Brendan P. Madden

Experience with Ultraflex expandable metallic stents in the management of endobronchial pathology.

BACKGROUND Experience with Ultraflex expandable metallic stents (Micro-invasive, Boston Scientific, Watertown, MA) in the management of endobronchial pathologies leading to airway compromise is reported. METHODS Between January 1999 and August 2000, twenty-eight expandable metallic stents were inserted into 25 patients (7 men and 18 women; median age, 65 years) who presented with respiratory distress. Each patient had comorbid medical conditions or end-stage malignancy that precluded formal surgical repair. Seventeen patients had intrinsic airway obstruction, 5 had extrinsic compression, 2 had a tracheal tear, and 1 had a tracheoesophageal fistula. Stents were inserted through a bronchoscope under direct vision. Eighteen patients received tracheal stents alone (1 of these patients received two tracheal stents), and 5 patients received bronchial stents only. Two patients received a tracheal and a bronchial stent. Twenty-one stents were covered and seven were uncovered. RESULTS All patients had successful stents with restoration of airway patency and closure of tracheal defects. One patient developed a respiratory infection early after the operation. Follow-up bronchoscopy confirmed satisfactory stent position in each patient. Late complications included sputum retention, halitosis, and granulation tissue formation. CONCLUSIONS Ultraflex expandable metallic stents should be considered in the management of airway compromise in selected patients for whom formal surgical repair is inappropriate or contraindicated.

Immunohistologic evidence of myocardial disease in apparently healthy relatives of patients with dilated cardiomyopathy

OBJECTIVES This study investigated whether apparently healthy relatives of patients with idiopathic dilated cardiomyopathy (DCM) who have left ventricular enlargement (LVE) have biopsy evidence of underlying myocardial disease. BACKGROUND Left ventricular enlargement with normal systolic function is common among asymptomatic relatives of patients with DCM. Although there is circumstantial evidence to suggest that LVE may be a marker of early DCM, its pathophysiologic significance remains uncertain. METHODS Over six years, 767 asymptomatic relatives of 183 consecutive patients with DCM were evaluated: 37 (5%) had DCM and 104 (14%) had LVE (left ventricular end-diastolic dimension >112% predicted) with normal systolic function. Right ventricular biopsy was performed in 32 relatives with LVE, 14 patients with symptomatic DCM and 6 control subjects with normal ventricular function undergoing elective coronary artery bypass graft surgery. Histologic and immunohistochemical analyses, including quantitative double immunofluorescence, were performed for leukocyte markers (CD3 and CD68), intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen class II antigens (DR and DQ). RESULTS Histologic findings consistent with DCM were present in 50% of the patients with DCM, 25% of the relatives with LVE and 0% of the control subjects. The median CD3 count was 2.4/mm(2) in patients with DCM, 4/mm(2) in relatives with LVE and 0 in control subjects (p = 0.04). Using a threshold of >7 cells/mm(2), 21% of patients with DCM and 25% of relatives with LVE were CD3-positive (p = 0.01). Quantitative analysis demonstrated DR expression on 55.8+/-22.8%, 63.5+/-18.8% and 30.9+/-15.7% of the endothelial surface in patients with DCM, relatives and control subjects, respectively (p = 0.003). Corresponding values for ICAM expression were 35.6+/-15.1%, 36.7+/-14.5% and 17.3+/-7.9% (p = 0.013). When combining inflammatory and histologic changes, 28 (86%) of LVE, 14 (100%) of DCM and no control biopsies were abnormal (p < 0.001). CONCLUSIONS Most asymptomatic relatives of patients with DCM with LVE have histopathologic and immunopathologic findings similar to those of patients with established disease. Clinical identification and follow-up of such individuals are warranted to prevent presentation with advanced DCM and to enable assessment of interventions aimed at attenuating disease progression.

Myocyte loss in chronic heart failure.

