tbuckley/cabot-search huggingface dataset:
A multicenter pragmatic study of an evidence-based intervention to improve adenoma detection: the Quality Improvement in Colonoscopy (QIC) study
Authors: Praveen Rajasekhar, Colin Rees, Mike Bramble, Douglas Wilson, Matthew Rutter, Brian Saunders, A. Hungin, James East
Journal: Endoscopy (2015)

Low adenoma detection rates (ADRs) at colonoscopy are linked to significantly higher interval cancer rates, and vary between colonoscopists. Studies demonstrate that lesion detection is improved by: withdrawal time of ≥ 6 minutes; use of hyoscine butylbromide; position change; and rectal retroflexion. We evaluated the feasibility of implementing the above "bundle" of interventions into colonoscopy practice, and the effect on ADR.A longitudinal cohort design was used. Implementation combined central training, local promotion, and feedback. The uptake marker was change in hyoscine butylbromide use. Comparisons were between the 3 months before and the 9 months after the implementation phase, globally, by endoscopy unit and by quartile when colonoscopists were ranked according to baseline ADR. Chi-squared or Fisher's tests were used to evaluate significance.12 units participated. Global and quartile analyses included data from 118 and 68 colonoscopists and 17 508 and 14 193 procedures respectively. A significant increase in hyoscine butylbromide use was observed globally (54.4 % vs. 15.8 %, P < 0.001), in all endoscopy units (P < 0.001) and quartiles (P < 0.001). A significant increase in ADR was observed globally (18.1 % vs. 16.0 %, P = 0.002) and in the lower two colonoscopist quartiles (P < 0.001), with a nonsignificant increase in the upper middle quartile and a significant fall to 21.5 %. in the upper quartile. The significant variations in ADR among the upper three quartiles disappeared.In routine clinical practice, introduction of a simple, inexpensive, evidence-based "bundle" of measures is feasible and is associated with higher global ADR, driven by improvements amongst the poorest performing colonoscopists.
BMA attacks GMC's revalidation proposals
Authors: Andrew Moscrop
Journal: BMJ (2001)

The BMA council has threatened to draw up its own proposals for revalidation and take them to the government, if an agreement with the General Medical Council, the body that regulates the medical profession in the United Kingdom, is not reached shortly.

The council attacked the GMC's revalidation proposals for their “lack of clarity and anomalies.” Speaking after the BMA's council meeting last week, Dr Ian Bogle, chairman of the council, said that the proposals “made the same mistakes” as earlier …
Fatal Rocky Mountain Spotted Fever
Authors: Michael A. W. Hattwick
Journal: JAMA (1978)

Forty-four fatal cases of Rocky Mountain spotted fever (RMSF) occurring in 1974 were compared with 50 nonfatal cases of similar age, sex, date of onset, and place of occurrence. Diagnosis and initiation of treatment in fatal cases were substantially delayed compared with nonfatal cases. Several reasons for this delay were identified: (1) the rash appeared later in the course of illness in the fatal cases, often not until the patient was terminal, (2) a history of tick bite was less often obtained during life or obtained late in the clinical course in fatal cases, and (3) initial nonspecific symptoms or unexpected symptoms led to an initial diagnosis of more common diseases. Only two fatal cases were treated with either tetracycline or chloramphenicol before the sixth day of illness. Presumptive diagnosis of RMSF and initiation of tetracycline therapy before onset of rash may be necessary to reduce mortality.
Single Nucleotide Polymorphisms of microRNA Machinery Genes Modify the Risk of Renal Cell Carcinoma
Authors: Yohei Horikawa, Christopher G. Wood, Hushan Yang, Hua Zhao, Yuanqing Ye, Jian Gu, Jie Lin, Tomonori Habuchi, Xifeng Wu
Journal: Clinical Cancer Research (2008)

MicroRNAs (miRNA) are a class of small noncoding RNA molecules that have been implicated in a wide variety of basic cellular functions through posttranscriptional regulations on their target genes. Compelling evidence has shown that miRNAs are involved in cancer initiation and progression. We hypothesized that genetic variations of the miRNA machinery genes could be associated with the risk of renal cell carcinoma.We genotyped 40 single nucleotide polymorphisms (SNP) from 11 miRNA processing genes (DROSHA, DGCR8, XPO5, RAN, DICER1, TARBP2, AGO1, AGO2, GEMIN3, GEMIN4, HIWI) and 15 miRNA genes in 279 Caucasian patients with renal cell carcinoma and 278 matched controls.We found that two SNPs in the GEMIN4 gene were significantly associated with altered renal cell carcinoma risks. The variant-containing genotypes of Asn929Asp and Cys1033Arg exhibited significantly reduced risks, with odds ratios (OR) of 0.67 [95% confidence interval (95% CI), 0.47-0.96] and 0.68 (95% CI, 0.47-0.98), respectively. Haplotype analysis showed that a common haplotype of GEMIN4 was associated with a significant reduction in the risk of renal cell carcinoma (OR, 0.66; 95% CI, 0.45-0.97). We also conducted a combined unfavorable genotype analysis including five promising SNPs showing at least a borderline significant risk association. Compared with the low-risk reference group with one unfavorable genotype, the median-risk and high-risk groups exhibited a 1.55-fold (95% CI, 0.96-2.50) and a 2.49-fold (95% CI, 1.58-3.91) increased risk of renal cell carcinoma, respectively (P for trend < 0.001).Our results suggested that genetic polymorphisms of the miRNA-machinery genes may affect renal cell carcinoma susceptibility individually and jointly.
A Case of Intestinal Obstruction Treated by Laparotomy: Recovery: Remarks
Authors: H. Marsh
Journal: BMJ (1888)

