Naloxone reversal of nystagmus associated with intrathecal morphine administration.
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Biomedical subjects
Publications and source records attributed to M Nishimura.
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Sixty-one patients ASA physical status 1-2 aged 1 month to 12 years undergoing elective surgery were included in the study. Anesthesia was induced via a mask with sevoflurane up to 5% and 66% nitrous oxide in oxygen. After paralysis with vecuronium (0.12 mg/kg iv), the trachea was intubated and the lungs were ventilated manually with 3% sevoflurane in oxygen until the end-tidal nitrous oxide decreased to less than 5%. Apnea was started by disconnecting the breathing circuit from the endotracheal tube. The time from the start of apnea to Spo2 of 95% was measured. Manual ventilation was reinstituted when Spo2 decreased to 95% and another set of vital signs was recorded. Twenty of 61 patients had symptoms of upper respiratory infection. The time to Spo2 of 95% correlated well with height, age, and body weight both by linear and non-linear regression analyses. The patients with symptomatic upper respiratory infection required less time for Spo2 to decrease to 95% compared to the asymptomatic children. We conclude that younger children require less time for Spo2 to decrease to 95%. The presence of upper respiratory infection is an additional factor increasing the susceptibility of small children to hypoxemia.
Regional hemodynamic responses to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, were compared with those to endothelin (ET) using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of these agents (16 and 160 mmol/kg of L-NMMA and 0.1 or 0.5 nmol/kg of ET-1) dose-dependently increased the blood pressure to the similar level. The cardiac index markedly decreased with ET-1, but was not greatly influenced by L-NMMA. Coronary and cerebral blood flow were not affected by these agents. ET-1 increased the bronchial arterial flow, and markedly decreased the flow in the other organs and tissues examined. L-NMMA almost homogeneously increased the regional vascular resistance to the lesser extent compared to ET-1. Although both ET-1 and nitric oxide are produced in the same cells and exhibit interrelationships, the present results indicate that the regional vascular effects of these agents are different: (a) ET-1 preferentially constricts arteries in all organs and tissues except the lung (where it increases flow) and the heart and brain where it has no wasted effects, leading to reduction in cardiac output, and (b) nitric oxide dilates arteries predominantly in the kidneys, muscle, and white adipose tissues.
As endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitric ions, we measured serum levels of nitrate (NO3-) concentrations as an index of endothelium-derived NO, to assess its role in blood pressure regulation. Because serum NO3- levels in men were significantly elevated compared to those in women, data from these two groups were analyzed separately. In men, multiple regression analysis revealed that NO3- significantly correlated with age, systolic blood pressure, body mass index (BMI), and total cholesterol. Blood pressure correlated with age, BMI, and NO3- with multivariate analysis. In women, NO3- significantly correlated with age, systolic blood pressure, and total cholesterol with a simple correlation. With multiple regression analysis, serum NO3- highly correlated with serum levels of triglyceride and total cholesterol and age. The blood pressure correlated with four parameters, i.e., total cholesterol, age, BMI, and NO3-. In summary, serum NO3- levels seem to relate to serum lipids and glucose levels and blood pressure, which strongly suggests that production of endothelium-derived NO is increased in the atherosclerotic process.
The development of ocular, renal, and neural lesions was examined in male diabetic WBN/Kob rats with endoexocrine pancreatic insufficiency. As for the ocular lesions, around 15 months of age, opacity of the lens began to appear. Opacity was first observed in the periphery of the lens, and then increased rapidly in severity, extending concentrically and centripetally, until total cataracts developed. The incidence of cataracts in male rats was gradually increased and reached almost 100% at 24 months of age. As for renal lesions, the 24-h urinary total protein began to increase at about 13 months of age and reached 50-300 mg/24 h at 13-28 month of age, which was significantly higher than in age-matched male Wistar rats (15-25 mg/24 h). Electrophoretic analysis revealed that the urinary protein was almost all albumin. Morphologically, an increased GBM thickness and glomeruli with segmental or global enlargement of mesangial areas were observed. As for neural lesions, a reduction in motor nerve conduction velocity was demonstrated electrophysiologically, and a marked decrease in density and diameter of myelinated fibers in the sciatic nerves were observed morphometrically. In conclusion, the WBN/Kob rat strain with slowly developing but severe lesions associated with pancreatopathy presents a suitable model for human diabetic complications.
Screening for leptomycin B (LMB)-resistant transformants in a gene library constructed in Schizosaccharomyces pombe with the chromosomal DNA of an LMB-resistant mutant of S. pombe and with multicopy plasmid pDB248' as the vector led to the isolation of a gene, named pmd1+, encoding a 1362-amino-acid protein. This protein showed great similarity in amino acid sequence to the mammalian P-glycoprotein encoded by the multidrug resistance gene, mdr, and the Saccharomyces cerevisiae a-factor transporter encoded by STE6. In addition, computer analyses predicted that the protein encoded by pmd1+ formed an intramolecular duplicated structure and each of the halves contained six transmembrane regions as well as two ATP-binding domains, as observed with the P-glycoproteins and the STE6 product. Consistent with this was that S. pombe cells containing the pmd1+ gene on a multicopy plasmid showed resistance not only to LMB but also to several cytotoxic agents. The pmd1 null mutants derived by gene disruption were viable and hypersensitive to these agents. All these data suggest that the pmd1+ gene encodes a protein that is a structural and functional counterpart of mammalian mdr proteins.
