tbuckley/cabot-search huggingface dataset:
Human Factor in Diagnosis
Authors: P. T. Macdonald
Journal: BMJ (1958)

<h3>Abstract</h3> There is increasing need for biodiversity monitoring, especially in places where potential anthropogenic disturbance may significantly impact ecosystem health. We employed a combination of traditional morphological and bulk macroinvertebrate metabarcoding analyses to benthic samples collected from Toronto Harbour (Ontario, Canada) to compare taxonomic and functional diversity of macroinvertebrates and their responses to environmental gradients. At the species rank, sites assessed using COI metabarcoding showed more variation than sites assessed using morphological methods. Depending on the assessment method, we detected gradients in magnesium (morphological taxa), ammonia (morphological taxa, COI sequence variants), pH (18S sequence variants) as well as gradients in contaminants such as metals (COI &amp; 18S sequence variants) and organochlorines (COI sequence variants). Observed responses to contaminants such as aromatic hydrocarbons and metals align with known patchy distributions in harbour sediments. We determined that the morphological approach may limit the detection of macroinvertebrate responses to lake environmental conditions due to the effort needed to obtain fine level taxonomic assignments necessary to investigate responses. DNA metabarcoding, however, need not be limited to macroinvertebrates, can be automated, and taxonomic assignments are associated with a certain level of accuracy from sequence variants to named taxonomic groups. The capacity to detect change using a scalable approach such as metabarcoding is critical for addressing challenges associated with biodiversity monitoring and ecological investigations.
Smoking, IgE, and occupational allergy.
Authors: S Bonini
Journal: BMJ (1982)

come known to me since that publication.There is no evidence for heterogeneity among these various sets of data so it seems reasonable to pool them.This yields 522 boys and 601 girls.When tested against an expected sex ratio of *514, this sample gives a chi-squared value of 10-86, p -0001.So taken together the data still powerfully support the hypothesis.As the techniques of hormonal monitoring improve, the amount of administered hormone will presumably decrease.So if the hypothesis is correct, the departures from expected sex ratios among children born following induced ovulation should become progressively less.Working with mice, Elbling 3 4has given strong evidence that under some circumstances the administration of gonadotrophin is associated with a subsequent low sex ratio in the pups.Smith and Chrisman5 failed to reproduce this result; but such is the strength of Elbling's evidence that one might infer not that the hypothesis may be safely dismissed but that a phenomenon does exist which is incompletely understood.It would be useful if other workers would repeat Elbling's experiment.I should also be glad to be contacted by anyone with unpub- lished data on the sex of infants following induced ovulation.
Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis
Authors: T Kelleher
Journal: Gut (2004)

<b>Background and aims:</b> While upregulation of divalent metal transporter 1 (DMT1) and iron regulated gene 1 (IREG1) within duodenal enterocytes is reported in patients with hereditary haemochromatosis (HH), these findings are controversial. Furthermore, the effect of HFE, the gene mutated in HH, on expression of these molecules is unclear. This study examines duodenal expression of these three molecules in HH patients (prior to and following phlebotomy), in patients with iron deficiency (ID), and in controls. <b>Methods:</b> DMT1, IREG1, and HFE mRNA were measured in duodenal tissue of C282Y homozygous HH patients, in ID patients negative for the C282Y mutation with a serum ferritin concentration less than 20 μg/l, and in controls negative for C282Y and H63D mutations with normal iron indices, using real time polymerase chain reaction. <b>Results:</b> DMT1 and IREG1 mRNA levels were not significantly different in non-phlebotomised (untreated) HH patients compared with controls. DMT1 expression was significantly increased in HH patients who had undergone phlebotomy therapy (treated) and in patients with ID compared with controls. IREG1 was significantly increased in ID patients relative to controls, and while IREG1 expression was 1.8-fold greater in treated HH patients, this was not statistically significant. HFE mRNA expression was not significantly different in any of the groups investigated relative to controls. <b>Conclusions:</b> These findings demonstrate that untreated HH patients do not have increased duodenal DMT1 and IREG mRNA, but rather phlebotomy increases expression of these molecules, reflecting the effect of phlebotomy induced erythropoiesis. Finally, HFE appears to play a minor role in the regulation of iron absorption by the duodenal enterocyte.
Aldosterone, C-Reactive Protein, and Plasma B-Type Natriuretic Peptide Are Associated With the Development of Metabolic Syndrome and Longitudinal Changes in Metabolic Syndrome Components
Authors: Solomon K. Musani, Ramachandran S. Vasan, Aurelian Bidulescu, Jiankang Liu, Vanessa Xanthakis, Mario Sims, Ravi K. Gawalapu, Tandaw E. Samdarshi, Michael Steffes, Herman A. Taylor, Ervin R. Fox
Journal: Diabetes Care (2013)

