tbuckley/cabot-search huggingface dataset:
Combined effects of rate membrane potential, and drugs on maximum rate of rise (Vmax) of action potential upstroke of guinea pig papillary muscle.
Authors: C Chen, L S Gettes
Journal: Circulation Research (1976)

We studied the effect of increasing the rate of stimulation on the maximum rate of rise of the action potential upstroke (Vmax) in guinea pig papillary muscles at various resting membrane potentials and after the addition of quinidine and lidocaine to the perfusate. Increasing rate caused a decrease in Vmax due to interaction of three factors: (1) a metabolic factor, presumably resetting of the Na-K pump, which caused a decrease in Vmax at all levels of resting potential between -90 and -60 mV, (2) a transient decrease in resting potential which influenced Vmax when the resting potential was less negative than approximately -80 mV, and (3) the recovery characteristics of Vmax which contributed to the decrease in this variable when rate was faster than 5/sec. As a result of these factors the steady state curve relating membrane potential to Vmax was itself rate-dependent. Lidocaine and quinidine exaggerated the rate-dependent decrease in Vmax; however, their effects differed. The effect of quinidine was consistent with its known depressant effect on the Na-K pump. The lidocaine effect was consistent with a slowing of recovery of Vmax. Our results help to explain the effects of an increase in rate on Vmax and conduction velocity in normal, partially depolarized, and drug-treated fibers
Independent review is needed to decide HFEA's fate
Authors: C. Dyer
Journal: BMJ (2011)

Should the UK Human Fertilisation and Embryology Authority (HFEA) be rescued from the axe, or should it, as the UK government proposes, be allowed to perish, its functions absorbed by larger, more general bodies?

At a panel discussion organised by the Progress Educational Trust at the Royal Society in central London, three of the four speakers favoured retaining a specialist regulator of infertility treatment and embryo research. But Alison Murdoch, professor of reproductive medicine at Newcastle University’s Institute of Human Genetics, disagreed and called for an independent review of the HFEA’s function in regulating treatment.

The authority is on a list of 192 quangos that the government proposes to abolish, in many cases transferring their functions to other bodies. The HFEA’s role in regulating and licensing fertility clinics should be taken over by …
Task force II: The relation of cardiovascular specialists to patients, other physicians and physician-owned organizations
Authors: William L. Winters, Henry D. McIntosh, Melvin D. Cheitlin, Rebecca Elon, Thomas B. Graboys, Spencer B. King, Carolyn Murdaugh, David Orentlicher, Thomas A. Ports, W.Gerald Rainer, Elliot Rapaport, William Y. Rial, Elijah Saunders, Daniel J. Ullyot, John G. Weg
Journal: Journal of the American College of Cardiology (1990)
THE ETIOLOGY AND TREATMENT OF TRENCH FOOT
Authors: JOSHUA E. SWEET
Journal: JAMA (1918)

The usual classification of the disease known as "trench foot" is based entirely on a clinical picture.From this clinical picture also the attempt is made to deduce the etiology, and the nature of the most severe type of case is such as to seem to warrant the conclu- sion that the disease starts from the outside of the foot.Therefore the most common form of treatment
Abstract 324: The integrin-linked kinase (ILK) / Rictor complex is required for TGFβ-1-induced epithelial to mesenchymal transition (EMT)
Authors: Isabel Serrano-Martinez, Paul C. McDonald, Shoukat Dedhar
Journal: Cancer Research (2012)

