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Biomedical subjects

C Pak

Publications and source records attributed to C Pak.

At least 19 recordsLinked to original sources
PubMed2001

Effects of methylprednisolone on intracellular bacterial growth.

Clinical studies have shown positive associations among sustained and intense inflammatory responses and the incidence of bacterial infections. Patients presenting with acute respiratory distress syndrome (ARDS) and high levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6, have increased risk for developing nosocomial infections attributable to organisms such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., compared to those patients with lower levels. Our previous in vitro studies have demonstrated that these bacterial strains exhibit enhanced growth extracellularly when supplemented with high concentrations of pure recombinant TNF-alpha, IL-1 beta, or IL-6. In addition, we have shown that the intracellular milieu of phagocytic cells that are exposed to supraoptimal concentrations of TNF-alpha, IL-1 beta, and IL-6 or lipopolysaccharide (LPS) favors survival and replication of ingested bacteria. Therefore, we hypothesized that under conditions of intense inflammation the host's micromilieu favors bacterial infections by exposing phagocytic cells to protracted high levels of inflammatory cytokines. Our clinical studies have shown that methylprednisolone is capable of reducing the levels of TNF-alpha, IL-1 beta, and IL-6 in ARDS patients. Hence, we designed a series of in vitro experiments to test whether human monocytic cells (U937 cells) that are activated with high concentrations of LPS, which upregulate the release of proinflammatory cytokines from these phagocytic cells, would effectively kill or restrict bacterial survival and replication after exposure to methylprednisolone. Fresh isolates of S. aureus, P. aeruginosa, and Acinetobacter were used in our studies. Our results indicate that, compared with the control, stimulation of U937 cells with 100-ng/ml, 1.0-microg/ml, 5.0-microg/ml, or 10.0-microg/ml concentrations of LPS enhanced the intracellular survival and replication of all three species of bacteria significantly (for all, P = 0.0001). Stimulation with < or =10.0 ng of LPS generally resulted in efficient killing of the ingested bacteria. Interestingly, when exposed to graded concentrations of methylprednisolone, U937 cells that had been stimulated with 10.0 microg of LPS were able to suppress bacterial replication efficiently in a concentration-dependent manner. Significant reduction in numbers of CFU was observed at > or =150 microg of methylprednisolone per ml (P values were 0.032, 0.008, and 0.009 for S. aureus, P. aeruginosa, and Acinetobacter, respectively). We have also shown that steady-state mRNA levels of TNF-alpha, IL-1 beta, and IL-6 in LPS-activated cells were reduced by treatment of such cells with methylprednisolone, in a concentration-dependent manner. The effective dose of methylprednisolone was 175 mg, a value that appeared to be independent of priming level of LPS and type of mRNA. We therefore postulate that a U-shaped relationship exists between the level of expression of TNF-alpha, IL-1 beta, and IL-6 within the phagocytic cells and their abilities to suppress active survival and replication of phagocytized bacteria.

Acinetobacter↗
PubMed1999

Effects of cytokines and endotoxin on the intracellular growth of bacteria.

Patients with unresolving acute respiratory distress syndrome (ARDS) have persistently elevated levels of proinflammatory cytokines in the lungs and circulation and increased rates of bacterial infections. Phagocytic cells hyperactivated with lipopolysaccharide (LPS), which induces high levels of proinflammatory cytokines in monocytic cells, are inefficient in killing ingested bacteria despite having intact phagocytic activity. On the other hand, phagocytic cells that are activated with an analogue of LPS that does not induce the expression of proinflammatory cytokines effectively ingest and kill bacteria. We hypothesized that in the presence of high concentrations of proinflammatory cytokines, bacteria may adapt and utilize cytokines to their growth advantage. To test our hypothesis, we primed a human monocytic cell line (U937) with escalating concentrations of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-6 and with LPS. These cells were then exposed to fresh isolates of three common nosocomial pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, and an Acinetobacter sp. In human monocytes primed with lower concentrations of proinflammatory cytokines (10 to 250 pg) or LPS (1 and 10 ng), intracellular bacterial growth decreased. However, when human monocytes were primed with higher concentrations of proinflammatory cytokines (1 to 10 ng) or LPS (1 to 10 micrograms), intracellular growth of the tested bacteria increased significantly (P <0.0001). These results were reproduced with peripheral blood monocytes obtained from normal healthy volunteers. The specificity of the cytokine activity was demonstrated by neutralizing the cytokines with specific antibodies. Our findings provide a possible mechanism to explain the frequent development of bacterial infections in patients with an intense and protracted inflammatory response.

