Mutation and Methylation Analysis of the Chromodomain-Helicase-DNA Binding 5 Gene in Ovarian Cancer

Chromodomain, helicase, DNA binding 5 (CHD5) is a member of a subclass of the chromatin remodeling Swi/Snf proteins and has recently been proposed as a tumor suppressor in a diverse range of human cancers. We analyzed all 41 coding exons of CHD5 for somatic mutations in 123 primary ovarian cancers as well as 60 primary breast cancers using high-resolution melt analysis. We also examined methylation of the CHD5 promoter in 48 ovarian cancer samples by methylation-specific single-stranded conformation polymorphism and bisulfite sequencing. In contrast to previous studies, no mutations were identified in the breast cancers, but somatic heterozygous missense mutations were identified in 3 of 123 ovarian cancers. We identified promoter methylation in 3 of 45 samples with normal CHD5 and in 2 of 3 samples with CHD5 mutation, suggesting these tumors may have biallelic inactivation of CHD5. Hemizygous copy number loss at CHD5 occurred in 6 of 85 samples as assessed by single nucleotide polymorphism array. Tumors with CHD5 mutation or methylation were more likely to have mutation of KRAS or BRAF (P = .04). The aggregate frequency of CHD5 haploinsufficiency or inactivation is 16.2% in ovarian cancer. Thus, CHD5 may play a role as a tumor suppressor gene in ovarian cancer; however, it is likely that there is another target of the frequent copy number neutral loss of heterozygosity observed at 1p36.     

18F‐fluorodeoxyglucose positron emission tomography imaging in brain tumours: The Western Australia positron emission tomography/cyclotron service experience

¹⁸F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scans in the first 49 patients referred with either possible brain tumour or brain tumour recurrence were reviewed. FDG‐PET imaging was reported with reference to anatomical imaging. Based on the report the FDG study was classified as either positive or negative for the presence of tumour. Thirty‐eight cases were included in the analysis, 21 having pathological data and 17 with diagnostic clinical follow up. Eleven were excluded, as they had inadequate follow‐up data. Of the 21 cases with pathology, 18 were shown to have tumour. In this group there were five false‐negative scans and two false‐positive PET scans. Seventeen cases were assessed by clinical follow up, nine were considered to have been tumour. There were two false negatives with one false positive. The overall sensitivity, specificity and positive and negative predictive values were 74, 73, 87 and 53% respectively. This is similar to figures previously quoted in published work. Despite relatively limited numbers, the utility of FDG PET imaging in our hands is similar to published reports. With a positive predictive value of 87%, a positive FDG study indicates a high likelihood that there is brain tumour present. A negative study does not exclude the presence of tumour.     

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy

The microscopic distribution of microspheres in human liver following hepatic infusion of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 microm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.     

Response of cutaneous A- and C-fiber nociceptors in the monkey to controlled-force stimuli

The goal of this study was to determine the capacity of primary afferent nociceptive fibers (nociceptors) to encode information about noxious mechanical stimuli in primates. Teased-fiber techniques were used to record from 14 A-fiber nociceptors and 18 C-fiber nociceptors that innervated the hairy skin. Stimulus-response functions were examined with an ascending series of force-controlled stimuli. Stimulus-interaction effects were examined with use of a series of paired stimuli in which the interval between the stimulus pairs was varied systematically. Both A-fiber and C-fiber nociceptors exhibited a slowly adapting response to the stepped force stimuli. The response of the A fibers increased monotonically with increasing force, whereas the response of the C fibers reached a plateau at low force levels. The slope of the stimulus-response function for the A fibers was significantly steeper than that for the C fibers, and the total response was greater. The A fibers also provided more discriminative information regarding stimulus intensity. The C fibers demonstrated a significant fatigue in response when the interstimulus interval between the paired stimuli was 相似文献   

Left ventricular function, cardiac dysrhythmias, atrial activation, and volumes in nondipper hypertensive individuals with left ventricular hypertrophy

