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[Study on platinum concentration in internal iliac venous blood after iliac artery cisplatin infusion for invasive bladder cancer].

We evaluated the usefulness of internal iliac artery infusion of cisplatin (CDDP) in the M-VAC therapy for bladder cancer. CDDP (average 72 mg) was administered into the internal iliac artery with an infusion time of 15 minutes in 8 cases of bladder cancers. After the end of CDDP intra-arterial injection, we measured the total and free platinum (Pt) levels in the internal iliac venous blood and systemic venous blood. Both total and free platinum levels in the internal iliac venous blood were about 4 times higher than those in the systemic vein. No significant difference was found in total or free platinum level in the systemic blood between the intra-arterial and intra-venous infusion methods. Intra-arterial CDDP therapy is effective in the treatment of the local tumor and systemic micrometastasis.

Aged↗

[Monitoring of plasma concentration of low molecular weight heparin--comparative evaluation with chromogenic and clotting assays].

The efficacy of low molecular weight heparin (LMWH) in the treatment of thrombosis is increasing interest in its clinical potential. However, the measurement of in vitro anticoagulant activities of LMWH has been controversial for its appropriate clinical dose. The study has been carried out to compare two methods for measurement of anti-factor Xa activity of LMWH (fragmin). One is 'HEPTEST' recently developed as a new clotting assay method and the other is an authentic chromogenic assay using S-2222. The coefficients of variation in intra-assay were 1.87-2.75% in clotting assay, and 0.61-0.89% in chromogenic assay. The sensitivity to detect minimum concentration was 0.02 IU/ml in clotting assay, and 0.04 IU/ml in chromogenic assay. The correlation between two methods was good (r = 0.935), whereas clotting assay has been revealed as a very simple rapid method. LMWH (fragmin) with 75 IU/kg/day was administered to three patients with coagulopathy; two disseminated intravascular coagulopathy (DIC) and one veno-occlusive disease (VOD). Hemostatic abnormalities have been improved serially after treatment in all patients. During treatment, the plasma concentration of LMWH was measured, showing 0.05-0.23 IU/ml in DIC and 0.02-0.10 IU/ml in VOD. These results suggest that measurement of plasma concentration of LMWH using the easy and rapid clotting assay method as 'HEPTEST' is clinically useful for monitoring to detect clinical dose of LMWH for DIC and thrombosis.

Anticoagulants↗

[Transdermal microparticle delivery by a supersonic-Helios gun system].

AIM: To investigate the effect of particle size and high speed flow of helium gas on the systemic absorption of indomethacin using a needle-less injection system. METHODS: Poly-L-lactic acid microspheres containing indomethacin was prepared by the o/w solvent evaporation technique. After anesthetizing the male hairless rat, microspheres filled in the tube cartridge was accelerated by a stream of helium gas at various velocity in the Helios gun system, and then was introduced to the abdominal skin. RESULTS: Introduction of indomethacin to the hairless rat skin was proportionally increased with enhancing the helium pressure (supersonic flow). Bioavailability and Cmax were also dependent on the helium pressure. CONCLUSION: This method can be used to deliver the powered drug and/or microparticulate systems into the skin tissues and the systemic circulation.

Administration, Cutaneous↗

[MR imaging of bone and soft tissue tumors].

One hundred sixty-one patients with tumors of bone or soft tissues underwent MRI. We believe to be able to differentiate benign from malignant lesions on the basis of imagings at internal, marginal, and peripheral properties. MR imagings demonstrated specific morphologic features that suggest the correct tissue diagnosis. MR imagings with STIR method or Gd-DTPA were more valuable. Because of the high contrast between the tumors and normal tissue, especially by STIR method, MRI provides improved detection and delineation of bone soft tissue tumors when compared to other diagnostic modalities.

Bone Neoplasms↗

[Fundamental studies on transcutaneous bilirubinometry in newborn infants using an organ scanning spectrophotometer].

