Neutrophil immunosurveillance for heart transplant rejection: a prospective study.

Immunologic surveillance for rejection detection in human heart transplantation offers many potential advantages. To date, investigative efforts have focused primarily on the acquired immune system, particularly the lymphocyte. Little attention has been given to aspects of innate immune function. We have previously reported that perioperative neutrophil adhesion molecule expression is associated with early rejection episodes after human cardiac transplantation. Herein we have investigated the utility of neutrophil immunosurveillance in human heart transplant recipients at later time points. We recruited patients more than 3 months after transplantation. Neutrophil assessment was performed simultaneously with an endomyocardial biopsy that showed rejection. No significant relationship was seen between neutrophil maturity (P = .622; n = 34), adhesion marker expression (P = .567; n = 34), respiratory burst (P = .604; n = 34), or apoptosis rates (P = .662; n = 34) and contemporary rejection status at >3 months after transplantation. However, interesting relationships were noted between neutrophil adhesion markers at this late stage and historical rejection status. Higher levels of the adhesion protein CD11b observed at this late stage were significantly associated with a history of higher rejection grades in the first postoperative biopsy (Spearman rank coefficient 0.359; R = 0.304; P = .005; n = 62). Other aspects of neutrophil function and persistence were not significantly associated with rejection history. This finding, combined with the previously reported findings, supports a role for an individual phenotype in neutrophil function in early rejection episodes after transplantation.

Pleuropulmonary blastoma type I following resection of incidentally found congenital lobar emphysema.

Pleuropulmonary blastoma (PPB) is an aggressive tumour accounting for less than 1% of all primary malignant lung tumours in the paediatric population. It can be associated with cystic pulmonary lesions, which may be evident at the time of diagnosis or predate the appearance of the tumour. There are contradictory reports about the value of prophylactic resection of pulmonary cysts in protecting patients from developing PPB. We report an individual case where asymptomatic congenital lobar emphysema was incidentally picked up on CXR. Following a period of surveillance the lesion was resected due to increasing size. The histology of the lesion revealed PPB Type I.

Statins alter neutrophil migration by modulating cellular Rho activity--a potential mechanism for statins-mediated pleotropic effects?

The ability of neutrophils to sense and migrate toward damaged tissue is a vital component of the innate immune response. Paradoxically, this same migration serves as the hallmark of a number of inflammatory conditions, including ischemic reperfusion injury, atherosclerosis, arthritis, and Crohn's disease. More recent evidence suggests that neutrophil infiltration into the cardiac allograft following transplantation is a contributing factor in allograft rejection. We have demonstrated previously a positive correlation between the degree of neutrophil migration and subsequent rejection grades in a cohort of cardiac transplant recipients. Intracellular signaling pathways that are intimately involved in neutrophil migration thus offer potential targets of manipulation in the treatment of such conditions. 3-hydroxy-3-methylyglutaryl-coenzyme A reductase inhibitors or statins are emerging as potential anti-inflammatory agents and have a proven survival benefit in the transplant population. Yet, little is known about their ability to modulate neutrophil function and their subsequent mechanism of action. We demonstrate here that pravastatin, simvastatin, and atorvastatin significantly reduce neutrophil transendothelial migration toward the chemoattractant fMLP. This effect is independent of any change in neutrophil adhesion or adhesion molecule expression but is related to the ability of statins to reduce fMLP-induced Rho activity in neutrophils. This was confirmed by the ability of the Rho precursor geranylgeranyl pyrophosphate to rescue the statin-mediated reduction in neutrophil transendothelial migration. Understanding the mechanisms of action of statins in the neutrophil allows for their use in targeting excessive migration in inappropriate inflammatory conditions.

Lung tissue storage: optimizing conditions for future use in molecular research.

The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P < .05) and resulted in better Test3 chips hybridization (p < .05), suggesting RNAlater was superior at preserving lung tissue nucleic acid.

