Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.     

Measurement of free and total hydroxyproline by automated flow injection of serum or urine samples from maintenance hemodialysis patients with renal osteodystrophy

An automated measurement of total and free hydroxyproline in serum or urine is presented that uses flow injection analysis. After exclusion of nonspecific substances, hydroxyproline was oxidized by chloramine- T and L-cysteine with Ehrlich's reagent. The linearity obtained was from 3.8μmole/ L to 1.22 mmole/L with good precision (CV <3%). Comparison of the proposed method with HPLC yielded r = 0.939 as the correlation coefficient. Reference intervals of free and total hydroxyproline are 1.4–9.7 μmole/L, 3.8–27.2 μmole/L for serum, and 10.0–72.5 μmole/L, 25.2–303.6 μmole/L for urine, respectively. Serum free and total hydroxyproline levels in renal osteodystrophy patients on maintenance hemodialysis (N = 71) were significantly higher than in controls (P<0.0001). This method is superior to the use of HPLC with regard to stability of the color reaction. The measurement of serum free and total hydroxyproline is a useful marker for therapeutic observation of renal osteodystrophy patients. © 1994 Wiley-Liss, Inc.     

Operative results with total composite replacement of the aortic valve and ascending aorta]

From December 1980 to December 1990, ten patients, 9 male and 1 female, ranging in age from 21 to 68 years, were operated on for aortic valve insufficiency associated with an aneurysm of the ascending aorta. The surgical treatment in all cases consisted of total replacement of the ascending aorta with Bentall's procedure (n = 4), or Cabrol's procedure (n = 6). In 5 patients an uncomplicated annulo-aortic ectasia existed. Three of them had annulo-aortic ectasia with an aortic dissection. One had aortitis syndrome, and one had syphilitic aortitis. The operative mortality for the entire group was 0% (0 death). Hospital survivors revealed satisfactory clinical improvement in NYHA class (mean value: 3.2 to 1.0). Late complications developed in 2 of the 10 patients. They had a picture of pseudoaneurysm formation at the anastomoses between the graft and the right coronary 46 months and 15 months, respectively, after the initial operation. Despite the reoperation, one died of hepatic failure 30 days after the operation, and the other died of postoperative bleeding at the anastomosis sites. We, furthermore, considered the difference in aortic cross clamp time and cardiopulmonary bypass time between Bentall's procedure and Cabrol's procedure. Aortic cross clamp time and cardiopulmonary bypass time were significantly shorter in Cabrol's procedure than in Bentall's procedure, if a probability value less than 0.20 was considered to be of statistical significance. We were able to conclude that the treatment of aortic valve regurgitation associated with an aneurysm of the ascending aorta by insertion of a composite graft is a reliable method with low operative mortality and excellent long term results, especially in Cabrol's procedure.     

Serum sialyl Tn antigen as a prognostic marker in patients with epithelial ovarian cancer]

Circulating serum sialyl Tn (STN) antigen levels were measured in 89 patients with epithelial ovarian cancer, 157 benign disease, and in 126 healthy controls. Serum antigen levels were increased in 48.3% of patients with ovarian cancer. The false positive rate is significantly low (4.0% in healthy controls and 9.6% in benign disease). The levels of STN antigen were significantly higher in sera of patients with cancer than in those in benign and healthy controls (p less than 0.05). The rise in serum STN antigen levels correlated to the size of the primary tumors. Of the histological type, it is interesting to note the high sensitivity in mucinous-type ovarian cancer. Survival at 1, 2, 3, 4 and 5 years for patients with STN-negative (serum STN levels less than 50 U/ml) versus STN-positive (serum STN levels greater than or equal to 50 U/mol) was 96.2, 92.3, 86.5, 82.7, and 76.9% versus 59.5, 29.7, 18.9, 10.8, and 10.8%, respectively (p less than 0.05). The overall survival probability was worse in patients with STN-positive sera. Percent progression-free survival at 1, 2, 3, 4 and 5 years for patients with STN-negative versus STN-positive was 90.4, 86.5, 76.9, 59.6, and 51.9% versus 35.1, 16.2, 8.1, 8.1, and 5.4%, respectively (p less than 0.05). The overall progression-free period of survival was shorter in patients with STN-positive sera. Multivariate regression analysis revealed that positive STN, stage, PS and histologic grade were the four variables of most importance in predicting survival. These results indicate that a positive STN antigen level in sera is an independent predictor of poor prognosis in ovarian cancer.     

Effects of a new immunosuppressive agent, FK 506, on the efferent limb of the immune responses.

