tbuckley/cabot-search huggingface dataset:
Urological surgery
Authors: N. Harrison
Journal: BMJ (1998)

Over 2,000 years ago Hippocrates recognised the value of specialist surgical skills: “I shall not cut for stone but leave it to those who are specialist in the art.” Just over 50 years ago, 66 surgeons formed the British Association of Urological Surgeons, and today the specialty's separation from general surgery is complete, consultant expansion continues, and many of the 470 consultant urologists in the United Kingdom are developing subspecialty interests within urology (uro-oncology, reconstruction, endourology, andrology, female urology, neurourology, and paediatric urology).

Few enter medical school knowing they want to be surgeons, yet alone urologists, and most are drawn to the specialty only after experiencing it as a house surgeon or senior house officer. They are attracted to its breadth of pathology; its combination of surgical skills, both endoscopic and open, and technology; its diagnostic precision; and the positive impact it can make on patients' lives - it has been called “a compassionate specialty.”

The minimum entry requirements for the specialty are completion of two years of basic surgical training in recognised posts and the MRCS or AFRCS. Competition for specialist registrar posts is intense, and most trainees find they need to spend at least a further year at senior house officer level or acquire some research experience before they become sufficiently competitive to get a specialist registrar post.

Each of the 15 deaneries in England and Wales, Scotland, Northern Ireland, and the Republic of Ireland have training programmes in urology which conform to the curriculum and standards set by the surgical royal colleges through the Specialist Advisory Committee in Urology. Smaller programmes may have only seven or eight trainees, while larger ones have over 30, divided into a number of rotations.

The specialist registrar training programme lasts five years, of …
Chronic cough and wheeze in children: do they all have asthma?
Authors: M Seear, D Wensley
Journal: European Respiratory Journal (1997)

In the experience of both authors, children referred for investigation of a chronic productive cough often do not fit conventional diagnostic categories. The aim of this study was to answer two questions: 1) do such diagnostic orphans exist? and, 2) if so, can they be classified in a clinically useful manner? Eighty one previously undiagnosed children referred with a history of more than 3 months productive or rattly cough were studied prospectively. Investigations consisted of a detailed history, physical examination, and an extensive set of clinical investigations. Sixty randomly selected asthmatic children served as demographic controls. Children fell into three groups: 23 had newly diagnosed conditions, such as cystic fibrosis, or were indistinguishable from asthma; 24 had a history of major medical interventions (cardiac surgery, chemotherapy, tracheo-oesophageal fistula repair); 34 had a history of significant early respiratory tract infections, usually combined with poor social conditions. The latter group differed significantly from asthmatic controls in a wide range of demographic and clinical comparisons. Native American children were overrepresented. The results of this study suggest that early respiratory insults (whether viral or medical) can induce self-perpetuating inflammation, manifesting as a chronic productive cough and intermittent wheeze. The associations between poverty and infant chest infections or early invasive medical treatment with subsequent chronic respiratory disease are clearly definable and probably justify diagnostic terms distinct from asthma, particularly for use in epidemiological studies.
Symptoms of Common Maternal Infections in Pregnancy and Risk of Islet Autoimmunity in Early Childhood
Authors: Lars C. Stene, Katherine Barriga, Jill M. Norris, Michelle Hoffman, Georgeanna Klingensmith, Henry A. Erlich, George S. Eisenbarth, Marian Rewers
Journal: Diabetes Care (2003)

OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age ≤15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3–15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD65, insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity. RESULTS—Children whose mother reported at least one symptom of infection during pregnancy (mostly respiratory or gastrointestinal) had a significantly lower risk of islet autoimmunity compared with other children (hazard ratio 0.48; 95% CI 0.27–0.83). After stratification, the association appeared among girls (0.21; 0.09–0.48) but not among boys (1.09; 0.47–2.51) with a P value for interaction of 0.005. Symptoms of neonatal infections, early daycare attendance, exposure to cats or dogs, and household crowding were not related to islet autoimmunity. CONCLUSIONS—Symptoms of maternal infections in pregnancy predicted a significantly lower risk of islet autoimmunity in young girls, suggesting a protective effect of such infections.
Abstract 4431: N-terminal portion of β-catenin is important in ISGylation of β-catenin by 90K glycoprotein in colorectal cancer cells
Authors: Somy Yoon, Jeong A Bae, Hangun Kim, Kyung-Sub Moon, Kyung Keun Kim
Journal: Cancer Research (2014)

