PubMed Health⌕ Search

Biomedical subjects

J W Jenne

Publications and source records attributed to J W Jenne.

At least 19 recordsLinked to original sources
PubMed2003

[Focused ultrasound surgery. Basics, current status, and new trends].

There is an increasing interest in high intensity focused ultrasound (HIFU) for thermo ablative tumor therapy. The attractiveness of this method is based on its ability to destroy tumor tissue non invasively while sparing surrounding tissue from outside the body. HIFU induced tissue necroses are sharply circumscribed. Therefore this method was termed focused ultrasound surgery (FUS). The therapeutic potential of FUS is under investigation in several clinical studies. Main objects of these studies are prostate carcinomas, breast kidney and liver tumors. The next innovative step will be the non invasive FUS treatment of brain through the intact skull. Combining FUS with magnetic resonance imaging (MRI) or diagnostic ultrasound allows accurate and online therapy guiding and monitoring. This article gives an overview of the basics, the latest developments and actual clinical studies in the field of focused ultrasound surgery.

Electrocoagulation↗
PubMed2001

A new noninvasive approach in breast cancer therapy using magnetic resonance imaging-guided focused ultrasound surgery.

An ideal vision of modern medicine includes tumor surgery with the human body remaining completely intact. A noninvasive therapy could avoid infections and scar formation; it would require less anesthesia, reduce recovery time, and possibly also reduce costs. This study investigated whether human breast cancer can be effectively treated with a novel combination of image guidance and energy delivery, noninvasive magnetic resonance imaging (MRI)-guided focused ultrasound (FUS). We have developed a FUS therapy unit guided by MRI for the treatment of human breast tumors in a clinical 1.5 T MR scanner. With interactive target segmentation on MRI, defined volumes could be noninvasively treated in a single session with on-line MR temperature control. The ultrasound waves were focused through the intact skin and resulted in the localized thermal tissue ablation at a maximum temperature of 70 degrees C. The therapy principle was first demonstrated in sheep breast in vivo and was then applied in a patient with core biopsy-proven invasive breast cancer 5 days before breast-conserving surgery. MRI proved suitable to delineate the breast cancer, served as stereotactic treatment planning platform, and delineated the FUS-related tissue changes such as interruption of tumor blood flow. Furthermore, MRI localized the hot spot in the tumor and measured temperature elevation during the treatment. This allowed us to monitor the efficacy and safety of FUS therapy. Immunohistochemistry of the resected specimen demonstrated that FUS homogeneously induced lethal and sublethal tumor damage with consecutive up-regulation of p53 and loss of proliferative activity. This effect was realized without anesthesia and damage to the surrounding healthy tissue or systemic effects. Overall, our results show that noninvasive MRI-guided therapy of breast cancer is feasible and effective. Thus, MRI-guided FUS may represent a new strategy for the neoadjuvant, adjuvant, or palliative treatment in selected breast cancer patients and in patients with other soft-tissue tumors.

Animals↗
PubMed2001

[Magnetic resonance-guided therapy with focused ultrasound. Non-invasive surgery of breast carcinoma?].

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has the potential to become an important therapy modality in the adjuvant, neoadjuvant or palliative cancer treatment. All ultrasound accessible regions are possible target areas, especially breast tumors. Ultrasound propagation is well predictable. The ultrasound energy can be focused to a defined spot through the intact skin, and temperatures of 60 degrees C to 85 degrees C can be induced locally for a few seconds that instantaneously necrose biological tissues, while sparing surrounding healthy tissue. In addition, MRI is sensitive to temperature allowing for online monitoring of the temperature focus. In this work we demonstrate our Heidelberg experiments from basic research and animal studies towards the clinical realization of MRgFUS in breast cancer patients. The most important of these experiments involved sheep as an appropriate model for the human breast. A new therapy setup is designated to treat human breast patients in a clinical 1.5 T MRI scanner. While the therapies have been successful so far without any side effects, the future clinical role of noninvasive MRgFUS has to be defined by clinical studies.

Animals↗
PubMed2001

MR monitoring of focused ultrasound surgery in a breast tissue model in vivo.

