Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated with renal hypouricemia.

Renal hypouricemia is a clinical disorder attributed to an increased renal urate excretion rate and is well known to involve a high risk of urolithiasis and exercise-induced acute kidney injury (AKI). This report concerns two interesting cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia. A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively), oliguria and NS. They were treated with prednisolone and temporary hemodialysis. Renal function improved, but hypouricemia persisted during hospitalization. Histological findings in both cases led to a diagnosis of minimal change nephrotic syndrome and identification of the diuretic phase of tubulointerstitial damage because of findings such as acute tubular necrosis. Furthermore, distal tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal. Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a homozygous mutation in exon 4 (W258stop) of each one. Our cases show that patients with renal hypouricemia may be susceptible to AKI without involvement of exercise if they possess some facilitators. Renal hypouricemic patients should therefore be carefully examined for all complications from renal hypouricemia because of high risk of AKI.

Cerebral venous thrombosis in adult nephrotic syndrome due to systemic amyloidosis.

Although venous thrombosis is one of the common complications in nephrotic patients, cerebral venous thrombosis (CVT) is rarely reported. CVT is so difficult to be detected by conventional diagnostic methods that it is sometimes overlooked despite its potential severity. We report a 79-year-old female with nephrotic syndrome due to systemic amyloidosis who suddenly altered mental status during her hospitalization. The underlying etiology had been not identified by physical examinations, various laboratory data, and repeated computed tomography, and finally she died. The post-mortem examination showed a massive thrombus impacted in intracranial left-sided transverse and sigmoid sinus. This case suggests that CVT can occur in a nephrotic patient who presents unexplained neurological signs and symptoms, which might not be detected only through conventional diagnostic tests.

Developmental and patterns of pituitary and plasma TSH in the normal and hypothyroid female rat.

The developmental patterns of thyroid-stimulating hormone (TSH) was examined in female Long-Evans rats by radioimmunoassay of pituitary and plasma from 5 through 80 days of age. The effects of hypothyroidism on normal TSH levels were examined in animals radiothyroidectomized at birth. Control animals showed a peak in circulating TSH levels at day 12 followed by lower levels through day 30, and even lower levels at day 80 when values were those of adult animals. Hypothyroid females had higher plasma TSH levels than controls from days 10 through 30 with no distinct peak at day 12. Pituitary content reached a peak at day 18 and was always higher in control than hypothyroid animals.

Direct association of LIS1, the lissencephaly gene product, with a mammalian homologue of a fungal nuclear distribution protein, rNUDE.

LIS1 is a product of the causative gene for type I lissencephaly characterized by a smooth brain surface due to a defect in neuronal migration during brain development and a regulatory subunit of platelet-activating factor acetylhydrolase (PAF-AH). It is also a mammalian homologue of the fungal nuclear distribution (nud) gene, nudF, which controls the migration of fungal nuclei. Using the two-hybrid system, we identified a novel LIS1-interacting protein, rat NUDE (rNUDE), and found that it is a mammalian homologue of another fungal nud gene product, NUDE, and Xenopus mitotic phosphoprotein 43 which is phosphorylated in a cell cycle-dependent manner. rNUDE and the catalytic subunits of PAF-AH interact with the N- and C-termini of LIS1, respectively. However, these proteins, instead of simultaneously binding to LIS1, appeared to bind to LIS1 in a competitive manner. These results suggest that LIS1 functions in nuclear migration by interacting with multiple intracellular proteins in mammals.

Effects of implantation on the mechanical properties of the polyurethane diaphragm of left ventricular assist devices.

Tensile properties of blood pump diaphragms made from a segmented polyether polyurethane (Toyobo TM5) were studied after implanting in goats for variable periods of time up to 72 days. The implantation decreased the tensile strength and ultimate elongation at break, while the elastic modulus increased very slightly. These changes in the strength and ductility were primarily caused by the contact of material with blood rather than by the mechanical fatigue of material. Mechanical stability was greatly improved by removing residual oligomers from the material by a refining procedure. The refined polyurethane has characteristics favourable for blood pump applications.

Extrarenal role of aldosterone in the regulation of blood pressure.

