tbuckley/cabot-search huggingface dataset:
Maternal mortality: stalemate or stagnant?
Authors: M J N C Keirse
Journal: BMJ (1994)

from the Population Council, warned the meeting that developing countries have little experience of delivering integrated services, which cost more than straightforward family planning.An all in one service may be unacceptable to users; clinics for sexually transmitted diseases and counselling on AIDS might stigmatise clinics for family planning if they were held in the same building.The meeting agreed that men must be included in pro- grammes for women's reproductive health, including family planning.Men remain fertile for longer than women and may have few incentives to curb their fertility.Trying to change the balance of power and responsibility within families in a great diversity of cultures may, however, be inappropriate.Monica Janowski, social development adviser for the Overseas Development Association, warned that agencies with Western values must not be prescriptive about changing men's attitudes in the developing world.Educating men, she said, must be done with great sensitivity to local family structures.Global initiatives towards safe motherhood, effective family planning, and increasing the status of women continue, but more needs doing, and the pace of change must quicken.In some places progress towards health goals made in the '60s and '70s has slowed or even gone into reverse.The burden of debt has made it even more difficult for developing countries to generate the political will to tackle women's reproductive health.7 Focusing on women's health is not, however, simply a matter of political correctness, social justice, or even human rights.Nations, including those in the developed world, depend on healthy women for their economic development.
GA201 (RG7160): A Novel, Humanized, Glycoengineered Anti-EGFR Antibody with Enhanced ADCC and Superior <i>In Vivo</i> Efficacy Compared with Cetuximab
Authors: Christian A. Gerdes, Valeria Gonzalez Nicolini, Sylvia Herter, Erwin van Puijenbroek, Sabine Lang, Michaela Roemmele, Ekkehard Moessner, Olivier Freytag, Thomas Friess, Carola H. Ries, Birgit Bossenmaier, Hans Joachim Mueller, Pablo Umaña
Journal: Clinical Cancer Research (2012)

Anti-EGF receptor (EGFR) antibodies and small-molecule tyrosine kinase inhibitors have shown activity in epithelial tumors; however, agents that work by blocking the EGFR growth signal are ineffective when the oncogenic stimulus arises downstream, such as in tumors with KRAS mutations. Antibodies of the IgG1 subclass can also kill tumor cells directly through antibody-dependent cell-mediated cytotoxicity (ADCC), and the efficacy of this is determined by the interaction of the Fc portion of the target cell-bound antibody and Fc receptors present on immune effector cells.We report the development of GA201, a novel anti-EGFR monoclonal antibody with enhanced ADCC properties. GA201 was derived by humanization of the rat ICR62 antibody. The Fc region of GA201 was glycoengineered to contain bisected, afucosylated carbohydrates for enhanced binding to FcγRIIIA.In vitro binding of GA201 to EGFR inhibited EGF ligand binding, EGFR/HER2 heterodimerization, downstream signaling, and cell proliferation to a similar extent as cetuximab. However, GA201 exhibited superior binding to both the low- and high-affinity variants of FcγRIIIA. This resulted in significantly enhanced induction of ADCC compared with cetuximab against both KRAS-wild-type and -mutant tumor cells lines. This enhanced ADCC translated into superior in vivo efficacy in a series of mouse xenograft models. Efficacy of GA201 was further increased when administered in combination with chemotherapy (irinotecan).These data suggest that GA201 may be more effective than cetuximab in patients with EGFR-positive solid tumors and may also represent a first-in-class treatment of patients with KRAS-mutated tumors. Clin Cancer Res; 19(5); 1126-38. ©2012 AACR.
Cloning and characterization of the urea transporter UT3: localization in rat kidney and testis.
Authors: H Tsukaguchi, C Shayakul, U V Berger, T Tokui, D Brown, M A Hediger
Journal: Journal of Clinical Investigation (1997)

