Cytological nuclear atypia classification can predict prognosis in patients with endometrial cancer.

OBJECTIVE: Endometrial cancer is one of the leading causes of malignancy in females. Nuclear findings are important for patients with cancer, and can provide valuable information to treating oncologists. We investigated whether nuclear findings were a useful prognostic factor in patients with endometrial cancer. METHOD: We investigated 71 cases of endometrial carcinoma with paired histology and cytology at Kurume University Hospital. We classified endometrial endometrioid adenocarcinoma (EEC) G1 and G2 as type I carcinomas, and uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC) and EEC G3 as type II carcinomas. For the establishment of the cytological nuclear atypia classification, we examined the following nuclear factors on the cytological smears: mitotic figures, prominent nucleoli, nuclear area and anisonucleosis. RESULTS: There was a significant difference in mitotic figures (P < 0.001) and anisonucleosis (P = 0.026) in cytological smears between type I and type II carcinomas. Based on these findings, we categorized cytological nuclear atypia into three groups, nuclear atypia-1 (57.7%), nuclear atypia-2 (19.7%) and nuclear atypia-3 (22.5%), and this classification system correlated well with prognosis in patients with endometrial cancer (P < 0.001). Furthermore, this classification system was able to extract patients with a good prognosis from those with high-grade carcinomas, such as UPSC+CC+EEC G3, and patients with a poor prognosis from those with EEC G1. CONCLUSIONS: Our system of cytological nuclear atypia classification based on endometrial cytology can predict patient prognosis. Cytological nuclear atypia classification and histological typing may be useful for the treatment and follow-up of patients with endometrial cancer, and should be routinely incorporated into cytological reports.

The clock gene cryptochrome of Bactrocera cucurbitae (Diptera: Tephritidae) in strains with different mating times.

Differences in mating time between populations can give rise to premating reproductive isolation. Tephritid fruit flies exhibit large variation in mating time among intra- or inter-specific populations. We previously cloned the clock gene period from two strains of melon fly, Bactrocera cucurbitae; in one the individuals mate early during the day, whereas in the other the individuals mate later. These strains were originally established by divergent artificial selection for developmental time, 'short' and 'long', with early and late mating times, respectively. The deduced amino acid sequences of PERIOD proteins for these two strains were reported to be identical. Here we cloned another clock gene cryptochrome (cry) from the two strains, and found two stable amino acid substitutions in the strains. In addition, the allele frequency at the two polymorphic sites of cry gene correlated with the circadian locomotor period (tau) across strains, whereas the expression pattern of cry mRNA in the heads of flies taken from the short strain significantly differed from that from the long strain. These findings suggest that variation in the cry gene is related to differences in the circadian behaviour in the two strains, thus implying that the cry gene may have an important role in reproductive isolation.

Can ultrasonographic evaluation of subcutaneous fat predict pressure ulceration?

High-resolution ultrasound may be able to detect pressure ulcers before clinical signs emerge. This retrospective study found that one such early indicator is inflammatory oedema in the subcutaneous fat, which resolves as healing occurs.

Improvement of temporal and dynamic subtraction images on abdominal CT using 3D global image matching and nonlinear image warping techniques.

Accurate registration of the corresponding non-enhanced and arterial-phase CT images is necessary to create temporal and dynamic subtraction images for the enhancement of subtle abnormalities. However, respiratory movement causes misregistration at the periphery of the liver. To reduce these misregistration errors, we developed a temporal and dynamic subtraction technique to enhance small HCC by 3D global matching and nonlinear image warping techniques. The study population consisted of 21 patients with HCC. Using the 3D global matching and nonlinear image warping technique, we registered current and previous arterial-phase CT images or current non-enhanced and arterial-phase CT images obtained in the same position. The temporal subtraction image was obtained by subtracting the previous arterial-phase CT image from the warped current arterial-phase CT image. The dynamic subtraction image was obtained by the subtraction of the current non-enhanced CT image from the warped current arterial-phase CT image. The percentage of fair or superior temporal subtraction images increased from 52.4% to 95.2% using the new technique, while on the dynamic subtraction images, the percentage increased from 66.6% to 95.2%. The new subtraction technique may facilitate the diagnosis of subtle HCC based on the superior ability of these subtraction images to show nodular and/or ring enhancement.

