Complex coarctation of the aorta requiring a third redo operation.

Coarctation of the aorta can require multiple redo surgeries. It is extremely pertinent to plan for this and ensure that each operation is performed with future repair in mind. We present a rare case and the subsequent management of competitive flow in coarctation of the aorta requiring a fourth operation for repair.

Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation.

BACKGROUND: Transforming growth factor (TGF)-beta1 is a profibrogenetic cytokine that has been implicated in the development of fibrosis in transplanted tissues. In this study, we have analyzed the genetic regulation of TGF-beta1 production in lung transplant recipients. METHOD: A polymerase chain reaction-single-stranded conformational polymorphism technique was used to detect polymorphisms in the TGF-beta1 gene from genomic DNA. Polymorphisms were shown to correlate with in vitro TGF-beta1 production by stimulated lymphocytes. A single-specific oligonucleotide probe hybridization method was devised to screen for these polymorphisms in lung transplant groups and controls. RESULTS: We have identified five polymorphisms in the TGF-beta1 gene: two in the promoter region at positions -800 and -509, one at position +72 in a nontranslated region, and two in the signal sequence at positions +869 and +915. The polymorphism at position +915 in the signal sequence, which changes codon 25 (arginine-->proline), is associated with interindividual variation in levels of TGF-beta1 production. Stimulated lymphocytes of homozygous genotype (arginine/arginine) from control individuals produced significantly more TGF-beta1 in vitro (10037+/-745 pg/ml) compared with heterozygous (arginine/proline) individuals (6729+/-883 pg/ml; P<0.02). In patients requiring lung transplantation for a fibrotic lung condition, there was an increase in the frequency of the high-producer TGF-beta1 allele (arginine). This allele was significantly associated with pretransplant fibrotic pathology (P<0.02) (n=45) when compared with controls (n=107) and with pretransplant nonfibrotic pathology (P<0.004) (n=50). This allele was also associated with allograft fibrosis in transbronchial biopsies when compared with controls (P<0.03) and with nonallograft fibrosis (P<0.01). CONCLUSION: The production of TGF-beta1 is under genetic control, and this in turn influences the development of lung fibrosis. Hence, the TGF-beta1 genotype has prognostic significance in transplant recipients.

CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis.

Interferon-gamma (IFN-gamma) is an inflammatory cytokine that has been implicated in the development of fibrosis in inflamed tissues. In this study we have analysed the association between genetically-determined high IFN-gamma production and development of fibrosis in lung transplants. The human IFN-gamma gene has a variable length CA repeat in the first intron. Our previous study showed that polymorphism of this microsatellite is associated with individual variation in the levels of IFN-gamma production. In vitro production of IFN-gamma showed significant correlation with presence of allele #2 (p < 0.01). In this study allele #2 was found to be associated with allograft fibrosis defined by transbronchial biopsy. An analysis of two groups of lung transplant recipients showed a significant increase in the frequency of allele #2 in the group which developed fibrosis after transplantation compared to the group that did not (p < 0.005). We postulate that the production of IFN-gamma, which is under genetic control, can influence the development of fibrosis in lung allografts.

Orthotopic cardiac transplantation: a comparison of standard and bicaval Wythenshawe techniques.

