Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma.

BACKGROUND: Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness. OBJECTIVE: This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma. METHODS: Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case-control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors. RESULTS: All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene-environmental interaction between GSTP1-105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64-21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01-17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose-response relationship with outdoor air pollution in children with Ile-105 homozygotes. CONCLUSION: Our result suggests a gene-environmental interaction between GSTP1-105 genotypes and outdoor air pollution on childhood asthma.

Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation.

The mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine (10(-5), 3.2 x 10(-5), and 10(-4) M), the nonselective adenosine agonist 5'-N-ethylcarboxamido-adenosine (NECA) (10(-8)-10(-7) M), the specific A(2A) agonist 2-p-(2-carboxyethyl)phenyl-amino-5'-N-ethyl carboxamidoadenosine (CGS-21680) (10(-8)-10(-7) M), and the adenosine agonist with higher A(1)-receptor affinity, R-N(6)-phenylisopropyladenosine (R-PIA) (10(-7), 3.2 x 10(-7), and 10(-6) M) elicited a similar degree of incremental increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium (K(ATP)) channel blocker glibenclamide (3.2 x 10(-6) M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sulfophenyl)-theophylline (3 x 10(-5) M) or the selective A(2A) antagonist 4-(2-[7-amino-2-(2-furyl)[1,2, 4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol (ZM-241385, 10(-6) M), but not by the selective A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (5 x 10(-8) M). Adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, 10(-5)M) effectively suppressed the vasodilator response of adenosine and forskolin. These results suggest that adenosine-induced vasodilation in rat diaphragm microcirculation is mediated through the stimulation of A(2A) receptors, which are coupled to adenylate cyclase activation and opening of the K(ATP) channel.

Disseminated zygomycosis simulating cerebrovascular disease and pulmonary alveolar haemorrhage in a patient with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) may be complicated with serious cerebrovascular accidents and pulmonary alveolar haemorrhage. The authors report an autopsy-proven angioinvasive zygomycosis in a patient with SLE. The clinical features of systemic zygomycosis in this patient masqueraded as SLE-related stroke and pulmonary haemorrhage. The case demonstrates that the simultaneous occurrence of complications that clinically suggest pulmonary haemorrhage and multiple brain infarcts in SLE patients should include the rare disseminated zygomycosis in the differential diagnosis.

Time course of pharmacological modulation of peak eosinophilic airway inflammation after mite challenge in guinea pigs: a therapeutic approach.

BACKGROUND: It is well known that eosinophilic airway inflammation develops after allergen challenge in sensitized humans and animals. However, the detailed time course of suppression of early eosinophilic airway inflammation by pharmacological agents given just after challenge has not been discussed. Therefore, we aimed to evaluate the time course relationship of the suppression of peak eosinophilia by anti-cytokines and pharmacological agents given several hours after the aerosol challenge by a therapeutic approach. METHODS: We used crude mite extract as an allergen to create a sensitization and inhalation challenge, and performed bronchoalveolar lavages (BAL) after the inhalation challenge to observe the degree of eosinophilic airway inflammation in guinea pigs. Various anti-cytokines (anti-IL-3 and anti-IL-5) and pharmacological agents (dexamethasone, theophylline, and roxithromycin) were given within several hours after the acute aeorosol challenge to evaluate the suppressive effect on peak eosinophilia in BAL fluid, which occurred 24 h after the challenge. RESULTS: Our results show that anti-IL-5 and dexamethasone, given within 4 and 8 h after the inhalation challenge, respectively, inhibit the acute allergen-induced peak eosinophilia in BAL fluid. However, anti-IL-3, theophylline, and roxithromycin had no effect on peak eosinophilic airway inflammation after challenge. CONCLUSION: These observations suggest that several hours are needed to complete the process of cytokine-induced recruitment of eosinophils from the blood to the airways after acute allergen challenge. This may be the optimal time to administer anti-cytokines and dexamethasone to attenuate the subsequent eosinophilic airway inflammation after acute allergen-induced asthmatic attacks.

Effects of N(omega)-nitro-L-arginine (L-NOARG) on blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension.

