Thyroid hormones in male workers exposed to urban stressors.

BACKGROUND: The occupational exposure to urban pollution may induce adverse effects on the human health. METHODS: Plasma levels of thyrotropin stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) of 50 outdoor workers and 50 indoor workers were compared. RESULTS: In the outdoor workers the TSH levels were significantly higher than in the control subjects (p =0.02) while the average of FT3 and FT4 values, was not significantly different compared to the controls (p > 0.05). CONCLUSIONS: The differences found for TSH levels between outdoor and indoor workers, though not high, suggest that, due to greater exposure to environmental pollutants, the outdoor workers are more susceptible to the development of function abnormalities of the thyroid gland compared to indoor workers.

Evaluation of some cardiovascular risk parameters in health professionals exposed to night work.

BACKGROUND: Shift work and night work in particular represent a risk factor for the health of exposed workers; aim of our study is to evaluate whether night work may cause alteration of some cardiovascular risk parameters in health workers. MATERIALS AND METHODS: The research was carried out on 415 health workers, 163 exposed to night work and 252 not exposed. A blood sample was taken from each worker, between 8.00 a.m. and 10.00 a.m. before lunch time, to test total cholesterol, HDL cholesterol, and triglycerides. Blood pressure and heart rate were also measured. Workers with cardiovascular diseases, thyroid diseases, diabetes mellitus, dyslipidemia, those who made use of antihypertensive drugs, hypoglycemic and/or lipid-lowering drugs, subjects with body mass index (BMI) (kg/m2) higher than 30 were excluded. RESULTS: In the group of exposed compared to controls, increasing values of arterial pressure and heart rate, were not significant. The mean values of total cholesterol and triglycerides were significantly higher in exposed compared to controls while values of HDL cholesterol were significantly lower. CONCLUSIONS: Night workers have clinically significant changes in blood levels of total cholesterol, HDL cholesterol and triglycerides, such alterations are presumably related to poor food hygiene and to psychosocial stressors.

HLA class II-like antiidiotypic antibodies from highly sensitized patients inhibit T-cell alloresponses.

The purpose of this study is to identify factors in the sera of highly sensitized (HS) patients (pts) that inhibit T-cell alloresponses. An in vitro assay was used to measure HLA class I and class II-like antiidiotypic antibodies (anti-ids). The stimulation index (SI) was used to measure PBL and T-cell responses to alloantigens. All HS sera (32 pts) and the IgG fraction inhibited PBL and CD4(+) T-cell responses to alloantigens. The SI with HS IgG was 7.9 +/- 1.7 as compared to 31.5 +/- 5.9 with normal IgG (p = 0.0003). In a subset of pts who were transiently sensitized, the SI was 6.6 +/- 1.0 with a high panel reactive antibody (PRA), but when their PRA was zero, the SI was 17.8 +/- 1.3 (p = 0.0000001). Anti-ids were found in 100% of 17 pts with a high PRA. The T-cell inhibitory factors reduced CD4(+) T-cell responses of HS pts to alloantigens in the presence of autologous anti-ids, were MHC restricted and were inactivated by in vitro generated antibodies to HLA class II-like anti-ids. The HLA class II-like anti-id IgG molecules bind to the TCR of CD4(+) T cells and may impair their ability to help in the downregulating antibody response to anti-ids.

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Coronary sinus sampling of cytokines after heart transplantation: evidence for macrophage activation and interleukin-4 production within the graft.

