Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 199 records · Page 11Linked to original sources

PubMed1997

Electrophysiologic effects of nitrous oxide, a volatile anesthetic, in dogs following myocardial infarction in comparison with other anesthetics.

The present study was undertaken to examine the electrophysiologic effects of nitrous oxide in the dog heart after inducing myocardial infarction, and to compare these with those of other anesthetics. Myocardial infarction was produced by two-stage ligation of the left anterior descending coronary artery in dogs. Seven days after ligation, bipolar electrodes were sutured on the ventricular surface of the infarcted and normal regions for applying electrical stimulation or recording ventricular activation. Ventricular activation time and QT interval on the bipolar electrocardiogram and PQ interval from the standard limb lead II were measured during atrial pacing. Nitrous oxide 80% did not significantly prolong ventricular activation time, PQ interval or QT interval. However, halothane 1 minimum alveolar concentration (MAC), thiopental 5 and 10 mg/kg and fentanyl 30 microg/kg did prolong ventricular activation time; thiopental and fentanyl prolonged the QT interval. Nitrous oxide did not potentiate the effects of fentanyl. Therefore, electrophysiologic effects of nitrous oxide are much weaker compared with those of thiopental, fentanyl or halothane.

Anesthetics, Inhalation↗

PubMed1997

Aggregation of human blood platelets by remnant like lipoprotein particles of plasma chylomicrons and very low density lipoproteins.

Remnant like lipoprotein particles (RLP) of partially catabolised human plasma chylomicrons (CM) and very low density lipoproteins (VLDL) were separated from CM and VLDL using two monoclonal antibodies, anti apo B-100 (JI-H) and anti apo A-I (H-12) coupled to Sepharose 4B gel to form an immunoaffinity column. Lipoproteins containing apo B-100 or apo E, including VLDL and LDL adsorb to (JI-H)-gel, while CM and HDL with apo A-I adsorb to (H-12)-gel. The unbound fraction (RLP) is rich in apo B-48, apo E and apo E rich apo B-100 which has not been recognized by JI-H. The RLP fraction with a total triglyceride of 12.35 +/- 6.22 mg/ml; total cholesterol, 0.32 +/- 0.08 mg/ml and total protein, 0.72 +/- 0.12 mg/ml (mean +/- S.E.M, n = 9) was added to blood from healthy persons at 2.5-200 microliters/ml and agitated gently at 37 degrees C for 40 s. Platelet aggregation was assessed by measuring the loss of single platelets. At 2.5-10 microliters, RLP induced platelet aggregation increased with the dose of RLP, but decreased at 25-200 microliters. Scanning electron microscopy revealed that within 20 s of agitation in the presence of RLP, activated platelets had appeared on the red cell membrane and within 40 s of agitation, platelet aggregates had formed on the red cells. The platelet responses were unaffected by aspirin (10 or 20 micrograms/ml) but were inhibited by cilostazol, a phosphodiesterase type III inhibitor (0.4 to 1.6 micrograms/ml). It is likely that the platelet effect of RLP is a consequence of RLP dependent red cell-platelet interaction. This is the first report of platelet aggregation induced by RLP without an added platelet agonist.

Adenosine Diphosphate↗

PubMed1997

[Clinical evaluation of faropenem against infections in pediatric fields].

The recent increases in the prevalence of penicillin-resistant Streptococcus pneumoniae becomes a point at issue clinically. We carried out a clinical study in 40 cases in the pediatrics department, as faropenem (FRPM) was proved to have an excellent antimicrobial activity against penicillin-resistant Streptococcus pneumoniae. The study was planned to investigate in detail the movement of stools that had been a problem in a clinical development studies out before. In this study, an observation of the daily movement of stools was one of the principal evaluation items, hence the patients were divided into two groups. One group (S-group) were administered FRPM only, the other group (E-group) were administered FRPM in combination with a medicine for intestinal disorders (Enteronon-R). An observed frequencies of any loose bowel movements were 94.7% in S-group, and 63.2% in E-group, hence the study suggested that the combination drug was effective. The patients observed higher frequencies of development of the movement of stools, all of them were recovered from in the course of administration or within 4 days after administration, however whether or not being treated symptomatic therapy. Clinical efficacy rates of FRPM on mainly respiratory infections were 94.6%. In this study, 4 strains (patients) of penicillin-resistant Streptococcus pneumoniae were isolated. Against penicillin-resistant Streptococcus pneumoniae, FRPM demonstrated more potent antibacterial activity than the oral penicillins and cephems tested here except cefditoren. Clinical efficacies was deemed effective in all of the 4 cases, and bacteriologically, 3 organisms were eradicated. As for side effects including diarrhea and loose stool, no serious side effects were observed. Based on the above results, FRPM is effective against most infections in the pediatric field which Streptococcus pneumoniae are isolated at high frequencies highly, and is considered to cases in be useful an attention will have to be paid to stool movement, however.