The role of N(omega)-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, in the control of blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension was investigated by means of laser Doppler flowmetry (LDF). Fifty-six Sprague-Dawley rats were divided into seven groups. Ten minutes after one-stage hemorrhage to 40-60% of initial blood pressure, the rats received 15 min topical superfusion of saline (group 1, time control), 0.1 mM L-NOARG (group 2), 10 mM L-arginine (group 3), or vehicle (0.1% DMSO and 0.9 mN NaOH, group 4). For groups 5 and 6, L-NOARG or its vehicle was superfused for 15 min without hemorrhage. In group 7, the vasodilator responses to the endothelium-dependent vasorelaxant acetylcholine (ACH) and the endothelium-independent vasorelaxant sodium nitroprusside (SNP) were assessed at rest and after 25 min of hemorrhagic hypotension. The results showed no significant differences in blood flow, fundamental frequency, or relative amplitude of the rat diaphragm microcirculation before or after administration of the test agents among the first four groups during hemorrhagic hypotension or in groups 5 and 6 during sham operation without hypoperfusion. Hemorrhagic hypotension significantly decreased the vasodilator response to ACH (p = 0.003), but not to SNP. We conclude that NO did not play an important role in the regulation of blood flow or vasomotion in rat diaphragm microcirculation during acute hemorrhagic hypotension.

Suplatast tosilate inhibits late response and airway inflammation in sensitized guinea pigs.

The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs. The animals were given an oral dose of 30 or 100 mg/kg of suplatast or vehicle (distilled water) daily for 1 wk before antigen challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage and lung fixation. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils and lymphocytes in the airways. After 1 wk of treatment with the high dose of suplatast, the late asthmatic response and the recruitment of eosinophils and lymphocytes into the airways were significantly inhibited, but the early asthmatic response was not affected. In situ hybridization revealed that challenge-induced increases in IL-5 mRNA-positive cells in lung tissue were significantly inhibited after treatment. Thus, suplatast inhibited airway obstruction in the late phase by specifically inhibiting the inflammatory process after mast cell degranulation.

Predicting factors for outcome of tube thoracostomy in complicated parapneumonic effusion for empyema.

STUDY OBJECTIVES: To determine the predicting factors for outcome of tube thoracostomy in patients with complicated parapneumonic effusion (CPE) or empyema. DESIGN AND SETTINGS: Retrospective chart review over a 55-month period at a tertiary referred medical center. PATIENTS AND MEASUREMENTS: The medical charts of patients with empyema or CPE were reviewed. Data including age, gender, clinical symptoms, important underlying diseases, leukocyte count, duration of preadmission symptoms, interval from first procedure to second procedure, the time from first procedure to discharge (recovery time), the amount of effusion drained, administration of intrapleural streptokinase, chest tube size and position, loculation of pleural effusion, and characteristics and culture results of pleural effusion were recorded and compared between groups of patients with successful and failed outcome of tube thoracostomy drainage. RESULTS: One hundred twenty-one patients were selected for study. One hundred of these patients had received tube thoracostomy drainage with 53 successful outcomes and 47 failed outcomes of chest tube drainage. Nineteen patients received decortication directly, and the other two received antibiotics alone. Univariate analysis showed that pleural effusion leukocyte count, effusion amount, and loculation of pleural effusion were significantly related to the outcome of chest tube drainage. Multiple logistic regression analysis demonstrated that loculation and pleural effusion leukocyte count < or = 6,400/uL were the only independent predicting factors related to failure of tube thoracostomy drainage. CONCLUSIONS: Loculation and pleural effusion leukocyte count < or = 6,400/microL were independent predicting factors of poor outcome of tube thoracostomy drainage. These results suggest that if the initial attempt at chest tube drainage fails, early surgical intervention should be considered in good surgical candidates with loculated empyema or pleural effusion with leukocyte count < or = 6,400/microL.

Varicella pneumonia complicated by acute respiratory distress syndrome in an adult.

