Filter cigarette smoking and lung cancer risk; a hospital-based case--control study in Japan.

Recent changes in the histology of lung cancer, namely a relative increase of adenocarcinoma compared to squamous cell carcinoma, might be due to a temporal shift from nonfilter to filter cigarettes. To investigate the association between type of cigarette and lung cancer by histological type, we conducted a case-control study in Japan, comprising 356 histologically confirmed lung cancer cases and 162 controls of male current smokers, who provided complete smoking histories. Overall, logistic regression analysis after controlling for age and prefecture revealed decreased risk, as shown by adjusted odds ratios, for both squamous cell carcinoma and adenocarcinoma among lifelong filter-exclusive smokers as compared to nonfilter or mixed smokers. This decrease was greater for squamous cell carcinoma than for adenocarcinoma. Among men under 54 years, filter-exclusive smokers displayed increased risk of adenocarcinoma, but decreased risk of squamous cell carcinoma. The recent shift in histology from squamous cell carcinoma to adenocarcinoma, particularly among younger smokers, might be due to changes in cigarette type. However, among subjects aged 65 years or more, no differences in histological type appeared related to type of cigarette smoked, implying that other factors are associated with increases in adenocarcinoma among older Japanese population.

[Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens].

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.

[The studies on tuberculosis present research ideas for medicine].

I started my medical career as medical mycologist following the first case of deep-seated candidiasis in Japan. On the other hand I have been seeing many patients with tuberculosis as well as respiratory diseases. In my sense the seeing of mycobacterial infections may still remain lot of clinical, biological or immunological research ideas in future. I did the studies on muramyl dipeptide (MDP) which derived from cell wall substance of mycobacteria. MDP seemed to be one of the enhancing immunomodulator for host defense mechanism in particular in the immunocompromised host.

[A clinical phase II trial of ulinastatin (MR-20) for nephrotoxicity of cisplatin].

UNLABELLED: MR-20 was administered to 37 lung cancer patients who presented with nephrotoxicity due to cisplatin (CDDP) treatment in an 11-institution cooperative trial during the period from September 1990 through March 1992 to study its suppressive effect on the nephrotoxicity as well as its safety. The results are reported in this paper. METHODS: MR-20 was administered at 3 daily doses, ie. 150,000, 300,000 and 600,000 units, in a nonblind manner. An efficacy rate of 27.3% was achieved in the group at 150,000 units; 44.4% in the group at 300,000 units; and 45.5% in the group at 600,000 units. Serum Cr levels remained significantly lower in the group at 300,000 units during the treatment period than in the screening period. No adverse reactions to MR-20 were observed. According to the above results, it was anticipated that MR-20 would suppress the nephrotoxicity of CDDP treatment and be safe, and that the drug at a dose of 300,000 units daily would be useful in suppressing the nephrotoxicity.

[A clinical phase III trial of ulinastatin (MR-20) for nephrotoxicity of cisplatin].

UNLABELLED: MR-20 was administered to 140 lung cancer patients who presented with nephrotoxicity due to cisplatin (CDDP) treatment at 59 institutions throughout Japan during the period from September 1992 through March 1994 to study its suppressive effect on the nephrotoxicity as well as its safety. The results are reported in this paper. METHODS: The efficacy and usefulness of MR-20 were studied in a placebo-controlled, double-blind manner. An efficacy rate of 58.7% was achieved in the MR-20 group, and 36.8% in the placebo group: MR-20 was significantly more effective for nephrotoxicity than placebo (U-test). Serum Cr, Ccr and FENa were prevented from significant variations in the MR-20 group, compared with the control group. It was considered that MR-20 is a safe drug, and that it is useful in suppressing the nephrotoxicity of CDDP treatment.

[Multicenter clinical trial of itraconazole in the treatment of pulmonary aspergilloma. Pulmonary Aspergilloma Study Group].

Itraconazole 100-200 mg was orally administered to 49 patients with pulmonary aspergilloma once a day in principle immediately after breakfast. Drug concentrations in fungus balls and in aspergilloma cavities were determined in each measurable case and the data were evaluated in terms of efficacy and safety. Overall evaluation was done considering the following 3 criteria: improvement of clinical symptoms, X-ray findings and mycological findings. The efficacy rate was 63.4% (26/41 cases). Out of 49 cases, adverse reactions and abnormal laboratory test values were observed in 8 (16.3%) and 13 (26.5%) cases, respectively. The safety rate was 81.6% (40/49 cases). 160 ng/g-4, 010 ng/g of itraconazole was detected in aspergilloma in 4 measurable cases. This finding showed that itraconazole had infiltrated into the fungus balls. Itraconazole was detected in aspergilloma cavities as well: drug concentration was 825 ng/g and 1,020 ng/g respectively. Based on overall view of clinical effects and drug concentrations in fungus balls and in the walls of lung cavities, it is concluded that itraconazole showed efficacy in reducing the size of aspergilloma and that this drug is useful also in terms of safety.

