Human herpesvirus 6 infection in adult living related liver transplant recipients.

To analyze human herpesvirus 6 (HHV-6) infection in adult living related liver transplantation, we performed a virological analysis, including viral isolation, serological assay, and real-time polymerase chain reaction, of serially collected blood samples from 67 recipients. In addition, cytokine levels were measured to determine their role in viral reactivation. HHV-6 was isolated from only 4 recipients (6.0%), and viral DNA was detected in 15 (22.4%) of the 67 recipients. A significant increase in HHV-6 immunoglobulin G antibody titers was observed in 19 (28.4%) of the 67 recipients. Finally, 26 recipients (38.8%) had HHV-6 reactivation 2-6 weeks after transplantation. HHV-6 associated clinical features were analyzed in the 17 recipients presenting with either viremia or DNAemia. Two recipients with viremia and 3 recipients with DNAemia had unexplained fever at the time of viral infection. An increase in aminotransferase levels was observed in 2 recipients with viremia and 3 recipients with DNAemia. Recipients with liver cirrhosis caused by hepatitis B virus or hepatitis C virus infection as the underlying disease were more likely to have HHV-6 infection (P = 0.025). Mortality at the last follow-up in recipients with HHV-6 reactivation was significantly higher than in those without viral reactivation (P = 0.0118). Plasma interleukin-6 levels were significantly higher in the recipients with HHV-6 viremia than in the recipients without viremia at 4 weeks post-transplant (P = 0.0411). Moreover, tumor necrosis factor alpha levels were also higher in recipients with HHV-6 viremia (P < 0.0001) or reactivation (P = 0.0011) than in recipients without viremia or reactivation 4 weeks post-transplant.     

Viability of liver grafts from fasted donor rats: relationship to sinusoidal endothelial cell apoptosis

Previous studies have shown that livers from fasted donors appear to tolerate long-term preservation better than livers from fed donors, but the mechanism is not clear. Some studies have shown that the apoptosis of sinusoidal endothelial cells (SEC) appeared to be a pivotal mechanism of ischemia/reperfusion injury in liver transplantation. The purpose of the present investigation was to evaluate the relation of SEC apoptosis to liver viability in rats after liver transplantation, comparing findings for fasted and fed donors. Wistar rats were used as donors and recipients. The fed group had access to solid feed and water ad libitum. The fasted group was allowed access only to water for 4 days prior to liver harvest. All rat livers were preserved with University of Wisconsin (UW) solution at 2 °C for 24 h. After preservation, the livers were orthotopically transplanted, and survival time was measured. Apoptosis was determined by in-situ staining for apoptotic cells, using a TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay and electron microscope (EM) examination separately. The 14-day survival rates after 24-h preservation were 0% (0/11) for recipients of livers from fed donors and 91% (10/11) for recipients of livers from fasted donors. There was no significant difference in the numbers of TUNEL-positive SEC after 24-h preservation between the two groups. However, at 6 h after transplantation, the number of TUNEL-positive SEC was significantly higher in the fed group than in the fasted group. These results suggest that donor fasting decreases SEC apoptosis after reperfusion alone, and that this may be related to the protection of the liver graft from reperfusion injury. Received: December 22, 2000 / Accepted: February 15, 2001     

Expression of the Prothymosin-α Gene as a Prognostic Factor in Lung Cancer

Prothymosin-α (PTα) is known to play a role in cell proliferation, and the PTα mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTα mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTα and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTα and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTα mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTα and c-myc. PTα mRNA overexpression in lung cancer was correlated with a poor prognosis. Received: October 13, 2000 / Accepted: May 15, 2001     

Diagnostic significance of digital rectal examination and transrectal ultrasonography in men with prostate-specific antigen levels of 4 ng/mL or less

Objectives. To investigate the usefulness of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for prostate cancer diagnosis and to propose a diagnostic algorithm for individual-based cancer screening in subjects with prostate-specific antigen (PSA) levels of 4.0 ng/mL or less.Methods. Between January 1992 and March 2000, 129 subjects with PSA levels of 4.0 or less and abnormal findings on DRE or TRUS underwent prostate biopsy. The subjects were divided into four groups according to the PSA range: 0 to 0.9 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL. The reliability of the DRE and TRUS and the clinicopathologic features of prostate cancer were investigated among these four groups.Results. Of the 129 subjects, 17 (13.2%) patients with prostate cancer were diagnosed. The detection rate was 2.2% (1 of 45), 0% (0 of 27), 20.6% (7 of 34), and 39.1% (9 of 23) in subjects with PSA levels of less than 1.0 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL, respectively. The proportion of patients with Stage II, III, and IV was 58.8%, 41.2%, and 0%, respectively. The percentage with Gleason scores of 8 to 10 was 17.6%. The detection rate of abnormal findings on DRE and TRUS was 14.4% (13 of 90) and 9.5% (7 of 74), respectively. Adding TRUS to DRE in the screening program of subjects with PSA levels of 2.0 to 4.0 ng/mL, increased the detection rate of prostate cancer to 30.8% (4 of 13).Conclusions. Routine prostate biopsy should not be undertaken except for highly suspicious DRE findings in subjects with PSA levels less than 2.0 ng/mL. The additional use of TRUS in subjects with PSA levels of 2.0 to 4.0 ng/mL would improve the sensitivity of prostate cancer detection. The diagnostic algorithm proposed in the present study is useful as a screening method for prostate cancer in subjects with PSA levels of 4.0 ng/mL or less.     

