tbuckley/cabot-search huggingface dataset:
Impact of S-Adenosylmethionine Decarboxylase 1 on Pulmonary Vascular Remodeling
Authors: Friederike Christine Weisel, Christina Kloepping, Alexandra Pichl, Akylbek Sydykov, Baktybek Kojonazarov, Jochen Wilhelm, Markus Roth, Karen Marie Ridge, Kazuei Igarashi, Kazuhiro Nishimura, Wolfgang Maison, Claudia Wackendorff, Walter Klepetko, Peter Jaksch, Hossein Ardeschir Ghofrani, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly, Norbert Weissmann, Grazyna Kwapiszewska
Journal: Circulation (2014)

Pulmonary hypertension (PH) is a life-threatening disease characterized by vascular remodeling and increased pulmonary vascular resistance. Chronic alveolar hypoxia in animals is often used to decipher pathways being regulated in PH. Here, we aimed to investigate whether chronic hypoxia-induced PH in mice can be reversed by reoxygenation and whether possible regression can be used to identify pathways activated during the reversal and development of PH by genome-wide screening.Mice exposed to chronic hypoxia (21 days, 10% O2) were reoxygenated for up to 42 days. Full reversal of PH during reoxygenation was evident by normalized right ventricular pressure, right heart hypertrophy, and muscularization of small pulmonary vessels. Microarray analysis from these mice revealed s-adenosylmethionine decarboxylase 1 (AMD-1) as one of the most downregulated genes. In situ hybridization localized AMD-1 in pulmonary vessels. AMD-1 silencing decreased the proliferation of pulmonary arterial smooth muscle cells and diminished phospholipase Cγ1 phosphorylation. Compared with the respective controls, AMD-1 depletion by heterozygous in vivo knockout or pharmacological inhibition attenuated PH during chronic hypoxia. A detailed molecular approach including promoter analysis showed that AMD-1 could be regulated by early growth response 1, transcription factor, as a consequence of epidermal growth factor stimulation. Key findings from the animal model were confirmed in human idiopathic pulmonary arterial hypertension.Our study indicates that genome-wide screening in mice from a PH model in which full reversal of PH occurs can be useful to identify potential key candidates for the reversal and development of PH. Targeting AMD-1 may represent a promising strategy for PH therapy.
Exercise testing provides additional prognostic information in angiographically defined subgroups of patients with coronary artery disease.
Authors: H Gohlke, L Samek, P Betz, H Roskamm
Journal: Circulation (1983)

We examined whether exercise testing with measurement of cardiac output during maximal exercise can provide additional prognostic information for medically treated patients in whom left ventricular function and extent of coronary artery disease are known. We followed 1034 patients with normal or mildly impaired left ventricular function; 410 of these patients (group 1) had single-vessel disease, 316 had double-vessel disease (group 2), and 308 had triple-vessel disease (group 3). In addition, 204 patients with double- or triple-vessel disease and moderately impaired left ventricular function (group 4) were followed. Mean follow-up in these 1238 patients was 4.5 years. End point of follow-up was death. Groups 1, 2, and 3 were divided into terciles according to the maximally achieved values of the following exercise variables: exercise tolerance, angina-free exercise tolerance, maximal heart rate, and cardiac output during maximal exercise. Group 4 was divided into halves accordingly. Survival curves (according to the method of Cutler and Ederer) for group 2 showed a 15% difference in 5 year survival rate between the highest and lowest terciles (p less than .005) by use of the noninvasive variables exercise tolerance, angina-free exercise tolerance, and maximal heart rate (95% vs 80%). The separation into terciles according to cardiac output during maximal exercise resulted in a significant difference in survival rates between the highest and lowest terciles (halves) in all groups of patients. The differences in 5 year survival rates were 9% (p less than .05), 16% (p less than .05), and 19% (p less than .005) for groups 1, 2, and 3, respectively, and 22% for group 4 (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
α <sub>1</sub> -Adrenergic Inhibition of the β-Adrenergically Activated Cl <sup>−</sup> Current in Guinea Pig Ventricular Myocytes
Authors: Lisa M. Oleksa, Livia C. Hool, Robert D. Harvey
Journal: Circulation Research (1996)

