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Biomedical subjects

U Althaus

Publications and source records attributed to U Althaus.

At least 55 records · Page 3Linked to original sources
PubMed1997

Lack of antitumour activity of human recombinant tumour necrosis factor-alpha, alone or in combination with melphalan in a nude mouse human melanoma xenograft system.

The most promising developments in the field of isolated limb perfusion have centred around the use of the recombinant cytokine tumour necrosis factor-alpha (rTNF-alpha) in combination with melphalan. While the results of clinical trials are impressive, the exact antitumour mechanisms of rTNF-alpha and its role in combination with melphalan remain unclear. Our aim was to study the antitumour activity of human rTNF-alpha with or without the combination of melphalan in a nude mouse human melanoma xenograft system. In a first attempt to define the maximal tolerated single dose of rTNF-alpha in this setting, 15 animals were exposed to increasing doses of rTNF-alpha (60-2500 microg/kg intraperitoneally). All but one animal survived and tumour growth was not influenced by these single dose applications of rTNF-alpha even at the very high doses. Anti-tumour activity of repeated application of melphalan (three times 9 mg/kg in group 2 and three times 6 mg/kg in group 3), of rTNF-alpha alone (nine doses of 50 microg/kg in group 4), and of rTNF-alpha in combination with melphalan (nine doses of 50 microg/kg rTNF-alpha and three times 6 mg/kg melphalan in group 5) was further compared with non-treated animals (group 1). Tumour growth was significantly inhibited in all animals treated with melphalan (group 2, 3 and 5), but was not decreased in animals treated with rTNF-alpha alone (group 4). Mean final tumour volumes and mean tumour weight were not different in group 2 (789 +/- 836 mm3, 0.38 +/- 0.20 g), group 3 (1173 +/- 591 mm3, 0.55 +/- 0.29 g) and group 5 (230 +/- 632 mm3, 0.37 +/- 0.29 g), but significant lower than group 1 (3156 +/- 1512 mm3, 2.35 +/- 0.90 g) and group 4 (3228 +/- 1990 mm3, 2.00 +/- 1.16 g). There were no significant differences between high and low dose melphalan treatment and between melphalan treatment in combination with rTNF-alpha. Histological examination did not show differences between treated and non-treated animals besides slightly inhibited mitotic activities of tumour cells in melphalan-treated animals. While tumour growth of human xenotransplanted melanoma in nude mice could be inhibited by melphalan, we failed to demonstrate any antitumour effect of rTNF-alpha. The combination of melphalan and rTNF-alpha did not enhance the antiproliferative effect of melphalan alone. Human xenotransplanted tumours on nude mice might not be the ideal experimental setting for studies of potential direct antineoplastic activity of rTNF-alpha, and these results support the concept that TNF-alpha exerts its antitumour activity indirectly, possibly by impairing the tumour vasculature and by activating the immune system.

Animals↗
PubMed1996

[Effect of postoperative retransfusion of autologous blood products on hemostasis in heart surgery].

In cardiac surgery a reduction of homologous blood products is mainly achieved by autologous blood salvage. Unprocessed retransfusion of autologous blood may induce changes in hemostasis. We assessed changes of activated clotting times (ACT) after retransfusion of unprocessed (1) oxygenator blood and (2) shed mediastinal blood. In 41 patients undergoing cardiac surgery (37 revascularization and 4 valve procedures) with a mean cardiopulmonary bypass time of 116.3 min, ACT was measured at the following time points: pre- and postoperatively, and before and after retransfusion of oxygenator blood and shed mediastinal blood. A significant prolongation of ACT values was only seen between pre- to postoperative blood (p < 0.003). Retransfusion of oxygenator blood changed ACT from 120 +/- 25 vs 116 +/- 17 sec and retransfusion of shed mediastinal blood showed a mean ACT of 118 +/- 14 vs 115 +/- 20 sec from before to after transfusion. There was a significant correlation between the ACT value in the unprocessed oxygenator blood and the ACT value measured in the patient after retransfusion (r = 0.41, p < 0.02). 6 patients receiving over 1 litre of unprocessed autologous blood (either from the oxygenator or the mediastinum) in less than 60 minutes showed a significant increase of ACT value after transfusion (p < 0.05). Hence, under normal conditions, retransfusion of unprocessed autologous blood will not significantly alter hemostasis measured by the ACT test in patients undergoing cardiac surgery.

Adult↗
PubMed1996

Intraoperative photodynamic therapy with m-tetrahydroxyphenylchlorin for chest malignancies.

