Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis.

BACKGROUND: Proteasomes are the main non-lysosomal proteolytic structures which regulate crucial cellular processes. Circulating proteasome levels can be measured using an ELISA test and can be considered as a tumour marker in several types of malignancy. Given that there is no sensitive marker of hepatocellular carcinoma (HCC) in patients with cirrhosis, we measured plasma proteasome levels in 83 patients with cirrhosis (33 without HCC, 50 with HCC) and 40 controls. METHODS AND RESULTS: Patients with HCC were sub-classified into three groups according to tumour mass. alpha-Fetoprotein (AFP) was also measured. Plasma proteasome levels were significantly higher in patients with HCC compared to controls (4841 (SEM 613) ng/ml vs 2534 (SEM 187) ng/ml; p<0.001) and compared to patients with cirrhosis without HCC (2077 (SEM 112) ng/ml; p<0.001). This difference remained significant when the subgroup of patients with low tumour mass (proteasome level 3970 (SEM 310) ng/ml, p<0.001) was compared to controls and patients with cirrhosis without HCC. Plasma proteasome levels were independent of the cause of cirrhosis and were weakly correlated with AFP levels. With a cut-off of 2900 ng/ml, diagnostic specificity for HCC was 97% with a sensitivity of 72%, better than results obtained with AFP. Diagnostic relevance of plasma proteasome measurement was also effective in low tumour mass patients (sensitivity 76.2% vs 57.1% for AFP). CONCLUSION: The plasma proteasome level is a reliable marker of malignant transformation in patients with cirrhosis, even when there is a low tumour mass.

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

BACKGROUND: The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). AIMS: To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. METHODS: We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. RESULTS: Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). CONCLUSION: Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use.

Left ventricular aneurysm, normal coronary arteries and embolization in a patient with systemic lupus erythematosus.

We describe a 30-year-old woman with a normal appearing coronary artery associated with SLE who suffered myocardial infarction with left ventricular aneurysm and systemic embolization including cerebral infarctions and saddle embolism. The patient was surgically treated with good results. To our knowledge this is the first reported case of systemic embolism due to myocardial infarction occurring in SLE with a normal coronary artery.

Preservation of pancreatic beta cell function with pulsatile cardiopulmonary bypass.

Pancreatic islet cell function and tissue metabolism were studied during and after cardiopulmonary bypass in 38 patients undergoing an open heart operation. Twenty patients were operated on with pulsatile cardiopulmonary bypass (group I) and 18, with nonpulsatile cardiopulmonary bypass (group II). Hyperglycemia was observed during and early after operation in both groups. In group I during cardiopulmonary bypass, the immunoreactive insulin and c-peptide levels and the insulin to glucagon molar ratio increased significantly compared with the preoperative values, but in group II, these variables did not alter significantly. An hour postoperatively, the immunoreactive insulin (71 +/- 34 muIU/mL) and c-peptide (8.3 +/- 3.0 ng/mL) levels and the insulin to glucagon molar ratio (11.0 +/- 5.2) in group I were significantly higher than those in group II (immunoreactive insulin, 29 +/- 20 muIU/mL; c-peptide, 4.8 +/- 1.8 ng/mL; insulin to glucagon molar ratio, 3.4 +/- 2.6). The blood lactate level in group I (41 +/- 22 mg/dL) was significantly lower than that in group II (78 +/- 30 mg/dL) an hour postoperatively. In conclusion, pulsatile cardiopulmonary bypass is quite effective in preserving pancreatic beta cell function and tissue metabolism during and early after open heart procedures.

Influence of coronary artery disease and left ventricular dysfunction on postoperative mortality in vascular surgery.

In an attempt to assess the influence of coronary artery disease and left ventricular dysfunction on postoperative mortality, 107 patients consisting of 32 AAA resections and 44 aortoiliac and 31 femoropopliteal reconstructions were reviewed. All patients had a preoperative coronary angiograms and underwent cardiac catheterization to prevent cardiac-related deaths. Severe coronary artery disease was angiographically demonstrated in 40.6% of AAA, 31.8% of AI and 3.2% of FP patients. Severe left ventricular dysfunction was found in 21.9% of AAA, 18.2% of AI and 6.5% of FP. Both of the early and 5 (45.5%) of the 11 late deaths were caused by cardiac events. The nine-year survival rate (53.3%) in the patients with a documented combination of coronary artery disease and left ventricular dysfunction was significantly lower than those in patients with normal disease, normal left ventricular function and either documented coronary artery disease or left ventricular dysfunction. It is suggested from this series that left ventricular dysfunction is one of the most important risk factors in patients who undergo AAA resection and AI reconstruction and that severe disease and postoperative mortality are possibly reduced by certain kinds of interventional coronary therapies.

