Early postoperative care and complications.
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Arrhythmias, Cardiac↗
Biomedical subjects
M Carrier
Publications and source records attributed to M Carrier.
The relationship between megakaryocyte nuclear DNA content and gene expression.
Megakaryocytes are a distinct population of bone marrow cells that have the unique feature of increasing their DNA content without undergoing division. The biological effect of ploidy distribution on gene expression, receptor expression and protein synthesis is still unknown. Using molecular hybridization techniques, we have started a systematic analysis of mRNA expression in megakaryocytes for a number of proteins involved in clot formation. These data will be related to ploidy. Platelets are the unnucleated product of megakaryocytes, having their protein content derived from the precursor cell. Therefore, the understanding of the molecular mechanisms regulating megakaryocyte biology and the consequent type and reactivity of platelets produced is of fundamental importance in both physiological and pathological conditions.
Blood Proteins↗
Bromocriptine as an adjuvant to cyclosporine immunosuppression after heart transplantation.
Prolactin, a pituitary hormone, has been shown to have an active role in the regulation of the immune system. Prolactin receptors have been described on the membrane of lymphocyte cells, and competitive binding to these receptors by cyclosporine and circulating prolactin has been demonstrated. Experimental evidence suggests a synergistic effect of cyclosporine and bromocriptine, an inhibitor of pituitary release of prolactin, on immunosuppression. Between July 1986 and January 1988, 54 patients were randomly assigned to two groups of immunosuppression treatment. Thirty patients (group 1) were administered cyclosporine, azathioprine, and prednisone and 24 patients (group 2), a modified protocol aimed at decreasing the level of circulating prolactin by adding bromocriptine to the immunosuppression regimen. The two groups were similar in regard to age, preoperative diagnosis, and duration of follow-up. Minimal side effects related to bromocriptine were observed. The overall incidences of rejection and infection were similar, although actuarial analysis showed that freedom from these complications among patients treated with bromocriptine was significantly higher throughout the first 2 months after heart transplantation compared with that of patients in the control group. Other variables such as serum cyclosporine levels and lymphocyte counts were similar in both groups. In conclusion, suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine, at least during the early postoperative period when the risk of rejection and infection is higher, and could be a promising avenue to successful hormonal manipulations of the immune process after organ transplantation.
Actuarial Analysis↗
[Coronary artery-right ventricular fistula in a patient with heart transplantation. A complication of endomyocardial biopsy].
Two cases of coronary artery right ventricular fistula were diagnosed during the yearly check-up of 38 of the 66 cardiac transplant patients of the Montreal Heart Institute between September 1982 and April 1989. In one case, the fistula involved the right anterior ventricular branch of the right coronary artery and in the other case, a septal branch of the left anterior descending artery. Histological examination of the biopsy fragments obtained before diagnosis of the fistula showed the presence of small calibre arteries, which was not the case in 10 control transplant patients. A review of the literature indicates that the risks of endomyocardial biopsy are minimal (less than or equal to 0.5%). However, the possibility of a coronary artery right ventricular fistula should be added to the list of known complications. The resulting shunt is negligible and has no haemodynamic consequences.
Adolescent↗
Tumour necrosis factor (TNF alpha) in leishmaniasis. I. TNF alpha mediates host protection against cutaneous leishmaniasis.
Genetically resistant CBA mice developed significantly larger lesions to Leishmania major infection when they were injected with rabbit anti-tumour necrosis factor (TNF)-specific antibodies compared to control mice injected with normal rabbit immunoglobulin. BALB/c mice recovered from a previous infection following prophylactic sublethal irradiation also developed exacerbated lesions when treated with the anti-TNF antibody. Injection of TNF into the lesion of infected CBA mice significantly reduced the lesion development. Furthermore, TNF activates macrophages to kill Leishmania in vitro. These data demonstrate that TNF plays an important role in mediating host-protection against cutaneous leishmaniasis.
Animals↗
[The effect of cyclosporin on renal function following cardiac transplantation: should one lessen the toxicity?].
Between 1983 and 1988, 50 patients underwent cardiac transplantation at the Institut de Cardiologie de Montréal. During this period, four immunosuppression protocols were used, each including cyclosporine. A combination of cyclosporine and prednisone was used in the first 24 patients (group 1). Triple combination immunosuppression (cyclosporine, prednisone and azathioprine) was given perioperatively in 13 patients (group 2). The prophylactic use of rabbit antithymocyte globulin and late administration (4 days postoperatively) of cyclosporine to prevent early renal failure associated with cyclosporine therapy was chosen in 13 other patients (group 3). Owing to serious deterioration of renal function in 15 of the 24 group 1 patients, the serum creatinine levels reaching 255 +/- 51 mmol/L and the creatinine clearance 34 +/- 2 ml/min between 6 months and 4 years after transplantation, immunosuppression was modified to triple-combination therapy by the addition of azathioprine and a reduction of the serum levels of cyclosporine (group 4). Twelve of the 15 patients showed a substantial improvement in renal function from 3 to 18 months after these changes were introduced. No patient in groups 2 and 3 had late renal insufficiency, and in all group 3 patients renal function remained normal as in the immediate postoperative period. In conclusion, important modifications in protocol permitted a reduction of early and late renal failure due to cyclosporine after cardiac transplantation.
