tbuckley/cabot-search huggingface dataset:
Acute obstructive hydrocephalus after subarachnoid haemorrhage.
Authors: Y M Kohi, R A Johnston, U P Devkota
Journal: BMJ (1984)

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional signals. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. We conducted a multi-population GWAS meta-analysis in 38,463 participants (2,440 cases) and population specific GWAS, discovering twelve significant associations (eight novel). Fine-mapping implicated specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk signal. Non-HLA loci colocalized with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs was lacking, but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associated with earlier disease onset in two independent cohorts. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers.
Letter: Maternal blood group A and pre-eclampsia.
Authors: S Harlap, A M Davies
Journal: BMJ (1974)

with oral conitraceptives.Without being able categorically to deny this possibility I think it unlikely for the following reasons.Retinol in human blood is predominantly bound to a specific transport-protedin known as the retinol-binding protein (RBP).Under physiological conditions RBP ibinds to pre- albumin.4The amount of free retinol is very small, indeed.Using a fluorescence assay5 measurements have been made of the amoun-t of RBP,in plasma from 10 women before starting to take a combined oral con- traceptive (Minovlar: 1 mg nocethisterone acetate and 50 ,ug ethynylestradiol) and again after three months' treatment.The mean pretreatment level of RBP was 42±8 (S.D.) ,ug/ml, but this rose to 75 ± 10 ug/ml during treatmenrt.This finding indicates that the rise in iseruum vitamin A level during the taking of oral contraceptives is due to an increased concentrtion of RBP.The amount of free retinod is unchanged.Hypervitaminosis A and the teratogeic effects of the vitamnm in pregnant animls are seen with doses which far exceed the binding capacty of RBP.I,t seems unlikely that an increase in protein-bound retinol is hazadous.A very analogous isiituation occurs with coricosterodds, where plasma levels are very high in women taking oral cotraceptives owng to an increase in,transcartin.6The increase in plasma RBP seen in women taking oral contraceptives is prob- ably due to the oestirogen component, for plasma retinol is not increased by progestogens alone.2Serum vitamin A is also raised in volunteers exposed to DDT,7 for this compound yields oestrogenic mexa- bolites.
Modulation of arteriolar blood flow by inhibitors of arachidonic acid oxidation after thermal injury: possible role for a novel class of vasodilator metabolites.
Authors: K G Proctor, S Shatkin, P M Kaminski, J R Falck, J H Capdevila
Journal: Circulation (1988)

To examine the contribution of arachidonic acid (AA) metabolites to the maintenance of cutaneous vasomotor tone after thermal injury, enzyme inhibitors were topically applied to the hamster cheek pouch before and after a spot burn. By use of video microscopy, blood flow was measured in adjacent arterioles that supplied the injured site. Ringer's solutions containing no drug (vehicle), indomethacin (cyclooxygenase inhibitor), BW755c (cyclooxygenase/lipoxygenase inhibitor), or ketoconazole (lipoxygenase/cytochrome P450 inhibitor) continuously suffused the entire tissue. There were no effects of these drugs on preburn blood flow at concentrations that blocked the vascular effects evoked by topical AA. In all groups, blood flow transiently increased after burn and thereafter decreased to levels that were altered by treatment. These results could not be attributed to alterations in vascular reactivity because neither the burn nor the drugs altered the vasodilation evoked by adenosine or prostacyclin. Relative to Ringer's, indomethacin had no effect, BW755c caused vasodilation, and ketoconazole caused vasoconstriction, which suggests that cytochrome P450 products might be vasoactive mediators in injured tissue. Therefore, purified synthetic compounds were compared with known vasodilators. The potency was prostacyclin greater than 12R-hydroxyeicostetraenoic acid greater than adenosine = 5,6 epoxyeicosatrienoic acid greater than AA, which supports the hypothesis that AA can be the source of a novel class of nonprostaglandin vasodilator compounds. In addition, at least one of the vasodilator responses was stereospecific. Nevertheless, the exact explanation for the differential effects of AA inhibitors on postburn blood flow is unknown.
Structural Basis of Renal Disease
Authors: Glenn C. Faith
Journal: JAMA (1968)

