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Biomedical subjects

E Kobayashi

Publications and source records attributed to E Kobayashi.

At least 37 records · Page 2Linked to original sources

Effects of the placement of endosseous implants in vascularized bone grafts on bone union in beagle dogs.

Recently, reconstructive surgery with revascularized osteocutaneous flaps has been used to restore function in patients with bone defects caused by surgery for oral cancer. However, few basic studies have addressed problems such as the union of bone segments after osteotomy, the effects of dental implant placement on blood flow, and bone formation at the bone:implant interface in grafted bone. Nine adult beagle dogs were divided into three groups of three dogs each. Each group received osteotomized vascularized tibial grafts, osteotomized tibial grafts with implants (implants placed in contralateral limbs as control), or simple (non-vascularized) tibial grafts. The development of bone around the implants was studied by histological examination, contact micro-radiography (CMR), and fluorescent bone labeling. In the dogs receiving osteotomized vascularized tibial grafts, bone bridging was confirmed at both the medial and distal junctions of the bone segments after 4 weeks. Additional newly formed bone was observed after 8 weeks, and bone union at the surface of the segments was completed after 12 weeks. In contrast, bone formation was clearly delayed in dogs receiving simple (non-vascularized) tibial grafts. Histologically, no difference in bone union was evident between limbs with dental implants in tibial bone and control limbs without implants, suggesting that implant placement does not negatively affect revascularization. Fluorescent bone labeling technique confirmed high vascularity of the vascularized tibial bone grafts but not of the simple (non-vascularized) tibial bone grafts early after the procedure. Our results suggest that osseointegration occurred around dental implants placed at the same time as reconstruction with osteotomized vascularized bone grafts in this animal model.

Animals↗

Evaluation of intraoperative infusion solution using a complete anhepatic model in baby pigs.

Compared to cadaveric liver transplantation, living-related liver transplantation (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes in the level of blood glucose and lactate usually occur during the anhepatic phase in LRLT. For pediatric patients, intraoperative infusions have the potential to maintain immature homeostasis during LRLT. In the present study, a complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which mimics the procedure of pediatric LRLT, was established using a heparin-coated tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas analysis, electrolytes, blood lactate, and glucose) changes were observed during the anhepatic phase. Although no major difference was observed in hemodynamic parameters, arterial blood gas data, or concentration of electrolytes among the three solution groups, significant progressive hyperlactatemia was observed in the LR group. Also, though severe hypoglycemia was found in the LR and AR groups, the AR-G group maintained blood glucose levels throughout the anhepatic phase. To conclude, using the simplified pig anhepatic model, we evaluated various solutions for pediatric LRLT.

Animals↗

Effect of continuous infusion of propofol on its concentration in blood with and without the liver in pigs.

In living donor liver transplantation, propofol, an intravenous anesthetic drug, has recently been used in both donors and recipients. Propofol is known to have intra- and extrahepatic metabolic pathways, but the effect of its continuous infusion during a long-term anhepatic state is yet to be determined. Recently, we successfully established a simplified pig model of the complete anhepatic state. In this state, we first evaluated hemodynamic parameters relating to the pharmacokinetics of continuously infused propofol (6 mg.kg(-1) x h(-1)). No significant changes in the concentration of hemoglobin or in hemodynamic parameters other than the heart rate were observed during the anhepatic phase when porpofol was continuously infused at the rate that maintains the state. Blood propofol concentrations in the mixed vein, artery, and portal vein were stable during the anhepatic phase. Finally, we confirmed the pharmacokinetics of continuously infused propofol using orthotropic liver transplantation in miniature pigs. The propofol concentration did not change markedly during the transplant procedure. In conclusion, the pharmacokinetics of continuously infused propofol was almost stable with and without the liver in pigs. Extrahepatic metabolism of propofol might help prevent changes in propofol concentrations.

Anesthetics, Intravenous↗

Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing.