OBJECTIVE Several pathomechanisms are implicated in the pathogenesis of metabolic syndrome (MetS), most of which have not been investigated in African Americans (AAs). We examined the contribution of a selected panel of biomarkers to the development of MetS in Jackson Heart Study (JHS) participants in this investigation. RESEARCH DESIGN AND METHODS We evaluated 3,019 JHS participants (mean age, 54 years; 64% women) with measurements for seven biomarkers representing inflammation (high-sensitivity C-reactive protein [CRP]), adiposity (leptin), natriuretic pathway (B-natriuretic peptide [BNP]), adrenal pathway (cortisol and aldosterone), and endothelial function (endothelin and homocysteine). We related the biomarker panel to the development of MetS on follow-up and to longitudinal changes in MetS components. RESULTS There were 278 (22.9%) of 1,215 participants without MetS at baseline who had development of new-onset MetS at follow-up. The incidence of MetS was significantly associated with serum aldosterone (P = 0.004), CRP (P = 0.03), and BNP (P for trend = 0.005). The multivariable-adjusted odds ratios (95% CI) per SD increment of log biomarker were as follows: 1.25 (1.07–1.45) for aldosterone, 1.20 (1.02–1.43) for CRP, and 1.54 (1.07–2.23) and 1.91 (1.31–2.80) for low and high BNP quartiles, respectively. Aldosterone was positively associated with change in all MetS risk components, except low HDL cholesterol and waist circumference. CRP concentration was significantly and directly associated with change in systolic blood pressure (SBP) and waist circumference but inversely associated with HDL cholesterol. For BNP, we observed a U-shape relation with SBP and triglycerides. CONCLUSIONS Our analysis confirms that, in AAs, higher circulating aldosterone and CRP concentrations predict incident MetS. The nonlinear U-shape relation of BNP with MetS and its components has not been reported before and thus warrants replication.
Staphylococcal bacteraemia, fusidic acid, and jaundice.
Authors: M W Humble, S Eykyn, I Phillips
Journal: BMJ (1980)

Fusidic acid was used to treat 131 out of 250 patients with staphylococcal bacteraemia over 10 years. Other antimicrobial agents were given to the 119 remaining patients. Thirty-seven patients were already jaundiced before antibiotic treatment was started. Jaundice developed during treatment in 38 out of 112 patients given fusidic acid (34%) and in two out of 101 patients given other antimicrobials. The incidence of jaundice was higher in patients given fusidic acid intravenously (48%) rather than by mouth (13%). Jaundice appeared within 48 hours after the administration of fusidic acid in 93% of these cases. When the drug was stopped serum bilirubin concentrations fell to normal values within four days in those patients in whom they had been previously normal and who survived the bacteraemic episode. Fusidic acid was associated with increasing jaundice in 13 of 19 patients (68%) already jaundiced before it was given. In six out of 32 patients who developed jaundice while receiving intravenous fusidic acid serum alkaline phosphatase activity was raised suggestive of cholestatic jaundice. The mechanism in the remaining patients was unknown. Fusidic acid, particularly the intravenous preparation, in invaluable in treating severe staphylococcal infection but should be used with caution in patients with abnormal liver function. Patients receiving intravenous fusidic acid should be given the oral form of the drug as soon as their clinical condition permits.
Pocket 4 of the HLA-DR(α,β 1*0401) molecule is a major determinant of T cells recognition of peptide.
Authors: X T Fu, C P Bono, S L Woulfe, C Swearingen, N L Summers, F Sinigaglia, A Sette, B D Schwartz, R W Karr
Journal: The Journal of Experimental Medicine (1995)

