Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with 99mTc-MAA perfusion and dynamic 133Xe SPET

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic 133Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster 133Xe half-clearance time (T(1/2)) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T(1/2) in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T(1/2) values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a lower susceptibility of peripheral parenchyma to the development of this disease.     

Postoperative hip motion and functional recovery after simultaneous bilateral total hip arthroplasty for bilateral osteoarthritis

Background  Simultaneous bilateral total hip arthroplasty (THA) can offer a potential benefit of greater postoperative hip motion without the negative influence of contralateral hip disabilities, compared to two-stage THA. However, postoperative changes in hip motion after simultaneous bilateral THA have rarely been reported. The purpose of this study was to clarify the efficacy of simultaneous procedures on postoperative hip motion and functional recovery. Methods  We retrospectively compared hip motion in 27 patients treated with simultaneous bilateral THA to those in 11 patients with two-stage bilateral THA, 35 patients with unilateral THA for unilateral disease, and 15 patients with unilateral THA for bilateral disease. We also evaluated the clinical manifestations according to the Japanese Orthopaedic Association (JOA) hip scores and compared the outcomes among the groups. All of the THA surgeries were primarily performed through a posterolateral approach using cement-less prostheses. The diagnosis at surgery was dysplastic osteoarthritis in all patients, and the patients were followed up for at least 4 years. Results  The postoperative improvement of motion in hip flexion was significantly greater in patients treated with simultaneous procedures compared to patients with two-stage THA and unilateral THA for bilateral disease. The differences in improvement of motion in hip abduction were less marked than the improvement in hip flexion among the groups. Although there were no significant differences in pain scores among the groups, the values for activity of daily living were significantly greater in patients treated with simultaneous bilateral THA and patients with unilateral THA for unilateral disease than in patients with unilateral and two-stage bilateral THA for bilateral disease. Conclusions  The simultaneous procedure was considered to be more effective in patients with bilateral hip osteoarthritis and demonstrated a substantial improvement in hip motion and functional recovery after THA.     

Introducing the clusterin gene into human renal cell carcinoma cells enhances their metastatic potential

PURPOSE: We recently reported a protective role of clusterin expression against apoptosis induced by a wide variety of stimuli in several human cancer models. In the current study we tested the hypothesis that clusterin over expression confers a benefit for the metastasis of renal cell carcinoma through the inhibition of apoptosis induced by the various obstacles the cancer cells may confront after detachment from their primary origin. MATERIALS AND METHODS: We introduced clusterin complementary DNA into human renal cell carcinoma ACHN cells, which do not express detectable level of clusterin expression, and generated the clusterin over expressing cell line ACHN/CL and the control vector only transfected cell line ACHN/C. In vitro anti-cell death activity under anchorage independent conditions among ACHN sublines was examined by limiting dilution assay and cell survival assay in suspension. To investigate the in vivo effects of clusterin over expression on metastatic potentials each cell line was injected into the tail vein or renal subcapsule of nonobese diabetic, severe combined immunodeficient mice and the metastatic features in all abdominal and thoracic organs were evaluated. RESULTS: ACHN/CL showed significantly enhanced growth in limiting dilution cultures compared with ACHN/C. The analysis of cell survival in the floating assay also revealed that ACHN/CL had a powerful survival advantage in suspension compared with ACHN/C. Furthermore, ACHN/CL formed more than 5-fold as many metastatic nodules in the lung after intravenous injection than ACHN/C. Similarly more marked lung metastasis was observed after implanting ACHN/CL cells into the renal subcapsule than after implanting ACHN/C cells. In contrast, there were no significant differences among ACHN sublines in the growth rates in vitro and in vivo, cell motility or invasive ability. CONCLUSIONS: These findings suggest that, if clusterin is over expressed, it prolongs cell survival under unfavorable conditions in the metastatic process, resulting in the enhanced metastatic potential of renal cell carcinoma.     

Angiotensin II type 1 receptor blockade ameliorates tubulointerstitial injury induced by chronic potassium deficiency

