PubMed Health⌕ Search

Biomedical subjects

K Kerr

Publications and source records attributed to K Kerr.

At least 19 recordsLinked to original sources

Immunopathology of Chlamydophila abortus infection in sheep and mice.

Chlamydophila abortus targets the placenta, causing tissue damage, inflammation and abortion (enzootic abortion of ewes). It is one of the main infectious causes of abortion in ewes, resulting in major economic losses to agricultural industries worldwide. Although ruminants and pigs are the principal hosts, humans are also susceptible to infection. Control of disease requires a host inflammatory response, which is likely to contribute to pathology and abortion. Mouse models have been widely used to provide insight into the role of specific immune cells in controlling infection and disease. The use of such model systems for investigating the mechanisms of abortion, latency, persistence, and immunity to reinfection will result in the identification of novel vaccine control strategies for sheep.

Abortion, Veterinary↗

Neuroendocrine differentiation in non-small cell lung cancer and its relation to prognosis and therapy.

AIMS: Histopathologists report the presence of neuroendocrine (NE) differentiation in non-small cell lung carcinoma (NSCLC) in up to a third of cases and are often questioned about its clinical relevance. The conclusions of previous studies have been inconsistent. This paper aims to provide an answer by examining a large series together with a comprehensive critique of the literature. METHODS AND RESULTS: Four hundred and thirty-nine cases of NSCLC were examined, immunohistochemically, using antibodies to chromogranin A (CGA), synaptophysin (SYN) and CD56/neural cell adhesion molecule (NCAM). Three hundred and forty-one cases had been treated with surgical resection and the remainder with chemotherapy. The results were compared with clinical outcome. Thity-six percent of cases had positive staining for at least one NE marker. CGA was positive in 5.5% of cases, SYN in 16.5% and NCAM in 28%. There was no association between the presence of NE markers and survival in either the surgically treated group or the chemotherapy-treated group. There was also no association between NE markers and response to chemotherapy in the latter group. CONCLUSIONS: The presence of immunohistochemically detected NE differentiation in NSCLC is not of prognostic significance.

Adenocarcinoma↗

Teaching animal welfare science, ethics, and law to veterinary students in the United kingdom.

Teaching veterinary students about animal welfare science, ethics, and law has been identified as a priority of the veterinary curriculum. Suggested content for such a course, the stage at which it should be taught, and possible methods of teaching and assessing the subject have been outlined. Critically, such a course needs to address the quantification of the impact of humans on animals (welfare science), the analysis of our moral obligations (welfare ethics), and knowledge of minimum welfare standards (welfare legislation). A mixture of both teaching methods and assessment techniques is needed to ensure that sufficient skills and knowledge and a deeper understanding are achieved.

Animal Welfare↗

Health and safety implications of injury in professional rugby league football.

BACKGROUND: Professional sport is characterized by high injury rates but is also covered by health and safety legislation. AIM: To examine the incidence of injury in professional rugby league as defined by the Reporting of Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR 95). METHODS: All injuries received during playing and training to both first-team and 'academy' (<19 years old) players during two playing seasons at one professional club were recorded. The length of time a player was unable to take part in full training and playing was used as a measure of severity. Injuries were classified into minor injuries (0-3 days), over 3 day injuries or major injuries, in which the final two categories corresponded with RIDDOR 95. RESULTS: Thirty-two per cent (95% confidence interval=26-39%) of all injuries received satisfied the RIDDOR 95 criteria. The overall injury rate was 8.5 per 1000 h (7.2-9.9) for the first team and 4.1 per 1000 h (3.2-5.4) for the academy team. During match play the first-team injury rate was 157.7 per 1000 h (133.5-185.1) and 67.7 (51-81.1) for the academy team. Training injury rates were lower, at 0.5 per 1000 h (0.2-1.0) and 0.3 per 1000 h (0.1-0.8), respectively. CONCLUSION: The injury rate for professional rugby league is much higher than reported in other high-risk occupations such as mining and quarrying. The large differences in injury rates between first and academy teams have implications for young players likely to progress to first-team status.

Adolescent↗

Transmission of colistin-resistant Pseudomonas aeruginosa between patients attending a pediatric cystic fibrosis center.

