Energetic soft-tissue treatment technologies: an overview of procedural fundamentals and safety factors.

BACKGROUND: Energy administered during soft-tissue treatments may cauterize, coagulate, seal, or otherwise affect underlying structures. A general overview of the functionality, procedural outcomes, and associated risks of these treatments, however, is not yet generally available. In addition, literature is sometimes inconsistent with regards to terminology. Along with the rapid expansion of available energetic instruments, particularly in the field of endoscopic surgery, these factors may complicate the ability to step back, review available treatment options, and identify critical parameters for appropriate use. METHODS: Online databases of PubMed, Web of Science, and Google Scholar were used to collect literature on popular energetic treatments, such as electrosurgery, plasma surgery, ultrasonic surgery, and laser surgery. The main results include review and comparison studies on the working mechanisms, pathological outcomes, and procedural hazards. RESULTS: The tissue response to energetic treatments can be largely explained by known mechanical and thermal interactions. Application parameters, such as the interaction time and power density, were found to be of major influence. By breaking down treatments to this interaction level, it is possible to differentiate the available options and reveal their strengths and weaknesses. Exact measures of damage and alike quantifications of interaction are, although valuable to the surgeon, often either simply unknown due to the high impact of tissue and application-dependent parameters or badly documented in previous studies. In addition, inconsistencies in literature regarding the terminology of used techniques were observed and discussed. They may complicate the formulation of cause and effect relations and lead to misconceptions regarding the treatment performance. CONCLUSIONS: Some basic knowledge on used energetic treatments and settings and a proper use of terminology may enhance the practitioner's insight in allowable actions to take, improve the interpretation and diagnosis of histological and mechanical tissue changes, and decrease the probability of iatrogenic mishaps.

MR-guided HDR prostate brachytherapy with teleoperated steerable needles.

Conformity of tumour volumes and dose plans in prostate brachytherapy (BT) can be constrained by unwanted needle deflections, needle access restrictions and visualisation limitations. This work validates the feasibility of teleoperated robotic control of an active steerable needle using magnetic resonance (MR) for guidance. With this system, perturbations can be counteracted and critical structures can be circumvented to access currently inaccessible areas. The system comprises of (1) a novel steerable needle, (2) the minimally invasive robotics in an MR environment (MIRIAM) system, and (3) the daVinci Research Kit (dVRK). MR scans provide visual feedback to the operator controlling the dVRK. Needle steering is performed along curved trajectories to avoid the urethra towards targets (representing tumour tissue) in a prostate phantom with a targeting error of 1.2 ± 1.0 mm. This work shows the potential clinical applicability of active needle steering for prostate BT with a teleoperated robotic system in an MR environment.

Comparing Global Initiative for Asthma (GINA) criteria with the Childhood Asthma Control Test (C-ACT) and Asthma Control Test (ACT).

Several tools are useful in detecting uncontrolled asthma in children. The aim of this study was to compare Global Initiative for Asthma (GINA) guidelines with the Childhood Asthma Control Test (C-ACT) and the Asthma Control Test (ACT) in detecting uncontrolled asthma in children. 145 children with asthma filled in a web-based daily diary card for 4 weeks on symptoms, use of rescue medication and limitations of activities, followed by either the C-ACT or ACT. For predicting uncontrolled asthma, score cut-off points of 19 were used for C-ACT and ACT. According to GINA guidelines, asthma was uncontrolled in 71 (51%) children and completely controlled in 19 (14%) children. The area under the curve in the receiver operating characteristic curves for C-ACT and ACT versus GINA guidelines were 0.89 and 0.92, respectively. Cut-off points of 19 for C-ACT and ACT resulted in a sensitivity of 33% and 66% in predicting uncontrolled asthma, respectively. C-ACT and ACT correlate well with GINA criteria in predicting uncontrolled asthma, but commonly used cut-off points for C-ACT and ACT seem to underestimate the proportion of children with uncontrolled asthma as defined by GINA.

Evidence of estrogen receptors in normal human osteoblast-like cells.

In seven strains of cultured normal human osteoblast-like cells, a mean of 1615 molecules of tritium-labeled 17 beta-estradiol per cell nucleus could be bound to specific nuclear sites. The nuclear binding of the labeled steroid was temperature-dependent, steroid-specific, saturable, and cell type-specific. These are characteristics of biologically active estrogen receptors. Pretreatment with 10 nanomolar estradiol in vitro increased the specific nuclear binding of progesterone in four of six cell strains, indicating an induction of functional progesterone receptors. RNA blot analysis demonstrated the presence of messenger RNA for the human estrogen receptor. The data suggest that estrogen acts directly on human bone cells through a classical estrogen receptor-mediated mechanism.