That this method of operating has much to recommend it 1 think there can be no doubt, as the time occupied in the operation is reduced, according to Dr. Senn, to from fifteen to twenty minutes.Surgeons in this country doubtless will decline to adopt this method of operating until such time as they have con- vinced themselves of its feasibility, as, in the first place, the method of passing tlhe sutures through the whole of the coats of tlhe stomaell and intestine is directly opposed to all rules of intesti- nal surgery of the present day.Dr. Senn, however, illustrates his paper withli numerous cases in which he has operated in this man- ner successfully on dogs, under the most adverse circumstances;and, if his reports are to be relied upon, I see no reason why similar operations should not be performed upon the human subject.These operations on the (lead body are perfectly easy of performance, and the time occupied is not a tithe of that consumed in the or(dinary operation.In any case I think the subject is well worthy the most careful consideration of sugeons who practise in this department.
Development of intestinal cell culture models for drug transport and metabolism studies
Authors: A. Quaroni, J. Hochman
Journal: Advanced Drug Delivery Reviews (1996)

Cell culture models offer many advantageous features for the analysis of drug transport and drug metabolism. From a basic research perspective, these systems offer the potential for manipulating the environment or cellular properties as a means to address mechanistic questions. From a drug discovery perspective, cell culture models can be used to expedite identification of compounds with favorable pharmacokinetic properties, and to evaluate structure-absorption/metabolism relationships. In this review, we will use the intestinal epithelium as an example for discussing issues associated with the development of new cell culture models for evaluating drug metabolism. Specifically, we will discuss biological properties of the intestinal epithelium and address biological and practical consideration in the application of tumor cell lines, short-term primary cultures, stem-like cell cultures, and oncogene immortalized cells as approaches to establishing models for the intestinal epithelium.
Regulation of myocardial amino acid balance in the conscious dog.
Authors: R G Schwartz, E J Barrett, C K Francis, R Jacob, B L Zaret
Journal: Journal of Clinical Investigation (1985)

The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.
Science, medicine, and the future: New techniques in laser therapy
Authors: S. G Bown
Journal: BMJ (1998)

From a medical point of view, lasers are a convenient but sophisticated source of light in the visible, ultraviolet, and infrared parts of the spectrum. They are easy to control, and the light beam (of a single colour) can be focused to a small spot and in many cases can be transmitted via thin flexible fibres, making internal delivery of light feasible. The range of clinical applications is enormous, from the simple carbon dioxide laser, used as a non-contact scalpel or for superficial tissue ablation, to the precision of the excimer laser, used for reshaping corneas, and the flash lamp pumped dye laser, used to close the small blood vessels of disfiguring port wine birthmarks. This review looks at how the precision of light delivery and the predictability of biological response possible with laser therapy is starting to be exploited for the in situ destruction of diseased tissue and how these techniques might be developed in the future.

The first requirement for successful clinical use of lasers is to understand how light at the wavelength used can interact with living tissue. Most of the simple applications are thermal, but the effect produced depends on how much heat is delivered, how fast it is delivered, and the volume of tissue in which it is absorbed. Increasingly, however, the new technique of photodynamic therapy (non-thermal effects from combining laser light and a photosensitising drug) is attracting interest. This review considers particularly the effects of low power thermal treatment and photodynamic therapy (see table).

