tbuckley/cabot-search huggingface dataset:
THE ANTIBODY RESPONSE IN RABBITS TO KILLED SUSPENSIONS OF PATHOGENIC T. PALLIDUM
Authors: Harry Eagle, Ralph Fleischman
Journal: The Journal of Experimental Medicine (1948)

The intravenous injection into rabbits of suspensions of dead T. pallidum derived from rabbit testicular chancres regularly caused the appearance of Wassermann and flocculation antibodies in significantly increased titer. Control suspensions of cultured treponemes (Reiter strain) added to extracts of normal testes were ineffective. This suggests that the Wassermann and flocculation reagin elaborated during syphilitic infection may be an antibody to T. pallidum which happens to cross-react with alcoholic extracts of mammalian tissue. The antisera did not cause the agglutination of suspensions of pathogenic T. pallidum, living or dead, did not give specific complement fixation with those suspensions, and did not usually cause the living treponemata to lose their infectiousness. Animals immunized with such aqueous suspensions for as long as 4 months, or with organisms suspended in a water-in-oil emulsion, were not demonstrably resistant to infection. As few as ten living organisms inoculated intradermally into animals "immunized" with as many as 38 billion dead treponemata regularly produced typical darkfield positive infections; and two of five animals inoculated intratesticularly with ten organisms were also infected. The contradiction involved in the production of antibodies cross-reacting with a non-specific antigen, and the non-appearance of specific antibodies against the organism used as antigen, is discussed in the text.
Mechanism of hemolysis induced by ferriprotoporphyrin IX.
Authors: A C Chou, C D Fitch
Journal: Journal of Clinical Investigation (1981)

Incubation of a 0.5% suspension of washed, normal mouse erythrocytes with ferriprotoporphyrin IX (FP) at 37 degrees C and pH 7.4 caused potassium loss, swelling, increased susceptibility to hypotonic lysis, and finally hemolysis. Hemolysis was not inhibited by incubation in the dark, malonyldialdehyde was not produced, and various free radical scavengers had no effect on the hemolysis. Only the sulfhydryl compounds, cysteine, dithiothreitol, and mercaptoethanol protected erythrocytes from FP. Potassium loss reached 90% within 30 min of exposure to 5 microM FP. This amount of FP caused greater than 50% hemolysis within 2.5 h. Sucrose (0.1 M) completely prevented hemolysis but had no effect on potassium loss. Likewise, reducing the temperature from 37 to 25 degrees C greatly retarded hemolysis but had no effect on potassium loss. These observations indicate that FP impairs the erythrocyte's ability to maintain cation gradients and induces hemolysis by a colloid-osmotic mechanism.
Dilemmas in managing intracerebral haemorrhage and thromboembolism
Authors: J. Chikwe, L. Ovens
Journal: Journal of the Royal Society of Medicine (2004)

Evidence-based and complementary medicine Dr Butterworth (March 2004 JRSM 1 ) describes how a relative of his was diagnosed as hypertensive and put on a succession of medicines with near disastrous consequences.This chain of events had nothing to do with the vogue for evidence-based medicine.Rather, it reflects the enormous difficulty of practising good and safe medicine in the era of effective but dangerous drugs.The proliferation of lifeprolonging as opposed to symptom-reducing drugs makes clinical medicine complex and time consuming-though no-one would guess this from the mass of guidelines and protocols and the devolution of traditional medical tasks to non-doctors, all based on a fundamentally faulty world view where everything is either right or wrong, good or bad, black or white.Such reductionist inanity now extends to assessments of massive hospitals or even the whole NHS.It was not what clinical trials have told us about treating hypertension that poisoned Dr Butterworth's relative.Whether he met any standard criteria for hypertension requiring drug treatment is not clear.To treat consequent dizziness with another drug appears simply crass; life, however, is complex, and we do not know the patient's blood pressure at the time this decision was made.Undertreated as well as over-treated hypertension can cause dizziness.The wise old general practitioner who took him off all medications may well have saved this man, but for all we know has over the years missed the opportunity to prevent dozens of strokes by adopting a 'common sense' approach to the management of hypertension in the asymptomatic elderly.Common sense, like evidence-based medicine, should be used only when appropriate.Thank goodness we live in the era of dangerous and powerful drugs.Though the public may think that brain surgeons or heart surgeons have the most challenging jobs in medicine, in future the most difficult tasks will be polypharmacy in the elderly with multiple medical problems, to achieve the best combination of wellbeing and longevity.To master those arts will require lifelong education, natural empathy and most importantly, time and desire to think before prescribing.It is not the concept of evidence-based medicine we need fear, it is that of immediately demonstrable value for money.
Assessment of cartilage loss at the wrist in rheumatoid arthritis using a new MRI scoring system
Authors: Fiona McQueen, Andrew Clarke, Alex McHaffie, Quentin Reeves, Megan Williams, Elizabeth Robinson, Jing Dong, Arista Chand, Desiree Mulders, Nicola Dalbeth
Journal: Annals of the Rheumatic Diseases (2010)

