tbuckley/cabot-search huggingface dataset:
Patient controlled analgesia in the emergency department
Authors: F. Lecky
Journal: BMJ (2015)

Reduces pain and increases autonomy

Acute severe pain that follows injury or onset of illness alerts patients to the likelihood of tissue damage (nociception) and drives much emergency department attendance.1 The prompt assessment and alleviation of pain is a quality benchmark for emergency departments internationally, and titrated intravenous opiates are the initial analgesic of choice for severe pain.2 3 Recent improvements in initial pain assessment and analgesic provision have occurred in UK emergency departments, but processes for referral to an inpatient team and time based standards for ward admission can interfere with effective pain management after the first dose of intravenous opiate. Recent surveys of patients and studies of care pathways suggest that current care is suboptimal in this regard.4

Two open label, multicentre, randomised trials of pain solutions in the emergency setting (PASTIES) by Smith and colleagues (doi:10.1136/bmj.h2988; doi:10.1136/bmj.h3147) provide new evidence to help us tackle this deficiency.5 6 The studies each enrolled a group of patients who commonly require parenteral analgesia throughout the first day of an emergency admission—adults with acute non-traumatic abdominal pain and adults with acute traumatic injury. …
Expression of the 67-kDa elastin receptor in perforating skin disorders
Authors: N. Fujimoto, A. Akagi, S. Tajima, A. Ishibashi, K. Nomura, A. Matsushita, Y. Nagai, K. Shishiba
Journal: British Journal of Dermatology (2002)

Perforating skin dermatoses include elastosis perforans serpiginosa (EPS), reactive perforating collagenosis, Kyrle's disease and perforating folliculitis. In addition to these four diseases, an acquired form of perforating dermatosis associated with diabetes mellitus and/or chronic renal failure has been reported for which the term acquired perforating dermatosis (APD) was proposed. The molecular mechanism of transepidermal elimination of dermal components in perforating skin dermatoses remains unclear. We recently demonstrated that the 67-kDa elastin receptor can be detected in the epidermis eliminating altered elastic fibres in EPS, suggesting that the elastin-keratinocyte interaction may play a role in transepidermal elimination in EPS.To determine whether the 67-kDa elastin receptor is involved in other perforating diseases.Paraffin-embedded skin specimens from new cases of EPS (n = 2), APD (n = 15) and perforating granuloma annulare (PGA; n = 2) were studied immunohistochemically using a specific antibody to the 67-kDa elastin receptor. In one case of EPS, two different sites from a single lesion, a central atrophic area and a peripheral keratotic area, were studied.Expression of the elastin receptor was detected in the epidermis surrounding the elastic materials in both cases of EPS. The elastin receptor was not detected in the central inactive area, whereas it was expressed strongly in the peripheral keratotic active area. The elastin receptor was also detected in three of 15 cases of APD in which a few elastic fibres were found in the eliminated dermal materials. In one case of APD, the elastin receptor was not detected in spite of the presence of a few elastic fibres in the eliminated materials. The elastin receptor was not detected in either case of PGA.Expression of the elastin receptor in EPS was seen in both cases studied and was dependent on the stage of the lesion. Expression of the elastin receptor in APD appeared to be related to the amount of elastic fibres in the eliminated materials. Thus, expression of the elastin receptor in perforating skin disorders may depend on the stage of the lesion and/or the content of elastic fibres in the dermal materials being eliminated.
Tobacco Smoke, Indoor Air Pollution and Tuberculosis: A Systematic Review and Meta-Analysis
Authors: Hsien-Ho Lin, Majid Ezzati, Megan Murray
Journal: PLoS Medicine (2007)

