Apparent improvement in survival for carcinoma of the cervix following the introduction of chemoradiation--a Will Rogers phenomenon.

The improved survival for bulky cervical cancers (> 4cm) reported with combination platinum based chemoradiation (1999) prompted a move away from surgery as these cases frequently received adjuvant radiotherapy and were exposed to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was compared with post-1999 (Group 2) when chemoradiation was the preferred treatment for bulky operable cervical cancer. Significantly more cases were treated surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001). Switching from surgery to radiotherapy improved survival in both treatment categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among surgically treated women with tumors < 4 cm, but significantly more in Group 2 with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1 vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).

Polycystic ovary syndrome and the peripheral blood white cell count.

This retrospective cross-sectional study examined if the white cell count (WCC) is increased in women with polycystic ovary syndrome (PCOS) and if so, is it due to PCOS or to the associated obesity? Body mass index (BMI) was calculated and body composition was measured using bioelectrical impedance analysis. Of the 113 women studied, 36 had PCOS and 77 did not. The mean WCC was higher in the PCOS group compared with the non-PCOS group (8.9 × 10(9)/l vs 7.4 × 10(9)/l p = 0.002). This increase was due to a higher neutrophil count (5.6 × 10(9)/l vs 4.3 × 10(9)/l; p = 0.003). There was a leucocytosis (WCC >11 × 10(9)/l) present in 19% of the PCOS group compared with 1% in the non-PCOS group (p < 0.001). The neutrophil count was abnormally high (>7.7 × 10(9)/l) in 14% of the PCOS group compared with 4% in the non-PCOS group (p < 0.001). On regression analysis, however, the only independent variable which explained both the increased WCC and the increased neutrophil count was PCOS. We found that PCOS is associated with an increased WCC due to increased neutrophils, which supports the evidence that PCOS is associated with low-grade inflammation. The increase appears to be due to the underlying PCOS, and not to the increased adiposity associated with PCOS.

Reference range of liver corrected T1 values in a population at low risk for fatty liver disease-a UK Biobank sub-study, with an appendix of interesting cases.

PURPOSE: Corrected T1 (cT1) value is a novel MRI-based quantitative metric for assessing a composite of liver inflammation and fibrosis. It has been shown to distinguish between non-alcoholic fatty liver disease (NAFL) and non-alcoholic steatohepatitis. However, these studies were conducted in patients at high risk for liver disease. This study establishes the normal reference range of cT1 values for a large UK population, and assesses interactions of age and gender. METHODS: MR data were acquired on a 1.5 T system as part of the UK Biobank Imaging Enhancement study. Measures for Proton Density Fat Fraction and cT1 were calculated from the MRI data using a multiparametric MRI software application. Data that did not meet quality criteria were excluded from further analysis. Inter and intra-reader variability was estimated in a set of data. A cohort at low risk for NAFL was identified by excluding individuals with BMI ≥ 25 kg/m2 and PDFF ≥ 5%. Of the 2816 participants with data of suitable quality, 1037 (37%) were classified as at low risk. RESULTS: The cT1 values in the low-risk population ranged from 573 to 852 ms with a median of 666 ms and interquartile range from 643 to 694 ms. Iron correction of T1 was necessary in 36.5% of this reference population. Age and gender had minimal effect on cT1 values. CONCLUSION: The majority of cT1 values are tightly clustered in a population at low risk for NAFL, suggesting it has the potential to serve as a new quantitative imaging biomarker for studies of liver health and disease.

Utility and cost evaluation of multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease.

BACKGROUND: Validated diagnostic tools that are accurate, cost effective and acceptable to patients are required for disease stratification and monitoring in NAFLD. AIMS: To investigate the performance and cost of multiparametric MRI alongside existing biomarkers in the assessment of NAFLD. METHODS: Adult patients undergoing standard of care liver biopsy for NAFLD were prospectively recruited at two UK liver centres and underwent multiparametric MRI, blood sampling and transient elastography withing 2 weeks of liver biopsy. Non-invasive markers were compared to histology as the gold standard. RESULTS: Data were obtained in 50 patients and 6 healthy volunteers. Corrected T1 (cT1) correlated with NAFLD activity score (ρ = 0.514, P < .001). cT1, enhanced liver fibrosis (ELF) test and liver stiffness differentiated patients with simple steatosis and NASH with AUROC (95% CI) of 0.69 (0.50-0.88), 0.87 (0.77-0.79) and 0.82 (0.70-0.94) respectively and healthy volunteers from patients with AUROC (95% CI) of 0.93 (0.86-1.00), 0.81 (0.69-0.92) and 0.89 (0.77-1.00) respectively. For the risk stratification of NAFLD, multiparametric MRI could save £150,218 per 1000 patients compared to biopsy. Multiparametric MRI did not discriminate between individual histological fibrosis stages in this population (P = .068). CONCLUSIONS: Multiparametric MRI accurately identified patients with steatosis, stratifies those with NASH or simple steatosis and reliably excludes clinically significant liver disease with superior negative predictive value (83.3%) to liver stiffness (42.9%) and ELF (57.1%). For the risk stratification of NAFLD, multiparametric MRI was cost effective and, combined with transient elastography, had the lowest cost per correct diagnosis.

Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation.

Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin-type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1-4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated nonseminoma, i.e. embryonal carcinoma, whereas teratomas expressed them all to some extent but in a disorganized manner. We concluded that simple mucin-type O-glycans and their transferases are developmentally regulated in the human testis, with profound changes associated with neoplasia. The restricted O-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell differentiation.

Cloning and characterization of the genes encoding the ankyrin repeat and SOCS box-containing proteins Asb-1, Asb-2, Asb-3 and Asb-4.

Members of the suppressor of cytokine signalling (SOCS) family of proteins have been shown to inhibit cytokine signalling via direct interactions with JAK kinases or activated cytokine receptors. In addition to their novel amino-terminal regions and SH2 domains that mediate these interactions, the SOCS proteins also contain carboxy-terminal regions of homology called the SOCS box. The SOCS box serves to couple SOCS proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Several other families of proteins also contain SOCS boxes but differ from the SOCS proteins in the type of domain or motif they contain upstream of the SOCS box. We report here the cloning, characterization, mapping and expression analysis of four members of the ankyrin repeat and SOCS box-containing (Asb) protein family.

A comparison of (18)F-dopa PET and inversion recovery MRI in the diagnosis of Parkinson's disease.

OBJECTIVE: To quantify structural changes in the substantia nigra of patients with PD with inversion recovery MRI and to compare these with striatal dopaminergic function measured with (18)F-dopa PET. METHODS: The authors studied 10 patients with PD and eight age-matched control subjects with a combination of MR sequences previously reported to be sensitive to nigral cell loss. Striatal regions of interest were defined on T1-weighted MRI coregistered to (18)F-dopa PET in all subjects. RESULTS: Discriminant function analysis of the quantified MR nigral signal correctly classified 83% of the combined PD patient/control group; three of 10 PD cases were incorrectly classified as "normal" (Wilks' lambda = 0.724, p > 0.05). Discriminant function analysis correctly classified 100% of PD patients and control subjects with (18)F-dopa PET based on mean caudate and putamen K(i) values (Wilks' lambda = 0.065, p < 0.001). Correlations between mean putamen K(i) and rostral and caudal nigral MR signal changes and mean caudate K(i) and caudal nigral MR signal changes were found (r = -0.76, -0.69, -0.80, p < 0.05). CONCLUSION: (18)F-dopa PET is more reliable than inversion recovery MRI in discriminating patients with moderately severe PD from normal subjects. However, the structural changes detected within the substantia nigra of patients with PD found using inversion recovery MRI correlate with measures of striatal dopaminergic function using (18)F-dopa PET.

Reduction of CSF artifacts on FLAIR images by using adiabatic inversion pulses.

The purpose of this study was to investigate the possibility that some artifactual high signals produced in CSF with fluid-attenuated inversion-recovery MR sequences could be due to inhomogeneity in the amplitude of the initial inversion pulse, and that this problem could be reduced or eliminated by the use of adiabatic inversion pulses. Studies with four volunteers showed dependence of high CSF signals in the posterior fossa on radiofrequency pulse amplitudes and that these signals could be eliminated by the use of adiabatic inversion pulses. Two illustrative clinical cases are included.

Reduction of CSF and blood flow artifacts on FLAIR images of the brain with k-space reordered by inversion time at each slice position (KRISP).