This study examined whether or not there is progressive loss of individual myocytes in established heart failure, accounting for the progressive left ventricular dysfunction; whether such loss is by necrosis or apoptosis; and whether such loss is more pronounced in ischaemic heart disease or idiopathic dilated cardiomyopathy. Tissue for patients undergoing cardiac transplantation for clinical end‐stage heart disease was used. The clinical diagnosis was not known to the observer at the time of analysis. Indices of potential myocyte loss were: detection of apoptotic nuclei in situ, using the TUNEL method, immunohistochemistry for CD120a, CD120b, CD95, perforin and granzyme B; binding of C9 complex; and lipofuscin deposition within macrophages. Interstitial macrophages and T cells and their relationship to myocyte loss were also examined. There is indeed low grade myocyte loss in chronic heart failure, but there was no difference between the disease groups; rather, there was marked patient‐to‐patient variation within each category. Thus in chronic heart failure myocyte loss does occur, and both necrosis and apoptosis contribute to this loss, irrespective of the underlying nature of the disease. Any mechanism which accounts for myocyte loss must be common to both conditions, rather than specific for a pre‐operative diagnosis. Copyright

Successful resection of obstructing airway granulation tissue following lung transplantation using endobronchial laser (Nd-YAG) therapy

OBJECTIVE Airway obstruction due to an excessive growth of granulation tissue at the level of the anastomosis is an important complication following lung transplantation which requires early diagnosis and treatment. We report encouraging experience in the management of this condition using endobronchial Nd:YAG laser therapy. METHODS Four adult lung transplant recipients developed airway anastomotic obstruction secondary to granulation tissue formation at 9, 10, 32 and 32 days following bilateral sequential lung transplantation (2 patients), en bloc double lung transplantation (1 patient) and single lung transplantation (1 patient). The diameter of the airways at the level of the anastomoses was reduced by 75, 30, 60, 60, 50 and 90%, respectively. Endobronchial Nd:YAG laser was applied via a fiberoptic bronchoscope introduced through a rigid bronchoscope. The granulation tissue was visualised and resected with photocoagulation with the laser using between 1000-2000 J depending on the amount of tissue present. Necrotic tissue was removed with large forceps. If the obstruction extended to the orifice of a lobar bronchus resection was undertaken in a staged fashion. RESULTS Airway patency was fully restored at two anastomotic sites, and restored to 90% patency at two and 80 and 75% at one each, respectively. This was associated with a significant improvement in pulmonary function in 3 patients. One patient had a subsequent bougie dilatation of a stenotic area and 2 patients received an endobronchial stent for tracheo or broncho-malacia. One patient died from a gastrointestinal haemorrhage. Three patients are well at 10, 17 and 18 months following transplantation and have no further granulation tissue recurrence. There were no complications directly attributable to laser therapy. CONCLUSION Our encouraging early experience leads us to suggest that Endobronchial Nd-YAG laser therapy should be considered in the management of airway anastomotic obstruction due to excessive granulation tissue formation after lung transplantation.

Regional Variations in Endothelin-1 and its Receptor Subtypes in Human Coronary Vasculature: Pathophysiological Implications in Coronary Disease

Endothelin-1 is a potent vasoconstrictor peptide and mitogen for vascular smooth muscle cells. Increased plasma or tissue levels of endothelin-1 have been described after myocardial infarction and in atherosclerosis, suggesting that this peptide may play a pathophysiological role in various coronary syndromes. Here, we have studied regional variations in ET-1 and its receptors in control and atherosclerotic human coronary vasculature using standard immunohistochemistry and in vitro autoradiography. ET-1 immunoreactivity was associated with luminal endothelial cells and smooth muscle cells at regions of atherosclerosis. ET(A) receptors were present on smooth muscle cells of coronary arteries and on cardiac myocytes. Medial ET(B) receptor binding at the proximal region of coronary arteries was weak, but increased significantly towards distal regions of this vessel (p<0.005 in control and p<0.0005 in ischaemic heart disease). Microvascular endothelial cells in the adventitia of coronary arteries, myocardial microvessels and the endocardial endothelium expressed the ET(B) receptor exclusively. The receptor variations revealed in this study provide supporting evidence that ET-1 is associated with (1) vascular smooth muscle and endothelial cell proliferation, including areas of intimal hyperplasia and regions of neovascularization (2) increased ET-1-induced reactivity of distal portions of the human coronary artery, (3) ET-1-mediated constriction of myocardial microvessels. These results provide new insights into different potential roles for this peptide in healthy and diseased human coronary vasculature.