Role of phasic dynamism of p38 mitogen-activated protein kinase activation in ischemic preconditioning of the canine heart.

Although ischemic stress, including ischemic preconditioning (IP), activates p38 mitogen-activated protein kinase (MAPK), the relationship between p38 MAPK activation and the underlying cellular mechanisms of cardioprotection by IP is not verified in vivo. We examined the effects of the selective p38 MAPK inhibition on the cardioprotective effect of IP in the open-chest dogs. The coronary artery was occluded 4 times for 5 minutes, separated by 5 minutes of reperfusion (IP) followed by 90 minutes of occlusion and 6 hours of reperfusion. We infused SB203580 into the coronary artery during IP and 1 hour of reperfusion, during IP alone, and during sustained ischemia in the IP group. p38 MAPK activity markedly increased during IP but did not additionally increase at the onset of ischemia and was even attenuated at 15 minutes of sustained ischemia, and heat-shock protein (HSP) 27 was phosphorylated and translocated from cytosol to myofibril or nucleus without affecting total protein level at the onset of ischemia compared with the control group. SB203580 treatment (1 micromol/L) only during IP blunted the infarct size limitation by IP (37.3+/-6.3% versus 7.4+/-2.1% in the IP group, P:<0.01) and attenuated either phosphorylation or translocation of HSP27 during IP. Although the SB203580 treatment throughout the preischemic and postischemic periods had no significant effect on infarct size (33.3+/-9.4%) in this model, treatment with SB203580 only during ischemia partially mimicked the infarct size limitation by IP (26.8+/-3.5%). Thus, transient p38 MAPK activation during ischemic preconditioning mainly mediates the cardioprotection followed by HSP27 phosphorylation and translocation in vivo in the canine heart.

A computer-aided temporal and dynamic subtraction technique of the liver for detection of small hepatocellular carcinomas on abdominal CT images.

It is often difficult for radiologists to identify small hepatocellular carcinomas (HCCs) due to insufficient contrast enhancement. Therefore, we have developed a new computer-aided temporal and dynamic subtraction technique to enhance small HCCs, after automatically selecting images set at the same anatomical position from the present (non-enhanced and arterial-phase CT images) and previous images. The present study was performed with CT images from 14 subjects. First, we used template-matching based on similarities in liver shape between the present (non-enhanced and arterial-phase CT images) and previous arterial-phase CT images at the same position. Temporal subtraction images were then obtained by subtraction of the previous image from the present image taken at the same position of the liver. Dynamic subtraction images were also obtained by subtraction of non-enhanced CT images from arterial-phase CT images taken at the same position of the liver. Twenty-one of 22 nodules (95.5%) with contrast enhancement were visualized in temporal and dynamic subtraction images. Compared with present arterial-phase CT images, increases of 150% and 140% in nodule-to-liver contrast were observed on dynamic and temporal subtraction images, respectively. These subtraction images may be useful as reference images in the detection of small moderately differentiated HCCs.

[Three-dimensional image of Adamkiewicz artery detected by using multidetector CT: preoperative assessment of thoraco-abdominal aortic aneurysm].

Images were obtained with the following parameter 0.5 sec/r, 1 mm collimation, pitch 3.5, 120 kV, 300 mA. One hundred ml of contrast material containing 350 mg I/ml was injected with a power injector (dual shot type) into an antecubital vein at a rate of 3.5 ml/sec (70 ml). Then remaining 30 ml and same volume of saline were infused at a rate of 1.5 ml/sec simultaneously. Twenty-five seconds after the injection, scan was performed from the level of L2 to T5 vertebrae. Transverse sections were reconstructed with a 1 mm thickness at 0.7 mm intervals. Imaging was done with multiplanar and curved planar reformations. In case of vertebral deformity, however, 3D images were made to depict the Adamkiewicz artery. In 141 patients, 107 (76%) Adamkiewicz arteries from the interverbral foramen to the hairpin-shaped union with the anterior spinal artery were visualized. Seventy-nine arteries of Adamkiewicz (73%) originated from the left side. Our method is useful for depicting Adamkiewicz artery.

