tbuckley/cabot-search huggingface dataset:
Stuart Clotting Defect. II. Genetic Aspects of a `New' Hemorrhagic State
Authors: John B. Graham, Emily M. Barrow, Cecil Hougie
Journal: Journal of Clinical Investigation (1957)

The literature is ambiguous regarding patients deficient in the clotting factor variously known as "SPCA," "proconvertin," and "Factor VII." Sera from some patients are normal in the thrombo- plastin generation test; those from others are ab- normal.Viper venom corrects the clotting de- fect in some cases, but fails to do so in others.Despite these contradictions, it has been generally assumed that the terms are synonyms for a single clotting factor with unique characteristics.In our preceding communication on the patient R. S. ( 1), previously reported by others as hy- poproconvertinemia (2), we pointed out that the assumption of identity must be incorrect, since the plasmas of our patient and the SPCA defi- cient patient of Alexander, Goldstein, Landwehr, and Cook (3) were mutually corrective, while our patient's plasma failed to correct that of the pa- tient of Crockett, Shotton, Craddock, and Leavell (4).This finding implied the existence of at least two BaSO4 adsorbable clotting factors whose lack prolongs the prothrombin time.We showed that, in contrast to certain other cases in the literature (5-8), the defect in our patient's plasma could not be corrected by Russell viper venom, and that his serum was inactive in the thromboplastin generation test.In this last respect our patient's defect resembled that of some of the previously reported cases (8-11) but differed from certain others (5, 6, 12-14).The factor deficient in our patient is being re- ferred to as the Stuart factor after the patient's surname.We wish to emphasize by this nomen- clature that only by cross-matching his plasma with that from other similar patients can an iden- tity be definitely established.The properties of Stuart factor and its role in blood coagulation were the subject of our earlier communication (1).In this paper the studies on the relatives of our patient will be reported.Our genetic studies in-
Improving the selection of patients for upper gastrointestinal endoscopy.
Authors: S A Naji, P W Brunt, S Hagen, N A Mowat, I T Russell, T S Sinclair, T M Tang
Journal: Gut (1993)

A retrospective study was undertaken to investigate how endoscopies yielding positive findings differ a priori from those yielding negative findings: and how those judged 9helpful9 (in the sense of influencing management) differ a priori from those judged 9unhelpful9. A total of 483 patients undergoing endoscopy was sampled and a wide range of data abstracted, including 48 patient characteristics available to the gastroenterologist at the time of the decision to perform endoscopy. Sixty nine per cent of endoscopies were positive. Multivariate statistical analysis identified four variables which taken together were strongly predictive of a positive endoscopy. The resulting mathematical formula correctly predicted the outcome of 76% of endoscopies. Eighty two per cent of the endoscopies were retrospectively classified by the gastroenterologists as helpful. Six variables were strongly predictive of a helpful endoscopy. The corresponding formula correctly predicted the finding of 84% of endoscopies. Comparison of the two analyses shows that the two sets of predictions differ substantially. Thus it is important that decision tools should be based not on the crude distinction between positive and negative, but on the more useful distinction between helpful and unhelpful in influencing management.
John Edward Buck
Authors: Farid Khan, William Scott
Journal: BMJ (2007)

John Edward Buck was born in Hove, the son of a general surgeon. His father retired after the end of the first world war and emigrated to Vancouver Island. John enjoyed the outdoor life there until his family returned to England in 1932. He went to school at Lancing and then on to Edinburgh to study medicine. He qualified in 1938 and, after house jobs, joined the army in 1940. He had an eventful war. …
Memory clinics could improve dementia care, say experts
Authors: Z. Kmietowicz
Journal: BMJ (2008)

The government’s proposals to set up memory clinics in every town to improve the care given to people with dementia and their families could help to improve dementia care in England provided that they are not set up simply as diagnostic centres, experts have said.