BACKGROUND AND PURPOSE: Our purpose was to test a new variant of the fluid-attenuated inversion-recovery (FLAIR) sequence that was designed to reduce CSF and blood flow artifacts by use of a non-slice-selective inversion pulse and k-space reordered by inversion time at each slice position (KRISP). METHODS: With the KRISP FLAIR sequence, the slice order was cycled so that each inversion time (TI) was associated with a region of k-space rather than a particular slice, and the effective inversion time (TI(eff)) was chosen to null the signal from CSF. Scans were obtained with both conventional and KRISP FLAIR sequences. Studies were performed in 20 adult patients with a variety of brain diseases. Images were evaluated for artifacts from patient motion, CSF, and blood flow, and scored on a four-point scale. The conspicuity of the cortex, meninges, ventricular system, brain stem, and cerebellum was evaluated, as was lesion number and conspicuity. RESULTS: The KRISP FLAIR sequence showed more patient motion artifacts but had a pronounced advantage over the conventional sequence in control of CSF artifacts around the foramen of Munro, in the third ventricle, aqueduct, and fourth ventricle, as well as in the basal cisterns and around the brain stem and cerebellum. Blood flow artifacts from the internal carotid, basilar, and vertebral arteries were also much better controlled. Spurious high signal in the sylvian branches of the middle cerebral artery was eliminated. The meninges, cortex, ventricular system, brain stem, and cerebellum were better seen due to improved artifact suppression and an edge enhancement effect. CONCLUSION: The KRISP FLAIR sequence can suppress CSF and blood flow artifacts and improve the conspicuity of the meninges, cortex, brain stem, and cerebellum. Its major disadvantage is its duration, which may be reducible with a fast spin-echo version.

Physiological stability of preterm infants during magnetic resonance imaging.

AIM: This study looked for evidence of physiological disturbance in preterm infants undergoing magnetic resonance imaging (MRI). METHODS: Intensive care was continued, as appropriate, throughout scanning in each infant. The heart rate, oxygen saturation (SaO2), temperature and mean arterial blood pressure (BP) was monitored during MRI in preterm infants, median gestational age at birth 27 (range 23-32) weeks and median postnatal age at initial MRI, 3 days (range 1-42). The acoustic noise level during imaging was also measured. RESULTS: 2087 min of data were obtained from 39 examinations in 23 infants. The median heart rate was 159 and no bradycardia < 100 or tachycardia > 200 bpm occurred. Although 42 episodes of desaturation < 90% were detected only three were < 80, and these occurred in one infant due to endotracheal tube blockage. The median axillary temperature was 36.9 degrees C (range 35.7-37.8) and median BP (n = 6) was 37 mmHg (24-48). The ambient noise level in the MR system during scanning was 67-72 dBA. CONCLUSION: In preterm infants who required intensive care during scanning, MRI could be performed without major physiological instability.

Ion-chromatographic analysis of mixtures of ferrous and ferric iron.

Determinations of the aqueous iron species Fe(II) and Fe(III) are essential for a fully-informed understanding of redox processes involving iron. Most previous methods for speciation of iron have been based on the calorimetric determination of Fe(II) followed by reduction of Fe(III) and analysis for total iron. The indirect determination of Fe(III) and the consumption of relatively large sample volumes have limited the accuracy and utility of such methods. A method based on ion-chromatography has been developed for simultaneous direct determination of Fe(II) and Fe(III). Sample pretreatment involves only conventional filtration and acidification. No interferences with the iron(II) determination were found; in determination of iron(III) the only interference observed was an artifact peak (of unknown origin) that occurred only when iron(II) was present, and had an area that was a function of the iron(II) concentration and could hence be corrected for. Solutions of iron(II) free from iron(III) can be prepared by treatment with a mixture of hydrogen and nitrogen in the presence of palladium black as catalyst, to reduce the iron(III). Photoreduction of iron(III) in acidified samples increases the Fe(II)/Fe(III) ratio; no means of circumventing this effect is known, other than storing the samples in the dark and analysing them as soon as possible.

Sources of acidity in lakes and streams of the United States.

Acidic (acid neutralizing capacity [ANC] < or = 0) surface waters in the United States sampled in the National Surface Water Survey (NSWS) were classified into three groups according to their probable sources of acidity: (1) organic-dominated waters (organic anions > SO4*; (2) watershed sulphate-dominated waters (watershed sulphate sources > deposition sulphate sources); and (3) deposition-dominated waters (anion chemistry dominated by inputs of sulphate and nitrate derived from deposition). The classification approach is highly robust; therefore, it is a useful tool in segregating surface waters into chemical categories. An estimated 75% (881) of acidic lakes and 47% (2190) of acidic streams are dominated by acid anions from deposition and are probably acidic due to acidic deposition. In about a quarter of the acidic lakes and streams, organic acids were the dominant source of acidity. In the remaining 26% of the acidic streams, watershed sources of sulphate, mainly from acid mine drainage, were the dominant source of acidity.

Adiposity induced by adenovirus 5 inoculation.

