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Biomedical subjects

H Kikuchi

Publications and source records attributed to H Kikuchi.

At least 685 records · Page 38Linked to original sources

Pitfalls in the surgical treatment of moyamoya disease. Operative techniques for refractory cases.

Eleven cases of moyamoya disease refractory to indirect non-anastomotic revascularization, including encephalomyosynangiosis in two, encephaloduroarteriosynangiosis in seven, and encephalomyoarteriosynangiosis in two, are described. The patients suffered from recurrent cerebral ischemic symptoms, and further operative intervention, including superficial temporal artery-middle cerebral artery anastomosis and intracranial omental transplantation, was performed. The choice of operative maneuver depended on the availability of scalp arteries and on the nature of the ischemic symptoms. Although indirect non-anastomotic revascularization procedures have the advantage of technical ease and most patients respond to these procedures alone, there are some patients like the 11 presented here who are not cured by such procedures. In such cases, direct anastomotic revascularization is necessary for the prevention of stroke.

Activities of Daily Living↗

Specific cytotoxic activity of T lymphocyte clones derived from a patient with gliosarcoma.

Eleven lymphocyte clones were established from the peripheral blood lymphocytes of a patient with gliosarcoma by means of autologous tumor stimulation and the limiting-dilution technique with recombinant interleukin-2. Ten of the 11 clones were cytotoxic against the autologous tumor cell line GI-1. Seven of the 10 clones were also cytotoxic against allogeneic brain-tumor lines and HeLa cells, one clone was cytotoxic against several target cells, and two clones were specifically cytotoxic against GI-1 and allogeneic brain-tumor cells. One of the 11 clones was not cytotoxic against any target cells tested. Lymphokine-activated killer cells induced by recombinant interleukin-2 alone exhibited cytotoxic activity against all target tumor cells tested. Surface phenotypic analysis revealed that all lymphocyte clones expressed CD3 antigen, some expressed CD4 antigen, and others expressed CD8 antigen. These clones seemed to be antigen-specific cytotoxic T lymphocyte clones. Analysis with these antigen-specific cytotoxic T lymphocyte clones may be useful in the elucidation of tumor-specific or tumor-associated antigens on autologous tumor cells.

Antigens↗

In vitro antibacterial activity of FK482, a new orally active cephalosporin.

FK482 is a new orally active cephem antibiotic which offers some advantages over the commercially available oral beta-lactam antibiotics. It displayed a broad spectrum of activity in vitro against stock strains of Gram-positive and Gram-negative aerobes and anaerobes. FK482 was more active in vitro than cefixime (CFIX), cefaclor (CCL) or cephalexin (CEX) against clinical isolates of Gram-positive organisms such as methicillin-sensitive Staphylococcus aureus, coagulase-negative Staphylococci including Staphylococcus epidermidis and strains of the Streptococcus group. Moderate activity was found against methicillin-resistant S. aureus and Enterococcus faecalis. Against clinical isolates of many Gram-negative species, including opportunistic pathogens, FK482 had good in vitro activity similar or slightly inferior to that of CFIX but superior to that of CCL or CEX. However, it was clearly inferior to CFIX in activity against Serratia marcescens, and was inactive against Pseudomonas aeruginosa. Strains of S. aureus resistant to methicillin were moderately susceptible to FK482. All tested strains of Klebsiella pneumoniae resistant to CCL and CEX were susceptible to FK482, as were all the strains of Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Branhamella catarrhalis resistant to amoxicillin (AMPC). FK482, like CFIX, was relatively stable to all type of beta-lactamases except Bacteroides fragilis and its stability was superior to that of CCL or CEX. The antibacterial activity of FK482 against CSH2 strains containing ampicillin-resistance plasmids was not affected by the presence of the ampicillin resistance determinants. FK482 showed higher affinity for the penicillin-binding proteins (PBPs) (3, 2 and 1) of S. aureus than did CFIX, CCL and CEX. FK482 also showed very high affinity for the PBPs (2 and 3) of E. faecalis and PBPs (3, 1a, 4, 2 and 1 bs) of E. coli. The bactericidal activity of FK482 against S. aureus was almost as strong as that of AMPC and superior to that of CCL or CEX. Against Gram-negative bacteria such as E. coli, K. pneumoniae and P. mirabilis, FK482 was similar to CFIX and superior to CCL and CEX in bactericidal activity.

