Inertia of success. A response to minimally invasive coronary bypass: a dissenting opinion.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Biomedical subjects
M Mack
Publications and source records attributed to M Mack.
Predominance of mononuclear cells expressing the chemokine receptor CCR5 in synovial effusions of patients with different forms of arthritis.
OBJECTIVE: To study the role of the chemokine receptors CCR5 and CCR2 in patients with arthritis. METHODS: CCR5 expression on peripheral blood leukocytes was compared with the expression on leukocytes isolated from the synovial fluid of 20 patients with different rheumatic joint diseases. Three additional samples were studied for CCR2 expression. The expression of chemokine receptors on blood and synovial fluid leukocytes was determined by 3-color flow cytometry analysis. To test CCR5 receptor down-modulation from the cell surface, leukocytes were incubated in vitro with a RANTES (regulated on activation, normal T cell expressed and secreted) derivative, aminooxypentane (AOP)-RANTES. Patients were genotyped for the delta32 CCR5 deletion by polymerase chain reaction. RESULTS: A high percentage of CCR5-expressing CD4+ and CD8+ T cells (74% and 81%, respectively), monocytes (51%), and natural killer cells (35%) was found in the synovial fluid of all patients, whereas in the peripheral blood, only a small percentage of these cells expressed CCR5 (13%, 32%, 7.8%, and 4%, respectively). Infiltration of CCR5-positive leukocytes was not reduced in CCR5-heterozygous patients. A similar, but less pronounced, distribution was observed for CCR2-positive T cells. In vitro, CCR5 was completely down-modulated on synovial fluid leukocytes by AOP-RANTES. CONCLUSION: The predominance of CCR5-positive mononuclear cells in the synovial effusions of patients with arthritis suggests an important role for CCR5 in the process of joint inflammation, and identifies CCR5 as a possible new target for therapeutic intervention.
Adolescent↗
[Value of MRI in traumatic disco-ligament instability of the lower cervical spine].
The diagnostic accuracy of magnetic resonance imaging (MRI) for traumatic discoligamentous instabilities of the lower cervical spine was evaluated. MRI findings were correlated with the intraoperative findings. Fifteen patients were included in the study (11 males, 4 females, 33 years old on average). Indication for surgery was established with dynamic a.p. instability under fluoroscopy. In the operation, all patients showed complete traumatic rupture of the intervertebral disc. In contrast, MRI sequences revealed only eight mild and four severe disc lesions. Intraoperatively ruptures of the anterior and posterior longitudinal ligaments were verified in 7 patients each. MRI studies depicted only five ruptures of the anterior and three ruptures of the posterior longitudinal ligaments. In three cases MRI demonstrated no pathological findings (3 of 15 false-negative results). MRI and intraoperative findings showed no statistical correlation. MRI is of only limited value in diagnosing traumatic discoligamentous instabilities of the lower cervical spine.
Adolescent↗
Robotically assisted endoscopic coronary artery bypass procedures without cardiopulmonary bypass.
Explore the source record for details and available documents.
Adult↗
Use of the voice-controlled and computer-assisted surgical system ZEUS for endoscopic coronary artery bypass grafting.
OBJECTIVE: With the aim of performing a completely endoscopic coronary bypass anastomosis, we have undertaken an experimental and clinical study using robotic instrumentation and voice-controlled camera guidance. METHODS: The ZEUS Robotic Surgical System (Computer Motion Inc, Goleta, Calif) consists of three interactive robotic arms and a control unit, allowing the surgeon to move the instrument arms in a scaled down mode. The third arm (AESOP, Computer Motion) positions the endoscope via voice control. PHASE I: In a phantom model, vascular grafts were anastomosed to the left anterior descending coronary artery (LAD) of 50 pig hearts with either 2- or 3-dimensional visualization. PHASE II: In 6 dogs (FBI 20-25 kg) the left internal thoracic artery (LITA) was harvested endoscopically. Then the animals were placed on an endovascular cardiopulmonary bypass system (Port-Access, Heartport, Inc, Redwood City, Calif). Anastomosis of the LITA to the LAD was performed endoscopically with the telemetric ZEUS instruments. Flow rates through the LITA were measured by Doppler analysis. PHASE III: Two patients were operated on with the ZEUS system. After endoscopic harvesting of the LITA and cardiopulmonary bypass with the Port-Access system, the bypass graft (LITA-LAD) was anastomosed endoscopically with the ZEUS system through three thoracic ports. RESULTS: In the dry laboratory, the time range required for the robotically assisted coronary anastomosis was 35 to 60 minutes with 2-dimensional visualization and 16 to 32 minutes with 3-dimensional visualization. In the animal experiments, the median time for endoscopic harvesting of the LITA was 86 minutes (range 56-120 minutes) and for the anastomosis, 42 minutes (range 35-105 minutes); flow rates through the LITA ranged between 22 and 45 mL/min. In the clinical cases, preparation times for the LITA were 83 and 110 minutes, respectively, and anastomosis times, 42 and 40 minutes, respectively. Doppler flow rates measured 125 and 85 mL/min, respectively. Both patients had an uneventful follow-up angiogram and postoperative course. CONCLUSIONS: With sophisticated robotic technology, a completely endoscopic anastomosis of the LITA to the LAD is possible, allowing technically precise operations within acceptable time limits.
