tbuckley/cabot-search huggingface dataset:
P3-14-17: Paclitaxel, Carboplatin, and Trastuzumab in a Neoadjuvant Regimen for HER2−Positive Breast Cancer: The TRAIN Study.
Authors: GS Sonke, IA Mandjes, M Holtkamp, M Schot, HM Oosterkamp, J Wesseling, Peeters M-JT Vrancken, S Rodenhuis, SC Linn
Journal: Cancer Research (2011)

Abstract Background: Treatment with trastuzumab is highly active in HER2 positive breast cancer, although cardiotoxicity is a well known side effect. The cardiotoxicity of trastuzumab may be aggravated by combined treatment with anthracyclines. Consequently, treatment with trastuzumab is often delayed pending the administration of anthracyclines. Both in vitro and in vivo data suggest that trastuzumab synergizes with a range of chemotherapeutic drugs, including taxoid drugs and carboplatin. In addition, prolonged pre-operative treatment leads to higher pathologic complete remission (pCR) rates. We report the results of a fase 2 trial integrating trastuzumab at the start of a non-anthracycline containing weekly paclitaxel-carboplatin based neo-adjuvant chemotherapy regimen in HER2−positive breast cancer. Patients and methods: One-hundred patients with stage II or III breast cancer, including inflammatory disease, with HER2 overexpression (immunohistochemistry and/or in situ hybridization) were treated with 24 weekly administrations of paclitaxel 70 mg/m2, carboplatin AUC=3 mg.ml-1.min, and trastuzumab 2 mg/kg (loading dose 4 mg/kg). In cycles 7, 8, 15, 16, 23, and 24 only trastuzumab was given. The primary end point was pathologic complete response (pCR) in both breast and axilla. The trial was preceded by an initial pilot cohort of 55 patients treated with the same regimen. Results: Final efficacy and safety results of all patients included in the phase 2 trial will be reported at the meeting. In the pilot cohort of 55 similarly treated patients, 33% had stage II disease, 69% was clinically node positive, and 49% was ER and PgR negative. Twenty-four patients (41%) had a pCR in breast and lymph nodes. pCR in ER negative patients was 67%, pCR in ER positive patients was 21%. The most commonly reported grade 3/4 toxicities were neutropenia (30%) and thrombocytopenia (27%). Dose reduction was required in 24% of the patients. Grade 3/4 left ventricular systolic dysfunction was not observed. Conclusion: A weekly carboplatin-paclitaxel-trastuzumab neo-adjuvant regimen is highly active in HER2 positive breast cancer with a good safety profile. A subsequent multicenter phase 3 trial will compare this regimen to a similar 16 week regimen preceded by 4 cycles of anthracyclines plus cyclophosphamide. The study protocol was developed at the joint ECCO-AACR-EORTC-ESMO Workshop on Methods in Clinical Cancer Research in Flims, Switserland. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-17.
An Association Between the Rheumatic Diseases and the Reticuloses
Authors: A. J. Lea
Journal: Annals of the Rheumatic Diseases (1964)

