Evaluation of international normalized ratios by a controlled field survey with 4 different thromboplastin reagents.

A nationwide survey has been performed in Japan involving 75 laboratories to assess the relative reliability of different methods of reporting prothrombin time results in anticoagulant control. The interchangeability of results using prothrombin time, prothrombin activity percentage, prothrombin ratio and international normalized ratios (INR) were compared with four different thromboplastin reagents and a range of coagulometers. A secondary batch of reference thromboplastin of human brain origin (BCT/454) was used to calibrate the local thromboplastins and for comparison of methods of reporting. The study revealed the closest agreement of the results between BCT and the other reagents, and the regression lines of these reagents were almost identical, when the results were reported as INR. Box-Whisker plot analysis showed that the distribution of the results was large with the more deficient plasmas with all methods of reporting. It was found by this analysis that the interchangeability of the results was greatest when the results were expressed by INR, because the mean values obtained of each plasma using different thromboplastin reagents gave the lowest CV and the frequency of the far-out data was least, compared with the other methods of expression. On the other hand, the type of coagulometer had almost as much effect as the thromboplastin reagent on the prothrombin time, even if INR was used. Interchangeability of INR would be further improved by providing ISI values for each reagent/instrument combination.

Suppression of the secretion of atrial and brain natriuretic peptide after total cavopulmonary connection.

OBJECTIVES: Among the modifications of the Fontan operation currently being used, total cavopulmonary connection offers the greatest potential for optimizing early and long-term postoperative outcomes. Although studies have established that abrupt increases in right atrial pressure elevate the plasma atrial natriuretic peptide level after the Fontan procedure, changes in plasma natriuretic peptide levels after total cavopulmonary connection have not been clarified. Our hypothesis is that secretion of atrial natriuretic peptide may be suppressed in patients undergoing total cavopulmonary connection because the atrium continues to function at low pressure in those patients. In this study, we measured plasma levels of atrial and brain natriuretic peptide before and during the postoperative period in patients undergoing total cavopulmonary connection. METHODS: We evaluated 60 patients: 30 patients underwent total cavopulmonary connection and 30 patients underwent definitive repair for Fallot's tetralogy. Blood samples for measurement of atrial and brain natriuretic peptide were obtained before the operation and in the postoperative period. RESULTS: Plasma levels of atrial and brain natriuretic peptide were significantly lower during the early postoperative period in patients undergoing total cavopulmonary connection than in patients undergoing definitive repair for Fallot's tetralogy. No correlations were identified between the atrial natriuretic peptide levels and central venous pressure after total cavopulmonary connection. CONCLUSION: These results suggest that total cavopulmonary connection attenuates the secretion of atrial and brain natriuretic peptide in the early postoperative period. The suppressed release of atrial and brain natriuretic peptide after total cavopulmonary connection may have clinical importance.

Reference values of hemostasis related factors of healthy Japanese adults. I: Circadian fluctuation.

The circadian fluctuation of hemostasis related parameters was examined on 16 healthy Japanese adults (male 9, female 7). Twenty one parameters were measured in this study, i.e. fibrinogen, the activity of F.II, F.V., F.VII, F.VIII, F.IX, F.X., F.XI, F.XII, antithrombin III, plasminogen, alpha 2-antiplasmin, as well as the antigen level of F.IX, von Willebrand Factor, protein C, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, plasmin-alpha 2-antiplasmin complex and FDP. Fluctuation was not significant in almost all of the parameters except F.VIII, F.IX, beta-thromboglobulin, platelet factor 4, tPA and PAI-1. Although the fluctuations of F.VIII, F.IX, beta-thromboglobulin and platelet factor 4 were statistically significant, they remained within the normal ranges. On the other hand, tPA and free PAI-1 showed significant circadian fluctuation, of which levels were highest at 9:00. It was postulated that the significant circadian fluctuation of fibrinolytic activity will be regulated by the balance between tPA and PAI-1 in plasma.

The geographic origin of the plants most commonly used for medicine by Hawaiians.

Twelve common Polynesian plants, 8 of which were probably brought in the canoe voyages perhaps 1500 years ago from southern and central Polynesia, constitute the most commonly used plants by Hawaiians for medicinal purposes. Herbal treatments of the most frequently encountered illnesses or physical conditions--purge or constipation, skin affections, respiratory affections, indigestion, fever, bruises and sprains--were tallied from all available sources. The herbs most frequently used are common species, grown around habitations and in adjoining agricultural fields. The hypothesis is advanced that while the Hawaiian Islands contain one of the world's largest percentages of endemic species in the flora, only a few of these species were used for illnesses, though many endemic species were used for building, tapa making, and the foundation of the elaborate and renowned feather cloaks. Owing to approximately 1200 years of geographic isolation, the Hawaiians probably did not find it necessary to exploit the native flora for more than a token number of species for their relatively mild illnesses.