To investigate the functional roles of individual HLA-DR residues in T cell recognition, transfectants expressing wild-type or mutant DR(alpha,beta 1*0401) molecules with single amino acid substitutions at 14 polymorphic positions of the DR beta 1*0401 chain or 19 positions of the DR alpha chain were used as antigen-presenting cells for five T cell clones specific for the influenza hemagglutinin peptide, HA307-19. Of the six polymorphic positions in the DR beta floor that were examined, mutations at only two positions eliminated T cell recognition: positions 13 (four clones) and 28 (one clone). In contrast, individual mutations at DR beta positions 70, 71, 78, and 86 on the alpha helix eliminated recognition by each of the clones, and mutations at positions 74 and 67 eliminated recognition by four and two clones, respectively. Most of the DR alpha mutations had minimal or no effect on most of the clones, although one clone was very sensitive to changes in the DR alpha chain, with loss of recognition in response to 10 mutants. Mutants that abrogated recognition by all of the clones were assessed for peptide binding, and only the beta 86 mutation drastically decreased peptide binding. Single amino acid substitutions at polymorphic positions in the central part of the DR beta alpha helix disrupted T cell recognition much more frequently than substitutions in the floor, suggesting that DR beta residues on the alpha helix make relatively greater contributions than those in the floor to the ability of the DR(alpha,beta 1*0401) molecule to present HA307-19. The data indicate that DR beta residues 13, 70, 71, 74, and 78, which are located in pocket 4 of the peptide binding site in the crystal structure of the DR1 molecule, exert a major and disproportionate influence on the outcome of T cell recognition, compared with other polymorphic residues.
Peer Review of Obstetric Mishaps
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1971)

AN old and valued Journal feature reappears in this issue. In the Massachusetts Medical Society section, the Society's Committee on Maternal Welfare is once again reporting cases of maternal deaths with an analysis of what went wrong. Those who read the Journal a decade ago will welcome the return of these revealing accounts of the specific obstetric, surgical and medical complications that make a disaster out of what should be a normal event in a woman's life. Beyond their specific clinical usefulness, however, these critical reports of obstetric crises have today broader implications that bear on the whole practice of . . .
Diminution in energy expenditure during lactation
Authors: J. D Cannon
Journal: BMJ (1986)

Cyanosis attributable to right to left shunt in the carcinoid syndrome SIR,-Dr G W Stewart and colleagues (1 March, p 589) described an interesting case of pronounced arterial hypoxaemia in a patient with the carcinoid syndrome.In the absence ofpulmonary metastases they attributed the hypoxaemia to intrapulmonary shunting through microscopic arteriovenous fistulas.The data presented, however, do not exclude an alternative explanation-right to left shunting through a patent foramen ovale.Although right to left shunting through the foramen ovale is well recognised in patients with pulmonary hypertension,'"3 it may also occur in the presence of normal pulmonary artery and right heart pressures, apparently as a result of reduced right atrial compliance.4Thus though mean left atrial pressure may exceed mean right atrial pressure, during atrial filling right atrial pressure rises disproportionately, causing phasic shunting across the interatrial septum.Right atrial compliance tends to diminish with age,5 but it is conceivable that in Dr Stewart and others' patient the typical endocardial thickening, seen in carcinoid heart disease, may have contributed.The distinction between intracardiac and intrapulmonary shunting could have been made quite easily by contrast angiography or injecting micro- spheres through a pulmonary artery catheter.Although this distinction may not have influenced management in Dr Stewart and others' patient, it may be important in other patients in whom severe, symptomatic arterial hypoxaemia may be abolished by surgical closure ofthe atrial septum.3 4
Double-Blind Studies in Dermatology
Authors: Adolph Rostenberg
Journal: JAMA (1973)

<h3>To the Editor.—</h3> Basically, Kligman has pointed out that double-blind studies can be used improperly. No one will dispute this. It is possible that studies may be done in which the choice of material is not clearly inappropriate, and consequently the study may furnish little or poor information, but that condemns the investigator, not the investigative technic. The point Dr. Kligman makes, that double-blind studies may interfere with the experimental format, I think is rarely, if ever, true. It is true that under certain circumstances it is difficult to utilize double-blind procedures. Obviously, if one wanted to compare the results of surgery in acute appendicitis vs no surgery, most would admit that it is difficult to do this in a double-blind fashion. Yet, even this can be solved by what, for lack of a better name, I shall call a triple-blind study (which means the addition of an investigator who
P96 A comparison between community based models of COPD care
Authors: P. T. Flood-Page
Journal: Thorax (2011)