A review of 15-year experience with anomalous origin of the left coronary artery.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare condition presenting in infancy with acute myocardial ischaemia. AIMS: A retrospective study was undertaken to assess the presenting features and long-term outcome of all cases of ALCAPA presenting to our institution over a 15-year period. METHODS: All the cases were located using the hospital discharge system and charts were reviewed. RESULTS: The mean age at diagnosis was 4.5 months (2 weeks to 16 months). The predominant presenting symptoms were irritability, pallor, and tachypnoea. The predominant electrocardiogram findings were Q waves and ST segment changes in the anterolateral chest leads. One died from the 11 patients in our series. CONCLUSION: The outcome for surgical re-implantation in infants with a diagnosis of ALCAPA is very good however, early diagnosis is crucial to survival. Although once successfully repaired, patients in general were free of symptoms, ventricular dysfunction was usually present, requiring long-term follow-up.

The increased need for liaison psychiatry in surgical patients due to the high prevalence of undiagnosed anxiety and depression.

BACKGROUND: Depression is the most common mental disease in patients hospitalized with physical illness. Disorders of anxiety and depression in general hospitals are frequently underdiagnosed and inappropriately treated. AIM: To assess the prevalence of undiagnosed anxiety and depression in surgical inpatients and assess the referral rate and utilization of liaison psychiatry services. METHODS: A prospective study of surgical admissions (n = 96) to two surgical services at two separate institutions between 01/01/05 and 31/12/05. The Hospital Anxiety and Depression (HADS) scale was used to evaluate all patients. RESULTS: About 12.5% of patients had significant depression, 18.75% had significant anxiety, and 8.3% had significant mixed anxiety and depression. About 22.9% of patients warranted referral to liaison psychiatry services for further assessment and management. CONCLUSIONS: Anxiety and depression are highly prevalent in surgical inpatients. An increased awareness of the possibility of undiagnosed psychiatric disorders is required, along with prompt and appropriate use of liaison psychiatry services.

Differential white cell count relationships with human cardiac allograft rejection.

The focus of research in allograft rejection has targeted the lymphocyte, with little attention given to the neutrophil. Recent data indicate that a perioperative neutrophil influx into the cardiac allograft influences early rejection. Factors that influence neutrophil transendothelial migration might offer predictive markers of rejection. We explored the relationship between the number of circulating neutrophils in heart transplant recipients and the development of rejection. Differential white cell counts were obtained prior to transplantation and concurrently with subsequent endomyocardial rejection surveillance biopsies for 53 heart transplant recipients undergoing 410 biopsies. Preoperative differential white cell counts had no relationship with rejection. In the first 3 months after transplantation, no relationship was found between contemporary differential white cell counts and rejection. However, more than 3 months following surgery, rejection grade positively correlated on univariate analysis with neutrophil counts and the usage of cyclosporine, prednisolone, and mycophenolate. There was no relationship with eosinophils or lymphocytes. Multivariate analysis demonstrated a persistent relationship among rejection severity, neutrophil count, and prednisolone usage. A significant positive association of higher steroid usage with higher rejection grades must reflect efforts to treat patients with rejection. The significant association of higher neutrophil counts with higher rejection severity might suggest a pathological contribution to rejection. However, given the neutrophilia response to acute steroid administration, we must conclude that the neutrophil association was related to steroid administration. The absence of a relationship between white cell counts and rejection suggests that functional rather than antiproliferative strategies may offer the greatest therapeutic potential.

A step towards being EWTD compliant: a single institution study of the cardiothoracic surgery experience.

The introduction of the European Working Time Directive has led to intensive debate regarding the working conditions, training and service delivery of Non Consultant Hospital Doctors. Surgical specialties are especially affected by the directive as they have always been associated with long working hours. These have been defended on the basis that these were required to achieve surgical competence. This study aims to survey the working hours and examine the activity of cardiothoracic surgery trainees, who traditionally worked long hours, in a single institution. Arising from the survey results, a novel working model is proposed.

The first 20 years of heart transplantation in Ireland.

BACKGROUND: The first Irish heart transplant was performed on the 10th of September 1985. Over the next 20 years, 229 transplants were performed in 228 recipients. AIMS: To evaluate the success of the first generation of cardiac transplantation in Ireland. METHODS: Analysis of clinical outcomes and survival statistics for patients undergoing heart transplantation in Ireland and comparison with international standards. RESULTS: There has been a steady improvement in transplant outcome over this time and survival figures for recipients between 2000 and 2004 show a hospital, 1-year and 5-year survival rate of 85.7%, 84.1% and 76.8% respectively. Thirty-eight of the 99 heart transplants performed between 1985 and 1994 are still alive more than 10 years later and the longest survivor is now 19 years post transplantation. CONCLUSIONS: The results compare favourably with international figures. Heart transplantation offers excellent longterm survival and quality of life but remains challenged by a shortage of suitable donor organs.