Cholesterol, phytosterol and polyunsaturated fatty acid levels in 1982 and 1957 Japanese diets.

The dietary intake of cholesterol, phytosterol and PUFA in Japanese was investigated to obtain information on dietary parameters related to coronary artery disease. Three daily menus for both 1957 and 1982 were prepared based on the daily per capita consumption of foods and nutrient intakes from national surveys. From 1957 to 1982, the average daily intake of cholesterol rose 2.1-fold from 183 to 376 mg while that of phytosterol remained at about 373 mg. Daily intakes of total fatty acid (19.2 g), PUFA (7.3 g), MUFA (5.8 g) and SFA (6.1 g) in 1957 increased in 1982 to 48.7 g, 11.9 g, 19.5 g and 17.3 g, respectively. The ratio of PUFA/SFA decreased to 56% from 1.23 in 1957 to 0.69 in 1982 and the PUFA/MUFA ratio also decreased to 48%. The PUFA/cholesterol ratio was lower in 1982 (31.8) than in 1957 (42.6), and the decrease in the phytosterol/cholesterol ratio to 46% was greater than that in the PUFA/cholesterol ratio (which only fell to 75% of the 1957 value). Thus, comparison of the 1982 and 1957 intakes indicated the increase in risk factors, cholesterol and SFA intake, and the decrease in the ratio of PUFA/SFA in the Japanese population during the past few decades.

[Study on changes of serum vitamin K1 level and K dependent coagulation factors in patients with coumarin derivatives (warfarin) therapy].

Serum level of vitamin K1 (= phylloquinone, hereinafter K1) and K dependent blood coagulation factors were determined by HPLC in normal subject, liver cirrhosis, hepatocellular carcinoma, acute hepatitis, chronic hepatitis, chronic renal failure with hemodialysis and patients under warfarin therapy. Normal range of serum K1 concentration was decided on 0.20-2.30 (0.87 +/- 0.53, n = 96) ng/ml. Serum K1 level showed no significant differences among normal subject, various diseases and warfarin therapy. Correlation between serum K1 level and F-VII (r = 0.879, p less than 0.001) or protein C activity (r = 0.839, p less than 0.01) was found in patients whose thrombotest was 20% and less. However serum K1 level didn't correlate with any K dependent coagulation factors in patients if thrombotest was over 20%.

[Proceedings of the workshop "The future aspect of clinical hematology laboratory and the role of medical technologists"].

In the workshop of the 34th in-service training course for University Hospital Medical Technologists in 2000 sponsored by the Ministry of Education, all participants discussed future aspects of the clinical hematology laboratory and the role of medical technologists. We report here a summary of the discussion.

[Evaluation of routine blood cell counts in predicting the mobilization of CD34 positive cells].

The collection of peripheral blood stem cells (PBSC) is a crucial step for successful PBSC transplantation. Routine hematological parameters utilized for predicting the optimal timing of collection include white blood cell (WBC) counts, high fluorescence ratio (HFR) of reticulocytes, and platelet counts. We compared these parameters with the CD34-positive rates in the peripheral blood. In regimen with high-dose chemotherapy where the WBC count at nadir was lower than 1,000/microliter, we found that the maximum mobilization of PBSC was observed on the day when the WBC count reached 10,000/microliter. This coincidence was within about one day (mean 0.44, standard deviation 0.53). However, the reliability of the WBC count as a marker of PBSC mobilization varied among different harvest regimens. In the regimen with regular-dose chemotherapy where the WBC count at nadir was above 1,000/microliter, we could not find such a tight coincidence between the WBC count and PBSC mobilization. These results suggested that, in some situations, the measurement of the CD34-positive rate is mandatory for an efficient PBSC collection. We also found that the number of CD34-positive cells in the peripheral blood correlated (x) well to the amount of the CD34-positive cells actually harvested (y) (y = 0.524x + 0.249, r = 0.787). Thus, rapid fluorescence activated cell sorter (FACS) analysis of peripheral CD34-positive rates seemed to be extremely useful to predict the yield of PBSC collection.

[Laboratory diagnosis of congenital thrombophilia].

