tbuckley/cabot-search huggingface dataset:
Bone marrow transplantation in mice leads to a minor population of hepatocytes that can be selectively amplified <i>in vivo</i>
Authors: Vincent O. Mallet, Claudia Mitchell, Eva Mezey, Monique Fabre, Jacques-Emmanuel Guidotti, Laurent Renia, Laure Coulombel, Axel Kahn, Hélène Gilgenkrantz
Journal: Hepatology (2002)

Cell-based therapy may some day be a therapeutic alternative to liver transplantation. Recent observations indicating that hematopoietic stem cells can differentiate into hepatocytes have opened new therapeutic prospects. However, the clinical relevance of this phenomenon is unknown. We have previously developed a strategy based on the protective effect of Bcl-2 against Fas-mediated apoptosis to selectively amplify a small number of hepatocytes in vivo. We now show that this approach can be used to amplify a minor population of bone marrow-derived hepatocytes. Normal mice were transplanted with unfractionated bone marrow cells from transgenic animals expressing Bcl-2 under the control of a liver-specific promoter. Recipients were then submitted to weekly injections of the anti-Fas antibody, Jo2. Upon sacrifice, the liver of the recipients showed bone marrow-derived clusters of mature hepatocytes expressing Bcl-2, which showed that the hepatocyte progeny of a genetically modified bone marrow can be selectively expanded in vivo. In contrast, no Bcl-2 expression could be detected without the selective pressure of Jo2, suggesting that differentiation of bone marrow cells into mature hepatocytes is very inefficient under physiologic conditions. We conclude that a selection strategy will be required to achieve a therapeutic level of liver repopulation with bone marrow-derived hepatocytes.
Platelet Cyclic Guanosine Monophosphate as a Biomarker of Phosphodiesterase Type 5 Inhibitor Efficacy in the Treatment of Erectile Dysfunction: A Randomized Placebo-Controlled Study
Authors: Vincenzo Mirone, Roberta d'Emmanuele di Villa Bianca, Emma Mitidieri, Ciro Imbimbo, Ferdinando Fusco, Paolo Verze, Dino F. Vitale, Raffaella Sorrentino, Giuseppe Cirino
Journal: European Urology (2009)
Predicting cholangiocarcinoma in patients with primary sclerosing cholangitis: An analysis of the serological marker CA 19-9
Authors: Steven A. Rogers, Daniel K. Podolsky
Journal: Hepatology (1994)

Primary sclerosing cholangitis (PSC) predisposes to the development of cholangiocarcinoma, a usually fatal complication that is difficult to diagnose. Serum concentrations of CA 19-9, a tumor-associated antigen, are frequently increased in patients with only cholangiocarcinoma. The aim of this study was to assess the value of an increased serum CA 19-9 level for the diagnosis of cholangiocarcinoma in patients with preexisting PSC. We analyzed serum samples from 9 patients with PSC and superimposed cholangiocarcinoma and from 28 patients with only PSC. Serum concentrations of CA 19-9 were measured in a blinded manner with use of an immunoradiometric assay. The serum CA 19-9 concentrations were increased in 8 of 9 patients (89) with PSC and cholangiocarcinoma (mean±SE, 391 ± 86 U/ml; range, 4 to 677), whereas they were increased in only 4 of 28 patients (14) with only PSC (mean ± SE, 61 ± 16 U/ml; range, 2 to 370). The sensitivity of a CA 19-9 value greater than 100 U/ml for cholangiocarcinoma in PSC was 89, and the specificity was 86. The measurement of serum concentrations of CA 19-9 is a promising test for detecting cholangiocarcinoma in patients with PSC.
Tackle deprofessionalisation and fragmentation
Authors: M. Moutoussis
Journal: BMJ (2010)

Rees and Wells point out important difficulties facing NHS research.1 However, local governance is not the key problem. Fragmenting the NHS into competing businesses profoundly undermines research. Forcing staff to compete and struggle for survival also pushes them to seek competitive advantage by cutting corners, externalising costs on to patients. The medical …
ERCG: Endoscopic Retrograde Catheterization of the Gallbladder
Authors: E.Ch. Foerster, J. Auth, U. Runge, Ch. Ell, W. Kerzel, W. Domschke
Journal: Endoscopy (1988)

