Systematic review of the influence of chemotherapy-associated liver injury on outcome after partial hepatectomy for colorectal liver metastases.

BACKGROUND: The impact of chemotherapy-associated liver injury (CALI) on postoperative outcome in patients undergoing partial hepatectomy for colorectal liver metastases (CRLM) remains controversial. The objective of this study was to clarify the effect of CALI (sinusoidal dilatation (SD), steatosis and steatohepatitis) on postoperative morbidity and mortality by investigating a large data set from multiple international centres. METHODS: PubMed and Embase were searched for studies published between 1 January 2004 and 31 December 2013 with keywords 'chemotherapy', 'liver resection', 'outcome' and 'colorectal metastases' to identify potential collaborating centres. Univariable and multivariable analyses were performed using binary logistic regression models, with results presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: A consolidated database comprising 788 patients who underwent hepatectomy for CRLM in eight centres was obtained. In multivariable analyses, severe SD was associated with increased major morbidity (Dindo-Clavien grade III-V; OR 1·73, 95 per cent c.i. 1·02 to 2·95; P = 0·043). Severe steatosis was associated with decreased liver surgery-specific complications (OR 0·52, 95 per cent c.i. 0·27 to 1·00; P = 0·049), whereas steatohepatitis was linked to an increase in these complications (OR 2·08, 1·18 to 3·66; P = 0·012). Subgroup analysis showed that lobular inflammation was the sole component associated with increased overall morbidity (OR 2·22, 1·48 to 3·34; P = 0·001) and liver surgery-specific complications (OR 3·35, 2·11 to 5·32; P < 0·001). Finally, oxaliplatin treatment was linked to severe SD (OR 2·74, 1·67 to 4·49; P < 0·001). CONCLUSION: An increase in postoperative major morbidity and liver surgery-specific complications was observed after partial hepatectomy in patients with severe SD and steatohepatitis. Postoperative liver failure occurred more often in patients with severe SD.

Flk-1 specific kinase inhibitor (SU5416) inhibited the growth of GS-9L glioma in rat brain and prolonged the survival.

BACKGROUND: Accumulating evidences suggest that tumor growth and metastasis depend on angiogenesis. At present, plenty of efforts are made to discover a chemical compound that specifically inhibits tumor angiogenesis either by reducing pro-angiogenic factor or increasing anti-angiogenic factors. OBJECT: SU5416, a novel, synthetic, potential inhibitor of angiogenesis specifically blocks the Flk-1/KDR tyrosine kinase activity. In vivo effect of SU5416 in the treatment of intracranial tumors has not been previously described. METHODS: We transplanted GS-9L cells into the right caudate nucleus of male Fisher 344 rats and administrated SU5416 intraperitoneally (i.p.) to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. Starting on Day 1 or Day 8, forty-two animals were treated with SU5416 at three different doses (e.g. 12.5, 25.0 and 50.0 mg/kg body weight) via i.p. injection every day until the end-point. As a control, seven animals received no treatment and after implant fourteen animals were treated with vehicle (DMSO) only. RESULTS: SU5416 prolonged the survival in the treated groups without any significant systemic adverse effect. Median survival in the treated group started on Day.1 was statistically longer compared to that in the control groups (p<0.01). Histological analysis of the treated tumors showed an increase in necroses and reduced in vascularity compared to the control tumors. Furthermore, the number of apoptotic cells increased in the treated tumors on a TUNEL stain. CONCLUSION: Small molecular compounds, such as SU5416 may be useful therapeutics that specifically inhibits the enzymatic activity of Flk-1 kinase and downstream events of tumor angiogenesis.

Measurement of iris color using computerized image analysis.

PURPOSE: To develop a standardized method for measuring from iris photographs, light and dark segments of areas and densities of iris color. METHODS: Computerized image analysis was used to measure the iris photographs. The reproducibility of this method was studied in 30 normal eyes with three different colored irides, green-brown, blue-grey brown and yellow-brown. Three photographs were taken of each iris with a slit lamp camera at three different exposures at baseline. The photographs were repeated with exposure providing for the best reproducibility at 6.5 +/- 1.7 months as a first follow-up after baseline and 3.6 +/- 0.8 months following the first follow-up visit. At least one measurement was made for each photograph. RESULTS: The mean percent coefficient of variation (standard deviation of triplicate measurements/mean x 100) ranged from 1.0 to 4.1% for area and density measurements. Furthermore, the range of mean percent differences between baseline and follow-up visits ranged from 1.2 to 6.3%. CONCLUSION: We have developed a standardized method which appears suitable for measuring changes over time in iris color.

