Grazing multispecies swards improves ewe and lamb performance.

A two-year (2015 and 2016) grazing study was established to compare ewe and lamb performance when grazed on a perennial ryegrass only sward compared to more diverse sward types. In that study four sward types were investigated: a perennial ryegrass (Lolium perenne) only sward receiving 163 kg nitrogen per hectare per year (N/ha/yr) (PRG); a perennial ryegrass and white clover (Trifolium repens) sward receiving 90 kg N/ha/yr (PRGWC); a six species sward (two grasses (perennial ryegrass and timothy (Phleum pratense)), two legumes (white and red clover (Trifolium pratense)) and two herbs (ribwort plantain (Plantago lanceolata) and chicory (Cichorium intybus)) receiving 90 kg N/ha/yr (6S); and a nine species sward containing cocksfoot (Dactylis glomerata), greater birdsfoot trefoil (Lotus pedunculatus) and yarrow (Achillea millefolium) in addition to the six species listed above, receiving 90 kg N/ha/yr (9S). Each sward type was managed as a separate farmlet and stocked with 30 twin-rearing ewes at a stocking rate of 12.5 ewes/ha under rotational grazing management from turnout post-lambing until housing. Lamb live weight was recorded fortnightly and lambs were drafted for slaughter at 45 kg. Ewe live weight and body condition score (BCS) were recorded on five occasions annually. Lamb faecal egg count (FEC) was recorded fortnightly and lambs were treated with anthelmintics when mean lamb FEC per sward type was above 400 eggs per gram. Ewes grazing the 6S and 9S swards had heavier (P < 0.01) live weights and BCS throughout the study than the ewes grazing the PRG sward. Lambs grazing the 6S sward were heavier than lambs grazing all other sward types of 14 weeks old (P < 0.05). Lambs grazing the PRG sward required more days to reach slaughter weight than lambs grazing all other sward types (P < 0.001). Lambs grazing the 6S and 9S swards required fewer anthelmintic treatments than lambs grazing the PRG or PRGWC swards. In conclusion, grazing multispecies swards improved ewe and lamb performance and reduced the requirement for chemical anthelmintics.

Alpha Air Sample Counting Efficiency Versus Dust Loading: Evaluation of a Large Data Set.

Dust loading on air sample filters is known to cause a loss of efficiency for direct counting of alpha activity on the filters, but the amount of dust loading and the correction factor needed to account for attenuated alpha particles is difficult to assess. In this paper, correction factors are developed by statistical analysis of a large database of air sample results for a uranium and plutonium processing facility at the Savannah River Site. As is typically the case, dust-loading data is not directly available, but sample volume is found to be a reasonable proxy measure; the amount of dust loading is inferred by a combination of the derived correction factors and a Monte Carlo model. The technique compares the distribution of activity ratios [beta/(beta + alpha)] by volume and applies a range of correction factors on the raw alpha count rate. The best-fit results with this method are compared with MCNP modeling of activity uniformly deposited in the dust and analytical laboratory results of digested filters. A linear fit is proposed to evenly-deposited alpha activity collected on filters with dust loading over a range of about 2 mg cm to 1,000 mg cm.

An investigation into the effects of maternal supplementation with excess iodine on the mechanisms and impacts of reduced IgG absorption in the lamb postpartum.

An experiment was conducted to determine: (1) the effect of excess maternal I supplementation on the thyroid hormone status of the ewe and her progeny; (2) potential mechanisms underpinning the failure of passive transfer associated with excess I and (3) the growing lambs' response to natural gastrointestinal infection. Twin-bearing ewes received one of two treatments (n 32/treatment group): basal diet (C) or C plus 26·6 mg of iodine/ewe per d (I), supplied as calcium iodate. Ewes were individually fed from day 119 of gestation to parturition. Progeny of I ewes had lower (P<0·01) serum IgG concentrations from 24 h to 28 d postpartum but higher serum IgG concentrations at day 70 postpartum (P<0·05). I supplementation increased the relative expression of Fc receptor, IgA, IgM high affinity and polymeric Ig receptor in the ileum of the lamb at 24 h postpartum; however, thyroid hormone receptor-ß (THRB) and ß-2-microglobulin (B2M) expression declined (P<0·05). Progeny of I ewes had higher growth rates to weaning (P<0·05) and lower faecal egg count (FEC) for Nematodirus battus (P<0·05) between weeks 6 and 10 postpartum. In conclusion, excess maternal I supplementation negatively affected the thyroid hormone status, serum IgG concentration, ileal morphology and the gene expression of THRB and B2M in the ileum and ras-related protein (RAB) RAB25 and the mucin gene (MUC) MUC1 in the duodenum of the lamb postpartum. These effects were followed by an enhancement of average daily gain and lower N. battus FEC in the pre-weaning period of I-supplemented lambs.

