tbuckley/cabot-search huggingface dataset:
Early Acquired Resistance to Endocrine Therapy: Extending the Neoadjuvant Model.
Authors: H. Anderson, H. Anderson, R. A'Hern, J. Salter, M. Hills, S. Detre, A. Larionov, A. Skene, W. Miller, J. Dixon, I. Smith, M. Dowsett, M. Dowsett
Journal: Cancer Research (2009)

Abstract Background: Neoadjuvant endocrine therapy allows biological studies of de novo response and resistance but not of acquired resistance based on clinical endpoints as surgery is usually carried out after around 4 months. Response is associated with a significant fall in Ki67 (proliferation) after 2 weeks treatment. However, at 12/16 weeks, c.15% of tumours show recovery of Ki67. We hypothesized that this recovery reflected rapidly acquired treatment resistance and have assessed its clinical relevance and association with tumour biomarkers.Methods: Ki67, ER, PgR and HER-2 (with FISH for 2+ cases) IHC measurements taken at baseline, 2 weeks and 12/16 weeks during neoadjuvant aromatase inhibitor (AI) treatment were available from three previously reported clinical trials [1-3] for a total of 177 ER+ patients. To allow pooling of data, ER and PgR levels were expressed as Allred scores. Long-term clinical follow-up data were available for 142 patients who received endocrine therapy within the IMPACT trial. Categories of response/resistance based on Ki67 change were created and patients classified accordingly: de novo resistance (&amp;lt;50% decrease in Ki67 from baseline to 2 weeks), acquired resistance (&amp;gt;50% decrease in Ki67 from baseline to 2 weeks, but overall fall at 12/16 weeks &amp;lt;50%) and maintained response (&amp;gt;50% decrease in Ki67 from baseline to 2 weeks and overall fall &amp;gt;50%).Results: Patients defined as showing acquired resistance had significantly worse RFS than those defined as showing maintained response (HR: 3.73, 95%CI: 1.18-11.79, p=0.025) and very similar to those with de novo resistance (HR: 3.66, 95% CI: 1.41-9.50, p=0.008). More HER-2+ cases showed Ki67 recovery than would be expected by chance (acquired resistance: 5/19 HER-2+, maintained response: 5/100 HER-2+; p=0.02). There was a weak suggestion that pre-treatment ER level may be lower for patients showing Ki67 recovery than those with persistent response (p=0.11), but no evidence was seen for an effect of pre-treatment PgR level (p=0.52).Conclusions: Tumours that exhibit an early Ki67 fall followed by Ki67 recovery at 12/16 weeks are associated with poorer RFS than those showing maintained suppression of Ki67 suggesting that Ki67 may act as a valid intermediate marker of acquired resistance. HER-2 positivity is associated with development of early acquired Ki67-based resistance, but other mechanisms for early acquired resistance exist.Supported by The Mary-Jean Mitchell Green Foundation.[1] Dowsett M et al., J Clin Oncol 2005. 23(11): 2477-92[2] Smith IE et al., J Clin Oncol 2007. 25(25): 3816-22[3] Miller WR et al., J Clin Oncol 2009. 27(9): 1382-7 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2005.
Prophylactic Eye Drops
Authors: E. Assinder
Journal: BMJ (1964)

We believe' that some if not most cases of this condition belong to the group of collagen disorders, many probably being connected in some way with rheumatoid disease.We are unconvinced by the arguments advanced that an alteration of nomenclature at this juncture for a condition whose aetiology remains obscure is likely to be of any advantaged-We are, etc.,
Evidence for lack of innervation of beta-2 adrenoceptors in the blood vessels of the gracilis muscle of the dog.
Authors: M P Russell, N C Moran
Journal: Circulation Research (1980)

Cardiac /S-l adrenoceptors respond to sympathetic nerve stimulation (SNS), but it is not clear that SNS evokes fi-2 adrenoceptor-mediated vasodilation.Sensitivity of B adrenoceptors to catecholamines and to SNS was evaluated in dogs.Norepinephrine (NE) and epinephrine (E) were equipotent vasoconstrictors (femoral artery blood flow or gracilis autoperfusion pressure) before aadrenoceptor blockade with dibozane (DIB).After DIB, NE was 1/100 as potent a vasodilator as E, which was equipotent with isoproterenol (ISO).SNS evoked gracilis muscle vasoconstriction before DIB and vasodilation after.Dilation induced by SNS or acetylcholine (ACH) after DIB was blocked by atropine (AT), but that caused by NE was not.Dilation evoked by NE, E, or I after DIB and AT was blocked by propranolol (PROP).Vasoconstrictor responses to NE, E, or SNS in dogs without DIB were not augmented by PROP at a dose that blocked the dilator effect of ISO.NE and E were equipotent and both 1/10 as potent as ISO as positive inotropic and chronotropic agents.Cardiac responses to NE, E, ISO, and SNS were antagonized by PROP.Subclassification of adrenoceptors that subserve cardiac stimulation as fi-1 and that subserve vasodilation as fi-2 was substantiated.Cardiac fi-1 adrenoceptors responded to SNS and to circulating E and NE.Vascular fi-2 adrenoceptors responded to circulating E, to ISO, and to high doses of NE, but not to SNS. fi-2 Adrenoceptors in blood vessels appear not to be innervated and may function as hormone receptors sensitive primarily to E released from the adrenal medulla, rather than to NE released from adrenergic nerves.
Clinical Heart Disease
Authors: James C. Broadbent
Journal: JAMA (1972)

