Risk factors for requiring intravenous antibiotic therapy in hospital and 30-day readmission for exacerbations of bronchiectasis.

BACKGROUND: The safety and efficacy of domiciliary intravenous (IV) antibiotic therapy compared to inpatient hospital treatment for exacerbations of bronchiectasis has been established. Factors that determine the setting for IV antibiotic therapy need to be characterized further. AIM: We aimed to identify factors at presentation that were associated with the requirement for IV antibiotic therapy delivered in hospital and 30-day readmission. DESIGN: Retrospective cohort study of all IV antibiotic courses administered to patients with bronchiectasis by a specialist respiratory unit over a 2-year period. METHODS: We assessed demographic data, treatment outcomes, morbidity, mortality, and 30-day readmission rates. Multiple linear regression analysis was performed to identify factors associated with inpatient IV antibiotics and 30-day readmission. RESULTS: One hundred six patients received 243 courses of IV antibiotic therapy in 2 years. Sixty-six cases (27.2%) were managed in hospital, 28 cases (11.5%) required initial admission prior to early supported discharge to complete IV antibiotics at home and 149 cases (61.3%) received domiciliary IV antibiotics. Bronchiectasis Severity Index (P < 0.0001) and emergency presentation with an exacerbation (P < 0.0001) were independent factors associated with the requirement for inpatient IV antibiotic therapy. There were no differences between mortality (P = 0.06) and morbidity (P = 0.1) between groups. Thirty-day readmission following early supported discharge was higher compared to inpatient or domiciliary therapy (P=0.0004). CONCLUSION: A higher Bronchiectasis Severity Index and emergency presentation with an exacerbation are independently associated with the need for IV antibiotics delivered in hospital. We could not identify any factors that predicted 30-day readmission in a multi-variable model.

Bosutinib plus capecitabine for selected advanced solid tumours: results of a phase 1 dose-escalation study.

BACKGROUND: This phase 1 study evaluated the maximum tolerated dose (MTD), safety, and efficacy of bosutinib (competitive Src/Abl tyrosine kinase inhibitor) plus capecitabine. METHODS: Patients with locally advanced/metastatic breast, pancreatic, or colorectal cancers; cholangiocarcinoma; or glioblastoma received bosutinib plus capecitabine at eight of nine possible dose combinations using an 'up-down' design to determine the toxicity contour of the combination. RESULTS: Among 32 enrolled patients, none of the 9 patients receiving MTD (bosutinib 300 mg once daily plus capecitabine 1000 mg m(-2) twice daily) experienced dose-limiting toxicities (DLTs). Overall, 2 out of 31 (6%) evaluable patients experienced DLTs (grade 3 neurologic pain (n=1); grade 3 pruritus/rash and increased alanine aminotransferase (n=1)). Most common treatment-related adverse events (AEs) were diarrhoea, nausea, vomiting, palmar-plantar erythrodysesthesia (PPE), fatigue; most frequent grade 3/4 AEs: PPE, fatigue, and increased alanine/aspartate aminotransferase. Although diarrhoea was common, 91% of affected patients experienced maximum grade 1/2 events that resolved. Best overall confirmed partial response or stable disease >24 weeks (all tumour types) was observed in 6 and 13% of patients. CONCLUSIONS: In this population of patients with advanced solid tumours, bosutinib plus capecitabine demonstrated a safety profile similar to that previously reported for bosutinib or capecitabine monotherapy; limited efficacy was observed.

Prospective evaluation of unmet needs of rural and aboriginal cancer survivors in Northern British Columbia.

BACKGROUND: The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities. METHODS: We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing "no unmet need" and 4 representing "very high unmet need." A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results. RESULTS: We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss. CONCLUSIONS: First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations.

Eight-weekly intravenous antibiotics is beneficial in severe bronchiectasis.

