Evaluation of five training courses in microsurgery.
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Biomedical subjects
Publications and source records attributed to W J Kort.
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Aspirin (group I, 20 mg/kg, 0.5 hour preoperatively, ip, xylocaine (group II, topical administration of 1 ml of a 2% solution), and ZK 36,374 (Iloprost) either pre- or per- or postoperatively (group III, 10 micrograms/kg 0.5 hour peroperatively iv; group IV, topical administration of 1 ml of a solution containing 25 micrograms/ml peroperatively; and group V, 10 micrograms/kg 0.5 hour postoperatively iv) were given to groups of BN female rats in order to improve the patency rate of small artery (less than 0.5 mm) anastomoses. The rats in group VI received saline peroperatively by topical application, this group served as a control. The patency was established by means of arteriography and macroscopical examination. Neither aspirin nor xylocaine improved the number of successful anastomoses. However, Iloprost administered topically, while performing the anastomosis, substantially improved the patency rate when compared with group VI, the control group. In the control group only five out of 21 animals showed patent anastomoses, whereas in group IV (Iloprost, topical administration) seven out of ten operations were successful. The results suggest that Iloprost applied locally could be helpful in clinical microsurgery for elective operations as well as in replantation surgery.
Growth of BN175, a malignant fibrosarcoma, was correlated with high plasma TXB2 and PGE2 levels. This statistically significant increase was first detected 17 days after inoculation of the tumor, at which time the tumors were 20 mms in diameter. A further increase in tumor size was associated with still higher PGE2 and TXB2 values. At the same time, progressive alterations in platelet function, as measured by ADP-induced platelet aggregation, were observed. 6-keto-PGF1 alpha levels remained normal throughout the whole experiment. It was concluded that tumor growth was associated with changes in PG synthesis and platelet function, although it remains unclear whether these changes were caused by some host immunological response towards the tumor or were predominantly the result of tumor PG-synthesis.
In a previous study, significant differences in the growth rate of a transplantable mammary adenocarcinoma were observed between rats receiving a diet rich in saturated fatty acids (lard, diet A), and rats on a diet in which the saturated fat was partly replaced by polyunsaturated fatty acid of the omega-3 type (Menhaden oil, diet B). In the present investigation, it was our aim to study tumor growth in rats on diet A and B, as well as in rats that had, at tumor inoculation, a change of diets, from diet A to diet B. Tumor growth of rats receiving diet A throughout the whole experiment was the same as in those rats that had a conversion of diets. The data shows that the observed inhibiting effect of diet B on tumor growth could not be obtained when this diet was given exclusively after tumor inoculation.
Rats fed diets containing different amounts of polyunsaturated fatty acids either of the n-3 or n-6 type, received cultured, syngeneic mammary tumor (BN472) cells intravenously. Animals were sacrificed 2 weeks after tumor inoculation, and the number of pulmonary tumor foci was counted. No significant differences in the number of metastatic foci were observed between the dietary groups. Prostaglandin measurements in the supernatant of tumor cells cultured in vitro showed that the tumor cells could produce thromboxane A2. Many investigators connected this tumor synthesis capacity with tumor metastatic activity. Yet in our study, diets rich in menhaden oil, with the known capacity to inhibit thromboxane synthesis, could not control tumor metastasis in this particular tumor model.
To study the biological characteristics of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in rats, 20 Sprague Dawley female rats received a single oral dose of 5 mg of this carcinogen. During the 35-week observation time 78 primary tumors were removed. While in most cases the primary tumor could be removed completely, 7 out of 20 animals eventually had to be sacrificed for inoperable local recurrence of the primary tumor. Notwithstanding, the long period of time given for tumor metastases to develop (mean time between tumor removal and termination was 18.5 weeks), tumor spread either to lungs or regional lymph nodes could not be established. This relatively benign behavior of the tumor was in contrast with the morphological characteristics of the tumor, which uniformly showed the features of adenocarcinomas. The difference in biological behavior between DMBA-induced mammary tumors in rats and malignant mammary tumors in humans suggests that as a model this system is of limited value for investigations of mechanisms of malignant behavior of human tumors.
BN/Bi inbred female rats fed diets containing different amounts of polyunsaturated fatty acids, either of the omega-3 or omega-6 type, each received an implant of a syngeneic mammary adenocarcinoma. When the diameter of the tumors reached 20 mm, they were surgically removed; 2 weeks thereafter the animals were sacrificed and lung metastases were counted. Cellular immune response was determined before tumor inoculation; certain prostaglandin values in plasma and platelet aggregation were measured before and after tumor inoculation. Plasma prostaglandin E2 and thromboxane B2 values were significantly decreased in those rats fed a diet containing menhaden oil. 6-Keto-prostaglandin F1 alpha, cellular immune response, and platelet function were not significantly different in either one of the diet groups. Tumor growth in the groups of rats receiving the omega-3 fatty acids in their diet was significantly inhibited in comparison with that in the rats receiving the omega-6 fatty acids. However, the number of metastases was not significantly altered.
