Cyclosporine, an immunosuppressant, attenuates phorbol-induced lung injury in rats.

OBJECTIVE: White cell activation in the lung plays a critical role to induce lung injury and lymphocytes in the thoracic duct system may also participate. We evaluated the effect of cyclosporine on phorbol myristate acetate (PMA)-induced lung injury. MATERIALS AND METHODS: We used an in situ isolated, blood perfused rat lung model to measure pulmonary arterial pressure (PAP) and lung weight gain (LWG; g) for 50 minutes after a bolus injection of PMA (0.05 microg/mL). Oxygen radical release was estimated by an LKB 1251 luminometer and by nitric oxide (NO) release as measured by an ENO-20 NO analyzer. RESULTS: In the group exposed to PMA alone, the mean PAP increased from 16.53 +/- 1.28 to 43.33 +/- 3.40 mm Hg (P < .001), and lung weight increased by 4.35 +/- 0.67 g during the 50-minute perfusion after PMA challenge (P < .001). In vitro measurement showed that PMA induced a significant increase in oxygen radical release (P < .001). PMA attenuated NO release (P < .001) into the perfusion system. Pretreatment with cyclosporine (3 mg/kg) for 3 days prevented the increases in both PAP (P < .01) and LWG (P < .001). NO release was maintained in cyclosporine-pretreated rats. Cyclosporine also showed dose-dependent attenuation of oxygen radical release by PMA-activated white blood cells. CONCLUSION: The mechanisms responsible for the protective effect of cyclosporine on the lung injury induced by phorbol may be related to an attenuation of oxygen radical production with maintenance of NO release.

Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion.

Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung. I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-alpha and interleukin-1beta in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue. Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg.kg(-1) body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.

Severe acute respiratory syndrome in Taiwan: analysis of epidemiological characteristics in 29 cases.

OBJECTIVES: To describe the clinical characteristics and outcomes of patients with severe acute respiratory syndrome (SARS). METHODS: Between March 28 and June 30 '2003, 29 patients with probable SARS seen at Shin Kong Wu Ho-Su Memorial Hospital, Taipei, were analysed. RESULTS: Presenting symptoms included fever (100%), cough (69.0%), chills or rigor (62.1%), and shortness of breath (41.4%). Mean days to defervescence were 6.8+/-2.9 days, but fever recurred in 15 patients (51.7%) at 10.9+/-3.4 days. Common laboratory features included lymphopenia (72.4%), thrombocytopenia (34.5%) and elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) (93.1, 62.1, 44.8%, respectively). All patients except one had initial abnormal chest radiographs and 20 (69.0%) had radiological worsening at 7.5+/-2.6 days. Nine patients (31.0%) subsequently required mechanical ventilation with four deaths (13.8%). Most patients with clinical deterioration responded to pulse corticosteroid therapy (14 out of 17) but six complicated with nosocomial infections. The risk factors associated with severe disease were presence of diarrhoea, high peak LDH and CRP, high AST and creatine kinase on admission and high peak values. CONCLUSIONS: Prudent corticosteroid use, vigilant microbiological surveillance and appropriate antibiotics coverage are the key to successful treatment.

Aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im detected together in strains of both Escherichia coli and Enterococcus faecium.

Escherichia coli SCH92111602 expresses an aminoglycoside resistance profile similar to that conferred by the aac(6')-Ie-aph(2")-Ia gene found in gram-positive cocci and was found to contain the aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im (only 44 nucleotides apart). aph(2")-Ib had been reported previously in Enterococcus faecium SF11770. aac(6')-Im had not been detected previously in enterococci and was found to be present also 44 nucleotides downstream from aph(2")-Ib in E. faecium SF11770. aph(2")-Ib and aac(6')-Im are separate open reading frames, each with its own putative ribosome binding site, whereas aac(6')-Ie-aph(2")-Ia appears to be a fusion of two genes with just one start and one stop codon. The deduced AAC(6')-Im protein exhibits 56% identity and 80% similarity to the AAC(6')-Ie domain of the bifunctional enzyme AAC(6')-APH(2"). Our results document the existence of a member of the aph(2") family of genes in gram-negative bacteria and provide evidence suggesting the horizontal transfer of aph(2")-Ib and aac(6')-Im as a unit between gram-positive and gram-negative bacteria.

The lung is the major site that produces nitric oxide to induce acute pulmonary oedema in endotoxin shock.

1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as Nomega-nitro-L-arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted.