OBJECTIVE: To investigate the effect of viral inoculation by adenovirus 5 (Ad5) on body composition in a mouse model. DESIGN: Longitudinal monitoring before and after a single injection of virus or saline. SUBJECTS: Two groups of CD1 mice, one group given a single intraperitoneal dose of Ad5 and the control group, saline. MEASUREMENTS: Bodyweights and food intake were recorded before and up to 21 weeks after inoculation. At the end of the study, whole-body 1H magnetic resonance spectroscopy (MRS) and localised in vivo 1H MRS spectroscopy of the liver was performed to assess whole-body adiposity and intrahepatic lipid content, respectively. RESULTS: Ad5-treated animals gained significantly more weight over a period of 21 weeks after inoculation than the controls, 21.8 g (18.8-25.0) and 18.8 g (17.3-19.8) respectively, (P<0.05). The gain in bodyweight in the former animals arises from increased deposition of adipose tissue as measured by whole-body 1H MRS. Adiposity was 6.7% (3.10-11.20%), and 2.40% (0.85-5.65%) for the Ad5-treated and control animals, respectively (P<0.05). No significant difference in intrahepatic lipid content or food intake was observed between the two groups. CONCLUSION: The significantly higher percentage of adipose tissue in the Ad5-treated mice suggest viral infection may play a contributory role to a predisposition to obesity, although its contribution relative to other factors remains to be determined.

Sulfate reduction in freshwater sediments receiving Acid mine drainage.

One arm of Lake Anna, Va., receives acid mine drainage (AMD) from Contrary Creek (SO(4) concentration = 2 to 20 mM, pH = 2.5 to 3.5). Acid-volatile sulfide concentrations, SO(4) reduction rates, and interstitial SO(4) concentrations were measured at various depths in the sediment at four stations in four seasons to assess the effects of the AMD-added SO(4) on bacterial SO(4) reduction. Acid-volatile sulfide concentrations were always an order of magnitude higher at the stations receiving AMD than at a control station in another arm of the lake that received no AMD. Summer SO(4) reduction rates were also an order of magnitude higher at stations that received AMD than at the control station (226 versus 13.5 mmol m day), but winter values were inconclusive, probably due to low sediment temperature (6 degrees C). Profiles of interstitial SO(4) concentrations at the AMD stations showed a rapid decrease with depth (from 1,270 to 6 muM in the top 6 cm) due to rapid SO(4) reduction. Bottom-water SO(4) concentrations in the AMD-receiving arm were highest in winter and lowest in summer. These data support the conclusion that there is a significant enhancement of SO(4) reduction in sediments receiving high SO(4) inputs from AMD.

Elimination of magnetic field foldover artifacts in MR images.

Foldover artifacts arise when the same imaging frequency occurs both at a desired location within a slice and at another location within the sensitive region of the radiofrequency (RF) coil. Foldover artifacts can be caused by nonlinearity in the gradient system and by inhomogeneity in B(0). This study investigates an approach in which an extra RF receiver coil and a postprocessing method are used to identify and remove foldover artifacts.

Diffusion-weighted imaging of the spine using radial k-space trajectories.

INTRODUCTION: Diffusion-weighted MR imaging (DWI) of the spine requires robust imaging methods, that are insensitive to susceptibility effects caused by the transition from bone to soft tissue and motion artifacts due to breathing, swallowing, and cardiac motion. The purpose of this study was to develop a robust imaging method suitable for DWI of the spine. METHODS AND SUBJECTS: A radial k-space spin echo sequence has been implemented, which is self-navigating because each acquisition line passes through the origin of k-space. Influence of cardiac motion and associated flow of cerebrospinal fluid is minimized by cardiac gating with a finger photoplethysmograph. The sequence has been tested on a 1.5T system. Diffusion-weighted images of six normal volunteers were acquired in the sagittal plane with 4 b values between 50 and 500 s mm(-2). Because of the symmetries of the cord, diffusion measurements in the head-foot (HF) or left-right (LR) directions were sufficient to measure the dominant effects of anisotropy. RESULTS: The apparent diffusion coefficients (ADCs) measured, respectively, in the LR and HF directions were (0.699+/-0.050)x10(-3) and (1.805+/-0.086)x10(-3) mm(2) s(-1) in the spinal cord, (1.588+/-0.082)x10(-3) and (1.528+/-0.052)x10(-3) mm(2) s(-1) in the intervertebral disks, and (0.346+/-0.047)x10(-3) and (0.306+/-0.035)x10(-3) mm(2) s(-1) in the vertebrae of the cervicothoracic spine. CONCLUSION: Diffusion-weighted spin echo sequences with radial trajectories in k-space provide a means of achieving robust, high quality diffusion-weighted imaging and measuring ADCs in the spine. The application of the diffusion-weighting gradients in different directions allows diffusion anisotropy to be measured.