The distribution of pemphigus vulgaris-IgG subclasses and their reactivity with desmoglein 3 and 1 in pemphigus patients and their first-degree relatives.

BACKGROUND: Pemphigus vulgaris (PV) autoantibodies (PV-IgG) have been found in 40-70% of sera of first-degree relatives of pemphigus patients. OBJECTIVES: To determine the possible role of PV-IgG subclasses in the pathogenesis of the disease. PATIENTS AND METHODS: Study groups comprised 25 PV patients, 55 unaffected family members and 56 sera of healthy individuals. Indirect immunofluorescence (IIF) staining and Western immunoblotting (WB) techniques were used to determine total PV-IgG and PV-IgG subclasses and their reactivity to desmoglein (Dsg) 1 and 3. RESULTS: By IIF staining, circulating PV-IgG were found in 64% of the patients, in 15% of the relatives and in none of the controls (P < or = 0.001); by WB the results were 91%, 49% and 12%, respectively (P < or = 0.001). The distribution of PV-IgG subclasses 1-3 was similar among patients and their relatives. PV-IgG4 was found in 62% of the patients but in only one relative and was absent in the controls (P < or = 0.001). PV-IgG1, 2 and 4 were found to react mainly with Dsg3 and PV-IgG3 mainly with Dsg1 and 3. CONCLUSIONS: These results support the concept of a genetic predisposition in pemphigus. The non-complement-fixing PV-IgG4 and at least one complement-fixing PV-IgG subclass appear to be involved in the pathogenesis of the disease. The absence of PV-IgG4 among relatives who were PV-IgG carriers seems to be linked to the fact that they do not develop pemphigus. The exact nature of this linkage is still unclear.

Predictors of perioperative morbidity and mortality in lung volume reduction surgery.

BACKGROUND: Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality. METHODS: We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity. RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%, TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/- SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.

A simplified method of harvesting and dilating the radial artery achieves acceptable clinical outcomes.

BACKGROUND: The recent successful revival of the radial artery as a coronary-bypass conduit has been attributed to a minimally traumatic harvesting technique without diathermy, combined with long-term oral calcium antagonist therapy. We describe a simplified technique of harvesting the radial artery, which reduces procurement time and maintains conduit relaxation. METHODS: Radial arteries were harvested using diathermy and topical glyceryl trinitrate-verapamil dilator solution. Postoperatively, intravenous glyceryl trinitrate, but no calcium antagonist was used. The clinical results in the first 100 consecutive patients receiving radial artery grafts (RA group), procured using this technique, were compared with a group of 100 patients receiving saphenous vein conduits (SV group) immediately prior to the introduction of the radial artery at our institution. RESULTS: There were no demographic differences between the two groups, other than the SV group being slightly older. There was one intraoperative death in each group. There was no difference in the rate of peri-operative myocardial infarction or length of stay in the intensive care unit. At a median follow-up time of 16 months for the RA group, and 25 months for the SV group, the survival rates were 97 and 94%, respectively. All survivors were in the New York Heart Association class I. In the SV group, two postoperative angioplasties were performed. CONCLUSIONS: These early results suggest that this method of procuring the radial artery using diathermy, glyceryl trinitrate and no postoperative calcium antagonists, is rapid, safe and effective. The continued use of this technique is justified, while awaiting the results of long-term angiographic studies.

Bilateral sequential single lung transplantation for pulmonary hypertension and Eisenmenger's syndrome.

BACKGROUND: Lung transplantation, with and without intracardiac repair for pulmonary hypertension (PH) and Eisenmenger's syndrome (EIS), has become an alternative transplant strategy to combined heart and lung transplantation (HLT). METHODS: Thirty-five patients with PH or EIS underwent either bilateral sequential single lung transplantation (BSSLT, group I, n = 13) or HLT (group II, n = 22). Another 74 patients, who underwent BSSLT for other indications, served as controls (group III). Immediate allograft function, early and medium-term outcomes, lung function, and 2-year survival were compared between the groups. RESULTS: Comparisons between groups I and II showed no significant difference in any variables except percent predicted forced vital capacity. Immediate allograft function was significantly inferior (p < 0.05) and the blood loss was greater (p < 0.01) in group I when compared with those in group III. However, this resulted in no significant difference in early and medium-term outcomes, and 2-year survival between the 2 groups. CONCLUSIONS: BSSLT for PH and EIS can be performed as an alternative procedure to HLT without an increase in early and medium-term morbidity and mortality. Results are comparable with BSSLT performed for other indications.

