tbuckley/cabot-search huggingface dataset:
Reliability and effectiveness of screening for hearing loss in high risk neonates.
Authors: R. J. McClelland, D. R. Watson, V. Lawless, H. G. Houston, D. Adams
Journal: BMJ (1992)

OBJECTIVE--To establish the reliability and effectiveness of screening for hearing loss by brainstem auditory evoked potential testing in high risk neonates. DESIGN--Seven year investigation of newborn babies admitted to a special care baby unit and monitored through a regional children9s audiology unit. SETTING--Special care baby unit and children9s audiology department, Belfast. SUBJECTS--405 neonates admitted to the baby unit, during 1 October 1982 to 31 March 1987. MAIN OUTCOME MEASURES--Presence of hearing impairment, type and severity of hearing impairment, mortality. RESULTS--85 children failed the screening test, 62 of whom were followed up. Five children had severe bilateral sensorineural impairment and 12 had conductive impairment requiring surgical intervention. A further 18 had severe neurological disorder detected. The sensitivity of screening was 100% and specificity was 88%. If the procedure was introduced into routine clinical practice the mean age at diagnosis for all children with severe perinatal hearing impairment would be 11 (median 1) months. The mean age at diagnosis with the health visitor screening service was 23 (19) months (difference 10 months, 95% confidence interval 6 to 16 months; p &lt; 0.0001). CONCLUSION--Screening for hearing loss in high risk neonates is highly reliable and cost effective. It also provides valuable neurophysiological information. Routine testing of these infants would result in over half of all children with severe bilateral perinatal sensorineural hearing impairment being identified by 2 months of age. This would make an important contribution to the habilitation of this socially, emotionally, and educationally vulnerable group.
Heterogeneity of plasma glucagon. Circulating components in normal subjects and patients with chronic renal failure.
Authors: S F Kuku, J B Jaspan, D S Emmanouel, A Zeidler, A I Katz, A H Rubenstein
Journal: Journal of Clinical Investigation (1976)

Plasma immunoreactive glucagon (IRG) concentrations were measured in 36 patients with chronic renal failure (CRF) and 32 normal subjects. In addition, the components of circulating IRG were analyzed by gel filtration in the fasting state and after physiological stimuli. Fasting IRG was elevated (P less than 0.001) in CRF patients (534 +/- 32 pg/ml) compared with the levels found in healthy subjects (113 +/- 9 pg/ml). Oral glucose suppressed plasma IRG in CRF patients from a basal level of 568 +/- 52 to a nadir of 354 +/- 57 pg/ml (120 min). This degree of suppression (38%) was comparable to that found in normal subjects (basal = 154 +/- 20 to 100 +/- 23 pg/ml) at 120 min (35%). Intravenous infusion of arginine (250 mg/kg) resulted in a 71% rise in IRG in CRF patients and a 166% increase in normal subjects. Gel filtration of fasting plasma from CRF patients showed three major peaks. The earliest (A) was found in the void volume (mol wt greater than 40,000) and constituted 16.5 +/- 4.7% of the elution profile. The middle peak (B) eluted just beyond the proinsulin marker (approximately 9,000 mol wt) and constituted the largest proportion of the elution profile (56.5 +/- 3.4%). The third peak (C) coincided with the standard glucagon and [125I]glucagon markers (3,485 mol wt) and comprised 27.0 +/- 4% of the IRG profile. In contrast, only peaks A and C were found in fasting plasma of normal subjects (53.6 +/- 10.4% in A and 46.4 +/- 10.4 in C). After oral glucose, glucagon immunoreactivity in the 3,500 mol wt peak (C) was markedly suppressed, while the B peak in patients with CRF declined to a lesser extent. The A peak in both groups was unchanged. After an arginine infusion only the C peak increased in both groups of subjects. Gel filtration of plasma in 3 M acetic acid gave similar profiles to those obtained in glycine albumin buffer. Exposure of serum to trypsin indicated that the B and C peaks were digestible, while the A peak was resistant to the action of the enzyme. In one sample, peak C increased after a 2-h exposure of serum to trypsin. We conclude that circulating IRG in normal subjects and patients with CRF is heterogenous. The hyperglucagonemia of renal failure is largely due to an increase in IRG material of approximately 9,000 mol wt, consistent with proglucagon, although the 3,500 mol wt component is also considerably elevated (threefold). The significance of circulating IRG levels should be interpreted with caution until the relative biological activity of the three components is established.
Risk factors for poor performance status in cancer patients: A multivariate analysis in 3,585 patients
Authors: R. Nair, M. Shirodkar, M. Mallath, A. D’Cruz, P. Shukla, R. Mistry
Journal: Journal of Clinical Oncology (2008)