Latest among recent books on the kidney is this collection of individual theses on various aspects of renal anatomy and pathology. The title, suggesting the approach, is appropriate to the contents. The intent of the book, as stated in the preface, is to compile recently acquired knowledge of renal pathology in convenient form. With some exceptions, it contains relatively little information not available somewhere in the existing literature. Nephrologists and renal pathologists will recognize many of the contributions. Those embarking upon this field, however, will find the text and illustrations informative, and the bibliographies excellent guides. The encyclopedic style may be cumbersome for the general medical reader or the average medical student, unless he is motivated to probe renal problems in considerable depth. Because of the multiple authorship, there are numerous examples of overlapping presentation and discussion, references, and even occasional illustrations that might have been sifted out by more
Futility and Avoidance: Medical Professionals in the Treatment of Obesity
Authors: Susan Calvert Finn
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The Commentary by Dr Frank<sup>1</sup>has attracted the attention of many of this association's members. As registered dietitians and dietetic technicians, we can certainly support Frank's calls for obesity treatment by credentialed professionals. And, given a coordinated, multidisciplinary approach, our members know from experience that, contrary to Frank's assertions, successful treatment of obesity can be achieved. Success comes through the efforts of a team of experts, including physicians, dietitians, nurses, and exercise physiologists. Today's dietitian brings much more to this team than the "litany of menu planning" that Frank references. Uniquely qualified to translate nutrition science into practical food choices, dietitians thoroughly assess a patient's diet and eating patterns before developing a highly individualized plan that will promote long-term weight loss. Counseling on what to eat and how to plan menus is only one component of a dietitian's involvement in obesity treatment. Dietitians continually monitor a
Contaminated hospital water supplies.
Authors: H J Black, E J Holt, K Kitson, M H Maloney, D Phillips
Journal: BMJ (1979)

These observations do not detract from the interesting points made by Verbeelen and Fuss with more modern methods, especially the induction of hypercalcaemia on oestrogen withdrawal, as well as of hypocalqaemia on oestrogen administration.They merely indi- cate that the latter phenomenon is a perennial one.
747. Plasmid Electrotransfer of Eye Ciliary Muscle: Principle and Therapeutic Efficacy in an Acute Inflammatory Model
Authors: Carole Bloquel, R. Bejjani, Pascal Bigey, Fethi Bedioui, M. Doat, David BenEzra, Francine Behar-Cohen, Daniel Scherman
Journal: Molecular Therapy (2006)

Due to its small size and particular isolating barriers, the eye is an ideal target for local therapy. The ocular delivery of recombinant proteins requires invasive and painful repeated injections. Alternatively, a transfected tissue might be used as a local producer of transgene-encoded therapeutic protein. We have developed a non damaging electrically mediated plasmid delivery technique (electrotransfer) restricted to the ciliary muscle, which is used as a reservoir tissue for the long lasting expression and secretion of therapeutic proteins. High and long lasting reporter gene expression was observed for various voltage and electric pulse time. Transgene expression was restricted to the ciliary muscle. Transgene expression was also observed in the absence of electric field, although with a lower efficiency. Plasmid coding for a chimeric TNF-alpha soluble receptor (hTNFR-Is) electrotransfer led to elevated protein secretion in aqueous humor and to drastic inhibition of clinical and histological inflammation scores in rats with endotoxin-induced uveitis. No hTNFR-Is was detected in the serum, demonstrating the local delivery of proteins using this method. Plasmid electrotransfer to the ciliary muscle, as performed in this study, did not induce any ocular pathology or structural damage. Thus, local and sustained therapeutic protein production through ciliary muscle simple DNA delivery and eventually electrotransfer is a promising alternative to repeated intraocular protein administration for a large number of inflammatory, degenerative, or angiogenic diseases. Figure: GFP reporter selective expression in ciliary muscle (green), colocalizing with smooth muscle actin (red).
Laboratory Testing in Primary Care
Authors: Ronald L. Hirsch
Journal: JAMA (1996)

