tbuckley/cabot-search huggingface dataset:
Predicting drug interactions using cultured human hepatocytes
Authors: Kenneth S. Lown, Paul B. Watkins
Journal: Hepatology (1991)

In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA. We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it. In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to “reproduce” in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA. Our results were in close agreement with the clinical reports. Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 μM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media. Conversely, these cultures exhibited erythromycin concentrationdependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 μM erythromycin. In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 μM) as expected, this macrolide being a specific substrate of P-450IIIA. Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity. Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors. Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine. Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocryptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone. Finally cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprime, amphotericine B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.
In Vitro Evidence for Cellular Hypersensitivity to Glomerular-Basement-Membrane Antigens in Human Glomerulonephritis
Authors: Ross E. Rocklin, Edmund J. Lewis, John R. David
Journal: New England Journal of Medicine (1970)

The macrophage inhibition assay was used to study in vitro the reactivity of human blood lymphocytes to a soluble preparation of glomerular-basement-membrane antigen. Twenty-one patients with various forms of renal disease, 10 with diseases not affecting the kidney and 13 normal subjects were evaluated. The lymphocytes from six of 14 patients with glomerulonephritis exhibited cellular hypersensitivity to glomerular-basement-membrane antigen, whereas with one exception, lymphocytes from the other subjects failed to do so. Immunofluorescence studies on four of the six patients with positive macrophage inhibition tests revealed that three had concomitant evidence of antibodies directed against the glomerular basement membrane. These results indicate that cellular hypersensitivity is present in certain forms of human glomerulonephritis, and suggest that sensitized lymphocytes may be involved in the pathogenesis of renal damage in this disease.
Manpower Salvage with Surgery in Pulmonary Tuberculosis
Authors: David E. Thomas
Journal: JAMA (1960)

Excisional surgery for pulmonary tuberculosis was evaluated from the standpoint of work rehabilitation on almost 400 patients operated on during the period 1953 through 1957. The selection and preoperative preparation of patients is explained and the ancillary diagnostic benefits of thoracotomy are mentioned. This study revealed that in 97% of the patients followed tuberculosis has remained inactive, and that 370 of 378 patients whose tuberculosis has remained inactive were capable of employment. The salvage of military manpower for return to duty was significant, resulting in monetary savings by avoidance of pensions. There were three operative deaths within 30 days of surgery, one patient was never cured of her disease, two patients have died of tuberculosis, and there have been two other recurrences.
Abstract P1-01-32: Usefulness of Clinical Exploration, Ultrasound and MRI for the Assessment of Axillary Lymph Nodes Status Previous to the Performance of Sentinel Node Depends on Tumor Molecular Subtype
Authors: D Sabadell, MDM Vernet-Tomas, C Colome, A Rodriguez-Arana, F Plancarte, R. Carreras
Journal: Cancer Research (2010)

