Coincidence of myoclonus and multiple sclerosis: dramatic response to clonazepam.
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Clonazepam↗
Biomedical subjects
C R Smith
Publications and source records attributed to C R Smith.
Anti-CD3 monoclonal antibody induction therapy. Immunological equivalency with triple-drug therapy in heart transplantation.
This study examines the hypothesis that induction immunosuppressive therapy with murine anti-CD3 monoclonal antibodies (OKT3) reduces the frequency of rejection episodes in heart transplant recipients receiving 3-drug maintenance therapy with cyclosporine, azathioprine, and steroids. A group of 26 adult heart transplant recipients requiring preoperative intravenous inotropic drugs or with elevated serum creatinine received OKT3 induction as well as long-term triple drug therapy. Cyclosporine was withheld for the first 4 postoperative days allowing for resolution of cardiogenic renal dysfunction. A corresponding group of 26 heart transplant recipients received triple drug therapy alone started immediately before transplantation. Both groups were comparable in age, sex distribution, and follow-up period. The frequency of rejection episodes was identical for the two groups (0.003 episodes per patient month). Time to first rejection episode in the induction group, however, was delayed twofold as compared with the noninduction group (42 versus 21 days, p less than 0.01). Actuarial survival at 6, 12, and 18 months was 88%, 81%, and 81% for the induction group and 92%, 92%, and 87% for the noninduction group (p = NS). Treatment for rejection was not required in 35% of the induction group and 38% of the noninduction group (p = NS). OKT3 provides satisfactory immunosuppression in heart transplant recipients with hemodynamic or renal compromise, yet it does not reduce the frequency of rejection episodes compared with patients receiving triple drug therapy alone. Although the time to first rejection may be delayed, routine adjuvant use of OKT3 for induction in all heart transplant recipients may incur needless expense without providing an important immunological advantage as compared with triple drug immunosuppression alone.
Antibodies, Monoclonal↗
Late complications in pediatric cardiac transplant recipients.
Late complications occurring more than 3 months after cardiac transplantation were analyzed in 29 pediatric patients in whom 31 cardiac transplantations were performed. Age at transplantation ranged from 3 months to 18 years (mean, 11.3 years) with follow-up ranging from 3.5 to 54 months (mean, 21.6 months). There were seven late deaths and two patients with retransplantations. Of nine grafts lost, eight were due to acute rejection, and one was due to coronary disease. Four of the grafts lost were secondary to patient noncompliance with prescribed immunosuppression. The mean rejection frequency more than 1 year after cardiac transplantation was significantly higher in those patients who eventually lost their grafts; however, these patients could not be distinguished by their rejection frequency in the first year. Eight patients had coronary disease, with five diagnosed at autopsy, two at cardiac retransplantation, and one by angiography. All eight patients were on double immunosuppression; none of the 19 patients on triple therapy had coronary disease with similar follow-up. There were 12 serious infections in eight patients (four associated with OKT3) with no deaths. Five patients had arrhythmias requiring treatment including two pacemakers; four of the five were associated with rejection episodes. Twelve of 29 patients developed early hypertension, and five developed late hypertension (greater than 1 year). There were two malignancies; one patient with Hodgkin's lymphoma was cured with chemotherapy, and one patient with histiocytic lymphoma was discovered at autopsy. Two patients had cholecystectomies, and five patients required laser gingivectomies.(ABSTRACT TRUNCATED AT 250 WORDS)
Child↗
High-risk reparative surgery. A neglected alternative to heart transplantation.
