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SummaryD-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary- care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50–76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (>250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1±16.4 vs. 81.7±11.6%, p=0.008) and a longer mean period of oxygen saturation below 90% (84.1±86.2 vs. 38.5±70.8 minutes, p=0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.

To detect Chlamydia pneumoniae in punch specimens of the aortic wall of 61 patients undergoing coronary-aortic bypass graft, and carotid atheromas of 32 patients undergoing carotid endarterectomy, cell culture (HEp-2 cells) and two polymerase chain reaction assays in two different laboratories were used. All cultures and polymerase chain reaction tests for Chlamydia pneumoniae were negative. Further studies are required to explore the complex relationship between Chlamydia pneumoniae and atherosclerosis.

Lymphoproliferative disorder is a well-recognized complication of lung transplantation. Risk factors include Epstein-Barr virus infection and immuno-suppression. The gastrointestinal manifestations of posttransplant lymphoproliferative disorder in lung transplant recipients have not been fully characterized. Case presentation and 16 previously reported cases of posttransplant lymphoproliferative disorder with gastrointestinal involvement are reviewed. Patient ages ranged from 25 to 65 (median, 52) years. Median time from lung transplantation to onset of posttransplant lymphoproliferative disorder was 36 (range, 1–109) months; 35 percent of cases (6/17) occurred within 18 months; Eighty-eight percent of patients (15/17) had positive Epstein-Barr virus serology before transplantation. In five patients (29 percent), the posttransplant lymphoproliferative disorder also involved sites other than the gastrointestinal tract. The most common gastrointestinal site of posttransplant lymphoproliferative disorder was the colon, followed by the small intestine and stomach. Clinical features included abdominal pain, nausea, and bloody diarrhea. Diagnosis was based on typical pathologic changes on gastrointestinal tract biopsy obtained mainly by colonoscopy. Treatment included a reduction in the immunosuppressive regimen in 15 of 17 cases (88 percent) and surgical resection in 10 (59 percent). One patient was untreated. Seven of 16 patients (44 percent) responded to treatment and 9 patients died. Median time from onset of posttransplant lymphoproliferative disorder to death was 70 (range, 10–85) days. Posttransplant lymphoproliferative disorder with gastrointestinal involvement is a unique entity that should be considered in all Epstein-Barr-Virus-positive lung transplant recipients who present with abdominal symptoms. Although immunosuppressive modulation and resection can lead to remission, the risk of death is 50 percent.

ObjectiveSeveral studies have recently reported an association between aortic valve calcification and atherosclerosis of the cardiovascular system, suggesting that aortic valve calcification might represent an atherosclerosis-like process. Hence the aim of the present study was to determine whether there is a similar association between aortic stenosis and aortic atheromas.MethodsWe evaluated the records and echocardiographic videotapes of 91 consecutive patients with severe aortic stenosis who underwent intraoperative transesophageal echocardiography before aortic valve replacement to measure the presence and characteristics of aortic atheromas. There were 50 men (55%) and 41 women (45%). The mean age was 71.9 ± 9.4 years (range, 34–91 years). These patients were compared with 91 sex-and age-matched patients without aortic stenosis who underwent transesophageal echocardiography for various indications. Aortic atheroma was defined as localized intimal thickening of 3 mm or larger. A lesion was considered complex if there was a plaque extending 5 mm or more into the aortic lumen; if the lesion was protruding, mobile, or ulcerated; or both.ResultsThe aortic stenosis group had significantly higher rates of aortic atheromas (85% vs 37%, P < .001) and complex atheromas (47% vs 9%, P < .001) compared with the control group. In the vast majority of patients in the aortic stenosis group, the aortic atheromas were localized in the aortic arch (60 [66%] patients, with 50% being complex aortic atheromas) and in the descending aorta (70 [77%] patients, with 45.7% being complex aortic atheromas); in only 4 (4.4%) patients, the aortic atheromas were localized in the ascending aorta (50% complex aortic atheromas).ConclusionsThere is a strong association between the presence of severe aortic stenosis and the presence and severity of aortic atheromas, suggesting that aortic stenosis might be a manifestation of the atherosclerotic process. These findings imply that (1) aggressive atherosclerotic risk-factor modification for patients with aortic stenosis might be advisable and (2) consideration of evaluation of the aorta by means of transesophageal echocardiography before aortic valve replacement in selected patients might be helpful.

