Whole-flock, metaphylactic tilmicosin failed to eliminate contagious ovine digital dermatitis and footrot in sheep: a cluster randomised trial.

The aim of this study was to evaluate the clinical success of whole-flock systemic tilmicosin and enhanced biosecurity in eliminating active contagious ovine digital dermatitis (CODD) from sheep flocks. Thirty flocks in the UK were randomly allocated to receive either treatment as usual (as per the farmer's normal routine) or whole-flock treatment with tilmicosin, together with isolation and extended treatment of clinically affected individuals and isolation and treatment of purchased sheep during the study period. All flocks were visited once at onset of the trial to examine all sheep. One year later, all sheep were re-examined to determine the presence/absence of clinical lesions. The primary outcome was the clinical elimination of CODD from flocks. Secondary outcomes were reduction in prevalence of CODD, clinical elimination of footrot and reduction in prevalence of footrot. The analysis included 11 control flocks and 13 intervention flocks, with initially 3460 and 4686 sheep, respectively. For CODD: at follow-up, in the intervention group, 6/13 (46 per cent) flocks had a prevalence of zero compared with 1/11 (9 per cent) in the control group (P=0.12). For footrot: at follow-up, no flocks had a prevalence of zero. Therefore, the intervention is not recommended for the elimination of CODD or footrot in the UK.

Outcome of surgical treatment for umbilical swellings in bovine youngstock.

Umbilical swellings are commonly identified in calves and can be caused by hernia formation, infection of the remnants of umbilical vessels or a combination of both. Ninety-one cases with umbilical swellings were admitted to the Leahurst Farm Animal Practice (LFAP) between July 2004 and February 2012; 55 were simple hernias and 36 had associated infection. Eighty-seven cases underwent surgery of which 86 survived until discharge. Postoperative complications occurred in 65/86 animals (73 per cent). In 51 cases (81 per cent) this was classified as minor requiring no additional treatment. Placement of a prosthetic mesh was associated with a higher OR for developing severe postoperative complication when compared with those not receiving a mesh (OR=19.3; 95% CI 4.5 to 83.5). Long-term survival results were available for 49 animals, 22 of which were remaining in the herd with a median age of 1346 days (3.7 years). Of the 27 animals which had exited the herd, 16 were adult dairy cows, 7 were dairy heifers, 2 were beef animals and 2 exited at an unknown stage. Umbilical surgery in calves carries a good prognosis, although placement of a mesh increases the risk of complications occurring in the postoperative period.

Effects of parenteral amoxicillin on recovery rates and new infection rates for contagious ovine digital dermatitis in sheep.

The present study is a randomised split-flock treatment trial, which compared the effect of foot bathing in a 1 per cent solution of chlortetracycline alone with a treatment protocol that added a single injection of a long-acting amoxicillin. Overall, the prevalence of contagious ovine digital dermatitis in the examined flock was 22 per cent, while 45.7 per cent of affected sheep had infections in two or more feet. Parenteral antibiotic treatment increased the odds of a recovery by 3.8 times (95 per cent confidence interval 1.05 to 14.0) (P=0.008). Moreover, the amoxicillin injection may also have had a preventative effect, reducing the rate of establishment of new infections from 2.5 per cent for foot bathing alone compared with 1.0 per cent with the addition of parenteral amoxicillin.

Clinical, ultrasonographic and pathological findings in a bull with segmental aplasia of the mesonephric duct.

On assessment for use in an AI stud, a 12-month-old bull was found to produce low volume ejaculates with 41% of the sperm having morphological abnormalities. No left epididymal tail was palpable and the head of the epididymis on the left was twice the size compared with the right. Ultrasound examination showed the left testis to contain a large central area of decreased echogenicity, which could be followed proximally to a 15-mm echolucent lesion at the site of the epididymal head. Postmortem examination revealed a 15-mm diameter cyst in the region of the left epididymal head, and absence of the body and tail of the epididymis. The mediastinum testis of the left testis was dilated, corresponding to the area of decreased echogenicity observed on ultrasonography. No left seminal vesicle was present and the ampulla was significantly smaller than the same structure on the right. Histological examination revealed incomplete or absent spermatogenesis involving the majority of seminiferous tubules in the left testis, and a small proportion of those of the right testis. The cystic structure at the site of the left epididymal head was lined by irregular, sometimes attenuated, epithelium and contained sparse spermatozoa. This case demonstrates the adverse impact, which segmental aplasia of the mesonephric duct had on the testicular and epididymal function of a bull, and highlights the importance of careful clinical assessment in its diagnosis.

The investigation and management of back pain in children.