The selection of patients for either high-risk reparative operations on the heart or for transplantation has become increasingly difficult as a result of improved results with both modalities. A retrospective review was done of patients referred for heart transplantation who were not considered candidates for conventional cardiac surgery, yet instead underwent reparative procedures rather than transplantation. Of 23 adult patients referred during a 7-year period, 18 had coronary artery disease, and five had valvular heart disease. All had New York Heart Association class IV symptoms. Preoperative left ventricular ejection fractions were in the range 0.08-0.63 (mean, 0.28). Ten of 18 patients with coronary artery disease required insertion of an intra-aortic balloon pump for hemodynamic support perioperatively. Seven patients had primary coronary artery bypass grafts, and 10 had reoperative coronary bypass procedures. One patient had a left ventricular aneurysmectomy, and one had endocardial stripping in addition to myocardial revascularization procedures. Of the patients with valvular disease, three had aortic valve replacement, of which two were reoperations, and two others had mitral valve replacements with tricuspid annuloplasties. With a mean follow-up of 25 months, 1-, 3-, 12-, and 24-month actuarial survival rates were 91%, 87%, 82%, and 76%, respectively. One patient who underwent aortic valve replacement in this study successfully received heart transplantation 19 months postoperatively. These results compare favorably with the current results for patients undergoing first-graft heart transplantation. All survivors enjoy New York Heart Association class I or II functional capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary Disease↗
Single-stage management of sternal wound infections.
Deep median sternotomy wound infection is a significant source of morbidity after cardiac operations. Accepted approaches in treating this complication include débridement with either sternal closure over an irrigation system or open dressings and closure by secondary intention. Muscle flaps are often used in subsequent procedures for wound closure. A single-stage procedure was developed to eliminate irrigation, open wound management, or reoperation for muscle flap closure. This approach consists of débridement and immediate closure with a pectoral musculocutaneous flap. The following report describes 31 patients treated by such a method. Compared with results of previous techniques in treating sternal wound infections, hospital study is decreased, fewer reoperations are needed, and patient management is simplified.
Cardiac Surgical Procedures↗
Ceftriaxone compared with cefotaxime for serious bacterial infections.
Ceftriaxone was compared with cefotaxime for the treatment of serious bacterial infections in a prospective, randomized, double-blind clinical trial. The dose of ceftriaxone was 2 g once a day, and the dose of cefotaxime was 2 g every 4 h. Metronidazole was added if anaerobic infection was suspected. Explicit criteria were used to define infections, clinical response, and adverse effects. Ceftriaxone was given to 88 patients and cefotaxime to 83. The two treatment groups did not differ in types of infection, infecting organisms, and severity of underlying disease. The response rate was 81% (71/88) for ceftriaxone and 80% (66/83) for cefotaxime. The power of the study to detect a 15% difference in response rate at P less than .1 was 90%. The frequency of diarrhea, thrombophlebitis, prothrombin time, prolongation, colonization, and superinfection did not differ between treatment groups. Ceftriaxone 2 g once a day was as safe and effective as cefotaxime 2 g every 4 h for suspected serious bacterial infections.
Adult↗
Improvement in post-traumatic spinal cord blood flow with a combination of a calcium channel blocker and a vasopressor.
We have recently shown that nimodipine, a calcium channel blocker, can increase spinal cord blood flow (SCBF) in normal rats and can improve SCBF after spinal cord trauma if the mean systemic arterial pressure (mSAP) is restored to normal levels by the vasopressor, adrenalin. The present study is a further analysis of the improvement in post-traumatic SCBF (measured with the hydrogen clearance technique) with the combination of adrenalin and nimodipine. In addition, image analysis was used to study the potential risk of this combination for exacerbating intramedullary hemorrhage in the injured spinal cord. SCBF, mSAP, and other physiologic parameters were measured preinjury, postinjury, and post-treatment. A 53.0-gram clip compression injury at the T1 spinal segment was delivered for 1 minute to three treatment groups (saline, adrenalin, and adrenalin plus nimodipine) comprised of five rats each. Injury caused a marked decline in SCBF and mSAP. Treatment with adrenalin alone or combined with nimodipine (1.5 micrograms/kg/min IV) improved mSAP to 100-125 mm Hg. However, adrenalin alone failed to improve SCBF, whereas nimodipine plus adrenalin produced a marked improvement of approximately 60% in post-traumatic SCBF. Morphometric analysis showed no significant difference between per cent area or volume of hemorrhage between the three treatment groups, although there was a trend for increased hemorrhage in the adrenalin-alone group perhaps due to the higher post-traumatic mSAP in this group. Further studies are required to find the minimal elevation in mSAP produced by a vasopressor that would still cause an improvement in post-traumatic SCBF by nimodipine, and to determine whether this combination improves function after spinal cord injury.