Effects of aprotinin on prostaglandin metabolism and platelet function in open heart surgery.

The effects of the protease inhibitor, aprotinin, on plasma prostaglandin levels and platelet function during and after cardiopulmonary bypass (CPB) were studied in a group of 23 patients which consisted of 11 untreated patients (control group) and 12 aprotinin-treated patients (aprotinin group). Thromboxane B2 (TXB2, a stable metabolite of thromboxane A2) and beta-thromboglobulin levels in the control group increased significantly during CPB compared with preoperative values. These increases were significantly suppressed in the aprotinin group. 6-Keto-PGF1 alpha (stable metabolite of prostacyclin) increased significantly during CPB in both groups, and there was no significant difference between the two groups. In the aprotinin group, the TXB2/6-Keto-PGF1 alpha ratio decreased significantly during CPB compared with the preoperative value, whereas no significant decrease was observed in the control group. Platelet counts decreased significantly during and after CPB in both groups. Platelet aggregability decreased significantly during CPB in the control group, whereas no significant decrease was found in the aprotinin group. In conclusion, aprotinin treatment improved prostaglandin metabolism and preserved platelet function during open heart surgery.

Scintigraphic evaluation along with CT and MR images in a case of huge gravitation abscess.

The authors presented a rare case of huge gravitation abscess. 67Ga scintigraphy was useful in the evaluation of the extent and activity of the disease. CT showed clearly the location and shape of the abscess. Enhanced MRI showed vertebral lesions as characteristic geographic and ring-like enhancement.

Lunate plasty for Kienböck's disease: use of a pedicled vascularised radial bone graft combined with shortening of the capitate and radius.

We treated eight patients with Kienböck's disease (two patients each with stage 1, 2, 3a and 3b disease by Lichtman's classification) by removing a pedicled, vascularised bone segment from the dorsal aspect of the distal radius and engrafting it into the lunate. Additional shortening of the radius was performed in patients with the ulna-minus or null variant. Shortening of the capitate and capito-hamate fusion were also performed in patients with stage 3 disease. All patients were relieved of their wrist pain at rest and during movement, and the mean grip strength increased from 37% of that in the contralateral hand before surgery to 80% after surgery. The mean post-operative range of motion in the affected wrist was 92% of that in the opposite wrist in patients with stage 1 and 2 disease, and 53% in patients with stage 3 disease. Post-operative assessment revealed that four patients had excellent results, three had good results, and one had a fair result.

[Clinical study on transfer into lung tissue of cefminox].

Nineteen patients who underwent pulmonary resection due to lung diseases were administered with 2 g of cefminox (CMNX) by intravenous drip infusion just before surgery. CMNX levels in the serum and lung tissue were determined and pharmacokinetic parameters were derived. The obtained results are summarized as follows: 1. Pharmacokinetic parameter (K1/K2) derived from serum and lung tissue concentrations using deconvolution method was 0.46. 2. CMNX was useful for prophylaxis of postoperative infections with lung resection.

[A young female case with simultaneous bilateral spontaneous pneumothorax operated upon submammarian incision for median sternotomy].

One of the characteristics of pneumothorax in female is considerably complicated with menses, histiocytosis X, diffuse pulmonary hamartoangiomyomatosis. So during thoracotomy, the thoracic cavity must be examined, as well as the hole of the diaphragm. And especially in female aesthetic attention is also required. A transverse submammarian skin incision with median sternotomy was used in a 18-year-old female with simultaneous bilateral pneumothorax. This approach was useful for the median sternotomy as well as more excellent aesthetics.

[Experiences of reoperative coronary artery bypass grafting by left thoracotomy without aortic clamping].