Abstract α-Adrenergic receptor stimulation regulates the activity of a number of different cardiac ion channels, including those underlying one or more distinct Cl − conductances. The whole-cell patch-clamp technique was used in the present study to investigate the effects of α-adrenergic stimulation on the β-adrenergically regulated Cl − current in guinea pig ventricular myocytes. Neither α 1 -adrenergic receptor stimulation with methoxamine (25 to 500 μmol/L) nor direct activation of endogenous protein kinase C (PKC) with phorbol 12,13-dibutyrate (PDBu, 100 nmol/L) evoked a Cl − current. On the contrary, the Cl − current activated by 30 nmol/L isoproterenol was inhibited by methoxamine, with an EC 50 of 6.7±2.6 μmol/L, and this response was blocked by prazosin, an α 1 -adrenergic receptor antagonist. Prazosin also decreased the EC 50 for current activation by norepinephrine from 53±7.1 to 18±3.8 nmol/L, demonstrating that the ability of this endogenous neurotransmitter to activate the Cl − current through β-adrenergic receptor stimulation is limited by its intrinsic ability to also activate α-adrenergic receptors. Methoxamine did not inhibit the Cl − current evoked by either direct activation of adenylate cyclase with forskolin or inhibition of phosphodiesterase activity with 3-isobutyl-1-methylxanthine, indicating that α-adrenergic stimulation inhibits β-adrenergic responses at a point upstream of adenylate cyclase activation. Methoxamine also did not inhibit the Cl − current activated by histamine, suggesting that α-adrenergic stimulation specifically inhibits β-adrenergic receptor–mediated responses. The inhibitory effect of methoxamine was not mimicked by PDBu, and it persisted in the presence of bisindolylmaleimide, a selective PKC inhibitor. However, methoxamine inhibition of the isoproterenol-activated Cl − current was sensitive to pertussis toxin. These results suggest that α-adrenergic receptor stimulation inhibits the β-adrenergically activated Cl − current, demonstrating a novel mechanism by which α-adrenergic receptors may regulate ion channel activity in the heart.
Full-thickness skin grafts for surgical defects of the nasal ala - a comprehensive review, approach and outcomes of 186 cases over 9 years
Authors: E. Tan, N. Mortimer, P. Salmon
Journal: British Journal of Dermatology (2013)

Skin cancers of the nasal ala are commonly encountered in dermatological surgery. Various techniques have been described to reconstruct surgical defects of the ala, including melolabial transposition flaps, interpolated melolabial flaps, bilobed and trilobed transposition flaps, island pedicle flaps and spiral flaps. Full-thickness skin grafts have received little attention in the reconstructive literature.We present our experience with full-thickness skin grafts for the reconstruction of partial thickness defects of the nasal ala in the largest series to date.A retrospective analysis of the Mohs micrographic surgery database over a 9-year period was performed. All cases of full-thickness skin grafts for reconstruction of the nasal ala were identified. Defect location, size and any postoperative complications were noted. All patients were reviewed at the time of suture removal, at 3 and 6 weeks postoperatively and at 1 year.There were 186 cases in total in 181 patients (88 men and 93 women). Their ages ranged from 31 to 88 years with a mean of 65 years (median 66). Defect size varied from 0·3 × 0·4 cm to 2·0 × 2·7 cm, with the average defect size measuring 1·0-1·2 cm in diameter. Thirty-six per cent (67 of 186) of cases underwent postoperative dermabrasion, and 8% (14 of 186) received postoperative intralesional triamcinolone. The incidence of graft failure and infection was low. Good-to-excellent cosmetic results were seen in all patients and postoperative complications were uncommon and minor.The use of full-thickness skin grafts for defects of the nasal ala is a simple and versatile reconstructive option with excellent functional and aesthetic outcomes.
Human milk bank in a district general hospital.
Authors: G McEnery, B Chattopadhyay
Journal: BMJ (1978)