<h3>Introduction</h3> Decentralisation of healthcare commissioning in the UK has led to the development of multiple models of community-based care for COPD. Despite the huge costs associated with these long term condition (LTC) teams there is little published data exploring the efficacy of these models of care. Until 2009 healthcare in Gwent, South Wales was delivered by five autonomous Local Health Boards (LHB). Different models of community-based COPD care were developed in each. This gave a unique opportunity to compare the efficacy of different models of healthcare among patients with similar demographic characteristics. The three main models of care were similar in primary objective: to reduce hospital admissions. In Caerphilly LHB COPD was managed by nurse specialists. In Newport and Monmouthshire generic nurses managed COPD with other chronic conditions. LTC nurses in these LHBs worked alongside GPs without secondary care. Services were introduced to some practices but not others. In Torfaen and in Blaenau Gwent COPD was managed by nurse specialists, GPs and Consultant Chest Physicians. <h3>Methods</h3> Hospital admission data were collected from the trust database. COPD admission data were compared for the 3 years before and after the introduction of services around 2006. <h3>Results</h3> Gwentwide 2003–2009 there was a 5.5% increase in COPD admissions. In Caerphilly the increase was 12.3%. In Newport and Monmouthshire for those practices working with LTC there was an increase of 20.8% and 43.4% respectively. This corresponded to an increase of 5.2% and 1.0% respectively in those practices in Newport and Monmouthshire that had no contact with LTC teams and continued to manage COPD in the same way (p&lt;0.01 for within LHB comparison) In Blaenau Gwent and Torfaen, however, the inclusion of secondary care was associated with a reduction in admissions of 3.8% and 5.1% respectively. (p&lt;0.01 for the comparison between pooled data for Torfaen/Blaenau Gwent and Newport/Monmouthshire/Caerphilly). <h3>Conclusion</h3> There is little evidence base to guide the huge sums of money invested in community care for COPD and other chronic conditions. Our data suggests that services with close communication between primary and secondary care may be more effective than those developed around primary care alone.
Commentary: Controversies in NICE guidance on chronic kidney disease
Authors: M. J Landray, R. J Haynes
Journal: BMJ (2008)

New NICE guidelines seek to improve health outcomes for individuals with chronic kidney disease. They emphasise the role of primary care in dealing with two important questions: how should we assess and reduce the risk of cardiovascular events that are present among all patients with chronic kidney disease; and how can we identify the minority of individuals who are likely to progress to advanced kidney disease (and require specialist nephrological services)?

One of the most controversial issues in writing such guidelines is the definition of chronic kidney disease, which relies on the ability to estimate glomerular filtration rate (GFR). As the NICE authors recognise, the current, creatinine based formulas are woefully inadequate among the 90-95% of the population who have “normal” or “moderately impaired” kidney function (GFR >45 ml/min/1.73m2). 

The staging system based on GFR largely ignores other measures of kidney damage—proteinuria, for example—which are useful indicators of the risk of progression of renal …
EHRLICH'S BIOCHEMICAL THEORY, ITS CONCEPTION AND APPLICATION
Authors: LOUIS HART MARKS
Journal: JAMA (1910)

rather dealing with a ipiadrilaleral spine, »something thai has more of the configuration of a rectangle.I feel, therefore, that it ») get away from (he designation of angles in these eases we may be serving cranial topography with moro accuracy, so far as this site of predilection for certain lumors is concerned.In Dr. drinker's paper.I think that, aside iron) the complete
Increasing dose intensity of anthracycline antibiotics improves outcome in patients with acute myelogenous leukemia
Authors: N. Novitzky, V. Thomas, L. Abrahams, C. du Toit, A. McDonald
Journal: American Journal of Hematology (2004)