For suppression of primary tumor growth and metastatic spread, aspirin and theophylline, either alone or combined, were given daily to inbred female BN rats after sc implantation of a syngeneic nonimmunogenic tumor. Treatment with 200 mg aspirin/kg (body wt) resulted in a statistically significant regression of tumor growth as well as of the number of metastases in the lungs. Aspirin given in a lower dose (20 mg/kg) did not show significant difference from the vehicle group. Theophylline (75 mg/kg) significantly increased primary tumor growth as well as lung metastases. Inhibition of in vitro platelet aggregation, determined in whole blood taken from non-tumor-bearing animals treated with the same therapeutic regimen, was most pronounced in those groups in which tumor growth and spread were significantly retarded. However, this positive correlation between inhibition of tumor spread and platelet aggregation was not associated with a favorable balance of prostacyclin and thromboxane A2 in these animals.
Diets high (17.7 cal%) and low (3.3 cal%) in linoleic acid were given to groups of Brown Norway female rats before and after inoculation of syngeneic tumor models with different characteristics, with regard to tumor spread, malignancy, immunogenicity, growth rate, rat strain, and histopathological features. Despite the differences in characteristics, in most tumor models, tumor growth was identical in both experimental groups. However, in 2 tumor models, an adrenal cortical carcinoma and a myeloid leukemia, differences in growth were noted. In rats given the diet low in linoleic acid, growth of the cortical carcinoma was significantly increased, whereas the opposite effect was seen in rats with myeloid leukemia.
As a way to induce mild chronic stress, light-dark (L-D)-shift stress was applied to inbred BN virgin female rats during their whole life-span (group I, 100 animals); the incidences of spontaneous tumor and nontumor processes were recorded. A group of rats (group II, 100 animals) exposed to a standard lighting system served as the control group. Total tumors of 128 in group I and of 154 in group II were found in 74 and 86 animals, respectively. Neither were these differences nor was the pattern of spontaneous tumors statistically significant. Although in earlier studies L-D-shift stress had proved to be effective, especially with regard to its capacity to induce a substantial decrease in cellular immune response, apparently such alterations did not unfavorably affect longevity of BN female rats. Although as a side issue of this study, a strong predisposition for tumor incidence appeared to exist, in particular for the incidence of Langerhans' islet tumors, in fat animals at weaning.
Hypertension secondary to renal transplantation was studied in our experimental model in the rat. In this model an intravenous injection of donor strain blood into recipients of allogeneic donor kidneys prior to transplantation was used to prolong the allograft survival. A reduced renal function associated with the hypertension was suggestive of incomplete prevention of the rejection process. We studied the effect of cyclosporin A, either alone or as adjuvant immunosuppressive therapy, on renal function and systolic blood pressure. Either way, cyclosporin A resulted in normotensive allograft recipients and in a better function of the graft when compared with recipients pretreated with donor strain blood only.
High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.
In an experimental model of post-renal transplantation hypertension in rats, we studied the effect of a reduction of sodium intake on the development of this type of hypertension. Systolic blood pressure, plasma renin concentration and renal function were measured regularly in recipients of an allogeneic kidney transplant that had previously undergone active immunological enhancement. Transplant recipients on a normal diet showed a rise in systolic blood pressure during the second week after transplantation. The systolic blood pressure of recipients on a low sodium diet remained normotensive throughout the 15 weeks follow-up period. The plasma renin concentration was low in the hypertensive recipients on a normal diet, as compared with unilaterally nephrectomized controls. Although the plasma renin concentration of recipients on a low sodium diet fell below that of unilaterally nephrectomized controls on a low sodium diet, it was higher than that of recipients on a normal diet. The renal function of transplant recipients was greatly reduced compared with that of control rats. The glomerular filtration rate was reduced to a greater extent than the effective renal plasma flow. In a separate experiment it was revealed that a similar reduction in the glomerular filtration rate of kidneys permanently damaged by temporary ischaemia did not result in an increase in the systolic blood pressure. Survival up to 6 weeks after transplantation was the same for both groups of recipients. Recipients on a low sodium diet, however, showed a better 15 weeks survival, probably owing to the absence of hypertension in this group.(ABSTRACT TRUNCATED AT 250 WORDS)
