Cross-sectional study of the prevalence of and risk factors for hoof disorders in horses in The Netherlands.

Information is scarce on the prevalence of hoof disorders in horses. In this study, we examined the prevalence of and risk factors for hoof disorders in a population of horses in The Netherlands. In a group of 942 randomly selected horses, hoof health was scored during regular foot trimming (one horse/farm). Hooves were assessed for the occurrence of one of 12 hoof disorders by a group of 21 certified farriers in two periods i.e. winter and summer of 2015. The mean age of the group of horses was 11.2±5.6years. They were mainly used for recreation (28.2%), dressage (26.8%), other disciplines (such as carriage driving and breeding) (18.7%), showjumping (17.6%) or combinations of these activities (8.6%). The horse farms studied were evenly distributed throughout the country. The horses were housed on different types of bedding, including straw (51.0%), shavings (17.5%), flax (16.1%) or other materials (11.0%), or were kept at pasture (4.4%). In 85% of the horses, at least one hoof disorder was observed during regular foot trimming. Most of the lesions were mild. The most frequently diagnosed hoof disorders were: thrush (T; 45.0%); superficial hoof wall cracks (SHWC; 30.4%); growth rings (GR; 26.3%); and sole bruises (SB; 24.7%). Less frequently observed hoof disorders included: perforating hoof wall cracks (PHWC; 16.4%); white line disease (WLD; 17.8%); and white line widening (WLW; 11.8%). Horizontal hoof cracks (5.2%), chronic laminitis (3.9%), quarter cracks (2.7%), keratoma (1.8%) and frog cancer (1.0%) were less frequently observed. Factors significantly associated with the occurrence of thrush comprised a wet stable floor (OR 1.6 and 2.9, for somewhat wet to wet respectively, compared to dry), the use of straw as bedding (OR=1.5, compared to flax), the housing strategy (e.g. permanent housing in contrast to permanent pasturing) (OR=1.7) and poor horn quality (OR=3.4). A higher prevalence of WLD was associated with less frequent hoof picking (OR=2.1 if performed weekly instead of daily), the use of flax bedding (OR=2.1, compared to straw) and poor horn quality (OR=8.1). A higher prevalence of SB was observed in horses used for multiple disciplines (OR=3.5, compared to dressage), with white-coloured hooves (OR=5.0, compared to black hooves), with longer intervals between trimming sessions (OR=4.8 in case of 8-10 weeks compared to weekly) and with poor horn quality (OR=5.4). A higher prevalence of WLW was observed in older horses (OR=15.5 for horses >19years, compared to <5years), in those with longer intervals between trimming sessions (OR=1.8 in case of 8-10 weeks compared to weekly), and in certain breeds (OR=3.2 for Friesian horses, 2.9 for Welsh ponies and 13.1 for Shetland ponies, all compared to Dutch Warmblood). In conclusion, although most of the hoof disorders identified were only in a mild stage, still an unexpectedly high prevalence of hoof disorders was observed during regular hoof trimming. Analysis of the data showed that some parameters, such as the use of flax bedding, may be protective for certain hoof disorders but a risk factor for others. This study provides useful guidelines for monitoring hoof health, reducing lameness and optimizing equine welfare.

Maximal neutropenia during chemotherapy and radiotherapy is significantly associated with the development of acute radiation-induced dysphagia in lung cancer patients.

BACKGROUND: Acute dysphagia is a distressing dose-limiting toxicity after concurrent chemoradiation or high-dose radiotherapy for lung cancer. We therefore identified factors associated with the occurrence of acute dysphagia in lung cancer patients receiving radiotherapy alone or combined with chemotherapy. PATIENTS AND METHODS: Radiotherapy, chemotherapy and patient characteristics were analyzed using ordinal regression analysis as possible predictors for acute dysphagia (CTCAE 3.0) in 328 lung cancer patients treated with curative intent. RESULTS: The most significant association was seen between the maximal grade of neutropenia during chemoradiation and dysphagia, with an odds ratio increasing from 1.49 [95% confidence interval (CI) 0.63-3.54, P = 0.362] for grade 1-2 neutropenia to 19.7 (95% CI 4.66-83.52, P < 0.001) for patients with grade 4 neutropenia. Twice-daily schedule, mean esophageal dose and administration of chemotherapy were significant predictive factors. By combining these factors, a high-performance predictive model was made. On an individual patient level, 64% of patients were correctly classified and only 1.2% of patients were misclassified by more than one grade. CONCLUSIONS: The maximal neutrophil toxicity during concurrent chemotherapy and radiotherapy is strongly associated with the development of acute dysphagia. A multivariate predictive model was developed.

