The effect of regioisomerism on the photophysical properties of alkylated-naphthalene liquids.

Novel regioisomeric alkylated-naphthalene liquids were designed and synthesized. In the solvent-free liquid state, 1-alkyloxy regioisomers showed excimeric luminescence, whereas 2-alkyloxy analogues exhibited monomer-rich luminescence features. Correlations among the molecular structures and the photophysical, calorimetric, and rheological properties are presented, demonstrating the impact of regioisomerism on the alkylated-chromophore liquid systems.

Influence of body fat on the onset of vecuronium induced neuromuscular blockade.

The onset time of vecuronium, a muscle relaxant, was measured after a bolus intravenous injection of 0.15 mg kg(-1) of vecuronium into 40 surgical patients aged 59-64 years. The onset time was then compared between male and female patients and the relationship between onset time and body fat (% of body weight) was analyzed. Arterial plasma concentrations of vecuronium were measured at 75, 195, and 375 sec after administration of vecuronium to 8 patients. The female patients (n = 23) showed a shorter onset time and more body fat than the male patients (n = 17). The onset time significantly decreased with increasing body fat in both groups. When only females with body fat of less than 30% (n = 10) were compared with the male group (all male patients had body fat of less than 30%), the body fat, onset time, and regression lines between the onset time and the body fat did not differ significantly. Except in the patient with the highest body fat, plasma concentrations at 195 and 375 sec significantly increased with increasing body fat. We concluded that the higher body fat in females is largely responsible for the faster onset of vecuronium action in females. A smaller distribution volume of vecuronium may also be one of the reasons for the faster onset of vecuronium in females.

Immunohistochemical expression of glutathione transferase-pi in untreated primary non-small-cell lung cancer.

Patients with unresectable non-small-cell lung cancer (NSCLC) usually have undergone chemotherapy; however, such problems as resistance to chemotherapeutic agents occur during the treatments. Recent studies have indicated that glutathione S-transferase-pi (GST-pi) may play an important role in the resistance of cancer cells to alkylating agents, including cisplatin compounds. We examined a possible relationship between immunohistochemical expression of GST-pi and the response to cisplatin plus etoposide chemotherapy in patients with untreated and unresectable primary NSCLC. Of the 89 patients, 50 (56.2%) were GST-pi-positive and 39 (43.8%) were GST-pi-negative. For the patients with negative GST-pi expression, the response rate was 66.7% (26 of 39 patients). In the patients with positive GST-pi expression, the response rate was 26% (13 of 50 patients). This difference was statistically significant (P = .0019). The results suggest that GST-pi expression in NSCLC tissues is related to response to cisplatin plus etoposide chemotherapy and may be useful as a predictor of chemotherapy response.

Technetium tin colloid test detecting symptomless dysphagia and ACE inhibitor prevented occurrence of aspiration pneumonia.

Symptomless dysphagia and swallowing disorders play a very important role in the pathogenesis of aspiration pneumonia. A videofluoroscopic examination and a simple two-step swallowing provocation test (STS-SPT) could be useful for detection of swallowing disorders in elderly patients with stroke, however, there is no report on such a test for detection of symptomless dysphagia. We administered 1 ml Technetium Tin Colloid (99mTC) to the patient during sleep via a nasal catheter placed in the mouth. At 09:00 h the next day, symptomless dysphagia was checked for by imaging. Improvement of the symptomless dysphagia was observed, and thus we could prevent the occurrence of aspiration pneumonia. The 99mTC test was particularly useful in detecting symptomless dysphagia in elderly patients with stroke.

Cytological diagnosis and telomerase activity of cells in effusions of body cavities.