AIM: The aim of our study was to assess the impact of 8-weekly intravenous (IV) antibiotics on exacerbation frequency and health-related quality of life in bronchiectasis. METHODS: Patients were recruited prospectively from June 2008 to December 2010. Patients with recurrent exacerbations (five or more exacerbations per year) and subjectively reporting ill health between antibiotic courses were recruited. Eight-weekly IV antibiotics (for 14 days) were initiated. Patients were followed up for 1 year. Main outcome was reduction in exacerbation frequency and improvement in health-related quality of life (HRQoL) at 1 year after starting intravenous antibiotic therapy. Other outcomes recorded were forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test (ISWT), 24-h sputum volume, sputum microbiology, body mass index (BMI), markers of inflammation--white cell count (WCC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). RESULTS: In total, 19 patients were recruited. Mean age was 64.1 years and 52.6% were female. With 8-weekly antibiotics, there was a significant reduction in the number of exacerbations [mean (SE): 9.3 (0.5) in the year before vs. 8.0 (0.4) in the year after; P = 0.02]. In 63.2%, Leicester Cough Questionnaire (LCQ) improved by ≥1.3 U (P = 0.006)] and in 42.1% St. George's Respiratory Questionnaire (SGRQ) improved by ≥4 U (P = 0.03). Exercise capacity increased by 58.7 m (P = 0.004). There was no improvement in the other end points. CONCLUSION: Treatment with 8-weekly intravenous antibiotics in severe bronchiectasis reduced exacerbation frequency and improved exercise tolerance and health-related quality of life.

A pilot study of pulmonary rehabilitation and chest physiotherapy versus chest physiotherapy alone in bronchiectasis.

AIM: The aim of our study was to assess the efficacy of pulmonary rehabilitation in addition to regular chest physiotherapy in non cystic fibrosis bronchiectasis. METHODS: Thirty patients with clinically significant bronchiectasis and limited exercise tolerance were randomized into either the control group receiving chest physiotherapy (8 weeks) or into the intervention group, receiving pulmonary rehabilitation in addition to chest physiotherapy (8 weeks). Both groups were encouraged to maintain their exercise program and or chest physiotherapy, following completion of the study. RESULTS: End of training (8 weeks) No improvement in control group. In the intervention group, incremental shuttle walk test (ISWT) improved by 56.7 m (p = 0.03), endurance walk test (EWT) by 193.3 m (p = 0.01), Leicester Cough Questionnaire (LCQ) improved by 2.6 units (p < 0.001) and St. George's Respiratory Questionnaire (SGRQ) by 8 units (p < 0.001). At 20 weeks (12 weeks post end of training) No improvement in control group. In the intervention group, ISWT improved by 80 m (p = 0.04) and EWT by 247.5 m (p = 0.003). LCQ improved by 4.4 units (p < 0.001) and SGRQ by 4 units (p < 0.001). CONCLUSION: Pulmonary rehabilitation in addition to regular chest physiotherapy, improves exercise tolerance and health related quality of life in non cystic fibrosis bronchiectasis and the benefit was sustained at 12 weeks post end of pulmonary rehabilitation. Clinical trials regn no. NCT00868075.

Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy.

BACKGROUND: This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. RESULTS: Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. CONCLUSIONS: Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.

Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis.

This study explored the utility of sputum colour in clinically stable patients with bronchiectasis. Interpretation of sputum colour between the doctor and the patient was reliable (intraclass correlation coefficient 0.83 (95% confidence interval 0.76-0.89). Sputum colour predicted bacterial colonisation (5% in mucoid sputum; 43.5% in mucopurulent sputum; 86.4% in purulent sputum; p<0.0001). On multivariate logistic regression analysis, independent factors associated with purulent sputum were bacterial colonisation, varicose or cystic bronchiectasis, forced expiratory volume in 1 s <80% predicted and diagnosis of bronchiectasis aged <45 yrs.

Validation of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis.