Risk factors for surgical wound infection and bacteraemia following coronary artery bypass surgery.

BACKGROUND: There has been no consensus from previous studies of risk factors for surgical wound infections (SWI) and postoperative bacteraemia for patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: Data on 15 potential risk factors were prospectively collected on all patients undergoing CABG surgery during a 12-month period. RESULTS: Of 693 patients, 62 developed 65 SWI using the Centres for Disease Control definition: 23 were sternal wound infections and 42 were arm or leg wound infections at the site of conduit harvest. There were 19 episodes of postoperative bacteraemia. Multivariate analysis revealed that: (i) diabetes, obesity and previous cardiovascular procedure were independent predictors of SWI; and (ii) obesity was an independent risk factor for postoperative bacteraemia. CONCLUSIONS: These findings suggest that improved diabetic control and pre-operative weight reduction may result in a decrease in the incidence of SWI. But further prospective studies need to be undertaken to examine (i) whether the increased SWI risk in diabetes occurs with both insulin- and non-insulin-requiring diabetes, and whether improved peri-operative diabetes control decreases SWI; and (ii) what degree of obesity confers a risk of SWI and postoperative bacteraemia, and whether pre-operative weight reduction, if a realistic strategy in this patient group, results in a decrease in SWI.

Outcomes of coronary artery bypass grafting: a 3 year analysis using the Society of Thoracic Surgeons Database.

BACKGROUND: Accurate risk factor analysis is a critical element in contemporary cardiac surgical practice. In the USA, the Society of Thoracic Surgeons Database allows institutions and individual surgeons to carry out detailed patient risk assessment and to review their cardiac surgical outcomes in a comparative fashion. METHODS: To evaluate outcomes of isolated coronary artery bypass grafting, data from all patients operated upon at the Alfred Hospital, Melbourne, Australia, over a 3 year period were entered into the Society of Thoracic Surgeons Database. RESULTS: Our results (mortality and morbidity) compared favourably with those contained within this large international database. CONCLUSION: It is hoped that a similar Australasian database can be established to facilitate a meaningful local risk assessment and a comparative analysis of outcomes of cardiac surgical procedures.

Impact of graft ischemic time on outcomes after bilateral sequential single-lung transplantation.

BACKGROUND: Graft ischemic time (GIT) is a potential limiting factor in lung transplantation. METHODS: Seventy-four patients who underwent bilateral sequential single-lung transplantation were divided into three groups: group I, GIT less than 5 hours (n = 20); group II, GIT between 5 and 8 hours (n = 39); and group III, GIT more than 8 hours (n = 15). We compared early allograft function (ratio of arterial oxygen tension to inspired oxygen fraction and alveolar-arterial oxygen gradient), blood loss, the need for tracheostomy, the duration of ventilation, intensive care unit stay, and hospital stay. We also compared prevalences of acute and chronic rejection, airway complications, lung function test, and 2-year survival. RESULTS: Early allograft function in group III was significantly worse than those in groups I and II. However, there was no significant difference in any other variables of early and medium-term outcomes among the three groups. No significant correlation was detected between GIT and duration of intensive care unit stay or hospital stay. CONCLUSIONS: The limitation of acceptable GIT could be extended from the traditionally approved 4 to 5 hours, to 5 to 8 hours or even longer.

Body mass index as a predictor of survival in adults with cystic fibrosis referred for lung transplantation.