Nifedipine-induced coronary vasodilation in ischemic hearts is attributable to bradykinin- and NO-dependent mechanisms in dogs.

BACKGROUND: Dihydropyridine calcium channel blockers protect endothelial cells against ischemia and reperfusion injury, suggesting that nifedipine may increase the in vivo cardiac NO level and thus coronary blood flow (CBF) in ischemic hearts. We tested this hypothesis. METHODS AND RESULTS: In open-chest dogs, coronary perfusion pressure (CPP) was reduced in the left anterior descending coronary artery so that CBF decreased to one third of the control level, and thereafter CPP was maintained constant (103+/-8 to 43+/-3 mm Hg, n=9). We obtained fractional shortening (FS) and lactate extraction ratio (LER) as indices of regional myocardial contraction and metabolism. Both FS (26.4+/-2.1% to 6.7+/-2.0%, n=9, P<0.001) and LER (32+/-6% to -37+/-5%, n=9, P<0.001) showed a decrease when CPP was reduced. After intracoronary infusion of nifedipine (4 microgram. kg(-1). min(-1)), CBF increased from 30+/-1 to 48+/-4 mL. 100 g(-1). min(-1) (P<0.01) without a change of CPP (n=9). Both FS (14.0+/-1.9%, n=9) and LER (-9+/-7%, n=9) also increased (P<0.01). Nifedipine increased the difference in the level of metabolites of NO (nitrate+nitrite; 9+/-3 to 25+/-5 nmol/mL, n=9, P<0.01) and bradykinin (22+/-5 to 58+/-4 pmol/mL, n=9, P<0.01) between coronary venous and arterial blood. L-NAME (an NO synthase inhibitor) or HOE-140 (a bradykinin receptor antagonist) attenuated (P<0.05) the increase in CBF (29+/-3 and 35+/-2 mL. 100 g(-1). min(-1), n=5 each), FS (4.8+/-0.6% and 6.9+/-1.7%, n=5 each), LER (-47+/-8% and -35+/-9%, n=5 each), and nitrate+nitrite (3+/-2 and 8+/-4 nmol/mL, n=5 each) due to nifedipine infusion. CONCLUSIONS: These results indicate that the calcium channel blocker nifedipine mediates coronary vasodilation and improves myocardial ischemia through both bradykinin/NO-dependent and -independent mechanisms.

Cardioprotective effect afforded by transient exposure to phosphodiesterase III inhibitors: the role of protein kinase A and p38 mitogen-activated protein kinase.

BACKGROUND: Phosphodiesterase III inhibitors (PDEIII-Is) improve the hemodynamic status of heart failure via inotropic/vasodilatory effects attributable to the increase in intracellular cAMP level. Direct cardioprotection by PDEIII-Is and its underlying mechanisms, however, have not been identified. We tested the infarct size-limiting effect of PDEIII-Is and the roles of cAMP, protein kinase (PK) A, PKC, and mitogen-activated protein kinase (MAPK) families in open-chest dogs. Methods and Results-- Milrinone, olprinone (PDEIII-Is), or dibutyryl-cAMP (db-cAMP) was injected intravenously 30 minutes before 90-minute ischemia, followed by 6 hours of reperfusion. Olprinone was also examined with an intracoronary cotreatment with a PKA inhibitor (H89), a PKC inhibitor (GF109203X), an extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) throughout the preischemic period. Either PDEIII-Is or db-cAMP caused substantial hemodynamic changes, which returned to control levels in 30 minutes. Collateral flow and percent risk area were identical for all groups. Both PDEIII-Is and db-cAMP increased myocardial p38 MAPK activity during the preischemic period, which was blocked by H89, but not by GF109203X. Both PDEIII-Is and db-cAMP reduced infarct size (19.1+/-4.1%, 17.5+/-3.3%, and 20.3+/-4.8%, respectively, versus 36.1+/-6.2% control, P<0.05 each). Furthermore, the effect of olprinone was blunted by either H89 (35.5+/-6.4%) or SB203580 (32.6+/-5.9%), but not by GF109203X or PD98059. H89, GF109203X, PD98059, or SB203580 alone did not influence infarct size. CONCLUSIONS: Pretreatment with PDEIII-Is has cardioprotective effects via cAMP-, PKA-, and p38 MAPK-dependent but PKC-independent mechanisms in canine hearts.