Animals↗
Frequency and determinants of adverse reactions induced by high-osmolality contrast media.
To determine the frequency of and risk factors for adverse reactions to high-osmolality contrast media, the authors prospectively studied hospitalized patients undergoing cardiac catheterization. The authors also studied patients undergoing peripheral angiography and contrast material-enhanced computed tomography (CT) of the head or body who met at least one of the following criteria thought to increase the risk of adverse reactions: age of more than 60 years, diabetes, renal or liver disease, concurrent nephrotoxic drug use, or a history of allergic reactions (n = 795). Criteria were defined and used to group adverse reactions into three classes of clinical severity. Overall, class I (mild), class II (moderate), and class III (severe) reactions occurred in 362 (45%), 44 (5.5%), and three (0.4%) patients, respectively. Class II reactions were relatively common (25%) in patients undergoing cardiac catheterization yet were uncommon (2%) in patients undergoing the other three procedures. Nephrotoxicity occurred in 18 of 651 patients who had follow-up creatinine levels obtained at 48-72 hours. With multivariate regression analysis, the only risk factor (P less than .05) for combined class II and III reactions was diabetes. Diabetes, furosemide use, and a history of atopy (odds ratio = 2.8) were associated with nephrotoxicity (P less than .05). Underlying renal insufficiency was not a risk factor for nephrotoxicity.
Adult↗
Primate cardiac allo-and xenotransplantation: modulation of the immune response with photochemotherapy.
Survival of heterotopic allo- and xenografts was studied in a primate cardiac transplantation model. Initially, animals were presensitized to donor xenoantigens by blood transfusion and treated with strategies designed to elicit pretransplant immunosuppression. These animals underwent rapid rejection whether treated with ciclosporin and conventional immunosuppression, autologous sera, sensitized lymphocytes, or photochemotherapy. In a nonsensitized xenograft study, xenografts were maintained for prolonged periods with a combination of ciclosporin and photochemotherapy. All animals treated with photochemotherapy demonstrated periodic suppression of the mixed leukocyte culture response to their donor. Inhibition of lymphocytotoxic antibody was achieved only in animals treated with both ciclosporin and photochemotherapy. Xenosensitized animals were secondarily exposed to donor alloantigens. These animals were successfully allografted. Ciclosporin therapy was terminated and the animals maintained by photochemotherapy alone. This preliminary trial indicates that a combination of ciclosporin and photochemotherapy may be of value in maintaining concordant xenografts and preventing antibody mediated rejection.
Animals↗
Bronchocentric mycosis occurring in transplant recipients.
Although a variety of long-term, probably immunologically induced pulmonary changes have been described in recipients of both combined heart-lung and bone marrow transplantation, pulmonary infections continue to remain causes of significant morbidity and mortality as well. Herein we describe three patients (two heart-lung and one bone marrow transplant recipient) who had bronchocentric granulomatous mycosis, a tissue manifestation of fungal infection not previously described in the setting of a transplant host. Although one patient was being treated successfully with antifungal agents for his mucormycosis, two other patients eventually died of invasive aspergillosis. This emphasizes that although this process is histologically somewhat similar to bronchocentric granulomatosis, a high index of suspicion for infection needs to be maintained when this pathologic process is identified in a transplant host.
Adult↗
Serum prolactin in uraemia: correlations between bioactivity and activity in two immunoassays.
