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Biomedical subjects

A Henze

Publications and source records attributed to A Henze.

At least 19 recordsLinked to original sources

Phase II trial of docetaxel and carboplatin in recurrent platinum-sensitive ovarian, peritoneal and tubal cancer.

OBJECTIVE: Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. METHODS: Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0-2 and normal bone marrow, renal and hepatic function. 25 patients (age 18-75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m(2) via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. CONCLUSION: Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.

Adult↗

Nucleoside transport inhibition in ischemic myocardium results in enhanced taurine efflux.

We measured with the microdialysis technique energy-related metabolites in ischemic myocardium over time in an experimental pig model. Emphasis was put on the dipyridamole effect when administered in the microdialysis probe inserted in ischemic myocardium. Not only adenosine but also taurine and pyruvate concentrations were significantly higher in the microdialysate during the periods of ischemia and extracorporeal circulation with cardioplegia. The enhanced efflux of taurine in ischemic myocardium induced by dipyridamole is a new finding. A mechanistic role of taurine in the prevention of Ca(2+) overload in ischemic myocytes is discussed. Also, taurine may have stimulatory effects on glycolysis in ischemic heart.

Adenosine↗

Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation.

In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the increased risk of heart surgery in connection with acute myocardial infarction.

Adenosine↗

Discrepant outcome between myocardial energy-related metabolites and infarct size limitation during retroperfusion of the coronary sinus.

The basic idea of retroperfusion of the coronary sinus (RCS) is to ameliorate detrimental consequences of myocardial ischaemia. Several experimental models of RCS have been introduced, most with an emphasis on functional myocardial status. Since only few studies have been devoted to energy metabolic considerations and none to continuous monitoring of energy-related metabolites of myocardium during RCS, we here present such a study using microdialysis. This study comprised the following components: Coronary occlusion and drainage on the beating heart with RCS-assist (60 min), hypothermic (30 degrees C) extracorporeal circulation (ECC) and cardioplegia (45 min), reperfusion and rewarming to 38 degrees C on ECC (30 min). The microdialysis analytical outcome mainly reflected anaerobic energy metabolism in potentially ischaemic myocardium. Additionally, a pronounced increase of microdialysate content of lactate, pyruvate and guanosine was observed in non-ischaemic myocardium especially during the reperfusion phase. The planimetric calculation revealed an infarct size reduction from 69% to 19% and was not correlated to clear-cut improvements of potentially ischaemic myocardial energy metabolism. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival.

Animals↗

Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery.

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.

Anticoagulants↗

Inflammatory response during simulated extracorporeal circulation with addition of nitric oxide.

BACKGROUND: Heart operations performed with extracorporeal circulation (ECC) are associated with an inflammatory response. This response is partially due to granulocyte activation. Leukocyte derived free radicals are involved in tissue injury. The purpose of this study was to observe whether nitric oxide influence the inflammatory response during simulated ECC. METHODS: In a model of simulated extracorporeal circulation, fresh whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for three hours. In five circuits NO was added to oxygen/air mixture (group N), while five other circuits were ventilated with oxygen/air mixture (group C). The methods for estimating the inflammatory response were determination of oxygen free radicals production capacity, using chemiluminescence, and measurements of concentration of granulocyte derived proteins (myeloperoxidase and human neutrophil lipocalin). RESULTS: All measured parameters were similarly independent of additional supply of nitric oxide almost throughout extracorporeal circulation time. The sole significant difference between the two groups was found at an early stage of extracorporeal circulation, when luminol-enhanced chemiluminescence in whole blood was higher in the N group (1,500, 1,470-1,950 vs 1,038, 750-1,050 in the control group; medians with quartiles). A similar tendency was observed in lucigenin-enhanced chemiluminescence at 60 min of extracorporeal circulation (625, 560-875 in the N group vs 400, 360-525 in the control group; medians with quartiles). CONCLUSIONS: Nitric oxide supply does not influence inflammatory response during three hours long extracorporeal circulation, although some protective effect on hydrogen peroxide production in whole blood was detected in the initial phase of extracorporeal circulation.

Acridines↗

Biomaterial-dependent blood activation during simulated extracorporeal circulation: a study of heparin-coated and uncoated circuits.