Abstract Introduction: A high detection of positive lymph nodes previous to the surgical procedure lowers the probability of a false negative sentinel node. The sensibility and specificity of different imaging methods could depend on the molecular features of each tumor Objective: The aim of this study was to study sensibility and specificity of clinical exploration, ultrasound and MRI to assess the status of axilar lymph nodes in different molecular subtypes. Material and Methods: we retrospectively reviewed T1 and T2 breast cancers not candidate for neoadjuvant chemotherapy, treated in our breast cancer unit from September 2008 to May 2010. Data on clinical exploration (CE), axillary ultrasound (AU) and MRI were reviewed for each patient. The pathology exam of the surgical specimen (sentinel node or lymph node dissection) was reviewed for each patient and sensibility and specificity were calculated for each exploration method. Sensibility and specificity were also calculated separately considering five different molecular subtypes: Tubular A, Tubular B, Triple negative tumors, cerbB2 positive tumors and lobular tumors. Results: 290 patients with T1 and T2 breast cancer were included in the study. Sensibility for CE was 26.76% and specificity 91%. Sensibility for AU was 38.46% and specificity 86.81%. Sensibility for MRI was 44.06% and specificity 86.02%. For Tubular A tumors, the highest sensibility was for MRI (40%) and the best specificity for CE (91.35%). For Tubular B tumors, the highest sensibility was for CE (33.33%) and the highest specificity for AU (100%). For Triple negative tumors, the highest sensibility was for MRI (100%) and the highest specificity for CE (89.47%). For cerbB2 tumors, the highest sensibility was for MRI (75%) and the highest specificity was for CE (100%). For Lobular tumors, the highest sensibility and specificity were for AU (50% and 93.33%, respectively). Conclusion: MRI is the exploration with a higher sensibility to assess the preoperative status of axillary lymph nodes considering all the tumors together and in Tubular A, Triple negative and cerbB2 positive tumors. MRI sensibility is specially high in Triple negative and cerbB2 positive tumors. When choosing different imaging methods to assess axilar status, molecular subtype should be considered. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-32.
Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis
Authors: Wendy C. Moore, Annette T. Hastie, Xingnan Li, Huashi Li, William W. Busse, Nizar N. Jarjour, Sally E. Wenzel, Stephen P. Peters, Deborah A. Meyers, Eugene R. Bleecker
Journal: Journal of Allergy and Clinical Immunology (2013)
Uncomplicated HL-A Matched Sibling Bone Marrow Graft for Combined Immune Deficiency
Authors: M. Yamamura, R. C. F. Newton, D. C. O. James, J. G. Humble, L. J. Butler, J. R. Hobbs
Journal: BMJ (1972)

When an apparently identical HL-A donor can be found and satisfactorily checked by the mixed lymphocyte reaction, it is worth attempting simple bone marrow grafting in a patient with combined immune deficiency syndrome who otherwise would die. Immunocompetence was given in this way to a baby girl by her 4-year-old brother and was confirmed by the presence of Y-chromosome in most of the transforming lymphocytes. IgA was late to emerge, presumably owing to the immaturity for IgA of the donor's bone marrow.
Abstract P6-11-13: <i>In vitro</i> antineoplastic evaluation of rationally designed naphtoquinone-derived drugs in triple-negative breast cancer cell line
Authors: KP Madeira, RD Daltoé, AL Herlinger, IS Guimarães, Filho JF Allochio, SF Teixeira, IC Valadão, S Greco, LBA Rangel
Journal: Cancer Research (2012)

Abstract Background: Breast cancer (BC) comprises multiple diseases harboring different genetic alterations, which subtypes respond differently to treatment, and are associated to distinct clinical outcomes. Likewise, triple negative breast cancer (TNBCs) are a heterogeneous subgroup of BC, immunophenotypically negative for estrogen and progesterone receptor, and HER2, that account for 10–15% of all invasive BC, affecting mostly African-American and Hispanic pre-menopausal women. Considering that TNBC have poor prognosis, and cannot be effectively treated with current targeted therapies, the discovery of new treatment options is imperative. Methods: Novel naphtoquinone-derived drugs were rationally designed to act through multiple pathways aiming the avoidance of drug-resistant phenotype acquisition by tumor cells, and were synthesized following high efficiency and low cost method. Drugs antineoplastic efficacy (AE) was accessed in claudin-low TNBC cell line, MDA-MB-231, through the evaluation of cellular metabolic viability (CMV) (MTT method). Drugs structures are protected by patent. Cells were cultured in RPMI media supplemented with 10% (v/v) FBS and antibiotics until subconfluence; then, 1.5×105 cells/well were subcultured for 72h prior to treatment with drugs (10−4, 10−5, 10−6, 10−7, and 10−8 M). After 24h, CMV was assessed. Experiments in which the lineage was treated with cisplatin, doxorubicin or paclitaxel were run in parallel. The mean and standard-deviation of the absorbancies were used to calculate CMV and drugs IC50 (PrismaGraphPad version 5.1). Findings: We screened the AE of 43 novel naftoquinones-derived drugs in MDA-MB-231 lineage; seven have decreased its CMV by, at least, 50%, as: PIC1 (IC50 1.15×10−4M; CMV decrease of 50%); PIC6 (IC50 4.24×10−5M; CMV decrease of 70%); PIC10 (IC50 5.07×10−5M; CMV decrease of 70%); PIC 20 (IC50 1.38×10−5M; CMV decrease of 90%); PIC21 (IC50 5.00×10−5M; CMV decrease of 70%); S5 (IC50 7.26×10−5M; CMV decrease of 60%); M20 (IC50 7.94×10−5M; CMV decrease of 60%). Their AE was significantly higher than that of cisplatin (IC50 1.56×10−4M; CMV decrease &amp;lt; 10%), doxorubicin (IC50 1.76×10−4M; CMV decrease of 38%), and paclitaxel (IC50 5.05×10−7M; CMV decrease of 20%). Interpretation: Altogether, our results present potential novel antineoplastic drugs to treat TNBC from a panel of in house rationally designed naftoquinones-derived compounds, developing an innovative and economically viable project. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-11-13.
UK cosmetic surgeons lack training, says report
Authors: Z. Kmietowicz
Journal: BMJ (2010)

