Advances in the differentiation of constrictive pericarditis and restrictive cardiomyopathy.

The diagnosis of constrictive pericarditis should be considered in any patient with unexplained right heart failure. The differentiation between constrictive pericarditis and restrictive cardiomyopathy is based on a combination of clinical presentation, history and imaging, and on occasion, on the basis of invasive hemodynamic studies or biopsy. Pertinent anatomic and physiologic findings on cardiac imaging modalities including echocardiography, computed tomography and cardiac magnetic resonance imaging are reviewed, and in many cases the diagnosis can be determined on the basis of imaging. Hemodynamic studies may clarify the diagnosis, and biopsy may find treatable causes of disease.

Interleukin-2 activates human peripheral blood eosinophils.

The effect of interleukin (IL)-2 on eosinophil survival and mediator release was investigated in vitro. Human peripheral blood eosinophils were isolated and purified from mildly atopic donors and cultured on albumin-coated wells with different concentrations of IL-2, interferon (IFN)-gamma, and granulocyte-macrophage colony stimulating factor (GM-CSF) and their viability was evaluated after 4 days in culture. Eosinophils were cultured with IL-2 (1000 u/ml), IFN-gamma (1000 u/ml), or GM-CSF (10 ng/ml) for 18 h, or with platelet activating factor (PAF) (10(-6) M) for 20 min, and the release of eosinophil peroxidase (EPO) and IL-6 was measured. Nedocromil sodium (10(-5) M) was added with each of the above cytokines to study the inhibitory effect of this drug on EPO release. A significant increase of EPO release was induced by IL-2, IFN-gamma, and GM-CSF after 18 h in culture. IL-2 as well as IFN-gamma induced a significant IL-6 release from eosinophils. Nedocromil sodium significantly inhibited EPO release from eosinophils induced by IL-2 or PAF. These results show that IL-2 can activate peripheral blood eosinophils to release granule mediators (EPO) and cytokines (IL-6). Taken together with the presence of IL-2 receptors on eosinophils, we conclude that IL-2 is an important mediator in allergic inflammation and a possible target for pharmacological modulation.

The effect of short-term dipyrone administration on cyclosporin pharmacokinetics.

BACKGROUND: A large number of drugs have been shown to affect the metabolism of cyclosporin A (CSA) and, since cyclosporin is characterized by a narrow therapeutic range, the consequences of such drug interactions may often be of clinical importance. OBJECTIVE: To evaluate the effect of short-term administration of dipyrone on steady state CSA pharmacokinetics. METHODS: Six kidney- and two heart-transplanted patients on chronic CSA therapy participated in this study, which consisted of two 4-day study periods separated by 3-week washout periods. The patients received, in addition to their usual drugs, dipyrone 500 mg or placebo t.i.d., as identical-looking tablets, and the order of administration was randomized. CSA concentrations were measured in whole blood by means of radio-immunoassay (CYCLO-Trac SP) daily during the study periods and periodically over 24 h on the fourth study day. RESULTS: CSA concentrations over time were reduced after dipyrone (ANOVA, P < 0.01), but statistical significance was noted only at 2, 4, 5 and 10 h after drug intake (P < 0.05). Peak CSA concentration was not altered by dipyrone, but the time required to reach maximal concentration was longer with dipyrone treatment than with the placebo (3.8 +/- 2.6 h vs 2.1 +/- 0.6 h, P < 0.05). No consistent changes were noted for CSA trough level, elimination half-life and area under the concentration-time curve from 0 h to 12 h. Separate analysis of the kidney transplanted patients yielded similar results. CONCLUSIONS: Short-term administration of dipyrone is associated with a mild decrease in CSA blood concentration, which is most prominent in the first few hours after drug intake. In practice, no dose adjustment of CSA seems to be indicated during a short course of dipyrone treatment.

Laparoscopic detorsion allows sparing of the twisted ischemic adnexa.

STUDY OBJECTIVE: To determine the safety and outcome of laparoscopic detorsion in the management of the twisted ischemic, hemorrhagic adnexa. DESIGN: Retrospective chart review and prospective follow-up (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Fifty-eight women with twisted black-bluish ischemic adnexa encountered at laparoscopy. INTERVENTION: Laparoscopic detorsion with adnexal sparing. MEASUREMENTS AND MAIN RESULTS: All patients had a benign immediate postoperative course. Transient temperature elevation occurred in seven women (12.1%). No signs of pelvic or systemic thromboembolism were detected in any patient. Long-term follow-up included transvaginal ultrasound, which revealed follicular development in the previously twisted adnexa in 54 women; normal macroscopic appearance at incidental subsequent surgery in 9; and in vitro fertilization with retrieval of oocytes from the previously twisted side in 4. CONCLUSION: Laparoscopic detorsion of the twisted ischemic, hemorrhagic adnexa is a safe procedure with minimal postoperative morbidity and a potential for the ovary to recuperate fully with preservation of normal function. Laparoscopic adnexa-sparing procedures should be performed in place of traditional salpingo-oophorectomy in women with this disorder who desire future fertility. (J Am Assoc Gynecol Laparosc 6(2):139-143, 1999)

Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action.

