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There are numerous conflicting epidemiological studies addressing correlations between cytochrome P450 1A1 (CYP1A1) genetic polymorphisms and lung cancer susceptibility, with associations plausibly linked to alterations in carcinogen bioactivation. Similarly, correlations between aryl hydrocarbon receptor gene (AHR) codon 554 genotype and CYP1A1 inducibility are controversial. The objective of this study was to determine whether smoking status, and CYP1A1, AHR, and glutathione S-transferase M1 gene (GSTM1) polymorphisms correlate with altered CYP1A1 activities. Lung microsomal CYP1A1-catalyzed 7-ethoxyresorufin O-dealkylation (EROD) activities were much higher in tissues from current smokers (n = 46) than in those from non-/former smokers (n = 24; 12.11 +/- 13.46 and 0.77 +/- 1.74 pmol/min/mg protein, respectively, mean +/- SD; P0.05). However, EROD activities in lung microsomes from current smokers CYP1A1*1/1 (n = 33) and heterozygous MspI variant CYP1A1*1/2A (n = 10) were not significantly different (12.23 +/- 13.48 and 8.23 +/- 9.76 pmol/min/mg protein, respectively, P0.05). Three current smokers were heterozygous variant CYP1A1*1/2B (possessing both *2A and *2C alleles), and exhibited activities similar to individuals CYP1A*1/1. One current smoker was heterozygous variant CYP1A1*4 and exhibited activities comparable with individuals CYP1A1*1/1 at that locus. EROD activities in microsomes from current smokers AHR(554)Arg/Arg (n = 41) and heterozygous variant AHR(554)Arg/Lys (n = 5) were not significantly different (12.13 +/- 13.56 and 12.01 +/- 14.23 pmol/min/mg protein, respectively; P0.05). Furthermore, microsomal EROD activities from current smokers with the GSTM1-null genotype (n = 28) were not significantly different from those (n = 18) carrying at least one copy of GSTM1 (12.61 +/- 14.24 and 11.34 +/- 12.53 pmol/min/mg protein, respectively; P0.05). Additionally, when genotypic combinations of CYP1A1, AHR, and GSTM1 were assessed, there were no significant effects on EROD activity. On the basis of microsomal enzyme activities from heterozygotes, CYP1A1*1/2A, CYP1A1*1/2B, CYP1A1*1/4, and AHR(554) Arg/Lys variants do not appear to significantly affect CYP1A1 activities in human lung, and we observed no association between CYP1A1 activity and the GSTM1-null polymorphism.

BACKGROUND: Descending necrotising mediastinitis is caused by downward spread of neck infection and has a high fatality rate of 31%. The seriousness of this infection is caused by the absence of barriers in the contiguous fascial planes of neck and mediastinum. METHODS: The recent successful treatment of seven adult patients with descending necrotising mediastinitis emphasises the importance of optimal early drainage of both neck and mediastinum and prolonged antibiotic therapy. The case is also presented of a child with descending necrotising mediastinitis, demonstrating the rapidity with which the infection can develop and lead to death. Twenty four case reports and 12 series of adult patients with descending necrotising mediastinitis published since 1970 were reviewed with meta-analysis. In each case of confirmed descending necrotising mediastinitis the method of surgical drainage (cervical, mediastinal, or none) and the survival outcome (discharge home or death) were noted. The chi 2 test of statistical significance was used to detect a difference between cases treated with cervical drainage alone and cases where mediastinal drainage was added. RESULTS: Cervical drainage alone was often insufficient to control the infection with a fatality rate of 47% compared with 19% when mediastinal drainage was added (p < 0.05). CONCLUSIONS: Early combined drainage with neck and chest incisions, together with broad spectrum intravenous antibiotics, should be considered standard care for this disease.

A case of blunt extraperitoneal rupture of the right hemidiaphragm and an accompanying abnormal hepatobiliary scan that revealed the rupture are presented. Associated major injuries, the fact that right-sided ruptures have less immediate herniation, and plugging of the defect by the liver are difficulties that can be encountered in establishing the diagnosis. Most diagnostic tests are not helpful and about half of these ruptures are found at laparotomy or thoracotomy. All should be closed surgically.