OBJECTIVE: Blood activation during extracorporeal circulation is associated with morbidity and mortality in cardiac surgery. This activation can be diminished by usage of heparin-coated circuits. Nitric oxide has also been reported to influence humoral and cellular components of blood. This study was performed to determine biomaterial-dependent part of blood activation. DESIGN: Fresh, whole human blood mixed with Ringer's solution was circulated through a heart-lung machine for two and half hours. Five circuits were heparin-coated (group HC), whilst five other circuits were uncoated (group NC). During the last half hour NO was added to the oxygen/air mixture. METHODS: Blood activation was estimated by measuring following parameters: interluekin 6, complement activation products C3a and terminal complement complex, and oxygen free radicals (OFR) production capacity, which was determined using chemiluminescence enhanced by serum opsonized zymosan (SOZ) and phorbol myristate acetate (PMA). Granulocyte activation was measured as release of myeloperoxidase (MPO) and human neutrophil lipocalin (HNL). RESULTS: OFR in granulocyte suspension stimulated by SOZ and PMA were significantly lower in the NC group, mostly later during ECC. Similarly, lower neutrophil and monocyte counts were observed in this group. NO increased superoxide production in the whole blood in heparin-coated circuits, but did not change OFR in isolated granulocytes. MPO was also affected by heparin-coating. NO supply seemed to increase release of MPO and HNL. It is concluded that heparin-coating contributed to reduction of biomaterial-dependent blood activation. An addition of NO at late stage of ECC tended to influence this activation.

Adult↗

Multiarterial coronary artery bypass grafting with special reference to small vessel disease and results in women.

From 1985 to 1991 a total of 220 patients underwent coronary artery bypass grafting (CABG) with at least two native pedicled artery grafts. Bilateral internal mammary artery (IMA) grafting was performed in 201 patients, IMA combined with gastro-epiploic artery (GEA) grafting in five, and double IMA plus GEA grafting in 14; in addition 156 patients received 1-3 vein grafts. The primary indication for elective multi-arterial CABG was coronary arteries of small calibre (small vessel disease) in 77 patients, repeat CABG in 17 (without small vessel disease), varicose/stripped saphenous veins in 57 (without small vessel disease), while the remaining 69 were routine cases; the distribution differed between women (42, 0, 47, and 11%, respectively) and men (33, 10, 19, and 38%, respectively; P < 0.0001). The women also were older (62 +/- 7 vs 56 +/- 9 years; P < 0.001), and had higher prevalences of systemic hypertension, diabetes mellitus, and hypercholesterolaemia. The number of artery grafts and total number of grafts were, however, similar for women and men. Early mortality (< or = 30 days) was 5.6% in women and 2.4% in men (ns). Early mortalities in relation to primary indications were: 7.8% for small vessel disease, 5.9% for repeat CABG, and 0% for both varicose/stripped saphenous veins and routine cases (P < 0.05). Logistic regression analysis identified small vessel disease, insufficient grafting, age of > = 60 years, a history of smoking, a family history of ischaemic heart disease, and female gender as independent risk factors for early mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Surgery for chronic left ventricular aneurysm. Benefits and side effects.

Seventy patients who underwent elective resection of symptomatic postinfarction apico-anterior left ventricular (LV) aneurysm with or without coronary revascularization are reviewed. The early (< or = 30 day) mortality was 5.7%. Mural thrombosis occurred in 29 cases (41.4%), unrelated to the degree of preoperative LV impairment and predictable from preoperative LV angiography in only seven cases. The response to surgery comprised significant overall improvement of global LV ejection fraction (LVEF) during rest and of all variables in stress testing. This LVEF recovery correlated significantly with that of peak ejections rate, a variable of myocardial contractility. Contrastingly, right ventricular ejection fraction (RVEF) at rest decreased slightly but significantly without correlation to preoperative RVEF or LVEF. In comparisons between patients with congestive heart failure or angina at rest as dominant symptom, the former group showed greater depression of preoperative watt and LVEF but better postoperative recovery of these variables, while right ventricular deterioration was significant only in the latter. Postoperative recovery was best in patients with poor preoperative LV function (LVEF < or = 20%), even when surgery comprised only aneurysmectomy in isolated but ungraftable LAD disease (5 cases). The observed RV deterioration may be 'nonspecific', but it must be kept in mind as a side effect of the operation, as it detracts unpredictably from postoperative ventricular recovery. Patients with well preserved preoperative LVEF, small LV aneurysm and marginal expected post-aneurysmectomy changes according to LaPlace's law are probably at risk, and surgery should then instead be directed towards preserving the remaining viable myocardium by direct revascularization.

Adult↗

Multiple intestinal duplications in a child with thoracic myelomeningocele and hydrocephalus.

An infant with thoracic spina bifida, myelomeningocele and hydrocephalus was found to have intrathoracic gastric duplication and noncontiguous tubular duplication along two-thirds of the small bowel. The myelomeningocele was closed and the hydrocephalus relieved with a shunt. The intrathoracic duplication was excised in toto and the intra-abdominal malformation successfully treated by stripping the entire mucosal tube from within the duplication.

Abnormalities, Multiple↗

Left ventricular aneurysmectomy in patients with poor left ventricular function.