We reported two cases which had reoperative coronary artery bypass grafting (CABG) through the left thoracotomy approach without aortic clamping with good results. Case 1. A 50-year-old man, who underwent a double CABG to left anterior descending coronary artery (LAD) and right coronary artery (RCA) in 1983, had a recurrent unstable angina due to new significant stenosis of the diagonal branch (DG) and obtuse marginal branch (OM) in 1989. He was reoperated upon, having a new double CABG to DG and OM through the left thoracotomy using hypothermic ventricular fibrillation without aortic clamping for the myocardial protection without any blood transfusion. Case 2. A 61-year-old man, who underwent a double CABG to LAD and RCA in 1982, had a recurrent unstable angina and a left ventricular aneurysm in 1991. He had a reoperation of a single CABG to OM combined with left ventricular aneurysmectomy by the same approach. Both cases showed satisfactory recoveries of the left ventricular function in the early postoperative period and patent grafts on postoperative angiograms. The left thoracotomy approach is a preferable alternative to median resternotomy for the reoperative CABG to OM, DG and left ventricular aneurysmectomy.

[Repeat open heart surgery using continuous warm blood cardioplegia].

Myocardial protection during repeat open heart surgery still remains to be further improved. The purpose of this study was to evaluate the usefulness of continuous warm blood cardioplegia (CWBC) comparing with intermittent cold GIK cardioplegia (ICGC) in repeat open heart surgery. Twenty-four patients underwent repeat open heart surgery through re-sternotomy (11 mitral, 6 aortic 5 double, 2 congenital) were divided into two groups, that is 10 received CWBC (warm group) and 14 ICGC (Cold group). Spontaneous recovery of heart beat was obtained in 9 of 10 patients (90.0%) in warm group, in contrast only 2 of 14 (14.3%) in cold group (p < 0.001) following aortic declamping. Postoperative peak level of serum CK-MB in warm group (25.9 +/- 7.4 IU/l) was significantly lower than that (83.1 +/- 24.6) in cold group. In warm group left and right ventricular stroke work index significantly increased at 24 hours postoperatively, whereas no significant increase was found in cold group. Postoperative bleeding in the first 24 hours was less (553.8 +/- 38.9 ml) in warm group than that (974.3 +/- 54.1 ml) in cold group. In warm group 3 patients were operated on without homologous blood transfusion, in contrast none in cold group. Our results clearly demonstrated that CWBC was preferable to ICGC for myocardial protection in repeat open heart surgery.

[Myocardial protection during aortic valve replacement: effectiveness of continuous warm blood cardioplegia].

Effectiveness of continuous warm blood cardioplegia (CWBC) during aortic valve replacement (AVR) was studied by comparing with intermittent cold GIK cardioplegia (ICGC) in 32 patients who underwent AVR using CWBC in 16 and ICGC in the other 16 patients. There was no operative nor hospital death in this series. In CWBC group, spontaneous recovery of the heart beat following aortic declamping was seen in 14 of 16 patients (87.5%), in contrast only in 4 of 16 (25%) in ICGC group. During the early postoperative period, left ventricular stroke work index (g.m/beat/m2) significantly increased from 41.0 +/- 14.4 to 55.9 +/- 8.0 (p < 0.001) in CWBC group, whereas no significant increase was found in ICGC group. Right ventricular stroke work index significantly increased only in CWBC group as well. In CWBC group, myocardial oxygen and lactate extraction rates were maintained within normal range during aortic cross-clamping, suggesting satisfactory myocardial preservation with an aerobic metabolism. In conclusion, CWBC is superior to ICGC as a myocardial protection during AVR.

[A case report of chest wall reconstruction utilizing microvascular surgery].

A 62-year-old man underwent left chest wall reconstruction after resection of the chest wall including 4-6th ribs for the metastatic tumor of squamous cell carcinoma of the left lung. The chest wall defect measuring 15 x 10 cm was reconstructed with double Marlex mesh in skeletal chest and covered with pedicled free mucocutaneous flap of tensor fasciae latae which was implanted by the vascular anastomoses to the thoracodorsal artery and vein using microvascular surgical technique. The flap was attached well and its blood supply was excellent on postoperative angiography.

[A clinical experience of continuous warm blood cardioplegia in two cases of repeat aortic valve surgery].

The continuous warm blood cardioplegia (CWBC) was used for myocardial protection during aortic cross clamping in two cases of repeat aortic valve operations with good results. Case 1: A 46-year-old man, who underwent an aortic valve replacement because of the rheumatic aortic regurgitation (AR) in 1978, have suffered from orthopnea due to para-prosthetic valvular regurgitation since 1983. He was revealed to have bi-ventricular hypertrophy with myocardial damage on ECG, EF 0.27 on UCG, PCWP 20 mmHg and severe AR on cardiac catheterization. Case 2: A 43-year-old man, who had an aortic valvuloplasty for the non-rheumatic incompetency in 1981, have had a recurrent regurgitation, resulting in left ventricular hypertrophy accompanied by chest pain. Both cases were reoperated upon, having aortic valve replacement with mechanical prosthetic valves through the re-median sternotomy, utilizing CWBC with good recovery. CWBC provides an ideal circumstances for myocardial oxygen utilization during aortic cross clamping and moreover a benefit that needs not the wide dissection of the heart in a redo case because it has no need of topical cooling and ventricular defibrillation following aortic declamping. In conclusion, CWBC is very useful in a repeat aortic valve surgery.