Health-related quality of life is a potentially important marker for evaluating existing and new therapies in bronchiectasis. The Leicester Cough Questionnaire (LCQ) is a symptom specific questionnaire designed to assess the impact of cough severity, a major symptom of bronchiectasis. This study aimed to validate the LCQ in bronchiectasis. The validity, responsiveness and reliability of the LCQ were assessed as follows: ability to discriminate severe and mild disease; change in score following antibiotic treatment for exacerbations; repeatability over a 6-month period in stable disease; and comparison with the St George's Respiratory Questionnaire (SGRQ). In total, 120 patients (51 with severe disease, 29 with moderate disease and 40 with mild disease) completed the LCQ and SGRQ. The area under the receiver-operator curve was good for both severe and mild disease (0.84 and 0.80 respectively, p<0.0001). Following 2 weeks' antibiotic treatment, the median LCQ score (interquartile range) improved from 11.3 (9.3-13.7) to 17.8 (15-18.8) (p<0.0001). The LCQ score was repeatable over 6 months in stable disease (intraclass correlation coefficient of 0.96 (95%CI 0.93-0.97), p<0.0001). Correlation between the LCQ and SGRQ scores was -0.7 in both stable disease and exacerbations (p<0.0001). The LCQ can discriminate disease severity, is responsive to change and is reliable for use in non-cystic fibrosis bronchiectasis.

Assessing response to treatment of exacerbations of bronchiectasis in adults.

The present study aimed to assess the effect of intravenous antibiotic therapy on clinical and laboratory end-points in exacerbations of noncystic fibrosis bronchiectasis and to determine whether the outcomes were influenced by the pathogenic organism isolated. A prospective cohort study was conducted from November 2006 to March 2008 of exacerbations requiring intravenous antibiotics. End-points included 24-h sputum volume, forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test, qualitative sputum microbiology, white cell count, erythrocyte sedimentation rate, C-reactive protein (CRP) and St George's Respiratory Questionnaire (SGRQ). Exacerbations due to Pseudomonas aeruginosa were compared with exacerbations due to other potential pathogenic organisms. In total, 32 exacerbations were studied. Following 14 days of intravenous antibiotics, all outcomes significantly improved independent of a pathogenic organism, except FEV(1) and FVC. The most responsive markers were: 24-h sputum volume (reduced in all patients and 80% had >/=50% reduction); sputum bacterial clearance (78.1%); CRP (>/=75% reduction in 62.5%) and SGRQ (>/=4 unit improvement in 89.7%). CRP, 24-h sputum volume and SGRQ improved independent of microbial clearance. In the current study, 24-h sputum volume, microbial clearance, C-reactive protein and St George's Respiratory Questionnaire were the most useful parameters to assess response to treatment of exacerbations of bronchiectasis. Outcomes were similar independent of the pathogenic organism with the exception of forced expiratory volume in one second and forced vital capacity.

[Erythema induratum Bazin. "Tuberculid" or tuberculosis?]. / Erythema induratum Bazin: "Tuberkulid" oder Tuberkulose?

A 66-year-old woman presented with erythematous nodules on both legs and told of a history of lymph node tuberculosis that had been treated with surgery and tuberculostatic therapy years before. A biopsy taken from a nodule showed nodular vasculitis. PCR for Mycobacterium tuberculosis-specific DNA on the paraffin-embedded tissue was positive. Based on the experience with our patient, positive PCR results for Mycobacterium tuberculosis-specific DNA in lesions of nodular vasculitis are discussed critically. The historical background of "tuberculids", such as erythema induratum Bazin, is elucidated.

The organization of genes tightly linked to the Ha locus in Aegilops tauschii, the D-genome donor to wheat.

The grain hardness locus, Ha, is located at the distal end of the short arm of chromosome 5D in wheat. Three polypeptides, puroindoline-a, puroindoline-b, and grain softness protein (GSP-1), have been identified as components of friabilin, a biochemical marker for grain softness, and the genes for these polypeptides are known to be tightly linked to the Ha locus. However, this region of the chromosome 5D has not been well characterized and the physical distance between the markers is not known. Separate lambda clones containing the puroindoline-a gene and the puroindoline-b gene have been isolated from an Aegilops tauschii (the donor of the D genome to wheat) genomic lambda library and investigated. Considerable variation appears to exist in the organization of the region upstream of the gene for puroindoline-b among species closely related to wheat. Using in situ hybridization the genes for puroindoline-a, -b, and GSP-1 were demonstrated to be physically located at the tip of the short arm of chromosome 5 of A. tauschii. Four overlapping clones were isolated from a large-insert BAC library constructed from A. tauschii and of these one contained genes for all of puroindoline-a, puroindoline-b, and GSP-1. The gene for puroindoline-a is located between the other two genes at a distance no greater than approximately 30 kb from either gene. The BAC clone containing all three known genes was used to screen a cDNA library constructed from hexaploid wheat and cDNAs that could encode novel polypeptides were isolated.

