources to assist applicants in this task have been limited; personal interviews are critical in this process. In the relatively new specialty of emergency medicine, medical students may fail to obtain optimal information during interviews. A list of suggested interview questions is provided. Judicious use of appropriate questions can help applicants obtain the proper information. Residency program directors and staff may also use these questions to assist applicants.

Emergency Medicine↗

Topical application of HIV DNA vaccine with cytokine-expression plasmids induces strong antigen-specific immune responses.

The topical application of DNA vaccine to the skin is a useful method of immunization because of its simplicity, painlessness and economy. But the immune responses that it elicits are relatively low. In this study, we administered human immunodeficiency virus type-1 (HIV-1) DNA vaccine with cytokine-expressing plasmids to the skin of mice by a new topical application technique involving prior elimination of keratinocytes using fast-acting adhesive. Our results revealed that the topical application of HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. Co-administration of the DNA vaccine with cytokine expression plasmids of IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by this new method raised the levels of both the HIV-specific cytotoxic T lymphocyte (CTL) response and delayed-type hypersensitivity (DTH) and facilitated the induction of substantial immune responses by DNA vaccine. Skin biopsy sections, thus, immunized showed significant increases of S-100 protein-positive dendritic cells (DCs). These results suggest that the topical application method described here is an efficient route of DNA vaccine administration and that the immune response may be induced by DNA plasmids taken in by DCs, Langerhans cells (LCs), or others such as antigen-presenting cells. This new topical application is likely to be of benefit in clinical use.

AIDS Vaccines↗

Nutrient losses by surface run-off following the application of organic manures to arable land. 1. Nitrogen.

Research was conducted on nitrogen (N) surface run-off losses following organic manure applications to land, utilising a purpose-built facility on a sloping site in Herefordshire under arable tillage. Different rates and timing of cattle slurry, farmyard manure and inorganic N and phosphorus (P) fertiliser were compared, over a 4-year period (1993-97). P losses from the same studies are reported in a separate paper. The application of cattle slurries to the silty clay loam soil increased the loss of solids and NH4(+)-N in surface water flow compared to control plots receiving inorganic fertiliser only, or no treatment, but had little effect on NO3(-)-N losses by this route. Results were consistent with other observations that rainfall events immediately after manure applications are particularly likely to be associated with nutrient run-off losses. Losses via subsurface flow (30 cm interflow) were consistently much lower than via surface water movement and were generally unaffected by treatment. Increasing slurry application rate and, in particular, slurry solids loading, increased solids and NH4(-)-N losses via surface run-off. The threshold, above which the risk of losses via surface run-off appeared to be greatly increased, was ca. 2.5-3.0 t/ha slurry solids, which approximates to the 50 m3/ha limit suggested for slurry within UK 'good agricultural practice'. Sealing of the soil surface by slurry solids appears to be a possible mechanism by which polluting surface run-off may occur following slurry application on susceptible soils. Total losses of NH4(+)-N and NO3(-)-N during the 4-year monitoring period were insignificant in agronomic terms, but average soluble N concentrations (NH4(+)-N + NO3(-)-N) in run-off, ranging from ca. 2.0 mg/l, up to 14.0 mg/l for the higher rate slurry treatments. Peak concentrations of NH4(+)-N > 30 mg/l, are such as to be of concern in sensitive catchments, in terms of the potential for contribution to accelerated eutrophication and adverse effects on freshwater biota.

Agriculture↗

Speciation of rare earth elements in soil and accumulation by wheat with rare earth fertilizer application.

