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Biomedical subjects

M Nishikawa

Publications and source records attributed to M Nishikawa.

At least 127 records · Page 7Linked to original sources

Diagnosis of disseminated intravascular coagulation by hemostatic molecular markers.

In the present study, the positive rate of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), and D-dimer for the diagnosis of disseminated intravascular coagulation (DIC) was evaluated. The study comprised 307 patients with DIC, 123 with pre-DIC, and 121 with non-DIC. Plasma levels of TAT, PPIC, sFM, and D-dimer were significantly higher in DIC and pre-DIC patients than in non-DIC patients. In DIC patients, the positive rate of sFM was high and that of D-dimer was low; the positive rate of PPIC was higher in patients with hematopoietic malignancy than in those without this disease. In pre-DIC patients, the positive rate of all markers was low (<0.16), and the positive rate of PPIC was relatively high. In non-DIC patients, the positive rate of all hemostatic markers was low (<0.16), that of sFM being the lowest. Scoring the positive rate of TAT, PPIC, and sFM disclosed the following results: 72% of DIC patients had three or more points, 17.6% of pre-DIC patients had three or more points, and almost all (96.6%) non-DIC patients had two or less points. Scoring the positive rate of TAT, PPIC, and D-dimer disclosed the following results: 52.9% of DIC patients and 27.4% of pre-DIC patients had three or more points and almost all (96.7%) non-DIC patients had 2 or less points. These data suggest that the combination of TAT, PPIC, and sFM is useful for making the diagnosis of DIC.

Antifibrinolytic Agents↗

Mononuclear cells and cytokines in the cerebrospinal fluid of echovirus 30 meningitis patients.

The local immune response to echovirus 30 meningitis in children was investigated in 2 ways: using flow cytometry to examine the mononuclear cell and lymphocyte subsets and enzyme-linked immunosorbent assays to examine the cerebrospinal fluid (CSF) levels of cytokines, including monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-gamma) and interleukin-12 (IL-12). The numbers of macrophages in the CSF were increased, in particular during the early part of the acute stage. The levels of MCP-1, which is responsible for the accumulation of macrophages, as well as those of IFN-gamma and IL-12, which play important roles in the activation of macrophages and T helper (Th) 1 cells, respectively, were increased in the CSF of patients compared with the levels found in the controls. Likewise, numbers of activated CD4 + and CD8 + T lymphocytes were increased in the CSF. Since the ratio of CD4/CD8 correlated with the age of the patients, CD8 + T lymphocytes in the CSF might play a more important role in younger children.

Cerebrospinal Fluid↗

Cross-talk between NO and oxyradicals, a supersystem that regulates energy metabolism and survival of animals.

Mammalian tissues have large amounts of available ATP which are generated by oxidative phosphorylation in mitochondria. For the maintenance of the human body, a large amount of oxygen is required to regenerate these ATP molecules. A small fraction of the inspired oxygen is converted to superoxide radical and related metabolites even under physiological conditions. Most reactive oxygen species react rapidly with a variety of molecules thereby interfering with cellular functions and induce various diseases. Nitric oxide (NO) is an unstable gaseous radical with high affinity for various molecules, such as hemeproteins, thiols, and related radicals. NO easily penetrates through cell membrane/lipid bilayers, forms dissociable complexes with these molecules and modulates cellular metabolism and functions. Because NO has an extremely high affinity for the superoxide radical, the occurrence of the latter might decrease the biological function of NO. Thus, superoxide radicals in and around vascular endothelial cells play critical roles in the pathogenesis of hypertension and vasogenic tissue injury. Because NO also reacts with molecular oxygen, it rapidly loses its biological activity, particularly under ambient atmospheric conditions where the oxygen tension is unphysiologically high. Thus, biological functions of NO are determined by the local concentrations of molecular oxygen and superoxide radicals.

Animals↗

Abnormal regional cerebral blood flow in childhood autism.

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Adolescent↗

Incidence of amantadine-resistant influenza A viruses in sentinel surveillance sites and nursing homes in Niigata, Japan.

