Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Subclinical gallbladder carcinoma.

Clinicopathologic features of 31 patients with subclinical gallbladder carcinoma were reviewed in an attempt to determine the parameters for a course of therapy. Subclinical gallbladder carcinoma was defined as a gallbladder carcinoma that was first diagnosed microscopically by surgical pathologists. Of 31 patients, there were 26 women and 5 men, ranging in age from 54 to 84 years (mean age: 68 years). All 31 patients had undergone cholecystectomy for presumed benign gallbladder conditions. The 31 gallbladder carcinomas consisted of 6 carcinomas limited to the mucosa or the muscle coat (m or pm) and 25 carcinomas extending into the subserosal layer with surgical margins free of malignant cells in 14 (ss ew [-]) and affected by malignant cells in 11 (ss ew [+]). Cumulative 1-year, 3-year, and 5-year survival rates of six patients with m or pm carcinoma were 100% (p less than 0.001, versus ss ew [+] at 1 year), 100% (p less than 0.05, versus ss ew [-] at 3 years), and 100% (p less than 0.05, versus ss ew [-] at 5 years) compared with 91% (p less than 0.01, versus ss ew [+] at 1 year), 65%, and 65% of 14 with ss ew (-) carcinoma and 43%, 0%, and 0% of 11 with ss ew (+) carcinoma. Thirteen of the 31 patients died of local recurrence and/or liver metastasis. Univariate logrank analysis of 10 prognostic factors showed that depth of invasion, venous invasion, and surgical margin were prognostic factors. Multivariate Cox-regression analysis of these three profound factors demonstrated that surgical margin and depth of invasion were independent variables. These results showed that m or pm subclinical gallbladder carcinoma does not necessarily require an additional operation, whereas ss ew (-) and ss ew (+) carcinomas necessitate additional resection and adjuvant treatment.     

Effect of fenbufen on the pharmacokinetics of sparfloxacin in rats.

The effects of fenbufen on the serum concentrations and penetration into the brain and CSF of sparfloxacin (AT-4140), a new quinolone antibacterial agent, were investigated in rats. At designated times after a bolus iv dose of sparfloxacin 10 mg/kg with or without fenbufen 20 mg/kg, arterial blood, CSF and whole brain were simultaneously collected from each rat. Sparfloxacin concentrations were assayed by HPLC. Serum concentration of sparfloxacin declined bi-exponentially with time and was not changed by coadministered fenbufen. Binding sparfloxacin to serum protein slightly decreased after the coadministration. No elevation of sparfloxacin concentrations was observed in either brain or CSF after coadministration with fenbufen except for only a few time-points. The pharmacokinetic analysis based on the physiological model indicated that fenbufen did not affect the permeability across the blood-brain or blood-CSF barrier. These results suggest that fenbufen may be unlikely to affect the pharmacokinetics, involving the entry into the central nervous system, of sparfloxacin.     

Role of eosinophils in the late asthmatic response

The occurrence of late asthmatic response (LAR) is effectively prevented by corticosteroids, but not all by beta-adrenergic drugs. LAR is considered to be of great clinical and therapeutic importance and to be involved in the progression of bronchial asthma into a severe or even an intractable form. However the exact mechanism of the occurrence of LAR remains obscure in many respects. LAR is believed to be due to type I allergy. In guinea pigs, a positive bronchial inhalation challenge following passive sensitization with allogeneic antibody does not induce LAR or eosinophilic infiltration of lung tissue. This experimental fact led us to surmise that LAR would seem likely to be elicited in passively sensitized animals if pronounced eosinophilic infiltration can be induced concurrently and to conduct an experiment with conjoined inhalation of platelet activating factor (PAF). PAF, which has a chemotactic activity for eosinophils, was administered to passively sensitized animals in attempt to examine a role of eosinophils in LAR. A goodly number of animals developed LAR on additional PAF inhalation. These animals, when compared with those without LAR, showed a significantly larger proportion of eosinophils in BALF (p less than 0.05) with an upward tendency for the proportion of neutrophils. Histologically, there was noted a striking association between LAR and eosinophilic infiltration of the bronchial submucosa. These results suggest that anti-IgE antibody is deeply involved in the elicitation of LAR, stressing the importance of eosinophilic infiltration.     

Intermittent claudication associated with persistent sciatic artery: Report of two cases

Two elderly women complaining of intermittent claudication complicated with persistent sciatic artery are herein reported. A direct femoral arteriogram showed hypoplasty of the superficial femoral artery and an unnatural anatomical relationship between the distal superficial femoral artery and the proximal popliteal artery, thus suggesting the presence of persistent sciatic artery. The diagnosis of persistent sciatic artery was finally made based on the aortography findings including the iliac arterial system and computed tomography (CT) scan. Magnetic resonance imaging (MRI) was helpful to demonstrate the entire image of this anomaly in cases with non-thrombolized sciatic artery. These diagnostic methods were useful in designing the optimal surgical strategy. The first case with a gluteal pulsating mass underwent exclusion of the persistent sciatic artery including the aneurysm through a retroperitoneal approach with a combination of femorotibial bypass, while the second case with thrombosed persistent sciatic artery only underwent femoropopliteal bypass. To recognize such a rare lesion, awareness of the differential diagnosis is important, and to provide appropriate treatment, an accurate whole image including adequate angiography, a CT scan, and magnetic resonance imaging is necessary.     