Physical performance and left ventricular (LV) function in the resting state were assessed in 22 patients with postinfarction anterior-apical left ventricular aneurysm (LVA) and global ejection fraction less than or equal to 20% who subsequently underwent radical LVA resection. The basic findings in the 20 survivors of surgery were significant improvement of global systolic LV function and more or less complete recovery of regional ejection fraction in the predominantly viable low and high lateral LV wall. This improvement was evident in patients with concomitant bypass grafting as well as in those with isolated and ungraftable lesions of the left anterior descending (LAD) coronary artery. We conclude that postinfarction anterior-apical LVA in a poorly functioning LV is suitable for surgical treatment, which can be accomplished with acceptable risk. All graftable stenotic major coronary arteries should be bypassed, in addition to the LVA resection, but a minority of patients with isolated, ungraftable LAD disease are likely to benefit from aneurysmectomy alone.

Adult↗

Flowmetric evaluation of internal mammary artery flap during repair of aortic coarctation.

Resection of the internal shelf through a longitudinal aortotomy and widening with the free end of the left in situ internal mammary artery (IMA) were steps in correction of aortic coarctation with isthmus hypoplasia in nine patients aged 9-14 (mean 10.5) years. Electromagnetic flowmetry was performed on the left IMA before and after the repair. The essential finding was considerably increased mean blood flow in the IMA flap during cross-clamping proximal to the completed repair, from 53 +/- 48 to 430 +/- 74 ml/min (378 +/- 78%). The IMA thus is a powerful conduit with extraordinary flow capacity when runoff is appropriate. Integration of IMA as a viable flap in the repair of aortic coarctation implies that this artery increases its collateral flow contribution to the distal aorta.

Adolescent↗

A "new" intraabdominal artery. The pedicled right gastroepiploic artery for myocardial revascularization.

The right gastroepiploic artery (GEA) was used as a pedicled conduit for direct coronary artery revascularization in 20 patients presenting with more or less exhausted saphenous vein resources. The early angiographic patency of the GEA conduit appears to be satisfactory when it is connected to the right coronary artery system. A distinct disadvantage of GEA grafting is the necessity to enter the abdominal cavity, which may lead to probably rare and as yet unrecognized morbidity. Future abdominal surgery may injure the GEA conduit unless its topographic relations to the prepyloric antrum, liver and diaphragm are properly recognized. The surgeon must then be prepared to encounter antegastric, retrogastric, antehepatic, transhepatic and retrohepatic routes of the redirected intraabdominal artery. The present paper addresses this problem. Preoperative angiography of the celiac trunk and superior mesenteric artery may be helpful in decision-making when a patient reports or records show that a graft has been harvested from the abdominal cavity.

Arteries↗

Revascularization of infarcted vs. viable myocardium. Effects on symptoms, physical performance and global/regional left ventricular function.

Symptoms, physical performance and global vs. regional left ventricular (LV) function were reviewed in 25 patients with postinfarction anterior-apical akinesia and minor dyskinesia who subsequently underwent revascularization of all graftable stenotic vessels. The observed postoperative improvement in functional NYHA capacity and physical performance was not related to significant change in any systolic or diastolic variable of global LV function. 'Nonspecific postoperative septal hypokinesia' developed in most cases. The regional ejection fraction showed slight (nonsignificant) mean increase in the infarcted apex and low anterior wall supplied by the left anterior descending artery, but marked increase in the noninfarcted lateral wall supplied by the left circumflex branch. Hearts with grafted left circumflex artery showed on average lower preoperative and postoperative ejection fraction in the lateral wall than did hearts without such grafting, but the rise in regional ejection fraction was significant only after left circumflex grafting. The clinical response to coronary artery surgery is attributed mainly to functional improvement of non-infarcted myocardium. Revascularization of viable myocardium occurs directly via bypass grafts, but collateral vessels may also contribute.

Adult↗

Revascularization of infarcted myocardium. Effect on myocardial perfusion assessed with quantified Tl-201 SPECT technique.

Myocardial perfusion was studied in 21 patients before and after revascularization of all graftable stenotic vessels following post-infarction anteroapical akinesia and minor dyskinesia. At preoperative and late postoperative evaluation, perfusion abnormalities in identified sectors were quantified with two methods, one (Q1) assessing the extent and the other (Q3) the severity of abnormal perfusion. The preoperative scores with both methods indicated permanent myocardial perfusion defects in all 21 patients and reversible defects, indicating myocardial ischemia, in 16 with Q1 and 14 with Q3. After bypass grafting there was overall reduction of myocardial perfusion defect and of abnormality scores: Notably, 13/21 patients (62%) had decreased permanent myocardial defect score, reflecting reactivation of 'hibernating myocardium'. The findings indicated that obstructed but graftable vessels supplying myocardium with loss of contractile function should be bypassed, since flow contribution to distant, viable myocardium is probable via preserved collateral circulation. This should be particularly relevant for the LAD, because of that artery's septal branches.

Adult↗