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J Froelich

Publications and source records attributed to J Froelich.

16 recordsLinked to original sources

Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.

BACKGROUND: The goal for tissue engineering of vascular grafts is the replacement of a diseased vessel with a functional and stable graft. We now introduce a new concept for the tissue engineering of vessels. The idea was to humanize a previously acellularized, but structurally intact, xenogeneic vessel by repopulation with human autologous cells. To this purpose, a gentle nondenaturing and nondeterging acellularization procedure for xenogeneic aortas was developed. This structure was reseeded with pre-expanded peripheral vascular endothelial cells (EC) and myofibroblasts using specifically designed bioreactors. METHODS: Aortas from 15-30 kg female landrace pigs were acelullarized with a 0.1% trypsin solution for between 24 and 96 hr. Human vascular cells were harvested from saphenous vein biopsy specimens. Acellularized vessels were reseeded with EC and myofibroblasts. Cell viability after reseeding was assayed by fluorescence staining. Morphologic features of the acellularized matrix and tissue engineered vessel was assayed by transmission and scanning electron microscopy and histologic analysis. Nitric oxide-synthetase activity was investigated by mass spectrometric analysis of bioreactor supernatants. The in vivo immune response was tested by subcutaneous implantation of acellularized porcine aortic tissue in a rat model. RESULTS: The acellularization procedure resulted in an almost complete removal of the original resident cells, and the 3-D matrix was loosened at interfibrillar zones. However, the 3-D arrangement of the matrix fibers was grossly maintained. The 3-D matrix was covered with a fully confluent human endothelial cell layer obtained by continuous stress challenge in the bioreactor. Myofibroblasts migrated into positions formerly occupied by the xenogeneic cells. Nitric oxide synthetase activity was maintained in the bioartificial graft. T-lymphocyte and CD18 positive leukocyte infiltrate were greatly reduced after acellularization of porcine aortic specimens after implantation in the rat. CONCLUSIONS: Porcine vessels were acellularized and consecutively fully repopulated with human EC and myofibroblasts. This approach may eventually lead to the engineering of vessels immunologically acceptable to the host using a relatively short preparation period of 2-3 weeks. We expect matrix turnover in vivo leading to a gradual assimilation of the matrix structure by the host mediated by the hosts autologous cells.

Animals↗

Paired comparison of vascular wall reactions to Palmaz stents, Strecker tantalum stents, and Wallstents in canine iliac and femoral arteries.

BACKGROUND: Palmaz stents, Strecker stents, and Wallstents, all used clinically, differ substantially in their physical characteristics, yet how differently the vascular wall reacts to them has not been demonstrated conclusively. We therefore undertook a side-by-side comparison. METHODS AND RESULTS: One stent was implanted into each canine external iliac and/or the flexing portion of the proximal femoral artery. In 9 dogs, Palmaz stents were placed vis-à-vis Strecker stents, with follow-up of 2 and 4 months. In 7 dogs, Palmaz stents were placed vis-à-vis Wallstents, with 4 months of follow-up. Angiographic midstent luminal diameters immediately after placement and at follow-up as well as midstent cross-sectional areas of neointima were compared for significant differences. In addition, neointimal maturation, medial atrophy, and stent-related trauma were assessed. Angiographically, all arteries remained open. The degree of luminal narrowing by recoil and neointima never reached 50% and was modest for Palmaz stents and Wallstents (P = .33) but significantly higher for Strecker stents (P < .0001 compared with Palmaz stents). This corresponded histologically to a significantly thicker neointima (P = .003) over Strecker than over Palmaz stents but not between Palmaz stents and Wallstents (P = .18). Neointimal buildup was generally more pronounced in the femoral artery segments than in the iliac segments. Maturation of the neointima over Palmaz stents was much further advanced than over Strecker stents and slightly more advanced than over Wallstents. Pressure-related atrophy of the tunica media was least for Strecker stents and more pronounced but similar for Wallstents and Palmaz stents. Wallstent wire ends caused some wall trauma; several femoral Palmaz stent struts protruded through the media. CONCLUSIONS: The lower-hoop-strength, higher-profile tantalum Strecker stent is affected by vascular wall recoil and evokes a greater degree of neointima formation than the lower-profile, higher-hoop-strength Palmaz stent and Wallstent. Medial atrophy is pronounced outside the latter two stents. The rigid Palmaz stent can penetrate through the vascular wall in flexing arteries.

Animals↗

Successful and unsuccessful approaches to imaging carcinoids: comparison of a radiolabelled tryptophan hydroxylase inhibitor with a tracer of biogenic amine uptake and storage, and a somatostatin analogue.

