Tranexamic acid: Preoperative prophylactic therapy for patients with hereditary angioneurotic edema

Short-term therapy of 96-hr duration with tranexamic acid was prophylactically effective as defined by the absence of attacks of angioedema in 14 patients with hereditary angioedema undergoing 10 dental and 4 general surgical procedures. Eight of the 14 patients had previously undergone dental extractions without prophylactic therapy with antifibrinolytic agents and each had experienced one or more attacks of angioedema. Seven of these 8 patients had a cumulative experience of 13 episodes of laryngeal edema after dental extractions and the eighth had a bout of cutaneous angioedema. Although the number of dental extractions conducted without prophylactic antifibrinolytic therapy cannot be accurately defined in retrospect, the prominence of laryngeal edema in this circumstance is striking when compared with the absence of attacks in the presence of prophylaxis with tranexamic acid. Methyltestosterone and impeded androgens are now known to be effective prophylaxis for spontaneous and, presumably, postoperative attacks when employed chronically because their administration is associated with correction of the biochemical defect of hereditary angioneurotic edema, but their chronic administration to children and women of childbearing age requires further definition because of their potential pituitary suppressive action. Tranexamic acid prophylaxis makes it possible to offer to untreated patients with hereditary angioneurotic edema dental work and other operative procedures that in the past were withheld or conducted with considerable risk.     

Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only 5 of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extrathyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.     

Syngeneic mixed lymphocyte reactions to murine Fc receptor-bearing, nonadherent low density lymph node cells and epidermal Langerhans cells

Both Langerhans cells from BALB/c mouse epidermis and nonadherent, low density (LD) cells, obtained from collagenase-treated minced lymph node, are stimulatory for isolated T cells in syngeneic mixed lymphocyte reaction (SMLR). The method of preparation of LD cells influences whether Fc receptor (FcR) can be detected on them. Fc receptors on nonadherent LD lymph node cells can be detected only if the same procedure is employed as that for Langerhans cell isolation, i.e., Ig-free bovine albumin must be used during gradient centrifugation and EA rosetting must be done overnight at 4 degrees C. Thus, both FcR+ and FcR- LD lymph node cells, as well as FcR+ Langerhans cells, stimulate SMLR. Although Ig+ cells in the LD fraction also stimulate the SMLR, their removal does not affect the stimulating capacity of the LD lymph node fraction.     

Assessment of donor liver steatosis: pathologist or automated software?

Steatosis in donor liver biopsy specimens has been shown to correlate with graft dysfunction after orthotopic liver transplantation. This 2-part (laboratory pilot, clinical retrospective) study compared the traditional interpretation of steatosis by a pathologist with an automated measurement determined by an image analysis system. In our pilot study, Sprague-Dawley rats were studied prospectively by feeding them a choline-deficient diet for up to 7 days. In our clinical group, data from 49 consecutive recipients of cadaveric liver transplantation were reviewed retrospectively. In both studies, the percentages of microvesicular fat, macrovesicular fat, and total fat content within liver biopsy specimens were determined by an automated image analysis software program and a pathologist using the same set of slides. The association between fat content of the donor liver and patient survival and graft survival, along with levels of aspartate aminotransferase, alanine aminotransferase, prothrombin time, and total bilirubin after transplantation, were also examined in the clinical study. A direct correlation was observed between levels of macrovesicular fat determined by a pathologist and the automated software using livers from rats fed a choline-deficient diet and livers from deceased donors. A significant association was observed between macrovesicular fat content in the donor liver biopsy and graft survival by both techniques. We conclude that an image analysis system can be used to automate the determination of fat content in liver biopsy specimens, and that its findings correlate with both the visual interpretation by a pathologist and graft survival. Further study is needed to determine the role of an automated technique in the evaluation of donor livers for transplantation.     

Nonenzymatic glycosylation of proteins and protease activities in granulation tissues in experimental diabetes

Serum proteins and hemoglobins show increased nonenzymatic glycosylation in diabetes mellitus. The measure of glycosylated proteins, particularly hemoglobin, is considered to be a preferred indicator in the control of diabetes. In a study of diabetes and inflammation, we assessed the extent of nonenzymatic glycosylation of proteins of granulation tissue from diabetic rats. Five, seven, and ten days after carrageenan injection, the granuloma proteins were extracted. Nonenzymatic glycosylation was measured in soluble and insoluble granuloma proteins by thiobarbituric acid assay. Protease activities and free amino groups were assayed in soluble extracts. Nonenzymatic glycosylation in soluble proteins of both groups reached a maximum on the seventh day. However, nonenzymatic glycosylation in soluble proteins of the diabetic granulomas was significantly greater than the controls on days five and seven. During the days after granuloma induction, nonenzymatic glycosylation in the insoluble granuloma tissue proteins gradually decreased without any significant differences between controls and diabetics. Significant decreases in the free amino groups in soluble proteins of the diabetic tissues were noted. Greater activities of cathepsins B and D were noted in diabetic tissues over controls. These observations suggest that, in addition to increased proteolysis, increased nonenzymatic glycosylation of tissue proteins could be associated with the impaired process of wound healing in diabetics.     

Effects of model traumatic injury on hepatic drug metabolism in the rat. IV. Glucuronidation

A previously validated small mammal trauma model, hind-limb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on hepatic glucuronidation activity. As was previously observed with hepatic oxidative drug metabolism, model trauma resulted in a significant decrease in the in vivo glucuronidation of chloramphenicol, with a 23% drop in clearance of this drug. The effect on in vivo pharmacokinetics appeared to result from a complex interaction between trauma's differential influences on conjugating enzyme(s), deconjugating enzyme(s), and hepatic UDP-glucuronic acid levels, as well as the relative physiological importance of these variables. Hepatic UDP-glucuronyltransferase activities towards both p-nitrophenol and chloramphenicol were elevated (44-54%) after model injury when measured in native hepatic microsomes. However, microsomes which had been "activated" by treatment with Triton X-100 showed no significant difference between control and traumatized animals. Serum beta-glucuronidase activities were elevated by 58%, while hepatic beta-glucuronidase rose by about 16%. Nevertheless, in vivo deconjugation showed no significant change. Model trauma also resulted in a 46% decrease in hepatic UDP-glucuronic acid content. Thus, the observed post-traumatic depression of in vivo chloramphenicol glucuronidation could be due either to a diminished availability of a necessary cofactor (UDP-glucuronic acid) or to an alteration in enzyme kinetics or function in vivo.     

Is an aggressive surgical approach to the patient with gastric lymphoma warranted?

At the Mayo Clinic, from 1970 through 1979, 84 patients (52 males and 32 females) had abdominal exploration for primary gastric lymphoma. All patients were observed a minimum of 5 years or until death. The histologic findings for all 84 patients were reviewed. Forty-four patients had "curative resection," and 40 patients had either biopsy alone or a palliative procedure. The probability of surviving 5 years was 75% for patients after potentially curative resection and 32% for patients after biopsy and palliation (p less than 0.001). The operative mortality rate was 5% overall and 2% after potentially curative resection. Increased tumor size (p less than 0.02), increased tumor penetration (p less than 0.01), and lymph node involvement (p less than 0.02) decreased the probability of survival, whereas histologic classification did not affect survival. Radiation therapy after surgery did not significantly affect the survival rate for the entire group or the survival rate for patients who had potentially curative resection. Resectability was associated with increased patient survival--independent of other prognostic factors--when our experience was analyzed by the Cox proportional-hazards model (p less than 0.005). It was concluded that an aggressive surgical attitude in the treatment of primary gastric lymphoma is warranted. The role of radiotherapy remains in question.