The proposal is part of the five year national dementia strategy to be launched in January. Medical students and GPs are also to receive training in the diagnosis of dementia to improve the early recognition of the disease.

A spokeswoman for the Department of Health said, “We want to make sure that every GP is trained to spot the first signs of …
Points from Letters: Conception after the Pill
Authors: K. V. Cooper
Journal: BMJ (1974)

average superannuable income of the 80 main Swansea principles for the year ended March 1974, a figure which included seniority payments.Published surveys have suggested that the local work load is up to twice the national average.Since April 1974 reorganization has brought all sectors of the profession into management participation with an ever- increasing number of managers in the Health Service whose duties and salaries are pub- lished.The nearest managers to the general practitioner are those at district level and the regional medical officers.For a five-day week they average a superannuable income of £7,500.General practitioners, with other clinicians, provide more than a five-day service but are unique in having to provide their own locums for sickness, study, and annual leave from income; and since reorganization parti- cipation in management through a host of new advisory committees, completely unpaid, make further inroads into the unsocial (leisure) periods.Kindersley recognized a shortfall in remuneration from 1966 which is still uncorrected and increasing.Achieve- ments with dynamism, buying added years, and threshold awards are only tinkering with the problem when the basic contract is faulty.We owe a duty to our dependants and successors to correct the discrepancy or our principal concern, the patient, will find the standard of his primary care in jeopardy.-I am, etc.,
Abstract 4569: Cell death-inducing ICAM-1 antibody has broad and potent anti-myeloma activity in vivo
Authors: Niina Veitonmaki, Markus Hansson, Zhan-chun Li, Anne Ljungars, Lena Danielsson, Frendeus Bjorn
Journal: Cancer Research (2011)

Abstract We previously developed combined target and drug discovery methodology enabling isolation of tumor cell death-inducing antibodies from the human antibody library n-CoDeR®. Among several antibodies targeting different tumor cell associated receptors with documented cell death-inducing properties, antibodies specific for intercellular adhesion molecule-1 (ICAM-1) – a receptor not previously associated with tumor cell death- were obtained. We here characterize the ICAM-1 specific antibody BI-505 with respect to in vivo anti-tumor activity in different well-established tumor disease models, and explore mechanisms underlying its anti-tumor activity. We demonstrate in different tumor xenograft models that BI-505 is equally or more efficacious in preventing CD20 positive B cell tumor growth and in pro-longing tumor-bearing mouse survival compared to CD20 mAb Rituximab in vivo. Moreover, BI-505 showed significant anti-tumor activity against a panel of CD20 negative myeloma tumors in vivo, and BI-505 conferred enhanced mouse survival compared to the proteasome inhibitor bortesomib – approved for treatment of relapsed refractory multiple myeloma – in an experimental model of advanced multiple myeloma. Preliminary data indicate that the BI-505 epitope is highly expressed on myeloma cells in patients with multiple myeloma. The differential in vitro and in vivo anti-tumor activities of BI-505 Fc-variants correlated with binding to recombinant human FcγRIIIa and mouse FcγRIV receptors, respectively. These differences could not be explained by altered antigen-binding properties as all Fc-variants retained near identical EC50 values for binding to recombinant or cell surface expressed ICAM-1 protein. These observations are consistent with cell death and FcγR-dependent anti-tumor immunity being important mechanisms underlying BI-505 therapeutic activity. Collectively, our results demonstrate proof-of-principle for our human antibody based combined target and drug discovery methodology, and provide a rationale for further pre-clinical and clinical evaluation of BI-505 in the treatment of MM. An open multicenter phase I dose-escalation clinical trial with BI-505 in relapsed/refractory MM has recently started in the United States and Sweden. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4569. doi:10.1158/1538-7445.AM2011-4569
Case 54-1962
Authors: Sydney S. Gellis, Wallace A. Jones
Journal: New England Journal of Medicine (1962)

