[Refractory respiratory tract infections. 4. Selection of chemotherapeutic agents and their administration. a. Gram-negative bacterial infections].
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Biomedical subjects
Publications and source records attributed to K Konno.
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Radioaerosol inhalation lung cine-scintigraphy and lung function tests were performed on ten patients with bronchial asthma in remission before and after inhalation of salbutamol following intravenously administered aminophylline. Radioaerosol inhalation lung cine-scintigraphy was very useful in revealing the changes not only in the deposition patterns of inhaled aerosol in the lungs but also in the dynamic transport of mucus on the airways. The bronchodilating effect of the combined treatment was significant; the inhaled aerosol deposited more homogeneously and less centrally in the lungs, the "penetration index" and the alveolar deposition ratio (ALDR) increased from 31 +/- 3 to 49 +/- 7%, and from 29 +/- 2% to 39 +/- 1%, respectively, while the airway deposition ratio (ADR) decreased from 72 +/- 2 to 61 +/- 1% immediately after the treatment. Lung function data including FVC, FEV 1.0, FEV 1.0%, MMF, V50 and Vp significantly improved after the treatment. There was, however, little visual or quantitative improvement in mucociliary clearance after the treatment.
As a part of the quality control of drugs The National Medicine Control Laboratory in Finland has started comparative bioavailability studies of synonym preparations in human volunteers by taking all the products containing the same active ingredients for absorption studies at the same time. The first study, which is presented as an example of the importance of these studies, covered three erythromycin stearate preparations containing 250 mg of erythromycin. 12 volunteers took 2 tablets of every product at one week intervals in a cross-over fashion, and the serum erythromycin levels were measured microbiologically for 12 hr. Disintegration and dissolution tests were also performed. One of the products was coated with an acid-resistant film and was not dissolved in pH 1.2, whereas the conventional tablets lost all antimicrobial activity after 15 min in pH 1.2. In phosphate buffer, pH 6.6, all the tablets dissolved rapidly and retained antimicrobial activity. One of the conventional tablets showed only a 50% bioavailability as compared to the two others and was subsequently withdrawn from the market. Thus, it is important to conduct comparative post-marketing bioavailability studies with drugs which earlier have shown good bioavailability.
The pattern of fibronectin (FN) distribution in human lung cancer was studied by indirect immunofluorescent staining, and by the peroxidase-antiperoxidase method in a total of 60 surgical specimens. They comprised 8 small cell carcinomas, 4 large cell carcinomas, 19 squamous cell carcinomas, 28 adenocarcinomas, and 1 adenoid cystic carcinoma. Of the 60 specimens 13 were FN-positive. They included 4 large cell carcinomas, 4 small cell carcinomas, 3 poorly differentiated squamous cell carcinomas, and 2 poorly differentiated and 1 moderately differentiated adenocarcinomas. On the other hand, none of the well differentiated carcinomas was FN-positive around tumor cells. Our data suggest that undifferentiated, or poorly differentiated carcinomas of the lung tend to be FN-positive.
Thirteen healthy subjects participated in a combined acute and subacute double-blind, cross-over trial of two H1-antihistamines diphenhydramine (DPH) and temelastine (SKF) against placebo. The doses were DPH 50 mg b.d. and SKF 100 mg b.d. Objective (digit symbol substitution, flicker fusion, Maddox wing, attention, tracking, choice reaction) and subjective (visual analogue scales, side-effects on questionnaire) tests were done on Days 1, 4 and 5, on each occasion before drug intake and after 90 min and 3 h. On Day 1 DPH caused clear sedation of unpleasant character and impaired flicker fusion, attention and digit symbol substitution. SKF shifted the VAS assessment "drowsy/alert" towards drowsiness at 90 min, without objective impairment. On Day 4 DPH reduced exophoria and impaired flicker fusion without subjective sedation. On Day 5, diazepam 0.3 mg/kg (DZ) given with the other drugs caused subjective sedation of pleasant character and impaired various functions in the objective tests. Neither SKF nor DPH increased the effects of DZ; DPH slightly counteracted the effect of DZ on exophoria. At home, SKF did not differ from placebo while DPH proved sedative. DPH did not improve sleep but caused dry mouth and blurred vision. Measurement of plasma levels of antihistamines on each test day revealed the development of tolerance to antihistamine-induced sedation. The concentration of DZ measured by bioassay was somewhat elevated in the presence of DPH. Since the majority of the performance tests were not influenced by temelastine, it appears to be an acceptable, novel H1-antihistamine for the treatment of allergic disorders.
