The efficacy of predeposited autologous blood transfusions in general pediatric surgery.

Allogeneic blood transfusions are associated with a risk of infection, immunological reactions, immunosuppression, and the induction of antibodies in blood cells. We report our results of giving predeposited autologous blood transfusions (PABT) to children when it was anticipated that transfusions would be required for an elective operation. Autologous blood was collected for deposit from 16 patients ranging in age from 1 to 11 years old (mean 5.6 years old, mode 4 years old), and weighing from 9.7 to 42 kg (mean 20.8kg). They included 12 patients with pectus excavatum (funnel chest) and 4 patients with choledochal cyst (CBD). Blood was collected once from 2 patients and twice from the other 14 patients, then centrifuged and stored in a freezer at -80 degrees C. Between 7 and 14 ml/kg was collected at one time, the total mean volume of predeposited blood being 21.0 +/- 3.3 ml/kg for the children operated on for funnel chest, and 16.2 +/- 4.5 ml/ kg for those operated on for CBD. None of the patients required allogeneic transfusions and no complications occurred. PABT was found to be a safe and effective means for elective general pediatric surgical procedures for avoidance of allogeneic blood transfusion.

Hypocholesterolemic effect of soymilk supplementation with usual diet in premenopausal normolipidemic Japanese women.

BACKGROUND: The hypocholesterolemic effect of soy protein concentrates on normolipidemic subjects still remains unclear. Our objective is to assess the effect of soymilk supplementation, a whole soy product, with usual diet on serum lipids in normolipidemic subjects. METHODS: We conducted a randomized controlled trial on 60 premenopausal normolipidemic Japanese women. After excluding 8 subjects whose initial serum concentration of total cholesterol or triacylglycerol was higher than 220 mg/dL (5.69 mmol/L) or 160 mg/dL (1.81 mmol/L), respectively, we encouraged the subjects in the soymilk-supplemented group (n = 27) to consume 400 mL (408 g) of commercial regular soymilk daily during two menstrual cycles. There were no significant differences in variables, including nutrient intake, between the soymilk-supplemented and control (n = 25) groups before the intervention. RESULTS: After the trial, we observed a significant decrease of 10.9 mg/dL, or 5.3%, in serum concentration of total cholesterol in the soymilk-supplemented group. During the intervention, nutrient intake assessment showed significant increases in nutrient densities of vitamin E, polyunsaturated fatty acids, isoflavones, and P/S ratio and decreases in total energy and nutrient densities of vitamin C and green tea in this group. A statistically significant decrease in serum total cholesterol could still be observed even after excluding the estimated hypocholesterolemic effects of soymilk's polyunsaturated fatty acids. CONCLUSIONS: Our results suggest the hypocholesterolemic effect of soymilk, a traditional whole soy product, in Asian countries in normolipidemic subjects.

11beta-hydroxysteroid dehydrogenase in human vascular cells.

Aldosterone selectivity in mineralocorticoid target tissues is mainly due to 11beta-hydroxysteroid dehydrogenase (11betaHSD), which converts cortisol to its inactive metabolite cortisone in humans. The defect of dehydrogenase activity would thus allow type 1 mineralocorticoid receptor (MR) to be occupied mostly by cortisol. It has been postulated that 11betaHSD type 2 (11betaHSD2) plays a significant role in conferring ligand specificity on the MR. We have demonstrated the diminished dehydrogenase activity in resistance vessels of genetically hypertensive rats. However, the mechanism that could link impaired vascular 11betaHSD activity and elevated blood pressure has been unclear. In this study, we showed the enzyme activity in human coronary artery smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by up-regulating the receptors of pressor hormones such as angiotensin II (Ang II). Next, we found that physiological concentrations of a cortisol-induced increase in Ang II binding were significantly enhanced by the inhibition of dehydrogenase activity with an antisense DNA complementary to 11betaHSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired dehydrogenase activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11betaHSD deficiency and after the administration of 11betaHSD inhibitors, suppression of dehydrogenase activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. These results show that vascular 11betaHSD activity could influence blood pressure without invoking renal sodium retention.

11beta-hydroxysteroid dehydrogenase in cultured human vascular cells. Possible role in the development of hypertension.

11beta-Hydroxysteroid dehydrogenases (11beta-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. The diminished dehydrogenase activity (cortisol to cortisone) has been demonstrated in patients with essential hypertension and in resistance vessels of genetically hypertensive rats. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) catalyzes only 11beta-dehydrogenation. However, a functional relationship between diminished vascular 11beta-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11beta-HSD2 and 11beta-HSD type 1 (which is mainly oxoreductase, converting cortisone to cortisol) in human vascular smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by upregulating the receptors of pressor hormones such as angiotensin II. We found that physiological concentrations of cortisol-induced increase in angiotensin II binding were significantly enhanced by the inhibition of 11beta-HSD2 activity with an antisense DNA complementary to 11beta-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11beta-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11beta-HSD deficiency and after administration of 11beta-HSD inhibitors, suppression of 11beta-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. In the present study we provide evidence for a mechanism that could link impaired vascular 11beta-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention.

Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women.

BACKGROUND: Estrogens have been implicated in the development of breast cancer. Preliminary evidence suggests that consumption of soy products, which contain isoflavones (phytoestrogens), can reduce serum estrogen levels. Our purpose was to determine the effect of soy consumption on serum estrogen levels in premenopausal women by use of a dietary intervention approach. METHODS: Premenopausal Japanese women were randomly assigned to receive either a soymilk-supplemented diet (n = 31) or a normal (control) diet (n = 29). The women in the soymilk-supplemented group were asked to consume about 400 mL of soymilk (containing about 109 mg of isoflavones) daily during a study period that involved three consecutive menstrual cycles. Follicular-phase blood samples were to be obtained in the menstrual cycles preceding (cycle 1) and following (cycle 3) the 2-month dietary intervention. All statistical tests were two-sided. RESULTS: At the end of the study period, estrone and estradiol levels were decreased by 23% and 27%, respectively, in the soymilk-supplemented group and were increased by 0.6% and 4%, respectively, in the control group. The changes for each hormone between the two groups were not statistically significantly different. In the soymilk-supplemented group, menstrual cycle length was increased by nearly 2 days, and, in the control group, it was decreased by approximately 1 day, a difference that was not statistically significant. A subgroup analysis restricted to subjects who provided follicular-phase blood samples on the same day or 1 day apart in menstrual cycles 1 and 3 showed a reduction in serum estrone levels in the soymilk-supplemented group that was of borderline statistical significance (P = .07 for change in serum estrone level in soymilk-supplemented group versus control group). CONCLUSION: Much larger studies will be required to confirm the ability of soy products to reduce serum estrogen levels.

Clinical usefulness of autologous transfusion--history, methodologies and problems with popularization.

Autologous transfusion(AT), using the patient's own blood for replacement during operation, is the most useful blood replacement method, as the blood is a perfect match for the patient. It can prevent alloimmunization and introduced viral infections completely. Predeposition, Hemodilution and Salvage are the three methods of collection. Each has already had sophisticated techniques developed for clinical application. Unfortunately, AT requires extensive man-power and is expensive. For these reasons, AT has been slow to gain popularity in the surgical field in Japan. For popularization of AT to be successful, not only must we have sufficient knowledge to implement these complicated techniques, but we must also build an AT center staffed by several specialists in each hospital.

Unapproved use of high-dose combined pills in Japan: a community study on prevalence and health characteristics of the users.

BACKGROUND: Because of the ban on oral contraceptive use in Japan, only high-dose combined pills (HDCP), permitted as treatment for menstrual disorders, can be used as a contraceptive. We determined the prevalence of the use of such preparations in a community in Japan and assessed the health characteristics of the users. METHODS: A total of 18,435 female residents age 35 years and over in a city of Gifu Prefecture, Japan, responded in 1992 to a health questionnaire that included questions on the use of HDCP, lifestyle, and dietary habits. The response rate was 92%. RESULTS: The rates of current and past HDCP use were 1.3 and 7.1%, respectively, among women ages 35-49 years, and 2.2% of the women had used HDCP for longer than any other method of contraception. Current HDCP users were more likely to be smokers. They had lower intakes of carotene, fiber, and vitamins C and E and a lower polyunsaturated/saturated fat ratio than never-users. CONCLUSIONS: The prevalence of HDCP use was 1.3% among Japanese women ages 35-49 years. Potential risk factors for cardiovascular diseases, such as smoking and a diet with lower intakes of antioxidants, were prevalent among current HDCP users.

Preoperative autologous blood donations in pediatric cardiac surgery.

BACKGROUND: Preoperative autologous blood donation is one of the most effective methods to avoid homologous blood transfusion in cardiac operations. However, there have been few reports about the safety and efficacy of autologous blood donation in children. METHODS: Since 1986, we have instituted a blood conservation program including preoperative autologous blood donations in children. Eighty children as young as 3 years old (mean +/- SD, 8.6 +/- 3.9 years) and weighing as little as 12.3 kg (29.2 +/- 14.5 kg) were enrolled in the program, and 735 +/- 388 mL of blood was donated during an average of 3.1 +/- 1.5 phlebotomies before the operations. RESULTS: Two episodes of mild vasovagal reaction were observed in 2 patients as a complication of the phlebotomy. Seventy-six percent of the collected blood was stored by cryopreservation; the remaining 24% was preserved by liquid storage. Seventy-eight of these patients (97.5%) underwent operations using cardiopulmonary bypass. Seventy-five patients (94%) were operated on successfully without the need for a homologous blood transfusion. As for the other 5 patients, 2 received only platelet concentrate. CONCLUSION: Preoperative autologous blood donation is a safe and effective method to avoid homologous blood transfusion in pediatric cardiac operations.