Presentation of CaseA three-year-old boy was admitted to the hospital because of edema and swelling of the abdomen.Four months previously the child entered another hospital because of intermittent swelling of the upper portion of the abdomen, at times accompanied by a sore throat. Physical examination showed marked hepatomegaly and splenomegaly and an insignificant heart murmur. The urine gave a positive test for urobilinogen but was otherwise normal. The hemoglobin was 64 per cent of normal; the white-cell count, a platelet count and a bone-marrow aspirate were normal. The bilirubin was 1.75 mg. per 100 ml., the cephalin flocculation . . .
Commentary: Female sexual dysfunction is a real but complex problem
Authors: S. Goldbeck-Wood
Journal: BMJ (2010)

When the desire for sex goes persistently missing, a few women may be untroubled but many become unhappy. Some are unhappy because they miss the pleasure, physical release, and emotional intimacy that sex can provide or because a lack of sex stands in the way of having children. Sometimes their unhappiness is social or relational: because they fear hurting, rejecting, frustrating, angering, and perhaps even losing their partner. Many endure sexual unhappiness for long periods alone, feeling too embarrassed, ashamed, unentitled, mistrustful, or hopeless to ask for help. It is difficult to speak to a strange doctor about such private distress; more difficult still given that many fear embarrassing their doctor.1 2

So women who consult doctors about sexual problems are those for whom the unhappiness has become so intractable, or is causing so many physical or relational problems, that they are forced into the open. Some present a sexual problem directly, others indirectly through secondary symptoms such as depression, recurrent vaginal discharge, or chronic pelvic pain.3

Faced with a woman in tears whose libido has disappeared and who is terrified of losing her partner, doctors can feel immense pressure to provide an immediate, effective solution. Given that most …
Adrenal function following topical steroid treatment in children with atopic dermatitis
Authors: L. PATEL, P.E. CLAYTON, G.M. ADDISON, D.A. PRICE, T.J. DAVID
Journal: British Journal of Dermatology (2010)

Adrenal suppression is a potential complication of topical corticosteroid treatment in atopic dermatitis. We used a low-dose adrenocorticotrophic hormone (ACTH) test (500 ng/1.73 m2) to detect subtle changes in adrenal glucocorticoid function in 14 prepubertal children with moderate or severe atopic dermatitis affecting 16-90% (median 58%) of the body surface area. All had received regular treatment with mild potency BNF (British National Formulary) classification topical corticosteroid ointments (hydrocortisone 48.7-223.2 mg/m2 body surface area/day; median 134.2) for 3-10 years (median 6.5 years). Nine children had also intermittently used moderate potency preparations. However, none had been treated with corticosteroids by any other route in the preceding 6 months. Fourteen prepubertal children with constitutional short stature, without atopic disease, served as controls. The basal, peak, increment and area-under-curve in plasma cortisol concentrations in children with atopic dermatitis were not significantly different from controls, indicating normal adrenal sensitivity to low-dose ACTH. However, the peak in plasma cortisol occurred earlier in children with atopic dermatitis (median 17.5 min) than in controls (median 25 min) (P = 0.02). In addition, there was a significant inverse relationship between time to peak and extent of atopic dermatitis (rs = -0.52; P < 0.05), but not topical steroid treatment dose or score in children with atopic dermatitis. These findings indicate accelerated adrenal responsiveness to ACTH in children with atopic dermatitis, which is independent of treatment. Mild to moderately potent topical corticosteroid ointments in these doses did not suppress adrenal glucocorticoid function in this sample of children with atopic dermatitis.
Polyethylenimine-modified Pluronics (PCMs) Improve Morpholino Oligomer Delivery in Cell Culture and Dystrophic mdx Mice
Authors: Mingxing Wang, Bo Wu, Peijuan Lu, Caryn Cloer, Jay D Tucker, Qilong Lu
Journal: Molecular Therapy (2012)

