tbuckley/cabot-search huggingface dataset:
A Placebo-controlled Randomized Trial of Antithrombin Therapy in Neonatal Respiratory Distress Syndrome
Authors: BARBARA SCHMIDT, PATRICE GILLIE, LESLEY MITCHELL, MAUREEN ANDREW, CHRIS CACO, ROBIN ROBERTS
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Neonatal respiratory distress syndrome (RDS) is associated with decreased plasma activity of antithrombin (AT) and increased formation of thrombin. We tested whether AT reduces thrombin formation, improves gas exchange, and decreases the duration of mechanical ventilation and supplemental oxygen. One hundred twenty-two infants were randomized to pasteurized AT concentrate or to placebo. Two ml/kg (equivalent to 100 IU AT/kg) were followed by 1 ml/kg (50 IU/kg) every 6 h for 48 h. Outcome measures included plasma AT activity, thrombin-AT (TAT) complex, prothrombin fragment (F1 + 2), the ratio of arterial to alveolar oxygen pressure [(a/a)Po 2], and the ventilator efficiency index (VEI). In the AT group (n = 61), mean (SD) birth weight was 1,198 (301) g, mean (SD) gestational age (GA) was 28.3 (2.0) wk, 54% were male. In the placebo group (n = 61), mean (SD) birth weight was 1,201 (315) g, mean (SD) GA was 28.8 (2.3) wk, 51% were male. In treated infants, AT activity was raised to means of 1.69 and 2.25 U/ml at 24 and 48 h, respectively. Corresponding means in control infants were 0.37 and 0.44 U/ml (p < 0.0001). F1 + 2, but not TAT, was significantly reduced by AT (p = 0.004). VEI and (a/a)Po 2 were similar in both groups throughout the first week of life. Median days receiving mechanical ventilation were 7.1 (AT) versus 4.8 (placebo), p = 0.0014. Median days receiving supplemental oxygen were 7.9 (AT) versus 5.5 (placebo), p < 0.0001. There were seven (11.5%) deaths in the AT group and three (4.9%) deaths in the placebo group. We conclude that treatment with AT cannot be recommended in premature infants with RDS.
Nuclear Threat: What About the Russians?-Reply
Authors: E. Grey Dimond
Journal: JAMA (1985)

In Reply.—  I have read  correspondence from Drs Deusenberg, Nernoff, and Seenewald. Dr Sennewald's comments have  grace of humor, or at least its extension, satire. When a situation is too painful, sometimes there is solace in wit. In reading  words of Drs Deusenberg and Nernoff, I am reminded of  song in South Pacific, You Have Got to Be Taught How to Hate.  These correspondents enthusiastically say why my essay is impossible. I recall similar negative, even hostile, remarks when several of us in 1971 proposed  get on with exchanges with  People's Republic of China although  were told their government was a cruel dictatorship. Each of us remembers  descriptions of the millions of Mao's blue ants. President Nixon in 1972 signed an agreement that in no manner changed  Chinese government but instead, we agree to disagree. Now there are thousands of students
Zidovudine and Red-Cell Distribution Width
Authors: Pablo Rivas, Miguel Górgolas, Manuel L. Fernández-Guerrero
Journal: New England Journal of Medicine (2005)

lymphocyte counts ranging from 400 to 1300 cells per cubic millimeter.In addition to testing for HIV infection, serum immunoglobulin levels were checked to rule out another potential source of immunodeficiency; they were normal.Since our patient had reversible predisposing factors for opportunistic infection (therapy with corticosteroids and infliximab), further testing (including assessment of CD4+ cell counts) and long-term prophylaxis were not recommended.The patient remains in good health without prophylaxis more than 24 months after his hospitalization.
Hyperglycemia-Induced Hyponatremia — Calculation of Expected Serum Sodium Depression
Authors: Murray A. Katz
Journal: New England Journal of Medicine (1973)