A human milk bank was organised in the special care baby unit of a district general hospital. The staff of the unit and members of a voluntary organisation helped to contact donors and arrange collection of milk samples. Over two years 2093 samples of expressed breast milk were collected from 187 donors and examined bacteriologically. Of these samples, 1171 (56%) grew no bacteria. If the organism count exceeded 2.5 X 10(6)/1 but was less than 1 X 10(9)/1 samples were subjected to mild heat treatment. If the count exceeded 1 X 10(9)/1 the milk was not fed to babies. Sixty-five babies received milk from the bank during the second year. Although these infants were vulnerable, mortality and morbidity were not adversely affected by the banked milk they received. The cost of establishing and running a human milk bank need not be high. Extensive resources such as extra staff and laboratory and transport facilities were not needed. Enthusiastic co-operation and good will between hospital staff, voluntary helpers, and donors contributed greatly to the success of the scheme.
Immunohistochemical and Quantitative Study of Mast Cells in La Peyronie&amp;rsquo;s Disease
Authors: O. Leopardi, F. Colombo, B. Frigo, A. Zucchi, E. Patelli, M. Colecchia, F. Mantovani, W. Naughten, E. Pisani
Journal: European Urology (2000)
Plasma androstenedione and oestrone levels in normal and osteoporotic postmenopausal women.
Authors: D H Marshall, R G Crilly, B E Nordin
Journal: BMJ (1977)

Plasma androstenedione and oestrone concentrations were measured in 72 postmenopasual women. The women included some who had undergone oophorectomy, some with osteoporosis, and normal controls; they were matched for years since menopause. Both hormone concentrations were significantly reduced in the women with osteoporosis. The women who had undergone oophorectomy had hormone concentrations intermediate between the normal and osteoporotic values. Oestrogen deficiency secondary to low androstenedione levels is a major risk factor in postmenopausal osteoporosis, and may be caused by failure of ovarian stromal androgen secretion or some abnormality in the pituitary-adrenal axis.
NHS trust is charged with corporate manslaughter over woman's death after emergency caesarean
Authors: C. Dyer
Journal: BMJ (2015)

Prosecutors have launched a corporate manslaughter prosecution against an NHS trust in the case of a 30 year old primary school teacher who died after an emergency caesarean section.

Maidstone and Tunbridge Wells NHS Trust has been charged with manslaughter over the death of Frances Cappuccini, who had a cardiac arrest after haemorrhaging and died within hours of the …
Primary Treatment of Waldenström Macroglobulinemia With Dexamethasone, Rituximab, and Cyclophosphamide
Authors: Meletios Athanasios Dimopoulos, Athanasios Anagnostopoulos, Marie-Christine Kyrtsonis, Konstantinos Zervas, Constantinos Tsatalas, Garyfallia Kokkinis, Panagiotis Repoussis, Argyris Symeonidis, Souzana Delimpasi, Eirini Katodritou, Elina Vervessou, Evridiki Michali, Anastasia Pouli, Dimitra Gika, Amalia Vassou, Evangelos Terpos, Nikolaos Anagnostopoulos, Theophanis Economopoulos, Gerasimos Pangalis
Journal: Journal of Clinical Oncology (2007)

Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC).Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5 (total dose, 1,000 mg/m2). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta2-microglobulin (43%).On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab.Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.
Coumadin and aspirin in prevention of recurrence after transluminal coronary angioplasty: a randomized study.
Authors: M A Thornton, A R Gruentzig, J Hollman, S B King, J S Douglas
Journal: Circulation (1984)

To determine the influence of adjunctive treatment with coumadin or aspirin on recurrence rate after percutaneous transluminal coronary angioplasty (PTCA), 248 patients in whom PTCA was assessed to be a primary success were randomized to either 325 mm aspirin daily or to coumadin treatment sufficient to maintain a prothrombin time 2 to 2.5 times the control value. The follow-up protocol included stress testing and coronary angiographic examinations 3 to 6 months after PTCA. All patients were followed for at least 9 months. Of the 122 patients randomized to coumadin 44 (36%) had recurrent stenoses as opposed to 34/126 (27%) of patients on aspirin, a difference that did not reach statistical significance at the .05 level. However, patients with at least a 6 month history of angina demonstrated a significantly different response to adjunctive treatment in that 19/43 (44%) of coumadin patients as compared with 10/48 (21%) of aspirin patients had recurrent stenoses (p less than .05). Thus, coumadin was not shown to be more effective than aspirin as adjunctive treatment after PTCA, while aspirin was shown to be superior to coumadin in patients with a longer history of angina.
Health Service in Rhodesia
Authors: R. M. Morris
Journal: BMJ (1947)

