Impact of early angiographic evaluation on the frequency of emergency reoperations after coronary bypass surgery.

BACKGROUND AND AIMS: early graft failure following coronary bypass surgery results in elevated morbidity and mortality. This study focused on the impact of angiographic graft evaluation. MATERIAL AND METHODS: of 5251 coronary artery bypass grafting (CABG) patients, 36 with postoperative persistent ischaemia underwent early angiography (23) or emergency resternotomy (13) 2000-2007 (Angiography era). Of the 23 patients, who underwent angiography, five were subsequently reoperated. Of 8807 CABG patients, 76 underwent postoperative emergency resternotomy 1988-1999 (Pre-angiography era) and served as controls. RESULTS: the angiography era patients were older (64.0 years vs. 58.2 years, P = 0.002) and the proportion of female patients (22% vs. 43%, P = 0.029) was smaller. The rate of emergency reoperations decreased (0.86% vs 0.34%, P < 0.001) during the Angiography era and graft repairs (P = 0.013) or additional grafts (P = 0.006) were less frequent, although occluded anastomoses were observed more often (P = 0.043). In 5 Angiography era patients graft complications were corrected with percutaneous coronary intervention. ICU stay (5.72 + 0.98 days vs. 5.53 + 0.68 days) and hospital stay (12.2 + 1.54 days vs. 13.1 + 1.63 days) did not differ between the groups, but the rate of myocardial infarction (63.8% vs. 92.1%, P < 0.001) and in-hospital death (22.2% vs. 46.1%, P = 0.015) decreased. CONCLUSION: after the introduction of early postoperative angiographic evaluation of CABG patients the rate of emergency reoperations and related morbidity and mortality decreased.

Tenascin is expressed in post-transplant obliterative bronchiolitis.

Tenascin is expressed in inflammatory and fibroproliferative processes, both contributing to posttransplant obliterative bronchiolitis (OB) in association with epithelial cell injury and airway obliteration. We studied bronchial allografts to elucidate the role of tenascin during this alloimmune response. Bronchial segments were subcutaneously implanted into eight pigs. Allografts and autograft controls were serially obtained until total obliteration in allografts and processed for histology and immunocytochemistry for CD4, CD8, and tenascin. Findings were graded on a scale from 0 to 3. In autografts the operative epithelial damage recovered and bronchi stayed patent with mild-graded fibrosis and inflammation. Partial recovery was observed in allografts on day 4, thereafter the epithelial loss gradually increased. Total recovery was achieved on day 11 (P < .001). Fibroblast proliferation resulted in total luminal obliteration on day 21 (P < .001). The number of inflammatory cells increased rapidly (P < .05) with numerous CD4+ and CD8+ cells on day 14 (P < .0001). Prior to total epithelial loss in allografts, tenascin expression was observed on day 7 in 69% of epithelial cells, whereas in only 5% of epithelial cells in recovered autografts. Paralleling the most intense fibroproliferation, tenascin-positive cells were observed in the bronchial wall on day 7 and day 11 (P < .001). Tenascin expression was demonstrated during the inflammatory response and fibroblast proliferation during the early stage of obliterative bronchiolitis showing that tenascin contributes to posttransplant obliterative bronchiolitis development.

Interferon maintenance therapy for small cell lung cancer: improvement in long-term survival.

Two hundred thirty-seven patients with small cell lung cancer (SCLC), who had responded to induction chemotherapy and radiotherapy, were randomly assigned to receive low-dose natural interferon-alpha (nIFN alpha) for 6 months; or 6 cycles of maintenance chemotherapy (CAP); or no maintenance therapy (control group). Although there was no difference in median survival between the groups, there was a significant difference (p = 0.04) in the long-term survival of patients with limited disease, in favour of nIFN alpha maintenance therapy. This finding is now confirmed by a further analysis of the most recent data. Ten percent of patients in the IFN group survived for five years or more, but the 5-year-survival rate in the CAP and control groups was only two percent. All long-term survivors had good performance status. The majority had limited disease and had achieved a complete response to the induction therapy. These results suggest that interferon-alpha improves the long-term survival of SCLC patients for whom other prognostic factors are favorable.

Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study.

Patients with any stage of small cell lung cancer were given low-dose interferon-alpha (IFN-alpha) from the first day of treatment as long as possible irrespective of changes in treatment dictated by disease progression. All patients received 6 cycles of the chemotherapy (CT): cisplatin 70 mg/m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1, 2, 3 every 28 days. Seventy-eight patients were assigned to arm 1: CT alone, 75 patients to arm 2: CT + natural IFN-alpha (3 MU three times a week i.m.), and 66 patients to arm 3: CT + recombinant IFN alpha-2a (3 MU three times a week i.m.). There was no difference in median survival between the arms (10.2 months, 10.0 months, 10.1 months, respectively), p = 0.32. The 2-year survival rates were 15%, 3%, and 11%, respectively. Grade 3 and 4 leukopenia occurred more frequently in the IFN arms than in the CT alone arm and resulted in dose reductions. Antibodies occasionally developed to recombinant IFN. We conclude that IFN-alpha can be administered concomitantly with chemotherapy but is probably better kept for maintenance therapy so that optimal full doses of induction CT can be given.

Interferons combined with chemotherapy in the treatment of stage III-IV non-small cell lung cancer--a randomised study.

80 patients with previously untreated stage III-IV non-small cell lung cancer (NSCLC) were randomly assigned to receive chemotherapy (CT) alone (arm I: 26 patients) or the same CT combined with either interferon (IFN)-gamma (arm II: 27 patients) or with both IFN-gamma and IFN-alpha (arm III: 27 patients). The CT comprised cisplatin 60 mg/m2 intravenously (i.v.) day 1 and etoposide 100 mg/m2 i.v. days 1, 3 and 5, once every 28 days; the IFN therapy comprised either recombinant IFN-gamma 1b 0.2 mg/m2, subcutaneously, three times a week until day 25, or recombinant IFN-alpha 2c 6 x 10(6) U given according to the same schedule, and simultaneously with IFN-gamma. A maximum of six cycles were given. The treatment was discontinued if progressive disease (PD) was demonstrated. The mean numbers of cycles per patient given in the different arms were 3.6 (arm I), 3.0 (arm II) and 2.9 (arm III). The main reason for discontinuation in all arms was PD. 17 (28%) of the 61 evaluable patients achieved partial responses (35% in arm I, 29% in arm II and 35% in arm III, non-significant). No complete response was recorded. Haematological toxicity was dose-limiting in all arms: leucopenia (WHO grade 3) was observed universally, but more frequently in arm III (in 18% of cycles given). Only two episodes of grade 4 leucopenia were seen (arms II and III) and six episodes of grade 3-4 thrombocytopenia (arm III). Median survival was 6-7 months in all arms. The survival curve for arm II was slightly more favourable (non-significant) than those for other arms. The addition of IFN-gamma alone or IFN-alpha plus IFN-gamma to platinum-based CT did not improve response rates nor did it produce any significant survival benefit for patients with NSCLC. Increased haematological toxicity was observed when both IFNs were administered concomitantly with CT.

Quality of life assessment during chemotherapy for non-small cell lung cancer.

Quality of life was assessed by linear analogue scales for patients with non-small cell lung cancer participating in a phase I-II trial. Chemotherapy consisted of cyclophosphamide 600 mg/m2 intravenously on day 1 and trimetrexate (five dose levels) intravenously on days 1-5, repeated every 21 days. Eleven subjective items were assessed by the patients. Nine of the scales related to performance, problems related to the disease itself and uncertainty about the value of treatment; two scales related to the major known side-effects of chemotherapy. Each patient completed the scales before treatment, on the last day of treatment (day 5) and once between cycles. Variation in the scores for items (e.g. for nausea or appetite) suggests that the method was useful in estimating the patient's perceived quality of life during repeated cycles of chemotherapy. Compliance was good and the method was easily accepted by both patients and nurses as part of a routine.

Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

Deterioration in lung function following hemithorax irradiation for pleural mesothelioma.

Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy.

Bronchoalveolar lavage fluid findings following radiotherapy for non-small cell lung cancer.

PURPOSE: To evaluate the diagnostic potential of bronchoalveolar lavage fluid analysis in radiation-induced lung injury. METHODS AND MATERIALS: Thirty patients with inoperable non-small cell lung cancer received either high-dose hyperfractionated radiotherapy or radiotherapy and interferon, a potential radiosensitizer, or radiotherapy and N-acetylcysteine, a potential radioprotector. Bronchoalveolar lavages were performed before and immediately after radiotherapy, and thereafter 6-8 weeks and 3 months after radiotherapy. Total and differential cell counts were measured from the bronchoalveolar lavage fluid samples. Urea measured in serum and in bronchoalveolar lavage fluid was used to calculate epithelial lining fluid. The concentrations of protein and phosphatidylcholine, the major surfactant phospholipid, in epithelial lining fluid were measured. The extent of radiation-induced lung injury was assessed from computed tomographies performed before radiotherapy, and 6-8 weeks and 3 months after radiotherapy. RESULTS: More patients in the interferon-arm developed radiation pneumonitis than did patients in the other groups, but no significant differences in alveolar fluid indices were noted between the groups. When all the patients were studied together, radiation was shown to have induced a significant relative increase of lymphocytes in bronchoalveolar lavage fluid 6-8 weeks and 3 months after the end of radiotherapy. The concentration of phosphatidylcholine in epithelial lining fluid decreased significantly 6-8 weeks and 3 months after treatment. The increase in protein concentration in epithelial lining fluid reached a statistically significant level 6-8 weeks after radiotherapy. CONCLUSION: Analysis of bronchoalveolar lavage fluid predicts the degree of radiation pneumonitis; however, radiology remains to be "the gold standard."

Procollagen-III in serum, plasminogen activation and fibronectin in bronchoalveolar lavage fluid during and following irradiation of human lung.

In the search for predictors of late radiation-induced lung injury we studied procollagen type III peptide concentration (P-III-P) in serum as well as fibronectin and plasminogen activation in bronchoalveolar lavage (BAL) fluid during and following irradiation of human lung. The patients received either high-dose hemithorax irradiation for pleural mesothelioma (11 patients) or high-dose irradiation with individually shaped fields for non-small cell lung cancer (12 patients). The severity of radiation fibrosis was assessed clinically from CT scans 6 months and 12 months after treatment. Four scores were used: severe, moderate, mild, or normal. Radiological lung injury varied from "severe" (9 patients) to near absence of injury-"normal" (6 patients). Serum levels of P-III-P, when measured weekly during the 5-week period of radiotherapy or at several time-points after treatment, did not show consistent changes, nor did the levels correlate with the score for radiation fibrosis as assessed by CT scanning. Changes in fibronectin levels or in markers of plasminogen activation in BAL fluid did not correlate with the development of late lung injury. The levels of BAL fluid plasmin and plasminogen activator as assessed zymographically, but not the free net enzyme values, showed a tendency to be elevated in patients with severe radiation-induced lung injury, suggesting a possible role for inhibitors of the plasminogen activation cascade in the process of radiation-induced lung injury.

Inhaled recombinant interferon gamma in patients with lung cancer: pharmacokinetics and effects on chemiluminescence responses of alveolar macrophages and peripheral blood neutrophils and monocytes.