FOR at least 1/4 century clinicians have recognized that hyperglycemia depresses serum sodium concentration.1 Since glucose is largely restricted to extracellular fluid, an increase in its concentration moves water out of cells, causing dilution of extracellular solute. It is useful to assess the expected sodium decrease for a given glucose level, because deviations from such a predicted value establish the diagnosis of hyponatremia or hypernatremia that may require therapy in addition to correction of the hyperglycemia. Most clinicians use the rule of thumb that there is a 2.8 mEq per liter decrease in serum sodium for every 100 mg per . . .
Constitutive overexpression of a novel 21 kDa protein by Hodgkin Lymphoma and Aggressive Non-Hodgkin Lymphomas
Authors: Minglong Zhou, Faisal M Fadlelmola, Jason B Cohn, Brian Skinnider, Randy D Gascoyne, Diponkar Banerjee
Journal: Molecular Cancer (2008)

CD30, a 120 kDa surface phosphorylated protein is a member of tumour necrosis/nerve growth factor receptor (TNF/NGFR) family and constitutively expressed by Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) and the neoplastic cells of Anaplastic Large Cell Lymphoma (ALCL). A disease-specific protein marker is yet to be identified in Hodgkin lymphoma cells. In order to define HL-specific biomarkers, novel murine monoclonal antibodies were developed in our laboratory.Murine monoclonal antibodies (mabs) were raised against the B3 sub clone of HL-derived cell line KM-H2. Two of these mabs (clone R23.1 mab and clone R24.1 mab) are IgG1 class antibodies that recognize a 21 kDa protein present at the cell membrane and in the cytoplasm in HL-derived cell lines. Clone R24.1 mab recognizes a formalin-resistant epitope and labels HRS cells in tissue samples from patients with HL of the classical type, ALCL, and subsets of T and B cell aggressive Non-Hodgkin Lymphomas (NHL). The antigen recognized by the clone R23.1 mab and clone R24.1 mab does not share epitopes with CD30 cluster regions A, B, or C, and, unlike CD30, is not expressed by phytohemagglutinin (PHA) activated T cells.The 21 kDa protein detected by clone R23.1 and clone R24.1 mabs is a novel membrane-associated protein that may be a potential marker for the diagnosis and targeted therapy of HL and aggressive T and B cell NHL.
MSF reconsiders Somali operations after fatal attack
Authors: P. Moszynski
Journal: BMJ (2012)

ABSTRACT. Estrogen deficiency results in a negative Ca<sup>2+</sup> balance and bone loss in postmenopausal women. In addition to bone, the intestine and kidney are potential sites for estrogen action and are involved in Ca<sup>2+</sup> handling and regulation. The epithelial Ca<sup>2+</sup> channel ECaC1 (or TRPV5) is the entry channel involved in active Ca<sup>2+</sup> transport. Ca<sup>2+</sup> entry is followed by cytosolic diffusion, facilitated by calbindin-D<sub>28K</sub> and/or calbindin-D<sub>9k</sub>, and active extrusion across the basolateral membrane by the Na<sup>+</sup>/Ca<sup>2+</sup>-exchanger (NCX1) and plasma membrane Ca<sup>2+</sup>-ATPase (PMCA1b). In this transcellular Ca<sup>2+</sup> transport, ECaC1 probably represents the final regulatory target for hormonal control. The aim of this study was to determine whether 17β-estradiol (17β-E<sub>2</sub>) is involved in Ca<sup>2+</sup> reabsorption via regulation of the expression of ECaC1. The ovariectomized rat model was used to investigate the regulation of ECaC1, at the mRNA and protein levels, by 17β-E<sub>2</sub> replacement therapy. Using real-time quantitative PCR and immunohistochemical analyses, this study demonstrated that 17β-E<sub>2</sub> treatment at pharmacologic doses increased renal mRNA levels of ECaC1, calbindin-D<sub>28K</sub>, NCX1, and PMCA1b and increased the protein abundance of ECaC1. Furthermore, the involvement of 1,25-dihydroxyvitamin D<sub>3</sub> in the effects of 17β-E<sub>2</sub> was examined in 25-hydroxyvitamin D<sub>3</sub>-1α-hydroxylase-knockout mice. Renal mRNA expression of calbindin-D<sub>9K</sub>, calbindin-D<sub>28K</sub>, NCX1, and PMCA1b was not significantly altered after 17β-E<sub>2</sub> treatment. In contrast, ECaC1 mRNA and protein levels were both significantly upregulated. Moreover, 17β-E<sub>2</sub> treatment partially restored serum Ca<sup>2+</sup> levels, from 1.63 ± 0.06 to 2.03 ± 0.12 mM. In conclusion, this study suggests that 17β-E<sub>2</sub> is positively involved in renal Ca<sup>2+</sup> reabsorption via the upregulation of ECaC1, an effect independent of 1,25-dihydroxyvitamin D<sub>3</sub>.
Care in the community: a conflict of interests?
Authors: S. Murray
Journal: BMJ (1996)