Objectives To develop and test an MRI cartilage scoring system for use at the wrist in rheumatoid arthritis (RA). Methods MRI scans were obtained using a 3T MRI scanner with dedicated wrist coil in 22 early and 16 established RA patients plus 22 controls. Axial and coronal T1-weighted (precontrast and postcontrast) and T2-weighted turbo spin echo sequences were obtained. Eight wrist joints were scored for cartilage narrowing: distal radioulnar, radiolunate, radioscaphoid, triquetrum-hamate, capitate-lunate, scaphotrapezoid, second metacarpal base-trapezoid and third metacarpal base-capitate, using a system based on the Sharp van der Heijde x-ray joint space narrowing (JSN) score by three radiologists. Fifteen sites at the wrist were also scored for synovitis, bone oedema and erosion using the RA MRI score. Results Interobserver (three-reader) and intraobserver reliability (readers 1 and 2) for the cartilage score were excellent: intraclass correlations (ICC (95% CI)) 0.91, (0.86 to 0.94), 0.98 (0.96 to 1.00) and 0.94 (0.87 to 1.00), respectively. Cartilage scores (median, range) were higher in the established RA group (11.9, 2.3–27.3) than the early RA group (2.15, 0–6) (p≤0.001) but early RA scores did not differ from healthy controls (2.3, 1–8.7). Cartilage scores correlated with synovitis (R=0.52), bone oedema (R=0.63) and erosion scores (R=0.66), p&lt;0.001 for all, and with x-ray JSN scores (R=0.68 to 0.78). Conclusion This MRI cartilage score demonstrated excellent reliability when tested in a three-reader system. However, cartilage loss in early RA could not be distinguished from that seen in healthy controls.
Apoprotein E is synthesized and secreted by resident and thioglycollate-elicited macrophages but not by pyran copolymer- or bacillus Calmette-Guerin-activated macrophages.
Authors: Z Werb, J R Chin
Journal: The Journal of Experimental Medicine (1983)

Macrophages are active secretory cells that display functionally distinct phenotypes that are regulated by inflammation. We have found that apoprotein E (ApoE), a component of plasma lipoproteins, was synthesized and secreted by resident and nonspecifically stimulated macrophages elicited with thioglycollate broth, but not by activated macrophages obtained from mice treated with bacillus Calmette-Guerin, pyran copolymer, whole Corynebacterium parvum, or bacterial endotoxin. ApoE represented approximately 1% of the newly synthesized protein and approximately 10% of secreted protein of resident and thioglycollate-elicited macrophages. ApoE from thioglycollate-elicited macrophages was indistinguishable from ApoE in mouse plasma lipoproteins, as determined by immunoreactivity, peptide mapping, and molecular weight. When specific antibodies were used to localize cell-associated ApoE, strong immunofluorescence was seen in the Golgi region of resident and thioglycollate-elicited macrophages immediately after removal from the peritoneal cavity, as well as after culture for up to 7 d. In contrast, activated macrophages did not synthesize or secrete ApoE to an appreciable extent and had no immunocytochemically detectable intracellular ApoE. When activated macrophages were cultured in medium containing serum, their activated state, as judged by production of H2O2, declined within 48-72 h in parallel with the induction of synthesis and secretion of ApoE and detection of intracellular ApoE by immunofluorescence. During prolonged culture the rate of synthesis and secretion of ApoE increased in both resident and activated macrophages. Therefore, the synthesis and secretion of ApoE may serve as markers for the functional state of macrophages.
Forging a link between cognitive and emotional repression
Authors: Esther Fujiwara, Marcel Kinsbourne
Journal: Behavioral and Brain Sciences (2006)