Traumatic rupture of the aorta in an 11-year-old patient: surgical considerations in the technique of repair.

We describe an 11-year-old child who presented with a traumatic aortic transection. This is an extremely rare occurrence in this age group. In managing the injury the future growth of the child must be considered. Primary repair is ideal when possible, but in choosing a graft, the choice of size and material should take cognisance of the risk of a coarctation-like syndrome in the future.

Heart transplant candidates: factors influencing waiting list mortality.

Cardiac transplantation is a successful treatment for end-stage heart disease. However the number of potential candidates is significantly greater then number of suitable organ donors. We reviewed the characteristics of new transplant candidates presenting for assessment for cardiac transplantation to the Irish Heart & Lung Transplant programme over a one year period. Of 44 patients referred for assessment, 24 (54.5%) were listed for cardiac transplantation. Six have died while awaiting transplantation, seven have been transplanted and eleven remain on the active transplant list. The six month survival rate on the transplant waiting list is 74%. Although the Irish system of organ donation has traditionally provided high organ donation rates in comparison with other countries, the demand for suitable heart donors exceeds supply. Newer methods of promoting and facilitating organ donation may prove beneficial in improving the number of donations and addressing the long waiting time for cardiac transplantation.

Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal impairment.

BACKGROUND: A common clinical problem following organ transplantation is the development of renal failure due to calcineurin inhibitors. Sirolimus offers the potential of providing appropriate immunosuppression without nephrotoxicity. This study evaluates the impact of sirolimus monotherapy on renal function in patients late following heart transplantation and correlates trough sirolimus levels with area-under-the-concentration time curve measurements. METHODS: Six male patients with renal impairment late following heart transplantation (mean 8 years) were offered sirolimus therapy. Calcineurin inhibition was discontinued in all patients on commencing sirolimus. Patients started on sirolimus 2 to 5 mg/d orally. Venous blood samples for pharmacokinetic studies and repeat creatinine clearance were performed before and 6 weeks after commencement of sirolimus in all subjects. RESULTS: Sirolimus trough levels accurately reflected sirolimus area-under-the-concentration time curve measurements. There was no change in renal function. Mean creatinine clearance prior to commencing sirolimus was 26.7 (12.2) mL/min and the post-sirolimus creatinine clearance performed 6 weeks later was 23.4 (11.7) mL/min (P = .64). CONCLUSIONS: Trough levels of sirolimus correlate with drug exposure and may be used to monitor sirolimus therapy. No improvement in renal function following calcineurin inhibitor withdrawal occurred in this cohort.

Calcification of homograft valves in the pulmonary circulation -- is it device or donation related?

OBJECTIVE: Homograft valved conduits are used in the reconstruction of right ventricular outflow tract (RVOT), and calcification is a recognised phenomenon in these devices. The purpose of this study was to assess the effect of type (pulmonary and aortic) and mode of harvest of these cryopreserved homografts (cadaveric and beating heart) on the incidence of calcification of these conduits when used in the pulmonary circulation. METHODS: A retrospective study was carried out on 60 patients with congenital heart defects who underwent reconstruction of RVOT using cryopreserved homograft valved conduits. The homografts were harvested from two different groups of donors; beating heart donors and cadaveric donors. The period of study was from 1st January 1990 to 31st December 2000. There were 34 males and 26 females, and the median age was 75 months. The 30-day mortality was 10 (16.7%). The 50 survivors were followed-up 3-108 months (median 36 months). Twenty-four had aortic homografts and 26 pulmonary homografts. Twenty-four devices were from cadaveric donors and 26 from beating heart donors. RESULTS: There were 10 (20%) calcified devices, all aortic in origin. In a logistic regression analysis, aortic homografts were significant risk factor for calcification (P=0.0006). However, source of harvest was not significantly related to the incidence of calcification (P=0.6). CONCLUSION: Cryopreserved pulmonary homografts placed in the right side of the heart are less likely to undergo calcification. Homografts harvested from beating heart donors do not appear to reduce the incidence of calcification.