To assess the hypothesis that aldosterone may have direct vasoconstrictive action, the acute effects of canrenoate potassium (Soldactone, S), an aldosterone antagonist, on hemodynamics and hormonal responses were determined before and after the intravenous administration of 2 mg/kg S in 11 patients with primary aldosteronism (PA), 9 patients with essential hypertension (EH), and 5 patients with renovascular hypertension (RVH). S caused a significant -12 +/- 2 mm Hg decrease in MBP in PA, -5 +/- 2 mm Hg in EH, and -4 +/- 1 mm Hg in RVH. Reduction in MBP was significantly higher in PA than in the others and there was a negative correlation between changes in MBP and basal PAC. The cardiac index did not change throughout the study in all groups, which led to a significant reduction in total peripheral resistance index (TPRI) in PA but not in the others. There was a significant correlation between changes in MBP and TPRI (r = 0.82, p less than 0.01). PRA did not change throughout the study, but PAC and cortisol were significantly elevated. There were no correlations between changes in MBP and hormonal responses. In conclusion, S resulted in a significant reduction of MBP mediated by a significant reduction of TPRI. These results suggest that aldosterone may have direct vasoconstrictive action and this extrarenal effect of aldosterone may be involved in the regulation of blood pressure.

Release of gastric inhibitory polypeptide (GIP) during calcium infusion and in hyperparathyroidism.

Gastric inhibitory polypeptide (GIP) is a candidate hormone for an incretin which stimulates or potentiates insulin secretion. We elucidated that, in five patients with hyperparathyroidism, GIP and insulin responded remarkably to glucose ingestion, and that hypercalcaemia appeared to have a stimulatory effect on glucose-induced GIP release as well as on insulin release. In nine healthy subjects a 2% calcium solution was continuously infused intravenously and a hypercalcaemic state was maintained. This caused GIP to respond significantly more to glucose ingestion. In spite of GIP being considered an incretin in the normoglycaemic state, GIP does not markedly stimulate insulin secretion. However, in the hypercalcaemic state in healthy subjects, glucose-induced GIP and insulin secretion is significantly greater than in the normocalcaemic state. The potentiated response of insulin to glucose may be caused, in part, by GIP.

Physiologic remodeling annuloplasty to retain the shape of the anterior leaflet: a new concept in mitral valve repair.

BACKGROUND AND AIMS OF THE STUDY: The Carpentier-Edwards (CE) ring was developed to restore the normal 3:4 ratio between the anteroposterior and transverse diameters of the mitral valve orifice during systole. It is difficult to use in patients in whom the ratio is more than 3:4. To overcome this problem, we developed an adjustable obturator, the ratio of which may be changed by sliding apart its two components. METHODS: Remodeling annuloplasty was performed using part of a flexible Duran ring or autologous pericardium and the adjustable obturator in 17 patients with severe MR, including two with high anterior leaflet. RESULTS: Physiologic remodeling annuloplasty was easily accomplished in all cases. Intraoperative echocardiography was performed in 14 patients, and it showed no regurgitant jet in 11 cases and only trivial jet in three. CONCLUSION: Physiologic remodeling annuloplasty to retain the natural shape of the anterior leaflet by using an adjustable obturator is a very useful technique that enables annuloplasty to be performed in all cases, irrespective of the shape of the anterior leaflet.

ATS prosthetic valve motion: an in vitro analysis.

BACKGROUND AND AIM OF THE STUDY: We have reported clinical findings that normally functioning open pivot ATS valves did not open completely. In order to analyze features of the ATS valve motion more precisely, in vitro tests were conducted. METHODS: Opening angles and pressure gradients of the ATS valve were measured and compared with those of the St. Jude Medical (SJM) valve under steady flow, but with various outlet configurations. Second, opening angles of the two valves were measured under pulsatile conditions in two different outflow configurations: (i) a 'straight outlet' where the leaflets did not extend into the tapering outflow chamber, and (ii) an 'abrupt enlargement outlet' where the leaflets extended directly into the enlarged outflow space. Third, flow visualization studies were made under steady flow conditions in the straight and abrupt enlargement outlet conduits, respectively. RESULTS: Under steady flow conditions, opening of the ATS valve was restricted in most outflow configurations; only when the outlet angle was 0 degrees did the valve open fully. The SJM valve opened completely in all downstream configurations. Despite restricted opening in the ATS valve, the pressure gradient was similar in both valves. Under pulsatile conditions, both valves opened fully in the straight outlet; however, in the abrupt enlargement outlet the ATS valve opened incompletely and the SJM valve completely. Substantial turbulent flow was observed at the outside of the leaflet and corners of the conduit, notably with the ATS valve. CONCLUSION: This study showed that the ATS valve did not open fully except when the outflow was straight, and the leaflet did not extend into an enlarged downstream chamber. Structural features of the ATS, such as its axis being located close to the straight edge and its leaflets extending further downstream from the ring orifice, may cause this unique valve behavior.

Echocardiographic findings in hemodialysis patients treated with recombinant human erythropoietin: proposal for a hematocrit most beneficial to hemodynamics.