This volume is more than a large monograph. It is a superb textbook in the great British tradition of an earlier era. It is ambitious, comprehensive, and yet delightfully readable. There are seven introductory chapters which concisely review applied embryology, anatomy, and physiology of the circulatory system, the clinical examination, auscultation, electrocardiography, vectorcardiography, radiology, and cardiac catheterization. Subsequent chapters comprehensively cover the entire field of clinical cardiology including the rheumatic triad, infective endocarditis, pericarditis, valvular disease, hypertension, ischemic and congenital heart disease, pulmonary heart disease dysrhythmias, heart failure, and cardiomyopathies. In addition, there are special chapters on traumatic and functional heart disease, cardiac emergencies, cardiac surgery, and diseases of vessels. Each chapter is followed by a unique summary entitled "Salient Features" wherein the reader may find selected gems of wisdom. A very few references to major monographs and papers conclude each chapter. An appendix presents a variety of handy data,
Th17‐ and Treg‐related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease
Authors: M. M.‐H. Guo, W.‐N. Tseng, C.‐H. Ko, H.‐M. Pan, K.‐S. Hsieh, H.‐C. Kuo
Journal: Allergy (2014)

Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease.Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-β, and mRNA expression levels of RORγt and Foxp3 were tested.Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A.Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.
Changes in Exeretion of Intestinal Cholesterol and Sterol Digitonides in Hyper- and Hypothyroidism
Authors: MEYER FRIEDMAN, SANFORD O. BYERS, RAY H. ROSENMAN
Journal: Circulation (1952)

The fecal output of cholesterol and of noncholesterol sterols was determined in hyper- and hypo-thyroid rats, and in a group of control animals. The intestinal excretion of cholesterol and of total digitonin-precipitable sterols was found to be considerably increased in the hyperthyroid, and considerably decreased in the hypothyroid animals. The relationship of these findings to the altered plasmal cholesterol content occurring in deranged thyroid states is discussed.
Local Gene Transfer and Expression Following Intramuscular Administration of FGF-1 Plasmid DNA in Patients With Critical Limb Ischemia
Authors: Iris Baumgartner, Nicolas Chronos, Anthony Comerota, Timothy Henry, Jean-Paul Pasquet, François Finiels, Anne Caron, Jean-François Dedieu, Richard Pilsudski, Pia Delaère
Journal: Molecular Therapy (2009)