This report describes a newly developed catheter system with the aid of which the cystic duct and gallbladder can be reliably catheterized, retrograde, via an endoscope. In 8 out of 10 autopsy preparations, transpapillary gallbladder catheterization was successfully achieved, with an average fluoroscopic duration of 12 minutes (range: 4-20 minutes). Neither macroscopic nor microscopic traumatization of the gallbladder was observed. The procedure described in this paper opens up a diagnostic and therapeutic approach to the gallbladder.
Cold Fracture on Bone Imaging in Secondary Hyperparathyroidism
Authors: GIOVANNA GIOVANNIELLO, BELUR CHANDRAMOULY, ROBIN P. CUNNINGHAM
Journal: Clinical Nuclear Medicine (1992)

A 54-year-old man with end stage renal disease and secondary hyperparathyroidism fell out of bed and had left hip pain and decreased range of motion. Radionuclide bone imaging was performed 36 hours later and demonstrated a linear photopenic area (cold fracture) in the left intertrochanteric region, seen best with pin-hole images. Fracture was confirmed by radiographic tomograms and at surgery.
Sublethal Exposure to Microwave Radar-Reply
Authors: Mauricio Castillo
Journal: JAMA (1988)

<h3>In Reply.</h3> —Dr Forman states that in our letter we did not specify the parameters of the microwave field to which our patient was exposed. We contacted the Air Force and were informed that this information is considered classified and not available to civilians. We were not aware that Forman and colleagues<sup>1</sup>as well as Williams and Webb<sup>2</sup>had previously described cases similar to ours; we regret this omission. The psychological symptoms that occurred in their patients as well as in our patient were attributed to posttraumatic stress disorder. There is evidence that radar technicians who suffered behavioral changes following exposure to 1 to 10 GHz of radiation demonstrated abnormal band patterns in cerebrospinal fluid protein electrophoresis.<sup>3</sup>It is unknown if this abnormal pattern could account for the symptoms observed. Dr Forman also points out that a previously reported case has been discredited.<sup>4,5</sup>The aforementioned case
Interferon alpha-2A in combination therapies for the treatment of chronic hepatitis C in prior non-responders to interferon monotherapy
Authors: J. Salmeron, M. Diago, R. Andrade, R. Perez, R. Sola, M. Romero, M. De La Mata, R. Granados, V. Torrente, J. Aguilar, R. Planas, J. Perez-Moreno, T. Casanovas
Journal: Journal of Hepatology (2003)
The coherence spectrum. A quantitative discriminator of fibrillatory and nonfibrillatory cardiac rhythms.
Authors: K M Ropella, A V Sahakian, J M Baerman, S Swiryn
Journal: Circulation (1989)

Previous work has suggested that a comparison of electrograms from two or more sites may best differentiate fibrillatory from nonfibrillatory rhythms. The coherence spectrum is a measure by which two signals may be compared quantitatively in the frequency domain. In the present study, the coherence spectrum was used to quantify the relation between spectral components of electrograms from two sites in either the atrium or ventricle during both fibrillatory and nonfibrillatory rhythms. Bipolar recordings of 35 rhythms from 20 patients were analyzed for coherence in the 1-59 Hz band. The 17 nonfibrillatory rhythms were sinus rhythm (six), paroxysmal supraventricular tachycardia (two), atrial flutter (four), and monomorphic ventricular tachycardia (five). The 18 fibrillatory rhythms were atrial fibrillation (12) and ventricular fibrillation (six). Nonfibrillatory rhythms exhibited moderate-to-high levels of coherence throughout the 1-59 Hz band, with peaks concentrated at the rhythm's fundamental frequency and its harmonics. Fibrillatory rhythms exhibited little coherence throughout the 1-59 Hz band, and harmonics were not evident. The mean magnitude-squared coherence (scale of 0 to 1) for the 1-59 Hz band ranged from 0.22 to 0.86 (mean +/- SD, 0.52 +/- 0.19) for nonfibrillatory rhythms and from 0.042 to 0.12 (0.067 +/- 0.021) for fibrillatory rhythms. Separation of fibrillatory and nonfibrillatory rhythms was possible whether signals were recorded by floating or fixed-electrode configurations. These findings indicate that comparison of two electrograms with magnitude-squared coherence measurements differentiates fibrillatory from nonfibrillatory rhythms. A recognition algorithm based on coherence spectra may provide a major variations in lead configuration.(ABSTRACT TRUNCATED AT 250 WORDS)
AN EVALUATION OF SHOCK THERAPY
Authors: LEON SALZMAN
Journal: American Journal of Psychiatry (1947)