We examined the incidence of thrombophilia in deep vein thrombosis (DVT). Of 38 cases, we found 4 cases of protein C abnormality, 2 cases each of protein S abnormality and lupus anticoagulant, 1 case of antithrombin III abnormality. The total incidence was 23.7%, whereas only 2 cases (6.2%) of plasminogen abnormality were found among 32 healthy individuals. The incidence of thrombophilia was apparently higher among patients with DVT than that of healthy subjects, although the incidence of Japanese DVT was lower than that of Caucasian DVT, as previously reported. By SSCP analysis in one case of protein C abnormality, we demonstrated an abnormality of exon 9-3. To establish laboratory diagnosis of thrombophilia, it is recommended that (1) severe liver diseases, DIC, and oral anticoagulant be ruled out, (2) abnormality be confirmed by repeated examination, (3) family study determine inheritance mode, if possible. It was strongly suggested that laboratory examination of thrombophilia should be routinely applied to cases of venous thrombosis including DVT, not only for diagnostic interest but also for appropriate treatment of these cases.

[Analysis of hemostatic abnormality in various disease using molecular-I. Liver disease].

We examined the hemostatic abnormality of liver disease using hemostatic molecular markers, i.e. TAT, FPA and SFMC for coagulation, B beta 15-42, FDP, D dimer and PIC for fibrinolysis, t-PA and TM for vessel wall. The molecular markers for coagulation were generally increased in cases of liver disease, which was most sensitively reflected by FPA. On the other hand, it was postulated that SFMC was a marker reflecting the complication of DIC in these cases. Hyperfibrinolysis of liver disease was sensitively reflected by the increase of B beta 15-42, and an occasional increase of SFMC or FDP was thought to indicate the complication of DIC in these cases. A high correlation was found between t-PA and TM. It was postulated that the increase of the both markers in liver disease was due to deteriorated clearance by liver dysfunction, although TM is regarded as a marker reflecting endothelial injury. It was expected that visualization of hemostatic disorder of liver disease was made practical with the use of radar chart of these molecular markers.

[Midterm results of bilateral enlargement of the aortic valve ring for valve replacement].

From 1989, 4 patients underwent bilateral enlargement of the aortic valve ring for valve replacement. Age at the operation ranged from 2 to 8 (mean 6) years; body weight ranged from 14.9 to 25.4 (mean 19.0) kg. This procedure enabled us to implant a prosthesis 3 to 4 sizes larger (19 to 23 mm) than that measured with the native aortic annulus (13 to 17 mm). There was no late death and no cardiac event over a mean follow-up period of 6.2 years. Pressure gradient across the prosthesis measured by echocardiography was 40 mmHg in 1 patient who underwent aortic valve replacement with the use of 19 mm St. Jude Medical valve at 2 years of age. There was no significant pressure gradient in other 3 patients. All patients showed normal left ventricular function. We conclude that bilateral enlargement of the aortic valve ring for valve replacement has provided good midterm results with no mortality and no cardiac event.

Enhanced vertical alveolar bone augmentation by recombinant human bone morphogenetic protein-2 with a carrier in rats.

This study aimed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on vertical bone regeneration of edentulous ridge. Bilateral upper first and second molars of 8-week-old Wistar rats were extracted and the ridges were allowed to heal for 3 weeks. Compressed poly(lactic-co-glycolic acid) copolymer/gelatin sponge (PGS) was used as a carrier of rhBMP-2. PGS alone (control group) or PGS with 5 mug rhBMP-2 (test group) was implanted at the top part of alveolar ridge. The sham group received no implantation. The rats were killed at 1, 2, 4, 8 and 12 weeks after implantation and examined histologically and histomorphometrically. In the test group, significant bone augmentation was evident on the alveolar ridge throughout the experimental period. Histomorphometric analysis revealed greater tissue volume and height of alveolar bone in the test group compared with the control and sham groups (P < 0.05) from 4 weeks onward and the augmented tissues (5 mm3 in tissue volume and 1.5 mm in bone height) were maintained until 12 weeks. Osteoblast surface increased at 2 and 4 weeks and osteoid thickness reached a peak (25 microm) at 2 weeks. Dynamic variables, which represented calcification, were higher in the test group than the control and sham groups at 4 and 8 weeks (P < 0.05). These results suggest that use of rhBMP-2/PGS may achieve vertical bone augmentation, and stabilizes denture prosthesis or makes up for inadequate bone mass for implant prosthesis.

Malignant schwannoma treated by Mohs surgical excision.

A 34-year-old white female with a 5-cm malignant schwannoma of the upper thigh underwent complete removal of the tumor by fresh-tissue Mohs surgical excision. The patient refused postoperative radiotherapy, and is without signs of recurrence 5 years after surgery. Mohs surgical excision in the treatment of malignant schwannoma has not to our knowledge been reported previously.