Back pain in children and adolescents is probably much less common than in adults, but its true incidence is unknown. Although back pain has traditionally been considered a rare and often sinister presentation in the paediatric age group, recent literature now suggests that a relatively high number of children do experience back pain, but only a small proportion seek medical attention. For the majority of children with back pain no underlying cause is identified, but some require investigation to exclude serious underlying pathology. Laboratory and imaging investigations should be targeted towards those with "red flag" symptoms and signs. Imaging studies, particularly MRI, have an important role in diagnosis of underlying pathology such as infection or malignancy.

Spinal cord compression by tophaceous gout with fluorodeoxyglucose-positron-emission tomographic/MR fusion imaging.

A 36-year-old woman presented with lower extremity paralysis. Her past medical history included gout. Conventional radiography and MR imaging revealed bone erosion and soft tissue lesions of the thoracic spine. Fluorodeoxyglucose-positron-emission tomographic (FDG-PET) images revealed hypermetabolic lesions of the thoracic spine. A CT-guided biopsy was diagnostic for inflammatory tophaceous gout. This case describes the CT, MR, and FDG-PET imaging characteristics of acute inflammatory gout. FDG-PET imaging characteristics of this disorder have not been previously described.

The effect of X-rays on bone: a pictorial review.

The deleterious effects of X-rays on bone have been recognised for almost a century and continue to be seen today because of improved survival in patients treated for malignancy with radiotherapy with or without other treatments. In this pictorial review we present the imaging features of radiation damage to bone highlighting the differences seen in the immature skeleton and post-skeletal fusion. In the former, damage is greatest to the physis resulting in growth disturbances. In the mature skeleton there is a spectrum of changes from mild osteopenia, through disordered attempts at healing with varying degrees of sclerosis, radionecrosis which may lead to acute fractures following minimal trauma and insufficiency fractures both with refractory healing to the dreaded complication of sarcomatous transformation. The imaging appearances are illustrated and the features that help distinguish malignant change from other complications stressed.

Imaging features of intraosseous ganglia: a report of 45 cases.

The aim of this study is to report the spectrum of imaging findings of intraosseous ganglia (IG) with particular emphasis on the radiographic and magnetic resonance (MR) features. Forty-five patients with a final diagnosis of IG were referred to a specialist orthopaedic oncology service with the presumptive diagnosis of either a primary or secondary bone tumour. The diagnosis was established by histology in 25 cases. In the remainder, the imaging features were considered characteristic and the lesion was stable on follow-up radiographic examination. Radiographs were available for retrospective review in all cases and MR imaging in 29. There was a minor male preponderance with a wide adult age range. Three quarters were found in relation to the weight-bearing long bones of the lower limb, particularly round the knee. On radiographs all were juxta-articular and osteolytic; 74% were eccentric in location, 80% had a sclerotic endosteal margin and 60% of cases showed a degree of trabeculation. Periosteal new bone formation and matrix mineralization were not present. Of the 29 cases that underwent MR imaging, 66% were multiloculated. On T1-weighted images the IG contents were isointense or mildly hypointense in 90% cases. Forty-one per cent of the cases showed a slightly hyperintense rim lining that enhanced with a gadolinium chelate. Thirty-eight per cent were associated with soft tissue extension and 17% with a defect of the adjacent articular cortex. Fifty-five per cent showed surrounding marrow oedema on T2-weighted or STIR images and two cases (7%) a fluid-fluid level prior to any surgical intervention. The authors contend that it is semantics to differentiate between an IG and a degenerate subchondral cyst as, while the initial pathogenesis may vary, the histological endpoint is identical, as are the imaging features apart from the degree of associated degenerative joint disease. IGs, particularly when large, may be mistaken for a bone tumour. Correlation of the typical radiographic and MR imaging features will indicate the correct diagnosis and obviate the need for biopsy.

Imaging of congenital cystic lung lesions.

Congenital cystic lung lesions are a rare but clinically significant group of anomalies, including congenital cystic adenomatoid malformation (CCAM), pulmonary sequestration, congenital lobar emphysema (CLE) and bronchogenic cysts. These conditions can all present on imaging studies as air or fluid filled cysts. Widespread use of antenatal ultrasound has led to increased detection of infants with congenital thoracic abnormalities in utero, resulting in a better understanding of the natural history of many of these lesions and also allowing provision to be made for delivery and postnatal management. More recently antenatal magnetic resonance (MR) imaging has provided further information on the nature of many of these lesions and helped to differentiate them from extrathoracic abnormalities such as congenital diaphragmatic hernia (CDH), which is important in parental counselling. Many children with congenital cystic lung lesions will present with symptoms resulting in the need for prompt diagnosis and treatment and imaging has an essential role in the management of these children. Some congenital lung lesions are treated surgically, whilst others are managed conservatively.