Comparison of energy rationing systems for late gestation ewes: Impacts on ewe and lamb performance.

The objectives of this study were 1) to compare the effects of a ME () or a NE () system for rationing ewes during late gestation on ewe and progeny performance and 2) to investigate incremental increases in NE allocation above 100% of recommendation during late gestation on ewe and progeny performance. Fifty-two twin-bearing ewes ( = 13 per treatment) were rationed to either 100% of recommended ME requirements (100% ME) or 100, 110, or 120% of recommended NE requirements (100% NE, 110% NE, and 120% NE) from d 112 of gestation to parturition. Mean energy intake, measured as ME and NE, from Day 112 of gestation to parturition was higher in all NE treatments compared with 100% ME ewes ( = 0.01). Ewes offered the 3 NE treatments had a higher live weight at parturition compared with 100% ME ewes ( = 0.02), with 100% NE and 120% NE ewes still being heavier than 100% ME ewes at 35 d postpartum ( = 0.02). Increasing NE allowance resulted in a linear decrease in the level of BCS loss prepartum ( = 0.01) and a linear increase in the level of BCS loss postpartum ( = 0.01). There was no difference observed between any of the treatments in total colostrum produced to 18 h postpartum ( = 0.29) or in total colostrum intake to 18 h postpartum ( = 0.27). Increasing maternal NE allowance led to a linear increase in lamb serum IgG concentration at 24 h postpartum ( = 0.03). The estimated milk production of 120% NE ewes tended to be higher than all other treatments at wk 6 of lactation ( = 0.08). Colostral SFA levels from 100% ME ewes was lower than that of all 3 NE treatments ( = 0.01), and unsaturated fatty acid (UFA) levels in colostrum of the 100% ME ewes were lower than those of the 100% NE ewes ( = 0.01). Cumulative levels of milk SFA, UFA, and MUFA did not differ between treatments ( = 0.19). Lamb growth rates during the first 5 wk postpartum were unaffected by treatment ( = 0.18) as were days to slaughter ( = 0.34). It can be concluded that both ME and NE systems used in this study are appropriate for formulating ewe diets during late gestation. Increasing NE allocation above 100% altered the pattern of body reserve mobilization during late gestation and early lactation without observed variations in lamb performance during this time.

Altering ewe nutrition in late gestation: I. The impact on pre- and postpartum ewe performance.

The present study was conducted to examine the effects of offering a single diet rationed to 80% (80% ME), 100% (100% ME), or 120% (120% ME) of recommended ME requirements from d 119 of gestation to lambing, with concurrent changes in other dietary nutrients. The effects on pre- and postpartum ewe performance, including estimated milk yield and milk fatty acid concentrations, were monitored. Sixty twin-bearing ewes were allocated to 1 of 3 dietary treatments ( = 20 per treatment) and individually fed for the final 4 wk of gestation. Metabolizable energy requirements were individually calculated for each ewe and amended according to treatment. Ewes were rationed daily on the basis of their treatment ME allocation, which led to concurrent alterations in other nutrient intakes. Diets were grass silage based and supplemented with concentrates to meet treatment ME allocation on an individual ewe basis. Ewes offered the 80% ME treatment had a lower liveweight ( = 0.04) and BCS ( = 0.03) at 24 h postpartum when compared with ewes offered the 120% ME diet. Although there was no difference in liveweight at either d 40 ( = 0.18) or 98 postpartum ( = 0.20), the difference in BCS persisted until d 40 postpartum ( = 0.02). Colostrum yield at 1 h postpartum ( = 0.03) and total yield up to 18 h postpartum ( = 0.04) was greater for ewes offered the 120% ME diet than either of the other treatment groups. Similarly, these ewes had a greater estimated milk yield during wk 3 of lactation ( = 0.04) and elevated concentrations of short-chain SFA ( = 0.02) and long-chain SFA ( ≤ 0.05) from wk 2 through 6 of lactation. In summary, the negative impact of applying a dietary insult to ewes in late gestation is reflected in colostrum and estimated milk yield and fatty acid composition, thus potentially influencing postpartum growth and development of the offspring.