In vivo reflectance spectra in the visible region were recorded on the blanched skin on the foreheads, chests, arms and legs of 140 newborn infants using an organ scanning spectrophotometer, and corresponding total serum bilirubin levels were determined. An elevation in the absolute spectra was observed in the 460 nm region for the higher bilirubin level, and the isosbestic point was located in the 510 nm region. A linear relationship was observed between the reflectance spectra difference and the serum bilirubin level. Although the best analysis results were obtained from the measurements of the reflectance spectra difference between 460 nm and 510 nm on the chests (r = 0.954, Y = 40.62X + 1.36), or on sums of 4 measuring sites (r = 0.973, Y = 46.59X + 0.61), there was no statistical difference from the values obtained between 460 nm and 550 nm on the foreheads (r = 0.913, Y = 33.55X + 5.30). The slopes and the Y-intercepts of the linear regressions differed considerably at various measuring sites. Marked decreases in the reflectance spectra differences were observed during the phototherapies and prominent rebounds followed for 24 hours after the cessation of phototherapies. The noninvasive and simple reflectance method was sensitive to the bilirubin level in the tissue and might be a better indicator of neonatal risk of kernicterus. However, the optical method has a certain limitations in representing the bilirubin concentration in the blood stream, especially during, and for 24 hours, after phototherapies.

Bilirubin↗

[Close classification method of undetermined cases of trophoblastic disease (author's transl)].

With the improvement of recovery ratio of trophoblastic disease by means of primary chemotherapy, undetermined cases of trophoblastic diseases, whose morphological examination has not been conducted, have increased. The respective sickly constitutions of these cases are extremely complicated, and we have deviced a new close classification of these cases from clinical standpoint. For the purpose, we have chosen out the following items.: A. Major subdivision 1. Types of antecident pregnancy. 2. Duration between the antecident pregnancy and the commencement of chemotherapy. 3. Urinary hCG secretion pattern following molar pregnancy. 4. Following treatment of hydatidiform mole. B. Minor subdivision 1. Urinary hCG titer at the commencement of chemotherapy. 2. BBT pattern. 3. Chest x-ray findings. 4. PAG. 5. Clinical signs. 6. Development of focuses (clinical). 7. Necessary reasons for chemotherapy. These items are expressed respectively by figures. This close classification method is based on the combinations of these figures. The authors believe, this method will enable the easy classification of early chemotherapy examples and will present a strong key for the analysis of enormous cases.

Chorionic Gonadotropin↗

Efficacy and safety of tacrolimus (FK506) in treatment of rheumatoid arthritis: a randomized, double blind, placebo controlled dose-finding study.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus (FK506) in patients with active rheumatoid arthritis (RA) exhibiting resistance to disease modifying antirheumatic drug (DMARD) therapy, and to determine the optimal dosage. METHODS: A total of 212 patients with DMARD-resistant RA were enrolled in this double blind, multicenter, randomized, placebo controlled study and allocated to 3 groups. Patients were administered tacrolimus at a dosage of 1.5 mg/day (68 patients) or 3 mg/day (70 patients), or placebo (74 patients), for 16 weeks. They were allowed to continue taking prednisolone (< or = 5 mg/day) and/or one nonsteroidal antiinflammatory drug (NSAID) during the study. Clinical assessment was based on the American College of Rheumatology (ACR) 20% criteria. RESULTS: ACR 20% response rates were higher in both tacrolimus groups (3 mg: 48.3%; 1.5 mg: 24.6%) than in the placebo group (14.1%), with the rate in the 3 mg group significantly higher. There were no significant differences between the tacrolimus groups and placebo group in the incidence of adverse events. The main adverse events in the tacrolimus groups, especially in the 3 mg group, were renal function abnormalities and gastrointestinal symptoms. However, no significant differences were observed among the 3 groups in the incidence of any adverse event except decrease in serum Mg level. CONCLUSION: Our findings demonstrate excellent dose-dependent efficacy of tacrolimus in patients with DMARD-resistant RA and strongly suggest the usefulness of tacrolimus for treatment of RA. The optimal dosage appears to be 3 mg/day in terms of efficacy and safety.