We describe an alternative technique for orthotopic cardiac transplantation (bicaval Wythenshawe technique), which maintains the right and left atrial anatomy. We compared the new bicaval technique with the conventional (Lower and Shumway) technique of orthotopic cardiac transplantation to identify any beneficial physiologic and clinical outcomes resulting from maintaining the normal anatomy. Seventy-five patients were randomized on an alternate basis to two groups: group A (n = 40) had orthotopic cardiac transplantation with the bicaval technique and group B (n = 35) had conventional orthotopic heart transplantation. All patients were studied with transthoracic echocardiogram, endomyocardial biopsies, and measurement of intracardiac pressures 1, 4, and 12 weeks after transplantation. There were no statistically significant differences in the demographic profile, ischemic time, bypass time, implantation time, transpulmonary gradient, or pulmonary vascular resistance between the two groups. The hemodynamic data were collected in the absence of histologic signs of rejection. In group A right atrial pressure (mean 3.6 mm Hg) was significantly lower (p < 0.03) than in group B (mean 8.8 mm Hg). The right atrial a wave was recorded in 38 patients in group A compared with seven patients in group B (p = 0.041). Atrial tachyarrhythmias occurred in two patients in group A compared with 11 in group B (p < 0.016). Temporary pacing was required in 10 patients in group A and 16 patients in group B (p = 0.034). Four cases of mitral regurgitation (all mild) were detected in group A in comparison with 12 cases (10 mild, 2 severe) in group B (p = 0.008). The mean ejection fraction in the first week after transplantation was 58% in group A and 46% in group B (p = 0.5). In the first 3 months the need for diuretics was less in group A (mean dose 80.8 mg furosemide daily) than in group B (mean dose 134 mg furosemide daily in the first week increasing to 160 mg furosemide daily). Hospital stay was shorter in group A (mean 23 days) than in group B (mean 27 days) (p < 0.015). There were no early deaths as a result of right ventricular failure in group A (n = 0/40) compared with four (n = 4/35; 9%) in group B (p < 0.034). This difference suggests that bicaval orthotopic cardiac implantation is associated with a lower right atrial pressure, a lower likelihood of atrial tachyarrhythmias, less need for pacing, less mitral incompetence, a lower diuretic dose, and a shorter hospital stay.(ABSTRACT TRUNCATED AT 400 WORDS)

Orthotopic heart transplantation hemodynamics: does atrial preservation improve cardiac output after transplantation?

BACKGROUND: We have described an alternative technique for orthotopic heart transplantation (bicaval Wythenshawe technique) which maintains the right and left atrial anatomy and contractility. METHODS: Fifty patients were randomized into two groups: group A (n = 25) who had orthotopic heart transplantation using the bicaval Wythenshawe technique and group B (n = 25) who had conventional (Lower and Shumway) technique of orthotopic heart transplantation. We compared the cardiac output (measured by thermodilution technique) with atrial activation (AAI pacing) to cardiac output without atrial activity (VVI pacing) in both groups to identify any beneficial hemodynamic effects. All patients were studied the first and second weeks after transplantation. The inaccuracies of comparing cardiac output measurements caused by different loading conditions, inotropic state, and systemic vascular resistance were eliminated by using the patient as his or her own control. RESULTS: The difference between the measured cardiac output with atrial pacing and ventricular pacing was 1.42 +/- 0.44 L/min in group A in comparison with 0.32 +/- 0.4 L/min in group B (p = 0.001 Wilcoxon signed rank). The percentage of atrial contribution to the cardiac output in group A was 30% +/- 12% (standard deviation), 95% confidence interval in comparison with 7% +/- 9%, 95% confidence interval in group B. The mean stroke volume in group A was higher in sinus rhythm (65 +/- 19.2 ml) and atrial pacing (62 +/- 17.7 ml) compared with ventricular pacing (49.17 +/- 16.43 ml) p = 0.001. In group B no statistical difference was found between stroke volume measured with atrial (47.71 +/- 6.23 ml) or ventricular pacing (46.9 +/- 6.35 ml). CONCLUSIONS: We conclude that the bicaval technique of orthotopic heart transplantation preserve the atrial kick and its contribution to cardiac output early after transplantation.

Single lung transplantation for emphysema: predictors for native lung hyperinflation.