Administration, Oral↗

In vivo antibacterial activity of FK482, a new orally active cephalosporin.

The therapeutic activities of orally administered FK482 were compared with those of reference antibiotics against systemic and local infections with a variety of bacteria in mice and rabbits. In systemic infections in mice, oral FK482 was almost as effective as oral cefaclor (CCL) and more effective than oral cephalexin (CEX) against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis infections. However, FK482 afforded superior protective activity when given subcutaneously against E. coli infection in mice, and this activity was more potent than that of subcutaneously given CCL. In comparison with CCL, the reason that the in vivo activity of orally given FK482 against mouse systemic infections was weaker than had been anticipated from its potent in vitro activity was due to its poor oral absorption in mice. In local infections in rabbits, a species in which FK482 was better absorbed than in mice, FK482 was more effective than CCL, CEX or amoxicillin (AMPC). Against pneumonia induced by S. aureus or Streptococcus pyogenes, FK482 was as effective as AMPC and more effective than CCL in reducing the number of viable bacteria in the lungs of infected rabbits. In the oral treatment of experimental ascending pyelonephritis in rabbits, FK482 was superior to CCL and AMPC against methicillin-resistant S. aureus infection, as effective as AMPC and more effective than CCL against Enterococcus faecalis infection, and as effective as cefixime (CFIX) and more effective than CCL and AMPC against E. coli infection in reducing the number of viable bacteria in the kidneys and urine.

Administration, Oral↗

Pharmacokinetics of FK482, a new orally active cephalosporin, in animals.

The pharmacokinetic profile of FK482 was studied in mice, rats, rabbits and dogs after oral dosing and compared with that of cefixime, cefaclor and cephalexin. Considerable differences in oral absorption of FK482 were observed among the animal species. Absolute bioavailabilities of FK482 were 12.6% in mice, 15.3% in rats, 32.3% in rabbits and 72.3% in dogs. In mice and rats, the absorption of FK482 was poor, and was the lowest of the reference antibiotics. FK482 was moderately well absorbed, with higher plasma levels than cefixime in rabbits and, like cefixime, gave higher plasma levels and a longer half-life than cefaclor or cephalexin in dogs. The increase in the area under the serum concentration time curve (AUC) of FK482 was strictly proportional to the increase in dose in the range of 2.5 to 40 mg/kg in rats and dogs, and 2.5 to 20 mg/kg in rabbits and the urinary recovery rates were almost constant. All tissue concentrations of FK482 in rats and rabbits were lower than those of the reference antibiotics and reflected its lower plasma concentrations in these animals. The urinary recovery rates of FK482 were 9.8% for mice, 15.5% for rats, 45.8% for rabbits and 47.1% for dogs. The biliary recovery rate of FK482 was low; 1.4% in rats and less than 0.1% in rabbits and dogs. No active metabolites were detected in the plasma, urine or bile samples from rats, rabbits or dogs. FK482 was mainly absorbed in the jejunum, and was inactivated in the large intestine. The serum-protein binding of FK482 was almost the same as that of cefixime: 60-77% for mouse, rabbit and human serum, and 90-93% for rat and dog serum.

Administration, Oral↗

Automated determination of drugs in serum by liquid chromatography with column-switching. I. Separation of antiepileptic drugs and metabolites.

This is a fully automated system for determining six common antiepileptic drugs and two principal metabolites of carbamazepine in serum. It is based on "high-performance" liquid chromatography (HPLC), with column switching. TSKprecolumn BSA-ODS and TSKgel ODS-120A (both from Toyo Soda) were used as the precolumn and analytical column, respectively. The former contains octadecylsilyl resins treated with bovine serum albumin (BSA), and does not adsorb macromolecules such as serum proteins but retains small lipophilic molecules such as antiepileptic drugs. Serum samples are directly injected onto the precolumn. After washing out the serum proteins from the precolumn with sodium phosphate buffer, we switch the column connections to introduce the retained substances onto the analytical column and elute with a step-gradient of acetonitrile/sodium phosphate buffer. The high analytical recovery (95-102%) and the reproducibilities (CV less than 5% within-run) indicate that this system is suitable for use in theraputic drug monitoring in clinical laboratories.

Acetonitriles↗

[An experimental study on SRCA (subrenal capsule assay)--using immunosuppressive maneuvers].

