tbuckley/cabot-search huggingface dataset:
Metabolic fuel selection: the importance of being flexible
Authors: Perry E. Bickel
Journal: Journal of Clinical Investigation (2004)

Studies in genetically engineered mice have shown the importance of cross-talk between organs in the regulation of energy metabolism. In this issue, a careful metabolic characterization of mice with genetic deficiency of the GLUT4 glucose transporter in adipocytes and muscle is reported. These mice compensate for decreased peripheral glucose disposal by increasing hepatic glucose uptake and lipid synthesis as well as by increasing lipid utilization in peripheral tissues. These findings are relevant to humans with type 2 diabetes, in whom a key feature is diminished peripheral glucose disposal.
Di Bella's method of curing cancer is becoming popular in Italy
Authors: R. Pellegrini
Journal: BMJ (1998)

EDITOR—Abbasi has summarised wellthe situation concerning “Di Bella's method” for cancer.1 This situation is more serious, however, than it seemed at the meeting in London that Abbasi attended, and it might rapidly contaminate other countries, even those more cold blooded than Italy. It is a clear case of wholesale insanity despite the repeated warnings of oncologists and pharmacologists. There are three newproofs of this.
Acupuncture and Knee Osteoarthritis
Authors: Hanns-Peter Scharf, Ulrich Mansmann, Konrad Streitberger, Steffen Witte, Jürgen Krämer, Christoph Maier, Hans-Joachim Trampisch, Norbert Victor
Journal: Annals of Internal Medicine (2006)

Despite the popularity of acupuncture, evidence of its efficacy for reducing pain remains equivocal.To assess the efficacy and safety of traditional Chinese acupuncture (TCA) compared with sham acupuncture (needling at defined nonacupuncture points) and conservative therapy in patients with chronic pain due to osteoarthritis of the knee.Randomized, controlled trial.315 primary care practices staffed by 320 practitioners with at least 2 years' experience in acupuncture.1007 patients who had had chronic pain for at least 6 months due to osteoarthritis of the knee (American College of Rheumatology [ACR] criteria and Kellgren-Lawrence score of 2 or 3).Up to 6 physiotherapy sessions and as-needed anti-inflammatory drugs plus 10 sessions of TCA, 10 sessions of sham acupuncture, or 10 physician visits within 6 weeks. Patients could request up to 5 additional sessions or visits if the initial treatment was viewed as being partially successful.Success rate, as defined by at least 36% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 26 weeks. Additional end points were WOMAC score and global patient assessment.Success rates were 53.1% for TCA, 51.0% for sham acupuncture, and 29.1% for conservative therapy. Acupuncture groups had higher success rates than conservative therapy groups (relative risk for TCA compared with conservative therapy, 1.75 [95% CI, 1.43 to 2.13]; relative risk for sham acupuncture compared with conservative therapy, 1.73 [CI, 1.42 to 2.11]). There was no difference between TCA and sham acupuncture (relative risk, 1.01 [CI, 0.87 to 1.17]).There was no blinding between acupuncture and traditional therapy and no monitoring of acupuncture compliance with study protocol. In general, practitioner-patient contacts were less intense in the conservative therapy group than in the TCA and sham acupuncture groups.Compared with physiotherapy and as-needed anti-inflammatory drugs, addition of either TCA or sham acupuncture led to greater improvement in WOMAC score at 26 weeks. No statistically significant difference was observed between TCA and sham acupuncture, suggesting that the observed differences could be due to placebo effects, differences in intensity of provider contact, or a physiologic effect of needling regardless of whether it is done according to TCA principles.
A STUDY OF CUTANEOUS SENSITIVENESS TO SCARLATINAL TOXIN IN PREGNANCY AND THE PUERPERIUM
Authors: H. Burt-White, L. Colebrook, G. Morgan, B. J. W. Jervis, G. E. Harre
Journal: BMJ (1930)

