Minimally Invasive Coronary Artery Bypass Grafting: A New Method Using an Anterior Mediastinotomy

The benefit of internal mammary artery (IMA) grafting as a long-lasting intervention for coronary artery disease is well recognized. However, largely because they are less invasive, catheter based alternatives are frequently chosen, particularly to treat single or double vessel disease. To retain the advantages of the IMA graft, and to offset the invasiveness of conventional coronary artery bypass grafting, we developed a new minimally invasive method using an anterior mediastinotomy for treating left anterior descending (LAD) or right coronary artery disease, or both. Feasibility studies using 16 pigs and a human cadaver led to approval by the Institutional Review Board for use of this procedure to treat six patients (four men, two women; mean age, 63.8 ± 13.6 [SD] yrs) who granted informed consent. Pedicle dissection of the IMA, using video assisted thoracoscopy if necessary, was made through a 2-to 3-inch horizontal anterior mediastinotomy. The underlying LAD artery was grafted during femoral vessel cardiopulmonary bypass, with cooling to 30°C, induced ventricular fibrillation, and left ventricular venting if required. Transesophageal echocardiography performed after bypass showed that two patients maintained normal wall motion and four had improvement from the original impairment. One patient suffered a recurrence of angina 4 weeks after the procedure; recatheterization showed an acutely angled IMA, subsequently corrected by balloon angioplasty. The results of follow-up dobutamine echocardiographic stress tests were negative in all patients. With this minimally invasive approach, the procedure should provide the benefits of IMA grafting with shorter hospital stay, more rapid recovery, and less overall cost.     

Viral cysteine proteinases

Summary Dozens of novel cysteine proteinases have been identified in positive single-stranded RNA viruses and, for the first time, in large double-stranded DNA viruses. The majority of these proteins are distantly related to papain or chymotrypsin and may be direct descendants of primordial proteolytic enzymes. Virus genome synthesis and expression, virion formation, virion entry into the host cell, as well as cellular architecture and functioning can be under the control of viral cysteine proteinases during infection. RNA virus proteinases mediate their liberation from giant multidomain precursors in which they tend to occupy conserved positions. These proteinases possess a narrow substrate specificity, can cleave in cis and in trans, and may also have additional, nonproteolytic functions. The mechanisms of catalysis, substrate recognition and RNA binding were highlighted by the recent analysis of the three-dimensional structure of the chymotrypsin-like cysteine proteinases of two RNA viruses.     

Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives

Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals.     

Crystallization of a copolyester in microlayers and blends with polycarbonate

The crystallization behavior of coextruded microlayered sheets comprised of 657 alternating layers of polycarbonate (PC) and a miscible copolyester of mainly 1,4-cyclohexanedimethanol and terephthalic acid (KODAR) was investigated as a function of annealing time when the KODAR was crystallized isothermally from the glass at 195°C. Comparisons were made with crystallization of KODAR alone, and with crystallization of KODAR from melt blends with PC. The kinetics of crystallization and the morphology of the crystallized KODAR were characterized with differential scanning calorimetry, and by examination of thin sections microtomed from annealed specimens in the polarized light microscope and the transmission electron microscope. The growth rate of small, birefringent KODAR spherulites was non-linear, and was strongly affected by diffusion of PC into the KODAR layers. Diffusion of amorphous PC into the KODAR layers retarded nucleation and spherulite growth and decreased spherulite density. The effect became more pronounced as the KODAR layer thickness was reduced. Spherulities nucleated randomly throughout the KODAR layers in the PC/KODAR 20/80 (w/w) microlayer and grew rapidly to form a continuous layer of impinged spherulites. In contrast, spherulites in the PC/KODAR 40/60 and 60/40 microlayers nucleated and grew along the center of the KODAR layers where the KODAR concentration was highest.     

Low sodium content formula for infants with congestive heart failure

Twenty-two infants of isolated ventricular septal defect with congestive heart failure were fed with lower-sodium content formula-Lonalac (Mead-Johnson) to study the clinical response of treatment for congestive heart failure. There were no significant changes of intake, urinary output, serum sodium, potassium and osmolality before, 2 days and 6 days after Lonalac feeding. The low sodium content formula may feed the infants with congestive heart failure in addition to the traditional anticongestive therapy.     

Phase II evaluation of merbarone in renal cell carcinoma

Summary The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m² IV continuous infusion days 1–5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1–15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.     

Cardiovascular collapse during anesthesia in a patient with preoperatively discontinued chronic MAO inhibitor therapy

We describe a patient in whom long-term monoamine oxidase (MAO) inhibitor therapy was discontinued 20 days before surgery with general anesthesia. This patient developed severe perioperative hypotension after administration of 10 mg of bupivacaine through an epidural catheter, which was corrected only after potent vasopressor therapy. We attribute this hemodynamic instability to attenuation of this patient's sympathetic tone based on several mechanisms: (1) residual effect of long-term administration of MAO inhibitor that caused a decrease in the number of β-adrenergic receptors (adrenergic subsensitivity due to receptor down-regulation), (2) recovered MAO activity causing effective degradation of sympathetic amines, and (3) combined attenuating effects of general and epidural anesthesia on sympathetic tone.     

Laparoscopic management of ureteral endometriosis: our experience

STUDY OBJECTIVE: Ureteral endometriosis is rare, accounting for less than 0.3% of all endometriotic lesions. The aim of our study is to evaluate the prevalence of extrinsic ureteral endometriosis in women undergoing laparoscopic surgery for severe endometriosis and to suggest that laparoscopic ureterolysis represents a mandatory measure in all cases to avoid ureteral injury. METHODS: A retrospective analysis was performed of all cases of patients who underwent laparoscopic surgery for severe endometriosis at the departments of obstetrics and gynecology at CMCO-SIHCUS and Hautepierre Hospital, Strasbourg, from November 2004 through January 2006. MEASUREMENTS AND MAIN RESULTS: We recorded 54 patients with a mean age of 31 years and a mean body mass index of 21.9. Reported symptoms were dysmenorrhea (88%), severe dyspareunia (88%), severe pelvic pain (38.8%), and infertility (74%). Five women presented with dysuria, frequency, recurrent urinary tract infections, and pain in the renal angle, and 2 patients had hydronephrosis. We observed 3 patients (5.6%) with ureteral stenosis, 35 (64.8%) with adenomyotic tissue surrounding the ureter without stenosis, and 16 (29.6%) with adenomyotic tissue adjacent to the ureter. It was on the left side in 47.4% of cases, on the right side in 31.6% cases, and bilaterally in 21% of cases. In 9 patients, ureteral involvement was associated with bladder endometriosis (16.7%). In all patients, ureterolysis was performed. There was 1 case of ureteral injury during the procedure, 2 of transitory urinary retention, and 1 of uretero-vaginal fistula after surgery. During the first year of follow-up, the disease recurred in 4 patients, with no evidence of the disease in the urinary tract. CONCLUSION: Conservative laparoscopic surgery to relieve ureteral obstruction and remove pathologic tissue is the management of choice. Resection of part of the ureter should be performed only in exceptional cases. Ureterolysis should be performed in all patients before endometriotic nodule resection to recognize and prevent any ureteral damage.