The objective of this study was to investigate MRI methods for monitoring focused ultrasound surgery (FUS) of breast tumors. To this end, the mammary glands of sheep were used as tissue model. The tissue was treated in vivo with numerous single sonications which covered extended target volumes by employing a scanning technique. The ultrasound focus position was controlled by online temperature mapping based on the temperature dependence of the relaxation time T(1). This approach proved to be reliable and offers thus an alternative to proton resonance frequency methods, whose application is hampered in fatty tissues. FUS-induced tissue changes were visible on T(2)- as well as on pre- and post-contrast T(1)-weighted images. According to our initial experience, noninvasive MRI-guided FUS of breast tumors is feasible.

Adipose Tissue↗
PubMed1996

Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model.

Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated, mechanically ventilated patients requires adequate delivery of aerosol to the lower respiratory tract. We determined the effect of ventilator mode, inspiratory flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery in a model of the trachea and bronchi. The model was ventilated through an endotracheal tube during controlled mechanical ventilation (CMV), assist control (AC), pressure support (PS), and continuous positive airway pressure (CPAP), separately with a dry and humidified ventilator circuit. Delivery of albuterol administered by a MDI and spacer on filter placed at the ends of the bronchi was measured by spectrophotometry (246 nm). Under dry conditions and with a frequency of 10 breaths/min, albuterol delivery with CMV (VT, 800 ml; 30.3 +/- 3.4%), AC (VT, 800 ml; 31.9 +/- 1.3%), PS 10 cm H2O (VT, 700 ml; 28.8 +/- 4.5%), or PS 20 cm H2O (VT, 800 ml; 30.9 +/- 1.8%) was lower than that observed with simulated spontaneous breaths with CPAP (VT, 800 ml; 39.2 +/- 1.4%) (p < 0.01 for all modes). Delivery was greater under dry (28.8 to 39%) than under humidified conditions (15.9 to 20.2%) (p < 0.005 in all modes). Albuterol delivery showed a linear correlation with both inspiratory time and duty cycle (r > 0.91). Lower respiratory tract delivery of aerosol from a MDI varied from 4.9 to 39.2%. We conclude that in addition to other known factors such as dose, type of spacer, and its position the technique of administering MDIs in mechanically ventilated patients markedly influences lower respiratory tract aerosol delivery.

Aerosols↗
PubMed1996

Dose-response to bronchodilator delivered by metered-dose inhaler in ventilator-supported patients.

In nonintubated patients, metered-dose inhalers (MDIs) are accepted as the most convenient, efficient, and cost effective method of administering inhaled bronchodilators. Recent studies have demonstrated the efficacy of MDIs in ventilator-supported patients; however, the optimal dose of a bronchodilator from a MDI is unknown. We determined the response to increasing doses of albuterol administered by a MDI and cylindrical spacer to 12 mechanically ventilated patients with chronic obstructive pulmonary disease (COPD). Four, eight, and 16 puffs of albuterol were given at 15-min intervals. Rapid airway occlusion were performed before and at 5-min intervals after albuterol for 80 min. Respiratory mechanics were also measured for 60 min in another group of seven patients with COPD who received four puffs of albuterol. Significant decrease in airways resistance occurred after administration of albuterol (p < 0.001). The decrease in airway resistance with four puffs of albuterol was comparable to that observed with cumulative doses of 12 puffs (p = 0.12) and 28 puffs (p = 0.25). Heart rate increased significantly (p < 0.01) after a cumulative dose of 28 puffs. The decrease in airway resistance was sustained for 60 min in the group that received only four puffs of albuterol (p < 0.003). In conclusion, four puffs of albuterol given by a MDI and spacer provided the best combination of bronchodilator effect and safety in stable mechanically ventilated patients with COPD.

Administration, Inhalation↗
PubMed1996

Serum albuterol levels in mechanically ventilated patients and healthy subjects after metered-dose inhaler administration.