Detection of patients with sick sinus syndrome by use of low amplitude potentials early in filtered P wave.

OBJECTIVES: This study sought to determine whether patients with sick sinus syndrome could be detected by analyzing the initial portion of the signal-averaged P wave corresponding to the electrical activity of the perinodal atrial myocardial cells. BACKGROUND: In sick sinus syndrome, pathophysiologic abnormalities have been shown not only in the sinus node, but also in the atrial muscle, especially the perinodal portion. METHODS: The study included 41 patients with sick sinus syndrome and 140 age-matched control subjects. Eighteen of 41 patients with sick sinus syndrome had paroxysmal atrial fibrillation. Signal-averaged P wave electrocardiograms (ECGs) were recorded through a bandpass filter of 40 to 300 Hz with a P wave-triggering technique. Signals of the orthogonal bipolar leads were combined into a spatial magnitude. The root mean square voltage for the initial 30 ms (EP30) and the duration of initial low amplitude signals < 4 microV (ED4) of the filtered P wave were measured. The root mean square voltage for the last 20 ms (LP20) and the duration of the filtered P wave were also measured. RESULTS: EP30 was significantly lower and ED4 was significantly longer in patients with sick sinus syndrome than in the control subjects (EP30 [mean +/- SD]: 2.18 +/- 0.90 vs. 3.94 +/- 1.45 microV, p < 0.0001; ED4: 31.7 +/- 14.5 vs. 14.0 +/- 7.4 ms, p < 0.0001), although there was no significant difference in LP20 between patients with sick sinus syndrome without paroxysmal atrial fibrillation and the control subjects. The duration of the filtered P wave was significantly but minimally longer in patients with sick sinus syndrome than in the control subjects (139.8 +/- 18.8 vs. 127.3 +/- 13.6 ms, p < 0.0001). The criteria of EP30 < 3.0 microV and ED4 > 22 ms as atrial early potential gave a sensitivity of 76%, a specificity of 91%, a positive predictive value of 74% and a negative predictive value of 93% for identification of patients with sick sinus syndrome. CONCLUSIONS: These results suggest that the long, low amplitude signals early in the filtered P wave on the signal-averaged ECGs are characteristic of sick sinus syndrome. Thus, the atrial early potential could be a useful marker to identify patients with sick sinus syndrome.

Epstein-Barr virus-activating principle in human semen.

During the screening of natural and physiological products for their Epstein-Barr virus (EBV)-activating potency, we found that a considerable number of human semen specimens obtained from infertility clinics (30 cases) possess a marked capacity to induce EBV early antigen (EA) in non-producer Raji cell system when assayed in combination with n-butyrate. The EBV EA-inducing activity of the semen samples was comparable to that of the most efficient EBV EA inducers, the plant diterpene esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Since many, if not all, of such active agents show overlapping with the tumor promoters in their biological reactions, these findings may provide a new insight for assessing the role of semen in the etiology of certain types of human genital malignancies.

The effects of age on the N200 component of the auditory event-related potentials.

This study was undertaken to determine the effects of development and aging on N200 of event-related potentials from childhood to adulthood. Event-related potentials were recorded from 164 normal subjects ranging in age from 4 to 77 years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed marked developmental changes. During childhood, the N200 latency decreased rapidly with age to the minimum (217 +/- 17.3 ms) at 16 years of age, while it was prolonged gradually with age during adulthood. The latency/age slope in the subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in those from 16 to 77. The N200-P300 interpeak latency remained constant in all age groups and showed no age-related changes. The N200 amplitude decreased as age increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in evaluating the developmental and aging processes in the central nervous system. The results of this study could be used as normative data in clinical practices.

