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.

Anaerobic metabolism as an indicator of aerobic function during exercise in cardiac patients.

To determine whether patients with heart disease depend more than normal subjects on anaerobic metabolism to perform the same level of exercise, the anaerobic threshold, slope of the increase in carbon dioxide output with respect to oxygen uptake (delta VCO2/delta VO2) and the slope of the increase in oxygen uptake with respect to the increase in work rate (delta VO2/delta WR) both below and above the anaerobic threshold during exercise were evaluated. A total of 106 patients with chronic heart disease and 42 healthy subjects performed a symptom-limited incremental exercise test in a ramp pattern on a cycle ergometer. Peak oxygen uptake was significantly lower in the patients with heart disease than in the normal subjects. The anaerobic threshold, which was 20 +/- 4.6 ml/min per kg in normal subjects, decreased significantly with progressing severity of functional class: 16 +/- 2.4, 14.1 +/- 2.5 and 11.3 +/- 1.5 ml/min per kg, respectively, in patients in class I, class II and class III. The slope of delta VO2/delta WR, which represents the degree of aerobic metabolism, was also decreased both below and above the anaerobic threshold with increasing severity of heart disease. delta VCO2/delta VO2 below the anaerobic threshold was approximately 0.9 (p = NS between normal subjects and patients). However, delta VCO2/delta VO2 above the anaerobic threshold became steeper with increasing severity of heart disease: 1.37 +/- 0.17 in normal subjects versus 1.55 +/- 0.24, 1.67 +/- 0.3 and 1.8 +/- 0.35 respectively, in patients in functional class I, class II and class III.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of plasma atrial natriuretic factor to experimentally induced aortic and mitral regurgitation in dogs.

STUDY OBJECTIVE: The correlations between the plasma concentration of atrial natriuretic factor and right atrial or left atrial pressure were studied in experimentally induced aortic regurgitation and mitral regurgitation in dogs. DESIGN: Aortic regurgitation was created by opening the tip of a basket wire catheter placed at the aortic annulus via the left ventricular wall, and terminated by pulling back the catheter. To create mitral regurgitation a basket catheter was inserted into the mitral annular position via a pulmonary vein. Regurgitation was induced by opening the tip of the catheter, and terminated promptly by closing it. EXPERIMENTAL MATERIAL: Seven beagle dogs were prepared for the aortic regurgitation model and six for the mitral regurgitation model (weights 11.5 to 14.5 kg). MEASUREMENTS AND MAIN RESULTS: The plasma concentration of atrial natriuretic factor was highly correlated with right atrial pressure (r = 0.78, SD = 0.07, n = 7) and left atrial pressure (r = 0.82, SD = 0.05, n = 7) in aortic regurgitation; and with right atrial pressure (r = 0.82, SD = 0.05, n = 6) and left atrial pressure (r = 0.84, SD = 0.05, n = 6) in mitral regurgitation. Further evaluation of the molecular forms of plasma atrial natriuretic factor revealed the alpha form in all 13 dogs and the gamma form in two (one with aortic and the other with mitral regurgitation); no evidence of the beta form was seen. CONCLUSIONS: Atrial natriuretic factor secretion responds rapidly to the circulatory changes caused by valvular incompetence.

Hemodynamic changes by recombinant erythropoietin therapy in hemodialyzed patients.

Recombinant human erythropoietin therapy was given to 15 patients undergoing long-term hemodialysis with normal cardiac function. None of the patients had hypertension before the erythropoietin therapy and had received no antihypertensive agents. Before and after the erythropoietin therapy M-mode and pulsed Doppler echocardiographic studies, measurements of plasma volume by radioiodinated human serum albumin, and measurements of atrial natriuretic factor were carried out. After 6 weeks of erythropoietin therapy, hematocrit increased from 20.0 to 33.0%. Cardiac output, stroke volume, left ventricular diastolic dimensions, and left ventricular wall stress were all significantly decreased. Total peripheral resistance, interventricular septal thickness, and left ventricular posterior wall thickness were significantly increased. In Doppler echocardiographic studies, the mean velocity of aortic ejection flow and left ventricular acceleration time were decreased. The blood volume derived from plasma volume and hematocrit was not changed, whereas plasma atrial natriuretic factor concentration was significantly decreased. These data suggest that recombinant human erythropoietin administration suppressed the hyperdynamic cardiac state that was required to maintain oxygen delivery to the peripheral tissues in severe uremic anemia.

Reproducibility of photogrammetric optic disc cup measurements.