We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)-conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw) ranging 2–6 k, with hydrophilic-lipophilic balance (HLB) 7–23, significantly enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter-based myoblast culture system. Application of optimized formulations of PCMs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. Consistent with our observations in vitro, optimization of molecular size and the HLB of pluronics are important factors for PCMs to achieve enhanced PMO delivery in vivo. Observed cytotoxicity of the PCMs was lower than Endo-porter and PEI 25 k. Tissue toxicity of PCMs in muscle was not clearly detected with the concentrations used, indicating the potential of the PCMs as effective and safe PMO carriers for treating diseases such as muscular dystrophy. We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)-conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw) ranging 2–6 k, with hydrophilic-lipophilic balance (HLB) 7–23, significantly enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter-based myoblast culture system. Application of optimized formulations of PCMs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. Consistent with our observations in vitro, optimization of molecular size and the HLB of pluronics are important factors for PCMs to achieve enhanced PMO delivery in vivo. Observed cytotoxicity of the PCMs was lower than Endo-porter and PEI 25 k. Tissue toxicity of PCMs in muscle was not clearly detected with the concentrations used, indicating the potential of the PCMs as effective and safe PMO carriers for treating diseases such as muscular dystrophy.
How necessary are elimination diets in childhood?
Authors: R. Mackarness
Journal: BMJ (1980)

may be responsible for stress.Though this possibility should not be overlooked, simple observation of increased smoking during war time suggests that smoking alleviates stress or fulfils some other basic human need (for example, relieves boredom) for many people, a view consistent with the US Surgeon-General's recognition of "significant beneficial effects of smoking primarily in the area of mental health."3Dr T Khosla and Professor H Campbell (2 February, p 331) suggested that, by restricting my attentions to those under 65, I had given a
Chickenpox pneumonia: experience with antiviral treatment.
Authors: R N Davidson, W Lynn, P Savage, M H Wansbrough-Jones
Journal: Thorax (1988)

Of 13 patients with chickenpox pneumonia (12 of them adults) treated during 1979-87, 10 received antiviral drugs--nine acyclovir and one vidarabine. Three died despite intensive treatment. Serious secondary infections occurred in six cases. There were no clear indications that antiviral treatment altered the natural history of the condition. Acyclovir may at present be used too late in the course of chickenpox pneumonia to alter its outcome.
A JOURNAL THAT CHANGED MY PRACTICE
Authors: S. Westin
Journal: BMJ (1996)

During one of those busy nights on call in our island community I had a call from a woman about her mother who lived alone in a modest old house by the sea. She was suffering from chest pain. When I arrived she was pale, pain stricken, and slightly restless—all reasons to suspect a myocardial infarction. Her condition improved a little after a morphine injection and I headed for the telephone to arrange for her immediate admission to the regional hospital's intensive care unit.

“Please doctor,” the old lady pleaded, “don't …
Pain and Spasticity in Patients with Spinal Cord Dysfunction
Authors: Lawrence I. Kaplan, Bruce B. Grynbaum, Kathleen Elliott Lloyd, Howard A. Rusk
Journal: JAMA (1962)

This retrospective and continuing follow-up study analyzes the incidence and treatment of pain and spasticity in disease of the spinal cord. Of 44 patients with upper motor neuron involvement, 31 had initial spasticity which persisted in 28 to the present and developed in 5 others during the interim. Pain, usually mild, was found in 19 initially; it was still present in 16 at follow-up examination and developed during the interim in 13 others. Spasticity tended to occur in the lower extremities, flexors, and extensors, and prevented daily activities. Drugs were mildly effective. Pain tended to persist but did not prevent daily function. It was commonly found in the lower extremities, at the level of the lesion, in the region of the lower abdomen, and elsewhere. It was often neglected therapeutically.
Adventitial remodeling with increased matrix metalloproteinase-2 activity in a porcine arteriovenous polytetrafluoroethylene grafts
Authors: Sanjay Misra, Michael G. Doherty, David Woodrum, Jay Homburger, Jaywant N. Mandrekar, Stephane Elkouri, Enrique A. Sabater, Haraldur Bjarnason, Alex A. Fu, James F. Glockner, Eddie L. Greene, Debabrata Mukhopadhyay
Journal: Kidney International (2005)
Positive Associations of Serum Concentration of Polychlorinated Biphenyls or Organochlorine Pesticides with Self-Reported Arthritis, Especially Rheumatoid Type, in Women
Authors: Duk-Hee Lee, Michael Steffes, David R. Jacobs
Journal: Environmental Health Perspectives (2007)