Imaging features of breast trauma: a pictorial review.

Accidental injury to the female breast can cause symptoms and signs which may mimic carcinoma and can also be painful or disfiguring. Nine women who sustained injury to the breast are presented, illustrating some of the manifestations of traumatic injury to the female breast, the majority of which are attributable to fat necrosis. A brief discussion of the clinical and imaging features of fat necrosis is included. These cases reinforce the importance of triple assessment in any woman presenting with a breast lump, even with a clear history of trauma.

Fine needle aspiration cytology of mammary duct ectasia: report of a case with novel cytologic and immunocytochemical findings.

BACKGROUND: Mammary duct ectasia (MDE), or periductal mastitis, is a well-defined clinical entity with a characteristic histopathologic appearance on breast biopsy specimens. However, the cytologic features of MDE have been described only recently in the cytopathology literature, and fine needle aspiration (FNA) cytologic findings are based mainly on a small number of case reports in the English-language literature. Therefore, awareness of this entity and recognition of its cytomorphologic features could aid in a more accurate diagnosis. We report the novel cytologic and immunocytochemical findings on a case of MDE that was confirmed by histologic examination on a subsequent biopsy. CASE: We report the findings of breast FNA cytology in a 50-year-old female with a mammographically and clinically suspicious lesion. Cytology displayed a paucicellular aspirate, typified by a few scattered, cohesive clusters of ductal epithelial cells with mild nuclear atypia and distinct, peripherally located myoepithelial cells. Intermingled within the ductal elements were numerous polygonal cells with abundant, finely vacuolated cytoplasm that were immunoreactive for macrophage-specific antibody, CD68. The background consisted of a variable number of foam cells and negligible amount of blood. CONCLUSION: The current case of MDE demonstrates cytomorphologic features that may pose diagnostic problems, particularly as a consequence of variable cytologic atypia this entity may present on FNA cytology. This diagnostic difficulty is compounded because of the abnormal mammographic and suspicious clinical findings that may be associated with MDE. CD68 immunoreactivity is a useful ancillary tool to verify the histiocytic, rather than epithelial and potentially neoplastic, nature of multivacuolated cells. To the best of our knowledge, there has been no prior reported case of MDE in the English-language literature studied utilizing CD68 antibody. This case report emphasizes that MDE is a heterogeneous entity with diverse cytomorphologic features. FNA cytology in conjunction with immunocytochemistry might permit accurate classification in the proper clinical setting.

The cyclization of farnesyl diphosphate and nerolidyl diphosphate by a purified recombinant delta-cadinene synthase.

The first step in the conversion of the isoprenoid intermediate, farnesyl diphosphate (FDP), to sesquiterpene phytoalexins in cotton (Gossypium barbadense) plants is catalyzed by delta-cadinene (CDN) synthase. CDN is the precursor of desoxyhemigossypol and hemigossypol defense sesquiterpenes. In this paper we have studied the mechanism for the cyclization of FDP and the putative intermediate, nerolidyl diphosphate, to CDN. A purified recombinant CDN synthase (CDN1-C1) expressed in Escherichia coli from CDN1-C1 cDNA isolated from Gossypium arboreum cyclizes (1RS)-[1-2H](E, E)-FDP to >98% [5-2H]and [11-2H]CDN. Enzyme reaction mixtures cyclize (3RS)-[4,4,13,13,13-2H5]-nerolidyl diphosphate to 62.1% [8,8,15,15,15-2H5]-CDN, 15.8% [6,6,15,15,15-2H5]-alpha-bisabolol, 8.1% [6,6,15,15,15-2H5]-(beta)-bisabolene, 9.8% [4,4,13,13-2H4]-(E)-beta-farnesene, and 4.2% unknowns. Competitive studies show that (3R)-nerolidyl diphosphate is the active enantiomer of (3RS)-nerolidyl diphosphate that cyclized to CDN. The kcat/Km values demonstrate that the synthase uses (E,E)-FDP as effectively as (3R)-nerolidyl diphosphate in the formation of CDN. Cyclization studies with (3R)-nerolidyl diphosphate show that the formation of CDN, (E)-beta-farnesene, and beta-bisabolene are enzyme dependent, but the formation of alpha-bisabolol in the reaction mixtures was a Mg2+-dependent solvolysis of nerolidyl diphosphate. Enzyme mechanisms are proposed for the formation of CDN from (E,E)-FDP and for the formation of CDN, (E)-beta-farnesene, and beta-bisabolene from (3RS)-nerolidyl diphosphate. The primary structures of cotton CDN synthase and tobacco epi-aristolochene synthase show 48% identity, suggesting similar three-dimensional structures. We used the SWISS-MODEL to test this. The two enzymes have the same overall structure consisting of two alpha-helical domains and epi-aristolochene synthase is a good model for the structure of CDN synthase. Several amino acids in the primary structures of both synthases superimpose. The amino acids having catalytic roles in epi-aristochene synthase are substituted in the CDN synthase and may be related to differences in catalytic properties.