Detection of the high-level aminoglycoside resistance gene aph(2")-Ib in Enterococcus faecium.

A new high-level gentamicin resistance gene, designated aph(2")-Ib, was cloned from Enterococcus faecium SF11770. The deduced amino acid sequence of the 897-bp open reading frame of aph(2")-Ib shares homology with the aminoglycoside-modifying enzymes AAC(6')-APH(2"), APH(2")-Ic, and APH(2")-Id. The observed phosphotransferase activity is designated APH(2")-Ib.

Respiratory management after self-extubation.

BACKGROUND AND PURPOSE: Self-extubation is a potentially life-threatening event, but may also provide an opportunity to wean patients who should have been extubated earlier. The purpose of this study was to determine the risk factors for re-intubation after self-extubation. METHODS: The medical charts of 69 self-extubated patients treated in Shin Kong Hospital, Taipei, from September 1996 through August 1998 were reviewed. Demographic data, ventilator settings before self-extubation, arterial blood gas values, and the type of respiratory management used after self-extubation were examined to determine their association with re-intubation. RESULTS: Of the 69 self-extubated patients, 38 fared well without further ventilatory support after self-extubation. Four factors were associated with extubation outcome: 1) mean pre-extubation FiO2 (fraction of inspired oxygen), which was significantly higher in the re-intubated group (RI) than in the not re-intubated group (NRI) (0.48 vs 0.33, p = 0.002)--all self-extubated patients receiving an FiO2 of more than 0.40 were re-intubated; 2) PaO2/FiO2 (ratio of arterial oxygen tension to inspired oxygen concentration), which was lower in the RI group than in the NRI group (259.4 vs 346.4, p = 0.005); 3) requirement for assist/control ventilatory mode--patients needing this type of ventilatory support had a greater likelihood of reintubation than those requiring partial ventilatory support (odds ratio [OR], 3.790; confidence interval [CI], 1.055-13.621; p = 0.041); and 4) female sex (OR 0.188; CI 0.048-0.732; p = 0.016). CONCLUSIONS: About half of self-extubated patients may not require re-intubation. Pre-extubation FiO2, PaO2/FiO2, and ventilator mode, as well as gender, may be useful in determining the likelihood that a self-extubated patient will require re-intubation.

Effect of early application of biphasic positive airway pressure on the outcome of extubation in ventilator weaning.

Extubation failure is significantly associated with increased morbidity and mortality in mechanically ventilated patients. In respiratory distress after extubation, non-invasive positive pressure ventilation (NIPPV) has been suggested to avoid the complications of invasive mechanical ventilation. The purpose of this study was to evaluate the effect of early application of NIPPV on extubation outcome. We conducted a prospective study in 93 extubated patients with a mean age of 72.7 +/- 14.7 years (range, 24-93). Elective extubation was performed in 56 patients and unplanned extubation occurred in 37 patients. After extubation, patients randomly received either biphasic positive airway pressure (BIPAP) therapy (n = 47) or unassisted oxygen therapy (n = 46). Non-invasive positive pressure ventilation was delivered via face mask in BIPAP group. Of the 93 extubated patients, 73 (78.5%) were successfully extubated, and 20 (21.5%) had to be re-intubated. There were no significant differences in age, sex, pre-extubation blood gas data between re-intubated patients and those who were not re-intubated. While seven of the 46 patients in the unassisted oxygen therapy group required re-intubation, 13 of the 47 BIPAP-treated patients also required re-intubation. This difference was not statistically significant. The postextubation respiratory management, BIPAP or unassisted oxygen therapy, did not correlate with the extubation outcome, but the elective extubation had significantly better outcome than unplanned extubation. Patients with excessive bronchial secretions and intolerance to the equipment are poor candidates for NIPPV. We conclude that early application of BIPAP support did not predict a favourable extubation outcome. Our experience did not support the indiscriminate use of NIPPV to facilitate ventilator weaning.

Modulatory effect of blood cells on hypoxic vasoconstriction response and nitric oxide release in rat lungs.

