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OBJECTIVE: To retrospectively determine DNA levels in blood polymorphonuclear leukocytes (PMNLs) of 21 heart transplant patients who suffered from HCMV infection and who were monitored by the antigenemia assay (pp65 test) during follow-up, by use of a quantitative competitive polymerase chain reaction (PCR) assay for human cytomegalovirus (HCMV) DNA. METHODS: Quantitation of HCMV DNA by PCR was expressed as genome equivalents (GE) per 200 000 PMNLs. RESULTS: Ten patients experienced symptomatic HCMV infection (five primary infections and five reactivations) with mild symptoms and received ganciclovir treatment, whereas 11 asymptomatic HCMV infections were not treated. Therapy was discontinued when a 90% reduction of the pretreatment antigenic load was achieved in a symptomless patient. The mean HCMV DNA and antigenic loads were significantly higher in symptomatic than in asymptomatic patients: 4.6 x 105 plus minus 4.7 x 105 GE and 1.1 x 104 GE (p0.0001) and 390 plus minus 350 versus 25 plus minus 12 pp65-positive PMNLs (p0.0001), and in primary than in secondary infections (583 plus minus 403 pp65-positive PMNLs versus 85 plus minus 111, p=0.002 and 5.2 x 105 plus minus 5.2 x 105 GE instead of 1.5 x 105 plus minus 3.2 x 105 GE, p=0.02). A single course of 14--21 days of ganciclovir caused a marked decrease of HCMV DNA and antigenemia in eight of 10 patients in whom a 90% reduction of the antigenic load correlated with a 98% DNA reduction of the pretreatment levels. In two primary infections, a 90% antigenic reduction was achieved by 21 days of ganciclovir treatment, but those data only correlated with a DNA load reduction of 28% and 60% of the pretreatment levels. Fifteen and 12 days later, respectively, the two patients relapsed and underwent a second ganciclovir course, at the end of which a 90% reduction of the antigenic load correlated with a98% DNA drop. GCV was discontinued and the patients recovered completely. In those two patients we retrospectively found persistent high DNA levels before the second ganciclovir course, whereas the antigenic load slowly increased after an apparent reduction. CONCLUSIONS: Our data suggest that: (1) DNA levels have the same trend as the pp65 antigen test---they are significantly higher in symptomatic and in primary HCMV-infected patients than in asymptomatic patients and those with secondary infection; (2) a 90% antigenic load reduction from the pre-treatment level may be a less reliable predictor of the efficacy of anti-HCMV therapy than DNA load, at least in primary infection, in which a much higher viral load and much more severe disease are present; and (3) a DNA load reduction of98% of the pretreatment value is required for therapeutic success.

The presence of human cytomegalovirus DNA was investigated in 103 unfixed endomyocardial biopsies, performed during the first 4 months in 17 heart transplant recipients by polymerase chain reaction. Results were correlated with human cytomegalovirus systemic infection, as detected by the test for the viral lower matrix phosphoprotein pp65 (antigenemia) and by polymerase chain reaction for viral DNA in blood leukocytes (DNAemia). Three patients out of 17 did not develop cytomegalovirus infection and 14 did : 5 had symptomatic disease treated with ganciclovir and 9 developed asymptomatic infection and were not treated. Viral DNA was detected in 24 out of 103 biopsies (23%) from 13 patients : 5 with symptomatic infection during the acute phase of disease (mean levels of pp65 : 125±232 pp65 positive leukocytes/200,000 examined cells) and 8 patients with asymptomatic infection when the mean antigenemia was 5±15/200,000 (4 patients) or when only DNAemia was present in blood (4 patients). No histological evidence of myocarditis was shown in viral DNA-positive biopsies. No difference in acute rejection was found in viral DNA-positive and viral DNA-negative biopsy specimens in symptomatic and asymptomatic infected patients. Our experience suggests that during systemic symptomatic and asymptomatic cytomegalovirus infection, polymerase chain reaction can detect a relatively frequent myocardial involvement, but this involvement is not associated with myocarditis or with a higher incidence of acute rejection. The presence of viral DNA in myocardial biopsies can be a result of high viremia, but it can also be due to a low level of viral DNA in circulating infected leukocytes. Polymerase chain reaction is the most sensitive method for cytomegalovirus DNA detection in biopsies, but its results need to be evaluated together with morphology-preserving methods and systemic markers of infection in order to make a correct diagnosis.

