A mechanical coil insertion system for endovascular coil embolization of intracranial aneurysms.

Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system.

Esophageal atresia with double tracheoesophageal fistula--a case report and review of the literature.

Esophageal atresia with double tracheoesophageal fistula (TEF) is a very rare anomaly, and the accurate preoperative diagnosis of proximal TEF is very difficult. This paper describes a baby girl who presented with esophageal atresia with double, proximal, and distal TEF. The distal TEF was diagnosed before operation, whereas the proximal TEF was found intraoperatively. Overlooking the presence of proximal TEF can lead to increased morbidity and mortality due to severe respiratory infection and the necessity of a second operation. Great care must therefore be taken to not overlook the presence of proximal TEF in patients with this anomaly.

Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes.

AIMS: To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes. METHODS: A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30-45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0-2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA(1c)), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected. RESULTS: Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA(1c) was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA(1c) levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 microEq/l vs. 237.3 microEq/l; P < 0.01) before a decrease in HbA(1c) was apparent. The change in FFA levels correlated with the change in HbA(1c) (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups. CONCLUSIONS: Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.

Effects of omega-3 fatty acids in rat allogenic small intestinal transplantation.

The aim of this study was to estimate the effect of omega-3 fatty acids on the recipient and graft immune response after rat allogenic small intestinal transplantation. Seven-week-old Lewis rats were randomly assigned to one of three groups according to the diet received: an FO group (fish oil supplemented), an SB group (soy bean oil supplemented) or a control group (normal rat chow). The recipient Lewis rats were each given their respective group diet for 12 days, and then, on the 19th day of gestation, a 2 cm jejunum from the donor fetal Fischer rat was transplanted into the abdominal wall of the recipient rats using a non-vascular anastomotic technique. The recipient rats were killed on day 2 after transplantation, and the recipient plasma IL-2, IFN-gamma and IL-1 beta levels were determined. In addition, the histological findings of the graft were analyzed. The cytokine levels of the FO group were significantly lower than the other two groups. In order to determine the grade of rejection, the morphological findings were blindly graded on a scale of 0-4. The mean grade of the FO group was also significantly lower than the other two groups. Omega-3 fatty acids are therefore considered to have an immunosuppressive effect on rat allogenic small intestinal transplantation based on the recipient plasma IL-1 beta, TNF and IL-2 levels and the histological findings of the grafts.

Usefulness of troglitazone administration to obese hyperglycaemic patients with near-normoglycaemia.

AIMS: We assessed the effectiveness of 400 mg/day of troglitazone administered to hyperglycaemic patients with near-normoglycaemia who were obese and who had hyperinsulinaemia. RESULTS: The area under the plasma glucose curve in oral glucose tolerance tests (OGTT) significantly decreased from 39.8 +/- 19.4-20.5 +/- 10.2 mg/dL. h and the area under the insulin-response curve from 31.8 +/- 22.5-12.2 +/- 5.7 microU/ml x h 4 months after the start of treatment. The level of HbA1c significantly improved from 6.6 +/- 0.2 to 6.3 +/- 0.2% (p < 0.05) by 1 month after administration, and that of serum 1,5-anhydroglucitol (1,5-AG) from 12.6 +/- 1.1-18.3 +/- 2.5 micro/ml (p < 0.05). In some cases, recovery of the first-phase insulin secretion was observed. CONCLUSIONS: These findings suggest that the administration of this insulin sensitizer is useful in the treatment of obese Japanese subjects with borderline or mild diabetics accompanied by hyperinsulinaemia.

Retarded gastric acid secretion in rats infected with larval Taenia taeniaeformis.

The influence of hepatic larval Taenia taeniaeformis infection on gastric acid secretory activity and gastric mucosal integrity was investigated. After 12 weeks of infection with 2,000 T. taeniaeformis eggs, the gastric pH values of control and infected rats were 4.1+/-0.6 (mean +/- SD) and 8.4+/-0.2, respectively. There was no difference in the basal acid secretion between control (1.7+/-0.7 micro Eq.H(+)/15 min) and infected (1.9+/-0.3) rats. However, infected rats failed to respond to histamine stimulation, the maximum acid output level being 2.8+/-0.4 in the infected rats, compared to 12.9+/-3.3 in control rats. Larval T. taeniaeformis infection resulted in the suppression of gastric acid secretion leading to hypergastrinemia.