Abstract To understand the effect of dose concentration in the overall survival of AML, we conducted a study on the efficacy and toxicity of a drug combination where the dose of daunorubicin was intensified. For this analysis, the outcome of patients entered into two consecutive prospective trials was compared. Inclusion criteria in both arms were identical and consisted of primary AML in adults. Treatment protocol for Cape Town Regimen 4 (CTR‐IV) comprised of cytarabine infusion (100 mg/m 2 ) and etoposide (100 mg/m 2 ), injection daily for 7 days in combination with daunorubicin (45 mg/m 2 ) on days 1, 2, and 3. Patients achieving remission were given two further courses of the same chemotherapy and received allogeneic or autologous transplantation. CTR‐V was a similar treatment program, except that daunorubicin was escalated on days 1, 2, and 3 to 75 mg/m 2 during induction and to 60 mg/m 2 during a single consolidation. Patients were also offered stem cell transplantation. Between 1990 and 1997, 78 patients (median age 33; range 13–67 years) fulfilled entry criteria and received CTR‐IV. From 1998 onwards, 35 patients (median age 36; range 15–66 years) were prospectively enlisted into the CTR‐V trial. The patient population in CTR‐V had fewer Caucasian individuals ( P = 0.02) and had significantly lower presentation hemoglobin ( P = 0.0002). Following initiation of induction chemotherapy, 40 patients failed to respond. Among these, 10 patients demised before day 28. Another 30 (25/69 CTR‐IV and 5/32 in CTR‐V groups; P = 0.01) had leukemia that was resistant to chemotherapy, and all died. Remission was achieved in 59% of patients treated with CTR‐IV and 77% of those receiving CTR‐V ( P = 0.03). CR occurred with a single course in 64% versus 88% ( P = 0.02), respectively. There were no differences in the toxicity profile between these two combinations. Disease recurred in 50% and 28% ( P = 0.07) of patients. For the 113 individuals, median follow up is 254 (range 19–4,451) and 304 (12–1,702; P = 0.03) days. Survival is 23% and 40%, respectively, favoring patients treated with CTR‐V (log rank; P = 0.03). Cox regression analysis showed that treatment group ( P &lt; 0.001), FAB type, hemoglobin level, and platelet count were independent factors for response to chemotherapy. Older age and not undergoing myeloablative therapy were the only adverse factors for survival. We conclude that increase in the treatment dose of daunorubicin in patients with AML led to a higher remission rate, particularly with a single course of chemotherapy and had an equivalent toxicity profile. This therapeutic modification is also likely to result in substantial reduction in patient stay in hospital and in the overall expenditure. Am. J. Hematol. 76:319–329, 2004. © 2004 Wiley‐Liss, Inc.
A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal Frameshifting to Selective Viral RNA Encapsidation
Authors: Mastooreh Chamanian, Katarzyna J. Purzycka, Paul T. Wille, Janice S. Ha, David McDonald, Yong Gao, Stuart F.J. Le Grice, Eric J. Arts
Journal: Cell Host & Microbe (2013)
Potassium and sodium transport along the loop of Henle: Effects of altered dietary potassium intake
Authors: Robert Unwin, Giovanni Capasso, Gerhard Giebisch
Journal: Kidney International (1994)

We assessed the effects of changes in potassium (K+) balance on the function of the loop of Henle by a combination of renal clearance and microperfusion experiments. Rat superficial cortical nephrons were perfused in vivo at 20 nl.min-1 from late proximal to early distal tubule with an artificial end-proximal solution containing either 3.8 or 1.8 mM potassium. Rats were fed a control diet, a low-potassium diet for at least three weeks, or a high-potassium diet for 10 to 14 days. When compared with the appropriate end-proximal potassium concentration in the perfusion fluid, potassium absorption along the loop of Henle (JK) increased in potassium-depletion whereas sodium (JNa) and fluid (Jv) absorption decreased. In rats fed a high-potassium diet, absorption of potassium, sodium and fluid was depressed. We propose that changes of external potassium balance affect the transport of electrolytes and fluid along the loop of Henle in vivo by modulating the transport of potassium and sodium primarily in the thick ascending limb. Changes in potassium reabsorption may also be affected by alterations of potassium-recycling.
Impact of Age on Weight Goals
Authors: R Andres, D Elahi, J D Tobin, D C Muller, L Brant
Journal: Annals of Internal Medicine (1985)

Although the health hazards due to excessive obesity and excessive leanness are multiple and diverse, weight recommendations for over 40 years have been based solely on the risk of dying. The weight recommendation tables in nearly universal usage have been derived from the experience of the life insurance industry. Those tables have not recommended any weight adjustments for age. An analysis of the actuarial data on which the most recent tables are based shows that minimal mortality occurs at progressively increasing body weight as age advances (20 to 29, through 60 to 69 years). There is, furthermore, no systematic sex difference in those weights. We have prepared height-weight tables that are age-specific and delete sex and body frame type as variables. These weight standards are lower for young adults and higher for older adults than those previously recommended. A review of 23 other reported populations confirms the need to adjust weight standards for age.