Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol.

1,4-Butanediol (BDO) is an important commodity chemical used to manufacture over 2.5 million tons annually of valuable polymers, and it is currently produced exclusively through feedstocks derived from oil and natural gas. Herein we report what are to our knowledge the first direct biocatalytic routes to BDO from renewable carbohydrate feedstocks, leading to a strain of Escherichia coli capable of producing 18 g l(-1) of this highly reduced, non-natural chemical. A pathway-identification algorithm elucidated multiple pathways for the biosynthesis of BDO from common metabolic intermediates. Guided by a genome-scale metabolic model, we engineered the E. coli host to enhance anaerobic operation of the oxidative tricarboxylic acid cycle, thereby generating reducing power to drive the BDO pathway. The organism produced BDO from glucose, xylose, sucrose and biomass-derived mixed sugar streams. This work demonstrates a systems-based metabolic engineering approach to strain design and development that can enable new bioprocesses for commodity chemicals that are not naturally produced by living cells.

Novel micro-bioreactor high throughput technology for cell culture process development: Reproducibility and scalability assessment of fed-batch CHO cultures.

With increasing timeline pressures to get therapeutic and vaccine candidates into the clinic, resource intensive approaches such as the use of shake flasks and bench-top bioreactors may limit the design space for experimentation to yield highly productive processes. The need to conduct large numbers of experiments has resulted in the use of miniaturized high-throughput (HT) technology for process development. One such high-throughput system is the SimCell platform, a robotically driven, cell culture bioreactor system developed by BioProcessors Corp. This study describes the use of the SimCell micro-bioreactor technology for fed-batch cultivation of a GS-CHO transfectant expressing a model IgG4 monoclonal antibody. Cultivations were conducted in gas-permeable chambers based on a micro-fluidic design, with six micro-bioreactors (MBs) per micro-bioreactor array (MBA). Online, non-invasive measurement of total cell density, pH and dissolved oxygen (DO) was performed. One hundred fourteen parallel MBs (19 MBAs) were employed to examine process reproducibility and scalability at shake flask, 3- and 100-L bioreactor scales. The results of the study demonstrate that the SimCell platform operated under fed-batch conditions could support viable cell concentrations up to least 12 x 10(6) cells/mL. In addition, both intra-MB (MB to MB) as well as intra-MBA (MBA to MBA) culture performance was found to be highly reproducible. The intra-MB and -MBA variability was calculated for each measurement as the coefficient of variation defined as CV (%) = (standard deviation/mean) x 100. The % CV values for most intra-MB and intra-MBA measurements were generally under 10% and the intra-MBA values were slightly lower than those for intra-MB. Cell growth, process parameters, metabolic and protein titer profiles were also compared to those from shake flask, bench-top, and pilot scale bioreactor cultivations and found to be within +/-20% of the historical averages.

A predictive high-throughput scale-down model of monoclonal antibody production in CHO cells.

Multi-factorial experimentation is essential in understanding the link between mammalian cell culture conditions and the glycoprotein product of any biomanufacturing process. This understanding is increasingly demanded as bioprocess development is influenced by the Quality by Design paradigm. We have developed a system that allows hundreds of micro-bioreactors to be run in parallel under controlled conditions, enabling factorial experiments of much larger scope than is possible with traditional systems. A high-throughput analytics workflow was also developed using commercially available instruments to obtain product quality information for each cell culture condition. The micro-bioreactor system was tested by executing a factorial experiment varying four process parameters: pH, dissolved oxygen, feed supplement rate, and reduced glutathione level. A total of 180 micro-bioreactors were run for 2 weeks during this DOE experiment to assess this scaled down micro-bioreactor system as a high-throughput tool for process development. Online measurements of pH, dissolved oxygen, and optical density were complemented by offline measurements of glucose, viability, titer, and product quality. Model accuracy was assessed by regressing the micro-bioreactor results with those obtained in conventional 3 L bioreactors. Excellent agreement was observed between the micro-bioreactor and the bench-top bioreactor. The micro-bioreactor results were further analyzed to link parameter manipulations to process outcomes via leverage plots, and to examine the interactions between process parameters. The results show that feed supplement rate has a significant effect (P < 0.05) on all performance metrics with higher feed rates resulting in greater cell mass and product titer. Culture pH impacted terminal integrated viable cell concentration, titer and intact immunoglobulin G titer, with better results obtained at the lower pH set point. The results demonstrate that a micro-scale system can be an excellent model of larger scale systems, while providing data sets broader and deeper than are available by traditional methods.

