tbuckley/cabot-search huggingface dataset:
Hypoglycaemia Due to Isolated Corticotrophin-deficiency
Authors: K. A. Woeber, R. Arky
Journal: BMJ (1965)

BDIAL O immediately treated.The Denis Browne splint offers an easy and entirely acceptable approach to the problem of keeping the child in the corrected position.It is light ; easily manageable by the mother; the child can be picked up and carried as in a portable crib; the child seemingly enjoys his position and placement in this splint ; and there is no problem such is found in placing these children into a cast or even a Milwaukee brace.Our approach, therefore, to the manage- ment of the child with idiopathic or other forms of scoliosis is to use our best judgment and avail ourselves of all the modalities of treatment which have been found to be useful.I place the Denis Browne splint in this category, and I would further say that if there is any form of treatment that should be carried out routinely on any infant with postural or structural curvature of the spine the Denis Browne splint offers the only logical means of handling this problem.While in many cases the treatment may be superfluous and unnecessary it certainly does no harm either to the emotions of the mother, the child, or to anyone else.In scoliosis I have the strong feeling that it is better to overtreat rather than to undertreat.I therefore agree with Sir Denis Browne's concepts of proper management of the infantile scoliotic, even though in many instances it might be postural and spontaneously resolving.-Iam, etc.,
Influenza Studies in General Practice in the Glasgow Area
Authors: W. Blair, W. K. Brown, W. F. Caldwell, A. Clarke, S. Dunn, D. Primrose, T. F. Stewart, N. R. Grist, R. G. Sommerville
Journal: BMJ (1959)

LONG SURVIVAL IN MITRAL STENOSIS It is, of course, impossible to say when the stenosis provided a serious mechanical embarrassment to the heart, but it seems likely that the pathological process was initiated in her teens.Possibly a minor degree of stenosis may in later years become more severe by accretion of atheromatous material leading to further fibrosis and calcification, but one can only speculate about this.My thanks are due to Dr. L. B.
Vulvodynia is important cause of vulval pain
Authors: B Kirby, J A Yell
Journal: BMJ (1999)

2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol-17β and the oral contraceptive agent 17-ethylestradiol. 2-ME was recently reported to inhibit endothelial cell proliferation. The current study was undertaken to explore the mechanism of 2-ME effects on endothelial cells, especially whether 2-ME induces apoptosis, a prime mechanism in tissue remodeling and angiogenesis. Cultured bovine pulmonary artery endothelial cells (BPAEC) exposed to 2-ME showed morphological (including ultrastructural) features characteristic of apoptosis: cell shrinkage, cytoplasmic and nuclear condensation, and cell blebbing. 2-ME-induced apoptosis in BPAEC was a time- and concentration-dependent process (EC<sub>50</sub> = 0.45 ± 0.09 μm, <i>n</i> = 8). Nucleosomal DNA fragmentation in BPAEC treated with 2-ME was identified by agarose gel electrophoresis (DNA ladder) as well as <i>in situ</i> nick end labeling. Under the same experimental conditions, estradiol-17β and two of its other metabolites, estriol and 2-methoxyestriol (≤10 μm), did not have an apoptotic effect on BPAEC. 2-ME activated stress-activated protein kinase (SAPK)/c-Jun amino-terminal protein kinase in BPAEC in a concentration-dependent manner. The activity of SAPK was increased by 170 ± 27% and 314 ± 22% over the basal level in the presence of 0.4 and 2 μm 2-ME (<i>n</i> = 3–6), respectively. The activation of SAPK was detected at 10 min, peaked at 20 min, and returned to basal levels at 60 min after exposure to 2-ME. Inhibition of SAPK/c-Jun amino-terminal protein kinase activation by basic fibroblast growth factor, insulin-like growth factor, or forskolin reduced 2-ME-induced apoptosis. Immunohistochemical analysis of BPAEC indicated that 2-ME up-regulated expression of both Fas and Bcl-2. In addition, 2-ME inhibited BPAEC migration (IC<sub>50</sub> = 0.71 ± 0.11 μm, <i>n</i> = 4) and basic fibroblast growth factor-induced angiogenesis in the chick chorioallantoic membrane model. Taken together, these results suggest that promotion of endothelial cell apoptosis, thereby inhibiting endothelial cell proliferation and migration, may be a major mechanism by which 2-ME inhibits angiogenesis.
Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.
Authors: W S Linn, K R Anderson, D A Shamoo, S A Edwards, T L Webb, J D Hackney, H Gong
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.
Oral Consumption of Pomegranate Fruit Extract Inhibits Growth and Progression of Primary Lung Tumors in Mice
Authors: Naghma Khan, Farrukh Afaq, Mee-Hyang Kweon, KyungMann Kim, Hasan Mukhtar
Journal: Cancer Research (2007)