Anastomosis, Surgical↗
Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity.
CCR5, a chemokine receptor expressed on T cells and macrophages, is the principal coreceptor for M-tropic HIV-1 strains. Recently, we described an NH2-terminal modification of the CCR5 ligand regulated on activation, normal T cell expressed and secreted (RANTES), aminooxypentane-RANTES (AOP-RANTES), that showed potent inhibition of macrophage infection by HIV-1 under conditions where RANTES was barely effective. To investigate the mechanism of AOP-RANTES inhibition of HIV infectivity we examined the surface expression of CCR5 using a monoclonal anti-CCR5 antibody, MC-1. We demonstrate that AOP-RANTES rapidly caused >90% decrease in cell surface expression of CCR5 on lymphocytes, monocytes/ macrophages, and CCR5 transfected Chinese hamster ovary (CHO) cells. RANTES also caused a loss of cell surface CCR5, although its effect was less than with AOP-RANTES. Significantly, AOP-RANTES inhibited recycling of internalized CCR5 to the cell surface, whereas RANTES did not. When peripheral blood mononuclear cells are cultured for prolonged periods of time in the presence of RANTES, CCR5 expression is comparable to that seen on cells treated with control medium, whereas there is no CCR5 surface expression on cells cultured in the presence of AOP-RANTES. Immunofluorescence indicated that both AOP-RANTES and RANTES induced downmodulation of cell surface CCR5, and that the receptor was redistributed into endocytic organelles containing the transferrin receptor. When RANTES was removed, the internalized receptor was recycled to the cell surface; however, the receptor internalized in the presence of AOP-RANTES was retained in endosomes. Using human osteosarcoma (GHOST) 34/CCR5 cells, the potency of AOP-RANTES and RANTES to inhibit infection by the M-tropic HIV-1 strain, SF 162, correlated with the degree of downregulation of CCR5 induced by the two chemokines. These differences between AOP-RANTES and RANTES in their effect on receptor downregulation and recycling suggest a mechanism for the potent inhibition of HIV infection by AOP-RANTES. Moreover, these results support the notion that receptor internalization and inhibition of receptor recycling present new targets for therapeutic agents to prevent HIV infection.
Animals↗
Policy statement: minimally invasive coronary artery bypass surgery. STS/AATS Ad Hoc Committee on New Technology Assessment. American Association for Thoracic Surgery.
Explore the source record for details and available documents.
Coronary Artery Bypass↗
Course guidelines for minimally invasive cardiac surgery. STS/AATS Ad Hoc Committee on New Technology Assessment. American Association for Thoracic Surgery.
Explore the source record for details and available documents.
Curriculum↗
Prognostic value of K-ras mutations, ras oncoprotein, and c-erb B-2 oncoprotein expression in adenocarcinoma of the lung.
This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene mutation in patients with adenocarcinoma of the lung. This was a retrospective study of 103 patients with adeno- or large-cell carcinoma of the lung who had available paraffin-stored tumor material. The relation of several clinical variables to survival was analyzed. Immunohistochemical techniques were used to determine expression of p21 and p185. Polymerase chain reaction (PCR) and sequencing were used to determine K-ras mutation status. Tumor stage was the only nonmolecular clinical variable predictive of survival (p=0.0001). A combination of K-ras mutation and p 185 expression (p=0.0144), ras mutation and strong p21 expression (p=0.0137), and K-ras mutation and the combined expression of p21 and p185 were predictive of poor survival (p=0.0415) in univariate analysis of all patients. The sole presence of K-ras mutation was predictive of survival. Additionally, when combined with elevated p21 or p185 expression in a subset of patients with 4 or more years of follow-up, negative correlation with survival was observed.