<h3>Introduction</h3> The Centre de Recherches Médicales de Lambaréné (CERMEL) in Gabon, member of the ‘VSV-EBola CONsortium’ (VEBCON), evaluated safety and immunogenicity of the rVSV∆G-ZEBOV-GP vaccine in African volunteers from an area with previous Ebola outbreaks before its use during the last outbreak in West Africa. <h3>Methods</h3> From November 2014 to April 2015 we performed an open-label, dose escalation phase 1 trial to assess safety, side-effect profile, and immunogenicity of rVSV-ZEBOV. A total of 115 healthy adults both male and non-pregnant or lactating female volunteers aged 18–50 years old living in Lambaréné (Gabon) were included. Participants were allocated to five vaccine dose groups: 3×10<sup>3</sup> PFU (n=20), 3×10<sup>4</sup> PFU (n=20), 3×10<sup>5</sup> PFU (n=20), 3×10<sup>6</sup> PFU (n=39) and 2×10<sup>7</sup> PFU (n=16). Here, we present data on adverse events (AE) and serious adverse events (SAE) between days 180 and 365 after vaccine injection (Day 0). <h3>Results</h3> From Month six to Month 12, the proportion of volunteers with AE as well as number and grade of AEs per volunteer were similar in the five groups. A higher total number of events occurred in the cohort 3×10<sup>6</sup> PFU, the largest group. Most symptoms were mild to moderate. No clinically significant laboratory changes were observed. Three events - two episodes of <i>P. falciparum</i> malaria and one snake bite - were graded as serious, because they required hospitalizations. Both SAE were judged as non-related to the vaccine and resolved without sequelae. None of the adverse events was related to rVSV-ZEBOV vaccine. <h3>Conclusions</h3> Our results confirmed an acceptable profile of safety and tolerability of rVSV-ZEBOV up to 12 months of follow-up. In order to investigate possible late-stage safety signals follow-up period of the study was extended to five years. Integrating data (assessment until 60 months) from all the VEBCON study sites is the next key step allowing a final conclusion about safety of rVSV-ZEBOV. The trial was registered on the Pan African Clinical Trials Network website with the number PACTR201411000919191
New bronchodilator aerosol preparations.
Authors: I W Grant
Journal: BMJ (1970)

hysteria or to altered xnedical perception in the community.Their erroneous conclusions about this illness may impair future inves- tigations of similar outbreaks.It is apparent that the authors failed to do their homework, and demonstrated a surprising lack of information about the principles of epidemiology and of psychia- try.Had they reviewed the literature on the
Extramedullary Hematopoiesis Within Paravertebral Masses Demonstrating Prominent Sestamibi and Thallium Uptake
Authors: Ryan D. Niederkohr, Edison Chiu, Kenneth R. K. Nielsen, Margaret Maclean
Journal: Clinical Nuclear Medicine (2009)