BACKGROUND: Single lung transplantation is an established procedure for the treatment of respiratory failure resulting from emphysema. Initial concerns suggested that ventilation/perfusion mismatch may result in an unsatisfactory outcome, but good clinical results proved those concerns to be unfounded. However, a proportion of patients have had development of native lung hyperinflation (NLH), with increased morbidity and mortality rates. This study was undertaken to evaluate the factors that might predict those patients with emphysema who are at greatest risk for development of NLH. METHODS: We retrospectively analyzed data from 27 patients who underwent 31 single lung transplantations for emphysema. The patients were divided into two groups: group A, 12 patients with development of acute or chronic NLH, and group B, 15 patients without development of hyperinflation. NLH was defined as radiologic mediastinal shift with flattening of the ipsilateral diaphragm associated with respiratory dysfunction or hemodynamic instability. All preoperative and postoperative data from recipients and data from donors were analyzed. RESULTS: There were no differences between the two groups regarding age, preoperative partial pressure of oxygen, partial pressure of carbon dioxide, acid-base status, donor lung size and physiological structure, side of transplantation, primary pathologic condition, rejection score, infection episodes and obliterative bronchiolitis in the transplanted lung after operation. Patients with NLH had a significantly higher preoperative mean pulmonary artery pressure of 31.6 mm Hg (confidence interval [CI] 26.7 to 35.7), transpulmonary gradient of 20.5 mm Hg (CI 17.4 to 23.5), a lower mean forced expiratory volume in 1 second of 427 ml (CI 352 to 502), and higher mean residual volume of 4450 ml (CI 3769 to 5132). The duration of ventilation, 168 hours (CI 45 to 290), and the postoperative mean pulmonary artery pressure of 26 mm Hg (CI 23 to 28.7) are significantly higher in the hyperinflation group. Early death in group A (n = 5) was higher than in group B (no deaths) (p = 0.02). Six patients in group A required surgical treatment (two early native lung volume reductions, two early ipsilateral retransplantations, and two late contralateral transplantations). Group A patients tended to have poorer long-term lung function after transplantation, with reduced forced expiratory volume in 1 second, forced vital capacity, and higher residual volume (p = NS). CONCLUSION: Patients with end-stage emphysema and relative pulmonary hypertension, severe airway obstruction, and air trapping are at greatest risk for development of early and late NLH. In this subgroup of patients, an alternative treatment strategy may be considered.

Transforming growth factor beta (TGF-beta) and obliterative bronchiolitis following pulmonary transplantation.

BACKGROUND: Obliterative bronchiolitis (OB) characterised by small-airway fibrosis is a major cause of morbidity and mortality after lung transplantation. TGF-beta has been implicated in the pathogenesis of fibrosis. METHODS: We immunohistochemically examined 380 transbronchial biopsies (from 91 pulmonary transplants) using TGF-beta polyclonal antibodies. OB and interstitial fibrosis were diagnosed and graded in all biopsies. Other potential histologic and clinical risk factors for OB were analysed. RESULTS: Procedures were heart and lung (n = 32), bilateral sequential lung (n = 18), and single lung transplantation (n = 41). The incidence of OB in this group was 28.5%. In all patients with OB, TGF-beta was immunolocalized in the airways and lung parenchyma. TGF-beta expression was greater in OB patients (median score 8, range 5-12) in comparison to patients without OB (median score 4, range 1-13), p < .0001. Positive TGF-beta staining preceded the histologic confirmation of OB by 6 to 18 months. The development of OB was associated with two HLA mismatches at the A locus (p = .02); recurrent acute rejection episodes (p < .0005); lymphocytic bronchiolitis (p = .0001); and tissue eosinophilia, regardless of the rejection grade (p < .0001). CONCLUSIONS: Increased expression of TGF-beta is a risk factor for the development of OB. Other risk factors are recurrent acute rejection, lymphocytic bronchiolitis, tissue eosinophilia, and two mismatches at the HLA-A locus. This suggests that the pathogenesis of progressive small airway fibrosis characteristic of OB may be inflammatory damage, followed by an aberrant repair process due to excessive TGF-beta production following allograft injury. Hence, modulation of TGF-beta levels or function by antagonists may represent an important approach to control OB.

Transforming growth factor-beta (TGF-beta1) genotype and lung allograft fibrosis.