Thermodynamically consistent relations involving plasticity, internal energy and thermal effects.

Experimental data associated with plastic deformations indicate that the temperature is less than that predicted from dissipation based on plastic work. To obtain reasonable correlation between theoretical and experimental results, the plastic work is often multiplied by a constant beta. This paper provides an alternative thermodynamic framework in which it is proposed that there is an additional internal energy associated with dislocation pile-up or increase in dislocation density. The form of this internal energy follows from experimental data that relates flow stress to dislocation density and to equivalent plastic strain. The result is that beta is not a constant but a derived function. Representative results for beta and temperature as functions of effective plastic strain are provided for both an uncoupled and a coupled thermoplastic theory. In addition to providing features that are believed to be representative of many metals, the formulation can be used as a basis for more advanced theories such as those needed for large deformations and general forms of internal energy.

[Pelvic artery embolization in gynecological bleeding]. / Beckenarterienembolisationen bei gynäkologischen Blutungen.

The most common reasons for gynecological bleeding are pregnancy-related disorders, fibroids of the uterus, and gynecological malignancies. Transarterial embolization is an effective treatment modality for gynecological bleeding regardless of its etiology. Depending on the underlying disease, a different technique of embolization is applied. In postpartal bleeding a temporary effect of embolization is desired, therefore gelatin sponge is used as embolizing agent. In fibroids and malignant tumors the effect should permanent, therefore PVA particles are used. Regardless the etiology, the technical and clinical success of transarterial embolization is at least 90 %. In nearly every patient a post-embolization syndrome can be observed, represented by local pain and fever. This post-embolization syndrome usually does not last longer than 3 days. If embolization is performed with meticulous attention to angiographic technique and handling of embolic material, ischemic damage of adjacent organs is rarely observed. Transarterial embolization should be an integrative modality in the treatment of gynecological bleeding.

Helical CT of the urinary organs.

Despite of the diagnostic potential of conventional CT (CCT), limitations being inherent in this technology reduce its diagnostic confidence and limit clinical CT applications as 3D imaging. Helical CT (HCT) has far overcome the limitations of CCT and has become the standard CT technology. After a short overview on the technique of HCT and its advantages over CCT, the impact of HCT on the detection of disorders of the urinary organs is discussed. Due to the high quality of 3D reconstructions, vessels are visualized free of artefacts resulting in a dramatic improvement and acceptance of CT angiography, which has become a clinically important examination in the evaluation of obstructive renal artery disease. Fast HCT provides a precise assessment of the three phases of the nephrogram and it is a prerequisite for an improved depiction of abnormal vascular perfusion and impaired tubule transit of contrast material. Helical CT enables an improved characterization of cystic mass lesions reducing the diagnosis of indeterminate masses and thus facilitating a better therapeutic management. The diagnosis of renal cell carcinomas (RCC) has improved due to an increased sensitivity in detecting small RCCs, and an increased specificity in the diagnosis of neoplastic lesions. Improved staging of RCCs is the result of accurate assessment of venous tumour extension. When planning nephron-sparing surgery 3D display of the renal tumour helps to determine the resectability of the mass depicting its relation to major renal vessels and the renal collecting system. In the evaluation of renal trauma HCT provides shorter scanning time and thus fewer artefacts in the examination of traumatized patients who cannot cooperate adequately. Three-dimensional postprocessing modalities allow the assessment of the renal vascular pedicel by CT angiography and improve the demonstration of complex lacerations of the renal parenchyma. In the evaluation of the upper urinary tract unenhanced HCT has become the imaging method of choice in the diagnosis and differential diagnosis of acute flank pain since it is highly sensitive and specific in detecting calculus disease. Unenhanced HCT may furthermore demonstrate causes of flank pain unrelated to urolithiasis. Gapless volume scanning and improved resolution in the z-axis during the excretory phase enables improved visualization of the renal collecting systems and ureters, resulting in a better demonstration of intraluminal and extraluminal pathology.