BACKGROUND: Chronic potassium (K+) deficiency, one of the well-known causes of renal tubulointerstitial injury, is associated with an alteration in vasoactive mediators including persistent generation of renal cortical angiotensin (Ang) II despite the suppression of plasma Ang II, and suppression of urinary nitrite/nitrate excretion. We tested the hypothesis that K+-deficiency-induced renal tubulointerstitial injury could be mediated by Ang II or a reduction in nitric oxide. METHODS: Rats were fed a K+-deficient diet (0.01% K+) alone, or with either losartan or l-arginine (L-Arg) in drinking water. Control rats were fed with a normal K+ diet (0.36% K+). At the end of 10 weeks, kidneys were excised and renal injury was evaluated. RESULTS: Serum K+ was similarly depressed in all three groups receiving the K+-deficient diet. Rats on the K+-deficient diet alone developed renal hypertrophy and tubulointerstitial fibrosis with an increase in tubular osteopontin expression, macrophage infiltration and type III collagen deposition. Administration of losartan significantly reduced renal hypertrophy and prevented tubulointerstitial injury in the cortex, although some medullary injury occurred. In contrast, administration of L-Arg did not attenuate tubulointerstitial injury in the cortex, despite a complete recovery of urinary nitrate excretion. Mild but significant improvement of tubular osteopontin expression and macrophage infiltration were observed in the medulla of L-Arg-treated hypokalemic rats. CONCLUSIONS: These results indicate that hypokalemic renal injury is mediated, at least in part, by Ang II via the Ang II type 1 receptor, with a lesser contribution mediated by a reduction in nitric oxide. Losartan may be beneficial in preventing hypokalemic tubulointerstitial injury.     

Rupture of previously documented asymptomatic unruptured aneurysms--aneurysm size: risk factor for aneurysm rupture

The natural history of asymptomatic unruptured aneurysms is not clear. We conducted a follow up study of 100 patients (since 1993) with 122 asymptomatic unruptured aneurysms that had not been operated on. We report five patients with previously documented asymptomatic unruptured aneurysms smaller than 10 mm in diameter that subsequently ruptured. Among the 100 patients, five had suffered subarachnoid hemorrhage (SAH) due to rupturing of an aneurysm. Of the 5 cases, 1 was male and 4 were female, with ages ranging from 59-73 years (mean age, 68 years). The aneurysms were on the MCA in 3, on the BA-SCA in 1, on the IC-PC in 1. The maximal diameter of the aneurysms at diagnosis ranged from 4.5 to 8 mm. The period from discovery to SAH was from 4 to 69 months and the cumulative rate of rupture of the aneurysms was 1.5 percent per year. Four of the 5 cases increased in size after the rupture. In our series, 2 of the 5 cases showed enlargement and the development of an aneurysmal bleb in the follow up MRA and 3D-CTA. The present study demonstrates that five asymptomatic unruptured aneurysms less than 10 mm in diameter subsequently ruptured. We ought to seriously consider the assertion published in the New England Journal of Medicine (Dec. 10, 1998), that unruptured aneurysms less than 10 mm in diameter have a very low probability of subsequent rupture.     

Endothelial nitric oxide synthase expression in ischemia-reperfusion injury after living related-donor renal transplantation

Ischemia-reperfusion injury during renal transplantation has been linked to early graft dysfunction and late graft failure. Nitric oxide (NO), produced by NO synthase (NOS), participates in the recovery from ischemia. We correlated the intensity of graft immunoreactivity for the endothelial NOS isoform (eNOS) during early reperfusion with graft function in 25 children receiving grafts from related donors. Renal allograft biopsy specimens were obtained before transplantation, 1 h after renal artery reperfusion, and 1 year after transplantation. Immunohistochemical staining for eNOS occurred mainly within the endothelium of glomerular capillaries and peritubular capillaries as well as in tubule cells. The mean intensity score for eNOS staining (0-9) was 3.0+/-1.4 before transplantation, 4.5+/-1.9 at 1 h, and 3.3+/-1.9 at 1 year (baseline vs 1 h, P<0.05). Creatinine clearance (ml/min) in patients with a 1-h eNOS score of below 5 and of at least 5, respectively, was 77.1+/-28.4 vs 104.3+/-25.3 at 1 month, 78.7+/-33.4 vs 105.2+/-24.4 at 3 months, 64.7+/-30.1 vs 100.1+/-25.3 at 1 year, 58.2+/-31.3 vs 84.7+/-18.8 at 3 years, and 71.2+/-19.7 vs 78.3+/-23.1 at 5 years ( P<0.05 for 1 month, 1 year, and 3 years). We concluded that elevated eNOS expression after reperfusion in living related-donor renal transplantation enhances the recovery from renal ischemia and, consequently, reduces late graft deterioration.     

Ability of bivariate cytokeratin and deoxyribonucleic acid flow cytometry to determine the biologic aggressiveness of resectable non-small cell lung cancer