Residential exposure to mould and dampness is associated with adverse respiratory health.

BACKGROUND: Indoor exposure to mould and dampness is frequently associated with asthma symptoms with and without lung function changes. However, the mechanisms contributing to this threat to respiratory health are only partly understood. OBJECTIVE: To investigate the contribution of recent exposure to mould and dampness in the living room or bedroom to respiratory health in a general practice-based cohort of 526 asthmatic children. METHODS: Parents were questioned about home characteristics, including moulds and dampness. The level of asthma control was evaluated in their participating children by means of asthma symptoms, peak expiratory flow (PEF) variability, severity of airway hyperresponsiveness (AHR), and medication usage. RESULTS: Children exposed to indoor moulds and dampness more often had severe AHR compared with non-exposed (42% vs. 16%; P< or =0.001). They also showed an increased PEF variability (11.3% vs. 8.4%; P=0.03) and, however, not significant, more frequent asthma symptoms. The use of controller medication was not significantly different between exposed and non-exposed children. After adjustment for gender, age, smoking, exposure to parental smoking, parental education, pet ownership, presence of inhalant allergy, use of controller medication, health care center, and season of study assessment, the odds ratio for severe AHR in exposed children was 3.95 [95% confidence interval (CI): 1.82-8.57]. CONCLUSION: We found a consistent association between reported moulds and dampness in the living room or the child's bedroom and an increased risk for severe AHR in a general practice-based cohort of asthmatic children, even after adjustment for gender, presence of inhalant allergy, and use of controller medication.

Severe airway hyperresponsiveness was not predictable with the use of current tools in asthmatic children in general practice.

OBJECTIVE: To evaluate whether moderate to severe airway hyperresponsiveness (AHR) could be suspected with the use of routinely available clinical and environmental information. STUDY DESIGN AND SETTING: Cross-sectional study of asthma in 526 asthmatics aged 7-17 years and treated in general practice. RESULTS: Moderate to severe AHR was present in 48% (n=253) of the participants. The presence of inhalation allergy, nocturnal symptoms, and usage of beta2-mimetics were significantly associated with moderate to severe AHR. If all three factors were present, the probability of the presence of moderate to severe and severe AHR was 76% and 36%, respectively. If all three were absent, the probability decreased to 11% and 5%, respectively. In 319 subjects (64%) AHR could not be adequately predicted with routinely available information. CONCLUSION: Moderate and severe AHR could not be suspected with the use of routinely available clinical and environmental information in the majority of children. Except for a subgroup of children, our models were not helpful in deciding in which child an inhaled corticosteroid should be started or whether the dose should be increased or decreased. We recommend measuring the severity of AHR in these children by means of an inhalation challenge test.

A nuclear binding assay to assess the biological activity of steroid receptors in isolated animal and human tissues.

This paper describes a nuclear binding assay (NB assay) which measures not only the presence of a steroid receptor in a tissue, but also the quantity of that receptor which is biologically active or functional, i.e. able to bind to nuclear acceptor sites. The assay involves the isolation viable cells from tissues and their incubation with an excess of radiolabeled steroid to encourage the activation and nuclear binding of all cellular receptors. The nuclei are isolated under conditions that remove unactivated (unbound) steroid-receptor complexes. This NB assay demonstrates, in both animal and human steroid target tissues, a saturable, tissue- and steroid-specific, and temperature- and time-dependent nuclear binding of radiolabeled steroids. These properties support a receptor-dependent nuclear binding of steroids. This assay is reproducible and requires relatively small amounts of tissue. The patterns of nuclear binding of the progesterone receptor, achieved with the assay in the avian oviduct model system, are shown to correlate with the nuclear binding of progesterone in vivo, the ability of the steroid to alter transcription, and the expression of a specific gene product, the protein avidin. The assay has been used to identify the existence of nonfunctional steroid receptors in endometrial and breast carcinomas. Therefore, this NB assay combined with the standard charcoal/hydroxylapatite methods of quantitating total cellular receptors should provide a means of assessing changes in the regulation of the biological activity of steroid receptors. Further, the assay should be useful to assess the ability of steroid analogs to properly activate their respective receptors for subsequent nuclear binding.

Real and pseudo late asthmatic reactions after submaximal exercise challenge in patients with bronchial asthma. A new definition for late asthmatic responses after exercise challenge.