Acinetobacter↗
PubMed1998

Enantiomeric separation of propranolol and selected metabolites by using capillary electrophoresis with hydroxypropyl-beta-cyclodextrin as chiral selector.

A capillary electrophoresis (CE) investigation of the enantiomeric separation of propranolol and some of its metabolites using CE was undertaken. Resolution of the enantiomers was achieved using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as the chiral selector. Parameters found to influence separation include cyclodextrin concentration, potential, pH and organic solvent/additive. It was observed that 17 mM HP-beta-CD gave optimum separation over the concentration range used in this study, however different racemates appear to have best resolution at different CD concentration. The potential does not have a great effect on enantiomer resolution, but appears to cause relative metabolite migration times to alter such that separation is affected. Carrier pH affects both migration time, and enantiomer resolution and metabolite separation. Above pH 5 inferior results are obtained. This is the first report of enantiomeric resolution of propranolol metabolites using CE.

Carbohydrate Sequence↗
PubMed1998

Dietary sulfate regulates the expression of the renal brush border Na/Si cotransporter NaSi-1.

Dietary inorganic sulfate (Si) intake is an important factor in the regulation of renal proximal tubular sodium-dependent Si transport (Na/Si cotransport). The purpose of the present study was to determine whether modulation of Na/Si cotransport activity by dietary Si is mediated through regulation of the renal expression of the recently cloned NaSi-1 protein located in the apical brush border membrane (BBM) of the proximal tubule. It was found that rats fed a high Si diet had a marked increase in the renal excretion of Si and a concomitant decrease in BBM Na/Si cotransport activity when compared with rats on a control Si diet. The 43% decrease in BBM Na/Si cotransport activity was associated with a 33% decrease in BBM NaSi-1 protein abundance, as determined by Western blotting, and a 2.7-fold decrease in cortical NaSi-1 mRNA abundance, as determined by Northern blotting. Furthermore, cortical mRNA from rats fed a high Si diet when injected into Xenopus laevis oocytes led to a 2.2-fold decrease in Na/Si cotransport activity compared with mRNA isolated from control Si diet rats. This study indicates that adaptation to a high Si diet is accompanied by a decrease in renal cortical NaSi-1 mRNA abundance, which results in reduced expression of the NaSi-1 protein at the level of the proximal tubular BBM.

Adaptation, Physiological↗
PubMed1997

Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia.

OBJECTIVE: To develop a revised equation reflecting the current practice of measuring unbound phenytoin at room temperature, and to evaluate the revised Winter-Tozer method of predicting normalized total phenytoin concentrations in two groups of patients with hypoalbuminemia-elderly nursing home patients and critically ill head trauma patients. DESIGN: Albumin, unbound phenytoin, and total phenytoin concentrations were obtained from two sources: prospectively from a group of elderly nursing home patients and by a retrospective chart review of trauma patients enrolled in a previous double-blind, placebo-controlled study. SETTING: Community nursing homes; a university-affiliated urban teaching hospital. PARTICIPANTS: Elderly nursing home patients (n = 46) taking chronic phenytoin therapy and patients enrolled in a double-blind, placebo-controlled study (n = 58) evaluating the use of phenytoin to prevent posttraumatic seizures. MAIN OUTCOME MEASURES: Prediction error analysis was performed by using the methods proposed by Sheiner and Beal. Bias and precision were evaluated by calculating the mean prediction error (MPE) and root mean squared error (RMSE), respectively. RESULTS: The Winter-Tozer equation consistently overpredicted the normalized phenytoin concentration in the elderly nursing home population (MPE = 3.2, RMSE = 5.9) and the trauma patients (MPE = 3.3, RMSE = 4.8). The equation was revised to reflect the increased protein binding of phenytoin with decreased temperature and resulted in significantly decreased bias in both groups of patients. CONCLUSIONS: The revised equation is useful in predicting normalized phenytoin concentrations in both elderly nursing home patients and critically ill trauma patients.

Adolescent↗
PubMed1992

[Studies on acute surgical therapy for DeBakey III aortic dissection: especially on the CT images and the operative indication].