Effects of a Dan Shen component, magnesium lithospermate B, in nephrectomized rats.

Magnesium lithospermate B, a compound newly isolated from Dan Shen, was given orally to rats for 70 days after excision of five-sixths of their kidney volume. As a result, mesangial proliferation, tubulo-interstitial lesions and glomerular sclerotic lesions, which were conspicuous in rats that were not given magnesium lithospermate B after nephrectomy, were inhibited. Furthermore, a decrease in blood urea nitrogen, improvement of hypoproteinemia, hypoalbuminemia and hypercholesteremia, and inhibition of urinary protein excretion were observed. The levels of creatinine, methylguanidine and guanidino-succinic acid, which accumulate in the blood with the progress of renal failure, were decreased significantly in rats given magnesium lithospermate B. These results indicate that magnesium lithospermate B, a component of an Oriental medicine has potential as a new therapeutic agent for inhibiting the progression of renal dysfunction.

Effects of ginseng in nephrectomized rats.

Ginseng extract and its active component, saponin, were administered orally to nephrectomized rats for 90 d, and changes in blood and urine parameters and renal tissue lesions were assessed. Rats given saponin showed a significant decrease in the concentrations of blood urea nitrogen, creatinine and methylguanidine and a significant increase in total protein and albumin in the blood, with reduce urinary excretion of protein. There was also slight amelioration of the degree of mesangial proliferation, the severity of extratubular lesions and glomerular sclerotic lesions, and the extent of tubular interstitial lesions. However, these histological changes were inconspicuous in nephrectomized rats given ginseng extract.

[Recombinant human erythropoietin (KRN5702) therapy for autologous blood transfusion in patients with rheumatoid arthritis undergoing joint replacement surgery--a multicenter phase II clinical trial].

In order to evaluate the effect of recombinant human erythropoietin (rHuEPO) on autologous blood transfusion in patients with rheumatoid arthritis (RA), we performed a phase II clinical trial in 65 RA patients undergoing elective surgery. rHuEPO was administered subcutaneously once a week and after observing erythropoiesis, autologous blood was collected. Fifty-seven of the 58 patients who completed treatment responded to rHuEPO and could donate more than 400 ml of autologous blood. Among them, 23 out of 28 patients undergoing total hip arthroplasty, 27 out of 28 undergoing total knee arthroplasty and 1 out of 1 undergoing spinal surgery did not need homologous blood transfusion perioperatively. During rHuEPO treatment, no significant changes of clinical parameters of RA activity were observed. Two patients discontinued the treatment because of mild and transient side effects. These results indicate that subcutaneous rHuEPO is safe and effective in eliminate the need for homologous blood transfusion, even in anemic RA patients undergoing elective orthopedic surgery.

Successful second autologous blood stem cell transplantation after G-CSF-combined conditioning for the treatment of high-risk acute myelogenous leukemia.

We describe a patient with acute myelogenous leukemia (AML) who received his second autologous blood stem cell transplantation (ABSCT) following a G-CSF-combined pre-transplant conditioning regimen. The patient underwent ABSCT during first remission but suffered a relapse 8 months later. After achieving second remission, he was prepared for his second ABSCT; recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered in combination with Ara C, in addition to the same conditioning regimen as that used before the first ABSCT. There was no increase in regimen-related toxicity after this second G-CSF-combined conditioning regimen when compared with that observed after the first ABSCT. To date, the patient's second remission following the second ABSCT has lasted 26 months, which has exceeded that following the first ABSCT. The G-CSF-combined pretransplant conditioning regimen for ABSCT may be effective in the treatment of high-risk AML by increasing the chemosensitivity of the residual leukemic cells.

Autologous blood transfusion with recombinant erythropoietin treatment. 22 arthroplasties for rheumatoid arthritis.

12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.

Clinical application of phosphoenolpyruvate (PEP) to autologous transfusion of patients with open heart surgery.