The late asthmatic reaction after exercise challenge remains a controversial issue. In this study, 21 patients recorded peak expiratory flow rate (PEFR) on two control days without performing exercise. There was no difference between both control days when PEFR at 1 h was compared with baseline PEFR and when PEFR at 4 to 13 hours was compared with baseline PEFR. After analyzing variation coefficients of baseline PEFR on a control day and exercise day, PEFR was not allowed to differ more than 15.3 percent in the same patient when comparing exercise day and control day for the late fall in PEFR in the study. In 17 of 81 patients, a late asthmatic reaction after exercise challenge was present when PEFR fall was greater than or equal to 20 percent compared with baseline PEFR value. In eight of the 17 patients, a real late asthmatic reaction to exercise challenge was present with a PEFR fall greater than or equal to 20 percent on at least three successive time points and who had a PEFR fall greater than or equal to 20 percent compared with corresponding clocktime on a control day. The late asthmatic reaction to exercise challenge is characterized not as a nonspecific epiphenomenon, but as a fall in PEFR of greater than or equal to 20 percent compared with baseline PEFR value and with corresponding clocktime on a control day on at least three successive time points. Graphic illustration of airway responses following exercises may facilitate the detection of a late asthmatic response.

Identification of putative nonfunctional steroid receptors in breast and endometrial cancer.

A nuclear binding assay was developed for the purpose of having available a more predictive assay for hormone responsiveness in human cancers. The BNB assay identified specific and saturable steroid nuclear binding in human target tissues and human carcinomas. When the BNB assay was applied to a large set of breast and endometrial carcinomas, we speculate that nonfunctional receptors were detected in 20%-50% of the patients who were receptor-positive by the DCC assay. Lastly, as responsiveness to hormonal therapy in these cancer patients becomes known, the predictive value of the BNB assay can be established.

Salmeterol/fluticasone propionate (50/100 microg) in combination in a Diskus inhaler (Seretide) is effective and safe in children with asthma.

The aim of this study was to compare the efficacy and safety in children of salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice daily) when delivered together via a single Diskus inhaler (Seretide; combination therapy) or concurrently using two separate Diskus inhalers (concurrent therapy). In a multicenter, randomized, double-blind, double-dummy, parallel-group study, 257 children with reversible airways obstruction who remained symptomatic on inhaled corticosteroids (200-500 microg daily) alone were randomized to combination or concurrent therapy for 12 weeks. Efficacy was assessed by measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol use. In addition, lung function tests were performed at each clinic visit. Safety assessments included monitoring of adverse events and morning serum cortisol concentrations. The primary efficacy parameter (mean morning PEF) increased during treatment in both groups; adjusted mean changes were 33 and 28 L/min for the combination and concurrent therapies, respectively. The 90% confidence interval for the difference in mean morning PEF between treatment groups was within the +15 L/min criterion for clinical equivalence. Similarly, there were improvements in pulmonary function, symptom score, and rescue salbutamol use during treatment in both groups, with no significant differences between the combination and concurrent therapy groups for any of these secondary efficacy parameters. Both treatment regimens were well-tolerated and had comparable adverse event profiles. Mean morning serum cortisol levels increased similarly in both groups during the study. In conclusion, salmeterol and fluticasone propionate therapy given as a new combination product is as safe and effective in children with asthma as the same drugs given concurrently via separate inhalers.

A new assay to assess steroid-hormone responsiveness in head and neck cancer.

A new assay has been developed to predict the effectiveness of steroid-hormone therapy in various tumors. The Biopsy Nuclear Binding assay measures the amount of biologically active receptor that binds both steroid hormone and acceptor sites in the nucleus. This assay does not measure the entire receptor population, only those that are biologically active; therefore, it should more accurately predict the response to steroid-hormone therapy. We applied this assay effectively in breast and endometrial carcinoma. Preliminary studies have shown that 40% of patients with head and neck squamous-cell carcinomas have biologically active (nuclear bound) progesterone receptors. If nuclear binding predicts a remission with hormonal therapy, then the quality of life of appropriately selected patients could greatly improve.

Progesterone receptors in carcinomas of the upper aerodigestive tract.

This study had three major goals: (1) to vigorously verify the presence of progesterone receptors in squamous cell carcinoma of the upper aerodigestive tract (HN-SCC). Antiprogesterone receptor monoclonal antibodies revealed a distinct band at approximately 120 kilodaltons in samples taken from two of four patients with HN-SCC. These results illustrate that progesterone receptor in HN-SCC has the same molecular weight as progesterone receptor in normal human uterus and human breast cancer. Steroid specificity and saturability results support the evidence that it is true progesterone receptors that are measured and not other receptors or sex steroid-binding globulins; (2) to confirm the biochemical function of progesterone receptors in HN-SCC by assessing the binding of progesterone receptor to acceptor sites on chromosomes in the nucleus; and (3) to establish the clinical significance of progesterone receptor measurement. Patients with positive assays were more likely to be free of disease a mean of 6 months after resection. We used logistic regression to account for site of primary disease, grade of tumor, and stage of disease. This logistic regression was significant with a p = 0.014. Patients with a binding index greater than 2 (19 of 73 patients) were 4.34 times more likely to be free of disease than patients with negative assays.