Despite advances in immunosuppressive therapy and prolonged graft and patient survival, infection after heart transplantation remains problematic. From January 1987 through June 1989, 104 heart transplantations were performed in 100 patients. Immunosuppression induction was by antilymphocyte globulin for 7 days, with oral cyclosporine introduced on stabilization of kidney function (day 3). Steroid therapy was rapidly tapered, and azathioprine was added only in cases of positive donor crossmatch or steroid-resistant rejection. No reverse isolation was used. Twenty-two deaths occurred, one from sepsis. Actuarial survival at 6 months, at 1 year, and at 2 years was 85% +/- 4%, 81% +/- 3%, and 75% +/- 4%, respectively. Fifty-four patients had 81 infections, of which 21 were bacterial; 83% of these episodes were treated. Sixty infections were opportunistic (85% viral), and only 23% necessitated treatment. Actuarial infection-free rates (all types necessitating treatment) at 1 month, at 6 months, and at 2 years were 83% +/- 4%, 75% +/- 5%, and 75% +/- 5%, respectively. Of the 100 transplant recipients, 66% were treated with azathioprine; 47 patients (69%) had an infection, whereas only seven (19%) of the patients not receiving azathioprine became infected (p less than 0.00001). Rejection was noted in 66% of patients, with a median time to the first episode of 4 weeks. A low-intensity immunosuppressive regimen has resulted in fewer serious infections, with acceptable graft loss from rejection. Increased infection surveillance is required for the first 30 days postoperatively and after treatment of rejection episodes.

The role of prostaglandin E1 (PgE1) and prostacyclin in enhancing the ischemic tolerance of single-lung grafts was investigated. Fifteen donor dogs underwent pulmonary artery flushing with 60 mL/kg of 4 degrees C modified Euro-Collins solution; 5 dogs each received a 15-minute infusion of PgE1, prostacyclin, or saline solution before flushing. After 12 hours of storage at 4 degrees C, left lung transplantation was performed in 15 recipient dogs. Measurements were performed after 10 minutes of right pulmonary artery snaring before transplantation, after transplantation, and after 2, 4, and 6 hours of reperfusion. At 6 hours, the oxygen tensions (on 100% O2) were 478 +/- 64, 296 +/- 75, 79 +/- 12, and 71 +/- 23 mm Hg in control (nontransplanted), prostacyclin-, PgE1-, and saline-treated dogs, respectively (p less than 0.05, prostacyclin or control versus saline and PgE1 dogs). Mean pulmonary artery pressures increased within each group during reperfusion, but were not significantly different among groups. Similarly, peak inspiratory pressures and wet weight to dry weight ratios were not significantly different among groups after 6 hours of reperfusion. We conclude that donor pretreatment with prostacyclin is associated with superior oxygen transfer in canine lung allografts after 12 hours of cold storage, transplantation, and 6 hours of reperfusion. In this model, donor pretreatment with PgE1 conferred no benefit to prolonged lung allograft preservation.

The results of heart-lung transplantation are improving with increasing experience in postoperative management, but obliterative bronchiolitis may still develop late postoperatively. We have performed 19 heart-lung transplants, with 1-month, 1-year, and 2-year actuarial survival rates of 95% +/- 5%, 84% +/- 8%, and 69% +/- 16%, respectively. Three early recipients died of bronchiolitis, and four patients who were operated on more than 2 years ago are currently being followed up with bronchiolitis. Since August 1988, 13 surviving recipients have undergone serial postoperative bronchoscopies and transbronchial biopsies with topical analgesia. Diffuse bronchomalacia, involving the main bronchi down to the fifth-order bronchi bilaterally, has developed in four patients with bronchiolitis 9 +/- 2 months after the diagnosis of bronchiolitis was confirmed. Pulmonary function tests have revealed a lower ratio of forced expiratory volume in 1 second to forced vital capacity, lower specific airway conductance, and higher airway resistance in heart-lung recipients with bronchomalacia than in patients with bronchiolitis alone. We conclude that diffuse bronchomalacia occurs frequently in heart-lung transplant recipients who have obliterative bronchiolitis. Bronchomalacia worsens the functional airflow obstruction caused by bronchiolitis and may play an important role clinically in the declining respiratory status of heart-lung transplant recipients.

To reduce perioperative hemorrhage following heart-lung transplantation, several technical modifications were introduced in June 1988 to secure better posterior mediastinal hemostasis. The intraoperative and postoperative use of blood and blood products, as well as the chest tube drainage in the first 24 hours postoperatively, were compared in the seven patients operated on since June 1988 with the nine patients operated on before that date. Significant (p less than 0.05) reductions were demonstrated in the intraoperative and postoperative transfusion of packed cells, in the postoperative administration of fresh frozen plasma, and in the chest tube drainage within the first 24 hours postoperatively. The one-month and total hospital mortality rates were 6 percent and 12.5 percent, respectively. It is concluded that newer techniques to obtain optimal posterior mediastinal hemostasis have significantly reduced blood loss following heart-lung transplantation in our experience and have contributed to our excellent early postoperative results.

The aim of this paper is to give a short but comprehensive review of the development, current nature and future of long distance passenger transport in Australia. Although the slant of the paper is essentially economic, data limitations for parts of some modes preclude a more technical analysis than the essentially descriptive approach followed. The paper is entitled Long Distance Passenger Transport because in Australia intercity transport is the dominant component of long distance passenger transport.