In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus.

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

Combined retrospective analysis of 498 rat multi-generation reproductive toxicity studies: on the impact of parameters related to F1 mating and F2 offspring.

The multi-generation reproductive toxicity study (OECD TG 416 and USEPA 870.3800) has been extensively used internationally to assess the adverse effects of substances on reproduction. Recently the necessity of producing a second generation to assess the potential for human health risks has been questioned. The present standardized retrospective analysis of the impact of the second generation on overall study outcome combines earlier analyses and includes 498 rat multi-generation studies representing 438 different tested substances. Detailed assessment of study reports revealed no critical differences in sensitivities between the generations on the basis of a consideration of all endpoints evaluated. This analysis indicates that the second generation mating and offspring will very rarely provide critical information. These findings are consistent with the conclusions of previous retrospective analyses conducted by RIVM, USEPA and PMRA and support adoption of the proposed OECD extended one-generation reproductive toxicity study protocol in regulatory risk assessment testing strategies.

Changes in AVM angio-architecture and hemodynamics after stereotactic radiosurgery assessed by dynamic MRA and phase contrast flow assessments: a prospective follow-up study.

OBJECTIVES: Assessment of changes in the hemodynamics of Arteriovenous malformations (AVM) induced by radiosurgery by MR Phase contrast (PC) measurements of the internal carotid arteries (ICA). METHODS: 65 patients shortly after or before stereotactic radiosurgery underwent MRI including morphological series, MR-Angiography (Time-of-flight, dynamic MRA) and bilateral ECG triggered MR phase contrast (PC) measurements of the ICA. Follow-up was performed in 34 patients. The observation period was up to 4 years. RESULTS: Over all subjects, a significant relationship between mean arterial blood flow in the ICA on the side of the lesion and AVM volume was revealed (p = 0,0002). In large (>10 ccm) and medium-sized AVMs, (>3, 5 ≤ 10 ccm) the blood flow was significantly increased on the side of the AVM (p = 0,0004; p = 0,047), whereas in lesions <3, 5 ccm, no significant rise of the mean blood flow was detectable. At follow-up, the mean blood flow in the ipsilateral artery was not increased anymore compared to the contralateral ICA (p = 0,11). These changes correlated with a significant reduction of the average AVM volume (p = 0, 0026). CONCLUSIONS: The AVM angioarchitecture has significant impact on the blood flow in feeding arteries. A significant reduction of the shunt volume by successful radiotherapy leads to normalization of the hemodynamics.

Incompatible kidney donor candidates' willingness to participate in donor-exchange and non-directed donation.

Although paired donation, list donation and non-directed donation allow more recipients to receive living donor transplants, policy makers do not know how willing incompatible potential donors are to participate. We surveyed 174 potential donors ruled out for ABO-incompatibility or positive cross-match about their participation willingness. They were more willing to participate in paired donation as compared to list donation where the recipient receives the next deceased donor kidney (63.8% vs. 37.9%, p < 0.001) or non-directed donation (63.8% vs. 12.1%, p < 0.001). Their list donation willingness was greater when their intended recipients moved to the top versus the top 20% of the waiting list (37.9% vs. 19.0%, p < 0.001). Multivariate logistic regression modeling revealed that potential donors' empathy, education level, relationship with their intended recipient and the length of time their intended recipient was on dialysis also affected willingness. For paired donation, close family members of their intended recipient (odds ratio (OR) = 3.01, confidence intervals (CI) = 1.29, 7.02), with high levels of empathy (OR = 2.68, CI = 1.16, 6.21) and less than a college education (OR = 2.67, CI = 1.08, 6.61) were more willing to participate compared to other donors. Extrapolating these levels of willingness nationally, a 1-11% increase in living donation rates yearly (84-711 more transplants) may be possible if donor-exchange programs were available nationwide.

Trichome dynamics and artemisinin accumulation during development and senescence of Artemisia annua leaves.