9628 Background: Poor performance status (PPS) is an important determinant of clinical outcomes in cancer patients. Few studies have attempted to identify independent risk factors associated with PPS. Our aim was to identify independent risk factors for PPS. Methods: A prospective observational study was done. All patients referred to our Clinical Nutrition Service in 2006 and 2007 were interviewed by research dieticians using structured questionnaire. Continious and categorical data pertaining to multiple risk factors were collected from each patient and was collated into a database. Malnutrition was graded by the Subjective Global Assessment (SGA) and performance status was graded by the ECOG scale. Multivariate analysis was performed to identify independent risk factors for PPS after converting the ECOG scores in to dichotomous variables: Good PS (ECOG-0&1) and PPS (ECOG 2–4). Results: There were 2,373 men and 1,382 women aged 1 to 95 (median 52) years. Cancer sites included: Hemato-lymphoid (121), breast (225), head and neck (1,096), GI- Tract (1,451), thorax (608), uterus and ovary (117), urinary (61) and other sites (76). Univariate analysis revealed a strong association of PPS and malnutrition [SGA-C (OR=153.7) and SGA-B (OR=17.2)]. Significant risk factors for PPS and their odds ratio by multivariate analysis in 3585 patients were: SGA-C (17.8); reduced food intake (4.1); SGA-B (2.6); age > 65 years (1.90; moderate weight loss (1.9); albumin<3.1 G/dl (1.8); BMI <20.0 Kg/M2 (1.3); male gender (0.7) and private care (0.7) (p<0.003). Several variables such as hemoglobin <10.0 G/dl, co-morbid illness, tobacco use, vegetarian and previous cancer treatments that were significant on univariate analysis, were not found to have significant association with PPS in the multivariate regression model. Conclusions: PPS is associated with several independent risk factors many of which are amenable for treatment. Moderate to severe anemia was not associated with PPS and may be a marker of malnutrition. The SGA scores have strong association with the ECOG scores and needs to be evaluated for its usefulness in identifying patients at risk well as in predicting clinical outcomes such as overall survival in future trials. No significant financial relationships to disclose.
Quality-adjusted life-years. Ethical implications for physicians and policymakers
Authors: J. La Puma
Journal: JAMA (1990)

Quality-adjusted life-years have been used in economic analyses as a measure of health outcomes, one that reflects both lives saved and patients' valuations of quality of life in alternative health states. The concept of "cost per quality-adjusted life year" as a guideline for resource allocation is founded on six ethical assumptions: quality of life can be accurately measured and used, utilitarianism is acceptable, equity and efficiency are compatible, projections of community preferences can substitute for individual preferences, the old have less "capacity to benefit" than the young, and physicians will not use quality-adjusted life-years as clinical maxims. Quality-adjusted life-years signal two shifts in the locus of control and the nature of the clinical encounter: first, formal expressions of community preferences and societal usefulness would counterbalance patient autonomy, and second, formal tools of resource allocation and applied decision analysis would counterbalance the use of clinical judgment. These shifts reflect and reinforce a new financial ethos in medical decision making. Presently using quality-adjusted life-years for health policy decisions is problematic and speculative; using quality-adjusted life-years at the bedside is dangerous.The quality adjusted life year (QALY) has been developed as a measure of health outcomes that reflects both lives saved and the values patients place on quality of life in alternative health states. QALYs represent a progression in the cost-effectiveness analysis of health care, and serious ethical questions have been raised about their use in allocation of health resources and in medical decision making. La Puma and Lawlor review the methodology and historical development of QALYs and attempt to identify the ethical issues they present. They regard current interest in QALYs as signaling shifts in the locus of control and the nature of the clinical encounter, shifts that reflect and reinforce the new "financial ethos" in health policy planning and in medical decision making.
Changes in Serum Lipid Levels During Pregnancy in Type 1 and Type 2 Diabetic Subjects
Authors: Christian S. Göbl, Ammon Handisurya, Katharina Klein, Latife Bozkurt, Anton Luger, Dagmar Bancher-Todesca, Alexandra Kautzky-Willer
Journal: Diabetes Care (2010)

