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Biomedical subjects

S Tobe

Publications and source records attributed to S Tobe.

At least 37 records · Page 2Linked to original sources

Early diagnosis of acute rejection by pulmonary hemodynamics after single-lung transplantation.

The aim of this study was to facilitate the early diagnosis of acute rejection after single-lung transplantation based on pulmonary hemodynamic findings. A Doppler flowmeter was placed in the ascending aorta and the pulmonary artery of adult mongrel dogs after single-lung transplantation. The pulmonary hemodynamics of the lung graft were then evaluated during the early postoperative period and during subsequent rejection. Twenty dogs were divided into three groups. Group 1 consisted of 6 dogs that underwent autotransplantation of the left lung. Group 2 was made up of 6 dogs that underwent allotransplantation of the left lung without immunosuppressant therapy. Group 3 consisted of 8 dogs that underwent allotransplantation of the left lung and were treated with 10 mg/kg of cyclosporine and 4 mg/kg of azathioprine. Pulmonary hemodynamics and chest roentgenograms were studied for more than 2 weeks postoperatively. Open lung biopsy was performed in some dogs to obtain graft specimens for histologic examination. The left pulmonary artery flow rate (percentage of pulmonary graft blood flow to cardiac output) decreased slightly after operation in group 1, and decreased to 14.4% after 1 week and to zero on postoperative day 10 in group 2. The pulmonary vascular resistance of the grafts in group 2 also increased exponentially. In contrast, the left pulmonary artery flow rates decreased to 29.1% on the day after operation in group 3, but recovered to 38.5% on postoperative day 14. Within a mean of 3.7 days of immunosuppressant discontinuation, the left pulmonary artery flow rates decreased to less than 12.7%, with a marked increase in pulmonary resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Central blood volume in cirrhosis: measurement with radionuclide angiography.

In patients with cirrhosis a diminished effective central arterial blood volume associated with systemic arterial vasodilation has been proposed as the mechanism that initiates renal sodium retention. Furthermore, total central blood volume has recently been reported as reduced in cirrhosis, and the controversy over the stimulus for sodium retention in cirrhosis remains. The aim of this study was to assess the central blood volume with radionuclide angiography to determine whether there is effective arterial underfilling in cirrhosis. Twenty-nine patients (13 with and 16 without ascites) and 10 age- and sex-matched control subjects were studied under metabolic conditions. Radionuclide ventricular volume and total central blood volume were determined from gated images, taking into account the 99Tc count activity per milliliter of blood volume and attenuation. The pulmonary volumes were similarly derived.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Design of hepatocyte-specific extracellular matrices for hybrid artificial liver.

For the development of an artificial liver which can assist multiple metabolic functions of liver, the effective cultivation of hepatocytes on substrate as extracellular matrix analogs was examined. Adult rat hepatocytes attached on an asialoglycoprotein model polymer, poly-N-p-vinylbenzyl-D-lactonamide (PLVA), formed anchored multilayer aggregates which had a stable three-dimensional structure when epidermal growth factor (EGF) and insulin were added to the culture medium. The formation of multilayer aggregates was also dependent on the specific cellular attachment mediated by asialoglycoprotein receptor of hepatocyte surface. Cells in the aggregates expressed higher level of albumin secretion and lower proliferative ability than those in monolayer cultures on collagen. It seemed likely that the cells in multilayer aggregates experienced stable differentiated states resembling in vivo status through the forming multilayer aggregates. The culture system described here has useful potentiality for the development of hepatic module systems for a hybrid artificial liver.

Animals↗

Refractory ascites in cirrhosis: roles of volume expansion and plasma atrial natriuretic factor level elevation.

