tbuckley/cabot-search huggingface dataset:
Husband says judge's ruling on wife's treatment was “inhumane”
Authors: Clare Dyer
Journal: BMJ (2007)

The husband of a woman in a persistent vegetative state (PVS) who was given a sleeping pill that was said to have “woken up” some patients has called for an urgent inquiry into the use of the drug on his wife. 

The president of the High Court's family division, Sir Mark Potter, sanctioned a brief trial of zolpidem on the woman, named only as J, before a final decision was taken to withdraw artificial nutrition and hydration and let her die. 

Sir Mark agreed to the treatment at the request of the then official solicitor, Laurence Oates, …
Cogwheel report in relation to the smaller hospital group.
Authors: F J Fawcett, R E Loder
Journal: BMJ (1972)

Diagnostic abdominal paracentesis was performed in 43 patients in whom the diagnosis was uncertain.It was found to be particularly useful in abdominal pain resulting from trauma.In 12 patients the findings led to their being spared a laparotomy while in several other patients they led to very early diagnosis of the lesion responsible enabling early surgical treatment to be undertaken.A false-negative result was obtained in only one patient.It is concluded that diagnostic abdominal paracentesis is an extremely reliable diagnostic aid and can lead to improved surgical care of the patient with, atypical acute abdominal pain.
Birth Defects
Authors: Virginia Apgar
Journal: JAMA (1968)

Abnormal conditions of congenital origin are a leading cause of death and disability in the United States. An estimated 500,000 fetal deaths and at least 62,000 deaths among the live-born are associated with birth defects each year. An estimated 15 million persons have one or more congenital defects which affect their daily lives. Birth defects constitute a leading cause of hospitalization of children.
LXRβ is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice
Authors: Rucha Patel, Monika Patel, Ricky Tsai, Vicky Lin, Angie L. Bookout, Yuan Zhang, Lilia Magomedova, Tingting Li, Jessica F. Chan, Conrad Budd, David J. Mangelsdorf, Carolyn L. Cummins
Journal: Journal of Clinical Investigation (2010)

Although widely prescribed for their potent antiinflammatory actions, glucocorticoid drugs (e.g., dexamethasone) cause undesirable side effects that are features of the metabolic syndrome, including hyperglycemia, fatty liver, insulin resistance, and type II diabetes. Liver x receptors (LXRs) are nuclear receptors that respond to cholesterol metabolites and regulate the expression of a subset of glucocorticoid target genes. Here, we show LXRβ is required to mediate many of the negative side effects of glucocorticoids. Mice lacking LXRβ (but not LXRα) were resistant to dexamethasone-induced hyperglycemia, hyperinsulinemia, and hepatic steatosis, but remained sensitive to dexamethasone-dependent repression of the immune system. In vivo, LXRα/β knockout mice demonstrated reduced dexamethasone-induced expression of the key hepatic gluconeogenic gene, phosphoenolpyruvate carboxykinase (PEPCK). In perfused liver and primary mouse hepatocytes, LXRβ was required for glucocorticoid-induced recruitment of the glucocorticoid receptor to the PEPCK promoter. These findings suggest a new avenue for the design of safer glucocorticoid drugs through a mechanism of selective glucocorticoid receptor transactivation.
Abstract PR16: Important bidirectional function in the Notch-Delta signaling in pancreatic carcinogenesis and metastasis
Authors: Pawel K. Mazur, Clara Lubeseder-Martellato, Barbara M. Grüner, Ewa Kaznowska, Bence Sipos, Martin Hrabé de Angelis, Roland M. Schmid, Julien Sage, Jens T. Siveke
Journal: Cancer Research (2011)