A mouse mastocytoma model was used to determine the biodistribution and tumour uptake of four radiopharmaceuticals developed to target the serotonin synthetic pathway in carcinoid tumours. Three of the compounds were competitive inhibitors of the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. Radiolabelled iodo-dL-phenylalanine (iodine-131 PIPA) was found to have the highest uptake and tumour-to-liver ratio. Four patients with known carcinoid tumours were then injected with 0.5 mCi 131I-PIPA and imaged at 1, 4, 24 and 48 h post-injection. The radiopharmaceutical, however, failed to localize in the known tumour sites. This result was in contrast to the authors experience of 131I- and 123I-MIBG imaging of carcinoid tumours. Seven patients with known metastatic carcinoid tumours, two patients with symptoms of recurrence following tumour resection, one patient with completely resected disease, and two patients with a flushing syndrome of uncertain aetiology were studied with 131I-MIBG. Three of the seven patients with known metastatic disease had positive 131I-MIBG scans. Both patients with clinical evidence of recurrent disease had negative scans, as did the patient who was considered to have had complete resection of her primary tumour. The two patients with idiopathic flushing syndrome also had negative scans. Among seven patients imaged with 123I-MIBG there were four true-negative scans and one false-negative, the latter in a patient with biochemical and CT evidence of recurrence. In a seventh patient with distant metastases there was variable uptake in some of the lesions. Four patients were studied with indium-111 pentetreotide . Two patients with metastatic carcinoid disease had positive scans, although hepatic metastases were not seen in one. Another two with idiopathic flushing syndrome had normal studies. The literature suggests that up 50% of carcinoid tumour cases are detected with 131I-MIBG, compared to a sensitivity of 87% reported with somatostatin receptor imaging using 111In-pentetreotide. The experience with 123I-MIBG is much less extensive. The mechanisms of carcinoid tumour localization for each of the three classes of radiotracers are discussed and contrasted to their varying sensitivities. The relative success of 131I-MIBG and 111In-pentetreotide relative to 131I-PIPA may be related to the fact that 131I-MIBG is actively taken up and stored by the enterochromaffin cells of the tumours and 111In-pentetreotide binds to cell surface receptors, whereas 131I-PIPA binds to tryptophan hydroxylase, which may be present in quantities too small to permit tumours to be imaged.

3-Iodobenzylguanidine↗

Anaesthetic management of a patient with myasthenia gravis and tracheal stenosis.

PURPOSE: The combination of myasthenia gravis and tracheal obstruction presents a number of difficulties for anaesthetic management. This case illustrates the advantages of careful planning. CLINICAL FEATURES: A 66-yr-old man with myasthenia gravis required resection of a stenosis at the site of an old tracheostomy. The primary goal was to accomplish safe management of the airway, a task made more difficult because the airway was shared with the surgeon. Awake fibreoptic examination of the tracheal stenosis performed in the operating room provided useful information in planning the subsequent anaesthetic. From this examination, it was found that the trachea could be intubated by a normal endotracheal tube passed through the stenosis over the fibreoptic bronchoscope. Intraoperatively, the orotracheal tube was withdrawn temporarily and replaced with an endotracheal tube placed by the surgeon into the distal trachea. Extubation was carried out judiciously and a plan for reintubation prepared in advance. The anaesthetic plan was modified because of the myasthenia gravis. Following careful investigation of the extent of the patient's disease and its treatment, an assessment was made of the patient's need for postoperative ventilation. The anaesthetic plan included maintenance of anticholinergic medications until the time of surgery and their early resumption postoperatively, avoidance of neuromuscular blocking agents, and careful monitoring of neuromuscular function during the anaesthetic. CONCLUSION: Careful examination of the area of tracheal stenosis and a carefully considered plan for reintubation are prerequisites for this type of surgery. Clinically well controlled myasthenia gravis was managed successfully using familiar principles.

Aged↗

Thiopentone induced enhancement of somatic motor responses to noxious stimulation: influence of GABAA receptor modulation.

PURPOSE: This study was conducted to determine whether hyperalgesic effects of subanaesthetic concentrations of thiopentone could be attributed to GABAA receptor effects. METHODS: All studies were performed on 50 rats in a prospective, randomized, blinded fashion using saline-injected animals as controls. Using a modified Randall-Selitto technique, the motor behavior stimulated by noxious stimulation was quantified by determining the lowest tail pressure required to provoke a withdrawal response (somatic motor response threshold, SMRT). In the first protocol (21 rats), we studied the effects of 0.5, 1.5 and 5 mg.kg-1 i.v. of the GABAA agonist, muscimol, on SMRT. In the second protocol (20 rats), the effects of administration of saline, muscimol 0.5 mg.kg-1, or the competitive GABAA antagonist, bicuculline 0.25 mg.kg-1, upon the SMRT-reducing effects of a standardized thiopentone infusion were observed. RESULTS: No dose of muscimol produced hyperalgesia. The highest dose of muscimol used (5 mg.kg-1) produced pronounced analgesic effects, raising the SMRT above 750 g. No change in SMRT was detected with the smaller doses of muscimol. Given in combination with muscimol (0.5 mg.kg-1), thiopentone produced analgesia, as shown by an increase in SMRT (P = 0.009). In the bicuculline treated animals, SMRT decreased linearly with increasing plasma thiopentone concentrations (P < 0.001). The slope of the relationship in the bicuculine group was not significantly different from that observed in the saline-treated group, indicating that bicuculline did not block the hyperalgesic effects of thiopentone. CONCLUSION: The results of these studies suggest that hyperalgesia associated with thiopentone is not mediated primarily by GABAA receptors.