Altering ewe nutrition in late gestation: II. The impact on fetal development and offspring performance.

The present study was conducted to evaluate the effects of offering Belclare X ewes a single diet rationed to 80, 100, or 120% of recommended ME requirements from d 119 of gestation to parturition, with concurrent changes in other dietary nutrients. The effects on the development of the fetus and subsequent offspring performance to weaning were monitored. Sixty twin-bearing ewes were allocated to 1 of 3 dietary treatments based on Agricultural and Food Research Council recommendations () as amended by as follows: 80% of predicted ME requirement, 100% of predicted ME requirement, and 120% of predicted ME requirement. Ewes were individually fed for the final 4 wk of gestation. Diets fed were grass silage based; however, when silage intake failed to meet ME requirements, ewes were offered varying quantities of concentrates, on an individual basis, to ensure they met their required daily ME allocation. Concentrates offered were composed of 40% barley, 22% beet pulp nuts, 20% distillers' dried grains, and 14% soybean meal, on a DM basis. At birth, lambs were weighed, behavioral and skeletal measurements were recorded, and plasma blood samples were collected. At 1 h postpartum, a subset of lambs ( = 10) per treatment was euthanized to assess organ weight and intestinal morphology. At birth, there was no effect of treatment on lamb live weight at birth ( = 0.31), although lambs born to ewes offered 120% ME had a larger thoracic circumference ( = 0.05). Lambs born to ewes offered the excess energy treatment (120% ME) were quickest to stand and attempt to suckle after birth, in addition to having a greater live weight at weaning ( = 0.01) and ADG from birth to weaning ( = 0.05). Nutritional treatment had no effect on the organ weights ( ≥ 0.11) or the ileal morphology ( ≥ 0.62) of the lamb measured at 1 h postpartum. In summary, the impact of applying a dietary alteration to ewes in late gestation is not directly reflected in organ weight or total live weight at birth but is present at weaning, therefore outlining the poor reliability of using birth weight as an indicator of maternal nutrition during late gestation.

Optimization and validation of CEDIA drugs of abuse immunoassay tests in serum and urine on an Olympus AU 400.

A preliminary initial cloned enzyme donor immunoassay (CEDIA) was optimized for serum and urine drug testing with respect to the German per se limits for driving under the influence of drugs (serum) and lowered cut-offs in cases of driving licence re-granting (urine). The tests were performed on an Olympus AU 400 auto analyzer. Validation revealed sensitivities between 93% and 100% based on comparison with data from gas or liquid chromatography coupled with mass spectrometry. Even if specificity ranged between 83% and 98 %, the tests can be considered useful for forensic purposes. Receiver operating characteristic (ROC) curves, Youden indices, as well as positive and negative predictive values are presented.

The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia.

The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2, 84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.

Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4µg/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study.

Multiple Oral Re-reading treatment for alexia: The parts may be greater than the whole.

This study examines the reasons for the success of Multiple Oral Re-reading (MOR; Moyer, 1979), a non-invasive, easily administered alexia treatment that has been reported in the literature and is currently in clinical use. The treatment consists of reading text passages aloud multiple times a day. Findings that MOR improves reading speed on practised as well as novel text have been inconsistent, making MOR's role in the rehabilitation of alexia unclear. We hypothesised that MOR's treatment mechanism works through repetition of high frequency words (i.e., bottom-up processing). We designed and controlled our text passages to test the hypothesis that participants would not improve on all novel text but would improve on text that includes a critical mass of the words contained in the passages they were re-reading. We further hypothesised that the improvement would be at the level of their specific alexic deficit. We tested four participants with phonological alexia and two with pure alexia during 8 weeks of MOR treatment. Contrary to the conclusions of previous studies, our results indicate that improvements in top-down processing cannot explain generalisation in MOR and that much of the improvement in reading is through repetition of the practised words. However, most patients also showed improvement when specific phrases were re-used in novel passages, indicating that practice of difficult words in context may be crucial to reading improvement.

