BACKGROUND

Duplex ultrasound scanning is currently the best available non-invasive method for vein graft surveillance. However, it is expensive and its results are highly operator dependent. The aim of the present study is to compare, another non-invasive method of graft surveillance, the transfer function index (TFI), with duplex ultrasound scanning in identifying significant stenoses in infrainguinal saphenous vein bypass grafts.

METHODS

Initially a retrospective pilot study was carried out between 1 January and 30 June 2002. Patients were identified from the vascular surgical operation database. The ultrasound report and TFI result of each patient were reviewed. Then a prospective comparative study was carried out between 1 July and 31 December 2002. Duplex ultrasound and TFI studies were undertaken at the 3 month interval. Comparisons were made between the accuracy and predictive value of ultrasound versus TFI in assessing significant graft stenosis.

RESULTS

In the present retrospective study TFI measurement was significantly lower in the at-risk grafts than in the normal grafts (P = 0.001). In the prospective group TFI was again found to be significantly lower in the at-risk group (mean TFI 0.86) than in the normal group (mean TFI 1.064, P = 0.001). The sensitivity and specificity of the TFI were 92% and 97%, respectively. The accuracy of TFI was calculated to be 98%.

CONCLUSIONS

TFI is an accurate non-invasive method of vascular graft surveillance. TFI can be carried out in the vascular clinic and is quick and inexpensive. Normally TFI could replace duplex ultrasound surveillance, with ultrasound being reserved for those with an abnormal TFI.

Mammalian neocortical development is regulated by neural patterning mechanisms, with distinct sensory and motor areas arising through the process of arealization. This development occurs alongside developing central or peripheral sensory systems. Specifically, the parcellation of neocortex into specific areas of distinct cytoarchitecture, connectivity and function during development is reliant upon both cortically intrinsic mechanisms, such as gene expression, and extrinsic processes, such as input from the sensory receptors. This developmental program shifts from patterning to maintenance as the animal ages and is believed to be active throughout life, where the brain's organization is stable yet plastic. In this study, we characterize the long-term effects of early removal of visual input via bilateral enucleation at birth. To understand the long-term effects of early blindness we conducted anatomical and molecular assays 18 months after enucleation, near the end of lifespan in the mouse. Bilateral enucleation early in life leads to long-term, stable size reductions of the thalamic lateral geniculate nucleus (LGN) and the primary visual cortex (V1) alongside a increase in individual whisker barrel size. Neocortical gene expression in the aging brain has not been previously identified; we document cortical expression of multiple regionalization genes. Expression patterns of Ephrin A5, COUP-TFI, and RZRβ and patterns of intraneocortical connectivity (INC) are altered in the neocortices of aging blind mice. Sensory inputs from different modalities during development likely play a major role in the development of cortical areal and thalamic nuclear boundaries. We suggest that early patterning by prenatal retinal activity combined with persistent gene expression within the thalamus and cortex is sufficient to establish and preserve a small but present LGN and V1 into late adulthood.

The aim of the study was to determine the internal consistency, test-retest reliability and measurement error of the Animated Activity Questionnaire (AAQ) for assessing activity limitations in hip and knee osteoarthritis (HKOA) patients.

A total of 1,177 patients, from six countries (the Netherlands, UK, France, Denmark, Italy and Spain), completed the AAQ, a questionnaire consisting of videos displaying 17 activities with 3-5 levels of performance, from which patients choose the video that best matches their own performance. Unidimensionality was assessed by means of confirmatory factor analysis (CFA), using the following fit indices: the Tucker-Lewis index (TFI) >0.95, comparative fit index (CFI) >0.95, and root mean square error of approximation (RMSEA) <0.06. Cronbach's alpha was computed. In 238 patients who completed the AAQ twice, the intra-class correlation coefficient (ICC) was calculated for test-retest reliability. The standard error of measurement (SEM) and the smallest detectable change (SDC) were calculated as parameters of measurement error.

The fit indices for unidimensionality were CFI 0.957, TLI 0.950, and RMSEA 0.144. Cronbach's alpha was 0.95. ICC for test-retest reliability was 0.93 (95% confidence interval 0.91 to 0.95), ranging from 0.85 to 0.98 across countries. SEM and SDC were 4.9 and 13.6, respectively, on a scale from 0 to 100, and ranging from 2.7 to 6.7, and from 7.5 to 18.4, respectively, across countries. The AAQ appeared to measure slightly more precisely in patients with knee problems and patients without prosthesis.