Background Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures and the risk of infection, disease, and death from TB. Methods and Findings We conducted a systematic review and meta-analysis of observational studies reporting effect estimates and 95% confidence intervals on how tobacco smoking, passive smoke exposure, and indoor air pollution are associated with TB. We identified 33 papers on tobacco smoking and TB, five papers on passive smoking and TB, and five on indoor air pollution and TB. We found substantial evidence that tobacco smoking is positively associated with TB, regardless of the specific TB outcomes. Compared with people who do not smoke, smokers have an increased risk of having a positive tuberculin skin test, of having active TB, and of dying from TB. Although we also found evidence that passive smoking and indoor air pollution increased the risk of TB disease, these associations are less strongly supported by the available evidence. Conclusions There is consistent evidence that tobacco smoking is associated with an increased risk of TB. The finding that passive smoking and biomass fuel combustion also increase TB risk should be substantiated with larger studies in future. TB control programs might benefit from a focus on interventions aimed at reducing tobacco and indoor air pollution exposures, especially among those at high risk for exposure to TB.
DETERMINANTS OF THE FLOW AND COMPOSITION OF BILE IN THE UNANESTHETIZED DOG DURING CONSTANT INFUSIONS OF SODIUM TAUROCHOLATE*
Authors: Henry O. Wheeler, Oswaldo L. Ramos
Journal: Journal of Clinical Investigation (1960)

Physiological factors affecting the flow and composition of bile may be divided into two gen- eral categories.First, the availability of bile salts (by hepatic synthesis and by reabsorption from the bowel) has a significant influence on the rate of bile production.The choleretic effect of natural bile salts and the phenomenon of enterohepatic cir- culation of these compounds were first demon- strated by Schiff in 1870 (1).These observa- tions have been confirmed by many workers since that time.It has been estimated that 85 to 90 per cent of the bile salt excreted in the bile is reabsorbed and returned to the liver (2, 3).For this reason the entry of bile itself into the duode- num provides a major stimulus for further bile production.Second, factors independent of the availability of bile salts can affect bile production.This category would include, for example, neural stimuli (4, 5), humoral agents such as secretin (6-8) and changes in vascular perfusion (5).During any investigation of biliary secretion in which bile is removed and not replaced, achievement of a steady state is thwarted by progressive depletion of bile salts which would normally un- dergo enterohepatic circulation.In the present studies this problem has been circumvented by constant intravenous infusion of sodium tauro- cholate.The results substantiate the important role of active bile salt secretion in the process of bile production and also suggest that the flow and composition of bile are modified by the addition of variable amounts of a solution which is similar in certain respects to pancreatic juice. METHODSAll studies were conducted on four trained adult female mongrel dogs (21 to 30 Kg.)
The effect of specific immunotherapy on T‐cell receptor repertoire in patients with allergy to house‐dust mite
Authors: K. Sade, S. Kivity, A. Levy, E. Fireman
Journal: Allergy (2003)

The precise mechanism of specific immunotherapy (SIT), long used for treating allergic diseases, remains undefined. SIT was shown to act by modifying the immune response of T lymphocytes to antigens. We examined the effect of SIT on the expression and use V-alpha, -beta, -gamma and -delta chains of T-cell receptors (TCR) in patients allergic to house-dust mite.Peripheral venous blood was taken for lymphocyte TCR analysis from 10 house-dust mite (HDM) allergic adults before initiating SIT and 6 months after initiating the treatment. Twelve similarly allergic patients without SIT served as controls. TCR chains were identified by fluorescence-activated cell sorter (FACS) using the following monoclonal antibodies: CD3, CD14, CD8, pan alpha-beta, pan gamma-delta, V-alpha2, V-alpha12.1, V-beta5a, V-beta5b, V-beta5c, V-beta8a, V-beta8b, V-beta3.1, V-beta13, V-beta12, V-beta6.7, V-delta1, V-delta2, V-gamma9, and V-gamma4.Analyzed before and 6 months after SIT initiation, lymphocyte TCR showed significantly increased V-beta5b, V-beta12 and V-alpha12.1 values compared to controls (without significant changes in other markers).SIT caused selective expansion of certain V-beta- and V-alpha-expressing T cells in patients allergic to HDM. Our results support the notion that the effect of SIT in patients with allergic rhinitis may be achieved by modifying the T lymphocyte response through the modulation of TCR usage.
Reconstituted High-Density Lipoproteins Inhibit the Acute Pro-Oxidant and Proinflammatory Vascular Changes Induced by a Periarterial Collar in Normocholesterolemic Rabbits
Authors: Stephen J. Nicholls, Gregory J. Dusting, Belinda Cutri, Shisan Bao, Grant R. Drummond, Kerry-Anne Rye, Philip J. Barter
Journal: Circulation (2005)