Validation of a web-based version of the asthma control test and childhood asthma control test.

RATIONALE: Recent guidelines focus on adjusting asthma treatment to the level of asthma control. The availability of a web-based asthma control questionnaire offers the possibility to assess asthma control without the need of outpatient clinic visits. The aim of this study was to evaluate the agreement between web-based and paper-based versions of the Asthma Control Test (ACT) and Childhood Asthma Control Test (C-ACT), short-term reproducibility and satisfaction with both versions. METHODS: One hundred seventy-three children with stable asthma and a normal lung function were randomized to fill in a web-based or paper-based version of the C-ACT (4-11 years) or ACT (12-18 years). According to a cross-over design, they completed the opposite version after 1 week. Reproducibility was evaluated by repeating the 2nd version (web- or paper-based) 7 days later. RESULTS: Eighty-eight children filled in the C-ACT, 68 children filled in the ACT. Intraclass Correlation Coefficient (ICC) for web-based versus paper-based C-ACT was 0.81 (95% confidence interval [95% CI] 0.72-0.87). For ACT this was 0.84 (95% CI 0.76-0.90). For web-based and paper-based C-ACT the reproducibility ICC was 0.82 (95% CI 0.67-0.90) and 0.75 (95% CI 0.59-0.85), respectively. The reproducibility ICC of the ACT for web- and paper-based versions was 0.93 (95% CI 0.87-0.97) and 0.77 (95% CI 0.59-0.88), respectively. Eighty-six percent of patients preferred the web-based version. CONCLUSION: The web-based version of the C-ACT and ACT is reproducible and comparable with the paper-based version in assessing asthma control. Most children and their parents prefer the web-based version.

Validation of a single concentration methacholine inhalation provocation test (SCIPT) in children.

A new method to assess bronchial hyperresponsiveness (BHR) using a single concentration methacholine has already been validated in adults with asthma. Because the geometrical dimensions of the airways in children are different, the results from studies in adults cannot be extrapolated to children. In this study, we validated the single concentration methacholine inhalation provocation test (SCIPT) in children. Twenty-two children performed three methacholine inhalation challenge tests in random order. Two challenges were performed according to the SCIPT: doubling doses (0.03-1.8 mg; maximal cumulated dose 3.6 mg) were administered with an Aerosol Provocation System (Masterscope, Jaeger). The third challenge was performed according to a standard dosimeter method (SDM): doubling doses (0.002-1.8 mg; maximal cumulative dose 3.5 mg) were administered with a DeVillbiss 646 nebulizer. The degree of BHR is expressed as a PD20. A difference of < 1.5 dose step was assumed to be due to intraindividual variation. We found an intraclass correlation of 0.91 between both tests according to the SCIPT and of 0.80 between the SCIPT and SDM. We found, according to the method of Bland and Altman, good agreement when comparing these two challenge tests. The single concentration inhalation provocation test is reproducible and shows good agreement with a standard dosimeter method to test bronchial responsiveness in children.

A nuclear binding assay for measurement of biologically active androgen receptors in animal tissues and human prostate cancer.

A nuclear binding (NB) assay has been developed for the measurement in intact viable cells of biologically active (functional) estrogen and progesterone receptors, i.e. those capable of binding to nuclear acceptor sites [Spelsberg et al., Endocrinology 121: 631 (1987)]. This paper describes the application of this assay to analyses of androgen receptors in the guinea pig seminal vesicle and in human prostatic carcinoma. Cells from fresh animal seminal vesicles or human prostate carcinoma are isolated using collagenase and are incubated with [3H]R1881 for 1 h at 22 degrees C, after which nuclei are isolated at 4 degrees C and assayed for DNA and radioactivity. This NB assay demonstrates a saturable, temperature dependent, steroid and tissue specific nuclear binding of [3H]R1881 for the guinea pig-seminal vesicle system. The nuclear binding is of high affinity and low capacity. The NB assay reveals several important aspects of the androgen and estrogen receptors in target tissues: (1) the nuclear acceptor sites for androgen receptor (AR) are steroid receptor specific; (2) there are different concentrations of the androgen and estrogen receptors between the epithelium and the fibromuscular components of the guinea pig seminal vesicle; and finally (3) some biopsies of human prostate cancer appear to contain biologically inactive AR. This assay may be useful in the analyses of functional receptors in biopsies of human cancer cells.