Animals↗

An intracerebral sonographic catheter as an adjunct to stereotactic guided endoscopic procedures.

To facilitate stereotactic biopsies of intracerebral tumor lesions, to obtain important additional diagnostic information during the procedure and to precisely guide biopsy instrumentation devices to spots of interest, catheter sonography was combined with intracerebral endoscopy intraoperatively in two patients. All catheter instrumentation was performed through the stereotactic puncture channels. A 30 Megahertz ultrasound transducer mounted on the tip of a flexible 5 French catheter is sufficiently penetrating surrounding brain tissue, resulting in high resolution images at a maximum radial penetration depth of 15 mm. Normal brain tissue could be differed from intracerebral tumor tissue in both patients. Smaller tumor lesions within the close surrounding of a solid intracerebral tumor mass clearly appeared in ultrasound. Since diagnostic endoscopy in stereotactic procedures is limited to the surface of a puncture channel, intracerebral ultrasound adds important information about the underlying type of tissue. We found that the combination of both methods facilitates guiding of biopsy instrumentation devices to the spots of interest in stereotactic procedures. In both examined patients all biopsy samples were histologically identified as intracerebral lymphoma. Since ultrasound clearly identified intracerebral blood vessels as tubular hyporeflective structures, the risk of biopsy related hemorrhage could be diminished.

Aged↗

Local cerebral glucose utilization in stimulated rats sedated with thiopental.

BACKGROUND: Recent studies have suggested that supraspinal structures are involved in barbiturate-induced enhancement of nociceptive processing. The goal of the study was to determine whether cortical and subcortical regions involved in nociception were relatively activated or depressed by noxious stimulation during infusion of small doses of thiopental. METHODS: Local cerebral glucose utilization (LCGU) was measured with the 14C-2-deoxyglucose radioautographic technique in 14 rats. During the LCGU experiment, pressure was applied to the tail every 2 min, and the somatic motor response threshold was recorded. Seven animals received thiopental infusions to produce a steady-state plasma concentration (target concentrations of 10 micrograms/ml), and seven untreated animals served as controls. RESULTS: A steady-state plasma thiopental concentration (11.1 +/- 1.8 to 13.0 +/- 2.1 micrograms/ml) was accompanied by a decrease in the somatic motor response threshold from 277 +/- 32 g (before thiopental) to 215 +/- 41 g (P < 0.001). The somatic motor response threshold remained unchanged in the control group. Average LCGU was 29% less in the thiopental-treated animals than in the untreated controls (P < 0.001). In cortical regions associated with nociception, LCGU was relatively increased (+3% +/- 14%) during the thiopental infusion in comparison to the visual and auditory cortices (-18% +/- 13%; P < 0.001). Individual structures that showed relative changes during thiopental infusion included the nucleus accumbens (+17%, P < 0.05) and the habenula (-17%, P < 0.05). Heterogenous relative changes (P < 0.05) in LCGU were observed in the auditory system: auditory cortex (-22%), medial geniculate (-16%), lateral lemniscus (+26%), superior olive (+38%). CONCLUSIONS: Noxious stimulation during low-dose thiopental infusions relatively increased LCGU in cortical regions postulated to be responsible for processing of noxious stimuli. Nuclei in the descending pain modulating system were not relatively depressed.

Animals↗

Injection characteristics and downstream contrast material distribution of flush aortography catheters: in vitro study.

Performance of 11 commercially available 4- and 5-F aortic flush catheters was evaluated with respect to the extent of upstream injection, catheter motion, and downstream homogeneity of a 10-, 15-, and 20-mL/sec bolus of 76% meglumine sodium diatrizoate at room temperature. Tests were made in a pulsatile aortic flow model containing circulating fluid isoviscous to blood. The injection process was recorded on videotape. Homogeneity of the contrast material bolus was determined spectrophotometrically from samples collected from the center and each of the four quadrants of the vessel lumen. Upstream contrast material injection between 1.5 and 7 cm in length emerged from all catheters; it was lowest with one of the "tennis racket" designs from one and a new spiral end-loop design (Halo) from another manufacturer. All catheters, except the most rigid and largest-caliber catheter (5.8 F) showed considerable shaft motion at the higher injection rates. Downstream contrast material mixing homogeneity was always best at the highest injection rate but altogether was better for the Halo catheter than for any other catheter tested. It is concluded that all tested 4- and 5-F aortic flush catheters show some undesirable features, but certain design modifications improve performance and comparative testing is helpful to distinguish such features.