BACKGROUND AND OBJECTIVE: Since there is no satisfactory treatment modality for diffuse malignant mesothelioma of the chest, we assessed surgical tumor resection followed by intraoperative photodynamic therapy with mTHPC in a phase I study. STUDY DESIGN/MATERIALS AND METHODS: Since 1990, eight patients have undergone intraoperative photodynamic therapy with m-tetrahydroxyphenylchlorin (mTHPC-PDT) following thoracotomy and surgical tumor resection. RESULTS: mTHPC-PDT-mediated tumor necrosis was characterized by tumor infarction due to tumor vessel necrosis and thrombosis, and its extent depended on drug-light conditions; 650 nm light delivered at 0.1 W/cm2 for 10 J/cm2 48 h after iv administration of 0.3 mg mTHPC/kg resulted in a 10-mm-deep complete tumor necrosis. Skin photosensitivity was related to the drug dose applied and occurred up to 17 days after iv administration of 0.3 mg mTHPC/kg, mTHPC-PDT of brachial plexus infiltrated by mesothelioma resulted in pain relief without deterioration of nerve function. CONCLUSION: Tumor resection and intraoperative mTHPC-PDT of the chest cavity is feasible under clinical conditions and offers local tumor control of sites involved. However, distant tumor spread was not prevented by this combined treatment modality and optimization of mTHPC-PDT is warranted for further intraoperative application.

Antineoplastic Agents↗
PubMed1996

Video-assisted mediastinal lymph node dissection assessed in an experimental setting.

BACKGROUND: Feasibility, completeness, and morbidity of videoscopic-assisted mediastinal lymph node dissection (VATS MLND) were compared to the standard surgical technique in an experimental study. METHODS: Right upper MLND--together with upper lobectomy in half of the cases--was performed in ten large white pigs. Six animals were operated using VATS (group 1), four using conventional open techniques (group 2). After 1 week, the animals were sacrificed and the mediastinum was assessed for remaining lymph nodes. RESULTS: All animals survived without intra- or post-operative complications. There was no significant difference in the operation time between the two groups (3.2 +/- 0.8 vs 3.2 +/- 0.2 h). The number of mediastinal lymph nodes harvested was 9.5 +/- 2.7 in group 1 and 11.5 +/- 0.5 in group 2 (n.s.). The post-mortem assessment of the mediastinum showed in two animals of group 1 and in two animals of group 2 that one lymph node was left behind. In addition, in one animal of group 1 four small retrotracheal lymph nodes were found. CONCLUSIONS: VATS MLND can be accomplished without morbidity and is as radical as that achieved with conventional surgery in the paratracheal and peribronchial areas in this experimental setting. However, retrotracheal lymph node dissection might not be as complete as achieved by conventional surgery.

Animals↗
PubMed1996

Congenital absence of the left pericardium with extreme intrathoracic displacement of the heart. Case report and review of the literature.

Large pericardial defects are exceptional and difficult to diagnose. A 62-year-old man underwent elective coronary surgery which was seriously complicated by the unexpected intrapleural position of the heart due to the absence of a large amount of pericardium on the left. It appeared retrospectively that the patient had presented typical signs of the malformation and these are described in detail.

Diagnosis, Differential↗
PubMed1996

Intraoperative internal mammary artery transit-time flow measurements: comparative evaluation of two surgical pedicle preparation techniques.

OBJECTS: Myocardial revascularization is performed preferentially with internal mammary artery grafts. Pedicle preparation and pharmacologic vasodilatory treatment vary greatly. Objective measurements are difficult since peripheral and later coronary vascular resistance and possible competitive flow of the native bypassed coronary artery will influence the results significantly. Our objectives were: (1) measurement of internal mammary artery graft flow with the transit-time flow technique; (2) comparison of two surgical take-down techniques (skeletonizing vs standard pedicle preparation); (3) quantitation of transit-time flow compared to the free pedicle flow and (4) the vasodilatory effect of papaverine on internal mammary artery flow. METHOD: Consecutive elective cases of coronary artery bypass grafting, performed by two surgeons using routinely either skeletonizing of the internal mammary artery (group A, n = 10) or classical pedicle preparation technique (group B, n = 10), were studied prospectively. Anesthesia, cardiopulmonary bypass and operative data were otherwise comparable; likewise, hemodynamic parameters showed no statistical differences between the two groups. Transit-time flow (CardioMed, Medi-Stim, Norway) was measured at the following time points: beginning (1) and end of take-down (2); after papaverine soaking: before (3) and on cardiopulmonary bypass (4); free flow into a beaker (5); after anastomosis; on (6) and off cardiopulmonary bypass (7). RESULTS: Measurement of mean flow showed the following results: (1) severe vasoconstruction of the internal mammary artery was detected in both groups regardless of the preparation technique (occurring earlier in group A); (2) papaverine soaking caused a moderate flow increase (up to 40%); (3) with corresponding cardiopulmonary bypass flow (4.4 vs. 4.1 l/min in group B) a higher free flow in group A was evident (67.7 vs. 50.7 ml/min); (4) after coronary grafting, transit-time flow showed no significant differences between the two groups and (5) using a 3 mm probe, a linear correlation was demonstrated between transit-time flow and simultaneously measured free flow (r = 0.89). CONCLUSION: Intraoperative transit-time flow measurement is a reliable method for assessing internal mammary artery and coronary artery bypass flow; considering the simple technical application, the procedure may be regarded as a valuable instrument of quality control.