Prediction of the effectiveness of long-term beta blocker treatment for dilated cardiomyopathy by signal averaged electrocardiography.

OBJECTIVE: To determine whether the effectiveness of long-term beta blocker treatment for idiopathic dilated cardiomyopathy can be predicted by signal averaged electrocardiography (ECG). PATIENTS: 31 patients with dilated cardiomyopathy and without bundle branch block were included in a retrospective study and 16 in a prospective study. METHODS: A signal averaged ECG was recorded before beta blocker treatment, and three variables were measured from the vector magnitude: QRS duration, root mean square voltage for the last 40 ms (RMS40), and duration of the terminal low amplitude signals (< 40 microV) (LAS40). In the retrospective study, these variables were compared among good responders (showing > or = 0.10 increase in ejection fraction 12 months after start of beta blocker treatment) and poor responders without such improvement. The validity of the signal averaged ECG criteria for prediction of the response to beta blocker treatment was examined in the prospective study. RESULTS: In the retrospective study, good responders (n = 16) had a shorter QRS duration (mean (SD): 122.9 (11) v 138 (14.4) ms, p < 0.005) and LAS40 (33.1 (8.9) v 42.5 (7.8) ms, p < 0.005), and a higher RMS40 (31.6 (16.3) v 19.0 (10.3) microV, p < 0.02) than poor responders (n = 15). Signal averaged ECG criteria for good response were defined as two or more of the following: QRS duration < 130 ms, RMS40 > 20 microV, LAS40 < 40 ms (sensitivity 81%, specificity 73%). In the prospective study, six of seven patients who met these criteria showed a good response to the beta blocker treatment, while eight of nine who did not showed a poor response (chi 2 = 6.1, p < 0.02). The signal averaged ECG criteria gave a sensitivity of 86% and a specificity of 89% for predicting the effectiveness of beta blocker treatment. CONCLUSIONS: A signal averaged ECG might be useful in predicting the effectiveness of beta blocker treatment for dilated cardiomyopathy.

Image feature analysis and computer-aided diagnosis in digital radiography: automated delineation of posterior ribs in chest images.

In order to facilitate computerized quantitative analysis of digital chest radiographs, an automated method for accurate delineation of posterior ribs in frontal chest images is being developed. This method is based on an analysis of vertical profiles in the lung regions and a statistical analysis of edge gradients and their orientations in small selected regions-of-interest (ROIs). A shift-variant function is fitted to vertical profiles to obtain initial estimates of locations of rib edges. Rib edges are then determined more accurately by analyzing cumulative edge gradients and their orientations in small ROIs that are located adjacent to the initially estimated edges. The present computerized method can achieve a good agreement between the detected and the actual rib structures for posterior ribs in 74% of 50 cases examined. This suggests that automated detection of posterior ribs by a computerized method is feasible, and may be useful for computer-aided diagnostic schemes in the chest.

Image feature analysis and computer-aided diagnosis in digital radiography: automated detection of pneumothorax in chest images.

In order to aid radiologists in the diagnosis of pneumothorax from chest radiographs, an automated method for detection of subtle pneumothorax is being developed. The computerized method is based on the detection of a fine curved-line pattern, which is a unique feature of radiographic findings of pneumothorax. Initially, regions of interest (ROIs) are determined in each upper lung area, where subtle pneumothoraces commonly appear. The pneumothorax pattern is enhanced by the selection of edge gradients within a limited range of orientations. Rib edges included in this edge-enhanced image are removed, based on the locations of posterior ribs that are determined separately. A subtle curved line due to pneumothorax is then detected by means of the Hough transform. The detected pneumothorax pattern is marked on the chest image displayed on a CRT monitor. With the present computer method applied to 50 chest images (28 normals and 22 abnormals with pneumothorax), we were able to detect 77% of pneumothoraces, with 0.44 false-positives per image.

Comparison of imaging properties of a computed radiography system and screen-film systems.