[Current status of diagnostic imaging of focal nodular hyperplasia of the liver]. / Aktueller Stand der bildgebenden Diagnostik der fokalen nodulären Hyperplasie der Leber.

Ranging behind hemangiomas, focal nodular hyperplasias (FNH) are the second most common benign solid liver lesions. Women between the age of 20 and 50 years are predominantly affected. In rare cases FNH may occur in children. Etiologically, an arteriovenous vascular malformation of the liver is discussed, which causes pseudotumorous growth of the surrounding liver parenchyma. Morphological features such as the presence of a radial vascular architecture and feeding arteries within a central scar are characteristic for the presence of FNH. Imaging techniques which enable the depiction of the arterial blood supply with a characteristic centrifugal filling pattern, the contrast enhancement in the early arterial phase, the absence of calcifications and of a tumour capsule and the typical enhancement of the central scar, are of particular importance. Knowledge of these features is important in order to differentiate FNH from other hypervascular focal liver lesions with tendency of scar formation, such as hepatic adenomas, giant hemangiomas, hepatocellular and fibrolamellar carcinomas, and metastases. Diagnosis and differential diagnosis of FNH will be enabled by a combined modality approach consisting of (Doppler) sonography and triphasic CT. To confirm the diagnosis of FNH, dynamic MRI is advisable. Because of the invasiveness of angiography as well as the limited sensitivity and spatial resolution of the various scintigraphic methods, these modalities no longer play a role in the diagnostic work-up of FNH. Lesions lacking typical features diagnostic for FNH remain subjects for biopsy and histological examination.

Electrical activation of artificial muscles containing polyacrylonitrile gel fibers.

Gel fibers made from polyacrylonitrile (PAN) are known to elongate and contract when immersed in caustic and acidic solutions, respectively. The amount of contraction for these pH-activated fibers is 50% or greater, and the strength of these fibers is shown to be comparable to that of human muscle. Despite these attributes, the need of strong acids and bases for actuation has limited the use of PAN gel fibers as linear actuators or artificial muscles. Increasing the conductivity by depositing platinum on the fibers or combining the fibers with graphite fibers has allowed for electrical activation of artificial muscles containing gel fibers when placed in an electrochemical cell. The electrolysis of water in such a cell produces hydrogen ions at an artificial muscle anode, thus locally decreasing the pH and causing the muscle to contract. Reversing the electric field allows the PAN muscle to elongate. A greater than 40% contraction in artificial muscle length in less than 10 min is observed when it is placed as an electrode in a 10 mM NaCl electrolyte solution and connected to a 10 V power supply. These results indicate potential in developing electrically activated PAN muscles and linear actuators, which would be much more applicable than chemically activated muscles.

Renal masses--evaluation by amplitude coded colour Doppler sonography and multiphasic contrast-enhanced CT.

OBJECTIVE: To assess the efficacy of amplitude coded colour Doppler US (aCDS) in the evaluation of renal masses as shown by multiphasic contrast-enhanced CT. MATERIAL AND METHODS: Eighty patients (155 kidneys) with suspicion of renal masses underwent aCDS and spiral CT. The findings were classified into normal kidneys, kidneys with tumours, kidneys with cysts, and those with "other findings" (i.e. bleeding, calcifications, inflammation, parenchymal hypertrophy). The aCDS findings were compared to CT results and to histological findings or clinical, laboratory and follow-up data. RESULTS: Eighteen renal cell carcinomas and 8 other tumours were found; 78 kidneys had cysts, 12 polycystic kidneys and 10 fibrotic kidneys were detected, 20 kidneys showed other findings. Diagnostic aCDS data were obtained in 129 kidneys (83.2%) showing pathology with an accuracy of 94%. CT adequately showed pathology in all patients with some diagnostic uncertainty in the evaluation of complicated cysts. CONCLUSION: Though contrast-enhanced multiphasic spiral CT is the method of choice for evaluating renal masses, US including aCDS can provide valuable information, particularly in differentiating vascularized from non-vascularized lesions and in the evaluation of complicated renal cysts.