BACKGROUND: The timing of referral and listing for lung transplantation in adults with cystic fibrosis is influenced by many factors including pulmonary function, body mass index (BMI), sex, and patient and physician choice. This study aimed to analyze the effect of these variables on waiting list and postoperative mortality rates. In particular, low BMI is suggested to portend a poor outcome after transplantation. METHODS: All patients with cystic fibrosis referred to our institution (n = 92) between 1989 and 1996 were reviewed, and the effect on survival of BMI, sex, and other covariates was analyzed by use of Cox proportional hazards regression. RESULTS: Forty-five transplantations were undertaken with a mean waiting time of 226 days (range 1 to 678). Fifteen of the 62 listed patients died before transplantation with a mean time to death of 160 days (range 8 to 533). Fifteen patients died after transplantation. BMI at the time of listing predicted waiting list mortality (P < .05). Female sex tended to increase waiting list mortality rates, such that the combination of BMI less than 18 kg/m2, and female sex was associated with a 21% 1-year waiting list survival without transplantation. Age, forced expiratory volume in 1 second, sex, BMI, and date of transplantation did not predict postoperative survival. CONCLUSION: Patients with cystic fibrosis (particularly women) referred for lung transplantation with a BMI less than 18 kg/m2 are at high risk of death over the next 12 months. With this in mind, they should not be denied transplantation unduly while attempts are made to increase weight, especially because pretransplantation BMI does not influence posttransplantation survival.

Continuous perfusion improves preservation of donor rat hearts: importance of the implantation phase.

BACKGROUND: Continuous hypothermic perfusion of donor hearts may provide extra protection for long ischemic times and suboptimal donors. The aim of three separate studies was to assess the effect of continuous hypothermic perfusion during simulated donor heart storage and implantation. METHODS: In study 1 twelve isolated rat hearts underwent 10 minutes of normothermic ischemia to simulate the effect of brain death on the heart and 5 hours of cardioplegic arrest, using University of Wisconsin solution. Six hearts were statically stored in University of Wisconsin solution at 2 degrees C, and six were perfused with University of Wisconsin solution. To assess the effect of simulated implantation, in study 2 an additional 12 hearts were statically stored for 5.5 hours in University of Wisconsin solution, six of which were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest. To assess the effect of simulated perfusion, in study 3 during implantation 12 hearts were rewarmed to a mean of 16 degrees C over the last 30 minutes of arrest, during which time six were perfused with 2 degrees C solution. RESULTS: Hearts perfused during storage demonstrated greater recovery of prearrest power, 85.8% +/- 1.8%, than hearts preserved by static storage, 72.7% +/- 3.0% (p < 0.01). The simulated warm implantation period reduced recovery of power from 68.3% +/- 5.1% to 40.2% +/- 2.0% (p < 0.001). Perfusion during warm implantation improved recovery to 61.8% +/- 3.9% (p < 0.01). In all experiments improved function was accompanied by improved metabolic energy status. CONCLUSIONS: During the implantation period of heart transplantation the donor heart sustains injury that could amount to 50% of total ischemic injury. Continuous perfusion during the cold storage phase and during simulated implantation improves recovery of the donor heart.

Lung volume reduction surgery for emphysema.

OBJECTIVE: To report the results of lung volume reduction surgery (LVRS) for severe emphysema in Australia. SETTING: A tertiary teaching hospital. DESIGN: A prospective study of a consecutive case series. PARTICIPANTS: 20 patients (mean age, 56 years) with severe emphysema--mean forced expiratory volume in one second (FEV1), 0.72 L (28% of predicted) and severe gas trapping (mean residual volume, 286% of predicted). INTERVENTION: Bilateral apical LVRS was performed via a median sternotomy with a linear stapler; bovine pericardial strips were used to reinforce the staple line. RESULTS: There was a 95% survival, and a mean (range) inpatient stay of 17 (8-45) days. No complications occurred in nine patients; a further six patients had only minor complications. Five patients had major complications (sputum retention requiring reintubation, persistent air leak requiring reoperation, duodenal perforation, and epidural haemorrhage); one patient died from multiorgan failure at 28 days. Intercostal drainage was left in situ for a mean of eight days. The results of FEV1, Medical Research Council (MRC) Dyspnoea Score and six-minute walk test improved in more than 90% of patients. FEV1 improved an average of 0.35 L (54% over baseline) (P < 0.001). Mean MRC Dyspnoea Score decreased from 3.4 to 2.1 (P < 0.001). Mean distance for the six-minute walk test increased from 306 to 431 metres (P < 0.001). CONCLUSION: Our experience confirms that LVRS produces worthwhile early outcomes for a subgroup of patients with severe emphysema. The clinical, economic and ethical questions raised by this new therapy will need to be assessed.