BACKGROUND: TGF-beta1 is a prosclerotic cytokine implicated in fibrotic processes. Fibrosis of the pulmonary parenchyma and airways is a frequent presentation in lung transplant recipients before and after transplantation. There are two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located at codon 10 (either leucine or proline) and at codon 25 (either arginine or proline). The codon 25 arginine allele is associated with higher TGF-beta1 production by cells activated in vitro. We tested the hypothesis that inheritance of alleles of the TGF-beta1 gene conferring higher production of TGF-beta1 may be responsible for over-expression of TGF-beta1 in transplant recipients resulting in lung allograft fibrosis. METHODS: We extracted DNA from leukocytes collected from 91 pulmonary transplants performed at our centre and 96 normal healthy volunteers between May 1990 and September 1995. Part of the first exon was amplified by PCR. Samples were genotyped by using sequence specific oligonucleotide probes. RESULT: The distribution of codon 10 alleles was similar in a normal healthy control group and in lung transplant recipients, regardless of their pretransplant lung pathology. By contrast, there was a significant difference in the frequency of codon 25 alleles between the control and transplant groups. In the normal control group 81% were codon 25 arginine/arginine (A/A) homozygotes, 19% were arginine/proline (A/P) heterozygotes and none were proline/proline (P/P) homozygotes. The distribution of codon 25 alleles was similar in lung transplant recipients who did not have a significant fibrosis in pretransplant pathology, but in transplant recipients who came to transplantation with lung fibrosis 98% (41 of 42 patients) were homozygous for the codon 25 A/A allele (p < .05). After lung transplantation 39 of 91 patients developed lung allograft fibrosis, and of these 92.3% (36 of 39 recipients) were of homozygous codon 25 A/A high TGF-beta1 producer genotype (p < .001). Lung transplant recipients who were homozygous for both codon 10 L/L and codon 25 A/A showed poor survival compared with all other TGF-beta1 genotypes (p < .03). CONCLUSION: Homozygosity for arginine at codon 25 of the leader sequence of TGF-beta1 that correlates with higher TGF-b production in vitro, is associated with fibrotic lung pathology before lung transplantation and with the development of fibrosis in the graft. In combination with the codon 10 leucine allele, homozygosity for the codon 25arginine allele is a marker for poor post-transplant prognosis and recipient survival.

Cardiac allograft rejection: do trough cyclosporine levels correlate with the grade of histologic rejection?

BACKGROUND: The introduction of cyclosporine to heart transplantation immunosuppressive protocols has been associated with an improvement in the long- and short-term survival rates. The ideal dose of cyclosporine that maximizes its immunosuppressive properties and minimizes its toxicity has remained an enigma since its introduction. This study was undertaken to evaluate which range of cyclosporine levels provided the most effective protection against graft rejection. METHODS: We studied the correlation between cyclosporine levels and histologic grade of rejection, cardiac function, and renal function by retrospectively analyzing the results of 1407 individual whole blood cyclosporine trough levels. One hundred seven heart transplant recipients were studied within 2 years of undergoing transplantation. As a historical comparison, we also studied 146 individual trough cyclosporine levels from a subgroup of patients (n = 14) who had acute cellular rejection with graft dysfunction or failure. We correlated trough cyclosporine levels with the histologic severity of cellular rejection, cardiac function (right cardiac catheterization), and serum creatinine in both groups. The correlation was performed within patient's own data rather than between patient groups to avoid interpatient variations. RESULTS: The mean cyclosporine level was significantly higher (206 ng/ml) when the patients had grade 0 cellular rejection in comparison to grade 3A, with a mean cyclosporine level of 173 ng/ml (p = 0.005). Patients with graft dysfunction or failure had higher mean cyclosporine level (230 ng/ml) when they had no rejection compared with 3A rejection with a mean cyclosporine level of 153 ng/ml (p = 0.001). Furthermore, lower cyclosporine levels were associated with graft dysfunction. There was no correlation between serum creatinine and cyclosporine levels (r = 0.059, r2 = 0.351%). CONCLUSION: We conclude that cyclosporine trough levels above 200 ng/ml in the first 2 years after heart transplantation are associated with reduced cellular rejection without deleterious effects on renal function.