Telomerase is a ribonucleoprotein that synthesizes telometric DNA on chromosome ends, and may be related to the aging and immortality of cells. Recently, a telometric repeat amplification protocol (TRAP) assay for telomerase activity, using the polymerase chain reaction, was developed. We examined the limitations of TRAP assay by applying it to a cultured colon cancer cell line (COLO320) and 58 human cytological materials from body cavity effusions, and obtained the following results; i) The limits of the TRAP assay were 20-50 cells for the COLO320 cell line; ii) One COLO320 cell per 100 normal blood white cells was detectable; iii) Seventeen of 58 samples were positive for telomerase activity in this study. The sensitivity was 69% (9/13) and the specificity was 87.5% (28/32) between cytological diagnosis and telomerase activity; iv) Among 29 malignant cases, 15 were positive for telomerase activity, while there were 11 cytologically positive cases. The positive cases detected by the combination of cytology and telomerase activity accounted for 21 of the total 29 cases (72.4%). These results suggest that the measurement of telomerase activity in body cavity effusions may be useful as an adjunctive tool for cytological and clinicopathological diagnosis and that this technique is potentially applicable to remnant cytological materials.

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system.

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean Cmaxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 micrograms ml-1, respectively. The mean Tmaxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 micrograms.h ml-1, respectively. For FT, Cmaxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 micrograms ml-1, and Tmaxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 micrograms.h ml-1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean Cmaxs of liquid preparations and solid preparations were 0.37 and 0.22 micrograms ml-1, respectively. The mean Tmaxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 micrograms.h ml-1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.

Application of telomerase activity for screening of primary lung cancer in broncho-alveolar lavage fluid.

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we used a telomerase assay to detect primary lung cancer in broncho-alveolar lavage fluid (BALF). A total of 58 BALF samples were examined by telometric repeat amplication protocol assay. Thirty-five (29 cancers, 2 salcoidoses, 2 pulmonary tuberculoses and 2 normal samples) of 58 (60.3%) cases were found to be positive for telomerase activity. The sensitivity of telomerase activity was 78.4%, compared with 64.7% of BALF cytology. Among 37 primary lung cancer patients diagnosed histopathologically, 24 had positive cytology and 29 had positive telomerase activity. The number increased to 32 patients when cytodiagnosis and telomerase activity were considered. Of patients in whom the presence of primary lung cancer was strongly suspected clinically, although there was no histopathological evidence, two were telomerase-positive, initially diagnosed as normal by cytological examination and histological examination but finally diagnosed as primary lung cancer (adenocarcinoma) in subsequent histological examination using operation specimens. These findings suggest that telomerase assay using BALF samples might be a useful screening method for primary lung cancer especially when combined with BALF cytology.

Bronchial asthma induced by rice.

A 43-year-old patient with rice-induced bronchial asthma was first admitted to our hospital for developing bronchial asthma induced by mite and house dust. At that time, there was no sign of allergic response to rice. Two years later, he was readmitted in an emergency state, with a severe attack of bronchial asthma. This time, however, the result of immunoglobulin E (IgE)-radioallergosorbent test (RAST) for rice was positive, with those to mite and house dust were unexpectedly negative. The causative factors and pathological mechanisms of various kinds of food allergies still remain unknown. The patient is now followed up in an ambulatory setting, and has been eating hypoallergenic rice with no bronchial asthma-induced attack. The present case, being an adult patient with severe grain-induced bronchial asthma previously allergic to mite and house dust, seems to be rather rare in the literature.

[Relationship between the dose of lidocaine administered endotracheally in small children and the serum lidocaine level--recommended dose prior to endotracheal intubation].

To determine the optimum dose of lidocaine administered in the trachea prior to endotracheal intubation, we divided 102 surgical patients 3-5 years of age into 3 groups, i.e., group 1; 1 mg.kg-1 was sprayed in the trachea, group 2; 2 mg.kg-1 was sprayed in the trachea, group 3; 1 mg.kg-1 was sprayed in the trachea, and 1 mg.kg-1 in the pharynx and the oral cavity simultaneously. The venous serum concentration of lidocaine was measured two times either 1.5, 3, 5, 10, 15, 20, 30 or 45 min after the spray in each case. In group 1, the mean concentration of lidocaine reached the maximum of 1.05 micrograms.ml-1 at 5 min and decreased gradually after that with a small inter-individual variation. In group 2, after reaching the mean maximum concentration of 3.51 micrograms.ml-1 at 3 min, the serum level dropped quickly and then gradually decreased. There were a few cases where serum level was over 7 micrograms.ml-1. In group 2, after reaching the mean maximum concentration of 1.38 micrograms.ml-1 at 5 min, the serum level decreased more slowly, suggesting a slow absorption from the pharynx and/or the oral cavity. We conclude that the recommended dose of lidocaine for endotracheal administration is less than 2 mg.kg-1.