As a compensatory mechanism for bone marrow dysfunction, patients with severe anemia (of any etiology) may develop sites of extramedullary hematopoiesis (EMH). We present the case of a 67-year-old woman with thalassemia intermedia who underwent dual isotope myocardial perfusion imaging showing prominent sestamibi and thallium uptake within large paravertebral masses which were biopsy-proven to represent EMH. Although the precise mechanism of thallium or sestamibi uptake within sites of EMH is not documented, it might be speculated that the increased metabolic activity (and associated increased perfusion requirements) associated with vigorous hematopoiesis (medullary or extramedullary) in anemic states would result in increased deposition of perfusion imaging agents such as thallium or sestamibi. This case emphasizes the importance of careful inspection of raw images for extracardiac findings which may be of clinical relevance. In addition, this case highlights the potential utility of reconstructing the raw/cine SPECT imaging set into transaxial slices for direct correlation with other cross-sectional imaging modalities (eg, CT/MRI).
Trichinosis — Preventable Yet Still with Us
Authors: Harry Most
Journal: New England Journal of Medicine (1978)

TRICHINOSIS as a clinical disease now occurs very infrequently in this country, and it is not surprising that physicians may not recognize it. For example, in a recent small epidemic involving 13 persons who acquired their infection while passengers on a cruise ship and subsequently became ill in various areas of the United States, in only four was the diagnosis made by their physicians; in the others the physicians were not aware of the diagnosis of trichinosis until informed by the Public Health Service, which had conducted a clinical and serologic survey of the infected passengers. Of interest in this . . .
Regulatory T cell response correlates with the severity of human hantavirus infection
Authors: Tuisku-Tuulia Koivula, Anni Tuulasvaara, Iivo Hetemäki, Satu Marjo Mäkelä, Jukka Mustonen, Tarja Sironen, Antti Vaheri, T. Petteri Arstila
Journal: Journal of Infection (2013)
Relation of the Duct of Santorini to the Pathogenesis of Duodenal Ulcer
Authors: Henry Reich
Journal: New England Journal of Medicine (1963)

THOUGH most emphasis is placed on hypersecretion of hydrochloric acid as a causative agent, it is also known that the absence of bile and pancreatic juice in the duodenum may be a factor in the development of duodenal ulcer.1 2 3 4 5 Surgical procedures today aim mainly at reducing this acid secretion. Medical management also depends upon the reduction of gastric hyperacidity by the administration of antacids as well as secretory depressants. The latter drugs of the belladonna group reduce gastric acidity by depressing vagus activity, but in addition they also reduce smooth-muscle spasm. This spasm is usually thought of as pylorospasm and . . .
Simple Method for Determining Isoniazid Acetylator Phenotype
Authors: D. W. Russell
Journal: BMJ (1970)

Methods have been developed for estimating acetylisoniazid and isoniazid in urine without a spectrophotometer. In experiments with volunteers the ratio of acetylisoniazid to isoniazid in urine samples collected the morning after three spaced oral doses each of 100 mg. was bimodally distributed.
Dicumarol, Coumadin, Marcumar and Tromexan
Authors: JORGE ESCUDERO, ELLEN MCDEVITT, IRVING S. WRIGHT
Journal: Circulation (1959)

There is considerable interest and some difference of opinion about the relative clinical usefulness of many oral anticoagulant agents. In this study the more commonly used agents are evaluated with respect to their action on the clotting process as measured by thrombelastography. This test does not necessarily provide an evaluation of all aspects of the clinical action of an anticoagulant.
Spontaneous persistent pseudomembranous colitis related to Clostridium difficile in ischaemic bowel disease.
Authors: A Wu
Journal: BMJ (1982)

Psittacosis presenting withReiter's syndrome Polyarthritis is a common feature of chlamydial respiratory infection in many animal species,' but this association, while recognised, is rarely reported in man.2We report such a case, which presented as Reiter's syndrome.
Chimeric CD19 antibody mediates cytotoxic activity against leukemic blasts with effector cells from pediatric patients who received T-cell–depleted allografts
Authors: Peter Lang, Karin Barbin, Tobias Feuchtinger, Johann Greil, Matthias Peipp, Susan J. Zunino, Matthias Pfeiffer, Rupert Handgretinger, Dietrich Niethammer, Georg H. Fey
Journal: Blood (2004)