BACKGROUND: Intravenous gammaglobulin (i.v.IG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by i.v.IG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ. METHODS: In this study, we investigated the possible use of i.v.IG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies. RESULTS: Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after i.v.IG infusions in all patients. i.v.IG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after i.v.IG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which i.v.IG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient. CONCLUSION: I.v.IG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to i.v.IG therapy.

Thrombolysis in acute myocardial infarction improves prognosis and prolongs life but will increase the prevalence of heart failure in the geriatric population.

This paper will review the hypothesis that early complete thrombolytic therapy in acute myocardial infarction reduces mortality and improves prognosis. ACE inhibitors improve remodelling and anti-platelet drugs or interventional procedures prevent reocclusion of the infarct related coronary artery. Most patients are left with significant myocardial damage and this effect is cumulative with subsequent infarction. The average age of death has increased by 10 years in the last three decades, so that many older patients survive. They have survived acute myocardial infarction and we now have a significant population with important heart failure despite good thrombolytic therapy.

Diffuse narrowing of coronary arteries in diabetic patients: the earliest phase of coronary artery disease.

Coronary arteries in diabetic patients appear to be narrower than in normal subjects, but this has not been examined systematically. To investigate this hypothesis we reviewed the data of 711 consecutive patients with angiographically 'normal coronary arteries'. Excluded were patients with valvular, myocardial or pericardial disease, and patients with hypertension or hyperlipidemia. Thirteen diabetic patients (10 men) and 22 nondiabetic persons (8 men) constituted the study and control groups, respectively. The diameters of the coronary arteries and their branches were measured and adjusted for body surface area. The sum of the proximal left anterior descending (LAD), circumflex and right coronary arteries (RCA) was calculated and defined as total coronary diameter (TCD). The sum of the distal LAD, first diagonal, first marginal and distal RCA was calculated and defined as total distal coronary diameter (dTCD). The clinical data of both groups were comparable. Adjusted TCD for body surface area was 5.4 +/- 1.1 and 6.5 +/- 1.1 mm/m2 (p < 0.05) in diabetics and nondiabetics, respectively, and adjusted dTCD was 4.9 +/- 1.2 and 6.1 +/- 1.2 mm/m2 (p = 0.01) in diabetics and normal subjects, respectively. Specific arteries and branches that were significantly smaller in diabetics included: left main coronary artery, distal LAD, first diagonal, proximal RCA, distal RCA, right ventricular branch, and posterolateral and posterior descending artery of RCA origin. Gender was not a confounding factor since the control group had a larger proportion of women and still larger arteries than the diabetic group. In conclusion, coronary arteries and their branches in diabetic patients have smaller diameters than normal subjects. This may be due to increased coronary tone, diffuse mild atherosclerosis or both.

An update on transplantation in the geriatric heart transplant patient.

Discussions of the ethics involved in allocating scarce resources often proceed without a grounding in factual experience. This study explored whether there was statistical evidence to support the use of set age limits in patient selection criteria for heart transplantation. Many transplant teams have selection criteria that include age limits, excluding patients more than 60 or 65 years of age from being considered as transplant candidates. The hypothesis was made that patients in the age bracket of 60-69 should have a comparable success rate with transplantation to that of younger recipients when selected by using the same medical and psychiatric criteria. Based on their clinical observations, the authors postulated that the elderly would report better quality of life postoperatively than younger control subjects.

Antibody response to influenza immunization in patients after heart transplantation.

The aim of this study was to evaluate post-heart transplantation (Htx) response to two-dose and three-dose influenza vaccine. Hemagglutination inhibition antibodies were monitored in HTx recipients immunized twice (n = 25) or three times (n = 17), and non-HTx controls (n = 8) once, with inactivated influenza vaccine. Post-first dose protective antibody titers (> or = 1:40) were demonstrated in 9/25 (36%) for A/Singapore/ (H1N1), 5/25 (20%) for A/Shanghai/(H3N2) and 2/25 (8%) for B/Yamagata compared with 4/8 (50%), 6/8 (75%) and 2/8 (25%), respectively, for controls. Post-second dose protective titers remained low, increasing following the third dose to 71%, 65% and 29%, respectively. The abnormally low antibody responses of HTx recipients to one-dose and two-dose influenza vaccine can be overcome by a third dose.

Coronary angiographic characteristics of patients with permanent artificial pacemakers.