To detect early glaucoma-associated changes in the optic disc cup, the authors analyzed reproducibility of optic disc cup measurements by photogrammetry of three age-matched groups: 10 normal, 10 ocular hypertensive, and 10 glaucomatous subjects. For each eye, three simultaneous stereophotographs were taken on the same day and one measurement was made for each stereophotograph. In order to reduce the effects of refractive error of the eye and photographic magnification, the authors computed cup parameters as relative measurements, ie, a ratio to the optic disc area. The median coefficients of variation for glaucomatous eyes were 4.5% for cup volume/disc area, 6.1% for cup depth/disc area, and 4.7% for cup area/disc area. Coefficients of variation of normal and ocular hypertensive subjects were slightly larger than those of glaucomatous subjects. Coefficients of variation generally were larger for quadrants than for total disc area. These findings suggest that the photogrammetric technique is highly reproducible and sensitive and could be a valuable quantitative technique for the clinical study of glaucoma.

Stereochronometry: quantitative measurement of optic disc cup changes.

The authors have developed an objective, quantitative method for detecting optic disc cup changes that occur with time. Called stereochronometry, this new technique uses a stereoplotter to measure changes recorded in the combination of two single photographs taken of the same optic disc at different times. The reproducibility and sensitivity of stereochronometry were evaluated using a model eye. Stereochronometric measurements were significantly correlated with calibrated changes of depth and width of the cup of the model eye. Standard deviations for five measurements of cup changes without camera shift range from 2 microns to 18 microns, and errors (deviations of the mean of measurements from calibrated cup changes) ranged from -26 microns to +33 microns. Standard deviations and errors in the measurement of cup depth and width were significantly increased when the camera was shifted by 2.5 mm between photographs to simulate possible changes in photographic conditions.

Interference fringe scale for absolute ocular fundus measurement.

Measurements of the human ocular fundus in the three spatial dimensions have not been absolute because measuring techniques have used the optical system of the eye as part of the total ophthalmoscopic system. The ophthalmoscopic magnification due to the total dioptric power of an individual eye can vary substantially from that of the average eye. A new method has been developed to form interference fringes on the fundus so that the fringe spacing can be calculated within a small error by using measured values. The photographed fringes then act as a scale at the fundus with the fringe spacings serving as the graduations, thus allowing accurate absolute measurements of the fundus through the interfering ocular media.

Conduction disturbances related to the site and severity of mitral anular calcification: a 2-dimensional echocardiographic and electrocardiographic correlative study.

To investigate an apparent association of mitral anular calcium (MAC) and electrocardiographic abnormalities, the relation between location of 2-dimensional (2-D) echo-quantified MAC and conduction disturbances was studied in 140 patients with MAC (MAC group) and in 135 age- and sex-matched patients without MAC (control group). The MAC group was subclassified regarding site and severity of calcium in the mitral anulus. The site of MAC was defined as Type I, near the primary conduction system--MAC located in the medial segment and/or extending to the anterior mitral leaflet; and Type II--MAC located at the central and/or lateral segments away from the primary conduction system. The severity of MAC was graded on 2-D echocardiography as mild (localized within 1 segment) and moderate to severe (greater than 1 segment). Seven patients with MAC, and only 1 control subject, had pacemakers in place. Conduction disturbances were present in 44 (31%) of 140 patients with MAC, and in 37 (27%) of 135 control patients (difference not significant). But there were more conduction disturbances in patients with Type I MAC (53%) than in those with Type II MAC (26%) (p less than 0.01). Specifically, complete left bundle branch block and intraventricular conduction delay were more prevalent when MAC was near the conduction system. Conduction disturbances also were more prevalent in patients with Type I MAC than in the control group: intraventricular conduction delay (Type I, 12% versus control, 4%; p less than 0.05) and total conduction disturbances (53 versus 28%; p less than 0.01). These data suggest that moderate to severe degrees of MAC located near the conduction system are associated with conduction disturbances, especially intraventricular conduction delay.

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.

Glaucomalike disks without increased intraocular pressure or visual field loss.

We studied 48 patients who had glaucomalike disks with increased cupping and pallor, superior or inferior extension of cupping and pallor and asymmetry of cupping and pallor between eyes without increased intraocular pressure or visual field loss, and open angles. We compared these patients with a randomly selected group of 48 patients with primary open-angle glaucoma. The mean age of the patients with glaucomalike disks (45.1 +/- 16.1 years) was significantly younger than the group with open-angle glaucoma (63.8 +/- 11.3 years). Of the patients with glaucomalike disks, 11 (23%) had a family history of glaucoma, 75% of 22 eyes with optic disk fluorescein angiograms had abnormal readings, and 59% of 43 eyes with retinal nerve fiber layer defects had abnormal readings. Photogrammetric measurements of the left disk cups were compared in 22 of the patients with glaucomalike disks to 16 matched patients with primary open-angle glaucoma. The only statistically significant difference was that the patients in the glaucoma group showed a larger cup area (surface opening) of the inferior quadrant. Our findings suggest that some glaucomalike disks may be one variant of primary open-angle glaucoma.