Abstract Pancreatic cancer is a dismal disease with a median survival of less than 6 months. Its high mortality is due to aggressive development and early lymphatic and hematogenic dissemination. Notch signaling has been shown to regulate pancreatic carcinogenesis; however, a specific role of the Notch ligands has not been extensively studied thus far. Here we investigate the role of Delta1 ligand in pancreatic carcinogenesis and metastasis. Our study using a reporter mouse indicates that Delta1 is mainly expressed in centroacinar and ductal cells as well as in pancreatic intraepithelial neoplasia (PanIN) lesions. Expression in those vulnerable cell compartments and preneoplastic lesions imply relevance for carcinogenesis. Moreover, during cancer development, Delta1 shows the highest relative increase in expression among all Notch ligands suggesting it predominantly functions in Notch pathway activation. Its potentially important role in tumorigenesis was investigated using a KrasG12D-driven pancreatic carcinogenesis mouse model inbreed with a Delta1LacZ/+ haploinsufficient mouse. In KrasG12D;Delta1LacZ/+ mice we observed a delay in PanIN progression and increased development of mucinous cystic neoplasia. Obtained results support our hypothesis. Moreover, in vitro data indicates that Delta1 is critical for Notch2 activation that directly regulates pancreatic cancer progression via cMyc induction. We also analyzed expression and role of the intracellular domain of Delta1 (Delta1-IC). We found that Delta1-IC is accumulated in pancreatic cancer distal metastasis. Our investigations strongly suggest that Delta1-IC can enhance metastatic potential by interaction with transducers of TGFβ signaling: Smad3 and Smad4. We found that Delta1-IC by co-binding to Smad3-regulated promoter proteins can increase TGFβ-induced transcriptional changes in the cell leading to increased cellular motility and EMT capacity. We establish that nuclear accumulation of Delta1-IC correlates with patients' poor outcome and presents of metastasis as well as tumor stage. Our investigation proofs the importance of Notch signaling and points to its bidirectional function in pancreas carcinogenesis and metastasis. This abstract is also presented as Poster A62. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR16.
Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease
Authors: Alex George, Suvarnamala Pushkaran, Diamantis G. Konstantinidis, Sebastian Koochaki, Punam Malik, Narla Mohandas, Yi Zheng, Clinton H. Joiner, Theodosia A. Kalfa
Journal: Blood (2013)
A Lecture on THE RELATION OF DIET TO HEALTH AND DISEASE: SOME RECENT INVESTIGATIONS
Authors: E. Mellanby
Journal: BMJ (1930)

rIHERE is but liti-le doutbt that soiime ofthle most imiportant (onitriblftions to mehliciie in the last few Years have come throuiglh thle study of dietetics and nutrition.Advances in knowi-ledge of these sulbjectslhax-e affected, or ought to have iffected, tme health of all m likind.I propose, therefore, a1s one whose lot it hals been to b3e intimately connected u-itli 11m estigatiotlis on thlis suibject, to relate something of the muork that has beeni carried out ini recent Vears.The lImited time at my disl)osal only allows ofa.cursoryglance at a feew of the problems, but nevertheless propOse to draw attention.niot onlv to points which, fromi a, practical aspect, may be-regarded as settled, but also to results wh llicvh sluggest that ther e are otller-patlhological coniditionis in whIichl it is probable that dietetics will be founld to play a (lomiiauit W)liat.What I want to (1o in this lecture is to give evidelnce whlicih shows that (liet, in additiou to supply-ing uiaterial for gr-owth anmd maintenance of the body and the necessary- energy for tIme performance of its work, also colltains two groups of substances-one which tends to produce pathio- logical changes anid ill health, and the otlher-whiclh helps the bodyl to l-rotCct itself, -not only agaiinst these toxic factors, bti also against othelr disease-produicing agelmts such, as miCiro-organisms.,/I (o1 not proposC to .liseiisstIme energry-bearing constitui- cnts of diet naely, pr oteins, fats, annd earholmovdrates.It is, of course, necessary thalt the aniouimt of food eaten mullst conitaium a certain ininmmli of energy according to the work performied atid heat lost by the individual.It is allso trite t hat tlhese energy-bearing sub.stances must ilnelude a minimumlal of biologically available pr(otein botlm for growth amld for miaintenance.Tihese aire truisnms which -ill alwayshiold ', whbatever rev'olutionary discoveries ml1ay 1he miade ill tlIe futuri-e iii (lietetics.The hisitory of the relatioin of food to diseas;e as iumiti- ated 1b tw o discoveries.One was time wzorlk of Eijkman, wlho plroved in 1897k that beri-beri was diie to the absence fi-om tIme (liet of a substaince fouind in imany foods, limit especially inl tIe gerim-of cereals, anid kiiowrn later as the ati-ber-beni, or the antiieuiritie, vitamini, us9uallydesciribed at the present time as vitamini B1.The other was tlhe (lis- c ov-er y -of lholst witd Fr6lihit in 19072 that fresh foods, especially-fru 1its anidl vegetables, contfainied a subistalice ilm
Reversible Dysfunction of Wild-Type p53 following Homeodomain-Interacting Protein Kinase-2 Knockdown
Authors: Rosa Puca, Lavinia Nardinocchi, Hilah Gal, Gideon Rechavi, Ninette Amariglio, Eytan Domany, Daniel A. Notterman, Marco Scarsella, Carlo Leonetti, Ada Sacchi, Giovanni Blandino, David Givol, Gabriella D'Orazi
Journal: Cancer Research (2008)