OBJECTIVE: Intraarticular osteoid osteoma is uncommon and presents diagnostic difficulties, which are important for both rheumatologists and orthopedic surgeons. Clinical symptoms, imaging procedures, differential diagnostic problems, and treatment results of intraarticular as compared with extraarticular osteoma are analyzed in this retrospective study. METHODS: Nineteen patients with intraarticular osteoid osteomas (Group A), with a mean followup period of 34 months, are compared with 15 others with extraarticular lesions (Group B). RESULTS: Nine intraarticular tumors were located in the hip, 3 in the elbow, 6 in the ankle, and one in the first metatarsal head. The nonspecific symptoms in Group A, such as chronic synovitis, decreased range of motion, joint effusion, contractures, and lack of the intense perifocal sclerotic margin on radiographs, led to significant delay in diagnosis (on average 26.6 mo in Group A, 8.5 mo in Group B). The extreme variety of previous diagnoses at referral reflect the problems of differential diagnosis. A detectable nidus is often absent on conventional radiograph. Bone scintigraphy is unspecific and often fails to visualize the nidus. Computed tomography scans were accurate in two-thirds of the intraarticular and in 90% of extraarticular cases. Magnetic resonance image findings, although sometimes controversial, provided essential additional information for the correct diagnosis and therapy. CONCLUSION: Clinical symptoms and imaging signs of intraarticular osteoid osteomas were significantly different from the classical hallmarks of extraarticular lesions. The 10% intraarticular occurrence of osteoid osteomas in this series is not as rare as some investigators suggest. The radiological and clinical findings are uncharacteristic and misleading, and the lesions are difficult to identify. Careful search for history data, such as nocturnal pain and positive salicylate test, in addition to extensive imaging procedures, led to the correct diagnosis prior to surgery in two-thirds of our patients with intraarticular osteoid osteomas.
The 14.6 kd rubber elongation factor (Hev b 1) and 24 kd (Hev b 3) rubber particle proteins are recognized by IgE from patients with spina bifida and latex allergy
Authors: Hoong Yeet Yeang, Kay Fong Cheong, Elumalai Sunderasan, Samsidar Hamzah, Nyu Ping Chewa, Sharifah Hamidb, Robert G. Hamilton, Mary Jane Cardosa
Journal: Journal of Allergy and Clinical Immunology (1996)

Two major water-insoluble proteins are located on the surface of rubber particles in Hevea brasiliensis latex. A 14.6 kd protein (Hev b 1), found mainly on large rubber particles (>350 nm in diameter), and a 24 kd protein (Hev b 3), found mainly on small rubber particles (average diameter, 70 nm), are recognized by IgE from patients with spina bifida and latex allergy. Although Hev b 1 (also called the rubber elongation factor [REF]) has previously been reported as a major latex allergen, this conclusion has been disputed on the basis of results from other studies. The allergenicity of Hev b 1 is verified in this study by testing the recombinant protein generated from its gene. Because allergenicity is confined to patients with spina bifida and not observed in adults sensitive to latex, it is not a major latex allergen. The identification of Hev b 3 as another allergen originating from rubber particles is confirmed by immunogold labeling and electron microscopy. Observations with the monoclonal antibody USM/RC2 developed against Hev b 3 show that the protein has a tendency to fragment into several polypeptides of lower molecular weight (from 24 kd to about 5 kd) when stored at −20° C. There is also indication of protein aggregation from the appearance of proteins with molecular weights greater than 24 kd. Fragmentation of Hev b 3 is induced immediately on he addition of latex B-serum, which is normally compartmentalized in the lutoids in fresh latex. In the preparation of ammoniated latex (used for the manufacture of latex products), the lutoids are ruptured, and the released B-serum reacts with Hev b 3 on the rubber particles to give rise to an array of low molecular weight polypeptides that are allergenic to patients with spina bifida. (J ALLERGY CLIN IMMUNOL 1996;98:628-39.)
Editorial on identifying melanomas in primary care was muddled
Authors: J. Bayley
Journal: BMJ (2012)

Newton-Bishop and Lorigan’s thinking on whether we can improve the identification of melanomas in primary care is muddled and their conclusions are lazy.1 They object to current referral rates for suspected melanoma, despite 91% compliance with referral guidelines, but offer no guidance on what referral rates should be. They give no international comparators to indicate whether UK …
One Giant Leap for Mankind
Authors: J. William Futrell
Journal: JAMA (1973)

<h3>To the Editor.—</h3> The rationale for surgical excision as the optimal treatment of choice for any malignant process is based on the assumption that the lesion originated in a defined area and continues to exist as a localized process for some variable although undeterminable period of time. During this period of localized growth, the potential for dissemination may or may not exist. Prior to the time that metastases do occur, however, the disease is presumably curable by local surgical extirpation and no treatment of the regional lymph nodes is necessary or warranted. When any originally confined cancer has ceased to be a localized process it is still potentially surgically curable provided that (1) the metastases have remained limited to the regional lymph nodes and (2) these nodes are accessible to surgical extirpation. The determination that dissemination has progressed to, but no further than, the local draining nodes is necessary at
Quality of Life Researchers Have New Tool and New Focus on Measurement
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (2008)