BACKGROUND: Arrhythmic patterns and left ventricular geometric adaptations to pressure overload were investigated in 76 patients with untreated borderline-to-moderate sustained essential hypertension studied by 2-dimensional and M-mode echocardiography, 12-lead, Holter, and signal-averaged electrocardiography, and ambulatory blood pressure monitoring. METHODS AND RESULTS: Sixty-two age- and sex-matched normal adults were chosen for data comparison. Hypertrophic hypertensive patients were subdivided into 2 subgroups: 44 patients with nocturnal blood pressure reduction (dippers) and 32 patients without it (nondippers). Common afterload and diastolic function indexes were found to be lower in combined nondipper and dipper groups, but only fractional shortening decreased in nondippers. The number of premature atrial and ventricular contractions per hour was high in dippers and nondippers, with no statistically significant differences between them; atrial and ventricular complex dysrhythmias were similar. Signal-averaged electrocardiography showed a prolonged P-wave duration in dipper and nondipper patients with high atrial volumes but no late ventricular potentials and no difference in quantitative P-wave analysis. Left atrial volumes, P-wave duration, and premature atrial contractions were found to be positively linked to left ventricular hypertrophy. In nondipper patients a linear correlation was observed between left atrial volume and P-wave duration, although supraventricular ectopic activity was connected to left atrial volume enlargement both in dipper and nondipper patients. CONCLUSIONS: These data suggest that the nondipper pattern is not linked to a worse arrhythmogenic substrate; only atrial volume increase may be related to significant supraventricular activity and prolonged atrial activation in nondipper patients, but late ventricular potentials are uncommon in hypertrophic hypertensive patients.     

Incidence of perforation with Goode T-tube

Two groups of patients from the same era were retrospectively studied in Cincinnati and Chicago. In Cincinnati two subgroups were studied. The first group received myringotomy with insertion of a 'T'-shaped ventilating tube (75 patients, 140 ears, 147 insertions). Fifty-eight ears still had the tube in place, 31 had healed after spontaneous extrusion, 17 had healed after removal of the tube, 20 had persistent perforation after the tube was gone, 2 had a cholesteatoma, and 4 patients (7 ears) were lost to follow-up. The second set received myringotomy and insertion of a small grommet (Donaldson tube, 71 patients, 140 ears, 164 insertions) tympanostomy tube. None could be documented to still have the tube in place, 156 ears healed after spontaneous extrusion, none required removal, 3 ears had a persistent perforation after the tube was gone, none had cholesteatoma, and 5 patients (5 ears) were lost to follow-up. The perforation rate for the T-tube is 13.6% and for the grommet is 1.8% (P = 0.0005). In Chicago, 93 patients who received the Goode T style tube (175 ears, 175 insertions) prior to March, 1986 were evaluated. The degree of retraction of the tympanic membrane preoperatively was recorded. No ears still had the tube in place, 145 had healed after spontaneous extrusion or removal of the tube, 30 had persistent perforation 12 months after the tube was gone, 4 had a cholesteatoma, and 8 patients (15 ears) were lost to follow-up. The rate of perforation is 18.8% which is not statistically different from the Cincinnati rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors associated with delay in diagnosis of childhood amblyopia

The prevention of permanent visual impairment from amblyopia is an important goal of pediatric vision screening. Unfortunately, many cases of amblyopia are not diagnosed until the child is too old to benefit maximally from treatment. A review of patient records from the practice of a private pediatric ophthalmologist confirmed that late detection is a frequent occurrence among children with amblyopia who have had good access to health care. A case-control study was then used to identify factors associated with delayed diagnosis, in which children with an adverse outcome (diagnosed at or after 5 years of age) were compared with those with an optimal outcome (diagnosed before 5 years of age). The chart review identified 161 children with amblyopia who participated in this study; 75 had late diagnoses (case patients) and 86 served as control patients. Children with early diagnoses more often had the following characteristics: a positive family history of strabismus, greater degrees of strabismus (when strabismus was present), higher maternal educational level, greater parental suspicion that an eye problem existed, and an increased chance that the parents requested the eye examination that led to the diagnosis. The parents of children with late diagnoses expressed less concern over the seriousness of amblyopia but were more likely to report that their children had suffered adverse consequences of amblyopia. When diagnosed early, amblyopia was more often detected by the child's primary health care provider. Physicians of the children with early diagnoses more often reported compliance with both the American Academy of Pediatrics guidelines for vision screening in infancy and referral for vision problems.(ABSTRACT TRUNCATED AT 250 WORDS)