Renal function is one of the most important prognostic factors following cardiac surgery. Whether aspirin affects cardiopulmonary bypass related renal injury is investigated in this study.Ninety-four patients with impaired renal function (creatinine = or1.5 mg/dl) undergoing coronary artery bypass grafting (CABG) were categorized into 2 groups according to aspirin administration before surgery. Serum creatinine, urinary output and creatinine clearance along with other perioperative factors were compared between the 2 groups prior to surgery, 24 hours and 48 hours following cardiopulmonary bypass.Creatinine levels increased significantly in the second postoperative day only in the non-aspirin (control) group (3.7+/-1.6 vs 2.9+/-1.7 mg/dl, p=0.03). Aspirin (study) group had lower creatinine levels in day 1 (p=0.03) and day 2 (p=0.001). Furthermore, in the study group creatinine clearance was higher in day 1 (34.3+/-14.3 vs 30.9+/-13.1 ml/min, p=0.01) and in day 2 (32.6+/-13.8 vs 26.4+/-9.8 ml, p0.0001). Creatinine levels at discharge were elevated compared to the preoperative levels in the control group (p=0.01). However, the study group had lower creatinine levels at discharge (2.6+/-1.4 vs 3.8+/-1.6 mg/dl, p0.0001). Urinary output was higher in the study group in the first postoperative day compared to the control group (p=0.01). Postoperative bleeding was slightly increased in the study group compared to the control group (760+/-230 ml vs 530+/-210 ml, p=0.01).Continuation of aspirin administration until the day of surgery may have a protective effect against renal injury resulting from cardiopulmonary bypass, with only a negligible increase in bleeding. Possible explanations for this effect are antiplatelet activity of aspirin during cardiopulmonary bypass causing inhibition of vasoconstrictive agents like thromboxane, and improvement of renal perfusion by reducing blood viscosity.

Itraconazole is often given for fungal prophylaxis to lung transplant recipients after transplantation. The aim of this study was to determine the extent of interaction between tacrolimus and itraconazole in lung transplant recipients and the efficacy of itraconazole prophylaxis.The study group included 40 lung transplant recipients followed for at least 12 months. All received prophylactic itraconazole, 200 mg twice a day, for the first 6 months after transplantation. Tacrolimus levels and dosage requirements were compared during and after itraconazole therapy. Rejection rate, fungal infection rate, and renal function were assessed. The mean cost per daily treatment of the itraconazole/tacrolimus combination and tacrolimus alone was calculated.The mean tacrolimus dose during itraconazole treatment was 3.26 +/- 2.1 mg/day compared with 5.74 +/- 2.9 mg/day after itraconazole was stopped (p0.0001) for a mean total daily dose elevation of tacrolimus of 76%. When the cost of itraconazole was taken into account, the average total daily cost of the combined treatment was US5.86 dollars less than the treatment with tacrolimus alone. No differences in the rejection or fungal infection rate, or in renal toxicity, were observed between the periods with and without itraconazole treatment, although less positive fungal isolates were identified during itraconazole therapy.Prophylaxis therapy with itraconazole is highly effective. Itraconazole reduces the dose of tacrolimus and therefore lowers the cost of therapy without causing an increase in rejection rate and with renal function preservation.

OSTTRANSPLANT diabetes mellitus (PTDM) has gained widespread attention due to the micro- and macrovascular complications that increase the morbidity and mortality rates of patients receiving solid organs. A higher incidence of PTDM has been associated with immunosuppressive therapy. This study compares glucose metabolism in heart transplant recipients receiving either FK506 or cyclosporine. METHODS Two groups of heart transplant recipients, differing in their immunosuppressive regimen—FK506 or cyclosporin—were followed for periods up to 6 years. Blood levels of glucose and of the respective immunosuppressive agent were measured regularly, and, if needed, anti-hyperglycemic treatment prescribed. The concomitant therapy with low-dose steroids and azathioprine was the same for both cohorts. T-test were performed to compare with the mean values of the two groups. RESULTS

T IS NOW well recognized that the gap between the supply of available transplantable human organs and the need is constantly increasing. Medical suitability is the basis of organ allocation, although the social, economic, psychologic, and demographic situation of each potential recipient represents important considerations. The ethical dilemma that we face is whether foreign, nonresident candidates should be placed on a national waiting list, and, if the answer is positive, under what terms? Organ transplantation, especially heart or lung, requires not only a well-trained group, but also an extensive infrastructure, which does not exist in each country. The lack of organs in the one hand and the lack of infrastructure in other countries on the other hand lead to the need for a mutual partnership among nations. Among the 100 organs transplanted in our center, 3 were donated by nonresident Palestinians who were treated in Israeli hospitals, 1 of whom was a victim of a violent act during the “Intifada.” The Palestinian population, although being provided with diverse medical services, is not entitled to be on the Israeli national waiting list. The ethical question that the medical community faces in these circumstances is whether to accept a family request to donate the organs to a close relative of the donor instead of offering them to all patients on the list. The other debate is whether the waiting list should be equally open to residents and nonresidents, now that they have became part of the potential population to donate.