John is tired and exhausted. Homeless, he is staying with a friend who says that he is “no bother.” His two black eyes suggest, however, that he is a bother to one of the other residents. He has AIDS and occasionally supplements the methadone I prescribe with pills and injections which he finds more to his liking. His wife and 16 month old child have left him. He has no interest in specialist hospital or community services for HIV or drug users. He was not impressed by a local dermatologist who was interested in his atypical psoriasis, or advice to start zidovudine treatment or PCP prophylaxis. What he wants is a small council flat where he can spend the rest of his days. He grudgingly accedes that …
Doctors may sometimes disclose a patient's genetic information to relatives without permission
Authors: C. Dyer
Journal: BMJ (2010)

Doctors may sometimes need to disclose confidential information to family members of a patient with an inherited disease against the patient’s wishes, advises the United Kingdom’s biggest organisation for advising and defending doctors.

The latest advice from the Medical Defence Union says that doctors should always ask the patient for permission to pass on the information to relatives. But occasionally patients will refuse, and in those cases doctors will need to be aware of their ethical obligations and “balance the patient’s right to confidentiality against potential harm to family members if they are not informed.”

The guidance (“Does it Run in the Family?”) appears in the April 2010 issue of Ward …
Action of Radiant-heat Cradles
Authors: G. M. Brown, D. S. Evans, K. Mendelssohn
Journal: BMJ (1943)

MEDICAL *OURNsA by the new diet is permissible even for the most unstable diabetic patients.The calorie control diet has proved to be as satisfactorv in every way as the older type of diet in use in these clinics.It is more simple to use, and it allows patients to replace foods that are scarce with foods that are plentiful.This has also meant that the diet is cheaper, since the carbohydrate foods in general are cheaper than the protein and fat foods which they have replaced.Finally, a group of patients, including some severe cases, have agreed to forgo the extra rations allowed to them by the Government, and they have remained just as stable and well without them.We believe, therefore, that even if the food rations have to be still further reduced and the diet of diabetic patients is affected they could be maintained in good health on the new diet.Summary A diabetic diet is described in which the total calorie value is kept constant but an unlimited variation in the proportion of carbohydrate, protein, and fat is permitted.The effect of this diet has been examined after one year's trial on a large series of cases and found to be satisfactory.
Detection of Depressive Disorder for Patients Receiving Prepaid or Fee-for-Service Care
Authors: Kenneth B. Wells
Journal: JAMA (1989)