Posterior fossa lesions may present with behavioural changes and/or progressive neurological deficit. Patients may have symptoms for long periods which may be attributed to other causes such as psychiatric diseases. We report a case of a 44-year-old woman with behavioural changes lasting for 5 years who lost her job, marriage and the guard of her sons. Latterly, she developed neurological deficit, hydrocephalus and intracranial hypertension. A giant left pontocerebellar angle mass was diagnosed. A retrosigmoid craniotomy was performed with total removal and cranial nerve function’s preservation. Histology revealed a grade I meningioma. The surgical approach for such huge lesions on pontocerebellar angle is controversial concerning patient’s positioning and surgical route. A brief revision is made. Since nowadays medical imaging is more easily accessible, it is mandatory to have a brain image in patients with behavioural changes and/or neurological deficit to exclude potential structural and curable causes such as in this case.
On to 1988 Olympics... With Lessons Learned
Authors: Virginia S. Cowart
Journal: JAMA (1987)

IF THERE IS ONE major lesson for physicians and others in sports medicine to take forward from the 1987 PanAmerican Games, it is that medical treatment programs at sports events generally work very well, but there still are pitfalls in large-scale drug testing of athletes. Everyone praised the Sports Medicine Drug Identification Laboratory at Indiana University Medical Center, Indianapolis, which tested 978 urine samples during the games and which reported finding the not-as-yet-banned uricosuric probenecid in an undisclosed number of athletes' urine samples. The International Olympic Committee (IOC) asked for tracking of the drug because of persistent rumors that probenecid is being used by athletes to mask the presence of anabolic steroids. (Probenecid can be used to prolong the action of penicillin-like antibiotics and thus is often prescribed for sexually transmitted diseases. Its other common use is for gout.) The problems with the drug testing program originated outside the laboratory
OBSERVATIONS ON THE FUNCTIONS OF THE COLON, WITH SPECIAL REFERENCE TO THE MOVEMENTS OF ENEMATA
Authors: H. Drummond
Journal: BMJ (1914)

LEUCOCYTE COUNT IN APPE NDICITIS.rJAN. 3 I9}4 frienids were at.first amused, and did niot realize that it was niot part of the enitertainment.Thiey tlheni camne to hiis help andl gav-e hiim a glass of water, which he was iuinable to swallow, the filuid reyurgitating through the nlose.This was followed the next day l)v paralysis of the left leg, left arm, anid left side of the face, including the upper part, and,.for a monitlh lie lhad to l)e fed with a tube.This hiappened in Japan; the doctor treated him by in-unction, anid after a montl lie was able to swallow anid speak.He vas senit to me on hiis returni from Japan suffering wvith the remaitns of a left-sided paralysis, including the uIpper facial muscles, anid there was also paresis of the left vocal cord anid soft palate.He atten(led my practice for some years witliout fuirther symptoms, and gradulally imiiproved.I. do not believe there is any reasonable grouind for quiestioning the sypliilitic oriain of my case, as it occurred as one of a series of syphiilitic pihenomenla wliiel yielded rapidly to specific treatimienit, and the patient's condition at the presenit titne is niot in.favour of its being a manifestation of that curiously irregtilar disease-disseminated sclerosis.
Genetic variation in ORM1‐like 3 (<i>ORMDL3</i>) and gasdermin‐like (<i>GSDML</i>) and childhood asthma
Authors: H. Wu, I. Romieu, J.‐J. Sienra‐Monge, H. Li, B. E. Del Rio‐Navarro, S. J. London
Journal: Allergy (2009)

Background: A genome‐wide association study identified ORM1‐like 3 (orosomucoid 1‐like 3, ORMDL3 ) as an asthma candidate gene. Single nucleotide polymorphisms (SNPs) in the region including ORMDL3 on chromosome 17q21 were related to childhood asthma risk and ORMDL3 expression levels in Europeans. Objective: We examined whether polymorphisms in ORMDL3 and the adjacent gasdermin‐like ( GSDML ) gene associated with asthma in the genome‐wide association study are related to childhood asthma and atopy in a Mexico City population. Methods: We genotyped rs4378650 in ORMDL3 and rs7216389 in GSDML in 615 nuclear families consisting of asthmatic children aged 4–17 years and their parents. Atopy was determined by skin prick tests to 25 aeroallergens. Results: Individuals carrying the C allele of rs4378650 or the T allele of rs7216389 had increased risk of asthma [relative risk (RR) = 1.73, 95% confidence interval (CI) 1.19–2.53, P = 0.003 for one or two copies of rs4378650 C, and RR = 1.64, 95% CI 1.12–2.38, P = 0.009 for one or two copies of rs7216389 T). Linkage disequilibrium between the two SNPs was high ( r 2 = 0.92). Neither of the SNPs was associated with the degree of atopy. A meta‐analysis of five published studies on rs7216389 in nine populations gave an odds ratio for asthma of 1.44 (95% CI, 1.35–1.54, P &lt; 0.00001). Conclusions: Our results and the meta‐analysis provide evidence to confirm the finding from a recent genome‐wide association study that polymorphisms in ORMDL3 and the adjacent GSDML may contribute to childhood asthma.
Colovesical fistula diagnosed by unconventional procedure.
Authors: C D Bach, B Resnik, W Flamenbaum, R J Hamburger
Journal: BMJ (1981)