The clinical significance of hyperprolactinaemia in uraemic patients is uncertain and discrepancies between immunoactivity and biological activity of serum hPRL have been reported. We have modified the Nb2 cell bioassay to improve specificity for hPRL and used this assay to measure hPRL bioactivity in sera from 26 uraemic patients and 40 control subjects. Seventeen patients were receiving regular haemodialysis and 9 continuous ambulatory peritoneal dialysis. Levels of hPRL bioactivity were compared with hPRL immunoactivity measured by RIA (PRL-RIA) and by immunoradiometric assay (PRL-IRMA). Serum hPRL levels measured by all three assays were significantly elevated in uraemic patients compared with control subjects (P less than 0.001). The immunoradiometric method gave significantly lower results than RIA in control subjects but not in uraemic patients (P less than 0.05). There was no significant difference in mean ratio of hPRL bioactivity to PRL-RIA between patients and control subjects (1.18 +/- 0.05 vs 1.11 +/- 0.03, mean +/- SEM). The ratio of hPRL bioactivity to PRL-IRMA was slightly decreased in uraemic patients compared with controls (P = 0.05). Serum hPRL bioactivity was closely correlated with immunoactivity in both immunoassays (r greater than or equal to 0.96) in patients and controls. These results confirm that elevated serum hPRL levels in uraemic patients represent biologically active hormone which may contribute to hypogonadism.
Adult↗
Pericardial flap-plasty for protection of the tracheal anastomosis in heart-lung transplantation.
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Fibrin Tissue Adhesive↗
Immunomanipulation of the response to cardiac allo and xenoreactive leukocytes.
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Animals↗
Long-term function of human cardiac allografts assessed by two-dimensional echocardiography.
Previous studies from our laboratory demonstrated increasing left ventricular mass in cyclosporine-treated cardiac allograft recipients over 30 days after transplantation, but the long-term evolution of this process and possible effects on allograft function are unknown. Accordingly, quantitative two-dimensional echocardiography was performed 2 and 23 days and 15 months postoperatively in 14 recipients treated with cyclosporine and prednisone. Changes in left ventricular ejection fraction, end-diastolic volume, mass, and end-systolic wall stress were analyzed. Comparison of studies at 2 and 23 days revealed significant (p less than 0.01) increases in ejection fraction (54% +/- 8% [standard deviation] to 62% +/- 4%), end-diastolic volume (84% +/- 32 ml to 96 +/- 31 ml), and left ventricular mass (118 +/- 45 gm to 136 +/- 41 gm). Comparison of studies at 23 days and 15 months revealed no significant change in end-diastolic volume or left ventricular mass, whereas ejection fraction decreased slightly (62% +/- 4% to 57% +/- 4%, p less than 0.01). End-systolic wall stress decreased when data at 2 days and 15 months were compared (83 +/- 24 gm/cm2 versus 66 +/- 18 gm/cm2, p less than 0.05), but no change in contractility was apparent from the ejection fraction/end-systolic stress relation. We conclude that left ventricular mass and end-diastolic volume increase early after transplantation in cyclosporine-treated cardiac allograft recipients, but these changes are not predictive of long-term results, which are characterized by no significant late variation in left ventricular mass, end-diastolic volume, or contractility.
Adolescent↗
Humoral immune responses after cardiac transplantation: correlation with fatal rejection and graft atherosclerosis.
Although the advent of cyclosporine has allowed dramatic improvement in survival rates after heart transplantation, long-term outcome remains limited by rejection and graft atherosclerosis. We have previously demonstrated the development of alloreactive lymphocytotoxic antibodies in baboon recipients of heterotopic cardiac transplants despite cyclosporine administration. The hypothesis of our study is that human heart transplant recipients given treatment with cyclosporine are also capable of generating strong humoral immune responses that might adversely affect clinical outcome. Serial serum specimens from 118 heart transplant recipients were tested against a reference panel of 70 cells for anti-HLA lymphocytotoxic antibodies. Patients with positive sera on at least three separate samplings at minimal intervals of 1 week were considered to be antibody producers (Ab+), and those with less than three positive sera samplings were considered nonproducers (Ab-). Donor lymphocytes were not available for most recipients for the assessment of the specificity of antibodies produced. Seventy-six of 118 patients (64%) were Ab+. One-year, 3-year, and 5-year actuarial survival rates were 81%, 70%, and 53%, respectively, for Ab+ patients compared with corresponding rates of 93%, 90%, and 90%, respectively, in Ab- patients (p less than 0.01). Graft atherosclerosis confirmed by coronary angiography or autopsy developed in 12 Ab+ patients (16%), compared with 1 of 42 Ab- patients (2.3%) (p less than 0.05). These data show that almost two thirds of heart transplant recipients produce anti-HLA antibodies after grafting that correlate strongly with adverse outcome. Immunotherapies directed at control of deleterious humoral immune responses need to be developed.
