Development of a novel automatic ascites filtration and concentration equipment with multi-ring-type roller pump units for cell-free and concentrated ascites reinfusion therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi-purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M-CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self-regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M-CART required the use of newly developed multi-ring-type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5-minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M-CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self-regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M-CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator.

Low-density lipoprotein apheresis in a pediatric patient with refractory nephrotic syndrome due to focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) often leads to refractory nephrotic syndrome (NS). A high level of low-density lipoprotein (LDL) is a risk factor for the progression of NS. An 8-year-old girl presented with severe proteinuria refractory to steroid therapy. She was diagnosed with non-IgA diffuse mesangial proliferative glomerulonephritis. Oral prednisolone, methylprednisolone (mPL) pulse therapy, and cyclosporine and cyclophosphamide therapy failed to achieve remission. Follow-up renal biopsy revealed FSGS. Her serum level of LDL was high, and LDL-apheresis (LDL-A) was performed five times, followed by mPL pulse therapy. Urinary protein decreased from 2-4 g x day(-) to 0.5-1.0 g x day(-). LDL-A may be beneficial in the treatment of multidrug-resistant FSGS.

Investigation of the new prediction method for Ht values during the plasma exchange.

There is a disorder that is called Guillain-Barre Symdrome(GBS). Currently, plasmapheresis and high-dose immunoglobulin therapy are used for GBS. Plasmapheresis is one of the blood purifications. When the blood purification is enforced, it should be careful to decrease the blood pressure. In the Tokushima University Hospital, the hematocrit(Ht) values are measured using Crit-Line Monitor(CLM), because the Ht values are rate of red cell in blood, and are relation of the blood pressure. Hence, it is important to predict Ht value using the prediction method. There are various prediction methods, but we proposed the new prediction method. The purpose of this study is the prediction of Ht value after 1,3, and 5 minutes during the plasma exchange using the new prediction method. As the results, rms errors were small in all prediction, but the predicted Ht values are same the measured Ht value before 1,3, and 5 minutes, because the measured Ht values are strong autocorrelation.

Influence of lipid emulsion for the hematocrit value measured with continuous hematocrit monitor.

Continuous monitoring of hematocrit with a CRIT-LINE monitor (CLM) is used to prevent excess ultrafiltration during hemodialysis and continuous renal replacement therapy. The presence of substances affecting the scattering and absorption rates of multiple wavelengths of near infrared rays of CLM in the blood may affect the measured values with CLM. We examined the influences of lipid emulsion (LE) on hematocrit and relative blood volume (RBV) which were measured with CLM using an in vitro experimental model with human blood. Additions of 10% or 20% of LE increased the hematocrit measured by LCM and decreased the percent change of RBV in proportion to the dose. One percentage of 20% LE in the plasma increased the expected hematocrit measured with CLM by 2.9%. The decrease of initial hematocrit from 48.1% to 43.4% decreased the expected percent change of RBV from -3.4% to -3.7% with the addition of 1 ml of 20% LE to 100 ml blood. These findings indicate that additions of LE increase hematocrit that is measured with CLM in proportion to the dose of LE. Low levels of initial hematocrit will increase the degree of expected percent change of RBV. Attention should be paid to the influence of LE during monitoring with CLM.

Kinetics of group IB and IIA phospholipase A2 during low-volume continuous hemodiafiltration in severe acute pancreatitis.