Cirrhotic patients with ascites refractory to diuretics also have blunted response to marked elevations of plasma atrial natriuretic factor levels alone or to moderate intravascular volume expansion by head-out water immersion. However, these patients usually undergo natriuresis after peritoneovenous shunting. To dissect the factors responsible for this response, we studied the effects on separate days of moderate intravascular volume expansion and highly elevated plasma atrial natriuretic factor levels (head-out water immersion and atrial natriuretic factor infusion) or marked volume expansion and moderate plasma atrial natriuretic factor level elevation (head-out water immersion and albumin infusion) in 13 alcoholic cirrhotic patients with massive ascites. Three of these patients, who responded to initial head-out water immersion with a negative sodium balance, served as controls. Unresponsiveness to head-out water immersion was confirmed in the remaining 10 patients on both days on the basis of blunted natriuretic response (urinary sodium excretion < 0.8 mmol/hr after 2 hr). In contrast, these 10 refractory patients were able to achieve negative sodium balance with both combinations. Mean urinary sodium excretion increased from a baseline level of 0.13 +/- 0.10 mmol/hr to a peak level of 2.29 +/- 0.61 mmol/hr after head-out water immersion and atrial natriuretic factor infusion and from 0.10 +/- 0.3 mmol/hr to 1.61 +/- 0.62 mmol/hr after head-out water immersion and albumin infusion. Both maneuvers were associated with suppression of plasma renin activity and serum aldosterone levels. With head-out water immersion and atrial natriuretic factor infusion, we noted a significant increase in 5' cyclic GMP levels, a second messenger of atrial natriuretic factor, indicating possible activation of atrial natriuretic factor receptors at the inner medullary collecting ducts. In contrast, with head-out water immersion and albumin infusion no such increase in levels occurred, indicating that the increase in urinary sodium excretion was mainly due to increased delivery of sodium to the cortical distal nephron, as indicated by a disproportionate increase in urinary potassium excretion. In conclusion, massive (as opposed to moderate) volume expansion or greatly elevated levels of plasma atrial natriuretic factor associated with moderate volume expansion can improve blunted atrial natriuretic factor responsiveness in cirrhotic patients with refractory ascites. This appears to be achieved by way of a marked increase in distal delivery of filtrate in the kidney, with or without activation of distal atrial natriuretic factor receptors in the inner medullary collecting ducts.

Adult↗

[Successful 24-hour pulmonary preservation in the use of hyperbaric oxygen].

24-hour lung preservation with modified Euro-Collins (E-C) solution under hyperbaric oxygen (OHP) was studied in the canine single lung transplantation model. A prostaglandin I2 (PGI2) was administered before cardiac arrest by St. Thomas solution. Lungs were flushed with modified E-C solution, then heart and lungs were excised en-bloc and immersed in 4 degrees C modified E-C solution for 24 hours in control group (N = 5). In OHP group (N = 5), heart and lung block were preserved similarly in the control group but placed in hyperbaric chamber (mixed gas 95% O2, 5% CO2) under 2 atmospheres absolute pressure. In the hyperbaric chamber, the lungs were expanded continuously by pressure difference between the inside and the outside of the lung. The left lung was transplanted into recipient dog and reperfused for 3 hours. Pulmonary function was assessed serially by measuring oxygen and carbon dioxide tensions in arterial blood and pulmonary vascular resistance by clamping the right pulmonary artery for 5 minutes. ATP before and after preservation was measured. In the control group, PaO2, after 24 hours preservation followed by reperfusion, was 177 +/- 88 mmHg, but decreased to 75 +/- 34 mmHg at 3 hours of reperfusion and bloody foamy sputum appeared in 4 dogs. Alternatively, PaO2 was 256 +/- 58 mmHg at 3 hours of reperfusion and foamy sputum did not appear in OHP group. There was a significant difference between the 2 groups (p < 0.05). PaCO2 at 3 hours of reperfusion was 41 +/- 3 mmHg in the control group, and 31 +/- 2 mmHg in the OHP group (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A successful case report of coronary artery bypass grafting with aortic no touch technique for the severely calcified ascending aorta].

Calcification of the ascending aorta may render aortic cross-clamping dangerous and aorta-coronary artery bypass grafting impossible. Coronary artery bypass grafting in a 72-year-old woman with drug resistant unstable angina and severely calcified ascending aorta owing to aortitis was successfully performed with aortic no touch technique which consisted of utilization of the left internal thoracic artery, fibrillatory arrest without aortic cross-clamping, left ventricular venting, and femoral artery perfusion. Her postoperative course was uneventful, and she is relieved of angina.

Aged↗

Receptor-mediated formation of multilayer aggregates of primary cultured adult rat hepatocytes on lactose-substituted polystyrene.