Adult↗
Porcine versus pericardial bioprostheses: a comparison of late results in 1,593 patients.
From 1976 to 1988, 1,593 patients underwent valve replacement with a porcine (878 patients) or a pericardial bioprosthesis (715 patients). There were 701 aortic, 678 mitral, and 214 multiple-valve replacements. Follow-up was obtained for 1,559 patients (98%). Early mortality was 9% (79 patients) in the porcine valve group and 5% (37 patients) among patients with a pericardial valve (p less than 0.01). Late survival after replacement with porcine valves was 80% +/- 1% and 62% +/- 3% at 5 and 10 years, respectively. With pericardial valves, 5-year survival was 79% +/- 2%. Among valve-related complications, rates of freedom from thromboembolism, endocarditis, and hemorrhage after 6 years were similar for both valve groups. Freedom from reoperation at 6 years was also similar after aortic (96% versus 91%) or multiple-valve replacement (95% versus 88%). However, for mitral valve replacement, freedom from reoperation was significantly better with porcine valves than with pericardial valves at 6 years (92% versus 68%; p less than 0.001). This difference was mainly due to the Ionescu-Shiley valve, which accounted for 83% of primary tissue failures among pericardial bioprostheses implanted in the mitral position (10/12 patients). After 6 years, freedom from primary tissue failure of mitral valves was 92% +/- 2% with porcine and 70% +/- 11% with pericardial bioprostheses (p less than 0.0001). The degree of clinical improvement among survivors was similar with both valve types. Thus, in the aortic position, pericardial valves compare with porcine valves up to 6 years, whereas in the mitral position, the durability of the former is significantly less, mainly because of the suboptimal performance of the Ionescu-Shiley pericardial bioprosthesis.
Adolescent↗
Distinct IL-3 activation profile induced by intravenous versus subcutaneous routes of immunization.
Lymphoid cells from mice immunized i.v. or s.c. with Leishmania major antigens were analyzed for their capacity to produce lymphokines when stimulated with specific antigens in vitro. Spleen cells from BALB/c mice immunized by the s.c. route produced significantly higher levels of IL-3 and IL-3 mRNA than those from mice immunized by the i.v. route. The differential production of IL-3 was maintained at a wide range of antigen concentrations tested in vitro and for different culturing times. T cell enrichment procedures and treatment with CD4+ mAb in vitro confirmed the T cell nature of the IL-3 producer population. However, the IL-3 production in the two populations of spleen cells was equally high after Con A stimulation in vitro. The IL-2 production by the two populations of cells was also not significantly different after antigen or mitogen stimulation in vitro. To our knowledge, this is the first report of a differential synthesis of IL-3 mRNA and secretion of IL-3 induced by different routes of immunization followed by specific-antigen stimulation in vitro. These findings may also explain earlier observations that i.v. immunization with leishmanial antigen induces protection, whereas s.c. immunization leads to exacerbation of L. major infection, since IL-3 has been previously shown to promote leishmanial infection. The fact that the phenomenon also extends to other antigen systems suggests that this finding may have a broader implication in immune regulation and vaccine development.
Animals↗
Efficacy and tolerability of tiapamil in patients with mild to moderate essential hypertension.
Although early experience with tiapamil, a new calcium antagonist structurally related to verapamil, showed good antihypertensive efficacy and minimal adverse effects, recent studies have shown conflicting results. This single-blind dose-titration study was designed to determine the therapeutic efficacy, duration of action, and safety profile of tiapamil in patients with essential hypertension. After a 2-week washout period, patients received placebo for 4 weeks. Patients with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg received tiapamil 300 mg twice daily with dose increments of 150 mg twice daily every 2 weeks to a maximum of 1,200 mg/day. Once blood pressure (BP) control was achieved or patients were receiving 600 mg twice daily, they were followed up for an additional 2 weeks. Twenty of the initial 31 patients completed the trial, and 17 patients were receiving the highest dose of tiapamil. Nine patients dropped out because of adverse effects. No significant decreases in BP and heart rate (HR) were either noted by the clinic or apparent by 24-h ambulatory BP readings. Random assays of drug supplies showed that patients received the required dosage. The incidence of adverse effects rose with increasing doses of tiapamil: 27.6% of patients at 300 mg twice daily, 48% at 450 mg twice daily, and 81.8% at 600 mg twice daily. Dizziness, headache, and palpitations were the most frequent adverse effects. These results show that tiapamil given at a daily dose of 600-1,200 mg exhibits very little effect in lowering BP in patients with mild to moderate essential hypertension. Moreover, the incidence of adverse effects is much higher than reported in earlier studies.