In this study, we investigated the modulatory effects of different types of blood cells on hypoxic pulmonary vasoconstrictive (HPV) response and nitric oxide (NO) release in isolated rat lungs. The lungs were perfused at a constant flow with physiologic saline solution (PSS). The changes in pulmonary arterial pressure (PAP) and NO release were observed. Two hypoxic challenges with a 5% CO2-95% N2 gas mixture were carried out in each experiment. Hypoxia induced pulmonary vasoconstriction, as reflected by an increase in PAP (0.88 +/- 0.22 cmH2O). At the same time, NO (342.9 +/- 78.3 mv) release from the lungs was also increased. Addition of white blood cells (WBCs, 0.70 to 0.88 x 10(5)/mL), platelets (1.48 to 1.96 x 10(5)/mL), or red blood cells (RBCs, 4.6 to 6.6 x 10(5)/mL) into the perfusate produced different effects on PAP and NO changes. WBCs decreased the pulmonary vasoconstriction response and this was accompanied by an increase in NO release. Platelets had no significant effects on either PAP or NO. RBCs significantly potentiated the PAP increase and attenuated the NO release. The results indicate that NO release during hypoxia tends to offset pulmonary vasoconstriction and that NO release and HPV response are modulated by different cell elements.

[Risk factors of lung cancer].

The relationship between various risk factors and lung cancer was evaluated in a case-control study. One hundred and forty-one cancer patients newly cytologically or pathologically diagnosed from May 1990 to July 1991 at Tri-Service General Hospital (TSGH) were recruited as cases. Two control groups were also studied: 282 hospital controls two-to-one matched with cases on sex, age, hospital of admission and insurance status were selected from the TSGH Ophthalmologic Department, and 282 neighborhood controls two-to-one matched on sex, age, and residence were randomly selected from eligible neighbors. A comparison of interview data between cases and hospital controls based on multiple conditional logistic regression revealed that cigarette smoking, keeping doves as pet, occupational exposure to cotton dust and working as a cook were risk factors for lung cancer. An inverse association between incense burning and lung cancer was noted. The comparison between cases and neighborhood controls showed lung cancer was significantly associated with cigarette smoking, keeping doves, prior chronic bronchitis, occupational exposure to cotton dust, asbestos and radiation, low frequency of burning incense, and low intake of vitamin A derived from vegetables and fruits. There was no association between lung cancer and working as a cook when cases were compared with neighborhood controls.

[A clinical study on 268 patients with cervical carcinoma].

Cancer is the leading cause of death in Taiwan with cervical carcinoma having the highest incidence rate (29.65 per 100,000) of all cancers among women. In the present study, we collected 268 consecutive cases of cervical carcinoma, seen in Tri-Service General Hospital from January 1983 to December 1984. The evaluation included a review of the case data including demographic features, symptoms, stage of cancer, reproductive history, pathology, and survival time (product limit method for survival). Results showed that in situ cervical carcinoma was diagnosed in 31 (11.5%) patients with a mean age of 47.7 years. Two hundred and thirty-seven patients (88.5%) with a mean age of 55.6 years were noted to have invasive carcinoma, showing stage I 22.4%, stage II 46.6%, stage III 10.1% and stage IV 9.3%. The ratio of invasive carcinoma to carcinoma in situ was 7.7:1. Ninety-two percent of patients were symptomatic on admission with vaginal bleeding (78%), vaginal discharge (16%) and abdominal pain (16%) being the most common, and the majority of these patients were symptomatic before cervical carcinoma was pathologically proved. Survival analysis showed five-year survival rates of 100%, 84.6%, 63.2%, 54.1% and 13.2% for stages O, I, II, III and IV, respectively. Low cervical carcinoma survival rates seemed clearly related to progression of the disease the presence of more extensive disease. The average age at the time of diagnosis was older and the clinical stage of disease was more advanced when compared with most developed countries.(ABSTRACT TRUNCATED AT 250 WORDS)

[The study of cancer pain and its correlates].

From August 1989 to December 1990, we collected 1523 cases of malignancy at Tri-service General Hospital (TSGH), and 470 cases (30.9%) of these malignancy had pain complaint. Moreover, we found that 68.1% (79/116 cases) of malignancy with bony metastasis had pain complaint. These informations were obtained from medical records. By counting the site of these 1523 cases, the leading sites in sequence were lung (207 cases), stomach (164 cases), cervix uteri (132 cases), breast (117 cases) and colon (91 cases). Regarding the incidence of cancer pain among these malignancy, bone cancer had the highest incidence (75.0%), followed by tongue (66.7%), brain (65.7%), liver (62.3%) and pancreas (60.0%). There was no difference of the incidence of cancer pain between male and female. The incidences of cancer pain in different age groups were different; the young patients had higher incidence than elderly patients. The analgesics for cancer pain used most frequently by physicians at TSGH were nonsteroid anti-inflammatory drugs and meperidine. Although the therapeutic management of cancer pain has been advancedly developed, we found that the treatments of cancer pain by physicians at TSGH were not aggressive enough. Therefore, promotion of the concept in advanced pain control and techniques is our important task in the near future.

