Heart and lung transplantation in patients with end stage lung disease.

Combined heart and lung transplantation was used to treat seven patients with end stage lung disease. All were severely disabled, and their disease carried a poor prognosis. Six patients were well four to 33 months after transplantation. One patient died after 44 days from a primary cytomegalovirus pneumonia transmitted from the donor. All the survivors had normal exercise tolerance and greatly improved lung function. It is concluded that heart and lung transplantation is a suitable treatment for selected patients with end stage chronic lung disease.     

Cardiac valve replacement: Experience in 2400 patients

In the series described here, 2400 patients over a 15-year period underwent surgery for correction of acquired valvular heart disease. Of these, 1586 patients had single valve replacement, 714 had double valve replacement, and 100 had triple valve replacement. Concomitant surgery for associated congenital and acquired lesions was done in 114 patients. The hospital mortality was 9.16%.     

Hybrid approach for complex coronary artery and valve disease: a clinical follow-up study

For patients suffering from complex coronary artery disease (CAD) with or without concomitant valve disease, no evidence is available in the current guidelines to propose a predefined treatment regimen. We sought to assess the clinical impact of an unconventional or extended definition of the hybrid approach that combines percutaneous coronary intervention (PCI) and cardiac surgery in subjects suffering from severe solitary CAD or combined with valve disease. Between July 2002 and August 2004, 18 consecutive patients with complex CAD with or without significant valve disease who qualified for a hybrid approach were enrolled in a clinical follow-up study. Four patients eventually did not complete the proposed interventions. One patient refused treatment after inclusion, one patient died before treatment could be undertaken and two patients died after surgery but before PCI. In the other 14 cases combined treatment was technically successful. After a mean follow-up period of 15±5 months two patients had died, one due to sudden cardiac death and one of a noncardiac cause. No other major adverse clinical events were reported. A marked increase in quality of life was reported in those alive. Hybrid approach had a favourable long-term outcome in patients with complex cardiovascular disease undergoing successful treatment; however, this was observed at the expense of significant periprocedural mortality in these high-risk subjects. Therefore we believe that hybrid approaches may provide an alternative for selected cases. (Neth Heart J 2007;15:329-34.)     

Native valve Aspergillus fumigatus endocarditis with blood culture positive and negative for galactomannan antigen. Case report and literature review

Native valve endocarditis caused by Aspergillus spp. is an uncommon disease with a high mortality rate. Generally, Aspergillus is isolated from affected valve in post-mortem or biopsy specimens. However, its isolation from blood cultures is exceedingly rare. We report a case of fungal endocarditis in a native mitral valve with the isolation of Aspergillus fumigatus both in valve vegetation and in blood culture bottles. The patient underwent valve replacement and antifungal treatment with voriconazole and caspofungin, but he died on post-operative day 45 with disseminated aspergillosis confirmed by necropsy. Paradoxically, galactomannan antigen detection in serum was negative. This is the third case of Aspergillus endocarditis with positive blood culture reported in the literature.     

The use of autologous fascia lata for cardiac valve replacement: Preliminary results

Since November 1969, 53 patients have been operated on at the Toronto General Hospital for cardiac valve replacement with valves fashioned from autologous fascia lata. Sixty-three such valves have been inserted, including single aortic and mitral, double and triple valve replacements. The preliminary results indicate that operative mortality, considering the status of the patient submitted to the procedure, is comparable to that of plastic prosthetic valve replacement at this centre. Early follow-up confirms that anticoagulation is unnecessary and thromboembolism can be avoided with this form of valve substitution.     

Replacement of the Aortic and Mitral Valves Using the Starr-Edwards Ball-Valve Prosthesis: A Report of 50 Cases

The aortic and mitral valves were replaced in 50 patients at the University of Alberta Hospital using the Starr-Edwards ball-valve prosthesis. The basis of the selection of 20 patients for isolated aortic valve replacement and 27 for mitral valve replacement using this type of prosthesis is presented, and the techniques of insertion of the aortic and mitral valve are described in detail. Of the 27 patients in whom the mitral valve was replaced by the Starr-Edwards prosthesis six died within 30 days of surgery and two after discharge from hospital at two and a half and four months, respectively. Left atrial thrombosis was the cause of death in four of these patients. In 20 patients in whom the aortic valve was replaced, four died in hospital and two died more than 30 days after returning home. Three of these six patients died from bleeding—the result of the use of anticoagulants. The difficulty in assessing whether or not anticoagulants are needed following replacement by a Starr-Edwards prosthesis is considered. It is felt, in our present state of knowledge, that anticoagulants should be used following mitral valve replacement but are probably not essential following replacement of the aortic valve. Two patients survived replacement of both aortic and mitral valves and have been followed up 18 months and seven months, respectively.     