Blood Flow Velocity↗
PubMed1996

Use of epoetin alfa in autologous blood donation programs for patients scheduled for elective cardiac surgery.

The optimum dosage of subcutaneous (s.c.) epoetin alfa was assessed in a double-blind study in 31 patients scheduled for cardiac surgery. Patients received a total of four doses of either epoetin alfa 150 IU/kg (n = 11), epoetin alfa 300 IU/kg (n = 10), or placebo (n = 10) administered as single s.c. injections at weekly intervals starting 23 days prior to surgery. AB was collected with isovolemic replacement prior to each of the first three doses of medication. During the AB donation period, Hb levels decreased significantly (P < .05) from baseline to surgery in the placebo group (16.5%), compared with no significant decrease in either of the epoetin alfa groups (8.1% and 9.7% in the 150 IU/kg and 300 IU/kg groups, respectively). In addition, the difference between groups with regard to the decrease in Hb level reached statistical significance (P < .05) for the 150 IU/kg group versus placebo. Epoetin alfa treatment was also associated with significantly higher reticulocyte counts and serum erythropoietin levels in the preoperative period compared with placebo.

Blood Transfusion↗
PubMed1995

[PTCA or bypass surgery in multi-vessel coronary disease? Viewpoint of the surgeon].

Recently several randomized studies have been devoted to a comparative analysis of angioplasty (PTCA) versus bypass surgery (CABG) in patients with multivessel coronary disease. Even though only a very limited number of the screened patients could be randomly assigned to undergo PTCA or CABG (less than 10% of the subjects originally evaluated), some valid conclusions may be drawn. With regard to perioperative mortality, no significant difference between the two treatment groups was evident; considering the incidence of peri-interventional myocardial infarction, a trend towards a slightly higher risk could be detected for the surgical patients (EAST and GABI trials). The most striking differences between the two procedures have been completeness of revascularization and incidence of restenosis. Thus, in the EAST and ERACI trials complete revascularization was achieved only in 75% and 51% respectively of the PTCA patients as compared with 99% and 88% respectively for the CABG patients. Beyond all doubt, the greatest drawback of PTCA is the occurrence of restenosis; in multivessel angioplasty several arterial segments are by definition exposed to development of narrowing at the site of PTCA, resulting in a higher risk of restenosis per patient. In a major angiographic study 50% of patients showed significant restenosis in at least one PTCA segment, and in 14% multiple restenosis were found. The occurrence of restenosis is a substantial reason for the high incidence of further interventions following multivessel angioplasty; thus, in the EAST trial only 46% of the PTCA patients did not require a subsequent revascularization procedure (versus 87% in the surgical group). Economic aspects do not counterbalance the limited efficacy of multivessel angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1995

Surgery for acute ascending aortic dissection: closed versus open distal aortic repair.

One hundred twelve consecutive patients with acute ascending aortic dissection and submitted to immediate surgery were retrospectively analyzed with regard to perioperative mortality and morbidity. The patients were divided into two groups according to whether distal aortic repair was carried out by the open procedure (using deep hypothermic circulatory arrest, group A: 68 patients) or by the closed technique (without circulatory arrest, group B: 44 patients). Patients' ages ranged from 24 to 78 years (mean 57.4 years). No significant difference was found between the two groups in terms of age and sex distribution. However, the prevalence in the extent of clinical and anatomical alterations was significantly higher in group A (hemodynamic instability, pericardial tamponade and neurological deficit). The duration of hypothermic circulatory arrest for group A patients averaged 25 min and ranged from 12 to 65 min. The overall perioperative mortality was 17% (19/112 patients); it was 20.6% (14/68) in group A and 11.4% (5/44) in group B; the difference was not statistically significant but consistent with a clear trend. The trend towards a higher mortality in group A mainly reflected the more severe and complex anatomical characteristics and could not be attributed to the circulatory arrest per se. The period of deep hypothermic circulatory arrest in the survivors (25 min) was similar to that of the group with lethal outcome (32 min). Among the non-lethal complications, however, group A patients more frequently showed clinical signs consistent with cerebral injury: apart from the transient symptoms suggestive in reversible diffuse cerebral damage, five patients in group A had a permanent focal neurological deficit (versus one patient in group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Assessment of hypothermia with a new "tympanic" thermometer.