Primary varicella infection is uncommon in adults, but carries a higher rate of morbidity and mortality than in children. Pneumonia is the most common complication of primary varicella infection in adults. However, varicella pneumonia complicated with acute respiratory distress syndrome (ARDS) is very rare. We report a case of ARDS secondary to varicella pneumonia in a 26-year-old man with primary varicella. The patient was otherwise healthy and had no evidence of human immunodeficiency virus infection. The initial chest radiograph showed bilateral reticulonodular infiltrates, which quickly evolved to diffuse alveolar consolidations. Arterial blood gas analysis revealed a ratio of arterial partial pressure to fraction of inspired oxygen of 87. Abnormal liver function and thrombocytopenia were also noted. Treatment consisted of mechanical ventilatory support and intravenous administration of acyclovir. His pulmonary condition gradually improved and he was successfully weaned from the ventilator 1 week later. He was discharged on the 15th hospital day with a favorable outcome. His pulmonary function improved progressively, with normal spirometry and lung volumes, but persistent mild impairment of diffusing capacity, 6 months after discharge.

Respiratory mechanics before and after hemodialysis in mechanically ventilated patients.

Hemodialysis, which leads to negative fluid balance, is often required in mechanically ventilated patients with renal failure. We conducted a prospective study on the influence of hemodialysis on the respiratory mechanics in 14 mechanically ventilated patients (10 men, 4 women, mean age 70.1 +/- 8.1 yr) with various causes of renal failure requiring hemodialysis in an intensive care unit. Respiratory mechanics were measured before and after hemodialysis using the interrupter technique under constant flow and constant volume. The values of several parameters of respiratory mechanics were significantly lower after hemodialysis: peak airway pressure (26.97 +/- 4.62 vs 23.45 +/- 4.13 cmH2O), airway pressure at zero flow (23.81 +/- 4.18 vs 21.50 +/- 3.79 cmH2O), airway plateau pressure (18.56 +/- 3.70 vs 16.48 +/- 3.07 cmH2O), and intrinsic positive end-expiratory pressure (4.03 +/- 2.90 vs 2.65 +/- 1.84 cmH2O). Minimal respiratory resistance and maximal respiratory resistance were significantly decreased after hemodialysis (4.38 +/- 1.26 vs 2.99 +/- 1.00 cmH2O/L/s and 9.93 +/- 2.50 vs 8.39 +/- 2.43 cmH2O/L/s, respectively), but effective additional respiratory resistance and static respiratory compliance were not. Significant correlations were found between body weight reduction by hemodialysis and changes in minimal respiratory resistance (r = 0.758, p < 0.01), maximal respiratory resistance (r = 0.544, p < 0.05), and static respiratory compliance (r = 0.703, p < 0.01). We conclude that hemodialysis significantly alters the respiratory mechanics in mechanically ventilated renal failure patients and that the alteration may be related to the negative fluid balance caused by hemodialysis.

Dose-response relationship and irreversible obstructive ventilatory defect in patients with consumption of Sauropus androgynus.

STUDY OBJECTIVES: To determine the dose-response aspect of pulmonary function impairment in patients with consumption of Sauropus androgynus for weight reduction. METHODS: A questionnaire and pulmonary function tests were performed in 194 patients with a history of consumption of S androgynus with or without chest symptoms. Patients with obstructive ventilatory defect received follow-up spirometry 22 to 24 months after beginning consumption of the vegetable. RESULTS: Data from 178 patients were analyzed. Patients generally consumed 150 g of S androgynus daily as raw juice (60.7%), sauteed (16.9%), mixed preparation (20.8%), or boiled (1.7%) for various periods of time. We divided patients into five groups according to the total dose consumed (group A, 0 to 1,799 g; group B, 1,800 to 3,599 g; group C, 3,600 to 5,399 g; group D, 5,400 to 7,199 g; and group E, > or =7,200 g). The frequency of obstructive ventilatory defect was higher in the high-dose group than in the low-dose group (A, 4/43=9.3%; B, 13/64=20.3%; C, 14/32=43.8%; D, 5/12=41.7%; and E, 13/27=48.1%; p < 0.01). In total, 49 patients (27.5%) had moderate to severe obstructive ventilatory defects without bronchodilator response. The FEV1 and FEV1 percent predicted in these 49 patients were 0.96+/-0.38 L (mean+/-SD) and 41.8+/-16.9%, respectively. Sixty-five percent of these 49 patients began to suffer from dyspnea in the third, fourth, or fifth month after taking the vegetable and no patient began to develop dyspnea later than 7 months after beginning consumption of the vegetable. Using stepwise multiple regression, we found that the FEV1 percent predicted was negatively associated with the total dose ingested (r=0.24, p < 0.01). Follow-up spirometry showed that the obstructive ventilatory defect was irreversible in all patients. CONCLUSIONS: Consumption of S androgynus can result in moderate to severe obstructive ventilatory defect within 7 months, and the disorder was irreversible in the observation period for 22 months.