Successful adoptive immunotherapy of minimal residual disease after chemoradiotherapy and transplantation of bone marrow purged of leukaemia with mafosfamide

Summary The effectiveness of adoptive immunotherapy in eliminating minimal residual disease in tumour-bearing mice after bone marrow transplantation was tested. This model mimics the human clinical condition when autologous bone marrow was purged ex vivo of leukaemia with mafosfamide or was not purged, and stored in liquid nitrogen before transplantation. Animals with minimal residual disease were prepared with marrow-ablative but leukaemia-noncurative doses of cyclophosphamide (CY) and total body irradiation followed by bone marrow transplantation. The next day after transplantation the recipients were injected with splenocytes immunized against the leukaemia cells (Imm-SPL) or monoclonal antibody (mAb). All the control mice died from leukaemia relapse, but 51% of purged bone marrow recipients, which received Imm-SPL, were cured. In similar conditions mAb did not exert a therapeutic effect. Imm-SPL were not able to eradicate minimal residual disease in the recipients of nonpurged bone marrow. Thus, in an animal model, we demonstrated that purging of bone marrow before grafting seems to be indispensable for successful adoptive immunotherapy of minimal residual disease (MRD) after autologous bone marrow transplantation.This work was supported by grant CPBP 04.01. from the Polish Academy of Sciences     

Survival after Orthotopic Liver Transplantation: A Follow-up Report of Two Patients

Two adult patients with terminal fatal liver disease were treated by orthotopic transplantation. One survived 11 months and died as a result of recurrent biliary intra-abdominal sepsis; the other patient is alive and well in the 18th month after transplantation and has virtually normal liver function. It is concluded that liver grafting can provide valuable therapy.     

Surgical treatment of infective endocarditis with special reference to prosthetic valve endocarditis.

Patients with native valve endocarditis treated surgically between 1968 and 1978 (n = 15) and all patients presenting with prosthetic valve endocarditis during this period (n = 21) were followed up for at least four years. Five of the patients with native valve endocarditis required urgent early surgical intervention, of whom two died. The remaining 10 underwent valve replacement after a course of antibiotic treatment: all survived, though one required further valve replacement. The 21 patients with prosthetic valve endocarditis suffered 25 attacks. Nine were cured by medical treatment alone; two died before surgical intervention was possible; 11 required valve replacement, of whom three died; and two required valve replacement after a course of antibiotic treatment. The incidence of early prosthetic valve endocarditis--that occurring within two months of operation--was 0.67%, but that of late prosthetic valve endocarditis could not be determined. Medical treatment when started early should cure endocarditis in most patients, but vigilance should be maintained for the appearance of indications for surgery. When such indications exist surgery should not be delayed.     

冠心病合并缺血性二尖瓣关闭不全的手术方案探讨

目的:探讨适用于冠心病合并缺血性二尖瓣关闭不全的手术方法及临床效果,为心外科手术提供参考。方法:选取2012年2月至2013年5月在我院心脏外科接受手术治疗的冠心病合并缺血性二尖瓣关闭不全的患者31例。根据手术方式的不同,将所选病例分为二尖瓣成形术组和二尖瓣置换术组。术后随访6-24个月,观察并比较患者手术前后的左心房内径(LAD)、舒张末期直径(LVEDD)、收缩末期直径(LVESD)、左心室射血分数(LVEF)及二尖瓣返流面积。结果:围术期死亡1例,手术成功率为96.7%。30例成功获得随访,随访率为98.8%。二尖瓣成形术组并发症的发生率为22.7%,二尖瓣置换术组并发症的发生率为23.3%,两组术后并发症的发生率无显著差异(P0.05)。与手术前相比,两组患者术后的左心房内径变小,左室舒张末直径和收缩末直径增加,左室射血分数升高,二尖瓣反流面积缩少,差异显著且具有统计学意义(P0.05)。结论:对于冠心病合并重度缺血性二尖瓣关闭不全的患者行二尖瓣成形术或置换术应根据患者的实际情况和病理特点选择最佳的手术方案,以提高手术的成功率和安全性。     