Adult↗

Gonadotropin and alkaline phosphatase producing occult gastric carcinoma with widespread metastasis of generalized bone.

A case is reported of a small primary occult gastric adenocarcinoma occurring in a 57-year-old man revealing widespread metastasis to generalized bone, and associated with high serum level of circulating human chorionic gonadotropin (hCG), carcinoembryonic antigen (CEA), and alkaline phosphatase (ALPase). The primary site of metastatic bone tumor was not clear until autopsy. Microscopic examination of the gastric primary revealed moderately differentiated tubular adenocarcinoma admixed with numerous signet-ring carcinoma cells without conspicuous trophoblastic differentiation. The elaboration of hCG and intestinal and placental isoenzyme of ALPase by carcinoma cells themselves was confirmed by the indirect immunoperoxidase method. The present case may be interesting because of unusual metastasis and simultaneous production of hCG, CEA, and intestinal and placental ALPase isoenzymes.

Adenocarcinoma↗

Prognostic significance of argyrophilic nucleolar organizer staining in soft-tissue sarcomas.

The utility of argyrophilic stain for nucleolar organizer region (AgNOR) for estimating proliferative activity and prognosis of soft-tissue sarcomas (STS) was examined. Formalin-fixed and paraffin-embedded sections of 38 cases with STS were used; the reaction product of AgNOR stain was observed as dots mainly in the nucleoli. The mean number of AgNOR dots per nucleus of tumor cells was calculated in 200 cells (AgNOR count). The AgNOR count, ranging from 1.4 to 16.1 (mean, 7.5), showed a good correlation with cellularity (r = 0.483, p less than 0.003) and histologic grade (r = 0.626, p less than 0.00005), but less shown with mitotic counts (r = 0.350, p less than 0.04). The prognosis of cases with AgNOR low-count group (5-year survival rate was 74.6%) was much better than those in high count group (33.3%) (p less than 0.0005). The AgNOR count correlated well with reactivity of tumor cells for Ki-67 staining, which was available only in freshly prepared sections. These findings suggested that the AgNOR staining is a simple and useful method for estimating tumor-cell proliferation and prognosis of patients with STS.

Adolescent↗

Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics.

The pharmacokinetics of racemic (rac) felodipine, rac-nitrendipine and nifedipine (all given as an oral dose of 20 mg in solution) have been investigated in a randomised cross-over study in 12 healthy male subjects using stereoselective assays. Both felodipine and nitrendipine exhibited stereoselective pharmacokinetics. On average, the AUCs of the active (S)-enantiomers of felodipine and nitrendipine were 139% and 104% higher than those of their optical antipodes, but the elimination half-lives of the enantiomers of each racemate were not different. The AUCs of nifedipine, rac-felodipine, rac-nitrendipine and of their enantiomers were highly correlated (all r > 0.83), suggesting closely related rate limiting steps in the in vivo first-pass metabolism of these high-clearance drugs. Stereoselectivity was only a minor contributor to inter-individual variability in the oral pharmacokinetics of these compounds in healthy subjects.

Administration, Oral↗

New evaluation method using preoperative magnetic resonance imaging for cervical spondylotic myelopathy.

A new method based on the score of preoperative magnetic resonance images (MRI) was devised to evaluate cervical spondylotic myelopathy and predict the results of cervical laminoplasty. On T1- and T2-weighted sagittal MRI, the intervertebral disc spaces at each level from the axis to the first thoracic spine were examined as to whether the anterior or posterior subarachnoid space would be maintained or not, and for the presence or absence of spinal cord deformity. The data were divided into six grades and rated, and the total score for all sites was regarded as the preoperative MRI cumulative score. In conclusion, our method was highly reliable and useful for a preoperative evaluation and prediction of results after cervical laminoplasty for cervical spondylotic myelopathy.

Adult↗

Direct RT-PCR method for detecting two chrysanthemum viroids using minimal amounts of plant tissue.

A direct reverse transcription-polymerase chain reaction (RT-PCR) method for detecting the chrysanthemum stunt viroid (CSVd) and chrysanthemum chlorotic mottle viroid (CChMVd) to screen for a viroid-free chrysanthemum plant at a small plant size was established and named microtissue direct RT-PCR. A razor or syringe needle was used for RNA template preparations. Under a stereoscopic microscope, a razor or syringe needle was used to pierce, a tissue sample to a depth of 0.1-0.2mm, and the sample was directly transferred to the RT mixtures. Methods using razors or needles for the preparation of templates could detect CSVd and CChMVd with a high sensitivity. The most sensitive method used a razor or syringe needle to acquire template from the shoot tips. Using the microtissue direct RT-PCR method, both viroids could be detected from the high- and low-viroid-concentration plants. The microtissue direct RT-PCR method was more sensitive than a conventional template preparation method. Using the microtissue direct RT-PCR method established in this study, the laborious subculture step could be omitted because detecting viroids and screening for viroid-free plants even at a small plant size before the subculture could be possible. In addition, the microtissue direct RT-PCR method could also be a powerful tool for clarifing the viroid distribution among microtissues, such as shoot apical meristems.

Chrysanthemum↗

Immunization by particle bombardment of antigen-loaded poly-(DL-lactide-co-glycolide) microspheres in mice.

In the present study, we investigated whether poly-(DL-lactide-co-glycolide) (50:50) microspheres (PLG MS) containing a model antigen, ovalbumin (OVA), were delivered into mouse skin and the immune responses induced using a microparticulate bombardment system, Helios gene gun system, which can painlessly deliver the powdered drug through the stratum corneum to the epidermal-dermal interface using a high velocity supersonic flow of helium gas to accelerate the particles. The introduction of OVA-loaded PLG MS shows helium pressure-dependence, so that improved introduction can be achieved by a higher helium pressure used, thereby inducing sufficient anti-OVA IgG level. Moreover, in order to determine the type of immune system induced using particle bombardment, we investigated helper T-cell response characterized by the cytokine production in the isolated splenocytes 6 weeks after immunization and consequent production of the anti-OVA IgG subclasses in the serum in mice. As a result, IL-4 production in splenocytes and anti-OVA IgG1 level were preferentially elicited by particle bombardment with OVA-loaded PLG MS compared with IFN-gamma and anti-OVA IgG2a level. It seemed likely that particle bombardment using this system led to a Th-2 type immune response, i.e. a humoral immune response. In conclusion, this microparticulate bombardment system is a promising immunization method, expected to become an alternative to needle injection used to administer a broad range of vaccines for the treatment of various diseases.

Air Pressure↗

Seroepidemiologic studies of acute hemorrhagic conjunctivitis virus (enterovirus type 70) in West Africa. I. Studies with human sera from Ghana collected eight years after the first outbreak.

In 1969 and early 1970, during the pre-epidemic period of acute hemorrhagic conjunctivitis (AHC) in the upper north regions of Ghana, 191 human sera were collected. In 1977, eight years after the first epidemic of AHC in Ghana, 1008 human sera were also collected in various regions of Ghana. These sera were examined for virus neutralizing (VN) antibody against the J670/71 strain of enterovirus type 70 (EV70). In the pre-epidemic 1969-1970 sera, a low prevalence rate (6%) of VN antibody, with a titer of greater than or equal to 1:8, was found; the geometric mean titer (GMT) was also very low (1:1.85). In the post-epidemic 1977 sera, a high prevalence rate (53%) of VN antibody was found in the Ghanaian population, and the calculated GMT was also high (1:7.36). A higher antibody prevalence was detected in coastal (Accra: prevalence rate of 58% and GMT of (1:7.84), forest (Kumasi: 58% and GMT 1:7.52) and peri-forest (Tamale: 51% and GMT 1:7.46) areas than in the tropical savanna area (Bolgatanga: 41% and GMT 1:5.13). The demonstration of VN antibody in children under seven years of age showed that EV70 was still widely distributed and highly active in Ghana. The VN antibody found in human sera was predominantly IgG.