Percutaneous transluminal coronary angioplasty improves oxygen uptake kinetics during the onset of exercise in patients with coronary artery disease.

STUDY OBJECTIVES: Although percutaneous transluminal coronary angioplasty (PTCA) is known to have beneficial effects on exercise capacity, its effects on the cardiovascular response during the onset of exercise have not been clarified. The present study was undertaken to determine the effects of PTCA on the kinetics of oxygen uptake (VO(2)) during constant-work-rate exercise in patients with coronary artery disease, as well as on their indexes of maximal work capacity. METHODS: Seventeen patients with coronary artery disease who received successful PTCAs performed a 50-W constant-work-rate exercise test for 6 min and a symptom-limited incremental exercise test both before and 4 months after the PTCA procedure. VO(2) was calculated from breath-by-breath analysis of respired gases. The time constant of VO(2) kinetics during the onset of 50-W exercise was determined by fitting a single exponential function to the VO(2) response. RESULTS: In 14 patients without coronary restenosis, the time constant of VO(2) kinetics was significantly shortened from (mean +/- SD) 57.4 +/- 12.6 before PTCA to 48.2 +/- 9.5 s after PTCA (p = 0. 0035), indicating improved kinetics of the VO(2) response. In these subjects, the peak VO(2) obtained during maximal exercise testing also increased from 23.1 +/- 3.5 to 26.5 +/- 3.2 mL/min/kg, respectively (p = 0.0005). However, there was no improvement in these indexes in the patients who had restenosis after undergoing PTCA (n = 3). CONCLUSION: Indexes of cardiopulmonary exercise testing, which reflect an efficiency of oxygen flow to the exercising muscle, can be used as an objective, noninvasive, and cost-effective guide for understanding which patients will not have coronary restenosis following PTCA.

Effects of resistance exercise training on mass, strength, and turnover of bone in growing rats.

To determine the effects of resistance exercise on mass, strength and local turnover of bone, 50 Sprague Dawley rats, 8 weeks of age, were assigned to five groups: a baseline control and two groups of sedentary and exercising rats. The trunk of the rats was kept upright during electrically stimulated jumping exercise for 1 h every other day. In 4 weeks, the trabecular mineralizing surface per bone surface (MS/BS), bone formation rate per bone surface (BFR/BS) and the compression load of the lumbar body increased and the number of osteoclasts decreased, but bone mineral density (BMD) and structure did not increase. In the mid femur, the cross-sectional area, the cortical bone area, the moment of inertia, the periosteal MS/BS, BFR/BS and the bending load increased in the exercise group. In 8 weeks, the increases in BMD, structure and load values were significant in both the lumbar and mid femur. At both 4 and 8 weeks, the MS/BS for the endocortical surface of mid femur were not increased and mineral apposition rate (MAR) remained reduced. These results show that jumping exercise increases the mass and strength of the lumbar vertebrae and mid femur by stimulating bone formation and accelerates cortical drift by both increasing periosteal bone formation and reducing the endocortical MAR.

Evaluation of the circulation in the retina, peripapillary choroid and optic disk in normal-tension glaucoma.