Nine patients with DeBakey type III aortic dissection (type III a; 6, type III b; 3) that underwent acute surgical therapy were studied with particular emphasis on the preoperative CT images and operative indication. It took 6 approximately 192 hours (mean 40.6 +/- 56.0) from onset of the disease to the operation. The reasons why operations were required in acute phase were prolonged pain; 2, fluid retensionin in thoracic cavity; 3, increasing fluid retension; 3, shock state; 1, anuria; 1.6 (75%) of 8 thoracic aortic dissection cases showed intra-thoracic fluid retension in chest roentogenogram or CT image. We performed prosthetic interposition of descending thoracic aorta in 8 patients and Y-graft interposition of abdominal aorta in a patient. During the operations, we found fluid retension in the thoracic and pericardial cavity in 83% (5 cases) of 6 non-ruptured cases. To diagnose ruptured aneurysm, CT image played very important role. But we could not discriminate between ruptured aneurysm and intrapleural serous fluid retension on the CT image. Puncture of intra-thoracic fluid is effective procedure to diagnose rupture of the aneurysms but it is impossible in some cases and traumatic tap may lead misdiagnosis. Therefore we think moderate or increasing fluid retension in the thoracic cavity should be added to the operative indication of acute DeBakey type III aortic dissection and that the early operation will make mortality rate lower.

Acute Disease↗
PubMed1992

[Surgical therapy of aortic regurgitation due to aortitis syndrome--effectiveness and extended indication of Bentall's operation].

Fourteen patients with aortic regurgitation due to aortitis syndrome that underwent surgical therapy were studied with particular emphasis on the long term merits of Bentall's operations over the conventional valve replacement. They were divided into two groups; Group A: 6 aortic valve replacements (AVRs) and Group B: 8 Bentall's operations. Post operative complications related to aortitis syndrome developed in 3 cases; a case of paravalvular leakage (Group A) and two cases of aneurysm formation at the coronary artery anastomotic sites (Group B). We speculated that these complications were due to abnormal healing and recurrent inflammatory process of the disease. Therefore we think that conventional valve replacement is not suited to cope with these problems. Since 1984, we have adopted the policy to perform Bentall's operations for all patients with aortitis requiring valve replacement. Bentall's operation required longer aortic cross-clamp time (212.1 +/- 53.9 min) than AVRs (73.0 +/- 25.0) and was more aggressive. However no patients with our current technique to reimplant the coronary artery button and distal graft to aorta anastomosis, which has been used since 1984, has developed pseudoaneurysm or valvular leakage. We conclude that our modified Bentall's operation is effective even for patients who have active aortitis syndrome or need redo operations.

Adult↗
PubMed1991

Optimization of the liposomes encapsulating a new lipopeptide CGP 31362 for efficient activation of tumoricidal properties in monocytes and macrophages.

The purpose of this study was to optimize a suitable liposomal carrier for CGP 31362, a new synthetic lipopeptide analogue of gram-negative bacterial cell walls. CGP 31362 was inserted into the membranes of different liposomes with different phospholipid composition. We determined the ability of these liposomes to activate tumoricidal properties in mouse peritoneal and bone marrow macrophages, and in human monocytes. The ideal liposome carrier for CGP 31362 consisted of phosphatidylcholine and phosphatidylserine in a 7:3 molar ratio. Subsequent to efficient binding and endocytosis, CGP 31362 in liposomes of this composition rendered mouse macrophages and human monocytes highly tumoricidal. Moreover, even in the absence of interferon-gamma, human monocytes released significant levels of tumor necrosis factor and interleukin-1. These data show that in a suitable liposomal carrier, the new synthetic lipopeptide in liposomes is a potent activator of tumoricidal properties in macrophages.

Animals↗
PubMed1991

[Treatment of mediastinal infection after coronary artery bypass surgery by transposition of the greater omentum].

From January, 1986 to May, 1990 twenty one adult patients (men 16, women 5, age 64 +/- 7 years old) underwent transposition of the greater omentum to control mediastinal infection after coronary artery bypass surgery. Upon diagnosing mediastinitis, the mediastinum was drained open and irrigated with 0.5% povidone iodine-saline solution until the omental transposition. The interval between the diagnosis of mediastinitis and the omental transposition ranged from 0 to 171 (mean 19) days. Three quarters of the patients had the omentum transposed within 14 days. In nineteen of 21 patients (90%) the mediastinitis was effectively controlled. In the remaining two patients the infection could not be controlled and proceeded to succumb from multiple organ failure. There was no complication related to the omental transposition in itself. We conclude that transposition of the greater omentum is a safe and effective method for treating mediastinal infection after coronary artery bypass surgery.

Aged↗
PubMed1991

[Bilateral diaphragmatic plication for an adult patient].

Bilateral phrenic nerve paralysis is a very rare complication in open-heart surgery. An 65-year-old woman sustained respiratory distress after coronary artery bypass grafting because of bilateral phrenic nerve paralysis. Bilateral diaphragmatic plication was performed on the 43rd postoperative day. She successfully weaned from ventilator support without difficulty a few days after plication. We believe that surgical plication of the diaphragm is a safe and effective technique for a distressed adult patient with paralyzed diaphragm.