Vasomotion in rat diaphragm microcirculation at rest and during stepwise arterial pressure reduction.

The effect of haemorrhagic hypotension on the incidence, frequency and relative amplitude of vasomotion in rat diaphragm microcirculation was assessed by laser Doppler flowmetry (LDF). Graded bleeding to four hypotension levels (80, 60, 40 and 30% of the control state) were performed in 24 Sprague-Dawley rats. The incidence of vasomotion was 83% in the control state, 96% at the 80% level, 100% at the 60% level, 96% at the 40% level, and 46% at the 30% level. The median fundamental frequency of vasomotion determined manually during the control state and at the hypotension levels (in descending order) was 4.11 (range, 3.29-5.58) cycles min-1 (cpm), 4.48 (3.21-5.92) cpm, 4.20 (3.5-5.56) cpm, 4.01 (3.33-5.36) cpm, 3.71 (3.25-4.49) cpm (P < 0.01 from the fundamental frequency at 80 and 60% hypotension levels). The median relative amplitudes determined manually during the control state and descending hypotension levels were 44.5% (range, 24.9-135.9%), 69.4% (26.6-147.2%), 84.0% (40.3-177.1%) (P < 0.01 from resting and last stage of bleeding), 90.40% (26.2-189.6%) (P < 0.01 from resting and last stage of bleeding), 69.2% (35.6-93.2%). We concluded first that during the resting condition, vasomotion was frequently present in diaphragm microcirculation, which is distinct from other vascular beds of skeletal muscles. Second, the relative amplitude of vasomotion during haemorrhagic hypotension plotted against decreasing blood pressure exhibited a reverse U-shaped curve with a maximum at 40-60% of the control blood pressure, while the frequency of vasomotion remained relatively constant until the last stage of haemorrhage and centred around 3-5 cpm.

Fatal acute pulmonary oedema after inhalation of fumes from polytetrafluoroethylene (PTFE).

The cases of three patients with acute pulmonary oedema caused by inhalation of fumes from heated polytetrafluoroethylene (PTFE) in a plastic factory are described. One patient died from profound hypoxaemia and shock shortly after admission, and the other two patients survived after medical treatment. This is the first report of fatal pulmonary oedema in a worker exposed to PTFE heated in a plastic extruding operation. From this observation, it appears that inhalation exposure to pyrolytic products from polytetrafluoroethylene can cause fatal respiratory complications. Special precautions are warranted in this kind of operation to prevent workers from being exposed to these substances.

Mite-induced allergic airway inflammation in guinea pigs.

BACKGROUND: Mites are the most common aeroallergen in human allergic asthma. However, no animal model of mite-induced allergic airway inflammation has been reported before. In this study, an animal model of mite-induced allergic airway inflammation in guinea pigs was developed. METHODS: Firstly, we found that two intraperitoneal injections of 100 micrograms crude mite extract (CME), but not multiple aerosol inhalations of 10 mg/ml CME, can cause sensitization in guinea pigs. The sensitization to mites was confirmed by the measurement of serum antimite antibody titer and the detection of anaphylactic bronchoconstriction after intravenous injection of CME solution. Then, single or multiple aerosol challenges with different concentrations (8, 4 or 1 mg/ml) of CME in these sensitized animals were performed. The total white cell and differential counts in the bronchoalveolar lavage (BAL) fluids were studied at different time intervals after challenge in different animals, and tracheal pathology was performed to detect the allergic airway inflammation. For comparison with the study in animals treated with CME, a BAL study in animals treated with ovalbumin was also performed. RESULTS: The inhalation challenge of CME aerosol in sensitized animals caused prolonged eosinophilia in BAL fluid which persisted for at least 7 days after single challenge. Neither inhalation challenge at higher concentrations of CME aerosol nor repeated inhalation challenges increased the degree of eosinophilia in BAL fluid compared to a single challenge. Using the same procedures, we also found that the mite model caused more eosinophilia in BAL fluid than did ovalbumin. CONCLUSION: This is the first report of an animal model of mite-induced allergic airway inflammation in guinea pigs which can provide us with a useful model to study airway inflammation of mite-induced asthma in humans.