The carbon dioxide laser (wavelength 10 600 nm in the far infrared) is well established as a non-contact scalpel in relatively inaccessible areas like the brain and upper airways and for ablating small lesions as on the skin. However, the beam cannot be transmitted via flexible fibres and can …
New-Onset IDDM Presenting With Diabetic Ketoacidosis in a Pregnant Adolescent
Authors: Irene N Sills, Robert Rapaport
Journal: Diabetes Care (1994)

OBJECTIVE To describe the presentation of insulin-dependent diabetes mellitus(IDDM) as ketoacidosis during pregnancy in a teenager. CASE A 14-year-old pregnant girl presented with ketoacidosis (bicarbonate 14 nM, 14 meq/l, pH 7.27, glucose 67 mM, 1,208 mg/dl) during the last month of pregnancy with a fetal demise. Two years of follow-up has confirmed that she has IDDM. CONCLUSIONS Diabetes presenting in pregnant adolescents is likely due to IDDM. Immediate insulin therapy and proper education about managing diabetes should be initiated to hopefully prevent the outcome described in this patient.
Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; Conversion to full donor chimerism
Authors: Anand P. Jillella, Danielle Shafer, Thomas R. Klumpp, Robert V.B. Emmons, Kenneth F. Mangan
Journal: American Journal of Hematology (2007)

Abstract Twenty‐one patients with hematologic malignancies were treated with the fludarabine (120–125 mg/m 2 ) and cyclophosphamide (120 mg/kg) nonmyeloablative conditioning regimen. Graft versus host disease (GVHD) and graft rejection prophylaxis was with tacrolimus and mycophenolate mofetil. Thirteen of the 21 patients (62%) had mixed chimerism (≤≤90% donor cells) at day 60 and 11 (52%) of these patients had mixed chimerism which persisted until day 100. Immunosuppression was discontinued in 12 of 13 patients and two of them converted to full chimerism by day 100. Eight patients received a donor lymphocyte infusion (DLI) and five of them converted to full donor chimerism with DLI alone. Two patients were given GM‐CSF in addition to a DLI with conversion to full donor chimerism. Three patients (14%) had graft failure requiring a second transplant using fludarabine (125 mg/m 2 ) and melphalan (140 mg/m 2 ). With a median followup of 2.8 years, 15 patients are alive—one with disease and 14 with no disease. Two patients died of acute GVHD, one of chronic GVHD, and three due to progressive disease. We conclude that the nonmyeloablative fludarabine/cyclophosphamide regimen results in a significant incidence of mixed chimerism and graft rejection but is well tolerated. We suggest a more intense regimen, such as fludarabine and melphalan, be used in patients with a high risk of early disease progression to establish early engraftment and graft versus tumor effect. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Mummies of the Pharaohs: Modern Medical Investigations
Authors: Jaime T. Benitez
Journal: JAMA (1991)

<i>Mummies of the Pharaohs: Modern Medical Investigations</i>, by Dr Maurice Bucaille, consists of 236 pages with 58 black-and-white illustrations, including x-ray films and photomicrographs. Six chapters cover mummification, medical examination of mummies, modern medical investigations, the pharaoh and Moses, the mummy of Ramesses II in Paris, and unsolved problems concerning this mummy. Dr Bucaille's research, as pointed out in the introduction, was focused on two pharaohs who may have reigned while Moses was alive and, in particular, on the mummies of Ramesses II, thought by many biblical scholars to have been the pharaoh of the Exodus, and of Menerptah, his son and successor. About the pharaoh Tutankhamun, we learn that the poor preservation of the mummy was not due to the excessive use of unguents, but rather to the crude method of unwrapping and dismembering the body in 1925. The myth of the curse of Tutankhamun is clearly dismissed. In
STUDIES OF GENETIC TRANSMISSION OF MURINE LEUKEMIA VIRUS BY AKR MICE
Authors: Wallace P. Rowe
Journal: The Journal of Experimental Medicine (1972)

AKR mice, which regularly contain infectious murine leukemia virus, were mated with four Fv-1(n) strains of mice which show little or no expression of virus. F(1), F(2), and first and second backcross generation hybrids were tested for virus in tail tissue at 2 and 6 wk of age. The segregation data indicate that the AKR mouse contains two unlinked, autosomal, chromosomal loci, either of which suffices to induce detectable levels of infectious virus in Fv-1(n) progeny by 6 wk of age. One of the loci (tentatively referred to as V(1)) is on linkage group I, 25-30 map units from the locus for albino; the gene order tentatively appears to be N(1)-c-Hbb.
BRaf and MEK Inhibitors Differentially Regulate Cell Fate and Microenvironment in Human Hepatocellular Carcinoma
Authors: Christian Breunig, Bernadett J. Mueller, Ludmila Umansky, Kristin Wahl, Katrin Hoffmann, Frank Lehner, Michael P. Manns, Heike Bantel, Christine S. Falk
Journal: Clinical Cancer Research (2014)