BACKGROUND: The usefulness of bone marrow cells in accelerating wound healing has not been evaluated despite increasing evidence that bone marrow contains mesenchymal stem cells that have multipotentiality to differentiate into various types of cells after they enter the microenvironment of a specific tissue (niche). OBJECTIVES: To determine the effects of bone marrow cells and occlusive dressings in promoting wound healing in rats. METHODS: We investigated by grafting, biopsy and immunohistochemistry whether various types of cells derived from green fluorescent protein (GFP)-transgenic rats would differentiate into wound component cells when administered topically on the wounds of rats. We also investigated whether topical application of bone marrow cells with an occlusive dressing would accelerate the healing of wounds with exposed bones, as measured by planimetry. RESULTS: GFP-labelled bone marrow cells contained multipotent stem cells that sufficiently differentiated into wound myofibroblasts presenting with alpha-smooth muscle actin in granulation tissue. Other types of cells, including myocytes, adipocytes, peripheral blood cells from buffy coat and dermal fibroblasts, did not express myofibroblast characteristics morphologically or immunohistochemically. Application of bone marrow cells and an occlusive dressing accelerated the repair of wounds with exposed bones, compared with an occlusive dressing only or with the topical administration of bone marrow cells plus a semidry to dry dressing. CONCLUSIONS: Our study indicates that bone marrow cells accelerate the healing of wounds at least in part through their differentiation into wound myofibroblasts. Thus, treatment of wounds with bone marrow cells and a supportive occlusive dressing is effective in promoting the formation of healthy granulation tissue and also for the preparation of an ideal wound bed.

Animals↗

A robotic wide-angle view endoscope using wedge prisms.

BACKGROUND: The aim was to develop a new type of robotic wide-angle view endoscope that does not require rotation or bending of the endoscope to move the field of view. This endoscope allows the surgeon to make extensive observations in a small space. It is safe because it avoids the possibility of hitting organs accidentally. METHODS: The system consists of an endoscope with a zoom facility and two wedge prisms at the tip. Each prism is set on its own sleeve at the end of the endoscope, and both prisms rotate independently about the axis of the endoscope. RESULTS: In the in vivo experiment, the high quality of the image was confirmed, and almost whole liver could be observed without the observer moving the endoscope itself. CONCLUSIONS: This system provides safe robotic endoscopic surgery because of the high quality of the image. It has great significance for future clinical use.

Animals↗

Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (MTLE) is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE), we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic) with FMTLE. We used NIH-Image for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1 hippocampal signal changes were found in 34% of all individuals: 42.5% of affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal head (first three slices) revealed T2 abnormalities in 73% of all individuals (74% of affected subjects and 72% of asymptomatic subjects) and T1 abnormalities in 59% (67% of affected subjects and 41% of asymptomatic subjects). Affected individuals had smaller volumes than controls (P < 0.0001). There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39% of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals) had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.

Analysis of Variance↗

Chronopharmacological studies of ketamine in normal and NMDA epsilon1 receptor knockout mice.

BACKGROUND: The effectiveness and toxicity of many drugs depends on the dosing-time schedule, relative to the circadian rhythms of biochemical, physiological, and behavioural processes. Previous studies have found chronopharmacology of ketamine, which is a N-methyl-d-aspartate (NMDA) receptor antagonist. The in vivo contribution of the NMDA receptor epsilon1 subunit (NR2A) in this effect is unclear. METHODS: In the present study, daily variations in the hypnotic effect of ketamine were determined in wild-type mice and NMDA epsilon1 knockout (KO) mice. RESULTS: The effect of ketamine had a definite daily variation in wild-type mice. No significant difference in blood concentration was observed at different dosing times (10:00 and 22:00). In NMDA receptor epsilon1 KO mice, the hypnotic effect of ketamine was weaker than in wild-type mice and there was no dependence on the time of administration. Significant pharmacokinetic differences were not observed between wild-type and KO mice. CONCLUSIONS: The enhanced hypnotic effect in the active phase of the circadian cycle is likely a result of changes with the time of day in the susceptibility of the central nervous system to ketamine. Knockout of the NMDA receptor epsilon1 subunit gene markedly reduced the effect of ketamine, and eliminated the time-dependent sensitivity to ketamine.

Anesthetics, Dissociative↗

Combined compression and elongation experiments and non-linear modelling of liver tissue for surgical simulation.