Mitral valve replacement via a right mini-thoracotomy in the dog: use of carbon dioxide to reduce intracardiac air.

OBJECTIVE: To develop a clinically applicable method of minimally invasive mitral valve replacement (MVR) with cardioplegia, and examine the ability of carbon dioxide (CO2) to improve de-airing. METHODS: MVR was performed via a 5 x 3-cm right lateral minithoracotomy in eight greyhounds. Peripheral cardiopulmonary bypass and an ascending aortic balloon catheter (endoaortic clamp) were used for cardioplegia and aortic root venting. The endoaortic clamp was inflated in the ascending aorta under fluoroscopy and cardioplegic solution was infused. In four dogs, CO2 at 2 l/min was used to displace air in the chest. A left atriotomy was made, the valve exposed and a mechanical valve implanted. After left atrial closure, retained intracardiac gas was aspirated from the aortic root and collected in a bubble-trap. The endoclamp was deflated and the animal weaned from bypass. RESULTS: A satisfactory MVR was performed in all cases. The clamp time was 64 +/- 13 min and all dogs were stable post-bypass. In the CO2 group, intrathoracic CO2 was maintained above 86% and 0.1 +/- 0.1 ml of gas was collected, compared to 1.3 +/- 0.8 ml in the non-CO2 group (P < 0.05). CONCLUSIONS: Femoro-femoral bypass and use of the endoaortic clamp allow a safe and efficacious MVR via a right minithoracotomy in the dog. A high intrathoracic CO2 concentration reduces the amount of retained intracardiac gas.

Early hemodynamic effects of left atrial administration of epinephrine after cardiac transplantation.

We studied the hemodynamic effects of left atrial (LA) administration of epinephrine in 10 patients after cardiac transplantation, using a prospective, randomized, double-blind, cross-over design. After allograft implantation, a LA catheter was inserted and epinephrine infusion commenced at 100 ng.kg-1.min-1. Each trial period consisted of 20 min, with the LA and right atrial (RA) lines switched over between each period; hemodynamic measurements were taken after each time period. Whether epinephrine was administered via the RA or LA did not significantly alter hemodynamics (RA versus LA): mean (SD) arterial blood pressure 67 (7.5) vs 64 (9.5) mm Hg (P = 0.16), mean pulmonary artery pressure 22 (4.0) vs 21 (9.4) mm Hg (P = 0.67), cardiac index 3.2 (1.1) vs 3.2 (1.1) L.min-1.m-2 (P = 0.83), pulmonary vascular resistance index 308 (157) vs 345 (157) dynes.s.cm-5/m-2 (P = 0.30) or right ventricular ejection fraction 35% (11%) vs 32% (9.8%) (P = 0.23). Arterial epinephrine plasma levels were similar (P = 0.16). There was no significant pulmonary extraction of measured catecholamines. We observed no hemodynamic benefit of LA epinephrine administration. It may be that the cardiac transplantation population reacts differently compared with other cardiac surgical patients (possibly because pulmonary extraction of catecholamines is reduced). Because we did not observe a hemodynamic advantage in patients immediately after cardiac transplantation, we would not recommend the use of LA epinephrine at the dose studied.

Reverse telescope anastomotic technique reduces the incidence of bronchial stricture.