More attention to quality of life (QOL) has been on the agenda of oncology groups for at least three decades. Most researchers agree that measuring QOL endpoints, such as pain or physical function, is important because they can affect adherence to treatment and outcome. QOL also matters because of increasing survival times among cancer patients. “If you’re looking at 5- to 10-year survival times, it makes sense to be interested in quality of life,” said Lori Minasian , M.D., who leads the National Cancer Institute Community Oncology and Preventive Trials Research Group. But using QOL endpoints in clinical trials has been challenging. Problems include the extra burden on patients and staff and the related issue of missing data — many people simply do not fi ll out QOL surveys. But the major challenge has been the
Fetal proteinuria in diagnosis of congenital nephrosis detected by raised alpha-fetoprotein in maternal serum.
Authors: H Thom, F D Johnstone, J I Gibson, G B Scott, D W Noble
Journal: BMJ (1977)

High concentrations of alpha-fetoprotein (alpha-FP) were found at 14, 19, and 21 weeks gestation in the serum of a woman with a history of unexplained fetal death in her previous pregnancies. The alpha-FP concentration of the liquor also was high at 21 weeks and the pregnancy was terminated. Though the fetus was macroscopically normal, measurement of albumin, alpha-FP, IgG, and alpha2-macroglobulin in the fetal urine showed a selective proteinuria, and congenital nephrosis was diagnosed after examination of the fetal kidneys by electron microscopy. Possibly some fetuses reported to be "false-positive for neural tube defect" may have had renal lesions of this nature. Examination of fetal urine may be the simplest initial diagnostic procedure in any future case.
RECURRENT PSYCHOTIC EPISODES IN MIDDLE LIFE
Authors: NORMAN R. BERNSTEIN
Journal: American Journal of Psychiatry (1953)

1. A case is reported of a man who had schizophrenic reactions at 37, 41, and 43, and who recovered from each one sufficiently to do complex business and technical work without evidence of disintegration of his personality. 2. His prepsychotic personality was obsessive, compulsive, extraverted, and energetic, and each illness was preceded by definite situational problems. 3. After each illness, the patient went back to handle these same problems more successfully.
Can C-reactive protein predict high risk coronary angiographic findings in patients with non-ST elevation acute coronary syndromes? A large prospective cohort study
Authors: Luis A. Guzman-Cuneo, Jose L.Navarro Estrada, Jose Gabay, Jose Alvarez, Carlos Sztejfman, Carlos Rojas Matas, Alejandra Farras, Ricardo Sarmiento, Jorge Mrad, Oscar Bazzino, Raúl A. De Miguel
Journal: Journal of the American College of Cardiology (2002)
Brachial plexus block. A double-needle technique via the axillary route
Authors: W. Wu
Journal: JAMA (1971)

A new double-needle technique for brachial plexus block via the axillary route has been used in 30 patients. The results have been evaluated against those of a control group in which the classic method for the block was used. Simplicity in performance, high success rate, and a reduced chance of traumatizing the neurovascular tissue stand out as advantages of the new technique.
Abstract 963: Characterizing acquired resistance mechanisms to targeted therapy in FGFR1-amplified lung squamous cell carcinoma.
Authors: Rachel G. Liao, Andrey Sivachenko, Gad Getz, Amit Dutt, Peter S. Hammerman, Matthew Meyerson
Journal: Cancer Research (2013)