Uniaxial stress-strain data were obtained from in vitro experiments on 20 porcine livers for compressions, elongations and cycles of compression and then elongation. There were about 70 cylindrical samples, with diameter 7mm and varying height (4-11 mm). The combined compression and elongation test provide a unified framework for both compression and elongation for applications such as computer-aided surgical simulation. It enable the zero stress state of the experimental liver sample to be precisely determined. A new equation that combined both logarithmic and polynomial strain energy forms was proposed in modelling these experimental data. The assumption of incompressibility was justified from a preliminary Poisson's ratio for elongation and compression at 0.43+/-0.16 and 0.47+/-0.15, respectively. This equation provided a good fit for the observed mechanical properties of liver during compression-elongation cycles and for separate compressions or elongations. The root mean square errors were 91.92+/-17.43 Pa, 57.55+/-13.23 Pa and 29.78+/-17.67 Pa, respectively. In comparison with existing strain energy functions, this combined model was the better constitutive equation. Application of this theoretical model to small liver samples and other tissues demonstrated its suitability as the material model of choice for soft tissue.

Animals↗

Kernohan's phenomenon associated with left ruptured occipital arteriovenous malformation.

A 23-year-old woman presented with ipsilateral hemiparesia due to rupture of a left occipital arteriovenous malformation (AVM). Emergency decompression (the onset-operation interval was 46 minutes,) was carried out and the patient could leave the hospital upon recovery without neurological deficits. In general, Kernohan's phenomenon is caused by the gradual displacement of the cerebral peduncle against the tentorial edge caused by compression by the contralateral mass. This phenomenon is very rare among the cases with spontaneous intracranial hemorrhage and only three cases including the present one have been reported in the literature. In all cases the onset-operation intervals of were very short. Kernohan's phenomenon associated with a ruptured AVM is a rare condition and emergency decompression is required.

Adult↗

Differences in memory performance and other clinical characteristics in patients with mesial temporal lobe epilepsy with and without hippocampal atrophy.

Mesial temporal lobe epilepsy (MTLE) is usually accompanied by memory deficits due to damage to the hippocampal system. In most studies, however, the influence of hippocampal atrophy (HA) is confounded with other variables, such as: type of initial precipitating injury and pathological substrate, effect of lesion (HA) lateralization, history of febrile seizures, status epilepticus, age of seizure onset, duration of epilepsy, seizure frequency, and antiepileptic drugs (AEDs). To investigate the relationship between memory deficits and these variables, we studied 20 patients with MTLE and signs of HA on MRI and 15 MTLE patients with normal high-resolution MRI. The findings indicated that (1) HA, earlier onset of seizures, longer duration of epilepsy, higher seizure frequency, and AEDs (polytherapy) are associated with memory deficits; and (2) there is a close relationship between deficits of verbal memory and left HA, but not between visual memory and right HA.

Adolescent↗

Characterization of hair follicles induced in implanted, cultured rat keratinocyte sheets.

Cultured rat keratinocyte sheets form hair follicles in combination with rat vibrissa dermal papillae when they are transplanted subcutaneously in syngeneic rats and athymic mice. In the present study, the histologic details of these induced follicles were analyzed by preparing cultured sheets mixed with normal rat keratinocytes and green fluorescent protein (GFP)-transgenic rat keratinocytes. Histologic examination demonstrated that some induced follicles maintained their size and morphology for at least 18 weeks, whereas others decreased in size and others totally differentiated into cornified structures between 3 and 6 weeks. The percentage of the grafts with GFP-positive cells decreased during the same period. This finding suggests that some GFP-positive cells were transient-amplifying cells that turned into terminally differentiated cells and were lost during this period. Some large follicles and some small follicles maintained their hair-producing ability and the proliferative activity in their hair matrix for 18 weeks. In addition, one 6-week-old follicle contained label-retaining cells in the outer root sheath. Seven of 25 follicles induced from chimera epithelium contained both GFP-positive cells and GFP-negative cells. These results suggest that stem cells are present in the induced follicle and the induced follicle consists of polyclonally derived cells. The presence of early anagen-like large follicles at week 6 and 9 and a telogen-like small follicle at week 18 also suggests that hair-growth cycle phases proceeded in the induced follicles. In conclusion, the follicles induced in the cultured keratinocyte sheets maintained hair-producing ability and proliferative activity for at least 18 weeks. This and the presence of label-retaining cells suggest that there are stem cells in the induced follicles, which seem to have a hair-growth cycle.