We used a lactose-substituted polystyrene, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), as a substratum for adult rat hepatocytes in primary culture. Spherical-shaped hepatocytes attached on PVLA substratum formed stable multilayer aggregates anchored on substratum through the stimulation of epidermal growth factor (EGF). The cells required calcium ion essentially to form the aggregates. The formation of multilayer aggregates was inhibited by colchicine, but not by cytochalasin B. The inhibition was also observed by added PVLA molecules in the culture medium and by treating surfaces of PVLA-coated dishes with allo A lectin. It was suggested that adult rat hepatocytes attached on PVLA substratum required the specific interaction between asialoglycoprotein receptors on the cell surface and PVLA substratum to form anchored multilayer aggregates.

Animals↗

Effect of prostaglandin I2 and superoxide dismutase on reperfusion injury of warm ischemic lung.

A prostaglandin I2 (PGI2) analogue and superoxide dismutase (SOD) were administered to dogs with pulmonary denervation, and their effects on warm ischemic damage to the lung were studied. Twenty-seven adult mongrel dogs were divided into a control group (6 dogs), a PGI2 group (7 dogs), an SOD group (6 dogs), and a heparin group (8 dogs). The left pulmonary hilum was dissected, with PGI2 (1 microgram/kg) being administered to the PGI2 group and heparin (100 U/kg) to the heparin group. Then the left lung was placed in a warm ischemic state for 1 hour. The SOD group also received 20 mg/kg of SOD intravenously 1 minute before reperfusion. Before warm ischemia, immediately after reperfusion, and 1 hour and 2 hours afterward, the blood gases, left pulmonary vascular resistance, and other data were measured under right pulmonary artery clamping. Arterial oxygen tension showed significantly better values in the SOD and PGI2 groups than in the control and heparin groups. The left pulmonary vascular resistance increased with time in the control group but did not increase in the PGI2 group. Pulmonary microangiography showed that dilatation of the pulmonary arterioles was prominent in the PGI2 group. The quantity of pulmonary extravascular fluid was significantly less in the PGI2 and SOD groups than in the control and heparin groups. Histological examination showed marked collapse of capillaries, intraalveolar hemorrhage, and edema in the control and heparin groups, whereas these changes were only slight in the PGI2 and SOD groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Left ventricular diverticulum with hypertrophy of the left ventricular apex.

A surgical case of diverticulum in the left ventricular apex is presented. A two-dimensional echocardiogram and magnetic resonance image showed a calcified tumor buried in the marked hypertrophied apex of the left ventricle. Enucleation of the oval and hard tumor (4 x 2.5 x 2.5 cm) was performed through the apex, and the defect was anastomosed by buttress sutures. Histologic examination demonstrated that the tumor cavity was filled with a thrombus encapsulated by thickened and calcified endocardium that extended to the left ventricular cavity. In this report, the etiology of the diverticulum with a hypertrophied myocardium is discussed.

Cardiomyopathy, Hypertrophic↗

Tissue reconstruction in primary cultured rat hepatocytes on asialoglycoprotein model polymer.

Adult rat hepatocytes attached on an asialoglycoprotein model polymer, poly-N-p-vinylbenzyl-D-lactonamide (PVLA), formed anchored multilayer aggregates that had stable three-dimensional structure when epidermal growth factor (EGF) and insulin were added to the culture medium. The formation of multilayer aggregates depended on the concentrations of EGF and insulin added. Furthermore, the formation was synergistically accelerated by the presence of both hormones. Cells in the aggregates expressed a higher level of albumin secretion and lower proliferative ability than those in monolayer cultures on collagen. It seemed likely that the cells in multilayer aggregates experienced stable differentiated states resembling those in vivo through the formation of multilayer aggregates. The culture system described here has potential use for the study of the process of liver regeneration and the development of hepatic module systems such as a bioreactor and a hybrid artificial liver.

Albumins↗

[Clinical study on surgical treatment of renal cell carcinoma with pulmonary metastases].

This study reviewed the surgical therapy for lung metastatic foci of renal cell carcinoma. During the 14 years from 1977 to 1991, lung metastatic foci were removed in 10 patients with renal cell carcinoma at our hospital. Six of them died of cancer and four are alive. The prognosis tended to be better the longer the interval from nephrectomy to lung metastasis. Neither the number of metastatic foci nor the surgical technique produced any difference in the prognosis. The prognosis tended to be better for patients with clear cell tumors than for those with granular cell tumors. For the treatment of lung metastasis of renal cell carcinoma, since we have no better therapy than surgical removal at the present, it is our duty to attempt to improve the prognosis of patients by the resection of metastatic foci whenever possible. However, the use of adjuvant therapy such as interferon should be considered, and the indications for operation and the timing of surgery reviewed.

Aged↗

Pharmacokinetics of single and chronic dose zidovudine in two HIV positive patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

The effect of continuous ambulatory peritoneal dialysis (CAPD) on zidovudine (ZDV) elimination was studied in two HIV-positive men. Serum and dialysate samples were collected after a single oral dose of 200 mg (patient 1) or 100 mg (patient 2) of ZDV, and again on at least one occasion during chronic therapy (100 mg every 8 h). Concentrations of ZDV and its glucuronide metabolite (GZDV) were measured by radioimmunoassay. ZDV serum half-lives on day 1 were 7.9 h (patient 1) and 2.6 h (patient 2). The apparent GZDV half-lives on day 1 were 19.9 h (patient 1) and 7.1 h (patient 2), with resultant accumulation of metabolite (up to 36 micrograms/ml) during chronic therapy. At 14 h following single dose, 8.2 +/- 0.4% of dose was recovered in dialysate as GZDV; ZDV accounted for less than 0.6% of dose recovered in dialysate after both single and multiple dose. After the initial dwell (tau) following single dose, peritoneal clearances of ZDV were 4.3 ml/min (tau = 4 h, patient 1) and 5.9 ml/min (tau = 5 h, patient 2), and GZDV clearances were 6.7 and 5.1 ml/min, respectively. ZDV serum protein binding was less than 10%. The small amount of unchanged ZDV removed by CAPD suggests that no supplemental doses are needed in HIV patients undergoing CAPD.

Acquired Immunodeficiency Syndrome↗

Muscle sympathetic nerve activity and renal responsiveness to atrial natriuretic factor during the development of hepatic ascites.

PURPOSE: Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive antinatriuretic forces such as the sympathetic nervous system and vasodilatory natriuretic agents such as atrial natriuretic factor (ANF). With the development of refractory ascites, cirrhotic patients become unresponsive to the natriuretic effect of ANF. Animal data suggest that the sympathetic nervous system plays a key role in mediating the refractoriness to ANF. We therefore studied the relationship between sympathetic nerve activity (SNA) and the natriuretic response to ANF in normal subjects and cirrhotic patients. We also attempted to localize the intrarenal site of refractoriness to ANF by lithium clearance. PATIENTS AND METHODS: Twenty-six patients with biopsy-proven cirrhosis and seven age- and sex-matched normal volunteers were studied after a week of 20 mmol/day sodium intake and no diuretics. Muscle SNA was recorded from the peroneal nerve (microneurography) and correlated with responsiveness to a 2-hour ANF infusion. Lithium clearance was used as a marker of sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action. Plasma norepinephrine, renin, and aldosterone levels were also determined. Patients were categorized into three groups: nine patients free of ascites (by ultrasonography), five ascitic patients who responded to a 2-hour ANF infusion (i.e., had a natriuretic response to ANF above 0.83 mmol/hour), and 12 ascitic patients who did not respond. RESULTS: Muscle SNA was greatly increased in the ascitic nonresponder patients compared with the normal subjects (64 +/- 4 versus 27 +/- 7 bursts/minute, p less than 0.001), moderately increased in ascitic responders (47 +/- 6 bursts/minute, p less than 0.05), but not significantly increased in nonascitic patients with cirrhosis (34 +/- 5 bursts/minute). SNA was positively correlated with plasma norepinephrine levels (r = 0.69; p less than 0.005) and inversely correlated with peak sodium excretion during the ANF infusion (r = -0.63; p less than 0.001). Plasma renin activity and aldosterone were markedly elevated in ascitic nonresponders, and normal in ascitic responders and nonascitic patients. Lithium clearance was reduced in ascitic patients compared with nonascitic patients, did not change after the ANF infusion, and correlated inversely with SNA (r = -0.61; p less than 0.01). CONCLUSION: These results support the concept that the sympathetic nervous system is a factor in renal sodium handling in cirrhosis, especially in the initiation of sodium retention and the development of refractory ascites. Refractoriness to ANF might be explained, at least in part, by increased neurally mediated sodium reabsorption proximal to the intramedullary collecting duct, the main site of ANF action.