Current status of the organ replacement approach for malignancies and an overture for organ bioengineering and regenerative medicine

Significant achievements in the organ replacement approach for malignancies over the last 2 decades opened new horizons, and the age of “Transplant Oncology” has dawned. The indications of liver transplantation for malignancies have been carefully expanded by a strict patient selection to assure comparable outcomes with non-malignant diseases. Currently, the Milan criteria, gold standard for hepatocellular carcinoma, are being challenged by high-volume centers worldwide. Neoadjuvant chemoradiation therapy and liver transplantation for unresectable hilar cholangiocarcinoma has been successful in specialized institutions. For other primary and metastatic liver tumors, clinical evidence to establish standardized criteria is lacking. Intestinal and multivisceral transplantation is an option for low-grade neoplasms deemed unresectable by conventional surgery. However, the procedure itself is in the adolescent stage. Solid organ transplantation for malignancies inevitably suffers from “triple distress,” i.e., oncological, immunological, and technical. Organ bioengineering and regenerative medicine should serve as the “triple threat” therapy and revolutionize “Transplant Oncology.”     

Open-Heart Correction of Mitral Valvular Disease: Review of 30 Cases

Thirty patients with mitral valve disease operated upon by the open-heart technique during the period 1958-1962 were studied. In 15 insufficiency predominated. Clinical, radiological and pathological findings included the following: aortic valve disease is the commonest associated lesion; cusp calcification is uncommon in mitral insufficiency; left atrial enlargement is more pronounced in mitral insufficiency; a relaxed annulus is the commonest pathological lesion associated with mitral insufficiency, with ruptured chordae in second place. Five of the 15 patients with mitral insufficiency and four of the 15 with mitral stenosis died during the postoperative period, while clinical improvement was apparent in seven and 11, in the respective groups. The standard techniques of annuloplasty, suturing of ruptured chordae, and open commissurotomy were found to provide satisfactory results. Partial Ivalon prosthetic replacement was unsatisfactory. The study suggests that a more liberal use of the open-heart procedure in surgical correction of complicated mitral valve lesions is indicated.     

老年瓣膜病患者瓣膜置换术术后死亡原因分析

目的:分析老年瓣膜病在瓣膜置换术后的死亡原因,为降低术后死亡率提供科学依据。方法:回顾分析我院以瓣膜置换术治疗的329例老年瓣膜病变患者的资料,对比分析生存患者和死亡患者之间的差异,总结瓣膜置换术后患者死亡的危险因素。结果:心脏瓣膜置换术后死亡率8.51%,单因素分析发现年龄、心功能分级、置换瓣膜数、LAD、LVEF、LVEDD、CPB时间、主动脉阻断时间、置换瓣膜数目与术后死亡有关联(P0.05),Logistic回归分析发现高龄、心功能差、LVEED、CPB为死亡独立危险因素(P0.05)。结论:高龄、心功能差、LVEED过度增大、CPB过长均是瓣膜置换术后的老年瓣膜病患者死亡的独立危险因素,建议临床在诊治中加以警惕。     

The Treatment of Multiple Coronary Occlusions by Internal Mammary Artery Implantation and Omental Graft: Report on Two Human Cases

The importance of triple coronary artery disease was evident in 125 patients undergoing internal mammary artery implantation, when some patients died from right coronary artery occlusion. This occurred even when the internal mammary artery was patent and revascularizing the left ventricle.In 1961 the free omental graft operation was developed to revascularize both right and left ventricles. In animals this operation has proved most effective in preventing death after application of Ameroid constrictors to all three coronary arteries. Arteriolar or larger-sized vessels rapidly formed between the aorta and omentum and the pericardium and omentum and the heart and omentum.Two patients with triple coronary artery disease underwent internal mammary artery implantation and free omental graft early in December 1962. Postoperative convalescence was uneventful. They have returned home and appear to be improved. Wrapping the entire heart with the free omental graft has produced little reaction, suggesting that, as in the animal, the grafts are surviving.     