Reference measurement procedure for Delta9-tetrahydrocannabinol in serum.

An isotope dilution gas chromatography/mass spectrometry (ID-GC/MS) reference measurement procedure for Delta9-tetrahydrocannabinol (THC) in serum was developed and validated. The method complies with the concept of a ratio primary reference measurement procedure. The uncertainty was determined for two concentrations of THC in serum (1 ng/mL and 2.4 ng/mL). The calculation procedure is based on the Guide to the Expression of Uncertainty in Measurement (GUM). The relative expanded uncertainty was found to be less than 2% for both concentration levels, corresponding to a 95% confidence interval. For the reference method, it was shown that the measurement of THC within the concentration range covered by the current threshold values is very accurate. The method has the potential to provide traceability for the methods used in practical forensics.

The role of level of representation in the use of paired associate learning for rehabilitation of alexia.

Patients with phonological alexia (difficulty reading pseudowords) frequently have concomitant difficulty reading functor words and verbs compared with concrete nouns. The current study compares two techniques for helping two patients with phonological alexia regain the ability to read functors and verbs. One technique follows the approach of reorganization of function, while the other relies on the stimulation approach. Study 1, employing a reorganization approach, resulted in both patients increasing their reading accuracy from approximately 10 to 90% or greater. Study 2, using a stimulation approach, resulted in significant improvement, however neither patient was able to achieve accuracy greater than 59%. Study 3 reverted back to the reorganization approach using the same words from Study 2. Both patients demonstrated significant success, achieving 90% or greater accuracy. Whereas the reorganization approach meets with far greater success than the stimulation approach, both approaches can be seen as instances of paired associate learning. An explanation of the advantage of the reorganization approach is developed which focuses on the nature of the pairings in the paired associate learning paradigm: it is proposed that pairings within the same level of representation are easier to learn than pairings that cut across levels of representation.

Influence of infected cell growth state on bacteriophage reactivation levels.

Reactivation of UV-C-inactivated Pseudomonas aeruginosa bacteriophages D3C3, F116, G101, and UNL-1 was quantified in host cells infected during the exponential phase, during the stationary phase, and after starvation (1 day, 1 and 5 weeks) under conditions designed to detect dark repair and photoreactivation. Our experiments revealed that while the photoreactivation capacity of stationary-phase or starved cells remained about the same as that of exponential-phase cells, in some cases their capacity to support dark repair of UV-inactivated bacteriophages increased over 10-fold. This enhanced reactivation capacity was correlated with the ca. 30-fold-greater UV-C resistance of P. aeruginosa host cells that were in the stationary phase or exposed to starvation conditions prior to irradiation. The dark repair capacity of P. aeruginosa cells that were infected while they were starved for prolonged periods depended on the bacteriophage examined. For bacteriophage D3C3 this dark repair capacity declined with prolonged starvation, while for bacteriophage G101 the dark repair capacity continued to increase when cells were starved for 24 h or 1 week prior to infection. For G101, the reactivation potentials were 16-, 18-, 10-, and 3-fold at starvation intervals of 1 day, 1 week, 5 weeks, and 1. 5 years, respectively. Exclusive use of exponential-phase cells to quantify bacteriophage reactivation should detect only a fraction of the true phage reactivation potential.

Dosimetry characterization of 32P catheter-based vascular brachytherapy source wire.