Alterations in maternal lipid metabolism could affect fetal programming and the susceptibility for atherosclerosis in the offspring; therefore, we studied differences in lipid profiles of pregnant women with type 1 and type 2 diabetes.A total of 173 diabetic pregnancies were studied prior to conception (V0), at each trimester (V1-V3), and after delivery and were compared with 137 healthy women at V3.During gestation, the increase in serum lipid concentrations was less pronounced in type 2 diabetic subjects. At V3, the lipid levels of type 1 diabetic women with normal glucose tolerance were similar but significantly higher then those of type 2 diabetic women. Elevated triglycerides and low HDL cholesterol at V3 were significant predictors for large-for-gestational-age (LGA) newborns.Our data suggest smaller changes in serum lipid concentrations during pregnancy in type 2 diabetic mothers. Additionally, we found a positive association between maternal triglycerides and LGA infants independently of chronic glycemic control.
Reducing investigation time for the diagnosis of the obstructive sleep apnoea syndrome (OSAS) by combining oximetry with a screening algorithim
Authors: John Benjamin, Ritesh Chaube, Chinappa Narendra
Journal: European Respiratory Journal (2011)

Introduction: Oximetry and limited channel sleep studies (LCSS) for the diagnosis of OSAS have sensitivities of 87% and 82-94% respectively and specificities of 65% and 82-100% respectively [1]; implying that oximetry is useful for confirming OSAS in high probability patients but not at ruling it out. LCSS seems useful for both. However,the average time taken for oximetry is 15 minutes compared with 75 minutes for LCSS. (Average times were pooled form 5 Welsh sleep centres). We proposed an investigative approach that combined a screening algorithm [2] that would allocate high probablity patients to oximetry and low probability patients to LCCS. High probability subjects with negative oximetry also proceeded to LCSS.

View this table:

Screening Algorithim





Methods: We recruited consecutive sleep referrals over a 5 month period. We compared the total and average time taken with this algorithim against a strategy (control arm) of LCSS for every patient. The study was powered for 50 patients, 30 had been recruited to date.

Results: N=30. Median age 53 years, 19 were male.See table for results; average time saving – 24.5 minutes per patient.

View this table:



Conclusion: We propose that allocating high probability subjects to oximetry and using LCSS for low probability subjects and for oximetry negative high probability subjects results in significant time and resource savings.

References: 

*   1. Flemons WW,et al.Chest 2003;124:1543-1579.

*   2. Netzer NC,et al.Ann Int Med 1989;131:485-491.
Downregulation of the Novel Tumor Suppressor DIRAS1 Predicts Poor Prognosis in Esophageal Squamous Cell Carcinoma
Authors: Ying-Hui Zhu, Li Fu, Leilei Chen, Yan-Ru Qin, Haibo Liu, Fajun Xie, Tingting Zeng, Sui-Sui Dong, Jiangchao Li, Yan Li, Yongdong Dai, Dan Xie, Xin-Yuan Guan
Journal: Cancer Research (2013)

Loss of chromosome 19p is one of the most frequent allelic imbalances in esophageal squamous cell carcinoma (ESCC), suggesting the existence of one or more tumor suppressor genes within this region. In this study, we investigated a role in ESCCs for a candidate tumor suppressor gene located at 19p13.3, the Ras-like small GTPase DIRAS1. Downregulation of DIRAS1 occurred in approximately 50% of primary ESCCs where it was associated significantly with advanced clinical stage, lymph node metastasis, and poor overall survival. LOH and promoter methylation analyses suggested that loss of DIRAS1 expression was mediated by epigenetic mechanisms. Functional studies established that ectopic re-expression of DIRAS1 in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation. Mechanistic investigations suggested that DIRAS1 acted through extracellular signal-regulated kinase (ERK1/2; MAPK3/1) and p38 mitogen-activated protein kinase (MAPK; MAPK14) signaling to trigger BAD Ser112 dephosphorylation and matrix metalloproteinase (MMP)2/9 transcriptional inactivation to promote apoptosis and inhibit metastasis, respectively. Taken together, our results revealed that DIRAS1 has a pivotal function in ESCC pathogenesis, with possible use as a biomarker and intervention point for new therapeutic strategies.
Is investigation of patients with haemoptysis and normal chest radiograph justified?
Authors: M Thirumaran, R Sundar, I M Sutcliffe, D C Currie
Journal: Thorax (2009)