Abstract Epithelial to mesenchymal transition (EMT) causes fibrosis, cancer progression and metastasis. Integrin-linked kinase is a focal adhesion adaptor and serine/threonine protein kinase that regulates cell proliferation, survival, and EMT. Elucidating the molecular mechanisms necessary for the development and progression of human malignancies is critical to predict the most appropriate targets for cancer therapy. Here we used transforming growth factor beta-1 (TGFβ-1) to promote EMT and migration in mammary epithelial cells. We demonstrate a requirement of ILK activity for TGFβ-1 mediated EMT in mammary epithelial cells. In addition to nuclear translocation of Snail and Slug, TGFβ-1 treatment also induced expression of the mTORC2 component Rictor as well as its phosphorylation on Thr1135. Interestingly, TGFβ-1 treatment also induced an interaction between ILK and Rictor. All of these TGFβ-1-induced processes were significantly suppressed by inhibiting ILK activity or by disrupting the ILK-Rictor complex using siRNA-mediated knockdown. Furthermore, we identified formation of the ILK/Rictor complex formation in cancer but not normal cell types, and this was accompanied by ILK-dependent phosphorylation of Rictor on residue Thr1135. Inhibition of ILK partially reversed the basal mesenchymal phenotype of MDA-MB-231 cells and prevented EMT in MCF10A cells following TGFβ-1 treatment. These data demonstrate a requirement for ILK function in TGFβ-1-induced EMT in mammary epithelial cells and identify the ILK/Rictor complex as a potential molecular target for preventing/reversing EMT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 324. doi:1538-7445.AM2012-324
Hypoglycemia Resulting from Insecticide Poisoning
Authors: T. B. Magath
Journal: JAMA (1963)

<h3>To the Editor:—</h3> It is unfortunate that in the present highly charged atmosphere in which the pesticide problem exists,The Journalshould publish a case report under the title, "Hypoglycemia Resulting from Insecticide Poisoning," when so little support for the title is contained in the report and when the authors hedge in their own stated conclusions (<b>184</b>:590 [May 18] 1963). The case has already made the newspapers of the country. The authors performed some experiments by injecting, intravenously and into the peritoneal cavity of mice, 0.05 mg and 0.1 mg of parathion. (This would be equivalent to 15 mg and 30 mg for the child whose case was reported. How would she have acquired that amount?) There followed an immediate fall in blood-sugar level (but not nearly so low as recorded for the child) which returned to normal in less than 2 hours. This is hardly comparable to the
Infliximab induction therapy for patients with severe plaque-type psoriasis: A randomized, double-blind, placebo-controlled trial
Authors: Alice B. Gottlieb, Robert Evans, Shu Li, Lisa T. Dooley, Cynthia A. Guzzo, Daniel Baker, Mohan Bala, Colleen W. Marano, Alan Menter
Journal: Journal of the American Academy of Dermatology (2004)
Expression of Nuclear Factor-κB and IκBα Proteins in Prostatic Adenocarcinomas
Authors: Jeffrey S. Ross, Bhaskar V. S. Kallakury, Christine E. Sheehan, Hugh A. G. Fisher, Ronald P. Kaufman, Prabhjot Kaur, Karen Gray, Bradley Stringer
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The nuclear transcription factor nuclear factor-κB (NFκB) and its inhibitor, IκB, regulate the transcription of various genes involved in cell proliferation, adhesion, and survival. The NFκB transcription factor complex plays a role in cancer development and progression through its influence on apoptosis. More recently, NFκB has been shown to be activated in human and androgen-independent prostate cancer cells. To our knowledge, this is the first study demonstrating the prognostic significance of NFκB immunoreactivity in prostate adenocarcinomas (PACs). Experimental Design: Using prostatectomy specimens, we performed immunohistochemical staining for NFκB and IκBα (Santa Cruz Biotechnology) on formalin-fixed, paraffin-embedded sections obtained from 136 patients with PAC. Cytoplasmic and nuclear immunoreactivity was scored for intensity and distribution, and results were correlated with preoperative serum prostate-specific antigen, tumor grade, stage, DNA ploidy (Feulgen spectroscopy), and biochemical disease recurrence. Results: Forty-nine percent of PACs overexpressed cytoplasmic NFκB, and 63% showed decreased IκB expression. Cytoplasmic NFκB overexpression correlated with advanced tumor stage (P = 0.048), aneuploidy (P = 0.022), and biochemical disease recurrence (P = 0.001). When we compared the means for the NFκB-positive and -negative subgroups, NFκB overexpression correlated with preoperative serum prostate-specific antigen (P = 0.04) and DNA index (P = 0.05). Fifteen percent of PACs expressed nuclear NFκB, which correlated with high tumor grade (P = 0.001) and advanced stage (P = 0.05). Decreased IκBα expression correlated with high tumor grade (P = 0.015). On multivariate analysis, tumor stage (P = 0.043) and NFκB overexpression (P = 0.006) were independent predictors of biochemical recurrence. Conclusion: These results support a role for NFκB pathway proteins in the tumorigenesis of PACs. The findings are also consistent with reported experimental studies suggesting a new strategy of combined chemotherapy and specific NFκB blockade in decreasing the rate of disease relapse.
High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments.
Authors: M Basta, M C Dalakas
Journal: Journal of Clinical Investigation (1994)