Inefficacy of high-dose transdermal fentanyl in a patient with neuropathic pain, a case report.

Pain partially responsive to opioids can lead to rapid escalating dosages due to tolerance development. In this report the case of a 58-year-old female with neuropathic pain using increasing transdermal (TTS) fentanyl dosages to a maximum dose of 3400 microg/h resulting in fentanyl plasma levels of 173 ng/ml is described. For pain relief an epidural infusion at the level T1-2 with bupivacaine was started. Immediate pain relief was accompanied by short lasting respiratory depression and drowsiness.

Inhibition of major groove DNA binding bZIP proteins by positive patch polyamides.

Cell permeable synthetic ligands that bind to predetermined DNA sequences offer a chemical approach to gene regulation, provided inhibition of a broad range of DNA transcription factors can be achieved. DNA minor groove binding polyamides containing aminoalkyl substituents at the N-1 of a single pyrrole residue display inhibitory effects for a bZIP protein which binds exclusively in the DNA major groove. For major groove protein inhibition, specific protein-DNA contacts along the phosphate backbone were targeted with the positively charged dimethylamino substituent on the backbone of a minor groove binding polyamide hairpin. Remarkably, these polyamides bind DNA with enhanced affinity and uncompromised specificity when compared to polyamides with the aminoalkyl moiety at the C-terminus. By adding bZIP transcription factors to the class of protein-DNA complexes that can be disrupted by minor groove binding ligands, these results may increase the functional utility of polyamides as regulators of gene expression.

Recognition of the DNA minor groove by pyrrole-imidazole polyamides: comparison of desmethyl- and N-methylpyrrole.

Polyamides consisting of N-methylpyrrole (Py), N-methylimidazole (Im), and N-methyl-3-hydroxypyrrole (Hp) are synthetic ligands that recognize predetermined DNA sequences with affinities and specificities comparable to many DNA-binding proteins. As derivatives of the natural products distamycin and netropsin, Py/Im/Hp polyamides have retained the N-methyl substituent, although structural studies of polyamide:DNA complexes have not revealed an obvious function for the N-methyl. In order to assess the role of the N-methyl moiety in polyamide:DNA recognition, a new monomer, desmethylpyrrole (Ds), where the N-methyl moiety has been replaced with hydrogen, was incorporated into an eight-ring hairpin polyamide by solid-phase synthesis. MPE footprinting, affinity cleavage, and quantitative DNase I footprinting revealed that replacement of each Py residue with Ds resulted in identical binding site size and orientation and similar binding affinity for the six-base-pair (bp) target DNA sequence. Remarkably, the Ds-containing polyamide exhibited an 8-fold loss in specificity for the match site versus a mismatched DNA site, relative to the all-Py parent. Polyamides with Ds exhibit increased water solubility, which may alter the cell membrane permeability properties of the polyamide. The addition of Ds to the repertoire of available monomers may prove useful as polyamides are applied to gene regulation in vivo. However, the benefits of Ds incorporation must be balanced with a potential loss in specificity.

Structural effects of DNA sequence on T.A recognition by hydroxypyrrole/pyrrole pairs in the minor groove.

