tbuckley/cabot-search huggingface dataset:
The Distribution of the Anticancer Drug Doxorubicin in Relation to Blood Vessels in Solid Tumors
Authors: Andrew J. Primeau, Augusto Rendon, David Hedley, Lothar Lilge, Ian F. Tannock
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Anticancer drugs gain access to solid tumors via the circulatory system and must penetrate the tissue to kill cancer cells. Here, we study the distribution of doxorubicin in relation to blood vessels and regions of hypoxia in solid tumors of mice. Experimental Design: The distribution of doxorubicin was quantified by immunofluorescence in relation to blood vessels (recognized by CD31) of murine 16C and EMT6 tumors and human prostate cancer PC-3 xenografts. Hypoxic regions were identified by injection of EF5. Results: The concentration of doxorubicin decreases exponentially with distance from tumor blood vessels, decreasing to half its perivascular concentration at a distance of about 40 to 50 μm, The mean distance from blood vessels to regions of hypoxia is 90 to 140 μm in these tumors. Many viable tumor cells are not exposed to detectable concentrations of drug following a single injection. Conclusions: Limited distribution of doxorubicin in solid tumors is an important and neglected cause of clinical resistance that is amenable to modification. The technique described here can be adapted to studying the distribution of other drugs within solid tumors and the effect of strategies to modify their distribution.
Routine pregnancies do not need obstetrician care
Authors: J. Wise
Journal: BMJ (1997)

Specialist participation in routine antenatal care should be reduced, says a report by the Audit Commission. Such a move would be popular with the public and save the NHS £10m ($16m).

The commission's survey of 2376 women, 500 GPs, and visits to 13 NHS trusts highlighted large differences in the way maternity services are provided in England and Wales. For example, the number of antenatal check ups provided varied between seven and 13 and the rates of caesarean section from 11% to 18% of all deliveries.

The report, First Class Delivery: Improving Maternity Services in England and Wales, found that some trusts …
A Prospective Clinical Trial of Pulse Therapy with Glucocorticoid and Cyclophosphamide in Moderate to Severe Paraquat-poisoned Patients
Authors: JA-LIANG LIN, MEI-LING LEU, YU-CHIH LIU, GUAN-HSING CHEN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Paraquat (PQ) is a widely used bipyridyl contact herbicide with a good safety record when used properly. Most cases of PQ poisoning result from PQ suicidal ingestion. There are three degrees of severity in PQ poisoning (1, 2). Mild poisoning can cause oral irritation and gastric upset, and brings complete recovery. Moderate to severe poisoning produces acute renal failure, and in severe cases, hepatitis followed by pulmonary fibrosis, leading to death after 2 to 3 wk. Acute fulminant poisoning results in death within 1 wk from multiple organ failure and cardiovascular collapse. Retrospective studies (3–6) show that good predictors of outcome may be plasma and urine concentrations within the first 24 h of intoxication. The urine PQ tests taken on admission are reasonable guides to predict the severity of poisoning and have the advantage that a qualitative or semiquantitative result may be easily and rapidly obtained in an emergency situation (5–7). The results of treatments for PQ poisoning, including absorbents, pharmacological approaches (8), radiotherapy (9), hemodialysis, and hemoperfusion (10), were disappointing. Although the high-dose cyclophosphamide (CP) and dexamethasone (DX) treatments, including intravenous CP 5 mg/kg/d and DX 24 mg/d for 14 d, had a 75% survival rate after PQ poisoning (11), a subsequent study (12) did not demonstrate the efficacy of this approach. Therefore, the efficiency of highdose CP and DX in PQ poisoning remains controversial. Recently, pulse therapy with CP and methylprednisolone (MP), including intravenous CP or MP 1 g/d for 2 to 3 d, has been used to treat effectively many patients with severe lung damage from systemic lupus erythematosus (SLE) and Wegener’s granulomatosis (13, 14), with greater efficacy and less side effects than those of high doses of CP therapy. In addition, our preliminary report (15) demonstrated that pulse therapy might be effective in treating patients with moderate to severe PQ poisoning. Because the previous study was not prospective and only included a small number of patients, we designed the prospective study to evaluate its efficacy in treating a large group of PQ-poisoned patients. METHODS
Diagnostic Procedures of Chronic Amoebiasis
Authors: Thomas Doxiades
Journal: JAMA (1964)