Allogeneic bone marrow transplantation for high risk non-Hodgkin's lymphoma during first complete remission

Allogeneic bone marrow transplantation from histocompatible sibling donors was performed in six patients with extranodal involvement of high grade lymphoma during first complete remission. Five patients had lymphoblastic lymphoma and one had diffuse undifferentiated lymphoma. The cytoreductive/immunosuppressive regimen consisted of total body irradiation and high dose cyclophosphamide. Four patients are alive in complete remission at 8 months, 14 months, 21 months and 47 months post transplantation. One patient who relapsed 7 months after his initial transplantation underwent a second transplantation but another relapse 17 months later led to his death. One patient died of chronic graft-versus-host disease and at autopsy there was no evidence of lymphoma. These data demonstrate that allogeneic bone marrow transplantation can produce durable remissions in patients with high grade lymphoma who present with bone marrow, central nervous system and/or skin involvement.     

Heparanase Promotes Engraftment and Prevents Graft versus Host Disease in Stem Cell Transplantation

Background

Heparanase, endoglycosidase that cleaves heparan sulfate side chains of heparan sulfate proteoglycans, plays important roles in cancer metastasis, angiogenesis and inflammation.

Design and Methods

Applying a mouse model of bone marrow transplantation and transgenic mice over-expressing heparanase, we evaluated the effect of heparanase on the engraftment process and the development of graft-versus-host disease.

Results

Analysis of F1 mice undergoing allogeneic bone marrow transplantation from C57BL/6 mice demonstrated a better and faster engraftment in mice receiving cells from donors that were pretreated with heparanase. Moreover, heparanase treated recipient F1 mice showed only a mild appearance of graft-versus-host disease and died 27 days post transplantation while control mice rapidly developed signs of graft-versus-host disease (i.e., weight loss, hair loss, diarrhea) and died after 12 days, indicating a protective effect of heparanase against graft-versus-host disease. Similarly, we applied transgenic mice over-expressing heparanase in most tissues as the recipients of BMT from C57BL/6 mice. Monitoring clinical parameters of graft-versus-host disease, the transgenic mice showed 100% survival on day 40 post transplantation, compared to only 50% survival on day 14, in the control group. In vitro and in vivo studies revealed that heparanase inhibited T cell function and activation through modulation of their cytokine repertoire, indicated by a marked increase in the levels of Interleukin-4, Interleukin-6 and Interleukin-10, and a parallel decrease in Interleukin-12, tumor necrosis factor-alfa and interferon-gamma. Using point mutated inactive enzyme, we found that the shift in cytokine profile was independent of heparanase enzymatic activity.

Conclusions

Our results indicate a significant role of heparanase in bone marrow transplantation biology, facilitating engraftment and suppressing graft-versus-host disease, apparently through an effect on T cell activation and cytokine production pattern.     

Defect in oxidative phosphorylation in LV papillary muscle mitochondria of patients undergoing mitral valve replacement

Mitochondria play a pivotal role in cellular metabolism, especially in energy production. Myocardial function depends on adenosine triphosphate (ATP) supplied by oxidation of several substrates. In the adult heart, this energy is obtained primarily from fatty acid oxidation through oxidative phosphorylation (OXPHOS). With this in view, we studied OXPHOS, Total-ATPase and cytochrome content in the mitochondria of the left ventricular (LV) papillary muscles in excised mitral valves of patients who underwent mitral valve replacement (MVR). The mitochondrial OXPHOS, cytochrome content and ATPase activity were studied in 70 patients (ranging from 22 to 40 years) operated on for mitral valve disease. Control study includes 25 normal mitral valves removed at necropsy from patients who died of extracardiac causes. In the presence of glutamate and succinate as substrates, the rate of mitochondrial oxygen consumption was significantly lower in LV papillary muscles of pathological mitral valves (P<0.001) by using with and without addition of ADP. The ADP/O ratio indices for glutamate and succinate were not significantly affected. Using glutamate as substrate, respiratory control index was significantly raised (P<0.05) as compared with control. A significant reduction of total cytochrome content and ATPase activity (P<0.001) was noted in LV papillary muscles of patients operated for mitral valve disease. Our results showed that OXPHOS, cytochromes 'a', 'b', 'c+c(1)' and ATP activity are significantly impaired in LV papillary muscles in patients with pathological mitral valve. Cardiac mitochondrial oxygen consumption is a very valuable tool to investigate the regulation of cardiac mitochondrial energy metabolism. There is increasing evidence that mitochondrial diseases, such as mitochondrial cardiomyopathy, valvular disease and some myopathies, can be responsive to treatment with metabolic intermediates such as coenzyme Q(10), thiamine, prednisone, and vitamin therapy.     