Continuous hemodiafiltration (CHDF) has been performed for the treatment of severe acute pancreatitis. Phospholipase A2 (PLA2) is one of the important mediators which exacerbate acute pancreatitis, but whether PLA2 can be removed by CHDF is unclear. In this study, the kinetics of group IB and group IIA PLA2 was examined at the first session of low-volume CHDF in eight patients with severe acute pancreatitis. CHDF was performed using polysulfone hemofilters (surface area: 0.7 m(2)) at a blood flow rate of 100 mL/min and a filtration and dialysate flow rate of 10 mL/min each. The plasma concentrations of group IB and IIA PLA2 before the start of CHDF were 47.4 +/- 52.0 microg/L and 352 +/- 390 microg/L, respectively, and did not change significantly. The clearances of group IB and IIA PLA2 achieved by the CHDF circuit 1 h after the start of CHDF were 20.7 +/- 11.6 mL/min and 16.7 +/- 4.4 mL/min, respectively, with both clearances decreasing significantly with time. The clearance of group IB PLA2 into the waste fluid tended to increase with time; however, the concentrations of group IIA PLA2 in the waste fluid were less than the measurable sensitivity. These results indicate that group IB PLA2 is adsorbed on the hemofilter membrane in preference to being removed into the waste fluid, while group IIA PLA2 is mainly removed by adsorption. However, low-volume CHDF is not effective at eliminating the group IB and IIA PLA2 plasma concentration.

Low-volume continuous hemodiafiltration with nafamostat mesilate increases trypsin clearance without decreasing plasma trypsin concentration in severe acute pancreatitis.

Continuous hemodiafiltration (CHDF) has recently been used for treatment of severe acute pancreatitis. CHDF is capable of eliminating small molecules from blood, but whether trypsin can be eliminated by CHDF is not clear. In this study, elimination of trypsin-like enzyme activity (TLE) and cationic trypsin-like immunoreactivity (TLI) using low-volume CHDF was examined at the first CHDF session in eight patients with severe acute pancreatitis. CHDF was performed with a polysulfone hemofilter (membrane area, 0.7 m2) and nafamostat mesilate, a protease inhibitor and anticoagulant, at a blood flow rate of 100 ml/min and a filtration and dialysis flow rate of 10 ml/min each. Before beginning CHDF, plasma TLE was 3.41 +/- 2.86 nmol/(ml.min), and TLI was 5,900 +/- 9,008 ng/ml. The average plasma clearances of TLE and TLI achieved by the circuit during the 12-hour therapy were 56.7 +/- 4.9 ml/min and 8.0 +/- 7.2 ml/min, respectively. The average plasma clearance of TLI into the waste fluid was 2.4 +/- 1.6 ml/min whereas TLE was below the measurable sensitivity. The plasma concentration of TLE and TLI remained unchanged. These results indicate that low-volume CHDF using nafamostat mesilate as an anticoagulant can increase trypsin plasma clearance. However, low-volume CHDF is not effective to eliminate the plasma trypsin concentration.

Influence of leukocytapheresis therapy for ulcerative colitis on anemia and hemodynamics.

In Japan, leukocytapheresis (LCAP) therapy has been carried out for ulcerative colitis as an effective therapy with a low incidence of side-effects. In the present study, we serially investigated the influence of LCAP therapy on anemia and hemodynamics in patients with ulcerative colitis using a non-invasive method with a Crit-Line monitor (CLM) (Hema Metrics Inc., Salt Lake City, UT and Boston, MA, USA). We carried out LCAP on 10 patients with ulcerative colitis using a CS-100 Cellsorba EX LCAP filter in 34 courses of LCAP. The mean hematocrit value, which was measured using the Crit-Line monitor, was 21.8 +/- 0.2% (21.0-22.4%), which showed no significant changes after each LCAP therapy. The actual erythrocyte count, hemoglobin and hematocrit values decreased by 244 000/mm3, 0.7 g/dL and 2.1%, respectively, however, the differences were insignificant. These values corresponded to 7.8, 8.0 and 7.6% of the values before LCAP, respectively. There were no significant changes in systolic blood pressure, diastolic blood pressure, or heart rate during LCAP. The results of this study suggest that one course of LCAP does not exacerbate anemia, and it does not influence hemodynamics. However, considering the exacerbation of anemia in patients with severe ulcerative colitis caused by massive melena, monitoring with a less invasive Crit-Line monitor and a vital information monitor might be useful.

Development of a clipped single-bag with bicarbonate replacement fluid to ensure proper mixing.