NV1FGF is an expression plasmid encoding sp.FGF-121–154 currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown. The study involved six patients with chronic critical limb ischemia (CLI) planned to undergo amputation. A total dose of 0.5, 2, or 4 mg NV1FGF was administered as eight IM injections (0.006, 0.25, or 0.5 mg per injection) 3–5 days before amputation. Injected sites (30 cm3) were divided into equally sized smaller pieces to assess spatial distribution of NV1FGF sequences (PCR), NV1FGF mRNA (reverse transcriptase-PCR), and fibroblast growth factor-1 (FGF-1)-expressing cells (immunohistochemistry). Data indicated gene expression at all doses. The distribution area was within 5–12 cm for NV1FGF sequences containing the expression cassette, up to 5 cm for NV1FGF mRNA, and up to 3 cm for FGF-1-expressing myofibers. All FGF receptors were detected indicating robust potential for bioactivity after NV1FGF gene transfer. Circulating levels of NV1FGF sequences were shown to decrease within days after injection. Data support demonstration of plasmid-mediated gene transfer and expression in muscles from patients with CLI. FGF-1 expression was shown to be limited to injection sites, which supports the concept of multiple-site injection for therapeutic use. NV1FGF is an expression plasmid encoding sp.FGF-121–154 currently under investigation for therapeutic angiogenesis in clinical trials. NV1FGF plasmid distribution and transgene expression following intramuscular (IM) injection in patients is unknown. The study involved six patients with chronic critical limb ischemia (CLI) planned to undergo amputation. A total dose of 0.5, 2, or 4 mg NV1FGF was administered as eight IM injections (0.006, 0.25, or 0.5 mg per injection) 3–5 days before amputation. Injected sites (30 cm3) were divided into equally sized smaller pieces to assess spatial distribution of NV1FGF sequences (PCR), NV1FGF mRNA (reverse transcriptase-PCR), and fibroblast growth factor-1 (FGF-1)-expressing cells (immunohistochemistry). Data indicated gene expression at all doses. The distribution area was within 5–12 cm for NV1FGF sequences containing the expression cassette, up to 5 cm for NV1FGF mRNA, and up to 3 cm for FGF-1-expressing myofibers. All FGF receptors were detected indicating robust potential for bioactivity after NV1FGF gene transfer. Circulating levels of NV1FGF sequences were shown to decrease within days after injection. Data support demonstration of plasmid-mediated gene transfer and expression in muscles from patients with CLI. FGF-1 expression was shown to be limited to injection sites, which supports the concept of multiple-site injection for therapeutic use.
<scp>EAACI</scp> taskforce position paper: evidence for autoimmune urticaria and proposal for defining diagnostic criteria
Authors: G. N. Konstantinou, R. Asero, M. Ferrer, E. F. Knol, M. Maurer, U. Raap, P. Schmid‐Grendelmeier, P. S. Skol, C. E. H. Grattan
Journal: Allergy (2012)

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA-DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new 'gold standard' for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.
Retaining personal medical records of children who have had chemotherapy and radiotherapy
Authors: M M Hawkins, A W Craft
Journal: BMJ (1994)

Most children who develop cancer can now expect their primary disease to be cured, and this is largely attributable to intensive chemotherapy and radiotherapy.1 Long term follow up, however, shows that effects related to treatment may become evident many years later.*RF 1-4*

When children have been exposed to radiotherapy or chemotherapy important clinical reasons exist for maintaining a detailed record of such treatments. The patients may present many years (possibly decades) after treatment and ask about their prospects of being fertile, the chance of an adverse outcome of pregnancy, or the chance of their children developing serious genetic disease. Cardiomyopathy or lung dysfunction related to treatment may be diagnosed. they may also present with a late recurrence of their cancer or with a second primary neoplasm. In all of these circumstances the details of previous exposure to radiotherapy and individual cytotoxic drugs are crucially important to diagnosis and rational and safe planning of further treatment.

Now that two thirds …
Factors protective against retinopathy in insulin dependent diabetics
Authors: I N Scobie, P H Sonksen
Journal: BMJ (1983)

The number of gastric ulcers in patients with rheumatic diseases who were taking steroid or non-steroidal anti-inflammatory drugs was not significantly different in men and women, and in any case it was too small for any variation in the male to female ratio to be determined.For duodenal ulcers the male to female ratio was 3:1.In this case too, although less obviously, there was a slight tendency towards a reduction in the percentage of men (r=0-28).In conclusion, the data from our case histories do not confirm Dr Lee's observations, and they confirm a higher male prevalence in the incidence of gastric and duodenal ulcers.We emphasise the tendency towards a reduction in this prevalence, however, although it was not significant, since it accords with the findings of Crown et all before the introduction of H2 blockers, and with Ela- shoff's and Grossman's subsequent findings.2Even if our study and that of Dr Lee are not large enough to justify significant epidemiological conclusions, we can hypothesise that widely differing geographical distributions and environmental and socioeconomic conditions in the two populations may explain the difference in the two studies.
Studies of Quantitative Ballistocardiography
Authors: VINCENZO MASINI, PAOLO ROSSI
Journal: Circulation (1953)

The speed of body displacement was calculated on 70 per cent of the ballistocardiograms recorded in 128 patients suffering from heart disease. Results show that the values are generally lower in cardliac patients than in normal subjects, with the exception of cases with high stroke volume. The diminution of the speed of body displacement is proportional to the severity of ballistic abnormalities and to the functional state of the heart. A tentative explanation of the findings is presented.
IL-22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versus-leukemia effect
Authors: M Couturier, B Lamarthée, J Arbez, J-C Renauld, C Bossard, F Malard, F Bonnefoy, M Mohty, S Perruche, P Tiberghien, P Saas, B Gaugler
Journal: Leukemia (2013)
Utility of consecutive repeat HIT ELISA testing for heparin‐induced thrombocytopenia
Authors: Maren Chan, Elizabeth Malynn, Beth Shaz, Lynne Uhl
Journal: American Journal of Hematology (2007)