OBJECTIVE: Rapid and accurate core temperature measurement is vitally important in trauma patients, especially in those with accidental hypothermia. We tested a new aural thermometer to measure "tympanic" temperatures and assessed its accuracy during normothermic and hypothermic cardiopulmonary bypass. METHODS: Tympanic, esophageal, and blood temperatures were compared in 10 patients undergoing open-heart surgery. In addition, the stability and reaction time of the tympanic thermometer was evaluated in 5 volunteers in a cold room, with and without facial fanning. RESULTS: We observed a good linear correlation between tympanic and esophageal (r = 0.96) and blood (r = 0.81) temperature measurements during normothermia and hypothermia. There was no evidence of iatrogenic ear lesions in any of the patients. In the cold-room tests, stability was excellent and the time for adjustment of tympanic temperature measurement was about 2 min (with and without facial fanning). CONCLUSION: The new tympanic thermoprobe is a simple, fast, and reliable device for measuring core temperature. The device was designed particularly for, and may be useful for, patients suffering from accidental hypothermia.

Adult↗
PubMed1994

Video-assisted thoracoscopic treatment of pleural empyema. A new therapeutic approach.

Pleural empyema is a disease which is not always recognized. Despite consecutive treatment and antibiotics its mortality rate is still high, especially in older patients with concomitant disease or in the case of delayed treatment. We report our experience with early video-assisted thoracoscopic surgery of pleural empyema in 13 patients, where chest tube drainage had failed. The clinical symptoms of empyema did not exceed 14 days, bacteriologic cultures were positive in 62%. In all patients the fever disappeared within 1 to 5 days (mean 3.5) post-operatively and they remained in hospital for an average of 11.5 days after video-assisted thoracoscopic surgery. Pulmonary function tests 6 months later revealed normal values without a substantial loss of lung volumes. No relapse of empyema occurred.

Adult↗
PubMed1994

Acute traumatic rupture of the thoracic aorta: immediate or delayed surgical repair?

The appropriate management of traumatic aortic rupture is often difficult to determine, particularly if the rupture is associated with severe additional lesions. Between 1986 and 1991, ten consecutive patients with acute traumatic rupture of the thoracic aorta (ATRTA) and concomitant injuries were initially treated medically and submitted to delayed aortic repair. Within the same period no other patient had emergency reconstruction of the thoracic aorta. Diagnosis of ATRTA was established immediately after admission in eight patients. Five patients underwent emergency surgery for severe concomitant injuries. With regard to the aortic lesion, all patients were managed medically and submitted to pharmacological treatment in an attempt to reduce cardiac shear forces. None of the patients developed clinical signs of imminent free rupture while waiting for aortic surgery. In the absence of a significant hemothorax and when no coarctation syndrome is evident, the risk of free aortic rupture is considered to be rather low if the patient reaches the hospital in a stable circulatory condition. Postponement of aortic reconstruction is particularly indicated when severe concomitant lesions preclude safe immediate repair of the aortic tear. Following the patient's recovery from associated major injury, aortic surgery can be performed as a low risk procedure using cardiopulmonary bypass which is recognised as the most effective technique to prevent spinal cord ischemia and to reduce the risk of paraplegia.

Acute Disease↗
PubMed1994

Hemofiltration during cardiopulmonary bypass: quality assessment of hemoconcentrated blood.

UNLABELLED: Hemofiltration is often used during cardiopulmonary bypass (CPB) for water removal. In a prospective random study 11 patients undergoing elective coronary artery surgery with hemofiltration during CPB were observed and compared to 11 patients without filtration. The quantitative and qualitative aspects of blood before and after filtration while still on CPB and until the first postoperative day were assessed. Intra- and postoperative volume requirements, standard hematology and chemistry, as well as hemolysis, complement activation, and coagulation factors were analysed at nine sequential points in time. RESULTS: There were no significant differences in pre- and postoperative patient data between the two groups except that the majority of patients in the study group (55%) were anticoagulated and required a significantly longer CPB time with higher doses of protamine and had higher postoperative drainage (2.9 vs. 1.4 L). Intra- and postoperative hemoglobin concentrations, transfusion and volume requirements were similar in both groups. 927 ml of plasma water were filtered during CPB within 4 min 20 s without hemodynamic changes or electrolyte imbalance. Hemoglobin and protein concentrations increased significantly during hemofiltration (Hb increases 3.6 g/dl). Hemolysis and activated complement fractions were elevated during CPB but showed no further increase during filtration; in contrast C4a, C5a, and prothrombin F1 + 2 increased significantly after cessation of CPB. In conclusion, hemofiltration during CPB is a safe and efficient method for water removal and for concentration of red blood cells and proteins without adverse effects on the patient's hemodynamics, blood quality, and volume requirements. More especially, no negative influence of hemofiltration could be determined with regard to activation of the coagulation and complement system.