We report on an outbreak of colistin-resistant Pseudomonas aeruginosa (CRPA) that occurred in a United Kingdom pediatric cystic fibrosis (CF) unit and involved six children over a period of 5 years. All CRPA-positive children had received aerosolized colistin therapy before first isolation of resistant organisms (mean duration, 3.1 years). Four of the 6 had also received courses of intravenous colistin in the year before the first isolation of CRPA. No impact of CRPA acquisition on respiratory function, clinical condition, or radiological parameters could be demonstrated. Four of the 6 children carried isolates of CRPA indistinguishable on genotyping. Two of these 4 children were sisters. The other 2 were on the same ward together at time of first isolation, and subsequently shared overlapping admissions with one of the sisters. While there is no conclusive evidence for the route of transmission, the frequency of overlapping in-patient admissions between 3 of these patients is suggestive of patient-to-patient transfer in the nosocomial setting.CF clinicians should be aware that colistin resistance can occur in P. aeruginosa, and some of these strains are capable of spread within CF units.

Anti-Bacterial Agents↗

Development of the thymus requires signaling through the fibroblast growth factor receptor R2-IIIb.

Mice deficient for fibroblast growth factor (Fgf)R2-IIIb show a block in thymic growth after embryonic day 12.5, a stage that just precedes its detection in thymic epithelial cells. Fgf7 and Fgf10, the main ligands for FgfR2-IIIb, are expressed in the mesenchyme surrounding the thymic epithelial primordium, and Fgf10-deficient mice also exhibit impaired thymic growth. Hence, Fgf signaling is essential for thymic epithelial proliferation. In addition to the proliferative block, most thymic epithelial cells fail to progress from an immature cytokeratin 5-positive to a cytokeratin 5-negative phenotype. Nevertheless, sufficient epithelial cell differentiation occurs in the severely hypoplastic thymus to allow the development of CD4/CD8-double-positive thymocytes and a very small number of single-positive thymocytes expressing TCRs.

Animals↗

Fibroblast growth factor receptor 2-IIIb acts upstream of Shh and Fgf4 and is required for limb bud maintenance but not for the induction of Fgf8, Fgf10, Msx1, or Bmp4.

Mice deficient for FgfR2-IIIb were generated by placing translational stop codons and an IRES-LacZ cassette into exon IIIb of FgfR2. Expression of the alternatively spliced receptor isoform, FgfR2-IIIc, was not affected in mice deficient for the IIIb isoform. FgfR2-IIIb(-/-) (lac)(Z) mice survive to term but show dysgenesis of the kidneys, salivary glands, adrenal glands, thymus, pancreas, skin, otic vesicles, glandular stomach, and hair follicles, and agenesis of the lungs, anterior pituitary, thyroid, teeth, and limbs. Detailed analysis of limb development revealed an essential role for FgfR2-IIIb in maintaining the AER. Its absence did not prevent expression of Fgf8, Fgf10, Bmp4, and Msx1, but did prevent induction of Shh and Fgf4, indicating that they are downstream targets of FgfR2-IIIb activation. In the absence of FgfR2-IIIb, extensive apoptosis of the limb bud ectoderm and mesenchyme occurs between E10 and E10.5, providing evidence that Fgfs act primarily as survival factors. We propose that FgfR2-IIIb is not required for limb bud initiation, but is essential for its maintenance and growth.

Animals↗

Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy.

We examined the cytotoxicity of the immunosuppressant agent rapamycin and its analogue CCI-779 in human brain tumor cell lines in vitro and in vivo as single agents and in combination with standard chemotherapeutic drugs. In the rapamycin-sensitive PNET/MB cell line DAOY, rapamycin exhibited additive cytotoxicity with cisplatin and with camptothecin. In vivo, CCI-779 delayed DAOY xenograft growth by 160% after 1 week and 240% after 2 weeks of systemic treatment, compared with controls. Single high-dose treatment induced 37% regression of tumor solume. Growth inhibition of DAOY xenografts was 1.3 times greater after simultaneous treatment with CCI-779 and cisplatin than after cisplatin alone. Interestingly, CCI-779 also produced growth inhibition of xenografts derived from U251 malignant glioma cells, a human cell line resistant to rapamycin in vitro. These studies suggest that the rapamycin analogue CCI-779 is an important new agent to investigate in the treatment of human brain tumors, particularly PNET/MB.

Animals↗

Intra-operative and post-operative hypercapnia leading to delayed respiratory failure associated with transanal endoscopic microsurgery under general anaesthesia.

We present an unusual case of hypercapnia and surgical emphysema during transanal endoscopic microsurgery, which led to delayed post-operative ventilatory failure. The hypercapnia and surgical emphysema were secondary to rectal insufflation with carbon dioxide used to facilitate visualization and resection of a rectal tumour. Despite a return to wakefulness after surgery, the patient's level of consciousness deteriorated in the recovery area as a result of hypercapnia. The PaCO2 rose to 16.8 kPa because of absorption of carbon dioxide from the surgical emphysema. On close examination, surgical emphysema was identified in unusual areas, including the anterior abdominal wall, both loins, both groins and the left thigh. Reventilation was required until these unusual carbon dioxide stores had dissipated. We discuss the need for prolonged post-operative vigilance in patients with surgical emphysema secondary to carbon dioxide insufflation, and the risk of delayed ventilatory failure.

Aged↗

An operational model to investigate contact sports injuries.

PURPOSE: A cyclical operational model is proposed to examine the interrelationship of a number of factors that are involved in sports injury epidemiology. In sports injury research, investigations often attempt to identify a unique risk factor that distinguishes an injured player. However, a wide variety of factors can contribute to a sports injury occurring, and an understanding of the cause of injury is important to advance knowledge. METHODS: The proposed model identifies a healthy/fit player initially, although the player may exhibit a number of intrinsic risk factors for sports injury. Before exposure to extrinsic risk factors, there is the opportunity for implementation of prevention strategies by coaching personnel and the sports medicine team. These strategies might include, among others, appropriate warm-up, adequate hydration, wearing protective equipment, and prophylactic taping. Additionally, preventative screening could take place to assess the various intrinsic and extrinsic risk factors that could lead to sports injury. DISCUSSION: Two examples of how the operational model relates to contact sports injury cases are presented. Participating in sport inevitably exposes the player to external risk factors that predispose toward injury. The treatment of the injured player aims to restore the player to preinjury playing status and to prevent the injury from becoming chronic. CONCLUSIONS: It is suggested that the application of this proposed cyclical model may lead to greater success in understanding the multifaceted nature of sports injuries and furthermore help minimize injury risk and support the rehabilitation of injured contact sports participants.

Athletic Injuries↗

Fibroblast growth factor signalling in mouse mammary gland development.

Fibroblast growth factors (Fgfs) and their receptors are important intercellular signalling molecules involved in many aspects of animal development. The aberrant expression of the Fgfs or the inappropriate activation of their cell surface receptors have been implicated in tumorigenesis. Here, we describe the evidence that as well as playing a critical role in the formation of the mammary primordia during embryogenesis, signalling by Fgfs is necessary for optimal lobuloalveolar development of the mouse mammary gland during pregnancy.

Animals↗

Subspecialty referrals for pauciarticular juvenile rheumatoid arthritis.

OBJECTIVES: To examine referral patterns from primary care physicians for children with pauciarticular juvenile rheumatoid arthritis (JRA) and to determine whether children with pauciarticular JRA referred to pediatric rheumatologists differ in clinical presentation from children referred to other specialists. DESIGN: A retrospective records review of 49 patients with pauciarticular jRA was performed. Records were reviewed to determine the specialty of the referring physician and whether the children referred had symptoms and signs compatible with a synovitis at the time primary care was sought. SETTING: Inner-city tertiary pediatric rheumatology referral center. PARTICIPANTS: Children with pauciarticular JRA. MAIN OUTCOME MEASURES: Identification of referral patterns of primary care physicians. Associated morbidity owing to JRA was ascertained at the time of referral. RESULTS: Most children with pauciarticular JRA (62%) were referred to orthopedic surgeons prior to referral for pediatric rheumatology care. No differences in clinical symptoms were seen between children referred to pediatric rheumatologists and those referred to orthopedic surgeons. Children referred initially to orthopedic surgeons were younger than those referred to pediatric rheumatologists. CONCLUSION: A notable number of children with pauciarticular JRA are referred to orthopedic surgeons prior to the establishment of that diagnosis, even when such children present with unequivocal signs of synovitis. This may be owing to the misconception that arthritis is rare in preschool-aged children or to the difficulty of ascertaining the presence of synovitis in younger children.