Adult↗
Effects of 4% pilocarpine gel on normotensive and glaucomatous canine eyes.
A 4% pilocarpine gel applied topically to eyes was evaluated in glaucomatous Beagles and normotensive Miniature Schnauzers to determine its efficacy in reducing intraocular pressure (IOP) and to assess any side effects. Pilocarpine gel significantly (P less than 0.05) reduced IOP for 24 hours after treatment, compared with baseline (pre-drug) values, untreated fellow eyes, and placebo-treated eyes. The IOP remained significantly lower (P less than 0.05) during 3 treatment days, as well as the first 2 days after treatment. The pupil sizes were significantly smaller (P less than 0.01) in all treated dogs after the first administration of pilocarpine, compared with baseline values, untreated eyes, and placebo-treated eyes. The subsequent pilocarpine gel administrations induced significant miosis (P less than 0.01), compared with baseline values, but the extent of miosis and duration were significantly less (P less than 0.01) as the number of treatments increased. Conjunctival irritation and blepharospasm were observed mainly in the first 2 days of treatment and were minimal after subsequent applications. There was no contralateral effect on IOP or pupil size, compared with baseline values and placebo-treated eyes.
Animals↗
Value of urinary polyamines as noninvasive markers of cardiac allograft rejection in the dog.
A noninvasive marker of cardiac allograft rejection would be useful clinically. Lymphocyte proliferation and organ rejection may cause changes in urinary polyamine excretion. To test this hypothesis, cervical heterotopic heart transplantations were performed in a group of 6 nonimmunosuppressed dogs and in a group of 9 dogs treated with cyclosporine (N = 3) or cyclosporine and steroids (N = 6). A group (N = 3) having a sham operation was also studied. Serial biopsies of the transplanted hearts were performed. Urinary polyamine levels were measured daily by high-pressure liquid chromatography of urine specimens. Between 2 and 4 days after transplantation, the transplanted hearts of all animals without immunosuppression demonstrated histological rejection. An early increase in putrescine levels and in total urinary polyamine levels was observed in this group. In the treated groups, histological rejection appeared from the second to the eighth day after transplantation. Each episode of rejection occurred from 1 day to 4 days after a significant increase in urinary polyamine levels compared with the preoperative baseline level (p less than 0.01). In contrast, polyamine excretion in 3 dogs after sham operations remained unchanged. Thus, urinary excretion of polyamines increases before the appearance of histological rejection; this suggests that changes in urinary polyamine levels may be a useful marker of cardiac allograft rejection.
Animals↗
Urinary polyamines as markers of cardiac allograft rejection. A clinical evaluation.
Histologic evaluation of endomyocardial biopsy specimens is the current method of monitoring rejection after cardiac transplantation. Unfortunately, this technique gives a discontinuous evaluation of the recipient immunologic status. A noninvasive marker of immunologic activation and of allograft rejection that would permit a more continuous monitoring than the biopsy technique would be clinically useful. Urinary polyamine excretion reflects cellular proliferation or degeneration and, as a marker of cellular metabolic activity, may also reflect lymphocyte proliferation and organ rejection. From July 1985 to December 1986, urinary polyamines were studied in 18 patients during hospitalization for heart and heart-lung transplantation. Endomyocardial biopsy was performed twice a week and histologic rejection was characterized by standard criteria. Urinary specimens were collected daily and analyzed for polyamines by high-pressure liquid chromatography. Concentrations of acetylputrescine and total urinary polyamines were significantly higher before the 20 rejection episodes than before the 80 biopsies yielding negative results. So that their clinical usefulness could be evaluated, an elevation of polyamines and a daily level variability of 28% or more was chosen to indicate increased metabolic cellular activity and to predict rejection in the next 8 days. On the basis of these definitions, the sensitivity of polyamine assays to predict rejection was 85%, the specificity 88%, and the positive predictive value 79%. Therefore, serial measurements of urinary polyamines may provide daily information on the recipient's immunologic status after cardiac transplantation.
Adult↗
How much does aortic and pulmonary artery area vary during the cardiac cycle?