The AAQ seemed to be unidimensional, and showed good internal consistency and test-retest reliability. The SDC indicated that changes in scores of at least 14% indicate real improvement in activity limitations.

Our aim was to investigate the gender disparity in the safety and efficacy of transradial percutaneous coronary intervention (PCI; TRI) and transfemoral PCI (TFI) by a meta-analysis. MEDLINE, Embase, and CENTRAL were searched to identify studies on vascular access with sex-specific events available or studies on sex difference with the events reported by vascular access. Fifteen studies involving 3 921 848 participants were included. Transradial PCI significantly reduced the risk of bleeding complications in both sexes (TRI-versus-TFI odds ratio [OR]: 0.37 in females vs 0.47 in males) and major adverse cardiac events (MACE) in females (OR: 0.70, P < .001) but not in males (OR: 0.83, P = .15) compared to TFI. Transradial PCI diminished the sex difference in the incidence of bleeding complications (female-versus-male OR: 1.82 with TRI vs 2.39 with TFI; interaction P = .01) and MACE (female-versus-male OR: 1.21 with TRI vs 1.41 with TFI; interaction P = .003) compared to TFI. Females were associated with higher crossover rate in the TRI subgroup but not in the TFI subgroup (interaction P = .05). In conclusion, TRI may improve the safety and efficacy of outcomes in both sexes and be an effective means to cut down the gender difference in prognosis.

Identifying molecular mechanisms that regulate insulin expression in bone marrow-derived mesenchymal stem cells (bmMSCs) can provide clues on how to stimulate the differentiation of bmMSCs into insulin-producing cells (IPCs), which can be used as a therapeutic approach against type 1 diabetes (T1D). As repression factors may inhibit differentiation, the efficiency of this process is insufficient for cell transplantation. In this study, we used the mouse insulin 2 (Ins2) promoter sequence and performed a DNA affinity precipitation assay combined with liquid chromatography-mass spectrometry to identify the transcription factor, chicken ovalbumin upstream promoter transcriptional factor I (COUP-TFI). Functionally, bmMSCs were reprogrammed into IPCs via COUP-TFI suppression and MafA overexpression. The differentiated cells expressed higher levels of genes specific for islet endocrine cells, and they released C-peptide and insulin in response to glucose stimulation. Transplantation of IPCs into streptozotocin-induced diabetic mice caused a reduction in hyperglycemia. Mechanistically, COUP-TFI bound to the DR1 (direct repeats with 1 spacer) element in the Ins2 promoter, thereby negatively regulating promoter activity. Taken together, the data provide a novel mechanism by which COUP-TFI acts as a negative regulator in the Ins2 promoter. The differentiation of bmMSCs into IPCs could be improved by knockdown of COUP-TFI, which may provide a novel stem cell-based therapy for T1D.

Pedicle screws for spinal fixation risk neural damage because of the proximity between screw and nerve root. We assessed whether spinal somatosensory evoked potential (SSEP) could selectively detect pedicle-screw-related acute isolated nerve injury. Because pedicle screws are too large for a rat's spine, we inserted a K-wire close to the pedicle in 32 rats, intending not to injure the nerve root in eight (controls), and to injure the L4 or L5 root in 24. We used sciatic-nerve-elicited SSEP pre- and postinsertion. Radiologic, histologic, and postmortem observations confirmed the level and degree of root injury. Sciatic (SFI), tibial (TFI), and peroneal function indices (PFI) were calculated and correlated with changes in potential. Although not specific for injuries to different roots, amplitude reduction immediately postinsertion was significant in the experimental groups. Animals with the offending wire left in place for one hour showed a further non-significant deterioration of amplitude. Electrophysiologic changes correlated with SFI and histologic findings in all groups. SSEP monitoring provided reliable, useful diagnostic and intraoperative information about the functional integrity of single nerve-root injury. These findings are clinically relevant to acute nerve-root injury and pedicle-screw insertion. If a nerve-root irritant remains in place, a considerable neurologic deficit will occur.