Acquired left ventricle-to-right atrium communications are a known complication of valvular heart surgery. Previous reports have described the clinical features and diagnosis using cardiac catheterization. We report two cases of acquired left ventricle-to-right atrium fistula following mitral valve replacement. Particular emphasis is placed on the diagnosis using transthoracic and transesophageal echocardiography, obviating the need for cardiac catheterization before repair.

HEART and liver transplantation have become the treatment of choice in end-stage heart or liver failure. Advances in surgical technique and the introduction of cyclosporine A have improved survival following transplantation, but allograft rejection is still common and remains a major cause of morbidity and late graft failure. Transplantation results in the recipient’s immune activation, however, because of baseline immunosuppressive therapy only some recipients manifest clinical symptoms of rejection. Induction immunosuppression after heart and liver transplantation has mainly been based on regimens previously used in renal transplantation. Modern regimens use triple-drug treatment: cyclosporine or FK 506, prednisone, and azathioprine for almost all organ recipients without questioning basic differences in immunoactivation. Beta-2-microglobulin (B2m) is a low molecular weight protein associated with HLA class I antigens and is of value for immunologic monitoring. B2m has been shown to significantly increase after heart, liver, or renal transplantation without clinical evidence for rejection. The purpose of this study was to explore differences in immunoactivation between stable heart and liver transplanted patients to improve long-term monitoring and immunosuppressive therapy.

Increasing numbers of elderly (aged80 years) patients are being referred for cardiac surgery, and results for coronary artery bypass grafting (CABG) are generally better than for combined CABG and valve replacement.During the past 55 months, 77 octogenarians underwent cardiac intervention in our institution. Forty-five patients (mean age 82.5 years) underwent CABG alone; surgery was elective in 33% of patients and 2.7 +/- 1.0 grafts per patient were performed. Thirty-two patients (mean age 82.4 years) underwent combined CABG and valve surgery (28 aortic, four mitral); 2.1 +/- 0.8 grafts per patient were performed and 65% of cases were emergencies.In patients undergoing CABG alone, the operative mortality rate was 2% and rose to 4% (n = 2) at the end of follow up. Mean NYHA functional class improved significantly from 3.5 +/- 0.5 to 1.4 +/- 0.3 after surgery (p0.05) and most patients reported marked improvement in their quality of life. In CABG + valve surgery patients, the operative mortality rate was 6% (n = 2) and reached 18% by the end of follow up. In these patients the complication rate was 24% and mean hospitalization stay 11.0 +/- 2.9 days, while mean NYHA functional class improved from 3.4 +/- 0.6 to 1.2 +/- 0.5. Data analysis revealed that mitral regurgitation combined with coronary artery disease (p0.03) and prolonged cross-clamping time (p0.01) were the most important independent factors for mortality.This study confirms that, in selected elderly patients, combined CABG and cardiac surgery can achieve good postoperative results.

Significant tricuspid regurgitation (TR) can contribute to increased morbidity and mortality in patients after mitral valve replacement (MVR), both in the immediate and late postoperative period. The aim of this study was to evaluate the prevalence and the clinical importance of TR late after MVR, as assessed both clinically and echocardiographically.The study group comprised 65 patients (39 women, 26 men; mean age 61+/-12 years) with rheumatic heart disease who had undergone MVR without tricuspid valve surgery between one and 30 years (mean 11.3+/-8 years) before their last clinical examination. All patients underwent a complete color-Doppler echocardiographic examination. The predominant presurgical mitral lesion was stenosis in 44 patients and regurgitation in 21. The severity of the tricuspid valve disease was assessed echocardiographically using color-Doppler flow images and flow direction in the inferior vena cava or hepatic veins, and by clinical evaluation.Echocardiography revealed significant late TR in 44 patients (67%), which was moderate in 16 and severe in 28, and evident on physical examination in 24 cases (37%). Age (relative risk (RR) = 1.1; C.I. 1-1.1) and female sex (RR = 1.8; C.I. = 1.0-3.2) were identified as statistically significant predictors for late clinical TR development, but only age was found as a statistically significant predictor for echocardiographic TR development. An elevated RR for organic TR and predominant mitral regurgitation was found. In contrast, pre- and postoperative pulmonary artery pressure, predominant mitral lesion, prosthetic valve gradient and regurgitation were similar in patients with and without late TR.Significant TR diagnosed by echocardiography late after MVR is common, and clinically evident in more than one-third of patients. Therefore, a lower threshold for tricuspid valve repair should be considered when mitral valve surgery is carried out.