Six-day SRCA using normal mice developed by Bogden et al. is one of the most promising methods for in vivo chemosensitivity tests. However, this method has a problem on the influence of the host reaction during six days. Therefore, we examined the tumour growth kinetics, host reaction and expression of antitumor effect on three immunosuppressive maneuvers; cyclophosphamide (EX), cyclosporin A (CSA), and total body irradiation (TBI). The tumour diameter increased until day 16 in EX and CSA-treated groups and day 10 in TBI-treated group, but the results of the histological examination showed that tumour cells were preserved in tissue on day 14 in CSA-treated group and day 6 in EX and TBI-treated groups. These results were supported by flow cytometrical analysis. The autoradiogram using 3H-TdR showed that labelling index of the tumour cells was not affected by these immunosuppressive maneuvers. From the investigation of the antitumour activity of adriamycin and mitomycin C, it was suggested that the 12-day assay was suitable if nude mice were used in SRCA, and six-day assay, if EX-treated normal mice were used. In CSA-treated group, toxicity of anticancer drugs was manifested than usual.

Adenocarcinoma↗

[Analysis of internal carotid-posterior communicating artery aneurysms with difficulty in clipping: with special reference to radiometry].

Although internal carotid-posterior communicating artery (ICPC) aneurysms seem to be one of the easiest to be operated on, some are known difficult to handle and could not be successfully clipped even with all sorts of preparations. It is, therefore, essential to analyze ICPC aneurysms with difficulty in clipping. Out of 106 cases with ICPC aneurysms admitted to Kyoto University Hospital since May 1977, 83 cases have been registered in this study to the exclusion of either non-operated cases or giant aneurysm cases. Cases with difficulty in clipping procedure are selected and classified depending on its causes, which were judged from operation records as well as operative photographs. Angiograms have been checked to discuss whether possible causes of difficulty in clipping could have been suspected preoperatively. Radiometry were also performed in the following items; distance between the anterior clinoid process (ACP) and proximal side of the aneurysmal neck (W) in AP view, distance of proximal side of the neck from ACP (D) and its height (H) from the baseline between the ACP and posterior clinoid process in lateral view. Causes of difficulty in clipping procedure can be grouped as follows: a) ventrally directed dome of the aneurysm (9 cases), b) incision of the plica petroclinoidea anterior (PPA) or removal of the anterior clinoid process (ACP) to identify proximal side of the neck (7 cases: b group), c) saucer-shaped dome with no apparent neck, d) branches of the internal carotid artery from dome.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid Artery Diseases↗

[Treatment of vasospasm after ruptured cerebral aneurysms by 'pellet-cisternal-drain: PCD' containing sustained-release vasodilators].

Diltiazem or papaverine hydrochloride as vasodilators were polymerized with silicon polymer (MDX-4-4210: Dow Co.). The silicon pellets containing the drugs were placed in cisternal drainage tubes made of silicon, and used for the continuous cisternal drainage after the operations of ruptured cerebral aneurysms. This system was tentatively termed 'pellet-cisternal-drain; PCD'. The rate of diffusion of the drug from the pellets was examined in 30 patients who underwent surgery for ruptured cerebral aneurysms in the acute phase on the 0-4th postical days. 73.3% of patients had severe subarachnoid hemorrhage as group 3-4 in Fisher's classification in CT scan. The concentration of either drug in the cerebrospinal fluid on the 2nd to 3rd postoperative days reached the level of the maximum concentration obtained after bolus injection, and the level on the 5th to 10th postoperative days was similar to that observed several hours after bolus injection. The data showed that the sustained release pellet can act as a vasodilator, and its effects on cerebral vessels after an episode of subarachnoid hemorrhage continue for 2 to 3 weeks. All patients except one showed excellent results and returned to normal life.

Adult↗

[Reversibility of cerebral cortical function after recirculation in experimental cerebral ischemia].