Retinoic acid (RA) is critical for embryonic development and cellular differentiation. Previous work in our laboratory has shown that blocking the RA-dependent increase in pre-β cell leukemia transcription factors (PBX) mRNA and protein levels in P19 cells prevents endodermal and neuronal differentiation. Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1) and steroidogenic factor (SF-1) were found by microarray analysis to be regulated by PBX in P19 cells. To determine the roles of DAX-1 and SF-1 during RA-dependent differentiation, P19 cells that inducibly express either FLAG-DAX-1 or FLAG-SF-1 were prepared. Unexpectedly, overexpression of DAX-1 had no effect on the RA-induced differentiation of P19 cells to either endodermal or neuronal cells. However, SF-1 overexpression prevented the RA-dependent loss of OCT-4, DAX-1 and the increase in COUP-TFI, COUP-TFII, and ETS-1 mRNA levels during the commitment stages of both endodermal and neuronal differentiation. Surprisingly, continued expression of SF-1 for 7 days caused the RA-independent loss of OCT-4 protein and RA-dependent loss of SSEA-1 expression. Despite the loss of well-characterized pluripotency markers, these cells did not terminally differentiate into either endodermal or neuronal cells. Instead, the cells gained the expression of many steroidogenic enzymes with a pattern consistent with adrenal cells. Finally, we found evidence for a feedback loop in which PBX reduces SF-1 mRNA levels while continued SF-1 expression blocks the RA-dependent increase in PBX levels. Taken together, these data demonstrate that SF-1 plays a dynamic role during the differentiation of P19 cells and potentially during early embryogenesis.

The primary aim of this cross-sectional survey was to assess the total fluid intake (TFI; sum of drinking water and all other fluids) and the intake of water and all other types of beverages in a sample of pregnant and breastfeeding women representative of Java-Island, Indonesia. Therefore, 299 pregnant and 296 breastfeeding women completed a 7-day fluid-specific record. A secondary aim was to estimate the total water intake (TWI; sum of water from fluids and food moisture), and one 24-h recall was performed to determine water intake from food moisture. The median TFI of pregnant and breastfeeding women were 2,250 (1,800-2,800) and 2,360 (1,954-2,968) mL/day, respectively. The largest contributor to TFI was water (72 and 77% for pregnant/breastfeeding women, respectively). Pregnant women to the extent of 42% and 54% of breastfeeding women did not reach the adequate intake (AI) of water from fluids. In pregnant and breastfeeding women, the median water intake from foods was 592 and 613 mL/day, representing 21 and 20% of TWI. Concluding that a high proportion of the pregnant and breastfeeding subjects did not reach the AI of water from fluid, it seems important to put in place actions such as providing education materials and ensuring access to safe water. Moreover, future surveys should dedicate attention to the assessment of fluid intake and hydration status among pregnant and breastfeeding women in other countries.

Telomeres shorten with physiological aging but undergo substantial restoration during cancer immortalization. Increasingly, cancer studies utilize the archive of formalin-fixed, paraffin-embedded (FFPE) tissues in diagnostic pathology departments. Conceptually, such studies would be confounded by physiological telomere attrition and loss of DNA integrity from prolonged tissue storage. Our study aimed to investigate these two confounding factors. 145 FFPE tissues of surgically-resected, non-diseased appendixes were retrieved from our pathology archive, from years 2008 to 2014. Cases from 2013 to 2014 were categorized by patient chronological age (0-20 years, 21-40 years, 41-60 years,>> 60 years). Telomere lengths of age categories were depicted by telomere/chromosome 2 centromere intensity ratio (TCR) revealed by quantitative fluorescence in situ hybridization. Material from individuals aged 0-20 years from years 2013/2014, 2011/2012, 2009/2010, and 2008 were compared for storage effect. Telomere integrity was assessed by telomere fluorescence intensity (TFI). Epithelial TCRs (mean ± SD) for the respective age groups were 4.84 ± 2.08, 3.64 ± 1.21, 2.03 ± 0.37, and 1.93 ± 0.45, whereas corresponding stromal TCRs were 5.16 ± 2.55, 3.84 ± 1.36, 2.49 ± 1.20, and 2.93 ± 1.24. A trend of inverse correlation with age in both epithelial and stromal tissues is supported by r = -0.69, p < 0.001 and r = -0.42, p < 0.001 respectively. Epithelial TFIs (mean ± SD) of years 2013/2014, 2011/2012, 2009/2010 and 2008 were 852.60 ± 432.46, 353.04 ± 127.12, 209.24 ± 55.57 and 429.22 ± 188.75 respectively. Generally, TFIs reduced with storage duration (r = -0.42, p < 0.001). Our findings agree that age-related telomere attrition occurs in normal somatic tissues, and suggest that an age-based reference can be established for telomere studies on FFPE tissues. We also showed that FFPE tissues archived beyond 2 years are suboptimal for telomere analysis.

CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3',4'-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the -121/-106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3',4'-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3',4'-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1 expression.

Transcription factors are trans-acting proteins that interact with specific nucleotide sequences known as transcription factor binding site (TFBS), and these interactions are implicated in regulation of the gene expression. Regulation of transcriptional activation of a gene often involves multiple interactions of transcription factors with various sequence elements. Identification of these sequence elements is the first step in understanding the underlying molecular mechanism(s) that regulate the gene expression. For in silico identification of these sequence elements, we have developed an online computational tool named transcription factor information system (TFIS) for detecting TFBS for the first time using a collection of JAVA programs and is mainly based on TFBS detection using position weight matrix (PWM). The database used for obtaining position frequency matrices (PFM) is JASPAR and HOCOMOCO, which is an open-access database of transcription factor binding profiles. Pseudo-counts are used while converting PFM to PWM, and TFBS detection is carried out on the basis of percent score taken as threshold value. TFIS is equipped with advanced features such as direct sequence retrieving from NCBI database using gene identification number and accession number, detecting binding site for common TF in a batch of gene sequences, and TFBS detection after generating PWM from known raw binding sequences in addition to general detection methods. TFIS can detect the presence of potential TFBSs in both the directions at the same time. This feature increases its efficiency. And the results for this dual detection are presented in different colors specific to the orientation of the binding site. Results obtained by the TFIS are more detailed and specific to the detected TFs as integration of more informative links from various related web servers are added in the result pages like Gene Ontology, PAZAR database and Transcription Factor Encyclopedia in addition to NCBI and UniProt. Common TFs like SP1, AP1 and NF-KB of the Amyloid beta precursor gene is easily detected using TFIS along with multiple binding sites. In another scenario of embryonic developmental process, TFs of the FOX family (FOXL1 and FOXC1) were also identified. TFIS is platform-independent which is publicly available along with its support and documentation at http://tfistool.appspot.com and http://www.bioinfoplus.com/tfis/ . TFIS is licensed under the GNU General Public License, version 3 (GPL-3.0).

The aim was to characterize the external structure, roughness, and absolute depth profile (ADP) of fluorotic enamel compared with healthy enamel. Eighty extracted human molars were classified into four groups [TFI: 0, control (C); 1-3, mild (MI); 4-5, moderate (MO); 6-9, severe fluorosis (S)] according to the Thylstrup-Fejerskov Index (TFI). All samples were analyzed by atomic force microscopy.The mean values of enamel surface roughness (ESR) in nm were: Group C, 92.6; Group MI, 188.8; Group MO, 246.9; and Group S, 532.2. The mean values of absolute depth profile in nm were: C, 1,065.7; MI, 2,360.7; MO, 2,536.7; and S, 6,146.2. The differences between mean ESR and mean ADP among groups were statistically significant (p < 0.05). This structural study confirms at the nanometer level that there is a positive association between fluorosis severity, ESR, and ADP, and there is an association with the clinical findings of fluorosis measured by TFI as well.

Morphological changes in the testis induced by chemotherapy given according to the Tokyo Children's Cancer Study Group (TCCSG) regimens were studied in children with acute lymphoblastic leukemia (ALL). After informed consent, testicular biopsies were performed 14 times in 12 patients at the end of treatment. The testicular morphology in all cases had sustained a degree of damage. The tubular fertility index (TFI), calculated as the percentage of seminiferous tubules containing identifiable spermatogonia, was from 0 to 42.8% (mean 33.4%) below the normal value. Infiltration of leukemic cells was the most significant factor contributing to the decrease in TFI. There were no differences in the TFI among the TCCSG protocols. Formation of sperm was recognized in six cases, whose ages were 7, 8, 9, 10, 15 and 19 years. In two children, testicular biopsy was performed twice. In the second biopsy, TFI was elevated and sperm formation with the maturation of Leydig cells was observed. A number of other pathological changes were observed: modification of spermatogonia, Sertoli cells and inclusion bodies in spermatogonia, abnormal maturation of Leydig cells, evidence of interstitial fibrosis and thickening of the basement membrane. These results suggest that recent strong chemotherapy for the treatment of ALL might cause severe but not fatal damage to children's testicular tissue. As chemotherapy escalates, more investigation of testicular function will be necessary.