Abstract β-catenin is a major transducer in Wnt signaling pathway, which is highly expressed in colorectal and other cancers. Previously, we have shown that β-catenin is down-regulated in colorectal cancer cells by glycoprotein, 90K, through ISGylation-dependent ubiquitination. The aim of this study is to further clarify a novel mechanism of β-catenin down-regulation pathway by 90K glycoprotein. To identify ISGylation site of β-catenin, deletion mutants of β-catenin lacking N- or C-terminal domain were employed. As only two lysine residues, K19 and K49, are reside in N-terminus of β-catenin, we sequenced cDNA of β- catenin from paired human colorectal cancer tissues to find the mutation and generated arginine point-mutation. As a result, there is no mutation on K19 and/or K49 in examined specimens and did not affect the 90K-mediated ISGylational degradation. To rule out the possibility of involving non-lysine residue in the ISG15 conjugation, such as serine or threonine, we constructed several deletion mutants and found that none are responsible for the ISG15 conjugation. Now, N-terminal portion of β-catenin is under screening for possible interactions with putative E3 ligases, and further detailed studies delineating the complex formation among ISG15 and β-catenin/E3 ligases are under way. Citation Format: Somy Yoon, Jeong A Bae, Hangun Kim, Kyung-Sub Moon, Kyung Keun Kim. N-terminal portion of β-catenin is important in ISGylation of β-catenin by 90K glycoprotein in colorectal cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4431. doi:10.1158/1538-7445.AM2014-4431
Low Ankle-Brachial Pressure Index Predicts Increased Risk of Cardiovascular Disease Independent of the Metabolic Syndrome and Conventional Cardiovascular Risk Factors in the Edinburgh Artery Study
Authors: Sarah H. Wild, Christopher D. Byrne, Felicity B. Smith, Amanda J. Lee, F. Gerald R. Fowkes
Journal: Diabetes Care (2006)

To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors.The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for approximately 15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55-74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors.We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1-2.1) for CVD mortality and 1.5 (1.2-1.8) for all CVD outcomes.Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.
Crossreactions of Escherichia coli K and O polysaccharides in antipneumococcal and anti-Salmonella sera.
Authors: M Heidelberger, K Jann, B Jann
Journal: The Journal of Experimental Medicine (1985)

Crossreactions of 24 K polysaccharides and 4 O polysaccharides of E. coli in antisera to 27 pneumococcal types, 3 anti-Salmonella sera, and anti-Klebsiella Kl serum are discussed in relation to structural features of the polysaccharides insofar as these are known. Predictions based on the crossprecipitations are also ventured for several instances in which structures are as yet undetermined.
MDR, XDR, TDR tuberculosis: ominous progression
Authors: Zarir F Udwadia
Journal: Thorax (2012)

> Any man's death diminishes me because I am involved in mankind, and therefore never send to know for whom the bell tolls; it tolls for thee… (John Donne, Meditation XV11) 

> The growing TB epidemic is no longer an emergency only for those who care about health, but also for those who care about justice. (P D O Davies) 

For 2 weeks in January, India coughed and the rest of the world paid attention. Drug-resistant tuberculosis (TB), languishing from a decade of neglect by the Indian Revised National Tuberculosis Control Program (RNTCP), was headline news in every Indian newspaper and several international ones as well.

What captured local and international attention was a report documenting the isolation of the first cases of totally drug resistant TB (TDR-TB) from India.1 The Indian government's response, after initial denial, swung from the ridiculous to the sublime. The WHO response was far more measured and authoritative. Paul Nunn, coordinator of WHO's STOP TB department in Geneva, described the cases as “a wake up call for countries to accelerate provision of proper care, particularly for multi drug-resistant patients”. Within a week WHO had a TDR link on its website with answers to frequently asked questions, was planning a new consensus definition of TDR-TB, and had planned an expert meeting to rethink strategy.