OBJECTIVES: This study was undertaken to evaluate the organ-specific release of cytokines after heart transplantation and to assess any correlation with transplant rejection. This cytokine profile should document the relative activation of mononuclear cell subsets within the graft. BACKGROUND: Up to 60% of mononuclear cells infiltrating the cardiac allograft during rejection are macrophages, but their role is undetermined. The T lymphocytes are activated, but the activity of specific T cell subsets is not known. We sought to assess for the first time in humans the in vivo activation of mononuclear cell subsets by measuring coronary sinus cytokine levels after heart transplantation. METHODS: Paired superior vena cava and coronary sinus serum samples were assayed for interleukin (IL)-2, IL-4 and IL-6, soluble IL-2 receptors, tumor necrosis factor-alpha and neopterin in 10 patients at the time of 40 routine endomyocardial biopsy procedures. All cytokine measurements were made by using enzyme-linked immunosorbent assay; neopterin was measured by using radioimmunoassay. RESULTS: Interleukin-2 levels were not detectable (< 0.8 U/ml) in either the superior vena cava or the coronary sinus in the presence or absence of rejection. Interleukin-2 receptor levels were uniformly elevated to 1,283 U/ml in the superior vena cava and to 1,232 U/ml in the coronary sinus, with no correlation with rejection severity. Interleukin-4 levels were consistently higher in coronary sinus serum than in peripheral blood (229 vs. 61 pg/ml, p < 0.0005), but there was no relation with rejection. Interleukin-6 levels were higher in the coronary sinus than in the superior vena cava (200 vs. 120 pg/ml, p < 0.05). Tumor necrosis factor-alpha showed consistently elevated levels in coronary sinus serum (68 vs. 17 pg/ml, p < 0.0005), with no relation with rejection. Neopterin, which is produced only by activated macrophages, was also consistently elevated in the coronary sinus (2.5 vs. 2.2 nmol, p = 0.08). CONCLUSIONS: The cardiac allograft is a major source of cytokines after heart transplantation. The cytokine profile allows the activity of subsets of the mononuclear cell infiltrate to be investigated. Elevated coronary sinus activity of the macrophage-specific metabolite neopterin suggests macrophage activation within the allograft. This possibility is supported by elevated coronary sinus levels of tumor necrosis factor-alpha and IL-6. The T lymphocytes are activated, as evidenced by high soluble IL-2 receptor levels, but IL-2 production was suppressed by conventional immunosuppressive therapy. Coronary sinus IL-4 levels represent T helper-2 cell activation within the graft despite immunosuppression. We could find no temporal relation between the coronary sinus or superior vena cava cytokine concentration or profile and severity of rejection on concurrent biopsy studies.

[Use of TLV-ACGIH (HAL) and Strain Index for the evaluation of the upper extremity biomechanical overload]. / Applicazione del TLV-ACGIH (HAL) e strain index per la valutazione del sovraccarico biomeccanico dell'arto superiore.

Pathologies due to repetitive activity of the upper limb, well known in scientific literature as WMSDs (Work Related Musculoskeletal Disorders), are considerably increased in the last years. At the moment, there are no validated methods for the assessment of the work-related risk. This study compares two different methods proposed in literature for the assessment of the work-related risk, combining objective and subjective measures.

Short-term effects of calcium antagonists on hemodynamics and cyclosporine pharmacokinetics in heart-transplant and kidney-transplant patients.

Effects of two calcium antagonists on hemodynamics and on cyclosporine pharmacokinetics were studied in eight transplant patients (four heart-transplant and four kidney-transplant patients) by use of a single-blind, randomized, crossover, and placebo-controlled design. Patients received, at least 1 week apart, either 90 mg diltiazem, 20 mg nifedipine (in tablet form), or placebo, given 1 hour before cyclosporine. Cyclosporine and its main metabolite (metabolite 17) were measured in plasma (separated at 25 degrees C) by use of HPLC. Both calcium antagonists tended to increase absorption rate and elimination rate, but none of the pharmacokinetic parameters of cyclosporine were significantly altered. Moreover, the area under the curve of plasma concentrations of metabolite 17 did not change. On the other hand, both nifedipine and diltiazem significantly altered the hemodynamics, but to a different extent in the two groups of patients. The heart-transplant patients showed larger decreases in systolic and diastolic blood pressure than the kidney-transplant patients after administration of both nifedipine and diltiazem, but they showed smaller increases in cardiac index and heart rate with nifedipine. In contrast, diltiazem caused small decreases in heart rate and cardiac index in heart-transplant patients and small increases in heart rate and cardiac index in kidney-transplant patients. We conclude that a single dose of either nifedipine or diltiazem does not affect, to a clinically significant extent, the pharmacokinetics of cyclosporine. In addition, heart-transplant patients show different hemodynamic responses to these two calcium antagonists than the responses shown by kidney-transplant patients, probably because of cardiac denervation.

Analyzing the number of "rejection episodes" in renal transplant studies.

