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Biomedical subjects

Y Ohtake

Publications and source records attributed to Y Ohtake.

90 records · Page 5Linked to original sources

[Clinical evaluation of SPECT in cerebrovascular disease].

In 131 patients with cerebrovascular disease, regional cerebral blood flow was determined by 123I-IMP (N-isopropyl (123I)-iodoamphetamine) or 99mTc-HM-PAO (99mTc (d, l)-hexamethyl propyleneamine oxime) SPECT and findings were compared with those of X-CT or MRI. The perfusion deficit detected by SPECT was larger than the deficit by X-CT or MRI in every cases. The perfusion deficit area was more clearly demonstrated by SPECT than by X-CT or MRI in patients with acute cerebral infarction. The hypoperfusion area determined by 123I-IMP SPECT was wider than that by 99mTc-HM-PAO SPECT. The crossed cerebellar diaschisis was observed in 56 out of 131 cases (43%). The results of operation were quantitatively evaluated by 123I-IMP SPECT in 25 patients.

Aged↗

[Perioperative water and electrolyte metabolism and its abnormalities in aged patients].

The number of aged surgical patients is increasing due to the increase of aged people in the general population. Aged surgical patients above 65 years of age constituted about 30% of all ICU patients in our institution. Perioperative care for aged patients has now become one of the most important clinical activities in the ICU. The perioperative management for those aged patients should be performed with great care because these patients have some abnormalities in water and electrolyte metabolism. Aged patients showed decreased blood levels of atrial natriuretic peptide (ANP) and decreased creatinine clearance even in the preoperative period. The ANP level and the creatinine clearance showed significant negative correlation, indicating that one of the reasons for impaired renal function among aged patients could be the decreased ANP level in blood. The intraoperative insults to the aged surgical patients undergoing radical operation for esophageal cancer tended to be smaller compared to that in the younger patients. Intraoperative infusion volume and urinary output were also smaller in the aged group compared to those in the younger group. The postoperative infusion therapy in the ICU mainly consisted of intravenous hyperalimentation with decreased Na content and the transfusion of fresh frozen plasma. This regimen should be more suitable for the aged patients. Even though the aged and the younger group received the same infusion therapy during their postoperative ICU stay up to the 7th day, the aged patients showed the tendency of Na and Cl retention and increase in anion gap. However, these abnormalities in water and electrolyte metabolism were not so severe as to cause clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Prognostic value of serum osmolality gap in patients with multiple organ failure treated with hemopurification.

Serum osmolality gap (OG), the difference between measured and predicted serum osmolality, has been shown to be an excellent parameter to express the amount of conventionally unmeasurable middle-molecular-weight substances. OG was determined on 29 patients with multiple organ failure (MOF) treated with or without hemopurification. OG significantly increased in proportion to the increase in the number of failed organs and correlated well with APACHE II score. Nonsurvivors showed persistently high OG. OG decreased with plasma exchange and hemoadsorption, but not with hemodialysis, indicating that pathogenic factors can be removed effectively with plasma exchange and hemoadsorption. The patients with OG greater than 20 mOsm/kg-H2O had very little possibility of survival. These results indicate that OG is an easily determinable, effective parameter to evaluate the severity of the patients' condition, efficacy of hemopurification in removing pathogenic middle-molecular-weight substances, and the prognosis of the patient in the treatment of MOF.

Hemoperfusion↗

[Metabolic abnormalities and nutritional management in postoperative multiple organ failure].

Despite its importance, very little has been known on metabolic abnormalities in the patients with postoperative multiple organ failure (POMOF). The present study was undertaken to investigate the metabolic abnormalities and to establish effective nutritional management on these patients. Systemic energy metabolism and hepatocellular mitochondrial function were studied with indirect calorimetry and arterial ketone body ratio measurements on 30 POMOF patients treated between 1984 and 1985. The POMOF patients were hypermetabolic and their hepatic mitochondrial function was impaired. Their caloric intake was depleted for the limitation in administrable water volume due to renal failure. Some of them could not utilize exogenous glucose given by total parenteral nutrition (TPN). To overcome these problems, on 26 POMOF patients treated between 1986 and 1987 continuous hemofiltration (CHF) was applied to remove excess water and ATP-Mg was administered to improve hepatic mitochondrial function during TPN. The sufficiency rate of energy intake (caloric intake/energy expenditure) was improved from 73.3 +/- 14.7% to 92.0 +/- 8.1% with simultaneous CHF and the hepatic mitochondrial function was also improved with ATP-Mg resulting in better utilization of exogenous glucose. These results indicate that CHF and ATP-Mg administration are effective adjunctive treatments in the nutritional management for POMOF.

Adenosine Triphosphate↗

Effects of ATP-MgCl2 and ATP-Na2 administration on renal function and cellular metabolism following renal ischemia.

The present study compared the effects of ATP-MgCl2 or ATP-Na2 administration on renal function and cellular metabolism following renal ischemia in rabbits. Following 100 min of ischemia, the blood flow to the kidney was allowed to reestablish itself, and the rabbits received either saline, ATP-MgCl2 (17.5 mumole/kg each), or ATP-Na2 (17.5 mumole/kg) intravenously. ATP-MgCl2 administration following ischemia significantly accelerated the recovery of renal function. However, administration of ATP-Na2 failed to show any beneficial effect on the recovery process. The changes in renal cellular ketone body ratio (acetoacetate/beta-hydroxybutyrate), energy charge, and pyruvate/lactate indicated that ATP-MgCl2, but not ATP-Na2, reversed ischemically induced impairment in renal cellular metabolism. Reduction in the renal blood flow caused by ischemia was also improved with ATP-MgCl2 treatment. These results indicate that ATP should be given in the form of ATP-MgCl2 for it to be effective following renal ischemia. The results also suggest that the salutary effect of ATP-MgCl2 following renal ischemia could occur through the improvement of cellular metabolism and concomitant improvement in tissue blood flow.

Acetoacetates↗

[Pathophysiology and treatment of multiple organ failure among hepatectomized cirrhotic patients].

Our previous studies have claimed that cirrhotic rats, induced with CCl4, showed depressed reticuloendothelial system (RES) function and increased susceptibility to infection. We have also shown that OK-432, a non-specific immunopotentiator, and ATP-MgCl2, which improves depressed intracellular energy metabolism, improve RES function of cirrhotic rats and that thereby improve survival following peritonitis or hepatectomy. The present study was undertaken to investigate whether OK-432 or ATP-MgCl2 could be beneficial for the prevention of multiple organ failure (MOF) following hepatectomy among the cirrhotics. The cirrhotics with hepatocellular carcinoma, who underwent partial hepatectomy (segmentectomy or subsegmentectomy) were given OK-432 (5 KE/day for 4 days) preoperatively or ATP-MgCl2 (50 mumole/kg) within 24 hours following the operation. The rates of postoperative pulmonary complication and the operative mortality were compared among OK-432 group, ATP-MgCl2 group and controls. The rates of posthepatectomy pulmonary complication and operative mortality were decreased with these treatments compared to the controls. The RES function was also improved with these treatments. These data suggest that the cirrhotic patients are the immunocompromised hosts showing the depressed RES function and that the enhancement of RES function with OK-432 or ATP-MgCl2 is beneficial for the prevention of posthepatectomy MOF among cirrhotics.

Animals↗

[Treatment of post-hepatectomy hepatic cellular energy crisis in cirrhosis with ATP-MgCl2 administration].

The present study was undertaken to investigate the effect of ATP-MgCl2 for hepatic cellular energy crisis following hepatectomy in cirrhosis. In experimental study, cirrhotic rats, induced by subcutaneous injection of CCl4 twice a week for 10 weeks, received ATP-MgCl2 (12.4 mumoles) (ATP group) or saline (control group) at 2 hours after 68% hepatectomy. The hepatic cellular energy charge (EC) and arterial ketone body ratio (AKBR), which were good indicators to evaluate the hepatic cellular metabolism, and reticuloendothelial system (RES) function were significantly improved among ATP group at 24 hours after hepatectomy compared to the control group. Survival at one week was also significantly improved with ATP-MgCl2 treatment. In clinical study, ATP-MgCl2 (30-50 mumoles/kg) was infused intravenously to twenty hepatectomized cirrhotic patients. The hepatic cellular energy metabolism, studied using AKBR, and RES function as well as the clinical course were improved with ATP-MgCl2) treatment compared to those of the conventionally treated controls. These data indicate that ATP-MgCl2 is beneficial as one of the therapeutic approaches to improve the hepatic cellular energy crisis after hepatectomy which is the major cause of death following hepatectomy among cirrhotic patients.

Adenosine Triphosphate↗

Experimental and clinical study on ATP-MgCl2 administration for postischemic acute renal failure.

The present study was undertaken to investigate the effect of ATP-MgCl2 on the recovery of renal function following renal ischemia. Bilateral renal ischemia was produced for 90 minutes in dogs. Immediately after the release of ischemia, ATP-MgCl2 (50 mumoles/kg) was given intravenously. Serum creatinine and FeNa were measured following the release of ischemia. Renal cellular energy charge, glomerular endothelial thickness and per cent circularity of interstitial cells were measured. Creatinine and FeNa were significantly lower in ATP-MgCl2 treated dogs compared to those in saline treated controls. Changes in energy charge, glomerular endothelial thickness and per cent circularity indicated ischemically induced renal cellular edema was reversed with ATP-MgCl2 through the improvement of energy metabolism. Taking those experimental data into consideration, ATP-MgCl2 was given to 16 acute renal failure patients and 13 patients survived. ATP-MgCl2 administration is effective for the treatment of acute renal failure.

Acute Kidney Injury↗

Improved survival and reticuloendothelial function with intravenous ATP-MgCl2 following hemorrhagic shock.