The waste tea fungal biomass produced during black tea fermentation was investigated as a dietary ingredient in poultry feeds. A small portion of fungal mat was used as starter culture for the next cycle while the major portion is discarded as waste. Hence a trial study was carried out to utilize the waste fungal biomass as a supplementary diet for broiler chicks. The fungal biomass contained 179.38 g of crude protein, 120 g crude fibre, 4.82 g phosphorus, 6.56 g of calcium and 8.92 MJ metabolizable energy per kilogram of biomass. The dried tea fungus showed phytase activity of 23 IU/mg protein. The supplementation of tea fungal inclusion (TFI) at 150 g/kg concentration in poultry feed increased the feed consumption, body weight, performance efficiency factor (PEF) and the carcass characters of test broilers significantly (P=0.01) over the control. The histopathological examination of liver showed no abnormalities and the mortality rate was zero.

Twenty patients with palmoplantar pustulosis (PPP) were treated with topical PUVA, oral etretinate (Re), or combined PUVA and etretinate (Re-PUVA). Re and Re-PUVA treated sites improved and/or cleared more rapidly than PUVA treated sites. Complete clearance was observed in six of ten sites treated with Re-PUVA, two of ten with Re, and one of ten sites with PUVA within 12 weeks. UVA-control sites failed to be cleared within 12 weeks. Remission periods after stopping the treatment were 1.5 +/- 0.5 weeks (n = 2) with Re, 10.5 +/- 11.4 weeks (n = 6) with Re-PUVA, and one year (n = 1) with PUVA. These results overall suggested that Re-PUVA is the most effective treatment for PPP. Tonsillar focal infection (TFI) and dental focal infection (DFI) were found in 6/20 and 17/20 patients, respectively. However, the presence of focal infection (FI), TFI and/or DFI, did not appear to interfere with the therapeutic activities of Re and/or PUVA, because the complete clearance rates and remission periods in FI(+) patients were comparable with those in FI(-) patients.

Hundreds of thousands of cis-regulatory DNA sequences are predicted in vertebrate genomes, but unlike genes themselves, few have been characterized at the functional level or even unambiguously paired with a target gene. Here we serendipitously identified and started investigating the first reported long-range regulatory region for the Nr2f1 (Coup-TFI) transcription factor gene. NR2F1 is temporally and spatially regulated during development and required for patterning and regionalization in the nervous system, including sensory hair cell organization in the auditory epithelium of the cochlea. Analyzing the deaf wanderer (dwnd) spontaneous mouse mutation, we traced back the cause of its associated circling behavior to a 53 kb deletion removing five exons and adjacent intronic regions of the poorly characterized Mctp1 gene. Interestingly, loss of Mctp1 function cannot account for the hearing loss, inner ear dysmorphology and sensory hair cell disorganization observed in dwnd mutants. Instead, we found that the Mctp1dwnd deletion affects the Nr2f1 gene located 1.4 Mb away, downregulating transcription and protein expression in the embryonic cochlea. Remarkably, the Mctp1dwnd allele failed to complement a targeted inactivation allele of Nr2f1, and transheterozygotes or Mctp1dwnd homozygotes exhibit the same morphological defects observed in inner ears of Nr2f1 mutants without sharing their early life lethality. Defects include improper separation of the utricle and saccule in the vestibule not described previously, which can explain the circling behavior that first brought the spontaneous mutation to attention. By contrast, mice homozygous for a targeted inactivation of Mctp1 have normal hearing and inner ear structures. We conclude that the 53 kb Mctp1dwnd deletion encompasses a long-range cis-regulatory region essential for proper Nr2f1 expression in the embryonic inner ear, providing a first opportunity to investigate Nr2f1 function in postnatal inner ears. This work adds to the short list of long-range regulatory regions characterized as essential to drive expression of key developmental control genes.