Computerized image analysis, including fluorescein angiography, was used to evaluate the retinal, choroidal and optic disk blood flow in 16 patients with normal-tension glaucoma (NTG) and to correlate this measurement with visual fields, retinal vessel width, optic disk pallor and blood pressure (BP). The angle of the ascending slope of the fluorescein dye curve was measured as an index of blood flow from the densitometric and time curves of the fluorescein angiograms in the optic disk, peripapillary choroid, retinal artery and vein for each quadrant. While the ascending slope as well as the retinal vessel width were most reduced in the inferior and nasal regions, the mean threshold was lowest in the superior and nasal quadrants. There were positive significant correlations between artery width and threshold value, between angles of slopes and pallor. In addition, systolic BP had a negative correlation with pallor, and diastolic BP had a positive one with slope in the choroid. These results indicated the probable association of a decrease in retinal, choroidal and optic disk blood flow in the inferior and nasal quadrants as well as vessel width in the inferior nasal quadrant with visual field loss in the superior quadrant, and also demonstrated an increasing blood flow for enlargement of pallor. A decrease in BP was found to be related to reduced blood flow in choroid and optic disk impairment.

Regional differences in optic disc and retinal circulation.

PURPOSE: To determine regional differences in the circulation of the optic disc, the peripapillary choroid and the retinal vessels using the techniques of computerized image analysis and fluorescein angiography. METHODS: Ten young normal subjects were studied. Fluorescein angiography was performed with a scanning laser ophthalmoscope. The rate of filling of fluorescein or slope was measured in the four quadrants of the optic disc, the peripapillary choroid and the major retinal arteries and veins. A total of 125 points was measured from each image of the fluorescein angiograms for a total of 20 to 30 images. Retinal vessel width was measured using computerized image analysis. RESULTS: Comparison of the rates of filling of fluorescein or slopes showed significant differences from zero among the four quadrants of the optic disc (p= 0.01 to <0.02), of the peripapillary choroid (p=0.01 to <0.05) and among the major retinal arteries (p=0.01 to <0.02) and retinal veins (p=0.02 to <0.05). No significant differences were noted between the quadrants for retinal arterial width with the retinal veins only showing a significant difference between the inferior nasal and inferior temporal vein (p=0.02 to <0.05). CONCLUSION: Evaluation of the circulation of the optic disc, retina, and peripapillary choroid should take into account regional differences among these structures.

Association of ocular pressure and optic disc cup volume with red blood cell sodium-potassium ATPase inhibition.

PURPOSE: To determine if there were significant differences between the number of red blood cell ouabain binding sites in normals and untreated ocular hypertensives plus one open-angle glaucoma patient. METHODS: We measured the binding of (3)H ouabain to erythrocyte membranes of 23 normals, 25 ocular hypertensives and one open-angle glaucoma. We also measured the levels of plasma cortisol and digoxin in these subjects. Characteristics of cupping of the optic disc and thickness of the retinal nerve fiber layer, as well as area of optic disc pallor of these subjects were measured by stereophotogrammetry and by computerized image analysis from single and stereo photographs. RESULTS: The number of (3)H ouabain binding sites was observed to be significantly less in the ocular hypertensives and one glaucoma compared to the normals (p = 0.0009). In multi-variate analyses, to determine what other factors affected this difference, there was a significant negative association with mean intraocular pressure (p = 0.003) (average of both eyes) and total cup volume (average of both eyes) (p = 0.005), diagnosis of ocular hypertension and glaucoma (p = 0.0005) and male gender (p = 0.019). There was a significant positive association with plasma cortisol levels (p = 0.048), and diastolic blood pressure (p = 0.037). CONCLUSIONS: The number of (3)H ouabain binding sites in red blood cells decreases significantly with increasing ocular pressure and increasing cup volume indicating the possible presence of an increased systemic endogenous digoxin-like inhibitor and/or difference in the isozymes of Na(+), K(+)-ATPase which may be associated with increased levels of plasma cortisol in ocular hypertensives and glaucomas.

Lipase-catalyzed degradation of polyesters in organic solvents. A new methodology of polymer recycling using enzyme as catalyst.

Enzymatic hydrolytic degradation of aliphatic polyesters in organic solvents has been examined. The degradation of poly(epsilon-caprolactone) took place using Candida antarctica lipase as catalyst in toluene at 60 degrees C to give oligomers with molecular weight of less than 500. The degradation behavior catalyzed by lipase was quite different than an acid-catalyzed degradation (random bond cleavage of polymer). After the removal of the solvent from the reaction mixture, the residual oligomer was polymerized in the presence of the same catalyst of lipase. These data provide a basic concept that the degradation-polymerization could be controlled by presence or absence of the solvent, providing a new methodology of plastics recycling.