Role of KATP channels on modulating diaphragmatic microvascular flow during hemorrhagic hypotension.

The effects of glibenclamide (GLB), a specific blocker of ATP-sensitive potassium (KATP) channels, and tetraethylammonium (TEA) on modulating the regulation of diaphragmatic microcirculation were assessed in anesthetized mechanically ventilated rats. With bicarbonate-buffered Ringer solution continuously suffusing the left hemidiaphragm, microcirculatory blood flow was recorded by laser-Doppler flowmetry (QLDF). Hemorrhagic hypotension (HH) was induced via bleeding into a pressure reservoir. Five sets of experiments were performed. In set 1 (n = 6), the vasodilator effect of diazoxide (3 x 10(-4) M) was abolished after a 30-min suffusion with GLB, whereas the vasodilator effect of sodium nitroprusside (3 x 10(-6) M) remained the same. In set 2 (vehicle + HH; n = 23), a stepwise reduction in systemic arterial blood pressure (ABP) induced two distinct patterns of microvascular responses. Regulation of QLDF could be observed in pattern A animals in a range of ABP from 113 to 52 mmHg, whereas QLDF in pattern B animals rose progressively with declining ABP. In set 3 (GLB + HH; n = 17), baseline values of QLDF were not significantly affected after a 30-min suffusion of GLB (10(-5) M). During HH, two microvascular patterns similar to those in set 2 were observed. GLB significantly potentiated the reduction in QLDF in pattern A animals. In contrast, GLB had no effect on QLDF in pattern B animals. In set 4 (TEA + HH; n = 17), similar microvascular responses, compared with the vehicle group, were observed during HH after a 30-min suffusion of TEA (2 x 10(-3) M). In set 5 (n = 5), baseline values of QLDF were not significantly altered during sham hypotension. We conclude that 1) KATP channels are functional but not active in the resting diaphragmatic microcirculation and 2) KATP channels can modulate regulation of the microcirculation in the resting diaphragm during HH.

Dermatophagoides-farinae-induced pulmonary eosinophilic inflammation in mice.

Dermatophagoides farinae (Der f) is one of the most common species of dust mites that induce asthma and allergic rhinitis. We have reported that Der f challenge on sensitized mice elicited a distinct type of hypersensitivity, called early-type hypersensitivity (ETH), in subcutaneous tissues and in airways. The airway ETH was accompanied by a series of inflammatory and immunological events including cytokine production, adhesion molecule expression, inflammatory cell infiltration, eosinophilia, and airway hyperreactivity. In the present study, we further defined the course of the Der-f-induced eosinophilia and examined the local cytokine gene expression and the roles of cytokines, mast-cell-derived vasoactive amines, and corticosteroids in the development of pulmonary eosinophilia. BALB/c mice were sensitized with crude extract of Der f in complete Freund's adjuvant and were intranasally challenged with Der f on day 14 after sensitization. The number of blood eosinophils, total and differential leukocyte counts in bronchoalveolar lavage (BAL) fluids, and the expression of cytokine genes in BAL cells were assessed at various time points after challenge for up to 12 days. The total number of leukocytes in the BAL fluids was increased 6 h after challenge (AC) and peaked at 72 h. The early cellular response in the BAL fluids was dominated by neutrophils which were subsequently replaced by a marked infiltration of eosinophils. The number of eosinophils in BAL fluids increased at 24 h and peaked at 72 h, making up 43% of all cells recovered by BAL. BAL eosinophils declined gradually to normal background levels around day 12. Concurrently, there was a significant reduction in the number of eosinophils in blood 24 h AC. The number of blood eosinophils increased thereafter, reached a peak at 72 h, and remained above baseline level for up to 10 days. Saline challenge did not induce eosinophilia in BAL fluids and blood of sensitized mice. Histopathological examination revealed a mixed granulocytic, monocytic pulmonary inflammation with a large number of eosinophils accumulating within the submucosa of the airways and blood vessels of sensitized mice after challenge. Der f challenge induced a sequential expression pattern of eight cytokine genes in BAL cells. The mRNA of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha strongly expressed throughout the course of the experiment. The IL-6 mRNA expression peaked at 0.5-72 h, IL-10 at 1-6 and 48-72 h, IL-4 at 6-72 h, IL-2 at 6-96 h, IL-5 at 24-72 h, and interferon-gamma at 24-96 h. Intraperitoneal injection of sensitized mice with monoclonal antibody (mAb) to murine IL-5 (TRFK5, 300 micrograms/mouse) 1 h before challenge caused 62% suppression of eosinophils in the BAL fluids. The concomitant accumulation of neutrophils and mononuclear cells, however, was not affected by this treatment. On the other hand, intranasal administration of mAb to murine TNF-alpha (MP6-XT3, 20 micrograms/ mouse), but not IL-5, 1 h before challenge and 24 h AC significantly reduced the numbers of eosinophils, neutrophils, and lymphocytes in the BAL fluids. The intraperitoneal injection of dexamethasone (50 mg/kg) for a total of four times resulted in total inhibition of the Der-f-induced cellular responses, whereas vasoactive amine antagonists (diphenhydramine, ketanserin and cyprohepatidine) did not show any effect.

Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation.

1. The effects of N omega-nitro-L-arginine (L-NOARG) and N omega-nitro-L-arginine methyl ester (L-NAME) on diaphragmatic microcirculation in male Sprague-Dawley rats were assessed under basal conditions and after acetylcholine (ACh) stimulation. In addition, L-arginine (L-arg) was used with the aim of preventing L-NOARG and L-NAME from inhibiting ACh-induced vasodilatation, in order to explore the possibility that L-NOARG is not only a nitric oxide (NO) synthase inhibitor but also a muscarinic receptor antagonist. 2. Male Sprague-Dawley rats were anaesthetized with urethane and mechanically ventilated. The left hemi-diaphragm of each rat was prepared and microvascular blood flow was recorded during continuous superfusion with bicarbonate-buffered prewarmed Ringer solution by using laser-Doppler flowmetry. The drugs were topically applied to the surface of the hemi-diaphragm. 3. Baseline microvascular blood flow was unaffected after 15 min superfusion with any one of the following agents: L-NOARG (0.1 mM). L-NAME (0.1 mM), L-arg (10 mM). 4. ACh (0.03 mM, 0.1 mM and 0.3 mM) elicited a significant increase of microvascular blood flow (171 +/- 16%, 214 +/- 55%, and 323 +/- 68% of baseline values, respectively), via interaction with the muscarinic receptor, for the vasodilator response was severely inhibited by 15 min superfusion with atropine (0.3 mM). 5. Following 15 min superfusion with either of the L-arg analogues (0.1 mM), the ACh-induced vasodilator response was significantly inhibited. Pretreatment with L-arg (10 mM) for 5 min, followed by co-administration of L-arg (10 mM) and L-NOARG (0.1 mM) for another 15 min significantly prevented the inhibitory effect of L-NOARG or ACh-induced vasodilatation. However, a similar pretreatment schedule with L-arg failed to prevent L-NAME from exerting its inhibitory effect. 6. Neither of the L-arg analogues potentiated sodium nitroprusside (10 microM and 30 microM)-induced vasodilatation. However, adenosine (0.1 mM)-induced vasodilatation was slightly but significantly attenuated by either L-NOARG (0.1 mM) or L-NAME (0.1 mM), an effect which was prevented by L-arg (10 mM). 7. In conclusion, an increase in endothelium-dependent blood flow stimulated by ACh may occur in diaphragmatic microcirculation of anaesthetized rats independently of low baseline NO activity. The results also suggest that L-NAME has muscarinic receptor antagonist action in addition to its ability to inhibit NO synthase. Thus, we suggest that L-NAME should not be used as a specific NO synthase inhibitor in the rat diaphragm in situations in which there is potential for muscarinic receptors to be stimulated.

Flavobacterium indologenes bacteremia: clinical and microbiological characteristics.

To our knowledge, Flavobacterium indologenes has never been reported as a cause of bacteremia in humans. F. indologenes bacteremia was diagnosed in 12 patients at a tertiary referral center in southern Taiwan between 1 January 1992 and 31 December 1994. Six of these patients had ventilator-associated pneumonia, two had primary bacteremia, and one patient each had pyonephrosis, peritonitis, biliary tract infection, and surgical wound infection. Five patients (42%) had malignancies, and three (25%) had multiple burns. Polymicrobial bacteremia was diagnosed in eight patients (67%). Two (17%) of the patients in this study died; both had polymicrobial bacteremia. Antimicrobial susceptibility testing of the blood isolates from the 12 patients showed that > 90% of the isolates were susceptible to piperacillin, cefoperazone, ceftazidime, and minocycline. The chromatograms of esterified fatty acids for the isolates were identical. F. indologenes should be considered an etiologic agent of bloodstream infection, especially in hospitalized patients with severe underlying diseases.