Transplantation has become the treatment of choice for many chronic and debilitating diseases. Generally, the primary endpoints in evaluating therapy are graft and patient survival time. However, an important secondary outcome is the number of "rejection episodes" experienced by study patients. This response has a distinctive statistical character. That is, it is a categorical variable since it assumes only a small number of integer values, but it is measured on a ratio-level scale since the ratio of any two values is scientifically meaningful. Historical methods for analyzing this endpoint, for example, t tests, logistic regression and Kaplan-Meier analysis, have failed to take these characteristics into account. In this study, we investigated statistical procedures for analyzing the number of rejection episodes arising during the first three months posttransplant. Data compiled by the Multiple Organ Retrieval and Exchange (MORE) of the Province of Ontario were used for this purpose. It was found that assumptions underlying normal distributional techniques were not satisfied by these data. An alternative model based on Poisson regression models was considered and was shown to provide an adequate fit.

A randomized controlled trial of verapamil on cyclosporine nephrotoxicity in heart and lung transplant recipients.

BACKGROUND: Cyclosporine (CsA) is a potent immunosuppressive drug widely used in organ transplantation and in the treatment of autoimmune diseases (1, 2). However, its common nephrotoxic effect is a major limiting factor. Short-term CsA treatment has been shown to cause reversible renal vasoconstriction, whereas long-term treatment can lead to an afferent arteriolopathy and chronic renal failure. METHODS: We performed a randomized controlled trial to examine the short-term renal effects of verapamil in 32 CsA-treated heart or lung transplant recipients. Sixteen patients each were randomized to receive a 6-week course of verapamil or control treatment (atenolol in hypertensive patients and placebo in normotensive patients) 1-2 months after transplantation. An 8-hr sequential clearance study of inulin and p-aminohippuric acid for estimating glomerular filtration rate and renal plasma flow, respectively, was performed at baseline and at completion of study. The integral area under the curve of the clearance parameter over 8 hr was then calculated to generate a clearance-time index. RESULTS: There was no difference in the clearance-time indices for inulin and p-aminohippuric acid between the two groups at baseline. However, at the completion of study, the within-group change in the glomerular filtration rate clearance-time index was different between the verapamil and control groups (48+/-20 vs. -35+/-17 ml/min/1.73 m2 x hr, respectively; P=0.0038). A similar trend was seen for renal plasma flow, but did not reach statistical significance. Mean arterial blood pressure and whole-blood CsA levels did not differ between the two groups during the study. Verapamil treatment was also associated with a decrease in CsA dose requirement (7.6+/-0.58 mg/kg/day at baseline vs. 4.6+/-0.40 mg/kg/day at completion; P<0.001) without any significant change in trough whole blood CsA levels. Rejection episodes did not differ between the two groups. CONCLUSIONS: The use of verapamil in the heart or lung transplant recipients may therefore provide both renal protective effects and cost savings.

Monocyte procoagulant activity and plasminogen activator. Role in human renal allograft rejection.

Currently the mechanism of renal allograft rejection is not well understood. This study was designed to determine whether induction of monocyte procoagulant activity (MCPA) is important in the pathogenesis of renal allograft rejection. The MPCA assay was performed utilizing a one stage clotting assay both in normal and in factor-VII-deficient plasma. There was no increase in spontaneous MPCA in 20 patients with endstage renal failure and in 10 patients following abdominal or orthopedic operation, as compared with 20 normal controls. MPCA was assessed daily in 18 patients who had received renal allografts. Rejection episodes (RE) were predicted on the basis of persistent elevation in MPCA as compared with pretransplant levels. Rejection was diagnosed clinically and treated on the basis of standard criteria. Treated RE were compared with those predicted by elevated MPCA, and 3 patients were assessed as having no RE by MPCA and by standard criteria. In 8 RE, MPCA correlated temporally with RE (same day) when compared with standard criteria. In 12 RE, MPCA was predictive of rejection preceding standard criteria by at least 24 hr. There were 7 false-positive predictions on the basis of MPCA; however, there was only 1 false negative. MPCA was shown to be a prothrombinase by its dependence only on prothrombin and fibrinogen for full activity. MPCA may be important in the pathogenesis of allograft rejection, and additionally it may be a useful adjunct in the clinical management of this disease.