We report two cases of eruptive tumors of the follicular infundibulum (TFI) with an unusual clinical presentation which has not been described previously in literature. In both cases, the appearance was strikingly similar, consisting of multiple asymptomatic hypopigmented macules on the buttocks of two Black African males, aged 38 and 55 years old. In both cases, the eruption had evolved over several months. The individual lesions were of similar size, approximately 1 cm, with irregular and ill-defined borders. Histopathological examination revealed a superficial and horizontal plate-like proliferation of keratinocytes emanating from the epidermis with multiple slender attachments. Pale keratinocytes were present within the epithelial plates. A Fontana stain showed a loss of melanin pigment from the epithelial plates. Orcein (elastic) stain highlighted an increase of the number of the elastic fibers surrounding the tumor. On the basis of these findings, a diagnosis of eruptive TFI was established for both cases. Among the various presentations of TFI, only the eruptive variant appears to be clinically distinctive, with asymptomatic hypopigmented macules usually located on the face, neck and upper trunk. Eruptive TFI should also be added to the clinical differential diagnosis of multiple hypopigmented macules on the buttocks of Black patients.

The distribution and relative intrafascicular contribution of myelin fibers derived from spinal segments L-4 to L-6 were analyzed in adult rat sciatic nerve and its main branches, using 200-kDa neurofilament subunit immunodetection in previously injured nerve sections in the L-4 or L-5 spinal branch or both. These branches' functional contribution was evaluated 16 days after the injury, using the method of J. Bain, S. Mackinnon, and D. Hunter (1988, Plast. Reconstr. Surg. 83: 129-136). A common topographic intrafascicular distribution was found in 69% of cases, with notable segregation of L-4 and L-5 fibers and a random distribution for L-6 fibers. At sciatic nerve main branch level, L-4 contributes almost entirely to the peroneal nerve, L-5 to the tibial nerve, and L-6 and other branches to the sural nerve. After injury to L-4, a significant reduction in peroneal nerve functional index (PFI) was observed, as was a reduction in print length (PL). Injury to L-5 caused a significant reduction in the sciatic (SFI) and tibial (TFI) functional nerve indices, an increase in PL, and a reduction in the spread between opposite toes (TS). Finally, transection of both L-4 and L-5 was followed by a significant reduction in all functional indices measured, an increase in PL, and a reduction in intermediate toe (ITS) and opposite toe spread (TS). The results indicate a direct relationship between the distribution and contribution of the spinal nerve fibers forming the sciatic nerve and the alteration in functional indices for sciatic, tibial, and peroneal nerves.

A new partial nerve lesion (PNL) model is needed to better simulate traumatic lesions seen clinically that result in both dysfunction and neuropathic pain. We assessed surgical variability and several outcome measures including histology during the acute postoperative period. A surgical lesion was created in the rat tibial nerve by removing a segment, later confirmed by myelinated axon counts. Variability in the model was assessed with four different outcome measures during the first postoperative week (n=24), with additional histological outcomes at 7 days (n=13) and pain testing at 21 days (n=9). At 7 days postoperative, the PNL resulted in a tibial functional index (TFI) of -41.3% distinct from a percent motor deficit (PMD) of -76.3%. However, the respective deficits from 2 to 7 days were similar. Either test could detect outliers, but PMD measurements had a lower coefficient of variation and were easier to perform and analyze. The deleted segment contained 26% of the myelinated axons and resulted in distal degeneration that was either 46% based on axon counts or 54% based on area. Replicated experiments confirmed the PMD, muscle atrophy, and formation of neuropathic pain. In conclusion, our partial lesion histologically progresses twofold during the first postoperative week with profound behavioral deficits involving both motor and sensory loss. These results based on sensitive and correlative outcome measures support the application of this novel model in experimental nerve lesion studies.

To assess the intake of water and all other beverages in children, adolescents and adults.

Three thousand six hundred eleven children (8 ± 2 years), 8,109 adolescents (13 ± 2 years) and 16,276 adults (40 ± 14 years) (47% men) were recruited in 15 cross-sectional surveys (liquid intake across 7 days, Liq.In7 study) and completed a 7-day fluid-specific record to assess total fluid intake (TFI), where TFI was defined as the sum of drinking water and other type of beverages.

The median TFI was 1.2, 1.2 and 1.8 liters/day in children, adolescents and adults respectively, with important differences observed between countries. Only 39% of children, 25% of adolescents and 51% of adults met the European Food Safety Authority adequate intake (AI) recommendations of water from fluids. In the surveys of Spain, France, Belgium, Germany, Turkey, Iran, Indonesia and China, water was the major contributor (47-78%) to TFI. In the adult surveys of UK, Poland, Japan and Argentina, hot beverages were the highest contributor to TFI. The fluid intake of children and adolescents in Mexico, Brazil, Argentina and Uruguay was characterized by a contribution of juices and sweet beverages that was as important as the contribution of water to TFI.