Cardiac output (CO), as measured by Doppler, is computed by multiplying vessel area by mean velocity. One unresolved problem is the magnitude of vessel area change during the cardiac cycle. Prior estimates have ranged from 2% to 30% area change during the cardiac cycle. The purpose of this study was to measure cyclic dimensional changes in the aorta and pulmonary artery of dogs by a very sensitive technique, mercury strain gauge plethysmography. Gauges were fixed around the pulmonary artery and the aorta and changes in vessel circumference were recorded under the following conditions: increased preload, increased afterload, decreased preload, and during administration of dobutamine, 5 and 10 micrograms/kg/min. Percent change in circumference of the aorta at baseline was small (mean circumference change = 4%, SD = 1%, SEE = 0.5). Percent change in the pulmonary artery at baseline was slightly larger (mean circumference change = 6%, SD = 5%, SEE = 2%). Mean aortic area change was 9% (SD = 2%) and for the pulmonary artery it was 12% (SD = 10%). No experimental manipulation significantly altered the percent cyclic change in vessel size from baseline except for clamping the inferior vena cava, in which mean percent change in aortic circumference decreased to 1% (SD = 1%, SEE = 5%) (p less than 0.05). Percent change in the aorta correlated only weakly with heart rate (r = 0.48), blood pressure (r = 0.4), and CO (r = 0.46). Similar values were obtained for the pulmonary artery. These data demonstrate a small but definite cyclic change in pulmonary artery area, and to a lesser extent in aortic area.
Animals↗
Selection of patients for cardiac transplantation.
Selection of potential cardiac recipients is not a simple process. Identification of patients who are declining from end-stage cardiac disease and may be expected to die within 12 months or less and deciding which of a number of cardiac invalids are reasonable candidates for cardiac transplantation involves prognostication as well as a working knowledge of the expected benefits and survival rates in cardiac transplantation. Screening by means of the currently accepted contraindications for cardiac transplantation is somewhat more difficult in 1986 than it was 10 years ago when these contraindications were changing less rapidly. However, for optimal use of the limited supply of donor organs and maintenance of reasonable survival rates such screening is absolutely necessary. A second area of restriction that is less approachable by the physician is that of financial limitations. It would appear that the working poor and lower middle class may be deprived of the opportunity for cardiac transplantation much as they are deprived of the opportunity for optimal medical care in our society today.
Age Factors↗
Prolactin as a marker of rejection in human heart transplantation.
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Adult↗
Clinical and hemodynamic assessment of the Omniscience prosthetic heart valve.
From 1980 to 1985, 154 Omniscience valve prostheses were implanted in 132 patients (mitral in 72, aortic in 33, and both in 27), 81 women and 51 men, aged 22 to 72 years. There were 13 early deaths (30 day mortality of 9.8%) and nine late deaths. The actuarial survival rate was 79.1% after 4 years, and survival rates after aortic, mitral, and multiple valve replacement were 71.8%, 80%, and 85.2%, respectively. After a postoperative follow-up period averaging 27 months, 96% of the survivors were in Class I or II. The linearized incidence of thromboembolism, hemorrhagic episodes, and reoperation was 3.8%, 3.4%, and 2.3% per patient-year, respectively. After 4 years, freedom from valve-related mortality, valve-related mortality and reoperation, thromboembolic episodes, and all valve-related complications was 93%, 89%, 88%, and 70%. Moderate hemolysis with increases of reticulocyte count and serum lactic dehydrogenase above normal values was found in 80% of the patients, but only one had hemolytic anemia. In 22 patients, the maximal opening angle of the prosthetic disc averaged 54 +/- 11 degrees. Postoperative hemodynamic evaluation was obtained in five patients with aortic prostheses and in 13 with mitral prostheses. Mean aortic gradient and effective orifice area averaged 17.6 mm Hg and 1.2 cm2 at rest and increased to 18.8 mm Hg and 1.7 cm2 with exercise. With mitral prostheses, these values averaged 6.5 mm Hg and 1.9 cm2 at rest and 15.4 mm Hg and 2.1 cm2 with exercise. Thus excellent clinical improvement is obtained with the Omniscience prosthesis; however, the hemodynamic performance of the valve and opening of the tilting disc are suboptimal, causing the prosthesis to be moderately obstructive to blood flow.
Actuarial Analysis↗
Cardiac transplantation in patients over 50 years of age.
Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (+/- SEM) of the patients over 50 was 53 +/- 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and five, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin. Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (greater than 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 +/- 0.5 episodes per patient in those patients over 50 and 1.9 +/- 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 +/- 14% in the group over 50 and 66 +/- 7% in the group under 50 years of age. These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure.
Age Factors↗
[Adenocarcinoma of the rectum. Analysis of the selective criteria in surgical curative treatment (106 cases) (author's transl)].
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Adenocarcinoma↗