The role of cold ischemia in a provincial organ-sharing program in the cyclosporine era.

Prolonged cold ischemia has been associated with impaired early cadaver renal allograft function. The role of CsA in potentiating these effects is not well understood, but CsA has been implicated in promoting delayed graft function and potentiating renal ischemic injury. In order to establish whether CsA is safely tolerated by kidneys subjected to protracted cold ischemia, we examined patient and graft outcome in a series of 1081 patients receiving cadaver-kidney transplants over an 8-year period (1981-1988). All patients received a standard immunosuppressive regimen that included CsA. Overall actuarial 1-year patient and graft survival rates were 96% and 80%, respectively. Renal preservation was achieved either by pulsatile perfusion (n = 261, 24%) or simple cold storage (n = 820, 76%). Results were analyzed according to total cold ischemic time as follows: 0-23 hr (n = 512; range, 0-23.9 hr); 24-35 hr (n = 380; range, 24.0-35.9 hr); 36-47 hr (n = 161; range, 36.0-47.7 hr); greater than or equal to 48 hr (n = 28; range, 48.0-70.6 hr). These groups did not differ significantly in recipient age, sex, incidence of diabetes, number of pretransplant blood transfusions, level of presensitization, or HLA match. There were no differences in overall actuarial 1-year patient or graft survival rates, incidence of rejection, or renal function at 1 year. There was a higher incidence of impaired early graft function for kidneys preserved greater than or equal to 48 hr, but eventual graft outcome, including serum creatinine at 1 year, was unchanged. Delayed introduction of CsA resulted in improved 1-year graft survival (84.4% vs. 74.7%, P less than 0.05) compared to CsA treatment begun at the time of transplantation ("initial CsA"). This improvement was present regardless of total cold ischemia time. The incidence of permanent graft nonfunction, which has been previously reported to increase with CsA therapy, was influenced by the timing of CsA therapy (initial: 12%; delayed: 3%, P less than 0.05) but was not affected by duration of cold ischemia. Thus, safe preservation of cadaver kidneys for up to 70 h can be achieved by standard techniques even when CsA is incorporated into the immunosuppressive regimen. The most important determinants of graft survival in these patients are the timing of CsA therapy and the presence of early graft function, not the duration of renal preservation.

The effect of exogenous lymphokines on immunoglobulin production and lymphocyte proliferation in renal transplant patients.

Peripheral blood mononuclear cells from stable long-term kidney transplant patients were activated in vitro by Staphylococcus Aureus Cowan I (SAC) (a B cell mitogen). The effect of exogenous interleukin 2 and/or B cell growth factor (BCGF) on these cells was measured by 3H-thymidine incorporation and immunoglobulin production. Both proliferation and Ig production were lower in SAC-activated cells from transplanted patients compared to controls (P less than 0.01). BCGF significantly enhanced blastogenesis (P less than 0.01) and Ig production (P less than 0.01) in SAC-treated cells from either patients or controls; however, the SAC- and BCGF-treated cells of transplant patients did not reach normal proliferation or immunoglobulin production values (P less than 0.001, P less than 0.01, respectively). The addition of IL-2 to SAC-activated cells also increased proliferation and Ig production both in controls (P less than 0.05) and patients (P less than 0.005). However, cells from transplant patients treated with SAC and IL-2 did not reach the normal levels of proliferation or immunoglobulin production (P less than 0.05 for both). IL-2 did not enhance the increase of immunoglobulin production brought about by BCGF. SAC-activated B cells from transplant patients do not proliferate normally and do not produce normal amounts of Ig. The addition of IL-2 and BCGF results in a partial but subnormal improvement in both proliferation and Ig production. We conclude that the B cell abnormality in transplant patients may be due to lack of T cell lymphokines and an intrinsic B cell defect. These results suggest that the administration of exogenous lymphokines to transplant patients with B cell dysfunction may be clinically useful.

In vitro immunoglobulin production in long-term renal transplant recipients.