<h3>To the Editor.</h3> —The study by Dr Nutting and colleagues<sup>1</sup>regarding problems in laboratory testing in primary care explores an issue that is becoming increasingly pertinent as managed care grows. Many managed care organizations are now signing exclusive contracts with national laboratories to perform the laboratory testing for their members. However, I was concerned by the authors' inclusion of the misstatement of the therapeutic range for prothrombin time by a referral laboratory as a problem judged to have a significant impact. It is noted that based on this, the patient developed a hematoma, presumably by an inappropriate adjustment in the warfarin dosage by the physician. This study took place during 1993, a time when many, if not most, laboratories were reporting the prothrombin time using either the time in seconds and the prothrombin time ratio, or, if the laboratory was progressive, also reporting the international normalized ratio (INR). Determining a
Neurology/internal medicine
Authors: D. J. Dalessio
Journal: JAMA (1980)

Disorders of the nervous system encompass broad categories of disease. It is impossible to review the clinical progress accomplished during the last year in a brief essay such as this. What follows are a few selected topics I have found to be unusually interesting, related to internal medicine, and liable to be of clinical importance to a general physician audience.  Toxic Pseudotumor Cerebri  Pseudotumor cerebri is characterized by headache, papilledema, and increased intracranial pressure, in the absence of an intracranial mass. Although the alternative term benign intracranial hypertension has also been used, because spontaneous recovery generally occurs, the process is not always benign; occasionally, visual acuity may be severely damaged.  Pseudotumor cerebri has many presumed causes. In only a few of them, however, is the mechanism of increase in intracranial pressure obvious. There may be increased venous pressure with a disproportion in the rate of formation and absorption of CSF
Israel investigates tobacco firms for misleading the public
Authors: Judy Siegel-Itzkovich
Journal: BMJ (2001)

Tobacco company executives who market their cigarettes in Israel as “lite,” “low tar,” “mild,” or “low nicotine” could face a prison sentence of one to two years.

This is the prescribed but little used punishment for violation of the 1981 Consumer Protection Law, which is the basis for a criminal investigation just launched by the ministry of commerce and industry against cigarette manufacturers and importers. They are suspected of misleading the public into believing that this form of tobacco is “safer” than ordinary cigarettes.

The investigation was initiated after the filing of a lawsuit in the Jerusalem district court last June by lawyers for Clalit Health Services, Israel's largest public health fund. They asked for an injunction to prevent cigarette manufacturers and importers from using the terms “light,” “mild,” “low tar,” and “low nicotine” to describe and market their …
Mitral valve replacement for an annular submitral aneurysm of the left ventricle.
Authors: A G Gokhale, N Lal, B Ashok, J Jacob, S Krishnaswami, P S Jairaj
Journal: Thorax (1993)

Successful surgical repair of an annular submitral aneurysm of the left ventricle in two patients is described. In both cases the diagnosis was made at surgery and they were treated successfully by transatrial closure of the aneurysm with Teflon felted sutures and mitral valve replacement. This is the first report of the use of mitral valve replacement for this condition.
Science, medicine, and the future : Gene therapy
Authors: S. J Russell
Journal: BMJ (1997)

In the eight years since the first human gene transfer experiment, in which a patient with malignant melanoma received genetically modified autologous T cells,1 about 30 gene therapy companies have been launched, three major gene therapy journals have been established, more than 200 human gene therapy protocols have been approved, and over 2000 patients have received gene therapy. As yet, however, only a handful of patients with rare conditions have benefited from gene therapy, and early optimism about this new treatment has given way to disillusionment. In this article I look at the current status of gene therapy research and discuss the key problems that must be overcome to realise the enormous potential of gene therapy to treat not just single gene disorders but many common diseases such as arthritis, cancer, hypertension, atherosclerosis, diabetes, and asthma.

Gene therapy is a term that can be applied to any clinical therapeutic procedure in which genes are intentionally introduced into human somatic cells. There are two main approaches: in vivo gene therapy, in which genes are delivered directly to target cells in the body, and ex vivo gene therapy, in which the target cells are genetically modified outside the body and then reimplanted (fig 1).