Caspase-3-like activity is necessary but not sufficient for daunorubicin-induced apoptosis in Jurkat human lymphoblastic leukemia cells.

In the present study we have shown that the cancer therapeutic drug, daunorubicin, induces apoptosis in the human lymphoblastic leukemia cell line Jurkat E6.1. This effect was both dose-and time-dependent with nuclear fragmentation detectable by 8 h. Caspases have been implicated in pro-apoptotic events. By utilizing synthetic fluorochrome-linked substrates of the caspases, we observed that a caspase-3-like enzyme had dramatically increased activity (3340 130% with respect to basal levels) in response to daunorubicin treatment. Furthermore, by using an inhibitor to caspase-3, Ac-DEVD-CHO, we have shown that activation of a caspase-3-like enzyme appears to be necessary for nuclear fragmentation and apoptotic body formation, but is not required for chromatin condensation. In contrast, a general caspase inhibitor, Z-VAD-fmk, inhibited all apoptotic parameters measured. Ceramide has been implicated in daunorubicin-induced apoptosis in human myeloid leukemia cells. However, in Jurkat cells, caspase activation does not appear to be a consequence of ceramide generation since, although ceramide levels were elevated through the action of ceramide synthase in response to daunorubicin treatment, this occurred with slower kinetics than either nuclear fragmentation or caspase activation. In contrast, caspase inhibitors abrogated ceramide elevation induced by DNR treatment, suggesting that ceramide synthase may be a downstream target for caspase action. Therefore, daunorubicin-induced apoptosis does not appear to be mediated by ceramide in the lymphoblastic leukemia cell line, Jurkat E6.1. Instead, caspase 3 activity appears to be necessary, but not sufficient for this process.

AP-1-mediated invasion requires increased expression of the hyaluronan receptor CD44.

Fibroblasts transformed by Fos oncogenes display increased expression of a number of genes implicated in tumor cell invasion and metastasis. In contrast to normal 208F rat fibroblasts, Fos-transformed 208F fibroblasts are growth factor independent for invasion. We demonstrate that invasion of v-Fos- or epidermal growth factor (EGF)-transformed cells requires AP-1 activity. v-Fos-transformed cell invasion is inhibited by c-jun antisense oligonucleotides and by expression of a c-jun dominant negative mutant, TAM-67. EGF-induced invasion is inhibited by both c-fos and c-jun antisense oligonucleotides. CD44s, the standard form of a transmembrane receptor for hyaluronan, is implicated in tumor cell invasion and metastasis. We demonstrate that increased expression of CD44 in Fos- and EGF-transformed cells is dependent upon AP-1. CD44 antisense oligonucleotides reduce expression of CD44 in v-Fos- or EGF-transformed cells and inhibit invasion but not migration. Expression of a fusion protein between human CD44s and Aequorea victoria green fluorescent protein (GFP) in 208F cells complements the inhibition of invasion by the rat-specific CD44 antisense oligonucleotide. We further show that both v-Fos and EGF transformations result in a concentration of endogenous CD44 or exogenous CD44-GFP at the ends of pseudopodial cell extensions. These results support the hypothesis that one role of AP-1 in transformation is to activate a multigenic invasion program.

Synthesis of a hybrid protein containing the iron-binding ligand of bleomycin and the DNA-binding domain of Hin.

The iron-binding and oxygen-activating domain of the natural product bleomycin [pyrimidoblamic acid-beta-hydroxy-L-histidine (PBA-beta-OH-His)] was attached to the NH2 terminus of the DNA binding domain of Hin recombinase (residues 139-190). This hybrid 54-residue protein PBA-beta-OH-His-Hin-(139-190) binds specifically to DNA at four distinct Hin binding sites with affinities comparable to those of the unmodified Hin(139-190). In the presence of dithiothreitol, Fe(II).PBA-beta-OH-His-Hin-(139-190) cleaves DNA with specificity remarkably similar to that of Fe(II).EDTA-Hin(139-190). Analysis of the cleavage patterns suggests that site-specific DNA cleavage is mediated by a localized diffusible species, in contrast with cleavage by bleomycin, which occurs through a nondiffusible oxidant. This has implications for the design of second-generation artificial sequence specific DNA cleaving proteins and defines limitations in current efforts to create atom-specific chemistry on DNA.