A clipped single-bag for bicarbonate replacement fluid was developed to ensure proper mixing before administering to the patient. Nonmixture can cause imbalances of electrolytes and pH, which is a key problem for the current double-bag type bicarbonate replacement fluid sets. To resolve this problem, this single bag properly mixes the solutions before use. The new bag consists of a clip that is placed in the middle to keep the two solutions separated and sealed. When the caregiver is ready to administer treatment, the bag is simply unfolded and the clip automatically detaches, releasing the fluids. Thereby, the bicarbonate fluids are effectively mixed. An optimal clip size with an outer diameter of 16 mm and thickness of 2 mm was determined using compression tests and drop tests. This bag may be a safer and more effective way to provide proper replacement fluid supply for both hemofiltration and hemodiafiltration.

Web-based integrated alarm monitoring system in the ICU.

A web-based monitoring system for the alarm of equipment has developed for the conventional environment of Intensive Care Unit (ICU). The system communicates with equipment using Data Collection Interface (DCI) that converts the protocol of the output of equipment from RS-232C to TCP/IP. The system creates a web-document that can be referred from any internet-connected personal computer in the hospital. Using the system, a staff can easily monitor the state of the patient and the equipment. If the system is installed in the ICU, monitoring and management for the equipment will be highly improved.

Comparison of mineral contents between the arteries in upper and lower limbs of Japanese monkeys.

To examine whether the calcium accumulation in aged arteries is related to the way of walking, the mineral contents were determined in the arteries of Japanese monkeys of quadrupedal walk by inductively coupled plasma-atomic emission spectrometry. Sixteen Japanese monkeys consisting of 7 males and 9 females ranging in age from 2 to 33 yr were studied. The accumulation of calcium, phosphorus, and magnesium occurred progressively in most, but not all, of the arteries with aging. It was found that independent of the upper and lower limbs, a higher accumulation of calcium, phosphorus, and magnesium occurred in the arteries of the proximal regions with aging, compared with the arteries of the distal regions. In a comparison between the arteries of anatomically corresponding regions of the upper and lower limbs, the accumulation of calcium and magnesium was 20-60% higher in the external iliac and femoral arteries of the lower limb than in the axillary and brachial arteries of the upper limb. Regarding phosphorus, the accumulation was 20-120% higher in the external iliac and femoral arteries than in the axillary and brachial arteries. It was known that in humans, the accumulation of calcium, phosphorus, and magnesium was three to seven times higher in the arteries of the lower limb than in the arteries of the upper limb. It is clear that there is a very significant difference in the accumulation of calcium and magnesium in the arteries of the lower limbs between Japanese monkeys and humans. The present study suggests that the accumulation of calcium and magnesium in the arteries of the lower limb with aging is affected by the way of walking.

Dissociation between titer of anti-ganglioside antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.

Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.

Mass ratios of magnesium to calcium and phosphorus in the arteries of Japanese and Thai.

To elucidate quantitative changes of Ca, P, and Mg in the arteries with aging, the authors investigated changes of the mass ratios of Mg to Ca and P in the arteries of Japanese and Thai by inductively coupled plasma atomic emission spectrometry. The arteries of Japanese that were used were the thoracic and abdominal aortas, coronary, common iliac, internal iliac, external iliac, and femoral arteries, in which very high accumulations of Ca and P occurred in old age. The arteries of Thai that were used were the abdominal aorta, ramifying site of the abdominal aorta, coronary, common iliac, internal iliac, and external iliac arteries. It was found that there were extremely significant correlations both between Ca and Mg contents and between P and Mg contents in all of the arteries of the Japanese and the Thai. With regard to the mass ratio, the mass ratios of Mg to Ca ranged from 1.5% to 2.1% in the six arteries of the Japanese, except for the thoracic aorta at 3.1%, at an advanced stage of atherosclerosis, being similar to each other. In the arteries of the Thai, the mass ratios of Mg to Ca ranged from 1.9% to 3.0%, except for the coronary artery at 0.5%, at an advanced stage of atherosclerosis. The mass ratios of Mg to P ranged from 2.5% to 2.7% in the six arteries of the Japanese, except for the coronary artery at 1.8%, at an advanced stage of atherosclerosis. With regard to the arteries of the Thai, the mass ratios of Mg to P ranged from 1.9% to 3.3%, except for the coronary artery at 0.7%, at an advanced stage of atherosclerosis. These results revealed that both the mass ratios of Mg to Ca and Mg to P were almost similar among the arteries of Japanese and Thai, except for the coronary arteries. Therefore, these results suggested that the inorganic deposits in the coronary arteries of Japanese and Thai were similar to those in the intimal tunica of the thoracic aorta, whereas in the other arteries, they were similar to those in the middle tunica of the thoracic aorta.