Artemisinin is a sesquiterpene lactone endoperoxide and an important antimalarial drug produced in Artemisia annua. To unravel the diverse processes determining artemisinin yield in A. annua crops, artemisinin accumulation during the development of individual leaves was studied in two field experiments. During the life cycle of a leaf, artemisinin was always present. Quantities were low at leaf appearance and increased steadily. In leaves studied until after senescence, maximum quantities and concentrations were achieved after the leaf had turned brown. The total quantity of possible artemisinin precursors per leaf (dihydroartemisinic acid and other upstream precursors) was highest early in the leaf cycle when the leaf was still expanding. Dihydroartemisinic acid was more abundant than the other compounds and its quantity declined during leaf development whereas that of artemisinin increased. Dihydroartemisinic acid was not converted directly into artemisinin, because on a per leaf basis the decline in molar quantity of precursors in the earliest formed leaves was not compensated for by a simultaneous increase in artemisinin. Our results suggest that a (putative) intermediate such as dihydroartemisinic acid hydroperoxide temporarily may have accumulated in considerable quantities. The number of mature, capitate trichomes on the adaxial leaf side increased after leaf appearance until the end of leaf expansion, and then decreased, probably due to collapse of trichomes. Artemisinin production thus (also) occurred when trichomes were collapsing. Later formed leaves achieved higher concentrations of artemisinin than earlier formed leaves, because of a higher trichome density and a higher capacity per trichome.

Technological transfers from the European space programs: a dynamic view and comparison with other R&D projects.

This article presents the results and lessons learned from a series of studies carried out by the BETA research team (University Louis Pasteur of Strasbourg, France) to measure the spin-offs and technological transfers that resulted from European space programs. Beyond the quantitative results that are analyzed in detail, the article examines some of the main qualitative characteristics that shape the technology transfer process generated by these programs. In particular, it is demonstrated that three main characteristics have a significant impact on the technology transfer process: the nature of the technologies at stake (their degree of maturity, their degree of diversity, the extent to which they are generic or specific), the nature of the network of participants to the programs (the degree of mutual trust, the existence of absorptive capabilities) and the nature of the organizational structure of those firms which participated in the projects (their degree of decentralization, their degree of vertical integration). The article concludes by discussing how these lessons learned could be used to shape the procurement policies to be followed by space agencies in order to favor a high potential for technological transfers arising from future space projects.

Annotated draft genomic sequence from a Streptococcus pneumoniae type 19F clinical isolate.

The public availability of numerous microbial genomes is enabling the analysis of bacterial biology in great detail and with an unprecedented, organism-wide and taxon-wide, broad scope. Streptococcus pneumoniae is one of the most important bacterial pathogens throughout the world. We present here sequences and functional annotations for 2.1-Mbp of pneumococcal DNA, covering more than 90% of the total estimated size of the genome. The sequenced strain is a clinical isolate resistant to macrolides and tetracycline. It carries a type 19F capsular locus, but multilocus sequence typing for several conserved genetic loci suggests that the strain sequenced belongs to a pneumococcal lineage that most often expresses a serotype 15 capsular polysaccharide. A total of 2,046 putative open reading frames (ORFs) longer than 100 amino acids were identified (average of 1,009 bp per ORF), including all described two-component systems and aminoacyl tRNA synthetases. Comparisons to other complete, or nearly complete, bacterial genomes were made and are presented in a graphical form for all the predicted proteins.

Omeprazole versus high-dose ranitidine in mild gastroesophageal reflux disease: short- and long-term treatment. The Dutch Reflux Study Group.