Value of echo-enhanced Doppler sonography in evaluation of transjugular intrahepatic portosystemic shunts.

OBJECTIVE: The value of echo-enhanced color and power Doppler sonography in the evaluation of transjugular intrahepatic portosystemic shunts (TIPS) was assessed and compared with that of unenhanced Doppler sonography and portal angiography. SUBJECTS AND METHODS: In a prospective randomized trial, 31 shunts in 30 patients underwent unenhanced conventional color and power Doppler sonography and portal venography including pressure measurements. The patients were allocated to either echo-enhanced conventional color Doppler sonography or echo-enhanced power Doppler sonography. For echo enhancement, a galactose-based suspension was administered IV. Shunt stenoses, if present, were quantified by percentage of stenosis and correlated with angiography, which was the gold standard. The diagnostic confidence of unenhanced and echo-enhanced Doppler sonography was assessed using a visual analog scale. RESULTS: In the diagnosis of shunt occlusion, echo-enhanced Doppler sonography yielded a sensitivity and a specificity of 100% and 100%, respectively, compared with 100% and 89%, respectively, for unenhanced Doppler sonography. Our evaluation of hemodynamically significant stenoses (portosystemic gradient > or = 15 mm Hg) found echo-enhanced Doppler sonography to be superior to unenhanced Doppler sonography (sensitivity and specificity of 82% and 83%, respectively, compared with 64% and 80%, respectively). In the detection of a shunt stenosis based on morphologic criteria only, echo-enhanced Doppler sonography yielded a sensitivity and a specificity of 78% and 100%, respectively, compared with 47% and 50%, respectively, for unenhanced Doppler sonography. Power Doppler imaging did not improve diagnostic accuracy but did increase diagnostic confidence for unenhanced Doppler sonography compared with conventional color Doppler sonography. The diagnostic confidence for sonographic evaluation of TIPS was significantly (p < .001) increased and the variability of hemodynamic measurements was markedly decreased with echo-enhanced sonography. CONCLUSION: Echo-enhanced Doppler sonography provides images of TIPS like those of angiography and allows morphologic assessment of the shunts, complementary to the essential pulsed Doppler waveform analysis that would be performed in a more guided manner. Also, echo-enhanced Doppler sonography significantly increases the sensitivity and specificity in the diagnosis of shunt dysfunction. The high diagnostic confidence and the diminished variability of spectral Doppler measurements may improve acceptance of sonographic evaluation of TIPS. Echo-enhanced Doppler sonography is safe and effective and may reduce the instances in which TIPS sonographic surveillance is nondiagnostic, in which case angiographic assessment is required.

[Benign non-organ-related diseases of the retroperitoneal space]. / Benigne, nicht organgebundene Erkrankungen des Retroperitonealraumes.

Because of the anatomic localisation of the retroperitoneal space, the detection and elucidation of pathology in the retroperitoneum calls for clinical acumen and the utilisation of imaging techniques. During the past two decades, efforts spearheaded by the work of M. A. Meyers led to an enhanced understanding of retroperitoneal anatomy and pathology. Conventional radiographic techniques are often incapable of detecting and/or characterising retroperitoneal abnormalities. Sonography may be limited by patient-dependent-factors. CT is unaffected by bowel gas and provides discrete cross-sectional images of the organs, fascial planes and retroperitoneal compartments, making it an ideal tool for assessment of retroperitoneal disease. In clinically stable patients MRT may be a useful modality for providing helpful and additional information in characterising retroperitoneal abnormalities. In this review article the diagnostic possibilities of benign not organ-related diseases of the retroperitoneum are described. This is intended to give the reader an insight into the etiology and distribution patterns of retroperitoneal fluid and gas collections as well as into diagnosis and differential diagnosis of benign retroperitoneal diseases. The diagnostic impact of the different imaging modalities is discussed.

