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M Carrier

Publications and source records attributed to M Carrier.

191 records · Page 11Linked to original sources

A novel method for large-area sources preparation for the calibration of beta- and alpha-contamination monitors.

A method is proposed for the preparation of large-area reference sources for the calibration of beta- and alpha-contamination monitors. It is based on the incorporation, by the ion-exchange mechanism, of the radionuclide in a thin film of a conducting polymer ion-exchanger preliminarily grown on a metal support. Conducting pyrrole-based polymer functionalized by carboxylic cation-exchange groups is used to prepare 60Co and 90Sr-90Y beta-particle sources. Electrochemical polymerization of the corresponding monomer on different conducting supports is studied and a special electrochemical equipment developed permitting the preparation of large-area polymer films of controlled and reproducible thickness. The ion-exchanger obtained is characterized in terms of chemical affinity for cations Co2+ and Sr2+. Incorporation of the radionuclides in the large-area ion-exchanger films thus obtained is studied and optimized with respect to the uniform distribution of the radionuclide. The performance of the procedure is demonstrated using the example of circular sources 44 mm in diameter prepared on stainless steel supports. The sources obtained are characterized in terms of activity, beta-particle flux, uniformity and source efficiency.

Journal Article↗

Infections with the CardioWest total artificial heart.

The CardioWest total artificial heart is a pneumatically driven device that totally replaces the failing ventricles. It is currently used as a bridge to heart transplantation in selected centers in the United States under a study by the Food and Drug Administration. Twenty-seven patients have undergone placement of the total artificial heart since 1993 with the intention to bridge to transplantation. Inclusion criteria included candidacy for heart transplantation, cardiac index (CI) < 2.0 L/min/m2, and maximal inotropic support. The population consisted of 25 men and 2 women of mean +/- SD age 46.5 +/- 10.3 years, body surface area 2.01 +/- 0.17 m2, and duration of implant 52 +/- 42 days. Initial diagnosis included ischemic cardiomyopathy (n = 10), idiopathic (n = 10), viral (n = 4), valvular (n = 2), and graft failure (n = 1). Infectious complications were defined as systemic (evidence of leukocytosis or fever) or local. The population experienced 64 infections (range, 0-9 per patient): 45 systemic and 19 local. Three patients did not experience any infection. Twenty-five patients reached transplantation, and were discharged home for a survival rate of 92.6%. Two patients died during the bridge, one because of mechanical failure, and one because of infection (mediastinitis). Therefore, death attributable to infections occurred in 3.7%. Previous reports of the total artificial heart experience in the late 1980s described death rates as high as 40%. Although infectious complications are common in patients who are bridged to heart transplantation with the total artificial heart, mortality from infections is 10 times less than previously reported. This may be the result of a better strategy for bridging to transplantation that includes patient selection, mobilization, early central line removal, and waiting until all possible infections are resolved before proceeding to transplantation.

Female↗

Influence of age on late results of valve replacement with porcine bioprostheses.

From 1976 to 1987, 877 patients, aged 13 to 80 years, underwent valve replacement with a Carpentier-Edwards porcine bioprosthesis--330 aortic, 421 mitral, and 126 multiple replacements. Patients were divided into 4 age groups, according to their age at the time of surgery: group I, less than 45 years (190 patients), group II, 45 to 54 years (203 patients), group III, 55 to 64 years (304), and group IV, 65 to 80 years (180 patients). Follow-up was 97.5 complete, averaged 85 months, and totalled 5624 patient-years. There were 79 early deaths (9%), and 181 late deaths. Overall survival was 80% and 64% at 5 and 10 years. Operative mortality increased significantly with age, and late survival was significantly better for group I. Intrinsic structural deterioration was the most common cause for reoperation and was responsible for 91% of the 143 reoperations. Incidence of intrinsic structural deterioration and of reoperation decreased significantly with increasing age, with respective freedom rates at 10 years of 57 and 54 in group I compared to 93 and 92% in group IV. Freedom from treatment failure (including early deaths, valve-related deaths, and valve-related complications with permanent disability) was similar for all 4 groups ranging from 78 to 85%, without any correlation with age of the patient. At last follow-up, a similar proportion of patients of each group remained asymptomatic, patients in functional class I ranging from 50 to 55%. Thus, age is a major determinant of durability of bioprostheses, but it does not appear to have a significant role in the overall success of valve replacement.

Actuarial Analysis↗

Migration and imaging of 111Indium-labelled lymphocytes in cardiac allograft rejection.