In patients with dermatomyositis (DM) the earliest lesion is microvasculopathy mediated by deposition of C5b-C9 membranolytic attack complex (MAC) on intramuscular capillaries. This leads sequentially to muscle ischemia, necrosis of muscle fibers, and muscle weakness. High-dose intravenous immunoglobulin (IVIG), which can modulate complement-dependent tissue damage in animal models, has been shown to be effective in the treatment of patients with DM. We used an in vitro C3 uptake assay to examine 55 coded sera from 13 patients with DM and 5 patients with other non-complement-mediated neuromuscular diseases, before and after treatment with IVIG or placebo. Patients with active DM had a significantly higher baseline C3 uptake compared with the others (geometric mean 12,190 vs 3,090 cpm). Post-IVIG but not post-placebo sera inhibited the C3 uptake, without depleting the complement components, by 70.6-93.4%. The maximum inhibition of C3 uptake occurred within hours after IVIG infusion, started to rebound 2 d later, and reached pretreatment levels after 30 d. The serum levels of SC5b-9 complex production were high at baseline but normalized after IVIG therapy. Repeat biopsies from muscles of improved patients showed disappearance of C3b NEO and MAC deposits from the endomysial capillaries and restoration of the capillary network. We conclude that IVIG exerts its beneficial clinical effect by intercepting the assembly and deposition of MAC on the endomysial capillaries through the formation of complexes between the infused immunoglobulins and C3b, thereby preventing the incorporation of activated C3 molecules into C5 convertase. These findings provide the first serological and in situ evidence that IVIG modulates complement attack in a human disease.
The Impact of Mississippi's Mandatory Delay Law on Abortions and Births
Authors: Theodore Joyce
Journal: JAMA (1997)

Beginning August 8, 1992, a woman in the state of Mississippi had to wait 24 hours after in-person receipt of state-mandated information regarding abortion and birth complications, fetal development, and alternatives to abortion before an abortion could be performed.To analyze the effect of the law on the abortion and birth rates of Mississippi residents.A retrospective analysis of abortion and birth rates before and after the law in Mississippi as contrasted with abortion and birth rates in 2 comparison states, Georgia and South Carolina. Neither Georgia nor South Carolina enforced a mandatory delay law, but both states began enforcement of parental notification statutes during the study period.Female residents of reproductive age in Mississippi, Georgia, and South Carolina between 1989 and 1994.We compared birth rates, abortion rates, the percentage of late abortions, and the percentage of abortions performed outside the state of residence for all women and then by age and race before and after August 1992 among women of Mississippi, Georgia, and South Carolina.We found that rate ratios (RRs) of resident abortion rates (rate after law implementation/rate before law implementation) declined 12% more in Mississippi than in South Carolina (95% confidence interval [CI], 8%-15%) and 14% more in Mississippi than in Georgia (95% CI, 10%-17%) in the 12 months after the law went into effect. Rate ratios for white adults declined 22% more in Mississippi than in South Carolina (95% CI, 17%-27%) and 20% more in Mississippi than in Georgia (95% CI, 15%-25%). Changes among nonwhite adults and white teens were more modest but also statistically significant (P<.05). For all women, RRs of the percentage of abortions performed after 12 weeks' gestation increased 39% more in Mississippi than in either South Carolina or Georgia (P<.05); the increase in the percentage of abortions after 12 weeks' gestation was observed for white and non-white adults (P<.05). We also show that the percentage of abortions performed out of state increased 42% more among women in Mississippi relative to women in South Carolina after the law (95% CI, 34%-50%).The timing of the decline in abortion rates in Mississippi, the lack of similar declines in comparison states, the rise in percentage of late abortions and abortions performed out of state and the apparent completeness of abortion reports suggest that Mississippi's mandatory delay statute was responsible for a decline in abortion rates and an increase in abortions performed later in pregnancy among residents of Mississippi. The effect of delay laws in other states will likely depend on whether statutes require 2 separate visits to the abortion provider (ie, clinics, hospitals, or physicians' offices where abortions are performed) and the availability of abortion services.
Delays in the diagnosis and surgical treatment of lung cancer.
Authors: J. S. Billing, F. C. Wells
Journal: Thorax (1996)