PURPOSE: A Phase I trial was conducted to investigate clinical toxicity, pharmacokinetics, and chemiluminescence (CL) responses of alveolar macrophages (AM) and peripheral blood neutrophils and monocytes after inhalation of recombinant interferon (r IFN)-gamma. METHODS AND MATERIALS: Eight patients with lung cancer inhaled r IFN-gamma as single doses of 0.1, 0.2, 0.6, 1.8, or 5.4 mg. Bronchoalveolar lavage was performed three times, 21 h before as well as 3 and 27 h after inhalation. RESULTS: Interferon-gamma was detectable in bronchoalveolar lavage fluid (BALF) samples taken 3 h after inhalation in doses of > or = 0.6 mg. Before inhalation, AM in four out of seven patients studied showed vigorous lucigenin-enhanced CL responses to N-formyl-methionyl-leucyl-phenylalanine and opsonized zymosan particles. Furthermore, the responses were markedly increased 3 h after inhalation. In three out of seven patients, AM in the pretreatment BALF samples showed low or no CL responses, and the responses did not increase after inhalation of IFN-gamma, suggesting that the patients were anergic. Postinhalation CL responses did not correlate with the dose of IFN-gamma inhaled. Circulating IFN-gamma was detected in one patient receiving the highest dose. No changes referable to IFN-gamma inhalation were found in the CL responses of blood neutrophils and monocytes. During the 24 h follow-up, two patients developed transient fever-reactions. CONCLUSIONS: The findings suggest that inhalation may provide a way to increase alveolar concentrations of IFN-gamma and to augment respiratory burst capacity of AM without any major side effects. This approach may have clinical implications for the treatment of tumors and infections of the respiratory tract.

Natural alpha-interferon in combination with hyperfractionated radiotherapy in the treatment of non-small cell lung cancer.

Our previous study in patients with small-cell lung cancer indicated that natural alpha interferon might be a radiosensitiser. In this study we considered 20 patients with inoperable non-small cell lung cancer, who were randomly assigned to receive either hyperfractionation radiotherapy alone, 1.25 Gy twice a day (6 hr interval), 60 Gy/48F/32d; or the same radiotherapy concurrently with alpha interferon. Patients in the radiotherapy+alpha interferon arm received 3 x 10(6) IU natural alpha interferon intramuscularly and 1.5 x 10(6) IU inhaled via a dosimeter-equipped jet nebulizer 30 min before each radiotherapy session. Tumor response and radiation-induced lung injury were assessed by serial chest radiographs, computerized tomography scans and lung function studies, during a 1 year follow-up period. No patient in either arm achieved complete response. On the other hand, five patients in the radiotherapy arm and six in the radiotherapy+interferon arm experienced partial response, and the corresponding figures for stable disease were three and one. Combined treatment with radiotherapy and inhaled and intramuscular interferon proved feasible but laborious, for both patients and staff. Pneumonitis and/or oesophagitis in the radiotherapy+interferon arm were moderate to severe, and only two patients tolerated the treatment without any modifications. No treatment modifications were necessary in the radiotherapy arm. The early deaths in the radiotherapy+interferon arm may have been treatment-related. The optimal way to combine interferon and radiotherapy to further evaluate its role as a radiosensitiser needs further studies in larger series.

Serum markers for prediction of pulmonary radiation syndromes. Part I: Surfactant apoprotein.

Detection of a biochemical marker indicating radiation lung injury prior to the onset of clinical pathologic events could prove valuable in patient management. An increased level of alveolar surfactant is one of the earliest detectable changes following lung irradiation, starting within hours of irradiation and persisting a maximum of 2-6 weeks. However, because broncho-alveolar lavage is impracticable and endothelial cell damage due to radiation results in changes in permeability of vessel wall with leakage of alveolar proteins into serum, identification of serum markers was sought. A series of experiments in rabbits are described that clearly demonstrate serum surfactant apoprotein is an accurate marker and predictor for later lethal radiation pneumonitis. At 3-7 days after graded single doses to lung, surfactant was found in the serum paralleling the dose response for lethality. Control studies with a physiologic agent such as terbutaline release alveolar surfactant, but no serum surfactant was detected. Monitoring serum surfactant could direct preventive intervention prior to clinicopathologic manifestation of pulmonary radiation syndromes.

Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation.

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.

Immune cells and immunosuppression in a porcine bronchial model of obliterative bronchiolitis.