Urea transport in the kidney plays an important role in urinary concentration and nitrogen balance. Recently, three types of urea transporters have been cloned, UT1 and UT2 from rat and rabbit kidney and HUT11 from human bone marrow. To elucidate the physiological role of the latter urea transporter, we have isolated the rat homologue (UT3) of HUT11 and studied its distribution of expression and functional characteristics. UT3 cDNA encodes a 384 amino acid residue protein, which has 80% identity to the human HUT11 and 62% identity to rat UT2. Functional expression in Xenopus oocytes induced a large (approximately 50-fold) increase in the uptake of urea compared with water-injected oocytes. The uptake was inhibited by phloretin (0.75 mM) and pCMBS (0.5 mM) (55 and 32% inhibition, respectively). Northern analysis gave a single band of 3.8 kb in kidney inner and outer medulla, testis, brain, bone marrow, spleen, thymus, and lung. In situ hybridization of rat kidney revealed that UT3 mRNA is expressed in the inner stripe of the outer medulla, inner medulla, the papillary surface epithelium, and the transitional urinary epithelium of urinary tracts. Co-staining experiments using antibody against von Willebrand factor showed that UT3 mRNA in the inner stripe of the outer medulla is expressed in descending vasa recta. These data suggest that UT3 in kidney is involved in counter current exchange between ascending and descending vasa recta, to enhance the cortico-papillary osmolality gradient. In situ hybridization of testis revealed that UT3 is located in Sertoli cells of seminiferous tubules. The signal was only detected in Sertoli cells associated with the early stages of spermatocyte development, suggesting that urea may play a role in spermatogenesis.
Oral calcium suppresses increased rectal epithelial proliferation of persons at risk of colorectal cancer.
Authors: P Rozen, Z Fireman, N Fine, Y Wax, E Ron
Journal: Gut (1989)

Dietary calcium may inhibit colonic carcinogenesis promoted by high fat, phosphate, and low fibre diets. In persons at risk for colon cancer oral calcium supplements significantly suppress increased rectal epithelial proliferation. This was studied in a cohort of 35 volunteers: 26 first degree relatives of colorectal cancer patients and nine who had had colonic adenomas (mean age 51.6 years, 17 (49%) men, all negative for large bowel neoplasia). 1.25-1.5 g elemental calcium was given in divided daily doses for three months. Rectal pinch biopsies were taken without bowel preparation, before and mean 8.4 weeks during and 7.2 weeks after treatment and incubated with tritiated thymidine. The mean number of labelled cells, as a ratio of the total number of crypt cells (labelling index-LI), and their crypt position, were determined. The mean number of labelled cells decreased during treatment by 29%, especially in the basal three-fifths of crypts. There was also a significant 10% increase in mean number of crypt cells during treatment. [Mean LI decreased by 36% (p less than 0.001) during calcium treatment and almost returned to basal values after cessation.] If a raised LI is a marker of potential malignancy and a randomised clinical trial confirms that calcium suppresses it, dietary intervention studies in high risk persons are indicated.
Follow-up of patients with breast cancer
Authors: R. A. Klaff
Journal: JAMA (1994)

To the Editor.  —The GIVIO Investigators 1 report that intensive follow-up clinical testing has no significant effects on quality of life and mean postoperative survival in patients with breast cancer. The criteria contained in quality-of-life indexes has been shown to be a consistent and valid predictor of survival time in patients with terminal and nonterminal illnesses. 2,3   The use of the measure of quality of life in this population to determine the effects of clinical procedures seems inappropriate. These patient indexes are often used as a means of determining the effects of intervention or treatment in individuals participating in experimental pharmacological protocols. This is where the strength of these tests as predictor variables may lie.  In multidose clinical drug trials, a quality-of-life questionnaire is invaluable. Affective states, relationship factors, overall health, and functioning are important factors that aid in determining dose-limiting toxicities and maximum therapeutic benefits. Pretreatment vs posttreatment quality-of-life
Genetics for the Clinician
Authors: A. Donald Merritt
Journal: JAMA (1965)