Haemoptysis is a common clinical symptom. A small proportion of patients present with haemoptysis and normal chest radiograph. The investigation strategy for this group of patients is unclear. The aim of this study is to see whether further investigations for this group of patients are justified.A retrospective analysis was conducted of consecutive patients presenting with haemoptysis and normal chest radiograph over a period of 56 months irrespective of their smoking status. These patients were investigated by CT of the thorax and fibreoptic bronchoscopy.275 episodes of haemoptysis with normal chest radiograph were investigated further in 270 patients (60% males). The median age was 60 years. Twenty-six patients were diagnosed to have respiratory tract malignancies (larynx, 1; trachea, 1; lung, 22; carcinoid, 1; and leiomyoma, 1). Eight (31%) of the 26 patients with respiratory tract malignancy had radical treatment. Fibreoptic bronchoscopy was diagnostic of cancer in 14 (54%) of the 26 patients with malignancy. CT of the thorax was suggestive of cancer in 24 (96%) of the 25 patients with malignancy.It is concluded that further investigation of haemoptysis in smokers is justified regardless of the amount or frequency of haemoptysis based on a 9.6% rate of malignancy in this consecutive series. It is recommended that these patients are investigated with CT of the thorax followed by fibreoptic bronchoscopy.
Plasma Progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia
Authors: Charles A. Strott, Teruya Yoshimi, Mortimer B. Lipsett
Journal: Journal of Clinical Investigation (1969)

Plasma 17-hydroxyprogesterone (17-OHP) concentrations in normal men averaged 0.094 mug/100 ml. Studies using suppressive doses of androgens and glucocorticoids showed that 90% of the 17-OHP originated from the Leydig cell. The 17-OHP production rate was 1.8 mg/24 hr. Plasma 17-OHP has a marked circadian variation, the 8 p.m. values being only 40% of the 8 a.m. values. Plasma luteinizing hormone measured in the same samples did not vary. The adrenal cortex has the capacity to synthesize and secrete 17-OHP and progesterone since adrenocorticotrophic hormone (ACTH) caused a fourfold increase in these plasma steroids. In children with congenital adrenal hyperplasia, plasma 17-OHP levels were 50-200 times those of normal men and plasma progesterone was increased 6- to 10-fold over normal men.
Dermatitis herpetiformis and established coeliac disease
Authors: D.J. GAWKRODGER, J.P. VESTEY, S. O'MAHONY, J.M. MARKS
Journal: British Journal of Dermatology (1993)

Fifteen (5.3%) of 282 patients with dermatitis herpetiformis (DH) were diagnosed as suffering from coeliac disease before the onset of their DH. This group showed a female preponderance, and a later than usual onset of DH. The mean age at which DH developed was 40.0 years, and there was a mean interval of 13.2 years between the two diagnoses. Seven patients had stopped their gluten-free diet, and a further four were poor compliers. Persistent gluten ingestion in coeliacs with a specific genetic predisposition may result in the development of DH.
Sex and reproduction: an evolving relationship
Authors: G. Benagiano, S. Carrara, V. Filippi
Journal: Human Reproduction Update (2009)