FIG 1 
Gene therapy strategies. With current vectors, cells are usually genetically modified outside the body before reimplantation (ex vivo gene therapy). Targetable injectable vectors would facilitate the direct delivery of genes to cells and tissues in the patient (in vivo gene therapy)



Gene transfer into human cells is not a new concept: viral genes are introduced into human cells when a viral vaccine is administered to protect against disease. However, the clinical goals of gene therapy are different and often depend on the prolonged survival of genetically engineered cells or tissues in the patient. The key technologies …
A keratin 14 ‘knockout’ mutation in recessive epidermolysis bullosa simplex resulting in less severe disease
Authors: K. Batta, E.L. Rugg, N.J. Wilson, N. West, H. Goodyear, E.B. Lane, M. Gratian, P. Dopping-Hepenstal, C. Moss, R.A.J. Eady
Journal: British Journal of Dermatology (2000)

Epidermolysis bullosa simplex (EBS) is a blistering skin disease caused in most cases by mis‐sense mutations in genes encoding the basal epidermal keratin (K) 5 and K14. The inheritance is usually autosomal dominant and the mutant keratin proteins appear to exert a dominant negative effect on the keratin intermediate filament cytoskeleton in basal keratinocytes. We report a child with a homozygous K14 mutation resulting in the complete absence of K14 protein in the epidermis; remarkably, he only had mild to moderate disease. Electron microscopy of a skin biopsy showed a marked reduction in numbers of keratin intermediate filaments in the basal keratinocytes. Immunofluorescence microscopy using monoclonal antibody LL001 against K14 showed no staining, suggesting a functional knockout of K14. Sequence analysis of genomic DNA revealed a homozygous mutation in codon 31 of K14 that resulted in a premature stop codon further downstream in exon 1. The child's mother, who is unaffected by the disease, is heterozygous for the mutation. The consanguineous father was unaffected and unavailable for testing. The resulting mRNA is predicted to encode a protein of 116 amino acids, of which the first 30 are identical to the normal K14 sequence, and the remaining 86 residues are mis‐sense sequence. Four previously reported cases of autosomal recessive EBS with functional knockout of K14 were severely affected by blistering, in contrast to our patient in whom the predicted protein has only the first 30 amino acids of K14 and is therefore the closest to a true knockout of K14 protein yet identified.
Na <sup>+</sup> /H <sup>+</sup> Exchanger Activity Does Not Contribute to Protection by Ischemic Preconditioning in the Isolated Rat Heart
Authors: Alex R. Shipolini, Hiroyuki Yokoyama, Manuel Galiñanes, Stephen J. Edmondson, David J. Hearse, Metin Avkiran
Journal: Circulation (1997)

Background Despite evidence that pharmacological inhibition of the Na + /H + exchanger (NHE) is cardioprotective, activation of NHE has been proposed as a protective mechanism of ischemic preconditioning (PC). Methods and Results In isolated rat ventricular myocytes (n=8 to 11 per group) loaded with the fluorescent pH indicator C-SNARF-1, we showed that HOE-642 (HOE) was a potent inhibitor of the sarcolemmal NHE (80% inhibition at 1 μmol/L); such inhibition was readily reversible by washout of the drug. We confirmed that 1 μmol/L HOE produces significant and reversible inhibition of NHE activity in isolated rat hearts as well (n=4), and in this model, we tested (n=8 per group) whether the presence of the drug during (1) the prolonged period of ischemia (40 or 60 minutes) or (2) the preceding brief periods of PC ischemia (3 minutes plus 5 minutes) modulates the protective efficacy of PC. In protocol 1, HOE was infused for 5 minutes immediately before the prolonged ischemic period. With 40 minutes of prolonged ischemia, the postischemic recovery of left ventricular developed pressure (LVDP) was 15±2% in controls and was improved to 45±7% with HOE ( P &lt;.05), 55±5% with PC ( P &lt;.05), and 68±2% with PC+HOE ( P &lt;.05 versus all groups). When the prolonged ischemic period was extended to 60 minutes, an additive effect of PC and HOE was readily apparent and LVDP recovery with PC+HOE (66±2%) was almost double that observed with HOE (37±4%) or PC (34±5%) alone ( P &lt;.05). In protocol 2, HOE was infused for 3 minutes immediately before each episode of PC ischemia and was subsequently washed out before a 40-minute prolonged ischemic period (HOE+PC). LVDP recovery was 34±4% in controls and was improved to 57±2% with PC ( P &lt;.05) and 55±3% with HOE+PC ( P &lt;.05). Improved recovery of LVDP was matched by reduced creatine kinase leakage in all cases. Conclusions Because coadministration of HOE (at a concentration sufficient to inhibit NHE activity) did not reduce the efficacy of PC in either protocol, we conclude that NHE activity does not contribute to the cardioprotective actions of PC. On the contrary, NHE inhibition during the prolonged ischemic period may enhance the protection afforded by PC.
Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery
Authors: Anna Dodero, Cristiana Carniti, Anna Raganato, Antonio Vendramin, Lucia Farina, Francesco Spina, Carmelo Carlo-Stella, Simona Di Terlizzi, Marco Milanesi, Paolo Longoni, Lorenza Gandola, Claudia Lombardo, Paolo Corradini
Journal: Blood (2009)
ANTIBODY RESPONSE TO HOMOGRAFTS
Authors: Paul I. Terasaki, John D. McClelland
Journal: The Journal of Experimental Medicine (1963)