[Coronary artery bypass grafting in patients with severe left ventricular dysfunction: internal mammary artery vs saphenous vein, evaluation immediately after surgery].

Comparative studies of the changes in left ventricular (LV) function immediately after aortocoronary bypass graftings (CABG) and early postoperative results were carried out in two groups of patients with severe LV dysfunction (ejection fraction less than 0.4), which consisted of 9 patients received internal mammary artery grafts (IMAG) to at least LAD and 14 with saphenous vein grafts (SVG) only. The utilization of IMAG was limited to the patients with stable preoperative hemodynamics, whereas SVGs were used even in the emergency CABG. Free flow of IMAG measured during operation was 55.7 +/- 25.5 ml/min, which was significantly lower than that (83.5 +/- 27.3) of SVG to LAD. Cardiac index, LV stroke volume index and LV stroke work index immediately after surgery were sufficiently maintained and recovered almost similarly in both groups. Postoperative peak CK-MB (19.7 +/- 10.4 IU/L) in IMAG group was significantly lower than that (23.9 +/- 10.7) in SVG group. There was no significant difference between the two groups in the incidences of postoperative IABP and noradrenaline dependence. There were two hospital deaths in SVG group, whereas no hospital death was experienced in IMAG group. These results indicate that an application of IMAG to LAD in the patients with severe LV dysfunction surely induces satisfactory recovery of hemodynamics immediately after CABG as well as SVG, provided that use of IMAG is limited to the patients with stable preoperative hemodynamics.

[Successfully treated intraoperative coronary artery spasm in a patient with type B dissecting aortic aneurysm: a case report].

A 65-year-old man with chronic type B dissecting aortic aneurysm, complicated by variant from of angina pectoris without any coronary artery obstructed disease on preoperative angiogram was operated upon through left posterolateral thoracotomy under the left heart bypass with Bio-pump system using preoperative Ca antagonists and intraoperative nitroglycerin infusion. Shortly before the end of operation the patient suddenly developed shock status definitely due to coronary artery spasm, associated with ST-elevation in II, III, aVF and bradycardia, then ventricular tachycardia, finally cardiac arrest. The patient was resuscitated by cardiac massage and administration of nifedipine and nitroglycerin. Such attacks repeated five times at ten or twenty minutes intervals. The coronary artery spasm could be successfully suppressed with the additive use of noradrenaline infusion. The patient had no attacks at all postoperatively and was discharged with good success. This case suggests that the prevention of intraoperative coronary artery spasm is essential, but if it occurs, additive use of noradrenaline infusion is effective for the cessation of coronary artery spasm.

[Acute occlusion of the iliac arteries due to blunt trauma].

Two cases of acute iliac occlusion due to blunt trauma are presented. The cause of injuries were a fall from bicycle in case 1 and a compression between an automobile and a wall in case 2. The end-to-end anastomosis was possible in case 2, but an interposition of an artificial prosthesis was necessary because of the length of damaged artery in case 1. Both cases were associated with the pelvic fracture, adding the perforation of small bowels and the bladder in case 2. Postoperative course was almost uneventful except fasciotomy was needed for the compartment syndrome of the right lower extremity in case 2.

Investigation of memory B cell responses to hepatitis B surface antigen in health care workers considered as non-responders to vaccination.

Up to 20% of health care workers are considered as non-responders to hepatitis B vaccination (anti-HBs<10 m UI/ml in serum). We have explored memory B cells differentiated in vitro into anti-HBs antibody-secreting cells (anti-HBs-SCs) by ELISPOT assay. Anti-HBs-SCs were detected in vaccinated responders (n = 11) and non-responders (n = 10) but IgG anti-HBs-SCs were significantly lower in the non-responder group (p<0.001). Low amounts of HBs antibodies were also quantified by ELISA in non-responders' sera. These results indicate that a suboptimal B cell response exists in non-responders to HBV vaccination. This B cell response may mediate a protection against clinically significant breakthrough hepatitis B infection.