Dosimetry measurements and Monte Carlo simulations for a catheter-based 32P endovascular brachytherapy source wire are described. The measured dose rates were obtained using both radiochromic dye film and an automated plastic scintillator. The investigated source has dimensions of 27 mm in length and 0.24 mm in diameter, and is encapsulated in NiTi. For the radiochromic film measurements, calibrated radiochromic dye film was irradiated at distances between 1 and 5 mm from the source axis in A-150 plastic, and read out with a high-resolution scanning densitometer. The depth-dose curve measured in A-150 is then converted to that in water using correction factors obtained from Monte Carlo calculations. For the scintillator system, direct measurements in water were acquired at distances between 1 and 6 mm from the center of the source, along the perpendicular bisector of the source axis. The scintillator was calibrated in terms of absorbed-dose rate in a reference beta-particle field at multiple depths. The measured dose rates obtained from the film and scintillator measurements were then normalized to the measured source activity, i.e., to convert the measured data to units of cGy/s/mCi. Theoretical dosimetry calculations of the catheter-based 32P wire geometry were also obtained from Monte Carlo simulations using the Electron Gamma Shower code (EGS4), the Monte Carlo N-particle transport code (MCNP4B), and CYLTRAN from the Integrated Tiger Series codes (ITS v.3) and found to be in good agreement. The results of both measurements and calculations are expressed as absorbed-dose rate in water per unit of contained activity (cGy/s/mCi). Comparisons indicate that the measured and calculated dosimetry are in good agreement (<10%) within the relevant treatment distances (1-5 mm). This work fully characterizes the radiation field around a novel 32P beta brachytherapy source in water. The depth-dose curve can be used to calculate the dose to the vessel wall from a 27 mm 32P source wire centered within the vessel lumen.

Rapid word identification in pure alexia is lexical but not semantic.

Following the notion that patients with pure alexia have access to two distinct reading strategies-letter-by-letter reading and semantic reading-a training program was devised to facilitate reading via semantics in a patient with pure alexia. Training utilized brief stimulus presentations and required category judgments rather than explicit word identification. The training was successful for trained words, but generalized poorly to untrained words. Additional studies involving oral reading of nouns and of functors also resulted in improved reading of trained words. Pseudowords could not be trained to criterion. The results suggest that improved reading can be achieved in pure alexia by pairing rapidly presented words with feedback. Focusing on semantic processing is not essential to this process. It is proposed that the training strengthens connections between the output of visual processing and preexisting orthographic representations.

The genetic locus NRC-1 within chromosome 3p12 mediates tumor suppression in renal cell carcinoma independently of histological type, tumor microenvironment, and VHL mutation.

Human chromosome 3p cytogenetic abnormalities and loss of heterozygosity have been observed at high frequency in the nonpapillary form of sporadic renal cell carcinoma (RCC). The von Hippel-Lindau (VHL) gene has been identified as a tumor suppressor gene for RCC at 3p25, and functional studies as well as molecular genetic and cytogenetic analyses have suggested as many as two or three additional regions of 3p that could harbor tumor suppressor genes for sporadic RCC. We have previously functionally defined a novel genetic locus nonpapillary renal carcinoma-1 (NRC-1) within chromosome 3p12, distinct from the VHL gene, that mediates tumor suppression and rapid cell death of RCC cells in vivo. We now report the suppression of tumorigenicity of RCC cells in vivo after the transfer of a defined centric 3p fragment into different histological types of RCC. Results document the functional involvement of NRC-1 in not only different cell types of RCC (i.e., clear cell, mixed granular cell/clear cell, and sarcomatoid types) but also in papillary RCC, a less frequent histological type of RCC for which chromosome 3p LOH and genetic aberrations have only rarely been observed. We also report that the tumor suppression observed in functional genetic screens was independent of the microenvironment of the tumor, further supporting a role for NRC-1 as a more general mediator of in vivo growth control. Furthermore, this report demonstrates the first functional evidence for a VHL-independent pathway to tumorigenesis in the kidney via the genetic locus NRC-1.

Can treatment for pure alexia improve letter-by-letter reading speed without sacrificing accuracy?

An experimental treatment study designed to improve both the accuracy and the speed of reading was administered to a patient with pure alexia and impaired letter naming. The study focused on the use of letter-by-letter reading. A two-stage approach was employed. The first stage implemented a tactile-kinesthetic strategy to improve accuracy. The second stage concentrated on speed. At the end of the treatment, patient DL was reading both trained and untrained words more accurately and with considerably greater speed than prior to treatment. Accuracy and speed of reading at the sentence level improved as well.