THIs paper is prlimlalyil conlcernled with the relation betwve ii ciutanteouLs senlsitiveness to streltococcal toxini il pIegeslta1it wIoileln anid tlie incidelnce of l)uerlperal sepsis.T'lie work was illidertakeil at tile suggestion of the 8trel)tococcal Commiiiiittee of the Medical Research Council follow-ing the relport of a lhunidrled cases similar ly investi- gated bv onie of us (H.B.-W.).Tlhe lelationsliil) betweenl a positive Dick test anid susceptibility to scar let fever is niow vell appreciated.The close relationiship between
A Prospective Study of Folate Intake and the Risk of Breast Cancer
Authors: Shumin Zhang
Journal: JAMA (1999)

ContextFolate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption.ObjectivesTo assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol.DesignProspective cohort study performed in 1980, with 16 years of follow-up.Setting and ParticipantsA total of 88,818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980.Main Outcome MeasureIncidence of invasive breast cancer by levels of folate and alcohol intake.ResultsA total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 µg/d compared with 150 to 299 µg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend=.001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 µg/d (for alcohol intake ≥15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 µg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93).ConclusionsOur findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.
Adipokines in liver diseases
Authors: Fabio Marra, Cristiana Bertolani
Journal: Hepatology (2009)

Abstract Adipokines are polypeptides secreted in the adipose tissue in a regulated manner. While some of these molecules are expressed only by adipocytes, resident and infiltrating macrophages and components of the vascular stroma markedly contribute to expression of other adipokines. As a result, adipose tissue inflammation is associated with a modification in the pattern of adipokine secretion. Leptin, adiponectin, and resistin are the best-studied molecules in this class, but cytokines such as tumor necrosis factor or interleukin-6 are also secreted at high levels by the adipose tissue. Several other molecules have been recently identified and are actively investigated. Adipokines interfere with hepatic injury associated with fatty infiltration, differentially modulating steatosis, inflammation, and fibrosis. Several studies have investigated plasma levels of adiponectin in patients with nonalcoholic fatty liver disease, to establish correlations with the underlying state of insulin resistance and with the type and severity of hepatic damage. Hepatitis C is another disease where adipokines may represent a link between viral infection, steatosis, and metabolic disturbances. Identification of the mediators secreted by expanded adipose tissue and their pathogenic role is pivotal in consideration of the alarming increase in the prevalence of obesity and of the detrimental role that this condition exerts on the course of liver diseases. (Hepatology 2009.)
Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy.
Authors: H Yoshida, T Mitarai, T Kawamura, T Kitajima, Y Miyazaki, R Nagasawa, Y Kawaguchi, H Kubo, I Ichikawa, O Sakai
Journal: Journal of Clinical Investigation (1995)

Studies conducted over the last decade demonstrated vari- able therapeutic efficacy of angiotensin converting enzyme (ACE) inhibitor on the progression of glomerular diseases, including IgA nephropathy.In this study, among patients with biopsy-proven IgA nephropathy, 53 patients in whom creatinine clearance had been monitored over 5 yr were recruited for study.These patients were classified into two groups according to whether or not renal function had de- clined as determined by the slope of creatinine clearance against time: group 1 had stable renal function; group 2 had declining renal function (average: -6.7±+1.3ml/min/ yr).21 of 53 patients were treated with ACE inhibitor and followed for 48 wk.Gene polymorphism consisting of inser- tion (I) or deletion (D) of a 287-bp DNA fragment (pre- sumed to be a silencer element) of the ACE gene was deter- mined by PCR. 46age-matched individuals without history of proteinuria were analyzed as controls.The DD genotype was significantly more frequent in group 2 (43%) than in controls (7% ) or group 1 patients with stable renal function (16%).48 wk after ACE inhibitor administration, proteinuria significantly decreased in patients with DD genotype but not in those with ID or II genotypes.The results indicate that deletion polymorphism in the ACE gene, particularly the homozygote DD, is a risk factor for progression to chronic renal failure in IgA nephropathy.Moreover, this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progres- sive deterioration of renal function.(J.Clin.Invest.
PREPARATION OF GENTIAN VIOLET SOLUTIONS FOR INTRAVENOUS INJECTION
Authors: VICTOR BURKE
Journal: JAMA (1926)