OBJECTIVE: Patients with reflux esophagitis suffer from a chronic condition that may cause considerable discomfort because of recurrent symptoms and diminished quality of life. This study was designed to evaluate acute and long-term treatment comparing standard doses of omeprazole and high-dose ranitidine. METHODS: Patients with endoscopically verified symptomatic esophagitis grade I or II were initially treated with omeprazole 20 mg daily or ranitidine 300 mg twice daily for 4-8 wk. Patients who were symptom free were randomized to maintenance treatment with omeprazole 10 mg daily or ranitidine 150 mg twice daily. Patients were seen every 3 months or at symptomatic relapse. RESULTS: The percentage of asymptomatic patients after 4 and 8 wk treatment were 61% and 74%, respectively, for omeprazole and 31% and 50%, respectively, for ranitidine. Of 446 patients treated initially, 277 were asymptomatic, of whom 263 entered the maintenance study. The estimated proportion of patients in remission after 12 months of maintenance treatment with omeprazole 10 mg daily (n = 134) and ranitidine 150 mg twice daily (n = 129) were 68% and 39%, respectively (p < 0.0001). CONCLUSIONS: Omeprazole 20 mg daily is superior to high-dose ranitidine in the symptomatic treatment of reflux esophagitis grade I and II. Furthermore, omeprazole at half the standard dose is more effective than ranitidine in a standard dose in keeping patients in remission for a period of 12 months.

Hormonal status and the neuroendocrine response to a novel heterotypic stressor involving subchronic noise exposure.

Despite a number of studies on noise-induced health effects, it is still unclear to what extent different neuroendocrine pathways are affected by noise exposure. Male Wistar rats were housed in sound-attenuated rooms isolated for noise from outside. Three groups of chronically cannulated rats were exposed to either background noise (+/-64 dB) only or irregular experimental white noise (90 dB, 2-22 kHz). Two protocols, with approximately the same total amount of noise but with different densities, were used: protocol N1 (180 min random noise per day for 18 days) or protocol N2 (540 min random noise per day for 8 days). Basal levels of circulating hormones (ACTH, corticosterone, prolactin and catecholamines) and plasma glucose were measured. In control animals, no significant changes in any of these parameters were observed over 18 days. Except for plasma prolactin, N1 did not induce a significant elevation in basal hormonal levels. N2 however induced significant elevation in basal prolactin, corticosterone and noradrenaline levels. At the end of the exposure period, all animals were subjected to a novel heterotypic stressor (restraint stress) to monitor differences in neuroendocrine activation (ACTH, corticosterone and prolactin). Compared to nonexposed control animals, N1 animals showed a normal ACTH and an enhanced corticosterone response, whereas N2 animals showed an increased ACTH but a normal corticosterone response. The prolactin response of both N1 and N2 animals was significantly decreased. Adrenal cell suspension experiments revealed that in noise-exposed rats both basal- and ACTH-stimulated corticosterone production were significantly increased as compared to control animals. These results indicate that chronic noise exposure at mild intensities induces subtle but significant changes in hormonal regulation.

Adjunctive interferon-alpha-2c in stage IIIB/IV small-cell lung cancer: a phase III trial.

Preliminary studies have shown bioactivity of interferons (IFNs) in the treatment of small-cell lung cancer (SCLC). The aim of the present study was to determine whether, in patients with advanced SCLC, a combination of recombinant IFN-alpha-2c and standard induction chemotherapy would improve response rates and survival at acceptable toxicity. Of the 85 patients recruited by 11 centres in Austria, 77 were evaluable for response after induction therapy; of these, 43 were randomized to receive the combined treatment (three cycles each of cyclophosphamide/vincristine/doxorubicin and cisplatin/etoposide plus subcutaneous IFN-alpha-2c), and 34 received chemotherapy alone. After the induction phase, patients in the IFN arm had higher rates of complete (30 vs 15%) and partial remission (42 vs 29%) than those who received chemotherapy alone. Accordingly, there was a lower rate of progressive disease in the interferon arm (21 vs 44%; p < 0.05). Whilst there were no significant differences in time to progression (7.6 vs 5.4 months) patients in the IFN arm survived longer than those in the chemotherapy arm (p < 0.02). Six of the patients treated with IFN (14%) survived for more than 2 yrs, whereas none in the chemotherapy arm did. We conclude that the addition of interferon-alpha-2c to induction chemotherapy may improve response rates and survival in advanced small-cell lung cancer.

Dobutamine effects on systole and diastole in rats with myocardial infarction.