Abstract About half of cancers sustain mutations in the TP53 gene, whereas the other half maintain a wild-type p53 (wtp53) but may compromise the p53 response because of other alterations. Homeodomain-interacting protein kinase-2 (HIPK2) is a positive regulator of p53 oncosuppressor function. Here, we show, by microarray analysis, that wtp53 lost the target gene activation following stable knockdown of HIPK2 (HIPK2i) in colon cancer cell line. Our data show that the stable knockdown of HIPK2 led to wtp53 misfolding, as detected by p53 immunoprecipitation with conformation-specific antibodies, and that p53 protein misfolding impaired p53 DNA binding and transcription of target genes. We present evidence that zinc supplementation to HIPK2i cells increased p53 reactivity to conformation-sensitive PAb1620 (wild-type conformation) antibody and restored p53 sequence-specific DNA binding in vivo and transcription of target genes in response to Adriamycin treatment. Finally, combination of zinc and Adriamycin suppressed tumor growth in vivo and activated misfolded p53 that induced its target genes in nude mice tumor xenografts derived from HIPK2i cells. Bioinformatics analysis of microarray data from colon cancer patients showed significant association of poor survival with low HIPK2 expression only in tumors expressing wtp53. These results show a critical role of HIPK2 in maintaining the transactivation activity of wtp53 and further suggest that low expression of HIPK2 may impair the p53 function in tumors harboring wtp53. [Cancer Res 2008;68(10):3707–13]
Mechanism of hypercalciuria in genetic hypercalciuric rats. Inherited defect in intestinal calcium transport.
Authors: D A Bushinsky, M J Favus
Journal: Journal of Clinical Investigation (1988)

Excessive urine calcium excretion in patients with idiopathic hypercalciuria may involve a primary increase in intestinal calcium absorption, overproduction of 1,25-dihydroxyvitamin D3 or a defect in renal tubular calcium reabsorption. To determine the mechanism of hypercalciuria in an animal model, hypercalciuria was selected for in rats and the most hypercalciuric animals inbred. Animals from the fourth generation were utilized to study mineral balance and intestinal transport in relation to levels of serum 1,25(OH)2D3. Both urine calcium excretion and net intestinal calcium absorption were greater in hypercalciuric males (HM) than in normocalciuric males (NM) and in hypercalciuric females (HF) than in normocalciuric females (NF). However, serum 1,25(OH)2D3 was lower in HM than in NM and not different in HF than in NF. Net calcium balance was more positive in HM than in NM and in HF than in NF. In vitro duodenal calcium net flux was correlated with serum 1,25(OH)2D3 in HM and HF and in NM and NF. However, with increasing serum 1,25(OH)2D3 there was greater calcium net flux in hypercalciuric rats than in normocalciuric controls. Hypercalciuria in this colony of hypercalciuric rats is due to a primary intestinal overabsorption of dietary calcium and not an overproduction of 1,25(OH)2D3 or a defect in the renal tubular reabsorption of calcium.
The applicability of the gland/wall ratio (Reid-Index) to clinicopathological correlation studies.
Authors: M Oberholzer, P Dalquen, M Wyss, H P Rohr
Journal: Thorax (1978)