Adolescent↗

PubMed1997

Enhancement by ticlopidine of the inhibitory effect on in vitro platelet aggregation of the glycoprotein IIb/IIIa inhibitor tirofiban.

We determined the effects of combining the glycoprotein IIb/IIIa inhibitor tirofiban (MK-383, Aggrastat) and ticlopidine on inhibition of ADP-induced platelet aggregation, inhibition of collagen-induced platelet aggregation, and prolongation of bleeding time in 5 healthy male volunteers. The study consisted of 2 periods. In period 1, tirofiban was administered intravenously as a bolus injection at a dose of 5.0 microg/kg for 5 min, then as a continuous infusion at a rate of 0.05 microg/kg/min for 5 h 55 min. In period 2, ticlopidine was given orally at a dose of 200 mg once daily for 4 days, after which tirofiban was administered in the same manner as in period 1, starting 2 h after the last dose of ticlopidine. The percent inhibition of platelet aggregation induced by ADP 5 microM at the end of tirofiban infusion in periods 1 and 2 was 73.6 +/- 2.6 and 87.1 +/- 5.7% (mean +/- SD), respectively. The corresponding values for inhibition of platelet aggregation induced by collagen 2 microg/ml were 45.4 +/- 36.1 and 82.8 +/- 27.0%, respectively. In contrast, the percent inhibition of platelet aggregation induced by ADP and collagen after treatment with ticlopidine alone was 15.8 +/- 20.2 and 2.2 +/- 4.8%, respectively. Compared with tirofiban alone, the combination of tirofiban and ticlopidine significantly enhanced inhibition of platelet aggregation induced by both ADP and collagen (p <0.02 and p <0.012, respectively). The inhibitory effects of ticlopidine alone were not statistically significant. Tirofiban prolonged bleeding time both in period 1 and in period 2. However, tirofiban and ticlopidine combined did not affect bleeding time. Ticlopidine administration did not alter the pharmacokinetics of tirofiban. In conclusion, at the doses of tirofiban and ticlopidine used in this study, the combination of the two drugs enhanced inhibition of platelet aggregation but did not prolong bleeding time, suggesting that appropriate doses of tirofiban can be used concomitantly with ticlopidine with no further safety concerns but with potential additional clinical effects.

Adult↗

PubMed1996

Effect of dexamethasone on invasion of human squamous cell carcinoma cells into collagen gel.

The effect of dexamethasone (Dex) on the ability to invade type I collagen gel was investigated in two cell lines of oral squamous cell carcinoma (SCC). At concentrations higher than 10(-8) M, Dex significantly suppressed the invasive growth of SCC cells into the gel. The same concentrations of Dex led to a decrease in urokinase type plasminogen activator (u-PA) synthesis and an increase in plasminogen activator inhibitor type 1 (PAI-1) synthesis by SCC cells. These findings suggest that Dex inhibits the invasiveness of SCC cells by decreasing their proteolytic activity.

Carcinoma, Squamous Cell↗

PubMed1996

A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas.

BACKGROUND: A large number of monoclonal antibodies (MoAbs) against human tumor cells have been generated and it has been shown that these MoAbs are useful tools in the diagnosis and treatment of cancer patients, as well as in the basic investigation of the oncogenesis and characterization of cancer cells. METHODS: The 22-1-1 MoAb was established by cell fusion between mouse myeloma cells and spleen cells derived from mice immunized with the human uterine cervical adenocarcinoma cell line, SiSo. The tissue distribution and biologic characteristics of the 22-1-1 antigen (Ag) were examined. RESULTS: The 22-1-1 Ag was distinct from the known tumor-associated antigens such as YH 206, GA 733, CA 125, carcinoembryonic antigen, and sialyl Le(x) molecules in an expression pattern in human tumor cell lines. An immunohistochemical study revealed that 22-1-1 Ag was expressed in 87.5% of uterine cervical adenocarcinomas, 66% of uterine endometrial adenocarcinomas, and 58.8% of ovarian carcinomas. Moreover, 22-1-1 Ag was detected in 87.7% of uterine cervical squamous cell carcinomas; however, it was not detected in 87.7% of uterine cervical or ovarian tissues, except in uterine endometrial glands, in which its expression was observed at low levels. The 22-1-1 Ag was secreted into cell culture supernatant fluids and was also detected in the vaginal discharges of uterine cervical carcinoma patients. The antigenic epitope of 22-1-1 Ag was shown to be a protein with a molecular weight of 78 kilodaltons using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. CONCLUSIONS: The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.