The difference in immunoregulation between stable renal transplant recipients and patients undergoing chronic rejection is unknown. In stable transplant recipients humoral responses to the allograft are controlled, but in patients with chronic rejection this control appears to be lost. In this study we evaluate B cell function in 24 stable transplant recipients and 5 patients with chronic rejection, using pokeweed mitogen (PWM)-stimulated in vitro lymphocyte production of immunoglobulin (Ig). Stable patients and patients with chronic rejection were similar with respect to time posttransplant, age, degree of HLA-A and B matching and immunosuppressive therapy. Unstimulated immunoglobulin production and serum immunoglobulin levels were similar in both groups and within the normal range. PWM stimulated IgG, and IgM production was significantly depressed in stable patients compared with normal controls and patients with chronic rejection. Patients with chronic rejection had normal PWM-stimulated Ig production. Mononuclear cell subsets--as determined by the monoclonal antibodies T4, T8, T11, B1, and M02, as well as the ratio of T4 to T8--were similar in the two patient groups and within the normal range. There was no correlation between decreased Ig production and decreased T4/T8 ratio. We conclude that stable renal transplant recipients have impaired in vitro humoral responses that may be important in maintaining allograft tolerance. In patients with chronic rejection PWM-stimulated responses have escaped control, and this may be important in the pathogenesis of antibody-mediated graft damage. Impaired Ig production in stable patients may be due to a suppressor cell mechanism--however, quantitative measurements of suppressor cells and the T4/T8 ratio do not predict humoral unresponsiveness.

Pretransplant crossmatch status and immunoglobulin production in renal transplant recipients.

The factors responsible for B cell regulation in stable renal transplant patients are unknown. To examine these control mechanisms, the B cell responses to 4 mitogens (pokeweed, wheat germ agglutinin, lipopolysaccharide, and SAC-1), which are known to stimulate B cells by different mechanisms, were measured in two groups of stable long-term (greater than 1 year post-transplant) renal transplant recipients. The first group were patients who had been transplanted under conditions of a negative crossmatch on all available pretransplant sera (negative crossmatch group) and the second group were patients who might have a unique regulation of B cell function in that they had been successfully transplanted under the conditions of a negative crossmatch using sera at the time of transplant but with pretransplant sera that gave a positive donor-specific T cell crossmatch (positive crossmatch group). Stable transplant patients were found to have significantly impaired responses to all four mitogens tested. Furthermore there were no differences in the responses of the negative crossmatch patients as compared with the positive crossmatch patients. The lack of response to mitogens was not due to a lack of proliferation of cells or to a loss of viability in culture. The number of cells in culture was the same in negative crossmatch patients and controls but was significantly less than controls in positive crossmatch patients (P less than 0.001). These findings suggest an intrinsic B cell defect in all stable transplant patients, and that the degree of the impaired B cell responses is the same in positive and negative crossmatch patients. In addition in positive crossmatch patients, there is a decrease in the percentage B cells that resulted after separation on a Ficoll-Paque gradient.

Outcome of kidney transplantation from high-risk donors is determined by both structure and function.

METHOD: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). RESULTS: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). CONCLUSION: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

A comparison of rabbit antithymocyte serum and OKT3 as prophylaxis against renal allograft rejection.

A total 166 first cadaveric renal allograft recipients were randomly assigned to receive either rabbit antithymocyte serum (RATS) (n = 83) or OKT3 (n = 83) for 10 to 14 days after transplant as prophylaxis against rejection. Both groups were similar with respect to age, sex, donor age, diabetes, time on dialysis, panel-reactive antibody, HLA matching, and transfusion before transplantation. All patients were followed for 1 year after transplantation. A comparison of the rejection rates between the 2 groups of patients showed that patients receiving OKT3 had a rate of first rejection 1.87 times higher than those receiving RATS (95% confidence interval 1.18-2.8, P = 0.007). Twenty-five steroid-resistant rejections occurred in OKT3-treated patients as compared with 12 in the RATS-treated group (P < 0.05). There was no significant difference in early or late renal function between the 2 groups of patients. Actuarial 1-year graft survival for the RATS group was 78% and for the OKT3 group, 80.7% (P = NS). Actuarial 1-year patient survival was similar: 89.5% in the RATS group and 94.6% in the OKT3 group (P = NS). Total hospitalization time was 29.8 +/- 19.9 days for RATS vs. 39.5 +/- 22.1 days for those treated with OKT3 (P < 0.006). A number of infections were observed but there were no significant differences between the groups. We conclude that RATS provides better prophylaxis than OKT3 in first cadaveric renal transplants because it is associated with fewer rejection episodes, less hospitalization, and no additional morbidity or mortality.