BACKGROUND: The cause of severe cardiac conduction disturbances is often uncertain. The aim of this study was to examine a group of patients with permanent pacemakers who underwent coronary arteriography to determine the extent of coronary atherosclerotic disease that might be responsible for the conduction disturbances. METHODS AND RESULTS: Forty-three consecutive patients with a permanent pacemaker and 36 matched control patients were investigated. The coronary angiographic study included measurement of diameter and stenosis severity, qualitative assessment of flow, and classification of pathological anatomy, particularly the blood supply to territories supplying the different segments of the conduction system. Among 43 patients with a permanent pacemaker, 27 had ischemic heart disease (17 after coronary artery bypass graft surgery). The conduction disturbance was infranodal in 28 patients, sinus nodal in 6, AV nodal in 4, and complete AV block of unspecified origin in 5. Patients with permanent pacemakers had a coronary artery pathology compromising blood flow to the septal branches and the right coronary artery (type IV anatomy). This pattern was significantly different from the matched control patients, in whom the most prevalent coronary anatomy was the combination of right coronary artery with distal left anterior descending artery (not involving the septal branches) lesions (P=.007). CONCLUSIONS: Patients with coronary artery disease and severe conduction disturbances that require implantation of permanent pacemakers are more likely to have a specific pathological coronary anatomy that combines a compromised blood flow to the septal branches of the left anterior descending artery with right coronary artery lesions. The location of lesions in the coronary tree rather than severe diffuse atherosclerosis appears to be responsible for the conduction disturbances.

Changing paradigms in thrombolysis in acute myocardial infarction.

Acute myocardial infarction occurs when a ruptured coronary artery plaque causes sudden thrombotic occlusion of a coronary artery and cessation of coronary artery blood flow. This paper reviews the underlying coronary pathology in progressive coronary atherosclerosis, mechanisms of plaque rupture and arterial occlusion and the time relationship between coronary occlusion and myocardial necrosis. Reperfusion can be achieved by chemical thrombolysis with different thrombolytic agents. Early lysis is achieved best by prehospital administration, a transtelephonic monitor, a mobile intensive care unit, active general practitioner treatment or by warning the emergency room of impending arrival of a patient. Thrombolytic therapy may be unsuccessful and not achieve Grade III TIMI flow in less than 4 h (or even 2 h) due to inadequate or intermittent perfusion or reocclusion. Adjuvant therapy includes aspirin and platelet receptor antagonists. Bleeding is a constant danger. Direct percutaneous transluminal coronary angioplasty (PTCA) may be as effective or better than chemical thrombolysis. Reperfusion protects the myocardium and salvages viable tissue. It also improves mechanical remodelling of the ventricle. Long-term follow-up has shown that quantum leaps of fresh coronary occlusion causes step-wise progression in patient disability and that further early, prompt reperfusion can salvage myocardium and prevent this inexorable progress of the disease.

[Solid organ retransplantation].

The need for solid organ retransplantation is a major factor in the shortage of available organs. Between 1972 and 1992, 56 out of 309 kidney transplants and 2 out of 20 liver transplants performed in our hospital were retransplantations. The present study evaluates local and world experience with organ retransplantations in terms of the medical and ethical issues.

Life-threatening retroperitoneal hematoma caused by anticoagulant therapy for myocardial infarction after SWL.

Extracorporeal shock wave lithotripsy, the primary treatment for renal and ureteral stones, is an elective procedure with a low rate of complications, although most patients have macrohematuria which lasts for a few hours, and as many as 25% develop a renal or perirenal hematoma. Therefore, SWL is not performed during anticoagulant therapy, and any blood dyscrasias should be corrected prior to the procedure. We present a case of a patient who had an acute myocardial infarction after SWL, was treated with anticoagulation and emergency coronary angioplasty, and subsequently developed a life-threatening retroperitoneal hemorrhage. Cessation of anticoagulation with fluid support and drainage of a pleural effusion eventually resulted in complete recovery.

Atherosclerosis studies by intracoronary ultrasound.

Intravascular ultrasound (IVUS) is a new technique of tomographic visualization of the coronary arteries: its lumen, wall and pathology. Three dimensional (3D) reconstruction shows the tubular structure of the arterial wall and its pathology. IVUS has many advantages over coronary angiography: it has better resolution and shows many hidden lesions. IVUS has helped uncover the underlying mechanisms of percutaneous transluminal coronary angioplasty (PTCA), restenosis, the use and value of other interventional techniques such as directional coronary atherectomy (DCA), rotational atherectomy and stent implantation, and has great value in planning complex interventional procedures. The new American Heart Association (AHA) classification of coronary atherosclerosis pathology can be demonstrated by IVUS. IVUS is sensitive for studies of atheroma regression and progression and shows the coronary artery lesions after cardiac transplantation.