Although sexual activity has, until very recently, been essential to reproduction, this did not preclude the non-reproductive importance of sexual relationships and non-conceptive copulations. Technological advances, however, now allow for both sex without reproduction and reproduction without sex. This review summarizes social and ethical commentaries on the new relationship between sex and reproduction. For each main area discussed, a systematic search was made using (depending on the subject) PubMed, Medline, ScienceDirect, classic books, Google and/or religious websites. The search focused on publications between 1975 and 2009, although some materials from the first part of the 20th century were also utilized. The classic picture of sex for reproduction and bonding between mating partners is increasingly being replaced by reproduction separate from sexual activity. Although not every advance in assisted reproduction produced, per se, a further separation from sexual intercourse, these two fundamental human activities are today increasingly carried out independently, as reproduction is possible, not only without sex, but even through the intervention of more than two partners. The possibility of reproduction with only one or even no gametes, although highly controversial and not yet feasible, is nonetheless being investigated. Technological advances in the field of reproductive biology have enabled couples considered infertile to conceive and have healthy babies, causing a revolution in culture and customs. Today the independence of sex and reproduction is established and in the future human reproduction may move even further away from the sexual act, an option definitely unacceptable to some ethicists.
Golimumab in combination with methotrexate in Japanese patients with active rheumatoid arthritis: results of the GO-FORTH study
Authors: Yoshiya Tanaka, Masayoshi Harigai, Tsutomu Takeuchi, Hisashi Yamanaka, Naoki Ishiguro, Kazuhiko Yamamoto, Nobuyuki Miyasaka, Takao Koike, Minoru Kanazawa, Takuya Oba, Toru Yoshinari, Daniel Baker
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To assess the efficacy and safety of golimumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA). <h3>Methods</h3> 269 Japanese patients with active RA despite treatment with MTX were randomised (1:1:1) to placebo + MTX (Group 1), golimumab 50 mg + MTX (Group 2) or golimumab 100 mg + MTX (Group 3). Subcutaneous golimumab/placebo was injected every 4 weeks; stable doses of oral MTX (6–8 mg/week) were continued. Patients were allowed to enter early escape (Group 1 added golimumab 50 mg, Group 2 increased golimumab to 100 mg, Group 3 continued golimumab 100 mg) based on swollen/tender joint counts at week 14. The primary study endpoint was achievement of at least 20% improvement in the American College of Rheumatology (ACR20) response criteria at week 14. To control for multiplicity of testing, treatment group comparisons were first made between combined Groups 2 and 3 versus Group 1, followed by comparisons of Group 2 and Group 3 versus Group 1. <h3>Results</h3> The proportion of patients with an ACR20 response at week 14 was significantly higher in combined Groups 2 and 3 (73.4%, 127/173) and in each of Group 2 (72.1%, 62/86) and Group 3 (74.7%, 65/87) compared with Group 1 (27.3%, 24/88; p&lt;0.0001 for all comparisons). Golimumab + MTX also elicited a significantly better response than placebo + MTX in other efficacy parameters, including disease activity score (DAS28) response/remission and radiographic assessments. During the 16-week fixed treatment regimen study period, 72.7%, 75.6% and 78.2% of patients had adverse events and 1.1%, 1.2% and 2.3% had serious adverse events in Groups 1, 2 and 3, respectively. <h3>Conclusion</h3> In Japanese patients with active RA despite MTX therapy, golimumab + MTX was significantly more effective than MTX monotherapy in reducing RA signs/symptoms and limiting radiographic progression with no unexpected safety concerns.
Prognostic Value of the Stage 4S Metastatic Pattern and Tumor Biology in Patients With Metastatic Neuroblastoma Diagnosed Between Birth and 18 Months of Age
Authors: Denah R. Taggart, Wendy B. London, Mary Lou Schmidt, Steven G. DuBois, Tom F. Monclair, Akira Nakagawara, Bruno De Bernardi, Peter F. Ambros, Andrew D.J. Pearson, Susan L. Cohn, Katherine K. Matthay
Journal: Journal of Clinical Oncology (2011)

Patients with neuroblastoma younger than 12 months of age with a 4S pattern of disease (metastases limited to liver, skin, bone marrow) have better outcomes than infants with stage 4 disease. The new International Neuroblastoma Risk Group (INRG) staging system extends age to 18 months for the 4S pattern. Our aim was to determine which prognostic features could be used for optimal risk classification among patients younger than 18 months with metastatic disease.Event-free survival (EFS) and overall survival were analyzed by log-rank tests, Cox models, and survival tree regression for 656 infants with stage 4S neuroblastoma younger than 12 months of age and 1,019 patients with stage 4 disease younger than 18 months of age in the INRG database.Unfavorable biologic features were more frequent in infants with stage 4 disease than in infants with 4S tumors and higher overall in those age 12 to 18 months (although not different for stage 4 v 4S pattern). EFS was significantly better for infants younger than 12 months with 4S pattern than with stage 4 disease (P < .01) but similar for toddlers age 12 to 18 months with stage 4 versus 4S pattern. Among 717 patients with stage 4S pattern, patients age 12 to 18 months had worse EFS than those age younger than 12 months (P < .01). MYCN, 11q, mitosis-karyorrhexis index (MKI), ploidy, and lactate dehydrogenase were independently statistically significant predictors of EFS and more highly predictive than age or metastatic pattern. MYCN, 11q, MKI, histology, and 1p were combined in a survival tree for improved risk stratification.Tumor biology is more critical than age or metastatic pattern for prognosis of patients age younger than 18 months with metastatic neuroblastoma and should be considered for risk stratification.