Adenocarcinoma↗

PubMed1996

Tranilast suppresses intimal hyperplasia after photochemically induced endothelial injury in the rat.

Intimal thickening in the femoral artery of spontaneously hypertensive rats (SHR) was initiated by endothelial damage induced by the photochemical reaction between green light and systemic rose bengal. This model represents a non-mechanical method of producing vessel wall denudation. Neointima formation was assessed by calculating the cross-sectional area of intima, media and lumen, using computer analysis. Tranilast (30, 100 and 300 mg/kg, p.o.), administered 2 days prior to endothelial injury, reduced intimal area by 29, 62 and 87%, respectively, compared to that of vehicle-treated controls. In cultured SHR-derived vascular smooth muscle cells, tranilast produced concentration-dependent inhibition of mitogenesis, whether stimulated by platelet-derived growth factor, basic fibroblast growth factor, insulin-like growth factor or fetal bovine serum. These results suggest that tranilast may be effective in preventing coronary restenosis.

Animals↗

PubMed1996

Antisense inhibition of parathyroid hormone-related peptide gene expression reduces malignant pituitary tumor progression and metastases in the rat.

A newly established metastatic rat pituitary tumor (mGH3) possesses a malignant phenotype that is invasive and hypervascular compared with the original GH3 tumors. mGH3 cells exhibit anchorage independence and expression of elevated levels of parathyroid hormone-related peptide (PTHrP) in vitro. To clarify the role of PTHrP in the development of the malignant phenotype, tumor cells were treated with phosphorothioate antisense PTHrP oligonucleotide. Treatment with antisense PTHrP resulted in a scattering phenomenon in the colony formation assay but did not inhibit cell growth in vitro. Inoculation of mGH3 cells in the cerebral ventricle resulted in a rapid growth of tumor cells within 3 weeks and dissemination throughout the entire ventricular system. Although treatment with sense or mismatched PTHrP oligonucleotide did not influence the subsequent tumor growth, the in vivo coinjection and injection of antisense PTHrP 1 week after tumor cell implantation into the right lateral ventricle markedly reduced tumor size and suppressed metastasis formation. The survival rate of mGH3 tumor-injected rats was prolonged by antisense PTHrP therapy. Our results demonstrated the biological involvement of PTHrP in malignant phenotype in rat pituitary tumors, suggesting that antisense PTHrP may provide a novel antimetastatic therapy for malignant somatotroph tumors.

Animals↗

PubMed1996

Expression of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in giant cell tumour of tendon sheath.

The giant cell tumour of tendon sheath (GCTTS) is mainly composed of mononucleated stromal cells (SC) and multinucleated giant cells (GC), so-called osteoclast-like GC. It is thought that GC are derived from SC, but their precise relationship is not fully understood. Parathyroid hormone (PTH)-related peptide (PTHrP) is now considered to be a cytokine for cell differentiation, which may stimulate osteoclast-like cell formation in haematopoietic cells. Five cases of GCTTS were evaluated immunohistochemically, using a variety of antibodies against PTHrP, PTH/PTHrP receptor, KP-1 as a histiocytic phenotypic antigen, fibronectin as a fibroblastic phenotypic antigen, and proliferating cell nuclear antigen (PCNA). In situ hybridization and immunohistochemistry revealed that in all cases both SC and GC expressed PTHrP. PTH/PTHrP receptor was observed only in histiocytic SC and GC, but not in fibroblastic SC. Almost all GC showed histiocytic features. PCNA immunoreactivity was detected only in the nuclei of SC, and not in GC. Moreover, SC with PTH/PTHrP receptor immunoreactivity were negative for PCNA. These results suggest that GC are derived from histiocytic SC expressing PTH/PTHrP receptor and losing proliferative activity in the process of transition from mononuclear to multinucleated. PTHrP produced by SC and GC may be involved in the formation of osteoclast-like cells in GCTTS by acting in an autocrine/paracrine fashion.