BACKGROUND: Bronchial stricture remains a major problem after lung transplantation. We hypothesized that a "reverse" telescope anastomosis, where the donor bronchus is sleeved external to the recipient bronchus, would be associated with a lower incidence of anastomotic stricture. METHODS: Over a 12-month period our Unit performed 35 consecutive single and bilateral sequential lung transplantations. The 56 bronchial anastomoses were constructed as a conventional (n = 27) or as a reverse (n = 29) telescope. RESULTS: Bronchial strictures developed in 48% of the conventional anastomoses but in only 7% of the reverse anastomoses (p < or = 0.05). Furthermore, the reverse telescope anastomosis eliminated the need for stenting. CONCLUSIONS: This technique greatly reduced the need for dilatation, debridement, and stent placement and may reduce the morbidity and mortality associated with anastomotic complications.

Pulmonary allograft ischemic time: an important predictor of survival after lung transplantation.

BACKGROUND: Traditionally organ availability in human lung transplantation has been limited by aiming to keep the graft ischemic time under 6 hours. To maximize organ supply in a country with a widely spread population, we have routinely procured organs beyond this time. Our experience outlines the clinical consequences of a prolonged allograft ischemic time. METHODS: Between 1990 and 1994 we performed 106 lung or heart-lung transplantations. The average graft ischemic time was 323 +/- 93 minutes. Lung preservation included a prostacyclin infusion (40 to 80 ng/kg/min for 10 minutes) and cold modified Euro-Collins solution flush. Organs were stored and transported on ice at 6 degrees to 10 degrees C. Graft ischemic time, transplant type, age, gender, cytomegalovirus status, and anesthetic time were subject to multivariate Cox regression analysis. RESULTS: Survival and graft ischemic times for heart-lung (n = 38), single lung (n = 33), and bilateral lung transplantation (n = 35) were not significantly different. Graft ischemic time was an independent predictor of survival (p < 0.01). Subgroup analysis notes the effect to be most pronounced beyond 5 hours (p = 0.02, hazard ratio 3.44, confidence interval 1.12 to 9.8). CONCLUSIONS: Pulmonary allograft ischemic time beyond 5 hours does not result in acceptable outcomes although survival is reduced. Attempts should be made to minimize graft ischemic times with careful coordination of transport and personnel.

Successful long-term outcome with prolonged ischemic time cardiac allografts.

BACKGROUND: The limited availability of cardiac allografts together with the increasing number of patients on the waiting list restricts treatment of this population with heart transplantation. An increase in the available donor pool has been facilitated by the use of allografts with prolonged ischemic time (> 240 minutes). METHODS: Short- and long-term outcomes were compared in 150 heart transplant recipients on the basis of allograft ischemic time (< 241 minutes, 241 to 300 minutes, and > 300 minutes). RESULTS: No difference was found in allograft functional capacity, the development of transplant-associated coronary disease, or actuarial survival in the short and long term. CONCLUSIONS: Improved population treatment with prolonged ischemic time cardiac allografts can be safely undertaken without long-term risk to heart transplant recipients.

Techniques and results in bilateral sequential single lung transplantation. The National Heart & Lung Replacement Service.

Lung transplantation continues to evolve as a therapeutic option for patients with end-stage lung disease. Bilateral sequential single lung transplantation (BSSLTx) is a recent addition to the lung transplant surgeon's armamentarium that incorporates the benefits of single lung transplantation in patients who require double lung replacement while avoiding the morbidity inherent in the en bloc double lung transplant procedure. Between November 1992 and October 1993, 17 recipients underwent 18 bilateral BSSLTx procedures for a variety of indications. In 53% of patients, the procedure was completed without the requirement for cardiopulmonary bypass. Telescoping of the bronchial anastomosis has proved satisfactory. Induction cytolytic therapy has not been utilized. Patients received methyl prednisolone from day 1 and as maintenance prednisolone therapy. Actuarial 1-year survival is 87%; 12 of the 15 survivors are in Functional Class I. BSSLTx is an evolving transplant option for patients who require double lung replacement. Definitive clinical diffusion of the procedure will depend upon intermediate and long-term outcomes for specific recipient pathologies.