Treatment recommendations for adrenal metastasis of non-small cell lung cancer

To evaluate the optimum treatment strategy for metastatic adrenal tumors derived from non-small cell lung cancer (NSCLC), we retrospectively analyzed 17 consecutive cases (8 resection cases: 4 synchronous and 4 metachronous: 9 non-resection cases: 3 synchronous and 6 metachronous) who received surgical resection for NSCLC. The patients included 12 males and 5 females with a mean age of 63.9 years. Of these, 9, 3, 2, 2, and 1 patient (s) were diagnosed as having adenocarcinoma, squamous cell carcinoma, pleomorphic carcinoma, large cell carcinoma, and adenosquamous cell carcinoma, respectively. The mean interval after lung resection and treatment of metachronous adrenal metastasis was 9.9 months. The mean time to progression from treatment of metachronous adrenal metastasis to disease progression was 8.9 months. A survival analysis showed no significant prognostic difference between the patient age, gender, pathological stage, synchronous/metachronous classification, CEA, and site of metastases. However, patients who received an adrenalectomy had a more favorable prognosis. The 2-year survival of patients following resection versus those who did not undergo a resection for adrenal metastasis was 62.5 and 22.8%, respectively. These data indicate that metastatic adrenal tumors should be resected if the patient can tolerate surgery after appropriate selection.     

JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis

This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis: (1) Severity assessment is indispensable to the selection of proper initial treatment in the management of acute pancreatitis (Recommendation A). (2) Assessment by a severity scoring system (JPN score, APACHE II score) is important for determining treatment policy and identifying the need for transfer to a specialist unit (Recommendation A). (3) C-reactive protein (CRP) is a useful indicator for assessing severity (Recommendation A). (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced magnetic resonance imaging (MRI) play an important role in severity assessment (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has been established as the criterion for hospital transfer (Recommendation A). (6) It is preferable to transfer patients with severe acute pancreatitis to a specialist medical institution where they can receive continuous monitoring and systemic management.     

Uremic toxin and bone metabolism

Patients with end-stage renal disease (ESRD) develop various kinds of abnormalities in bone and mineral metabolism, widely known as renal osteodystrophy (ROD). Although the pathogenesis of ESRD may be similar in many patients, the response of the bone varies widely, ranging from high to low turnover. ROD is classified into several types, depending on the status of bone turnover, by histomorphometric analysis using bone biopsy samples [1,2]. In the mild type, bone metabolism is closest to that of persons with normal renal function. In osteitis fibrosa, bone turnover is abnormally activated. This is a condition of high-turnover bone. A portion of the calcified bone loses its lamellar structure and appears as woven bone. In the cortical bone also, bone resorption by osteoclasts is active, and a general picture of bone marrow tissue infiltration and the formation of cancellous bone can be observed. In osteomalacia, the bone surface is covered with uncalcified osteoid. This condition is induced by aluminum accumulation or vitamin D deficiency. The mixed type possesses characteristics of both osteitis fibrosa and osteomalacia. The bone turnover is so markedly accelerated that calcification of the osteoid cannot keep pace. In the adynamic bone type, bone resorption and bone formation are both lowered. While bone turnover is decreased, there is little osteoid. The existence of these various types probably accounts for the diversity in degree of renal impairment, serum parathyroid hormone (PTH) level, and serum vitamin D level in patients with ROD. However, all patients share a common factor, i.e., the presence of a uremic condition.     

Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer: trends over time and 20-year institutional experience.

OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study was to report the clinical characteristics, operative results, survival, and late outcomes over 20 years in patients who underwent sleeve lobectomy and pneumonectomy at our institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL group) and 110 who underwent pneumonectomy (PN group). Comparisons of the demographics, morbidity, and survivals between the groups were performed by unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent a pneumonectomy showed a significantly advanced pathological stage, and a larger tumor size than those who received a sleeve lobectomy, whereas there were no significant differences in histology, ratio of combined resection and induction therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL group and four (3.6%) in the PN group. Local relapse and distant recurrence incidence were similar between the two groups. The 5-year-survival rates of the SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were no differences in 5-year survivals in patients with pathological stage I/II (SL, 59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%) between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were performed with an acceptable risk of operative mortality and satisfactory 5-year survival rate. The indication of pneumonectomy is aimed to perform a curative resection for locally advanced lung cancer, particularly after induction therapy that is otherwise unresectable, and the selected patients will likely benefit from a complete resection.     

Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

REP-1 gene mutations in Japanese patients with choroideremia

· Background: Choroideremia (CHM) is an X-linked progressive dystrophy of the choroid, retinal pigment epithelium, and retina. Recently, the REP-1 gene was isolated and the causative mutations in the gene were detected in patients with CHM. In a previous study, we described a Japanese family with CHM who had a mutation in the REP-1 gene. In the present study, we performed extensive analysis of the REP-1 gene in patients with CHM from several institutions in Japan. · Methods: Twenty-six patients with CHM and 5 unaffected females from 22 independently ascertained families were examined. Exons 1–15 of the REP-1 gene were screened by single-strand conformation polymorphism. The DNA fragments suspected of any variations were directly sequenced. · Results: Fifteen different mutations, including one previously reported mutation, were detected in 18 families. In addition, carrier status was proven in four unaffected females found to be heterozygous for the mutant allele. · Conclusions: Fifteen different mutations of the REP-1 gene were detected in 18 Japanese families. There were no hot spots for the mutations and no missense mutations. The results show that REP-1 gene defects cause CHM in Japanese patients, and the mutations in these Japanese patients differed from the mutations reported for CHM patients in Europe, Canada, and America except for R267X and 1313delTC. These findings suggest that the mutations occurred independently in the Japanese patients. Received: 13 August 1998 Revised version received: 16 November 1998 Accepted: 9 December 1998