[KRP-297, MCC-555].

KRP-297 and MCC-555, which are being developed in Japan as thiazolidinediones, uniquely bind and activate peroxisome proliferator-activated receptors(PPAR). KRP-297, unlike other thiazolidinediones, effects on not only PPAR gamma but also PPAR alpha. Furthermore, this compound acts directly on basal glucose uptake in the rat skeletal muscle. KRP-297 decreased plasma glucose and insulin levels, and also blood triglyceride and free fatty acid in diabetic animal models. MCC-555 has significant antidiabetic properties yet its binding affinity for PPAR gamma is less than 1/10 that of BRL 49653. Thus, it is regarded now as a PPAR gamma modulator rather than agonist, depending on cell type. At present, clinical phase II studies of both drugs are under way.

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance.

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824, P<0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539, P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

Manganese intoxication during intermittent parenteral nutrition: report of two cases.

BACKGROUND AND METHODS: The administration of trace elements is thought to be needed in patients receiving long-term parenteral nutrition. Recently, manganese intoxication or deposition was documented in such patients. We report two cases of manganese intoxication during intermittent parenteral nutrition including manganese. Manganese had been administered for 4 years at a frequency of one or two times per week in one case and for 5 years at a frequency of one or two times per month in the other case. Both cases showed mild symptoms with headache and dizziness. One case had mild hepatic dysfunction and the other did not. The whole-blood manganese level increased in one case, but not in the other case. T1-weighted magnetic resonance images revealed symmetrical high-intensity areas in basal ganglia and thalamus in both cases. After the administration of manganese was stopped, these symptoms all disappeared and the magnetic resonance images abnormalities gradually improved in both patients. Mild long-term manganese intoxication is thus considered to occur regardless of the frequency of using a manganese supplement. CONCLUSIONS: Patients should be carefully monitored when receiving long-term parenteral nutrition including manganese, even when the manganese dose is small and the frequency of receiving a manganese supplement is low.

Outcome of fetal cystic hygroma and experience of intrauterine treatment.

OBJECTIVE: To review our cases of fetal cystic hygroma and to examine the prognostic factors with the goal of establishing criteria for the intrauterine treatment for cystic hygroma. PATIENTS AND METHODS: Thirty-one cases of fetal cystic hygroma were managed by us from January 1988 to December 1997, and 21 cases were available for analysis. Three prognostic factors, namely chromosomal abnormality, structural anomaly and hydrops fetalis, were evaluated. We treated 2 cases of cystic hygroma associated with hydrops fetalis in utero using OK-432 injection under ultrasound guidance. RESULTS: The fetuses without any of the prognostic factors listed above showed a good prognosis throughout the fetal and neonatal periods. However, in this group, 2 infants with large tumors died of hemorrhage from the tumor at 6 months and 3 years of age, respectively. Cases with hydrops fetalis without chromosomal abnormalities or structural anomalies (5 cases) resulted in either intrauterine fetal death (IUFD, 2 cases) or early perinatal neonatal death (early PND, 3 cases). The cause of early PND was circulatory failure. Most of the hydrops cases with either a chromosomal abnormality or structural anomaly resulted in IUFD before 22 weeks of gestation. The size of the cyst decreased in 1 of 2 cases treated in utero. CONCLUSIONS: The fetal cases of cystic hygroma showing hydrops fetalis without chromosomal abnormalities or structural anomalies are considered to be possible candidates for intrauterine therapy. Those with very large cystic hygroma without any of the three prognostic factors are also thought to be candidates for fetal treatment. Based on our clinical experience, sclerotherapy using OK-432 is considered to be a treatment option in selected cases with fetal cystic hygroma.

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.

The validity of bioelectrical impedance phase angle for nutritional assessment in children.