Accumulation of elements in the arteries and cardiac valves of Thai with aging.

To elucidate whether the extent of element accumulation in the arteries and cardiac valves with aging was different between different races, the authors investigated the accumulation of elements in the arteries and cardiac valves of the Thai with aging and the relationships among elements in the cardiac valves. After ordinary dissection at Chiang Mai University was finished, 16 arteries and 4 cardiac valves were resected and element contents were determined by inductively coupled plasma-atomic emission spectrometry. In the 16 arteries, the average content of calcium was the highest in the site of the abdominal aorta ramifying into the common iliac arteries, and it decreased in the order internal iliac, coronary, abdominal aorta, common iliac, external iliac, superior mesenteric, inferior mesenteric, thoracic aorta, brachial, radial, common carotid, subclavian, ulnar, axillary, renal, and internal thoracic arteries. The average contents of phosphorus and magnesium in respective arteries were parallel with the average contents of calcium, except for the coronary artery. In comparison with the arteries of the Japanese, the trend of calcium accumulation in the arteries of the Thai was almost similar to that in the arteries of the Japanese, except for the coronary artery and thoracic aorta. The calcium accumulation in the coronary artery was much higher in the Thai than in the Japanese, whereas that in the thoracic aorta was lower in the Thai than in the Japanese. Regarding elements in the cardiac valves, the calcium content increased remarkably in the seventies in the aortic valve and in the nineties in the pulmonary valve, but it hardly increased in both the mitral and tricuspid valves with aging. The average content of calcium was the highest in the aortic valve, and it decreased in the order pulmonary, tricuspid, and mitral valves. Regarding the relationship among elements in the aortic valves, it was found that there were extremely significant direct correlations among the contents of calcium, phosphorus, and magnesium, whereas there were significant direct correlations between zinc and either calcium or phosphorus contents. Although significant correlations were found between sulfur and the other element contents in the aortic valves fo the Japanese, no significant correlations were found between them in the aortic valves of the Thai. In the mitral valves, extremely or very significant direct correlations were found among the contents of calcium, phosphorus, magnesium, and sulfur, with some exceptions that there were no significant correlations between phosphorus and either magnesium or sulfur contents. in addition, no significant correlation was found in the calcium content between the aortic valve and coronary artery in the same individuals.

Age-related changes of elements in human thoracic ducts and azygos veins and relationships among elements.

To elucidate compositional changes of the thoracic duct with aging, the authors investigated age-related changes of elements in the thoracic ducts in comparison with the azygos veins. The subjects consisted of 22 men and 1 woman, ranging in age from 65 to 95 yr. After ordinary dissection, the thoracic ducts and azygos veins were resected from the subjects and element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that calcium appeared to increase in the thoracic duct with aging, but the other elements, such as phosphorus, sulfur, magnesium, iron, zinc, and sodium, did not change significantly with aging. In the azygos vein, both calcium and sulfur increased significantly with aging. Regarding the relationship among elements, extremely significant direct correlations were found among calcium, phosphorus, sulfur, and magnesium in the thoracic ducts, except for phosphorus and magnesium contents with a very significant direct correlation. In the azygos veins, significant direct correlations were found between calcium and sulfur contents and between sulfur and magnesium contents. However, no significant correlations were found among calcium, phosphorus, and magnesium in the azygos veins. These results revealed that with regard to the relationship among calcium, phosphorus, and magnesium, the thoracic duct was similar to the arteries, but not to the azygos vein.

Compositional changes of human mitral valves with aging.