The crude extract from the skin secretion of the oriental catfish, Plotosus lineatus, contained at least one hemolysin, two lethal factors and two edema-forming factors; the lethal and edema-forming factors seem to be identical. The molecular weights of the hemolysin and the lethal factors (edema-forming factors) were estimated to be 180,000 and 12,000, respectively. Peculiar secretory cells, which resembled the venom glandular cells of the dorsal and pectoral stings, were observed in the epidermis.
Smoking habits of the 827 lung cancer patients aged 40 years or over who were treated in the Sendai Kosei Hospital from 1977-82 were compared with those in the general population of a non-metropolitan district in northern Japan, which we recently surveyed by mail questionnaire. The relative risks of lung cancer by histologic type adjusted by age and area of residence were as follows: 1.9 for adenocarcinoma, 4.3 for squamous cell carcinoma, 3.9 for small cell carcinoma and 3.4 for large cell carcinoma in men, and 2.9, 6.4, 4.5 and 4.0 for these histologic types, respectively, in women. These elevated risks were all statistically significant (p less than 0.05). These findings suggest that smoking habits should be carefully considered when studying the etiology of any cell type of lung cancer, even adenocarcinoma, which often has been thought to be unrelated to smoking habits.
A varicella-zoster virus (VZV) strain resistant to 5-iodo-2'-deoxyuridine (IdUrd) and 5-bromo-2'-deoxyuridine (BrdUrd) but sensitive to (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdUrd) and (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdUrd) was isolated. The 2'-deoxythymidine (dThd) kinase of this mutant (Ito) strain was characterized; it was much less efficient in phosphorylating dThd, 2'-deoxycytidine, and BrdUrd than were the dThd kinases from wild-type (CaQu, Kobayashi) VZV strains. The Ito dThd kinase had a markedly decreased affinity for dThd, 2'-deoxycytidine, and BrdUrd but only a slightly decreased affinity for IVdUrd than had the wild-type VZV dThd kinase. BrdUrd was incorporated to a much lesser extent in VZV (Ito strain)-infected cells than wild-type VZV-infected cells, but IVdUrd was incorporated in Ito VZV-infected cells as efficiently as in wild-type VZV-infected cells. While resistant to IdUrd and BrdUrd, the Ito strain was susceptible to inhibitors of de novo thymidylate biosynthesis such as aminopterin.
Tryptic and chymotryptic peptides of the LC-1 light chain of squid mantle muscle myosin were isolated and sequenced by conventional methods, so that the whole amino-acid sequence of the light chain was established. The light chain consisted of 159 amino-acid residues, and its N-terminal alpha-amino group is blocked. Comparing the established sequence with those of vertebrate muscle myosin light chains, only 35% sequence homology was recognized, but a conservative structure was observed in the third domain.
A proposed simplification of radioaerosol inhalation lung cine-scintigraphy, namely 60 min measurement of radioactivity without repeating measurement at 24 hr later and calculation of alveolar deposition ratio (ALDR) by the regression formula of ALDR = -48.08 + 0.47 X FEV1.0% + 0.59 X LRR60, was found useful and applicable even to the evaluation of a drug on mucociliary clearance mechanisms. The simplified method indicated a very similar evaluation of the effect of bromhexine on airway clearance efficiency with those actually revealed by the original method.