TB exists on an epic scale in India. It resolutely remains India's biggest public health problem. India bears a disproportionately large burden of the world's TB, one a developing country can ill afford, with an estimated economic loss of US $43 billion and 100 million productive days lost annually directly due to this disease. The facts speak for themselves: India is the highest TB burden country in the world with 300 million Indians infected, accounting for 21% …
Facial Soft-Tissue Fillers: Assessing the State of the Science conference---Proceedings report
Authors: C. William Hanke, Rod J. Rohrich, Mariano Busso, Alastair Carruthers, Jean Carruthers, Steven Fagien, Rebecca Fitzgerald, Richard Glogau, Phyllis E. Greenberger, Z. Paul Lorenc, Ellen S. Marmur, Gary D. Monheit, Andrea Pusic, Mark G. Rubin, Berthold Rzany, Anthony Sclafani, Susan Taylor, Susan Weinkle, Michael F. McGuire, David M. Pariser, Laurie A. Casas, Karen J. Collishaw, Roger A. Dailey, Stephen C. Duffy, Elizabeth Jan Edgar, Barbara L. Greenan, Kelly Haenlein, Ronald A. Henrichs, Keith M. Hume, Flora Lum, David R. Nielsen, Lisle Poulsen, Lori Shoaf, William Seward, Wendy Smith Begolka, Robert G. Stanton, Katherine J. Svedman, J. Regan Thomas, Jonathan M. Sykes, Carol Wargo, Robert A. Weiss
Journal: Journal of the American Academy of Dermatology (2011)
Engrailed-2 (EN2): A Tumor Specific Urinary Biomarker for the Early Diagnosis of Prostate Cancer
Authors: Richard Morgan, Angela Boxall, Aagna Bhatt, Michael Bailey, Richard Hindley, Stephen Langley, Hayley C. Whitaker, David E. Neal, Mohammed Ismail, Hamish Whitaker, Nicola Annels, Agnieszka Michael, Hardev Pandha
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Prostate cancer (PC) is the second most common cause of cancer related death in men. A number of key limitations with prostate specific antigen (PSA), currently the standard detection test, has justified evaluation of new biomarkers. We have assessed the diagnostic potential of Engrailed-2 (EN2) protein, a homeodomain-containing transcription factor expressed in PC cell lines and secreted into the urine by PC in men. Experimental Design: EN2 expression in PC cell lines and prostate cancer tissue was determined by semi-quantative RT-PCR and immunohistochemistry. First pass urine [without prior digital rectal examination (DRE)] was collected from men presenting with urinary symptoms (referred to exclude/confirm the presence of prostate cancer) and from controls. EN2 protein was measured by ELISA in urine from men with PC (n = 82) and controls (n = 102). Results: EN2 was expressed and secreted by PC cell lines and PC tissue but not by normal prostate tissue or stroma. The presence of EN2 in urine was highly predictive of PC, with a sensitivity of 66% and a specificity of 88.2%, without requirement for DRE. There was no correlation with PSA levels. These results were confirmed independently by a second academic center. Conclusions: Urinary EN2 is a highly specific and sensitive candidate biomarker of prostate cancer. A larger multicenter study to further evaluate the diagnostic potential of EN2 is justified. Clin Cancer Res; 17(5); 1090–8. ©2011 AACR.
Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules.
Authors: T P Schaub, J Kartenbeck, J König, O Vogel, R Witzgall, W Kriz, D Keppler
Journal: Journal of the American Society of Nephrology (1997)

A novel ATP-dependent export pump for amphiphilic anionic conjugates, which has been cloned recently from liver, was identified in rat kidney and localized to the apical membrane domain of proximal tubule epithelia. This 190-kD membrane glycoprotein (Mrp2) has been described previously as the hepatocyte canalicular isoform of the multidrug resistance protein and as the canalicular multispecific organic anion transporter. Mrp2 was identified in kidney by reverse transcription PCR followed by sequencing of the amplified 786-bp fragment and by immunoblotting, using an antibody specifically reacting with the carboxy terminus of rat Mrp2. Double immunofluorescence and confocal laser-scanning microscopy showed the presence of Mrp2 in the brush-border membrane domain of segments S1, S2, and S3 of proximal tubule epithelia. Mrp2 was not detectable in other segments of the nephron. The onset of Mrp2 expression during development occurred in a very early stage of nephron development. Mrp2 represents the first cloned ATP-dependent export pump for amphiphilic organic anions identified in kidney and localized to the apical membrane domain of proximal tubule epithelia. Mrp2 may contribute to cellular detoxification and to the secretion of endogenous and xenobiotic anionic substances, most of which are conjugates, from the blood into urine.
Assessment of Hormone Dependence of Comedo Ductal Carcinoma In Situ of the Breast
Authors: P. A. Holland, A. D. Baildam, N. J. Bundred, W. F. Knox, C. S. Potten, A. Howell, E. Anderson
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Ductal carcinoma in situ (DCIS) represents 20%-30% of breast cancers detected by clinical screening (i.e., mammography). More than 50% of DCIS lesions may be estrogen receptor negative and, therefore, hormone independent. However, the role of estrogen in the natural history of DCIS is unknown. Purpose: A novel in vivo (i.e., xenograft) model was developed to determine to what degree DCIS lesions depend on estrogen for growth. Methods: Specimens of breast tissue were collected from 52 women during diagnostic or therapeutic surgical procedures. Portions of each specimen were randomly selected and analyzed by histology and thymidine labeling (to measure cell proliferation). The remainder of each specimen was implanted into five to 18 athymic BALB/c nu/nu mice (depending on the amount of tissue available), with eight pieces of approximately 2 mm × 2 mm × 1 mm implanted at different locations on the back of each mouse. Half of the mice received implants containing estrogen (2 mg 17β-estradiol), and the other half received placebo implants. Levels of cell proliferation in xenografts, recovered after 14, 28, 42, or 56 days in the mice, were measured by thymidine labeling or by immunohistochemistry through use of an antibody specific for the Ki-67 nuclear antigen. Immunohistochemistry was also used to measure the levels of estrogen receptor in the tissue specimens. Serum 17β-estradiol levels in the mice were measured by radioimmunoassay. Results: Initial levels of cell proliferation were approximately 10-fold higher in 10 specimens with estrogen receptor-negative, comedo (i.e., more malignant in appearance) DCIS than in four specimens with estrogen receptor-positive DCIS (mean proliferation indices: 22% versus 1.9%, respectively; two-sided P <.001). Xenografts from the majority of specimens survived up to 56 days in the mice and maintained good architectural and cellular preservation. Estrogen treatment of the xenograft-bearing mice had no effect on the high level of cell proliferation observed in estrogen receptor- negative, comedo DCIS specimens (two-sided P = .89). In contrast, increased levels of cell proliferation in response to estrogen supplementation were measured in three estrogen receptor- positive, noncomedo DCIS specimens (two-sided P <.001). However, even with estrogen treatment, cell proliferation levels in estrogen receptorpositive DCIS specimens did not reach those seen in estrogen receptornegative DCIS specimens. Conclusion and Implication: Estrogen receptornegative, comedo DCIS lesions appear to be estrogen independent; therefore, antiestrogen (e.g., tamoxifen) therapy may not benefit patients with comedo DCIS.
Identifying some determinants of “jet lag” and its symptoms: a study of athletes and other travellers
Authors: J Waterhouse, B Edwards, A Nevill, S Carvalho, G Atkinson, P Buckley, T Reilly, R Godfrey, R Ramsay
Journal: British Journal of Sports Medicine (2002)