Adenocarcinoma↗
Regulation of riboflavin biosynthesis in Bacillus subtilis is affected by the activity of the flavokinase/flavin adenine dinucleotide synthetase encoded by ribC.
This work shows that the ribC wild-type gene product has both flavokinase and flavin adenine dinucleotide synthetase (FAD-synthetase) activities. RibC plays an essential role in the flavin metabolism of Bacillus subtilis, as growth of a ribC deletion mutant strain was dependent on exogenous supply of FMN and the presence of a heterologous FAD-synthetase gene in its chromosome. Upon cultivation with growth-limiting amounts of FMN, this ribC deletion mutant strain overproduced riboflavin, while with elevated amounts of FMN in the culture medium, no riboflavin overproduction was observed. In a B. subtilis ribC820 mutant strain, the corresponding ribC820 gene product has reduced flavokinase/FAD-synthetase activity. In this strain, riboflavin overproduction was also repressed by exogenous FMN but not by riboflavin. Thus, flavin nucleotides, but not riboflavin, have an effector function for regulation of riboflavin biosynthesis in B. subtilis, and RibC seemingly is not directly involved in the riboflavin regulatory system. The mutation ribC820 leads to deregulation of riboflavin biosynthesis in B. subtilis, most likely by preventing the accumulation of the effector molecule FMN or FAD.
Bacillus subtilis↗
Biologic properties of a bispecific single-chain antibody directed against 17-1A (EpCAM) and CD3: tumor cell-dependent T cell stimulation and cytotoxic activity.
Anti-CD3 x anti-tumor-bispecific Abs have been used to redirect cytotoxic T cells to tumor cells in an MHC-unrestricted fashion and to induce their rejection in vivo. We have recently described a recombinant bispecific single-chain Ab that combines four different V regions of two Abs, anti-17-1A and anti-CD3, on one polypeptide chain. It folds correctly to a 60-kDa globular protein and is secreted in fully functional form by a high producer Chinese hamster ovary cell line. In this work, we report that its remarkable cytotoxicity against 17-1A+ tumor cells is exerted via T cells without an apparent engagement of a detectable costimulatory pathway. T cells are activated only by the bispecific Ab when coincubated with 17-1A+ target cells. In a chromium release assay, CD8+ T cells reach maximal tumor cell cytotoxicity within 4 h, while CD4+ T cells need about 20 h to reach similar levels of cytotoxicity. Addition of costimulatory CD28 Abs did not lead to a further increase in cytotoxicity. Its remarkable stability at 37 degrees in serum, the ease of production, and purification by affinity chromatography via polyhistidine tail make this smaller version of a bispecific Ab a promising candidate for a therapeutic trial in patients with solid tumor. Because adjuvant therapy with an intact, much less cytotoxic IgG2a Ab against the 17-1A target had already increased the 7-yr survival of colorectal cancer patients by 30%, the presented small bispecific construct lacking the immunogenic murine Fc region as well as autochthonous T lymphocyte stimulatory activity warrants a therapeutic trial in patients with minimal residual 17-1A+ cancer.
Animals↗
Conversion of glutaconate CoA-transferase from Acidaminococcus fermentans into an acyl-CoA hydrolase by site-directed mutagenesis.
The heterooctameric (alphabeta)4 glutaconate CoA-transferase (EC 2.8.3.12) from the anaerobic bacterium Acidaminococcus fermentans catalyses the transfer of CoASH from acetyl-CoA to the 1-carboxylate of glutaconate. During this reaction the glutamate residue 54 of the beta-subunit (betaE54) forms a CoA-ester. The single amino acid replacement betaE54D resulted in a drastic change of enzymatic function. The CoA-transferase activity decreased from 140 to less than 0.01 s(-1), whereas the acyl-CoA hydrolase activity increased from less than 0.01 to 16 s(-1). The new enzyme was able to catalyse the hydrolysis of glutaryl-CoA, acetyl-CoA and 3-butenoyl-CoA. Since the mutants betaE54A and betaE54N showed neither acyl-CoA hydrolase nor CoA-transferase activity, it was concluded that the aspartate carboxylate of the mutant betaE54D acted as a general base which facilitated the attack of water at the thiolester carbonyl. Surprisingly, Km for glutaryl-CoA hydrolysis by the mutant (0.7 microM) as compared to CoA-transfer by the wild-type (28 microM) was 40 times lower. A 65 kDa protein, obtained by fusing the genes, gctA-gctB, coding for glutaconate CoA-transferase, retained 30% of the wild-type activity. Comparison of the amino acid sequences of 13 related enzymes demonstrated that Nature already has applied gene fusion in the case of pig heart CoA-transferase and has been using the E --> D mutation for catalysis by a yeast acetyl-CoA hydrolase.