The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the reliability, construct validity, and sensitivity to change of the Lower Extremity Functional Scale (LEFS). SUBJECTS AND METHODS: The LEFS was administered to 107 patients with lower-extremity musculoskeletal dysfunction referred to 12 outpatient physical therapy clinics. METHODS: The LEFS was administered during the initial assessment, 24 to 48 hours following the initial assessment, and then at weekly intervals for 4 weeks. The SF-36 (acute version) was administered during the initial assessment and at weekly intervals. A type 2,1 intraclass correlation coefficient was used to estimate test-retest reliability. Pearson correlations and one-way analyses of variance were used to examine construct validity. Spearman rank-order correlation coefficients were used to examine the relationship between an independent prognostic rating of change for each patient and change in the LEFS and SF-36 scores. RESULTS: Test-retest reliability of the LEFS scores was excellent (R = .94 [95% lower limit confidence interval (CI) = .89]). Correlations between the LEFS and the SF-36 physical function subscale and physical component score were r=.80 (95% lower limit CI = .73) and r = .64 (95% lower limit CI = .54), respectively. There was a higher correlation between the prognostic rating of change and the LEFS than between the prognostic rating of change and the SF-36 physical function score. The potential error associated with a score on the LEFS at a given point in time is +/-5.3 scale points (90% CI), the minimal detectable change is 9 scale points (90% CI), and the minimal clinically important difference is 9 scale points (90% CI). CONCLUSION AND DISCUSSION: The LEFS is reliable, and construct validity was supported by comparison with the SF-36. The sensitivity to change of the LEFS was superior to that of the SF-36 in this population. The LEFS is efficient to administer and score and is applicable for research purposes and clinical decision making for individual patients.

[Progression of foot deformities in rheumatoid arthritis--a radiologic follow-up study over 5 years]. / Progression von Fussdeformitäten bei rheumatoider Arthritis--Eine radiologische Verlaufsbeobachtung über fünf Jahre.

OBJECTIVE: The typical changes of the foot in patients with rheumatoid arthritis (RA) are the rear foot valgus and the flattening of the longitudinal arch as well as the splayfoot with hallux valgus and little toe deformities. These foot deformities are not so much a cosmetic problem, but are very painful and limit the patient's mobility. METHODS: The progression of rheumatic foot deformities with a follow-up of five years was described in 36 patients (70 feet) with RA and an average duration of the disease of 19.2 years (+/- 9.8 years). The analysis was based on standardized X-rays of the feet using the index of Larsen, Dale, and Eek. The number of affected joints and their predominant locations were evaluated. RESULTS: In the course of the follow-up, the first MTP joint was affected most frequently in 57%. Especially the tarsometatarsal joints of the Lisfranc-joint-line showed progressive changes. Altogether, a radiological progression of arthritic changes and a worsening of the foot statics were observed in 97% of the patients. CONCLUSION: In view of the rapid progression of rheumatic foot disorders, there is need not only for a consequent pharmacotherapy but also for strict clinical controls and a disease stage oriented local therapy.

Physical and functional mapping of a tumor suppressor locus for renal cell carcinoma within chromosome 3p12.

Using a functional genetic approach, we previously identified a novel genetic locus, NRC-1 (Nonpapillary Renal Cell Carcinoma 1), that mediated tumor suppression and rapid cell death of renal cell carcinoma (RCC) cells in vivo. For these experiments, a defined subchromosomal fragment of human chromosome 3p was transferred into a sporadic RCC cell line via microcell fusion, and microcell hybrid clones were tested for tumorigenicity in vivo. The results indicated functional evidence for a novel tumor suppressor locus within the 3p14-p12 interval known to contain the most common fragile site of the human genome (FRA3B), the FHIT gene, and the breakpoint region associated with the familial form of RCC. We now report the physical mapping of the NRC-1 critical region by detailed microsatellite analyses of novel microcell hybrid clones containing transferred fragments of chromosome 3p in the RCC cell background that were phenotypically suppressed or unsuppressed for tumorigenicity in vivo. The results limit the region containing the tumor suppressor locus within chromosome 3p12. The FHIT gene, FRA3B, and the familial RCC breakpoint region were excluded from the NRC-1 critical region. Furthermore, the NRC-1 locus falls within a well-characterized homozygous deletion region of 5-7 Mb associated with a small cell lung carcinoma cell line, U2020, suggesting that a more general tumor suppressor gene may reside in this region.