To compare the diagnostic quality of images obtained with a computed radiography (CR) system based on storage phosphor technology with that obtained with conventional screen-film systems, a dual-image recording technique was devised. With this technique, a CR imaging plate is placed behind a screen-film system in a conventional cassette. This makes it possible to obtain two images simultaneously, one from each system, in a clinical examination with the same patient positioning, the same degree of patient motion, the same geometric unsharpness, and no additional exposure. The modulation transfer functions (MTFs) of the CR system with and without the dual-image recording technique were greater at low frequencies, but lower at high frequencies, that the MTFs of the screen-film systems used. The noise Wiener spectra of the CR images at the plane of the imaging plate were greater than those of the screen-film systems, but were comparable to those of the screen-film systems at the plane of the printed film due to the reduction in image size. Clinical chest images obtained with the dual-image recording technique appeared comparable, probably because of the image size reduction and the use of mild unsharp mask processing.

Effects of high-dose antiepileptic drugs on event-related potentials in epileptic children.

N200 and P300 of event-related potentials (ERPs) were recorded from 22 epileptic children receiving high-dose antiepileptic drugs. The patients were undergoing monotherapy with supratherapeutic serum level and were not mentally retarded. P300 latency was prolonged in 5 of 8 patients (62.5%) of the carbamazepine (CBZ) group and in 4 of 7 patients (57.1%) of the phenytoin (PHT) group. Only one child of the PHT group showed abnormality in brain-stem auditory evoked potentials (BAEPs). Abnormality of P300 was more frequent than that of BAEP. In patients of the PHT group who underwent examinations consecutively before and after changing the dose, P300 latency was prolonged rapidly when the PHT level exceeded 30 micrograms/ml. This suggested that the prolongation was dose dependent. In all patients of the valproic acid (VPA) group, P300 latency was normal. Only 2 patients of the PHT group had P300 prolongation simultaneously with clinical signs of intoxication. Others demonstrated changes in P300 without symptoms of side effects.

New tissue substitutes representing cortical bone and adipose tissue in quantitative radiology.

To employ quantitative radiology more accurately, we examined phantom materials for cortical bone and adipose tissue as calibration standards and as experimental phantoms. New tissue substitutes for cortical bone and adipose tissue composed of liquid phantom were verified by computing their attenuation coefficients and observing their chemical properties. We showed that a potassium pyrophosphate (K4P2O7) solution for cortical bone was comparable to a dipotassium hydrogen phosphate (K2HPO4) solution. Also, the use of methyl alcohol for adipose tissue was more suitable than ethyl alcohol as a phantom material because of its physical and chemical properties.

Suppression-burst patterns in intractable epilepsy with focal cortical dysplasia.

We report on a patient with early-onset spasms in series and partial seizures associated with focal cortical dysplasia whose EEGs showed suppression-burst patterns during early infancy. These electroclinical characteristics suggested a diagnosis of Ohtahara syndrome, but the EEG findings were atypical because of the lack of suppression-burst patterns during wakefulness. In addition, the patient did not have severe psychomotor retardation. With high-dose pyridoxal phosphate therapy, seizures were suppressed and suppression-burst patterns disappeared at 2 months of age. Focal motor seizures recurred later and they often evolved into epilepsia partialis continua. Patients with early-onset intractable seizures associated with suppression-burst patterns on EEGs have several different etiologies, and these patients should be categorized according to their etiology in addition to their syndromic diagnosis.

Changes in blood flow of the middle cerebral artery during absence seizures.

Blood flow velocities (BFVs) of the middle cerebral artery were measured by transcranial Doppler blood flowmeter in 2 patients with childhood absence epilepsy; a total of 8 absence seizures were recorded. BFV began to decrease 7-9 sec after the appearance of diffuse bilateral 3 Hz spike-and-wave bursts on electroencephalography, reaching the trough 0-8 sec after the disappearance of spike-and-wave bursts which was followed by BFV recovery with rebound phenomenon. BFV then returned to the pre-ictal value within 1 min after the seizure ended. Pulsatility index increased in accordance with BFV decrease.