Gene/Protein Disease Symptom Drug Enzyme Compound
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A method for an ex situ operation of the liver is presented with the example of such an operation in a 40-year-old patient. With this operation bilateral liver metastases of a leiomyosarcoma--which were otherwise regarded as irresectable--were resected. Function of the liver after reimplantation was good. Liver protection was performed by perfusion with cardioplegic HTK-solution (Bretschneider). The techniques of liver ex- and implantation are based on the methods of liver transplantation. Extracorporal femoro-porto-axillary bypass for decompression of the inferior caval vein and portal vein was used throughout the anhepatic period of 6 h. It is supposed that the method described here--which according to the authors' knowledge has been performed for the first time in a patient--will open up new perspectives for the surgery of malignant and occasionally of benign tumors, if necessary also for other surgical liver diseases. As an additional possibility, in situ protection of the liver with consecutive operation of the bloodless liver in situ is discussed. This procedure will correspond for the most part to the ex situ technique described here.
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PMID:[Ex situ operation on the liver. A new possibility in liver surgery]. 328 72

The vast majority of modern surgical open-heart procedures require a period of global myocardial ischaemia due to the interruption of the coronary circulation, since a bloodless operative field is of great importance for delicate surgical techniques. Several cardiac protective measures have been applied in order to minimize ischaemic damage to the heart muscle: 1. Intermittent myocardial ischaemia, combined with mild to moderate hypothermia: ischaemic periods of 15-30 min at 28-32 degrees C are tolerated. Multiple ischaemic periods are possible after intermittent (3-5 min) reperfusion. 2. Deep hypothermia, combined with ischaemia: myocardial cooling to 18-23 degrees C protects the heart for ischaemic periods of up to 45-60 min. 3. Cardioplegic arrest, combined with hypothermia: a great variety of cardioplegic solutions are still used today in clinical practice. a. Interruption of electrical activity: most cardioplegic solutions use K+ (15-35 mmol/l); complete suppression of electrical processes is not always achieved. b. Interruption of electrical activity and buffering of glycolytic end products. St. Thomas-, Kirklin-Solution, blood cardioplegia and their multiple variations can result in an 3-5 fold tolerance to myocardial ischaemia. c. Interruption and blockade of electro-mechanical activity, combined with an effective buffering. Bretschneider-HTK cardioplegia equilibrates the extracellular space due to a 6-10 min infusion of the cold, crystalloid solution and allows uninterrupted ischaemic periods of more than 2 h under clinical conditions. In order to achieve optimal cardiac tolerance to global ischaemia a careful protocol of perioperative myocardial proection has to be followed. Most heart centers use a combination of hypothermia and effective cardioplegia.
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PMID:[Clinical aspects of global ischemia of the heart]. 344 89

In order to improve dog kidney perfusion in situ with a protective solution, a perfusion catheter was constructed which allowed continuous pressure measurement in the center of the catheter tip during perfusion. Using this catheter, the equilibration of the extracellular space with a protective solution (HTK solution) was found to be pressure dependent. Continuous pressure and resistance control is therefore a prerequisite for reliable organ protection.
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PMID:Construction and experimental application of a catheter for selective arterial kidney perfusion in situ. 392 9

The influence of temperature (5, 15, 25, and 35 degrees C) on the degree of tissue acidification was examined using 74 canine kidneys with simple ischemia or after protection of the kidneys with Euro-Collins solution or with the HTK-solution of Bretschneider. At an incubation temperature of 5 degrees C, the intrarenal pH value in HTK-protected kidneys is continuously higher than 7.3 during 36 hr of ischemia. In Euro-Collins kidneys the pH value decreases to a pH of 6.4 during this time. In simple ischemic kidneys pH is 6.3 after 36 hr. At 15 degrees C the pH value falls to a lower level in Euro-Collins kidneys than in purely ischemic kidneys, but the pH in HTK-protected kidneys is higher than 6.9 for 24 hr. At 25 degrees C, and especially at 35 degrees C the intrarenal acidosis in Euro-Collins kidneys is much stronger than in unprotected kidneys, and the pH in HTK-protected kidneys does not decrease below 6.7. The lactate production in simple ischemic kidneys and in HTK-protected kidneys is nearly the same (80-100 mumol/gdw), although Euro-Collins kidneys have a steeper increase and reach higher lactate levels (330 mumol/gdw). The HTK solution guarantees satisfactory protection against damaging acidosis over the whole temperature range (5-35 degrees C), but the Euro-Collins solution leads to a stronger and more dangerous acidosis the higher the temperature.
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PMID:Effects of preservation conditions and temperature on tissue acidification in canine kidneys. 399 49