Successful liver transplantation in babies under 1 year.

OBJECTIVE--To review the outcome of liver transplantation in babies aged less than 1 year. DESIGN--Prospective evaluation of survival, clinical complications, and nutritional and developmental status before and one year after liver transplantation. SETTING--The Children''s Hospital and Queen Elizabeth Hospital, Birmingham. SUBJECTS--All 25 babies who received liver transplantation from January 1989 to December 1992 were included. Median age was 9 months and median weight was 7.0 kg. Seven babies were assessed but were not given transplants because they died while on the waiting list (two) or had severe extrahepatic disease (five). RESULTS--24 babies had severe decompensated liver disease and 20 were severely malnourished despite nutritional support. Six babies received a whole liver graft and 19 received a reduction hepatectomy. Postoperative complications included primary nonfunction of the transplanted liver (one baby), hepatic artery thrombosis (two), biliary obstruction (seven), acute and chronic rejection (six), and sepsis (18). Three babies required a second transplant; all survived. Three babies, two of whom presented with fulminant hepatic failure, died. The overall actuarial survival rate (4 months to 4 years) is 88%. Review at 12 months showed a dramatic improvement in growth (p < 0.001) and normal psychosocial development with good quality of life. CONCLUSION--The improvement in survival rates and quality of life in this group of very sick babies is related not only to the development of reduction hepatectomy but also to advances in medical and nursing expertise. Early referral for liver transplantation is justified even if babies are critically ill.     

Balloon dilatation of the aortic valve for inoperable aortic stenosis.

The place of balloon dilatation of the aortic valve in the treatment of calcific aortic stenosis is controversial. Thirty two patients (mean age 76) in whom valve replacement was contraindicated were followed up for three to 24 months (mean 8); 25 were in functional class III or IV according to the New York Heart Association''s classification. Major complications of the procedure occurred in four patients. Echocardiography and Doppler studies were performed before operation and before discharge in 28 patients, and the area of the valve was measured again six to 50 (mean 23) weeks after operation in 11 patients. The peak to peak aortic pressure gradient fell from a mean of 65 (SD 24) to 46 (20) mm Hg, but the area of the aortic valve, measured by Doppler echocardiography, in 18 patients showed a modest but significant increase, from 0.61 (0.16) to 0.74 (0.23) cm2. One month after dilatation, 29 patients were alive, of whom 17 had improved symptoms. Only two had lasting clinical benefit. Sixteen patients died, 12 of a cardiac cause. The estimated one year survival rate was 49%. Six patients underwent or required valve replacement because of persisting symptoms. In view of its limited long term efficacy balloon dilatation of the aortic valve should be used only for patients with severe symptoms whose life expectancy is limited by other disease or who are considered to be unsuitable for valve replacement. It may have a role in improving the condition of patients who present with cardiogenic shock or pulmonary oedema before valve replacement is undertaken.     

Current status of the organ replacement approach for malignancies and an overture for organ bioengineering and regenerative medicine

Significant achievements in the organ replacement approach for malignancies over the last 2 decades opened new horizons, and the age of “Transplant Oncology” has dawned. The indications of liver transplantation for malignancies have been carefully expanded by a strict patient selection to assure comparable outcomes with non-malignant diseases. Currently, the Milan criteria, gold standard for hepatocellular carcinoma, are being challenged by high-volume centers worldwide. Neoadjuvant chemoradiation therapy and liver transplantation for unresectable hilar cholangiocarcinoma has been successful in specialized institutions. For other primary and metastatic liver tumors, clinical evidence to establish standardized criteria is lacking. Intestinal and multivisceral transplantation is an option for low-grade neoplasms deemed unresectable by conventional surgery. However, the procedure itself is in the adolescent stage. Solid organ transplantation for malignancies inevitably suffers from “triple distress,” i.e., oncological, immunological, and technical. Organ bioengineering and regenerative medicine should serve as the “triple threat” therapy and revolutionize “Transplant Oncology.”