Orthotopic cardiac transplantation technique: a survey of current practice.

BACKGROUND: The Lower and Shumway technique has been the gold standard for orthotopic heart transplantation (OHT) for the past 35 years. In the last decade the bicaval and total techniques have been introduced but it is unclear how these alternative techniques have influenced the current surgical practice of OHT. METHODS: A worldwide survey of 210 International Society of Heart and Lung Transplantation centers was conducted by questionnaire: 169 replies were received; a response rate of 80%. RESULTS: Seventy-four centers (44%) use a combination of more than one technique with the remaining centers (n = 95 centers) employing one technique exclusively. The bicaval technique is the most frequently used technique in the majority of transplant procedures in 92 (54%) centers. In only 38 centers (22%), the standard technique was the most frequently employed technique. The total technique was the choice in 8 centers (5%). The maximum acceptable ischemic time varied from 3 to 9 hours with a median of 5.7 hours. Only 92 centers (54%) do not use cardioplegia during implantation. CONCLUSIONS: Since its introduction, the bicaval technique has become the most commonly used procedure for OHT. The long-term advantage of right atrial preservation with the bicaval technique will require further studies.

Treatment of mediastinitis: early modified Robicsek closure and pectoralis major advancement flaps.

BACKGROUND: The treatment of sternal wound complications is controversial. It is our practice to combine early aggressive debridement, a modified Robicsek sternal closure, and bilateral pectoralis major advancement flaps with or without closed irrigation in a single procedure. We reviewed our experience to determine the efficacy of this approach. METHODS: Grade II to IV mediastinitis (dehiscence and infection) developed in 47 patients 3 to 14 days after routine open heart operations between 1990 and 1995. Culture-positive infection was identified in 60% (n = 28); 62% (n = 29) had septicemia. Thirty patients underwent incision, drainage, and surgical assessment of the wound. Once systemic signs of infection were under control (no pyrexia, normal white blood cell count), formal single-stage debridement of all infected soft tissues and bones was performed. Sternal stability was achieved using a modified Robicsek closure and bilateral pectoralis major advancement flaps. Seventeen patients were treated with staged procedures. RESULTS: Early sternal closure and coverage with pectoralis major advancement flaps can be associated with a low mortality (0%), low morbidity (13%; n = 4: three superficial wound infections, one seroma), and shortened hospital stay (median, 22 days, compared with a median of 82 days in patients managed with conservative staged treatment; p < 0.05). Sternal stability with excellent functional and aesthetic results has been achieved in all patients. CONCLUSIONS: The combination of aggressive early surgical debridement, sternal closure, and the placement of bilateral pectoralis major advancement flaps is a simple procedure associated with a low mortality and morbidity and a short hospital stay.

Significance of raised natriuretic peptides after bicaval and standard cardiac transplantation.

BACKGROUND: High levels of plasma atrial natriuretic peptide (ANP) and ventricular natriuretic peptide (BNP) have been identified after standard orthotopic cardiac transplantation. It has been postulated that the high ANP levels are a result of persistent secretion from the large residual atrial mass after transplantation. This study was undertaken to investigate the significance of raised ANP and BNP levels after standard and bicaval orthotopic heart transplantation. METHODS: Plasma ANP and BNP levels were measured in 40 ambulatory, randomly selected cardiac transplant patients (group A, n = 20 had bicaval transplantation; group B, n = 20 had standard transplantation) and 10 healthy volunteers (group C). Cardiac transplant patients underwent endomyocardial biopsy and hemodynamic evaluation. RESULTS: Plasma levels of ANP and BNP were elevated in the transplant recipients in comparison with normal volunteers (p = 0.0001 and p < 0.0001, respectively). There was no significant difference in the ANP levels between group A and group B, whereas BNP levels were higher in group B compared with group A (p = 0.03). Linear regression analysis showed that a faster heart rate, high mean pulmonary artery pressure, high pulmonary capillary wedge pressure, and high transpulmonary gradient were associated with higher levels of BNP (p < 0.05). Lower mean systemic pressure was associated with higher levels of ANP (p < 0.05). CONCLUSIONS: High levels of ANP and BNP are synthesized and secreted by the transplanted denervated human heart regardless of the surgical technique. The level of BNP correlates with ventricular performance and afterload. The bicaval technique seems to be associated with better left ventricular and right ventricular diastolic performance.