Intercostal arteriovenous fistula due to pleural biopsy.

A 32 year old woman had a pleural biopsy for a left pleural effusion, which showed caseating granuloma typical of tuberculosis. When the fourth biopsy specimen was removed considerable bleeding occurred from the puncture site. Four days later a bruit was audible over the punctured area, radiating to the back. Eight days after the procedure the patient had a massive bleed into the left pleural space. Selective aortic angiography showed an arteriovenous fistula between the 9th intercostal artery and vein and a pseudoaneurysm in the intercostal punctured area. Thoracotomy showed bleeding from the site of the pleural biopsy. The intercostal vessels were ligated and pleural decortication was performed, and the patient recovered uneventfully.

[Survival of lung cancer patients of different histologic types].

The survival curves of primary lung cancers are significantly different by histologic type. The purpose of this study was to analyze the survival curves and prognostic factors of primary lung cancers according to the histologic type at the Tri-Service General Hospital for the years from 1983 to 1988. All records of new patients admitted to TSGH with primary lung malignancies were retrieved from the tumor registry. The survival curve was estimated by Kaplan-Meier Limit Estimate. The prognostic significance of 6 clinical and pathologic factors (sex, age, stage of disease, primary location, histologic differentiation and treatment) were analyzed by single variable analysis and by Cox multivariate regression. There were 448 male and 199 female patients with a mean age of 61.5 years. Adenocarcinoma was the most common histologic type found in both sexes, 37.9% in the men and 72.8% in the women. Patients in the advanced stage with distant metastasis comprised 52.8%. The most frequent location was the upper lobe (37.8%). Methods of treatment were: a) no therapy (39.7%), b) radiotherapy (34.7%), c) surgery with radiotherapy (8.7%), and d) other treatment (16.9%). The median survival of the 647 patients was 6.8 months after diagnosis. The overall one-year, three-year, and five-year survival rates were 26%, 10% and 5%, respectively. Survival curves according to the histopathologic type demonstrated that patients with small cell carcinoma had the lowest cumulative survival and patients with adenocarcinoma had a lower cumulative survival than those with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

[Small cell lung cancer: survival analysis of 96 cases].

Existing records of 96 patients with small cell lung cancer (SCLC) at TSGH from 1983 to 1987 were analyzed to determine the relationship of survival rate and prognostic factors including age, sex stage, symptomatic history, liver metastasis, bone metastasis, albumin level, hemoglobin value, and choice of treatment. For the SCLC patients the median survival time (MST) is only 7.2 month, the 1-year survival rate is 25.1%, and the 2-year survival rate is 5.1%. The prognosis for patients with liver or bone metastasis was poor. Sixteen prognostic variables were evaluated in a Cox proportional hazard regression model analysis to assess their prognostic value. It is suggested that improving survival rate for patients with SCLS can be obtained by using selective combined therapy.

The effects of alpha 2-adrenergic agonism with clonidine on the pulmonary and collateral resistances in the canine lung challenged with histamine.

In anesthetized dogs, we studied the effects of colonidine on the changes in pulmonary collateral resistance in response to histamine challenge. In the whole lung, an intravenous histamine increased the inspiratory (Ri), and expiratory (Re) resistance by 142 +/- 12%, and 229 +/- 30% over the control, respectively. Pretreatment with clonidine (0.05 mg/kg, iv) significantly attenuated the increases to 76 +/- 16% (Ri), and 114 +/- 22% (Re) (p less than 0.05). However, the responses to histamine were restored after an addition of yohimbine (0.15 mg/kg, iv) before clonidine. A bronchoscope wedge technique was used to measure the collateral resistance (Rcs) in the lung periphery. Histamine was administered in aerosolized form to a wedged sublobar segment. The local histamine challenge significantly increased Rcs. Pretreatment with clonidine did not discernibly affect the histamine-induced increase in Rcs. On the other hand, pretreatment with isoproterenol (0.02 mg/kg, iv) remarkably attenuated the Rcs response to histamine. The results indicate that alpha 2-adrenergic agonism with clonidine inhibits the bronchoconstriction induced by histamine. alpha 2- antagonism with yohimbine abolishes the antiasthmatic effect of clonidine. In the lung periphery, the Rcs response to histamine is not altered by alpha 2, but by beta 2 adrenergic agonism with isoproterenol.