We surveyed the incidence of amantadine-resistant influenza A viruses both at sentinel surveillance sites and at nursing homes, and verified their types of change by partial nucleotide sequence analysis of the M2 protein. Fifty-five influenza A viruses from 27 sentinel surveillance sites during six influenza seasons from 1993 to 1999, and 26 influenza A viruses from 5 nursing homes from 1996 to 1999 were examined for susceptibility to the drug by virus titration in the presence or absence of amantadine. While amantadine-resistant viruses were not found in sentinel surveillance sites, a high frequency of resistance (8/26, 30.8%) in nursing homes was observed. Resistant viruses can occur quickly and be transmitted when used in an outbreak situation at nursing homes, where amantadine is used either for neurologic indications or for influenza treatment. Eight resistant viruses had a single amino acid change of the M2 protein at residue 30 or 31. In vitro, all 11 sensitive viruses turned resistant after 3 or 5 passages in the presence of 2 microg/ml amantadine, and they showed an amino acid change at residue 27, 30, or 31. The predominant amino acid substitution in the M2 protein of resistant viruses is Ser-31-Asp (a change at 31, serine to asparagine). The results indicate that a monitoring system for amantadine-resistant influenza viruses should be established without delay in Japan.

Amantadine↗

[Antibody induction and frequency of adverse reactions to influenza vaccines in the elderly].

A total of 1,223 elderly people in nursing homes in Niigata Prefecture, Japan, were immunized with one or two doses of commercial trivalent split vaccine formulation, against strains including A/HN, A/H3N2 and B for three seasons (1996-1999). The frequencies of adverse reactions and antibody induction were assessed. Frequent side effects of vaccination were local reactions such as redness and tenderness at the site of injection, but there were no serious reactions, suggesting that the vaccine was quite safe for the elderly. Furthermore, antibody induction by immunization was relatively high and independent of the degree of activities of daily living (ADL). Annual repeated influenza vaccination did not diminish protection against influenza. However, antibody induction against antigens was insufficient in the 1997/1998 season, and further improvement in the combination of quantities of the four included antigens may by required. A booster dose after the first dose did not enhance immune responses in the nursing staff, and the one dose method appeared to be indicated for the elderly.

Aged↗

A case of serial homicide by injection of succinylcholine.

The abstract of this paper was presented at the 14th Meeting of the International Association of Forensic Sciences, Tokyo in 1996. We report a bizarre criminal case of suspected serial homicide by injection of a muscle relaxant (succinylcholine). Five victims were found buried in a rural area. In two victims showing moderate decomposition (about three months after death), intense pulmonary oedema with pleural effusion was observed. Evidence of a puncture site was found in one of the victims. Succinylcholine could not be detected in the victims, but was identified in a syringe found near the corpses. The 40-mg ampule dose of succinylcholine administered intramuscularly to the victims, possibly causing prolonged apnea, was considered to be at least around the minimum lethal dose, although the combined effect of the sedation with hypnotics also used was not negligible.

Adult↗

Elevated tissue factor levels in leukemic cell homogenate.

Tissue factor (TF) antigen and activity were measured in leukemic cell homogenates. In leukemic cell homogenate, especially that of acute promyelocytic leukemia (APL), both TF antigen and activity were significantly higher than these levels in the mononuclear cells obtained from healthy volunteers. Both TF antigen and activity were significantly higher in myelocytic leukemia than in lymphocytic leukemia cells. In leukemic cell homogenates, there was a close correlation between TF antigen and TF activity. The TF activity/TF antigen ratio was significantly higher in myelocytic leukemia than in lymphocytic leukemia cells. As the TF activity was not increased in lymphocytic leukemia cell homogenates to which were added phospholipids, the decrease in TF activity in lymphocytic leukemia might not be due to phospholipid in the leukemic cell membrane. Values for TF activity, TF antigen, and the TF activity/TF antigen ratio in leukemic cell homogenate from patients with disseminated intravascular coagulation (DIC) were significantly higher than those in patients without DIC. Therefore, the measurement of TF antigen and activity in leukemic cells could be useful for the prediction of DIC.

Antigens, Neoplasm↗

Hemostatic abnormalities in patients with thrombotic complications on maintenance hemodialysis.