We studied at necropsy the bronchi of 49 subjects whose lung function has been measured during life. In each case the glands were examined in three bronchi by measuring the gland/wall ratio (Reid-Index) and by point-counting. The results of the two methods were compared: the data of the gland/wall ratio were normally distributed while those of the volume density established by point-counting were not. Gland/wall ratio and volume density of glands correlated moderately (RSp = 0.524). The function between them was not linear, in contrast with that between gland/wall ratio and gland thickness. The stereological background of these functions is discussed. In 34 subjects without restrictive lung disease FEV1 correlated inversely with the volume density of glands (RSp = -0.396), but not with the gland/wall ratio (Reid-Index)(RSp = -0.243). This discrepancy probably results from the different distribution of the data obtained by the two methods and from the non-linear function between them. These findings indicate that the gland/wall ratio (Reid-Index) is less applicable to clinicopathological correlations than the volume density of glands established by point-counting.
The Physiologic Replacement of Insulin
Authors: John A. Oates, Alastair J.J. Wood, Bernard Zinman
Journal: New England Journal of Medicine (1989)

ALTHOUGH insulin was discovered and first administered more than 65 years ago,1 , 2 the goal of physiologic replacement remains elusive, despite major advances in our understanding of insulin's physiologic effects, chemistry, kinetics, and action. In this article I shall evaluate the pharmacologic features and use of insulin in the context of current practices in the management of insulin-dependent diabetes mellitus.As background, it will be useful to review briefly the physiology of insulin synthesis and secretion.3 Insulin is synthesized in the beta cells of the islets of Langerhans as a single polypeptide precursor, preproinsulin, which is subsequently converted to proinsulin, an . . .
Hospital Admission and Absence from Work Attributed to Asthma
Authors: V. H. Springett
Journal: BMJ (1969)

Study of a 10% sample of hospital admissions for asthma in England and Wales shows that in each age and sex group deaths have increased by at least a half between 1959 and 1964, while for males aged 15-44 years they have doubled. The number of deaths in hospital has risen in a similar way, and hence the hospital fatality rate has not changed over this period. Since study of certified absences from work has shown no comparable increase, it is suggested that the increase has occurred in the number of attacks of severe asthma requiring admission to hospital.
Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy
Authors: Jin Hyen Baek, Felice D’Agnillo, Florence Vallelian, Claudia P. Pereira, Matthew C. Williams, Yiping Jia, Dominik J. Schaer, Paul W. Buehler
Journal: Journal of Clinical Investigation (2012)

Massive transfusion of blood can lead to clinical complications, including multiorgan dysfunction and even death. Such severe clinical outcomes have been associated with longer red blood cell (rbc) storage times. Collectively referred to as the rbc storage lesion, rbc storage results in multiple biochemical changes that impact intracellular processes as well as membrane and cytoskeletal properties, resulting in cellular injury in vitro. However, how the rbc storage lesion triggers pathophysiology in vivo remains poorly defined. In this study, we developed a guinea pig transfusion model with blood stored under standard blood banking conditions for 2 (new), 21 (intermediate), or 28 days (old blood). Transfusion with old but not new blood led to intravascular hemolysis, acute hypertension, vascular injury, and kidney dysfunction associated with pathophysiology driven by hemoglobin (Hb). These adverse effects were dramatically attenuated when the high-affinity Hb scavenger haptoglobin (Hp) was administered at the time of transfusion with old blood. Pathologies observed after transfusion with old blood, together with the favorable response to Hp supplementation, allowed us to define the in vivo consequences of the rbc storage lesion as storage-related posttransfusion hemolysis producing Hb-driven pathophysiology. Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients.
Cadmium burden of men and women who report regular consumption of confectionery sunflower kernels containing a natural abundance of cadmium.
Authors: P G Reeves, R A Vanderpool
Journal: Environmental Health Perspectives (1997)