Several kinds of monitoring systems to evaluate cerebral function have been introduced such as somatosensory evoked potential, visual evoked potential and auditory brain stem response. Although these monitoring systems are employed in practice in neurosurgical operations, the reversibility of these cerebral functions after ischemia insult is little known. In this study the reversibility of direct cortical response (DCR) as well as EEG from global ischemia was investigated using total 60 cats. Cortical cerebral blood flow was also measured continuously by the thermal diffusion flow probe with a peltier stack calibrated by hydrogen clearance. Global ischemia was made by the occlusion of innominate and left subclavian arteries. Although the EEG was abolished soon after occlusion of these arteries, DCR was preserved and it started to decay at the cortical CBF of about 21 ml/100 g/min. It had completely disappeared at the CBF of about 8 ml/100 g/min. Recovery of DCR was not correlated with the occlusion time, but it was well correlated with the interval of loss of DCR. When the DCR was not completely lost, DCR amplitude was completely recovered about 3 hours after ischemia insult with the CBF below 20 ml/100 g/min. Moreover, in all 8 cats which were recirculated within 5 minutes after loss of DCR, complete recovery of DCR amplitude was obtained. However, it was observed in 10 of 12 cats (83%) with 10 minutes loss of DCR, 5 of 12 cats (42%) with 15 minutes loss of DCR, 4 of 14 cats (29%) with 20 minutes loss of DCR, and only one of 11 cats (10%) with 30 minutes loss of DCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Continuous lumbar subarachnoid pressure monitoring as an indicator of shunt operation for so-called normal pressure hydrocephalus].

Lumbar subarachnoid pressure (LSP) was continuously monitored via intrathecally introduced polyethylene catheter to select the patients for shunt operation. A total of seventy cases included so-called normal pressure hydrocephalus (NPH) secondary to subarachnoid hemorrhage (SAH; 34 cases), idiopathic NPH (17 cases), secondary NPH whose symptoms developed after operations for brain tumors, head injuries or meningitis (12 cases) and other intracranial diseases including pseudotumor cerebri or meningeal carcinomatosis, etc. (7 cases). Shunt operation was effective in 36 cases and not effective in 9 cases, while 25 cases were not shunted since LSP was not elevated or clinical manifestations were slight. Mean values of baseline pressure and maximum pressure in shunt effective group, shunt non-effective group and non-shunted group were 14.5, 12.7, 9.0 and 29.9, 25.0, 17.9 mmHg, respectively. Statistical difference was observed between shunt effective group and non-shunted group. Frequency of pressure waves was also significantly higher in shunt effective group than in non-shunted group. Above all, measurement of LSP was regarded as useful in idiopathic NPH. However, preoperative clinical symptoms had a closer relationship to shunt response than results of LSP in post SAH patients. Complication related to this monitoring was negligible except in one case of meningitis which was easily treated by administration of antibiotics. Follow-up study also justified our selection since no further deterioration was noted in non-shunted group. The present study indicates that measurement of LSP would be useful in selecting the patients who will benefit from shunting and in eliminating unnecessary shunt operations because this simple method is easily performed at bed side without perforating the skull.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Experimental study of the usefulness of evoked potentials in predicting the reversibility of the brainstem function following infratentorial epidural balloon compression].

With few warnings signs, posterior fossa mass lesions can affect life-supporting brainstem systems directly and cause a precipitous failure of vital functions. Consequently, a technique, by which brainstem dysfunction could be detected at its reversible stage, would have clinical value. Recently manly reports have suggested that the evoked potentials might be advantageous in assessing a developing brainstem dysfunction and might be a more sensitive or reliable detector of deteriorating neurological function than the physical or neurological signs. To explore this possibility, we recorded somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) serially during inflation and deflation of balloons placed in the suboccipital epidural space of cats, as a model of an acutely expanding posterior fossa lesion. The results were correlated simultaneously recorded cardiovascular and pupillary function and with supratentorial and infratentorial epidural pressure. In this study, N1 of cortical SEP (CSEP), wave IV of BAEP, and wave III of short latency SEP (SSEP) were found to be useful parameters in predicting the electrophysiological reversibility. Experimental results were as follows: 1) As the infratentorial epidural balloon was expanded, CSEP, wave IV of BAEP and wave III of SSEP showed remarkable changes both in latency and in amplitude. Decrease in blood pressure and pulse rate preceded or developed at the same time as the apparent change in CSEP. Futher expansion of the balloon resulted in Cushing phenomenon and lability of blood pressure.2) As long as wave IV of BAEP remained, and decompression was started within 15 minutes after N1 of CSEP were completely suppressed, changes in SEP. BAEP and cardiovascular function were all reversible.2+ decompression. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