It IS CONSIDERED that the diagnosis of amoebiasis should be effected through the detection of<i>End-amoeba histolytica</i>in the stools. This method is not at all satisfactory, since a negative stool examination for amoebae does not exclude amoebiasis any more than a negative sputum examination for<i>Bacillus koch</i>excludes tuberculosis of the lungs.<sup>1</sup> An ideal solution would be a new serodiagnostic method, since the existing method has not as yet yielded satisfactory results. Failing this, we have tried to find other diagnostic procedures, both in chronic amoebiasis and diffuse nonsuppurative chronic hepatitis.<sup>2</sup>Thus all patients who were clinically suspected of suffering from chronic amoebiasis, chronic amoebic hepatitis, or both, were submitted to proctosigmoidoscopic examination with rectal biopsy. This report, therefore, is based on the observations and conclusions drawn from the application of this method to our patients. In our department during the year 1962, 695 patients who were
Abdominal Hemangiopericytoma Scintigraphically Simulating an Accessory Spleen
Authors: MICHAEL M. LUNDY, PETER W. BLUE, GAYLA J. CRAWFORD, STEVE H. PARKER
Journal: Clinical Nuclear Medicine (1988)

Hemangiopericytoma is a soft tissue tumor composed histologically of pericytes of Zimmerman, which line capillaries. These neoplasms have been observed throughout the body in soft tissue and bone. Presented here is a case of abdominal hemangiopericytoma proven histologically that simulated an accessory spleen on a number of studies including Tc-99m sulfur colloid imaging.
Cholera El Tor in Calcutta
Authors: S. Mukerjee
Journal: BMJ (1964)

Cholera El Tor, which had been confined for several decades to its original home in the Celebes islands, began to spread out in a pandemic form in 1961.By 1963 most of the islands in the Western Pacific were involved in the pandemic, as were also many countries in South and South-east Asia.By the end of 1963 cholera El Tor had penetrated into East Pakistan, and from April 1964 it has also been present in Calcutta.Thus the Indo-Pakistan subcontinent is now having for the first time a mixed infection of classical cholera and cholera El Tor.In this paper some bacteriological, epidemiological, and immuno- logical problems arising from this situation are discussed. Materials and MethodsStrains of El Tor Vibrios.-Inall 35 strains of Vibrio el tar isolated from patients admitted in the Infectious Diseases Hos- pital, Calcutta, and Satya Bala Debi Hospital, Howrah, were available for bacteriological tests.Twenty-three strains were obtained by courtesy of Dr. D. L. Shrivastava, of the Cholera Research Centre, Calcutta.Five strains were kindly forwarded by Dr. D. Barua, of the School of Tropical Medicine, Calcutta, and seven strains were isolated in our laboratory.The strains were derived from patients residing at widely separated areas in Calcutta and Howrah.Haemolysis Test.-To a 24-hour culture of the vibrio strain in nutrient broth at pH 7.4 was added an equal volume of 1 % sheep erythrocyte suspension.Readings were taken after two hours' incubation at 370 C. and then overnight in the refrigerator.Haemagglutination Test.-This was done according to the method described by Finkelstein and Mukerjee (1963).Tests of Susceptibility to Cholera Typing Phages.-Thetest was carried out with the four groups of cholera typing phages as described earlier (Mukerjee et al., 1957).In our earlier studies the group IV cholera phages were found to have no lytic affinity for El Tor strains.However, further observations with larger series of strains have shown that when used undi- luted this phage may lyse some of the V. el tor strains to varying degrees ; but at the critical test-dilution for Vibrio cholerae, strains of El Tor vibrios are universally resistant to lysis by it.For differcntiation between the two O-group I vibrios all the four cholera typing phages were used at the critical test dilutions for V. cholerae.Besides the group IV phages, group II phages are also not lytic for any of the V. el tor strains.Polymyxin Sensitivity Test.-This test was carried out according to the method of Gan and Tija (1963), using " bactosensitivity" disks (Difco Laboratories) containing 50 units of polymyxin B per disk.Soda-serum-agglutination Test.-The technique described by Tanamal (1959) was used.El Tor Phage-typing.-Thiswas carried out according to our tentative scheme (Mukerjee, 1964a) with the help of five phages isolated from lysogenic strains of V. el tor.
Lineage switch in childhood acute leukemia: An unusual event with poor outcome
Authors: Jorge G. Rossi, Andrea R. Bernasconi, Cristina N. Alonso, Patricia L. Rubio, Marta S. Gallego, Carolina A. Carrara, Myriam R. Guitter, Silvia Eandi Eberle, Mariela Cocce, Pedro A. Zubizarreta, María S. Felice
Journal: American Journal of Hematology (2012)