Because of inherent genetic and physiological characteristics, the natural concentration of cadmium in the kernels of sunflowers grown in uncontaminated soils of the northern Great Plains region of the United States is higher than in most other grains. We tested the hypothesis that a habitual consumption of sunflower kernels will increase the body burden and health effects of cadmium in humans. Sixty-six men and women who reported consuming various amounts of sunflower kernels were recruited and divided by sex and kernel consumption: those who consumed less than or equal to 1 ounce(oz)/week and those who consumed more than 1 oz/week. Cadmium intake was assessed by calculation from 7-day food diaries, cadmium burden by whole blood cadmium, red blood cell (RBC) cadmium and urine cadmium concentrations, and health effects by urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) activity and beta2-microglobulin (beta2MG). The results showed that high intakes of sunflower kernels (>1 oz/day) significantly increased the intake of cadmium (p<0.004). However, the amount of cadmium in whole blood or RBCs was not affected by cadmium intake. Urinary excretion of cadmium also was not affected by cadmium intake. Urine NAG activity and the amount of urinary beta2MG were significantly elevated in the urine of high sunflower kernel consumers when the values were expressed on a urine volume basis (p<0.03), but not when expressed on a creatinine basis (p>0.05). Because normal ranges for the excretion of these protein markers have not been established, it was not possible to determine if these elevated values were meaningful. However, given the knowledge that habitual consumption of sunflower kernels with natural cadmium concentrations higher than most other food products will increase the average intake of dietary cadmium, the potential exists for an increased body burden of cadmium. Controlled feeding studies in humans should be pursued in order to determine if the body burden does indeed increase and, if so, is it a cause for concern.
Doctor is suspended for prescribing a drug for pornography "addiction" without giving the risks
Authors: C. Dyer
Journal: BMJ (2011)

A doctor in private practice has been suspended for six months by the General Medical Council for giving the unlicensed hallucinogenic drug ibogaine to a man obsessed with internet pornography without fully explaining the drug’s risks.

Peter Brackenridge, who saw private patients in London’s Harley Street, was medical director of Ibogaine Therapy UK, which advertised the treatment on a website.

The drug, which has been used experimentally as a one-off “detox” treatment for heroin addicts because it can minimise or eliminate withdrawal symptoms, puts those who take it into a dreamlike state. Its initial effects usually last for 20-30 hours, during which someone must be with …
Intubation in Epiglottitis
Authors: Ralph W. Rucker
Journal: JAMA (1974)

To the Editor.—  The recent article by Bass et al (229:671, 1974) again points vividly to the unequivocal need for early, rapid intervention in epiglottitis to assure a patent airway. For example, in the group that was apparently watched on a pediatric ward with equipment on hand, but without intervention, 3 of 12 patients suffered either death or brain damage. This agrees well with experiences of others, 1,2 illustrating the prohibitive mortality risk from watching and waiting, even in a pediatric intensive care unit with surgeons and equipment available.  Because of this disastrous experience with delay, it has become the policy of our pediatric pulmonary service to intervene routinely in any child with epiglottitis. Yet, in our hospital as in others, there is a distinct reluctance to examine every croup patient in the operating room with the ear, nose, and throat service ready to operate. As our pediatric house officers are
Prognostic Factors in Psychotherapy
Authors: Lee R. Chutkow
Journal: JAMA (1963)

<h3>To the Editor:—</h3> The concluding sentence of Drs. Brill and Storrow in their article "Prognostic Factors in Psychotherapy" (<i>JAMA</i><b>183</b>:913 [March 16] 1963) is challenging and raises several questions. A patient's motivation for psychotherapy is as variable as the kind of psychotherapy to which he may be expected to fit. In what mode of psychotherapy would the poorly motivated patients seen at the UCLA Neuropsychiatric Clinic be regarded as showing treatable symptoms, rather than as "an irritation that is to be avoided"? Do the authors imply that only highly motivated patients have a "great desire for help which involved more than just symtomatic relief"? What kinds of "help" and "relief" do such diverse and poorly motivated patients as alcoholics, psychotics, and sociopaths want? What kinds of relationships with therapists are they trying to establish ( or re-establish )? The authors' remarks on the "ability ( of patients ) to elicit or stimulate a
A Newly Recognized Occupation Palsy
Authors: E. Kenneth Mladinich
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Various palsies and neuritides have been reported to occur with occupations and pastimes. Tennis players suffer entrapment of the deep branch and the recurrent epicondylar branch of the radial nerve in the so-called tennis elbow. Hod carriers sustain damage to the long thoracic nerve by carrying weight on their shoulder. Pneumatic drillers and racing cyclists develop compression neuritis involving the deep branch of the ulnar nerve from prolonged pressure exerted on the hypothenar region. In our clinic, we had the occasion to observe another nerve palsy secondary to an occupation. <h3>Report of a Case.—</h3> A 23-year-old white female professional guitar player came to our clinic complaining of dragging of the left foot. Further history revealed that she played the guitar at a night club and often would sit for three hours at a time on the stage with her left leg crossed on her right leg, after