Massive spontaneous hemothorax is a very uncommon, life-threatening situation. Acute dissection and ruptured aorta can be one of the differential diagnoses, but usually the clinical feature is completely different, and very few patients have survived this event and received medical attention. Among other causes of spontaneous bleeding, some are extremely rare, demanding precise diagnosis and judicial and immediate intervention. We describe a patient who presented with a massive hemothorax. There was no immediately apparent cause. Emergent angiography revealed active bleeding from an extremely unusual source: aneurysmal dilatation of the internal thoracic artery.

Improved medical care over the years has increased life expectancy and consequently the number of aged persons suffering from cardiac disease. During the past 3 years, 42 consecutive octogenarians, with an average age of 82.1 years, were evaluated. Thirty patients had coronary artery bypass graft surgery (CABG), 5 had aortic valve replacement (AVR), and 7 had combined CABG-AVR surgery. Among the ischemic patients 70% had suffered from unstable angina pectoris, and an average of 2.78 +/- 1 grafts per patients were performed. The left internal mammary artery was used in 12 patients (32%). Overall mortality was 7.1% (3 patients), while operative mortality was 2.4% (1 patient). Another two patients who expired during the 34 month follow-up period underwent AVR. The average hospitalization period was 10.2, 12 and 17.6 days for patients undergoing CABG, combined CABG-AVR, and AVR alone, respectively. Complications occurred in 10 patients (24%) and included neurologic deficits (in 2 patients), severe wound infection (in 2), cardiac arrhythmia (in 4), renal failure (in 1) and adult respiratory distress syndrome (in 1). The use of the left internal mammary artery was not associated with an increased incidence of complications. The low rate of mortality and major complications and the substantial improvement in quality of life led us to conclude that, when indicated, surgical treatment should be offered to selected elderly individuals who otherwise are in good physical and mental health.

THE NUMBER of patients awaiting organ transplantation has progressively increased over the last decade. The progression of the discrepancy between suitable donors and potential recipients on waiting lists will have the consequence of an increasing use of organs from marginal donors. Organs that would have been thought unsuitable for transplantation not so long ago are currently used for transplantation. Advanced age, prolonged CPR, heavy inotropic support, or coronary lesions define marginal donors. Marginal recipients are advanced in age, have other diseases as limiting factors, or have been hospitalized in critical condition. From a total number of 100 transplantations (heart and/or lung) performed in our center, we present three cases in which ethical difficulties arose.

TYPE THE WORDS “kidney transplantation” or “heart transplantation” or a similar combination into one of the more robust search engines on the World Wide Web and you will retrieve hundreds of thousands of different sites that refer to the specialty in some manner. Most international and national transplant associations have web sites, and a world of news, research, clinical cases, and statistical data are available on-line over the Internet. The aim of this study was to search international and national transplantation databases

THE OBJECTIVE of all scientific publications regardless of their type or size, is the international exchange of knowledge and new ideas. The United States, Germany, United Kingdom, Japan, and European countries are the leading contributors to medical science. In particular, the contribution of individual countries may depend on factors such as the language spoken and the population size. Organ transplantation in Israel is a therapeutic modality for end-stage organ diseases. The number of transplantations has increased since 1963. In the present study, we evaluated the contributions of Israel and of other nations in the field of organ transplantation according to their population size.

Age as an important risk factor in surgery has always been debatable. Between January 1991 and December 1992, 35 consecutive octogenarian patients (23 males and 12 females; average age 82.3 years) were retrospectively evaluated. Twenty-five patients had only coronary artery by-pass graft operations (CABG), five had aortic valve replacements (AVR) and five had combined AVR-CABG operations. Twenty-five of the 30 patients (83%) who underwent CABG alone or a combined procedure had suffered from unstable angina. The mean ejection fraction was 40% in this group. An average of 2.8 grafts per patient was performed. The left internal mammary artery (LIMA) was-used in nine patients (30%). The average hospitalization period was 11.5 days. Operative mortality (within 30 days) was zero. Patients who underwent AVR only were hospitalized for an average of 17.6 days and there were two cases (6%) of mortality in this group. All patients who underwent AVR and CABG were discharged within 14 days. Overall complications occurred in nine patients (25.7%); cardiac arrythmias, (4) neurological deficits (2), severe wound infections (2), and adult respiratory distress syndrome (1). The use of the LIMA was not associated with an increased incidence of bleeding or sternal infection. The low rates of mortality and major complications lead us to conclude that, when indicated, surgical treatment including the use of LIMA in selected cases, should be offered to this group of patients, even in the presence of moderate LV dysfunction.

ATRIAL fibrillation (AF) is the most common dysrhythmia seen early after major thoracic surgery. Atrial dysrhythmia has been observed in children undergoing lung transplantation, but AF after adult lung transplantation in the early postoperative period has not previously been reported. A Heart and Lung Transplantation Unit in the Department of Cardiothoracic Surgery in a university hospital is the setting for this retrospective analysis.