[A case of pulmonary tuberculosis complicated with gingival lesions].

A case of secondary gingival tuberculosis is presented. The case is 51 year-old male who had been suffering from undetected pulmonary tuberculosis visited a dentist because of chronic periodontal inflammation around the gingiva of the right upper and left lower molar teeth lasting for one year. The lesions remained unchanged and painful granulomatous swelling sustained in spite of the conservative treatment. The case was treated with the extraction of six teeth due to continued toothache. By pathohistological examination of gingiva and chest X-ray examination, the case was diagnosed as tuberculosis. Chest roentgenogram showed active pulmonary tuberculosis, and bacteriological examination of sputum showed tubercle bacilli. The administration of INH, RFP and EB was started, and the response to the treatment was good and the pain in the gingiva disappeared within three weeks. Secondary gingival tuberculosis is manifested as local granulomatous lesions with severe pain. The incidence of gingival tuberculosis is very rare, but we have to keep in mind that the oral tuberculosis secondary to pulmonary tuberculosis could occur.

[Report of questionnaire about enterohemorrhagic Escherichia coli cases caused in the area including Sakai City in 1996].

Many outbreaks of EHEC O157 were occurred in Japan in 1996. There was the biggest outbreak involving approximately 6000 victims in area of Sakai City. We conducted a questionnaire survey on the EHEC infection to the physicians who treated these patients and the microbiologists. For physicians we asked mainly clinical manifestation of patients they observed and treatment they did and their outcome (Answer A). Microbiologists were also required to answer the opinion about treatment (Answer B). Eighty-five of physicians replied about their 222 patients and 209 of microbiologists answered their opinions. In this report we summarized the data and obtained following results: 1) We observed higher frequency of HUS/TTA complication in female than male. 2) Higher HUS/TTP complication was accompanied with patients complained symptoms of fever, bloody diarrhea, and general fatigue. 3) The most patients (96%) were received antimicrobial agents, especially fosfomycin (84%), followed by new quinolon (17.8%) and Cefems (12.2%). Later starting of treatment with antimicrobial agents than 7 days from onset of symptoms increased HUS/TTP complication. 4) Anti-diarrhoeal agents seems to be one of risk factors for HUS/TTP complications.

[A cooperative clinical study on the evaluation of an antibody detection test kit (MycoDot Test) for mycobacterial infections. Cooperative Study Group for MycoDot Test].

To determine the usefulness of a diagnostic kit for mycobacterial infection, we performed a five-hospital cooperative clinical study using serodiagnosis kits (MycoDot Test) to detect antibody for lipoarabinomannan (LAM) which is a membrane-derived component of mycobacterial species. We tested LAM antibody in the sera of patients with mycobacterial infection as well as healthy persons. Procedures for using the serodiagnosis kit are actually simple. Out of 130 cases of active pulmonary tuberculosis, 103 cases (79%) were positive for anti-LAM, and cases out of 24 cases of active atypical mycobacterial infection, 15 (63%) were positive. On the contrary, only 4% of healthy volunteers (1 out of 25 persons) were positive on this test. In conclusion, this diagnostic kit might be a useful test for early and supportive diagnosis of mycobacterial infections based on its sensitivity and specificity.

[Double blind controlled study of ubenimex (Bestatin) against squamous cell lung cancer--a multicenter cooperative study].

To investigate effects of the combination of ubenimex, chemotherapy, and radiotherapy against unresectable advanced squamous cell carcinoma of the lung, a placebo controlled double-blind study was performed. Of 365 registered cases, there were 258 cases in the complete radiation group in which the treatment as specified in the protocol (irradiation of 40 Gy or more to the thorax subsequent to chemotherapy) was conducted; the 50% survival time was 449 days and 363 days in the ubenimex group and the placebo group, respectively. A significant (p = 0.0473) prolongation of the survival time was noted in the ubenimex group, and the response rate was 60.9% and 50.0% (p = 0.087). From these results it was confirmed that ubenimex, when used in combination with chemotherapy and radiotherapy, not only enhances the tumor-reducing effect but also prolongs the survival time.

Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL/6 mice.