Endovascular treatment of renal artery aneurysms with conventional non-detachable microcoils and Guglielmi detachable coils.

OBJECTIVE: To evaluate the efficacy and safety of endovascular occlusion of true renal artery aneurysms (RAAs) with conventional non-detachable microcoils (NDCs) and Guglielmi detachable coils (GDCs). PATIENTS AND METHODS: Over a 5-year period, 12 RAAs were treated by endovascular selective embolization. Four RAAs were occluded using NDCs and eight were treated with GDCs. All coils were delivered through a microcatheter. Eight RAAs were located in the bifurcation of the main renal artery, two in the main renal artery and two were intrarenal. Before treatment, four patients presented with hypertension, one associated with renal infarction and a second had flank pain due to microembolization. Two other patients had renal infarction, associated with haematuria in one; one other patient also had haematuria and five patients were asymptomatic. All patients were followed using clinical and angiographic examinations after 6 months, 1 and 2 years. RESULTS: All RAAs were occluded successfully. In two patients treated with NDCs there were minor complications, i.e. one subsegmental peripheral infarction and one misembolization, both without clinical symptoms. In the group treated with GDCs there were no complications. Five of seven patients were clinically improved, while two patients remained clinically unchanged. CONCLUSION: Superselective endovascular treatment of RAAs with microcoils is a safe, efficient, and less invasive alternative to surgical treatment. The high flexibility and softness of the GDC and the controlled detachment enables a safer and more complete occlusion of RAA than current alternatives.

[Endovascular embolization treatment for intractable epistaxis]. / Endovaskuläre Embolisationsbehandlung bei unstillbarer Epistaxis.

BACKGROUND: Intractable epistaxis has been treated with surgical intervention for many years, including ligation of the internal maxillary artery. As an alternative approach, endovascular therapy has gained increased acceptance. The purpose of our study was to evaluate the efficacy and safety of endovascular treatment of untractable epistaxis. METHODS: Embolotherapy was performed in 26 patients. The indication for embolization was persistent epistaxis even after anterior and posterior nasal packing. In all but two patients, who required general anesthesia, the procedure was performed in local anesthesia. Endovascular embolization of the internal maxillary artery was performed by using microcatheters, which were introduced intraarterially. Particulate embolic agents were used in all but one patient, who was treated by means of minicoils. RESULTS: The embolization of the territory of the internal maxillary artery was possible in all cases, the technical success rate was 96%, the clinical success rate was 100%. No complications were encountered. Because of an acute recurrent bleeding in one case, a second embolization was performed. No delayed hemorrhages were noted. CONCLUSIONS: Endovascular embolotherapy seems to be an excellent, safe, and less invasive alternative to surgery in patients with intractable epistaxis.

Multiphasic helical CT of the kidney: increased conspicuity for detection and characterization of small (< 3-cm) renal masses.

PURPOSE: To evaluate the potential of thin-section multiphasic helical computed tomography (CT) in the detection and characterization of small (< 3.0-cm) renal masses. MATERIALS AND METHODS: Identically collimated helical CT of the kidney was performed before and after administration of contrast material in 93 patients with small renal masses. Helical CT scans were obtained during the corticomedullary and nephrographic phases. Differences between attenuation of the lesion and that of the kidney were measured quantitatively. The presence of a mass or absence of disease was confirmed with clinical, imaging, and histologic findings. RESULTS: The number of masses smaller than 3.0 cm detected on corticomedullary-phase scans (n = 211) was statistically significantly fewer than those on nephrographic-phase scans (n = 295) (P < .01). Mean differences in enhancement between the renal cortex and masses were 148 HU +/- 54 and 137 HU +/- 44 during the corticomedullary and nephrographic phases, respectively, and the difference in attenuation of the renal medulla and that of the masses was statistically significantly greater during the nephrographic phase (P < .01). False-positive results (n = 9) occurred only on corticomedullary-phase scans because of lack of enhancement of the renal medulla. CONCLUSION: Nephrographic-phase scans enabled greater lesion detection and better characterization of small renal masses than corticomedullary-phase scans. Nephrographic-phase scans should be obtained when only monophasic scanning is used to detect small renal masses.

