tbuckley/cabot-search huggingface dataset:
Post-partum Hypercalcaemia in Treated Hypoparathyroidism
Authors: A. D. Wright, G. F. Joplin, H. G. Dixon
Journal: BMJ (1969)

Two patients with post-thyroidectomy hypoparathyroidism were observed throughout three pregnancies. Their normal maintenance treatment with vitamin D remained unaltered. Serum calcium levels remained normal until shortly before delivery but rose rapidly in the immediate postpartum period to peak levels of 7.8, 6.0, and 6.8 mEq/l. while still on normal or reduced maintenance treatment. This apparent increased sensitivity to vitamin D after delivery persisted for as long as three months.
Is Nef the elusive cause of HIV-associated hematopoietic dysfunction?
Authors: Frank Kirchhoff, Guido Silvestri
Journal: Journal of Clinical Investigation (2008)

HIV-associated hematological abnormalities involve all lineages of blood cells, thus implying that the virus impairs the function of early HSCs. However, the underlying mechanisms of this defect are unknown, particularly since HSCs are largely resistant to HIV-1 infection. In this issue of the JCI, Prost and colleagues show that the viral accessory protein Negative factor (Nef) plays a potentially critical role in the pathogenesis of HIV/SIV-associated hematopoietic dysfunction by affecting the clonogenic potential of HSCs (see the related article beginning on page 1765). Soluble Nef induces PPARγ in uninfected HSCs, thereby suppressing the expression of STAT5A and STAT5B, two factors necessary for proper HSC function. The identification of this novel activity of extracellular Nef defines a new mechanism of HIV/SIV pathogenesis and suggests that approaches aimed at increasing STAT5A and STAT5B expression may be considered in HIV-infected individuals with prominent hematological abnormalities. The results also raise the question of whether dysregulation of hematopoiesis by extracellular Nef plays a role in the development of T cell immunodeficiency and the high levels of chronic immune activation associated with AIDS.
“To do or not to do?” Modeling the control of behavior
Authors: John D. Swain, James E. Swain
Journal: Behavioral and Brain Sciences (2005)

The author of this fascinating book explores the problem of decision-making. As a basis, he uses hyperbolic discounting theory to discuss many basic assumptions related to self-control. In an accessible conversational tone, he succeeds in capturing many current problems in decision science and presents a rational framework for further work.
American Drug Index, 1962
Authors: Joseph B. Jerome
Journal: JAMA (1962)

Two texts, in this reviewer's opinion, are outstanding in the presentation of nomenclature information in the drug field. They are not mutually exclusive. One is the subject of this review; the other is the<i>Merck Index</i>. The<i>American Drug Index</i>, by virtue of its more frequent publication schedule, provides more nomenclature information on newer drug products. It identifies these products in terms of all designations ( nonproprietary names and trademarks) that have been brought into use. While not, as yet, fully implemented, a significant feature of the present edition is the identification of those nonproprietary names adopted as a result of formal processes ( USP, NF, or AMA, the latter covering names adopted by the AMA Nomenclature Committee or its successor the AMA-USP Nomenclature Committee). The<i>American Drug Index</i>presents, in well-organized fashion, adequate information to permit identification of the listed drug products in terms of other existing names, manufacturer, and therapeutic
Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone
Authors: David J Graham, Rita Ouellet-Hellstrom, Thomas E MaCurdy, Farzana Ali, Christopher Sholley, Christopher Worrall, Jeffrey A Kelman
Journal: JAMA (2010)