Small molecule inhibitors of the mitogen-activated protein kinase (MAPK) pathway, such as sorafenib, represent novel treatment options for advanced hepatocellular carcinoma. The aim of our study was to identify downstream targets as biomarker candidates that are directly linked to the oncogenic MAPK pathway in hepatocellular carcinoma and correlate with inhibition of this pathway by multikinase inhibitors.Hepatocellular carcinoma cell lines and fresh tumor and tumor-free liver tissues from patients with hepatocellular carcinoma were incubated with different BRaf or MEK inhibitors and analyzed for kinase phosphorylation, proliferation, induction of apoptosis, and chemokine secretion.Hepatocellular carcinoma cell lines responded differentially to these inhibitors in a dose-dependent manner, even those targeting the same kinase. Sorafenib inhibited both MEK1 and ERK1/2 phosphorylation at high but increased signaling at low concentrations. Similarly, PLX4720 increased MEK/ERK signaling independently from mutations in BRaf or NRas. MEK inhibitors decreased ERK1/2 phosphorylation in a dose-dependent manner. These signaling characteristics correlated with inhibition of proliferation, induction of apoptosis, and chemokine secretion. Fresh tissues derived from patients diagnosed with primary hepatocellular carcinoma responded to these inhibitors with changes in their microenvironment following the patterns observed in hepatocellular carcinoma cells.Oncogenic signaling of the MAPK pathway influences hepatocellular carcinoma sensitivity to treatment with BRaf and MEK inhibitors about cell fate independently from mutations in BRaf and NRas. MAPK inhibitors have a strong impact on chemokine secretion as a consequence of interference with oncogenic signaling. Therefore, novel biomarker candidates associated with the hepatocellular carcinoma microenvironment may be developed for prediction and monitoring of treatment response to small molecule inhibitors.
No cure, no pay
Authors: Claus M⊘ldrup
Journal: BMJ (2005)

Not paying for a drug unless it works sounds great for patients and healthcare funders, but it could also benefit manufacturers. 

Tensions between the pharmaceutical industry and health authorities over drug marketing have increased in recent decades. The authorities want to get the most possible drug for their money whereas drug companies want to get the most money for their drugs.1 2 The current situation is untenable first and foremost for the industry but also for the authorities, and, in the end, the patients. This article proposes how a no cure, no pay strategy could meet the needs of all parties and contribute to a sustainable future for the medical environment as a whole.

Marketing tensions are neither new nor odious, but two factors in particular have put the two opposing sides on a collision course. On one side, the authorities have fewer financial resources at their disposal relative to the many drug options available and the increasing need for treatment caused by a swell in the ageing population. Fewer resources naturally lead to increased focus on how money should be spent and what the return is in practice. This has caused the authorities to focus more on clinical evidence and relevance in the choice of drug treatment. In turn, this has led to the introduction of the concept of rational pharmacotherapy as a political tool for ordering priorities (box 1).3 4

### Box 1: Rational pharmacotherapy

Rational pharmacotherapy is defined as drug treatment that provides the greatest effect with the least serious and fewest side effects at the lowest possible price.5 The following equation is used to illustrate the idea: Effect (clinical studies)+extent of side effects/price = extent of rational pharmacotherapy

On the other side, drug companies have had to become more competitive as a result of the falling number of …
Residual MHC Class II Expression on Mature Dendritic Cells and Activated B Cells in RFX5-Deficient Mice
Authors: Björn E Clausen, Jean-Marc Waldburger, Frieder Schwenk, Emmanuèle Barras, Bernard Mach, Klaus Rajewsky, Irmgard Förster, Walter Reith
Journal: Immunity (1998)
Deficient Red-Cell Spectrin in Severe, Recessively Inherited Spherocytosis
Authors: Peter Agre, Eugene P. Orringer, Vann Bennett
Journal: New England Journal of Medicine (1982)

RED-CELL-membrane architecture has been extensively studied in recent years.1 , 2 When the cells are hypotonically lysed and washed free of hemoglobin, the resulting membrane ghosts consist of the lipid bilayer and associated proteins. When ghosts are extracted with non-ionic detergents, lipid and integral membrane proteins are removed, leaving a cytoskeleton3 that is thought to be responsible for the shape, strength, and reversible deformability of the cell. The cytoskeleton consists of an assembly of polypeptides: spectrin (the largest and most abundant protein of the membrane), band 4.1, and actin. The cytoskeleton is attached to the membrane by the association of spectrin with . . .
THE PERIPHERAL BLOOD PRESSURE IN FIBRILLATION OF THE AURICLES
Authors: Alfred E. Cohn, Christen Lundsgaard
Journal: The Journal of Experimental Medicine (1918)

1. Experiments on dogs show that whereas the pulse pressure in the larger arteries (femoral) varies extensively, it varies within narrow limits only in the small ones (dorsal artery of the foot). These results supply an experimental explanation for the fact that in man uniform pressure readings were obtained by Gaertner's method at the digital artery. 2. The experiments show likewise that in certain instances the level of pressure is maintained when fibrillation of the auricles sets in. It is therefore clear that when the mechanism of the heart beat in man changes to fibrillation of the auricles, a change, that is a fall, in pressure need not necessarily develop.