Amino Acid Sequence↗
Glutaconate CoA-transferase from Acidaminococcus fermentans: the crystal structure reveals homology with other CoA-transferases.
BACKGROUND: Coenzyme A-transferases are a family of enzymes with a diverse substrate specificity and subunit composition. Members of this group of enzymes are found in anaerobic fermenting bacteria, aerobic bacteria and in the mitochondria of humans and other mammals, but so far none have been crystallized. A defect in the human gene encoding succinyl-CoA: 3-oxoacid CoA-transferase causes a metabolic disease which leads to severe ketoacidosis, thus reflecting the importance of this family of enzymes. All CoA-transferases share a common mechanism in which the CoA moiety is transferred from a donor (e.g. acetyl CoA) to an acceptor, (R)-2-hydroxyglutarate, whereby acetate is formed. The transfer has been described by a ping-pong mechanism in which CoA is bound to the active-site residue of the enzyme as a covalent thiol ester intermediate. We describe here the crystal structure of glutaconate CoA-transferase (GCT) from the strictly anaerobic bacterium Acidaminococcus fermentans. This enzyme activates (R)-2-hydroxyglutarate to (R)-2-hydroxyglutaryl-CoA in the pathway of glutamate fermentation. We initiated this project to gain further insight into the function of this enzyme and the structural basis for the characteristics of CoA-transferases. RESULTS: The crystal structure of GCT was solved by multiple isomorphous replacement to 2.55 A resolution. The enzyme is a heterooctamer and its overall arrangement of subunits can be regarded as an (AB)4tetramer obeying 222 symmetry. Both subunits A and B belong to the open alpha/beta-protein class and can be described as a four-layered alpha/alpha/beta/alpha type with a novel composition and connectivity of the secondary structure elements. The core of subunit A consists of seven alpha/beta repeats resulting in an all parallel central beta sheet, against which helices pack from both sides. In contrast, the centre of subunit B is formed by a ninefold mixed beta sheet. In both subunits the helical C terminus is folded back onto the N-terminal domain to form the third layer of helices. CONCLUSIONS: The active site of GCT is located at the interface of subunits A and B and is formed by loops of both subunits. The funnel-shaped opening to the active site has a depth and diameter of about 20 A with the catalytic residue, Glu54 of subunit B, at the bottom. The active-site glutamate residue is stabilized by hydrogen bonds. Despite very low amino acid sequence similarity, subunits A and B reveal a similar overall fold. Large parts of their structures can be spatially superimposed, suggesting that both subunits have evolved from a common ancestor.
Amino Acid Sequence↗
Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.
OBJECTIVES: We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons. STUDY DESIGN: Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol. RESULTS: During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1. CONCLUSIONS: These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness.
Double-Blind Method↗
Minimally invasive thoracoscopically assisted coronary artery bypass surgery.