Increased IL-5 and IL-10 transcription in bronchial cells after Sauropus androgynus ingestion.

An outbreak of rapidly progressive obstructive lung disease in Taiwan was noted in some patients regularly ingesting the vegetable Sauropus androgynus because of its perceived weight reducing properties. Bronchoalveolar lavage (BAL) prior to administration of medication was performed in two women who had regularly ingested this vegetable and had developed obstructive ventilatory defects. Both patients showed a significant increase in neutrophils and, to a lesser extent, of eosinophils in the lavage fluid as compared to two unrelated controls. Interleukin (IL)-1 beta, IL-2, IL-5, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha in cells recovered from BAL fluid were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Augmented expression of the IL-10 gene was detected in only two patients who had regularly ingested S. androgynus. Our results suggest that altered cytokine expression and infiltration of eosinophils and neutrophils may be involved in the pathology of obstructive lung disease caused by regular ingestion of S. androgynus.

Isoniazid-induced fever.

A rare case of isoniazid (INH)-induced fever is described. A 27-year-old woman diagnosed with miliary tuberculosis (TB) began to receive combined anti-TB treatment including INH, ethambutol, rifampicin and pyrazinamide on the second day of hospitalization. A spiked fever developed in the afternoon of the seventh hospital day. There was no evidence of a hypersensitivity reaction. All examinations including liver function tests, routine biochemistry tests, serum titer of antinuclear antibody and rheumatoid factor were within normal limits. The blood leukocyte count was also within normal range and no evidence of infection at other sites was found. Following the discontinuance of anti-TB agents, the patient's body temperature gradually returned to normal. When the patient was rechallenged with INH, the high fever recurred. The fever subsided again after the discontinuance of INH, and her recovery followed a smooth course thereafter, on combination therapy with rifampicin, ethambutol and pyrazinamide. This experience demonstrates the potential of INH to cause an isolated fever without other manifestations, which may be misdiagnosed as an infectious process. Though it is very rare, INH-induced fever must be considered when fever develops during anti-TB treatment.

Invasive Streptococcus pneumoniae infection associated with rapidly fatal outcome in Taiwan.

We observed 42 cases of invasive Streptococcus pneumoniae infections from 1991 through 1993 in southern Taiwan. The antimicrobial susceptibilities and distribution of serotypes of the 42 isolates from these invasive infections were determined. Serotypes 14, 3, 6, 23, 15 and 4 were most commonly identified. Serotypes 14 and 6 most frequently caused infections in pediatric patients, while serotypes 3, 14 and 23 were commonly encountered in adults. Overall, 85.7% of the isolates were included in the serotypes represented in the 23-valent pneumococcal vaccine. Three isolates were intermediately resistant to penicillin and none were fully resistant. Resistance rates were: erythromycin, 61.9%; clindamycin, 47.6%; chloramphenicol, 19%; and tetracycline, 73.8%. Resistance to three or more classes of antibiotics was found in 33.3% of the isolates, in which the majority were serotypes 14 and 6 and nontypeable isolates. Bacteremic pneumonia and primary bacteremia accounted for 64.3% of the infections. Mortality was 42.6%. Factors associated with higher mortality included age of > 16 years, the presence of underlying diseases, development of one or more septic complications, bacteremic pneumonia and the presence of serotype 3 isolates. Rapidly fatal outcome (the illness developed less than 48 hours prior to admission and the death occurred within 48 hours of hospitalization) occurred in 12 (66.7%) of the 18 patients who died. All these patients received adequate antibiotic treatment and aggressive intensive care, indicating the fulminant nature of this infection. Mucoid serotype 3 isolates caused rapidly fatal outcomes. Given the severity of these infections despite adequate antibiotic therapy and the vulnerability of patients with altered immune responses, there is a dire need for introduction of new therapeutic options and preventive measures to prevent mortality due to invasive S. pneumoniae infections.