Gene Expression↗

PubMed1996

Morphological study of thymus stromal cells (TEL-2 cell) which play a role in the elimination of double positive immature thymocytes by phagocytosis.

BACKGROUND: The process of the selective elimination of immature double positive thymocytes, during culture with TEL-2 cells (an epithelial cell line from the thymus stroma), is initiated by the contact between thymocytes and TEL-2 cells (Nakashima et al. 1990 Eur. J. Immunol., 20: 47-53; Hirata et al. 1991 Anat. Rec., 230: 524-530). METHODS: Our approach was to follow the process of thymocyte internalization as a sequelae of this interaction with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and electron microscopic cytochemistry for the hydrolytic enzyme acid phosphatase (Ac Pase). RESULTS: With SEM, numerous thymocytes lay underneath the TEL-2 cells. An enhanced activity of the TEL-2 cell membrane, consisting of several thin thread-like projections either with or without an expanded termination, was involved with contacting the thymocytes. With TEM, close appositions were noted either at adjacent segments of the cellular membrane or between thick plump local protrusions of the plasma membrane. Blunt pseudopodia and deep invaginations on indented portions of the TEL-2 surface engulfed one or more thymocytes. With Ac Pase histochemistry: 1) the incorporation of thymocytes into a phagosome was indicated by the Ac Pase negative thymocytes enclosed in a membrane beneath the protuberance of a TEL-2 cell surface without fusion to the TEL-2 lysosomes; 2) most of these thymocytes were morphologically intact, whereas the rest were already damaged, having changes similar to apoptosis; and 3) a few Ac Pase positive dense bodies of the TEL-2 cell, mostly with the morphology of secondary lysosomes, fused with the thymocyte-enclosing membrane after which the digestion of several thymocytes proceeded. CONCLUSIONS: With the prominent activity of the plasma membrane involving the initial attachment and subsequent phagocytosis, a murine thymic epithelial cell line TEL-2 plays a demonstrating role in the mechanism of the elimination of double positive thymocytes.

Acid Phosphatase↗

PubMed1996

Pharmacokinetics and safety of a novel, long-acting, prodrug-type potassium channel opener, Y-27152, in healthy volunteers.

The pharmacokinetics and safety of a novel, long-acting, prodrug-type K(+)-channel opener, Y-27152, were investigated in healthy male volunteers. In the first phase, single oral doses of 0.1, 0.25, 0.5, 0.75, and 1.0 mg of Y-27152 (n = 3-6 per dose) were given after overnight fasts in a dose-escalating manner. The 0.75-mg dose was given both after an overnight fast or after food to examine the effects of food intake. In the second phase, multiple doses of Y-27152 were taken after meals once daily for 7 consecutive days. In part A of this phase, either placebo (n = 3) or 0.5 mg of Y-27152 (n = 6) was taken for 7 days, and in part B of this phase 0.5-, 0.75-, and 1.0-mg doses were taken in a dose-escalating manner for 1,3, and 3 days, respectively (n = 9). In the single-dose study, peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of main active metabolite (Y-26763; M1) increased in parallel with dosage. This dose-linearity was less obvious with Y-27152, which had an AUC approximately 6 to 10 times less than that of M1. Administration with food at 0.75 mg resulted in a small but significant decrease (approximately 10%) in the Cmax and AUC of M1. At doses of 0.5 mg or higher, participants experienced headaches and palpitations, which were probably due to the vasodilatory effects and did not require treatment. Mean diastolic blood pressure significantly decreased and pulse rate increased at doses of 0.5 mg or higher compared with predose values. Plasma renin activity was significantly elevated 4 hours after the administration of the 0.75- and 1.0-mg doses, but showed no significant change at 0.5 mg. In the multiple-dose study, the time profile of the plasma concentration of M1 approximately coincided with the simulation curves worked out using the pharmacokinetic parameters obtained in the singledose study. The incidence of headaches tended to increase with dose in part B, but drug administration was not discontinued in any case. Plasma renin activity again increased 4 hours after administration. In phase B of the multiple-dose study, diastolic blood pressure decreased and pulse rate increased compared with predose values. Y-27152 was metabolized to M1 and well tolerated in healthy volunteers, and its pharmacologic effects were likely caused by vasodilation, which could make it an effective antihypertensive agent.