In mechanically ventilated patients, systemic blood levels of inhaled drugs reflect absorption from the lower respiratory tract alone since, unlike nonintubated patients, oropharyngeal and gastrointestinal absorption cannot occur. To determine the efficiency of aerosol administration by a metered-dose inhaler (MDI), we measured serum albuterol levels after administration by a MDI and spacer to nine mechanically ventilated patients (10 puffs) and to 10 healthy subjects (six puffs). Serum albuterol levels (+/- SEM) quantitated by high-performance liquid chromatography and electrochemical detection were: 0.09 +/- 0.04 mg/ml/puff at baseline, 0.66 +/- 0.10 at 5 min, 0.98 +/- 0.10 at 10 min, 0.56 +/- 0.08 at 15 min, and 0.37 +/- 0.03 at 30 min in mechanically ventilated patients versus zero at baseline, 0.89 +/- 0.12 at 5 min, 1.27 +/- 0.13 at 10 min, 0.84 +/- 0.09 at 15 min, and 0.53 +/- 0.07 at 30 min in control subjects (p > or = 0.07 at 5, 10, and 30 min; p < or = 0.05 at baseline and at 15 min). Area under the curve (AUC0-30) in the mechanically ventilated patients was 16.8 +/- 1.4 versus 23.4 +/- 1.9 ng/ml/puff x min in control subjects (p = 0.014). In summary, administration of albuterol with a MDI achieved a profile of serum levels in mechanically ventilated patients similar to that in healthy control subjects, but the peak serum level and systemic bioavailability (AUC0-30) were lower in the patients. In conclusion, serum levels reliably assess lower respiratory tract deposition of albuterol, and show that MDIs are more efficient for aerosol delivery in mechanically ventilated patients than was previously reported in studies using radiolabeled aerosols.

Aged↗
PubMed1992

Theophylline produces over-additive relaxation of canine tracheal smooth muscle when combined with beta-agonists: the dose-response relationship.

The interaction between theophylline (T) and the beta-agonists albuterol (A) and isoproterenol (I) was examined using canine cervical tracheal smooth muscle devoid of epithelium contracted with 0.1 or 0.3 microM methacholine. Greater functional antagonism with beta-agonists vs. T was confirmed and an ability of T to potentiate beta-agonist relaxation was demonstrated. The EC50 for T increased from 0.13 +/- 0.02 to 0.37 +/- 0.07 mM (mean +/- SEM) in preparations contracted with 0.1 or 0.3 microM methacholine, respectively, while that for I increased from 0.036 +/- 0.008 to 0.17 +/- 0.03 microM, a significantly larger change (P < 0.025). In tissues contracted with 0.3 microM methacholine and pretreated with 10 micrograms/ml of T IC50 values from composite concentration-response curves for I and A were displaced to the left and Emax was increased (56.6 to 71.5% for I, 44 to 61% for A, P < 0.0002). Addition of 10 micrograms/ml T resulted in relaxations which exceeded that calculated by the fractional product method for additive, independent action (P < 0.0001 for I, P < 0.0002 for A at 0.3 microM methacholine), suggesting that at least part of T's action was over-additive. Five, 10 and 20 micrograms/ml T enhanced the effectiveness of single concentrations of I by factors of 1.47 +/- 0.14 (P < 0.05), 2.72 +/- 0.26 (P < 0.01) and 5.34 +/- 0.55 (P < 0.01), respectively, in preparations contracted with 0.1 microM methacholine: I enhanced the effectiveness to a lesser degree. Using two approaches, positive interaction or over-additivity between T and beta-agonists has been demonstrated.

Adrenergic beta-Agonists↗
PubMed1987

In vivo functional antagonism between isoproterenol and bronchoconstrictants in the dog.

The functional antagonism between isoproterenol and methacholine, histamine and serotonin, as described in vitro in respiratory smooth muscle was explored in vivo in a canine model. Infusions of isoproterenol were administered during brief peaks of bronchospasm produced by aerosolized methacholine and histamine, or during sustained bronchospasm produced by infused serotonin. In eight mongrel dogs anesthetized with pentobarbital sodium, the mean protection by infused isoproterenol against methacholine challenge decreased from 60.6 to 29.1% as the mean lung resistance (RL) was increased from 78 to 232% over base line by a fourfold increase in methacholine (P less than 0.002). In six dogs, the mean protection by isoproterenol against histamine decreased from 55.5 to 26.9% as the opposing RL increased from 80 to 182% over base line with a fourfold increase in histamine (P less than 0.02). However, with serotonin infusions there was only a small 18% mean decrease in protection (P = 0.05), associated with a correspondingly small 37% mean increase in dose of serotonin despite a 269% mean increase in resistance (P = 0.02). In all cases, the loss of protection correlated more closely with the dose of constrictant than the resistance increase over base line. These findings demonstrate in vivo functional antagonism between isoproterenol and the dose of bronchoconstrictant but not necessarily resistance increase per se.