Travelling across multiple time zones disrupts normal circadian rhythms and induces "jet lag". Possible effects of this on training and performance in athletes were concerns before the Sydney Olympic Games.To identify some determinants of jet lag and its symptoms.A mixture of athletes, their coaches, and academics attending a conference (n = 85) was studied during their flights from the United Kingdom to Australia (two flights with a one hour stopover in Singapore), and for the first six days in Australia. Subjects differed in age, sex, chronotype, flexibility of sleeping habits, feelings of languor, fitness, time of arrival in Australia, and whether or not they had previous experience of travel to Australia. These variables and whether the body clock adjusted to new local time by phase advance or delay were tested as predictors for jet lag and some of its symptoms by stepwise multiple regression analyses.The amount of sleep in the first flight was significantly greater in those who had left the United Kingdom in the evening than the morning (medians of 5.5 hours and 1.5 hours respectively; p = 0.0002, Mann-Whitney), whereas there was no significant difference on the second flight (2.5 hours v 2.8 hours; p = 0.72). Only the severity of jet lag and assessments of sleep and fatigue were commonly predicted significantly (p<0.05) by regression analysis, and then by only some of the variables. Thus increasing age and a later time of arrival in Australia were associated with less jet lag and fatigue, and previous experience of travel to Australia was associated with an earlier time of getting to sleep. Subjects who had adjusted by phase advance suffered worse jet lag during the 5th and 6th days in Australia.These results indicate the importance of an appropriate choice of itinerary and lifestyle for reducing the negative effects of jet lag in athletes and others who wish to perform optimally in the new time zone.
Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment.
Authors: M Breban, R E Hammer, J A Richardson, J D Taurog
Journal: The Journal of Experimental Medicine (1993)

We have previously produced lines of rats transgenic for HLA-B27 and human beta 2-microglobulin (h beta 2m) that develop a progressive inflammatory disease sharing many clinical and histologic features with the B27-associated human spondyloarthropathies, including gut and male genital inflammation, arthritis, and psoriasiform skin lesions. Other transgenic lines that express lower levels of B27 and h beta 2m remain healthy. To investigate the cellular basis for the multisystem inflammatory disease in these rats, we transferred lymphoid cell populations from disease-prone transgenic lines to irradiated disease-resistant transgenic and nontransgenic recipients. In recipients of cells from two different disease-prone lines, successful transfer required engraftment of bone marrow cells. Transfer of disease with fetal liver cells suggested that neither mature effector cells nor active disease in the donors was necessary for induction of disease in the recipients. Remission of the spontaneous disease in irradiated transgenic rats was induced by engraftment of nontransgenic bone marrow. These results suggest that the expression of HLA-B27 in bone marrow-derived cells alone is sufficient for the development of B27-associated disease, and that disease transfer requires engraftment of a bone marrow precursor cell for which mature cells in spleen or in lymph node cannot substitute.