Changes in brain natriuretic peptide concentrations following open cardiac surgery with cardioplegic cardiac arrest.

Elevated brain natriuretic peptide (BNP) concentration in peripheral blood reflects impaired cardiac ventricular function. We investigated the release pattern of BNP following cardioplegic cardiac arrest during heart surgery. In particular, we sought to discover whether there is an increase in peripheral BNP concentrations following reperfusion of the ischaemic heart. A secondary aim of the study was to investigate whether allopurinol, an anti-oxidant, has any effect on BNP release. A total of 29 patients scheduled for elective coronary artery bypass grafting were recruited, of whom 12 were randomly allocated to receive allopurinol with their pre-medication. Blood specimens were taken at six time points from the indwelling arterial catheter, the first before surgery and the last 2 h following the termination of cardiopulmonary bypass (CPB). BNP was found to decrease markedly when the aortic cross clamp was applied and the heart was isolated from circulation (P=0.0001). There was a slight increase in BNP following cross clamp release and myocardial reperfusion (P=0.04). A more substantial increase occurred with weaning from CPB when ventricular filling occurred (P=0.0015). Only the final BNP value, 2 h after CPB, was elevated compared with baseline (P=0.0013). Allopurinol had no demonstrable effect on changes in BNP.

The threshold for air leak: stapled versus sutured human bronchi, and experimental study.

BACKGROUND: Little is known about the integrity of staple-closure of the bronchus and its tolerance to normal mechanical stresses (cough, sneezing, etc.) in the immediate early post-operative period. There are few studies which tested the mechanical strength of stapled bronchial closure compared with manually closed bronchi using the threshold for fluid leak across the bronchial suture line which differs from air. MATERIAL AND METHODS: Intact cadaveric tracheobronchial tree (n = 40) were selected, age range from 55 to 70, of which 60% were males. They were divided into two groups: group A, 20 left bronchi were closed with RLV 30 Ethicon 4.8 mm bronchial stapler; group B, 20 were closed with 4 0 Prolene simple interrupted sutures. All specimens were intubated with endotracheal tube and submerged under water before testing the immediate air leak with the standard 40 mm Hg inflation pressure. Inflation pressure was increased until air leak was detected. The stapled closures were resected and subjected to radiological examination. RESULTS: No air leak was detected in any bronchus at 40 mmHg regardless of the closure technique. The median leakage pressure was significantly higher in the hand sutured bronchi compared to the stapled group (200 vs. 105 mmHg, respectively) and 50% (n = 10) leaked from multiple sites in the stapled group compared with leakage from one site only in group B, this difference was statistically significant P < 0.001. The radiological appearance of the staples maintained the B configuration, recommended by the manufacturer as a sign of sound application. CONCLUSION: Hand sutured bronchi tolerated higher inflation pressure compared with the stapled ones before leaking air. Air leak at high pressure occurs in the presence of intact staples.

Traumatic cardiogenic shock due to massive air embolism. A possible role for cardiopulmonary bypass.

Systemic arterial embolism is a potentially lethal complication of bronchopulmonary venous fistula in trauma patients with blunt chest trauma or isolated penetrating lung injury on positive pressure ventilation. A high index of suspicion, early diagnosis and management in specialized centres are keys to a successful outcome.

Severe mitral valve dysfunction due to unsuspected granulomatous myocarditis: successful cardiac transplantation following attempted mitral valve repair.