Although rarely, switches between lymphoid and myeloid lineages may occur during treatment of acute leukemias (AL). Correct diagnosis relies upon confirmation by immunophenotyping of the lineage conversion and certification that the same cytogenetic/molecular alterations remain despite the phenotypic changes. From a total of 1,482 AL pediatric patients, we report nine cases of lineage conversion (0.6%), seven from lymphoid (four Pro-B, two Pre-B, one Common) to myelo-monocytic, and two from myeloid (bilineal, with myeloid predominance) to Pro-B. Eight patients were infants. Switches were suggested by morphology and confirmed with a median of 15 days (range: 8 days-6 months) from initiation of therapy. Of note, in five cases switches occurred before day 15. Stability of the clonal abnormalities was assessed by cytogenetic, RT-PCR/Ig-TCR rearrangement studies in all patients. Abnormalities in 11q23/MLL gene were detected in seven cases. Treatment schedules were ALL (two pts), Interfant-99 (five pts) and AML (two pts) protocols. Despite changing chemotherapy according to the new lineage, all patients died. Our findings support the association of lineage switches with MLL gene alterations and the involvement of a common lymphoid B-myeloid precursor. New therapies should be designed to address these rare cases. Possible mechanisms implicated are discussed.
Health of cohort of heroin addicts from London clinics: 22 year follow up
Authors: C. Tobutt, E. Oppenheimer, R. Laranjeira
Journal: BMJ (1996)

Data are limited on the long term health consequences of drug misuse in the United Kingdom. In the United States results from longitudinal studies differ over whether heroin addicts misuse alcohol after they stop misusing opiates.1 2 We recently followed up a cohort of heroin addicts after 22 years and found that 43 (34%) of the original sample of 128 had died3; in this report we describe the health of the remainder.

The original sample in 1969 was a random one in three sample of (prescribed) heroin injectors attending 13 of the 15 London drug clinics. This group was followed up in 1976-7.4 The tracing methods for the 22 year follow up, begun in 1991, have been described.3 The personal interviews were partly structured and covered prescribed and illicit drug use, …
Prohibitin Attenuates Colitis-Associated Tumorigenesis in Mice by Modulating p53 and STAT3 Apoptotic Responses
Authors: Arwa S. Kathiria, William L. Neumann, Jennifer Rhees, Erin Hotchkiss, Yulan Cheng, Robert M. Genta, Stephen J. Meltzer, Rhonda F. Souza, Arianne L. Theiss
Journal: Cancer Research (2012)

Abstract Although inflammatory bowel disease is associated with higher risk of colorectal cancer, the precise pathogenic mechanisms underlying this association are not completely understood. Prohibitin 1 (PHB), a protein implicated in the regulation of proliferation, apoptosis, and transcription, is decreased in intestinal inflammation. In this study, we have established a key function for PHB in mediating colitis-associated cancer. Wild-type and transgenic (Tg) mice specifically overexpressing PHB in intestinal epithelial cells were subjected to a classical two-stage protocol of colitis-associated carcinogenesis. In addition, wild-type and p53 null human cell models were used to assess PHB interaction with STAT3 and p53. Wild-type mice exhibited decreased mucosal PHB protein expression during colitis-associated carcinogenesis. Tg mice exhibited decreased susceptibility in a manner associated with increased apoptosis, p53, Bax, and Bad expression plus decreased Bcl-xL and Bcl-2 expression. PHB overexpression in wild-type but not p53 null human cells increased expression of Bax, Bad, and caspase-3 cleavage. In wild-type p53 cells, PHB overexpression decreased basal and interleukin-6-induced STAT3 activation and expression of the STAT3 responsive genes Bcl-xL and Bcl-2. PHB coimmunoprecipitated with phospho-STAT3 in addition to p53 in cultured cell lysates and colon mucosa. This is the first study to show interaction between PHB and STAT3 in vivo. In summary, our findings suggest that PHB protects against colitis-associated cancer by modulating p53- and STAT3-mediated apoptosis. Modulation of PHB expression in intestinal epithelial cells may offer a potential therapeutic approach to prevent colitis-associated carcinogenesis. Cancer Res; 72(22); 5778–89. ©2012 AACR.
Edinburgh emergency asthma admission service.
Authors: G K Crompton, I W Grant
Journal: BMJ (1975)