In this article, the authors attempt to determine the effect of catecholamine stimulation on the systolic and diastolic properties of the left ventricle (LV) in rats with chronic infarction. Male Sprague-Dawley rats underwent coronary artery ligation at 8-10 weeks of age. Baseline hemodynamics were measured 1-2 months after infarction. Dobutamine was administered in bolus injections of increasing concentrations, and peak hemodynamic response after each dose was recorded. Rats were divided into three groups: controls (n = 14), rats with infarct size less than 30% of LV (n = 13), and rats with infarct size at least 30% of LV (n = 9). Baseline hemodynamics were similar among the three groups. There was no significant difference in the maximal response of LV systolic pressure and heart rate between the three groups. Left ventricle +dP/dt increased with dobutamine in all three groups, but rats with infarct size of at least 30% had a significantly smaller increase above baseline as compared with control rats. In contrast, LV -dP/dt increased to a similar degree in all three experimental groups with dobutamine. Although hemodynamics can be affected by loading conditions in the intact animal, the magnitude of the change in +dP/dt with unaltered -dP/dt suggests that there is an impaired inotropic but not lusitropic response to catecholamine stimulation in rats with large chronic myocardial infarcts. The findings imply a differential effect of beta-agonist stimulation on systolic and diastolic properties of the heart.

Contraction band necrosis: its modification by the free radical scavenger N-2-mercaptopropionyl glycine.

Contraction band necrosis (CBN) may represent infarct extension from free radical generation during reperfusion. We sought to limit CBN with the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 20 mg/kg). Sixteen chronically instrumented Beagles (8 control, and 8 MPG treated) underwent 90-min left anterior descending coronary artery (LAD) occlusion followed by 6-h reperfusion. Coronary blood flow (CBF) was measured by the radioactive microsphere technique. The dogs were killed, and the hearts were perfused with red and blue dyes to determine area at risk (AAR), stained with nitroblue tetrazolium for infarct localization, and sectioned for histologic analysis and BF measurements. In controls and MPG-treated animals, infarct/risk ratios were 40 +/- 5 and 38 +/- 6%, and epicardial collateral BFs were 0.21 +/- 0.037 and 0.15 +/- 0.034 ml/g/min, respectively (p = NS). Hemodynamic measurements did not differ between the two groups. However, CBN as a percentage of total infarct was reduced in controls (22 +/- 3%) as compared with MPG-treated animals (35 +/- 2%, p = 0.002). Thus, MPG altered the histologic composition of infarcts in this model, surprisingly increasing the amount of CBN without altering overall infarct size (IS). These results raise questions about the role of free radical scavengers in generation of CBN and suggest that a population of cells exists in which treatment with MPG may alter the mechanism of cell death.

[Injury of the popliteal artery as a complication of knee dislocation]. / Die Verletzung der Arteria poplitea als Komplikation der Kniegelenksluxation.

Dislocation of the knee is rarely seen. Only 15 patients with a knee dislocation were treated in the surgical department of the university hospital in the last 18 years. One patient had bilateral dislocation of the knee. Injury to the popliteal artery is severe and often endangers the extremity. In seven patients with knee dislocation arterial ischemic was detected. Five patients were treated for arterial damage (31.25%).

Feasibility of recanalization of human coronary arteries using high-intensity ultrasound.