The uniformly favorable results obtained by Young and Hill<sup>1</sup>in the treatment of acute septicemia by the use of dyes have attracted the attention of clinicians and have led to a more extensive use of dyes in the treatment of septicemia and also in local infection. The results obtained with the dyes are not uniformly encouraging; in fact, unfavorable results are being reported with sufficient frequency to check the development of dye therapy. It may be advisable, at this time, to call a halt to the indiscriminate use of dyes until the treatment has been standardized. However, the case against the dyes is not so much that they contribute to the course of the infection as that they fail to check it in an unknown percentage of cases. Toxic results occasionally follow the intravenous injection of dyes, particularly mercurochrome-220 soluble.<sup>2</sup>It is evident that much experimental work, both
Tomographic Scintigraphy of a Retrotracheal Goiter
Authors: MICHAEL A. CAWTHON, MICHAEL F. HARTSHORNE, ROBERT D. KARL, CRAIG S. HAMMES, WILLIAM H. HOWARD, STEPHEN R. BUNKER
Journal: Clinical Nuclear Medicine (1984)

Thyroid tissue can be found in ectopic locations, including the retrotracheal space. This may be asymptomatic or may present as a cause of upper airway obstructive symptoms or dysphagia (1). Seven-pinhole imaging of the thyroid has been suggested for routine clinical use to take advantage of simultaneous anterior and oblique views, with the potential for subsequent tomographic reconstruction (2,3,4).
Integrated dialysis and renal transplantation: small is beautiful.
Authors: A J Nicholls, G R Catto, N Edward, J Engeset, J R Logie, M Macleod
Journal: BMJ (1980)

Many patients in Britain with chronic renal failure suitable for renal replacement treatment die because not enough treatment facilities are available. Moreover, the number of renal transplants performed is insufficient to meet even present needs, so the number of patients on dialysis is rising. The integrated dialysis and transplant unit in Aberdeen, which has a population base much smaller than the average British unit, meets community needs for dialysis and transplantation. The problem of harvesting cadaver kidneys has been solved; the present supply has not only enabled the number of patients on dialysis to remain stable but has resulted in a net export of kidneys. The Aberdeen unit shows how estimated needs for chronic dialysis and renal transplantation may be met.
Direct Genetic Analysis of Single Disseminated Cancer Cells for Prediction of Outcome and Therapy Selection in Esophageal Cancer
Authors: Nikolas H. Stoecklein, Stefan B. Hosch, Martin Bezler, Franziska Stern, Claudia H. Hartmann, Christian Vay, Annika Siegmund, Peter Scheunemann, Paulus Schurr, Wolfram T. Knoefel, Pablo E. Verde, Uta Reichelt, Andreas Erbersdobler, Roger Grau, Axel Ullrich, Jakob R. Izbicki, Christoph A. Klein
Journal: Cancer Cell (2008)
Trial of Pentoxifylline for Diabetic Impotence
Authors: William J Georgitis, John A Merenich
Journal: Diabetes Care (1995)

