An imbalance in plasma prostanoids in patients with Raynaud's phenomenon and pulmonary vasospasm.

Raynaud's phenomenon has been suggested as a predisposing factor for pulmonary vasospasm which may lead to pulmonary hypertension, but the occurrence of cold stimulus-induced pulmonary vasospasm has been inconsistent. Such inconsistent pulmonary vascular responses may be caused by differences in the production of endogenous vasodilators and vasoconstrictors among patients. Fourteen patients with Raynaud's phenomenon associated with mixed connective tissue disease (n=10) or systemic sclerosis (n=4) participated in the study. Right heart catheterization was performed before and after a cold pressor test, immersing a hand in cold water (15 degrees C) for 5 min. Plasma levels of 6-keto prostaglandin (PG)F1alpha, thromboxane (TX)B2 and endothelin (ET)-1 in the mixed venous blood were measured. Mean pulmonary artery pressure increased after the cold pressor test in five of 14 patients, and the patients were divided into those with pulmonary vasospasm (responders) and those without vasospasm (nonresponders). After the cold pressor test, levels of 6-keto PGF1alpha increased significantly in nonresponders (p<0.01) and decreased significantly in responders (p<0.05). The ratios of 6-keto PGF1alpha to TXB2 significantly increased in nonresponders (p<0.01) but not in responders and the difference between responders and nonresponders after the cold pressor test was also statistically significant (p<0.05). No significant change in plasma ET-1 levels occurred in either responders or nonresponders. The results suggest that an impaired production of prostaglandin I2 and an imbalance between prostaglandin I2 and thromboxane A2 are associated with the occurrence of pulmonary vasospasm induced by Raynaud's phenomenon.

[Clinical evaluation of urinary leukotriene E4 levels in asymptomatic bronchial asthma].

To evaluate the significance of peptide leukotrienes (LTC4, D4, E4) in asymptomatic asthmatic patients, we measured urinary LTE4 levels which is thought to reflect in vivo production of peptide LTs. Urinary LTE4, was extracted using C18 solid phase column and measured by radioimmunoassay. There was no significant difference in urinary LTE4 levels among asthmatics with different severity or between atopic and non-atopic asthmatics. Urinary LTE4 levels were significantly elevated in asthmatics compared with normal controls (p < 0.05). When compared with normal controls, urinary LTE4 levels were significantly elevated in moderate to severe asthma (p < 0.05), and non-atopic asthmatics (p < 0.001). Urinary LTE4 levels were significantly elevated in aspirin-sensitive asthmatics compared with aspirin-tolerant asthmatics (p < 0.05). There was no significant difference in urinary LTE4 levels among aspirin-sensitive asthmatics with different severity. These results suggest that increased production of peptide LTs is a characteristic in aspirin-sensitive asthma, and that the severity and type of asthma and the presence of aspirin-sensitive asthma should be taken into consideration in the analysis of urinary LTE4 levels.

Effect of rush immunotherapy in house-dust-mite (HDM)-sensitive adult bronchial asthma: changes in in vivo and in vitro responses to HDM.

An open study was conducted to evaluate the changes in in vivo and in vitro responses to house-dust-mite (HDM) after rush immunotherapy (RI). A 7-day RI protocol using an extract containing HDM allergen was administered to 12 subjects with HDM-sensitive asthma, and the effects on bronchial responsiveness and serum antibody levels were evaluated up to 16 or 20 weeks after RI. The levels of HDM-specific IgG, IgG1 and IgG4 antibodies were significantly elevated from 4 or 8 weeks after RI. Provocative doses causing a 20% fall in FEV1 (PD20) by allergen inhalation were elevated in all subjects at 16 to 20 weeks after RI. There was a high correlation between the increase in log-PD20 and the increase in the ratio of HDM-specific IgG4 to IgG1 (r = 0.68, p < 0.05). The results suggest that RI elicits the improvement of allergen-specific bronchial responsiveness and the increase in serum antibody levels within a relatively short period.

[Improvement of intractable nocturnal asthma treated by therapeutic awakening].

A 33-year-old female was admitted to our hospital because of intractable asthma which had not been improved by intensive treatment at another hospital. Her asthmatic attacks were improved within a week by treatments including systemic corticosteroids and mechanical ventilation. However, in a few weeks nocturnal asthma recurred frequently, and it was resistant to various bronchodilators and steroids. Therapeutic awakening, that is, awakening the patient quietly at 3 a.m. with inhalation of 2.5 mg salbutamol was started. Her symptoms and physical findings rapidly improved thereafter. It was concluded that therapeutic awakening may be effective for the treatment of refractory morning dipping of asthma.