The effects of expermentally induced hyper- and hypothyroidism on the growth and development of spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) cells were studied in a murine system. Progression of 3LL tumors growing in mice was associated with significant reduction in the serum levels of T3 and T4. Subcutaneous (s. c.) injections (3 times/week) of T3 resulted in a hyperthyroid state with elevated T3 and reduced T4, whereas treatment with T4 induced a hyperthyroid state with elevated T3 and T4 levels. On the other hand, treatment with methimazole induced hypothyroidism with reduced T3 and T4 levels. Under these experimental conditions, treatment with T3 significantly inhibited spontaneous pulmonary metastases, and prolonged survivals of the mice. Methimazole suppressed primary and metastatic tumor growth and prolonged survival. In contrast, treatment with T4 enhanced primary tumor growth and development of pulmonary metastases of 3LL cells. Alveolar macrophages showed enhanced cytotoxicity against 3LL tumor cells after injections of thyroid hormones (T3 and T4) for 4 weeks. The NK activities of spleen cells of mice treated with T4 or methimazole were much lower than those of control mice, and were not affected by treatment with T3. These results imply that changes in thyroid functions may have important influence on natural host defenses against primary and metastatic lung cancer in humans.

[Clinical effect of miconazole gel against upper digestive tract mycosis].

A total of 43 patients, comprising 41 patients with oral candidiasis and 2 with esophageal candidiasis, were treated with miconazole (MCZ) gel to assess its efficacy and safety in treating upper digestive tract mycosis. The efficacy of the drug was evaluable in 33 of them, consisting of 32 patients with oral candidiasis and 1 with esophageal candidiasis. The clinical efficacy rate of the drug against oral candidiasis was 87.5% (28/32 patients), and the clinical response was good in the 1 evaluable patient with esophageal candidiasis. The safety of the drug was assessed in 40 patients. In 3 (7.5%) of them, nausea occurred as an adverse event, but was not particularly serious in any of them. No abnormal laboratory test values caused by the drug were observed. The results suggested that MCZ gel would be a very useful drug in treating oral and esophageal candidiasis.

Initial appearance of an ill-defined shadow on a chest roentgenogram in a patient with aortitis syndrome.

A 20-years-old woman with fever and an abnormal shadow on a chest roentgenogram was admitted to our hospital. High grade fever continued even after gradual disappearance of the ill-defined shadow on the right upper lobe (S3) with minor fissure deviation upward, while neck pain and bruit gradually developed. She was diagnosed as aortitis syndrome from a digital subtraction angiography. The initial appearance of an ill-defined shadow on a chest roentgenogram, considered as pulmonary infarction, is rare in the aortitis syndrome and this kind of onset is interesting in relation to the pathogenesis and diagnosis of this syndrome.

[Muramyl dipeptide derivative and its clinical application].

Muramyl dipeptide (MDP) and its synthetic derivatives which comes from the major constituent of bacterial cell wall has various biological activities as host defence mechanisms. One of the synthetic MDP derivatives, MDP-Lys (L 18), muroctasin has potent biological activities with less adverse reactions among various MDP derivatives. Muroctasin has proved to be safe to use clinically as the results of phase I clinical study. We attempted to evaluate its clinical usefulness and safety from the view point of restorative activity in leukopenia that was induced by cancer chemotherapy in patients with malignancies. It is concluded that muroctasin is effective as well as useful on the restorative activities against leukopenia in lung cancer patients after cancer chemotherapy, with the optimal daily dosage of 200 micrograms for six times by subcutaneous injections through phase II and phase III clinical cooperative studies in Japan. Supposed mode of action of muroctasin for granulocytosis may be the results of CSF production due to stimulation of macrophage by muroctasin. This first clinical success of restoration of leukopenia in patients with cancer receiving cancer chemotherapy by MDP derivative, muroctasin, might be not only advantageous for cancer chemotherapy and/or radiation therapy but also for preventing infections occurring in compromised host due to neutropenia in cancer patients by means of cytotoxic cancer chemotherapy or irradication.

[Restorative effect of muroctasin, MDP-Lys (L 18), on leukopenia caused by anticancer chemotherapy in lung cancer--comparative study by envelope method].

Muroctasin, a derivative of MDP, is known to augment the number of WBC via colony-stimulating factor. Muroctasin has been expected to be promising for application to leukopenia caused by anticancer chemotherapy. When WBC decreased to less than or equal to 3,000/mm3 after the 1st course of chemotherapy, 131 patients with lung cancer, who were previously classified by chemotherapy combination, were enrolled in the study and randomized into 3 groups, 200 micrograms (H), 100 micrograms (L) and untreated control (C) groups. The patients were then subcutaneously treated once daily for 6 consecutive days. WBC and its differential count were measured on days 4, 7 and 15 after commencement of the study. WBCs in H and L groups showed greater recovery than in C group. In WBC differential count, the recovery of neutrophil was prominent in muroctasin-treated groups. A portion of immature neutrophil in bone marrow was also increased by muroctasin treatment. In the present study, the usefulness of muroctasin in leukopenia was indicated when administered at dosages of 200 micrograms for 6 days.