We estimated clinicians' awareness of depression for patients with current depressive disorder (N = 650) who received care in either a single-specialty solo or small group practice, a large multispecialty group practice, or a health maintenance organization in three US sites. Depressive disorder was determined by independent diagnostic assessment shortly after an office visit. Detection and treatment of depression were determined from visit-report forms completed by the treating clinician. Depending on the setting, from 78.2% to 86.9% of depressed patients who visited mental health specialists had their depression detected at the time of the visit, compared with 45.9% to 51.2% of depressed patients who visited medical clinicians, after adjusting for case-mix differences. Among patients of mental health specialists, there were no significant differences by type of payment in the likelihood of depressive disorder being detected or treated. Among patients of medical clinicians, however, those receiving care financed by prepayment were significantly less likely to have their depression detected or treated during the visit than were similar patients receiving fee-for-service care.
Contribution of mesenchymal stem cells, or fibroblast-like synoviocytes to the vicious circle leading to chronic inflammation in RA, through promotion of Th17 cells
Authors: A. Eljaafari, M.-L. Tartelin, P. Miossec
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> TH17 cells have been involved in the initiation and maintenance of inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA). In this study, we hypothesised that interaction of T cells with mesenchymal cells, such as synoviocytes (FLS), or mesenchymal stem cells (MSC) could participate in the activation of the TH17 pathway, with the help of the inflammatory environment. <h3>Methods</h3> To investigate this possibility, peripheral blood mononuclear cells (MNC) from RA patients, or from healthy blood donors, were co-cultured with FLS issued from either RA or osteoarthritic (OA) patients, or with MSC issued from healthy bone marrow donors. In addition, synovial T cells were cocultured with autologous RA-FLS. Cocultures were exposed to PHA for 1–2 days. IL17-A, TNFα and or/IFNγ were added or not to these co-cultures.Q-RT-PCR,ELISA, and cytoflurometry techniques were used to assess for IL17-A production. <h3>Results</h3> We observed that the interaction of healthy MNC with MSC resulted in an extinction of TH1 and TH2 cell activation, but induced a strong production of IL-17A, as soon as 24 h post activation, as assessed by (1) the increase of RORC, and IL17-A at the mRNA levels, (2) IL17A secretion in Elisa assays, and (3) Th17 staining, by flow cytometry. The levels of IL17A secretion further increased at 48 h. Moreover, IL6, IL8 and IL1β mRNA levels increased as well, and were potentiated when IL17-A, TNFα, and or/IFNγ cytokines were added in these co-cultures. Interestingly, co-cultures of RA-MNC or healthy MNC with FLS from either OA or RA patients, also resulted in a strong induction of IL17-A, but not in a complete extinction of TH1 cytokines. In the presence of autologous FLS, RA-synovial T cells increased their levels of IL17-A, as well. Finally, TH17 production was partially inhibited in the presence of anti-IL6 mAbs, or CTLA4-Ig fusion molecules, demonstrating thus the roles of IL6 and cell-cell interaction in such a production. <h3>Conclusion</h3> We show herein, that interaction of MSC, or FLS from RA or OA patients, with MNC, or synovial T cells, results in enhancing the inflammatory response through production of IL-17-A, IL6, IL-8 and IL-1β cytokines. Moreover, in the context of an inflammatory environment, that is, the presence of IL-17-A, TNFα, and/or IFNγ, such an interaction of MNC with MSC or FLS results in further amplifying the production of pro-inflammatory cytokines, leading thus to a vicious circle, that may participate in the chronicity of inflammation, in RA.
IgG antiendothelial cell autoantibodies from scleroderma patients induce leukocyte adhesion to human vascular endothelial cells in vitro. Induction of adhesion molecule expression and involvement of endothelium-derived cytokines.
Authors: D Carvalho, C O Savage, C M Black, J D Pearson
Journal: Journal of Clinical Investigation (1996)

IgG autoantibodies that bind human endothelial cells (AECA) were detected by ELISA in 30 of 42 samples of sera from patients with scleroderma. Pretreatment of human umbilical vein endothelial cells with AECA-positive scleroderma sera, or IgG purified from these sera, led to a dose- and time-dependent increase in the ability of the cells to bind human U937 monocytic cells. Threshold-active IgG concentrations were 1-10 micrograms/ml; effects were significant after 3 h and maximal after 6-12 h. IgG from AECA-negative sera or normal sera were without effect. Increased adhesion of U937 cells was accompanied by increased expression of endothelial intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Transfer of endothelial cell-conditioned media after pretreatment with AECA and immunodepletion of IgG demonstrated the presence of transferable activity that mimicked the effects of AECA. Treatment with neutralizing anticytokine antibodies indicated that IL-1, generated by the endothelial cells in response to AECA, was involved in the upregulation of adhesion molecules and U937 cell adhesion. We conclude that AECA can play a pathogenic role in scleroderma by activating endothelial cells, in part due to autocrine or paracrine actions of IL-1.
Extravasation of Contrast Agent in Renal Damage
Authors: Benedict R. Harrow
Journal: JAMA (1963)