To develop novel mechanism-based preventive approaches for lung cancer, we examined the effect of oral consumption of a human achievable dose of pomegranate fruit extract (PFE) on growth, progression, angiogenesis, and signaling pathways in two mouse lung tumor protocols. Benzo(a)pyrene [B(a)P] and N-nitroso-tris-chloroethylurea (NTCU) were used to induce lung tumors, and PFE was given in drinking water to A/J mice. Lung tumor yield was examined on the 84th day and 140 days after B(a)P dosing and 240 days after NTCU treatment. Mice treated with PFE and exposed to B(a)P and NTCU had statistically significant lower lung tumor multiplicities than mice treated with carcinogens only. Tumor reduction was 53.9% and 61.6% in the B(a)P + PFE group at 84 and 140 days, respectively, compared with the B(a)P group. The NTCU + PFE group had 65.9% tumor reduction compared with the NTCU group at 240 days. Immunoblot analysis and immunohistochemistry were used to determine effect on cell survival pathways and markers of cellular proliferation and angiogenesis. PFE treatment caused inhibition of (a) activation of nuclear factor-kappaB and IkappaBalpha kinase, (b) degradation and phosphorylation of IkappaBalpha, (c) phosphorylation of mitogen-activated protein kinases (extracellular signal-regulated kinase 1/2, c-Jun NH(2)-terminal kinase 1/2, and p38), (d) phosphatidylinositol 3-kinase (p85 and p110), (e) phosphorylation of Akt at Thr(308), (f) activation of mammalian target of rapamycin signaling, (g) phosphorylation of c-met, and (h) markers of cell proliferation (Ki-67 and proliferating cell nuclear antigen) and angiogenesis (inducible nitric oxide synthase, CD31, and vascular endothelial growth factor) in lungs of B(a)P- and NTCU-treated mice. Thus, our data show that PFE significantly inhibits lung tumorigenesis in A/J mice and merits investigation as a chemopreventive agent for human lung cancer.
Favorable Effects of Insulin Sensitizers Pertinent to Peripheral Arterial Disease in Type 2 Diabetes
Authors: Andrew D. Althouse, J. Dawn Abbott, Kim Sutton-Tyrrell, Alan D. Forker, Manuel S. Lombardero, L. Virginia Buitrón, Ivan Pena-Sing, Jean-Claude Tardif, Maria Mori Brooks
Journal: Diabetes Care (2013)

The aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms.The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91-1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes.During an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P<0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51-0.83], P<0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59-0.96], P=0.02).In participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.
15-Lipoxygenase-1 Prevents Vascular Endothelial Growth Factor A– and Placental Growth Factor–Induced Angiogenic Effects in Rabbit Skeletal Muscles via Reduction in Growth Factor mRNA Levels, NO Bioactivity, and Downregulation of VEGF Receptor 2 Expression
Authors: Helena Viita, Johanna Markkanen, Emmi Eriksson, Markku Nurminen, Kati Kinnunen, Mohan Babu, Tommi Heikura, Sanna Turpeinen, Svetlana Laidinen, Teemu Takalo, Seppo Ylä-Herttuala
Journal: Circulation Research (2007)

Human 15-lipoxygenase-1 (15-LO-1) is an oxidizing enzyme capable of producing reactive lipid hydroperoxides. 15-LO-1 and its products have been suggested to be involved in many pathological conditions, such as inflammation, atherogenesis, and carcinogenesis. We used adenovirus-mediated gene transfers to study the effects of 15-LO-1 on vascular endothelial growth factor (VEGF)-A 165 – and placental growth factor (PlGF)-induced angiogenesis in rabbit skeletal muscles. 15-LO-1 significantly decreased all angiogenic effects induced by these growth factors, including capillary perfusion, vascular permeability, vasodilatation, and an increase in capillary number. The effects are attributable to the reduction in the amount of VEGF-A 165 and PlGF transcripts by 15-LO-1, resulting in reduced protein expression. The most likely mediator of the VEGF family–induced capillary vasodilatation is nitric oxide (NO), which is produced by NO synthases. Endothelial NO synthase protein expression and NO synthase activity were significantly induced by VEGF-A 165 , and these inductions were reduced by 15-LO-1. VEGF-A 165 induces its angiogenic effects primarily via vascular endothelial growth factor receptor (VEGFR)2, and also PlGF mediates angiogenic signaling via VEGFR2, even though it binds to VEGFR1. VEGFR2 expression is induced by peroxisome proliferator-activating receptor γ. We showed by quantitative RT-PCR and immunohistochemistry that expression of endogenous rabbit peroxisome proliferator-activating receptor γ and VEGFR2 were significantly increased in the growth factor–transduced muscles, but these inductions were efficiently prevented by 15-LO-1. In conclusion, the results suggest that expression of 15-LO-1 has an efficient antiangiogenic effect in vivo via reduction in growth factor mRNA levels, NO bioactivity, and VEGFR2 expression.
Abstract OT3-4-03: Prospective neo-adjuvant registry trial linking MammaPrint, subtyping and treatment response: Neo-adjuvant Breast Registry – Symphony Trial (NBRST)
Authors: P Whitworth, M Gittleman, S Akbari, B Nguyen, P Baron, M Rotkiss, J Beatty, J Gibson, L Stork-Sloots, F de Snoo, P Beitsch
Journal: Cancer Research (2012)