Depression in patients with schizophrenia during an acute psychotic episode.

There is disagreement about whether depressive symptoms in schizophrenia are part of the basic disease process, or whether they represent adverse effects of treatment with antipsychotic medications. In a sample of initially antipsychotic drug-free acutely hospitalized patients with schizophrenia (N = 104), we measured change in depressive symptoms after 4 weeks of treatment. We also examined the relationship of changes in depressive symptoms to changes in positive and negative schizophrenic symptoms. Depressive symptoms improved after 4 weeks of antipsychotic medication treatment, and their improvement corresponded with improvement in both positive and negative schizophrenic symptoms. These results suggest that depressive symptoms in schizophrenia are related to the disease process itself, at least during acute exacerbations of schizophrenia. Depressive symptoms may be responsive to antipsychotic medications directly or as a secondary response to improvement in positive and negative symptoms.

A comparison of the Allen Cognitive Level Test and the Wisconsin Card Sorting Test in adults with schizophrenia.

OBJECTIVE: This study examines the relationship among executive function, visuospatial problem solving, and measures of occupational functioning in 33 adult men with schizophrenia or schizoaffective disorder. METHOD: Three measures were administered in a one-time assessment session. The Wisconsin Card Sorting Test (WCST) was used to measure executive functioning, abstract reasoning, and problem-solving abilities. The Allen Cognitive Level (ACL) Test was used to measure learning, problem solving, and visuospatial abilities. The Routine Task Inventory (RTI) measured the level of performance in activities of daily living. RESULTS: Using multiple regression controlling for age, the WCST significantly predicted performance on the ACL the RTI. Perseverative errors on the WCST were negatively correlated with the ACL (r = -.47) and RTI scores (r = -.59). The ACL and RTI were also significantly correlated (r = .67). CONCLUSION: Both the WCST and the ACL are sensitive to similar domains of functioning and are predictive of task performance. The results support the use of the ACL as a quick measure of a person's cognitive and functional abilities.

Striae and acne following cardiac surgery in a child.

We report a 13-year-old girl with extensive striae and an acneiform eruption following surgery for complex congenital heart disease. These findings were associated with elevated serum and urinary cortisol levels with loss of diurnal rhythm. The resolution of the eruption and the fading of her striae coincided in time with normalization of her blood parameters on day 72 postoperatively. We conclude that the cause of steroid excess in our patient was stress induced by the cardiac surgery and a complicated and protracted postoperative course. To our knowledge, this is the first report in the English language literature of skin changes due to endogenous hypercortisolaemia caused by intense physical and emotional stress.

Long-term clinical outcome following coronary artery bypass grafting for isolated stenosis of the left anterior descending coronary artery.

AIMS: To detail the clinical and angiographic profile, and long-term outcome in consecutive patients with isolated stenosis of the left anterior descending coronary artery undergoing bypass surgery. METHODS: A retrospective study of all patients (n = 301) (January 1984-December 1990) and undergoing coronary artery bypass grafting for isolated left anterior descending disease, in the Irish Republic, was performed. Survival was compared with that of an exact age- and gender-matched cohort. RESULTS: Mean age was 53 (+/- 9.3) years. There were 238 (79%) males. In 241 (80%) patients an internal thoracic arterial bypass graft was used. Operative mortality was 1.3%. Of the 280 (93%) patients alive (16 cardiac deaths) at 7.1 (+/- 1.9) years, 105 (35%) had angina, 26 (9%) suffered an interval myocardial infarction, and repeat revascularization was required on 29 (10%). Female gender (P = 0.002), pre-operative myocardial infarction (P = 0.02), significant diagonal disease (P = 0.04) and postoperative myocardial infarction (P = 0.0001) were independently associated with survival. Females were more likely to develop congestive cardiac failure (P = 0.01) or postoperative angina (P = 0.03) than their male counterparts. CONCLUSIONS: Survivorship (97%) and event-free survival (96%) at 5 years following coronary artery bypass grafting for isolated left anterior descending coronary artery disease is excellent and equivalent to an age-matched and gender-matched cohort.