The Radial Artery: An Applicable Approach to Complex Coronary Angioplasty.

The purpose of this study was to assess the clinical value of the transradial approach (TRA) in coronary angioplasty. During the 18Ðmonth period from June 1994 to December 1995, 250 patients (mean age 61 +/- 11) underwent coronary angioplasty using the transradial approach. In 7 (2.8%) radial puncture was unsuccessful and in 6 (2.4%) additional femoral access was needed to complete the procedure. Ninety patients (36%) had angioplasty of two or three vessels and 49.5% had type B2 or C lesions. Sixty-five patients (22%) had additional procedures: stent implantations in 50 (16%) and rotational ablation in 15 (6%). Angiographic success was 97% and there were no deaths. Major procedural complications included: Q-wave myocardial infarction in 2 (0.8%), non-Q-wave myocardial infarction in 5 (2.0%), urgent coronary artery bypass grafting in 2 (0.8%) and CVA in 2 (0.8%). Local vascular complication included: compartment syndrome necessitating fasciotomy in 1 patient (0.4%), mild hematoma in 6 (2.4%) and a small pseudo-aneurysm treated by local compression in 4 (1.6%). Radial pulse was palpated in 93% before discharge and in 3% adequate flow could be heard with Doppler. No patient suffered from ischemia of the hand. Complex coronary angioplasty can be performed safely using the TRA with few vascular complications.

The diameter of the epicardial coronary arteries in patients with dilated cardiomyopathy.

We investigated the diameter of epicardial coronary arteries in 12 patients (ten men) with dilated cardiomyopathy, and compared to 21 normal persons (14 men). Dilated cardiomyopathy patients were younger than controls with no difference in height, weight and body surface area. Ejection fraction was lower in dilated cardiomyopathy compared to normals (31+/-10% and 73+/-7%, respectively, P<0.001). Left ventricular mass was significantly larger (P=0.04). The sum of diameters of the proximal left anterior descending, circumflex and right coronary arteries (Total Coronary Diameter) in the dilated cardiomyopathy and controls was 13.4+/-2.7 and 10.5+/-1.5 mm (P<0.001). Absolute diameters of the left main, left anterior descending, circumflex, proximal right coronary artery and the right ventricular branch in dilated cardiomyopathy were also significantly larger as was Total Coronary Diameter adjusted for body surface area. Total Coronary Diameter adjusted for left ventricular mass, was significantly smaller (103.42+/-30.38, 146.00+/-41.59 mm/mg, respectively, P<0.03). Specific arteries in the dilated cardiomyopathy adjusted for left ventricular mass were significantly smaller, or had a tendency for smaller diameter compared to normals. There was no correlation between age and coronary diameter in each group. After adjusting for left ventricular mass there was no difference in coronary artery diameter between men and women. Thus, coronary arteries of patients with dilated cardiomyopathy have increased absolute diameter compared to normals, but decreased diameter when adjusted for left ventricular mass. This may contribute to patients' complaints and to the natural history of the disease.

Isolated coronary artery transplantation in pigs: a new model to study transplantation arteriosclerosis and humoral rejection.

BACKGROUND: Graft atherosclerosis is a major cause of death after heart transplantation; its causes are multifactorial and poorly understood. To determine whether specific sensitization to coronary artery antigens is a contributing factor, we developed an isolated coronary artery allotransplantation model in pigs. METHODS: Of 46 Yucatan minipigs, 32 received a segment from a farm pig coronary artery into the common carotid artery (coronary allograft group) and 14 had a left to right common carotid artery autotransplant (carotid autograft group). No immunosuppressive drugs were given; all pigs received heparin for 5 days. We examined patency rates, histologic changes, and endothelial deposition of immunoglobulin G and M. RESULTS: In the coronary allograft group, patency rates were 100% (11 of 11) at 1 to 29 days, 20% (2 of 10) at 30 to 89 days, and 0% (0 of 11) after 90 days (overall 40.6%, 13 of 32). Histologic findings included endothelial cell hyperplasia, intimal proliferation, medial necrosis, adventitial inflammation, and ultimately luminal thrombosis. Deposition of immunoglobulin G and M was examined in the patent grafts and was seen in 90.9% (10 of 11) of grafts from days 1 to 29 and in the two patent but partially occluded grafts at 41 and 56 days. All carotid autografts except one (92.8%, 13 of 14) were patent up to 140 days and showed no or mild focal intimal thickening with normal media and adventitia. Deposition of immunoglobulin could not be detected in the autograft group. CONCLUSIONS: In this pig model of coronary artery allotransplantation, typical histologic findings of graft atherosclerosis are produced. Deposition of immunoglobulin G and M occurs early and is associated with endothelial cell hyperplasia and intimal proliferation. This model may be useful for the study of graft atherosclerosis and assessment of interventions designed to halt its progression.