Administration, Oral↗

PubMed1996

The role of T cells expressing TcR V beta 13 in autoimmune thyroiditis induced by transfer of mouse thyroglobulin-activated lymphocytes: identification of two common CDR3 motifs.

The transfer of lymphocytes from mouse thyroglobulin (mTg)-immunized CBA/J (H-2k) mice following in vitro activation with mTg initiates experimental autoimmune thyroiditis (EAT) in syngeneic recipients. We have analyzed the T cell receptor (TcR) V gene families used by the intrathyroidal lymphocytic infiltrate of such mice. Using a radiolabeled RT-PCR technique with oligonucleotides detecting 17 mouse TcR V beta gene families to examine the heterogeneity of the amplified V-D-J (CDR3) fragments, we demonstrated that only the TcR V beta 13 amplifications consistently showed two similar homogeneous CDR3 sizes consistent with two clonally expanded T cell populations. Sequencing of the homogeneous RT-PCR products from these V beta 13++ populations confirmed the presence of clonal expanded T cells and identified two recurrent CDR3 motifs LTGKDTQ and LGEQ present in six of the seven samples. Both these motifs had been found as contributors to the T cell population in our previous studies of CBA/J mouse thyroiditis induced by active immunization with heterologous human (h) Tg. These data suggest that the autoepitope recognized was shared between hTg and mTg. It appears, therefore, that in transfer thyroiditis the intrathyroidal T cell clonal proliferation follows the homing of V beta 13 antigen-specific T cells which have been expanded by a brief (3 day) in vitro activation to mTg and utilize two distinct CDR3 motifs. CDR3 size heterogeneity in many of the other expressed V gene families also suggested the accumulation and recruitment of selected bystander T cells responding to additional but limited Tg or other self epitopes, perhaps on the basis of CDR3 shape rather than sequence. Such T cells may also have integral roles in the development of autoimmune thyroiditis.

Amino Acid Sequence↗

PubMed1996

Comparative electrophysiological effects of the antidepressants fluvoxamine and amitriptyline in the canine heart after myocardial infarction.

We studied the effects of fluvoxamine and amitriptyline on epicardial activation delay of premature excitations, the effective refractory period, and the incidence of ventricular arrhythmias by programmed electrical ventricular stimulation in the canine heart after myocardial infarction. Additionally, we investigated whether the inhibition of norepinephrine reuptake by amitriptyline contributes to epicardial activation delay or arrhythmias by combination with propranolol pretreatment. Amitriptyline, at a dose of 3 mg/kg, significantly prolonged epicardial activation delay of premature excitations in the infarcted zone in a frequency-dependent manner (n = 10). Amitriptyline also prolonged epicardial activation delay of premature excitations in the normal zone (n = 10). The effective refractory period in the infarcted zone was significantly prolonged by amitriptyline at a dose of 3 mg/kg (n = 8). Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). Propranolol did not affect the epicardial activation delay caused by amitriptyline or the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 6). Fluvoxamine, on the other hand, had no significant effect on epicardial activation delay of premature excitations (n = 10) or the effective refractory period (n = 8) in both the infarcted and normal zones. Fluvoxamine did not increase the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8).

Amitriptyline↗

PubMed1996

Design of a suitable formulation of FK613, a novel antiallergic agent, based on its pharmacokinetic and pharmacodynamic properties in healthy subjects.

The pharmacokinetic and pharmacodynamic properties of FK613, a novel indolyl piperidine derivative, were investigated after oral administrations of 5, 10 and 20 mg in hard gelatin capsules to healthy male volunteers. FK613 was rapidly and almost completely absorbed, and >89% was recovered in the urine as the unchanged form. The urinary excretion of FK613 was linearly correlated with plasma concentration and its low water solubility was the main concern regarding the safety. In another experiment using a double-blind crossover design, in which 0 (placebo), 5 and 20 mg FK613 were administered to determine the plasma concentration-effect relationship, suppression of the intradermal histamine-induced skin reaction by FK613 was observed. Thus, the maintenance of a plasma concentration of FK613 in the range of 80-250 ng center dot ml-1 was recommended to ensure the suppression of histamine-induced wheal by >50% and not to exceed the solubility in urine. To achieve this, a new hydrogel-type formulation of FK613 was developed, with the aim both of delaying its absorption, so as to suppress the sharp rise in plasma concentration, and of maintaining the effective concentration for a longer period of time. This formulation was administered after meals at the doses of 20, 30, 40, 50 and 60 mg, and at repeated doses of 40 mg twice daily for 6.5 days to evaluate the pharmacokinetics and safety in healthy subjects. The area under the plasma concentration curve increased linearly with dose, whereas maximum plasma concentration (Cmax) tended to peak as dose increased, indicating the desirable properties of this formulation. Although Cmax exceeded 250 ng/ml at doses of 30 mg or more, no urinary crystal formation was observed on careful inspection of urine.