Blood Cell Count↗
PubMed1994

Three years' experience in video-assisted thoracic surgery (VATS) for spontaneous pneumothorax.

In a prospective study (June 1990 to June 1993), 79 patients were treated for spontaneous pneumothorax by video-assisted thoracoscopic methods with regular follow-up. The observation time was from 3 to 36 months (mean 19.6 months) and was more than 24 months in 27 patients. In 57 patients spontaneous pneumothorax was primary and in 22 secondary. The 53 male and 26 female patients were aged between 17 and 87 years (mean 37 years). Twenty-one patients were treated thoracoscopically for first episode, 22 for persistent pneumothorax (> 7 days), and 36 for a recurrence. Endoscopic examination failed to reveal any lung alteration in four patients (5.1%), and treatment then consisted of simple drainage. Leaks were sealed 26 times by means of a Roeder loop with local anesthesia and 14 times by wedge resection with endotracheal anesthesia and one-lung ventilation; 34 patients were treated by pleurectomy. No deaths occurred. Surgical morbidity was 3.8%, and the postoperative complication rate was 5.1%. One patient was excluded from the follow-up study after conversion to a thoracotomy for control of arterial bleeding. We noted six recurrences; four occurred in the first 21 days and three after ligation of the leak with a Roeder loop. We conclude that video-assisted thoracoscopic treatment of spontaneous pneumothorax by wedge resection and pleurectomy has a recurrence-free rate of 93.8% (45/48) and is therefore an effective treatment for all forms of spontaneous pneumothorax.

Adolescent↗
PubMed1993

Photodynamic therapy with m-tetrahydroxyphenylchlorin in vivo: optimization of the therapeutic index.

The therapeutic index of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (mTHPC-PDT) was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Equal doses of 650 nm laser light were delivered to the tumour and to an equal-sized area of the hind leg (control site) after i.p. administration of mTHPC. Twenty-one groups of 6 animals each were treated under various drug-light conditions and at drug-light intervals ranging from 4 hr to 6 days. After light delivery the extent of tumour necrosis and the depth of alterations in normal tissue were assessed by light microscopy of standardized histological sections. A therapeutic index (TI) of mTHPC-PDT was defined as the cross-sectional area of tumour necrosis per depth of visible tissue injury at the control site. This TI was strongly related to the conditions of treatment. In particular, it was increased by prolonging the drug-light interval up to 5 days and by increasing the dose of light for any dose of drug. The most profound increase of TI was obtained by increasing the intensity of light administered at the chosen interval while reducing the dose of drug. Our findings suggest that threshold conditions operate in PDT and have important implications for clinical application of the treatment.

Animals↗
PubMed1993

Effect of drug-light interval on photodynamic therapy with meta-tetrahydroxyphenylchlorin in malignant mesothelioma.

The influence of the time interval (TI) between drug administration and laser activation on selectivity of meta-tetrahydroxyphenylchlorin(mTHPC)-mediated photodynamic therapy (PDT) for tumour tissue was assessed in BALB/c nude mice bearing human malignant mesothelioma xenografts. Following i.p. administration of 0.3 mg/kg mTHPC, a light dose of 10 J/cm2 and 0.1 W/cm2 was delivered at 650 nm on the tumour and an equal-sized area of the hind leg after 4, 12, 24 and 36 hr and 2, 3, 4, 5 and 6 days to groups of 6 animals (surface irradiance). Then, 72 hr after light delivery, the depth of necrosis was measured in the tumour and in the skin and underlying muscle of the hind leg. Photosensitized necrosis occurred in normal tissue at TI from 4 hr to 3 days and in the tumour at TI from 12 hr to 4 days. The therapeutic ratio of mTHPC-PDT varied significantly with the time interval between drug administration and laser activation and was greatest at an interval of 3 days. mTHPC concentration was measured in 3 control unirradiated animals at all time points in normal tissues and in tumour tissue, and found to be the same in both tissues. Thus the tissue concentration of mTHPC was of limited use as regards the prediction of photosensitizing effects in the tumour model.

Animals↗