BACKGROUND: Patients admitted for resection of lung tumours frequently experience lengthy delays in diagnosis and preoperative investigations. This study was conducted to quantify this delay between presentation and definitive treatment and to assess the factors responsible for such a delay. METHODS: All patients undergoing lung resection for a tumour at a single surgical unit in 1993 were studied. The date of each consultation, investigation, and referral was identified, and the extent of any delay determined. RESULTS: The mean total delay from presentation to operation was 109 days. Within this period an average of one month occurred before referral to a respiratory specialist who then spent two months investigating the patient. After referral to a surgeon, surgery took place within a mean interval of 24 days. CONCLUSIONS: These delays to definitive treatment appear unacceptable. Points at which the efficiency of the diagnostic process could be improved are discussed. The length of delay did not correlate with tumour stage in this study.
Coagulation and Fibrinolytic Mechanisms During and After Normal Childbirth
Authors: J. Bonnar, G. P. McNicol, A. S. Douglas
Journal: BMJ (1970)

A detailed sequential study of the coagulation and fibrinolytic systems in 15 healthy women during normal childbirth showed that striking changes in keeping with activation of the clotting mechanism take place during and after placental separation. Shortening of the clotting-test results, a sharp increase of factors VIII and V, and a decrease of the plasma fibrinogen were found as the placenta separated. Within one hour of normal delivery the levels of fibrin/fibrinogen degradation products increased and fibrinolytic activity returned to normal non-pregnant levels. In the early puerperium a secondary increase took place in the plasma fibrinogen level, factor VIII remained raised, and the platelet count showed a pronounced rise; these changes may explain the increased predisposition to thromboembolic complications in the puerperium.
Ring-opening metathesis polymerization-based synthesis of polymeric nanoparticles for enhanced tumor imaging in vivo: Synergistic effect of folate-receptor targeting and PEGylation
Authors: Koji Miki, Kazuaki Oride, Satoru Inoue, Yoshiaki Kuramochi, Rati R. Nayak, Hideki Matsuoka, Hiroshi Harada, Masahiro Hiraoka, Kouichi Ohe
Journal: Biomaterials (2009)
CHOREA INSANIENS: REPORT OF A CASE WITH RECOVERY
Authors: Orlando H. Petty
Journal: JAMA (1925)

Osler<sup>1</sup>writes of having seen two cases of chorea insaniens and reports twelve other cases from the literature. All these were fatal and, at necropsy, showed vegetations of the mitral valves. While the mortality of this type of chorea is very high, Osler calls attention to the fact that only the more severe cases, usually ending in death, are reported. The case reported here is of a white girl, aged 12 years. Her mother had chorea at 13 years of age. An aunt on her mother's side died of chorea, at the age of 14, and an aunt and cousin of her mother's also suffered from chorea in youth. The girl had had measles, chickenpox, scarlet fever, influenza and, at the age of 7, a glandular fever of short duration. She had had several attacks of tonsillitis. During the last attack, Dec. 14, 1924, she was in bed three
Baby and Child
Authors: P. Leach
Journal: BMJ (1978)

<h3>Abstract</h3> Cardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolated a pan-LPM enhancer in the zebrafish <i>draculin</i> (<i>drl</i>) gene that provides specific LPM reporter activity from early gastrulation. <i>In toto</i> live imaging and lineage tracing of <i>drl</i>-based reporters captured the dynamic LPM emergence as lineage-restricted mesendoderm field. The <i>drl</i> pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncovered specific <i>drl</i> reporter activity in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, <i>Ciona</i>, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.
Japanese governor signs agreements with Johns Hopkins and Harvard medical schools to open first US medical school in Japan
Authors: G. Blair
Journal: BMJ (2014)

Japan’s first US medical school is to be established in Kawasaki City, Kanagawa Prefecture, south of Tokyo. 

