Antisense oligodeoxynucleotide combination therapy of primary chronic myelogenous leukemia blast crisis in SCID mice

The proliferation of chronic myelogenous leukemia (CML) cells and the transformation of normal hematopoietic cells by BCR-ABL appear to require the expression of a functional MYC protein, suggesting an approach to treatment of Philadelphia leukemias based on simultaneous targeting of BCR-ABL and c-MYC. To test this hypothesis, CML-blast crisis (CML-BC) primary cells were treated in vitro with bcr-abl and c- myc antisense phosphorothioate oligodeoxynucleotides ([S]ODNs), individually or in combination. Compared with antisense ODNs targeting of individual oncogenes, downregulation of both BCR-ABL and c-MYC by specific antisense [S]ODNs resulted in a synergistic antiproliferative effect. Colony formation of normal bone marrow cells was not affected by either treatment. To assess the therapeutic potential of multiple oncogene downregulation, SCID mice injected with CML-BC primary cells were treated systematically with equal doses of bcr-abl or c-myc antisense [S]ODNs or with a combination of both antisense [S]ODNs. Compared with mice treated with individual compounds, the disease process was significantly retarded in the group treated with both [S]ODNs as revealed by flow cytometry, clonogenic assay, and RT-PCR analysis to detect leukemic cells in mouse tissue cell suspensions. These effects correlated with a markedly increased survival of leukemic mice treated with both antisense [S]ODNs. Leukemic cells harvested from antisense [S]ODN-treated mice were sensitive to the effects of antisense [S]ODNs in vitro, suggesting that the treatment can be successfully repeated. These data demonstrate the therapeutic potential of targeting multiple cooperating oncogenes.     

Myocardial Protection during Reoperative Cardiac Surgery: Early Experience with a New Technique

We recently introduced a new adjunct to myocardial preservation in patients with a patent left internal mammary artery graft who were undergoing reoperative cardiac surgery. The purpose of this study was to review our early experience with this technique.The technique consists of preoperative insertion of a suitably sized angioplasty balloon catheter into the proximal part of the graft under fluoroscopic guidance. Intraoperative inflation of the balloon results in occlusion of the graft during aortic cross-clamping. We have used this technique in 9 patients. The case records of these patients were retrospectively reviewed.There were 5 men and 4 women with a mean age of 71 ± 11 years and a mean Euro-SCORE of 10 ± 3. The median time interval from previous cardiac operation to reoperation was 6 years (interquartile range, 2–11 yr). After the balloon catheter was inserted successfully into the left internal mammary artery graft, the balloon was inflated intraoperatively for successful occlusion of the graft in all patients. There was no in-hospital death, and no significant complications were observed.The early results of this technique seem favorable. A prospective randomized study is needed in order to evaluate the potential advantages of this method over other techniques of myocardial protection during cardiac reoperations.Key words: Angioplasty balloon, catheterization, peripheral, coronary artery bypass, graft occlusion, vascular, internal mammary artery, reoperation/methods, vascular patencyReoperative cardiac surgery is becoming increasingly common but is associated with a higher risk of perioperative morbidity and death than is primary surgery.^1,2 This increased risk is partly due to the characteristics of the patient population, since patients undergoing reoperations tend to be older and have more comorbid conditions and worse cardiac function, but it is also due to the complexity and technical challenges of reoperations.^1,2 One of the common technical challenges of cardiac reoperations is the dissection and external control of a patent left internal mammary artery (LIMA) graft in patients who have undergone previous coronary artery bypass surgery. Control of this artery becomes necessary when cardioplegic techniques are used for myocardial protection, because blood flowing through a patent graft would otherwise wash away the cardioplegic solution. Mobilization and external clamping of a patent LIMA graft can cause injury to the vessel, leading to adverse short- and long-term outcomes. Angioplasty balloon occlusion of the LIMA graft—an interesting alternative to external clamping—was first described in 2001 by Grinda and colleagues.³ The principle of the technique is preoperative placement of a suitably sized angioplasty balloon in the LIMA graft followed by intraoperative inflation of the balloon during aortic cross-clamping. The purpose of this retrospective study was to review our early experience with this technique.     

Early prosthetic valve failure in a patient with rheumatoid arthritis

Abstract   Heart lesions in patients with rheumatoid arthritis (RA) are well documented in literature; however, in the majority of cases these are incidental findings at postmortem. Most patients do not require cardiac surgical intervention unless they develop complications such as significant valvular regurgitation. Patients with RA often require orthopedic operations and therefore a bioprosthetic valve replacement is normally advocated to avoid problems related to anticoagulation. We report a case of a 64-year-old woman with seropositive RA who had undergone bioprosthetic aortic valve replacement three years previously. She re-presented with early prosthetic valve failure due to accelerated degeneration and calcification. This was treated successfully with redo replacement with a mechanical prosthesis. Here, we discuss our experience and debate the various valve choices available that should be considered in patients with rheumatoid disease.     