Human Genetics.  By Victor A. McKusick, 148 pp, with illus. $2.95, paper; $4.95, cloth. Prentice-Hall, Englewood Cliffs, NJ, 1964  The rapid upsurge of interest in genetics among clinicians in the last decade has brought forth a number of textbooks in the field of medical genetics. In this area Dr. Clarke's text has admirably filled a needed role in informing the physician about basic concepts and the problems that are of practical interest.  The first eight chapters present the groundwork, without which the beginner will have difficulty in approaching a problem in human genetics; here he becomes acquainted with the simple rules of mendelian genetics, the nature of the gene, human cytogenetics, the concepts of linkage and gene interactions, and the rudiments of population genetics. The last chapter introduces the elementary ideas in statistics which are of paramount importance in many areas of genetics.  The remaining chapters deal with the many
Stunned Thyroid after High-dose 1–131 Imaging
Authors: HEE-MYUNG PARK
Journal: Clinical Nuclear Medicine (1992)

A patient with papillary carcinoma of the thyroid was scanned with 10 mCi of 1–131 postoperatively before thyroablation therapy. Two weeks later, the patient was given 100 mCi of 1–131. The posttherapy scan showed very little uptake in the thyroid remnant, suggesting that the thyroid was stunned before therapy. This case was compared with another in which the patient was scanned with 1–123 followed by 1–131 therapy. There was excellent uptake of the therapy dose. Pretherapy scanning with a high dose of 1–131 may suppress the thyroid tissue and inadvertently prevent maximum uptake of a subsequently administered therapy dose of 1–131.
Cancer care in England lags behind other countries, confirms review
Authors: Z. Kmietowicz
Journal: BMJ (2011)

Late diagnosis, delayed and poor access to surgery and radiotherapy, and age bias are the main reasons why cancer survival rates are worse in England than in other countries, says a report from the health policy think tank the King’s Fund. However, access to drugs is not a major factor in England’s poor performance.

The report, which reviewed international evidence, acknowledges that overall cancer survival rates in England are improving and that these speeded up slightly between 2004 and 2007, probably as a result of the publication of the NHS Cancer Plan in 2000. Survival rates of breast cancer, for example, are catching up with other higher performing countries with 83% of women diagnosed in England surviving for at least five …
Effects of pentobarbital on upper airway patency during sleep
Authors: M. Eikermann, D. J. Eckert, N. L. Chamberlin, A. S. Jordan, S. Zaremba, S. Smith, C. Rosow, A. Malhotra
Journal: European Respiratory Journal (2009)

We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure (<i>P</i><sub>crit</sub>). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO<sub>2</sub> concentration and upper airway resistance were greater; and <i>P</i><sub>crit</sub> was unaffected (pentobarbital mean±sd -11.7±4.5 <i>versus</i> placebo -10.25±3.6 cmH<sub>2</sub>O; p = 0.11). Pentobarbital increased the time to arousal (297±63s <i>versus</i> 232±67 s; p&lt;0.05), at which time phasic genioglossus EMG was higher (6.2±4.8% maximal <i>versus</i> 3.1±3%; p&lt;0.05) as were CO<sub>2</sub> levels. The increase in genioglossus EMG after CO<sub>2</sub> administration was greater after pentobarbital <i>versus</i> placebo. Pentobarbital did not affect the genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it also increases upper airway resistance during sleep.
EFFECTS OF PROPRANOLOL ON THE RESPONSE OF HUMAN ECCRINE SWEAT GLANDS TO ACETYLCHOLINE
Authors: K. G. FOSTER, J. R. HASPINEALL, C. L. MOLLEL
Journal: British Journal of Dermatology (2006)

Summary.— Propranolol had no marked effects on the acetylcholine-induced sweat response in normal subjects. The only effects were (1) a slight and transient prolongation of the secretion; (2) a very slight and transient anti-cholinergic activity. These findings do not support the existence of a β-receptor inhibitory mechanism affecting sweat gland activity as postulated by Hemels (1970).
Cyanosis During Anaesthesia: An Unusual Case
Authors: W. Sniper
Journal: BMJ (1961)