In view of these findings, it becomes imperative that shock studies concentrate on investigating the readmission and deteriorating aspects of shock therapy. The findings tend to indicate that shock therapy increases the frequency of readmission and thus raises the question of whether the time saved in the hospital at the first admission is not lost by the early readmission following shock treatment. This is particularly significant since it seems likely that shock therapy does produce deterioration and personality changes which may explain this increased readmission frequency. It is hoped that this paper may stimulate some research in this direction and that more extensive studies will be made.
Optimal dose of salbutamol respiratory solution: comparison of three doses with plasma levels.
Authors: E H Walters, A Cockroft, T Griffiths, K Rocchiccioli, B H Davies
Journal: Thorax (1981)

Salbutamol solution is usually administered by nebuliser in a dose of 5 mg. Little evidence exists that this is the optimal dose for bronchodilatation or that this dose is without side-effects. Twelve patients with asthma were given increasing doses of salbutamol 1.5 mg, 3.0 mg, 7.5 mg, and placebo. Treatments were administered twice daily for four days in a double-blind manner. Measurements of ventilatory capacity, pulse rate, and tremor were recorded before and for three hours after treatment. There was a significant dose-related response for FEVI and peak flow rate. There was also a significant dose-related response in pulse rate and tremor. The incidence of palpitations was similarly related to dose. Plasma levels of salbutamol were measured before and after treatment with salbutamol and showed a dose related increase in salbutamol absorption which begins to be evident after the 3.0 mg dose. Three milligrams of salbutamol nebuliser solution may be an optimal dose, producing satisfactory bronchodilatation but fewer side-effects related to systemic absorption.
Pharmacokinetics of pancreatic polypeptide in man.
Authors: T E Adrian, G R Greenberg, H S Besterman, S R Bloom
Journal: Gut (1978)

Pure bovine pancreatic polypeptide (PP) was infused into 23 healthy subjects at doses of 1, 3, and 5 pmol/kg/min over 60 minutes and plasma PP was measured by radioimmunoassay. During the infusions mean plasma levels of 203 +/- 34, 575 +/- 73, and 930 +/- 48 pmol/l respectively were achieved. Mean disappearance half time on stopping the infusion was 6.9 +/- 0.3 min (mean +/- SEM). The metabolic clearance rate was 5.1 +/- 0.2 ml/kg/min (mean +/- SEM) and the apparent volume of distribution was calculated to be 51 +/- 3 ml/kg (mean +/- SEM). This study provides for the first time pharmacokinetic data for PP in man.
Changes required to health bill will lead to delays, says Clegg
Authors: N. Hawkes
Journal: BMJ (2011)

Nick Clegg, the deputy prime minister, has said that the reforms to the NHS are highly likely to be delayed with GP consortiums only taking on the role of commissioning when they are ready rather than by the April 2013 deadline set out in the health bill, published in January ( BMJ 2011;342:d418 doi:10.1136/bmj.d418).

In a speech to patients and staff at University College London Hospital on 26 May Mr Clegg said, “Change won’t happen overnight and arbitrary deadlines are no good to anyone. So yes, family doctors should be more involved in the way the NHS works. But they should only take on that responsibility when they are ready and willing, working with other medical professionals too.”