Background— HDLs have antiinflammatory and antioxidant properties in vitro. This study investigates these properties in vivo. Methods and Results— Chow-fed, normocholesterolemic New Zealand White rabbits received a daily infusion of (1) saline, (2) reconstituted HDL (rHDL) containing 25 mg apolipoprotein (apo) A-I and 50 mg of either 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC) or 1,2-dipalmitoyl phosphatidylcholine (DPPC), (3) 25 mg lipid-free apoA-I, or (4) 50 mg of either PLPC-small unilamellar vesicles (SUVs) or DPPC-SUVs on each of 3 consecutive days. Nonocclusive carotid periarterial collars were implanted after the second dose of treatment. Forty-eight hours after insertion of the collars, the arteries were removed and analyzed for the presence of reactive oxygen species, the infiltration of neutrophils, and the expression of adhesion proteins and chemokines. Insertion of the periarterial collar induced a 4.1-fold increase in presence of vascular wall reactive oxygen species. This effect was completely abolished in the animals infused with rHDL. The periarterial collar was associated with a dense infiltration of the arterial wall by polymorphonuclear leukocytes. This infiltration was inhibited by 73% to 94% in the animals infused with rHDL, by 75% in the animals infused with lipid-free apoA-I, and by 51% to 65% in animals infused with SUVs. There were no significant differences between the effects of PLPC and DPPC in either the rHDL or SUVs. Endothelial expression of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 was also increased by the collar insertion and inhibited by rHDL, lipid-free apoA-I, and, to a lesser extent, also by the SUVs. Conclusions— Infusion of rHDL, apoA-I, and phospholipid-SUVs inhibits the early pro-oxidant and proinflammatory changes induced by a periarterial collar in normocholesterolemic rabbits.
Origin and Evolution of a Novel DnaA-Like Plasmid Replication Type in Rhodobacterales
Authors: J. Petersen, H. Brinkmann, M. Berger, T. Brinkhoff, O. Pauker, S. Pradella
Journal: Molecular Biology and Evolution (2010)

Large extrachromosomal elements are widespread among Alphaproteobacteria, but it is unclear how up to a dozen low-copy plasmids can stably coexist within the same cell. We systematically analyzed the distribution of different replicons in about 40 completely sequenced genomes of the Roseobacter clade (Rhodobacterales) and surprisingly identified a novel plasmid replicon type. The conserved replication module comprises the characteristic partitioning operon (parAB) and a hitherto unknown replicase. The latter shows a weak homology to the chromosomal replication initiator DnaA and was accordingly named "DnaA-like." Phylogenetic analyses of the adjacent parAB genes document a common ancestry with repA- and repB-type plasmids and moreover indicate the presence of two dnaA-like compatibility groups. This conclusion is supported by conserved palindrome sequences within the replication module that probably represent crucial centromeric anchors for plasmid partitioning. The functionality of dnaA-like replicons was proven by transformation experiments in Phaeobacter gallaeciensis BS107 (DSM 17395). This Roseobacter strain furthermore allows the phenotypical monitoring of plasmid incompatibility, based on a 262-kb dnaA-like replicon required for the brown pigmentation of the bacterium. Uptake of an incompatible construct induces its loss, hence resulting in white colonies. Accordingly, we could substantiate the in silico predictions about stable maintenance of dnaA-like plasmids and thereby functionally validate our approach of plasmid classification based on phylogenetic analyses.
Niche recycling through division-independent egress of hematopoietic stem cells
Authors: Deepta Bhattacharya, Agnieszka Czechowicz, A.G. Lisa Ooi, Derrick J. Rossi, David Bryder, Irving L. Weissman
Journal: The Journal of Experimental Medicine (2009)

Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that ∼1–5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.
Use of endoscopy for management of acute upper gastrointestinal bleeding in the UK: results of a nationwide audit
Authors: S. A. Hearnshaw, R. F. A. Logan, D. Lowe, S. P. L. Travis, M. F. Murphy, K. R. Palmer
Journal: Gut (2010)

<h3>Objectives</h3> To examine the use of endoscopy in the UK for acute upper gastrointestinal bleeding (AUGIB) and compare with published standards. To assess the organisation of endoscopy services for AUGIB in the UK. To examine the relationship between outcomes and out of hours (OOH) service provision. <h3>Design</h3> Multi-centre cross sectional clinical audit. <h3>Setting</h3> All UK hospitals accepting admissions with AUGIB. <h3>Patients</h3> All adults (≥16 yrs) presenting with AUGIB between 1st May and 30th June 2007. <h3>Data Collection</h3> A custom designed web-based reporting tool was used to collect data on patient characteristics, comorbidity and haemodynamic status at presentation to calculate the Rockall score, use and timing of endoscopy, treatment including endoscopic, rebleeding and in-hospital mortality. A mailed questionnaire was used to collect data on facilities and service organisation. <h3>Results</h3> Data on 6750 patients (median age 68 years) were analysed from 208 hospitals. 74% underwent inpatient endoscopy; of these 50% took place within 24 h of presentation, 82% during normal working hours and 3% between midnight and 8 am. Of patients deemed high-risk (pre-endoscopy Rockall score ≥5) only 55% were endoscoped within 24 h and 14% waited ≥72 h for endoscopy. Lesions with a high risk of rebleeding were present in 28% of patients of whom 74% received endoscopic therapy. Further bleeding was evident in 13% and mortality in those endoscoped was 7.4% (95% CI 6.7% to 8.1%). In 52% of hospitals a consultant led out of hours (OOH) endoscopy rota existed; in these hospitals 20% of first endoscopies were performed OOH compared with 13% in those with no OOH rota and endoscopic therapy was more likely to be administered (25% vs 21% in hospitals with no OOH rota). The risk adjusted mortality ratio was higher (1.21, p=0.10, (95%CI 0.96 to 1.51)) in hospitals without such rotas. <h3>Conclusions</h3> This audit has found continuing delays in performing endoscopy after AUGIB and underutilisation of standard endoscopic therapy particularly for variceal bleeding. In hospitals with a formal OOH endoscopy rota patients received earlier endoscopy, were more likely to receive endoscopic therapy and may have a lower mortality.
Squamous cell carcinoma in a patient with non-bullous congenital ichthyosiform erythroderma
Authors: K. Arita, M. Akiyama, Y. Tsuji, F. Iwao, K. Kodama, H. Shimizu
Journal: British Journal of Dermatology (2003)