To the Editor:  —In the worthwhile and excellent article in the June 1 edition ofThe Journal( 184: 716) by Mullady and his associates, on the effects of diatrizoate sodium on kidney function, an important point was omitted. In the clinical examples from the medical literature of severe renal damage following aortography, careful evaluation reveals that most were due to actual extravasation of contrast agent outside the glomerular membranes. In these cases a dense nephrogram persisted for many minutes and even hours after injection. Since the usual nephrogram would be present in a dense form for only a few seconds, extravasation of contrast agent into tissues was evident. It is the extravasation of these agents that produces renal damage which extravasated saline will not cause. Our experience with injecting various plastics into the renal artery of animals, and then digesting the surrounding renal substance with hydrochloric acid, showed how little
Interferon-γ Prevents Apoptosis in Epstein-Barr Virus-Infected Natural Killer Cell Leukemia in an Autocrine Fashion
Authors: Shin-ichi Mizuno, Koichi Akashi, Koichi Ohshima, Hiromi Iwasaki, Toshihiro Miyamoto, Naoyuki Uchida, Tsunefumi Shibuya, Mine Harada, Masahiro Kikuchi, Yoshiyuki Niho
Journal: Blood (1999)
Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin
Authors: Jeffrey B Carroll, Simon C Warby, Amber L Southwell, Crystal N Doty, Sarah Greenlee, Niels Skotte, Gene Hung, C Frank Bennett, Susan M Freier, Michael R Hayden
Journal: Molecular Therapy (2011)

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo. Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo.
Molecules and markers for endosonographers: What do we need to know and measure?
Authors: M. Al-Haddad, M. Wallace
Journal: Endoscopy (2006)

Endoscopic ultrasound (EUS) has become an indispensable tool for the diagnosis and staging for gastrointestinal and thoracic malignancies. Thanks to the safety and reliability of fine needle aspiration (FNA), this has become the method of choice for tissue acquisition from lymph nodes and tumors in various locations within the thoracic and abdominal cavities.
Hepatocellular carcinoma in urban born blacks: frequency and relation to hepatitis B virus infection.
Authors: M C Kew, C Kassianides, J Hodkinson, A Coppin, A C Paterson
Journal: BMJ (1986)

Chronic hepatitis B virus infection is far less common in urban born than in rural born southern African blacks, who also have a high incidence of hepatocellular carcinoma. A case-control study was carried out to determine the relative frequency of hepatocellular carcinoma and its relation to hepatitis B virus infection in urban born blacks. Three hundred and ninety two black patients with hepatocellular carcinoma and matched controls seen at two city hospitals were classified by questioning as urban born or rural born. The ratio of rural born to urban born blacks among the controls was 1.1:1.0 (207/185), whereas in the patients with cancer the ratio was 4.8:1.0 (324/68) (p less than 0.0001). Analysis of the prevalence of hepatitis B markers in 62 urban born and matched rural born blacks with hepatocellular carcinoma showed no differences in the frequency of current or past hepatitis B virus infection. It is concluded that urban born blacks are less likely than rural born blacks to develop hepatocellular carcinoma, but when they do the tumour is equally likely to be related to infection with hepatitis B virus. The findings lend further support to an important role for chronic hepatitis B virus infection in the aetiology of hepatocellular carcinoma.
Selective endothelin B receptor blockade does not influence BNP-induced natriuresis in man
Authors: K. van der Zander, A.J.H. M. Houben, D.J. Webb, E. Udo, B. Kietselaer, L. Hofstra, J.G.R. De Mey, P.W. de Leeuw
Journal: Kidney International (2006)
Rationing: the case for "muddling through elegantly"
Authors: D. J Hunter
Journal: BMJ (1995)

EDITOR,--Chris Ham's editorial on health care rationing1 misrepresents my position on the issue. He suggests that I subscribe to an approach to rationing by muddling through. My actual position is rather more subtle, hence the description “muddling through elegantly.” I emphasise “elegantly” because I do not seek to defend the previous closed system, in which resource allocation decisions were often dressed up as clinical ones and hidden from public scrutiny.

I, too, support greater transparency in decision …