In December 1968 an emergency service was set up in Edinburgh to enable patients with severe asthma to be admitted to hospital without delay. Up to 31 August 1975, 82 such patients had been admitted on 162 occasions, on 116 without the intervention of a general practitioner. The service is extended to patients particularly at risk of developing fatal asthma, and since it began no patient has died from asthma outside hospital. One patient, however, died from tension pneumothorax that developed after admission. We believe that similar services should be available throughout Britain.
BMA settles in race discrimination cases
Authors: Owen Dyer
Journal: BMJ (2004)

The BMA has paid £130 000 to settle racial discrimination claims brought jointly by five Indian doctors who say the organisation unfairly refused to back them in discrimination litigation against their employers. The settlement was reached hours before a Manchester employment trial was to begin hearing the case.

The five doctors will share the award, but, like the BMA, they will have to bear their own legal costs. The details of individual settlements remain confidential. The five are Fahtima Farook from Cardiff, Sheedhar Vasdo Vaidya from the East Midlands, Kumar Ghosh from Manchester, Vijay …
Medical Aspects of Ambulance Design
Authors: R. Snook
Journal: BMJ (1972)

Various observations have shown that the interior layout of many ambulances leaves much to be desired. The lighting levels are inadequate, heat loss could be prevented, vehicle identification and passage through traffic could be improved, and measurable differences exist between the ride characteristics of commercially available ambulances, a prototype purpose-built ambulance, and a private car. Moreover the condition of some patients may be affected by the motion of the vehicle either directly or indirectly. Even though they form a small percentage of the total number carried, they represent a very considerable financial risk. A personally conducted survey of ambulance chief officers showed a deep interest and involvement in the upgrading of the service with a general dissatisfaction with many of the vehicles currently available. Hence there is a market for the purpose-built ambulance, which would benefit the patient and the ambulanceman alike. The inadequacies of many vehicles currently in use as ambulances have been shown to work against the interests of the patient requiring life support treatment, and it is suggested that this warrants urgent attention and action. A more extensive research project involving medical observations on the supine sick and injured, attendant task performance, and instrumentation analysis of linear and angular vehicle motions should enable the harmful effects of ride motion to be identified. None of these investigations, however, will be of any value unless they are used in developing future ambulances. Such development must also parallel an increase in the awareness of the importance of ambulance design and its relation to the increased comfort and chance of survival of the patients carried.
Transient urinary tract dilatation associated with hypokalaemia.
Authors: R R Ghose, H R Jivan
Journal: BMJ (1985)

The association of neonatal hypocalcaemia with hypovitaminosis D in Asians was described 14 years ago, and it is tragic that we still see pregnancy related complications of hypovitaminosis D: neonatal secondary hyperparathyroidism4 and maternal pathological fractures.5We are grateful to Sharon Houlder for measuring 25-hydroxyvitamin D; to Dr M Thomas for assaying parathyroid hormone; and to Pamela Dale for preparing the manuscript.
Airways Obstruction and the Risk for Lung Cancer
Authors: Melvyn S. Tockman, Nicholas R. Anthonisen, Elizabeth C. Wright, Michele G. Donithan
Journal: Annals of Internal Medicine (1987)

The presence of airways obstruction identify middle-aged male smokers at increased risk for lung cancer. This hypothesis was tested in a sample of patients with moderate to severe obstruction from the Intermittent Positive Pressure Breathing Trial and a sample of patients with no obstruction to moderate obstruction from the Johns Hopkins Lung Project, all of whom were followed for the development of lung cancer. On follow-up, the risk of developing lung cancer was found to be associated with entry values for age, smoking, and ventilatory status by linear, proportional hazard, and log-linear adjustment techniques. Among cigarette smokers, the presence of airways obstruction was more of an indicator for the subsequent development of lung cancer than was age or the level of smoking. The risk for lung cancer also increased in proportion to the degree of airways obstruction. These data suggest that smokers with ventilatory obstruction are at greater risk for lung cancer than are smokers without obstruction.
Drug companies in US spent millions pushing for weight loss drug approvals, investigative report finds
Authors: M. McCarthy
Journal: BMJ (2015)