Brain tumours have been successfully located by probe-counting after the intra-arterial injection of 50 Sc of 32P.The pattern of uptake of various tumours has been the same by this method as after intravenous injection of isotope.The inconveniences of handling the larger quantities of 32P necessary for intravenous use are reduced.
Could inflammatory arthritis be triggered by progenitor cells in the joints?
Authors: C Jorgensen
Journal: Annals of the Rheumatic Diseases (2002)

Fetal morphogenesis genes are expressed in rheumatoid synovial tissue and the presence of undifferentiated mesenchymal cells can also be shown. Possibly, these events are related to remodelling/repair processes, which could lead to the development of new methods of treatment, or they may be harmful and play a part in the immune process.
Transrectal Ultrasonography: Is It Ready for Routine Use?-Reply
Authors: Gerald W. Chodak
Journal: JAMA (1988)

<h3>In Reply.—</h3> In the recent editorial on transrectal ultrasonography, the efficacy of ultrasonically guided radioactive seed implants was judged to be investigational because the use of surgically placed<sup>125</sup>I seeds has not been as effective as external beam radiation in controlling this disease.<sup>1</sup>Nevertheless, Dr Baumgartner cites a recent study<sup>2</sup>in which the rate of positive prostate biopsy findings following interstitial radiation therapy was similar to the rate observed following external beam radiation therapy. Based on these data, he apparently concludes that interstitial radiation is as effective as external beam radiation. There are two problems with the study cited. First, there may have been a substantial selection bias, because 60% of the patients did not undergo a prostate biopsy following treatment. Second, although the number of cases in each group was small, the rates of positive prostate biopsy findings were higher for patients with moderate and poorly
Value of intracellular bacteria detection in the diagnosis of ventilator associated pneumonia.
Authors: A Torres, M El-Ebiary, N Fabregas, J Gonzalez, J P de la Bellacasa, C Hernandez, J Ramirez, R Rodriguez-Roisin
Journal: Thorax (1996)

BACKGROUND: Markers of ventilator associated pneumonia are of interest for confirming the diagnosis and for guiding the initial management of this frequent complication of mechanical ventilation. The detection of intracellular organisms in the polymorphonuclear leucocytes (PMNLs) and/or macrophages of bronchoalveolar lavage (BAL) fluid has been suggested as a specific test for the early indication of an infectious pulmonary process. METHODS: The diagnostic value of detecting intracellular organisms in two types of BAL fluid--protected (P-BAL) and conventional (C-BAL)--in 25 patients who died in one unit was prospectively studied. Immediately after death both P-BAL and C-BAL were performed bilaterally. Through a minithoracotomy on both sides of the chest bilateral bronchoscopically guided open lung biopsy samples were obtained from the same area, and an average of eight open lung blind biopsy samples (not bronchoscopically guided) were taken from each lung for histological examination. BAL fluid was examined for quantitative cultures (threshold 10(4) cfu/ml) and for the presence of intracellular organisms and extracellular organisms, and differential cell counts were also performed. RESULTS: Using the histopathology of the bronchoscopically guided open lung biopsies as the gold standard, detection of intracellular organisms in P-BAL (&gt; or = 5%) and C-BAL (&gt; or = 5%) fluids yielded 75% and 57% positive predictive values, and 83% negative predictive values, respectively. Prior treatment with antibiotics decreased the positive and negative predictive values of intracellular organism detection for both types of BAL fluid. The presence of intracellular organisms was correlated with the quantitative cultures of P-BAL and C-BAL samples. Quantitative cultures from P-BAL fluid were less sensitive (22% versus 45%) and more specific (100% versus 55%) than those from C-BAL samples. The percentage of extracellular organisms and the differential cell count in P-BAL and C-BAL samples could not discriminate between the presence or absence of pneumonia. CONCLUSIONS: The presence of &gt; or = 5% intracellular organisms infecting PMNLs or macrophages in P-BAL or C-BAL fluids is a specific marker of ventilator associated pneumonia.
A model for managing epilepsy in a rural community in Africa.
Authors: A. E. Watts
Journal: BMJ (1989)