Abstract Inhibitors targeting specific genomic alterations have revolutionized cancer therapy and dramatically improved patient outcomes; nonetheless, after a period response, patient tumors almost universally develop resistance to these inhibitors and recur. In the case of squamous cell carcinoma of the lung, it has been demonstrated that focal amplifications of the FGFR1 gene occur in at least 10% of patients and that a subset of these events are sensitive to FGFR targeted therapies. Here, we describe the generation of resistant clones of the cell line NCI-H2077 to several FGFR inhibitors with clinical potential. This cell line is a squamous lung line with a focal amplification of FGFR1 that demonstrates dependency in the presence of both small molecule inhibitors and knockdown of the FGFR1 protein. After generation of resistant clones, we performed RTK phosphorylation arrays in the presence and absence of inhibitor to determine whether there were changes in the activity of other kinases, and the lines were sequenced to determine whether secondary mutations in FGFR1 had arisen. Follow-up experiments were performed to determine alternative sensitivities of the resistant clones. These experiments contribute to our growing understanding of the resistance mechanisms that arise in response to kinase inhibitors, and it is our hope that they will benefit patients undergoing treatment for FGFR1-amplified lung squamous cell carcinoma. Citation Format: Rachel G. Liao, Andrey Sivachenko, Gad Getz, Amit Dutt, Peter S. Hammerman, Matthew Meyerson. Characterizing acquired resistance mechanisms to targeted therapy in FGFR1-amplified lung squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 963. doi:10.1158/1538-7445.AM2013-963
Mixed immunobullous disease of childhood: a good response to antimicrobials
Authors: J. Powell, G. Kirtschig, J. Allen, D. Dean, F. Wojnarowska
Journal: British Journal of Dermatology (2001)

Background Immunobullous diseases are uncommon in childhood. In contrast to adults, the most commonly seen is IgA‐mediated chronic bullous disease of childhood (CBDC), while IgG‐mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare. We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with 'mixed immunobullous disease of childhood'. Objectives To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis. Methods We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated. Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed. Results Six of the eight patients presented with clinical features of CBDC. In two others, it was uncertain whether they had CBDC or BP. Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF. Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97‐kDa protein and laminin 5). Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone. The clinical course was not protracted. Five are in remission 1–4 years following treatment, and three still have active disease suppressed by treatment after 6 months−2 years. Conclusions Although we do not know why these children have 'mixed immunobullous disease' (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response.
Abstract 2152: Akt/survivin pathway inhibition synergizes the apoptotic cell death induced by A-santalol in prostate cancer cells
Authors: Ajay Bommareddy, Lauren Lockus, Jonathan Seward, William Eggelston, Stacy Prelewicz, Andrea Antal, Sarah Fillman, Christian Castro, Adam L. VanWert, Sreevidya Santha, Chandradhar Dwivedi
Journal: Cancer Research (2014)

Abstract α-santalol, a major component of sandalwood oil inhibits growth of cultured prostate cancer cells in vitro by causing apoptosis. The present study was undertaken to investigate the mechanistic details associated with the induction of apoptosis by α-santalol in cultured prostate cancer cells (LNCaP and PC-3). Expressions of major proteins studied in the present investigation were determined using standard Western blot protocol and analyzed by LICOR-Odyssey infra-red scanner. Activity of survivin was confirmed employing survivin ELISA kit. The cell viability was determined by trypan blue dye exclusion assay and caspase-3 activity was confirmed using caspase-3 (active) ELISA kit. Treatment of prostate cancer cells with α-santalol (20, 40 µM) resulted in the down regulation of survivin, XIAP and p-AKT (s-473) levels. Furthermore, α-santalol significantly reduced the activity of survivin as evidenced by survivin ELISA assay. Inhibition of PI3K/Akt by pharmacological inhibitor LY294002 synergized the apoptotic cell death induced by α-santalol as determined by cell viability, active caspase-3 activity and expression of cleaved PARP, caspase-3 levels. In conclusion, the present study reveals that α-santalol downregulates activity and expression of survivin and that inhibition of PI3K/Akt pathway synergize the apoptotic cell death by downregulating survivin. This study was supported by Mentoring Task Force, Type I grant by Wilkes University and by Translational Cancer Research Center funded by South Dakota Governor's Office of Economic Development. Citation Format: Ajay Bommareddy, Lauren Lockus, Jonathan Seward, William Eggelston, Stacy Prelewicz, Andrea Antal, Sarah Fillman, Christian Castro, Adam L. VanWert, Sreevidya Santha, Chandradhar Dwivedi. Akt/survivin pathway inhibition synergizes the apoptotic cell death induced by A-santalol in prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2152. doi:10.1158/1538-7445.AM2014-2152
Psychological approach to managing irritable bowel syndrome
Authors: Bu'Hussain Hayee, Ian Forgacs
Journal: BMJ (2007)