Antigenic differences between certain inbred strains of mice which could not be revealed by hemagglutination techniques were readily disclosed by lymphocyte cytotoxicity. With an improved cytotoxicity test lymphotoxic titers were as high as 1:512 with non-hemagglutinating A anti CBA antisera. In other mouse strain combinations, a close parallel of both types of antibody activity was obtained. Though both activities were absorbed from antisera proportionally by erythrocytes and lymph node cells, 100 to 1000 times as many erythrocytes as lymphocytes were necessary to produce an equivalent reduction in antibody activity. These findings suggest that erythrocytes may possess only subthreshold quantities of certain antigens which are present in readily detectable levels on lymphocytes. Lymphocyte cytotoxicity therefore may assay a wider range of allogenic antigens than hemagglutination.
TCT-300 HASBLED Scale Utility after Percutaneous Coronary Interventions
Authors: Adriana De la Rosa Riestra, Roberto Del Castillo Medina, Ester Canovas Rodriguez, Alfonso Freites Esteves, Javier Alonso Bello, Lorenzo Hernando Marrupe, Pablo Salinas, Botas Javier Rodriguez
Journal: Journal of the American College of Cardiology (2013)
THE RELATION OF THE HOSPITAL TO MEDICAL EDUCATION AND RESEARCH.
Authors: WILLIAM H. WELCH
Journal: JAMA (1907)

The most urgent need of the medical schools of this country at the present time is the possession of well organized and well equipped hospitals, available for teaching, and I esteem it a great privilege to bring greetings and congratulations to the Jefferson Medical College on this splendid addition to its educational resources. Coming, as so many of us do, directly from the meeting of the American Medical Association in Atlantic City, my colleagues, representing the medical profession of this country, will surely be glad to have me express on this happy occasion in their behalf congratulations to this college and to this city. We must all rejoice in the enlarged opportunities for bedside teaching supplied by this fine hospital to the Jefferson Medical College, which from its foundation over eighty years ago has laid especial emphasis on clinical instruction, which has sent forth so many graduates who have achieved
The Potential Supply of Organ Donors
Authors: Roger W. Evans
Journal: JAMA (1992)

To estimate the potential supply of organ donors and to measure the efficiency of organ procurement efforts in the United States.A geographic database has been developed consisting of multiple cause of death and sociodemographic data compiled by the National Center for Health Statistics. All deaths are evaluated as to their potential for organ donation. Two classes of potential donors are identified: class 1 estimates are restricted to causes of death involving significant head trauma only, and class 2 estimates include class 1 estimates as well as deaths in which brain death was less probable.Over 23,000 people are currently awaiting a kidney, heart, liver, heart-lung, pancreas, or lung transplantation. Donor supply is inadequate, and the number of donors remained unchanged at approximately 4000 annually for 1986 through 1989, with a modest 9.1% increase in 1990. Between 6900 and 10,700 potential donors are available annually (eg, 28.5 to 43.7 per million population). Depending on the class of donor considered, organ procurement efforts are between 37% and 59% efficient. Efficiency greatly varies by state and organ procurement organization.Many more organ donors are available than are being accessed through existing organ procurement efforts. Realistically, it may be possible to increase by 80% the number of donors available in the United States (up to 7300 annually). It is conceivable, although unlikely, that the supply of donor organs could achieve a level to meet demand.