Persistent organic pollutants (POPs) can influence the immune system, possibly increasing the risk of rheumatoid arthritis (RA). In addition, as metabolic change due to obesity has been proposed as one mechanism of osteoarthritis (OA), POPs stored in adipose tissue may be also associated with OA.Our goal in this study was to examine associations of background exposure to POPs with arthritis among the general population.We investigated cross-sectional associations of serum POPs concentrations with the prevalence of self-reported arthritis in 1,721 adults >/= 20 years of age in the National Health and Nutrition Examination Survey 1999-2002.Among several POPs, dioxin-like polychlorinated biphenyls (PCBs) or nondioxin-like PCBs were positively associated with arthritis in women. After adjusting for possible confounders, odds ratios (ORs) were 1.0, 2.1, 3.5, and 2.9 across quartiles of dioxin-like PCBs (p for trend = 0.02). Corresponding figures for nondioxin-like PCBs were 1.0, 1.6, 2.6, and 2.5 (p for trend = 0.02). Organochlorine (OC) pesticides were also weakly associated with arthritis in women. For subtypes of arthritis, respectively, RA was more strongly associated with PCBs than was OA. The adjusted ORs for RA were 1.0, 7.6, 6.1, and 8.5 for dioxin-like PCBs (p for trend = 0.05), 1.0, 2.2, 4.4, and 5.4 for nondioxin-like PCBs (p for trend < 0.01), and 1.0, 2.8, 2.7, and 3.5 for OC pesticides (p for trend = 0.15). POPs in men did not show any clear relation with arthritis.The possibility that background exposure to PCBs may be involved in pathogenesis of arthritis, especially RA, in women should be investigated in prospective studies.
Bruising in thyrotoxicosis.
Authors: J A Thomson
Journal: BMJ (1977)

Whether Drs Brooks and Harrington's patient developed malignancy after the diagnosis of coeliac disease was made and some clinical improvement was obtained after gluten withdrawal or whether it was present initially, precipitating overt manifestations of gluten intolerance, it is not possible to say.It is certainly believed that failure of a patient with newly diagnosed coeliac disease to respond to gluten withdrawal or relapse occurring after previous control by diet is suggestive of the development of malignancy.'The view that intestinal malignancy may cause flattening of the jejunal mucosa and present as "the coeliac syndrome" is no longer held.
Mannitol as Asmotic Diuretic
Authors: Charles H. Carter
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Although there have been references to the use of diuretics for the relief of pulmonary edema,<sup>1, 2</sup>mannitol has not been specifically indicated as an agent. My own experience with this drug at Sunland Hospital (a 1,000-bed hospital for severely retarded, permanently nonambulatory, and physically handicapped patients) suggests that mannitol may be of significant value in the management of pulmonary edema. I have administered experimentally 100 to 500 ml of mannitol intravenously to 51 patients suffering from preterminal pulmonary edema of various causes. Most interesting and significant were the results in six patients with bronchopneumonia with secondary pulmonary edema that was considered irreversible. In these patients, diuresis began 30 minutes after treatment with mannitol and was followed by a rapid decrease in pulmonary congestion with respiratory exchange improving to such an extent that the patients showed a definite, unexpected recovery. <h3>Report of a Case:—</h3> A 12-year-old