Dual-Energy CT for Imaging of Pulmonary Hypertension: Challenges and Opportunities

Computed tomography (CT) is routinely used in the evaluation of patients with pulmonary hypertension (PH) to assess vascular anatomy and parenchymal morphology. The introduction of dual-energy CT (DECT) enables additional qualitative and quantitative insights into pulmonary hemodynamics and the extent and variability of parenchymal enhancement. Lung perfusion assessed at pulmonary blood volume imaging correlates well with findings at scintigraphy, and pulmonary blood volume defects seen in pulmonary embolism studies infer occlusive disease with increased risk of right heart dysfunction. Similarly, perfusion inhomogeneities seen in patients with PH closely reflect mosaic lung changes and may be useful for severity assessment and prognostication. The use of DECT may increase detection of peripheral thromboembolic disease, which is of particular prognostic importance in patients with chronic thromboembolic PH with microvascular involvement. Other DECT applications for imaging of PH include low-kilovoltage images with greater inherent iodine conspicuity and iodine-selective color-coded maps of vascular perfusion (both of which can improve visualization of vascular enhancement), virtual nonenhanced imaging (which better depicts vascular calcification), and, potentially, ventricular perfusion maps (to assess myocardial ischemia). In addition, quantitative assessment of central vascular and parenchymal enhancement can be used to evaluate pulmonary hemodynamics in patients with PH. The current status and potential advantages and limitations of DECT for imaging of PH are reviewed, and current evidence is supplemented with data from a tertiary referral center for PH.

Thrombolysis for massive pulmonary embolism in pregnancy - A report of three cases and follow up over a two year period

We read with interest the recent literature review submitted by te Raa et al regarding treatment options in massive pulmonary embolism during pregnancy [1]. As highlighted venous thromboembolism is a leading cause ofmaternal mortality in the UK [2]. Treatment options for pregnant patients that develop pulmonary embolism are often considered high risk with possible effects to both mother and foetus. We describe our total experience of thrombolysis for the treatment of massive PE in pregnancy over the last 5 years.

Tacrolimus as a rescue immunosuppressant after heart transplantation

OBJECTIVE The purpose of this retrospective study is to review our experience with tacrolimus as a rescue immunosuppressant for heart transplant recipients with refractory rejection or cyclosporine intolerance. METHODS From June 1995 to November 1998, 15 cardiac transplant recipients were converted from our standard cyclosporine-based immunosuppressive regimen to a tacrolimus-based treatment. Each patient had been treated with cyclosporine, azathioprine and steroids. Six were switched to tacrolimus for persistent rejection, four for recurrent acute rejection and five for severe debilitating side-effects attributed to cyclosporine. All ten patients converted to tacrolimus because of rejection had been treated with high-dose methylprednisolone intravenously and four had also received anti-lymphocyte globulin (ALG; one patient) or anti-thymocyte globulin (ATG; three patients) preparations. RESULTS The time between transplantation and conversion to tacrolimus ranged from 44 to 1866 (median, 380) days. The range of follow-up after conversion was 84-1379 (median, 806) days. Eleven patients are alive with a follow-up period of 764+/-435 (median, 820) days. Four patients died between 90 and 930 (median, 464) days after conversion. The average number of episodes of acute rejection/recipient decreased from 2.1+/-1.6 on the cyclosporine regimen to 0.2+/-0.4 on the tacrolimus regimen (P<0.001). When the incidence of acute rejection was normalized for follow-up times (episodes/100 patient-days), the results were 1.1+/-1.4 and 0.07+/-0.2, respectively (P<0.01). The persistent/recurrent rejection resolved in all ten patients who were converted to tacrolimus. None of the five cyclosporine intolerant patients converted to tacrolimus experienced rejection after the changeover. CONCLUSIONS In our experience, conversion from a cyclosporine-based to a tacrolimus-based maintenance immunosuppression has been shown to be an effective and safe approach to the management of patients with persistent or recurrent cardiac allograft rejection or those with cyclosporine intolerance.

A retrospective review to evaluate the safety of right heart catheterization via the internal jugular vein in the assessment of pulmonary hypertension.

Right heart catheterization (RHC) is important in the evaluation of pulmonary hypertension, but is not without risk.

A review of the health effects of smoking shisha

There is emerging evidence, although at early stages, of various detrimental health effects after smoking shisha. With regard to the cardiovascular system, there is a significant acute rise in cardiovascular markers, such as heart rate and blood pressure. The long-term effects on the cardiovascular system are yet to be established. Shisha smoking has also been significantly associated with lung cancer. Various other forms of cancer have also been documented, but have not reached statistical significance and require further research. Finally, shisha smoking increases the risk of infection and has been associated with outbreaks in the Middle East. Therefore, with the increasing consumption of shisha in Europe, especially in the UK, more research is required to tackle this potential public health threat.