Little attention has been paid to the changes in renal function that occur after kidney transplantation when donor and recipient differ markedly in size. We studied this phenomenon after isogeneic kidney transplantation in rats of varying body weight (BW). Renal functional parameters, such as the glomerular filtration rate (GFR), the effective renal plasma flow (ERPF), and the plasma levels of creatinine (Pcr) and urea (Pur) were determined at regular intervals following transplantation. In the initial experimental series, juvenile (BW approximately 150 g) and adult (BW approximately 300 g) rats were used. Four groups of transplant recipients were studied. These consisted of 2 groups of adult recipients of juvenile or adult donor kidneys, and 2 groups of juvenile recipients of juvenile or adult donor kidneys. These 4 groups were compared with adult and juvenile control rats, as well as with unilaterally nephrectomized (NX) rats. A comparison between the 2 groups of juvenile recipients revealed no significant difference in the GFR, ERPF, Pcr, or Pur levels after the transplantation of adult or juvenile donor kidneys. Nor were any significant differences found when comparing the functional parameters of the 2 groups of adult recipients after transplantation of adult or juvenile donor kidneys. The transplanted kidneys generally functioned at a level amounting to 80-90% of the GFR and 90-100% of the ERPF of NX rats of comparable BW. These observations are a clear indication of functional adaptation after kidney transplantation. The compensatory functional response is augmented--in case of a young donor kidney transplanted into an adult recipient, or attenuated--in case of an adult donor kidney transplanted into a juvenile recipient. In an additional experiment, kidneys were transplanted from very young rats (BW approximately 50 g) to adult recipients. It appeared that as early as two weeks after transplantation, renal function had reached adult kidney levels, as observed in the first experimental series. In conclusion, after isogeneic kidney transplantation in rats, the transplanted kidney generally adapts rapidly to the size of the recipient and functions like an inherent part of the recipient's body.
A group of 80 female retired breeder inbred Brown Norway (BN) rats with recorded breeding histories was followed for 150 weeks with regard to spontaneous occurrence of tumors. The median survival time of the whole group was 134 weeks. Ninety tumors (42 benign tumors, 23 sarcomas, and 25 carcinomas) were found in 64 animals. Compared with previous findings on virgin female BN rats, the retired breeders used in the present study had a strikingly higher incidence (34%) of tumors of the genital system but a lower incidence (4%) of breast tumors. The breeding histories revealed no relationship between the recorded number of litters, number of newborns, age of the mother at the time of her first litter, preweanling mortality, and the occurrence of cancer or survival in general. Although all animals were kept under identical environmental conditions, animals born in the period July-December appeared to have a lower incidence of utero-vaginal tumors than animals born in the first half of the year. The growth rates of 32 tumors inoculated into syngeneic rats were monitored for 26 weeks. They did not correlate with the histopathologic characteristics of the specific tumor. Malignant or benign tumors showed the same growth variability.
The effects of feeding saturated and eucaloric unsaturated fat-rich diets on lipemia and insulinemia in female Brown Norway rats have been compared. The relative hyperlipemia in the unsaturated fat group at 8 a.m. has declined at 10 a.m., whereas the saturated fat group at 8 a.m. gives lower values than at 10 a.m. It suggests that saturated fat feeding requires a longer absorption period. The insulin levels in the unsaturated fat groups are higher at 8 a.m. than at 10 a.m., whereas insulin levels in the saturated fat group are higher at 10 a.m. than at 8 a.m. It also suggests retarded resorption of food in the saturated fat group. The relative hyperlipemia at 10 a.m. in the saturated fat group applies to triacylglycerol, free cholesterol, free fatty acids and particularly phosphatidylcholine. It was almost 50% higher than phosphatidylcholine in the unsaturated fat group and coincided with the accumulation of an apolipoprotein E-rich high density lipoprotein.
In 65 replantations and 18 free tissue transfers (6 toe-to-thumb and 12 free flaps) transcutaneous oxygen levels were used as a postoperative monitoring system of the microcirculation. In successful replants and successful free tissue transfers an identical pattern of oxygen levels was observed. In failing replants or free tissue transfer, PO2 levels react immediately to changes in microcirculation and these changes in PO2 appear several hours earlier than the clinical symptoms or changes in temperature. This enables salvage operations after circulatory failure caused by thrombosis to be performed before irreversible tissue damage occurs.
A model was developed to study post-transplant hypertension after allogeneic kidney transplantation between two inbred normotensive rat strains. Prolongation of graft survival was achieved by 'active immunological enhancement'. Renal function, systolic blood pressure and plasma renin concentration were determined. The systolic blood pressure started to rise in the second week after allogeneic transplantation. The glomerular filtration rate was impaired to a greater extent than the effective renal plasma flow. Histopathological changes occurred indicating immunological reactions in the renal graft. The plasma renin concentration was lower in transplant recipients than in controls. We hypothesize that retention of sodium is mediately involved in the post-transplant hypertension observed in this model.