Intraocular pressure and the rate of visual field loss in chronic open-angle glaucoma.

We measured the rate of change of visual field threshold values over time (mean follow-up, 44.9 +/- 17.4 months) by trend analysis in 40 eyes of 40 patients with chronic open-angle glaucoma. Twenty-eight eyes had stable visual fields, and two eyes had significant visual field improvement. Ten eyes had significant visual field deterioration and showed a correlation between indices of intraocular pressure (standard error of the mean, P = .02; standard deviation, P = .04; and range, P = .05) and the rate of visual field loss in the superonasal region of the visual field, such that the greater the variation of intraocular pressure the greater the rate of loss. The group losing visual fields had a higher mean visual field threshold value and significantly less optic disk pallor and cupping at the start of the study than the stable visual field group. Thus, a significant rate of visual field loss occurred at an earlier stage of the disease and showed a correlation with intraocular pressure in this stage.

Optic disk cupping and pallor measurements of patients with a disk hemorrhage.

We evaluated whether the rate of occurrence of glaucomatous disk damage in eyes with an optic disk hemorrhage differed from the rate of occurrence in control eyes. We compared 24 patients with a disk hemorrhage to 24 control patients, who had been matched for diagnosis, disk appearance, and visual fields. Cup volume and cup-to-disk area ratio of the optic disk were measured using the stereophotogrammetric technique, and area of pallor was measured using computerized image analysis. We found that diabetes increased the probability that a patient would have a disk hemorrhage, and that a hemorrhage was associated with progression of glaucomatous disk changes in half of the cases during the mean 3.1-year follow-up period. However, the mean rate of glaucomatous disk damage in patients with a hemorrhage was not different from matched control patients. A disk hemorrhage is a sign of later disk damage, but it does not alter the rate of glaucomatous disk progression.

Optic nerve head circulation in untreated ocular hypertension.

AIMS: The laser Doppler technique was used to compare the capillary blood speed measured at localised sites of the optic nerve head in stable, untreated ocular hypertensive patients with that measured in healthy normal subjects. The stereophotogrammetric technique was also used to measure the retinal nerve fibre layer thickness at the disc margin in the eyes of the patients. METHODS: Doppler broadening measurements were made at superior and inferior temporal disc sites in 18 eyes of 10 ocular hypertensive patients and in 12 eyes of seven age and sex-matched normal subjects. RESULTS: On average, Doppler broadening and, hence, capillary blood speed were significantly higher (p = 0.018) in the patients than in the normal subjects. The largest values of Doppler broadening in the patients were measured at sites adjacent to the thinnest retinal nerve fibre layer. Linear regression analysis showed a significant inverse relation (p = 0.0004) between Doppler broadening and nerve fibre layer thickness in left eyes, and a nearly significant relation (p = 0.06) in right eyes. At temporal sites of the optic nerve head there is a compensatory relation between a thinning nerve fibre layer and a locally increasing blood supply to the optic nerve head. CONCLUSION: Together with previous observations of fluorescein filling defects in similar patients, these results indicate that there is spatial heterogeneity of blood flow in the optic nerve head in stable, untreated ocular hypertensive patients.

Retinal nerve fiber layer thickness measurements in ocular hypertensive patients with timolol treatment.

OBJECTIVES: We studied the quantitative effects on retinal nerve fiber layer thickness in a double-masked, prospective clinical trial in which patients were randomized to timolol or placebo groups.

Reversal of optic disc cupping and pallor in patients with ocular hypertension using timolol therapy.

OBJECTIVES: We studied the quantitative effects on optic disc cupping and pallor in a double-masked, prospective clinical trial in which patients were randomized to timolol and placebo groups.

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.

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.

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.

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.

Acute febrile mucocutaneous lymph node syndrome (Kawasaki disease) in an adult.

The patient is a 31-year-old man with a febrile condition accompanied by mucocutaneous changes and swelling of cervical lymph nodes. Clinical features and laboratory data meet the criteria for acute febrile mucocutaneous lymph node syndrome (MCLS). In addition, coronary artery aneurysms and stenotic lesions were observed in the coronary arteriograms. Previously reported cases of MCLS in adults have been extraordinarily rare.