> “It is more important to know what sort of person has a disease than to know what sort of disease a person has.” Hippocrates 

The medical management of patients with irritable bowel syndrome is often unsatisfactory. Doctors are still taught that irritable bowel syndrome is a diagnosis of exclusion, and patients readily sense that they are being told that nothing is really wrong with them. Many people soon come to appreciate that the range of medical treatments available is limited in both scope and efficacy. The mood of negativity, once established, is difficult to dispel.

#### Summary points

Current medical treatment includes drugs that alter intestinal motility—such as antispasmodics, 5-hydroxytryptamine antagonists, antidiarrhoeals, and laxatives—and dietary changes, including fibre supplementation and identification of food intolerances.1 Response may vary, but the failure rate of these “physical” treatments is high, which may lead to the conclusion that irritable bowel syndrome has a strong psychological component. A diagnosis of exclusion has been made—again with negative, rather than positive therapeutic, connotations.

Although many doctors are aware that antidepressants have been used in irritable bowel syndrome, they seem reluctant to prescribe such agents, not least because suggesting this as a valid option to patients who are clearly not depressed …
Contact points between lexical retrieval and sentence production
Authors: Gabriella Vigliocco, Marco Zorzi
Journal: Behavioral and Brain Sciences (1999)

Speakers retrieve words to use them in sentences. Errors in incorporating words into sentential frames are revealing with respect to the lexical units as well as the lexical retrieval mechanism; hence they constrain theories of lexical access. We present a reanalysis of a corpus of spontaneously occurring lexical exchange errors that highlights the contact points between lexical and sentential processes.
Clopidogrel for Percutaneous Coronary Revascularization
Authors: David J. Moliterno, Steven R. Steinhubl
Journal: JAMA (2005)

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Is gastric emptying faster or slower in patients with early stage of non-insulin dependent diabetes mellitus?
Authors: I Y Chung
Journal: Gut (1992)

adult human liver,4 and have since investigated expression in a number of other fetal tissues.We found evidence of expression in tongue, brain, intestine, mandible, eye, sternum, pancreas, spleen, and in placenta and umbilical cord, but not in adrenals, thymus, skin, or lungs; high expression, however, was only observed in liver, intestine, and placenta.'3This pattern makes its unlikely that expression of the 6 Kb HGF mRNA merely reflects haemopoiesis.Finally, for completeness there are now two mRNA species for HGF, the most recently described being an alternatively spliced I 5 Kb transcript with an identical 5 prime cDNA sequence for the first 856 nucleotides downstream of the initiation of translation site, but completely divergent at the 3 prime end.'4 In summary, although the concept that only one growth factor is entirely responsible for liver regeneration is outmoded, the insights and implications of the HGF story seem likely to have an impact on our understanding of benign and perhaps malignant liver cell growth for many years to come.
Heterogeneity of Cardiac Allograft Vasculopathy: Clinical Insights From Coronary Angioscopy
Authors: Mandeep R Mehra, Hector O Ventura, Suresh P Jain, Keshav Ramireddy, Arshad Ali, Dwight D Stapleton, Frank W Smart, Stephen R Ramee, Tyrone J Collins, Christopher J White
Journal: Journal of the American College of Cardiology (1997)