Dissecting aneurysms of coronary arteries are a rare finding and have never been reported in a cardiac allograft. We found two spontaneous dissecting aneurysms on the middle third of both the left anterior descending and the right coronary arteries in a female cardiac transplantation recipient. She died 43 days after cardiac transplantation after developing human cytomegalovirus pneumonia and pancreatitis. Dissecting coronary aneurysms, microfoci of subendocardial coagulative necrosis, and area of subepicardial dystrophic calcifications were discovered at necropsy examination.

OBJECTIVE: To establish whether polymerase chain reaction (PCR) for cytomegalovirus deoxyribonucleic acid (DNA) can provide clinical information for the management of the infection. METHODS: Leukocytes in 30 heart transplant recipients were monitored by pp65 antigen testing and PCR for 82 to 365 days after transplantation. RESULTS: Of the 30 patients, 26 developed cytomegalovirus infection, nine of whom were symptomatic. Altogether, 300 leukocyte samples were examined. The concordance between PCR and pp65 antigen test was 82.6%. In symptomatic patients after surgery, PCR detected cytomegalovirus infection after 38 plus minus 16 days and the pp65 antigen test, after 48 plus minus 15 days. Symptomatic infection correlated with a higher number of pp65-positive leukocytes than did asymptomatic infection: 310 plus minus 356 vs 24 plus minus 35 (p0.005)/200,000 examined, respectively. Clearance of virus was observed by PCR after 125 plus minus 73 days (range 29 to 225) in symptomatic, and after 82 plus minus 70 days (range 16 to 301) in asymptomatic, cases of infection. CONCLUSIONS: The positive predictive value of PCR for symptomatic infection was 34.6%. Our findings correlate with previous reports and show that the qualitative detection of cytomegalovirus DNA is not associated with overt disease whereas quantitation of pp65-positive leukocytes closely correlate with symptom onset. Insofar as the results are not quantitative, PCR is not a marker of clinically apparent infection. Careful monitoring of cytomegalovirus infection based on quantitative pp65 antigen assay can fulfill all clinical needs for early diagnosis and proper management of the infection

A total of 879 paraffin-embedded endomyocardial biopsy specimens from 69 heart transplant recipients were studied. In 30 biopsy specimens, the presence of human cytomegalovirus was investigated by routine histologic and immunohistochemical evaluation, in situ hybridization, and polymerase chain reaction. These 30 biopsies were performed in seven patients with clinical human cytomegalovirus infection (four primary and three recurrent infections) and in eight patients with asymptomatic human cytomegalovirus recurrent infection. These endomyocardial biopsy specimens showed grade 0 (n = 9), 1A (n = 12), 1B (n = 7), or 2 (n = 2) acute rejection. No myocarditis with human cytomegalovirus-like inclusion bodies was observed by routine histologic evaluation. Human cytomegalovirus DNA or antigens were not shown by in situ hybridization or by immunohistochemical evaluation, respectively. Viral DNA was detected by polymerase chain reaction in two grade 1A endomyocardial biopsy specimens from two patients with systemic human cytomegalovirus primary infection. These two biopsy specimens were shown to be positive by polymerase chain reaction at the time of the acute phase of the infection as shown by laboratory findings. Therefore cytomegalovirus DNA detected by polymerase chain reaction could result from viral carriers, that is, leukocytes of rejection-related infiltrates or within intramyocardial vessels as a result of a more aggressive expression of the systemic infection in seronegative recipients with cytomegalovirus seropositive donors. Polymerase chain reaction is the most sensitive method for viral DNA detection on paraffin-embedded biopsy specimens, but a multitechnologic approach, including routine histologic evaluation, is required for a proper diagnosis of human cytomegalovirus myocardial infection.