To elucidate compositional changes of the mitral valve with aging, the authors investigated the relationships among element contents in the mitral valves. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. After the ordinary dissection, mitral valves, lower parts of the interventricular septa, and terminal crests containing the sinoatrial nodes were resected and the element contents were determined by inductively coupled plasma-atomic emission spectrometry. The interventricular septa and sinoatrial nodes were used to compare with the mitral valves. With regard to the mitral valve, it was found that extremely significant correlations were found among the contents of Ca, P, Mg, and Na, but no significant correlations were found between the contents of S and elements such as Ca, P, or Mg. Regarding the interventricular septum, it was found that an extremely significant correlation was found between P and S contents; very significant correlations were found between Ca and Mg contents and between Mg and S contents; and a significant correlation was found between P and Mg contents. However, no significant correlation was found between Ca and P contents in the interventricular septa. In the terminal crest containing the sinoatrial node, significant correlations were found among the contents of Ca, P, Mg, and S. The present study revealed that with regard to the relationships among element contents, the compositional change of the mitral valve was intermediate between those of the thoracic aorta and the interventricular septum.

Relationships among element contents in the internal jugular vein similar to the arteries.

To elucidate compositional changes of the veins with aging, the authors investigated the relationships among element contents in the internal jugular veins, in which a higher accumulation of calcium and phosphorus occurred with aging. The subjects consisted of 15 men and 10 women, ranging in age from 40 to 98 yr. The element contents of the internal jugular veins were determined by inductively coupled plasma-atomic emission spectrometry. It was found that there were extremely significant direct correlations among the contents of calcium, phosphorus, magnesium, and sodium in the internal jugular vein. In addition, very significant direct correlations were also found both between zinc and either iron or silicon contents and between sulfur and iron contents in the vein. As calcium and phosphorus increased in the internal jugular vein, the mass ratios of Mg/Ca and Mg/P decreased gradually in the vein, whereas the mass ratio of Ca/P hardly decreased. These results indicated that with regard to both the relationships among the contents of calcium, phosphorus, and magnesium and the changes of the mass ratios of Mg/Ca and Mg/P, the internal jugular vein was very similar to the arteries.

Compositional changes of the aortic valve similar to the artery with aging.

To elucidate compositional changes of the cardiac valves with aging, the authors investigated the relationships among element contents in the aortic valves, in which the accumulation of calcium and phosphorus was the highest. The subjects consisted of 10 men and 14 women, ranging in age from 65 to 102 yr. Extremely significant direct correlations were found among the contents of calcium, phosphorus, magnesium, sodium, and zinc in the aortic valves. In contrast, significant inverse correlations were found between the contents of sulfur and the other elements, such as calcium, phosphorus, magnesium, and sodium. It should be noted that these correlations present in the aortic valves were very similar to those in the arteries, especially those in the thoracic aortas. The changes of the mass ratios of Mg/Ca and Mg/P in the aortic valves were similar to those in the thoracic aortas. As calcium and phosphorus increased in the aortic valve, the mass ratios Mg/Ca and Mg/P decreased reversely in the aortic valve. These results suggest that the compositional change of the aortic valve is very similar to that of the thoracic aorta.

Elements of calcified sites in human thoracic aorta.

To elucidate the manner of element accumulation in the arteries with aging, the authors investigated the element contents in the calcified and surrounding sites of the thoracic aortas by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of three men and five women, ranging in age from 45 to 99 yr. The calcified, calcification-surrounding, and control (which appeared normal) sites were removed from the thoracic aortas and the element contents were determined. It was found that the contents of calcium, phosphorus, magnesium, zinc, and aluminum were higher in the calcified site than in the control site, whereas the contents of sulfur, iron, and lead were lower in the calcified site than in the control site. The contents of the elements in the surrounding site were intermediate between those of the calcified and control sites, except for the magnesium and lead contents, which were the lowest. The mass ratios of magnesium to calcium and phosphorus were lower in the calcified site compared with the surrounding and control sites, and as calcium and phosphorus increased in the aorta, the mass ratios lowered gradually in the aorta.