Sir, Non‐bullous congenital ichthyosiform erythroderma (NBCIE) is a rare autosomal recessive disease characterized by hyperkeratosis and generalized erythema from birth. Although there are some reports concerning skin cancers associated with congenital ichthyoses including ichthyosis hystrix,1 Netherton's syndrome,2 KID syndrome3 and MAUIE syndrome,4 the occurrence of squamous cell carcinoma (SCC) in NBCIE has not been reported in the literature, as far as we know. We report here a Japanese male with NBCIE who exhibited SCC on his neck. A 44‐year‐old Japanese man has been seen for 28 years in the Department of Dermatology, Hokkaido University Graduate School of Medicine. He had been suffering from NBCIE since birth. He had been treated with oral etretinate, 10 mg daily, for about 20 years. Physical examination at 42 years of age revealed generalized erythema with slight pityriatic scales over almost his entire body (Fig. 1). Mild ectropion was observed. There were severe hyperkeratoses and fissures on the palms and soles, and nail deformity was present on all the fingers and toes. There were no bullous or erosive lesions. Ichthyosis linearis circumflexa, the characteristic clinical features of Netherton syndrome, were not observed. His hair was sparse, but hair shafts did not show trichorrhexis invaginata. A skin biopsy taken from the left shoulder revealed parakeratotic hyperkeratosis with acanthosis. No granular degeneration was observed. Immunofluorescent staining with B.C1 antibody for TGase 1 showed normal expression of TGase 1 molecule in the patient's epidermis. In situ TGase activity assay, performed as previously described,5 revealed normal enzymatic activity. Electron microscopy did not show any obvious abnormality in keratin filament, lamellar granule, or cornified cell envelope in the patient's epidermis.
Combination of Empagliflozin and Linagliptin as Second-Line Therapy in Subjects With Type 2 Diabetes Inadequately Controlled on Metformin
Authors: Ralph A. DeFronzo, Andrew Lewin, Sanjay Patel, Dacheng Liu, Renee Kaste, Hans J. Woerle, Uli C. Broedl
Journal: Diabetes Care (2015)

OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. RESEARCH DESIGN AND METHODS Subjects were randomized to a combination of empagliflozin 25 mg/linagliptin 5 mg (n = 137), empagliflozin 10 mg/linagliptin 5 mg (n = 136), empagliflozin 25 mg (n = 141), empagliflozin 10 mg (n = 140), or linagliptin 5 mg (n = 132) as add-on to metformin for 52 weeks. The primary end point was change from baseline in HbA1c at week 24. RESULTS At week 24, reductions in HbA1c (mean baseline 7.90–8.02% [62.8–64.1 mmol/mol]) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin; adjusted mean (SE) changes from baseline were −1.19% (0.06) (−13.1 mmol/mol [0.7]) with empagliflozin 25 mg/linagliptin 5 mg, −1.08% (0.06) (−11.8 mmol/mol [0.7]) with empagliflozin 10 mg/linagliptin 5 mg, −0.62% (0.06) (−6.8 mmol/mol [0.7]) with empagliflozin 25 mg, −0.66% (0.06) (−7.2 mmol/mol [0.7]) with empagliflozin 10 mg, and −0.70% (0.06) (−7.6 mmol/mol [0.7]) with linagliptin 5 mg (P &amp;lt; 0.001 for all comparisons). In these groups, respectively, 61.8, 57.8, 32.6, 28.0, and 36.1% of subjects with baseline HbA1c ≥7% (≥53 mmol/mol) had HbA1c &amp;lt;7% (&amp;lt;53 mmol/mol) at week 24. Efficacy was maintained at week 52. The proportion of subjects with adverse events (AEs) over 52 weeks was similar across treatment arms (68.6–73.0%), with no hypoglycemic AEs requiring assistance. CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated.
Prevalence of Abnormal Glucose Tolerance and Risk Factors in Urban and Rural Malaysia
Authors: Norlaila Mustafa, Nor Azmi Kamarudin, Ab Aziz Ismail, Amir Sharifuddin Khir, Ikram Shah Ismail, Kamarul Imran Musa, Khalid Abdul Kadir, Nor Azwany Yaacob, Osman Ali, Siti Harnida Md Isa, Wan Mohamad Wan Bebakar, Wan Nazaimoon wan Mohamud
Journal: Diabetes Care (2011)

To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
Description of the natural course and clinical manifestations of ichthyosis with confetti caused by a novel KRT10 mutation
Authors: B. Burger, I. Spoerri, M. Schubert, C. Has, P.H. Itin
Journal: British Journal of Dermatology (2011)

Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings.