Showing papers by "William Wallace published in 2011"

A validated model of serum anti-Mullerian hormone from conception to menopause

Abstract: Background: Anti-Mullerian hormone (AMH) is a product of growing ovarian follicles. The concentration of AMH in blood may also reflect the non-growing follicle (NGF) population, i.e. the ovarian reserve, and be of value in predicting reproductive lifespan. A full description of AMH production up to the menopause has not been reported. Methodology/Principal Findings: By searching the published literature for AMH concentrations in healthy pre-menopausal females, and using our own data (combined n = 3,260) we have generated and robustly validated the first model of AMH concentration from conception to menopause. This model shows that 34% of the variation in AMH is due to age alone. We have shown that AMH peaks at age 24.5 years, followed by a decline to the menopause. We have also shown that there is a neonatal peak and a potential pre-pubertal peak. Our model allows us to generate normative data at all ages. Conclusions/Significance: These data highlight key inflection points in ovarian follicle dynamics. This first validated model of circulating AMH in healthy females describes a transition period in early adulthood, after which AMH reflects the progressive loss of the NGF pool. The existence of a neonatal increase in gonadal activity is confirmed for females. An improved understanding of the relationship between circulating AMH and age will lead more accurate assessment of ovarian reserve for the individual woman.

Abdominal aortic aneurysm growth predicted by uptake of ultrasmall superparamagnetic particles of iron oxide: a pilot study.

Abstract: Background— Abdominal aortic aneurysms are a major cause of death. Prediction of aneurysm expansion and rupture is challenging and currently relies on the simple measure of aneurysm diameter. Using MRI, we aimed to assess whether areas of cellular inflammation correlated with the rate of abdominal aortic aneurysm expansion. Methods and Results— Stable patients (n=29; 27 male; age, 70±5 years) with asymptomatic abdominal aortic aneurysms (4.0 to 6.6 cm) were recruited from a surveillance program and imaged using a 3-T MRI scanner before and 24 to 36 hours after administration of ultrasmall superparamagnetic particles of iron oxide (USPIO). The change in T2* value on T2*-weighted imaging was used to detect accumulation of USPIO within the abdominal aortic aneurysm. Histological examination of aneurysm tissue confirmed colocalization and uptake of USPIO in areas with macrophage infiltration. Patients with distinct mural uptake of USPIO had a 3-fold higher growth rate (n=11, 0.66 cm/y; P =0.020) than those with no (n=6, 0.22 cm/y) or nonspecific USPIO uptake (n=8, 0.24 cm/y) despite having similar aneurysm diameters (5.4±0.6, 5.1±0.5, and 5.0±0.5 cm, respectively; P >0.05). In 1 patient with an inflammatory aneurysm, there was a strong and widespread uptake of USPIO extending beyond the aortic wall. Conclusions— Uptake of USPIO in abdominal aortic aneurysms identifies cellular inflammation and appears to distinguish those patients with more rapidly progressive abdominal aortic aneurysm expansion. This technique holds major promise as a new method of risk-stratifying patients with abdominal aortic aneurysms that extends beyond the simple anatomic measure of aneurysm diameter. Clinical Trial Registration— URL: . Unique identifier: [NCT00794092][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00794092&atom=%2Fcirccvim%2F4%2F3%2F274.atom

Accuracy of cell typing in nonsmall cell lung cancer by EBUS/EUS–FNA cytological samples

Abstract: Endoscopic ultrasound-guided transbronchial or transoesophageal lymph node aspiration is increasingly used as a method of diagnosing nonsmall cell carcinoma. Data validating the accuracy of cell typing of nonsmall cell carcinoma using these cytological samples has not been assessed. 23 samples were identified in Edinburgh, UK and a further 25 in Cambridge, UK, with matching histological samples. The morphological cell type, as assessed on the cytological preparations and cell blocks, was recorded and immunohistochemical staining was performed, where possible, as an adjunct. The final cell type, as assessed by morphology with or without immunohistochemistry, was correlated with that reported in the paired histological samples. Cell blocks with tumour were available in 39 out of 48 cases. The accuracy of cell typing when no cell block was available was four out of nine cases. This increased to 25 out of 39 when a cell block was available, increasing to 33 out of 39 with the addition of immunohistochemistry. The overall accuracy of classification was 37 out of 48 cases. Accurate cell typing of nonsmall cell carcinomas can be performed using endoscopically derived fine-needle aspirates. The importance of obtaining sufficient material for the production of cell blocks is critical in allowing optimal assessment.

Pathobiology and prevention of cancer chemotherapy-induced bone growth arrest, bone loss, and osteonecrosis.

Abstract: Cancer chemotherapy has been recognized as one severe risk factor that influences bone growth and bone mass accumulation during childhood and adolescence. This article reviews on the importance of this clinical issue, current understanding of the underlying mechanisms for the skeletal defects and potential preventative strategies. Both clinical and basic studies that appeared from 1990 to 2010 were reviewed for bone defects (growth arrest, bone loss, osteonecrosis, and/or fractures) caused by paediatric cancer chemotherapy. As chemotherapy has become more intensive and achieved greater success in treating paediatric malignancies, skeletal complications such as bone growth arrest, low bone mass, osteonecrosis, and fractures during and/or after chemotherapy have become a problem for some cancer patients and survivors particularly those that have received high dose glucocorticoids and methotrexate. While chemotherapy-induced skeletal defects are likely multi-factorial, recent studies suggest that different chemotherapeutic agents can directly impair the activity of the growth plate and metaphysis (the two major components of the bone growth unit) through different mechanisms, and can alter bone modeling/remodeling processes via their actions on bone formation cells (osteoblasts), bone resorption cells (osteoclasts) and bone "maintenance" cells (osteocytes). Intensive use of multi-agent chemotherapy can cause growth arrest, low bone mass, fractures, and/or osteonecrosis in some paediatric patients. While there are currently no specific strategies for protecting bone growth during childhood cancer chemotherapy, regular BMD monitoring and exercise are have been recommended, and possible adjuvant treatments could include calcium/vitamin D, antioxidants, bisphosphonates, resveratrol, and/or folinic acid.

Sarcoidosis complicating treatment with natalizumab for Crohn's disease

Abstract: Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.

Evaluation of adjunct immunohistochemistry on reporting patterns of non-small cell lung carcinoma diagnosed histologically in a regional pathology centre.

Abstract: Morphological sub-classification of non-small cell carcinoma in small biopsy specimens presents difficulties for pathologists and recent advances in chemotherapy have resulted in increased pressure to more robustly differentiate between squamous carcinoma and adenocarcinoma. The results of audits examining classification of non-small cell lung carcinoma by pathologists working in a specialist team within a regional centre and the effect of introducing adjunct immunohistochemistry into the reporting pathway are presented. It is concluded that the use of a limited immunohistochemical panel substantially reduces the number of cases when a specific cell type cannot be identified or ‘favoured’ (34% to 6%) and that the classification obtained correlates well with that found in subsequent resection specimens. In addition the introduction of immunohistochemistry substantially reduces the variability in reporting practice between pathologists.

Oxford Desk Reference - Obstetrics and Gynaecology

Abstract: This irreplaceable reference compiles the most up-to-date and relevant material on obstetrics and gynecology into one volume. Strongly evidence-based, it includes the latest knowledge and guidelines from a wide range of sources and contains the key recommendations that a practicing obstetrician or gynecologist needs to know; presenting them in a uniform and accessible way, allowing for quick diagnosis and optimal care.

Cytological recognition of herpes simplex virus infection in bronchoscopic samples from the respiratory tract

Abstract: Cytological features suggesting herpes simplex virus (HSV) infection in samples obtained at bronchoscopy have been described only very rarely in routinely processed samples. We report four cases where evidence of HSV infection was identified morphologically in samples processed using thin-layer techniques, with polymerase chain reaction confirmation of the presence of virus in three cases. We suggest that the increased morphological clarity provided by this technique for processing these cytology samples may result in the morphological features of viral infection being seen more frequently. Pathologists reporting such samples need to be aware of this possibility in order to avoid potential misinterpretations. In addition, however, respiratory and intensive care physicians unused to receiving cytology reports indicating 'HSV infection' need to be aware that the significance is uncertain and in most cases it is likely to indicate the reactivation of a latent infection.

Pathology of lung tumours

Abstract: Lung cancer is a major cause of morbidity and mortality. Approaches to diagnosis and management are evolving, based on both technological and scientific advances. In the UK setting, patient management is determined by a multidisciplinary team (MDT). A basic understanding of the classification of lung tumours, and the approaches to their pathological diagnosis is important for all those involved in the lung cancer MDT. To this end, we present an overview of the current World Health Organization classification of lung tumours, briefly discuss the aetiology and pathogenesis, and then describe pathological aspects of the diagnosis and staging of lung cancer.