Extracranial aneurysm and arteriovenous fistula: embolization with the Guglielmi detachable coil.

PURPOSE: To evaluate the feasibility and safety of Guglielmi detachable coils for endovascular treatment of extracranial aneurysm and arteriovenous fistula. MATERIALS AND METHODS: Embolization with Guglielmi detachable coils delivered through Tracker-18 microcatheters was performed in 16 patients. This patient group had eight renal artery aneurysms and 11 arteriovenous fistulas (three cases of patent ductus arteriosus, one associated with aneurysm; one fistula between the maxillary artery and jugular vein; two fistulas between the subclavian and pulmonary arteries; four fistulas between the pulmonary artery and vein; and one fistula between the anterior tibial artery and vein). Efficacy of the procedure was assessed by means of short-term follow-up (clinical examination, angiography, and/or Doppler sonography) 3 and 6 months later. RESULTS: No complications were encountered. Embolization was technically and clinically successfully in all eight aneurysms (100%) and in nine arteriovenous fistulas (82%). In two cases (fistula between the subclavian and pulmonary arteries and fistula between the anterior tibial artery and vein) endovascular placement of Guglielmi detachable coils failed to occlude the vessel. Results of short-term follow-up examinations confirmed the initial results in all cases. CONCLUSION: Guglielmi detachable coils are feasible, safe, and effective for endovascular treatment of extracranial aneurysm and arteriovenous fistula.

Differentiation of delayed kidney graft function with gadolinium-DTPA-enhanced magnetic resonance imaging and Doppler ultrasound.

RATIONALE AND OBJECTIVES: The authors differentiate acute tubular necrosis from transplant rejection in patients with delayed kidney graft function using gadolinium (Gd)-DTPA enhanced magnetic resonance (MR) imaging. METHODS: Twenty-four patients after renal transplantation (10 with normal graft function, 14 with delayed graft function) underwent conventional and Doppler sonography and MR imaging examination after bolus application of Gd-DTPA. Within a time period of 512 seconds, 39 single-slice MR images were obtained. Measurements of signal intensity in three regions of interests (cortex, medulla, renal pelvis) resulted in a graphic description of the dynamics of the contrast enhancement. The time between the start of the scan and the peaks of the curves was measured. RESULTS: In patients with normal graft function the curves reached the peaks between 39 and 55 seconds (cortex), 44 and 61 seconds (medulla), and between 161 and 318 seconds (renal pelvis). Six patients with acute tubular necrosis showed normal values for the curves 1 and 2 but markedly prolonged time for curve 3 (between 420 and 512 seconds). In all patients with histologically proven transplant rejection, the peaks of all curves were not reached before the ends of the scans. CONCLUSION: The authors' preliminary results suggest that MR imaging seems to be a sensitive, noninvasive diagnostic tool to differentiate acute tubular necrosis from transplant rejection in the critical early postoperative period.

Distribution pattern of computed tomography findings in patients with bronchiolitis obliterans organizing pneumonia.