Between 1954 and 1984 41 primary testicular tumours were treated in 40 children at the age of 0 to 9 years as well as 9 secondary testicular tumours in malignant systemic diseases or metastases. The histological reclassification of the number of cases revealed 15 yolk-sac-tumours, 10 differentiated teratomas of immature subtype, 1 intermediary malignant teratoma, 3 undifferentiated malignant teratomas, 2 Sertoli-cell-tumours (1 double-sided) and 5 rhabdomyosarcomas. 2 children each with undifferentiated malignant teratomas and rhabdomyosarcomas died, all before 1970. 5 children with yolk-sac-tumours and 2 with rhabdomyosarcomas who since 1974 have been treated with Ablatio testis and combination chemotherapy live without tumour. Histological classification and division into stages are proved and form the basis of a therapy conception which in all testicular tumours apart from the Ablatio testis contains the chemotherapy of different intensity (HTK-84), taking into consideration form of tumour, stage and age of the children. The retroperitoneal lymphadenectomy is recommended only in the proof of metastases.
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PMID:[Therapy of testicular tumors in childhood]. 403 83

Since intermittent cardioplegic reperfusion during an ischemic period may reduce the ischemic stress of the heart at least by lowering myocardial temperature, we compared the post-ischemic recovery of the dog heart following cardioplegia and subsequent continuous ischemia of 1 X 300 minutes at 22 +/- 1 degree C (model 1) and following cardioplegia and subsequent 3 X 100 minutes of ischemia at 17 +/- 1 degree C with intermittent 4-minute cardioplegic reperfusion every 100 minutes (model 2). The parameters of post-ischemic recovery were the cardiac O2 consumption per beat at work (MVO2-E0): HR), the stability of cardiac rhythm, the left ventricular content of high-energy phosphates, and ultrastructure. Solution HTK with a magnesium concentration of 9 mM/L, in clinical use up to the beginning of 1984, resulted in a significantly better post-ischemic recovery in model 1, despite about 40% lesser ischemic stress in model 2. A reduction of Mg concentration from 9 to 4 mM/l, as in the HTK solution clinically tested since February 1984, did facilitate the post-ischemic recovery in model 1 as indicated by the stability of cardiac rhythm but led to a significant improvement of all parameters of recovery in model 2. Moreover, recovery in model 2 after reduced Mg was also clearly better than in model 1 corresponding to the lesser ischemic stress. The parameters myocardial O2 consumption (MVO2) and potassium loss during HTK perfusion containing 9 and 4 mM/l, respectively, gave indications of specific membrane labilizing effects of Mg in the cardioplegic solution HTK.
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PMID:Different effects of cardioplegic solution HTK during single or intermittent administration. 608 14

Preischaemic doubling of the myocardial buffer capacity optimizes the energy supply of the ischaemic heart by anaerobic glycolysis. For osmotic reasons this method of improving ischaemia tolerance can only be realized in combination with cardioplegia by extracellular Na+ and Ca2+ reduction. The cardioplegic solution 'HTK' which has been developed according to these considerations. (1) delays the decay velocity of myocardial ATP by a factor of 7-8 in comparison with pure ischaemia; (2) leads to a good myocardial recovery with regard to metabolic, morphological, and functional criteria after an ischaemic stress of 300 min at 23 +/- 1 degrees C--especially after the addition of quinine; (3) is considerably reduced in its protective efficacy by adding 50 mumol l-1 Ca2+; (4) causes a calcium paradox if it is infused for 30 min at 35 degrees C; this does not happen if it is infused for 60 min at 25 degrees C or for 120 min at 15 degrees C; on adding 50 mumol l-1 Ca2+ to the solution the risk of a calcium paradox is significantly reduced, even after infusion for 35 min at 35 degrees C; (5) effects an evident delay of recovery, if a continuous ischaemic stress of 300 min at 23 degrees +/- 1 degree C is reduced to 3 X 100 min of ischaemia at 17 +/- 1 degrees C by intermittent cardioplegic reperfusion; (6) considerably improves the myocardial recovery even after intermittent cardioplegia if 50 mumol l-1 Ca2+ are added or Mg2+ is reduced from 9 to 4 mmol l-12. The metabolic, morphological, and functional results are equivalent to those after 300 min of continuous ischaemia. Further investigations must show to what extent the 'membrane stabilizing effect' of [Ca2+]o can be achieved by taking advantage of mutual ionic interaction on the level of plasmalemma (e.g. H+-Mg2+-Ca2+) or by adding membrane effective substances (quinine).
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PMID:Calcium-free cardioplegia--pro. 666 28