One hundred and fifteen patients with chronic type B, D and non-A, non-B hepatitis treated with recombinant α-interferon were tested for six different autoantibodies prior to or during therapy, and the course of treatment was compared in autoantibody-positive and -negative patients. Three out of 25 (12%) hepatitis B patients, 14 out of 30 (47%) hepatitis D patients and 19 out of 60 (32%) chronic non-A, non-B hepatitis carriers had baseline or post-therapy autoantibodies. The rate of response between patients with and without autoantibodies among B, D and non-A, non-B patients was, respectively, 67 vs. 79%, 23 vs. 25%, 70 vs. 61% ( p = N.S.). No adverse reaction was observed in the 36 patients who had or developed nuclear, smooth muscle, parietal cells and thyroid autoantibodies during therapy. A patient with baseline antibodies against liver and kidney microsomes developed an icteric acute hepatitis at the fourth month of therapy, but five other patients with this reactivity responded to therapy uneventfully. The presence of autoantibodies before therapy or their induction following therapy is not a contraindication to the use of interferon in patients with chronic viral hepatitis.

Eighty patients with chronic non-A, non-B hepatitis completed a randomized controlled trial of the therapeutic efficacy of recombinant interferon alfa-2b. Twenty-nine received 1 million units and 26 received 3 million units of interferon subcutaneously thrice weekly for 6 months, and 25 were controls. Normalization or a significant decrease of alanine aminotransferase values was obtained in 19/29 (66%) patients treated with 1 million units, in 18/26 (69%) patients treated with 3 million units and in one control patient (4%, p less than 0.05). However, when control patients were randomized after the initial 24 weeks to receive 1 or 3 million units of interferon for 48 weeks, 12/14 (86%) patients receiving 3 million units responded to therapy versus 3/11 patients receiving 1 million units (27%, p less than 0.05). After a 1 to 6 months follow-up period post treatment, an alanine aminotransferase relapse was observed in 18/30 (60%) responders to 3 million units and in 17/22 (77%) responders to 1 million units. Cirrhotic patients responded less than patients with non-cirrhotic disease (47 vs. 78%, p less than 0.05). Only responders treated with 3 million units significantly ameliorated their histologic picture (pre-therapy Knodell's index = 8.9, post-therapy = 6.0, p less than 0.05). The data confirm that treatment with interferon is of benefit in patients with chronic non-A, non-B hepatitis.

We report a successful transplantation of a human tricuspid valve in a human. We used a fresh tricuspid homograft with its chordae tendineae and papillary muscles, harvested 5 days earlier under sterile conditions from a multiorgan donor a few minutes after cardiectomy (the heart was not suitable for cardiac transplantation) and immediately stored at 4 °C We elected to implant the homograft in a young heroin addict. Our experience demonstrates that the implantation of an atrioventricular homograft in the orthotopic position is technically feasible and can achieve good results, at least in the short term.

This study was undertaken to evaluate the myocardial preservation obtained by adding a Ca++ channel blocker, nifedipine, to cold potassium cardioplegia (4 mcg/Kg/L) in 24 patients undergoing coronary artery surgery. They were randomly divided into a treated (N) and a control (C) group. Significant differences between the two groups were noted in the cardiac arrest time (p less than 0.001), in the mechanical recovery mode (p less than 0.01) and in the inotropic support needed (p less than 0.01). Cardiac index increased significantly in group N but decreased in group C (p less than 0.01). Peripheral delta P/delta t and endocardial viability ratio (EVR) decreased in both groups. Coronary sinus and serum CK and CK-MB release were significantly lower in the treated group. ECG ischaemic changes occurred in 8 patients in group C but only in 1 case in group N (p less than 0.001). Arrhythmias occurred in 3 cases in group C (p less than 0.05). The incidence of perioperative myocardial infarction was not significant (2 cases in group C). These data suggest that nifedipine can protect the myocardial cell from ischaemic injury without depressing myocardial contractility or AV conduction.