We investigated the hemodynamic effects of the correction of anemia with recombinant human erythropoietin (rHuEPO) in 28 hemodialysis patients with severe anemia. Echocardiograms were recorded before the administration of rHuEPO (period I) with a hematocrit of 19.2 +/- 1.5% (mean +/- SD) and repeated twice (periods II and III) when the hematocrit was increased to 25.7 +/- 1.1% and to 30.0 +/- 1.0%. Left ventricular end-diastolic dimension (LVDd) decreased from 51.0 +/- 6.1 to 48.8 +/- 5.8 and to 48.3 +/- 7.1 mm, but no changes were observed in left ventricular end-systolic dimension. Cardiac output (CO) decreased from 5.89 +/- 1.46 to 5.00 +/- 1.44 and to 4.67 +/- 1.33 l/min. The thickness of the interventricular septum and the left ventricular posterior wall remained unchanged. Blood pressure was kept rather constant, although antihypertensive therapy needed to be adjusted to prevent the occurrence or aggravation of hypertension. Total peripheral resistance increased from 1481 +/- 359 to 1832 +/- 487 and to 1946 +/- 493 dynes.sec/cm5. The decreases in LVDd and CO were significant between periods I and II, without further changes between periods II and III. More antihypertensive therapy was needed in period III than in period II. Similar echocardiographic results were observed in 10 patients in whom antihypertensive therapy was not required throughout the study. In conclusion, an increase in hematocrit to 25% would be appropriate in order to obtain an effective hemodynamic improvement with rHuEPO therapy in dialysis patients although a higher hematocrit level might be desirable in order to improve working capacity.

Comparison of the closing dynamics of mechanical prosthetic heart valves.

To compare the closing dynamics of mechanical tilting disk prosthetic heart valves (OmniScience 25 [OS25], Medtronic-Hall 25 [MH25], Bjork-Shiley Monostrut 29 [BS29]) and bileaflet valves (CarboMedics 29 [CM29]) in the mitral position, an x-ray high speed video camera (XHVC) and a mechanical mock circulator were used. From the continuous images taken with the XHVC, the starting point of closing and the period during closing (PDC) were measured. Pressures and flow rate were recorded at 500 Hz synchronously with the XHVC. A pressure difference across the valves at the onset of closing (dpc) was newly introduced to compare the closing response. Using 60 and 100 bpm, the following results were obtained: 1) the CM29 had less PDC and maximum backflow rate than the BS29; 2) the dpc and the PDC at 100 bpm were larger than those at 60 bpm; 3) the dpc of the MH25 was the lowest; and 4) the PDC of the CM29 was the shortest. With regard to the effect of valve design on closing dynamics, it was shown that: 1) less momentum of inertia of the occluder and disk traveling angle resulted in lower dpc and shorter PDC, and 2) the higher the dpc and the PDC became, the larger the maximum backflow rate that was generated, and 3) low final closing speed will be achieved for small disk travelling angle.

An intraventricular axial flow blood pump integrated with a bearing purge system.

The future development of implantable axial flow blood pumps must address two major issues: mechanically induced hemolysis and shaft seal reliability. The recent revisions to our miniature intraventricular axial flow left ventricular assist device (LVAD) were aimed particularly at addressing these concerns. To improve hemocompatibility, a new impeller has been designed according to the following criteria: 1) gradual pressure rise along the blade chord; 2) minimized local fluid acceleration to prevent cavitation; 3) minimum surface roughness; and 4) radius edges. Subsequent in vitro hemolysis tests conducted with bovine and ovine blood have demonstrated very low hemolysis (normalized index of hemolysis = 0.0051 +/- 0.0047 g/100 L) with this new impeller design. To address the need for a reliable seal, we have developed a purged seal system consisting of a miniature lip seal and ceramic pressure groove journal bearing that also acts as a purge pump. Several spiral grooves formed on the bearing surface provide viscous pumping of the purge fluid, generating more than 3,000 mmHg at 10,000 rpm. This purge flow flushes the lip seal and prevents blood backflow into the bearing. We have found this purge pump to offer several advantages because it is simple, compact, durable, does not require separate actuation, and offers a wide range of flow, depending upon the groove design. In vivo animal tests demonstrated the potential of the purged seal system.

A miniature intraventricular axial flow blood pump that is introduced through the left ventricular apex.