To investigate the feasibility of ultrasonic recanalization of obstructed human coronary arteries in vitro, high-intensity ultrasound was applied to 16 coronary arteries obtained at autopsy, using a prototype instrument enabling insonification through a catheter tip. It was a 119 cm long, 0.95 mm thick wire in an 8Fr catheter connected to an external ultrasonic transformer and power generator. A 5 MHz phased-array 2-dimensional echocardiography instrument was used to determine minimal luminal diameter and percent diameter narrowing before and after ultrasound application. The ultrasonic energy was delivered at 21.5 kHz and with a 52 +/- 19 micrometer average amplitude of tip displacement. The mean percent luminal diameter narrowing, flow rate and mean pressure gradient before ultrasound exposure were 74 +/- 11%, 97 +/- 61 ml/min, and 92 +/- 18 mm Hg, respectively. After recanalization, the mean percent luminal diameter narrowing decreased to 45 +/- 17% (p < 0.001), the mean flow rate increased to 84 +/- 92 ml/min (p < 0.001), and the mean pressure gradient was reduced to 45 +/- 24 mm Hg (p < 0.001). Of the debris particles, 95% had a diameter < 9 microns (range 5 to 12). Arterial perforation occurred in 5 of 16 arteries (31%) and all 5 occurred due to stiff wire manipulation and without ultrasound application. Mechanical fracture of the wire occurred in 8 cases (50%). No signs of thermal injury were found on histology. Thus, ultrasonic recanalization of human coronary arteries in vitro is feasible. It may reduce obstruction and improve blood flow. Debris sizes are sufficiently small to minimize the hazard of peripheral embolization.

Morphological effects of pulsed ultrasound in the lung.

We have previously described the induction of subcapsular hemorrhage in the murine lung by extracorporeal shock wave lithotripsy at exposures of 2 MPa (Hartman et al. 1990) and pulsed ultrasound (Child et al. 1990). Since extravasation of erythrocytes and alveolar flooding are prominent, we proposed to determine whether or not the injury was progressive, by continuing to develop following termination of exposure, and by localizing where the injury was developing. Mice were exposed to 10 microsecond impulses at 1.6 MPa for 3 min and sacrificed either immediately or 5 min following exposure. When observed with both light and transmission electron microscopy, there was no gradation in lung injury, with a sharp demarcation of the hemorrhagic area. Moreover, both type I pneumocytes and capillary endothelial cells were injured, causing direct continuities between vessel lumina and alveolar spaces. In the absence of extravasation, the tissue appeared normal. There was no evidence that injury increased in severity during the first 5 min after exposure.

[Diagnostic value of secretory products of eosinophils and neutrophils in bronchoalveolar lavage in patients with idiopathic lung fibrosis]. / Aussagekraft der Sekretionsprodukte von Eosinophilen und Neutrophilen in der bronchoalveolären Lavage bei Patienten mit idiopathischer Lungenfibrose.

Idiopathic pulmonary fibrosis (IPF) is characterized by a chronic inflammatory process in the lower respiratory tract of unknown etiology and poor prognosis. There is evidence that cytotoxic mediators released by neutrophils and eosinophils, such as myeloperoxidase (MPO) and eosinophil cationic protein (ECP) play a central role in the pathogenesis of this disease. The aim of this study was to assess disease activity in patients with IPF by measuring MPO and ECP concentrations in bronchoalveolar lavage (BAL). 14 patients with IPF had significantly higher concentrations of BAL-MPO and ECP (median = 117.2 micrograms/l, range: 4-217 micrograms/l and median = 16 micrograms/l, range: 4-34 micrograms/l, respectively) than patients with sarcoidosis (n = 9) (median = 6.5 micrograms/l, range: 4-12 micrograms/l and median = 7.1 micrograms/l, range: 2-13 micrograms/l, respectively) or pneumonia (n = 13) (median = 10.8 micrograms/l, range: 5-14 micrograms/l and median = 7.6 micrograms/l, range: 3-10 micrograms/l, respectively) (p < 0.01). Follow-up of MPO and ECP concentrations in BAL was performed in 8 patients with IPF before and after 4 weeks high-dose and 12 months low-dose corticosteroid therapy. Changes in MPO and ECP levels paralleled the clinical course and successful treatment resulted in a significant decrease of both MPO and ECP concentrations (p < 0.05), while clinical deterioration or treatment failure was associated with an increase of BAL-MPO and ECP levels. Increased MPO and ECP concentrations in BAL seem to reflect ongoing disease activity and may be useful prognostic markers in the management of patients with IPF.

Ability of high-intensity ultrasound to ablate human atherosclerotic plaques and minimize debris size.