The new facility, which will be a joint venture between leading US and Japanese universities, is part of a plan by the Kanagawa governor, Yuji Kuroiwa, to turn the prefecture into a centre of healthcare excellence. The provisionally named Medical Innovation School …
P116 Observational study to characterise 24-hour COPD symptoms: cross-sectional results from the ASSESS study: Abstract P116 Table 1.
Authors: M Miravitlles, H Worth, J Soler-Cataluña, D Price, F De Benedetto, F Roche, N Skavalan Godtfredsen, T van der Molen, C Löfdahl, L Padullés, A Ribera
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Little is known about the 24-hour profile of COPD symptoms. This study assessed the frequency/severity of 24-hour symptoms and their impact on patients’ well-being. <h3>Methods</h3> This cross-sectional, observational study was conducted in patients with stable COPD. Baseline night-time, early-morning and day-time symptoms (symptom questionnaire), dyspnoea (modified Medical Research Council dyspnoea scale [mMRC]), health status (COPD Assessment Test [CAT]), anxiety/depression levels (Hospital Anxiety and Depression Scale [HADS]) and sleep quality (COPD and Asthma Sleep Impact Scale [CASIS]) were assessed. Primary endpoint: baseline frequency, severity and inter-relationship of night-time, early-morning and day-time symptoms; secondary endpoints: relationship between 24-hour symptoms and dyspnoea, health status, anxiety/depression and sleep quality. <h3>Results</h3> 727 patients were recruited from eight countries: 65.8% male, mean ± SD age 67.2 ± 8.8 years, mean ± SD% predicted FEV<sub>1</sub> 52.7 ± 20.6%. Early-morning/day-time symptoms were most frequent; however night-time symptoms were common (Table). Symptom severity was comparable during the night-time, early-morning and day-time. In the week prior to baseline, 56.7% patients had symptoms throughout the 24-hours (79.9% in 2 or 3 parts of the day). Breathlessness was most common (71.4% patients); its prevalence increased throughout the 24-hours (32.1% night-time, 51.6% early-morning, 65.2% day-time). Dyspnoea, health status, anxiety/depression and sleep quality were worse in patients with night-time, early-morning or day-time symptoms versus patients without symptoms in each period (all p &lt; 0.001). Most patients with more severe dyspnoea (mMRC scale ≥2) had 24-hour symptoms (range 61.5–68.2%); patients with 24-hour symptoms had the worst health status (mean CAT score 20.0 vs range 8.1–14.9 in all other patients). Patients with any combination of night-time/early-morning symptoms had the highest anxiety (mean HADS scores 6.7–7.5 vs 3.6–5.8 in patients without this combination); depression levels were lowest in patients with no symptoms/only early-morning symptoms (mean HADS scores 4.2–5.4 vs 6.5–7.8 in all other patients). Patients with any night-time symptom had worse sleep quality than patients without night-time symptoms (mean CASIS scores 41.6–51.1 vs 31.6–35.5). <h3>Conclusions</h3> Most patients had COPD symptoms throughout the 24-hours. Dyspnoea, health status, anxiety/depression levels and sleep quality were significantly worse in patients who had symptoms in any part of the day.
Pyridoxine supplements in the carpal tunnel syndrome
Authors: T R C Boyde
Journal: BMJ (1995)

due to adhesions as a result of mesh being in contact with viscera are unknown.This contrasts with the low long term recurrence rate of less than 0-5-2%, minimal complications, and no deaths after many thousands of elective open repairs in unselected patients reported from many centres.If comparative trials are to be carried out then it is important that local anaesthesia is used for the open repair.Payne et al,3 Brooks,4 and Rudkin and Maddern5 have done so, and the latter two papers favoured the open mesh technique.Cost effectiveness must be considered.Taylor and Loosemore report on 700 laparoscopic pro- cedures.Laparoscopic disposables cost up to about ,C450 a case, so C315 000 would be required.Disposables for a mesh repair are £35 and would thus amount to £24 500 for 700 repairs.This difference in costs cannot be justified.Training surgeons in the laparoscopic technique is associated with a long learning curve and extra indirect costs.There are about 2500 general surgeons in England and Wales.I have taught experienced general surgeons the mesh techniques in a day.Brooks concluded that the open mesh repair (with local anaesthesia) is a "minimally invasive procedure, is appropriate for the greatest number of patients, is the least expensive and has the fewest short-and long-term complications."4Already three major hospitals in California have banned the laparoscopic hernia operation.