Erdelyi distinguishes between cognitive and emotional forms of repression, but argues that they use the same general mechanism. His discussion of experimental memory findings, on the one hand, and clinical examples, on the other, does indeed indicate considerable overlap. As an in-between level of evidence, research findings on emotion in neuroscience, as well as experimental and social/personality psychology, further support his argument.
Combination of Raltitrexed and Oxaliplatin Is an Active Regimen in Malignant Mesothelioma: Results of a Phase II Study
Authors: K. Fizazi, H. Doubre, T. Le Chevalier, A. Riviere, J. Viala, C. Daniel, L. Robert, P. Barthélemy, A. Fandi, P. Ruffié
Journal: Journal of Clinical Oncology (2003)

The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks.Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported.The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.
Color vision of ancestral organisms of higher primates
Authors: M Nei, J Zhang, S Yokoyama
Journal: Molecular Biology and Evolution (1997)

The color vision of mammals is controlled by photosensitive proteins called opsins. Most mammals have dichromatic color vision, but hominoids and Old World (OW) monkeys enjoy trichromatic vision, having the blue-, green-, and red-sensitive opsin genes. Most New World (NW) monkeys are either dichromatic or trichromatic, depending on the sex and genotype. Trichromacy in higher primates is believed to have evolved to facilitate the detection of yellow and red fruits against dappled foliage, but the process of evolutionary change from dichromacy to trichromacy is not well understood. Using the parsimony and the newly developed Bayesian methods, we inferred the amino acid sequences of opsins of ancestral organisms of higher primates. The results suggest that the ancestors of OW and NW monkeys lacked the green gene and that the green gene later evolved from the red gene. The fact that the red/green opsin gene has survived the long nocturnal stage of mammalian evolution and that it is under strong purifying selection in organisms that live in dark environments suggests that this gene has another important function in addition to color vision, probably the control of circadian rhythms.
Freshly Isolated CD11c+ mDC Express The TSLPR And Responds To TSLP While pDC And In Vitro Cultured MoDC Do Not
Authors: P.A. Würtzen, G.K. Koed, G. Grauert, D. Papazian, S. Hansen, K. Lund
Journal: Journal of Allergy and Clinical Immunology (2011)
Nicotine Patch Therapy Based on Smoking Rate Followed by Bupropion for Prevention of Relapse to Smoking
Authors: Richard D. Hurt, James E. Krook, Ivana T. Croghan, Charles L. Loprinzi, Jeff A. Sloan, Paul J. Novotny, Carl G. Kardinal, James A. Knost, Maria Tria Tirona, Ferdinand Addo, Roscoe F. Morton, John C. Michalak, Paul L. Schaefer, Patricia A. Porter, Philip J. Stella
Journal: Journal of Clinical Oncology (2003)