Animals↗

Genetic mapping of quantitative trait loci affecting body weight, egg character and egg production in F2 intercross chickens.

Phenotypic measurements of chicken egg character and production traits are restricted to mature females only. Marker assisted selection of immature chickens using quantitative trait loci (QTL) has the potential to accelerate the genetic improvement of these traits in the chicken population. The QTL for 12 traits (i.e. body weight (BW), six for egg character, three for egg shell colour and two for egg production) of chickens were identified. An F2 population comprising 265 female chickens obtained by crossing White Leghorn and Rhode Island Red breeds and genotyped for 123 microsatellite markers was used for detecting QTL. Ninety-six markers were mapped on 25 autosomal linkage groups, and 13 markers were mapped on one Z chromosomal linkage group. Eight previous unmapped markers were assigned to their respective chromosomes in this study. Significant QTL were detected for BW on chromosomes 4 and 27, egg weight on chromosome 4, the short length of egg on chromosome 4, and redness of egg shell colour (using the L*a*b* colour system) on chromosome 11. A significant QTL on the Z chromosome was linked with age at first egg. Significant QTL could account for 6-19% of the phenotypic variance in the F2 population.

Analysis of Variance↗

Induction of immune tolerance by neonatal intravenous injection of human factor VIII in murine hemophilia A.

Inhibitory antibody formation is the most serious complication of factor (F)VIII replacement therapy in hemophilia A patients. FVIII-deficient mice were used to study new approaches for induction of immune tolerance. Neither antiFVIII inhibitory antibodies nor antiFVIII IgGs were observed in 13 of 14 adult mice that received 0.05 U g(-1) body weight of human FVIII intravenously within 24 h after birth and repeated injections as adults. In contrast, high FVIII antibody titers (>50 Bethesda Units mL(-1)) developed in seven of 13 mice injected on day 3 postpartum and in all adult mice not treated neonatally. One of nine mice and three of 17 mice developed high-titer antiFVIII inhibitory antibody when they were treated initially with 2-fold (0.1 U g(-1) body weight) and 10-fold higher doses (0.5 U g(-1) body weight) FVIII on day 0, respectively. A human FVIII-specific T-cell proliferative response was absent in splenocytes from neonatally treated mice. The tolerance was FVIII specific because antitoxoid antibodies developed after immunization with tetanus toxoid. Splenocytes failed to proliferate or produce interferon (IFN)-gamma in response to FVIII stimulation, yet still secreted interleukin-2. A proliferative response was restored with exogenous IFN-gamma or interleukin-12, suggesting that lack of inhibitor to FVIII was due to IFN-gamma-dependent anergy. Thus, exposure on day 0 to physiological levels of FVIII antigen might be important for induction of immune tolerance. This immune tolerance model may provide a basis for new approaches to prevention of FVIII inhibitors during replacement therapy.

Animals↗

Removal of large acoustic neurinomas (vestibular schwannomas) by the retrosigmoid approach with no mortality and minimal morbidity.

OBJECTIVE: To evaluate the safety and efficacy of removing large acoustic neurinomas (> or =3 cm) by the retrosigmoid approach. METHODS: Large acoustic neurinomas (mean (SD), 4.1 (0.6) cm) were removed from 50 consecutive patients by the retrosigmoid suboccipital approach while monitoring the facial nerve using a facial stimulator-monitor. Excision began with the large extrameatal portion of the tumour, followed by removal of the intrameatal tumour, and then removal of the residual tumour in the extrameatal region just outside the porus acusticus. The last pieces of tumour were removed by sharp dissection from the facial nerve bidirectionally, and resected cautiously in a piecemeal fashion. RESULTS: There were no postoperative deaths. The tumour was removed completely in 43 of 50 patients (86%). The facial nerve was anatomically preserved in 92% of the patients and 84% had excellent facial nerve function (House-Brackmann grade 1/2). One patient recovered useful hearing after tumour removal. Cerebrospinal fluid leak occurred in 4%, but there were no cases of meningitis. All but two patients (96%) had a good functional outcome. CONCLUSIONS: The method resulted in a high rate of functional facial nerve preservation, a low incidence of complications, and good functional outcomes, with no mortality and minimal morbidity. Very favourable results can be obtained using the retrosigmoid approach for the removal of large acoustic neurinomas.

Adolescent↗