Studies have suggested that the use of rosiglitazone may be associated with an increased risk of serious cardiovascular events compared with other treatments for type 2 diabetes.To determine if the risk of serious cardiovascular harm is increased by rosiglitazone compared with pioglitazone, the other thiazolidinedione marketed in the United States.Nationwide, observational, retrospective, inception cohort of 227,571 Medicare beneficiaries aged 65 years or older (mean age, 74.4 years) who initiated treatment with rosiglitazone or pioglitazone through a Medicare Part D prescription drug plan from July 2006-June 2009 and who underwent follow-up for up to 3 years after thiazolidinedione initiation.Individual end points of acute myocardial infarction (AMI), stroke, heart failure, and all-cause mortality (death), and composite end point of AMI, stroke, heart failure, or death, assessed using incidence rates by thiazolidinedione, attributable risk, number needed to harm, Kaplan-Meier plots of time to event, and Cox proportional hazard ratios for time to event, adjusted for potential confounding factors, with pioglitazone as reference.A total of 8667 end points were observed during the study period. The adjusted hazard ratio for rosiglitazone compared with pioglitazone was 1.06 (95% confidence interval [CI], 0.96-1.18) for AMI; 1.27 (95% CI, 1.12-1.45) for stroke; 1.25 (95% CI, 1.16-1.34) for heart failure; 1.14 (95% CI, 1.05-1.24) for death; and 1.18 (95% CI, 1.12-1.23) for the composite of AMI, stroke, heart failure, or death. The attributable risk for this composite end point was 1.68 (95% CI, 1.27-2.08) excess events per 100 person-years of treatment with rosiglitazone compared with pioglitazone. The corresponding number needed to harm was 60 (95% CI, 48-79) treated for 1 year.Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older.
Allergy to Apple, Carrot and Potato in Children with Birch Pollen Allergy
Authors: Sten Dreborg, Tony Foucard
Journal: Allergy (1983)

Skin sensitivity to apple, carrot and potato, clinically related to birch pollinosis was investigated. Different skin test techniques using fresh fruit were compared. A simple prick test (SPI) technique with a lancet piercing the apple peel just before pricking the skin was shown to be the most practical and to give reproducible results. The allergenic activity in apple was found to be heat labile and deteriorated during storage at room temperature, Apple, carrot, potato, hazelnut and birch reactivity was transferable in Prausnitz‐Küstner test like IgE antibodies. SPT reactivity to fresh material from apple, carrot and potato was investigated in 174 children of whom 128 suffered from pollen allergy. Positive SPT results were obtained almost exclusively in children who were SPT positive to a birch pollen extract. Children who noticed clinical symptoms when eating apple, raw carrot or potato were found to have a significantly larger SPT reaction than children with a negative history.
The alcohol harm reduction strategy for England
Authors: Martin Plant
Journal: BMJ (2004)

Overdue final report omits much that was useful in interim report 

The United Kingdom as a whole has a serious problem in relation to the increasing levels of the adverse effects of drinking across gender and age groups.1–4 The report from the prime minister's strategy unit has been awaited with great interest. It is years overdue. Counterparts in Northern Ireland, Scotland, and Wales have been published for some time. The production of the strategy was undertaken by civil servants who consulted widely and produced an interim report that had much to commend it.5 A postgraduate thesis could be written to document and analyse the differences between the interim report, the final report, and the inconsistencies between different sections of the final document.6 The latter has been neutered. Issues such as sex, children of problem drinkers, and pregnancy have virtually disappeared.

The harm minimisation strategy states that binge drinking and chronic drinking are the main targets of proposed action to reduce the “further increase in alcohol related harms in England.” That this statement seems to accept the current high level of alcohol problems rather than setting out to reduce them substantially is depressing. Dates and targets for this would …
A gamma methionine-310 to threonine substitution and consequent N-glycosylation at gamma asparagine-308 identified in a congenital dysfibrinogenemia associated with posttraumatic bleeding, fibrinogen Asahi.
Authors: K Yamazumi, K Shimura, S Terukina, N Takahashi, M Matsuda
Journal: Journal of Clinical Investigation (1989)

In an abnormal fibrinogen with severely impaired polymerization of fibrin monomers, we identified a methionine-to-threonine substitution at position 310 of the gamma chain. Furthermore, asparagine at position 308 was found to be N-glycosylated due to a newly formed consensus sequence, asparagine(308)-glycine(309)-threonine(310). The two structural defects in the mutant gamma chain may well perturb the conformation required for fibrin monomer polymerization that is specifically assigned to the D domain of fibrinogen. This alteration also seems to affect the intermolecular gamma chain cross-linking of fibrin and fibrinogen, although the amine acceptor gamma glutamine-398 was found to function normally. These functional abnormalities may well be related to posttraumatic hemorrhage as observed in a 33-yr-old man with moderate hemorrhagic diathesis related to injuries since his early adolescence. The structure of the extra carbohydrate moiety attached to asparagine-308 was found to be identical with those derived from the normal B beta and gamma chains as evidenced by HPLC.
A Ubiquitous Splice Variant and a Common Polymorphism Affect Heterologous Expression of Recombinant Human SCN5A Heart Sodium Channels
Authors: Jonathan C. Makielski, Bin Ye, Carmen R. Valdivia, Matthew D. Pagel, Jielin Pu, David J. Tester, Michael J. Ackerman
Journal: Circulation Research (2003)

Amino acid sequence variations in SCN5A are known to affect function of wild-type channels and also those with coexisting mutations; therefore, it is important to know the exact sequence and function of channels most commonly present in human myocardium. SCN5A was analyzed in control panels of human alleles, demonstrating that the existing clones (hH1, hH1a, hH1b) each contained a rare variant and thus none represented the common sequence. Confirming prior work, the H558R polymorphism was present in ≈30% of subjects. Quantitative mRNA analysis from human hearts showed that a shorter 2015 amino acid splice variant lacking glutamine at position 1077 (Q1077del) made up 65% of the transcript in every heart examined. Age, sex, race, or structural heart disease did not affect this proportion of Q1077del. Estimated population frequencies for the four common variants were 25% SCN5A, 10% [H558R], 45% [Q1077del], and 20% [H558R;Q1077del], where the reference sequence SCN5A is GenBank AC137587. When expressed in HEK-293 cells, these common variants had a more positive mid-point of the voltage dependence of inactivation than the standard clone hH1. Also, channels containing Q1077 expressed smaller currents. When H558R was present with Q1077 ([H558R]), current expression was profoundly reduced despite normal trafficking to the cell surface. Thus, four variant sequences for SCN5A are commonly present in human myocardium and they exhibit functional differences among themselves and with the previous standard clone. These results have implications for the choice of background sequence for experiments with heterologous expression systems, and possibly implications for electrophysiological function in vivo.
Adult Immunization With Acellular Pertussis Vaccine
Authors: Kathryn M. Edwards
Journal: JAMA (1993)

To evaluate the safety and immunogenicity in adults of several different concentrations of an acellular pertussis vaccine.Double-blind, randomized, placebo-controlled trial.Medical center immunization clinic.One hundred eighteen healthy adult volunteers.Participants received standard adult tetanus-diphtheria vaccine alone or combined with full-strength, half-strength, or quarter-strength concentrations of a currently licensed acellular pertussis vaccine used for booster doses in young children. Full-strength vaccine contained 40 micrograms of pertussis proteins, consisting of 86% filamentous hemagglutinin, 8% pertussis toxin, 4% 69-kd outer-membrane protein, and 2% agglutinogens.Local and systemic reactions were assessed for 14 days after vaccination. Serum samples for antibody assay were obtained before, 1 month after, and 1 year after immunization.Adverse reactions were few and minor and did not differ in frequency or severity among the four study groups. The groups receiving acellular pertussis vaccine showed strong antibody responses to pertussis antigens, which did not significantly differ by concentration of vaccine. After 1 year, levels of antibody to pertussis had declined by approximately 50% but remained substantially higher than preimmunization levels. The four groups did not differ in antibody responses to tetanus or diphtheria toxoids.Routine reimmunization of adults with a vaccine containing acellular pertussis antigens in addition to diphtheria and tetanus toxoids can substantially enhance pertussis antibody levels without an increase in adverse reactions or diminution in response to the diphtheria and tetanus components. Such a program might materially reduce respiratory illness among both adults and children.
Not to be taken as directed
Authors: M. Marinker
Journal: BMJ (2003)

When the medicines that doctors prescribe fail to produce the benefit they expect, they often respond by varying the dose or selecting an alternative medicine. Thus doctors seem to behave as though non-compliance is a problem for other doctors. Although we know that about half of the medicines prescribed for patients with long term conditions are not taken as prescribed,1 the concerns of health professionals have focused almost exclusively on improving the quality of their own prescribing choices. Similarly, attention and resources devoted by pharmaceutical companies to discovering, developing, and promoting new drugs utterly dwarf their efforts to see that medicines are taken by patients. Yet non-compliance continues to represent a serious therapeutic deficit at the core of medical practice, with consequent massive personal, societal, and economic cost.

Patients do not comply with medication for several reasons.2 Non-compliance may be intentional or involuntary. It may relate to the quality of information given, the impact of the regimen on daily life, the physical or ental incapacity of patients, or their …
Correlation of dasatinib (DAS) peak levels with interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels in patients with castration-resistant progressive prostate cancer (CRPC).
Authors: F. Dayyani, G. E. Gallick, J. T. Thompson, G. C. Trudel, C. Logothetis, J. C. Araujo
Journal: Journal of Clinical Oncology (2010)

4665 Background: IL-8 has been reported to promote CRPC growth [Am J Path1999;1503]. Further, MCP-1 mediates tumor- induced osteoclastogenesis and bone resorption [Cancer Res 2007;3646]. Dasatinib (DAS), a potent SRC-family kinase inhibitor, affects tumor growth and bone turnover induced by CRPC, the latter, by potentially blocking osteoclast activation Thus, the effects of DAS in CRPC might in part be mediated through reduction of either IL-8 and/or MCP-1 levels. Here, we analyzed the correlation between serum peak DAS levels with IL-8 and MCP-1 levels in the phase II portion of a phase I/II study of DAS and docetaxel (D) for treatment of metastatic CRPC. Data was analyzed for patients enrolled at M. D. Anderson Cancer Center (MDACC). Methods: Male pts with progressive CRPC and testosterone levels ≤50 ng/dL requiring chemotherapy were enrolled. Escalating doses of DAS and D were evaluated. The doses selected for the included pts was DAS 100mg QD and D 75mg/m2 Q21D. DAS, IL-8 and MCP-1 levels were measured on day 14 of cycle 1, at 0 and 2hrs, post-administration. The correlation coefficient was calculated to establish linear relationship. Results: Serum was available for 18/33 pts for analysis. Trough and 2-hr peak DAS levels were 1.7ng/ml (range:1.1-7.1) and 59.1ng/ml (14.7-93.1), respectively. Higher increases of DAS levels from baseline were significantly associated with a decline in IL-8 (P=0.032) and MCP-1 levels (P=0.030). 14/18 pts had a PSA response >50%, radiologic PR/CR was seen in 10/14 pts with lymph node mets and SD in 9/10 pts with bone mets. Furthermore, among all pts enrolled at MDACC, a ≥35% decrease of the bone turnover marker uNTX was observed in ∼50% of evaluable pts. Conclusions: The combination of DAS + D is effective in CRPC. The magnitude of the increase in DAS levels significantly correlates with the decline of the cytokines IL-8 and MCP-1, possibly providing a mechanism of action for DAS plus D. The serum t1/2 of IL-8 might be altered in this setting. These findings will be validated in the ongoing phase 3 trial of DAS and D in pts with CRPC and might prove to be a predictive marker for DAS activity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A
Authors: Nae-Yun Heo, Young-Suk Lim, Jihyun An, Sun-Young Ko, Heung-Bum Oh
Journal: Clinical and Molecular Hepatology (2012)

Background/Aims The early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA. Methods Samples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA. Results The concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an "equivocal" result was regarded as positive; and 79.1% and 100%, respectively, when an "equivocal" result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA. Conclusions The qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti-HAV and may be more sensitive during the window period. Keywords: Hepatitis A; Hepatitis A antibodies; RNA; Polymerase chain reaction
A Randomized Controlled Trial of Cognitive Therapy versus Intensive Behavior Therapy in Obsessive Compulsive Disorder
Authors: Jean Cottraux, Ivan Note, Sai Nan Yao, Sylviane Lafont, Brigitte Note, Evelyne Mollard, Martine Bouvard, Alain Sauteraud, Marc Bourgeois, Jean-François Dartigues
Journal: Psychotherapy and Psychosomatics (2001)