Actuarial Analysis↗
The evaluation of intranasal topical beclomethasone spray in the treatment of children with non-purulent rhinitis using rhinometric, cytologic and symptomatologic assessment.
The diagnosis and treatment of non-purulent rhinitis in the pediatric population poses a challenge to the clinician. In this randomized double blind study, the authors conclude that rhinometry is more effective than cytologic or symptomologic assessment in children with non-purulent rhinitis treated with either intranasal beclomethasone or placebo spray. Intranasal beclomethasone spray produced significant reductions in nasal airflow resistance values compared to the placebo-treated group.
Administration, Intranasal↗
Relation between survival and development of coronary artery disease and anti-HLA antibodies after cardiac transplantation.
The importance of chronic humoral rejection in cardiac transplant patients has not been studied extensively. In an attempt to determine whether lymphocytotoxic antibodies are related to heart allograft survival, we evaluated 123 patients whose sera were monitored for cytotoxic antibodies against HLA antigens after transplantation. Patients underwent serial sampling of peripheral blood at the time of right-heart catheterization and endomyocardial biopsy. Patients with three or more sera containing lymphocytotoxic antibodies were considered alloantibody producers (81 of 123 patients). With similar follow-up, mortality was greater for antibody producers (27 of 81 patients) than for nonproducers (three of 42 patients, p less than 0.01). Among antibody producers, the mortality rate was higher when multiple samples obtained during the first 6 months after transplantation contained anti-HLA class I or class II antibodies. Coronary artery disease was documented in 12 of 81 antibody producers and only one of 42 nonproducers (p = 0.05). The presence of anti-HLA antibodies in the serum showed no association with the presence of lymphocytic infiltrates in myocardial biopsies or with hemodynamic abnormalities. However, histologic rejection was present in 14 of 19 antibody producers who died. Thus, the presence of anti-HLA antibodies was associated with increased mortality and the development of coronary artery disease and was a major correlate of the clinical course after cardiac transplantation. High- and low-risk groups can be differentiated within the first 6 months after transplantation.
Coronary Disease↗
Optimal timing of pediatric heart transplantation.
Despite success in adults, heart transplantation (HT) is still considered by many as only desperation therapy for children with end-stage heart disease. Thus, of 30 pediatric patients undergoing HT at our center, only seven (23%) patients had not developed pulmonary hypertension with increased pulmonary vascular resistance (PH) or hemodynamic decompensation (HD) requiring inotropic support at the time of transplantation. We have retrospectively reviewed the effect of preoperative PH, HD, and seven other potential risk factors on survival of our pediatric heart transplant recipients. All 30 patients, aged 5 days to 18 years, had New York Heart Association class III or IV symptoms. Twenty had idiopathic cardiomyopathy, nine had congenital lesions, and one infant had a large left ventricular tumor. A univariate and multivariate Cox proportional-hazards analysis was performed examining the effects of nine variables on survival after transplantation: PH, HD, age, need for hospitalization, congenital heart disease, need for surgical pulmonary artery reconstruction, prior stroke, history of cardiac arrest(s), and mechanical ventilator dependence. One-year actuarial survival for the entire series was 66% and was 100% for the seven patients with neither PH nor HD. None of the nine potential risk factors was a statistically significant predictor of risk, yet the combined presence of PH and HD represented a highly significant predictor of mortality (relative risk, 4.08: 1; p less than 0.002). One-year actuarial survival of the 10 patients with this combination was 30% versus 84% of those without the combination.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiomyopathy, Dilated↗