Adolescent↗

Evaluation of the bitterness of antibiotics using a taste sensor.

The bitterness of nine commercial antibiotics (clarithromycin, erythromycin, cefdinil, doxycycline, vancomycin, tetracycline, minocycline, oxytetracycline and bacampicillin) was evaluated in human gustatory sensation tests with nine volunteers. The bitterness of 0.1-0.3 mM solutions (or suspensions in the case of clarithromycin) of the antibiotics was then measured using an artificial multichannel taste sensor. In the sensor measurements, three variables were used to predict estimated bitterness in single and multiple regression analysis and principal component analysis: sensor output as relative value (R), the change of membrane potential caused by adsorption (C) and C/R. Particularly good correlation was obtained between obtained bitterness scores and predicted scores using C from channel 2 of the sensor (r2=0.870, P<0.005) and C/R values for channels 2 and 3 (r2=0.947, P<0.005). The taste sensor was also successful in assessing the bitterness intensity of clarithromycin powder suspensions of various concentrations. Clarithromycin has a low aqueous solubility but is the most bitter of the nine antibiotics. Sensory data from channel 3 of the sensor predicted the bitterness of clarithromycin powder suspensions and their filtered solutions well. Finally, the bitterness intensity of a commercial clarithromycin dry syrup product (Clarith dry syrup, Taisho Pharmaceutical Co. Ltd, Tokyo, Japan) was evaluated in gustatory sensation tests and using the taste sensor. In Clarith dry syrup the drug is coated with aminoalkyl methacrylate polymer using a spray congealing method. The taste sensor results confirmed that the polymer was successful in almost completely masking the bitter taste of the dry syrup product.

Anti-Bacterial Agents↗

Difference of glucose values due to analytical instruments, methods and samples.

This study was carried out to obtain exact blood glucose differences due to samples, analytical methods and instruments. Glucose values obtained with autoanalyzer having deproteinizing system were lower than those obtained by the instrument without deproteinizing system, but the difference was less when the analyzer had no deproteinizing procedure but a dual wave length system. The difference between Hoffman's method and glucose-oxidase method was 10 mg/dl. Plasma glucose values were higher than those of whole blood and the difference varied with glucose values.

Autoanalysis↗

Squamous cell carcinoma of the external auditory canal: two cases treated with high dose rate 192Ir remote afterloading system (RALS).

We report two cases of early-stage external auditory canal cancer treated by intracavitary irradiation with a high dose rate (HDR) 192Ir remote afterloading system (RALS) for preoperative treatment. A 6-Fr catheter for the HDR 192Ir remote afterloader, fixed by a plastic earplug, was inserted into the external auditory canal in two cases (case 1, T2N0M0; case 2, T1N0M0). The total intracavitary radiation dosages were 50 Gy (10 Gy/2 Fr/wk for 5 wks) for case 1, and 42 Gy (15 Gy/5 Fr/wk for 3 wks) for case 2. No external irradiation was given in either case. Surgical resection was performed in both cases, three to four weeks after irradiation. Histopathological examination confirmed the post-irradiation changes of necrosis, hyalinosis, and calcification, although vivid cancer cells remained. In preoperative irradiation of external auditory cancer, this method, although limited to treating early-stage cancers, may be a modality of choice for its efficacy and less severe side effects.

Brachytherapy↗