To investigate whether high-intensity ultrasound can destroy atherosclerotic plaques while sparing the normal arterial wall, 279 normal human aortic sites and 119 fibrous and 193 calcified plaques, obtained from 24 necropsies, were insonified in a water tank, at 20 kHz and at 5 different power intensities, ranging from 68 W/cm2 (P1) to 150 W/cm2 (P5). These intensities were associated with a total excursion of the ultrasound irradiation apparatus tip from 90 to 268 microns, respectively. Time to perforate normal aortic sites and fibrous and calcified plaques was recorded at each intensity. There was no difference in perforation time between normal aortic sites and fibrous and calcified plaques when high-power levels (P2 to P5) were used. However, at the lowest power (P1), perforation time for the normal aortic wall was significantly longer than for fibrous and calcified plaques: 30 +/- 18 seconds (166 observations), 14 +/- 7 seconds (p less than 0.001) (78 observations) and 12 +/- 8 seconds (p less than 0.001) (115 observations), respectively. When perforation times for normal vessel wall versus fibrous plaque and normal vessel wall versus calcified plaque from the same necropsy specimen were compared in a pairwise manner, the results were: 29 +/- 13 vs 16 +/- 7 (p less than 0.001) (48 paired observations) and 26 +/- 9 vs 10 +/- 5 seconds (p less than 0.001) (55 paired observations), respectively. Regardless of whether paired or unpaired comparison was applied, no significant difference was found in perforation time between fibrous and calcified plaques. The debris did not differ in size as measured separately for normal sites and fibrous and calcified plaques by a computer-interfaced Channelizer and Coulter Counter system.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmunity in premature ovarian failure.

We performed laparoscopic ovarian biopsies in 17 of 19 cases with premature ovarian failure. Primordial follicles were found in three cases, corpora albicanti in two, and epithelial-lined cysts in two cases. Chromosome analysis revealed a normal 46XX karyotype in 15 patients, 46XY in two, 45XO in one, and 46XO/46XX mosaicism in one patient. Immunofluorescence studies were performed on ovarian tissue obtained by laparoscopic biopsy in 12 cases with premature ovarian failure. Blood serum was analyzed for circulating anti-ovary and other autoantibodies in all 12 cases. Circulating autoantibodies were found in the serum of six patients, but not in healthy controls. Direct immunofluorescence was positive in 5 of 12 ovarian tissue samples with predominantly vascular wall staining. Indirect immunofluorescence was positive in 10 of 12 cases; antibodies reacting with ovarian stromal components were present in eight cases, antibody reacting with follicular epithelium was present in one case, and antibodies reacting with nuclear antigens were present in five cases. Two of the patients had anti-thyroid microsomal antibodies, and one had antitesticular antibody. We conclude that a significant number of patients with ovarian failure have serologic and biopsy findings suggestive of and consistent with autoimmunity, even though there are no overt clinical manifestations of autoimmune disease.

Pressure threshold for shock wave induced renal hemorrhage.

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

[Significance of expiratory bronchiolar collapse symptoms in the diagnosis of emphysema]. / Wertigkeit exspiratorischer Bronchiolenkollapszeichen in der Emphysemdiagnostik.

A club-shaped resistance curve as recorded using wholebody plethysmography, as an expression of expiratory bronchial collapse is often interpreted as a sign of pulmonary emphysema. Within the framework of a prospective study involving 32 consecutive patients, a quantification of the resistance loops was carried out. The results obtained indicate that dynamic airway collapse is not specific to emphysema. Rather, there is a highly significant correlation between the degree of bronchial collapse and the elevation of total lung capacity irrespective of whether the latter is due to a reversible hyperinflation associated with bronchospasm or to emphysema of the lungs. It can, however, be seen that, in patients with reversible hyperinflation, intensive anti-obstructive treatment also leads to a decrease in, or the disappearance of, the signs of bronchiole collapse with simultaneous decrease in TLC. We conclude from this that a repeat wholebody plethysmographic examination following a lengthy period of treatment is suitable for distinguishing between bronchiole collapse in reversible hyperinflation and emphysema.