Hurthle cell adenoma of the mediastinum: intraoperative cytology and differential diagnosis with correlative gross, histology, and ancillary studies.

A 66-year-old man was found to have a 7.5 cm mediastinal mass detected on routine chest X-rays as part of his preoperative work up for an inguinal hernia repair. An orthotopic (normally located) nongoitrous thyroid gland without evidence of connection to the mediastinal mass was also identified. The clinical differential diagnoses included lymphoma, thymoma, and germ cell tumor. Fine-needle aspiration (FNA) biopsy smears and touch imprints of the mediastinal mass showed a loosely cohesive, highly cellular population of relatively uniform cells with abundant granular cytoplasm, low nuclear to cytoplasmic (N/C) ratios, and prominent nucleoli consistent with a Hurthle cell (HC) neoplasm. Subsequently, the diagnosis of HC adenoma was confirmed on the surgically excised mediastinal mass. To the best of our knowledge, the surgical pathology and cytologic features of an HC adenoma of the mediastinum have not been reported in the literature. The gross, histologic, immunohistochemical, and electron microscopic (EM) findings, in addition to the cytologic features, are presented along with a differential diagnosis of this mediastinal neoplasm.

Detection of nascent polyproline II helices in solution by NMR in synthetic insect kinin neuropeptide mimics containing the X-Pro-Pro-X motif.

The conformations of three synthetic peptide analogs containing the dPro-dPro-dXaa motif (dXaa = dThr, dGlu, dAsn) in aqueous solution were studied by a combination of NMR and molecular modeling simulations. The three compounds were identified from a random D-amino acid tripeptide library on the basis of their ability to either mimic or block the diuretic activity of neuropeptides of the insect kinin family. TOCSY and ROESY correlations, as well as abnormal secondary chemical shifts for protons on the D-proline residues were employed to obtain conformational ensembles consistent with the experimental NMR data for the three analogs using an in vacuo simulated annealing protocol. Similar secondary structures were found for the three molecules after refinement, in agreement with the similarities observed between their NMR spectra. Unrestrained molecular dynamics simulations with explicit water representation indicate that the structural motifs found in vacuo are stable in aqueous solution. The three analogs can be considered initiators of right-handed poly D-proline II helices, mirror images of the poly L-proline II left-handed helical motifs normally found in proline-rich proteins. The role of these secondary folds on binding of the analogs to the kinin receptors is discussed.

Synthesis, biological activity, and conformational studies of insect allatostatin neuropeptide analogues incorporating turn-promoting moieties.

Allatostatins are 6-18 amino acid peptides synthezed by insects to control production of juvenile hormones, which in turn regulate functions including metamorphosis and egg production. Four insect allatostatin neuropeptide analogues incorporating turn-promoting pseudopeptide moieties in the region responsible for biological activity were prepared by solid phase peptide synthetic methods. Bioassay indicated that activities approached those of the natural neuropeptides, and molecular models based on NMR data showed similar conformations and the presence of a beta-turn in the active core region for the four analogues. Differences in activity are believed to be due to differences in bulk and relative position of atoms in the unnatural portion of the analogues, and their differing degrees of conformational freedom. The studies support the feasibility of development of neuropeptide-based insect control agents resistant to peptidase deactivation.

Conformational studies of paclitaxel analogs modified at the C-2' position in hydrophobic and hydrophilic solvent systems.

The conformations of two paclitaxel analogs modified at the C-2' position, 2'-deoxypaclitaxel and 2'-methoxypaclitaxel, were studied in hydrophobic and hydrophilic solvent systems by a combination of NMR spectroscopy, CD measurements, and molecular modeling. Both analogs have hydrophobic and hydrophilic conformations that resemble those of paclitaxel itself in the same media. Since the two have diminished biological activities in a number of bioactivity assays and the hydrogen-bonding capability of the 2'-hydroxyl group has been eliminated, we postulate that this group is involved in hydrogen bonding with tubulin and plays an important role in molecular recognition. The results of this study are in agreement with our earlier report on paclitaxel 2'-acetate, an analog in which the 2'-hydroxyl group hydrogen-bonding capacity has also been eliminated.