To evaluate mucociliary clearance mechanisms of the lungs, 14 patients with pulmonary interstitial fibrosis and 8 with sarcoidosis were studied by lung function tests and radioaerosol inhalation lung cine-scintigraphy. Although all these patients showed interstitial densities on chest x-rays, only the patients with pulmonary interstitial fibrosis indicated restrictive and diffusion abnormalities by lung function tests and those with sarcoidosis did not show either of these functional abnormalities. Mucociliary clearance mechanisms were well maintained qualitatively and quantitatively in these patients with interstitial lung disease.
Nine anti-herpes compounds, idoxuridine (IDU), bromovinyldeoxyuridine (BVDU), bromovinylarabinofuranosylurasil (BVaraU), carbocyclic bromovinyldeoxyuridine (C-BVDU), chloroethyldeoxyuridine (CEDU), acyclovir (ACV), dihydroxypropoxymethylguanine (DHPG), adenine arabinoside (Ara-A), and phosphonoformate (PFA) were examined for their inhibitory activities against the replication of twenty-six newly isolated clinical strains of varicella-zoster virus (VZV) in human embryonic fibroblast cell cultures. The order of (decreasing) efficacy was: BVaraU greater than BVDU greater than or equal to C-BVDU greater than CEDU greater than or equal to IDU greater than ACV greater than Ara-A greater than DHPG greater than PFA. There was little variation in the susceptibility of the 26 VZV strains to each particular compound, except for one strain which was resistant to IDU.
An antibiotic FOM was found to be preventive of the side effect of an antineoplastic drug CDDP on the peripheral T lymphocytes in lung cancer patients. Whereas finding a significant decrease in T3+ cells (p less than 0.01) and T4+ subset (p less than 0.05) with CDDP alone, the initial levels of these cell populations were kept unchanged in combination with FOM. T8+ subset showed no substantial change. A protective effect of FOM on T4+ subset was suggested to be an additional aspect of its action at least in combination with CDDP.
The localization of fibronectin was examined in normal human lung using immunoelectron microscopy. Fibronectin staining was present not only in the endothelial, alveolar epithelial and bronchial epithelial basal laminae and associated with interstitial collagen fibrils and elastic fibers, but also in basal laminae of fibroblasts and smooth muscle cells. There was a periodicity in the staining of fibronectin on collagen fibrils. Reaction products against fibronectin were present in intracellular organelle including cisternae of smooth endoplasmic reticulum of endothelial cells and those of rough endoplasmic reticulum of fibroblasts. No other cells contained reaction products. The localization of fibronectin was compared with that of ruthenium red staining in normal human lung. The localization of fibronectin was consistent with that of proteoglycan.
The antitumor activity of lipopolysaccharide (LPS) was investigated in BCG-treated mice. C3H/He mice and CDF1 mice were injected with BCG and then were inoculated with syngeneic mouse hepatoma MH134 and mastocytoma P815 respectively. Hemorrhagic necrosis and retarded growth of tumor were observed after an intravenous (i.v.) injection of LPS, when tumor cells had been inoculated subcutaneously (s.c.). However an intraperitoneal (i.p.) injection of BCG plus LPS did not increase the mean survival time of mice that had been inoculated with tumor cells i.p. Sera from mice that had been treated with BCG plus LPS i.v. were cytotoxic for cultured tumor cells. These results seemed to indicate that growth-inhibitory effects of LPS on tumors inoculated s.c. were mediated by a humoral factor.
The immunoregulatory T lymphocyte subsets (CD4+, CD8+) in 39 patients with primary lung cancer were analyzed as for the possible correlation with tumor histology. Compared to the healthy controls (n = 36), cancer lymphocytes were generally characterized by a higher proportion of CD8+ subset (p less than 0.01) with no difference in either CD4+ subset or CD3+ cells. There was, however, a significant difference (p less than 0.05) between one extreme of epidermoid carcinoma with the highest CD8+ and the lowest ratio (CD4+/8+) and the other end of adenocarcinoma with the lowest CD8+ and the highest ratio. Large cell and small cell carcinomas were of the intermediate values. A spectrum of the subset marker profiles was thus found in associated with tumor histology. A diversity in the host immune status was suggested in primary lung cancer, although clinical implication remains to be clarified.