&lt;i&gt;Background:&lt;/i&gt; The study was designed to compare cognitive therapy (CT) with intensive behavior therapy (BT) in obsessive-compulsive disorder (OCD) and to study their change process. &lt;i&gt;Methods:&lt;/i&gt; Sixty-five outpatients with DSM-4 OCD were randomized into 2 groups for 16 weeks of individual treatment in 3 centers. Group 1 received 20 sessions of CT. Group 2 received a BT program of 20 h in two phases: 4 weeks of intensive treatment (16 h), and 12 weeks of maintenance sessions (4 h). No medication was prescribed. &lt;i&gt;Results:&lt;/i&gt; Sixty-two patients were evaluated at week 4, 60 at week 16 (post-test), 53 at week 26 and 48 at week 52 (follow-up). The response rate was similar in the 2 groups. The Beck Depression Inventory (BDI) was significantly more improved by CT (p = 0.001) at week 16. The baseline BDI and Obsessive Thoughts Checklist scores predicted a therapeutic response in CT, while the baseline BDI score predicted a response in BT. At week 16, only the changes in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a scale measuring the interpretation of intrusive thoughts correlated in CT, while the changes in Y-BOCS, BDI, and interpretation of intrusive thoughts correlated in BT. Improvement was retained at follow-up without a between-group difference. The intent-to-treat analysis (last observation carried forward) found no between-group differences on obsessions, rituals and depression. &lt;i&gt;Conclusions:&lt;/i&gt; CT and BT were equally effective on OCD, but at post-test CT had specific effects on depression which were stronger than those of BT. Pathways to improvement may be different in CT and BT. The outcomes are discussed in the light of an effect size analysis.
Disorders of the Small Intestine
Authors: E. Spriggs
Journal: BMJ (1939)

The small intestine is the essential part of the alimentary tube.Health can be maintained or life can be endured without the stomach or the colon, and without the function of the gullet; but a good piece of the small bowel must remain.In structure it is primitive yet complex, made up nearly all of active cells, secreting, absorbing, or moving, with a rich blood and nerve supply and a minimum of binding fibres.It curls, twists, pales, and flushes as it mixes, digests, and chooses the foodstuffs and passes on what is left.It is responsive to the rest of the body through messages carried in nerves and blood, but can be as independent as any organ, keeping in life and on duty when almost all else has failed.The vital importance of the small bowel, with its expanse of absorbing cells, is shown by the marasmus which follows if too much of it is removed, by the intense toxaemia set up by acute enteritis, cholera, or enteric fever, and by the disaster of obstruction.The effects of faulty absorption may be seen in coeliac disease and in infantilism from tuberculous strictures and some cases of chronic ileitis.It is not surprising that if it is interfered with in any other way persistent and distressing symptoms should arise.Except for such conditions, and general infections like tuberculosis, the small intestine has a remarkable immunity as compared with other parts of the alimentary tube.Regional ileitis and carcinoid tumours, both uncommon, seem to be the only diseases peculiar to it.In this brief review it is not proposed to discuss any disease fully.A more detailed illustrated survey was published in 1937.A few words should be said about "flatulence," "wind," and "distension," for these are the commonest symptoms complained of in intestinal disorders, except perhaps constipation; and distension causes more distress in the small than in the large intestine.[The lecturer then described the composition and pressure of intestinal gases (Boycott and Dannant, 1907-8; Lloyd-Jones and Liljedahl, 1934; Wangensteen, 1937), and the circulation in the gut (Spriggs, 1931); and con- tinued:] For these reasons wind is a feature of any delay of bowel movement resulting in irregular spasms and inhibitions, as in disorders of the stomach or gut, in- cluding disturbance from unwise food or drink, and con-
Treatment of Deep-Vein Thrombosis
Authors: Shannon M. Bates, Jeffrey S. Ginsberg
Journal: New England Journal of Medicine (2004)

A 52-year-old woman with no history of venous thromboembolism presents with a four-day history of discomfort in her left calf. Proximal deep-vein thrombosis is diagnosed by compression ultrasonography. How should her case be managed?