Pediatric heart transplantation: improving results in high-risk patients.

OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

Recycled heart valves from transplant patients.

Forty heart transplantations were performed at the Toronto Western Hospital, University of Toronto, from October 1987 to December 1989. Each heart extracted from a recipient was examined with the view of using the aortic valve as a homograft for another patient requiring aortic valve replacement. Of the 40 explanted hearts, 26 had normal aortic valves that were potentially suitable for homografting, and 14 had aortic valves judged as unsuitable. Of the potentially suitable valves, four were preserved for ex vivo arrhythmia studies requiring aortic root perfusion and four were damaged during harvesting. The remaining 18 usable valves were sized at the time of explantation and stored in an antibiotic solution at 4 degrees C. Thirteen valves were transplanted within 10 days of harvesting, and five were discarded because no suitable recipients were available within this period. There were no operative deaths or valve-related complications in the 13 homograft valve recipients. Mean follow-up was 13 months (range, 3 to 27 months). One patient required replacement of the homograft with a mechanical prosthesis because of insufficiency and stenosis. All patients are alive, are New York Heart Association functional class status I, and have insignificant valve gradients based on Doppler echocardiography. Although hearts removed from transplant recipients are severely diseased, the aortic valves are frequently normal and should be considered for use as homografts for other patients requiring aortic valve replacement.

Myocardial vacuolization, a marker of ischemic injury, in surveillance cardiac biopsies posttransplant: Correlations with morphologic vascular disease and endothelial dysfunction.

Allograft vasculopathy (AV) causes intimal thickening with progressive luminal obstruction, endothelial dysfunction, and abnormal vasomotion. Subendocardial vacuolization indicating ongoing ischemia was observed at autopsy in transplanted hearts with severe AV. Whether myocyte vacuolization can be observed with lesser degrees of AV in cardia transplant patients has not been reported. Thirty-nine cardiac transplant patients without flow-limiting disease in large epicardial arteries underwent invasive assessment of AV. Eight to 10 segments of the left anterior descending artery were analyzed by intracoronary ultrasound, and an average intimal index was calculated. Endothelial response to acetylcholine was assessed with serial quantitative angiography. Endomyocardial biopsies taken 5 to 7 days prior to the invasive studies were histopathologically reviewed for the presence of small intramyocardial arteries and myocyte vacuolization. Myocyte vacuolization was evident in biopsies from 20 patients (51%). Intramyocardial arteries were observed in 30 cases (76%); 14 had abnormal arteries. All patients had some degree of intimal thickening by intracoronary ultrasound, and 7 (17 %) had severely abnormal average intimal index (>0.2). Endothelial dysfunction was present in 23 patients (58%). Vacuolization failed to show an association with abnormal small artery histology or large epicardial artery ultrasound disease. However, a significant association between vacuolization and endothelial dysfunction was observed (p = 0.05). Myocyte vacuolization, possibly indicating ischemic injury, is common in biopsies from cardiac transplant patients and is associated with abnormal acetylcholine response in large epicardial arteries. We speculate that myocyte vacuolization may be caused at least in part by impaired coronary flow associated with endothelial dysfunction.

Cutaneous malignant neoplasms in patients with renal transplants.

There is an increased risk of developing cutaneous neoplasms in patients with renal transplants who are receiving immunosuppressive therapy. We studied 523 consecutive white patients who had received renal transplants at a Canadian medical center. Malignant neoplasms developed in 7.5% of these patients, and 72% of these neoplasms were cutaneous in origin. Compared with the general population, the rate of development of all skin cancers, squamous cell carcinoma, and basal cell carcinoma was 3.2, 18.4, and 1.4 times, respectively. In our study the squamous cell carcinoma to basal cell carcinoma ratio was 2.3:1, compared with 0.2:1 in the general population. There was no significant difference in the site of development of skin cancer in patients with renal transplants compared with the general population. There was, however, a propensity for the development of multiple skin cancers at an earlier age, especially on sun-exposed areas. The results of this study have been compared with those of other world medical centers.