Given that a relatively high proportion of subjects, especially children and adolescents, failed to meet the recommended AI of water from fluids and that water intake was not the highest contributor to TFI in all countries, undertaking actions to increase water intake are warranted.

OBJECTIVE

To investigate the prognosis of patients with Hodgkin's lymphoma (HL) who relapse following a complete remission (CR) achieved by chemotherapy with or without radiotherapy (CT+/-RT), and to identify prognostic factors for freedom from second progression (FF2P).

METHODS

We analyzed the prognostic significance of the initial CT regimen (4 vs. 7-8 drugs), treatment-free interval (TFI), and demographic, clinical, and laboratory factors at the time of relapse and diagnosis, in 113 patients with HL, who relapsed after a CR achieved by CT+/-RT.

RESULTS

Conventional salvage CT+/-RT was administered in 107 patients, while six received RT only. The 5-yr FF2P was 24%, while the 10-yr survival after relapse (O2S) was 39% and was not afffected by the initial CT regimen. Multivariate analysis revealed that extranodal disease at relapse (P<0.001), TFI<6 month (P<0.001),>> or =5 involved sites at diagnosis (P=0.04) and anemia at relapse (P=0.03) were independent predictors of FF2P. 55% of patients had 0 or 1 of these adverse prognostic factors. The 5-yr FF2P of patients with 0, 1 or 2 adverse factors was 58%, 34% and 5% (P<0.0001). The corresponding rates for 10-yr O2S were 68%, 51% and 25%, respectively (P=0.002).

CONCLUSIONS

Our data confirmed the significance of TFI and extranodal relapse and demonstrated a potential role for anemia at relapse and number of involved sites at diagnosis, for the prognosis of patients with HL relapsing after CT+/-RT. The combination of these prognostic factors defines a sizeable subgroup of patients with favorable outcome following conventional salvage therapy.

Tumour of the follicular infundibulum (TFI) is an uncommon, benign lesion of the skin adnexae. Four cases are reported of periocular TFI. In all cases a clinical diagnosis of basal cell carcinoma was made before surgery; however, histopatholog ca examination revealed TFI. This is an epithelial tumour showing differentiation along the lines of the follicular infundibulum. Characteristic features are a shelf-like proliferat on of pale epithelia cells in the upper dermis, attachment to the epidermis and the upper portions of the pilosebaceous units, a dense border of elastic fibres, and palisading of the peripheral cell layer of the tumour plate. This benign tumour has not, to the authors' knowledge, been reported in the ophthalmic literature. It has a non-specific appearance and may be clinically misdiagnosed as naevus sebaceous, xanthoma, seborrhoeic keratosis, or basal cell carcinoma.

The etiology of tumor of the follicular infundibulum (TFI) is unknown. Eruptive forms of TFI are rare. We present the case of a 49-year-old woman with multiple lesions on the arms, shoulders, trunk, buttocks, and legs of more than 3 years' duration. On clinical and histologic examination, a diagnosis of multiple TFI was made. Additionally, the patient presented with other rare remarkable features including severe pruritus, the Köbner phenomenon, and underlying inflammatory cell infiltration of the tumors. These findings strongly suggest that eruptive TFI may represent a kind of cutaneous reaction.

The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial ovarian cancer (REOC). For determination of suPAR, pre-chemotherapeutic blood samples from the patients with REOC were processed into plasma (EDTA) within one working day from venipuncture. The plasma suPAR level is not correlated with performance status (p=0.41), FIGO stage (p=0.09), treatment-free interval (TFI) of 12 months (p=0.26), site of recurrence (peritoneum, p=0.50 or pelvis, p=0.44), age (p=0.43), or serum CA125 (p=0.09). Univariate as well as multivariate analyses cannot demonstrate that high pre-chemotherapeutic levels of plasma suPAR (p=0.22, p=0.80) are associated with shorter survival of REOC patients. Multivariate analysis showed that only TFI of 12 months (p=0.001) and performance score status of 2 (p=0.02) were independent prognostic factors. Our study indicates that pre-chemotherapeutic measurement of plasma suPAR level in REOC patients may not be useful to identify a subgroup of patients with poor prognosis.