BACKGROUND: To study obliterative bronchiolitis (OB), we have developed a porcine heterotopic bronchial model. Allografts obliterate within 3 weeks, the immunosuppression cyclosporine (CsA)-azathioprine (AZA)-methylprednisolone (MP) delays OB, but OB is prevented when AZA is switched to 40-0-(2-hydroxyethyl)-rapamycin (RAD). To characterize our model, we studied immune cells under various immunosuppressive conditions. METHODS: The groups studied were autografts (U), allografts (A), and allografts given either CsA-RAD-MP (R), or CsA-AZA-MP (C). The implants were harvested at 3, 7, 10, 14, 21, 30, 60, and 90 days after transplantation. Epithelial damage and obliteration were graded histologically, and the number of CD4, CD8, MHC class II expressing cells, macrophages, and B lymphocytes were counted (mean+SEM)/high-power visual field. RESULTS: In group U, normal epithelium was regained with no obliteration and only few immune cells. In group A, consistent with initially acute ejection, an influx of CD4 (105+23), CD8 (166+23), and class II (92+20) cells was seen up to day 21, when total obliteration preceded by epithelial destruction had already developed. Some macrophages were seen and B cells were scarce. In group R, epithelial damage and obliteration were insignificant, but moderate numbers of CD4, CD8, and class II cells were seen. In group C, epithelial damage and obliteration were only delayed, but the immune cell response was clearly blunted. CONCLUSIONS: In our model, rejection with significant immune cell influx was still active when obliteration was total in nontreated allografts. In immunosuppressed allografts, decrease in the number of immune cells alone did prevent OB. These results support OB being T-cell mediated. RAD may have additional important effects on growth factors and proliferation in prevention of OB.

Obliterative lesions in a heterotopic bronchial xenograft model--a preliminary study.

BACKGROUND: We further developed our heterotopic pig model of obliterative bronchiolitis to study airway obliteration in xenografts. METHODS: Four domestic piglets each received 40 bronchial xenografts s.c. from a donor lamb. Piglet X was not immunosuppressed. The other animals received daily oral cyclosporine, 15 mg/kg (XC), or SDZ RAD, 1.5 mg/kg (XR), or both (XCR). Five implants at a time were serially removed from each animal during 17 days for histological assessment. RESULTS: In contrast to the grafts of the others, the xenografts of XCR recovered after initial ischemic damage. No epithelial damage (P<0.01) or mural necrosis occurred on day 7. Airway obliteration developed in all, but was significantly delayed in XCR. CONCLUSIONS: Invariably developing airway obliteration in nontreated xenografts was delayed by immunosuppression, making the model useful, especially in testing the efficacy of immunosuppressive drugs in a xenogeneic system.

Alloimmune injury preceding airway obliteration in porcine heterotopic lung implants: a histologic and immunohistologic study.

BACKGROUND: Obliterative bronchiolitis (OB), the major long-term complication of lung transplantation, has thus far lacked a good large-animal model. Our goal was to develop such a model on the basis of previous rodent models with tracheal implants. METHODS: Fragments of pulmonary tissue with structures of terminal bronchi were subcutaneously transplanted to four random-bred domestic piglets. Each animal received 10 autograft and 10 allograft implants. The histologic findings were graded from 0 to 3 for implants harvested repeatedly over 2 months. RESULTS: In autografts, partial destruction of the respiratory epithelium and gradual luminal obliteration as well as mild damage to the cartilage and the bronchial wall underwent rapid reversal after initial ischemic injury. In the allografts, epithelial destruction and gradual obliteration were total within 14 days, the difference being statistically significant (P<0.05) in both. The histologic features of the obliterative plug were similar to those of human OB. In the allografts, cartilaginous destruction and pericartilaginous inflammation increased gradually to severe levels, significantly worse than in the autografts (P<0.05). Necrosis and inflammation of the bronchial wall were also more severe in the allografts (P<0.05). CONCLUSIONS: At the end of follow-up, all autografts were vital, whereas the allografts were almost totally rejected and were without native structures. All bronchi in the allografts exhibited accelerated obliteration with histologic features characteristic of human OB, thus providing a model for research into OB and its prevention.