Abstract Background: The FDA-approved MammaPrint 70 gene profile is performed on a diagnostic multi-gene array. This platform enables additional gene expression profiles to be analyzed simultaneously on one tumor specimen. One such gene expression profile is BluePrint, an 80 gene molecular subtyping profile that discriminates between three distinctive subtypes; Basal-type, Luminal-type, and HER2-type. By combining MammaPrint and BluePrint, patients can be stratified into the following subgroups: Luminal-type/MammaPrint Low Risk; Luminal-type/MammaPrint High Risk; HER2-type and Basal-type. Marked differences are observed in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint [Glück et al. ASCO 2012]. Trial design: NBRST is a prospective observational, case-only study linking MammaPrint and BluePrint to neo-adjuvant treatment response and Distant Metastases-Free Survival (DMFS) and Relapse-Free Survival (RFS). MammaPrint and BluePrint are assessed on fresh or formalin-fixed, paraffin-embedded core needle biopsy samples. Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. Eligibility: The study will include women aged 18–90 with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy or neo-adjuvant hormonal therapy, after successful MammaPrint and BluePrint assessment, and who provide written informed consent. Additional inclusion criteria are that women must have had no excisional biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for the treatment of breast cancer. Objectives: The main objectives of this registry study are to: 1. Measure chemosensitivity (as defined by pathological complete response [pCR]) or endocrine sensitivity (as defined by decrease in longest tumor diameter or RCB1) in the molecular subgroups as determined by combining MammaPrint and BluePrint results.2. Compare local IHC and FISH results with TargetPrint results and BluePrint results.3. Document impact of MammaPrint, TargetPrint and BluePrint results on treatment decisions.4. Assess the 2–3 and 5-year DMFS and RFS for the different molecular subgroups. Statistical methods: Comparison of response rates between different molecular subgroups will be conducted using the Pearson Chi-square test. Accrual: The trial started in August 2011 and there are currently 36 participating sites in the US. To date (June 06, 2012), 158 of the planned 400 patients have been enrolled.Clinical trial registry number: NCT01479101. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-03.
Rate-related suppression and facilitation of conduction in isolated canine cardiac Purkinje fibers.
Authors: R F Gilmour, J J Salata, D P Zipes
Journal: Circulation Research (1985)

Previous studies have shown that antegrade conduction through damaged His Purkinje tissue may be suppressed following rapid ventricular pacing (overdrive suppression of conduction). We studied this phenomenon using isolated Purkinje fibers placed in a three-chamber bath. Superfusates for the left, middle, and right segments of the fiber were altered to produce action potentials that resembled those of normal bundle branch, damaged His bundle, and normal His bundle, respectively. To produce anisotropic conduction, the left segment of the fiber was adjusted to be three to four times longer than the right segment. Pacing the right segment at intermediate rates produced maximal action potential amplitude in the middle segment and 1:1 right-to-left conduction, whereas pacing at faster or slower rates reduced action potential amplitude and produced block. Pacing the left segment at fast or slow rates also reduced action potential amplitude in the middle segment, but conduction was maintained (anisotropy). After rapid or slow left segment pacing, action potential amplitude in the middle segment remained low during subsequent right segment pacing at intermediate rates, and transient block occurred (overdrive or underdrive suppression of conduction). With time, action potential amplitude normalized and conduction resumed. In other more severely depressed preparations, conduction block occurred even at intermediate right segment pacing rates prior to left segment pacing. Under these conditions, pacing the left segment at intermediate rates increased action potential amplitude in the middle segment and temporarily permitted 1:1 conduction at intermediate right segment pacing rates (overdrive facilitation of conduction).(ABSTRACT TRUNCATED AT 250 WORDS)
Studies to elucidate the thyroid hormone dependence of morris hepatoma 44
Authors: Raphael Pollack, Shaindel Y. Mishkin, Harold P. Morris, Mordechai A. Yalovsky, Seymour Mishkin
Journal: Hepatology (1982)