Effect of mouse epidermal growth factor on plasma concentrations of FSH, LH and progesterone and on oestrus, ovulation and ovulation rate in merino ewes.

The 24 h i.v. infusion of Merino ewes with 60 or 100 microgram mouse epidermal growth factor (EGF)/kg body weight on Days 4, 9 or 14 of the oestrous cycle decreased the strength of wool attachment and caused marked changes in subsequent reproductive performance. In ovaries removed 2 days after EGF treatment all follicles greater than or equal to 0.6 mm diameter were atretic. After 7 days either a normal pattern of atresia or no atresia was evident while after 12 days the pattern of follicular atresia was similar to that in controls. Irrespective of stage of cycle EGF caused dose-dependent increases in plasma FSH concentrations that persisted for up to 14 days. Changes in plasma LH concentrations were generally similar after infusion on Days 4 and 14, but were smaller and shorter-lived after infusion on Day 9. Irrespective of dose, the infusion of EGF on Days 4 and 14 caused immediate luteolysis then the formation of a luteinized follicle in many ewes. Most ewes treated on Day 4 returned to oestrus between Days 17 and 21 with the same ovulation rate (1.3) as the controls. Of those infused on Day 14 oestrus occurred about a cycle length later than expected and their ovulation rate then (1.9) was also similar to that of the controls (1.7). Luteal function was not affected in ewes infused on Day 9, and most returned to oestrus between Days 17 and 20 with an ovulation rate of 3.2. Fertile rams were not placed with the ewes until after the differences in ovulation rate had been observed. Mating occurred generally 2-4 weeks after treatment, and there were no differences between EGF-treated and control ewes in fertility or fecundity. The results are interpreted as indicating that mouse EGF induces ovarian follicular atresia but has differential effects on luteal function according to the stage of the oestrous cycle at which it is given. As a consequence of these two effects, which lead to differential changes in gonadotrophin secretion, ovarian function may be temporarily impaired, little affected or improved.

Combined chemotherapy and radiation therapy for non-small-cell lung cancer.

In a previous study of patients with recurrent or disseminated non-small-cell lung cancer (NSCLC), the combination of bleomycin, etoposide, and cisplatin (BEP) produced objective responses in ten of 17 (59%) patients with large-cell anaplastic carcinoma and in 14 of 35 (40%) with squamous-cell carcinoma. These results prompted a pilot study of combined modality therapy in which two cycles of BEP were administered prior to split-course radiation therapy. Thirty patients with surgically unresectable stage II or III squamous- or large-cell cancer, were entered into the study, of whom 25 were evaluable for response to chemotherapy. One patient (4%) had a complete response (CR), ten (40%) with measureable disease had a partial response (PR), and four (16%) with evaluable disease had significant disease regression prior to radiotherapy (overall response rate, 60%). After radiotherapy, six of 22 (27%) evaluable patients achieved a CR, and six (27%) a PR, for an overall response rate of 55%. Symptom control was achieved with chemotherapy in the majority of patients. The median survival time after the initiation of BEP had not been reached at 52 weeks. The results of this pilot study suggest that a phase III study comparing BEP plus radiation therapy with radiation therapy alone should be undertaken in this subgroup of patients with NSCLC.

Haemodynamic and plasma vasopressin responses during high-dose fentanyl or sufentanil anaesthesia.