[Cancer-associated retinopathy].

A variety of paraneoplastic syndromes affect the central nervous system including eye. So far, two types of retinopathy are known to be associated with patients with malignancies, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy (MAR). CAR is associated with epithelial cancers, mostly lung small cell carcinoma, and is characterized by retinitis pigmentosa-like retinal degeneration. Usually CAR can be found before an underlying primary cancer is diagnosed. MAR is associated with cutaneous malignant melanoma and is characterized by the relatively sudden onset of photophobia and nyctalopsia. The flash electroretinogram (ERG) of MAR patients shows a negative waveform, reduced b-wave amplitude, and reservation of a-wave amplitude, suggesting that bipolar cells may be affected. CAR and MAR are believed to result from an autoimmune response. In CAR, a calcium binding protein called recoverin, a 70 kDa protein, and neurofilaments are the retinal antigens recognized by the patient's serum. In contrast, the retinal antigens in MAR have not yet been identified, although patient sera specifically recognized retinal bipolar cells in immunocytochemistry.

Application of a colon delivery capsule to 5-aminosalicylic acid and evaluation of the pharmacokinetic profile after oral administration to beagle dogs.

Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the does of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.

Correlation between the immunohistochemical and mRNA expression of glutathione S-transferase-pi and cisplatin plus etoposide chemotherapy response in patients with untreated primary non-small cell lung cancer.

Patients who have inoperable lung cancer usually undergo chemotherapy and have problems such as a resistance against chemotherapeutic agents during the treatment. Glutathione S-transferase (GST) is one of the detoxication-related enzymes. We studied the relationship between immunohisto-chemical staining of GST-pi type and cisplatin + etoposide chemotherapy in patients with untreated primary non-small cell lung cancer (NSCLC). Of patients diagnosed as having primary lung cancer, 60 cases (49 men, 11 women; median age, 75.2 years, 35 squamous cell carcinomas and 25 adenocarcinomas) with stage, which were not surgically treatable, were examined immunohistochemically by using anti-GST-pi antibody. Chemotherapy (cisplatin 100 mg/m(2) i.v. day 1, etoposide 100 mg/m(2) i.v. days 1-3) was administered for all 60 patients and was repeated at 28 days for two cycles. After two courses of treatment, the therapeutic response was evaluated. Of 60 cases, 36 (60%) were GST-pi positive and 24 (40%) negative at pretreatment. In 24 patients with GST-pi negative expression, the chemo-therapeutic response rate was 66.7% (16/24), while the response rate was 25% (9/36) in the 36 GST-pi positive patients. The mRNA levels of GST-pi were similar to the immunohistochemical expressions in some of these cases by using reverse transcription-polymerase chain reaction analysis. The results suggest that GST-pi: expression in cancer tissues is related to response to cisplatin + etoposide chemotherapy in untreated primary NSCLC patients, and may be useful as a predictor of chemotherapy response.

Use of epidural anesthesia in non-cardiac surgery in two cases complicated by hypertrophic cardiomyopathy.

Two patients with hypertrophic cardiomyopathy (HCM) who underwent non-cardiac surgery were managed successfully using epidural anesthesia as the principal intraoperative anesthesia. Epidural block was induced by inserting an epidural catheter from the lumbar vertebrae toward the caudal side. Epidural anesthesia is usually avoided in HCM patients because of the risk of a decreased preload or afterload causing stenosis in the left ventricular outflow tract. However, in surgery that requires an anesthesia level at L1 or below, which has little effect on sympathetic nerves, epidural anesthesia that maintains a stabilized hemodynamic state appears to be an excellent option.