Before hemodialysis (HD), plasma levels of tissue factor (TF), free-TF pathway inhibitor (TFPI) and thrombomodulin (TM) were significantly higher in patients with HD than in healthy volunteers. Plasma levels of (T-F) TFPI and plasmin plasmin inhibitor complex (PPIC) were significantly higher in patients with HD than in healthy volunteers. During HD, plasma levels of TF and (T-F) TFPI were not significantly increased, but plasma levels of total TFPI and free TFPI at 1 hour after and at the end of HD were significantly increased, compared with levels before start of HD. Plasma level of PPIC 1 hour after start of HD was significantly higher than before start of HD, and plasma levels of thrombin antithrombin complex (TAT), PPIC, D-dimer, TM, and protein C (PC) at the end of HD were significantly higher than before start of HD. In patients with thrombosis complications, plasma TF levels were significantly higher than in patients without thrombotic complications during HD. Plasma levels of PC were significantly lower in patients with thrombotic complications than in patients without thrombotic complications. There was no significant difference between both groups during HD in hemostatic parameters, with the exception of TF and PC. Hemostatic abnormalities existed in patients with HD; especially, increased TF and decreased PC might cause thrombotic complications.

Antifibrinolytic Agents↗

Effect of sarpogrelate hydrochloride on platelet-derived microparticles and various soluble adhesion molecules in diabetes mellitus.

We measured platelet-derived microparticles, activated platelets, and various adhesion molecules in 48 patients with diabetes mellitus. We also performed a comparative study of these parameters before and after administration of sarpogrelate hydrochloride. The numbers of platelet-derived microparticles and activated platelets were increased significantly in diabetic patients, and CD63-positive platelets were increased in patients with diabetic complications and poorly controlled blood glucose. Soluble adhesion molecules and thrombomodulin were also increased significantly. After administration of sarpogrelate hydrochloride, not only CD62p- and CD63-positive platelets, but also platelet-derived microparticles were decreased significantly. Soluble adhesion molecules and thrombomodulin were also significantly decreased after the treatment. These data suggest that (a) in patients with diabetes, antiplatelet therapy with sarpogrelate hydrochloride is a useful antithrombin therapy because it suppresses the production of intrinsic coagulants by activated platelets; and (b) sarpogrelate hydrochloride decreases endothelial cell damage via adhesion molecules.

Antigens, CD↗

Embolic cerebellar infarction caused by spontaneous dissection of the extracranial vertebral artery--two case reports.

Spontaneous dissection of the extracranial vertebral artery (VA) may cause ischemic stroke in the posterior circulation. A 22-year-old female and a 38-year-old male presented with sudden onset of vertigo and nausea without trauma. Angiography was initially interpreted as normal, but retrospective examination disclosed extracranial VA dissection in the V3 segment in both cases. Arterial dissection resulting in embolic stroke in the territory of the ipsilateral posterior inferior cerebellar artery was highly suspected. Both patients were treated conservatively without sequelae. Careful angiographic interpretation is important for the diagnosis of extracranial VA dissection. Spontaneous extracranial VA dissection should be suspected in young patients presenting with ischemic stroke but without predisposing risk factors or associated trauma.

Adult↗

Pharmacokinetics and in vivo gene transfer of plasmid DNA complexed with mannosylated poly(L-lysine) in mice.

To achieve mannose receptor-mediated, cell-specific, in vivo gene transfer by intravenous injection of plasmid DNA, mannosylated poly(L-lysine) (Man-PLL) was synthesized as a carrier molecule, and mixed with a plasmid DNA encoding chloramphenicol acetyltransferase (CAT) gene to form DNA/Man-PLL complex. The particle size and zeta potential of DNA/Man-PLL (prepared at 1:0.7 on a weight basis) were determined to be 220 nm and +12 mV, respectively. The pharmacokinetics of the DNA/Man-PLL complex was assessed in mice using 32P-labeled DNA ([32P]DNA). After intravenous injection of [32P]DNA/Man-PLL, the radioactivity in plasma fell rapidly and was recovered mainly in the liver nonparenchymal cells. The amount in the liver reached more than 80% of the dose. Radioactivity observed in kidney, lung, and spleen was very low compared to that in the liver. Then, the in vivo gene expression after intravenous injection of DNA/Man-PLL was examined by a CAT assay. Highest CAT activity was detected in the liver, but no activity was detected in the lung, kidney, and spleen. These results clearly indicate that a cell-specific gene delivery system can be developed by regulating the biodistribution of DNA/carrier complex through the control of its physicochemical properties.