This study compared the haemodynamic and arginine vasopressin responses of patients to fentanyl or sufentanil anaesthesia for coronary artery bypass surgery. Fourteen normotensive patients with normal left ventricular function were studied. Patients were induced with fentanyl (N = 7) 37.5 micrograms X kg-1 or sufentanil (N = 7) 7.5 micrograms X kg-1 by intravenous infusion over three minutes. Clinically important chest wall rigidity, bradycardia and recall of intraoperative events did not occur. All of the fentanyl patients became hypertensive after induction and five required vasodilator therapy since they did not respond to boluses of fentanyl (12.5 micrograms X kg-1). Two of these five patients had S-T depression greater than 1 mm. Five patients in the sufentanil group became hypertensive after induction. Four of these patients responded to additional sufentanil (3.75 micrograms X kg-1) while one required vasodilator therapy for concomitant S-T depression. Sufentanil attenuated the increase of arginine vasopressin during cardiopulmonary bypass. Levels of arginine vasopressin in the fentanyl group were significantly higher than those of the sufentanil group during bypass. Levels of AVP after bypass were higher in the sufentanil group. The incidence of hypertension was similar in both groups. The hypertension was more easily treated with sufentanil but concomitant vasodilators (nitroglycerine) were required in both patient groups. Neither fentanyl in doses up to 128 +/- 8.7 micrograms X kg-1 nor sufentanil in doses up to 23 +/- 1.4 micrograms X kg-1 can be used as sole agents for anaesthesia in adult coronary artery bypass patients with good ventricular function when induction times are three minutes and bolus top-up doses are used.

Combination chemotherapy with bleomycin, etoposide, and cisplatin in metastatic non-small-cell lung cancer.

Fifty-three patients with recurrent and advanced stage (III and IV) non-small-cell lung cancer (NSCLC) were treated with a combination of bleomycin, etoposide (VP-16-213), and cis-diamminedichloroplatinum (BEP). Forty-eight patients were appraisable for response. The response rates were 44% for the entire group, 57% in 30 patients with combined squamous-cell and large-cell carcinoma, and 22% in 18 patients with adenocarcinoma (40%, 50%, and 19%, respectively, if patients not appraisable for response are included as nonresponders). The median survival time of patients with squamous-cell and large-cell carcinoma was slightly longer than that of patients with adenocarcinoma (23 weeks v 19 weeks). Patients with responsive disease survived significantly longer (median, 34 weeks) than did patients with unresponsive disease (median, 16 weeks) (P = .001). In the entire group, the median survival time of patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was better (23 weeks) than of those with a status of 2 or 3 (15 weeks), but this difference was not seen in the subgroup with squamous-cell and large-cell carcinoma (24 weeks v 23 weeks, respectively). Thus, the performance status was not of prognostic value in the histologic subgroups experiencing the best response rate. There were two treatment-related deaths, but otherwise the toxicity of BEP was acceptable. Only four of the 119 treatment cycles were followed by fever even though there was significant neutropenia (0.5 X 10(9)/L) after 20 of 97 treatment cycles. The majority of patients receiving BEP experienced relief of cough, hemoptysis, pain, and fatigue associated with their disease. There was a good correlation between objective responses and palliation of symptoms. Thus, BEP offers good palliation, particularly for patients with squamous-cell and large-cell lung cancer.

Haemodynamic and plasma vasopressin responses with high-dose fentanyl anaesthesia during aorto-coronary bypass operations.

Twelve male patients were given high dose fentanyl (75-100 microgram.kg-1) anaesthesia with oxygen during elective aorto-coronary bypass operations, and their haemodynamic and vasopressin responses were determined during induction, sternotomy, cardiopulmonary bypass, post-bypass and recovery periods. For comparison, a group of 12 male patients were anaesthetized with morphine, halothane 0.5 per cent, nitrous oxide and oxygen, and were similarly studied. Significant alterations in haemodynamics included increased mean arterial pressure after sternotomy in the fentanyl group, increased heart rate in both groups, increased systemic vascular resistance after sternotomy only in the halothane group, and decreased left ventricular stroke work index in both groups following induction, bypass, and during the recovery periods. Plasma vasopressin levels increased significantly in both groups during the bypass period, but returned to baseline levels following bypass. Serum sodium and osmolality did not change significantly, and urinary sodium and potassium excretion rose with the progress of the operation in both groups. A positive correlation was found between mean arterial pressure and vasopressin only in the halothane group. Systemic vascular resistance was correlated to vasopressin levels in both groups. Vasopressin response in both groups was similar, with significant but relatively low increases in levels during cardiopulmonary bypass. Fentanyl-oxygen anaesthesia did not provide haemodynamic stability in eight of 12 patients.