1. To elucidate the antiarrhythmic mechanism of promethazine, its effects on the fast Na+ current (INa) were examined in single guinea-pig ventricular myocytes by whole-cell voltage clamp methods. 2. Promethazine blocked INa with a KD of 42.6 microM and Hill's coefficient of 1.1 at a holding potential of -140 mV. 3. The INa blockade was enhanced at a less negative holding potential of -80 mV with a change of KD to 4.4 microM. Although 10 microM promethazine did not change the inactivation time constants of INa, it shifted the steady-state inactivation curve (h infinity curve) toward more negative potentials by 19.5 mV with the slope factor unaffected. 4. Double pulse experiments revealed that the development of blockade followed two-exponential functions having time constants of 7 and 220 ms at -20 mV. 5. Promethazine slowed the repriming of INa. This was associated with the development of slow phase having a time constant of 1160 +/- 59 ms. 6. Promethazine produced a profound use-dependent block when the cell was repeatedly stimulated with interpulse intervals shorter than 1 s. However, short pulses of 2 ms duration hardly produced such a use-dependent block. Hence, open channel blockade is considered to play a minor role in the promethazine action on INa. 7. These results suggest that promethazine blocks cardiac INa in a manner similar to class I antiarrhythmic drugs and that this effect may account for its antiarrhythmic action.
In an in vitro complicated cystitis model, the concentrations of the urinary antimicrobial agents were determined using a computer-controlled automatic urine concentration simulator. The effects on the bacterial count curves showing the presence or absence of PAE in antimicrobial agents were studied by comparing the times required for regrowth to the concentration at the initial inoculation, i.e., effective regrowth time (ERT). The following results were obtained. 1. When beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the gram-negative rods were tested, the ERT of the gram-negative rods were about two hours shorter than that of the gram-positive coccus. 2. When new quinolone antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that possess PAE against both the gram-positive and negative organisms were used there was no difference between ERT of the gram-negative rods and gram-positive coccus. Therefore, it was demonstrated that the presence or absence of PAE is also reflected in the cell number curve in the case of this in vitro model, more closely related to clinical cases, when the antibiotics is simulated in urinary concentration shifting.
Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.
Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary concentration by employing an in vitro complicated cystitis model operated by a computer-controlled automatic simulator for urinary concentration, and administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa: P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects by single treatment with ISP or PIPC on cell number curves were examined. Further, significance of the combined treatment with ISP and PIPC were investigated by changing the order of each treatment. And following the results were obtained. 1. In a single treatment with PIPC the cell concentration was minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth to the same level as the initial concentration was observed at 16th hour. 2. In the case of single treatment with ISP, the cell concentration became minimum (10(2) cfu/ml) at 13th hour after the treatment and raised to the same concentration as the initial one at 25th hour. 3. In the combined treatment, the cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case of prior treatment with ISP. Thereafter, regrowth was observed and the cell concentration at 42nd hour reached to the initial cell concentration. 4. In simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was minimum (10(1) cfu/ml) and reached to the same level as the initial one after regrowth. From these results, it was found that the combined treatment with ISP and PIPC caused more reduction of the cell concentration than either single treatment. Further, regrowth of the cells was suppressed for longer duration.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains.
We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1-positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1-transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1-negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N-linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome.
BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.
Rigid spine syndrome is a rare myopathy characterized by mild axial and proximal muscle weakness, limitation of neck and trunk flexion, scoliosis and mild joint contractures. We describe a 20-year-old woman with this syndrome who developed severe respiratory muscle failure disproportionate to the well-preserved extremity muscles. Nocturnal home care ventilation has completely restored her arterial oxygen desaturation during a 5-year follow-up.
Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes.
Effects of acute, progressive isocapnic hypoxia on heart rate (HR) and ventilation were determined in 31 patients with chronic obstructive pulmonary disease (COPD) and in 24 normal control subjects. There was an inverse linear relationship between heart rate and SaO2 in each subject. The slope factor (delta HR/delta SaO2) obtained from the regression line was significantly higher in the patients with COPD than in the normal control subjects (0.888 +/- 0.309 SD beats/min/% fall in SaO2 versus 0.693 +/- 0.287; p less than 0.05), whereas the ventilatory response (delta VE/delta SaO2) was not significantly different between the two groups. To elucidate factors responsible for the augmented heart rate response to hypoxia in the patients with COPD, we examined the relationships of delta HR/delta SaO2 with age, physical characteristics, pulmonary function data, and arterial blood gas data in all the subjects. A weak but significant relationship was found only between delta HR/delta SaO2 and FEV1/VC, %FEV1, RV/TLC, and %RV. Because the HR response to hypoxia correlates only with parameters that reflect the grade of airway obstruction, we believe that the enhanced HR response seen in patients with COPD is a result of the disease process in the airway and tissue, although the precise mechanism was not specified in this study.
In this open study, 41 hypertensive patients with non-insulin dependent diabetes mellitus were treated with the combined alpha- and beta-adrenoceptor blocker amosulalol hydrochloride for 24 weeks, either alone or added to existing antihypertensive therapy. The effects on blood pressure, glucose and lipid metabolism were examined. Daily administration of 20 to 60 mg amosulalol caused a significant reduction in both systolic and diastolic blood pressure within 2 weeks. This effect was stable, lasting for the entire trial period. The mean systolic and diastolic blood pressure decreased from 174 +/- 13/92 +/- 9 mmHg at the beginning to 148 +/- 16/80 +/- 11 mmHg at the end of the trial. Heart rate was not affected. Plasma glucose and haemoglobin Alc levels showed a tendency to decrease without any statistical significance. Total and HDL-cholesterol and triglyceride levels also remained unchanged. Although 3 patients had complained of dizziness, all were easily manageable. The results indicate that amosulalol is effective in the treatment of hypertension in non-insulin dependent diabetics and does not affect glucose and lipid metabolism.