Granulomatous involvement of the myocardium is a rapidly fatal disease of uncertain aetiology rarely diagnosed premorbidly. We report a patient who presented with mitral valve incompetence and congestive cardiac failure who underwent a successful mitral valve repair but could not be weaned from cardiopulmonary bypass. Urgent heart transplantation was successfully performed and histological studies of the explanted heart revealed granulomatous myocarditis involving the mitral subvalvular apparatus. Endomyocardial biopsy may be necessary in young patients presenting with mitral valve disease of unknown aetiology.

The effect of 'renal-dose' dopamine on renal tubular function following cardiac surgery: assessed by measuring retinol binding protein (RBP).

OBJECTIVE: Acute renal failure complicating open heart surgery is not uncommon. Dopamine infusion (2.5-4.0 microg/kg per min) has often been advocated for prophylactic 'renal protection' in this setting despite little objective evidence of real benefit. We aimed to investigate whether dopamine offers any 'renal protection' in patients with normal heart and kidney functions undergoing routine coronary artery bypass grafting (CABG). Urinary excretion of retinol-binding protein (RBP), previously validated as a sensitive and accurate marker of early renal tubular injury, was used to assess the renal effects of dopamine during the first postoperative week. METHODS: Forty consecutive patients from the elective waiting list were prospectively randomized into two equal groups: those in Group A received dopamine infusion at 'renal dose' (2.5-4.0 microg/kg per min) starting from induction of anaesthesia for 48 h, whereas those in Group B served as untreated controls. Daily measurements were made of weight-adjusted urine output (ml/kg), fluid balance (input/output), serum creatinine, blood urea and urinary RBP. Statistical comparisons were made using Mann-Whitney U-test. RESULTS: The two groups matched in terms of age, time and temperature on cardiopulmonary bypass, number of grafts performed and perioperative haemodynamic status. No differences were detected in the weight-adjusted urine output, fluid balance, serum creatinine and blood urea between the groups. Control subjects (Group B) showed an increase in urinary RBP during the first and second postoperative days (323+/-4 microg/ mmolCr and 50+/-3 microg/mmolCr; mean+/-SD). However, patients treated with dopamine (Group A) demonstrated much greater urinary excretion of RBP over the same period (1257+/-15 microg/mmolCr and 449+/-21 microg/mmolCr; P = 0.0006 and 0.03) than those in Group B. CONCLUSIONS: Dopamine given at 'renal-dose' appears to offer no renal protection in patients with normal heart and kidney functions undergoing elective coronary surgery. On the contrary, it exacerbates the severity of renal tubular injury during the early postoperative period. Based on these findings we do not recommend the use of dopamine for routine renal prophylaxis in this group of patients.

Transforming growth factor-beta1 and lung allograft fibrosis.

OBJECTIVES: Transforming growth factor beta1 (TGF-beta1) is a potent immunosuppressive cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components. The repair process following lung allograft injury is due to rejection or infection replaces lung parenchyma by fibrotic tissue, leading to pulmonary dysfunction. The role of TGF-beta1 in this excessive healing process and increasing the risk of infection is unknown. METHODS: We analysed our patient data to investigate the relevance of different factors on allograft fibrosis and its correlation with TGF-beta1. Fibrosis was graded in H and E stained sections. TGF-beta1 genotype was determined in all patients. RESULTS: Patients were aged between 16 and 62 years (mean age of 39.6 years). Procedures were heart/lung (n = 32), double lung (n = 18), and SLT (n = 41). A total of 46 patients had lung allograft fibrosis diagnosed in transbronchial biopsies sections. Patients who had developed interstitial fibrosis had significantly more acute rejection episodes (mean 3.4 +/- 2.8) compared with patients without fibrosis (mean 2.1 +/- 2.2) (P = 0.024). The presence of eosinophils in the interstitium preceded and were associated with the development of fibrosis regardless of the rejection grade (P = 0.0001). TGF-beta1 was heavily expressed in sections with fibrosis with a mean score of 6.8 +/- 2.9 compared with 2.4 +/- 0.6 in sections with no fibrosis (P < 0.0001). TGF-beta1 expression correlated positively with fibrosis grades (P < 0.0001). The mean survival for patients with a fibrosis score > 6 is 892.4 +/- 73 days compared with mean survival 427 +/- 78 in patients with scores < 6 (P = 0.0001). Patients who developed fibrosis had homozygous TGF-beta1 genotype that correlates with excessive TGF-beta1 expression (P = 0.01). The use of cardiopulmonary bypass was associated with the development of excessive fibrosis (P = 0.02), and 7 patients who had severe fibrosis died of septicaemia (17.5%). FEV1 (forced expiratory volume) was significantly higher in patients without fibrosis (1870 +/- 111 ml versus 1590 +/- 160; P = 0.02). CONCLUSIONS: The risks of lung allograft fibrosis increases with recurrent rejection, tissue eosinophilia, homozygous TGF-beta1 genotype and the use of bypass machine. Fibrosis was associated with higher mortality and morbidity might be explained by the TGF-beta1 immunosuppressive and fibrotic properties. Immunological strategies to down-regulate TGF-beta1 production might improve survival and function of lung allografts.

Should we stitch the subcutaneous fat layer following saphenous vein excision for coronary revascularization?

We report a prospective trial to establish whether a subcutaneous fat stitch reduces the incidence of haematoma formation, infection and wound dehiscence following saphenous vein excision for coronary revascularization. Two groups of patients undergoing coronary revascularization were studied. In the first group of 100 patients the saphenous vein was harvested from both legs. Legs were randomized to have either a fat stitch or no fat stitch during wound closure. By using both legs of each patient we eliminated the effect of general factors on wound healing, thus the patients acted as their own controls. In the second group of 200 patients, the saphenous vein was harvested from the thigh, and patients randomly allocated to either a fat stitch or no fat stitch during wound closure. The wounds were examined daily for 7 days, and again after 6 weeks at the follow-up. There was no difference in the rate of wound complication in the fat stitch groups (9%) compared with the no fat stitch groups (8%), however, the fat stitch groups required more surgical intervention for skin edge necrosis. It appears that closure of the subcutaneous fat following saphenectomy is unnecessary, and may be detrimental to skin healing.

Spinal osteomyelitis presenting with a life-threatening pleural empyema.

STUDY DESIGN: This case report illustrates a rare presentation of spinal osteomyelitis that initially manifested as a life-threatening pleural empyema leading to misdiagnosis. OBJECTIVES: A high index of suspicion is required to make the correct diagnosis of spinal osteomyelitis, especially with unusual presentations. Appropriate antibiotic management should be commenced immediately the diagnosis is made. SUMMARY OF BACKGROUND DATA: A review of the literature reveals five previous cases of vertebral osteomyelitis associated with pleural effusions. In three of these, the effusions were reactive and sterile. There is only one previous case of a pleural empyema related to primary spinal osteomyelitis. There also is one case report of vertebral osteomyelitis presenting as a mediastinal abscess. METHODS: A case is presented of a man thought to have bronchogenic carcinoma with a destructive vertebral metastasis who was sent for palliative radiation therapy. A life-threatening pleural effusion subsequently developed, and after additional investigation, he was found to have spinal osteomyelitis with a pleural empyema. RESULTS: The empyema was drained through an indwelling chest tube, and the patient was administered appropriate antibiotics. He made a complete and uneventful recovery. CONCLUSIONS: The case illustrates a rare presentation of spinal osteomyelitis. It exemplifies the dictum that if a malignant disease is suspected, every effort has to be made to establish a histologic diagnosis to prevent inappropriate management and the potentially devastating consequences of an incorrect diagnosis. It also high-lights the difficulties in diagnosis of vertebral osteomyelitis with empyema. With correct management, the prognosis is excellent.