BACKGROUND: The diagnosis of cardiac allograft rejection is based on routine endomyocardial biopsy. To study an alternative method the authors evaluated the migration and scintigraphic imaging of 111Indium-labelled lymphocytes in a model of acute heart allograft rejection. METHODS AND RESULTS: Cervical heterotopic heart transplantation was performed in 10 dogs. Blood samples were harvested at 24 and 48 h after surgery for labelling of 36 +/- 6 x 10(6) lymphocytes with 6.62 +/- 0.56 MBq of 111Indium. Daily blood samples and heart biopsies were obtained for nuclear counting on the next three days; animals were sacrificed and both donor and native hearts were studied. Between 20 and 31% of autologous labelled lymphocytes remained in circulation until 72 h after injection. Maximal plasma 111Indium activity was 315 +/- 90 compared with 5513 +/- 1483 cpm/mL in whole blood (P less than 0.05). An average of 10,176 +/- 3444 labelled lymphocytes per gram of tissue were present in allograft biopsies while histological evaluation showed mild to moderate acute rejection. The ratio of tissue biopsy to blood 111Indium counts varied from 0.7 +/- 0.2, 6 h after autologous injection to 8.5 +/- 3.8 48 h later (P less than 0.05). At autopsy, 298 +/- 66 labelled cells per gram of tissue were present in native hearts compared with 2686 +/- 711 in allografts (P less than 0.05). Scintigraphic imaging using holospectral acquisition was performed; six lateral projections showed an indium activity ratio (transplanted heart to background tissue) of 2.8, 24 to 72 h after autologous injection of labelled cells. CONCLUSIONS: Labelling of a small number of lymphocytes with 111Indium gave a stable population of circulatory lymphocytes for studying migration of labelled cells into allografts and a noninvasive scintigraphic approach to diagnose cardiac allograft rejection.

Animals↗

Analysis of risk factors for acute allograft rejection after heart transplantation.

The diagnosis of cardiac allograft rejection is currently based on endomyocardial biopsy and histologic evaluation. Since the introduction of cyclosporine, cardiac biopsy has been recognized as the only reliable method of diagnosis. From July 1985 to June 1986, 22 transplant patients were studied during the early posttransplant period to evaluate other characteristics of allograft rejection. The immunosuppressive protocol included cyclosporine, azathioprine, prednisone, and prophylactic rabbit antithymocyte globulin. Acute rejection was established by standard histologic criteria. Twenty-four positive and 123 negative biopsy findings were obtained. Clinical variables (age, sex, immunosuppressive regimen, cyclosporine dosage, ECG voltage), biologic variables (level of cyclosporine, white blood cells, blood urea nitrogen, creatinine, bilirubin, prolactin, urinary polyamines, blood type, HLA typing), and immunologic variables (T-cell subsets) were analyzed in regard to the histologic diagnosis of acute rejection. Four variables (WBC, prolactin, total urinary polyamines, N-acetyl putrescine) were found to have a significant univariate association with acute rejection. These variables were studied by multivariate discriminant analysis. The only factors found to have independent predictive value for acute rejection were prolactin and N-acetyl putrescine peaks occurring before acute rejection. When we used these factors, a discriminant function correctly predicted acute rejection episodes, as well as negative biopsy results, in 74% of the cases in this group of patients.

Biopsy↗

Urinary polyamines are noninvasive markers of heart allograft rejection.

Histologic evaluation of the heart allograft biopsy is currently the generally accepted method to monitor for rejection after transplantation. A noninvasive marker of host prerejection immunologic activation might be a useful clinical tool and provide the basis for a more continuous evaluation than is available with the biopsy technique. Urinary polyamine levels, in the context of immune activation, may fluctuate as an indicator of lymphocyte proliferation and organ rejection. To test this hypothesis cervical heterotopic heart transplantation was performed in six dogs that did not receive immunosuppression therapy. Daily percutaneous transmural biopsy of the transplanted heart and urine samples were collected. Urinary polyamines were measured by high-pressure liquid chromatography. Between 2 and 4 days after transplantation all allografts showed a histologic picture of mild to moderate rejection. The urinary excretion of total polyamines and putrescine fraction increased during the rejection process after transplantation, attaining a maximum from the first to the third day after operation. This early elevation suggests that urinary polyamines are markers of immune activation and unmodified heart allograft rejection. Further studies need to be done to define a potential clinical application of urinary polyamines as markers of cellular metabolic activity of the immune system and allograft rejection.

Animals↗

Prolactin as a marker of rejection in human heart transplantation.

Prolactin has been shown to play a role in the modulation of the immune system. In addition, recent laboratory evidence suggests that circulating prolactin might fluctuate as a function of immunologic events. To evaluate the role of prolactin as a predictor of rejection, 22 heart and heart-lung transplant patients were studied from July 1985 to May 1986. Daily plasma prolactin levels were measured by radioimmunoassay. Endomyocardial biopsy and histologic evaluation of the allografts were used to define rejection episodes. Thirteen of 14 documented rejection episodes were preceded by a specific elevation of circulating prolactin. A significant elevation of prolactin occurred 6 and 8 days before 14 rejection episodes that were diagnosed by biopsy but not before 109 biopsies were taken that had negative results. The normal values for circulating prolactin are defined by a preoperative mean in a range of 0 to 15 ng/ml (95% confidence limit). The sensitivity of prolactin to predict rejection is 79%, the specificity is 92%, and the positive predictive value is 61%. A large data variability gives a low accuracy to the test as a predictor of allograft rejection. To be useful clinically, the accuracy needs to be improved through a better understanding of prolactin physiology and its relation to the immune system.