Different imaging methods in the assessment of radiation-induced lung injury following hemithorax irradiation for pleural mesothelioma.

We have characterized the radiation-induced lung injury on serial chest X-rays, CTs and ultralow field MRs and evaluated the clinical value and cost/benefit ratio of the different imaging methods in 30 patients receiving high-dose hemithorax irradiation for pleural mesothelioma. Lung injury was severe in all patients, but non-specific and essentially as described in text-books. CT provided no clinically relevant, cost effective diagnostic advantage over conventional X-rays in the detection of early or late radiation-induced lung injury, but it was necessary for the evaluation of the disease status of mesothelioma. The possible advantage of MR over CT could not be evaluated and needs further studies. Optimal time-points for imaging CTs or MRs to detect early radiation-induced lung injury following high dose hemithorax irradiation were during the latter part of treatment or very shortly after the end of irradiation. Late injury or irreversible fibrosis developed rapidly after 6 months and was clearly documented by chest X-rays. We recommend serial chest X-rays at 1-2, 6 and 12 months following radiotherapy as a cost-effective method for the detection of radiation-induced lung injury with additional CTs to document the stage of mesothelioma, when needed.

N-acetylcysteine in combination with radiotherapy in the treatment of non-small cell lung cancer: a feasibility study.

N-Acetylcysteine (NAC) is a free radical scavenger and could therefore act as a radioprotector. To test the feasibility of administering NAC in combination with radiotherapy, we studied 10 patients with inoperable non-small cell lung cancer who were receiving hyperfractionated radiotherapy (RT) of 1.25 Gy B.I.D. (6-h interval) up to a total dose of 60 Gy/48 fractions/32 days. They were given NAC concomitantly with RT: 100 mg/kg i.v. 30 min before the first RT session followed by 30 mg/kg as an i.v. infusion over 7 h; and 600 mg inhaled 30 min before and after each RT session. The patients were assessed by serial CT scans and lung function studies during a 1-year follow-up period. The treatment regime was feasible, but expensive in time and resources. Normal tissue reactions and tumour responses were similar to those in a control group.

Sleep-related disordered breathing during pregnancy in obese women.

STUDY OBJECTIVES: This study was designed to evaluate sleep-related disordered breathing in obese women during pregnancy. Obesity is known to predispose to sleep-related breathing disorders. During pregnancy, obese mothers gain additional weight, but other mechanisms may counteract this effect. DESIGN: A case-control study to compare sleep-related breathing in obese pregnant women (mean prepregnancy body mass index [BMI] > 30 kg/m(2)) with pregnant women of normal weight (mean BMI, 20 to 25 kg/m(2)). SETTING: University teaching hospital with a sleep laboratory. PARTICIPANTS: We recruited 11 obese women (BMI, 34 kg/m(2); mean age 31 years) and 11 control women (BMI, 23 kg/m(2); mean age 32 years). INTERVENTIONS: Overnight polysomnography was performed during early (after 12 weeks) and late (after 30 weeks) pregnancy. MEASUREMENTS AND RESULTS: During pregnancy, obese mothers gained 13 kg and control women gained 16 kg. Sleep characteristics did not differ between the groups. During late pregnancy, the women in both groups slept more poorly and slept in supine position less. During early pregnancy, their apnea-hypopnea indexes (1.7 events per hour vs 0.2 events per hour; p < 0.05), 4% oxygen desaturations (5.3 events per hour vs 0.3 events per hour; p < 0.005), and snoring times (32% vs 1%, p < 0.001) differed significantly. These differences between the groups persisted in the second polysomnography, with snoring time further increasing in the obese. Preeclampsia and mild obstructive sleep apnea were diagnosed in one obese mother. One obese mother delivered a baby showing growth retardation (weight - 3 SD). CONCLUSIONS: We have shown significantly more sleep-related disordered breathing occurring in obese mothers than in subjects of normal weight, despite similar sleeping characteristics.