After the speech, he added that the changes sought were such as to require the bill to be re-examined in committee. It has already passed the committee stage …
Gynecology: Carcinoma of the Endometrium
Authors: Joe Vincent Meigs
Journal: New England Journal of Medicine (1945)

CANCER originating in the endometrial lining of the uterus has been given varied nomenclatures, such as "cancer of the fundus," "cancer of the body," "cancer of the uterus" and "cancer of the endometrium." Inasmuch as this tumor arises from the cells of the endometrium, it is proper to speak of it as cancer of the endometrium. This tumor is not so frequent as is carcinoma of the cervix, and, until far advanced, it is not nearly so lethal. At the Pondville Hospital since 1927 there have been approximately 1500 cases of cervical cancer and 300 cases of endometrial cancer, a . . .
EUS and EMR/ESD: Is EUS in patients with Barrett’s esophagus with high-grade dysplasia or intramucosal adenocarcinoma necessary prior to endoscopic mucosal resection?
Authors: I. Waxman
Journal: Endoscopy (2006)

The management of patients with HGD in BE remains controversial, largely because the natural history of this condition is so poorly defined. For example, Reid et al. reported a 59 % 5-yr cumulative cancer incidence among 76 patients with HGD in BE [1],whereas Schnell et al. found that only 12 (16 %) of their 75 patients with HGD developed adenocarcinoma during a mean follow-up period of 7.3 yr [2]. Four management options have been proposed for patients with HGD in BE: (1) esophagectomy, (2) endoscopic ablative therapies, (3) EMR, and (4) intensive endoscopic surveillance, in which invasive therapy is withheld until biopsy specimens show evidence of invasion [3]. Clearly, there are risks associated with all of these approaches, and all would benefit from accurate staging of the neoplasia.
Work intensity must be tackled
Authors: L. Beecham
Journal: BMJ (1995)

Although the contracted hours of junior doctors have been reduced, many are working at greater intensity while they are on duty. Speakers at last week's junior doctors conference endorsed a proposal from the East Anglian regional committee concentrating on the maximum of 56 hours of actual work for all posts. After that attention could be given to reducing the hours of duty for non-hardpressed posts.

Just reducing hours meant many doctors were working harder when on duty, Mr Andrew Hobart, a senior house officer in Cambridge, pointed out. But contracted hours were easier for managers to measure.

He was supported by Dr Fiona Kew, a senior house officer in Liverpool, whose regional committee believed that the implementation …
Middle Lobe Bronchiectasis
Authors: Gordon K. Danielson
Journal: JAMA (1967)

In an unusual family, four of five siblings had extensive bronchiectasis of the middle lobe. Three have undergone lobectomy and the fourth will probably require a resection. A strong history of allergy is present in both affected and nonaffected members of the family. Although some possible congenital and acquired factors have been investigated, the cause of the middle lobe disease in this family remains unknown.
Course and Prognosis of Chronic Obstructive Lung Disease
Authors: Benjamin Burrows, Richard H. Earle
Journal: New England Journal of Medicine (1969)

To document the course and prognosis of chronic obstructive lung disease, 200 patients with the disorder were enrolled in a prospective standardized study four to eight years ago. Their disease progressed in a more regular and more predictable fashion than had been anticipated from casual clinical observations. Reasonably precise predictions of longevity could be made on the basis of initial findings. Measurements of ventilatory capacity, resting heart rate and carbon dioxide levels were the best indicators of prognosis. Prediction of survival was further improved by consideration of the course of physiologic abnormalities over a two-year follow-up period. Most features of the disease showed a systematic tendency to worsen, but yearly changes were relatively small, often becoming evident only with long-term observation. Data are compatible with the concept that chronic obstructive lung disease is a slowly progressive disorder that begins many years before the onset of clinical symptoms.
Needs for Physicians' Assistants
Authors: John H. McGrath
Journal: JAMA (1970)