Synthetic polyamides composed of three types of aromatic amino acids, N-methylimidazole (Im), N-methylpyrrole (Py) and N-methyl-3-hydroxypyrrole (Hp) bind specific DNA sequences as antiparallel dimers in the minor groove. The side-by-side pairings of aromatic rings in the dimer afford a general recognition code that allows all four base-pairs to be distinguished. To examine the structural consequences of changing the DNA sequence context on T.A recognition by Hp/Py pairs in the minor groove, crystal structures of polyamide dimers (ImPyHpPy)(2) and the pyrrole counterpart (ImPyPyPy)(2) bound to the six base-pair target site 5'-AGATCT-3' in a ten base-pair oligonucleotide have been determined to a resolution of 2.27 and 2.15 A, respectively. The structures demonstrate that the principles of Hp/Py recognition of T.A are consistent between different sequence contexts. However, a general structural explanation for the non-additive reduction in binding affinity due to introduction of the hydroxyl group is less clear. Comparison with other polyamide-DNA cocrystal structures reveals structural themes and differences that may relate to sequence preference.

Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch.

BACKGROUND: Gene-specific targeting of any protein-DNA complex by small molecules is a challenging goal at the interface of chemistry and biology. Polyamides containing N-methylimidazole and N-methylpyrrole amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to many naturally occurring DNA-binding proteins. It has been shown that an eight-ring hairpin polyamide targeted to a specific minor-groove contact within a transcription factor binding site can inhibit protein-DNA binding and gene transcription. Polyamides and certain major-groove-binding proteins have been found to co-occupy the DNA helix, however. To expand the number of genes that can be targeted by pyrrole/imidazole polyamides, we set out to develop a class of polyamides that can selectively inhibit major-groove-binding proteins. RESULTS: An eight-ring hairpin polyamide conjugated to a carboxy-terminal Arg-Pro-Arg tripeptide was designed to deliver a positive residue to the DNA backbone and interfere with protein-phosphate contacts. Gel mobility shift analysis demonstrated that a polyamide hairpin-Arg-Pro-Arg binding in the minor groove selectively inhibits binding of the transcription factor GCN4 (222-281) in the adjacent major groove. Substitution within the Arg-Pro-Arg revealed that each residue was required for optimal GCN4 inhibition. CONCLUSIONS: A pyrrole-imidazole polyamide that binds to a predetermined site in the DNA minor groove and delivers a positive patch to the DNA backbone can selectively inhibit a DNA-binding protein that recognizes the adjacent major groove. A subtle alteration of the DNA microenvironment targeted to a precise location within a specific DNA sequence could achieve both gene-specific and protein-specific targeting.

[Benign bone tumors in the growth years--osteoid osteoma and osteoblastoma]. / Benigne Knochentumoren im Wachstumsalter--Osteoidosteom und Osteoblastom.

Osteoid osteoma (ICD: 9191/0) and osteoblastoma (ICD: 9200/0) are closely related entities of osteoblastic-type tumors. Osteoid osteoma is a small benign (lesion 1-2 cm or less) neoplasm that is richly vascularized. Nerve fibers within the tissue surrounding the nidus lead to the characteristic pain. A typical finding is the perifocal osseous reaction around the nidus. Osteoblastoma is a progressively growing lesion of a diameter larger than 2 cm; it is sometimes painful and is characterized by the absence of any reactive perifocal bone formation. For both tumors the treatment is complete surgical excision. If the nidus of the osteoid osteoma is removed, the patient will be free of pain. For the osteoblastoma the treatment depends on the stage and localization of the tumor. Forty-seven patients with osteoid osteoma and 10 patients with osteoblastoma have been treated in Heidelberg since 1980. The radiological investigations and surgical treatment are discussed.

The power to reduce the cost of technology.

Technology has been made the scapegoat for the increasing cost of health care. Government action in the form of congressional legislation, administrative regulations, funded research, health care payments, etc., has been an important contributing factor in this increasing cost. Microcomputer/microprocessor-based systems such as MUMPS, PROMIS, COSTAR, GeMSAEC, and ASPECT have underutilized potential for producing economies of scale. Quantitative comparative cost data should be developed by every government-sponsored study or project to forcefully prove that more technology results in lowered costs.