Adult↗

Glue-sniffing and distal renal tubular acidosis: sticking to the facts.

An index case is presented to introduce the subject of the acid-base and electrolyte abnormalities resulting from toluene abuse. These include metabolic acidosis associated with a normal anion gap and excessive loss of sodium and potassium in the urine. The major question addressed is, what is the basis for the metabolic acidosis? Overproduction of hippuric acid resulting from the metabolism of toluene plays a more important role in the genesis of the metabolic acidosis than was previously believed. This conclusion is supported by the observation that the rate of excretion of ammonium was not low during metabolic acidosis in six of eight patients, suggesting that distal renal tubular acidosis was not an important acid-base abnormality in most cases where ammonium was measured. The excretion of hippurate in the urine unmatched by ammonium also mandates an enhanced rate of excretion of the cations, sodium and potassium. The loss of sodium causes extracellular fluid volume contraction and a fall in the glomerular filtration rate, which may transform the normal anion gap type of metabolic acidosis into one with a high anion gap (accumulation of hippurate and other anions). Continuing loss of potassium in the urine leads to hypokalemia. An understanding of the metabolism of toluene provides the basis for the unusual biochemical abnormalities seen with abuse of this solvent.

Acid-Base Equilibrium↗

Characterization of peritoneal transport in patients with failed renal allografts receiving CAPD.

Many patients with failed renal transplants elect to receive continuous ambulatory peritoneal dialysis (CAPD) as their modality of dialysis. For others, cardiovascular considerations or access difficulties make CAPD a necessary option when these patients return to dialysis. It is unclear what effects renal transplantation, chronic immunosuppressive therapy and graft rejection might have on the integrity of the peritoneal membrane. We report on thirteen patients receiving CAPD who had peritoneal equilibration test (PET) studies after a failed renal transplant. Three of these patients had studies done pre and post transplantation. Our solute equilibration studies demonstrated that for 10 patients studied with the older 4.25% technique the mean post transplantation D/P creatinine was 0.688 (SE:0.039) on the border of high and low average, and the mean D/Do glucose was 0.228 (SE:0.024) in the high transporter range. Three patients tested pre and post transplantation (upon their return to CAPD after graft failure) had no change in these values. From the above data, 13 patients with peritoneal equilibration testing post transplantation have well-functioning peritoneal membranes allowing for adequate dialysis and flexibility in dialysis prescription. We conclude that renal transplantation does not adversely affect peritoneal membrane function if these patients return to CAPD after graft failure.

Biological Transport↗

[Experimental studies on the effects of superoxide dismutase on warm ischemic-reperfusion injury of the lung].

Transient impairment of the transplanted lung in early postoperative period is one of difficult problems in lung transplantation. It is likely that reperfusion injury of the warm ischemic lung is contributory. The purpose of this study is to evaluate the effects of superoxide dismutase (SOD) on reperfusion injury of warm ischemic lung. Thirty mongrel dogs were divided into four groups. In group I (n = 6), the left lung with complete hilar stripping was placed in warm ischemic state under deflation for 1 hour. In group II (n = 9), the left lung with complete hilar stripping was kept in warm ischemic condition under inflation. Group III (n = 6) animals with same manipulation as group I received superoxide dismutase (SOD 20 mg/kg) before reperfusion. Group IV (n = 9) animals underwent same manipulation as group II and received SOD (20 mg/kg) before reperfusion. Before warm ischemia, immediately after reperfusion, and 1 and 2 hours, blood gases, left pulmonary vascular resistance were measured under the occlusion of right pulmonary artery. Extra vascular lung water content (EVLW) was measured at autopsy and lung was processed for histology. In group II, III and IV, blood gases and EVLW showed significantly better values than group I. In group I and III, left pulmonary vascular resistance increased prominently after reperfusion, however did not change in group II and IV. From these results, we concluded that inflated lung reduced the extent of pulmonary edema after reperfusion and SOD was effective in preventing warm ischemic damage even in deflated lung.

Animals↗