<h3>To the Editor.—</h3> Much recent discussion suggests the need for new categories of health personnel to assist physicians. Before making any decisions regarding training programs for our own medical community, we elected to survey the physicians of the state of Delaware to ascertain their opinions regarding the need for physicians' assistants (PA), their willingness to use this type of personnel, and their willingness to participate in PA training programs. Of copies of a questionnaire sent to all members of the Medical Society of Delaware, 151 of 158 returned were sufficiently complete to be analyzed (Table). Some quite unexpected data appear. The percentage of total physicians who would use physicians' assistants is consistently greater than the percentage who see a need for them ( +20%). As a group, the greatest discrepancy (32%) in answers to<i>See need</i>and<i>Would use</i>categories is among the surgeons. The smallest discrepancy (4%) is within the
Chronic Fatigue: Symptom and Syndrome
Authors: Simon Wessely
Journal: Annals of Internal Medicine (2001)

Chronic fatigue is common, is difficult to measure, can be associated with considerable morbidity, and is rarely a subject of controversy. The chronic fatigue syndrome also presents problems in definition and measurement, is associated with even more morbidity than chronic fatigue itself, and is often controversial. Particularly unclear is the way in which chronic fatigue and the chronic fatigue syndrome relate to each other: Is one the severe form of the other, or are they qualitatively and quantitatively different? We know that many things can cause chronic fatigue, and this is probably true for the chronic fatigue syndrome, too. We can anticipate that discrete causes of the chronic fatigue syndrome will be found in the future, even if these causes are unlikely to fall neatly along the physical–psychological divide that some expect. The causes of chronic fatigue are undoubtedly many, both in a population and in any individual person, even when a discrete cause, such as depression or cancer, is identified. Social, behavioral, and psychological variables are important in both chronic fatigue and the chronic fatigue syndrome. Interventions that address these general variables can be successful, and currently they are often more successful than interventions directed at specific causes.
Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries
Authors: A Forte
Journal: Cardiovascular Research (2003)

Background: Milan hypertensive rats (MHS) are characterised by an increase in renal sodium reabsorption mainly related to adducin mutations. Interest in this model relies on the genetic link between adducin polymorphisms and primary hypertension, observed also in a subset of patients. Objectives: To investigate the molecular and morphological events involved in carotid stenosis and triggered by surgery in MHS model. Methods: Stenosis was induced through arteriotomy. At different times after injury, the expression profiles of various gene families were investigated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), while histological techniques were used to follow morphometric and morphological changes. Apoptotic nuclei were revealed by terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL). Results: mRNAs coding for transcription factors c-jun, c-fos and c-myc were rapidly induced by injury. Analysis of apoptosis-related genes revealed a decrease of the Bcl-2/Bax ratio 4 h after vascular trauma (P<0.05), followed by a recovery of antiapoptotic factors 24 and 48 h later. ETA and receptor mRNAs decreased after the injury and were replaced by ETB and AT2 mRNAs. Both ETA and AT1 turned to basal level 48 h after injury. Expression profiles of chatepsins B and D were also determined. A marked neoadventitia led to maximal 60±9% lumen reduction (P<0.05) 30 days after surgery. Media substitution by fibrotic and granulomatous tissue was also evident. Maximal 47±2% apoptotic nuclei were detected 48 h after the injury (P<0.05). Conclusions: The injury applied to MHS carotids induces negative remodelling and a limited apoptotic reaction. These findings could arise from the balancing among proliferative factors, apoptosis-related molecules and relaxant anti-proliferative receptors, all stimulated by the injury.
Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive, Locally Advanced, or Metastatic Breast Cancer
Authors: Kathy D. Miller, Véronique Diéras, Nadia Harbeck, Fabrice Andre, Reshma L. Mahtani, Luca Gianni, Kathy S. Albain, Diana Crivellari, Liang Fang, Glenn Michelson, Sanne L. de Haas, Howard A. Burris
Journal: Journal of Clinical Oncology (2014)

Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2) -targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer (MBC).Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR).Sixty-four patients (43 patients in the second-line or greater setting [advanced MBC]; 21 patients in the first-line setting [first-line MBC]) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade ≥ 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively).T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.