Surface wave delay line acoustooptic devices for signal processing.

Several acoustooptic devices have been developed for use as electronic signal processors at the Harry Diamond Laboratories. These devices use the Bragg interaction between a coherent light beam and surface acoustic waves propagating in a transparent crystalline delay line. Both real-time convolution and correlation of signals have been performed, and a real-time continuous Fourier transform has also been achieved. A programmable memory correlator has been demonstrated. This device uses a newly discovered photorefractive effect to store an image of a surface acoustic wave in a lithium niobate delay line. An acoustooptic implementation of the triple-product convolver is under active development. This device has been proposed for use in conjunction with charge-coupled-device chirp-Z-transform modules to perform very long discrete Fourier transforms and to do omega-k beam forming.

IgG subclasses in bronchoalveolar lavage fluid from patients with asthma.

We have measured Immunoglobulin G (IgG) subclasses in serum and bronchoalveolar lavage fluid (BALF) from 12 non-smoking patients with stable asthma and 9 non-smoking healthy volunteers to obtain information on their possible role in local immunological reactions. The quotients (concentration of IgG subclass in BALF)/(concentration of IgG subclass in serum) were calculated. In controls QIgG3 were lower than QIgG1, QIgG2 and QIgG4. The IgG subclasses in BALF and epithelial lining fluid (ELF) from patients with asthma were significantly higher than in controls, mainly due to increased leakage from the blood. Again QIgG3 were lower than Q of other subclasses. In the analysis of local production of IgG, albumin or ceruloplasmin was used as reference protein. Several patients showed a local production or a preferential accumulation of one or more IgG subclasses. We conclude that in healthy persons the IgG subclasses in ELF originate from the systemic circulation by passive permeation. In patients with asthma, the permeability of the respiratory membrane may be increased resulting in increased concentrations of subclasses in lung-lining fluid. In some patients with asthma, an additional local production of IgG subclasses occurs.

Immediate and late asthmatic responses induced by exercise in patients with reversible airflow limitation.

The existence and prevalence of late asthmatic responses to exercise in patients is uncertain. We investigated whether the late falls of peak expiratory flow rate (PEFR) after exercise challenge were still significant after comparison with the corresponding clocktime PEFR on a control day. We examined 86 patients with reversible airflow limitation, 79 with asthma and 7 with chronic obstructive pulmonary disease (COPD), all under regular treatment with bronchodilators and/or anti-inflammatory agents. Patients were randomized for a control day and an exercise day and PEFR was recorded hourly. On the exercise day, each patient underwent an 8 minute bicycle ride at 90% of predicted heart-rate. An early and a late asthmatic response to exercise were considered to occur when PEFR decreased by 10% or more on the exercise day compared to the corresponding clocktime PEFR on the control day. Thirty-three patients (38%) had a 10% or greater fall of PEFR at 4 to 13 hours after exercise when PEFR was compared with the corresponding clocktime on a control day. Seven (8%) had an isolated late asthmatic response, and 26 (30%) had a dual asthmatic response. We conclude that true late asthmatic responses develop after exercise in a significant number of patients with well controlled reversible airflow limitation.

Microassay for nuclear binding of steroid receptors with use of intact cells from small samples of avian and human tissue.

A micro version of a nuclear binding assay to assess the biological activity of receptors for steroid hormones was developed for application to small (needle) biopsies of human tumors for the purpose of predicting responses to steroid therapy. This easier assay requires 10-fold less tissue than the original nuclear binding assay described for progesterone receptors in the avian oviduct, endometrium, and endometrial carcinomas (Spelsberg TC, et al., Endocrinology 1987;121:631). We describe the application of this micro assay to normal avian oviduct and cancers of the human breast, and we demonstrate a tissue specificity and saturation of nuclear binding. The micro assay reliably measured as little as 0.5 mg equivalents of tissue per assay tube. Results for breast tumors determined to be estrogen-receptor-positive by the standard dextran-coated charcoal method were also determined with this nuclear binding assay. As described previously for progesterone receptors in endometrial carcinomas, some receptor-positive breast biopsies displayed negligible capacity for nuclear binding. Therefore, with the present assay we have identified nonfunctional receptors in these biopsies, which may be useful for accurate prediction of patients' responses to therapy with hormones.