BACKGROUND/PURPOSE: Bioelectrical impedance analysis (BIA) is a quick and noninvasive method for estimating body composition. Many prediction equations have been reported recently using bioelectrical impedance to calculate fat free mass (FFM) and fat mass (FM). These equations are based on the assumption that the composition and density of FFM are stable. In children, the composition and density of FFM vary according to age and clinical state, so the use of these equations is limited. However, phase angle is directly determined from resistance (Rz) and reactance (Xc) without equations and reflects body cell mass. The authors, therefore, investigated the validity of phase angle for nutritional assessment in children. METHODS: Bioelectrical impedance analysis and anthropometric measurements were performed in 81 patients, including 71 well-nourished and 10 malnourished children. RESULTS: Phase angle correlated with body weight (R = 0.818) and arm muscle circumference (r = 0.901) in well-nourished children. Malnourished patients showed lower phase angle than that of well-nourished children. CONCLUSION: Bioelectrical impedance phase angle is a useful parameter for nutritional assessment in children.

The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol levels.

The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which originates mainly in the diet, is used in Japan as a new marker for glycemia. To evaluate the potential interference of 1, 5-AG measurements by traditional Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of concentrated dosage forms of Kampo using high performance liquid chromatography (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g dry weight), contained large amounts of 1,5-AG. Six others contained small amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2 diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9 to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking Kampo which contains Polygalae radix.

Low-dose dobutamine radionuclide ventriculography for prediction of myocardial viability: quantitative analysis of regional left ventricular function.

BACKGROUND: It is important to distinguish viable myocardium from necrotic tissue in order to decide upon therapy in patients with ischemic heart disease. HYPOTHESIS: We verified the hypothesis that quantitative analysis of regional left ventricular function using low-dose dobutamine radionuclide ventriculography (RNV) can sensitively predict myocardial viability and compared its usefulness with thallium-201 (201Tl) single-photon emission computed tomography (201Tl-SPECT). METHODS: Radionuclide ventriculography at rest and during low-dose dobutamine infusion (5 micrograms/kg/min), 201Tl-SPECT, and coronary angiography were performed in 51 subjects with severe ischemia-related stenosis of coronary arteries and 3 subjects without coronary artery disease. 201Tl uptake was assessed as normal (control), low perfusion (LP), or defect. We compared the response of regional function to dobutamine with the regional 201Tl uptake. The accuracy of both methods for identifying viable myocardium was investigated in 17 patients who underwent successful coronary revascularization, with a resulting improvement in wall motion. RESULTS: The increase in regional ejection fraction (delta r-EF) in response to dobutamine was significantly greater in the control (12 +/- 6%) and LP (16 +/- 11%) regions than in the defect (5 +/- 10%) regions. The increase in one-third regional ejection fraction (delta r-1/3EF) was also significantly higher in the control (14 +/- 7%) and LP (10 +/- 8%) regions than in the defect regions (5 +/- 6%). We defined myocardial viability as a delta r-EF > 5% or a delta r-1/3EF > 2%. The sensitivity and specificity of the delta r-EF for identification of myocardial viability were 91.4 and 55.5%, respectively. The sensitivity and specificity of the delta r-1/3EF were 91.4 and 66.6%, respectively; the corresponding values for 201Tl SPECT were 74.2 and 77.8%. CONCLUSION: Low-dose dobutamine RNV with quantitative analysis of regional left ventricular function was more sensitive for identification of viable myocardium than 201Tl-SPECT.

Transport of 1,5-anhydro-D-glucitol into insulinoma cells by a glucose-sensitive transport system.

The uptake of 1,5-anhydro-D-glucitol (1,5-AG) occurs by passive mechanisms in cells or tissues that have passive glucose transporters. It is known that serum 1,5-AG concentrations are reduced in patients with diabetes mellitus. To elucidate the metabolism of this substance and its physiological role in pancreatic beta-cells, we assayed 1,5-AG transport in the insulinoma-derived cell lines, RINr and MIN6. Both cell lines showed an insulin-insensitive, concentration-dependent uptake of 1,5-AG with a saturation time of approximately 120 min, and most of the 1,5-AG in the cytoplasm was in the free form. A biphasic saturation curve was obtained using a wide range of 1,5-AG concentrations, suggesting that accumulation was mediated by a high affinity and a low affinity transporter. The high affinity transporter had a K(m) of 10.4 in RINr cells and 13.0 mM in MIN6 cells, and the low affinity transporter had a K(m)100 times, being much higher than the physiological concentrations of 1,5-AG. These results indicate that the 1,5-AG carrier system in insulinoma cells is distinct from that in either the somatic cells or renal tubular cells. These findings also suggest that a unique 1,5-AG transport system is present in pancreatic beta-cells.