Diversity of response of optic nerve head circulation to timolol maleate in gel-forming solution.

PURPOSE: This randomized, double-masked, placebo-controlled, two-period crossover study was conducted to investigate the effects of 0.5% timolol maleate in gel-forming solution on intraocular pressure (IOP) and blood circulation in the optic nerve head in patients with untreated ocular hypertension. METHODS: The effects of 0.5% timolol in gel-forming solution on IOP and optic nerve head capillary blood speed were studied in 12 patients with untreated ocular hypertension. Optic nerve capillary blood speed was measured using the laser Doppler technique before and at the end of each treatment period. RESULTS: In each patient, IOP decreased after treatment with timolol (mean decrease 16.8% versus placebo). Systemic blood pressure and pulse rate did not differ significantly after treatment with topical timolol from values after placebo. The mean change from baseline in Doppler broadening was 10.6% greater after treatment with timolol than after placebo. There was no significant change in mean Doppler broadening from baseline after treatment with either timolol or placebo. However, optic nerve head capillary blood speed increased in six patients, and was within the range of placebo response in six patients after treatment with timolol. Spearman correlation analysis of the baseline with Doppler broadening measurements after treatment showed a correlation for placebo but not for timolol. The percent change in Doppler broadening after timolol treatment was correlated with iris color. CONCLUSION: These results indicate that administration of timolol for 4 weeks reduces IOP in patients with ocular hypertension and generally does not change the blood circulation in the optic nerve head. Individual patients, however, showed variable changes in optic nerve head circulation after topical administration of timolol. Although the sample size was small, these changes in optic nerve head circulation were correlated with iris color.

[An autopsy case of elderly idiopathic enlargement of the right atrium].

We report an autopsy case of an 88-year-old man with idiopathic enlargement of the right atrium which is considered to be the oldest case reported. The patient was given a diagnosis of atrial fibrillation at the age of 75 years, when he developed congestive heart failure. Bradycardia associated with partial atrial standstill was detected and, the patient underwent implantation of a pacemaker at age 77. An echocardiogram revealed marked enlargement of the right atrium and moderate enlargement of the left atrium. Thus, idiopathic enlargement of the right atrium was diagnosed. He had recurrent congestive heart failure before admission to our hospital because of malnutrition and anemia. Although he was treated with high calorie intravenous infusion and blood transfusion, he died of pneumonia and heart failure. Postmortem examination revealed that the heart weighed 430 g, and there was marked dilatation of the right atrium which had an extremely thin wall. The annular circumference of the tricuspid valve was markedly dilated, 170 mm, resulting in tricuspid regurgitation. The left atrium was moderately dilated and the right and left ventricles were slightly dilated. Histologically, the free wall of the right atrium was totally replaced by fibrous tissue and atrioventricular valves did not reveal any rheumatic changes. These pathological findings were compatible with idiopathic enlargement of the right atrium. There has been no previous case report of idiopathic enlargement of the right atrium in a patient aged 80 years of age or over.

Mitral valve aneurysm as a sequela of infective endocarditis: review of pathologic findings in Japanese cases.

Mitral valve aneurysm is defined as a localized protrusion of the valve with a different radius from that of the remaining portion of the valve. The medical records and pathological findings of seven patients with mitral valve aneurysm [aged 48-69 years (mean 64), 4 males] and the pathological findings of other 29 Japanese cases were reviewed. All seven patients were diagnosed pathologically as infective endocarditis, but two patients had no documentation of clinical symptoms suggestive of infective endocarditis (latent infective endocarditis). The underlying lesion of the heart was aortic valve disease and/or fibrosal degeneration of the mitral valve. Only 29 of 36 Japanese case reports stated a precise description of the valve pathology. Of these 29 cases, 23 were associated with infective endocarditis, two with rheumatic valvular disease with fusion and/or shrinkage of the chordae tendineae, three with mitral valve prolapse or myxomatous degeneration of the mitral valve, and one with aortitis syndrome. Neovascularization was described in eight cases. Neovascularization with thick wall should be considered as post-inflammatory vascularization. This review indicates that patients with latent infective endocarditis and mitral valve aneurysm should be considered as potential candidates for valve surgery.