OBJECTIVE: Minimally invasive techniques have been widely used in other surgical fields including video-assisted thoracic surgery (VATS) in thoracic surgery. These concepts are now being applied to cardiac surgery. The opportunities to make cardiac surgery less invasive include elimination of the median sternotomy incision, elimination of cardiopulmonary bypass and no manipulation of the aorta. MATERIALS AND METHODS: From January 1992 through September 1996, various aspects of minimally invasive cardiac surgery have been examined in the inanimate endoscopic trainer, animal model, human cadaver and in human clinical studies. Techniques of endoscopic sutured anastomosis as well as alternatives to suturing were first perfected in the inanimate trainer. Twenty animals then underwent endoscopic coronary artery bypass using the left internal mammary artery to the left anterior descending with circulatory support from an axial flow pump. Fifty eight minimally invasive coronary artery bypass procedures have been performed in humans using thoracoscopic assistance for internal mammary artery harvest. RESULTS: One hundred fifty endoscopic coronary anastomoses were performed in the inanimate trainer with the endoscopic suturing technique being the preferred method. Time required to perform an anastomosis decreased from greater than 60 min to a mean of 20 min as technique and instruments were developed. In animals, methods of access as well as enabling surgical instruments to allow crossclamp of the aorta and performance of the anastomosis were developed. Fifty-eight humans underwent coronary artery bypass using the left internal mammary artery placed to the left anterior descending under direct vision through a limited anterior thoracotomy on a beating heart. The procedure was successful in 52 patients with conversions required in six patients. Techniques were developed for immobilization for performance of the anastomosis. DISCUSSION: The ability to perform an endoscopic anastomosis still remains the rate limiting step for totally endoscopic coronary artery bypass surgery. The present MIDCAB (minimally invasive direct coronary artery bypass grafting) procedure is a significant advance in cardiac surgery, but still has limitations that make performance of an exact anastomosis still somewhat difficult and applicable only to single-vessel disease. Present efforts are directed toward extending the MIDCAB procedure by various immobilization and circulatory support devices and combining the MIDCAB procedure with catheter techniques for treating more advanced disease.
Animals↗
[Volumetric and morphological CT parameters for assessing prognosis and treatment control in hepatocellular carcinoma undergoing arterial chemoembolization].
PURPOSE: To evaluate volumetric CT data as a guide for indication and assessment of prognosis for transarterial chemo-embolisation (TAE) of hepatocellular carcinomas (HCC). MATERIAL AND METHOD: 74 patients with HCC were treated with repeated TAE. 50 mg Adriblastin/m2 body surface, 50 mg cisplatin/m2 body surface and 10 ml lipiodol were combined with 2-10 ml Spherex and injected selectively (25 cases) or superselectively (49 cases); in 28 patients a single injection and in 46 patients multiple injections were used. RESULTS: CT findings before and after the procedure showed a solitary lesion in 17 patients, two lesions in 18 patients and in 39 patients there were three or more lesions. Mean expectation of life was 523 days (median = 372 days; 57% of one year survival probability). In 29 patients with > 75% lipiodol retention, mean survival was 819 days; in 17 patients with < 75% lipiodol retention it was 382 days; lower lipiodol retention of < 50% it was 231 days (< 25% 192 and < 10% 152 days). A statistically significant relationship (p < 0.0001) could be established between survival time and tumour volume, relationship of tumour to liver volume, intratumoral lipiodol retention, the type of tumour growth and the number of liver segments involved. CONCLUSION: TAE provides best survival rates after repeated injections of solitary HCC with tumour volumes < 50 ml and > 75% intra-tumoral lipiodol retention.
Aged↗
Hepatocellular carcinoma: evaluation with dynamic and static gadobenate dimeglumine-enhanced MR imaging and histopathologic correlation.
PURPOSE: To analyze the potential of gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging for the characterization and diagnosis of hepatocellular carcinoma (HCC) by using static and dynamic sequences. MATERIALS AND METHODS: Twenty-eight patients with histopathologically proved HCC were evaluated with T1- and T2-weighted spin-echo and static and dynamic gradient-echo sequences before, during, and after intravenous administration of 0.1 mmol/kg gadobenate dimeglumine (0.5 mol/L). RESULTS: During the perfusion phase of the dynamic sequence, all 16 nodular well-differentiated HCC lesions showed a rapid increase in signal intensity 10-30 seconds after injection followed by a progressive decrease in signal intensity. The nine poorly differentiated HCC lesions showed no rapid increase in signal intensity. All eight large (> 3 cm), nodular, well-differentiated HCC lesions showed a hypointense rim before injection and both hypo- and hyperintense rims (double-ring sign) immediately after injection, compared with normal liver parenchyma. About 55 seconds after injection, substantial single-rim enhancement was detected in 21 of the 28 HCC lesions. CONCLUSION: Dynamic gadobenate dimeglumine-enhanced MR imaging allows improved characterization of HCC lesions, which show rapid increase in signal intensity during the early, arterial phase in well-differentiated HCC lesions and a double-ring sign in large well-differentiated nodular HCC lesions.
Carcinoma, Hepatocellular↗