The effects of a novel immunosuppressant, FK 506, on the efferent limb of the immune response were studied in the experimental autoimmune uveoretinitis (EAU) in the rat, using two different treatment schedules. First, rats actively immunized with S-antigen were treated with FK 506 only after the onset of EAU. FK 506 (1 or 3 mg kg-1 day-1) reduced the intensity of EAU as compared to that of non-treated rats. Especially, a daily dose of 3 mg kg-1 completely suppressed further development of EAU. It is, therefore, suggested that FK 506 treatment is effective in suppressing the ongoing process of the immune response, even after the disease has been initiated. Second, FK 506 (0.3 mg kg-1 day-1) was given only to the recipient rats which received IRBP-sensitized lymphocytes. None of FK 506-treated recipients developed EAU, while all control recipients developed the disease approximately 4 days after the cell transfer. The immune responses of FK 506-treated rats in the two experiments were also significantly suppressed. The antibody levels to S-antigen, the antigen-specific proliferative responses of lymphocytes, and even the proliferative responses to Con A were markedly suppressed in the rats in which FK 506 was given only during the efferent limb of the immune response.     

Effects of minaprine and sulpiride injected into the amygdaloid nucleus on the duration of immobility in rats forced to swim

We examined the effects of minaprine and sulpiride injected into the medial amygdaloid nucleus on the duration of immobility in rats forced to swim. Minaprine (50 micrograms/microliter) significantly reduced the duration of immobility, while sulpiride (50 micrograms/microliters) remarkedly enhanced it. These results suggest that the medial amygdaloid nucleus might be involved in the suppressive effect of minaprine on the duration of immobility, as was seen with the tricyclic antidepressants. The pattern of behavior seen with sulpiride administrations differs considerably from that seen with the tricyclic antidepressants.     

Uptake and biotransformation of sevof lurane in humans: A comparative study of sevof lurane with halothane, enflurane, and isoflurane

Study Objective: To compare the volatile anesthetic sevoflurane with halothane, enfurane, and isof urane on the uptake and biotransformation in humans.

Design: Prospective pharmacokinetic study of sevofurane administration in human subjects.

Setting: Inpatient surgery clinic at a university medical center.

Patients: Thirty-two Japanese patients, free of systemic diseases, undergoing minor elective surgery with endotracheal general anesthesia.

Interventions: The patients were assigned randomly to one of four groups: halothane, enflurane, isofurane, or sevofurane. One of the four volatile anesthetics being investigated [equivalent to 1.1 minimum alveolar concentration (MAC): halothane, 0.85%; enfurane, 1.85%; isofurane, 1.27%; and sevofurane, 1.88%; in inspired concentrations throughout the first hour of anesthesia] was administered for 60 minutes.

Measurements and Main Results: In all patients, serum and urinary fluoride concentrations were measured. The concentrations of all gases were measured separately with a mass spectrometer. The cumulative uptake of each anesthetic agent during a certain period was calculated as an integration of the uptake rate per minute. The results for one-hour inhalation of sevofurane (1.1 MAC) showed an uptake (corrected for body surface area and MAC) of 490 ml/m²/MAC and estimated degradation rate of 3.3%. For purposes of comparison, similar studies of halothane (uptake, 653 ml/m²/MAC; degradation rate 15.7%), enfurane (1150 ml/m²/MAC; 1.3%), and isofurane (439 ml/m²/MAC; 0.6%) were also conducted. Sevofurane had a peak serum inorganic fluoride concentration of 19.3 μmol/L, and no abnormality in hepatic or renal functions was observed in any of the subjects during the two weeks postoperatively.

Conclusions: Accurate determinations of uptake and degradation rate for sevoflurane and three other volatile anesthetics in Japanese patients were obtained. These findings have established that, despite its relatively large MAC *1.71%), sevoflurane has a small uptake due to its low solubility. However, the degradation rade was shown to be as high as 3.3%, resulting in a higher serum fluoride concentration than seen after administration of isoflurane, halothane, and (possibly) enflurane.     

Rare Case of Small-Cell Carcinoma Arising from the Endometrium with Paraneoplastic Retinopathy

We present the fourth known case of endometrial carcinoma, and the second case of endometrial small-cell carcinoma, to be associated with paraneoplastic retinopathy. Initial symptoms were decreased visual acuity and a narrowing of the visual field. Endometrial carcinoma was diagnosed several months later. An antibody to 34-kDa bovine retinal antigen was detected in the patient's serum. Thus, autoimmunity was suspected as the cause of the retinopathy. In patients with endometrial carcinoma with visual disturbance of unknown cause, paraneoplastic retinopathy should be suspected.