Aged↗
PubMed1991

[Coronary artery bypass surgery for chronic total occlusion of the left main coronary artery by means of intermittent antegrade cold blood cardioplegia].

From January, 1984 to May, 1990 eleven patients (men 9, women 2) underwent coronary artery bypass surgery for chronic total occlusion of the left main coronary artery by means of intermittent antegrade cold blood cardioplegia. The ages ranged from 33 to 74 (mean 56) years. The causes of the total occlusion of the left main coronary artery were atherosclerosis in 10 patients and aortitis syndrome in one. Four patients had history of a previous myocardial infarction. Preoperative selective coronary arteriography revealed well developed collateral vessels from the RCA to the LCA in all patients. One to five coronary arteries were bypassed. Myocardial protection was obtained in the usual fashion: antegrade intermittent cold blood cardioplegia with topical cardiac cooling. All patients were successfully weaned off from cardiopulmonary bypass without the need of IABP assist. No patient developed perioperative myocardial infarction. All grafts were patent postoperatively. Treadmill testing was negative in all patients. We believe that coronary artery bypass surgery for chronic total occlusion of the left main coronary artery can be performed safely with intermittent antegrade cold blood cardioplegia.

Adult↗
PubMed1990

[Free internal mammary artery for coronary bypass].

We studied 12 cases of free internal mammary artery (IMA) grafting. We used IMAs as free grafts mainly because of its shortness (6 cases 50%) and injury during dissection (4 cases 33%) and found the varicose change of saphenous vein in 5 cases (42%). Most of the grafting sites are distal parts of coronary arteries. Proximal anastomosis sites are other vein grafts (3 cases), other IMA grafts (3 cases), vein grafts interposing to the aorta (3 cases), and aorta (1 case). Patency rate of the free IMA grafts 4 weeks after operations was good (82%). Free IMA grafting is safe alternative to in situ IMA grafting when IMA grafts are short or injured and saphenous vein grafting is impossible.

Adult↗
PubMed1990

[Repair of pure mitral insufficiency--experience in 50 patients].

Between February 1982 and March 1987, 50 adults underwent mitral valve repair for pure mitral insufficiency representing 54% of all adults having mitral valve surgery for pure mitral insufficiency. Ages ranged from 20 to 73 years (50.0 +/- 11.6). Anterior leaflet prolapse was present in 11, posterior leaflet prolapse in 26 and annulus dilation in 13. The mitral valve was repaired by quadrangular resection in 21, triangular resection in 2, plication without resection in 4, chordal shortening in 8 and annuloplasty alone in 15. Commissural annuloplasty was performed in addition to leaflet repair or chordal shortening in other 14 patients. The competence of the mitral valve was usually evaluated under beating conditions. 79% of the attempted repairs was considered successful in the posterior leaflet, contrasting to only 37% in the anterior leaflet. Prolapse of the anterior leaflet remains a surgical challenge. There were two early deaths (4%). During the follow up period (Mean 1.9 years, range 0.2-5.2 years), 2 late deaths (4%) were observed, one of them from thromboembolism, before adopting the policy of routinely anti-coagulating these patients during the first few months. 4 patients (9%), early in our experience, required reoperation within 4 months of surgery: two for severe mitral insufficiency and two for severe mechanical hemolysis. At reoperation, residual insufficiency was present in one, valve suture tear due to technical imperfection in two and complete disruption of the valve tissue at the suture line in one. Four additional patients had transient mechanical hemolysis requiring no specific therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Coronary endarterectomy].

From July, 1984, to December, 1986, coronary bypass grafting was performed in 314 patients, 70 (22%) requiring coronary endarterectomy (RCA; 48 pts, LAD; 10 pts, LAD + RCA; 10 pts, Others; 2 pts). Coronary endarterectomy patients (END group) were younger and often with the risk factor of hyperlipidemia than non-endarterectomy patients (NON group). The over-all hospital mortality rate of END group was 7 per cent; perioperative myocardial infarction occurred in 7 per cent of patients. Early postoperative angiogram (4 weeks after the operation) was performed in 54 patients. The patency rate of RCA endarterectomy was 81.8 per cent, and that of LCA endarterectomy was 75 per cent. This result was poor compared with the patency rate of non-endarterectomy graft (86.6%). However without endarterectomy, with all likelihood the patency rate of those grafts would have been poorer. The results of right coronary endarterectomy are satisfactory and better than those of the left coronary artery system. This experience suggests that coronary endarterectomy is safe and an useful adjunct of saphenous vein bypass grafting procedures in the management of diffuse coronary disease, especially in RCA lesions.

Adult↗