Airway Resistance↗
PubMed1987

Theophylline as a bronchodilator in COPD and its combination with inhaled beta-adrenergic drugs.

The bronchodilating action of theophylline in COPD has been examined, with emphasis on its combined use with inhaled beta 2 agonists. The suggestion is made that failure to recognize the nonlinearity of the dose-response curves for bronchodilators has resulted in underestimating their combined action. Recent studies suggest that systemic theophylline has somewhat different actions on the airways in COPD than inhaled beta agonists, and that more bronchodilation may be possible when the two are used together than large doses of either one. By analogy, with asthma the suggestion is also made that the addition of theophylline is also likely to provide a more constant bronchodilation, reducing peak-trough variations in flow. The most complete clinical comparison to date suggests that, in currently sanctioned doses, a regimen containing both theophylline and an inhaled beta 2 agonist provides significantly greater bronchodilation than either drug alone, with fewer patient withdrawals. Further carefully designed studies are needed to resolve this issue, and particularly, to identify those patients who will derive the greatest benefit from a combined regimen.

Adrenergic beta-Agonists↗
PubMed1986

Effect of disease states on theophylline elimination.

Host factors play an important role in the dosing requirements of theophylline. Theophylline metabolism and clearance depend principally on liver cell function rather than on hepatic flow. The effects of acute hypoxemia require more study; however, patients with chronic obstructive pulmonary disease who have chronic hypoxemia appear to have some impairment of clearance. Clearance is variably and sometimes drastically reduced in patients with liver disease and heart failure, and is reduced by some viral infections. It is not impaired by renal failure. Current split-virus vaccine mixtures do not appear to affect clearance. Clearance is increased in patients with cystic fibrosis and hyperthyroidism. The depressed clearance seen in the severely ill patients who require intensive care improves with improvement in the patient's condition, but the individual factors involved have not been identified. An area requiring more study is the effect of pH on the apparent distribution volume for theophylline. In the presence of liver disease, heart failure, or serious illness, caution must be applied in theophylline dosing, with frequent monitoring of serum levels. Stable patients also warrant an initially conservative dose until serum levels are obtained to guide further dose adjustments.

Animals↗
PubMed1986

Comparison of tremor responses to orally administered albuterol and terbutaline.

This study was designed to compare the initial tremor response to 4.0 mg albuterol and 5.0 mg terbutaline orally administered and to study the question of tachyphylaxis by rechallenge after 3 wk of maintenance dosing. Twenty fasting patients with severe COPD in whom orally administered sympathomimetics were withheld for 2 wk were challenged with single doses of each drug in a crossover, randomized fashion 1 wk apart. Then after a further 3 wk of dosing 3 times a day of the second medication (10 patients received each medication), they were challenged once more 16 h after the last dose. Rest and postural tremor were measured at zero and 2 h using an accelerometer affixed to the finger, and measurements of subjective tremor, tremor power spectrum, plasma cyclic AMP and lactate, and forced vital capacity were also made. Postural tremor increased from 25.05 to 36.20 relative units for albuterol, an increase of 11.15 units, and from 24.90 to 57.70 units for terbutaline, an increase of 32.80 units (difference significant at p = 0.01). Plasma cyclic AMP (p less than 0.01) and lactate (p = 0.05) increases were also less for albuterol, and the FEV1 and FVC responses, though about one third less, did not differ significantly. After 3 wk, mean baseline tremor for both drugs was elevated even 16 h after the last 3 times a day dosing (38.00 and 33.10) for albuterol and terbutaline (difference, NS), and responses were much less to the single tablet (3.40 and 9.10, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