Adult↗

Histopathology of acute myocardial necrosis: effects of immunosuppression therapy.

Endomyocardial biopsy is currently the best method to monitor cardiac allograft rejection. The histologic criteria of infiltration by mononuclear cells with pyroninophilic cytoplasm and acute myocyte necrosis indicate immunologic activation and require an increase of immunosuppressive therapy. Of particular concern is the persistence of necrotic fibers on biopsies for some time after ischemic episodes associated with the transplant procedure and after acute rejection episodes. Because the presence of acute myocyte necrosis plays a key role in the clinical decision on immunotherapy, we evaluated the resolution pattern of acute necrotic fibers under standard immunosuppression treatment. Myocardial infarction of the posterior papillary muscle was surgically induced in two groups of dogs that were killed (three from each group) at 4, 7, 14, and 21 days after surgery. The first group consisted of 12 control animals, and the second group was composed of 12 dogs, immunosuppressed with cyclosporine, methylprednisolone, and prednisone. The histologic sections demonstrated a persistence of myocyte necrosis for 14 days after infarction in the treated group but for only 7 days in the untreated control group. This slow resolution pattern needs more emphasis in clinical practice. Criteria other than myocyte necrosis should be used to differentiate ongoing from resolving rejection after the first rejection episode. Preservation injury may persist for 2 weeks after transplantation and be misinterpreted as acute rejection.

Animals↗

Cardiac troponin T and creatine kinase MB isoenzyme as biochemical markers of ischemia after heart preservation and transplantation.

An ischemic preservation period of less than 4 to 6 hours for the donor heart is considered safe in heart transplantation. To determine the severity of myocardial cell damage, we measured serum creatine kinase MB isoenzyme activity, creatine kinase MB isoenzyme mass concentration, and troponin T release in 14 patients during the first 48 hours after heart transplantation. All donors had normal cardiac function at echocardiographic evaluation. The heart was arrested with cold crystalloid cardioplegic solution and preserved in a hypothermic solution. All patients survived the first week after transplantation. Total ischemic time averaged 126 +/- 33 minutes (range 88 to 195 minutes). Maximal creatine kinase MB isoenzyme activity, creatine kinase MB isoenzyme mass concentration, and troponin T serum values after transplantation averaged 130 +/- 44 IU/L, 140 +/- 121 ng/ml, and 3.3 +/- 1.4 ng/ml, respectively. No significant correlation was found between ischemic time and peak levels of creatine kinase MB isoenzyme activity (r = 0.22), creatine kinase MB isoenzyme mass (r = 0.37) and troponin T (r = 0.12). A moderate correlation between ischemic time and the initial slope of time-activity curve of creatine kinase MB isoenzyme mass (r = 0.66, p = 0.01) and of troponin T release (r = 0.55, p = 0.03) was observed. Ischemic time and donor age were significantly related to creatine kinase MB isoenzyme mass (R2 = 0.61) and to troponin T (R2 = 0.47) initial release slopes. In conclusion, during a short period of ischemic preservation, myocardial cell damage appears to be mild and best reflected by the elevation and the time-activity curves of release of cardiac troponin T and creatine kinase MB isoenzyme mass.

Adult↗

Role of thromboxane and angiotensin in cyclosporine-induced renal vasoconstriction in the dog.

Cyclosporine is associated with renal insufficiency characterized by a reduction in glomerular filtration rate that may result from renal vasoconstriction. Injection of cyclosporine in the isolated renal artery perfused at a constant flow induces a potent dose-dependent vasoconstriction of renal arterial vessels in the dog. The present study was designed to investigate the role of thromboxane A2, angiotensin, and endothelial-dependent vasodilation in the cyclosporine-induced renal vasoconstriction. A specific thromboxane A2-receptor antagonist (pinane-thromboxane A2), administered at a dose of 150 micrograms, significantly decreased the renal vasoconstriction response to cyclosporine from 103 +/- 26 mm Hg to 45 +/- 11 mm Hg (p < 0.05), with cyclosporine serum levels at the end of injection averaging 382 +/- 105 and 421 +/- 150 nmol/L before and after injection of the antagonist. In contrast, pharmacologic blockade of angiotensin receptors by saralasin had no effect on the cyclosporine arterial vasoconstriction in the kidney. The endothelium-dependent vasodilation to acetylcholine was not modified during cyclosporine injection. Thus cyclosporine renal vasoconstriction appears independent of the renin-angiotensin system and of endothelium-dependent vasodilation. It is at least partly mediated by thromboxane A2. Prevention of cyclosporine vasoconstriction by thromboxane A2-receptor antagonist may likely be possible, with more potent agents having more affinity to thromboxane A2 renal receptors.

Acetylcholine↗