OBJECTIVE: The purpose of this study was to clarify the significance of bivariate cytokeratin and DNA flow cytometry for analysis of the biologic aggressiveness of resectable non-small cell lung cancer. METHODS: In 92 patients who underwent curative operations, the DNA ploidy status and S-phase fractions of the cancer cell populations inside the tumors were analyzed by a cytokeratin gating technique with paraffin-embedded specimens and were correlated with the surgical results. RESULTS: Ninety tumors yielded assessable DNA histograms. DNA diploidy was detected in 25 tumors with a mean S-phase fraction of 14.3% +/- 4.7%, and DNA aneuploidy was detected in 65 tumors with a mean S-phase fraction of 15.1% +/- 7.1%. The 5-year overall and recurrence-free survivals were 73.3% and 70.3%, respectively. Multivariate analysis showed that only TNM staging was a prognostic factor after surgery. There was a negative correlation between the logarithms of S-phase fraction and the disease-free interval for 22 patients with proven recurrence (P =.006). The tumors with high S-phase fractions recurred more rapidly than did those with low S-phase fractions. CONCLUSION: In a bivariate analysis of cytokeratin and DNA flow cytometry in resectable non-small cell lung cancer, the S-phase fraction appeared to be correlated with the disease-free interval. However, DNA ploidy and S-phase fraction were not predictive of either recurrence or survival after operation. Thus DNA flow cytometry may be of limited use for the analysis of the biologic aggressiveness of lung cancer.     

An evaluation of quality of life in patients who underwent orthotopic bladder replacement after cystectomy: comparison of ileal neobladder versus colon neobladder

OBJECTIVE: The objective of this study was to determine whether the quality of life (QOL) in patients who underwent orthotopic bladder replacement after radical cystectomy was affected by the intestinal segment used for the creation of a neobladder. MATERIALS AND METHODS: A total of 52 patients who underwent radical cystectomy for bladder cancer were included in this study; i.e., 24 patients with an ileal neobladder and 28 patients with a sigmoid neobladder. QOL was evaluated using the SF-36 health-related QOL survey and a questionnaire designed to evaluate the continent status. RESULTS: The mean follow-up periods for patients with an ileal and a sigmoid neobladder was 40.2 and 43.1 months, respectively. The SF-36 survey revealed that patients with colon neobladder had a significantly higher score for role-emotional functioning than those with ileal neobladder, while there was no significant difference in the remaining seven scores between patients with ileal and colon neobladders; however, general health and social functioning in patients with both types of neobladder appeared to be significantly lower than those in the general population in the United States. The results of the questionnaire analyzing the continent status were also similar between these two groups, including the desire to urinate, the incidence of both day- and nighttime urinary leakage, the frequency of pad exchange, and the concern of urine odor. CONCLUSIONS: Six of the eight scales concerning health-related QOL were favorable with both patients with ileal and colon neobladders, and the health-related QOL in orthotopic neobladder patients except for role-emotional functioning was not affected by the segment of the intestine used for neobladder construction. Moreover, no significant differences were observed in the QOL associated with continent status between these two groups. Therefore, patients with both types of orthotopic neobladder were generally satisfied with their health-related as well as disease-specific QOL.     

A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency

A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted. A second renal biopsy 6 months later confirmed the initial diagnosis of dense deposit disease (DDD) based on electron-dense deposits in the GBM. C3 nephritic factor (C3NeF) and a deficiency of complement factor H (CFH) were not evident. A nephritis-associated plasmin receptor (NAPlr), nephritogenic group A streptococcal antigen, and the plasmin activity by in situ zymography were been in both the first and second biopsy specimens. The patient received combined immunomodulatory therapy with prednisolone and mizoribine, and the urinary protein decreased to a mild level at 27 months after disease onset. These findings suggest that persistent glomerular NAPlr deposition may be associated with the pathogenesis of DDD in some patients without the involvement of C3NeF or CFH mutation and that DDD patients of this type may respond to immunomodulatory treatment.     

Sentinel Lymph Node Detection in Breast Cancer Patients by Real‐Time Virtual Sonography Constructed With Three‐Dimensional Computed Tomography‐Lymphography

Abstract: Ultrasonography (US) is one tool for preoperative diagnosis of lymph node metastases in breast cancer. However, US cannot detect true sentinel lymph nodes (SLNs). We identified SLNs in 60 clinically node‐negative breast cancer patients using a real‐time virtual sonography (RVS) system to display in real time a virtual multi‐planar reconstruction obtained from computed tomography (CT) volume data corresponding to the same cross‐sectional image from US. CT volume data were obtained from our original three‐dimensional CT lymphography (3DCT‐LG), which accurately detects SLNs in breast cancer. SLN metastases were assessed by shape and visibility of the hilum. All patients underwent SLN biopsy and SLN metastases were examined pathologically. In all 60 patients, we were able to detect the same SLNs visualized by 3DCT‐LG. Suspicious SLN metastases were identified in seven of the 60 patients, and four of seven patients were pathologically positive. Positive predictive value was 57%. The remaining 53 patients displayed non‐suspect SLNs in which absence of metastasis from the SLN was confirmed histologically. Overall accuracy was 95%. This is a first attempt at preoperatively identifying SLNs using US guided by the RVS system in breast cancer patients. Although evaluation of SLN metastases was unsatisfactory, this method may be useful for preoperative fine‐needle aspiration cytology for diagnosis of SLN metastases.