Aortography↗

Utility of lymphoscintigraphy in directing surgical therapy for melanomas of the head, neck, and upper thorax.

Lymphoscintigraphy with technetium99m antimony sulfur colloid or technetium99m human serum albumin helped direct the surgical management of 24 patients who had melanomas of the head, neck, and upper thorax. Eighteen (75%) patients had documented lymphatic flow to other than a single adjacent predictable lymph nodal group. Nineteen patients underwent lymphadenectomy. Availability of the scan altered surgical management in nine patients (47%) who required resection of nodes in addition to resection of adjacent nodes. The discovery of metastatic disease in one patient was clearly attributable to lymphoscintigraphy. This demonstrates the unpredictable lymphatic anatomy of this region and suggests that preoperative lymphoscintigraphy may be useful in directing the surgical management of cutaneous melanomas in which lymph node dissection is planned.

Adult↗

Optimisation of indices of external pneumatic compression for prophylaxis against deep vein thrombosis: radionuclide gated imaging studies.

The amount and rate of blood expelled with different modes of intermittent external pneumatic compression applied to the lower leg were studied on a regional basis in a series of experiments on healthy human volunteers. Radionuclide imaging of the labelled blood pool, with acquisition of counts synchronised to the pressurisation cycle, provided data on regional blood volumes in the leg in relation to time. To determine the changes in blood volume of the lower leg resulting from external pneumatic compression labelled red blood cell counts were determined during 10 different types of compression cycle. Since venous stasis is considered to be a major cause of venous thrombosis the red blood cell counts were used to calculate regional values of the fraction of blood ejected as well as comparative indices proportional to regional flow rate, regional velocity, and regional wall shear stress. All these indices should be maximised for optimal prophylaxis against deep vein thrombosis. The four compartment cuff in each compression mode applied a mean pressure of 45 mm Hg, but different combinations of values were used for intercompartmental pressure gradation (delta p) and for intercompartmental time sequencing to the onset of compression (delta t). Uniform compression (delta p = 0; delta t = 0) was substantially inferior to cycles with gradation and sequencing. The optimal values of delta p were in the range 5-10 mm Hg and of delta t in the range 0-0.5 seconds.

Adolescent↗

99mTc red blood cells for detection of gastrointestinal bleeding: experience with 80 patients.

Imaging was done in 80 patients with gastrointestinal hemorrhage using red blood cells labeled with 99mTc by a modified in vivo technique. Bleeding was detected in 65% of 40 patients with bright red blood per rectum, 71% of 35 patients with melena, and in none of the five patients with occult bleeding and chronic anemia. No clinical evidence of further gastrointestinal hemorrhage occurred in 26 of the 29 patients who were negative on imaging. The imaging study could be carried out for over 24 hr which increased the sensitivity of the test, since only 16% of the studies were abnormal on the initial images. Neither the need for blood replacement nor the presence of bright red blood per rectum correlated strongly with early image positivity, supporting the contention that patients with gastrointestinal hemorrhage do not necessarily bleed continuously. Labeled red cell imaging was more sensitive in the detection of bleeding than angiography. It corresponded to the overall angiographic findings in 23 of 31 cases and in 17 of the 18 patients who had demonstrable extravasation. 99mTc red blood cells may be used effectively in patients with melena as well as with bright red blood per rectum, and thus would seem to be the preferred radiopharmaceutical for imaging.

Erythrocytes↗

SAR reduced pulse sequences.

Three techniques were considered for reducing the RF (radiofrequency) power deposition in the body while maintaining scan time efficiency: reducing the RF peak amplitude while increasing the pulse width, substituting gradient echoes for spin echoes, and reducing the flip angle of the phase reversal pulse. The use of gradient echoes was found to be the most efficient means to reduce the power delivered to the patient and to obtain rapid data acquisition. The effect upon SAR (specific absorption rate) and SNR (signal-to-noise ratio) was demonstrated on a phantom when the phase reversal pulse was reduced from the standard 180 degrees to 90 degrees. Data in the body indicated a fairly constant SNR down to a refocusing flip angle between 110 degrees and 135 degrees. An initial clinical evaluation was performed at three institutions using the method of reducing the flip angle of the phase reversal pulse. The scan with theta = 120 degrees was rated by readers in a blinded study as having acceptable diagnostic image quality while the 135 degrees scan had comparable image quality to a conventional 90 degrees - 180 degrees pulse sequence. The use of reduced phase reversal pulses was seen as an efficient protocol to obtain T1-weighted images at rapid data rates while reducing the power delivered to the body by about 40%.

Humans↗