As most Malawians with epilepsy consider treatment of seizures to be the domain of traditional healers and attend hospital only when they require treatment for burns which they suffer during fits, steps were taken to encourage people with epilepsy to attend hospital for regular treatment with anticonvulsant drugs. At first only a few patients attended, but within two years 461 had registered at the hospital and two mobile clinics. Publicity was spread through the area action committee, which was organised by the area chief. The main drug used was phenobarbitone. After treatment was given for six months seizures were fully controlled in 40 (56%) out of 71 patients. A further 20 (28%) had greatly improved. As news of the clinics spread other health units adopted the model, and eventually over 3000 patients with epilepsy were receiving regular treatment at 45 units throughout Malawi.
Antitumor activity of poly(ethylene glycol)–camptothecin conjugate: The inhibition of tumor growth in vivo
Authors: Deshan Yu, Ping Peng, Sonia S. Dharap, Yang Wang, Mary Mehlig, Pooja Chandna, Hong Zhao, David Filpula, Karen Yang, Virna Borowski, Gerrit Borchard, Zhihua Zhang, Tamara Minko
Journal: Journal of Controlled Release (2005)
Chromatin modifications induced by the AML1-ETO fusion protein reversibly silence its genomic targets through AML1 and Sp1 binding motifs
Authors: A Maiques-Diaz, F S Chou, M Wunderlich, G Gómez-López, F V Jacinto, S Rodriguez-Perales, M J Larrayoz, M J Calasanz, J C Mulloy, J C Cigudosa, S Alvarez
Journal: Leukemia (2012)
Normal Qualitative and Quantitative Tc-99m Sestamibi Myocardial SPECT: Spectrum of Intramyocardial Distribution During Exercise and at Rest
Authors: JEAN LETTE, MICHELLE CARON, MICHEL CERINO, DANIEL MCNAMARA, SERGE METAYER, SUZI D??AOUST, MARIE-CLAIRE EYBALIN, ANDR?? LEVESSEUR, JEAN GR??GOIRE, ANDR?? ARSENAULT
Journal: Clinical Nuclear Medicine (1994)

Exercise myocardial perfuslon imaging with Tc-99m sestaMIBI is routinely used to detect underlying coronary stenoses. Ischemia is diagnosed in regions that display decreased tracer uptake during exercise as compared to rest. Tc-99m sestaMIBI SPECT images of 42 healthy volunteers were assessed both qualitatively (tomographic slices) and quantitatively (sectored polar map) for potential sources of misinterpretation. On the myocardial tomographic slices, the most common culprit artifacts were diaphragmatic attenuation and bowel interposition, which caused fixed or reversible “perfusion defects” in the Inferior and posterior regions (In 19/35 abnormal segments), and artifacts related to the presence and shift of hot spots (observed in 11/28 men; In women, they were more difficult to demonstrate because of the overriding effect of breast attenuation). Hot spots shifts between exercise and rest usually resulted in pseudo-reversible defects in the anterolateral and lateral walls. The quantified polar map display of the myocardium showed a physiologic decrease in sestaMIBI activity in the basal anterolateral and basal posterolateral areas in men during exercise. There are many normal variants that may mimic coronary artery disease on tomographic sestaMIBI images. Before reporting an area of decreased activity as either a fixed or reversible perfusion defect, the interpreter should ensure that It does not represent an artifact or a normal variation in the intramyocardial distribution of sestaMIBI during exercise.
All about letters
Authors: J. Smith
Journal: BMJ (2009)

If you are busy in this first full week of the new year and have time to read only two pages, then make it the Letters. In a short space they illustrate well the range of issues that preoccupy doctors—and our pages: core clinical skills, the use of technology, doctors’ duties to society, improving the way services are delivered, and despair at non-evidence-based practices.

Thus Stephen Hayes urges the importance of teaching primary care doctors the key clinical skill of detecting melanomas (doi:10.1136/bmj.a3138). In doing so he bemoans the lack of teaching in dermatology received by most British undergraduates these days. That lament is …