Patients undergoing surgery for cardiac valve replacement were autologously transfused after their cryopreserved blood was treated with phosphoenolpyruvate. Five patients received red cells treated on the day of operation with a solution containing phosphoenolpyruvate, the other 6 serving as a control group. None of the patients received homologous blood. The treated red cells had a normal adenosine triphosphate concentration; in the control group a 10% decrease was noted. The 2,3-bisphosphoglycerate concentration was 211% of normal in red cells of the treated group and 69% of normal in the control group. The P50 values (mmHg) were 31.1 +/- 3.5 (treated), 20.3 +/- 1.7 (untreated), and 26.1 +/- 0.6 (fresh, not cryopreserved), respectively. Both the 2,3-bisphosphoglycerate and P50 values of the circulating blood were significantly (p < 0.02) increased in the patients receiving treated red cells. The increase in the 2,3-bisphosphoglycerate and P50 remained for 6 hours after transfusion at which time the levels of the 2,3-bisphosphoglycerate were 14.5 +/- 2.2 mumol/gHb (treated group) and 10.5 +/- 0.8 mumol/gHb (control group). Those of P50 were 28.1 +/- 1.5 mmHg (treated group) and 25.9 +/- 0.9 mmHg (control group). The adenosine triphosphate levels were not significantly different. The postoperative values of pH and hematocrit did not differ between the two groups. It was estimated that the oxygen delivery capacity in the circulating blood was about 30% higher in the patients receiving phosphoenolpyruvate treated blood than in those receiving untreated blood.

[A case of esophageal carcinoma complicated by Crohn's disease].

A case of an esophageal cancer complicated by Crohn's disease is reported. A 76-year-old female was admitted to the Nara National Hospital with symptoms of melena and dysphagia. An esophageal X-ray study revealed a circular, stenotic lesion at the lower intra-thoracic esophagus. Histological examination of a specimen confirmed a moderately differentiated squamous cell carcinoma. A barium enema was then given which showed an irregular stenotic lesion, 28 cm in length, at the terminus of the ileum. Thus, an esophageal blind resection and a resection of the terminal portion of the ileum was jointly performed. A histological examination of the resected ileum confirmed Crohn's disease.

Antitumor activity of quinocarmycin (KW2152) against various cultured leukemia and lymphoma cell lines in vitro.

Growth inhibitory activity of quinocarmycin citrate (KW2152) against 25 human cultured cell lines derived from leukemias and lymphomas was assessed quantitatively by regrowth assay. EC90 values (drug concentration required for 90% growth inhibition of treated cells) measured at 1-h exposure to the drug in vitro were more than 16 micrograms/ml in five of six T-cell lines derived from T-lymphoma/leukemia, hence they were insensitive to KW2152. On the other hand, four of six B-cell lines derived from B-lymphoma and three of four cell lines derived from non-T, non-B acute lymphoblastic leukemia were sensitive to KW2152 with EC90 values of 0.3 to 2.2 micrograms/ml at 1-h exposure. Six myelomonocytoid cell lines derived from acute myelogenous leukemia were also sensitive with EC90 values of 1.8 to 3.0 micrograms/ml on 1-h exposure, but two myeloid cell lines derived from chronic myelogenous leukemia and one cell line derived from erythroleukemia were insensitive with EC90 values of more than 16 micrograms/ml. The EC90 values of most cell lines decreased as exposure time increased, and those measured at 24-h exposure were similarly low and mostly in the 0.02 to 0.06 micrograms/ml range. The kinetics analysis of growth inhibitory activity of KW2152 revealed that the drug showed time-dependent action. These in vitro results, as correlated with in vivo results reported elsewhere (K. Fujimoto, T. Oka, and M. Morimoto, Cancer Res., 47: 1516-1522, 1987), suggest that daily consecutive or continuous dose therapy as well as single or intermittent large-dose therapy would be worthy of testing in the clinical trial of KW2152.

[Adjuvant chemotherapy for gastric cancer--relation between long-term administration of FT-207 and prognosis].

The effect of adjuvant chemotherapy with FT-207 on survival rates in gastric cancer patients was evaluated. Patients who underwent curative gastrectomy in our Department were classified into the four groups: (A) short-term chemotherapy; total doses of 5 g 5-fluorouracil, or 1/2 MF (F') C alone (futraful 400mg/day, or 5-fluorouracil 250 mg/day for 3 weeks, mitomycin C 2 mg and cytosine arabinoside 20 mg twice a week for 3 weeks; (B) intermediate term chemotherapy; 1/2 MF (F') C followed by the oral administration of futraful 0.6g/day for less than 6 months; (C) long-term chemotherapy; 1/2 MF (F') C followed by futraful 10.6g/day longer than 6 months (D) control; no chemotherapy No significant difference back ground factors among four groups was found. Patients who recurred during the administration of drugs were excluded from this study. The survival rate of Group (C) in stage III was significantly higher than that of Group (A), (B) and (D) (generalized Wilcoxon test, p less than 0.03). There was no difference between (B) and (D). The survival rate of Group (A) was lower than Group (D). The effectiveness of chemo- therapy was not observed in patients with stage I and II. Survival rates of patients receiving futraful longer than 3 months continuously were significantly higher compared to patients who had to discontinue the drugs due to side effects. These results suggested that the adjuvant chemotherapy with futraful lasting more than 6 months prolonged the survival time, but short-term chemotherapy decreased the survival rate when compared with no chemotherapy group.