Adult↗

PubMed1996

Autopsy case of colocalized tumors of hepatocellular carcinoma and malignant lymphoma.

We present a rare case of colocalized tumors of hepatocellular carcinoma (HCC) and malignant lymphoma in the liver and bone marrow. A 64-year-old man with hepatitis B virus (HBV)-induced cirrhosis was admitted after detection of elevated serum alpha-fetoprotein level. He was diagnosed as having HCC and treated with chemotherapy and radiotherapy, but the size of the tumors did not diminish. After 11 months' hospitalization, he died due to rupture of esophageal varices. Autopsy revealed two heterogenic malignant tumors, HCC and malignant lymphoma (B cell type), in the liver. These tumors showed colocalization in the liver and bone marrow. The carcinogenetic process of colocalized tumors of HCC and lymphoma was not clarified, but the possibility that persistent HBV infection play a role in promoting hepatocarcinogenic and hematopoietic tumor growths in the reticuloendothelial organs could not be excluded.

Autopsy↗

PubMed1996

Measurement of 5-fluorouracil in scalp hair: a possible index of patient compliance with oral adjuvant chemotherapy.

OBJECTIVE: Little is known about patient compliance with oral adjuvant chemotherapy. It is estimated to be poor especially in Japan, where it is still unusual for patients to be directly informed of their diagnosis of malignancy. 5-Fluorouracil (5-FU) was measured in hair samples to assess patient exposure to 5-FU, and its potential usefulness is discussed as an index of compliance with postoperative adjuvant chemotherapy. METHODS: Hair samples obtained from 55 patients, who had received oral 5-FU (total dose 27-41 g) as postoperative adjuvant chemotherapy over a 6-month period, were used for the analysis of 5-FU. The drug was extracted from the hair using ethyl acetate, and its fluorescence derivatization was employed for measurement with HPLC. The detection limit of 5-FU in hair was 0.01 ppm. RESULTS: In 22 out of 55 samples 5-FU content was under the detection limit, whereas in the remaining 33 samples the drug was detected in a range of 0.006-2.125 ng per hair strand; in addition, drug content showed a lognormal distribution. 5-FU was detected in the hair collected from those patients who were possibly compliant with the postoperative oral adjuvant chemotherapy. CONCLUSION: As many as 40% of the patients analysed were supposed to be much less compliant. Even in the possibly compliant patients, the degree of compliance with the therapy varied according to a log-normal distribution.

Animals↗

PubMed1996

A chemiluminescent detection of superoxide radical produced by adherent leucocytes to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery.

Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.

Animals↗

PubMed1996

Serial magnetic resonance images in a patient with congenital sensory neuropathy with anhidrosis and complications resembling heat stroke.

We report the results of serial computerized tomography (CT) and magnetic resonance imaging (MRI) in a 9-month-old Japanese girl with the rare disorder, congenital sensory neuropathy with anhidrosis (CSNA). She developed a prolonged high fever, anorexia, and weight loss with laboratory findings of hemoconcentration and elevated levels of GOT, LDH and creatine phosphokinase (CK) in May 1995, and was hospitalized. The cerebrospinal fluid (CSF) was normal on admission. Elevation of CSF myelin basic protein on the 16th hospital day suggested a destruction of the myelin sheath. The first MRI performed on the 16th hospital day revealed no marked abnormalities when the patient exhibited a high fever, generalized tonic-clonic convulsions, and impaired consciousness. The patient had a persistent high fever, and developed a second generalized tonic clonic convulsion and became comatose. A second MRI on the 20th hospital day showed a bilateral symmetrical paracentral hypo-intensity of the white matter with occipital hypo-intensity on T2-weighted images. MRI findings were considered to represent the complications of the high fever with a loss of water from the cerebral cortices and deep white matter. MRI and CSF findings indicated the presence of brain damage due to the high fever.

Biopsy↗