A greenhouse study was conducted to investigate the accumulation of rare earth elements (REEs), La, Ce, Pr and Nd, in winter wheat (Triticum aestivum L.), and the speciation of these elements in soil following the application of REE-based fertilizers. Improved crop yield was confirmed by the experiment. The accumulation behavior of La, Ce, Pr and Nd in wheat varied depending on the concentration of REE fertilizer application, i.e. increased with increasing REE concentration at low fertilization application, constant over the medium REE range, and decreased with increasing REE concentration at high fertilizer application. Significant negative correlation was obtained between REE contents in roots and soil pH (r = -0.5787 to -0.8442 for La). REEs in both the fertilized and unfertilized soils were fractionated by a three-stage sequential extraction procedure into three chemically distinct fractions: water soluble, exchangeable and carbonate bound (B1), Fe-Mn oxide bound (B2), and organic and sulfide bound (B3). REEs in fertilized soils were found mainly in the B2 and B3 fractions, with only a small amount in the B1 fraction. REEs in B1 and B2 fractions were negatively correlated with soil pH (r = -0.6892 to -0.8927 and -0.7462 to -0.9482). Significant correlation was obtained between REEs in B1 fraction and REE contents in root. The correlation coefficients ranged from 0.6159 to 0.7410 when fertilizer application was lower than 20.0 mg/kg soil. No acceptable relationship was observed between REE contents in shoot and any of the extractable fractions in soils.

China↗

Removal of pollutants from surface water and groundwater by nanofiltration: overview of possible applications in the drinking water industry.

During the last decade, nanofiltration (NF) made a breakthrough in drinking water production for the removal of pollutants. The combination of new standards for drinking water quality and the steady improvement of the nanofiltration process have led to new insights, possible applications and new projects on lab-scale, pilot scale and industrial scale. This paper offers an overview of the applications in the drinking water industry that have already been realised or that are suggested on the basis of lab-scale research. Applications can be found in the treatment of surface water as well as groundwater. The possibility of using NF for the removal of hardness, natural organic material (NOM), micropollutants such as pesticides and VOCs, viruses and bacteria, salinity, nitrates, and arsenic will be discussed. Some of these applications have proven to be reliable and can be considered as known techniques; other applications are still studied on laboratory scale. Modelling is difficult due to effects of fouling and interaction between different components. The current insight in the separation mechanisms will be briefly discussed.

Disinfection↗

Impaired tensile strength after shock-wave application in an animal model of tendon calcification.

Extracorporeal shock-wave application facilitates dissolution of rotator cuff calcifications. Therefore, disappearance or disintegration of tendon calcifications by shock waves might be appropriate for any kind of tendon calcification. Here, shock waves with various energy flux densities were applied to the mineralized medial gastrocnemius tendon of turkeys as an animal model. After application of shock waves in vivo, with energy flux density of 0.6 mJ/mm(2), histologic examination and microradiography did not show dissolution or disintegration of tendon calcifications. After shock-wave application in vitro, even for energy flux density of 1.2 mJ/mm(2) neither dissolution nor disintegration of tendon calcifications were observed. Biomechanical testing revealed significant impairment of tensile strength following shock-wave application in vitro, with energy flux density of 1.2 mJ/mm(2), but not with 0.6 mJ/mm(2). These results are important for considerations of clinical extracorporeal shock-wave application on tendon calcifications, as well as on tendon ossifications.

Animals↗

Effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA) cream on spontaneous and evoked pain in post-herpetic neuralgia.

The analgesic effects of single and repeated applications of a eutectic mixture of local anaesthetics (EMLA) cream on both spontaneous and evoked pains were evaluated in 11 patients with post-herpetic neuralgia (PHN). Detection thresholds, pain thresholds and the responses to suprathreshold mechanical and thermal stimuli were quantitatively determined at baseline, 30 min after the first application and after a series of daily applications over six consecutive days (duration of application: 5 h/day). In the acute situation, EMLA produced an overall anaesthetic effect without significantly reducing spontaneous ongoing pain and mechanical allodynia. Repeated applications significantly reduced paroxysmal pain and both the dynamic and static subtypes of mechanical hyperalgesia. The effects on spontaneous ongoing pain were more variable. They were inversely correlated to the magnitude of the thermal deficit at baseline, and were significant only in patients with dynamic mechano-allodynia. Pathophysiological implications of these results are discussed.

Aged↗