This study was undertaken to evaluate the potential role of a perioperative calcium-channel blocker (Diltiazem) infusion in improving myocardial preservation. Forty consecutive CAD patients were randomly assigned to a control (C; n = 20) and a treated (D; n = 20) group. In patients in the latter group diltiazem was continuously infused at 0.5 to 2.0 mcg/kg/min i.v. from anesthesia induction until the aortic cross-clamping, and from myocardial reperfusion till the 48th postoperative hour. During the preCPB phase hypertension occurred less frequently in group D (3 vs 12 cases, p = 0.0033). In the immediate postischemic period, depression of contractility and the need for inotropic support were observed in 3 cases in group D and in 9 in group C (p = 0.0384). Postoperatively, group D patients had a lower incidence rate of hyperkinetic arrhythmias or conduction disturbances (p = 0.0218), as well as of ECG signs of ischemia (p = 0.0016). Significant CK enzyme level increase was noted in 13 patients in group C versus 4 in group D (p = 0.0040). Two perioperative myocardial infarctions were diagnosed, both in group C. These clinical data show that continuous perioperative infusion of diltiazem can effectively increase myocardial preservation during ischemic arrest, without unfavorable effects on the hemodynamics, electrical activity or mechanical performance of the heart.

In order to identify factors affecting early mortality in patients undergoing CABG for unstable angina, several risk factors have been analysed in a group of 120 patients. Systemic hypertension and left ventricular impairment were shown to be significant risk factors (Systemic hypertension, P less than 0.01; EF less than or equal to 0.35, P less than 0.01; LVEDP greater than or equal to 20 mmHg, P less than 0.025). Overall mortality rate was 5% (6/120). No influence could be recognized for age, sex, previous MI, emergency surgery, extension of coronary disease, completeness of revascularization and mode of onset of symptoms.

This study was undertaken to evaluate the myocardial preservation obtained by adding a calcium channel blocker, diltiazem (200 mcg/kg of body weight) to cold potassium cardioplegia in 24 patients with coronary artery disease who underwent myocardial revascularization, and were randomly divided into a treated Group D and a Control Group C. No significant differences were noted between the groups in cardiac electrical arrest and recovery time, recovery rhythm, mechanical function recovery, inotropic support, stroke index, or cardiac index. After cardiopulmonary bypass, the stroke index decreased by 13.1% in Group D and by 20.7% in Group C; cardiac index increased in both--18.6% and 14.0%, respectively--but the results were possibly from compensatory heart rate increases. Peripheral deltaP/deltat and endocardial viability ratios decreased in both groups. Coronary sinus enzymes and serum CK were slightly lower in the treated group. Serum CK-MB, however, was significantly higher in the Control Group. Electrocardiographic ischemic changes occurred in four patients, all in Group C (p =.046). Hyperkinetic arrhythmias occurred in five of the controls, but in none of the treated patients (p =.018). One perioperative myocardial infarction was diagnosed in the Control Group. These data suggest that diltiazem has no negative side effects on hemodynamics or cardiac rhythm and does not reduce impairment of myocardial function due to ischemia, but it does decrease the incidence of ischemic lesions in patients undergoing coronary artery bypass procedures.

This work aimed to evaluate serology in relation to non-quantitative polymerase chain reaction (PCR) and pp65-antigenemia for the follow-up of cytomegalovirus (CMV) infection in heart transplant recipients. Besides conventional serology, antibodies were also detected by immuno Western blotting (IWB) and by recombinant enzyme immunoassay (EIA). Twenty-five CMV infected patients were evaluated. Twelve of them experienced symptomatic infection and underwent 9-(1,3-dihydroxy-2-propoxymethyl) guanine (DHPG) therapy whereas 13 asymptomatic infections were not treated. Risk factors for developing a symptomatic infection were a high antigenemia level as well as a high and delayed IgM response to ppUL44 (p52) and a low IgG response to the virus. PCR was the most sensitive procedure for detecting CMV infection (24 out of 25 infected patients and a mean time of 40 days after transplant), followed by IWB-IgM (23 patients and 40 days) and antigenemia (22 patients and 41 days). All the 12 symptomatic infections could be detected by one of the three above-mentioned methods, whereas no single test could identify all the 13 asymptomatic infections. The combination of two tests that could detect all the 25 CMV infections was PCR plus a serological procedure (IWB-IgM or recombinant EIA for p52) and pp65-antigenemia associated with IWB-IgM. As PCR results did not correlate with the onset of CMV symptomatic infection, the present data indicate that the most rational follow-up for CMV infection in heart transplant recipients can be obtained by antigenemia and IWB-IgM.