Adolescent↗

Myocarditis and cardiomyopathy associated with clozapine.

BACKGROUND: Clozapine is effective for resistant schizophrenia. After two sudden deaths in physically well young men soon after starting clozapine, we investigated the cardiovascular complications for this drug. METHODS: From January, 1993, to March, 1999, 8000 patients started clozapine treatment in Australia, and were registered with a mandatory monitoring service. We identified cases of myocarditis and cardiomyopathy from voluntary reports to the Australian Adverse Drug Reaction Committee and sought details of the relevant diagnostic studies, necropsies that had been done in suspicious cases, or both. FINDINGS: 23 cases (20 men, three women, mean age 36 years [SD 9]) were identified: 15 of myocarditis and eight of cardiomyopathy associated with clozapine treatment. Six patients died. All cases of myocarditis (five deaths) occurred within 3 weeks of starting clozapine. Cardiomyopathy (one death) was diagnosed up to 36 months after clozapine was started. Necropsy results showed mainly eosinophilic infiltrates with myocytolysis, consistent with an acute drug reaction. INTERPRETATION: Clozapine therapy may be associated with potentially fatal myocarditis and cardiomyopathy in physically healthy young adults with schizophrenia.

Adolescent↗

Reoperative pulmonary thromboendarterectomy.

BACKGROUND: Recurrent symptomatic pulmonary hypertension is uncommon after primary pulmonary thromboendarterectomy (PTE). We reviewed our experience with patients undergoing repeat PTE to determine the risk factors for recurrent disease, and the selection criteria, relative risks, and functional outcomes of reoperative PTE. METHODS: Since 1990, 13 of 870 (1.5%) patients underwent reoperative PTE at our institution. These 7 men and 6 women (mean age 38.6 years) were contrasted with the most recent 225 patients (111 men, 114 women, mean age 52.7 years) who underwent primary PTE for whom complete hemodynamic data are available. The preoperative evaluation of all patients was similar. Pulmonary hemodynamic data and outcome measures were compared between groups. RESULTS: Of 13 reoperated patients: 69% (9/13) had their primary operation at another institution, 54% (7/13) initially underwent unilateral PTE, 38% (5/13) had identifiable coagulation disorders, 38% (5/13) had ineffective caval filtration, 31% (4/13) had suboptimal anticoagulation management, and 31% (4/13) had complete unilateral pulmonary artery obstruction. The mean interval to reoperation was 5.2 years (range 0.7 to 10.9 years). All control patients underwent bilateral PTE using hypothermic circulatory arrest. Operative mortality was 7.7% (1/13) with reoperation vs 8.4% (19/225) in controls. No difference (p = NS) was observed between groups in the preoperative pulmonary artery pressure (PAP) or pulmonary vascular resistance; however, the control group had a significantly (p < 0.05) greater reduction in the postoperative PAP (46/19, mean 28 mm Hg vs 59/23, mean 35 mm Hg) and PVR (271 +/- 172 vs 399 +/- 154 dynes/s/cm(-5)) compared with the redo group. No substantial difference in morbidity or functional outcomes was observed between groups. CONCLUSIONS: Reoperative PTE can be performed with a perioperative risk comparable with primary PTE, although the improvement in pulmonary hemodynamics is not as favorable. Bilateral primary operation, effective caval filtration, and vigilant anticoagulant management would prevent the need for most reoperative PTEs.

Adult↗

Mutational analysis of an RNA recognition element that mediates localization of bicoid mRNA.

Localization signals are RNA regulatory elements that direct the localization of mRNAs to subcellular sites. Localization signals presumably function by mediating RNA recognition events through which the mRNA becomes associated with the localization machinery. At present little is known about individual RNA recognition events, which in turn has limited progress in identifying the trans-acting binding factors involved in these events. Here we describe a detailed characterization of the RNA elements required for the RNA recognition event, event A, that initiates localization of bicoid mRNA in the Drosophila ovary. One element is a helix in which nucleotide identities are not important, suggesting that it plays a primarily structural role. Immediately adjacent to the helix is a recognition domain in which the identities of some, but not all, nucleotides are important for function. Comparison of two related but different RNAs that both support recognition event A further defines the important features of the recognition domain.

Animals↗