Purpose: To determine whether (1) tailored nicotine patch therapy that is based on smoking rate can be carried out in a multisite oncology investigative group practice setting, (2) long-term use of bupropion reduces the rate of relapse to smoking in smokers who stop smoking with nicotine patch therapy, and (3) bupropion can initiate smoking abstinence among smokers who have failed to stop smoking after nicotine patch therapy. Participants and Methods: Fourteen North Central Cancer Treatment Group sites recruited generally healthy adult smokers from the general population for nicotine patch therapy and based the patch dosage on smoking rates. At completion of nicotine patch therapy, nonsmoking participants were eligible to be assigned to bupropion or placebo for 6 months (for relapse prevention). and smoking participants were eligible to be assigned to bupropion or placebo for 8 weeks of treatment. Results: Of 578 subjects, 31% were abstinent from smoking at the end of nicotine patch therapy. Of those subjects not smoking at the end of nicotine patch therapy who entered the relapse prevention phase, 28% and 25% were not smoking at 6 months (the end of the medication phase) for bupropion and placebo, respectively (P = .73). For those still smoking at the end of nicotine patch therapy, 3.1% and 0.0% stopped smoking with bupropion or placebo, respectively (P = .12). Conclusion: Tailored nicotine patch therapy for the general population of smokers can be provided in a multisite oncology investigative group setting. Bupropion did not reduce relapse to smoking in smokers who stopped smoking with nicotine patch therapy. Bupropion did not initiate abstinence among smokers who failed to stop smoking with nicotine patch therapy.
Genetic Testing for Long-QT Syndrome
Authors: Suraj Kapa, David J. Tester, Benjamin A. Salisbury, Carole Harris-Kerr, Manish S. Pungliya, Marielle Alders, Arthur A.M. Wilde, Michael J. Ackerman
Journal: Circulation (2009)

Background— Genetic testing for long-QT syndrome (LQTS) has diagnostic, prognostic, and therapeutic implications. Hundreds of causative mutations in 12 known LQTS-susceptibility genes have been identified. Genetic testing that includes the 3 most commonly mutated genes is available clinically. Distinguishing pathogenic mutations from innocuous rare variants is critical to the interpretation of test results. We sought to quantify the value of mutation type and gene/protein region in determining the probability of pathogenicity for mutations. Methods and Results— Type, frequency, and location of mutations across KCNQ1 (LQT1), KCNH2 (LQT2), and SCN5A (LQT3) were compared between 388 unrelated “definite” (clinical diagnostic score ≥4 and/or QTc ≥480 ms) cases of LQTS and &gt;1300 healthy controls for each gene. From these data, estimated predictive values (percent of mutations found in definite cases that would cause LQTS) were determined according to mutation type and location. Mutations were 10 times more common in cases than controls (0.58 per case versus 0.06 per control). Missense mutations were the most common, accounting for 78%, 67%, and 89% of mutations in KCNQ1 , KCNH2 , and SCN5A in cases and &gt;95% in controls. Nonmissense mutations have an estimated predictive value &gt;99% regardless of location. In contrast, location appears to be critical for characterizing missense mutations. Relative frequency of missense mutations between cases and controls ranged from ≈1:1 in the SCN5A interdomain linker to infinity in the pore, transmembrane, and linker in KCNH2. These correspond to estimated predictive values ranging from 0% in the interdomain linker of SCN5A to 100% in the transmembrane/linker/pore regions of KCNH2. The estimated predictive value is also high in the linker, pore, transmembrane, and C terminus of KCNQ1 and the transmembrane/linker of SCN5A. Conclusions— Distinguishing pathogenic mutations from rare variants is of critical importance in the interpretation of genetic testing in LQTS. Mutation type, mutation location, and ethnic-specific background rates are critical factors in predicting the pathogenicity of novel mutations. Novel mutations in low-estimated predictive value regions such as the interdomain linker of SCN5A should be viewed as variants of uncertain significance and prompt further investigation to clarify the likelihood of disease causation. However, mutations in regions such as the transmembrane, linker, and pore of KCNQ1 and KCNH2 may be defined confidently as high-probability LQTS-causing mutations. These findings will have implications for other genetic disorders involving mutational analysis.
Neandertal Origin of Genetic Variation at the Cluster of OAS Immunity Genes
Authors: F. L. Mendez, J. C. Watkins, M. F. Hammer
Journal: Molecular Biology and Evolution (2013)

Analyses of ancient DNA from extinct humans reveal signals of at least two independent hybridization events in the history of non-African populations. To date, there are very few examples of specific genetic variants that have been rigorously identified as introgressive. Here, we survey DNA sequence variation in the OAS gene cluster on chromosome 12 and provide strong evidence that a haplotype extending for ∼185 kb introgressed from Neandertals. This haplotype is nearly restricted to Eurasians and is estimated to have diverged from the Neandertal sequence ∼125 kya. Despite the potential for novel functional variation, the observed frequency of this haplotype is consistent with neutral introgression. This is the second locus in the human genome, after STAT2, carrying distinct haplotypes that appear to have introgressed separately from both Neandertals and Denisova.
Falling Insulin Requirements Are Associated With Adverse Obstetric Outcomes in Women With Preexisting Diabetes
Authors: Suja Padmanabhan, Mark McLean, N. Wah Cheung
Journal: Diabetes Care (2014)