Since 2010, makers of diet drugs have spent more than $60m (£40m; €56m) on lobbying, medical society sponsorships, and payments to physicians to get their weight loss drugs to the market, says a joint investigative report by the medical news website MedPage Today and the Milwaukee Journal Sentinel .1

The size of the market is considerable: the US Centers for Disease Control and Prevention has estimated that over a third (34.9%; 78.6 million) of US adults are obese. The new report alleged that many efforts by drug companies have been aimed at pressuring the US Food and Drug …
Electrocardiographic Changes in a Case of Left Ventricular and Septal Hypertrophy Resembling Anterior Myocardial Infarction
Authors: AARON BURLAMAQUI BENCHIMOL, PAUL SCHLESINGER
Journal: Circulation (1950)

In certain instances of left ventricular hypertrophy, deep Q waves observed in the precordial electrocardiogram may resemble those of anterior myocardial infarction. Such a case is reported in a patient with syphilitic aortic insufficiency. Pathologic examination ruled out the diagnosis of infarction and revealed marked hypertrophy of left ventricular wall and the interventricular septum. The latter was of unusual degree and was probably responsible for the presence of large Q waves in precorldial leads representing, the normal activation of the upper part of the interventricular septum which in cases of septal hypertrophy presumably originates a vector of greater magnitude.
Prevention of Coronary Artery Heart Disease
Authors: Meyer Texon
Journal: JAMA (1971)

To the Editor.—  Your editorial ( 215 :1813, 1971) Prevention of CHD: The Fat's in the Fire compels me to point out the fallacies that are both expressed and implied.  Dietary and lipid studies in relation to heart disease and atherosclerosis can result only in statistical associations, and statistical associations do not constitute scientific proof of a causative mechanism. Similarly, epidemiological and enviroimental studies can only yield statistical associations. A primary causative mechanism for atherosclerosis must be a common denominator operating in all cases so that it determines its presence as well as its absence in any given case.  Data from human specimens, model hydraulic systems, and the experimental production of hemodynamically induced arterial lesions in dogs support the hemodynamic concept of atherosclerosis ( 194 :1226, 1965). The biological response of blood vessels and mechanical factors are integrated by the hemodynamic concept of atherosclerosis which considers the effect of the laws of
Prospective Phase II Study of Gefitinib for Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer With Epidermal Growth Factor Receptor Gene Mutations
Authors: Akira Inoue, Takuji Suzuki, Tatsuro Fukuhara, Makoto Maemondo, Yuichiro Kimura, Naoto Morikawa, Hiroshi Watanabe, Yasuo Saijo, Toshihiro Nukiwa
Journal: Journal of Clinical Oncology (2006)

This study was undertaken to investigate the efficacy and the feasibility of gefitinib for chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations.The EGFR gene status in various tumor samples obtained from chemotherapy-naïve advanced NSCLC patients was examined by DNA sequencing of EGFR exons 18 to 23. Patients harboring EGFR mutations received gefitinib (250 mg/d) alone. The response rate, progression-free survival (PFS), and toxicity profile were assessed prospectively.Between June 2004 and October 2005, 75 patients were examined for the EGFR status, and 25 patients (33%) harbored EGFR mutations. EGFR mutations were significantly frequent in females (P < .01) and never or light smokers (P < .001). Sixteen patients with EGFR mutations were enrolled onto the study. The overall response rate in these patients was 75% (95% CI, 54% to 96%), and the disease control rate was 88% (95% CI, 71% to 100%). The median PFS time of these patients was 9.7 months (95% CI, 7.4 to 9.9 months). No life-threatening toxicity was observed.Treatment with gefitinib alone for chemotherapy-naïve NSCLC patients with EGFR mutations could achieve a high efficacy with acceptable toxicity. To assess the proper timing of gefitinib in such patients, a subsequent randomized trial comparing gefitinib with standard chemotherapy is warranted.
Factors predicting inhaled corticosteroid responsiveness in African American patients with asthma
Authors: Wendy Gould, Edward L. Peterson, Gloria Karungi, Amanda Zoratti, John Gaggin, Ghazwan Toma, Shiqing Yan, Albert M. Levin, James J. Yang, Karen Wells, Mingqun Wang, Robert R. Burke, Kenneth Beckman, Danijela Popadic, Susan J. Land, Rajesh Kumar, Max A. Seibold, David E. Lanfear, Esteban G. Burchard, L. Keoki Williams
Journal: Journal of Allergy and Clinical Immunology (2010)