The objective of these studies was to elucidate further the mechanisms of the thyroid dependency of Morris Hepatoma 44. In vivo experiments indicated that while exogenous thyroxine (8 μg per kg) reversed the hypothyroid–mediated inhibition of primary hepatoma growth, no such effect was noted with the administration of ovine prolactin (100 μg per kg s.c.) and bovine growth hormone (100 μg per kg, s.c). In contrast, ovine prolactin significantly stimulated tumor growth in euthyroid animals. We have documented the presence of nuclear triiodothyronine (T 3 ) receptors in Morris Hepatoma 44. The dissociation constant Kd (4.38 ± 0.84 n M ) and binding capacity (2.16 ± 0.84 pmoles per mg DNA) of these receptors was significantly greater than those of host liver tissue (1.48 ± 0.41 n M and 0.93 ± 0.32 pmole per mg DNA, respectively). The binding capacity of hepatoma nuclear T 3 receptors was markedly reduced in the hypothyroid state, while liver nuclear receptor capacity was not significantly changed. In addition, the binding of T 3 to cytoplasmic proteins was greater in hepatomas relative to host liver. Analogous to the observations with nuclear receptors, the binding of T 3 to hepatoma cytosol was significantly reduced in the hypothyroid state, while the binding activity of liver cytosol was unchanged. These results are consistent with a possible role for nuclear receptors and/or cytoplasmic binding proteins for T 3 in mediating the direct influence of thyroid hormones on the growth of Morris Hepatoma 44. Our results, however, do not preclude a role for other hormones (i.e., pituitary hormones acting via the hypothalamo–hypophyseal axis) as modulators of Morris Hepatoma 44 growth.
Deficient Counterregulation: A Possible Risk Factor for Excessive Fetal Growth in IDDM Pregnancies
Authors: Barak M Rosenn, Menachem Miodovnik, Jane C Khoury, Tariq A Siddiqi
Journal: Diabetes Care (1997)

OBJECTIVE The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24–28 and at 32–34 weeks' gestation, using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (&amp;lt; 165 pmol/l above baseline) and nine women (responders) had a moderate response (244–764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P &amp;lt; 0.05). CONCLUSIONS Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased caloric intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.
Gabapentin may cause reversible visual field constriction
Authors: Svein Ivar Bekkelund, Hallvard Lilleng, Stig Tønseth
Journal: BMJ (2006)

<h3>Abstract</h3> <h3>Objective</h3> To study the relation between rainfall and outpatient visits for joint or back pain in a large patient population. <h3>Design</h3> Observational study. <h3>Setting</h3> US Medicare insurance claims data linked to rainfall data from US weather stations. <h3>Participants</h3> 1 552 842 adults aged ≥65 years attending a total of 11 673 392 outpatient visits with a general internist during 2008-12. <h3>Main outcome measures</h3> The proportion of outpatient visits for joint or back pain related conditions (rheumatoid arthritis, osteoarthritis, spondylosis, intervertebral disc disorders, and other non-traumatic joint disorders) was compared between rainy days and non-rainy days, adjusting for patient characteristics, chronic conditions, and geographic fixed effects (thereby comparing rates of joint or back pain related outpatient visits on rainy days versus non-rainy days within the same area). <h3>Results</h3> Of the 11 673 392 outpatient visits by Medicare beneficiaries, 2 095 761 (18.0%) occurred on rainy days. In unadjusted and adjusted analyses, the difference in the proportion of patients with joint or back pain between rainy days and non-rainy days was significant (unadjusted, 6.23% <i>v</i> 6.42% of visits, P&lt;0.001; adjusted, 6.35% <i>v</i> 6.39%, P=0.05), but the difference was in the opposite anticipated direction and was so small that it is unlikely to be clinically meaningful. No statistically significant relation was found between the proportion of claims for joint or back pain and the number of rainy days in the week of the outpatient visit. No relation was found among a subgroup of patients with rheumatoid arthritis. <h3>Conclusion</h3> In a large analysis of older Americans insured by Medicare, no relation was found between rainfall and outpatient visits for joint or back pain. A relation may still exist, and therefore larger, more detailed data on disease severity and pain would be useful to support the validity of this commonly held belief.