To investigate the clinical significance of falling insulin requirements in women with preexisting or overt diabetes in pregnancy.A retrospective review of 139 pregnancies was conducted in women, with preexisting diabetes, delivering between January 2010 and January 2013. Women with falling insulin requirements of 15% or more from the peak total daily dose in late pregnancy were considered case subjects (n = 35). The primary outcome consisted of a composite of clinical markers of placental dysfunction, including preeclampsia, small for gestational age (SGA, ≤5th percentile for gestational age), stillbirth (>20 weeks), and premature delivery (≤30 weeks).A total of 25.2% of women had >15% fall in insulin requirements with nulliparity as the only predictor at baseline (odds ratio [OR] 2.5 [95% CI 1.1-5.7], P = 0.03). Falling insulin requirements were associated with an increased risk of preeclampsia (OR 3.5 [1.1-10.7], P < 0.05) and the composite of clinical markers of placental dysfunction (4.4 [1.73-11.26], P = 0.002). Although falling insulin requirements were associated with higher rates of SGA (3.4 [1.0-11.3], P = 0.048), they were not associated with other adverse neonatal outcomes. However, there was a higher incidence of neonatal intensive care unit admission (15.5 [3.1-77.6], P = 0.001) and earlier delivery in this group (median 37.7 weeks [IQR 34.3-38.4] vs. 38.3 weeks [37.4-38.9], P = 0.014).Falling insulin requirements, in women with preexisting diabetes, are associated with an increased risk of complications related to placental dysfunction. Further prospective studies are needed to guide clinical management.
Homocysteine in Health and Disease
Authors: P. Vallance
Journal: Journal of the Royal Society of Medicine (2002)

Bodies Politic: Diseases, Death and Doctors in Britain, 1650±1900How do you picture history?Conventional visual images from the past portray their subjects in an ostensibly realistic manner, but others convey more personal messages from the artist.Such messages may be coded, or transmitted with brutal directness.Individual people, events and places are transformed into stereotypes and metaphors to provide comment on more general social or political situations, usually with strong overtones of parody, protest or subversion.The subjects are to varying degrees remodelled to form caricatures, which range from the comical to the repulsive.Such images are often supplementary to or indeed directly linked with verbal images in the novels, plays, poems and pamphlets of the times and, to this extent, the visual and the verbal cannot be separated.Both provide valuable commentary on the historical contexts in which they are set.Bodies Politic 1 is one of a new series entitled `Picturing History', and British medicine between 1650 and 1900 provides abundant material for Professor Roy Porter to develop several questionsÐnotably, `How did the body and healing practices . . .supply metaphoric commentary upon the wider world of politics and the body politic?'.The emphasis inevitably falls on `the long eighteenth century', on metropolitan rather than provincial practice, and on patients `of the better sort' with time and money at their disposal.Views of the body itself were inherently con¯icting during this periodÐloathsome object or divine handiwork?Thus Gibbon disliked `. . . the naked frankness of Montaigne who exposes all his malady and the operation of each dose of physic on his nerves and bowels', and he was painfully distressed by his own last and unpleasant illnessÐ `varnish the business for the ladies'.Gibbon's less fastidious contemporaries were, however, deeply interested in other people's bodily misfortunes.Publicity was guaranteed for giants, dwarfs and the malformed, and visits to `the Poore lunatiques' at Bethlem hospital provided (according to taste) edi®cation or raucous sport up until 1770.Mary Toft from Godalming, who claimed to give birth to litters of rabbits, was displayed in London in 1726, and was recorded by Hogarth.Rare but profound enjoyment was to be had from botched executions, and the case of Ann Green, hanged in Oxford in 1650, was widely reported.Anthony a Á Wood recorded that `she was carried away to be anatomized by