The effects of high-energy shock waves (HESW) on the human renal cell carcinoma were examined. The kidneys were available from 32 patients treated by radical nephrectomy due to renal cell carcinoma. Immediately after nephrectomy the kidneys were perfused with cold HTK solution and stored for a maximum of 4 h in hypothermia at 8 degrees C. The tumors were treated with 4,000 shocks (65 mPa = 0.6 mJ/mm2) in an electromagnetic lithotriptor (Siemens Co., Erlangen, Germany). Microscopic and immunohistological examinations of the tumors were performed after treatment, and cell proliferation rates of treated and untreated specimens were analyzed by cell cultures in 10 cases. HESW induce severe microscopic damage in the tumor tissue as complete rupture of the vessel walls and destruction of the tubular-formed tumor masses in the focal area. Immunohistochemistry shows intact immune reactive endothelial cells by factor 8-associated antibodies until the border to histological damage. Around this region a zone of negative antibody reaction against collagen type 4 is found. In cell cultures the proliferation rates of treated specimens were significantly lower compared to untreated. The human renal cell carcinoma seems to be susceptible for treatment with shock waves. HESW induce direct damage of tumor cells and vascular damage in the tumor which may be the primary cause of tumor necrosis.
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PMID:Treatment of human renal cell carcinoma with high-energy shock waves--a new in vivo/in vitro model. 757 Nov 74

The aims of this study were (1) to investigate the effect of R 75231, a nucleoside transport inhibitor, on renin-angiotensin release after renal ischemia-reperfusion and (2) to establish a possible protective effect of this drug on renal function. We used a canine model for auto- transplantation of kidneys that had been subjected to 30 min of warm ischemia and subsequently to 24h of cold storage in HTK preservation solution, with immediate contralateral nephrectomy. R 75231 was injected intravenously into six dogs in two equal portions of 0.05 mg/kg both 30 min and 10 min before reanastomosis was established. Another six dogs were used as a control group. At 2 weeks post-transplantation, five out of six dogs in the R 75231 group and one out of six in the control group were still alive. Starting on day 4, serum creatinine was lower in the R 75231 group than in the control group (p < 0.005). In contrast to the control group, an inversion of the median preischemia adenosine/inosine ratio was observed in the R 75231 group after reperfusion (0.4 preischemia vs 4.0 after 60 min of reperfusion). Reperfusion of the graft resulted in an immediate increase in renin, angiotensin I, and angiotensin II venous blood levels in the control group. In the R 75231 group, renin, angiotension I, and angiotensin II levels were significantly lower. We conclude that administration of R 75231 before reperfusion has a protective effect on post-transplant function of kidneys that have been subjected to prolonged warm ischemia. This effect may, at least in part, be ascribed to inhibition of the breakdown and disposal of endogenous adenosine which, in turn, inhibits the excessive stimulation of the renin-angiotensin system in the early phase of reperfusion.
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PMID:Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade. 762 81

To construct recombinant retroviruses with only a single active promoter, we introduced point mutations into the TATA box region of the 3'-LTR, and successfully obtained high-titer virus with sufficient self-inactivating activity. However, the viral titer could not be determined by the number of G418 resistant colonies since the neomycin resistance gene was under 5'-LTR control, because of inactivation of the selection marker in target glioma cells. To overcome this problem, we constructed PCR primers with homology to a gene under the control of the internal promoter of recombinant retrovirus, and to retrovirus-specific sequences. There was good correlation between the amount of PCR-amplified product and the number of colony forming units when glioma cells were transduced with the retroviruses containing both the neomycin resistance gene and the HTK gene. Amplified PCR products quantitated by densitometry after glioma cells were transduced with SIV retrovirus vectors, and there was good correlation between density and sensitivity to GCV following transduction. Therefore, detection of HTK PCR products from glioma cells transduced with HTK-bearing retroviruses is useful for determining the appropriate packaging cell for efficient production of viral particles. This detection system is especially useful for isolating high titer clones producing SIV-type retroviruses.
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PMID:A simplified general method for determination of recombinant retrovirus titers. 764


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