A new intraventricular axial flow blood pump has been designed and developed as an implantable left ventricular assist device (LVAD). The pump consists of a tube housing (10 cm in length and 14 mm in diameter), a three-vane impeller combined with a guide vane, and a DC motor. This pump is introduced into the LV cavity through the LV apex, and the outlet cannula is passed antegrade across the aortic valve. Blood is withdrawn from the LV through the inlet ports at the pump base, and discharged into the ascending aorta. A pump flow of > 8 L/min was obtained against 90 mmHg differential pressure in the mock circulatory system. In an acute dog model, this pump could produce a sufficient output of 200 ml/kg/min. In addition, the pump flow profile demonstrated a pulsatile pattern, although the rotation speed was fixed. This is mainly due to the changes in flow rate during a cardiac cycle--that is, during systole, the flow rate increases to the maximum, while the differential pressure between the LV and the aorta decreases to the minimum. Thus, this simple and compact axial flow blood pump can be a potential LVAD, with prompt accessibility and need for less invasive surgical procedures.

Development of a miniature intraventricular axial flow blood pump.

A new intraventricular axial flow blood pump has been designed and developed as a totally implantable left ventricular assist device (LVAD). This pump consists of an impeller combined with a guide-vane, a tube housing, and a DC motor. The pump is introduced into the LV cavity through the LV apex, and the outlet cannula is passed antegrade across the aortic valve. Blood is withdrawn from the LV through the inlet ports at the pump base, and discharged to the ascending aorta. Our newly developed axial flow pump system has the following advantages: 1) it is a simple and compact system, 2) minimal blood stasis both in the device and the LV cavity, 3) minimal blood contacting surface of the pump, 4) easy accessibility with a less invasive surgical procedure, and 5) low cost. A pump flow > 5 L/min was obtained against 100 mmHg differential pressure in the mock circulatory system. The pump could produce a passive pulsatile flow effect with a beating heart more efficiently than other non-pulsatile pumps because of minimal pressure drop and inertia along the bypass tract. Anatomic fit studies using dissected hearts of dilated cardiomyopathy (DCM) cadavers showed that this pump could smoothly pass through the aortic valve without any interference with mitral valve function. Recently, a dynamic pressure groove bearing and a miniature lip seal have been developed. The dynamic pressure groove bearing has a simple structure and acts as a pressure resistant sealing mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

An implantable centrifugal blood pump for long term circulatory support.

A compact centrifugal blood pump was developed as an implantable left ventricular assist system. The impeller diameter is 40 mm and the pump dimensions are 55 x 64 mm. This first prototype was fabricated from titanium alloy, resulting in a pump weight of 400 g including a brushless DC motor. Weight of the second prototype pump was reduced to 280 g. The entire blood contacting surface is coated with diamond like carbon to improve blood compatibility. Flow rates of over 7 L/min against 100 mmHg pressure at 2,500 rpm with 9 W total power consumption have been measured. A newly designed mechanical seal with a recirculating purge system ("Cool-Seal") is used as a shaft seal. In this seal system, seal temperature is kept under 40 degrees C to prevent heat denaturation of blood proteins. Purge fluid also cools the pump motor coil and journal bearing. The purge fluid is continuously purified and sterilized by an ultrafiltration filter incorporated into the paracorporeal drive console. In vitro experiments with bovine blood demonstrated an acceptably low hemolysis rate (normalized index of hemolysis = 0.005 +/- 0.002 g/100 L). In vivo experiments are currently ongoing using calves. Via left thoracotomy, left ventricular apex-descending aorta bypass was performed utilizing a PTFE (Polytetrafluoroethylene) vascular graft, with the pump placed in the left thoracic cavity. In two in vivo experiments, pump flow rate was maintained at 5-8 L/min, and pump power consumption remained stable at 9-10 W. All plasma free hemoglobin levels were measured at < 15 mg/dl. The seal system has demonstrated good seal capability with negligible purge fluid consumption (< 0.5 ml/ day). Both animals remain under observation after 162 and 91 days of continuous pump function.

Long-term animal experiments with an intraventricular axial flow blood pump.

A miniature intraventricular axial flow blood pump (IVAP) is undergoing in vivo evaluation in calves. The IVAP system consists of a miniature (phi 13.9 mm) axial flow pump that resides within the left ventricular (LV) chamber and a brushless DC motor. The pump is fabricated from titanium alloy, and the pump weight is 170 g. It produces a flow rate of over 5 L/min against 100 mmHg pressure at 9,000 rpm with an 8 W total power consumption. The maximum total efficiency exceeds 17%. A purged lip seal system is used in prototype no. 8, and a newly developed "Cool-Seal" (a low temperature mechanical seal) is used in prototype no. 9. In the Cool-Seal system, a large amount of purge flow is introduced behind the seal faces to augment convective heat transfer, keeping the seal face temperature at a low level for prevention of heat denaturation of blood proteins. The Cool-Seal system consumes < 10 cc purge fluid per day and has greatly extended seal life. The pumps were implanted in three calves (26, 30, and 168 days of support). The pump was inserted through a left thoracotomy at the fifth intercostal space. Two pursestring sutures were placed on the LV apex, and the apex was cored with a myocardial punch. The pump was inserted into the LV with the outlet cannula smoothly passing through the aortic valve without any difficulty. Only 5 min elapsed between the time of chest opening and initiation of pumping. Pump function remained stable throughout in all experiments. No cardiac arrhythmias were detected, even at treadmill exercise tests. The plasma free hemoglobin level remained in the acceptable range. Post mortem examination did not reveal any interference between the pump and the mitral apparatus. No major thromboembolism was detected in the vital organs in Cases 1 or 2, but a few small renal infarcts were detected in Case 3.