RATIONALE AND OBJECTIVES: The authors evaluated high-resolution computed tomography (HRCT) findings in 15 patients with biopsy-proven bronchiolitis obliterans organizing pneumonia (BOOP). Special attention was paid to lobar distribution to establish a predominant distribution pattern for this disease. SUBJECTS AND METHODS: Fifteen patients (average age, 61.8 years) with BOOP underwent computed tomography examinations. The examination technique included a slice thickness of 4 mm with a 4-mm interval; matrix size was 256 x 256 pixels. In all patients, additional HRCT images with a 2-mm slice thickness and a 10-mm interval (matrix, 512 x 512 pixels) were obtained. Interpretation included assessment of pulmonary, pleural, and mediastinal involvement. Special attention was paid to the distribution pattern of pulmonary abnormalities. RESULTS: High-resolution computed tomography in all patients demonstrated areas of air space consolidation in a multifocal but peripheral distribution. The right lower lobe was involved in 60% of the patients, the left lower lobe in 53%, the middle and right upper lobes in 20%, and left upper lobe in 23%. Five patients had ground-glass opacities in addition to the areas of air space consolidation, with the incidence in these patients being 100% in the right lower lobe. 80% in the left lower and middle lobes, 60% in the right upper lobe, and 20% in the left upper lobe. Nodules were found in two patients, and the left lower and middle lobes were affected in both. In one patient, the right lower lobe was affected. The interstitium was thickened in 66%, with axial involvement in 20%, septal thickening in 30%, and peripheral regions affected in 50%. Bronchiectasis was present in 60% of all patients studied, predominantly located in the lower lobes. CONCLUSION: Bronchiolitis obliterans organizing pneumonia presents a predominant peripheral, bilateral, and nonsegmental distribution, with the lower and middle lobes affected more than the upper lobes.

Extended infusion of rtPA lysis of pulmonary emboli: influence of time after onset of symptoms on outcome.

PURPOSE: Evaluate efficacy and safety of short-term thrombolysis with recombinant human-tissue plasminogen activator (rtPA). METHODS: Thrombolysis with rtPA was performed in 29 patients with angiographically documented severe acute pulmonary embolism (Miller score of 20/34 or more). All patients received 100 mg rtPA through peripheral veins within the first 2 hr, followed by a continuous infusion of rtPA (0.05 mg/kg/hr) over a 4-hr period. Concomitant intravenous heparin 1000 U/hr infusion was applicated for the first 6 hr. RESULTS: Using this treatment, 83% of our patients showed clinical improvement objectified by the Miller score, by the clinical stage (Grosser), and by the pulmonary artery mean pressure (PAPm). The treatment regimen was unsuccessful if the clinical history lasted more than 3 days. Complications occurred in 10 patients (34%), and 3 patients (10%) died of acute right heart failure. CONCLUSION: The success of rtPA treatment appears to depend on the interval between onset of symptoms and start of thrombolytic therapy. Otherwise the technique leads to objectifiable improvement within 6 hr with an acceptable bleeding risk.

[Fluoroscopically guided percutaneous fine-needle biopsy of the lung using the ROTEX needle: results in 890 patients with focal lung lesions]. / Durchleuchtungsgezielte perkutane Feinnadelbiopsie der Lunge mit der ROTEX-Nadel. Ergebnisse bei 890 Patienten mit fokalen Lungenläsionen.

Fluoroscopically guided transthoracic fine needle biopsies were performed in 890 patients (380 female, 582 male, mean age: 56 years). In 795 patients (89.4%) the first biopsy was successful. The success rate of biopsy correlated closely with the size of the lesion and increased with larger size. Sensitivity in the diagnosis of malignant lesions was 94.6%, specificity 99.5%. Due to cytological, histological, and clinical confirmation of benign lung lesions in 300 patients (33.7% of all patients), the number of unnecessary diagnostic thoracotomies for benign disease could be reduced significantly. In 9 of 113 cases (8%) histological reclassification of the cytologic results was necessary. Reclassification was not necessary in the differentiation between benign and malignant lesions and between small cell and non-small cell carcinomas. The overall complication rate was 24.7% (220 patients). Only 36 patients (4% of all patients) required chest-tube insertion. There were no fatal complications. Percutaneous fluoroscopically guided transthoracic fine needle biopsy of the lung, performed with the Rotex needle, is a time-effective, safe, and efficient method for diagnosing focal pulmonary lesions.