Anti-Candida albicans activity of essential oils including Lemongrass (Cymbopogon citratus) oil and its component, citral]

The effects of 12 essential oils, popularly used as antifungal treatments in aromatherapy, on growth of Candida albicans were investigated. Mycelial growth of C. albicans, which is known to give the fungus the capacity to invade mucosal tissues, was inhibited in the medium containing 100 micro g/ml of the oils: lemongrass (Cymbopogon citratus), thyme (Thymus vulgaris), patchouli (Pogostemon cablin) and cedarwood (Cedrus atlantica). Not only lemongrass oil but also citral, a major component of lemongrass oil (80%), in the range of 25 and 200 micro g/ml inhibited the mycelial growth but allowed yeast-form growth. More than 200 micro g/ml of citral clearly inhibited both mycelial and yeast-form growth of C. albicans. These results provide experimental evidence suggesting the potential value of lemongrass oil for the treatment of oral or vaginal candidiasis.     

Effects of N-(2-ethylhexyl)-3-hydroxybutyramide hydrogen succinate on the metabolisms of monoamines in the rat brain

N-(2-Ethylhexyl)-3-hydroxybutyramide hydrogen succinate (M-2H) has been reported to increase REM sleep. The effects of M-2H on the metabolisms of monoamines which have been implicated in the regulation of the sleep-wakefulness cycle were studied in rats. M-2H (500 mg/kg p.o.) increased the levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in various regions of the rat brain. However, no appreciable changes occurred in levels of serotonin (5-HT), norepinephrine, dopamine, or 3,4-dihydroxyphenylacetic acid. The effect of M-2H (500 mg/kg p.o.) on 5-HT metabolism was investigated with intraventricularly-injected [14C]-5-HT. Although [14C]-5-HT level was not significantly changed, [14C]-5-HIAA level was above control level in four brain regions such as the hypothalamus, hippocampus, midbrain and pons-medulla at 3 h after the administration of M-2H. M-2H retarded the efflux of intraventricularly-injected [14C]-5-HIAA in all brain regions except the cortex. These results suggest that M-2H preferentially impaired the transport system for acid metabolites of monoamines, resulting in increase of monoamine metabolite levels in the brain.     

In vivo activity and metabolic fate of 2-(2,3,3-triiodoallyl)tetrazole (ME1401), a novel antifungal agent

2-(2,3,3-Triiodoallyl)tetrazole (ME1401), a novel antifungal agent, showed therapeutic effectiveness in topical treatment of experimental dermal infections with Trichophyton mentagrophytes and Candida albicans in guinea-pigs. Addition of diethyl sebacate to the ME1401 preparations increased its in vivo antifungal activity and its penetration into the skin. When the estimation of efficacy of treatment with active formulations was made on the basis of skin lesion and the rate of negative skin cultures in comparison with those for infected, untreated or placebo-treated controls, the in vivo activity of 0.5% ethanol tincture or gel of ME1401 was comparable to that of reference antimycotic drugs such as clotrimazole, haloprogin and others. Pharmacokinetic studies in the experimental animals demonstrated that ME1401 was unstable in vivo, being readily converted to an active metabolite 2-(3-iodopropargyl)tetrazole (CN144) first and then to 2-propargyltetrazole (CN151). CN144 showed potent in vitro and in vivo antifungal activities, while the in vitro activity of CN151 was negligible.     

A case of metastatic optic nerve head and retinal carcinoma with vitreous seeds

Metastasis directly to the optic nerve head without choroidal involvement is rare. We report a case of metastatic adenocarcinoma of the optic nerve head and retina with vitreous seeds which was observed in a 45-year-old Japanese male. The primary site of the lesion was clinically the upper lobe of the left lung. Tumor emboli were observed in the central retinal vein. Vitreous seeds appeared to have arisen from a necrotic area and papillary projections of the tumor.     

Anterior and posterior association cortex contributions to the somatosensory P300

A P300 (P3)-evoked response is generated in a variety of mammalian species upon detection of significant environmental events. The P3 component has been proposed to index a neural system involved in attention and memory capacity. We investigated the contribution of anterior and posterior association cortex to somatosensory P3 generation. Somatosensory event-related potentials (ERPs) were recorded in controls (n = 10) and patients with unilateral lesions in temporal-parietal junction (n = 8), lateral parietal cortex (n = 8), or dorsolateral frontal cortex (n = 10). Subjects pressed a button to mechanical taps of the fifth finger (targets; p = 0.12), randomly interposed in sequences of taps to the second (standards; p = 0.76) and the third or fourth finger (tactile novels; p = 0.06). Occasional shock stimuli were delivered to the wrist (shock novels; p = 0.06). The scalp-recorded P3 was differentially affected by anterior and posterior association cortex lesions. Subjects with temporal-parietal lesions showed markedly reduced P3s to all types of stimuli at all scalp locations. The reductions were largest at the parietal electrode site over the lesioned hemisphere. Parietal patients had normal P3s for all stimulus types except for contralateral shock novels, which generated reduced P3s. Frontal lesions had reductions of the novelty P3 over frontal sites with minimal changes in the target P3. The data support the existence of multiple intracranial P3 sources. The data further indicate that association cortex in the temporal-parietal junction is critical for generating the scalp-recorded target and novelty P3s, whereas dorsolateral frontal cortex contributes preferentially to novelty P3 generation. The N2 component was reduced by parietal and frontal lesions in patients who had intact target P3s, suggesting that different neural systems underlie N2 and P3 generation.