OBJECTIVE To test the effectiveness of pentoxifylline as a therapy for diabetic impotence. RESEARCH DESIGN AND METHODS A 3-month placebo-controlled double-blind treatment study was conducted at a single center. Therapeutic response was assessed subjectively by serial self-appraisals of erectile function and objectively by nocturnal penile tumescence (NPT) monitoring. RESULTS This cohort of impotent diabetic men displayed substantial neurological and penile vascular dysfunction. Age, body mass index, duration of diabetes, duration of impotence, glycemie control, mode of therapy for non-insulin-dependent diabetes, mean testosterone, mean prolactin, and penile brachial indexes were similar in the treatment (n = 34) and placebo groups (n = 26). NPT monitoring revealed infrequent erectile events, diminished average rigidity, and decreased tumescence. Pentoxifylline did not alter overall glycemie control and did not improve neurological, vascular, or erectile function. In fact, a slight decrease in average percent rigidity from 22 ± 3 to 17 ± 2% (mean ± SE, P &amp;lt; 0.05) was observed in the pentoxifylline-treated group. Although eight (24%) pentoxifylline-treated and five (19%) placebo-treated men reported benefit, no objective improvement was observed in nocturnal tumescence. CONCLUSIONS Pentoxifylline is not an effective treatment for diabetic erectile dysfunction.
Systematic review of the effect of on-site mental health professionals on the clinical behaviour of general practitioners
Authors: P. Bower
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To review the published literature concerning the effects of on-site mental health professionals on general practitioners9 management of mental health. <b>Design:</b> Systematic review of controlled trials. <b>Setting:</b> Primary care. <b>Participants:</b> General practitioners and mental health professionals. <b>Main outcome measures:</b> Consultation rates, prescribing of psychotropics, and referrals to secondary care mental health services by general practitioners. <b>Results:</b> The effect of on-site mental health professionals on consultation rates was inconsistent. Referral to a mental health professional reduced the likelihood of a patient receiving a prescription for psychotropics or being referred to secondary care, although the effects were not consistent. An on-site mental health professional did not alter prescribing and referral behaviour towards patients in the wider practice population. <b>Conclusions:</b> The secondary effects of mental health professionals on the clinical behaviour of general practitioners are comparatively modest and inconsistent and seem to be restricted to patients directly under the care of the mental health professional.
Clinical databases can complement controlled trials
Authors: L. Plenderleith
Journal: BMJ (2002)

EDITOR—We were interested to read the article by Padkin et al on the serendipitous use of the database of the Intensive Care National Audit and Research Centre (ICNARC) to complement the results of clinical trials.1 There is at least one other such high quality database in Britain.

Since 1995 the audit group of the Scottish Intensive Care Society, with national funding from the Clinical Resource and Audit …
Cannabis and psychosis: Let's start from the null hypothesis
Authors: D B Double
Journal: BMJ (2006)

EDITOR—Fergusson at al say that it is better to reach interim conclusions about the relation between cannabis and psychosis despite the uncertain evidence.1 This is contrary to the scientific principle of starting from the null hypothesis. The null hypothesis should be overturned only if there is sufficient evidence.

Moreover, the argument they use to tip the …
Correction of Dystrophin Expression in Cells From Duchenne Muscular Dystrophy Patients Through Genomic Excision of Exon 51 by Zinc Finger Nucleases
Authors: David G Ousterout, Ami M Kabadi, Pratiksha I Thakore, Pablo Perez-Pinera, Matthew T Brown, William H Majoros, Timothy E Reddy, Charles A Gersbach
Journal: Molecular Therapy (2014)

Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the absence of dystrophin protein expression. Oligonucleotide-induced exon skipping can restore the dystrophin reading frame and protein production. However, this requires continuous drug administration and may not generate complete skipping of the targeted exon. In this study, we apply genome editing with zinc finger nucleases (ZFNs) to permanently remove essential splicing sequences in exon 51 of the dystrophin gene and thereby exclude exon 51 from the resulting dystrophin transcript. This approach can restore the dystrophin reading frame in ~13% of DMD patient mutations. Transfection of two ZFNs targeted to sites flanking the exon 51 splice acceptor into DMD patient myoblasts led to deletion of this genomic sequence. A clonal population was isolated with this deletion and following differentiation we confirmed loss of exon 51 from the dystrophin mRNA transcript and restoration of dystrophin protein expression. Furthermore, transplantation of corrected cells into immunodeficient mice resulted in human dystrophin expression localized to the sarcolemmal membrane. Finally, we quantified ZFN toxicity in human cells and mutagenesis at predicted off-target sites. This study demonstrates a powerful method to restore the dystrophin reading frame and protein expression by permanently deleting exons. Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the absence of dystrophin protein expression. Oligonucleotide-induced exon skipping can restore the dystrophin reading frame and protein production. However, this requires continuous drug administration and may not generate complete skipping of the targeted exon. In this study, we apply genome editing with zinc finger nucleases (ZFNs) to permanently remove essential splicing sequences in exon 51 of the dystrophin gene and thereby exclude exon 51 from the resulting dystrophin transcript. This approach can restore the dystrophin reading frame in ~13% of DMD patient mutations. Transfection of two ZFNs targeted to sites flanking the exon 51 splice acceptor into DMD patient myoblasts led to deletion of this genomic sequence. A clonal population was isolated with this deletion and following differentiation we confirmed loss of exon 51 from the dystrophin mRNA transcript and restoration of dystrophin protein expression. Furthermore, transplantation of corrected cells into immunodeficient mice resulted in human dystrophin expression localized to the sarcolemmal membrane. Finally, we quantified ZFN toxicity in human cells and mutagenesis at predicted off-target sites. This study demonstrates a powerful method to restore the dystrophin reading frame and protein expression by permanently deleting exons.
Abstract P2-13-01: The Brazilian founder TP53 p.R337H mutation is uncommon in Portuguese women diagnosed with breast cancer
Authors: J Giacomazzi, RL Correia, EI Palmero, JF Gaspar, M Almeida, C Portela, SA Camey, RM Reis, P Ashton-Prolla
Journal: Cancer Research (2013)

Abstract Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern regions of Brazil, both in the general population and in patients from high risk breast cancer families with adrenocortical, choroid plexus and breast carcinomas, there has been controversy on the origin of this mutation. Preliminary analysis of the small subset of Brazilian mutation carriers that defined the founder haplotype using 29 tag SNPs revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families (one Portuguese and one German) (Chompret et al., 2000; Herrmann et al. 2012). Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer in Southern Brazil are p.R337H carriers, we initiated TP53 genotyping in a Portuguese cohort of women with breast cancer recruited from the cities of Lisboa and Braga. Median age at diagnosis of breast cancer among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening was performed using Real-Time PCR (taqman assays), and failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study of 815 breast cancer-affected women from Southern and Southeastern Brazil, which has reached frequencies of 12.1 and 5.1% in pre- and post-menopausal women, respectively (Ashton-Prolla et al. 2012; ASCO Annual Meeting, ref 1522). We conclude that there is a significant difference in mutation frequency observed between the two cohorts (p&amp;lt;0.001). These findings suggest that TP53 p.R337H is not a common molecular alteration in Portuguese breast cancer-affected patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-13-01.
Loss-of-function mutation in<i>AAGAB</i>in Chinese families with punctuate palmoplantar keratoderma
Authors: M. Li, L. Yang, H. Shi, B. Guo, X. Dai, Z. Yao, G. Zhang
Journal: British Journal of Dermatology (2013)

Punctate palmoplantar keratoderma (PPPK, OMIM 148600) is a rare hereditary disorder characterized by multiple punctate keratoses on the palms and soles. Recently, mutations in the genes α- and γ-adaptin-binding protein p34 (AAGAB) and collagen, type XIV, α1 (COL14A1) have been reported to cause PPPK.To identify mutations in the genes AAGAB and COL14A1 in three Chinese families with PPPK.Genomic DNA of the family members and 100 healthy individuals was isolated. Direct sequencing of all polymerase chain reaction products of the whole coding regions of AAGAB and COL14A1 was performed to identify the mutation.A heterozygous nonsense mutation c.61C>T (p.Q21X) was identified in AAGAB in two Chinese families with PPPK. We failed to detect any mutations in AAGAB or COL14A1 in family 3.A novel loss-of-function mutation within AAGAB associated with PPPK was identified from two Chinese pedigrees.