Animals↗

Subarachnoid hemorrhage from vertebral artery dissecting aneurysms involving the origin of the posteroinferior cerebellar artery: report of two cases and review of the literature.

OBJECTIVE AND IMPORTANCE: Few reports have been published on ruptured vertebral artery dissecting aneurysms in which the posteroinferior cerebellar artery (PICA) arises from the aneurysm wall, and there is ongoing debate as to the proper management of this type of aneurysm. This article describes two patients. CLINICAL PRESENTATION: Both patients presented with subarachnoid hemorrhage and were admitted to our institution on the day of rupture. Computed tomography revealed that the subarachnoid hemorrhage was located mainly in the posterior fossa. Cerebral angiography demonstrated a vertebral dissecting aneurysm involving the origin of the PICA. In one patient, the PICA was very large. INTERVENTION: One patient was treated by trapping, with the PICA involved in the trapped segment. Postoperatively, the patient experienced transient mild hoarseness and dysphasia but recovered completely. The other patient, whose PICA was very large, was initially treated by endovascular proximal occlusion. This resulted in marked enlargement of the distal part of the aneurysm, indicating a need for surgical treatment. A clip was applied to the origin of the PICA after anastomosis of the occipital artery to the PICA. The patient recovered well and was discharged with no neurological deficits. CONCLUSION: The ideal method of treatment for patients with dissecting aneurysms of the vertebral artery involving the PICA origin is complete isolation of the aneurysm by trapping, with revascularization of the PICA. However, trapping alone is one possible treatment option. If proximal clipping alone is carried out, follow-up angiography is mandatory to observe any changes in the aneurysm.

Adult↗

[Effect of epilepsy surgery based on magnetic resonance imaging (MRI) classification].

We prospectively analyzed the effect of surgical procedures in epilepsy patients, except for those with mesial temporal lobe epilepsy. Twenty patients with a mean age of 26 years (range 3 to 58 years, 10 male and 10 female) underwent the surgical procedures. These patients were divided into 3 groups according to MRI findings, as follows; group A (localized type): localized lesions such as angiomas or benign tumors, group B (widespread type): widespread lesions such as regional encephalitis or stroke, visible on anatomical neuroimaging, and group C (cryptic type): no lesion visible on anatomical neuroimaging. Following surgery, 11 (85%) of the 13 patients in group A were seizure-free, one showed worthwhile improvement, and one, whose lesion was not removed totally, was unchanged. In group B, two patients (50%) were seizure-free and 2 (50%) showed worthwhile improvement. All the patients in group C showed worthwhile improvement. Lesionectomy, cortical excision, multiple subpial transection (MST) or a combination of these procedures were effective in groups A and B. Patients in group C had a chance to obtain worthwhile improvement by corpus callosotomy or cortical excision. Intracranial EEG recording provides useful information for epilepsy surgery in intractable cases.

Adolescent↗

[Cervical pyogenic spondylodiscitis: 4 cases report and a review of the literature].

We report 4 cases of cervical spondylodiscitis presenting neurological and/or neuroradiological abnormalities. Such a lesion is rare in the cervical spine of adults, but should be suspected when the patient has radiculopathy and/or myelopathy associated with inflammatory signs. We discussed the clinical characteristics and the procedures of the diagnosis and treatment of cervical spondylodiscitis. Early and definitive diagnosis can be achieved by cervical X-ray, MR imaging and biopsy. It is very important to evaluate the pyogen for the lesion by needle biopsy. When the patient has the compression of the spinal cord and/or nerve roots and the neurological findings of radiculopathy and/or myelopathy, surgical exploration and decompression of the spinal cord and/or nerve roots should be carried out as soon as possible. Anterior debridement and fusion should be performed using the effective antibiotics. We were able to achieve good prognosis by treatment following this procedure of diagnosis in the four cases of cervical spondylodiscitis mentioned.

Adult↗

Design of polymeric prodrugs of PGE1 for cell-specific hepatic targeting.