Colovesical fistula diagnosed by unconventional procedureFistulous connection between the colon and the urinary tract is associated with diverticulitis and other inflammatory bowel diseases, and is managed by surgical correction of the anatomical abnormality.'-3Many patients, however, may present with associated symptoms to physicians and nephrologists, and diagnosis depends on a high index of suspicion as well as on the results of laboratory and radiological investigations.We describe a patient who presented to the renal service with recurrent urinary tract infections and in whom an unconventional procedure confirmed the diagnosis. Case reportA 63-year-old white man was referred with a six-month history of increasing left-sided flank pain, an intermittent "hiss" on micturition, suprapubic tenderness, a single episode of passing dark granular ("meaty") material per urethra, and culture-positive urinary tract infection.Six months before
The Role of Surgery in Peptic Ulcer
Authors: James C. Thompson
Journal: New England Journal of Medicine (1982)

IN this issue of the Journal, Ross and his colleagues1 confirm previous reports of an increase in late mortality after surgery for peptic ulcer. They found that life expectancy was shortened by a mean of nine years in 779 Scottish men who were followed for a minimum of 15 years after operation. They conclude that the excess mortality was due chiefly to diseases associated with smoking, and that the operation itself was not the direct cause. Of note was their finding that the incidence of gastric carcinoma was not increased, although this complication is often reported after subtotal gastrectomy . . .
Hormone Excretion before and after Castration and Adrenalectomy
Authors: J. Hartwell Harrison, Craig Leman, Paul L. Munson, John C. Laidlaw
Journal: New England Journal of Medicine (1955)

FOURTEEN years have passed since Huggins and Hodges1 demonstrated the efficacy of castration and estrogen therapy in the treatment of carcinoma of the prostate. The frequently observed response of this malignant process to hormonal therapy remains the most striking and promising phenomenon yet discovered in the study of cancer. However, the exact biologic mechanisms whereby retrogression of the neoplastic cell is brought about have not been elucidated. Further studies of the metabolic processes resulting from changes in hormonal environment will help define these mechanisms. In the first place it is indicated to measure the hormonal changes that occur during the . . .
THE ROLE OF EPINEPHRINE IN THE REACTIONS PRODUCED BY THE ENDOTOXINS OF GRAM-NEGATIVE BACTERIA
Authors: Lewis Thomas
Journal: The Journal of Experimental Medicine (1956)

Extensive lesions of dermal hemorrhagic necrosis occurred in rabbits when epinephrine (or norepinephrine) was injected into the skin within 4 hours after an intravenous injection of endotoxin. As little as 5 microg. of intradermal epinephrine, and 1 microg. of intravenous endotoxin, were sufficient to produce lesions. Similar lesions, but smaller in size and surrounded by a zone of acute inflammation, were produced by intradermal injection of a mixture of comparable amounts of endotoxin and epinephrine. No lesions were produced by combinations of endotoxin with serotonin, pitressin, or ephedrine. Both types of epinephrine-endotoxin lesion were prevented by pretreatment with cortisone, dibenzyline, and chlorpromazine. They were not prevented by heparin or nitrogen mustard. The lesions produced by intradermal mixtures of epinephrine and endotoxin were greatly enhanced in size and severity in animals treated with nitrogen mustard. Both types of lesion were prevented in rabbits rendered "tolerant" by repeated injections of sublethal amounts of endotoxin. It is concluded that endotoxin has the property of altering the reactivity of blood vessels to epinephrine in such a way that this hormone becomes a potent necrotizing agent. The possibility that this effect may represent a basic mechanism in the various intoxicating actions of endotoxin, and certain implications of this hypothesis, are discussed.