Intraosseous meningioma with a dural defect.

A 56-year-old female presented with a rare intraosseous meningioma associated with an unusual dural defect caused by invasion of the tumor. The underlying dura mater is normal or thickened in most cases of intraosseous meningiomas. Most intraosseous meningiomas are benign histologically, but they should be extirpated before invasion into the subdural space occurs.

[Ultrasound scattering properties of Albunex microspheres].

In Japan, clinical and basic investigations of Albunex were started from 1989, and was firstly approved by the government as a commercially available contrast agent for the cardiovascular disorders. Although it has recently evacuated from the market, its acoustic properties proven by the many investigators were valuable for preparation of the second generation of contrast agents. Therefore, we summarized our data of the ultrasonic properties of Albunex both in vitro and experimental dog studies using RF signals. In conclusion, Albunex was a extremely sensitive blood flow tracer in evaluating intracardiac blood flow as well as intramyocardial perfusion.

[Review: the overviews of contrast echocardiography in cardiovascular disorders].

The contrast echocardiography used to be applied for the diagnosis of congenital heart diseases, analysis of right side heart hemodynamics, and the evaluation of peripheral blood flow profiles. Recently, myocardial contrast echocardiography is evoked for estimating regional coronary blood flow as a parallel procedure of interventional therapy for ischemic patients. Advanced technology such as harmonic imaging, rf signal processing and digital storage of the data are extremely supportive for the quantitative evaluation of myocardial blood flow. In addition, new contrast agents which enable interpretation of myocardial contrast could be administered by peripheral injection.

Computerized measurement of the three-dimensional distribution of optic disc pallor.

PURPOSE: To describe a method which provides quantitative measurements of the surface area of pallor in each quadrant of the three-dimensional optic cup, using photogrammetric measurements from simultaneous stereophotographs and computerized image analysis. METHODS: Simultaneous stereophotographs of one normal subject and two subjects with primary open angle glaucoma were digitized and analyzed for depth measurements. The boundaries of the optic disc, optic cup and region of pallor were identified. Pallor/disc and pallor/cup ratios were subsequently calculated for the superior, temporal, inferior and nasal walls. RESULTS: A digitized photograph and a Laplacian-filtered image were obtained for each eye to be studied. After processing each stereo pair through a similarity sequential detection-based algorithm, depth measurements are represented as a grey scale image, a contour plot, and a wire mesh, with the boundaries of the optic disc, optic cup and pallor superimposed. Ratios are given of the surface area of pallor to the surface area of the disc and the surface area of pallor to the surface area of the cup, by quadrant. CONCLUSIONS: Determination of surface area of pallor to cup may be useful in detecting early visual field loss in glaucoma and neurological disease.

HTLV-I-infected T cells activate autologous CD4+ T cells susceptible to HTLV-I infection in a costimulatory molecule-dependent fashion.

A vigorous production of human T lymphotropic virus type I (HTLV-I)-infected CD4+ T cells is closely associated with the development of adult T cell leukemia (ATL) and neurological disease. However, the immunological mechanisms leading to generation of the HTLV-I-infected cells are not fully clarified. The modulation of CD80 and CD86 expression on the HTLV-I-infected cells and its physiological role in the interaction of infected CD4+ T cells with uninfected CD4+ T cells was examined. The HTLV-I-infected CD4+ T cell lines established from ATL patients and normal donors by infecting their CD4+ T cells with the virus expressed CD80, CD86, and HLA-DR, and induced a proliferation of autologous and allogenic CD4+ T cells. While the CD4+ T cells stimulated with the autologous HTLV-I-infected cells for 7 days expressed CD80 and CD86 but not HTLV-I gene products, they expressed HTLV-I gag antigen after 4 weeks. The interaction of HTLV-I-infected and -uninfected CD4+ T cells was profoundly suppressed by a combination of CD80 and CD86 monoclonal antibodies. These results suggest that the induction of CD80 and CD86 on HTLV-I-infected CD4+ T cells participates actively in the generation of the virus-infected progenitor cells.