[A case of allergic bronchopulmonary candidiasis treated with amphotericin B inhalation].

A 77-year-old man underwent emergency admission for nocturnal asthmatic attack. Although his asthmatic attack improved within a few days with treatment including systemic corticosteroid, bilateral recurrent infiltrative shadows developed in his chest roentgenogram in association with a further exacerbation of dyspnea. Various antibiotic agents were given; however, the pulmonary infiltration did not improve. He was transferred to our department with the diagnosis of intractable pneumonia. C. albicans was detected in the sputum, and both IgE antibody and precipitating antibody specific for C. albicans were positive. Immediate cutaneous reactivity to C. albicans was positive even with a million-fold dilution of antigen extract C. albicans was also detected in bronchoalveolar lavage fluid. A diagnosis of allergic bronchopulmonary candidiasis was made. Chest roentgenographic findings as well as clinical symptoms improved with inhalation of 50 mg of amphotericin B.

[Bronchial lavage in the treatment of status asthmaticus].

Bronchial lavage was performed in 10 cases with status asthmaticus who were mechanically ventilated. The mean value of PaCO2 was 64.4 +/- 17.4 Torr before bronchial lavage, and it significantly decreased to 51.9 +/- 11.0 Torr after lavage. In 7 out the 10 cases, bronchial lavage was judged to be effective from the clinical point of view. In 5 cases with values of PaCO2 of over 55 Torr before lavage, massive mucus plugs were recovered. Bronchial lavage was judged to be effective in all of them, whereas three out of the another five cases whose values of PaCO2 were less than 55 Torr showed exacerbation of hypercapnia, and the state of asthma worsened and/or continued for a longer period. The ratio of PaO2/FiO2 did not improve even in effective cases. These results indicated that bronchial lavage is a useful tool to improve the hypercapnic state in patient with status asthmaticus being mechanically ventilated, if the value of PaCO2 is over 55 Torr.

[The influence of repirinast, an anti-allergic drug, on theophylline pharmacokinetics in patients with bronchial asthma].

In order to clarify whether repirinast, an inhibitor of chemical mediator release, could influence the pharmacokinetics of theophylline, a loading test using intravenous injection of aminophylline was performed in 10 subjects with bronchial asthma before and after treatment with 300 mg/day of repirinast. There was no significant difference in theophylline half-life before treatment (7.25 +/- 2.43 hr) and after treatment (7.82 +/- 3.35 hr). There was no significant difference in theophylline clearance before treatment (0.047 +/- 0.018 L/kg/hr) and after treatment (0.047 +/- 0.020 L/kg/hr). These results demonstrated that repirinast does not modify theophylline pharmacokinetics significantly.

[A cured case of adult respiratory distress syndrome caused by septicemia of Staphylococcus aureus].

A 33-year-old woman was admitted as an emergency case because of shock condition after delivery. Physical examination revealed fever, cyanosis and coarse crackles throughout the entire chest. Laboratory data showed leukocytosis and increase of CRP value. Adult respiratory distress syndrome (ARDS) was diagnosed based on progressive severe hypoxemia and bilateral diffuse alveolar shadows on chest X-ray film. The cause of ARDS was considered to be septicemia as staphylococcus aureus was cultured from lochia. The patient was intubated, then artificially ventilated employing PEEP. Chemotherapy using three different kinds of antibiotics was started, combined with the administration of corticosteroid and a protease inhibitor, Urinastatin. The patient finally recovered completely.

[Combination chemotherapy with bronchial arterial infusion (BAI) and systemic chemotherapy in advanced non-small cell lung cancer].

Five patients of advanced non-small cell lung cancer with atelectasis and/or poor performance status were treated with combination MVP therapy consisting of bronchial arterial infusion (BAI) using cisplatin (50 mg) and simultaneous systemic MVP therapy. The tumor size reduced more than 50% in three patients, and less than 25% in one patient. In another patient the tumor size was not measurable. Four of five patients showed disappearance of atelectasis, and three of four patients showed improvement of performance status. Average time taken was 13 and 17 days, respectively. We expect that combination MVP therapy has beneficial effects not only for relieving local symptoms and improving performance status within shorter period, but also achieving a better prognosis.