Based on the relationship between in vivo disposition of macromolecules and their physicochemical and biological characteristics obtained through clearance concept-based pharmacokinetic analysis, polymeric prodrugs of prostaglandin E1 (PGE1) were designed stepwise and evaluated on their targeting and therapeutic efficiencies. Although galactosylated poly-L-glutamic acid with a ethylene diamine (ED) spacer (Gal-ED-PLGA) showed good targeting efficacy in mice, its PGE1 conjugate synthesized by the carbonyldiimidazole method failed to show therapeutic effects probably due to inactivation of PGE1 during conjugation and lack of release in the tissue. In order to overcome these problems, PGE1 was conjugated to galactosylated poly-(L-glutamic acid) hydrazide (Gal-HZ-PLGA) via hydrazone bond. The PGE1-Gal-HZ-PLGA conjugate labeled with [111In] or [3H]PGE1 rapidly accumulated in the liver parenchymal cells after intravenous injection. In addition, PGE1 conjugate effectively inhibited the increase of GPT level in plasma, while free PGE1 indicated no therapeutic efficacy even at more than ten times higher doses, in carbon tetrachloride-induced hepatitis mice. These findings suggest potentials of polymeric targeting systems of PGE1 to hepatocyte utilizing galactose recognition.

Acute Disease↗

[Rerupture mechanism of ruptured intracranial dissecting aneurysm in the vertebral artery following proximal occlusion].

Proximal occlusion is commonly employed to prevent rebleeding of intracranial dissecting aneurysms of the vertebral artery (VA), but rebleeding sometimes occurs. To determine the cause of such rebleeding we reviewed nine cases, including eight reported in the literature and one treated at our hospital. We classified the techniques used to proximally occlude the VA into two types. In Type I, occlusion is performed immediately proximal to the aneurysm so that there are no perforating arteries or the posterior inferior cerebellar artery (PICA) between the clip and the aneurysm. In Type II, occlusion is performed proximal to the PICA so postoperative retrograde flow persists from the contralateral VA through the aneurysm into the ipsilateral PICA. Among the four Type I cases reviewed, it was found that the interval between occlusion and rebleeding was very short: three developed rebleeding within four hours of occlusion, and the fourth showed rebleeding on the fourth day. In the five Type II patients, rebleeding occurred more than four days (mean 15.2 days) after occlusion. It is thought that in Type I occlusion, retrograde flow into the aneurysm immediately after occlusion may raise the intraaneurysmal pressure enough to cause rerupture within just a few hours of occlusion. In Type II occlusion, postoperative retrograde flow through the aneurysm into the ipsilateral PICA exists, so the intraaneurysmal pressure is not likely to rise as rapidly, with the result that rebleeding occurred after more than four days probably due to recurrence of dissection. The short interval between proximal occlusion and rebleeding, especially in Type I cases, suggests that postoperative angiography is only of limited usefulness in evaluating the possibility of rebleeding. The mortality rate reported for cases with reruptured vertebral dissecting aneurysms after proximal occlusion is very high (55.6%). These data indicate that surgical trapping or endovascular intraluminal occlusion, which is difficult to perform in some patients, should be considered the most suitable procedure from the view point of preventing postoperative rebleeding.

Cerebral Hemorrhage↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). I. Susceptibility distribution].

The frequencies of bacterial isolation and susceptibilities to antimicrobial agents were investigated on 538 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1998 to May 1999. Of the above bacterial isolates, Gram-positive bacteria accounted for 30.3% and Gram-negative bacteria accounted for 69.7%. Susceptibilities of several isolated bacteria to antimicrobial agents were as follows; against Enterococcus faecalis isolated from patients with UTIs, vancomycin (VCM), ampicillin (ABPC) and imipenem (IPM) had strong activities. Among E. faecalis strains, those with low susceptibilities to all drugs have increased in 1998, compared with those in 1997. VCM showed the highest activity against MRSA isolated from patients with UTIs. The MICs of VCM for all 34 strains were equal to or lower than 2 micrograms/ml. Arbekacin (ABK) was also active against MRSA with the MIC90s of 2 micrograms/ml. Against Escherichia coli and Klebsiella pneumoniae, all drugs except penicillins were active. Particularly, meropenem (MEPM) showed the highest activity with the MICs of 0.125 micrograms/ml or below. Almost all the drugs except minocycline (MINO) showed high activities against Proteus mirabilis. Against Pseudomonas aeruginosa, all drugs were not so active, with the MIC90s of 16 micrograms/ml or above. MEPM, IPM and gentamicin (GM) showed high activities against Serratia marcescens. Generally, it seemed that resistant strains of S. marcescens had decreased since 1996.

Anti-Bacterial Agents↗