Relapse is a major problem after transplantation in children with acute B-lineage leukemias, and new therapies are needed to increase graft-versus-leukemia (GvL) effects without inducing graft-versus-host disease (GvHD). Here, we studied the ability of effector cells recovered from patients after transplantation with positive-selected stem cells from alternative donors to induce antibody-dependent cellular cytotoxicity (ADCC). For this purpose, a chimeric CD19 antibody, CD19-4G7chim, was generated. This antibody efficiently mediated ADCC against primary acute lymphoblastic leukemia (ALL) blasts by using purified natural killer (NK) cells from healthy donors or mononuclear cells from patients as effector cells. Increased lysis was obtained after stimulation of effector cells with interleukin-2 (IL-2). ADCC was not prevented by inhibitory effects mediated by HLA class I. We propose that treatment with chimeric CD19 antibodies leading to ADCC by donor-derived NK cells may become a therapeutic option for the post-transplantation treatment of minimal residual B-lineage ALLs.
The Medical Therapist
Authors: L. C. Weaver
Journal: JAMA (1969)

To the Editor:—  We have read with much interest, The Creation of the Medical Therapist, by Paul S. Derian, MD, ( 206 :2524, 1968). It would be interesting to know the curriculum envisioned for this new health professional by Dr. Derian. One could speculate that it just might be similar to the curricula found in some of the more progressive colleges of pharmacy. Pharmacy students have long been well-trained in the area of drugs as chemicals and pharmacological agents. However, they have had little experience in the actual therapeutic application of drugs in the clinical environment. We have involved our students for the past two years in a patient-oriented program in the wards of the university hospitals and affiliates. We are convinced that in the future many of our graduates could serve the role of Dr. Derian's medical therapist, as our clinical program grows in sophistication and more time is spent
Multimodality Imaging of Coiled‐Coil Mediated Self‐Assembly in a “Drug‐Free” Therapeutic System
Authors: Rui Zhang, Jiyuan Yang, Te‐Wei Chu, Jonathan M. Hartley, Jindřich Kopeček
Journal: Advanced Healthcare Materials (2015)

Two complementary coiled‐coil peptides CCE/CCK are used to develop a “drug free” therapeutic system, which can specifically kill cancer cells without a drug. CCE is attached to the Fab′ fragment of anti‐CD20 1F5 antibody (Fab′‐CCE), and CCK is conjugated in multiple grafts to poly[ N ‐(2‐hydroxypropyl)methacrylamide] (P‐(CCK) x ). Two conjugates are consecutively administered: First, Fab′‐CCE coats peptide CCE at CD20 antigen of lymphoma cell surface; second, CCE/CCK biorecognition between Fab′‐CCE and P‐(CCK) x leads to coiled‐coil formation, CD20 crosslinking, membrane reorganization, and ultimately cell apoptosis. To prove that two conjugates can assemble at cell surface, multiple fluorescence imaging studies are performed, including 2‐channel FMT, 3D confocal microscopy, and 4‐color FACS. Confocal microscopy shows colocalization of two fluorescently labeled conjugates on non‐Hodgkin's lymphoma (NHL) Raji cell surface, indicating “two‐step” targeting specificity. The fluorescent images also reveal that these two conjugates can disrupt normal membrane lipid distribution and form lipid raft clusters, leading to cancer cell apoptosis. This “two‐step” biorecognition capacity is further demonstrated in a NHL xenograft model, using fluorescent images at whole‐body, tissue and cell levels. It is also found that delaying injection of P‐(CCK) x can significantly enhance targeting efficacy. This high‐specificity therapeutics provide a safe option to treat NHL and other B cell malignancies.
European Perspectives on Therapeutic Cloning
Authors: Kathinka Evers
Journal: New England Journal of Medicine (2002)

Although recent advances in stem-cell research hold promise for therapeutic use, this promise has been accompanied by social, political, economic, legal, religious, and ethical questions. These questions have touched a raw nerve, and numerous laws and regulations have been implemented or are being considered in order to control the use and spread of this new technology. The legal situation is particularly complex in Europe, where each country is governed through both national legislation and the international European legislation passed by the European Union. Since there are deep social and political disparities among countries within the union that stem in part . . .