The right choice of prosthesis for patients undergoing aortic valve surgery: searching the truth

Aortic valve surgery is suggested when native aortic valve is diseased and complications outweigh the risks. Choice of prosthesis for aortic valve surgery is vastly undetermined, in part due to the varied options (bioprosthetic, mechanical prosthesis, homografts and allografts) available. The technical issues during valve surgery and the anticoagulation concerns along with the patient type with respect to age, ethnicity, sex and quality of life do contribute to the challenge for deciding the type of valve prosthesis best substituted to the diseased native valve. Here we attempt to unravel the controversies and present a holistic approach towards settling on the best possible prosthesis for a diseased aortic valve.     

Endourological renal salvage in patients with calculus nephropathy and advanced uraemia.

OBJECTIVE: To document our experience with percutaneous nephrolithotripsy (PCNL) for the treatment of calculus nephropathy and advanced renal failure. PATIENTS AND METHODS: Between October 1989 and April 1996, 78 patients with calculus nephropathy (51 males and 27 females, mean age 42 years, range 16-67; mean serum creatinine level 663.8 micromol/L, range 282.8-1449.7) were treated in our department. Forty-six of the patients had bilateral upper urinary calculi, while the remaining 32 had a solitary functioning kidney obstructed by stone. Thirty-two patients had a normal urine output, 26 were oliguric and 20 presented with anuria. A preliminary percutaneous nephrostomy (PCN) was performed under local anaesthesia in 64 patients, and stone retrieved subsequently through the same nephrostomy track after improvement in their uraemic status. In the remaining 14 patients, the stones were removed at the first session. Of the 46 patients with bilateral stones, 21 underwent stone retrieval by PCNL on the contralateral side after an interval of 2-3 weeks, while 25 patients underwent simultaneous JJ stenting on the contralateral side, followed, after improvement in uraemic status, by delayed PCNL or extracorporeal shock wave lithotripsy on that side. RESULTS: There were three deaths, caused by overwhelming sepsis; 64 of the remaining 75 patients recovered well from uraemia, while 11 showed no improvement, suggesting irreversible renal damage. Complications included five patients with nonfatal sepsis and five with secondary haemorrhage. At the last follow-up 2.5-9 years after presentation, the mean serum creatinine level (271.3 micromol/L) was significantly better than the mean preoperative level. Six patients are on maintenance haemodialysis. CONCLUSIONS: It is not uncommon in developing countries for patients with urolithiasis to present with advanced uraemia caused by long-standing obstruction, almost invariably complicated by infection. A percutaneous endourological approach offers the best hope for these patients, and in our experience a significant percentage of these cases can be salvaged.     

Pancreaticojejunostomy with invagination of spatulated pancreatic stump into a jejunal pouch

BACKGROUND: Pancreaticoenteric anastomosis after pancreatic resection is of major concern as anastomotic leak continues to be common. There is no unanimity for the preferred technique and overall incidence of pancreatic leak is reported to be 2% to 14%. METHODS: A new safe method of anastomosing pancreatic stump to a jejunal pouch is described. A 15-cm length of the jejunal end is detubularized and reconfigurated into a U-shaped patch. The pancreatic stump is mobilized for about 3 cm and the duct is spatulated posteriorly and anastomosed to a cut in convex margins of the patch. This is converted into a pouch invaginating the spatulated pancreaticojejunal anastomosis. RESULTS: Eleven cases of periampullary malignancy after pancreaticoduodenectomy have been operated on with no pancreatic leak. CONCLUSIONS: Even a bulky pancreas can be invaginated into the pouch. The resulting anastomosis is completely intraluminal. Spatulated mucosa to mucosa anastomosis should reduce the chances of late stenosis.     

Traumatic carotid cavernous fistula: Anatomical variations and their treatment by detachable balloons

Endovascular balloon occlusion has become a standard mode of therapy in carotid cavernous fistulas. Many angio-architectural variations are, however, encountered in individual cases, some of which influence the therapeutic mode and outcome. We report on three patients with carotid cavernous fistulas treated by endovascular techniques.     

Nontuberculous mycobacterial infection in AIDS: clinical, pathologic, and radiographic features

The medical records, radiographs, and pathologic specimens of ten patients with the diagnoses of nontuberculous mycobacterial infection and acquired immunodeficiency syndrome (AIDS) were examined. The radiographic findings of alveolar or nodular infiltrates and adenopathy were relatively nonspecific but in most cases led to bronchoscopic study or open-lung biopsy, which established the diagnosis. Bronchoscopic washings or sputum cultures, which frequently provided the first confirmation of infection, were always followed by positive blood or tissue cultures. In contrast to nontuberculous infection in immunocompetent hosts, disseminated infection was common, with evidence of extrapulmonary involvement in nine patients. On the basis of these findings, we recommend that any AIDS patient with sputum or bronchoscopic washings demonstrating nontuberculous mycobacterial organisms be tentatively classified as having disseminated infection while being evaluated with blood, bone-marrow, stool, and urine cultures, even if the chest radiograph shows no disease.