There is controversy concerning the efficacy of ATP-MgCl2 in improving survival following hemorrhagic shock. To resolve this issue, the effect of ATP-MgCl2 infusion on survival following shock was reinvestigated. Rats were bled to and maintained at a mean arterial blood pressure of 40 mmHg for 90 min. Following reinfusion of the remaining shed blood, the animals were treated with ATP-MgCl2 (25 mumoles each) or saline. Survival was measured in one group of animals, and in another group of animals reticuloendothelial (RE) function was determined with 131I gelatinized test lipid emulsion in search of the mechanism of the beneficial effect of ATP-MgCl2 following hemorrhagic shock. The results indicate that survival was significantly improved if the animals were treated with ATP-MgCl2 following hemorrhagic shock. In addition, RE function, which was markedly depressed following hemorrhagic shock, was significantly improved by ATP-MgCl2 treatment, indicating that the beneficial effect of ATP-MgCl2 for hemorrhagic shock could be through the improvement of RE function.

Adenosine Triphosphate↗

Determination of felodipine enantiomers using chiral stationary phase liquid chromatography and gas chromatography/mass spectrometry, and the study of their pharmacokinetic profiles in human and dog.

A stereoselective and sensitive method for the determination of the enantiomers of felodipine, a dihydropyridine calcium antagonist, has been developed and the pharmacokinetic profiles of the enantiomers comparatively studied after oral administration to dogs and humans. D6-Felodipine, the internal standard, was added to the plasma, extracted with a solvent and then optically resolved into S(-) and R(+) enantiomers on a high performance liquid chromatographic Chiralcel OJ column. Each enantiomer in the effluent was analysed by capillary column gas chromatography/positive ion electron impact mass spectrometry. After oral administration of the felodipine racemate, the Tmax and t1/2 values hardly differed between the two enantiomers in dogs and humans. The Cmax and AUC0-24 h values of the S(-) enantiomer were slightly higher than those of the R(+) enantiomer in humans but the difference between the enantiomers was not significant. These results suggested that there is no large difference in the absorption, distribution and elimination of felodipine enantiomers after oral administration of the racemate in either dog or human.

Adult↗

A muscle powered cardiac assist device for right ventricular support: total assist or partial assist?

A muscle powered cardiac assist device (MCAD) for right ventricular support requires optimized diastolic filling to obtain full stroke and acceptable fluid dynamics. A valved and spring-assembled skeletal muscle ventricle (SMV) was designed as a prototype MCAD, regardless of fluid dynamics. The present study addresses the optimal bypass method for right ventricular support, and predicts the future design for an implantable MCAD. Latissimus dorsi muscle (LDM) of 11 dogs were conditioned electrically for a one year maximum, and transformed into fatigue-resistant muscles (Type I fibers). Superior and inferior vena cavae were anastomosed using one arm of a Y-shaped vascular graft, as an inflow conduit, and the outflow conduit was placed on the main pulmonary artery. SMV was wrapped with transformed LDM and the bypass method was varied by SVC and/or IVC ligation. SMV demonstrated sufficient right ventricular support on total bypass (70% compared with control output), and the maximum pump off-to-on flow ratio (200%) was obtained. Maximum SMV power output was 0.27 X 10(6) erg, which was equivalent to that of canine right ventricle. Right atrial-to-pulmonary artery bypass was also constructed by using SMV in another 14 dogs, and also showed that total bypass was preferable for optimal SMV diastolic filling. In conclusion, specific requirements for a future MCAD include a subsystem assembly such as a spring, magnet, or alternative auxiliary muscle pump assembly for MCAD filling, and total bypass with optimized fluid dynamics and anatomic fitting.

Animals↗

Receptor-mediated gene delivery using the Fab fragments of anti-epidermal growth factor receptor antibodies: improved immunogene approach.

We previously developed the "immunogene" approach toward cancer gene therapy using epidermal growth factor receptor (EGFR)-mediated endocytosis. Here, we describe an improved immunogene system, in which the antigen-binding (Fab) fragments of the monoclonal antibody (Ab) B4G7 against the human EGFR were conjugated with poly-L-lysine to form a gene delivery vehicle (designated Fab "immunoporter"). Within 12 hours, the beta-galactosidase beta-gal) gene was transferred via the Fab immunoporter to virtually all of the nuclei of human squamous carcinoma A431 cells that overproduce the EGFR, and the beta-gal enzyme activity was detected within 24 hours and retained for more than 3 days. The beta-gal gene was not transferred into human and mouse cells that were deficient in EGFRs, but it was delivered if those mouse cells were transformed with human EGFR genes. Beta-gal gene transfer via the Fab immunoporter was inhibited by pretreatment with excess amounts of the Fab fragment. The transfer efficiency of the beta-gal gene to A431 cells via the Fab immunoporter was approximately 2%, which is as high as the lipofection method and 20- to 100-fold higher than the whole Ab immunoporter. The transfer of the herpes simplex virus thymidine kinase gene into A431 tumor cells as a form of the thymidine kinase/Fab immunogene was successful, and subsequent treatment with ganciclovir induced remarkable suicide effects which conferred 1000-fold higher drug sensitivity. Thus, the Fab immunogene was substantially improved with regard to the whole Ab immunogene and could be used as a potent gene transfer vehicle for the in vivo targeting of EGFR-hyperproducing tumor cells.

Animals↗