Relationship of blood pressure and pump flow in an implantable centrifugal blood pump during hypertension.

The purpose of this study was to evaluate the real time relationship between pump flow and pump differential pressure (D-P) during experimentally induced hypertension (HT). Two calves (80 and 68 kg) were implanted with the EVA-HEART centrifugal blood pump (SunMedical Technology Research Corp., Nagano, Japan) under general anesthesia. Blood pressure (BP) in diastole was increased to 100 mm Hg by norepinephrine to simulate HT. Pump flow, D-P, ECG, and BP were measured at pump speeds of 1,800, 2,100, and 2,300 rpm. All data were separated into systole and diastole, and pump flow during HT was compared with normotensive (NT) conditions at respective pump speeds. Diastolic BP was increased to 99.3+/-4.1 mm Hg from 66.5+/-4.4 mm Hg (p<0.01). D-P in systole was under 40 mm Hg (range of change was 10 to 40 mm Hg) even during HT. During NT, the average systolic pump flow volume was 60% of the total pump flow. However, during HT, the average systolic pump flow was 100% of total pump flow volume, although the pump flow volume in systole during HT decreased (33.1+/-5.7 vs. 25.9+/-4.0 ml/systole, p<0.01). In diastole, the average flow volume through the pump was 19.6+/-6.9 ml/diastole during NT and -2.2+/-11.1 ml/diastole during HT (p<0.01). The change in pump flow volume due to HT, in diastole, was greater than the change in pump flow in systole at each pump speed (p<0.001). This study suggests that the decrease of mean pump flow during HT is mainly due to the decrease of the diastolic pump flow and, to a much lesser degree, systolic pump flow.

Effect of hyaluronic acid on the development of porcine 1-cell embryos produced by a conventional or new in vitro maturation/fertilization system.

In pigs, it is difficult to produce normal fertilized embryos from immature oocytes in vitro. However, a new maturation/fertilization system in which the percentage of normal fertilized embryos is comparatively high has been developed recently. In the present study, porcine 1-cell embryos were produced both by a conventional and a new system and then cultured in NCSU-23 supplemented with hyaluronic acid at various concentrations. In the conventional system, the percentage of oocytes with monospermic penetration and 1 male pronucleus and 1 female pronucleus was only 6%. At 144 h after insemination, the percentage (5%) of embryos developing to the blastocyst stage in medium supplemented with 0.5 mg/mL hyaluronic acid was significantly (P<0.05) higher than that (2%) in medium without hyaluronic acid. When oocytes were matured and inseminated using the new system, monospermic penetration and the formation of 1 male and 1 female pronucleus were observed in 69% of the penetrated oocytes. However, blastocyst formation (8 to 14%) at 144 h after insemination was not affected by the concentration (0 to 1.0 mg/mL) of hyaluronic acid. These results indicate that the effect of hyaluronic acid on the development of in vitro-produced porcine embryos varies with the conditions of oocyte maturation and fertilization.

Seasonal changes in inhibin activity in seminal plasma and serum concentrations of FSH, LH and testosterone in the male goat (Capra hircus).

Inhibin activity in goat seminal plasma was measured by in vitro assay throughout successive 9 months and its relationship with the serum FSH, LH and testosterone concentrations was investigated. Total inhibin activity (TIA) in seminal plasma gradually increased from spring to summer, reduced in autumn (P<0.05) and recovered toward winter (P<0.05). Serum FSH and LH reached a peak in mid-summer (P<0.01) and returned to the low levels in autumn. Serum testosterone also increased in mid-summer and kept the high levels until the early winter (P<0.05). Some positive correlation was found in monthly levels between seminal TIA and serum FSH (r=0.305; P<0.05). Results suggest that the summer increase of inhibin activity in seminal plasma relates with the mid-summer rise of serum FSH levels in the male goat.