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0-0.132, medium = 0.133-0.267, and high = 0.268-0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT.
Systolic Time Intervals in Severe Aortic Valve Disease
Authors: ALFRED F. PARISI, STEPHEN H. SALZMAN, ELIOT SCHECHTER
Journal: Circulation (1971)

Systolic time intervals were recorded in 25 consecutive patients before and after aortic valve surgery. Ten patients with dominant aortic stenosis (AS) and 10 with dominant aortic insufficiency (AI) received a Starr-Edwards prosthesis; five underwent repair procedures for AS or subaortic lesions. Before operation, the mean rate-corrected left ventricular ejection time (LVET c ) was prolonged; postoperatively LVET c decreased significantly. Conversely, preoperative mean rate-corrected preejection period (PEP c ) was short and increased postoperatively. Serial measurement of LVET c in a patient who had two aortic valve replacements suggested its value in quantitating prosthetic malfunction. In AS, preoperative LVET c correlated closely with cardiac index; normal ejection times were associated with the most severely depressed flows. Preoperative variations in PEP c in AS related inversely to the first derivative of the left ventricular pressure curve (maximal LV dp/dt). In AI, PEP c correlated with the quotient: [see Equation in PDF File] where Adbp — LVed = transaortic end-diastolic pressure difference (aortic diastolic pressure minus LV end-diastolic pressure), and dp/dt = maximal LV dp/dt. This study identifies the flow and pressure parameters which correlate with abnormalities of PEP c and LVET c with severe AS and AI. The sensitivity of this technique to the hemodynamic changes of corrective surgery makes it a potentially useful noninvasive means to measure prosthetic valve function.
Graves' Disease Following Irradiation for Hodgkin's Disease
Authors: Miljenko V. Pilepich, Ivor Jackson, John E. Munzenrider, Rosalind S. Brown
Journal: JAMA (1978)

THE THYROID gland is commonly included in the radiation field in patients with Hodgkin's disease treated with radiation therapy. The so-called mantle field routinely includes the neck. A substantial number of patients with non-Hodgkin's lymphoma, head and neck tumors, and breast carcinoma also receive neck irradiation. The thyroid was traditionally considered a radioresistant organ. However, several reports on thyroid dysfunction following neck irradiation have appeared in recent years. Glatstein et al<sup>1</sup>reported a 44% incidence of elevated serum thyroid-stimulating hormone (TSH) concentration in patients with lymphomas who had lymphangiography and received neck irradiation. In 11% of these patients, clinical hypothyroidism or evidence of thyroid hypofunction (according to laboratory tests other than serum TSH determination) developed. Although the exact incidence and pathogenesis are not known, hypothyroidism is a recognized complication of thyroid irradiation. Graves' disease following thyroid irradiation, manifested either as hyperthyroidism or ophthalmopathy, is not a well-recognized entity. <h3>Report</h3>
Characteristics and Outcomes of Subjects With Diabetic Foot Ulceration
Authors: Mussarat Riaz, Zahid Miyan, Syed Itaat Zaidi, S. Faraz Danish Alvi, Asher Fawwad, Muhammad Yakoob Ahmadani, Asim Bin Zafar, Rayaz A. Malik, Abdul Basit
Journal: Diabetes Care (2012)

Foot ulcers are a major cause of morbidity and hospitalization in patients with diabetes. The incidence of diabetic foot ulceration is higher in developing countries because of various sociocultural factors. The majority of amputations in patients with diabetes are preceded by foot ulceration; hence it is important to identify patients at risk for this complication.

Studies show that the prevalence of diabetic foot ulceration is between 4 and 10% in Pakistan (1), and the amputation rate following foot ulceration is 8–21% (1,2), depending on the methodology used for treating foot ulceration. We identified diabetic patients at risk for ulceration and compared the clinical and metabolic characteristics of patients with and without foot ulceration together with an analysis of outcomes following ulceration.

We included 8,989 patients with diabetes attending the Baqai Institute of Diabetology and Endocrinology, a tertiary …
Rare diseases are overlooked by doctors, policy makers, and guidelines, says think tank
Authors: J. Wise
Journal: BMJ (2012)

The NHS in England is neglecting rarer diseases, with the result that delays in diagnosis are common, says a report from the centre right think tank 2020Health.1

Julia Manning, its chief executive, said, “The conclusions of this report are sobering: there is still too much variation in care across the NHS, too little information on rare diseases, and not enough done to empower patients to look after themselves. A paternalistic approach by the NHS is unsustainable and unhealthy, and this needs to be considered alongside greater awareness of rare conditions in medical training.”

The …